maestria_docs/para Zulimary de luci/1 Memorias Escritas Primera Edición/Software Adanay/Colección/MED_doc.txt

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correlation between maternal and fetal plasma levels of glucose and free
fatty acids .                                                           
  correlation coefficients have been determined between the levels of   
glucose and ffa in maternal and fetal plasma collected at delivery .    
significant correlations were obtained between the maternal and fetal   
glucose levels and the maternal and fetal ffa levels . from the size of 
the correlation coefficients and the slopes of regression lines it      
appears that the fetal plasma glucose level at delivery is very strongly
dependent upon the maternal level whereas the fetal ffa level at        
delivery is only slightly dependent upon the maternal level .           
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changes of the nucleic acid and phospholipid levels of the livers in the
course of fetal and postnatal development .                             
  we have followed the evolution of dna, rna and pl in the livers of rat
foeti removed between the fifteenth and the twenty-first day of         
gestation and of young rats newly-born or at weaning . we can observe   
the following facts..                                                   
  1. dna concentration is 1100 ug p on the 15th day, it decreases from  
the 19th day until it reaches a value of 280 ug 5 days after weaning .  
  2. rna concentration is 1400 ug p on the 15th day and decreases to 820
during the same period .                                                
  3. pl concentration is low on the 15th day and during foetal life (700
ug) and increases abruptly at birth .                                   
  4. the ratios rna cyto/dna and pl cyto/dna increase regularly from the
18th day of foetal life .                                               
  5. nuclear rna and pl contents are very high throughout the           
development .                                                           
  6. these results enable us to characterize three stages in the        
development of the rat liver.. - from the 15th day to the 18th day of   
foetal life.. stage of growth through hyperplasia without hypertrophy,  
  - from the 19th day of foetal life to the 3rd day of post-natal life,.
stage of cellular reorganisation,                                       
  - after the 3rd day of post-natal life.. stage of growth through      
hyperplasia and hypertrophy .                                           
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surfactant in fetal lamb tracheal fluid .                               
  lambs delivered by cesarean section with intact fetal circulation have
a fluid filling the trachea . analysis revealed that this fluid         
contained material high in surface activity in lambs delivered near     
term, but less surface activity in premature lambs .                    
  administration of 10 per cent oxygen to the ewe for 1 hour prior to   
delivery did not alter the surfactant properties of the fetal tracheal  
fluid .                                                                 
  two analyses of the fetal tracheal fluid revealed it to contain 146   
and 198 mg. of lipid per 100 ml., 30 to 40 per cent of which was        
phospholipid, part of the active component of surfactant .              
  the investigations reported here offer a model for further research   
into possible intrauterine factors in the pathogenesis of hyaline       
membrane disease .                                                      
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placental and cord blood lipids.. comparison in a set of double ovum    
twins, a stillborn and a live-born .                                    
  1. determinations of phospholipid, total and free cholesterol,        
triglyceride and nefa have been made on placental tissue and cord blood 
in a set of double ovum twins, one stillborn and one live-born .        
  2. similarities occurred in all fractions studied except the cord     
blood triglyceride and nefa levels .                                    
  3. the serum of the stillborn infant contained one-third as much      
triglyceride and 21/2 times as much nefa as did the live-born infant .  
  4. the phospholipid content and the total lipid content of the        
stillbirth placenta were the highest studied in this laboratory which   
includes determinations on 26 live births .                             
  5. the suggestion is made that increased lipoprotein lipase activity  
in the cord blood may accompany intrauterine fetal death .              
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free fatty acid concentration in maternal plasma and fetal body fat     
content .                                                               
  subcutaneous injection of 200 u.s.p. units of heparin into female     
sprague-dawley rats produced large and sustained elevations of plasma   
free fatty acids but no significant change in blood glucose . a group of
pregnant rats received such injections of heparin 3 times daily         
throughout pregnancy . the fetuses from mothers of this group, at 191/2 
and 211/2 days of gestation, had significantly more body fat than the   
fetuses from uninjected mothers . the hypothesis is presented that the  
maternal free fatty acid concentration in part determines fetal fat     
accumulation . it is proposed that the body composition changes noted in
babies of mothers with diabetes might thus be ascribed to abnormally    
high maternal plasma free fatty acid concentrations .                   
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the concentration of non-esterified fatty acids in maternal and fetal   
plasma in intact, alloxan-diabetic and x-ray-irradiated rats .          
  determinations of the non-esterified fatty acids in the plasma of     
pregnant rats showed that there do not exist any increases in the       
concentrations depending on pregnancy during the period from the 20th - 
22nd day of pregnancy . in the fetal plasma the concentrations of       
non-esterified fatty acids only amounted to 40 - 50 per cent of the     
maternal values .                                                       
  with alloxan diabetes produced 2 days prior to the test the           
concentration in the maternal plasma increased three- to fivefold, while
at the same time a significant rise was absent in fetal plasma with     
slightly increased average values .                                     
  whole-body x-ray exposures (dose.. 400r, dose output.. 40r/min) of    
non-pregnant female and of pregnant rats beginning on the 17th day of   
pregnancy did not result in any changes of the concentration of         
non-esterified fatty acids immediately after irradiation .              
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lipid metabolism in toxemia and normal pregnancy .                      
  the amount and fatty acid composition of total lipid extract from     
serum were examined in normal pregnant women in the first, second, and  
third trimesters, and early postpartum period, and in patients with mild
and severe preeclampsia and with essential hypertension . placentas at  
term were also examined for total lipid and its fatty acid composition .
in the normal women, total serum lipid increased during pregnancy . the 
rise was less pronounced in those with preeclampsia or hypertension .   
serum palmitate was mildly but significantly elevated in preeclampsia . 
total lipid and arachidonic acid were elevated in the placentas of      
preeclamptic women . the findings are compared with those obtained from 
animals developing eclampsia on an experimental basis .                 
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essential fatty acids and acids with trans-configuration in the         
subcutaneous and visceral fat of the newborn .                          
  we made an investigation of the subcutaneous and visceral fat in the  
newborn . we estimated the contents of linolic and linolenic acid and of
acids with trans-configuration spectrophotometrically .                 
  we were able to show the penetration of these acids through the       
placental barrier . the essential fatty acid contents of fat in the     
newborn is low . in immature ones about 7-14 g, there is a rising trend.
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acetoacetate formation by livers from human fetuses aged 8-17 weeks .   
  slices and homogenates from livers of human fetuses aged 8-17 weeks   
have a low rate of acetoacetate formation which can be raised by        
addition of acetate or octanoate to the incubation medium . it was not  
possible to demonstrate acetoacetate formation by isolated liver        
mitochondria from 17-week-old fetuses, probably because mitochondria are
injured during isolation .                                              
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changes in blood glucose and non-esterified fatty acids in the foetal   
and newborn lamb after injection of adrenaline .                        
  changes in blood glucose and non-esterified fatty acids after         
intravenous adrenaline were measured in foetal, newborn and adult sheep 
in the foetus and immediately after birth there was very little       
increase in either blood glucose or non-esterified fatty acids after    
adrenaline . the response of blood glucose to adrenaline had reached    
adult levels at twenty-four hours of age . the response of non-esterifi-
ed fatty acids to adrenaline increased gradually over the first week .  
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electron-microscopic observatations on transference of fat through the  
human placenta .                                                        
  from the results of our previous and present studied on the           
transportation of fat through the human placenta by means of electron   
microscopy, we obtained the following conclusions .                     
  1) neutral fat can permeate through the human placenta without        
dissociation .                                                          
  2) almost all processes of fat permeation seem to be due to the       
biological activity . pinocytosis is most representative, but the       
authors newly found several facts such as dissolution-like change in the
basement membrane and transport via the stroma cell . the authors       
believe that these results will bring a clue to explain the mechanism of
biological transportation of materials through the placenta .           
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the content of phosphatides, triglycerides and cholesterol in placentas,
maternal, fetal and new-born liver of the white rat .                   
  thin-layer-chromatographic examinations in the maternal rat liver     
showed different rise of the triglycerides and a significant increase of
the esterified cholesterol, however, no striking changes in the content 
of free cholesterol and lipid phosphorus with the fractions examined    
(lecithin, colamine cephalin, sphingomyelin and lysolecithin) .         
  as compared to the liver of adult rats, the fetal liver contains a    
little less than 50 per cent lipid phosphorus . the difference is       
conditioned by the concentrations of lecithin, and colamine cephalin .  
on the 19th day the content of triglycerides is lower than in the mother
rat . referred to the dry weight, there results a decrease of all       
phosphatide fractions, as well as of the free cholesterol and a slight  
rise of the triglycerides from the 19th to the 22nd day .               
  the rise of the phosphatide concentrations to the values of adult rats
occurs immediately after birth under the influence of milk food, which, 
moreover, leads to a considerable increase of the triglyceride values . 
phospholipid- and triglyceride concentrations of the placenta correspond
to those of the fetal liver . solely the content of free cholesterol is 
higher at the end of pregnancy . the content of triglyceride drops      
towards the 22nd day .                                                  
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analysis of mammalian lens proteins by electrophoresis .                
  lens proteins of different mammalian species were analyzed by         
two-dimensional starch gel electrophoresis . the number of fractions    
detected by this means varied from 11-20 . a-crystallin was resolved    
into two to three components, b-crystallin into 5-11, and y-crystallin  
into three to five components . this technique provides a sensitive     
method for the fractionation of lens proteins and for analyzing species 
differences .                                                           
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an autoradiographic study on cell migration in the eye lens epithelium  
from normal and alloxan diabetic rats .                                 
  lenses from normal and alloxan diabetic rats with and without cataract
were investigated by autoradiography 4 hours, 4 days and 8 days after an
intraperitoneal injection of h3-thymidine (0.4 uc/g body weight) . the  
rats were made diabetic 8 days prior to the injection of thymidine at an
age of 4 weeks . the position of labelled nuclei of the lens epithelium 
was noted and their grain numbers counted . the diabetic rats had a     
lower frequency of labelled nuclei than the controls but after 4 hours  
their grain counts were equal . frequency diagrams of labelled nuclei   
are given for each of the three experimental periods . a predominant    
peak appears after 4 hours at a distance of 30-60 cells in front of the 
beginning of the nuclear arc . a successive shift towards this area was 
observed for the longer experimental periods . the shift of the peaks   
was more restricted in the diabetic animals . this result may best be   
interpreted as an effect of an increased time of cell generation .      
  as an appendix a histotechnique for the eye lens is given in          
collaboration with mrs. gertraude moewis .                              
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lens development.. the differentiation of embryonic chick lens          
epithelial cells in vitro and in vivo .                                 
  the behavior of lens epithelial cells from six-day chick embryos was  
studied in three different experimental situations.. (a) explantation   
into several different fluid culture media, (b) explantation followed by
reimplantation into lensectomized embryonic eyes, and (c) explantation  
followed by reimplantation into the embryonic coelomic cavity .         
specimens were examined histologically, and the total volume of the lens
material of each specimen was determined from the planimetry of serial  
sections . the results were interpreted as follows..                    
  1. with a small amount of protein supplement in the culture medium,   
embryonic lens epithelial cells are capable of a limited amount of      
independent cytodifferentiation . without protein supplement they fail  
to undergo any fiber formation .                                        
  2. when returned to the eye environment, cultured epithelial explants 
will respond with a resumption of growth, with further cellular         
differentiation, and with at least some of the morphogenetic changes    
necessary to form a lens . the embryonic coelom will not support these  
responses .                                                             
  3. the initiation of the formation of lens fibers is not sufficient   
for their complete autonomous maturation .                              
  4. the internal architecture of the developing lens is not the only   
determinant of its overall shape .                                      
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treatment of active chronic hepatitis and lupoid hepatitis with         
6-mercaptopurine and azothioprine .                                     
  6-mercaptopurine or azothioprine ('imuran') was used successfully in 3
patients with active chronic hepatitis and 2 with lupoid hepatitis, for 
periods up to 1 year . these drugs allowed modification and even        
abolition of discomforting corticosteroid regimes . their action in     
chronic hepatitis may be analogous to their anti-immune action in       
suppressing homograft rejection .                                       
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treatment of collagen diseases with cytostatics .                       
  22 patients with collagen diseases and 3 patients with other          
immunological diseases were treated with the cytostatic antimetabolites 
('purinethol') 6-mercaptopurine and ('imuran') azathioprine for an      
average period of four months (range one to eleven months) . improvement
was obtained in 17 patients,. and, in 20 out of 22 patients who had been
on long-term glucocorticoid medication, the steroid therapy could be    
permanently discontinued . serious complications occurred, in the form  
of two deaths from pancytopenia and sepsis . the treatment requires     
careful supervision of the patients, and should only be instituted, on  
strict indications, when the alternative is long-term glucocorticoid    
medication .                                                            
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bilateral popliteal cysts in a patient with rheumatoid arthritis .      
  a case of bilateral popliteal cysts and multiple joint subluxations in
a patient with rheumatoid arthritis on corticosteroid medication for    
many years is reported . the effect of long-term corticosteroid therapy 
on all periarticular connective tissue structure and the relationship of
articular disease and popliteal knee cysts to this therapy have been    
discussed .                                                             
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systemic lupus erythematosus and renal transplantation.. report of two  
cases .                                                                 
  two cases of systemic lupus erythematosus along with terminal uremia  
secondary to lupus nephritis are presented . both patients were treated 
with renal hemodialysis and transplantation . certain mechanical,       
infectious, and immunologic problems were responsible for their death . 
there was no evidence of resurgence of lupus erythematosus in either    
patient, and the transplanted kidneys did not show evidence of lupus    
nephritis . renal transplantation should be considered as a last resort 
in treatment of patients with terminal lupus nephritis .                
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arteritis and localised periosteal new bone formation .                 
  1. three patients with localised periosteal new bone formation        
associated with periosteal arteritis and other evidence of systemic     
lupus erythematosus are described .                                     
  2. systemic steroid therapy was valuable in the management of this    
condition .                                                             
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fine structure of subtilis phage sp-50 .                                
  some structural details and anomalous forms of subtilis phage sp-50   
are described .                                                         
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genetic transcription during morphogenesis .                            
  messenger rna's from bacillus subtilis undergoing sporulation,        
germination, or step-down transition have been characterized and        
compared . hybrid competition experiments indicate that these messengers
are derived from distinct genetic loci . the results are consistent with
the hypothesis that differential transcription of the genome occurs     
during morphogenesis . the data also complement previously observed     
changes in morphology and enzymatic activity in sporulating bacteria .  
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renal amyloidosis a clinicopathological study .                         
  the clinical and histopathological data from 40 cases of renal        
amyloidosis diagnosed by percutaneous renal biopsy are presented .      
  twenty-two cases were labelled as 'secondary' amyloidosis, as definite
aetiological factors responsible for renal amyloidosis could be         
discovered . the predisposing disease states leading to amyloid deposits
in the kidney in the order of frequency were fibrocaseous pulmonary     
tuberculosis, bronchiectasis, lung abscess, and ileocaecal tuberculosis 
five cases were labelled as suspected 'primary' amyloidosis as a      
definite evidence of the predisposing disease could not be obtained     
although the skiagram of chest revealed minimal healed foci . no cause  
could be determined in thirteen cases, which were, therefore, labelled  
as 'primary' amyloidosis .                                              
  albuminuria was a constant feature in all the cases and 32 cases      
presented as nephrotic syndrome . the rest of the cases presented with  
hypertension or renal failure in addition to albuminuria .              
  the ancillary procedure, viz., congo-red test, gingival and liver     
biopsies proved to be of limited value in the diagnosis of renal        
amyloidosis .                                                           
  the importance of percutaneous renal biopsy as a diagnostic tool has  
been emphasised .                                                       
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idiopathic autoimmune hemolytic anemia and idiopathic thrombocytopenic  
purpura associated with diffuse hypergammaglobulinemia, amyloidosis,    
hypoalbuminemia and plasmacytosis .                                     
  a case is reported of a sixty-nine year old woman with severe,        
idiopathic, autoimmune hemolytic anemia which was initially controlled  
by splenectomy . a relapse associated with the development of severe,   
autoimmune, thrombocytopenic purpura failed to respond to large doses of
prednisone, but was controlled to a variable degree with imuran .       
  associated features included diffuse hypergammaglobulinemia, excessive
gamma-u proteins in the urine, idiopathic hypoalbuminemia with a greatly
reduced total exchangeable albumin pool, amyloidosis in the spleen and  
other organs, and diffuse plasmacytosis of the bone marrow, lymph nodes,
and thoracic and peritoneal fat . these features and their              
interrelationships are discussed . there was no deficiency in the       
synthesis of specific neutralizing antibodies against viruses,          
indicating that a qualitative immune deficiency did not exist .         
  the frequency of occurrence of thrombocytopenic purpura in such a case
is discussed, as is the prognosis . the mechanism of action of          
antimetabolites in inducing a remission in autoimmune hemolytic anemia, 
as well as the etiology of the disease, is reviewed .                   
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corticosteroid therapy of amyloid nephrotic syndrome .                  
  the results of treatment with prolonged adrenal corticosteroids in 26 
adults with amyloid nephrotic syndrome are presented . eight subjects   
were observed in this series, and 18 additional cases were summarized   
from the literature . twenty-two of the patients were male and four were
female . the diagnosis was established by renal biopsy in 19 instances  
and by autopsy in the others, with 18 patients considered to have       
primary amyloidosis and 8, secondary amyloidosis .                      
  the majority of the subjects died in renal failure with an average    
survival after onset of the disease of 17.6 months . the renal disease  
was indistinguishable from that seen in other forms of the nephrotic    
syndrome, with the possible exceptions of (a) a high incidence of       
purpuric skin lesions, (b) a low or negligible incidence of hypertension
(at times actual hypotension was prominent), and (c) a rapid and        
inexorable progression of azotemia despite persistence of the clinical  
and biochemical characteristics of the nephrotic syndrome . amyloidosis 
was found by percutaneous renal biopsy in 12 per cent of 83 adults with 
the nephotic syndrome .                                                 
  corticosteroids did not appear to affect the progress of the disease  
and were neither beneficial nor detrimental . in view of the high       
incidence of deleterious side effects of prolonged corticosteroid       
therapy and the availability of potent diuretic agents which may be     
helpful in relieving edema in this disorder, it is felt that            
corticosteroids are contraindicated in the treatment of amyloid         
nephrotic syndrome .                                                    
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renal amyloidosis.. a biopsy study .                                    
  the relationship of the amount of amyloid deposition in the kidney to 
the clinical picture is reviewed in 14 cases of renal amyloidosis       
diagnosed by renal biopsy . the large percentage of patients who had the
nephrotic syndrome (11 patients) probably reflects the criteria for     
renal biopsy at this institution . the etiology of the amyloid          
deposition did not seem to be clearly correlated with either the amount 
of amyloid deposition in the kidney or the severity of the clinical     
renal disease . all patients had deposits in the glomerulus, and the    
heavier the deposition the severer the renal disease . of 7 patients who
had biopsy of the bone marrow, all had abnormal types or numbers of     
plasma cells . the age range in primary amyloidosis appeared to be about
the same as that in amyloidosis secondary to myeloma . amyloidosis      
should be suspected in patients with proteinuria, the nephrotic         
syndrome, or renal failure .                                            
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amyloid goitre a case report .                                          
  a case of amyloid goitre in an indian female, aged 27 years, occurring
as a sequelae to pulmonary tuberculosis, is reported .                  
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amyloid.. starch gel electrophoretic analysis of some proteins extracted
from amyloid .                                                          
  proteins extracted by strong urea from washed tissue of patients with 
amyloidosis secondary to several diseases or associated with familial   
mediterranean fever have common major electrophoretic components . in   
hearts of primary amyloidosis one component in common with the secondary
amyloid may be present . however, primary amyloid is much more difficult
to dissolve and does not regularly give the components observed when the
secondary amyloid is extracted . the big question remains as to what    
constituent or constituents comprise the fibrils now known to be a part 
of amyloid .                                                            
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selectivity of protein excretion in patients with the nephrotic syndrome.
  with a gel diffusion precipitin technique and commercially prepared   
antisera, urine/plasma ratios of specific proteins were determined .    
individual protein clearances, expressed as a percentage of transferrin 
clearance, were plotted as ordinates against respective molecular       
weights on a log-log graph . a straight line was evident graphically,   
its constants were estimated by the method of least squares, and the    
slope, expressed as , was determined . the slope of the line may be said
to express the degree of glomerular selectivity to protein excretion .  
sixty-five determinations were performed in 48 patients . 45 satisfying 
the usual criteria of the nephrotic syndrome .                          
  1) those patients with primary renal disease and the nephrotic        
syndrome who displayed high selectivity types of proteinuria ( greater  
than the average for the group + 1 sd) usually respond initially to     
steroid therapy, regardless of the acute or subacute glomerular changes 
observed on renal biopsy .                                              
  2) those patients with chronic renal disease and the nephrotic        
syndrome display an average and frequently a low selectivity type of    
proteinuria .                                                           
  3) there appears to be no characteristic type of selectivity for a    
given pathologic group of patients with the nephrotic syndrome .        
  4) the degree of selective protein excretion is not related to the    
total daily amount of protein being excreted at any one time and remains
fairly constant despite fluctuation in the amount of protein being      
excreted .                                                              
  5) there is a slight correlation of borderline significance between   
the degree of selective protein excretion and the duration of the       
disease, and the initial para-aminohippuric acid clearance .            
  6) a statistically significant correlation exists between the initial 
blood urea nitrogen or inulin clearance and the selectivity type of     
protein excretion . those patients who were not azotemic and had        
initially near-normal inulin clearances had an average selectivity type 
or better .                                                             
  7) it is suggested that if the adult patient is initially azotemic and
has a grossly abnormal inulin clearance, response to therapy is         
unlikely, whereas if the blood urea nitrogen is normal and the inulin   
clearance is near normal, response to therapy cannot be predicted with  
any degree of accuracy . further studies of adult patients with the     
nephrotic syndrome are required to substantiate this premise .          
.I 30
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some aspects of haemostasis after open-heart surgery .                  
  synopsis in two groups of patients undergoing extracorporeal          
circulation with hypothermia, changes were found in the coagulation     
mechanism which were probably due to the dosage of polybrene            
administered .                                                          
  the role of heparin and polybrene and the concept of activation of the
coagulation mechanism in the production of bleeding after perfusion are 
discussed .                                                             
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a case of interventricular septal defect with dextrocardia and situs    
inversus treated by surgery .                                           
  a case of interventricular septal defect associated with situs        
inversus and dextrocardia in twenty year old male patient was presented 
along with discussion on three types of dextrocardial complexes and with
emphasis on the rarity of occurrence of the intracardiac anomalies in   
true /mirror-image/ dextrocardia with total situs inversus . a comment  
was also made on kartagener's syndrome which was excluded by appropriate
radiographic procedures in this case .                                  
  the closure of the interventricular septal defect with extracorporeal 
circulation was successfully performed under moderate hypothermia .     
.I 32
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excretion patterns of urinary metabolites of estradiol-4-c14 in         
postmenopausal women with benign and malignant disease of the breast .  
  a study of the excretion patterns of the urinary metabolites of       
estradiol-4-c1j administered to a group of 43 postmenopausal women, 38  
with advanced mammary carcinoma prior to endocrine therapy and 5 with   
benign mammary dysplasia, is reported . a chromatographic method was    
employed for the determination of estradiol, estrone, and estriol and   
other estrogen metabolites . the urinary excretion pattern is defined by
(a) the extent of excretion of isotope in each of 3 successive 24-hr.   
collection periods, (b) the percentage of the urinary radiometabolites  
enzymatically hydrolyzed, (c) the relative concentration of the several 
metabolites in the hydrolyzed fraction . wide subject-to-subject        
variations were found . the metabolites other than estradiol, estrone,  
and estriol comprised a large portion of the total estrogens excreted . 
a significantly lower amount of estradiol was noted in the group of     
women with mammary carcinoma as compared to the amount found in the     
group of women with benign mammary dysplasia, suggesting that the former
group metabolizes more rapidly the administered estradiol . although the
excretion patterns of patients who failed to respond to estrogen        
treatment (nonresponders) differed the greatest from the patterns       
associated with benign disease, distinctive patterns of the urinary     
excretion of isotopic estrogens which allowed a statistically           
significant or clinically useful separation between responders and      
nonresponders to subsequent estrogen therapy were not discovered .      
.I 33
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the localizing significance of limited simultaneous visual form         
perception .                                                            
  a patient presenting with an isolated /spelling dyslexia/ and         
impairment in picture interpretation (simultanagnosia) was shown by     
tachistoscopic studies to have a pathological limitation of simultaneous
form perception . at autopsy a localized lesion was found within the    
inferior part of the left occipital lobe .                              
  these findings are discussed in relation to the problem of the        
disorder of function underlying /agnosic alexia/ .                      
.I 34
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visual anosognosia in cortical blindness anton's symptom .              
  denial of blindness in a case of bilateral hemianopia is presented to 
acquaint ophthalmologists with this symptom which is well-known to      
neurologists but is rarely seen by opthalmologists .                    
.I 35
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the development of social attachments in infancy .                      
  this report is devoted to the formation and development of social     
attachments in infancy . it is suggested that the core of the attachment
function is represented by the tendency of the young to seek the        
proximity of certain other members of the species and that the most     
suitable operational definition may be found in the behavior of the     
individual when deprived of such proximity .                            
  the study takes the form of a longitudinal follow-up, in which 60     
infants were investigated at four-weekly intervals from the early weeks 
on up to the end of the first year and again at 18 months of age . with 
the use of an attachment scale, based on seven everyday separation      
situations, the following three main parameters were explored.. the age 
at onset of specific attachments, the intensity of such attachments, and
the number of objects to whom attachments are formed . a measure of     
fear-of-strangers was also included .                                   
  results indicate that the age at onset of specific attachments is     
generally to be found in the third quarter of the first year, but that  
this is preceded by a phase of indiscriminate attachment behavior,. that
the intensity of specific attachment increases most in the first month  
following onset and that thereafter fluctuations occur in individual    
cases which make long-term prediction difficult,. and that multiplicity 
of objects can be found in some instances at the very beginning of the  
specific attachment phase, becoming the rule in most of the remaining   
cases very soon thereafter . correlations between the attachment        
variables, as well as with the fear-of-strangers measure, are presented,
and an examination is also made of the conditions eliciting protest at  
proximity loss, of the manner in which protest is expressed, and of the 
conditions necessary to terminate protest .                             
  individual differences with regard to the three main parameters were  
explored in a subgroup of 36 infants . a number of variables were       
examined in relation to these individual differences, and suggestions   
made regarding the conditions which affect the manifestation of the     
attachment function .                                                   
  the data are discussed in relation to four themes which emerged from  
the findings.. the nature of the attachment function, its developmental 
origins, its developmental trends, and the influence of the social      
setting .                                                               
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separation anxiety as a cause of early emotional problems in children . 
  in summary, three cases of disturbed behavior in children have been   
discussed, with particular emphasis on disturbances in feeding,         
sleeping, and motility . some of the hypotheses have been presented of  
why such behavior should develop,. the significance of attachment       
behavior and separation anxiety in infants has been particularly        
stressed . difficulties in mothering care are threatening to the child's
sense of security and lead to greater experience of separation anxiety, 
which may then be reflected in various disturbances or alterations in   
his behavior . this experience of separation anxiety is the result of   
early life experience, may reach pathologic proportions, and may account
for many later problems in children and adults .                        
.I 37
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the production of malignant tumours by nickel in the rat .              
  powdered metallic nickel when injected intramuscularly into rats      
produced tumours of striated muscle origin, most of which were very well
differentiated .                                                        
.I 38
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studies of nickel carcinogenesis fractionations of nickel in            
ultracentrifugal supernatants of lung and liver by means of dextran gel 
chromatography .                                                        
  chromatographic fractionations have been performed on the             
ultracentrifugal supernatants of homogenates of rat lung and liver by   
the use of columns of dextran gel (sephadex g-100) . a major proportion 
of nickel in these tissue supernatants has been demonstrated to be      
firmly bound to macromolecular constituents . following acute and       
chronic inhalation of carcinogenic levels of nickel carbonyl, the       
predominant increases in the concentrations of nickel have been observed
in the macromolecular fractions . these findings are consistent with the
previous demonstration of nickel in purified preparations of ribonucleic
acids (rna) from several rat tissues, and with the observation of       
increased concentrations of nickel in high-molecular weight rna from    
lung and liver following the inhalation of nickel carbonyl .            
.I 39
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a study of the inhibitory effect of ethylenediaminetetra-acetic acid on 
the thrombin-fibrinogen reaction .                                      
  1. ethylenediaminetetra-acetic acid reversibly inhibits the           
thrombin-fibrinogen reaction by means of a time-dependent diminution in 
fibrinogen reactivity .                                                 
  2. this alteration of fibrinogen is due to some property of the edta  
molecule in an unchelated form, and is not due to the removal of trace  
metal ions .                                                            
  3. possible explanations for this phenomenon are discussed .          
.I 40
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intradermal test using cobalt chloride .                                
  selected groups of patients with cobalt allergy and nickel allergy as 
well as normal controls were tested intradermally with cobalt chloride  
in the dilutions 10 to 10 . reactions of the wheal and flare type appear
during the first hours and make the 24-hour reading misleading . the    
papular response to cobalt chloride 10, when read 48 to 96 hours after  
the injection, appears to be a reliable test for cobalt allergy .       
patients with combined nickel-cobalt allergy were excluded from the     
study, and the question of group reactions is not discussed . nickel    
allergics give a somewhat stronger reaction than controls to the        
slightly impure cobalt chloride . it would be preferable if the degree  
of purity of the cobalt chloride were ten times greater .               
.I 41
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measurements of nickel in biological materials by atomic absorption     
spectrometry .                                                          
  an atomic absorption procedure has been developed which facilitates   
quantitative measurements of nickel in biological materials, including  
urine, ribonucleic acids (rna), and serum proteins .                    
  the sensitivity of detection of nickel by the atomic absorption       
spectrometer (0.10 p.p.m.) was insufficient to permit direct            
measurements of nickel in normal urine . therefore, it was necessary to 
employ a dimethylglyoxime extraction procedure to concentrate the       
nickel, prior to atomic absorption spectrometry .                       
  the coefficients of variation of measurements of nickel in urine and  
human b- globulins were 6.3 and 5.9 per cent, respectively . the        
recovery of nickel added to urine averaged 96 per cent, with a range    
from 94 to 97, and the recovery of nickel added to human b-globulin     
averaged 101 per cent, with a range from 96 to 104 .                    
  the mean concentration of nickel in 24-hr. collections of urine from  
17 normal subjects was 1.8 ug. per 100 ml. (s.d. = 0.8), with a range   
from 0.4 to 3.1 . the mean urinary excretion of nickel was 19.8 ug. per 
24 hr. (s.d. = 10.0), with a range from 7.2 to 37.6 .                   
  the mean concentration of nickel in 5 preparations of ribonucleic     
acids from ultracentrifugal supernatants of homogenates of rat lung was 
48 ug. of ni per gm. of rna, with a range from 34 to 64 . the mean      
concentration of nickel in 5 preparations of rna from ultracentrifugal  
supernatants of homogenates of rat liver was 29 ug. of ni per gm. of    
rna, with a range from 21 to 39 .                                       
  measurements of nickel were performed upon fractions of human serum   
proteins, prepared by continuous-flow electrophoresis, and by           
cold-ethanol precipitation . the highest concentrations of nickel were  
found in preparations of serum b-globulins .                            
.I 42
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properties of activity of 5'-nucleotidase in human serum, and           
applications in diagnosis .                                             
  the influence of mg , ni , and l-histidine on purified preparations of
bone and intestinal alkaline phosphatases and 5'-nucleotidase, and on   
various mixtures of these enzymes has been studied . the extent to which
these findings can be utilized in the quantitative assay of             
5'-nucleotidase in serum has been evaluated . results are presented on  
the possible utilization of l-histodine in the simultaneous evaluation  
of serum alkaline phosphatase and 5'-nucleotidase activity .            
.I 43
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some 2-iminoselenazolidin-4-ones and related compounds .                
  a series of 2-iminoselenazolidin-4-ones, selenazolidine-2,4-diones and
some 2-alkylidenehydrazones have been synthesised . wide-range screening
for biological activity failed to reveal any compounds of promise .     
.I 44
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the influence of methemoglobinemia on the lethality of some toxic       
anions, 1. azide .                                                      
  the time course and extent of the methemoglobinemia induced by        
intraperitoneal sodium nitrite and p-aminopropiophenone (papp) have been
characterized in female mice . the peak methemoglobin formation (34 ) is
achieved in about 40 minutes . comparable levels from papp (15 mg/kg)   
are achieved more quickly (between 5 and 10 minutes) but decline more   
rapidly to normal . both nitrite- and papp-induced methemoglobinemia    
afford a significant degree of protection against poisoning by sodium   
azide when administered in an appropriate time sequence . it was not    
possible under the same circumstances to protect mice against death from
fluoride, cyanate, thiocyanate, selenate, or borate, although some      
prolongation of survival time was seen after fluoride . the formation of
the azide-methemoglobin complex has been demonstrated within intact     
mouse red blood cells, and small amounts of the complex were identified 
in vivo in an antidotal situation . we think it important that the      
protective action of methemoglobinemia has been demonstrated to date    
only against established inhibitors of cytochrome oxidase .             
.I 45
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selenium as a trace element .                                           
  an account is given of the discovery of selenium by berzelius and gahn
the toxic behaviour of large selenium quantities in soils upon        
vegetation, animals, and man is surveyed . a review is also given of the
role of trace amounts of selenium in the prevention of myopathies in    
animals . finally, some recent theories on the importance of retinal    
selenium to vision are mentioned .                                      
.I 46
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toxicity of inorganic selenium salts to chick embryos .                 
  the effects of selenite and selenate treatment by air cell injection  
on mortality and growth of 14-day chick embryos during a 64-68 hour     
period were studied . the ld for selenite-se was about 0.5 ppm, based on
weight of the egg contents, and that for selenate-se about 1.8-2.0 ppm .
growth depression was evident from these treatments, but other gross    
effects were not prominent . the treatment of embryos with selenite and 
sulfate together caused a greater mortality than treatment with selenite
alone .                                                                 
.I 47
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lesions of the islets of langerhans during injections of sodium selenite
administered intravenously .                                            
  sodium selenite was administered intravenously in rabbits and in dogs 
  repeated injections can lead to the development of a diabetic syndrome
in the rabbit .                                                         
  the histological examination of the pancreas in the poisoned animals  
(dogs and rabbits) has shown the existence of lesions of the islets of  
langerhans, mostly of the b cells which lose their granules partly or   
completely .                                                            
  these changes seem analogous to the ones produced by alloxan,. these  
two poisons act at first by inactivating the sh groups, which leads to a
deficiency to which the b cells are very sensitive .                    
.I 48
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toxicity of sulfur-35, selenium, and tellurium to avian embryos .       
  continuous internal irradiation of chick embryos with sulfur-35       
administered on the 4th or 8th day of incubation produced abnormalities 
similar to those observed in selenium toxicosis of avian embryos . the  
highest level of sulfur-35 (1600 uc) injected into eggs containing 4-day
embryos produced morphological abnormalities more severe than those     
produced by the same level of radiosulfur administered to 8-day embryos,
or by any level of stable selenium tolerated . selenium at levels       
greater than 30 ug killed all the embryos within 24 hours after         
injection . nearly 20 times more tellurium than selenium was required to
kill all the embryos within 24 hours.. no abnormalities were observed in
the tellurium-injected embryos .                                        
.I 49
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the effect of selenium on the upper respiratory passages .              
  results are reported of examination of workers exposed to selenium,   
with special reference to chronic changes in the respiratory passages . 
the findings are the same as reported in the literature . we emphasize  
the occurrence of teleangiectasias on the uvula and on the posterior    
palatinal arcs and on the epiglotis . we describe the occurrence of the 
first poisoning with selenium xyde in this country . the poisoning      
healed within a few days under symptomatic treatment . the patient had  
however to be transferred into another shop owing to frequent symptoms  
due to toxic effect of selenium . we report also on secondary findings  
in examination of chronic changes and we emphasize particularly the     
finding of profesional selenium external otitis .                       
.I 50
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the influence of small selenite doses upon the toxic fatty degeneration 
of the liver .                                                          
  sodium selenite (10 ug/kg) manifests a lipotropic effect after        
toxication of the rat by tetrachlorocarbon . this effect is absent when 
the selenite dose is increased to 50 ug/kg . the level of the total     
lipides of the liver after ethionine toxication is not significantly    
influenced by 10 ug selenite/kg . it is increased by 50 ug selenite/kg. 
.I 51
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selenium-caused tumours .                                               
  in 10 out of 23 heterozygous rats administered 10 mg na seo per 1 kg  
food (containing 12 protein) and surviving for 18 months, cancer of the 
liver (with metastases in the lungs) along with sarcoma and adenoma was 
recorded . in another series of the yet incompleted experiment the      
animals were fed higher quantities of protein and selenium . toward     
14-19 months in three of them sarcoma was noted.. in two sarcoma of the 
lymphatic nodes, and in one- of the mediastinum .                       
  it is suggested that the changes caused by selenium compounds are to  
some extent due to their antagonistic relationship with methionine .    
.I 52
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blood and bone marrow damage caused by drugs .                          
  drug side effects on blood and bone marrow are briefly reviewed . they
embrace a wide variety of symptoms and pathogenetic mechanisms, and in  
recent years study of these effects has made important contributions to 
our knowledge of the immunology, biochemistry and metabolism of the     
blood cells .                                                           
.I 53
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hypothermia.. physiologic effects and clinical application .            
  a survey of the background, physiologic effects, indications,         
technique and complications of hypothermia is presented . the           
application of this technique is straightforward and safe when used at  
the proper levels with the proper indications .                         
.I 54
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ehrlich ascites tumor cells agglutination.. the interference exerted by 
epsilonaminocaproic acid (eac) and its acetyl derivative (eaca) .       
  the activity of epsilon-aminocaproic acid (eac) and of its acetyl     
derivative (eaca) was studied on antigen-antibody reactions, membrane   
antigens and immune globulins .                                         
  in vitro eac and eaca do not affect immune globulins, but they do     
alter the membrane antigens of ehrlich ascites tumor cells and inhibit  
the agglutination reaction induced by a specific antiserum . inhibition 
is only partially due to the antigenic alteration observed, and it      
represents more prominently a direct interference at the level of the   
antigen-antibody reaction .                                             
  the membrane antigen alternations induced by the drugs and by nitrogen
mustard were compared, taking into account their toxicity.. eac and eaca
were found to be much more active and more specific than nitrogen       
mustard .                                                               
.I 55
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study on the behavior of tumor tissue in diffusion chambers against     
penetrating host cells in tumor-resistant rats .                        
  tumour cells in diffusion chambers, which were implanted in           
tumour-resistant rats, were only destroyed by penetrating immunized host
cells when membrane filters of large pore size were used, whereas with  
filters of small pore size the tumour cells survived and remained       
virulent .                                                              
.I 56
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current status of hypothermia .                                         
  moderate hypothermia has been recommended for many and varied         
conditions . today its value is being questioned in the light of        
controlled groups of patients . at the moment its use is justified in   
certain cardiac and other operations where circulation may be           
interrupted for short periods.. in general surgical procedures where    
massive, sudden blood loss may be anticipated.. in neurosurgical        
operations where a /relaxed/ brain is required.. following acute hypoxia
such as seen in cardiac arrest.. and perhaps in the therapy of acute    
septicemic shock .                                                      
  profound hypothermia in association with extracorporeal circulation   
rests on shakier premises, but can be of value in major cardiac         
operations where asystole is required and in certain neurosurgical      
procedures where complete interruption of circulation is indicated .    
  there is a great hazard in the development of inadvertent or          
unrecognized hypothermia in the anesthetized patient . monitoring of    
body temperature is an important feature of the care of the patient in  
the operating theater and in the recovery room .                        
.I 57
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hyperglycemic coronary perfusion.. effect of hypothermia on myocardial  
function during cardiopulmonary bypass .                                
  in a series of 84 animal experiments hyperglycemic perfusion of the   
heart gave significant protection to the anoxic heart . this protection 
was evaluated by ventricular function and contractile force studies and 
was observed after aortic occlusion at 37, 28 and 10 degrees c .        
  metabolic data revealed a considerable myocardial glucose uptake,     
higher coronary ph, higher po and lower pco in the glucose-perfused     
groups as compared to controls .                                        
  a hypothesis for the protective effect may be an alteration in        
metabolic pathway and support of the myocardial enzyme systems          
associated with high glucose concentration and utilization .            
.I 58
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specific carcinoembryonic antigens of the human digestive system .      
  a wide variety of human adult and fetal tissues were studied by       
immunodiffusion techniques in agar gel to determine whether they        
contained the tumor-specific antigen(s) previously found in colonic     
cancers . in the adult tissues it was demonstrated that identical       
antigens were present in all tested specimens of malignant tumors of the
entodermally derived epithelium of the gastro-intestinal tract and      
pancreas, but were absent from all other tested adult tissues . the     
common antigenic constituents, therefore, represent system-specific     
cancer antigens of the human digestive system . system-specific cancer  
antigens have not previously been demonstrated in humans .              
  experiments with fetal tissues demonstrated that identical antigens   
were also present in fetal gut, liver, and pancreas between 2 and 6     
months of gestation . these components were named /carcinoembryonic/    
antigens of the human digestive system . on the basis of the present    
findings and the recent work regarding control of the expression of     
genetic potentialities in various genetic potentialities in various     
types of cells, it was concluded that the carcinoembryonic antigens     
represent cellular constituents which are repressed during the course of
differentiation of the normal digestive system epithelium and reappear  
in the corresponding malignant cells by a process of                    
derepressive-dedifferentiation .                                        
.I 59
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the course of influenza virus infection in mice.. organ tissues of      
infected mice tested by electron microscope .                           
  using the electron microscope the presence of inclusions could be     
shown in the lungs and liver of mice infected with the pr 8 strain . the
inclusions contained particles of size and shape closely resembling the 
most frequently seen forms of influenza virus . the presence of         
inclusions in liver tissue might perhaps speak for the possibility of   
virus multiplication in this organ .                                    
.I 60
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comparative bone marrow study using two aspiration needles and two      
biopsy sites .                                                          
  bone marrow aspiration is now widely used in the diagnosis of         
hematologic diseases and many conditions not primarily affecting the    
blood system . a number of techniques have been devised by which a      
suitable specimen of marrow can be obtained with relatively little      
discomfort to the patient . the two needle sets described in this paper 
have been found to be equally reliable in obtaining bone marrow for     
microscopic study and diagnosis . comparative studies of bone marrow    
aspirated simultaneously from the iliac crest and the sternum in 26     
patients show no significant difference . however, there were four      
instances of dry tap at the iliac site . this fact, in addition to the  
observation that less discomfort was experienced by the patient when the
sternum was used, might indicate that the sternal area is a more        
reliable and efficient site for obtaining bone marrow .                 
  it was also observed during this study that patients experienced less 
discomfort when the university of illinois needle was used . the major  
objection to the use of this needle is the inability to obtain a bone   
core for biopsy .                                                       
.I 61
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cell populations in the bone marrow of the normal guinea-pig .          
  quantitative data have been obtained for cell-populations in the bone 
marrow of the normal 400g guinea-pig based on a study of 25 animals .   
there was good agreement between two independent groups of observations 
and an average of 1880000 nucleated cells per c. mm. was found . of this
total, 27 were lymphocytes, 31 granulocyte precursors and 26 nucleated  
erythrocyte precursors . whole body populations have been computed and  
the implications of the findings discussed .                            
.I 62
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pneumocystis carinii pneumonia.. case studies with electron microscopy .
  this paper deals with the clinicopathologic findings in 2 patients    
with pneumocystis carinii pneumonia . the first example was in a        
51/2-month-old white female infant without an underlying disease . the  
second occurred, in association with cytomegalic inclusion disease of   
the lungs, in a 46-year-old white woman who had received steroid        
therapy, cytotoxic agents, and irradiation to the thorax for hodgkin's  
disease . an electron microscope was used for the study of the          
morphology of the organisms in tissue removed at autopsy .              
.I 63
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the effect of dehydroepiandrosterone on the dehydroxycorticosteroids in 
the plasms in various stages of breast cancer and mastopathy .          
  the depressing effect of dehydroepiandrosterone on plasma             
corticosteroids is, on an average, shortened in advanced breast cancer  
(stage iv) . the lowest corticosteroid values have been found with the  
three groups of patients 6 hours after infusion of                      
dehydroepiandrosterone phosphate . the effect of dehydroepiandrosterone 
being, still provable after 12 hours with the group suffering from      
mastopathy, the breast cancer group of stage iv had at this time already
reached the level of the initial values . the breast cancer group of    
stage iv had at this time already reached the level of the initial      
values . the breast cancer group of stage i/ii behaved intermediately . 
the less lasting effect of dehydroepiandrosterone is attributed to its  
accelerated transformation in advanced breast cancer .                  
.I 64
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the meaning of ph at low temperatures during extra-corporeal circulation
  a review of the temperature gradients occurring during profound       
hypothermia is made in regard to acid base changes in general, and to ph
readings in particular . it is concluded that terms such as 'body',     
'mean', 'average' and 'core' temperature should be discarded and that   
when a temperature is quoted it should be referred to the site at which 
it was measured .                                                       
  the main circumstances in which blood ph is measured at a temperature 
different from that at which the blood is equilibrated with respiratory 
gases are reviewed by describing the changes which occur during         
tonometry experiments . in this way fundamental changes can be          
understood before considering the more complicated sequences of events  
taking place in the living body .                                       
  the alterations that occur in the concentrations of protein and       
bicarbonate ion when whole blood is cooled are reviewed, together with  
their influence on 'correction factors' . the reasons why these factors 
should not be applied to blood when the living body is undergoing       
hypothermia involving the use of an extra-corporeal circulation are     
discussed .                                                             
  examples of the numerical values for blood ph during the two main     
methods for producing profound hypothermia, one using autogenous lung   
perfusion and the other a pump-oxygenator are given, with reference to  
the influence of pco2 upon these values .                               
  the existing methods of acid-base measurement appear to be            
sufficiently accurate to reflect the metabolic component during profound
hypothermia .                                                           
.I 65
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induced tumour resistance in rats .                                     
  the human sarcoma hs has been grown in weanling rats treated with     
cortisone . this growth was modified by prior injection of various      
tissue antigens . active /immunity/ was produced by using human placenta
or embryonic tissue as antigen, and similar results were obtained using 
suspensions of rapidly growing human tumours .                          
  the response to other human tissues varied.. foetal muscle and spleen 
were active, whereas adult plasma was inactive except from some patients
with extensive malignant disease .                                      
  passive protection was produced by using certain human sera at the    
time of challenging with hs . sera from five women who aborted showed   
this characteristic . where the pregnancy continued to term,            
antisubstances were not found,. and they were present in the puerperium 
in only two out of fifty cases .                                        
  further groups of rats were given rat embryonic tissues as antigen,   
and the tumour challenge was then made with walker tumour,. the results 
were variable .                                                         
  with a benzpyrene-induced tumour in a pure line of /wag/ rat the      
effect was not obtained except in isolated cases .                      
  in experiments in mice, using as challenge an irondextran induced     
mouse sarcoma, prior injection with embryonic mouse liver or placenta   
increased the resistance to the growth of the tumour, but the tumour has
not as yet been produced in a pure-line mouse . on the other hand mouse 
experiments, using as challenge the crocker tumour, proved negative .   
  it is suggested that immune reactions may play a part in causing some 
abortions .                                                             
.I 66
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urinary steroid estimations in the prediction of response to            
adrenalectomy or hypophysectomy .                                       
  a clinical trial has been carried out to test the use of the          
discriminant in assessing the suitability of patients with advanced     
breast cancer for hypophysectomy or adrenalectomy .                     
  patients with positive discriminants submitted to hypophysectomy have 
a much better prognosis than patients with negative discriminants       
submitted to adrenalectomy .                                            
  patients selected for adrenalectomy because of negative discriminants 
have a significantly worse response to the operation than patients      
selected by random sample .                                             
  patients selected for hypophysectomy because of positive discriminants
tend to have a better response to the operation than do patients        
selected by random sample, but the difference is not significant .      
  adrenalectomy is not recommended for patients with negative           
discriminants .                                                         
.I 67
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primary epidermoid cancer of the lung.. ultrastructural study .         
  the early epidermoidic epithelioma of the human lung are initiated by 
the proliferation of body cells whose structure is analogical to that of
the medium cells and/or the modificated basal cells of the normal       
bronchial wall .                                                        
  the presence of desmosomes and tonofibrils in the cells of the stratum
germinativum of the bronchial epithelium and in the cells derived from  
it, allows us a better understanding of the malpighian metaplasis of    
this wall and gives account of the epidermoidic evolution of the        
bronchial epithelioma .                                                 
  certain nuclear and cytoplasmic modifications suggest the possibility 
of a causal virus .                                                     
.I 68
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biosynthesis of glycoproteins i. incorporation of glucosamine- c into   
liver and plasma proteins of the rat .                                  
  it has been shown that glucosamine-1- c administered intravenously to 
fed rats is rapidly removed from the blood stream and appears first as  
trichloroacetic acid-soluble derivatives in the tissues . this is       
followed by a conversion to macromolecules . at least 80 of the         
administered compound can be recovered in tissues . the liver is by far 
the most active organ in accumulating glucosamine . this is rapidly     
converted to protein-bound components of the liver particulate fraction 
(microsomes and mitochondria) and is then released to the plasma without
appreciable accumulation in the soluble proteins of the liver . it is   
concluded that the glucosamine is transferred to the peptide chains of  
glycoproteins at some stage before these proteins are released from the 
liver particulate fraction .                                            
.I 69
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acute experimental pneumococcal (type i) pneumonia in the mouse.. the   
migration of leucocytes from the pulmonary capillaries into the alveolar
spaces as revealed by the electron microscope .                         
  in this preliminary study of experimental pneumococcal pulmonary      
pneumonia in the mouse the leucocytes were observed to pass from the    
capillaries into the interstitial tissue and eventually into the        
alveolar spaces through the intercellular junctions of the endothelial  
and epithelial cell membranes .                                         
.I 70
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a light and electron microscope study of developing respiratory tissue  
in the rat .                                                            
  1. light microscopic observations on the development of the rat lung  
have shown the presence of glandular, canalicular and alveolar stages . 
  2. these same three stages can be identified by electron microscopy   
and all may be present in different parts of the lung at one time, e.g. 
at 40 and 45 mm. c.r. length .                                          
  3. in the glandular stage, the lung tissue itself has an immature     
appearance by light microscopy and by electron microscopy individual    
cells also are immature in respect of organelles . glycogen is present  
in immature cells .                                                     
  4. during the canalicular stage, lung tissue becomes more vascular .  
  5. throughout all stages of development, the 'duct' or 'air' spaces   
are always lined by a continuous and complete epithelium, and blood     
vessels by a complete endothelium .                                     
  6. lamellated inclusion bodies are present in epithelial (endodermal) 
cells at an early stage of development .                                
  7. micropinocytotic vesicles are present in large numbers in both     
epithelial and endothelial cytoplasm and it is suggested that in the    
foetus they may indicate absorption of amniotic fluid from alveolar     
spaces .                                                                
  8. the mechanism of alveolar distension is discussed and its nature   
remains uncertain .                                                     
  9. respiratory tissue of the rat is not fully differentiated at birth 
and the importance of this fact in human infants is discussed .         
  10. the adult blood-air barrier, consisting of epithelium, zona       
diffusa and endothelium, varies in thickness .                          
  this project was performed whilst both of us were in receipt of grants
from the medical research council of canada, for which gratitude is     
expressed . our gratitude is also expressed to miss sylvia smith for    
typing the manuscript .                                                 
.I 71
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the pathogenesis of viral influenzal pneumonia in mice .                
  the pathogenesis of influenzal pneumonia in mice was studied by       
electron microscopy . mice were inoculated with 1.5 ld of pr8 influenza 
virus and killed at varying intervals after inoculation . observations  
by light microscopy were correlated with those by electron microscopy in
order to evaluate the lesions produced .                                
  at the periphery, the earliest lesions were focal areas of edema of   
alveolar lining cells, the capillary endothelium and the interposed     
basement membrane . this caused an appreciable thickening of the        
blood-air pathway . hypertrophy, degeneration and desquamation of the   
alveolar lining and proliferation of alveolar macrophages resulted in   
complete consolidation, which was progressive up to 1 week after        
infection .                                                             
  the central areas of the lung were affected somewhat differently . at 
3 days after infection, the nonciliated bronchiolar cells showed        
considerable hyperplasia of endoplasmic reticulum and apical cytoplasmic
edema . viral particles matured at the lumen surface of these cells and 
were then released into the bronchiolar lumen . the bronchiolar cells,  
both ciliated and nonciliated, underwent degeneration and sloughed into 
the bronchiolar lumen . the regenerating epithelium was stratified, and 
the surface cells were elongated and flattened . the peribronchiolar    
interstitial tissue gradually became totally infiltrated by cells,      
mostly of the mononuclear type .                                        
.I 72
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studies on aging with horse crystalline lens gel as a contribution to   
biomorphosis of the mammalian crystalline lens .                        
  the effects of biomorphosis -dash the continuous material change in   
the chemical composition of the organs and tissues -dash are studied on 
the horse crystalline lens in respect of its amino acid content subject 
to substantial variations in the course of life . it is shown by        
electrophoretic and paperchromatographic methods that the qualitative   
composition of horse crystalline lenses remains quite the same, but that
within the individual age stages there occur quantitative variations    
between the individual amino acids .                                    
.I 73
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the role of alveolar inclusion bodies in the developing lung .          
  the developing alveolar epithelium of man and rat contains            
characteristic inclusion bodies which are heterogeneous structures but  
basically consist of a system of membranous profiles and a limiting     
membrane of the unit type .                                             
  inclusion bodies appear to result from focal cytoplasmic degradation  
which occurs in the rapidly changing cuboidal alveolar epithelium . some
inclusion bodies in the developing rat lung are similar to the so-called
/lamellar transformed mitochondria./ however, evidence is presented     
suggesting that alteration of all cytoplasmic membranes may be involved 
in the process of inclusion body formation . certain images associated  
with the golgi complex are interpreted as early forms of inclusion      
bodies . there is also evidence that inclusion bodies enlarge by        
accretion of membranes which finally are extruded into the alveolar     
space . inclusion bodies are formed and /secreted/ in greater number    
late in fetal life and in early infancy, i.e., at the time when the     
cuboidal alveolar epithelium is differentiating to the mature flattened 
type . the latter contains no inclusion bodies .                        
  on the basis of the morphologic characteristics of the inclusion      
bodies and the distribution of the acid phosphatase reaction, it is     
concluded that inclusion bodies are lysosomal structures active during  
remodeling of the developing alveolar epithelium .                      
  the possible interrelationship of inclusion bodies and pulmonary      
surfactant is discussed .                                               
.I 74
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retinal detachment, cataract, keratoconus as ocular symptom complex in  
endogenous eczema .                                                     
  with reference to personal observations the authors describe the      
ovular changes encountered in endogenous eczema . besides the cataract  
which has been known to occur already for a long time, retinal          
detachment, keratoconus and keratoconjunctivitis do still belong to the 
symptom complex .                                                       
.I 75
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postural changes in blood distribution and its relation to the change in
cardiac output .                                                        
  (1) cardiac output and the blood content indices of the several parts 
of the body were measured in 18 subjects including patients with various
diseases using external radioisotope counting techniques . changes in   
these 2 parameters induced by standing were compared with each other .  
  (2) average changes in blood distribution produced by standing were as
follows . decrease in blood content in the /lung/ (-25 ) and in the     
/heart/ (-26 ) and increase in the /thigh/ (+56 ) were statistically    
significant . no significant change was revealed in the /head/, /palm/, 
/liver/ and /abdomen/ .                                                 
  (3) cardiac output and stroke volume decreased by standing in most of 
the cases . recent data were added to those reported previously and were
treated statistically . average decrease in cardiac output was -13 in 6 
control cases, -35 in 16 cases with neurocirculatory asthenia and -35 in
10 cases with hyperthyroidism . the difference was significant between  
control and neurocirculatory asthenia . standing induced a substantial  
increase in cardiac output in a case of idiopathic nodal rhythm,        
although there remains a doubt whether it is the ordinary response in   
this disease .                                                          
  (4) significant linear correlation was revealed between per cent      
change of blood content in the /thigh/ or in the /lung/ and that of     
cardiac output or stroke volume induced by standing . minimal blood     
shift was observed when the latter was extreme, and vice versa . this   
implies as follows.. reactivity of the heart might be influenced by     
posture, and transmural pressure of veins and or capillaries is probably
adjusted, as in arterioles, to compensate for changes in cardiac output 
.I 76
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comparative studies of the glycogen content of heart, liver and brain   
before and after iodine treatment and under conditions of asphyxia .    
  blood sugar level and glycogen concentration in the heart, brain and  
liver of rabbits after treatment with inorganic iodine, depot insulin,  
iodine and insulin combined, hostacortine and hostacortine and iodine   
combined are being examined . a control group remains untreated . in a  
second test series the glycogen determination under asphyxia (the       
trachea is being pinched off for three minutes) is repeated .           
  contrary to the brain the glycogen content of the heart muscle is not 
dependent upon the blood sugar level . after iodine treatment a lowering
of the blood sugar becomes noticeable, but also an increase in heart    
glycogen . the liver glycogen shows greater variations . the levels     
achieved in these test series therefore show no significant differences 
during asphyxia there is a significant lowering of glycogen in all    
three organs . preliminary treatment with iodine succeeds in stopping   
the lowering of glycogen in the heart muscle and the brain . the        
possible causes for this phenomenon are being discussed .               
.I 77
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altered immunologic activity in sarcoidosis .                           
  studies in 16 patients with sarcoidosis revealed evidence of          
immunologic alterations other than impaired delayed hypersensitivity .  
transient impairment of the response of lymphocytes cultured from       
patients with sarcoidosis to phytohemagglutinin stimulation was found to
parallel the clinical severity of the disease . the hemolytic activity  
of serum complement was increased . a disproportionate increase in serum
iga was found characteristic of the hyperglobulinemia of sarcoidosis .  
these observations indicate that an altered immune response may be      
important in the pathogenesis of sarcoidosis . a simple hypothesis as to
the specific kind of interaction of infectious agent and immunity which 
might result in the immunologic alterations observed is formulated and  
presented .                                                             
.I 78
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electron microscopy of cytoplasmic inclusions within /macrophages/ of   
human tissue .                                                          
  the fine structure of inclusions found within the cytoplasm of        
macrophages of human lung, spleen, skin, lymph node, and rectum has been
described .                                                             
  the inclusions appear as concentric or whorled lamellae arranged      
around a core . each lamella is constructed of discrete, parallel       
filaments . the inclusions do not resemble currently described viruses  
or virus-like particles, nor do they resemble asbestos bodies or other  
known atmospheric pollutants or ingestants .                            
  there is some resemblance to lipid phase systems as well as mast cell 
granules,. possibly the inclusions represent partial intracellular      
digestion of phagocytized tissue membranes or ingested mast cell        
granules, respectively . differences and similarities exist between the 
inclusion bodies of macrophages and the granules of mast cells . such   
variations could be due to alterations in mast cell granule morphology  
before or after macrophage ingestion .                                  
  cytologic distinctions between macrophages laden with mast cell       
granules and mast cells proper, remains obscure and requires additional 
experimental evidence for clear electron microscopic differentiation of 
these two cell types .                                                  
  the exact nature of these highly structured bodies remains speculative
.I 79
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histological research on the lens in condition of hypoxia, changes in   
the mitotic activity of the epithelium .                                
  the effect of hypoxia on the mitotic activity of the cells of the lens
epithelium was studied in 24 rats of the same strain and weight . the   
hypoxia was obtained in the decompression chamber .                     
  the results show that the mitotic activity of the lens epithelium is  
depressed at any of the examined altitudes (6.500, 8.000, 9.500 m),. in 
particular, a marked reduction in the number of the prophases and an    
accumulation in metaphase was observed .                                
  the results were examined from the statistical standpoint and         
discussed .                                                             
.I 80
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rate of change of carbon dioxide tension in arterial blood, jugular     
venous blood and cisternal cerebrospinal fluid on carbon dioxide        
administration .                                                        
  1. the rate of change of p in arterial blood and cisternal c.s.f., was
measured following 5 percent co administration in eight anaesthetized   
patients undergoing routine air encephalography . ventilation was       
maintained constant throughout the procedure by a respirator . in three 
of the experiments the rate of change of p in the jugular venous blood  
was also measured .                                                     
  2. the rise in p varied between 25.7 and 14.8 mm hg . the final       
samples of blood and c.s.f. were taken 20-25 min after the start of co  
administration in five experiments . at this time the mean rise in p was
65.9 (maximum range 68.1-61.6 percent) of the rise in p . in the        
remaining three experiments the final samples were taken at 15 min when 
the rises in p were 53.2, 39.4 and 38.1 percent of the arterial change .
  3. the increases in p were 57.5, 76.2 and 76.1 percent of those in the
arterial blood . the changes in p in the c.s.f. were smaller than in the
jugular venous blood in all three experiments . in two of the           
experiments the final samples were taken 15 min after the start of co   
administration when the increases of p in the c.s.f. were 68.5 percent  
and 50 percent of those in jugular venous blood . in one experiment     
where the final samples were taken at 20 min the increase in p was 89   
percent of the rise in p .                                              
  4. there was a delay, following the start of co administration, in the
rise of p in jugular venous blood and in the c.s.f . this delay was     
about 1 min in the jugular venous blood but in the c.s.f. it varied from
1.6 to 4.2 min (mean 2.3) .                                             
  5. the rise of p in blood and c.s.f. was exponential . the rise in p  
in all experiments consisted of a fast component with time constants    
which varied between 0.2 and 0.9 min (mean 0.5) and a slow component    
with time constants varying between 6.7 and 14.7 (mean 11.6) .          
  the rise in p and p consisted of only one component . the time        
constants for the changes in jugular venous blood were 2.1, 3.8 and 4.3 
min, whilst in the c.s.f. they varied between 6.7 and 14.7 (mean 11.6) .
  6. it is probable that about 40 percent of the increase in ventilation
following co administration is due to stimulation of an area in the     
antero-lateral surface of the medulla sensitive to changes in ph or p   
(mitchell et al. 1963) . this area is superficial and ventilation is    
affected by changes in the p of the overlying c.s.f . it can be         
predicted from our experiments that the rise in p on co administration  
will take some 30 min to be complete . this may explain the slow rise in
ventilation on co breathing when compared with the rate of rise of      
arterial and jugular venous p .                                         
.I 81
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studies on the compound lipids from x-ray irradiated animal, ii.        
biological and biochemical properties of the compound lipids in the     
x-ray irradiated rabbit organs .                                        
  for the purpose to clarify the causes of x-ray disturbances a series  
of experiments have been conducted on biological and biochemical        
properties of compound lipids extracted from normal and x-ray irradiated
rabbit organs with a special reference to the p -labeled compound lipids
uptake, inhibitory action to l cell proliferation and uncoupling of     
oxidative phosphorylation, and the following results have been obtained 
  the compound lipids (lysophosphatide rich fraction) isolated from the 
x-ray irradiated rabbit organ have been found to possess a strong       
hemolytic action and also an action to inhibit the cell proliferation as
well as to accelerate the respiration of the mitochondria in the rabbit 
liver and spleen . it has also been proven that they act as to induce a 
marked swelling of mitochondria, to impede the formation of high energy 
phosphate as well as to act as an uncoupler of oxidative phosphorylation
in vivo . in the test to see the uptake of p -labeled compound lipids by
various organs, a marked uptake has been observed in spleen, bone       
marrow, and liver of both irradiated and non-irradiated groups .        
further, the uptake of p -labeled compound lipids in the rabbits given  
intravenous injections of compound lipid fraction for 30 consecutive    
days previously has been found to be greatest in pancreas followed by   
bone marrow, spleen, liver in the order mentioned in male group, whereas
it is greatest in spleen, followed by liver and bone marrow in the      
female group .                                                          
  with these results the discussion was conducted concerning the        
relation between the lipid metabolism and x-ray disturbances .          
.I 82
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cesium-131 uptake and distribution in the human heart.. an analysis of  
cardiac scans in 104 patients .                                         
  when properly used, cesium-131 is a satisfactory agent for the study  
of cardiac morphology by photoscanning, which we believe is a useful    
adjunctive diagnostic procedure in patients for whom the results of     
other methods of evaluation are at variance with the clinical symptoms  
of cardiac disease . the studies reported here suggest that perhaps     
infarction of a subclinical type, size, or location may occur earlier   
than has been previously thought and that the damage it leaves may not  
be detectable by any means other than autopsy or a technique such as    
scanning . we have not yet been able to measure the actual concentration
of cesium-131 in the heart at autopsy so that the cold and cool areas   
could be examined by histologic sections .                              
.I 83
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oxygen consumption of paralysed men exposed to cold .                   
  1. oxygen consumption and carbon dioxide output were measured when    
human subjects were cooled for 80-210 min . two subjects were normal,   
one had been almost completely paralysed below the neck by              
poliomyelitis, and two were unconscious as a result of intracranial     
damage and were observed with and without paralysing doses of muscle    
relaxants (d-tubocurarine and gallamine) .                              
  2. when normal subjects and unconscious subjects receiving no drugs   
were cooled, oxygen consumption and carbon dioxide output rose .        
  3. when subjects paralysed by disease or drugs were cooled, oxygen    
consumption and carbon dioxide output were not increased .              
  4. these observations are consistent with the view that in man the    
increase in metabolism on cooling for periods up to 31/2 hr occurs      
solely in skeletal muscle .                                             
.I 84
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heparin levels during and after hypothermic perfusion .                 
  1. perfusion-temperature influences the rate of heparin-loss during   
extracorporeal circulation, and therefore, the requirement of           
re-heparinization .                                                     
  2. heparin half-lives of approximately 13/4 hours and 21/2 hours were 
calculated during perfusions conducted at average temperatures of 31.5  
and 22.6 c. respectively .                                              
  3. the rate of heparin-loss during extracorporeal circulation is      
inconstant in an individual, and variable between individuals, so that  
exact neutralization requires an accurate estimation of the heparin     
concentration present at the end of perfusion .                         
  4. the protamine titration test provides a crude but simple and       
satisfactory means of monitoring free-heparin levels .                  
  5. complete neutralization of heparin is an important factor in       
minimizing postoperative blood losses .                                 
  6. protamine is a less efficient neutralizing agent than polybrene at 
the same dosage level . it may be most effective in divided dosage .    
  7. /rebound/ was detected in 5 of 45 cases studied, although in only  
one instance was it of a degree likely to be significant .              
  8. significant prolongation of the clotting-time resulting from excess
neutralizing agent, was not evident in this study .                     
.I 85
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platelet sequestration in man . i. methods .                            
  current methods of labeling platelets with chromium using             
ethylenediamine tetraacetate (edta) as an anticoagulant were found to   
cause rapid hepatic sequestration of nearly all the transfused platelets
about 50 returned to the circulation but then were partially destroyed
in the spleen . less than one-third survived . evidence is presented    
which indicates that edta is injurious to platelets .                   
  when an acid-citrate medium that buffered plasma at ph 6.5 was used as
an anticoagulant, 36 to 85 of the labeled platelets survived (average,  
62 ), and marked temporary sequestration did not occur . studies in     
thrombocytopenic persons showed that circulating platelet cr activity   
measures the true survival of such transfused platelets .               
  the survival and sequestration of platelets were studied in normal    
subjects . the survival data support the concept that platelets die     
chiefly by a process of senescence . external scintillation scanning of 
the various organs suggests that normally the majority of platelets is  
destroyed in the liver .                                                
.I 86
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acute leukemia associated with phenylbutazone treatment.. a review of   
the literature and report of a further case .                           
  the possible toxic reactions to phenylbutazone have been listed, and a
review of the literature of haematological complications has shown that 
16 deaths attributable to agranulocytosis, aplastic anaemia and         
thrombocytopenia have been recorded . the association between leukaemia 
and phenylbutazone first suggested by bean (1960) has been amplified by 
further reports, which have been reviewed .                             
  a further case history has been presented . of the 15 patients with   
acute leukaemia in which the association has been recorded, there were  
other possible leukaemogenic factors in three, and in a further three   
the drug had been given for only a short time before the leukaemia was  
diagnosed . however, in the remaining nine, the histories are such that 
the phenylbutazone ingestion may have been associated with the          
development of the leukaemia . further studies, which should include    
matched controls, are indicated, and will be required before a definite 
opinion can be given as to any causal relationship between the drug and 
the disease .                                                           
.I 87
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absorbed radiation dose and excretion of cesium-131 in humans .         
  data relating to the effective half-life, absorbed dose of radiation, 
and excretion rates of cesium-131 have been presented . cesium-131 is an
excellent material for cardiac scanning, since a very low amount of     
radiation is absorbed -dash a dose of the order of one twentieth that   
received in diagnostic x-ray studies of the gastrointestinal tract .    
absorption of radiation can be reduced further by the administration of 
a thiazide type of diuretic and, probably, by catharsis after the scan .
.I 88
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radiocardiography.. principles and methods .                            
  the aa show the importance of radiocardiography, as a method to       
evaluate the cardiac output, the ventricular volumes and the pulmonary  
blood volume .                                                          
  in this first paper, they are particulary concerned with some         
technical aspects, which are very important to collect data .           
  the position of the collimator on the precordium, the injection of    
isotopes through a catheter, just behind the ventricle near the         
tricuspid valve, the selection of ratemeter constants the velocity of   
paper on the recorder and the way to read the area of the curve, were   
specially discussed .                                                   
  finally, they present the formula used to calculate cardiac output,   
ventricular volumes and pulmonary blood volumes .                       
.I 89
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reaction of the adrenal cortex during controlled experimental           
hypothermia .                                                           
  the stress reaction caused by hypothermia was studied in rabbits      
subjected to controlled hypothermia by immersion in an icebath . some of
the animals were re-warmed . to anesthetize the animals, pentobarbitone 
sodium (nembutal) was given intraperitoneally, and, in some cases,      
followed by ether anesthesia . further, the stress reaction produced by 
pentobarbitone alone was studied in five animals, and that of ether     
anesthesia alone in three . no anesthesia was given to the three rabbits
placed in the refrigerator . the variation in distribution and amount of
adrenocortical lipids served as an indicator for evaluation of the      
stress reaction .                                                       
  in all the hypothermia tests there occurred changes in the            
distribution and amount of cortical lipids, denoting a stress reaction  
brought about by hypothermia . in rabbits, the barbiturate did not seem 
to inhibit the stress reaction . this may be attributed partly to the   
test animal, as such and partly to the fact that shivering of some      
extent always occurred during the hypothermia experiments .             
.I 90
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use of a cross-circulation technique in studying respiratory responses  
to co .                                                                 
  the effect of hypercapnia and hypocapnia on ventilation was           
investigated in cross-circulated dogs in which the recipient dog's head 
and neck regions were perfused by blood from a donor dog . hypercapnia  
of the donor dog was produced by administering co -o -n gas mixtures in 
the inspired air . hypocapnia was produced by hyperventilating the donor
dog with the aid of a respiratory pump . when the donor dog was         
hyperventilated, the ventilation of the recipient was maintained at or  
just below its resting level and it was independent of the arterial pco 
of the donor . the donor dog was apneic when the artificial             
hyperventilation was suspended and this response was not abolished by   
vagotomy . bilateral vagotomy caused an increase in ventilation in the  
recipient when its head was perfused by hypocapnic blood . bilateral    
removal of the carotid receptors did not influence the response to co   
qualitatively although there was some reduction in the ventilation of   
the recipient to cephalic hypercapnia . the ventilation of the recipient
dog was best correlated to the ph and pco of its cerebrospinal fluid in 
both hypercapnic and hypocapnic states .                                
.I 91
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action of phytohaemagglutinin in vitro on the lymphocytes of chronic    
lymphoid leukaemia .                                                    
  the in vitro action of phytohaemagglutinin has been the subjects of a 
comparative investigation of the lymphocytes of 13 normal subjects and  
of 15 cases of chronic lymphatic leukaemia .                            
  in both groups there is cellular change shown by the appearance of    
large basophil nucleolated cells showing mitotic activity .             
  in all the cases of lymphatic leukaemia the percentage of cells       
undergoing such change is lower than in normal subjects, and the        
transformation occurs more slowly .                                     
  the two phenomena are more striking the higher the initial            
leucocytosis .                                                          
  these results suggest, in chronic lymphatic leukaemia, the cells      
affected by the transformation are residual normal lymphoid elements .  
leukaemic lymphoid cells appear to be incapable of this transformation .
.I 92
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demonstration of ventricular aneurysms by radioisotope scanning .       
  radioisotope scanning of the cardiac blood pool after the intravenous 
injection of i -labeled iodipamide was carried out in 14 patients with  
ventricular aneurysm . in 4, the aneurysm could be demonstrated on      
neither the anteroposterior chest roentgenogram nor the scan . in 5, the
aneurysm was apparent on the radiograph, but the blood pool did not     
enter the area, suggesting a thrombus within the aneurysm . in 5, the   
aneurysm was detectable on the film and was also seen to be filled with 
radioactivity on the scan . presumably these findings showed that a     
thrombus had not yet formed . blood pool radioisotope scanning appears  
to be another tool in the diagnosis of ventricular aneurysm, useful also
in demonstrating in some patients the presence or absence of an         
intraluminal clot within the aneurysm .                                 
.I 93
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propagation of lactic dehydrogenase-elevating virus in cell culture .   
  primary cultures of adult mouse lung, spleen, and liver and of mouse  
embryo support the multiplication of the lactic dehydrogenase-elevating 
virus . such cultures produced virus continuously until they had been   
subcultured 2-3 times . this corresponded to 20 weeks in the case of    
lung and spleen and to 2-3 weeks with cultures of embryo . viral        
multiplication was not accompanied by cytologic alterations in the cells
or by changes in their rate of synthesis of nucleic acids or protein .  
infection did not cause detectable changes in either the production of  
ldh or in its release from cells .                                      
.I 94
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transformation of bovine cells in vitro after inoculation of simian     
virus 40 or its nucleic acid .                                          
  cells of bovine embryonic lung tissue in culture were inoculated with 
simian virus 40 (sv 40) or a phenol extract of a high titer suspension  
of sv 40 . both the virus and the nucleic acid preparation induced      
proliferative morphological changes characteristic for sv 40            
transformation . non-infected control cultures and cultures which were  
inoculated with a preparation of nucleic acid exposed to dnase and      
maintained under the same conditions as infected cultures showed a      
regular fibroblastic growth .                                           
  cell lines of rapidly growing transformed cells have been obtained .  
most attempts to isolate virus from the transformed cells were negative,
but minute amounts of virus were recovered from occasional passages .   
.I 95
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rapid transformation of human fibroblast cultures by simian virus 40 .  
  the risk of systemic embolism is assessed in a group of 754 patients  
with chronic rheumatic heart disease followed over a period of 5,833    
patient-years .                                                         
  the incidence of embolism was 1.5 per patient-year for the whole group
it was seven times higher in atrial fibrillation than in sinus rhythm 
when the duration of atrial fibrillation was known, it was found that 
one-third of the emboli occurred within one month and two-thirds within 
12 months after the onset of atrial fibrillation . the incidence of     
embolic recurrences was 8 per patient-year, irrespective of the nature  
of the cardiac rhythm, but 66 of the recurrences took place within 12   
months of the initial embolic episode .                                 
  mitral valvotomy did not eliminate the danger of embolism . it is     
questionable whether it reduced its incidence .                         
  anticoagulant treatment reduced the incidence of embolic recurrences .
.I 96
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the tissue reaction to hyperbaric oxygen .                              
  hyperbaric oxygen damages tissues exposed in vitro, but their         
sensitivity varies . if exposure is limited some tissues may recover .  
the effect appears to depend on oxygen tension rather than raised       
pressure per se . the tissue reaction may be involved in the clinical   
application of hyperbaric oxygen .                                      
.I 97
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attitudinal factors in congenital heart disease .                       
  this study considers the behavioral implications of congenital heart  
disease for the pediatric patient, his siblings, and his parents . the  
effects of a disease on the child, on his siblings, and on his parents  
and the interplay among these individuals are explored . the impact of  
the physician's diagnosis is illustrated by the induced significant     
changes in family attitudes, which are not necessarily related to       
disease severity or child incapacity .                                  
  poorer adjustment and anxiety in the cardiac child related more highly
to maternal anxiety and pampering than to his degree of incapacity .    
maternal protectiveness and pampering were significantly greater in the 
cardiac than in the normal group and were highest in the cyanotic group 
the best predictor of maternal protectiveness was maternal anxiety,   
and it was found that the addition of other variables such as incapacity
and child dependence failed to improve prediction substantially .       
maternal anxiety seemed related to the presence rather than to the      
severity of the heart condition .                                       
.I 98
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maternal anxiety during pregnancy and adequacy of mother and child      
adjustment eight months following childbirth .                          
  fifty pregnant women were administered a battery of psychological     
tests . on the basis of scores obtained from the manifest anxiety scale,
these pregnant women were dichotomized into a /high anxiety/ group and a
/low anxiety/ group . eight months following childbirth, the mothers and
children were seen for a psychological assessment . it was found that   
the women in the /high anxious/ group evidenced significantly more      
negative childrearing attitudes . that is, the /high anxious/ mothers   
obtained significantly higher scores on the hostility and control       
factors measured by the pari . on the basis of the examiner's ratings of
the mother's personality traits, it was found that the women who were   
highly anxious during pregnancy received much less favorable personality
ratings at the time of the 8-month assessment . moreover, there was a   
significant difference in the proportions of mothers in the two groups  
who received a favorable rating from the examiner on the basis of his   
observation of the mother-child interaction during the session . in     
studying the children of these mothers, it was found that the children  
of the /low anxious/ mothers received a significantly higher            
developmental quotient on the infant mental scale . in keeping with this
finding, they also obtained a higher developmental quotient on the motor
scale, although on this aspect of the intellectual assessment the       
difference was not statistically significant . also, the children from  
the /low anxious/ mothers tended to receive a score indicative of a more
favorable general emotional tone than did the offspring of the /high    
anxious/ mothers . this difference between the two groups of children   
was not statistically significant . in general, the findings were       
consistent with the predictions that the children who were being reared 
by women who had been highly anxious during pregnancy would fare less   
well on tests of intellectual development and indices of emotional      
adjustment . the findings also were in keeping with the prediction that 
the highly anxious women during pregnancy would evidence less desirable 
parental attitudes during their child's early development and that they 
would present a less favorable personality picture at a time            
approximately 8 months following pregnancy .                            
.I 99
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maternal separation in the rhesus monkey .                              
  the present study involved separation of eight monkey mother-infant   
pairs for a period of two weeks and measurement of the behavior of the  
infants before, during and after reunion with their mothers, and of the 
mothers before and after reunion . all infants showed emotional         
disturbance in response to separation and drastic decreases in play and 
other complex social behaviors while separated .                        
  it is clear that infant-mother separation produces emotional          
disturbance in both human and macaque infants and that the patterns of  
responses following separation are similar in both species . the results
obtained in studies of monkey infant-mother separation indicate that    
sheer physical separation is the crucial aspect of maternal separation  
for monkeys . undoubtedly other factors associated with separation from 
the mother are vitally important for human children, and may account in 
part for the absence or rarity of the detachment stage (as seen in human
response pattern) in separated monkey infants . the overall results show
considerable similarity in the responses of human children and infant   
monkeys to separation from the mother .                                 
.I 100
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the ophthalmologist's role in the management of dyslexia .              
  dyslexia is a clinical entity characterized by subnormal reading      
ability in a person of average or above average intelligence .          
  it is a disease which has different causes in different children . the
causes include brain damage in the /language area,/ hereditary          
predisposition and such ophthalmic factors as hyperopia, muscle         
imbalance, aniseikonia or visual immaturity . emotional disturbances,   
educational immaturity and cerebral dominance may also play some role in
the etiology of this condition .                                        
  the universal symptom is poor reading ability . however, these cases  
frequently have other associated symptoms such as poor writing,         
difficulty in reading and writing numbers, inability to read or write   
musical notes and disorientation for left and right . many of these     
patients develop personality maladjustments . visual fields often reveal
a hemianopia .                                                          
  in any group of poor readers, a large percentage will have ocular,    
neurologic, psychiatric or psychologic abnormalities and/or a strong    
hereditary tendency . the degree to which reading can be learned depends
upon the ability of the individual to adjust to the psycho-physiologic  
needs that are present at the time he reaches /reading age/ in school . 
if compensating abilities are present, and if the child's reaction is a 
favorable one, he may read well in spite of unfavorable factors,. if    
not, he may become a /poor reader/ . these children should be recognized
in their first year of school .                                         
  a complete medical work-up should be managed by an ophthalmologist . a
complete ophthalmic examination should first be performed and all       
possible visual anomalies should be corrected . the ophthalmologist may 
want a psychometric evaluation, a neurologic opinion to determine the   
role of organic brain damage, psychiatric consultation for evaluation of
emotional disturbances, pediatric consultation for evaluation of the    
status of the general health and/or consultation by an otolaryngologist 
to determine the patient's hearing ability . with all the necessary     
information at hand, the ophthalmologist will be able to recommend      
corrective medical therapy and to advise the parents and teachers about 
available remedial reading aids .                                       
  the prognosis is good for most patients since they are of average or  
above average intelligence,. nearly all cases can be helped .           
.I 101
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unusual course of internal carotid artery accompanied by bitemporal     
hemianopia .                                                            
  a case is reported with bitemporal relative hemianopia, craniotomy    
showing internal carotid arteries to have an unusual course,            
corresponding to the carotid siphon, with resultant change in shape of  
the optic nerves .                                                      
  abnormalities of the carotid siphons could not be detected on         
reviewing the carotid angiograms . evaluation of the optic nerve's      
relationship, as can be measured on the pneumograms, indicated that the 
optic nerves in this case were exposed to compression from the abnormal 
arteries .                                                              
.I 102
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frontal lobes and vision .                                              
  the influence of the frontal lobe on vision is discussed based on the 
presentation of a rather unusual case . after the operation of a right  
frontal brain abscess, which never had led to papilledema, there was a  
pronounced diminution of the visual capacities of the patient,.         
gradually these disturbances regressed to the point of return of full   
visual acuity,. but there remained a hemianopic field defect . this and 
psychological defects in the sense of a partial visual agnosia (which   
latter are also regressing very well) prompted a discussion of those    
neuroanatomical and neurophysiological observations pertinent to the    
findings in this patient . the many data on the fronto-occipital        
connections in subhuman primates point to the role of the frontal lobe  
(area 8) in the development of visual disturbances in the sense of a    
temporary hemianopia with partial visual agnosia and some intellectual  
deficits . contrary to a single observation in an anthropoid ape, our   
case would seem to indicate that the aforementioned combination of      
symptoms may originate in the frontal lobe,. and we hope it will prompt 
other long-term follow-up studies of similar patients . the continued   
observation of this patient and perhaps of others will give a           
possibility to gain insight into the role of the frontal lobe in vision,
as has been assumed for animals .                                       
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physiologic bitemporal hemianopsia in pregnancy .                       
  a severe case of bitemporal hemianopsia occurring late in pregnancy is
presented . the patient illustrated a typical rapidly progressive course
and rapid recovery with complete return of visual fields and visual     
acuity after delivery was accomplished . the presumed pathologic        
physiology of this entity is briefly reviewed .                         
.I 104
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evoked response in visual disorders .                                   
  1. erg and ver have been recorded from eyelid and lateral occipital   
electrodes in response to diffuse stroboscopic stimulation . in 45      
normal subjects ver was found to be composed of an early triphasic      
potential arising from the occipital region . wave i was present in 67  
percent of subjects, wave ii in 97 percent, and wave iii in 100 percent 
later waves were inconstant and contained components from the vertex  
reference . no overall asymmetry in ver from right to left was found in 
normal subjects, although average asymmetry with smaller side compared  
to larger was 19 percent 12.5 . on monocular stimulation the            
contralateral ver was regularly larger than the ipsilateral reflecting  
predominant retinal representation of the temporal field .              
  2. a statistically determined criterion of 50 percent depression in   
wave ii successfully identifies most patients with hemianopic defects   
involving the central 10 percent of visual field on tangent screen      
campimetry .                                                            
  latency asymmetry of six msec. or more and grossly asymmetrical       
aberrant wave forms are seen in some patients with diffuse cerebral     
disease and hemianopic defects .                                        
  3. severe or diffuse retinal disease is associated with alteration or 
loss of erg and ver on stimulation of the involved eye .                
  4. optic nerve disease is indicated by bilateral loss or suppression  
of ver on stimulation of the involved eye . erg is normal .             
  5. bilateral prechiasmal involvement is associated with complete      
suppression of ver . if only waves i and ii are lost, disease is        
probably, but not conclusively, demonstrated .                          
  6. involvement of nasal retinal fibres is indicated by reversal of the
normal contralateral preponderance of ver on monocular stimulation .    
these changes are observed in chiasmal disease .                        
  7. retrogeniculate blindness is associated with loss of early ver and 
preservation of late response . nonspecific projections are felt to     
contribute to the late cortical response to photic stimulation .        
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optokinetic nystagmus and occipital lesions .                           
  six cases are presented to invalidate the rule that horizontally      
symmetric optokinetic responses indicate a vascular etiology in patients
with occipital lobe type hemianopias . the converse of this rule is, in 
our experience, still a valuable observation . that is, asymmetry of    
horizontal optokinetic responses accompanying an occipital type field   
defect is a strong indication of a mass lesion . optokinetic nystagmus  
may be helpful, therefore, as corroborative evidence in diagnosing      
occipital lobe tumor but not in ruling it out .                         
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anaphylactoid shock induced by oral penicillin and resulting in         
gerstmann's syndrome .                                                  
  an anaphylactoid reaction to oral penicillin in a 46-year-old woman is
described.. after hours of unconsciousness and weeks of confusion she   
was left with a residual gerstmann's syndrome . these reactions are less
rare than is generally supposed . symptomatology, treatment, diagnosis, 
and mechanism are discussed, and some of the relevant literature is     
briefly reviewed .                                                      
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disturbances of the verbal body image.. a particular syndrome of sensory
aphasia .                                                               
  1. the pto syndrome of the dominant hemisphere varies according to the
extent and depth of the lesion in the angular and supramarginal areas . 
the mildest clinical syndrome consists of a vague contralateral sensory 
impairment associated with dyscalculia, dysgraphia, dyslexia and        
difficulty in naming . a more extensive lesion is needed to cause the   
wide variety of classical signs described in parietal lobe disease,     
among them being gerstmann's syndrome, which is usually found in        
association with other manifestations of parietal loss (case 1) . an    
even more extensive corticosubcortical lesion in the area leads to      
complete disintegration of naming and understanding of speech (cases 3, 
4 and 5) .                                                              
  2. attention is drawn to the difficulties arising from lack of        
differentiation between the concrete gnostic body image and the abstract
verbal body image in investigation of these patients . the aphasic      
syndrome should be differentiated from disturbances of gnosis by        
application of separate, non-verbal methods of testing to elicit the    
impairment of the gnostic body image . the latter may be well           
compensated for and it is apparently unimpaired in the presence of an   
aphasic syndrome limited to the verbal body image .                     
  3. disturbances of speech in pto lesions if investigated along        
quantitative scales of impairment of repetition, understanding and      
naming, show a regular interrelation . nomination is the most affected, 
understanding is less affected . repetition is the best preserved       
function (cases 1-4) . the same interrelation of these functions is     
found with regard to the verbal body image . however, understanding and 
naming of parts of the body show far greater disintegration than        
understanding and naming of any other categories of words (all cases    
presented here) . if the aphasic syndrome is subsiding, finger aphasia  
with some other minor disturbances of verbal body image associated with 
acalculia may persist (case 1) . thus gerstmann's /finger agnosia/ may  
represent a partial impairment of the verbal body image and be limited  
to finger aphasia .                                                     
  4. it is assumed that the verbal body image differs from other        
categories of verbal symbols owing to the mainly proprioceptive,        
vestibular and tactile experience forming its specific physiologic      
background . telereceptive experience is of minor importance in the     
initial development of the understanding of words defining the body     
image .                                                                 
  in the patients described here, the selectively worse aphasic         
impairment of the verbal body image, as compared with other categories  
of words, seem to confirm this assumption .                             
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chromosomal patterns in cancer patients during treatment .              
  radiation damages the chromosomes of human cells, and through         
short-term cultures of white blood cells some of this damage can be     
assessed . patients with cancer were selected for this study because of 
the large portions of the blood-forming tissues irradiated in the course
of treatment . chromosomal damage may be quantitative with variations   
from the normal number of 46, or qualitative, thereby showing structural
aberrations . counting the chromosomes in cells from cultures grown     
prior to therapy and at intervals during treatment enables us to        
determine the variation .                                               
  stained preparations examined microscopically allow us to recognize   
these abnormalities which are apparent before, during, and after        
radiotherapy . the damage appears to be largely random in the           
chromosomes affected in the different cancers, and the specific         
aberrations differ from cell to cell . however, there does seem to be   
some correlation between the appearance of persistent aberrant          
chromosomes and their frequency . while the peak incidence or /plateau/ 
may remain unchanged, the frequency may change .                        
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a few interesting neurologic manifestations of migraine .               
  migraine is a complex vascular phenomenon presumably of genetic origin
which, through changes induced by either vasoconstriction or            
vasodilitation, can produce interference with the neurologic system and 
result in many bizarre and alarming clinical pictures . a few examples  
of the more interesting neurologic manifestations have been shown .     
.I 110
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visual neglect .                                                        
  clinical trainees in nursing and in psychology from boston college and
simmons college, boston, mass., collected data and observed patients    
under the direction of the authors in a pilot program designed to       
measure visual spatial neglect and to develop rehabilitative material . 
these measurements and exercises might also be used by nurses in their  
care of those patients who have had cerebral vascular accidents .       
  the diversity of daily activities in which the patient becomes        
involved during his hospitalization should provide some indication of   
the extent to which the compensatory visual neglect therapeutics have   
been effective . more formal estimates can be obtained by               
re-administering the battery of visual neglect tests at periodic        
intervals . nursing personnel adopting a program of therapeutics such as
this must bear in mind that patients suffering cerebral insult are      
usually less adaptive than their nonbrain-injured peers . they develop  
new habit patterns slowly and regression often will follow apparent     
fixation at a more adaptive level of response habituation(11) . however,
experimental inquiry has shown that the dimension of behavioral         
difference between the brain-injured adults and normal adults is one of 
degree rather than kind -dash a difference that skilled nursing can     
often reduce(12) .                                                      
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respiratory changes after open-heart surgery .                          
  patients who undergo cardiac surgery with extracorporeal circulation  
develop significant alveolar-arterial oxygen tension differences and    
venous admixture in the early post-operative period . up to 50 of this  
abnormality is due to anatomical right to left shunting through the     
lungs.. the remainder is most likely to be due to ventilation-perfusion 
inequality . the changes appear to be completely reversible . the       
cardiopulmonary bypass procedure may be responsible for initiating the  
underlying pathology, since changes of this magnitude were not found in 
cardiothoracic surgery patients in whom this technique was not required 
.I 112
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cardiac malformations associated with ventricular septal defect .       
  in this study, 46 necropsy-proved cases of ventricular septal defect  
associated with another anomaly but not part of a recognized complex    
were selected .                                                         
  the associated anomalies were classified as (1) obstructive or        
positional anomalies of the great vessels, (2) anomalies responsible for
additional shunts, (3) anomalies causing intraventricular obstruction   
and (4) aortic valvular insufficiency .                                 
  clinical findings were often those of the ventricular septal defect,  
and the findings related to the associated lesion were frequently       
obscure . even with special studies, including cardiac catheterization  
and angiocardiography, there was often failure to arrive at a complete  
diagnosis . the findings which led to an erroneous or incomplete        
diagnosis have been presented . when a complete diagnosis was made      
preoperatively, the procedures leading to it have been outlined . while 
the diagnostic approach varies with the malformations which may coexist 
with ventricular septal defect, it was observed that aortography and    
selective left ventricular angiocardiography were most commonly helpful 
in identifying occult malformations associated with ventricular septal  
defect . it is therefore recommended that complete studies, including   
left-sided cardiac catheterization with left ventricular                
angiocardiography and aortography, should be considered in all cases in 
which the clinical, electrocardiographic, and right-sided cardiac       
catheterization studies are not entirely typical for isolated           
ventricular septal defect .                                             
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anatomic types of single or common ventricle in man morphologic and     
geometric aspects of 60 necropsied cases .                              
  in 60 necropsied cases of single or common ventricle in man, four     
major unrelated ventricular malformations were found.. (1) absence of   
the right ventricular sinus, in 47 cases (78 percent), designated type  
a,. (2) absence of the left ventricular sinus, in 3 cases (5 percent),  
type b,. (3) absence or rudimentary development of the ventricular      
septum, in 4 cases (7 percent), type c,. and (4) absence of both        
ventricular sinuses and of the ventricular septum, in 6 cases (10       
percent), type d .                                                      
  three types of relationship between the great arteries were present.. 
a normal (solitus) interrelationship, in 9 cases (15 percent),          
designated type 1,. d-transposition, the transposed aortic valve lying  
to the right (dextro, or d), relative to the transposed pulmonary valve,
in 25 cases (42 percent), type ii,. and l-transposition, the transposed 
aortic valve lying to the left (levo or l), relative to the transposed  
pulmonary valve, in 26 cases (43 percent), type iii . in none was the   
inversus interrelationship, type iv, displayed .                        
  three types of visceral and atrial situs were found.. solitus, or     
normal, in 50 cases (83 percent),. inversus, an exact apparent mirror   
image of normal, in 2 cases (3 percent),. and heterotaxy, the uncertain 
visceral and atrial situs associated with asplenia, in 8 cases (13      
percent) .                                                              
  the 60 cases were classified segmentally, according to the anatomy of 
the three cardiac segments.. the great arteries, the ventricular        
sinuses, and the atria .                                                
  the classic single ventricle with a rudimentary outlet chamber was    
found morphologically to be a large left ventricle with a right         
ventricular infundibulum, the sinus of the right ventricle being absent 
(type a) .                                                              
  the myocardium of the right ventricular infundibulum, of the right    
ventricular sinus, and of the left ventricular sinus was identified by  
the distinctive gross morphologic characteristics of each .             
  the planes of the atrial and ventricular septa, and the relationships 
between the great arteries at the semilunar valves, were measured as    
projections upon the horizontal plane, relative to the anteroposterior  
line .                                                                  
  an approach to cardiac anatomy is presented which is segmental,       
morphologic and geometric . this approach has angiocardiographic,       
electrocardiographic and embryologic applications .                     
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congenital heart disease in the adult .                                 
  events in the natural course of 310 adult patients with proved        
significant congenital cardiac anomalies have been reviewed to determine
incidence, longevity, complications and cause of death .                
  atrial septal defect and patent ductus arteriosus were the most       
frequently encountered lesions and comprised over one third of the      
entire series . ventricular septal defect and pulmonic stenosis made up 
almost a quarter of the group . twenty-two instances of the eisenmenger 
syndrome secondary to a variety of shunting lesions are included .      
  bacterial endocarditis, sudden death and cardiac decompensation were  
the greatest threats to these patients . symptoms were minimal until the
appearance of heart failure, which was the most common cause of death,  
especially with older patients . sudden death occurred most often in    
patients with ventricular septal defect .                               
  although the clinical features are usually characteristic of a        
congenital malformation, young adults with acyanotic congenital heart   
disease are often misdiagnosed as rheumatic,. and in older patients,    
presenting manifestations are frequently attributed to arteriosclerotic 
heart disease . at times an associated acquired cardiovascular disorder 
may alter the basic syndrome .                                          
  three quarters of the patients survive and continue under observation 
the ability of many to live active, productive lives and to withstand 
stress, surgery, both cardiac and non-cardiac, and pregnancy was        
impressive . further observation of the patient with congenital heart   
disease but without surgical intervention is essential for accurate     
evaluation of the long term efficacy of cardiac surgery .               
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a study of ventricular septal defect associated with aortic             
insufficiency .                                                         
  clinical, electrocardiographic, radiographic, and hemodynamic findings
in 12 children with the combination of a ventricular septal defect and  
aortic insufficiency are presented . the left-to-right shunt was        
determined to be small or moderate in all, and significant aortic       
insufficiency was documented by aortography in 11 patients . clinical   
indication of aortic insufficiency as manifested by an aortic diastolic 
murmur first appeared at an average age of 6 years in 7 patients, with  
concomitant widening of the pulse pressure in 4 . progressive left      
ventricular hypertrophy was noted electrocardiographically, with        
progressive cardiac hypertrophy and aortic dilatation on x-ray          
examination in 2 patients . progression of the hemodynamic disability   
does not appear to be common in childhood, however .                    
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ventricular septal defect and aortic regurgitation clinical, hemodynamic
and surgical considerations .                                           
  the clinical, hemodynamic, angiographic and anatomic findings in      
fifteen patients with ventricular septal defect complicated by aortic   
regurgitation are presented . in this combination of malformations the  
aortic regurgitation is acquired and results from prolapse of an aortic 
valve leaflet into the septal defect . the strategic location of the    
septal defect in relation to the aortic leaflets appears to be more     
important to the development of this complication than the size of the  
defect or the magnitude of the shunt through it . the onset of aortic   
regurgitation occurs during early childhood and, once present, tends to 
become more severe . careful observation of patients with these defects 
is indicated following the appearance of aortic regurgitation since     
rapid progression to severe left ventricular failure is not uncommon .  
ventricular septal defect and aortic regurgitation must be distinguished
from other cardiovascular abnormalities producing a wide pulse pressure 
with a continuous or to-and-fro murmur . cardiac catheterization and    
thoracic aortography are the diagnostic procedures most helpful in this 
differentiation . the operative treatment of ventricular septal defect  
and aortic regurgitation is reviewed and, on the basis of the present   
and previously reported results, suggested plans for surgical management
are presented .                                                         
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current techniques in the surgical approach to aortic and mitral        
valvular disease .                                                      
  1. the aortic and mitral valves can be operated upon successfully and 
totally replaced with a prosthetic device of the ball-valve type with   
good long-term results . seventy-four cases are reported .              
  2. in aortic valvular disease the outcome in the immediate            
postoperative period is influenced primarily by the presence of calcific
aortic stenosis as well as the presence or absence of disease in the    
coronary arteries .                                                     
  3. we have significantly decreased the appearance of a low-output     
syndrome postoperatively in patients who are suffering from severe      
mitral disease by leaving the papillary muscle-chordae tendineae-mural  
leaflet relationship intact . we feel this adds strength to each        
contraction .                                                           
  4. there have been no late deaths in the follow-up period to date     
(thirty months) in any patient with replacement of aortic or mitral     
valves with the ball-valve prosthesis .                                 
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effects of aortic regurgitation on left ventricular performance direct  
determinations of aortic blood flow before and after valve replacement .
  the volume of regurgitant blood flow and its effects on the           
performance of the left ventricle were assessed at operation in 14      
patients with varying degrees of aortic regurgitation . instantaneous   
forward and regurgitant flows in the ascending aorta were measured with 
a sine-wave electromagnetic flowmeter simultaneously with left          
ventricular and aortic pressures . in eight patients who had aortic     
regurgitation without associated stenosis, 63 to 75 percent of the total
forward stroke volume regurgitated during the succeeding diastole . the 
calculated regurgitant orifice areas ranged from 0.13 to 0.44 cm /m .   
after replacement of the aortic valve with a starr-edwards prosthesis,  
the absence of regurgitant flow was proved in every patient, and the    
records of aortic blood flow closely resembled those seen in patients   
with normal aortic valves . net forward blood flow increased by an      
average of 60 percent, total left ventricular stroke volume fell 42     
percent, and the mean aortic pressure rose 29 percent . the pressure    
work of the left ventricle was elevated preoperatively in five of the   
eight patients (average 89 g-m stroke/m ) and fell significantly to an  
average of 34 g-m stroke m after valve replacement . kinetic ventricular
work was high in seven of the eight patients and comprised 10 percent of
total work before replacement but only 4.8 percent afterward .          
  similar observations were made in five patients with aortic stenosis  
and associated aortic regurgitation, ranging in severity from 24 to 72  
percent of total forward stroke volume . in four patients in whom the   
valve was replaced, no residual regurgitation was present afterward, and
net forward flow rose an average of 49 percent . kinetic left           
ventricular work was extremely high in every patient and averaged 26    
percent of total work preoperatively and 13 percent after valve         
replacement . in this group, pressure work was variable both before and 
after operation .                                                       
  the studies described provide definitive information concerning the   
effects of aortic valve disease on left ventricular performance in man  
and document the favorable changes in flow, pressure, and left          
ventricular work which immediately follow aortic valve replacement .    
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the absorption and hepatic uptake of orally ingested radioactive vitamin
b in hepato-splenic bilharziasis .                                      
  the absorbed plasma radioactivity and hepatic uptake of orally        
ingested vitamin b tagged with co were measured in 52 subjects, 26      
normals and 26 suffering from bilharziasis .                            
  the results of the present work indicate that the absorption and      
hepatic uptake of this vitamin are within normal limits in hepatosplenic
bilharziasis irrespective of the stage of the disease, the size of the  
organs affected and the presence or absence of associated peripheral    
neuritis .                                                              
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early effects of digitalis on central hemodynamics in normal subjects . 
  the intravenous administration of lanatoside c in 7 normal subjects   
had the following effects..                                             
  1. an early significant reduction of heart rate .                     
  2. a significant transient reduction of cardiac output .              
  3. a significant increase of the stroke volume initially accompanied  
by a significant rise of the end-diastolic volume with unchanged        
systolic rate of emptying . the increase of end-diastolic volume seems  
to be related to the lengthening of the diastolic filling period . later
on, the systolic emptying rate increases, and the ventricular volumes   
decrease, suggesting an inotropic effect of the drug .                  
  4. a significant increase of pulmonary blood volume, parallel to the  
increase of the stroke volume, suggestive of a passive relation between 
the two variables .                                                     
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measurement of pericardial fluid correlated with the i -cholografin and 
ihsa heart scan .                                                       
  in 23 patients undergoing open-heart surgery in whom the pericardial  
contents were accurately measured, and in 11 additional patients        
examined at autopsy or by pericardiocentesis, isotopic photoscans of the
heart were made and the results were correlated .                       
  the most accurate means of diagnosis of pericardial effusion was found
to be the ratio of the maximum transverse cardiac diameters on scan and 
roentgenogram . in patients with less than 100 cc of pericardial fluid  
this ratio was greater than 0.80, and it was less than this in cases of 
effusion of 200 cc or more .                                            
  measurement of the difference of these diameters, and visible         
separation of the cardiac blood pool from the pulmonary vasculature and 
liver aided in the diagnosis .                                          
  pericardial effusions of 200-300 cc or greater can be detected by     
isotopic photoscanning . although cardiac dilatation and/or hypertrophy 
decrease the sensitivity of the technique somewhat, a definite diagnosis
of pericardial effusion can be made even when cardiomegaly exists .     
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aneurysm of the membranous septum .                                     
  1. aneurysms of the membranous septum are relatively rare lesions     
presumably developing on a congenital basis . these aneurysms originate 
in the left ventricle immediately beneath the aortic valve and bulge    
into the right ventricle, the septal leaflet of the tricuspid valve or  
into the right atrium .                                                 
  2. many of these aneurysms do not produce symptoms . others may cause 
right ventricular outflow tract obstruction or may rupture and result in
a septal defect . the resulting shunt will be from the left ventricle   
into the right atrium or ventricle .                                    
  3. an aneurysm of the membranous septum may be an isolated abnormality
or be associated with other congenital cardiac defects, particularly    
aortic valvular insufficiency . membranous septal aneurysms may be the  
site of bacterial endocarditis or thrombus formation .                  
  4. aneurysms resembling those arising from the membranous septum may  
occur as part of the complex of deformities produced by an endocardial  
cushion defect . however, the angiographic features diagnostic of a     
cushion defect can still be recognized .                                
  5. the presence of a septal aneurysm can be established only by       
angiocardiography . the diagnostic features as seen on the left         
ventricular angiocardiogram are presented .                             
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distribution of transfused tritiated cytidine-labeled leukocytes and red
cells in the bone marrow of normal and irradiated rat .                 
  in normal rats and after total body irradiation with 550 r of x-rays, 
the fate in the bone marrow of labeled nucleated and red cells of       
transfused peripheral blood was observed autoradiographically .         
  labeled nucleated cells, most of which were lymphocyte-like cells,    
readily migrated into the marrow parenchyma in normal animals (2 cells/ 
1,000 parenchymal cells/hr.) . following irradiation to at least 27-51  
hr., this migration appeared to be relatively increased . beyond this   
time, parenchymal areas were more difficult to be defined as such .     
  labeled red cells were rarely observed to enter parenchyma despite the
presence of nonlabeled erythrocytes within the parenchymal structure    
after irradiation .                                                     
  the vascular bed following irradiation increased greatly as the       
parenchyma diminished to a minimum of less than 10 percent control at 75
hr . despite these changes in the architecture of the marrow, the       
average density of labeled cells per area of marrow corresponded to     
values expected on the assumption of a free-flowing circulation . the   
technique used at present did not allow us to distinguish, at all times,
between a free-flowing circulation through intact sinusoids or through  
areas in which the sinusoidal wall, as such, was destroyed .            
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factors limiting survival after circulatory occlusion under hypothermia 
and hyperbaric oxygenation .                                            
  thirty minutes of circulatory occlusion with mild hypothermia and     
hyperbaric oxygen ventilation resulted in a mortality of 83.3 percent in
animals . when coronary perfusion from a reservoir was added, the       
mortality rate was 22 percent . ventricular fibrillation was much more  
easily reversed after coronary perfusion . there was no evidence of     
brain damage in survivors which leads to the conclusion that the brain  
tolerates circulatory arrest better than the heart under these          
conditions .                                                            
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the effect of hypothermia on circulatory reflexes in the human .        
  total circulatory occlusion and release result in hemodynamic         
phenomena which provide an index of integrity of some cardiovascular    
reflexes . these include carotid sinus and aortic baroceptors,          
arteriolar vasomotor tone, and venomotor reactivity .                   
  baroceptor depression appears at a more moderate level of cooling than
does the sympathetic, vasomotor, depression . below 28 degrees c. both  
are significantly depressed, although probably not totally abolished .  
  the level of 28 degrees c. is a critical physiological level and may  
represent an important limit in the clinical use of hypothermia .       
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studies in perfusion hypothermia with special reference to /deep        
hypothermia/ and circulatory arrest .                                   
  1. perfusion hypothermia produces large temperature gradients within  
the body since organs are cooled roughly in proportion to their basal   
blood flows . the difference between the coldest and the warmest portion
of the body after 30 minutes of perfusion exceeds 25 c .                
  2. the average body temperature, which provides a proper measure of   
total body cooling, may be calculated from the arteriovenous temperature
difference and the extracorporeal flow rate .                           
  3. true /deep/ hypothermia is not obtainable by reasonable periods of 
perfusion alone .                                                       
  4. an important rise of core temperatures occurs during circulatory   
arrest in hypothermia because of relatively high average body           
temperature .                                                           
  5. high average body temperatures lead to continuing production of    
lactic acid in muscle tissue, whereas low core temperatures impair      
lactic acid metabolism . thus metabolic acidosis is progressive in      
prolonged perfusion hypothermia, and is accentuated by total circulatory
arrest . progressive acidosis may be minimized by uniform profound      
cooling by combining external with perfusion hypothermia .              
  6 diluents appear to have little effect on total body heat exchange   
during perfusion cooling .                                              
  7. perfusion warming has a differentially greater effect on core      
organs . though these are readily brought to a normal range, much of the
animal may remain cold .                                                
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application of the emission spectrograph to the analytical needs of the 
industrial hygiene laboratory .                                         
  examples of unique applications of the principles of emission         
spectroscopy to industrial hygiene problems are provided . a discussion 
of qualitative, semiquantitative and quantitative methods of            
spectrographic analysis is presented . these methods include            
representative applications which are made for the analysis of the      
metallic constituents of body tissues and fluids from human and animal  
subjects, industrial process materials, ores, and environmental dusts   
and fumes . brief descriptions of sample preparation techniques required
for successful analyses are also presented .                            
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nickel carbonyl.. its detection and potential for formation .           
  recent recommendations for control of nickel carbonyl exposures have  
been considered in the design of a simple, sensitive field method for   
sampling nickel carbonyl in air and process gases . the method involves 
collection in dilute aqueous hcl, ph adjustment, nickel complex         
development with alpha-furildioxime, and extraction with chloroform .   
color intensity is compared visually (or for greater accuracy,          
spectrophotometrically) with liquid standards . sensitivities on the    
order of 0.001 ppm are obtainable . a detailed development of the       
thermodynamics associated with the formation of nickel carbonyl is also 
presented to show the maximum concentrations of nickel carbonyl that may
be formed over a wide range of co concentrations, temperatures and      
pressures .                                                             
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polarographic determination of heavy metals in air samples .            
  the polarograph possesses the required sensitivity and specificity to 
make it the method of choice for analysis for a variety of heavy metals 
in air . two commercial polarographs are compared and both found        
adequate on the basis of analysis for lead . determinations may be made 
for antimony, copper, lead, cadmium, chromium, nickel, cobalt,          
manganese, and others .                                                 
.I 130
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the inorganic constituents of human teeth and bone examined by x-ray    
emission spectrography .                                                
  x-ray emission spectrography has been applied to study of the         
elemental composition of human teeth, enamel, dentine and bone . the    
material consisted of eight crushed teeth, enamel and dentine powder    
separated from eighteen teeth, and four pieces of buccal cortical       
mandibular bone . the teeth did not have fillings . the whole material  
contained nineteen elements, of which the main ones were calcium and    
phosphorus . in all the samples of tooth material, there were found ca, 
p, cl, fe, zn, sr and k, and the bone also contained ni . the time      
needed for a semi-quantitative analysis compares very favourably with   
that needed for other methods .                                         
.I 131
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a kinetic study of nickel(ii), complexes of sulfur-containing amino acid
  the rate expression for the ethylenediaminetetraacetic acid (edta)    
ligand exchange reaction with nickel(cysteine) is.. rate = k(complex) + 
kedta (complex)(edta) . this two-term rate expression is characteristic 
of square planar complexes and agrees with the square planar            
configuration of ni(cysteine) reported on the basis of spectral studies 
the edta-independent term of the rate expression is an acid-catalyzed 
term and can be written k (h) (complex) . the value of kn is 2.5 x 10 m 
sec while the value of kedta is only on the order of 10 -10 m sec . the 
edta reaction with ni(cysteine) methyl ester) is very similar to the    
reaction with ni(cysteine) . when the sulfur-containing amino acid      
ligand contains a thiol ether, the kinetic differences are striking .   
  ligand exchange reactions of edta, triethylenetetramine, and          
diethylenetriamine with nickel-methionine complexes are several orders  
of magnitude faster and give products that are mixed-ligand complexes . 
the results of this kinetic study of amino acid complexes containing    
sulfhydryl and thiol ether sulfur groups support other studies at       
equilibrium which suggest sulfur coordination and square planar         
complexes for the sulfhydryl groups and octahedral complexes with no    
sulfur coordination for thiol ethers .                                  
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the action of metal ions on tobacco mosaic virus ribonucleic acid .     
  added transition metal ions stabilize the secondary structure of      
tobacco mosaic virus ribonucleic acid (tmv-rna) as evidenced by a       
reduction in the absorbancy change of heated nucleic acid solutions . in
spite of this stabilization of secondary structure, heating in the      
presence of metal ions results in the loss of biological activity due to
the hydrolysis of phosphodiester bonds . thus, all heavy metal ions of  
the iib and first-transition elements studied caused a rapid loss of    
biological activity of tmv-rna at ph 6.5 and 65 . calcium and magnesium 
ions, while not affecting secondary structure at 65 and ph 8.5, caused a
rapid loss of biological activity . at ph 5.8 and room temperature lead 
ions catalyzed the hydrolysis of rna to i'(3')- mononucleotides,. on    
long standing, nucleosides were formed .                                
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chromium, lead, cadmium, nickel and titanium in mice.. effect on        
mortality, tumors and tissue levels .                                   
  about 700 mice were given throughout their lives 5 ppm cadmium, lead, 
chromium, nickel or titanium in drinking water while fed a diet         
deficient in cadmium and low in other metals . tissue concentrations    
comparable to those of man were observed . sex differences appeared .   
mortality of females was unaffected . mortality of males on cadmium,    
lead and nickel was increased compared with that of the chromium group, 
and of those on cadmium and lead compared with the controls . longevity 
of the oldest 10 of both sexes was less in lead and titanium groups, and
of males in cadmium group, compared with controls . no metal was        
carcinogenic,. incidence of tumors in males on cadmium and lead, and in 
females given nickel was decreased . body weights at death were greater 
in titanium, chromium and lead groups . large increments of titanium,   
moderate increments of cadmium and nickel, and lesser increments of     
chromium and lead were observed in 5 organs, compared with controls .   
higher concentrations of cadmium and titanium occurred in younger mice  
and the other metals did not increase markedly in tissues with age . all
metals except chromium exhibited one or more signs of innate toxicity . 
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synergistic effects between antioxidants and selenium or vitamin e .    
  several antioxidants when fed to chicks at relatively high levels in  
an experimental diet were ineffective in preventing the exudates and    
mortality from a combined deficiency of selenium and vitamin e . some of
the compounds were toxic, as evidenced by sudden death or subcutaneous  
hemorrhages . when amounts of either selenite or a-tocopheryl acetate,  
which individually had little or no effect on symptoms, were given with 
the antioxidants signs of deficiency and mortality were prevented, and  
toxicity also was eliminated .                                          
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the expression of urine analysis results -dash  observations on the use 
of a specific gravity correction .                                      
  urine analyses are very useful for measuring the extent of exposure to
certain toxic substances . the types of specimen obtainable from persons
employed in industry, and the effect of concentration variations are    
discussed . in expressing the results of analysis it is shown that a    
concentration correction is essential . the correction based on specific
gravity is the easiest to apply . the mean specific gravity for persons 
resident in the u.k. has been found to be around 1.016, a figure        
considerably lower than the mean of 1.024 used by many workers          
(particularly in the u.s.a.) . the implications of this on the results  
of urine analysis are indicated .                                       
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activation and inactivation of p-hydroxyphenylpyruvate hydroxylase .    
  1. p-hydroxyphenylpyruvate hydroxylase (ec 1.99.1.14) is reversibly   
inactivated by dialysis, storage, purification involving ammonium       
sulfate fractionation, and treatment with oxidizing agents . the        
inactive enzyme is reactivated by various reducing agents .             
  2. metal-chelating agents inhibited enzyme activity . 1,10-           
phenanthroline and 4,7-diphenyl-1,10-phenanthroline (fe sensitive)      
strongly inhibited, but 2,9-dimethyl-1,10-phenanthroline (cu specific)  
did not . 1,10-phenanthroline-treated p-hydroxyphenylpyruvate hydroxyl- 
ase was reactivated specifically by fe in the presence of a reducing    
agent, indicating a role for fe in enzyme activity .                    
  3. nonoxidative sulfhydryl reagents did not materially inhibit the    
enzyme activity under various conditions .                              
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responses of b. subtilis (atcc 558) to streptomycin .                   
  to observe in detail the influence of streptomycin on the growth of sm
dependent type, the author chose b. subtilis (atcc 558) and made        
experiments on its responses to streptomycin, with special reference to 
the relation of the sm concentration with spore formation of its sm     
dependent type together with germination and outgrowth of the spores    
formed . the results are as follows .                                   
  1. among 18x10 cells of wild type of b. subtilis (atcc 558) about     
3,200 cells of sm resistant and one cell of sm dependent are found as   
its mutant .                                                            
  2. b. substilis (atcc 558) shows normal growth at sm concentration    
below 10 r/ml, but the growth declines rapidly between sm 10 r/ml-20 r/m
l, and the growth stops entirely at sm concentration 20 r/ml .          
  3. sm resistant type grows well between sm 0.1 r/ml-sm 2,000 r/ml, the
growth declines rapidly at about sm 10,000 r/ml .                       
  4. sm dependent type shows normal growth between sm 10,000 r/ml-20 r/m
l, the growth get worth below sm 10 r/ml, and the cell shape elongates  
several times, at sm below 1 r/ml each cell becomes filamentous form and
has several ten times length of normal cell, as if the cells have       
stopped to divide at low sm concentration .                             
  6. the germination and outgrowth of spores of the sm dependent type   
slow down with decline of sm concentration, but the germinated spores   
grow in normal forms until sm concentration reaches 7.8 r/ml, then the  
germination becomes much slower, and the cells grow in filamentous forms
or irregular forms . at extremely low sm concentration both germination 
and outgrowth nearly stop .                                             
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phospholipids of the bovine, rabbit, and human lens .                   
  the phospholipids of bovine, rabbit, and human lenses contain cephalin
lecithin, and sphingomyelin but their distribution differs with each    
species . there is suggestive evidence that there may also be           
plasmalogen in the lens, but, if so, it represents a minor phospholipid 
component . the fatty acid composition of each phospholipid differs in  
each species, with most of the differences centering around 16..0,      
18..1, and 24..1 .                                                      
.I 139
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surgical aspects of heart disease in pregnancy .                        
  the ideal management of the pregnant woman with heart disease is      
medical, if feasible . the operative experience with mitral valvulotomy 
in pregnancy has expanded . this procedure is now indicated when        
progressive cardiac disability develops during the first or second      
trimester and when the proven dominant lesion is mitral stenosis . when 
other lesions are present, especially those requiring pump oxygenator   
perfusion, the risk must be carefully measured . damage to the fetus may
result from reduced placental blood flow .                              
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traumatic lesions of the optic chiasma.. a report of four cases .       
  case histories of four patients who suffered severe head trauma       
resulting in complete bitemporal hemianopia are presented . the optic   
chiasm was visualized in only one patient . it was markedly swollen and 
disintegrated . this appearance was consistent with multiple minute     
tears of the crossed fibres in the median sagittal plane . other        
theories to explain the bitemporal field defect are discussed .         
.I 141
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lung cancer.. an evolutionary approach .                                
  lung cancer is presented as an example of somatic mutation . in       
contrast to previous theories the following are defined.. (a) the major 
growth controlling mechanism,. (b) the mutation found in cancer,. and   
(c) the environmental changes in the lungs of patients who smoke        
cigarettes which can select this mutant .                               
.I 142
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the effects of electrophoretically separated lens proteins on lens      
regeneration in diemyctylus viridescens .                               
  in the present study, lenses were removed from the eyes of adult      
anesthetized newts, macerated in 0.03 m borate buffer at ph 8.6, and    
separated by starch gel electrophoresis . upon staining with amido black
10-b, seven distinct staining areas appeared in the blocks . three bands
moved toward the anode, and three toward the cathode . in addition, a   
seventh moiety represented by a smear of material moved toward the anode
one millimeter times five tenths millimeter plugs were removed from   
each of these areas and were placed into freshly lentectomized eyes .   
plugs from most strongly positive and most weakly negative proteins     
inhibited lens regeneration . in addition, plugs from the area          
containing the weakly negative protein induced either lenses with       
aberrant polarity or double centered lenses with centers of opposed     
polarity . all other protein bands had no significant effect on         
regeneration .                                                          
  in addition to the above experiments, homogenates and                 
proteinasedigested homogenates of lenses were injected into eyes        
following lentectomy . three 5-ul samples were injected in each case    
over a six day period . injection of the plain homogenate stimulated    
lens regeneration markedly, while the proteinase destroyed the          
stimulatory activity .                                                  
  theoretical considerations of the above data are discussed .          
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enzymic synthesis of deoxyribonucleic acid xviii. the repair of         
partially single-stranded dna templates by dna polymerase .             
  a partially single-stranded dna, prepared by limited digestion of each
strand with exonuclease iii, can be restored to its native, fully       
double-stranded structure by escherichia coli dna polymerase . the rate 
of synthesis observed in the repair of such a partially degraded primer 
in the polymerase system is faster than that seen with a native dna .   
the newly synthesized dna is covalently attached to the primer . the    
fully repaired dna resembles the original native dna as judged by its   
appearance in electron micrographs, cscl density-gradient analysis,     
denaturability and genetic activity . dna synthesis which follows the   
repair phase produces a structure that is not covalently linked to the  
primer and resembles, in its nondenaturability, branched appearance, and
lack of genetic activity, the product obtained with a native dna primer 
(schildkraut, richardson + kornberg, 1964) .                            
.I 144
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on the mechanism of genetic recombination in transforming bacillus      
subtilis .                                                              
  the molecular fate of transforming dna in competent bacillus subtilis 
has been studied . the physical differentiation of transforming dna and 
the genetic material of recipient bacteria was effected by employing the
isotopes n and p . competent bacteria labeled with n and p were allowed 
to incorporate n p-labeled transforming dna intracellularly . dna was   
isolated from these recipient cells and centrifuged in cesium chloride .
analysis of drop fractions collected at equilibrium showed the presence 
of radioactivity in a region of density corresponding to recipient dna .
material contribution from donor dna to the resident dna did not occur  
when genetically inert bacillus cereus dna was substituted for          
homologous dna . it was concluded that radioactivity appearing in the   
unlabeled resident dna was not the result of degradation of input (     
p)dna and subsequent incorporation by normal metabolic processes . since
single-stranded dna of donor origin was not detected, nor was there     
evidence for the non-specific aggregation of donor and recipient dna, it
was concluded that the observed physical association of transforming and
recipient dna occurs as a result of genetic recombination in transformed
b. subtilis .                                                           
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physical and biological studies on transforming dna .                   
  bacillus subtilis transforming dna prepared by the method described,  
has an average molecular weight of 11.6 million . the dna is            
heterogeneous, as judged by chemical composition, thermo-spectral and   
pyenographic properties . these properties have been used to fractionate
some of the biologically active molecules which show higher specific    
activities in transforming respective auxotrophs .                      
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comparison of mutation and inactivation rates induced in bacteriophage  
and transforming dna by various mutagens .                              
  inactivation and mutation rates were measured for t4 phages and       
bacillus subtilis transforming dna treated by low ph, nitrous acid, or  
hydroxylamine at different temperatures . the frequency of mutants      
increased linearly with time for all three agents, whereas the logarithm
of survival gave a linear plot only for nitrous acid and low ph . an    
arrhenius plot showed the same slopes for both inactivation and mutation
rates after treatment with low ph or nitrous acid,. for the latter agent
the slope remained unaltered even when the dna was treated in the       
denaturated state . in contrast, mutation rates obtained after the      
exposure to hydroxylamine differed greatly for native or denatured dna, 
phage t4 being intermediate .                                           
  treatment by low ph or nitrous acid interrupted the genetic linkage   
between tryptophan and histidine, the interrupting hits being about 1/3 
as frequent as lethal hits, independent of the temperature .            
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autolysis of bacillus subtilis by glucose depletion .                   
  in cultures in minimal medium, rapid lysis of cells of bacillus       
subtilis was observed as soon as the carbon source, e.g. glucose, had   
been completely consumed . the cells died and ultraviolet-absorbing     
material was excreted in the medium . the results suggest that the cells
lyse because of the presence of autolytic enzymes . in the presence of  
glucose the damage to the cell wall caused by these enzymes is repaired 
immediately .                                                           
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plasma 17-hydroxycorticosteroids and 17-oxosteroids in patients with    
breast cancer and in normal women .                                     
  (1) 17-hydroxycorticosteroids (17-ohcs) and 17-oxosteroids were       
measured in the plasma of normal women, patients with early breast      
cancer and in patients with advanced metastatic disease .               
  (2) the mean plasma 17-ohcs level was found to be normal in the early 
stages of the disease but was raised in the advanced disease . in both  
groups of patients the variance was significantly greater than in normal
women .                                                                 
  (3) the mean plasma 17-oxosteroid level in both early and advanced    
breast cancer was not significantly different from the normal level but 
the variance was increased .                                            
  (4) there is a significant correlation between the plasma 17-ohcs and 
17-oxosteroids in normal women which was not found in the cancer        
patients .                                                              
  (5) in patients with advanced breast cancer, the levels of plasma 17- 
oxosteroids were significantly correlated with the amounts of 11-deoxy- 
17-oxosteroids found in the urine . there was no correlation between    
plasma and urinary 17-ohcs .                                            
  (6) the physiological significance of these findings is discussed .   
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hormone therapy in metastatic breast cancer.. clinical response and     
urinary gonadotrophins .                                                
  the total urinary gonadotrophin output of a group of post menopausal  
women with metastatic breast carcinoma undergoing hormone therapy, which
in every case initially consisted of treatment with diethylstilboestrol,
des (ca. 20 mg/d), has been studied for periods varying from seven      
months to 31/2 years .                                                  
  no correlation between gonadotrophin output and clinical response was 
found, except that in all cases showing objective regression urinary    
gonadotrophin remained low throughout the remission period . a low level
of gonadotrophin output was not, however, necessarily indicative of a   
good clinical remission . following withdrawal of des, and independent  
of the period of therapy, recovery to pre-treatment levels was the rule 
rather than the exception .                                             
  a small group of patients maintained on a lower dose of des (3-5 mg/d)
showed the same degree of suppression of urinary output as those        
receiving 20 mg/d, and several of these exhibited objective remissions .
  the study has emphasised the importance of site specificity in the    
response to hormone therapy, and underlines the difficulties of relating
the clinical response of the patient as a whole to changes in hormonal  
environment .                                                           
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plasma androgens in women i. normal and non-hirsute females,            
oophorectomized and adrenalectomized patients .                         
  1. in a group of 20 normal non-hirsute females age 17 to 38, 18 non-  
hirsute patients with varied genito-urinary disorders, 8 oophorectomized
and or adrenalectomized patients plasma testosterone was measured by the
method of finkelstein et al. (1961) . conjugated androsterone and       
conjugated dhea were determined by a modified method of migeon + plager 
(1955) .                                                                
  2. mean baseline values in normal females were .11 .06 ug/100 ml      
testosterone, 11.8 5.5 ug/100 ml conjugated androsterone, and 29.5 15.5 
ug/100 ml conjugated dhea . no significant response to hcg could be seen
dexamethasone affected the conjugated dhea significantly, but did not 
seem to affect conjugated androsterone or testosterone .                
  3. the non-hirsute patients showed essentially the same pattern . an  
effect of dexamethasone on the levels of conjugated androsterone was    
demonstrated .                                                          
  4. oophorectomized women had baseline values for the conjugates in the
range of normals . testosterone, however, was low with an average of    
 .016 ug/100 ml . in the adrenalectomized patients no androgens were     
detectable .                                                            
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oophorectomy and cortisone treatment as a method of eliminating         
oestrogen production in patients with breast cancer .                   
  the urinary excretion of oestrone, oestradiol-17b, oestriol, and 17-  
hydroxycorticosteroids has been estimated in 55 premenopausal and 91    
postmenopausal women with breast cancer at various stages of the disease
before therapy . the depletion of oestrogen excretion caused by         
oophorectomy combined with cortisone treatment was studied in the       
patients with metastasising breast tumours (32 premenopausal and 56     
postmenopausal subjects) .                                              
  patients with disseminating breast cancer excreted significantly      
larger quantities of oestriol than healthy women of the same age,       
whether pre- or postmenopausal . the excretion of oestrone and          
oestradiol-17b was similar in cancer patients and healthy women of      
corresponding age .                                                     
  oophorectomy reduced the oestrogen excretion not only in premenopausal
subjects but also in quite a number of postmenopausal patients,         
particularly in those who were still excreting significant amounts of   
oestrogens . this decrease in the oestrogen output was transient and was
followed by a compensatory increase, possibly of adrenal origin .       
  cortisone administered within a month after the oophorectomy at a     
dosage of 50 mg per day rapidly depressed the secondary rise in the     
oestrogen output to a level of about 4 to 5 ug/24 h irrespective of the 
age of the patient . this excretion level was unchanged as long as      
cortisone was given in an adequate dose, but increased rapidly when the 
cortisone treatment was discontinued .                                  
  oophorectomy combined with adequate cortisone treatment seems to offer
an alternative to the extensive surgical porcedures undertaken to       
eliminate oestrogen production in breast cancer patients .              
.I 152
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some reactions of cytotoxic antibodies against previously unknown mouse 
isoantigens .                                                           
  the antiserum produced in c3h/he against c3h/st lymphosarcoma 6c3hed  
contains a mixture of at least two antibodies of different properties   
and specificities . anti h-5a is a hemagglutinating antibody removed by 
absorption with red cells and many tissues . anti v is a cytotoxin      
reacting with c3h/st tissue and 6c3hed but not with red cells.          
  the reciprocal antiserum c3h/st anti c3h/he sarcoma mc1m is more      
complex . it contains the hemagglutinin anti h-6a and a variety of      
cytotoxins . one appears to be specific for c3h/he tissues and the      
   tumor mc1m . another reacts with antigens on the c3h/go carcinoma    
bp8. two additional cytotoxins may also be present .                    
  immunization between sublines of the same inbred strain can result in 
the production of a variety of antibodies directed against unrelated    
antigens present on even long transplanted cells . the significance of  
.I 153
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on the value of thymectomy in adult mice as a means of potentiating the 
immunosuppressive action of melphalan (l-phenylalanine mustard) .       
  thymectomy has been found to be ineffective as a means of potentiating
the immunosuppressive action of melphalan in adult cba-p mice challenged
with a-strain mammary carcinoma transplants . this was true when the    
thymectomy was performed 2 days, 4 weeks or 7 weeks prior to injection  
of a single dose (15 mg/kg body weight) of melphalan, administered 24   
hours prior to tumour transplantation, and also when thymectomy was     
combined with multiple doses of melphalan given before and after tumour 
transplantation . these findings are discussed .                        
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studies on the kinetics of transplantation immunity .                   
  using the parameter of the number of tumor cells necessary to produce 
s.c. tumors in allogeneic animals at varying intervals after antigenic  
stimulation, immunity was found to be in force as early as 2 days after 
primary antigenic stimulation . it reached a peak at 8-10 days and had  
largely subsided by the end of a month . this method was also applied to
the quantitative study of the onset, degree, and duration of immunity   
elicited by skin grafts . the results obtained with inocula of large    
numbers of tumor cells (10 percent) were comparable to those obtained   
with massive skin grafts .                                              
  the differences in the degree of antigenic stimulation resulting from 
different routes of inoculation were studied . it was found that the    
intradermal (i.d.) route of inoculation resulted in a more intense      
antigenic stimulation than the s.c. route . when both routes of         
inoculation were used simultaneously the pattern of growth of the s.c.  
tumor was influenced by the i.d. inoculation.. an i.d. inoculum given 24
or 48 hr earlier caused marked suppression of growth of the s.c. tumor, 
while when an i.d. inoculation was preceded by an s.c. inoculation,     
although there was an appreciable effect on the growth size, the growth 
curves of the 2 tumors were always parallel .                           
  there was no correlation between cytotoxic activity and the degree of 
immunity in force at a given time .                                     
.I 155
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evidence for an immunological reaction of the host directed against its 
own actively growing primary tumor .                                    
  cells isolated from primary benzo(a)pyrene-induced fibrosarcomas in   
rats of a pure line were tested for their ability to grow as autografts 
when injected back into the autochthonous host . the autograft did not  
take if the primary tumor had been removed but grew occasionally in     
animals in which the major part of the tumor was left . in every        
instance the sarcoma cells grew when injected into syngeneic recipients 
in these recipients the growth of the sarcoma cells was prevented or  
retarded when they were mixed in vitro, prior to injection, with spleen 
cells from animals that had been immunized against the tumor .          
autochthonous spleen cells taken from the animal with the tumor behaved 
in this test like those from immunized animals as long as the spleen was
taken 3 weeks after removal of the tumor . when the spleen and tumor    
were removed at the same time, however, autochthonous spleen cells did  
not behave like spleen cells from immunized animals and did not         
interfere with the growth of the tumor . the results of both the        
autograft and spleen cell experiments suggest that rats react actively  
against their own growing primary tumors, but that the tumor exhausts   
the supply of lymphocytes responsible for this reaction . after the     
tumor is removed, the concentration of antitumor lymphocytes in the     
spleen builds up and the animals can reject an autograft .-j nat cancer 
inst 36.. 29-35, 1966 .                                                 
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a comparison of the cytologic effects of leurosine methiodide and       
vinblastine in tissue culture .                                         
  comparison of the degree and duration of arrest of metaphases in      
tissue culture cells by leurosine methiodide and vinblastine was made,. 
colchicine and demecolcine were included for reference purposes . all   
four drugs produced a similar cytologic effect, but vinblastine was most
active and remained active for the longest period of time .             
.I 157
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comparison of central aortic and peripheral artery pressure curves .    
  brachial artery and central aortic pressures were compared in 50      
consecutive patients subjected to retrograde left heart catheterization 
in order to re-emphasize the fact that the two pressures are not        
necessarily identical . in 43 cases the systemic systolic pressure peaks
exceeded those in the central aorta while in seven these pressures were 
equal . the average pressure difference was 22.6 mm. hg . the greatest  
differences occurred in cases of aortic regurgitation and could be      
extreme, the brachial artery systolic pressure exceeding that in the    
aorta by more than 100 mm. hg in some instances . the least differences 
occurred in cases of aortic stenosis but significant differences        
occasionally existed, leading to erroneous estimation of valve orifice  
size if the systemic rather than the aortic systolic pressure was used .
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changes in sphingosine and fatty acid components of the gangliosides in 
developing rat and human brain .                                        
  rat brain increases in weight after birth in three stages.. (i)       
rapidly for the first 2 weeks, (ii) at a lower rate from 2 to 5 weeks,  
and (iii) at a still lower rate from 5 weeks to 5 months . during the   
succeeding period, designated iv, it maintains constant weight up to 1  
year of age . brain ganglioside content increased linearly during i and 
ii, more slowly during iii, and diminished during iv . the appearance of
measurable amounts of brain sphingomyelin and cerebroside succeeded that
of ganglioside .                                                        
  ceramide with c -sphingosine and c fatty acid was found in a large    
proportion of all three sphingolipids upon their first appearance in    
measurable quantity . c fatty acid in cerebroside rapidly declined to a 
negligible level, while in gangliosides and sphingomyelin it declined   
slowly but remained the major fatty acid component .                    
  cerebrosides and sphingomyelin contained c -sphingosine almost        
exclusively at all stages of rat brain growth . gangliosides contained c
-sphingosine almost exclusively at birth, but subsequently accumulated c
-sphingosine until they had nearly equal quantities of each base type . 
  changes in human brain gangliosides resemble those in rat . in        
tay-sachs disease, gangliosides have c -sphingosine predominantly, and a
high content of c fatty acid .                                          
.I 159
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studies of the generalized shwartzman reaction induced by diet vi.      
effects of pregnancy on lipid composition of serum and tissues .        
  pregnancy induced profound alterations in the lipid composition of    
serum and tissues . (1) there is an elevation of total serum lipid,     
phospholipid, triglyceride, free fatty acid and cholesterol,. (2) while 
the total lipid of the liver and kidney are increased, that of the depot
fat is decreased,. (3) palmitate and oleate are increased in serum and  
liver,. (4) arachidonate and stearate are decreased in serum and liver,.
and (5) placentas contain more stearate than the other organs of the    
pregnant rat and also have a higher water content . the decrease in     
depot total fat,. elevation of serum, liver and kidney total fat,. and  
elevation of serum free fatty acids suggest that pregnancy induced      
mobilization of depot fat . the increase in proportion of liver and     
serum palmitate suggests that pregnancy induces increased lipogenesis   
from the acetate pool . the appearance of an increased amount of        
long-chain fatty acids in the liver may be due to the increased intake  
of dietary fat . the decrease in arachidonate and stearate in serum and 
liver suggests a relative decrease in mitochondrial fatty acid synthesis
.I 160
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electron microscopy of the bovine lung.. the normal blood-air barrier . 
  lungs of 20 healthy, mature cattle were fixed in oso , embedded in a  
polyester resin, and studied via electron microscopy . the blood-air    
barrier was widely variable in thickness and consistency . there was a  
continuous epithelial alveolar lining . the cytoplasm of some of the    
epithelial cells contained membrane-bound aggregates of granules which  
may be secretory structures . the epithelium rested on a basement       
membrane, which in turn was continuous with or rested on an adjacent    
capillary endothelial basement membrane, or continued into merging      
connective tissue . the capillary endothelium was not fenestrated,. it  
was a continuous cellular membrane . both the epithelium and endothelium
contained numerous caveolae and pinocytotic vesicles . cells of the     
alveolar wall included fibroblasts, lymphocytes, macrophages, and an    
occasional mast cell . very little elastin was observed .               
.I 161
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a sensitive and specific fluorescence assay for tissue serotonin .      
  a sensitive and specific method for the estimation of serotonin in    
biological materials is described . in this method, serotonin is reacted
with ninhydrin to form a product whose fluorescence is eight times more 
intense than the native fluorescence of serotonin in strong acid        
solution . with this method it is possible to measure serotonin in      
organs in which endogenous serotonin had not been previously detected   
and to study the subcellular distribution of this amine in the rat      
pineal and adrenal glands .                                             
.I 162
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effects of ruminal insufflation on cerebral circulation and metabolism  
in the goat .                                                           
  the effects of nitrogen insufflation of the cannulated rumen were     
studied in 10 goats . parameters which were measured included cerebral  
blood flow, mean carotid arterial pressure, pressure in the confluence  
of sinuses, cerebrospinal fluid pressure, blood oxygen and carbon       
dioxide contents, packed cell volume (pcv), and hemoglobin concentration
values for cerebrovascular resistance and cerebral o utilization were 
calculated .                                                            
  increased ruminal pressure had little effect on cerebral blood flow   
and cerebrovascular resistance . cerebral o utilization was decreased   
when the intraruminal pressure was increased . this decrease was caused 
by a reduction in arterial o content and a consequent decrease in       
cerebral arteriovenous o difference . mean arterial, venous sinus, and  
cerebrospinal fluid pressures were increased as the intraruminal        
pressure was increased . increases in pcv and hemoglobin concentration  
were not related to the elevated intraruminal pressure .                
  central nervous system signs in goats with acute ruminal tympany may  
be caused by cerebral hypoxia . the nature of the hypertensive changes  
associated with increased ruminal pressure were demonstrated, but due to
the influence of multiple factors on fluid compartments, no conclusions 
could be made about the mechanism of these pressure responses .         
mechanical factors, however, may be involved .                          
.I 163
.W
a comparison between inhaled dust and the dust recovered from human     
lungs .                                                                 
  experiments on the loss of dust particles during breathing indicate   
total deposition in the respiratory tract,. subjection of the results to
qualitative arguments may give information about alveolar deposition .  
measurements of insoluble dust recovered post mortem from human lungs   
give the absolute retention of dust which was deposited in the alveoli  
and subsequently shifted, probably to a large extent, to the lymphatic  
vessels of the lungs .                                                  
  experimental results for total deposition and absolute retention are  
discussed in connection with the health risk due to inhaling insoluble  
particles, such as plutonium dioxide .                                  
.I 164
.W
dual cation activation of bovine lens autolysis .                       
  the autolytic activity of bovine lens extracts at 55 c. and ph 7.4 has
been shown to be markedly influenced by the simultaneous presence of    
mono- and divalent cations . of the cations tested, na at 2.5 to 5 mm . 
and mg at 5 to 10 mm. produce the best activation . the stimulation is  
synergistic . on the basis of results obtained here and in other        
laboratories, the suggestion is made that this combination of cations   
may be required for activation of the neutral proteinase of the lens .  
in the presence of mg and average physiologic lenticular levels of both 
na and k , autolysis is suppressed to the basal level obtainable in the 
presence of mg alone .                                                  
.I 165
.W
nucleic acid metabolism in the lens iii. effect of x-radiation .        
  a previous communication reported an increased in vivo incorporation  
of p-32 into the albuminoid rna fraction of the rat lens 6 hours after  
the animal had been exposed to x-radiation (1,500 r) .                  
  in the present study, the in vitro uptake of p-32 and c-14-adenine by 
albuminoid, ribosomal, and soluble rna fractions of normal and x-       
irradiated rat lenses was measured . the rna fractions were extracted by
sodium dodecyl sulfate in 0.9 per cent nacl . the specific rna fractions
were also hydrolyzed, chromatographed (on paper), and the activity of   
the individual nucleotides (as well as the specific rna fractions) was  
determined . an experiment was also performed in which the capsules were
removed (after the 3 hour incubation period) and the activities         
determined in the nucleic acids extracted from the capsules and in the  
three rna fractions of the remaining lens matter .                      
  the results of these experiments indicate that the incorporation of   
p-32 and c-14-adenine into albuminoid rna was markedly stimulated 1 hour
after 1,500 r whole body radiation . there was no significant effect on 
ribosomal or soluble fractions .                                        
  the effect of formaldehyde and heating on x-irradiated albuminoid rna 
was much less than on the albuminoid rna derived from control animals . 
.I 166
.W
changes in dna, rna, and protein synthesis in the developing lens .     
  lens cell dna, rna, and protein synthesis in the developing mouse eye 
were studied with the use of tritium-labeled thymidine, uridine, and l- 
leucine and autoradiographic techniques . in the mouse embryonic lens,  
epithelial cells undergoing dna synthesis were found over the entire    
anterior lens surface . from birth and until the eyes opened the        
percentage of epithelial cells undergoing dna synthesis rapidly         
decreased . later the percentage of epithelial cells undergoing dna     
synthesis was nearly constant as the germinative zone became localized  
in the lens equator region . rna synthesis occurred in all nucleated    
cells of the developing lens from the embryonic stage until the eyelids 
opened . with lens maturity the h uridine was incorporated into the rna 
of only the more superficial cells . a similar pattern of tritium       
incorporation was seen with h l-leucine .                               
.I 167
.W
amino acid transport in the lens in relation to sugar cataracts .       
  the steady state distribution of free amino acids between the lens and
aqueous humor is significantly reduced in diabetic rabbits and also in  
rats fed rations containing high concentrations of xylose or galactose .
  the reduction in the level of amino acids in the lens is apparently a 
direct effect of the high concentration of sugars, but it is doubtful   
whether it is related to cataract formation .                           
.I 168
.W
visco-elastic properties of the lens .                                  
  the dynamic visco-elastic properties of human, monkey and rabbit      
lenses have been measured with a dynamic rheometer . the value for the  
apparent elastic modulus (young modulus) of the lens was found to be 10 
-10 dyne/cm in humans and 10 -10 dyne/cm in monkeys and rabbits . the   
value for the loss tangent was 0.3-0.4 in the human lens and 0.3-0.6 in 
rabbit and monkey lenses .                                              
  elastic moduli and loss tangents of the lenses showed poor dependence 
on temperature at 15 -55 c and on frequency of oscillation at 0.01-25 c/
s . the lenses showed linear visco-elasticity when the amplitude of     
oscillation was below 0.02 mm, and they showed nonlinear visco-         
elasticity when the amplitude exceeded 0.03 mm .                        
.I 169
.W
carbonic anhydrase distribution in rabbit lens .                        
  the distribution of carbonic anhydrase activity in the mature rabbit  
lens was determined . the activities in nucleus, cortex, epithelium with
anterior capsule, anterior capsule, and posterior capsule were,         
respectively, 2484 ( 256), 1571 ( 87), 545 ( 93), 159 ( 39) and 65 ( 49)
moles co /kg wet tissue wt per hr at 0 c . it was concluded, on the     
basis of the available evidence, that carbonic anhydrase cannot play a  
primary role in the cation transport system of the lens .               
.I 170
.W
changes in weight and adenosine triphosphate content in the lens of the 
xylose-fed rat .                                                        
  xylitol and sorbitol accumulated in the lens of the xylose-fed rat two
days before loss of adenosine triphosphate, and cataractous changes,    
were apparent . the maximum degree of cataract occurred when the level  
of the polyols was at its highest . regression of cataract was          
accompanied by decrease in polyol concentration and restoration of the  
level of atp . the lens of the xylose-fed rat did not usually increase  
in weight .                                                             
.I 171
.W
identification of species-specific and organ-specific antigens in lens  
proteins .                                                              
  the species-specific and organ-specific antigens of lens were         
investigated by gel diffusion and immunoelectrophoresis techniques . it 
was found that rabbit antiserum to bovine lens showed cross reaction    
with other bovine tissues . these cross-reacting antigens were the b- - 
and y-crystallins . there were two major and a minor organ-specific     
antigen in lens . both the major antigens had a mobility and were       
identified as the a-crystallin of lens .                                
.I 172
.W
an electron microscopic study of wolffian lens regeneration in the adult
newt .                                                                  
  changes in the morphology of cells during the regenerative tissue     
transformation of the pigmented epithelium of the iris into lens in the 
adult newt triturus viridescens were studied in ultrathin sections using
the electron microscope . in addition, quantitative analyses with       
electron micrographs were performed . the cells of the normal iris are  
characterized by an abundance of melanin granules, an extensive smooth--
surfaced endoplasmic reticulum, and irregular indentations of the       
nuclear membrane . after lens removal, the first visible changes are    
detected in nuclei of the mediodorsal iris cells and involve an increase
in the number of primary nucleoli . later, the nuclei enlarge and become
spherical, and prominent nucleoli appear . these nucleoli can be        
distinguished from the normal nucleoli by the presence of the granular  
cortex surrounding the fibrous core . the pigment granules seem to be   
completely extruded into the intercellular spaces and subsequently taken
up by leucocytes . the endoplasmic reticulum disintegrates gradually and
finally almost disappears . there is a significant increase of ribosomes
in the cytoplasm . later, the cytoplasmic matrix also acquires fibrous  
elements (about 50 a wide) of low density, probably corresponding in    
nature to the main components of a normal lens cell . these and other   
changes in the transforming cells are discussed .                       
.I 173
.W
growth of several human cell lines in newborn rats .                    
  when injected intravenously into newborn rats, eight human            
tissue-cultured cancer cell lines -dash h.ep. 2, detroit 6, j-111, rp   
41, rp 212, adeno cx 1, ovary 2, and mac 21 -dash grew progressively in 
lung and other organs of more than 50 per cent of the animals and       
commonly caused death after 5-8 weeks . two other human cell lines -dash
the carcinoma h.ep. 1 and the presumably normal amnion b -dash grew less
frequently and rarely caused death or illness .                         
.I 174
.W
the human tumor-egg host system iii. tumor-inhibitory properties of     
tenuazonic acid .                                                       
  the fermented broth of a culture of alternaria tenuis auct. inhibited 
the growth of the human adenocarcinoma (h.ad. 1) in the embryonated egg 
with the aid of studies in the egg-tumor system the active agent was  
isolated and identified as tenuazonic acid . tenuazonic acid was        
produced by a number of alternaria isolates and by an aspergillustamarii
and a phoma sp . compared with tenuazonic acid, on a molar basis, about 
20 times as much hadacidin or 6-mercaptopurine, 2 times as much         
azaserine, but only 1/20 as much triethylenemelamine (tem) were required
to achieve the same inhibition of h.ad. 1 tumor growth in the egg .     
tenuazonic acid was more effective against h.ad. 1 than against another 
transplantable human tumor, a-42 . tenuazonic acid, compared with       
puromycin, more specifically inhibited tumor growth in the egg-tumor    
system .                                                                
.I 175
.W
the occurrence of biologic crystals in tumor and nontumor cultures of   
c3h/hej mice .                                                          
  crystalline structures of various types have been found in primary    
tissue cultures of neoplastic and non-neoplastic tissues from c3h/hej   
mice . all of the cultures of mammary carcinoma tissue contained the    
crystals . the crystals were found in varying incidence in the cultures 
of several other tissues with the exception of those from the kidney . a
'dialysis compartment' was not essential for the formation of the       
crystals . the development of the crystals was accelerated by a         
modification of the culture medium .                                    
.I 176
.W
a comparison of the fine structure of cultured mac-21 and hela cell .   
  the fine structure of a cultured mucoid adenocarcinoma cell of human  
lung (mac-21) is described and compared with the fine structure of the  
hela cell . the differences in fine structure between the two strains   
are primarily quantitative . the mac-21 cell differed, however, in the  
following respects.. a spindle-shaped cell with larger nucleus and      
increased nuclear membrane invaginations, and considerably larger       
amounts of perinuclear golgi apparatus . the cytoplasm contained areas  
of low density, undefined by a limiting membrane, which are thought to  
be accumulations of mucin .                                             
  the two cell strains contained numerous multivesicular bodies, some   
with lamellae in various stages of development, suggesting that these   
organelles may be involved in the formation of the lipide-rich,         
myelinated structures observed in both hela and mac-21 cells . the      
number of myelinated bodies was found to be inversely proportional to   
the ph of the medium .                                                  
.I 177
.W
effect of parathyroid and other human tumors and tissues on bone        
resorption in tissue culture .                                          
  mouse calvaria were grown in tissue culture in combination with single
or multiple fragments of a variety of human tumors and glandular tissues
to determine their capacity to enhance bone resorption . single         
fragments of parathyroid adenoma tissue consistently enhanced resorption
in both the frontal and the parietal bones . except for one squamous--  
cell carcinoma of the lung which had some activity all other tissues    
tested as single fragments had no enhancing effect . on the other hand, 
all human tissues enhanced resorption when multiple fragments were      
placed in a halo around the calvarium, suggesting the presence of lesser
amounts of resorption-enhancing factors in other human tissues .        
.I 178
.W
limited growth period of human lung cell lines transformed by simian    
virus 40 .                                                              
  summary--infection of human cell strains with simian virus 40 induced 
virus replication and cell transformation with the changes in morphology
and cytology described by previous investigators . although             
transformation greatly enhanced growth potentials of the strains, only 2
of 23 transformed cultures appear to have attained autonomous growth.--j
nat cancer inst 33.. 227-236, 1964 .                                    
.I 179
.W
bacteriophages that lyse mycobacteria and corynebacteria, and show      
cytopathogenic effect on tissue cultures of renal cells of cercopithecus
aethiops.. a preliminary communication .                                
  bacteriophages isolated from sputum and resection specimens of pa-    
tients suffering from carcinoma of the lung were found to lyse coryne-  
bacteria and mycobacteria, and to produce a cytopathogenic effect on    
certain cells in tissue cultures . from the same and other patients with
neoplastic disease, bacteria were isolated and described as coryne-my-  
cobacteria because of bacteriological features they shared with both    
species . these bacteria, which either were sensitive to mycobacterio-  
phages and corynebacteriophages or were phage-immune lysogenic bacteria,
could be induced to produce lytic particles with phagolytic activity on 
corynebacteria and mycobacteria and a cytopathogenic effect on hela     
cells and on the renal cells of cercopithecus .                         
.I 180
.W
gel filtration of the soluble proteins from normal and cataractous human
lenses .                                                                
  the soluble proteins of normal and cataractous lenses were separated  
according to their molecular size on the polysaccharide gel sephadex    
g-100 . in cataractous as well as in normal lenses 4 different compo-   
nents were obtained . during the evolution of cataract there is a pre-  
ferential decrease of the low molecular weight proteins of the lens .   
these disappeared completely in mature and hypermature cataract . on the
other hand, the proteins of high molecular weight (e.g., -crystallin)   
are very resistant to the pathological process . the electrophoretic    
pattern of the low molecular weight proteins in the normal lens revea-  
led several fractions distributed over a large mobility area . after    
immunoelectrophoresis, 3 different precipitin lines were obtained .     
.I 181
.W
the insoluble proteins of bovine crystalline lens .                     
  the insoluble lens proteins, the albuminoids, of the adult bovine lens
cortex can be rendered soluble by raising the ph of their washed        
suspension in 0.9 nacl to 10.5 and then reducing it again to ph 7.4 .   
the sedimentation constant of the dissolved protein is 10.8 s,. its     
molecular weight is estimated to be 360,000 12,000 . the amino acid     
composition is approximately the same as that of the soluble -crysta-   
llin fraction, a kinship which is also apparent from their immunochemi- 
cal properties . it is suggested that the initial insoluble protein is a
molecular aggregate of -crystallin, which is dissociated in alkaline    
solutions to molecules exhibiting a sedimentation constant of 10.8 s .  
.I 182
.W
glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase  
in lens and blood of different species .                                
  the activities of glucose 6-phosphate and 6-phosphogluconate dehydro- 
genase were measured in the lens and erythrocytes of man and several    
other species . there is a wide variation between individuals of the    
same species, but there seemed no correlation between the activity of   
either enzyme in the lens and their activity in the erythrocytes of the 
same species . there is a wide range of activity of both glucose 6-phos-
phate dehydrogenase and 6-phosphogluconate dehydrogenase in the lens and
in the blood of different species . several species had glucose 6-phos- 
phate dehydrogenase activity in erythrocytes below the level considered 
/deficient/ in man . the sorbitol content of the lens was not correla-  
ted with glucose 6-phosphate dehydrogenase activity .                   
.I 183
.W
nucleic acid metabolism in the lens iii. effect of x-radiation .        
  a previous communication reported an increased in vivo incorporation  
of p-32 into the albuminoid rna fraction of the rat lens 6 hours after  
the animal had been exposed to x-radiation (1,500 r) .                  
  in the present stody, the in vitro uptake of p-32 and c-14-adenine by 
albuminoid, ribosomal, and soluble rna fractions of normal and          
x-irradiated rat lenses was measured . the rna fractions were extracted 
by sodium dodecyl sulfate in 0.9 per cent nacl . the specific rna       
fractions were also hydrolyzed, chromatographed (on paper), and the ac- 
tivity of the individual nucleotides (as well as the specific rna frac- 
tions) was determined . an experiment was also performed in which the   
capsules were removed (after the 3 hour incubation period) and the      
activities determined in the nucleic acids extracted from the capsules  
and in the three rna fractions of the remaining lens matter .           
  the results of these experiments indicate that the incorporation of   
p-32 and c-14-adenine into albuminoid rna was markedly stimulated 1 hour
after 1,500 r whole body radiation . there was no significant effect on 
ribosomal or soluble fractions .                                        
  the effect of formaldehyde and heating on x-irradiated albuminoid rna 
was much less than on the albuminoid rna derived from control animals . 
.I 184
.W
an investigation of mitotic control in the rabbit lens epithelium .     
  a water soluble substance which inhibits mitosis in the rabbit lens   
epithelium has been found to be present in young and old rabbit lenses .
it has a high molecular weight and is relatively stable at room tempera-
ture . the inhibitory factor is associated with the y-crystallin frac-  
tion and exists throughout the young lens, although the activity in the 
nuclear region (on a wet weight basis) is less than half that of the    
cortex and epithelium .                                                 
.I 185
.W
the identification of lysosomal enzymes in bovine lens epithelium .     
  biochemical studies are described for the isolation of lysosomes      
(identified as such by the activities of their enzymes) in the cells of 
the bovine lens epithelium . the various fractions assayed for lysosomal
enzymes showed contamination of mitochondrial and soluble cytoplasmic   
material in the two isolation procedures employed .                     
.I 186
.W
protein synthesis and polyribosomes in the calf lens .                  
  a cell-free system capable of incorporating amino acid into protein   
has been isolated from calf lens . polyribosomes have been shown to be  
present in the ribosomal fraction and to be responsible for most of the 
protein-synthesizing capacity of this fraction . the polyribosomes have 
been examined by electron microscopy and appear to be composed of long  
strands of ribonucleic acid, ranging from 7,000 a to 20,000 a, and con- 
taining a large number of ribosomes with an average diameter of about   
140 a .                                                                 
.I 187
.W
measurement of oxygen tensions in cerebral tissues of rats exposed to   
high pressures of oxygen .                                              
  brain and cerebrospinal oxygen tensions have been measured in rats    
breathing air or in various high pressures of oxygen (ohp) . addition of
5 percent co2 to the inspired oxygen raised cerebral oxygen tensions    
when rats were exposed to 2 atm abs or above . inhibition of 75         
hemoglobin saturation by para-aminopropriophenone lowered cerebral po in
rats breathing air, but not in rats exposed to ohp . the rate of rise of
cerebral po to a steady level after rapid compression was found to be   
faster than the rate of fall to a steady level following decompression .
addition of co to the inspired gas mixture increased the rate of rise of
cerebral po . the anesthetics urethane and pentobarbital sodium did not 
affect cerebral po in rats breathing air or oxygen at 4 atm . the       
results are discussed in relation to factors contributing to oxygen     
poisoning at high pressures .                                           
.I 188
.W
release of free fatty acids from adipose tissue obtained from newborn   
infants .                                                               
  summary the role played by mobilization of free fatty acids (ffa) from
adipose tissue in producing the typically high serum ffa levels of human
infants has been studied . ffa concentrations in the serum and subcuta- 
neous adipose tissue from the gluteal region were determined during     
postnatal development . a maximum level was reached within 24 hr after  
birth, after which there was a gradual fall . in serum the ffa level at 
the end of 12 months was still higher than that in adults, while the ffa
level in adipose tissue was lower at 3 months than in adults .          
  incubation of small pieces of adipose tissue in krebs-ringer phosphate
buffer containing 4 albumin led to release of ffa into the medium . this
release could be suppressed by the addition of glucose (200 mg/100 ml)  
for tissue from all age groups except the youngest (0-15 hr after birth)
.I 189
.W
detection of pericardial effusion by radioisotope heart scanning .      
  a marked difference between the cardiac silhouette on the six-foot    
chest roentgenogram and the cardiac blood pool, determined by radioiso- 
tope scanning, has been shown to be consistent with pericardial effusion
and/or thickening . it has also been observed that the cardiac blood    
pool is separated from the liver margin by the interposition of peri-   
cardial fluid and/or thickening . this separation was not demonstrated  
in the presence of a normal pericardium . to appreciate these features, 
400 c. of radioiodinated human serum albumin and 50 c. of colloidal     
radiogold were used for scanning . the former outlined the blood pool   
and the latter demonstrated the position of the liver .                 
.I 190
.W
on the mechanism of erythropoietin-induced differentiation iv. some     
characteristics of erythropoietin action on hemoglobin synthesis in     
marrow cell culture .                                                   
  some of the characteristics of the erythropoietin stimulation of hemo-
globin synthesis by rat marrow cells in culture have been studied . the 
relationship between cell number and rate of hemoglobin synthesis at va-
rious levels of erythropoietin is sigmoid rather than linear suggesting 
a cooperative action among the sensitive cells . the magnitude of the   
erythropoietin effect on the cells increases with time of contact with  
the hormone,. at the time of one-half maximal effect there is no discer-
nible loss of erythropoietin from the culture medium . a previously des-
cribed lag time in the response to erythropoietin appears to be largely 
due to the conditions of culture and disappears when the cells are pre--
incubated for 9 h . replacement of a large fraction of the medium at    
24-h intervals enabled the cells to continue hemoglobin synthesis for an
additional 24 h .                                                       
.I 191
.W
the occurrence of megakaryocytes in the peripheral blood of dogs .      
  a study of megakaryocytes in buffy coat smears from 26 dogs revealed  
that no unusual characteristics were consistently associated with appea-
rance of megakaryocytes in the peripheral blood .                       
.I 192
.W
moderate hypothermia in man.. haemodynamic and metabolic effects .      
  studies were performed on four patients undergoing intracranial opera-
tion during the induction and reversal of surface hypothermia to 30 c . 
oxygen uptake decreased an average of 26 per cent from 34 to 30 c to a  
mean value of 48 per cent of predicted basal uptake . at the same time, 
cardiac output decreased only 11.5 per cent, resulting in a consistent  
rise in calculated mixed venous oxygen saturation from a mean of 76 to  
81 per cent at 30 c . as a result of this and the effect of cooling on  
oxygen dissociation, the estimated tension of oxygen in mixed venous    
blood remained virtually unchanged . when shivering was allowed to occur
in two patients, oxygen uptake increased approximately 50 per cent      
without any concomitant increase in cardiac output . observed right     
atrial and svc oxygen saturations correlated well with calculated mixed 
venous oxygen saturations with regard to direction and magnitude of     
change with change in temperature .                                     
.I 193
.W
the spectrum of lupus nephritis .                                       
  fifty cases of sle have been collected over a ten year period and the 
incidence and clinical picture of ln reviewed in the light of other     
published data .                                                        
  lupus nephritis, like sle, has a variable pattern of its own with a   
wide spectrum of renal involvement -dash evaluation of therapy and      
prognosis will have to be conducted against this background .           
  lupus nephritis may present as a renal syndrome only, without any of  
the other manifestations of sle .                                       
  renal involvement in sle is common, but this does not necessarily     
indicate a poor short-term prognosis . in the peter bent brigham        
hospital series a sustained raised blood pressure and the onset of renal
insufficiency influenced the prognosis adversely .                      
.I 194
.W
comparison of ultraviolet sensitivity of bacillus subtilis bacteriophage
spo2 and its infectious dna .                                           
  deoxyribonucleic acid extracted from a clear plaque mutant of the     
temperate phage, spo2, was infectious when incubated with competent     
cultures of bacillus subtilis 168 m . the relationship between numbers  
of infectious centers and dna concentration was linear .                
  the sensitivity of the infectious dna to ultraviolet light was much   
greater than that of the free phage when b. subtilis 168 m was used as  
host . acriflavin, which inhibits host cell reactivation, increased the 
rate of ultraviolet inactivation of the free phage so that it approached
the inactivation rate of the phage dna . acriflavin had little effect on
the survival curves of the infectious dna .                             
  non-host reactivating mutants (hcr ) of b. subtilis 168 m were        
isolated . the survival curves of spo2 phage were much steeper when the 
hcr mutant was used as a host than those obtained when the hcr parental 
strain was used as a host .                                             
  ultraviolet sensitivity of the phage dna was still greater than that  
of the free phage even when b. subtilis hcr was used as host, but the   
difference in sensitivity was much less than the difference obtained    
with b. subtilis hcr as a host .                                        
  possible explanations for the greater ultraviolet sensitivity of the  
infectious dna are discussed .                                          
.I 195
.W
the isolation and morphology of some new bacteriophages specific for    
bacillus and acetobacter species .                                      
  the best natural habitat for bacteriophages is probably a semi-solid  
medium containing actively dividing host bacteria . such conditions are 
provided for bacillus and acetobacter species in rotting grass and      
apples, respectively . the bacillus phages found included one with a    
large head and a contractile tail, and also a so-called killer particle,
which had a 350 a head and a long contractile tail . this particle had  
the property of killing but not multiplying within a sensitive cell . a 
new morphological type of virulent bacillus phage was also isolated,.   
its head was oblong and the tail consisted of a short needle and a plate
the one acetobacter phage found resembled coliphage t3 but was of     
particular interest because of the prominence of the head capsomeres and
the three-pronged tail .                                                
.I 196
.W
characterization of bacillus subtilis bacteriophages .                  
  brodetsky, anna m. (university of california, los angeles), and w. r. 
romig . characterization of bacillus subtilis bacteriophages . j.       
bacteriol. 90..1655-1663. 1965.--a group of six phages, sp5, sp6, sp7,  
sp8, sp9, and sp13, which use the marburg strain of bacillus subtilis as
host was characterized . these phages, referred to as group 1, were     
examined for the following properties.. host range, plaque morphology,  
stability, adsorption kinetics, one-step growth characteristics, calcium
requirements, serum neutralization, thermal inactivation, and           
inactivation by ultraviolet irradiation . five unrelated b. subtilis    
phages, sp3, sp10, pbs1, sp alpha, and sp beta, were included in the    
studies . when first isolated, none of the group 1 phages was able to   
replicate efficiently on b. subtilis sb19, a mutant of the /transforming
/ b. subtilis 168 . host range mutants capable of growth in sb19 were   
isolated for all of the group 1 phages except sp13, and are designated  
the /star/ phages (sp5 through sp9 ) . for characterization, sb19 was   
used as host for the star phages, and another b. subtilis mutant, 168b, 
was host for sp13 .                                                     
.I 197
.W
transduction in bacillus subtilis .                                     
  (i) comparative examinations have shown that the temperate subtilis   
phages can be divided into two groups . b. subtilis strain nrs 231 was  
an adequate common host sensitive to all the examined temperate phages .
  owing to certain technical advantages this strain was found suitable  
for the titration subtilis phages .                                     
  (ii) some cultural differences have been revealed among substrains of 
b. subtilis 168 ind auxotrophs maintained in various laboratories .     
cells in one of these cultures were partly capable and partly incapable 
of using ammonia . ammonia assimilation was transducible to ammonia     
negative bacteria .                                                     
  (iii) after mitomycin c or ultraviolet ray induction the examined b.  
subtilis strains liberated /bacteriocin/-like principles . this finding 
is probably analogous to that of seaman et al. concerning pbsx defective
phages . on the basis of bacteriocin production the examined strains    
were divided into two groups .                                          
  (iv) several temperate phages isolated in our laboratory were         
presumably identical with phage pbs 1 . phage sp 10 differed from these 
agents both in antigenic structure and in host range .                  
  (v) transduction by some lysates of pbs 1-type phages was observed at 
frequencies of the order of 10 . considerably more and less effective   
phage materials were yielded by some lysogenic transductants . thus     
transducing phages active in the order of 10 were prepared .            
  (vi) transduction frequency, in addition to the properties of the     
phage, was influenced by the physiological condition of bacteria .      
  (vii) transduction of indole and histidine loci was studied by use of 
his derivatives of strain 168 ind .                                     
.I 198
.W
the carrier state of bacillus subtilis infected with the transducing    
bacteriophage sp10 .                                                    
  bacteriophage sp10 may infect bacillus subtilis to form a carrier     
system . the infected bacteria give rise to infected organisms after six
or more successive single-colony isolations . about 60 of the spores    
derived from such an infected culture yield clones that produce phage,  
and such spores retain their ability to produce phage even after        
treatment with antiserum and heating at 80 . four hours' incubation of  
carrier spores in nutrient broth yields cultures having more than 10    
infective centers per bacterium . cultivation of infected organisms in  
medium containing sp10 antiserum leads to loss of phage and loss of     
immunity to phage infection . dna with a density characteristic of viral
dna can be detected in infected bacteria . extracts of infected bacteria
contain a phage-induced deoxyribonuclease activity which attacks both   
phage and bacterial dna in vitro . the phage-bacterial complex is       
therefore best described as a carrier state .                           
  the dna of the phage and of b. subtilis are chemically different .    
enzymatically prepared complementary virus rna has no homology with     
bacterial dna . the lack of homology of this transducing phage dna with 
the dna of its host and the failure to form a truly lysogenic           
relationship reinforce previous conclusions that transducing bacterial  
dna is incorporated into the sp10 virus particle without any            
recombination between viral and bacterial dna .                         
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infectivity of dna isolated from bacillus subtilis bacteriophage, sp82 .
  sp82, a newly isolated bacteriophage of bacillus subtilis, is         
described . sp82 is closely related to sp8, but differs from sp8 in the 
density of its denatured dna and in its plating effciency on b. subtilis
strain sb-1 .                                                           
  dna isolated from this phage can be recovered in molecular weight     
equivalent to the amount contained in a single phage (approximately 130 
x 10 daltons) . dna of this molecular weight, but not half pieces, is   
infective in competent b. subtilis . the response of plaque-forming     
ability to dna concentration suggests that four whole molecules are     
required to initiate an infective center . recombination studies with   
mixed dna's of two non-allelic temperature-sensitive mutants confirm the
existence of an obligatory co-operative infective process . a second    
infective procedure that utilizes extracted phage dna is described . in 
this system, low concentrations of wild-type dna are exposed to the     
cells . at these concentrations the multiple-event nature of phage dna  
infection precludes the formation of unaided plaques . however, by      
subsequently superinfecting the dna-infected cells with a               
temperature-sensitive mutant and plating under selective conditions,    
genetic rescue of the infecting dna is accomplished and detected .      
infective centers elicited by this /marker rescue/ phenomenon are       
directly proportional to dna concentration . the time of attainment of  
dnase resistance by phage dna infective centers that have irreversibly  
adsorbed dna can be measured . phage dna infective centers require at   
least 13 minutes to become totally dnase resistant . the reasons for the
failure of single phage dna molecules to carry out an infection are     
discussed in terms of a specific breakage-reunion                       
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psychology of children's dental treatment .                             
  the communication deals with influences involved in the development of
the child's attitude to dental treatment . they are extrinsic           
(educational etc.) and intrinsic (constitutional and hereditary) . their
understanding helps to determine the correct psychological policy for   
the management of the child in the surgery .                            
  the aim of psychology applied in dentistry is to discover a mode of   
treatment procedure which would ensure that the child will not be       
subject to any psychic traumatization (psychophylaxis) . its second aim 
is the management of the so called difficult child and his treatment .  
  to understand better the child's frame of mind during dental treatment
the situation in the surgery is dealt with step by step as the child    
experiences it through his senses and his psyche . beside the basic     
senses -dash hearing and seeing -dash others are also affected.. touch  
(pressure sensation), smell and taste .                                 
  children during dental treatment are nearly always in a state of      
raised emotional tension and are susceptible to anxiety reactions .     
according to the degree of fear which they manifest children may be     
classed into categories of cooperating and difficult patients . the     
psychological procedure for the treatment of children of both groups is 
based on the principles summarized in the section 'psychophylaxis in    
dentistry' . in difficult children it is often necessary to employ yet  
other psychological measures-psychotherapy, suggestion etc . in         
extremely exacting cases premedication helps sometimes to find contact  
with the child .                                                        
  the experimental part of the work demonstrates the following findings 
 1. dental treatment consists of a series of interdependent           
traumatizing impulses . many of them appear only after a close analysis 
of the situation . 2. the adverse response similar to that elicited by  
pain may be due also to sensory impressions with a negative emotional   
background . 3. psychic traumatization of the child during dental       
treatment can be prevented by relatively simple psychological measures .
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relation of emotional changes during pregnancy to obstetric             
complications in unmarried primigravidas .                              
  this study was designed to assess the psychological changes           
experienced by white unmarried primigravidas during pregnancy, the      
relationship between manifest anxiety and clinical factors such as labor
time and mean birth weight, and the personality differences between     
/normal/ and /abnormal/ obstetric cases . the kent egy intelligence     
scale, the taylor manifest anxiety scale, and the mmpi were administered
to 160 obstetric patients at the beginning of the third trimester of    
pregnancy, with the mmpi and taylor being readministered post partum .  
reliable group personality changes observed from pre- to postdelivery   
supported the contention that pregnancy is a time of emotional upset .  
  following delivery, each patient was classified as normal or abnormal 
dependent on the clinical course of parturition, delivery, and condition
of the offspring . there were no significant differences between these  
groups with respect to age or intelligence . reliable differences were  
found, however, for manifest anxiety and total labor times . in         
addition, a positive relationship was found between manifest anxiety and
birth weights . personality differences found at predelivery between the
subgroups were largely attributable to the abnormal group's greater     
neuroticism, anxiety, and use of the ruminative ego defenses .          
  post partum, the personality characteristics of the subgroups were    
quite similar . both groups showed greater personality stability        
following delivery, with the most striking changes from predelivery     
demonstrable in the abnormal group . the magnitude of these changes were
interpreted as emotional lability and related to obstetric complications
by activation of various physiological regulator systems .              
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stranger and separation anxiety in infancy .                            
  anxiety responses to strangers and to separations from mother were    
studied longitudinally in 19 infants between the ages of three and 23   
months by direct observations and by interviews with the mother .       
benjamin's hypotheses concerning the differentiation and immediate      
dynamics of infantile stranger and separation anxiety were supported by 
the findings . differences in onset, period of highest intensity,       
termination, and ratios in individuals were found between the two       
anxieties . tests of the relationship between the two anxieties were    
supportive of deductive predictions made by benjamin . sex differences  
in intensity of the two anxieties were found .                          
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mental retardation related to hypercalcaemia .                          
  for more than 20 years a number of retarded children and adolescents  
have been observed who show points of striking similarity . we recognise
in them a well-defined type that is clearly distinguishable from other  
forms of mental deficiency . they are therefore described in detail .   
some of the children have had infantile hypercalcaemia but it is assumed
that other aetiological factors are also involved .                     
  there is a characteristic facies and usually congenital heart disease 
ordination is poor . there is a constant failure to thrive in infancy,
with episodes of vomiting, often with constipation . mentally the       
children also show great similarities . their iq is about 40-50 but they
show outstanding loquacity and a great ability to establish interper-   
sonal contacts . this stands against a background of insecurity and     
anxiety .                                                               
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psychological effects of circumcision .                                 
  in order to evaluate the psychological effects of circumcision, a     
small study was arranged in which twelve children, from average and low 
socio-economic level, were given goodenough dam test, cat, rorschach and
two sets of stories, prior to the operation and following it . the      
results of the tests showed that circumcision, performed around the     
phallic stage is perceived by the child as an act of aggression and     
castration . it has detrimental effects on the child's functioning and  
adaptation, particularly on his ego strength . by weakening the         
controlling and defensive mechanisms of the ego, and initiating         
regression, it loosens the previously hidden fears, anxieties, and      
instinctual impulses, and renders a feeling of reality to them . what is
expressed following the operation is primitive, archaic, and            
unsocialized in character . as a defensive control and protection       
against the surge of the instinctual forces coming from within and the  
threats coming from outside, the ego of the child seeks safety in total 
withdrawal, thus isolates and insulates itself from disturbing stimuli .
  the results of the study raised some questions concerning certain     
psychoanalytic formulations, for which further research was suggested . 
possibilities for future research were also discussed .                 
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changes in children's behavior after hospitalization some dimensions of 
response and their correlates .                                         
  changes in 387 children's behavior following hospitalization were     
evaluated by means of a questionnaire sent to parents a week after      
discharge . factor analyses revealed that children's responses to       
hospitalization and illness were of six types.. (i) general anxiety and 
regression, (ii) separation anxiety, (iii) anxiety about sleep, (iv)    
eating disturbance, (v) aggression toward authority, and (vi)           
apathy-withdrawal . scores for these six factors (types of responses) as
well as a total score, were analyzed by univariate and, in most cases,  
multivariate analyses of variance . four variables -dash sex, prior     
hospitalization, degree of pain experienced during hospitalization, and 
birth order -dash were essentially unrelated to any type of response by 
any analysis . age, duration of hospitalization, and occupational status
were each significantly related to one or more types of responses .     
comparison of the mean factor and total scores for the full sample with 
the levels indicative of no overall change indicated that the           
combination of illness and hospitalization is a psychologically         
upsetting experience for children in general, resulting in increased    
separation anxiety, increased sleep anxiety, and increased aggression   
toward authority .                                                      
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isozymes of lactic dehydrogenase.. sequential alterations during        
development .                                                           
  applications of isozymes in various biological contexts have been     
reviewed . diagnosis of several disease states has been facilitated by  
examination of the serum isozyme pattern which has been shown to        
correlate in some conditions with the isozyme pattern of pathologically 
involved tissues . physico-chemical studies of human ldh isozymes have  
revealed differences among isozymes in affinity for a given substrate . 
comparative studies of ldh isozymes within the erythrocyte from various 
vertebrate species demonstrated a marked species variation in the number
of ldh isozymes, in the distribution of total ldh activity among them,  
and in their electrophoretic mobilities . during development of chick,  
rabbit, and human tissues characteristic sequential alterations in the  
ldh isozyme pattern occurred and consisted for liver and muscle in loss 
of the most rapidly migrating anodal bands and increased activity in the
cathodal bands and slower migrating anodal bands . in heart the reverse 
changes were observed . if high enough ldh activities of early fetal    
tissue extracts were applied to the gel the full complement of ldh      
isozymes was observed,. however, in lower concentrations the cathodal   
bands, which in the starch gel disappear more rapidly on dilution than  
do the anodal bands, were not observed . a species-specific isozyme     
pattern is obtained in long term culture of rabbit, chick, and human    
cells . independently of the tissue of origin, there occurs in cells in 
culture a sequential series of isozyme alterations characterized by     
decreased intensity of rapidly migrating anodal bands . the shift toward
prominence of cathodal isozymes during both fetal development and tissue
culture can be explained by postulating the increased activity of the   
gene producing one of the subunits of ldh with a concomitant decrease in
the activity of the gene producing the second subunit . practical       
applications of the study of isozymes in tissue culture were discussed .
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establishment of a cell line in vitro from a case of human lung cancer .
  1) one cell line has been established from the pneumonectomized       
specimen of a case with lung cancer, which was diagnosed as             
undifferentiated cell carcinoma and partially adenocarcinoma by its     
histological findings and was characterized with intracytoplasmic fat   
droplets in them .                                                      
  2) the morphological changes of the cells were repeated but they have 
been stabilized to their epithelial shapes after the 35th transfer . the
cell atypy of the culture was remarkable . phagocytosis of the cell line
has not been observed . it was characterized that the intracytoplasmic  
droplets found in the original cancer cells have been maintained in the 
cultured cells, even in their mitotic stage, throughout the cultural    
course .                                                                
  3) concerning the chromosomal constitution diploid cells were only 15 
per cent . the range of chromosome number did not show sharp peak,      
forming two groups of near diploid and near tetraploid ranges .         
  4) transplanting the cell to cheekpouches of golden hamsters, the     
implanted cells grew from the inoculum of 10 cells in conditioned animal
but did not show the invasiveness to neighbour tissue and metastasis to 
other organs .                                                          
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factors influencing development of tumors in frogs .                    
  (1) study of 75 spontaneous tumors of vermont frogs showed three      
pathological grades of malignancy present.. aggressive renal            
adenocarcinoma in some 30 per cent, medium adenocarcinoma in 50 per     
cent, and lower grade mixed with tumors of undetermined origin in the   
remaining 20 per cent .                                                 
  (2) correlation with parasite infections (trematodes) was demonstrable
in only few cases in the kidney . hyperplasias and neoplasias grading   
into lung primary carcinoma have been found in the lung in r. pipiens . 
temperatures below 15 c. protected animals from lung as well as kidney  
disease . higher temperatures disturbed the host-parasite relationships 
and led to higher incidence of malignancy . in the bullfrog, precancer  
was clearly associated with the worm attachment discs .                 
  (3) other histological types of tumors in vermont frogs included      
lymphosarcomas, liposarcoma, mesothelioma, epithelioma, and adrenal and 
cartilage tumors of uncertain malignancy .                              
  (4) improved methods of obtaining tumor filtrates allowed greater     
probability of inducing malignancy with direct renal injection . in 106 
frogs 37 per cent developed histologically provable cancers in the      
ranges of three to seven months . twenty-six per cent showed some       
pre-cancer response and 43 per cent were negative . within the series   
receiving filtrate from high malignancy donors one group yielded 100 per
cent positive, the others 50 and 38 per cent, respectively .            
  (5) among animals injected with /low/ malignancy filtrate, fewer      
tumors resulted . some of these were clearly vesicular carcinomas and   
could be classed as lung tumors .                                       
  (6) improved tissue culture methods allowed explants to live in liquid
media under perforated cellophane up to one year . slower growth, aided 
by lower temperatures (16 c.) improved the microecology of cell types   
and allowed detailed daily observations of each cell's intranuclear and 
intranucleolar physiology for extended time-lapse cine-photography .    
  (7) mechanisms for malignant transformation are related to increased  
activity and production of nucleolar dna and rna . the infective dna    
hypothesis is not classical virus theory, but it does offer detailed    
support .                                                               
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mitotic lymphocytes in primary tissue cultures of normal and neoplastic 
human lung .                                                            
  normal and tumor tissue explants from 33 resected human lungs were    
studied in vitro . lymphocyte mitoses were observed in tissue cultures  
derived from 12 of the lungs . the ability of lymphocytes to undergo    
mitotic division in human lung tissue culture has not been reported     
previously . in the autologous systems used lymphocyte mitoses were much
more common in cellular outgrowths derived from non-neoplastic tissue   
than they were in the outgrowths derived from cancer-bearing explants . 
no differences were observed in the total number of nondividing         
lymphocytes present in the non-neoplastic and neoplastic preparations . 
the in ritro systems employed are promising tools for further           
contributions to an already well established clinicopathologic          
relationship between lymphocytes and cancer cells .                     
  phase contrast and time-lapse cinephotomicrographic records were      
obtained of the mitotic process and special attention was paid to the   
structural details . certain findings were of particular interest,      
namely the formation of a dense chromatin ring during telophase, the    
variable occurrence of cytoplasmic bubbling, and the death of           
lymphocytes during early metaphase (/exploding/ metaphase) . an         
elaboration and discussion of these findings have been presented .      
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studies on transformation of syrian hamster cells by simian virus 40    
(sv40).. acquisition of oncogenicity by virus-exposed cells apparently  
unassociated with the viral genome .                                    
  lines of syrian hamster lung and liver cells originally exposed as    
primary cultures to large doses of sv40 exhibited increased growth rate,
high plating efficiency, morphological transformation, and, in some     
instances, oncogenic potential after unusually long intervals . in at   
least two lines acquisition of oncogenic potential occurred             
independently of morphological transformation . in none of a total of 11
cell lines studied in detail was conclusive evidence for the presence of
the sv40 genome obtained .                                              
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eye and kidney tissue reactions to heterologous anti-uveal antibodies . 
  the uvea, lens capsule and kidney glomerulus in the albino wistar rat 
have a common antigenic component(s) . the uvea and lens capsule in the 
pigmented bovine eye also have a common antigenic component(s) . these  
results were demonstrated by the immunofluorescence technique . the     
common antigenic sites in the uvea were assumed to be the basement      
membrane surrounding the vascular trees in the tissues . the possibility
of the basement membrane participation as an antigenic source for       
inducing sympathetic ophthalmia is discussed .                          
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experiments dealing with the role played by the aqueous humor and retina
in lens regeneration of adult newts .                                   
  1. these three groups of experiments involve approximately 140 eyes of
adult newts, triturus v. viridescens . they were devised to examine     
what, if any, role the aqueous humor plays during lens regeneration from
the dorsal iris .                                                       
  2. many daily injections of aqueous humor from normal eyes were made  
in lentectomized eyes for as long as 96 days in some cases . as controls
some lensless eyes were daily injected with holtfreter's solution . in  
others aqueous humor was merely withdrawn .                             
  3) procedures for the injection experiments are difficult to control .
however, the most successful cases showed varying degrees of inhibition 
and retardation of lens regeneration .                                  
  4. pairs of eyes were united at large adjacent wound openings to      
provide a common reservoir of aqueous humor bathing both lenses and     
dorsal irises . in some cases the eyes were placed on the side of the   
body . in others more successful unions were made by fusing a           
transplanted eye to the right eye of a host .                           
  5. approximately three months after operation one of two large lens   
regenerates in a pair of perfectly fused eyes was removed . six weeks   
later a new large lens regenerate reappeared in most of the             
lentectomized units in the presence of the intact lens of the other unit
  6. there is a strong possibility that the more than normal amount of  
neural retina present provided a more powerful retinal factor for lens  
regeneration than the inhibiting influence of the intact lens in the    
environment .                                                           
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correlation between the mast cells and histamine content of the eye in  
cattle .                                                                
  the authors have examined the mast cell content of the eyes of cattle 
and have established that most of the mast cells are contained in the   
conjunctiva, the optic nerve and the ocular muscles,. fewer occur in the
sclera and iris, and least in the ciliary body and choroid . cornea,    
lens and retina do not contain mast cells . the histamine content of the
ocular tissues and their mast cell contents generally run parallel .    
however, the cornea is exceptional in that its histamine does not occur 
in a bound state but in some form which is readily available to a mild  
process of extraction (tyrode solution at 4 c) .                        
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studies in sickle cell anemia xxi. clinico-pathological aspects of      
neurological manifestations .                                           
  neurologic manifestations are frequent in patients who have sickle    
cell disease . these manifestations may be the earliest presenting signs
and symptoms and they are so variable that the patient may be           
erroneously diagnosed as having conditions such as meningitis,          
poliomyelitis, subdural hematoma, neoplasm, subarachnoid hemorrhage,    
lead encephalitis, subacute bacterial endocarditis, and congenital      
malformations of the brain . furthermore, development of these          
manifestations cannot be predicted on the basis of the type of crisis   
involved .                                                              
  prognosis following neurological involvement is unpredictable, but    
recurrent episodes, together with abnormal electroencephalographic      
readings suggest a poor outcome . such patients die or are the victims  
of rather severe neurological deficits .                                
  neurological examination of these patients suggests diffuse           
involvement of the cerebral hemispheres . examination of the            
pathological material, however, often fails to reveal thromboses . the  
striking findings are infarcts in the white matter and perivascular     
hemorrhages .                                                           
  the thesis that the abnormal neurological findings in these patients  
are actually due to sickle cell disease is supported by the fact that   
all such symptoms appear in association with clinical circumstances     
known to induce sickling . these include surgery and anesthesia, fever  
and infection .                                                         
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attenuation curves of the human eye under normal and pathological       
conditions .                                                            
  a method is described which allows the determination of /attenuation  
curves/ of the human eye . those curves are obtained by plotting the    
critical depth of modulation (cmd) as a function of the critical fusion 
frequency (cff) . routine experiments were carried out for a 2 test     
field showing a sinusoidal periodical variation of its luminance,       
surrounded by an extensive area with a luminance equal to the average   
luminance of the test field . attenuation curves were obtained for      
normal observers under different experimental conditions and for a      
number of patients . it is shown that this method affords us information
which cannot be obtained by means of the classical methods for measuring
the cff .                                                               
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central nervous system manifestations of periarteritis nodosa .         
  in the 114 cases of pathologically proved periarteritis nodosa        
reviewed, 53 patients (46 percent) had symptoms and signs of central    
nervous system or cranial nerve involvement . thirty-nine patients had  
both cerebral manifestations and neuropathy, 38 had neuropathy alone,   
and 14 had only cerebral symptoms and signs .                           
  the most common cerebral manifestation was that of mental derangement,
usually an organic psychosis or confusional state . headache,           
convulsions, blurred vision, vertigo, and sudden unilateral visual loss 
were the most common symptoms referable to the central nervous system . 
the most common abnormalities on examination were retinopathy,          
hemiparesis, and signs of a brainstem lesion . there was no difference  
in duration of life, after onset of disease, in those with and those    
without central nervous system involvement .                            
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see-saw nystagmus an unusual sign of lesions near the third ventricle . 
  a case of see-saw nystagmus in a child with craniopharyngioma and     
bitemporal hemianopsia is described, and reference is made to previous  
case reports . the basis for this curious sign is not clear, but the    
site of the lesion must be considered to be in the region of the third  
ventricle, since bitemporal hemianopsia is a necessary part of the      
syndrome . the sign is not common but when present points to a lesion   
near the third ventricle .                                              
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implications of gerstmann's syndrome .                                  
  of 465 consecutive patients subjected to a standardized battery of    
neuropsychological tests, 111 had one or more components of gerstmann's 
syndrome . each of these 111 patients had some evidence of organic brain
dysfunction in addition to gerstmann components . as the number of      
gerstmann components increased, the responsible brain lesions tended to 
be larger, more highly destructive of tissue, and to cause greater      
neurological impairment . every patient with four gerstmann components  
had associated evidence of severe impairment of brain functions and the 
lesion or underlying disease was likely to compromise survival of the   
patient . the syndrome is not to be regarded as an autonomous entity,   
but merges with numerous other neurological deficits, notably dysphasia 
in agreement with benton, we find no justification for singling out   
the four gerstmann components as a separate syndrome, unless one is also
prepared to recognize that any other arbitrary groups of concurrent     
deficits are also separate syndromes .                                  
  in at least three of 23 patients with all four gerstmann components,  
the angular gyrus, as shown by necropsy examination, was not involved by
the lesion . however, the probability that the left hemisphere contained
a lesion increased with the number of gerstmann components, and the     
probability of involvement of the left posterior parasylvian area also  
increased with the increase in the number of gerstmann components . with
two, three, or four gerstmann components, the lesions were never        
restricted to the angular gyrus but tended to spread widely over the    
parietal, temporal, and occipital lobes . as to localizing significance,
gerstmann's syndrome has approximately the same degree of cogency as    
dysphasia .                                                             
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alterations of visual evoked response in the presence of homonymous     
visual defects .                                                        
  the visual evoked response (ver) was studied by means of computer     
averaging in 32 normal subjects, nineteen patients without visual       
disorder but with unilateral cerebral lesions, and 30 patients with     
homonymous visual field defects . an early negative-positive-negative   
complex was recorded between laterally placed occipital electrodes and a
vertex reference . latencies were prolonged in the hemianopic patients .
some amplitude asymmetries were noted in the brain-damaged controls but 
were more pronounced in patients with visual defects . the recordings in
the hemianopic patients were differentiated from those in both control  
groups by the presence of aberrant wave forms (2 cases),. prolonged     
latencies (3 cases),. and amplitude depression of greater then 50 per   
cent of the positive wave on the abnormal side (16 cases) . pathologic  
verification was obtained in three patients and demonstrated a          
correspondence between alterations in the ver and the presence of       
lesions of the geniculocalcarine system .                               
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cerebro-vascular lesions and livedo reticularis .                       
  extensive livedo reticularis has been observed in one man and five    
women who have suffered from a series of cerebrovascular lesions . the  
neurological disabilities have included aphasia, homonymous hemianopia  
and hemiplegia but have been remarkable for the degree of recovery which
has occurred . it is presumed that the livedo which has been found in   
only one patient without neurological lesions is related to the         
cerebrovascular incidents . investigations have failed to show any      
evidence of polyarteritis nodosa, disseminated lupus erythematosus and  
thrombocythaemia and an arteritis of unrecognized type is suggested as  
the etiology .                                                          
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seesaw nystagmus case report elucidating the mechanism .                
  the eighth recorded case of see-saw nystagmus is reported . features  
in this case are analyzed and evidence to suggest that this form of     
nystagmus is ocular rather than central in origin is offered . see-saw, 
nystagmus, unlike true vertical nystagmus, is not of itself indicative  
of a brain stem lesion .                                                
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supratentorial paratransversal meningiomas .                            
  the author describes 6 cases of supratentorial paratransversal        
meningioma . clinically, the development of these tumours is slow and   
the chief neurological signs are.. homonymous hemianopia, contralateral 
hemiparesis and speech disorders when the tumour is on the dominant side
radiologically, carotid angiography permits identification of these   
tumours easily . surgically, the tumours were removed completely and,   
although in 2 cases the transverse sinus had to be resected, this caused
no damage . one patient, who was operated on twice and whose            
histological specimen on the second occasion showed that the meningioma 
was malignant, died seven months after the second operation . the other 
patients are well and free of neurological deficits from 1 to 12 years  
after operation .                                                       
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life span and lymphoma-incidence of mice injected at birth with spleen  
cells across a weak histocompatibility locus .                          
  newborn cogenic c h mice receiving injections across a weak (h-i h-i )
histocompatibility barrier exhibited life-shortening and a high         
incidence of lymphomatous disease during mid-adult life . in control    
experiments (h-i h-i ) lymphomatous disease developed much later life . 
both mouse strains when not given injections as new-borns manifest only 
a negligible incidence of lymphoma or leukemia . these findings are     
variably interpretable in terms of oncogenic virology, and of the       
immunologic theories of aging and cancer by analogy with transplantation
disease mechanisms .                                                    
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the heterogeneity of rheumatoid factors and the genetic control of      
polypeptide chains of globulin .                                        
  (1) evidence is presented that most rf proteins are heterogeneous in  
their antigenic composition although occasional ones are homogeneous and
thus resemble the paraproteins .                                        
  (2) studies pointing out some of the difficulties encountered with    
currently available preparations of polypeptide chains in the genetic   
mapping of globulin are described .                                     
.I 225
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progynon, a depot preparation with oestrogenic action, in the treatment 
of prostatic carcinoma .                                                
  a derivative of a natural oestrogen -dash oestradiol undecylate,      
progynon-depot -dash was given in depot form by injection to a group of 
patients with prostatic carcinoma . the study showed progynon-depot to  
reduce the excretion of androgen metabolites in the urine . the results 
suggest that the preparation reduced the testicular production of       
androgens but probably not that of the adrenal glands . the depot effect
and clinical action of the preparation are described briefly .          
.I 226
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/urinary 17-ketosteroid excretion study in radiation induced menopause  
in carcinoma breast./ .                                                 
  (1) urinary 17-ketosteroid estimation results are given in 11 patients
subjected to radiotherapeutic sterilisation .                           
  (2) a high dosage level was used in all these cases .                 
  (3) results indicate some suppression of ovarian function within 2    
weeks of sterilisation .                                                
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prostatic cancer of a young person with primary hypogonadism .          
  the prostatic carcinoma of a 34 years old man with primary            
hypogonadism was presented . endocrine environment of relative          
estrogenic excess is suspected to have played the leading part in       
pathogenesis of this case .                                             
.I 228
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urinary excretion of neutral 17-ketosteroids and pregnanediol by        
patients with prostatic cancer and benign prostatic hypertrophy .       
  urinary neutral 17-ketosteroid fractions and pregnanediol excreted by 
21 patients with prostatic cancer, 17 patients with benign hypertrophy, 
and 59 clinically well subjects were assayed to determine whether       
differences exist .                                                     
  patients with prostatic cancer and those with benign hypertrophy      
excreted significantly less androsterone than the clinically well       
subjects . a disproportionately lower level of androsterone than        
etiocholanolone resulted in a significantly lower                       
androsterone/etiocholanolone ratio in both groups .                     
  the specificity of the findings is discussed . the lower levels of    
androsterone excreted by patients with benign hypertrophy were          
associated with an extended period of hospitalization . patients        
hospitalized less than 5 days excreted androsterone at levels not       
significantly different from the clinically well subjects .             
  lower levels of androsterone excreted by patients with prostatic      
cancer were not explained by the presence of metastasis, the duration of
hospitalization, loss of appetite, or other definable differences, when 
each was considered singly . the possible interrelationships of clinical
differences prevent assigning lower excretion levels to the cancer state
alone .                                                                 
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i. urinary excretion of neutral 17-ketosteroids and pregnanediol by     
patients with breast cancer and benign breast disease .                 
  urinary levels of neutral 17-ketosteroid fractions and pregnanediol   
excreted by 114 women, 56 premenopausal and 58 postmenopausal, were     
determined . subjects studied were included in 4 premenopausal groups   
(breast cancer 6, benign breast disease 18, sick control 8, well control
24) and 3 postmenopausal groups (breast cancer 21, sick control 17, well
control 20) .                                                           
  levels of androsterone and etiocholanolone excreted by premenopausal  
patients with breast cancer were significantly less than levels excreted
by other premenopausal groups, and they did not differ significantly    
from levels excreted by postmenopausal patients with breast cancer .    
  disproportionately lower levels of the 11-desoxy-17-ketosteroids than 
11-oxy-17-ketosteroids excreted by premenopausal patients with cancer   
resulted in significantly lower ratios than those found in other        
premenopausal groups . ratios associated with premenopausal patients    
with cancer did not differ significantly from those of postmenopausal   
patients with cancer .                                                  
  lower levels of androsterone and etiocholanolone were not explained by
debilitation .                                                          
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the morphologic demonstration of an alveolar lining layer and its       
relationship to pulmonary surfactant .                                  
  the presence of an alveolar lining layer was histologically           
demonstrated in animal lungs by ultraviolet microscopy . this layer     
appeared as a thin fluorescent line at the air-tissue interface .       
  the fluorescent lining layer could be abolished from lung sections by 
extraction with chloroform..methanol and was diminished by digestion    
with cl.welchii a-toxin lecithinase, suggesting that the structure was a
lecithin-containing lipid . an alveolar lining structure was also       
identified by the use of phosphatide and polysaccharide stains,         
suggesting that the lipid was a phosphatide, but that a                 
mucopolysaccharide component might also be present .                    
  bilateral cervical vagotomy resulted in diminution or loss of the     
fluorescent alveolar lines and abnormal surface tension properties of   
lung extracts . this suggested that the presence of the fluorescent     
material was associated with the surface activity of the lung .         
  alveolar lining structure could not be demonstrated by electron       
microscopy, even with special staining techniques .                     
.I 231
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experimental emphysema basis, review, and critique .                    
  normal lung structure has been described as a rich capillary bed in a 
finely partitioned airspace with unique surface-active effects .        
morphologic criteria of the lesions of human pulmonary emphysema include
evidence of destruction, residual vascular remnants, the absence of     
significant amounts of fibrosis, and altered conducting airways without 
anatomic obstruction .                                                  
  experimental studies relating to the pathogenesis of emphysema have   
been reviewed and critically evaluated . stress has been placed on the  
necessity to control the biologic factors influencing the action of any 
specific etiologic agent .                                              
.I 232
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alveolar lining cells and pulmonary reticuloendothelial system of the   
rabbit .                                                                
  complete freund's adjuvant was injected intravenously into rabbits and
the cellular response in the lungs was investigated . the population of 
cells within the alveolar spaces was contributed to by monocytes of the 
circulation, mesenchymal cells of the alveolar walls and epithelial     
lining cells of the alveoli . the abnormal epithelial lining during the 
proliferative phase was the result of an increase in size and number of 
the cells that line the normal alveoli . as healing progressed, a       
structurally normal alveolar lining was found .                         
.I 233
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time course of changes in surface tension and morphology of alveolar    
epithelial cells in co2-induced hyaline membrane disease .              
  atelectasis and hyaline membranes produced by exposure of guinea pigs 
to 15 percent co2 were found to be associated with disappearance of     
lamellar bodies in the large alveolar lining cells (granular            
pneumocytes) and an associated decrease in surfactant as indicated in   
the rise of minimal surface tension of the lungs . this process is      
limited to the uncompensated phase of respiratory acidosis and is       
reversed during the compensatory phase . the parallel time course in    
changes of surface tension and alterations of lamellar bodies in the    
granular pneumocytes provides additional evidence for the identification
of the latter as the cells responsible for the secretion of surfactant .
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cortisone and atypical pulmonary /epithelial/ hyperplasia further       
studies including electron microscopy, tissue culture, animal           
transplantation and long term observations .                            
  previous work in rabbits showed that there was a proliferation of     
cells within pulmonary alveoli following intratracheal injection of     
nitric acid and that the proliferation was greatly enhanced by the      
administration of cortisone to the animals .                            
  electron microscopic observations indicated that these were           
morphologically large alveolar lining cells . tissue culture studies of 
damaged and normal lung with and without cortisone showed no evidence   
for a direct effect of the drug on the proliferation of these cells .   
  this observation, together with the knowledge that fibrosis was       
delayed in the cortisone treated animals, support the thesis that the   
cortisone effect is an indirect one . transplantation of damaged lung   
tissue to hamster cheek pouch failed to reveal evidence of growth .     
within the period of observation (99 to 420 days) there was evidence    
that the proliferation subsided considerably and no neoplasms developed 
.I 235
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some observations on myelin-glial relationships and on the etiology of  
the cerebrospinal fluid exchange lesion .                               
  the present paper presents cytological observations from developing   
kitten spinal cord and from spinal cord white matter reacting to injury 
it also presents some recent experiments on the mechanism of etiology 
of the csf exchange lesion . drawing on these various sources, the      
authors propose specific functions for some of the cell types present in
spinal cord white matter .                                              
.I 236
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lactate and pyruvate in the brain of rats during hyperventilation .     
  experiments on anesthetized and curarized rats under artificial       
ventilation show that during hyperventilation lactate and pyruvate are  
markedly increased both in blood and in brain . the lactate/pyruvate    
ratio which remains in blood the same as in control conditions, is      
systematically decreased in brain . during hypoxia (ventilation with 7  
oxygen in nitrogen) lactate rises markedly in blood and in brain . the  
lactate/pyruvate ratio which is strongly increased in blood shows a     
small rise in brain . these observations could indicate that a different
mechanism is responsible for the rise of lactate in brain during hypoxia
and hyperventilation . the important augmentation of lactate in brain   
during hyperventilation can give an explanation for the delayed rise    
which is seen in the lactate level in cerebrospinal fluid in these      
conditions .                                                            
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cisternal fluid oxygen tension in man .                                 
  using a beckman micro-oxygen-electrode we have studied the oxygen     
tension simultaneously in the cisterna magna, the internal jugular vein 
and in arterial blood under various conditions . the results suggest    
that the cisternal oxygen tension to some degree reflects the average   
oxygen tension of the surrounding brain tissue and besides reflecting   
the available free oxygen to the brain it registrates changes of short  
duration in the cerebral blood flow .                                   
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ventricular septal defect with prolapsed aortic valve and outflow tract 
obstruction .                                                           
  a case of ventricular septal defect combined with aortic valvular     
lesion and infundibular pulmonic stenosis is described . the right      
coronary cusp of the aortic valve, protruding through the ventricular   
septal defect, was demonstrated by right ventricular angiocardiography  
as a polyp-like mass in the right ventricular outflow tract . cardiac   
catheterization and angiocardiography showed progressive right          
ventricular outflow obstruction .                                       
.I 239
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functional adaptations of the right ventricular outflow tract in        
congenital heart disease .                                              
  functional adaptations in the right ventricular outflow tract have    
been discussed in relation to the development of acquired /pulmonary    
stenosis/ .                                                             
  it is concluded that physical forces as well as structural            
abnormalities may greatly influence both the clinical picture and the   
life history of many patients with congenital heart lesions .           
  the importance of further serial haemodynamic studies to provide a    
fuller understanding of the natural course of many lesions is stressed, 
so that better advice about prognosis and the optimal time for surgical 
treatment may be given .                                                
.I 240
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mitral atresia associated with pulmonary venous anomalies .             
  pulmonary venous anomalies were observed in 5 among 29 specimens with 
mitral atresia . in 4 of these 5 the anomalous pulmonary veins took the 
form of anomalous pulmonary venous connexion . in the remaining case the
pulmonary venous anomaly was represented by cor triatriatum . in 3      
(group i), mitral atresia and premature closure of the foramen ovale    
coexisted . the anomalous pulmonary venous connexions in this group     
provided collateral routes for the flow of pulmonary venous blood, and  
can be understood as developing en response to obstruction at the       
foramen ovale when the mitral valve is atretic . in the remaining 2     
(group ii) no such causative factor could be invoked . in one of the    
latter group total anomalous pulmonary venous connexion coexisted with a
common atrium . in the other, cor triatriatum coexisted with a patent   
foramen ovale .                                                         
  pulmonary venous obstruction occurred in each of the 5 cases .        
.I 241
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basal metabolic rate after cardiovascular surgery .                     
  the basal metabolic rate and respiratory equivalent of patients were  
determined during 8 days of convalescence from cardiovascular surgical  
operations performed with or without cardiopulmonary bypass . the       
results were compared in patients who had undergone operation for       
different diseases . metabolic rate in the majority of cases was        
increased but was commensurate with body temperature . some patients,   
particularly those requiring open operation on the aortic valve, had    
raised metabolic rates which could not be explained solely by pyrexia . 
  all types of patients in this series had elevated respiratory         
equivalents which persisted throughout convalescence . these equivalents
were greater in patients treated with cardiopulmonary bypass than in    
patients treated without bypass .                                       
.I 242
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surgical treatment of ventricular septal defect .                       
  the surgical technique of closure of ventricular septal defects in 80 
cases (37 cases of isolated defects and 43 cases of tetralogy of fallot)
is discussed in the light of the follow-up results . the use of a patch 
for closure has reduced the incidence of recurrence to 4 percent, com-  
pared with 18 percent when direct suture was performed . the incidence  
of heart block also decreased from 15 percent, when direct suture was   
used, to 4 percent with a patch . the transatrial approach is preferred 
for isolated ventricular septal defects,. the ventricular approach is   
preferred for cases with tetralogy of fallot . in cases combined with   
aortic insufficiency only small defects are closed through the aorta .  
larger defects are closed in the usual way at a first stage operation,  
and a total valve prosthesis is introduced at a second operation . there
was an operative mortality of 6 percent in isolated ventricular septal  
defects, compared with 27 percent in cyanotic patients with tetralogy of
fallot .                                                                
.I 243
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some hemodynamic observations in congenital heart disease with special  
reference to pressure curves in ductus arteriosus .                     
  hemodynamic observations in 100 congenital heart disease cases are    
made based on data in the department of pediatrics, kyoto university    
between may 1961 and december 1963 . we have classified these 100 cases 
according to the malformation from the hemodynamic view point . our     
cases were classified into the following groups .                       
  (1) ventricular septal defect                             35 cases    
      small ventricular septal defect                       20          
      moderate ventricular septal defect                     9          
      marked ventricular septal defect                       4          
      ventricular septal defect with pulmonary stenosis      2          
  (2) patent ductus arteriosus                              21          
  (3) atrial septal defect                                  19          
      atrial septal defect                                  14          
      atrial septal defect with pulmonary stenosis           5          
  (4) pulmonary stenosis                                     5          
  (5) tetralogy of fallot                                   14          
  (6) aortic stenosis                                        3          
  (7) aortic insufficiency                                   3          
      aortic insufficiency with ventricular septal defect    2          
      aortic insufficiency with pulmonary stenosis           1          
  in sonre small ventricular septal defect, we tried the vasoactive     
drugs . phenylephrine was injected slowly into the right ventricle via  
the catheter, a rapid rise in femoral arterial pressure associated with 
bradycardia and intensiffication of the systolic murmur was observed .  
after the administration of amyl nitrite, a rapid fall in femoral       
arterial pressure associated with tachycardia and softening of the sys- 
tolic murmur was observed .                                             
  in patent ductus arteriosus, when the cardiac catheter is withdrawn   
slowly from the aorta into the pulmonary artery, the outstanding        
pressure curve is recorded in ductus arteriosus . the systolic pressure 
curve in the ductus arteriosus is the same as the systolic pressure in  
the aorta and the diastolic pressure curve in the ductus arteriosus has 
a diastolic dip followed by a late diastolic pressure peak .            
  in patent ductus arteriosus, when the cardiac catheter is withdrawn   
from the left pulmonary artery to the right ventricle, the pressure     
curve reveals a considerable characteristic rise in pulmonary arterial  
pressure which is regarded as an effect of the transmission of systemic 
pressure through the ductus arteriosus .                                
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a study on the direction of inscription of the vectorcardiographic      
t-loop in left and right ventricular hypertrophy .                      
  (1) frank lead vectorcardiogram was recorded in 30 normal persons and 
in 323 cases with hypertension and acquired and congenital heart disease
the t-loop was classified into 8 types according to the directions of 
inscription in 3 planar projections . frequently observed types were    
examined with the direction of the maximal t vector .                   
  (2) in majority of normal cases, the t-loop was inscribed             
counterclockwise in horizontal and clockwise in sagittal planes .       
  (3) in left ventricular hypertrophy, abnormal inscription of the      
t-loop was observed with abnormal rightward and superior deviation of   
its maximal vector and the t-loop oriented more than 120 in horizontal  
plane was usually accompanied by abnormal inscription . percentage of   
abnormal inscription was higher in cases with cardiac complaints .      
  (4) in right ventricular hypertrophy, directional change of the t-loop
was relatively small but changes in inscription of it were common . the 
t-loop was always inscribed abnormally in cases with abnormal           
inscription of the qrs-loop .                                           
  (5) the concept of the polar vector was found to be valuable in       
studying the inscription and the direction of the t-loop . significance 
of changes in inscription of the t-loop was discussed .                 
.I 245
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pulmonary vascular plexiform lesion pathogenetic studies .              
  an attempt was made to test the theory that in pulmonary arterial     
hypertension, the plexiform lesion is a jet lesion beyond points of     
arterial stenosis resulting from nonspecific intimal thickening .       
  in 39 subjects with such congenital communications as are associated  
with pulmonary arterial hypertension, the lungs were studied            
histologically . in each, there was an additional element of pulmonary  
venous obstruction . it is likely that in the absence of pulmonary      
venous obstruction, adult patients with only the congenital             
communication would have developed plexiform lesions .                  
  in the three adult patients in the study, no plexiform lesions were   
identified . among the 36 infants or children, one subject showed       
plexiform lesions, a 53-day-old girl with mitral atresia, ventricular   
septal defect, and patent ductus arteriosus .                           
  while the findings in the three adult subjects support the theory     
regarding the genesis of plexiform lesions, the findings in the one     
infant with plexiform lesions appear to contradict it .                 
.I 246
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renal hemosiderosis (blue kidney) in patients with valvular heart       
disease .                                                               
  anatomic evidence of intravascular hemolysis, i.e., renal             
hemosiderosis, was found at necropsy in 4 of 132 patients who died of   
severe valvular heart disease . the aortic valve in each of these 4     
patients was heavily calcified, immobile, and portions of the calcific  
deposits were in direct contact with the blood . hemolysis in each      
patient was attributable to direct trauma to erythrocytes traversing the
stenotic valve, and the frequency of trauma was increased by an         
associated regurgitant flow . renal hemosiderosis was not observed in   
any patient with isolated mitral valve disease, or in those with        
combined mitral and tricuspid valve malformations .                     
.I 247
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tumor scanning with radioactive cesium .                                
  fourteen patients with cancer were scanned 10 minutes to 48 hours     
after injection of radioactive cs. and satisfactory scans of the tumors 
were obtained in seven . positive scans were obtained in large,         
superficial tumors, in a pulmonary lymphoma, and in a carcinoma of the  
upper third of the esophagus . the negative scans were all in abdominal 
tumors . correlations were made with data obtained from external        
counting and by well scintillation counting of biopsy specimens . two   
modes of uptake are suggested.. (a) early uptake due to vascularity and 
probably not proportional to stable cesium content.. and (b) a later    
uptake based upon greater alkali metal content of tumors than of normal 
tissue .                                                                
.I 248
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lung scanning with colloidal risa .                                     
  the use of colloidal risa injected intravenously in a particle size of
10.50 microns followed by lung photoscanning offers a practical,        
atraumatic method of visualizing pulmonary artery occlusions in the dog 
the fact that the particles have a relatively short biological        
half-life appears to decrease the radiation dose delivered and the      
duration of occlusion of pulmonary capillaries as compared to ceramic   
microspheres . work is in progress to apply this technique to the study 
of pulmonary artery occlusion in the human .                            
.I 249
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multivariate comparison of results of treatment in chronic lymphocytic  
and chronic granulocytic leukemia .                                     
  the results of several clinical trials have been analyzed by          
multivariate procedures which rely completely on laboratory findings and
do not involve scoring specific changes or subjective evaluations .     
statistically significant differences among drugs after three months of 
therapy were demonstrated . a relationship between the multivariate     
method and the subjective evaluation was demonstrated which indicates   
that if the subjective evaluation is an estimate of the physiologic     
state or prognosis of the patient, then so are the completely objective 
techniques used here .                                                  
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oxacillin--apparent hematologic and hepatic toxicity .                  
  bone marrow depression and hepatocellular dysfunction developed in an 
allergic woman receiving 3.0 gm. of sodium oxacillin by mouth daily for 
nearly three months . discontinuing the drug and administering          
corticosteroids and antibiotics resulted in apparent recovery . the     
toxic potentialities of oxacillin should be appreciated .               
.I 251
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drugs and neonatal jaundice .                                           
  this paper is not intended as an exhaustive review of bilirubin       
metabolism nor of the many factors which may result in exaggerated      
physiologic jaundice.. for such a review the interested reader is       
referred to the excellent articles by zuelzer and brown . brief mention 
has been made of the mechanism by which certain drugs may contribute to 
the development of hyperbilirubinemia . a few drugs, the water-soluble  
vitamin k derivatives, sulfasoxazole (gantrisin), the salicylates, and  
novobiocin have been unequivocally shown to affect adversely the newborn
infant's ability to handle bilirubin . in time other compounds will     
definitely be incriminated .                                            
  it is important to remember that the administration of a drug to a    
mother just prior to delivery may result in appreciable concentrations  
of the compound in the infant's serum, and that drugs administered to   
the nursing mother may be excreted in breast milk and thereby absorbed  
by the infant . careful consideration of the drugs given not only to the
newborn but also to the mother is therefore essential if we are to avoid
what may be termed iatrogenic hyperbilirubinemia .                      
.I 252
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amputation in patients over 80 years of age .                           
  although patients over 80 years of age can be expected to have poor   
physical reserve and many co-existing diseases, our observations show   
that nevertheless they can be subjected to surgical procedures without  
undue mortality . the mortality rate can be maintained at a minimum if  
the surgeon considers the factors that contribute to its increase in the
elderly . this necessitates.. 1) careful evaluation of the patient and  
treatment of any pre-existing or co-existing disease, 2) proper control 
of electrolytes, 3) avoidance of infection, 4) prompt correction of any 
postoperative hypotension, 5) postoperative pulmonary ventilation and   
tracheal cleansing, and 6) avoidance of prolonged surgical procedures . 
  a group of 26 patients past the age of 80 years underwent amputation  
of a lower extremity, without undue mortality (9 deaths) .              
  lumbar sympathectomy is not considered advisable in these aged pa-    
tients .                                                                
  the standard mid-thigh operation can be questioned in the younger     
patient, but it is the procedure of choice for removal of a gangrenous  
extremity in patients over 80 years of age .                            
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radical operation for ventricular septal defect in infancy .            
  ventricular septal defect is the most common congenital anomaly of the
heart in infancy, and has a poor prognosis . we have operated upon 18   
infants all under one year of age for ventricular septal defect . there 
has been successful repair in 16 cases .                                
  at present, hypothermia with a surface cooling method has proved to be
superior to the artificial heart-lung machine because of the simplicity 
and the good operative results with its use . in addition, early        
operation during the infantile period will cause less psychological     
impact on infants . these advantages are sufficient for us to advocate  
radical operation of ventricular septal defect in infancy, even         
including the severely ill children .                                   
.I 254
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specific suppression of tumor growth by isolated peritoneal macrophages 
from immunized mice .                                                   
  methods were presented by which macrophages may be isolated from the  
peritoneal cell population of mice . these cells, and for comparison    
peritoneal lymphocytes and lymph node cells, were tested for immunologic
activity by injecting a mixture of the test cells and tumor cells       
subcutaneously into irradiated mice . each cell type, when obtained from
immunized mice, was capable of suppressing the growth of the specific   
tumor cells . the results are discussed with respect to a possible      
specific immunologic function for macrophages in graft rejection .      
.I 255
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effect of heterologous antiserum and complement on glycolysis of tumor  
cells .                                                                 
  the effect of heterologous antiserum and complement on glucose        
metabolism of rat ascites tumor cells was examined to clarify the       
mechanism of the cytotoxic effect of antibody .                         
  1. lactate-production of the target cells was inhibited by the        
cooperation of antiserum and complement, while no inhibition was        
observed when the cells were subjected to either antiserum or complement
alone . the inhibition of lactate-production was observed under both    
acrobic and anacrobic conditions . no effect of the antiserum and       
complement was observed on the oxygen consumption of the cells .        
  2. the amount of antiserum necessary for the inhibition of            
lactate-production of the cells was determined in the presence of a     
definite amount of complement, and it was found that the degree of      
inhibition was not in parallel with the concentration of antiserum      
beyond a certain threshold . on the other hand, a parallelism was       
observed between the amount of complement and the rate of inhibition of 
lactate-production when different amounts of complement were added to a 
definite amount of antiserum .                                          
  3. similar inhibitory effects of the antiserum and complement on      
lactate-production of the cells from glucose, fructose-1, 6-diphosphate,
and pyruvate suggested that the inhibition occurred toward the final    
step of glycolytic process of the cells .                               
.I 256
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soluble tissue antigens in human brain tumor and cerebrospinal fluid .  
  an a-2 globulin antigen present in human glioblastomas and            
immunologically identical with antigens present in human brain, liver,  
spleen, and metastatic carcinoma cyst fluid has been described . this   
protein antigen is not present in plasma, wbc, or normal csf . it has   
been demonstrated in the csf of three of 27 patients with tumors of the 
central nervous system . when present, it may represent a specific      
tissue protein fraction contributed by either the tumor itself or the   
adjacent cns tissue . the major protein components of normal and        
abnormal csf are derived from, or, at least, antigenically identical to,
the plasma proteins .                                                   
.I 257
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the apparent immunofluorescence of tissue mast cells .                  
  both rat mast cells and rat cosinophils exhibited fluorescence in blue
violet light after treatment with fitc-conjugated rabbit anti-rat       
g-globulin and in each cell this fluorescence was immunologically       
nonspecific .                                                           
  whereas cosinophils fluoresced after treatment with fluorescein alone,
mast cells fluoresced only after treatment with a protein conjugate     
containing g-globulin .                                                 
  the phenomenon was observed in cells from different organs and the    
fluorescence was seen to be associated with the cytoplasmic granules    
normally present in these cells .                                       
.I 258
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the determinants of cerebrospinal fluid po2 the effects of oxygen and   
carbon dioxide breathing in patients with chronic lung disease .        
  the lumbar cerebrospinal fluid po2 of some hypoxemic hypercapnic      
patients with chronic lung disease is the same as that of patients      
without chronic lung disease . breathing 95 oxygen with 5 carbon dioxide
increased lumbar cerebrospinal fluid po2 more than breathing 95 oxygen  
with 5 nitrogen . the change in cerebrospinal fluid po2 is closely      
related to the change in arterial pco2, and this relationship is similar
to the relationship between arterial pco2 and cerebral blood flow in    
patients with and without hypercapnia . interpretation of these         
observations must be qualified by the following.. cisternal             
cerebrospinal fluid po2 differs from lumbar cerebrospinal fluid po2 in  
its response to breathing oxygen with carbon dioxide,. regulation of    
blood flow to the spinal cord and nerve roots is not known to be        
comparable to that of the brain,. and factors other than blood flow may 
have contributed to the changes of cerebrospinal fluid po2 .            
.I 259
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the behavior of lymphocytes in primary explants of human lung cancer in 
vitro .                                                                 
  the activity of lymphocytes within outgrowths from explanted tissue   
fragments of 20 human lung cancers has been studied . the study included
cancer-bearing tissue explants from all cases and noncancerbearing lung 
tissue from 4 of the 20 cases . five major categories of lymphocytic    
behavior were derived from the study, namely.. (1) emigration and       
migration of lymphocytes from the explant,. (2) clustering of           
lymphocytes around /target/ cells,. (3) ameboid transformation of       
lymphocytes,. (4) lymphocytic congregation,. and (5) emperipolesis .    
criteria for these different lymphocytic activities have been amplified 
or introduced .                                                         
  findings of particular interest were.. (1) the frequency of both via  
ble and nonviable lymphocytes within the vacuoles of other cells . this 
observation is considered to be an absolute criterion for the recogni-  
tion of emperipolesis . a subsequent /inclusionbody/ appearance of the  
dead lymphocytes has been observed . (2) the intimate relationship of   
ameboid forms of lymphocytes to selected cells, resulting in a          
juxtanuclear and frequently unipolar crowding of one cell by numerous   
lymphocytes while nearby cells were totally devoid of ameboid           
lymphocytes . reasons are given to support the impression that this     
phenomenon is re lated to sensitization . there is also the possibility 
that the phenomenon may indicate that the lymphocyte is /conditioned/ . 
(3) the apparent entry of the lymphocyte into the cell has been recorded
by timelapse cinematography .                                           
  a lymphocyte relationship to cancer cells was infrequently found      
although explants of 15 of the 20 cases produced identifiable cancer    
cells and lymphocytes emigrated from the explants of all 20 cases . it  
is not apparent from this limited study whether this is a significant   
finding .                                                               
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ventricular septal defect with aortic insufficiency a clinical and      
hemodynamic study of 18 proved cases .                                  
  eighteen patients with the combination of ventricular septal defect   
and aortic insufficiency were studied . nine also had infundibular      
pulmonary stenosis . seventeen were treated by open-heart operations .  
  the physical findings were those of a typical ventricular defect      
murmur and thrill together with an aortic insufficiency blow and a wide 
pulse pressure . a systolic murmur at the upper left sternal border with
thrill is strongly suggestive of the additional lesion of infundibular  
pulmonary stenosis, but the presence or absence of infundibular         
pulmonary stenosis was indicated most accurately at cardiac             
catheterization and on inspection at operation . it was not of          
sufficient severity for signs of additional right ventricular           
hypertrophy to appear on the electrocardiogram .                        
  retrograde aortography serves to demonstrate the severity of the      
aortic regurgitation .                                                  
  the problem of the surgical correction of these lesions will be the   
subject of a separate communication .                                   
.I 261
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radioisotope photoscanning as a diagnostic aid in cardiovascular disease
a safe, simple method for diagnosing pericardial effusion and aneurysm .
  radioisotope scanning is a safe, simple, and useful method for the    
diagnosis of pericardial effusion and aortic aneurysm . the whole-body  
radiation dose, approximately 25 millirads from 300 of i 131-sodium     
iodipamide, is no greater than the dose received from a standard        
posteroanterior chest roentgenogram or a blood volume determination .   
there are no side effects or complications from the procedure, and it is
well tolerated by the patient . the scan can be repeated at intervals to
assess progress of the disease or response to treatment . cardiovascular
scanning with radioactive isotopes can be recommended as a useful and   
safe diagnostic tool .                                                  
.I 262
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studies of hematology and bone marrow morphology in vitamin e-deficient 
pigs .                                                                  
  forty-four pigs were used in two experiments whose purpose was to     
produce a deficiency of vitamin e . the anemia and changes in bone      
marrow morphology occurring in the vitamin e-deficient state are        
described . the hematologic disorders include low hemoglobin and        
hematocrit values, leucocytosis and granulocytosis . nuclear            
abnormalities were observed in the erythroid precursors in the bone     
marrow, many of the cells being multinucleated . giant multinucleated   
cells of megakaryocyte type were frequently found .                     
.I 263
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significance of blood groups in homotransplantation of marrow in the dog
  ten dogs were given 1,500 r whole-body irradiation and an infusion of 
allogeneic marrow from a donor matched with respect to six erythrocyte  
antigens . methotrexate was given to reduce secondary syndromes . four  
dogs survived . in a similar experiment with 10 dogs, in which no effort
was made to match donors and recipients, three dogs survived . it was   
concluded that matching of donor and recipient for these six red cell   
antigens did not increase significantly the longterm survival rate of   
lethally irradiated dogs with allogeneic marrow grafts .                
.I 264
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radioautographic studies of bone marrow lymphocytes in vivo and in      
diffusion chamber cultures .                                            
  radioautography with tritiated thymidine has been utilized to examine 
the turnover rate and origin of small lymphocytes in the bone marrow of 
the guinea-pig .                                                        
  very few marrow lymphocytes were initially labeled by a single        
injection of tritiated thymidine, but thereafter the number of labeled  
lym phocytes rapidly increased to high maximum levels at 3 days .       
analysis of the labeling curves and grain counts indicates that the     
population of marrow lymphocytes is maintained in a dynamic steady state
with an average turnover time of 3 days or less .                       
  suspensions of bone marrow cells were isolated from the circulation   
within intraperitoneal diffusion chambers after short-term labeling with
tritiated thymidine in vivo . although very few small lymphocytes were  
labeled when introduced into the diffusion chambers, a considerable     
percentage became labeled during the subsequent culture period .        
  tritiated thymidine was also administered intravenously whilst        
excluded from one hind limb by the application of an occlusive          
compression bandage for 20 minutes . very few labeled small lymphocytes 
were found after 72 hours in the tibial marrow of the initially occluded
limb, whereas the normal high percentage was labeled in the control     
tibial marrow .                                                         
  these experiments do not demonstrate any large-scale influx of small  
lymphocytes from the blood stream into the marrow parenchyma . they     
suggest that newly formed small lymphocytes appear in the marrow as a   
result of the division of locally situated precursor cells, but the     
mechanism of intramedullary lymphocytopoiesis is uncertain .            
/transitional/ cells, intermediate in morphology between blast cells and
small lymphocytes, synthesize dna and are actively proliferative, but   
they do not appear to account fully for the rate of lymphocyte          
production .                                                            
  certain large, undifferentiated labeled cells appeared in the bone    
marrow as a result of hematogenous migration . some implications of     
these findings are discussed .                                          
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autoradiographic study on the origin and fate of small lymphoid cells in
the dog bone marrow.. effect of femoral artery clamping during in vivo  
availability of h3-thymidine .                                          
  the origin and fate of small lymphoid cells in the dog bone marrow    
were studied autoradiographically by observing the effect of clamping of
the femoral artery during in vivo availability of h3-thymidine . heavily
labeled small lymphoid cells appeared in the bone marrow of the clamped 
leg 3 hours after injection of the tracer and increased in number up to 
6 days . the labeling indices of these cells, however, were             
significantly lower than those of control marrow . a possible           
interpretation is that dog bone marrow contains two populations of small
lympho id cells, one migrating into the marrow via the blood stream, the
other originating from local precursor cells within the marrow . there  
was no evidence for a transformation of migrated small lymphoid cells   
into erythroblasts during the first 48 hours after injection of         
h3-thymidine .                                                          
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the lymphocyte in guinea-pig bone marrow .                              
  the structure and distribution of lymphocytes in the bone marrow of   
normal 400 g guinea-pigs have been studied by means of light microscopy,
electron microscopy, and radioautography . the study of structural      
organization by all three techniques confirms the morphological identity
of the marrow small lymphocytes with small lymphocytes in other         
situations and affords added proof of the presence of a series of cells 
transitional in appearance between small lymphocytes and blast cells .  
unlike the small lymphocytes, transitional cells show evidence of dna   
synthesis . marrow small lymphocytes and transitional cells are         
diffusely scattered throughout the parenchyma, often situated in close  
proximity to the sinusoidal endothelium . they are also found           
characteristically concentrated within some of the sinusoids,. this is  
termed /lymphocyte loading/ .                                           
  the findings are discussed with particular reference to the possible  
origin, interrelationship and fate of these cells .                     
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surgical treatment of atrial septal defect under hypothermia .          
  the technique of inflow occlusion under 30 c. hypothermia was adopted 
for direct visual correction in 133 consecutive cases of atrial septal  
defect of the secundum variety and the associated anomalies .           
  the use of extracorporeal circulation combined with hypothermia was   
reserved for the repair of two cases of ostium primum defects .         
  the over-all operative mortality was 4 .                              
  post-operative evaluation showed that the results have been good in   
almost all patients, including those with pulmonary hypertension .      
  since an ostium primum defect requires cardio-pulmonary bypass for its
closure, the pre-operative recognition of the defect is highly desirable
in the selection of patients for operation and in planning the procedure
itself .                                                                
  the information derived from the clinical examination and appropriate 
diagnostic studies has been found to be consistently accurate in the    
pre-operative differentiation of the primum from the secundum defect .  
therefore, the unexpected discovery of a primum defect at operation was 
not a problem .                                                         
  in our experience, open-heart surgery under 30 c. hypothermia for the 
repair of an atrial septal defect of the secundum type and the          
associated anomalies is a safe and practical technique and effectively  
corrects the anomaly with minimal risk .                                
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internal cooling for general hypothermia .                              
  a further presentation is offered on the advantageous use of          
intragastric temperature control as an adjunct in general hypothermia . 
a device is described which accomplishes this end with no encountered   
deleterious side effects, minimal technical involvement, and minor      
expense . observations are recorded on rates of temperature change      
according to sex, weight, and type of surgery performed .               
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late effects of regional renal hypothermia .                            
  in summary, one can safely conclude that no deleterious effects were  
created in dogs observed over a period of 3 years following renal       
ischemia of 6 hours' duration protected by hypothermia . the blood      
pressure failed to climb, there was no evidence of azotemia, and careful
microscopic studies failed to reveal histological evidence of renal,    
vascular or cardiac damage . renal function, as demonstrated by         
creatinine and pah, was preserved and there was no delay in wound       
healing .                                                               
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mesenteric vascular response to hypothermia .                           
  1. total and segmental resistances were studied in the mesenteries of 
37 dogs, and the effects of hypothermia, changes in blood viscosity and 
epinephrine on these resistances were compared .                        
  2. cooling to 15 c. caused an increased mesenteric resistance in 94   
per cent of animals with approximately 90 per cent of the resistance    
rise contributed by the arterial segment . small vessel resistance      
increased in 52 per cent . there was no evidence of venous constriction 
  3. blood viscosity appeared to play a minor role .                    
  4. it is suggested that hemorrhagic necrosis of the bowel wall is due 
to intense vasoconstriction in the precapillary vessels with subsequent 
distal anoxia and cellular damage .                                     
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the response of dogs to perfusion and arrest of circulation at near zero
cerebral temperatures .                                                 
  1. twenty-six dogs were cooled by a whole body, closed chest perfusion
technique to end perfusion brain temperatures of 14.1 to 0.2 c.         
inclusive .                                                             
  2. there were no deaths in the group of six dogs in which the end     
perfusion brain temperature was 10.0 c. or higher .                     
  3. in the 17 dogs cooled to brain temperatures of 5.0 c. or less there
were nine deaths, of which five occurred quickly from cardiovascular    
failure, while four resulted from gross neurologic disturbances .       
  4. there was no evidence of aortic incompetence during whole body,    
closed chest hypothermic perfusion .                                    
  5. the lower the temperature of the brain at the end of the cooling   
perfusion, the greater was the passive transfer of heat from the        
environment .                                                           
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effects of graded hemorrhage on cardiopulmonary functions of hypothermic
dogs .                                                                  
  experiments were conducted on anesthetized dogs subjected to moderate 
hypothermia (28 c.) and then bled in percentages of the estimated blood 
volume . respiratory work was not influenced by the degree of hemorrhage
pulmonary ventilation, respiratory rate and tidal volume were not     
influenced significantly as a result of blood withdrawal . physiologic  
dead space as a percentage of tidal volume increased with hemorrhage .  
oxygen consumption decreased as the hemorrhage was made more severe,    
whereas carbon dioxide production was unchanged, indicating a shift in  
the respiratory exchange ratio . cardiac output decreased 78 per cent   
from control level when 35 per cent of the estimated blood volume was   
withdrawn . systemic arterial pressures decreased markedly but heart    
rate was not changed as a result of blood withdrawal . comparison of    
responses to hemorrhage in hypothermia and normothermia is discussed .  
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hypothermia in management of acute renal failure .                      
  1. prolonged hypothermia begun in the period immediately following the
infusion of epinephrine into the renal artery appears to give partial   
protection against renal damage .                                       
  2. shorter periods of hypothermia do not appear to be beneficial .    
  3. prolonged hypothermia at 28 to 30 c. has a mortality rate of 50    
percent
to 60 percent .
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2803. effect of dosage on endotoxin-induced changes in the reticuloendothelial
system of rabbits
tissues were removed from rabbits 4
and 24 hr. following an i.v. injection of 5,
25, or 200 ug of endotoxin.  explants of
tissues from normal and injected animals
were grown in a coagulated plasma medium
and in medium containing 1 ug/ml of
endotoxin.  the migration and growth of cells
were observed during the following week
of incubation.  the inhibition or stimulation
of cells of the reticuloendothelial system
(res) at different host sites after endotoxin
administration depended on the dosage
and on the known capacity of different organs
to take up circulating endotoxin.  macro-
phage migration was suppressed in cultures
of spleen removed 4 hr. after a dose of
hibited by 200 ug, but macrophages in
lymph node, testis, and thymus showed an in-
crease in numbers, in extent of migration
and in phagocytic activity.  widespread
res stimulation was seen in tissues removed
24 hr after the largest dose.  in ad-
dition to the restoration of re cell activity in
spleen and lung there was a marked
increase in the migration of large phagocytic
cells from bone marrow, as well as
other organs.  macrophages from endotoxin-injected
animals were as sensitive as
normal macrophages to added endotoxin in vitro.
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3075. vaccinia pneumonia in mice.  a light and electron microscopic and viral
assay study
swiss white mice between 2 and 4 days of age
developed generalized vaccinia viral
infection 2 to 7 days after intranasal inoculation.
gross and histologic evidence of
pneumonia was seen in more than 80% of
approximately 300 mice.  virus was re-
covered in relatively high titers from the
lungs (10   pfu per g) during the per-
iod when pneumonia developed; viremia
was also present, but virus titers in the
blood stream remained much below those
in the lungs.  histologically, vaccinia
pneumonia was characterized by large swollen
mononuclear cells giving rise to
marked widening of alveolar septa.  only
scattered neutrophils were noted, usually
in association with cell necrosis.  exudation
of edema fluid and red cells into al-
veoli was considered the result of viral
replication and cytopathic effect on cells
comprising alveolar septa.  various forms
of vaccinia virus were observed by elec-
tron microscopy within both 'type i' and
'type ii' alveolar lining cells, capillary
endothelial cells, and interstitial cells
within alveolar walls.  these infected inter-
stitial cells were probably derived from
fixed macrophages and were noted also
around bronchioles.  virus particles were
similarly observed in bronchiolar epi-
thelium and surrounding smooth muscle
cells.  the earliest pathologic ultrastruc-
tural change noted in virus infected cells
was intracellular edema, evidenced by
low electron density of the background
cytoplasmic material and dilatation of the
endoplasmic reticulum.  more extensive
changes resulted in cell necrosis with
release of virus particles into the extracellular space.
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1161. electron microscopy of the bovine lungs  lattice and lamellar structures
in the alveolar lumen
in an electron microscopic study of samples
from the lungs of 20 normal cattle,
and from 4 with high mountain disease, lattice
and lamellar structures were obser-
ved free in the alveolar lumens in 25% of the
normal cattle and in 100% of those with
high mountain disease.  in one specimen, a
lattice and lamellar structure was ob-
served in a vacuole within an alveolar epithelial
cell.  all others were extracellular.
the shape and dimensions of these lattice and
lamellar structures were similar to
those described by other workers in experiments
involving intratracheal injections
of silicon and oleic and linoleic acid.  this is the
first report of the structures free
in the alveolar lumens of apparently normal cattle.
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1162. electron microscopy of the bovine lungs  the blood-air barrier in acute
pulmonary emphysema
electron microscopic studies of experimentally
induced acute pulmonary emphy-
sema in 2 cows yielded the following findings
alveolar epithelial edema and cyto-
lysis, endothelial 'thinning' and cytolysis,
excessive elastic and collagenous alveo-
lar wall fibrosis, hyperplasia of alveolar
wall smooth muscle, numerous intra-
alveolar lattice and lamellar bodies, hyaline
membrane formation, hypertrophied
endothelial perikaryons, numerous alveolar
macrophages, and alveolar epithelial
secretion of an electron-dense amorphous mass.
it was postulated that the lattice
and lamellar bodies were a result of degenerating
alveolar epithelial cells.
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1560. the ultrastructure of the lungs of lambs.  the relation of osmiophilic
inclusions and alveolar lining layer to fetal maturation and experimentally
produced respiratory distress
the lungs in 69 fetal and newborn lambs
were studied.  osmiophilic inclusion bodies
first appeared at about 121 days gestation
and their total number increased with
maturation.  normal surface activity of
lung extracts was detectable a few days
following the appearance of inclusion
bodies.  the excretory nature of the type ii
alveolar epithelial cell, the phospholipid
nature of the inclusion body content, the
decrease in the number of inclusion
bodies and their loss of density associated
with respiratory distress and with the
loss of normal surface activity of lung ex-
tracts provide strong evidence that
inclusion bodies are the source of pulmonary
surfactant.  a dense osmiophilic alveolar
lining layer in mammals is described.
since the presence of such a layer is
well correlated with surface tension values
and the number of inclusions, it is
suggested that this layer consists of surface
active substances.  the difficulty in
detecting such an osmiophilic layer in other
mammals is thought to be, at least
in part, due to species differences in the compo-
sition of materials constituting the
pulmonary surfactant.  cytologic immaturity
exists until lamb fetuses reach 135
days gestation.  this is considered to be the
basis for the susceptibility of immature
lambs to respiratory distress.  fibrin with
230 a periodicity is a component,
although a small one, of hyaline membranes in
lambs.  in view of the fact that mature
fibrin appearing as bundles of fibrils is rare-
ly found, it is suggested that the bulk
of the hyaline membrane is not a mature fi-
brin, but probably consists of polymers
of fibrinogen and serum protein.
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1685. differentiation of exfoliative broncho-alveolar disease from desquamative
interstitial pneumonia
three cases are presented of the pulmonary
disease described by liebow and asso-
ciates and named by them desquamative
interstitial pneumonia.  the cases support
the existence of the entity and the contention
that it had not been previously described.
a differential diagnosis between exfoliative
bronchoalveolar disease and desquamative
interstitial pneumonia is submitted.  clinical,
roentgenologic and histopathologic mani-
festations are tabulated for each condition
and the differences between them are em-
phasized.  additional symptoms, changes
and phenomena not previously recorded are
introduced.  the most distinctive differences
between the 2 diseases were found in
the histopathologic manifestations.
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3831. lysosomes in the rat sciatic nerve following crush
peripheral nerves undergoing degeneration
are favorable material for studying the
types, origins, and functions of lysosomes.
the following lysosomes are described
(a) autophagic vacuoles in altered schwann
cells.  within these vacuoles the myelin
and much of the axoplasm which it encloses
in the normal nerve are degraded (wal-
lerian degeneration).  the delimiting
membranes of the vacuoles apparently form
from myelin lamellae.  considered as
possible sources of their acid phosphatase are
golgi vesicles (primary lysosomes), lysosomes
of the dense body type, and the endo-
plasmic reticulum which lies close to the vacuoles.
(b) mebranous bodies that accu-
mulate focally in myelinated fibers in a zone extending
2 to 3 mm distal to the crush.
these appear to arise from the endoplasmic reticulum
in which demonstrable acid
phosphatase activity increases markedly within 2 hours
after the nerve is crushed.
(c) autophagic vacuoles in the axoplasm of fibers
proximal to the crush.  the break-
down of organelles within these vacuoles may have
significance for the reorganization
of the axoplasm preparatory to regeneration.
(d) phagocytic vacuoles of altered
schwann cells.  as myelin degeneration begins, some
axoplasm is exposed.  this
is apparently engulfed by the filopodia of the schwann
cells, and degraded within the
phagocytic vacuoles thus formed.  (e) multivesicular
bodies in the axoplasm of myelina-
ted fibers.  these are generally seen near the nodes of ranvier.
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2431. histochemistry of surface epithelial and pleural mucins in mammalian
lung.  the demonstration of sialomucin in alveolar cuboidal epithelium
sialo- and sulfomucins have been demonstrated
histochemically in the surface
layer of the lung and pleura from rabbit,
syrian hamster, guinea pig, mouse, and
man.  sialomucin predominates in the distal
bronchial tree and covers the alveolar
epithelial surface.  the possible significance
of these observations is discussed.
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617. maturation of postnatal human lung and the idiopathic respiratory distress
syndrome
maturation and pathologic alterations of the lung
in 19 newborn infants who died of idiopathic respiratory
distress syndrome were studied by light-and electron
microscopy.  normal lungs from 6 fetuses and 11 new-
borns served as controls.  in all infants with idiopathic
respiratory distress syndrome, respiratory bronchio-
les and alveolar ducts usually presented the histologic
pattern of mature lungs, i.e. they were predominantly
lined by type i cells, which also formed the epithelial
component of most blood-air barriers.  well expanded
alveoli exhibited a similar pattern, whereas collapsed
alveoli were lined by numerous type ii cells which par-
ticipated in the formation of poorly developed blood-air
barriers.  the capacity of type ii cells to produce in-
clusion bodies seemed to increase with survival beyond
the 14th hr of age.  secretion of inclusion bodies and
presumably surfactant into alveolar spaces did occur
but only in the lungs of infants older than 2 days.  how-
ever, this process was not accompanied by reduction
in the number of type ii cells per alveolus as in the nor-
mal lung.  the distribution of pathologic changes in idio-
pathic respiratory distress syndrome appeared to be
determined by the degree of maturity of the air sacs.
structurally mature air sacs were associated with da-
mage of epithelial lining and hyaline membrane forma-
tion.  in contrast, collapsed alveoli revealed an intact
epithelial lining and marked septal edema but were free
of hyaline membranes.  the findings of this study sug-
gested that transudation of plasma through well develop-
ed blood-air barriers was responsible for epithelial
damage and hyaline-membrane formation in air sacs.
they also suggested that alveolar collapse and presuma-
bly lack of surfactant were related to abnormal matura-
tion of the epithelial lining and to septal edema.
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903. lattice structures and osmiophilic bodies in the developing
respiratory tissue of rats
osmiophilic inclusions have been observed in the
lungs of rats particularly in the 20-day rat embryo and
newborn up to 3 days post partum.  these inclusions
are present in the large alveolar cells as dense lamin-
ated structures of variable size and configuration.  they
generally consist of concentrically arranged membranes
and have the appearance of myelin figures, usually with
a dense center.  these osmiophilic inclusions are fre-
quently seen in direct contact with the cell membranes
and the alveolar space.  the alveolar space contains
numerous osmiophilic myelin figures which are thought
to originate from the intracellular osmiophilic inclu-
sions.  they may extrude through a channel formed in-
side the cell or by rupture of the cell membrane.  secre-
tion materials may occasionally be seen in the cyto-
plasm of the large alveolar epithelial cells.  these cells
appear to be in the process of degeneration.  their cell
surfaces are disrupted and the cytoplasm is continuous
with materials in the air space.  the lattice structure
in the alveolar space may originate from the cytoplas-
mic secretion material.  the cytoplasmic secretion ma-
terial in the cell and the lattice structures in the air
space disappear after the rats are 3 days old.  (i,t*)
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454. xanthogranuloma (xanthoma) of choroid plexus.  the origin of foamy
(xanthoma) cells
a case of a 3-month-old infant with intense pro-
liferation of choroidal epithelium with foamy cells, a
second similar case in a 9-month-old infant with gener-
alized glycogen storage disease and a case of a 51-year-
old male with bilateral xanthogranuloma of choroid
plexus and proliferation of the choroidal epithelial cells
are discussed.  the pathogenesis of the foamy xanthoma
cells in the stroma of the choroid plexus, particularly,
is discussed.  the authors believe that the origin of foamy
cells and the mode of formation of such a xanthogranuloma
can be explained by the proliferative capability and the
phagocytic activity of the choroid epithelium.  choroidal
epithelial cells can be regarded as fixed macrophages
which becomes wandering phagocytes after detachment.
disintegration of these foamy cells then releases the
lipid content into the interstitium and provokes a re-
sponse of macrophages and multinucleated giant cells
of the foreign-body type.  hemorrhage is also considered
as a factor involved in the formation of xanthogranuloma.
.I 285
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4. mixed hematopoietic and pulmonary origin of 'alveolar macrophages' as
demonstrated by chromosome markers
the origin of alveolar macrophages was investiga-
ted in mouse chimeras in which the hematopoietic cells
could be identified by marker chromosomes.  by chro-
mosome analysis it was found that in both normal lungs
and in lungs exposed to an irritant, approximately two-
thirds of the dividing cells which could be recovered by
lung washing arose from the hematopoietic system and
one-third were of pulmonary origin.
.I 286
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632. pulmonary alveolar proteinosis.  a study using enzyme histochemistry,
electron microscopy, and surface tension measurement
lung biopsies from 4 patients with pulmonary al-
veolar proteinosis were studied using histochemical me-
thods, electron microscopy, and surface tension mea-
surement.  the lipid-rich intraalveolar fluid contained
material with the staining reactions and ultrastructure
of phospholipid.  although many alveoli were lined by
enzymatically active, secreting granular pneumonocy-
tes, extracts of proteinotic tissue were not surface
active, and, in fact, inhibited normal surfactant.  some
of the cells free in the intraalveolar material were de-
generating sloughed granular pneumonocytes.  at the
margins of the lesions were lipid-filled macrophages
which appear to play a role in the removal of the mate-
rial.  these observations indicate that alveolar protein-
osis is not a primary overproduction of surfactant and
are consistent with the concept that the alveolar clear-
ing process is defective in this disease.
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1688. surface phenomena in lungs in health and disease
in summary, the authors have attempted
to bring together the multiple observations
which seem germane to the understanding
of surface phenomena in lungs in health
and disease.  to this end, the contributions
of anatomists and pathologists on the
fine structure of alveolar cells and their
lining are fundamental.  the concepts of
alveolar stability required the special
insights of physiologists who were concerned
with the causes of bubble stability as
they related to the particular problems posed
by a lung of several millions of bubbles
arranged in parallel.  soon the contributions
of the chemists became significant as
methods of identification and assay of the al-
veolar lining material were of interest.
clinicians asked what relevance these studies
had to atelectasis as it occurs in disease,
and soon the question of when the surfac-
tant appeared in development occurred to
those concerned with premature infants.
students of metabolism began to focus on
the lung as a site of phospholipid synthesis,
and their tools seem most promising at
this time in unearthing possible errors in
metabolism which may express themselves
in disease.  surgeons who undertake per-
fusion of the isolated lung ask the
requirements of that organ with respect to the
nutrients and environment of the alveolar
cells, and anesthesiologists inquire into
the possibilities of mechanical injury
to the alveoli during artificial respiration.
the problems posed to the reviewers
of a subject which touches so many disciplines
are obvious.  doubtless some pertinent
studies have been omitted although uninten-
tionally; others may have been
misinterpreted through lack of qualifications as spe-
cialists in all specialties.  the
authors hope they have provided evidence that the
forces of surface tension cannot
be ignored in an organ with an air-liquid interface
of some 70 m2.  they further hope
they have described some of the properties of
the film at the alveolar-air interface
which operate to produce stability of the alveoli.
they hold the belief that study of the
metabolism of the alveolar lining layer will
further their understanding of a number
of disease processes in which it may be
altered.  and lastly, they hope for much
closer communication between workers in
many disciplines who can elucidate this
remarkable subject best through cooperative
studies.
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1689. alterations in pulmonary surface active lipids during ex-
posure to increased oxygen tension
the syndrome of progressive respiratory
distress, pulmonary edema, and increased
pulmonary surface tension was induced in
8 dogs by exposure to oxygen tensions
greater than 550 mm hg for 44.5 and 52
hours.  pulmonary surfactant was extracted
by endobronchial washing for measurement
of lipid composition and surface activity.
five dogs developed respiratory distress
without pulmonary edema.  in these dogs
endobronchial wash surface tension was
normal or slightly increased, and total
lipid distribution was essentially normal.
esterified fatty acids in the lecithin frac-
tion were consistently altered with a
reduction in palmitate and total saturated fatty
acids.  three dogs developed pulmonary
edema with increased surface tension, in-
creased total lipid and protein, and
relatively decreased total phospholipid in the
endobronchial washings.  esterified
fatty acids in the lecithin fraction were marked-
ly altered with palmitate levels about
1/3 normal.  esterified arachidonate was pre-
sent that was attributed to intra-alveolar
plasma.  electron micrographs of the lung
after oxygen exposure showed thickening
of alveolar basement membrane and altera-
tions in the structure of the lamellar bodies
of the type ii alveolar epithelial cells.
.I 289
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3805. cisternal fluid oxygen tension in man
measurement of cerebral oxygen tension
in man has been hampered by technical dif-
ficulties.  the authors present a method
in which a beckman microelectrode was
introduced into the cisterna magna and
oxygen tension measured, the hypothesis
being that measurement of oxygen tension
in a fluid which equilibrates with the
average cerebral oxygen tension should
give reliable measure of cerebral oxygen
tension.  in their subjects, inhalation of
pure oxygen produced an increase in the
oxygen tension in the cisternal fluid as
well as in the arterial blood without any
alteration of the oxygen tension in the
bulb of the internal jugular vein, whereas
inhalation of 95% oxygen and 5% carbon
dioxide increased the oxygen tension in the
cisternal fluid as well as in the arterial
and venous blood.  5% carbon dioxide in
air produced an increase in the cisternal
oxygen tension; a fall in arterial blood
pressure associated with the introduction
of the suboccipital needle was accom-
panied by a decrease in cisternal oxygen
tension which then rose simultaneously with
the increase in arterial blood pressure
that followed infusion of dextran.  intravenous
injection of xanthinol niacinate induced
in all patients a more or less pronounced fall
in arterial blood pressure and at the
same time the cisternal oxygen tension fell;
administration of aramine was associated
with a rise in arterial blood pressure
plus a rise in cisternal oxygen tension.
.I 290
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4181. cerebrospinal fluid in man native to high altitude
csf ph was shown in a prior report to
remain essentially constant during 8 days
of acclimatization to 3,800 m.  in order
to further evaluate the possible role of
csf acid-base equilibria in the regulation
of respiration, 20 peruvian andean na-
tives were studied at altitudes of 3,720-4,820 m.
in 10 subjects at 3,720 m, means
were  csf ph 7.327, pco, 43, hco3-21.5,
na+136, k+2.6, cl-124, lactate 30 mg/
100 ml.  arterial blood  ph 7.43, pco, 32.5,
hco3-21.3, na+136, k+4.2, cl-107,
hematocrit 49, sao, 89.6.  in 6 subjects at
4,545 m and 4 at 4,820 m csf values
were not significantly different; mean arterial
pco, was 32.6 and 32.3, respectively.
the only significant variations with altitude
were the expected lowering of pao, to
47 and 43.5 mm hg, and of sao, to 84.2 and
80.7, and increase of hematocrit to
67% and 75%, respectively.  the natives
differed from recently acclimatized sea-
level residents in showing less ventilation
(higher pco,) in response to the ex-
isting hypoxia, and less alkaline arterial
blood.  the difference appears to relate
to peripheral chemoreceptor response
to hypoxia rather than central medullary
chemoreceptor.
.I 291
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1116. na, k, ca, mg, and cl concentrations in choroid plexus fluid
and cisternal fluid compared with plasma ultrafiltrate
in 7 cats the concentrations of na,
k, ca, mg, and cl were measured in plasma
ultrafiltrate, newly formed choroid
plexus fluid, and cisterna magna fluid.  the
choroid plexus fluid did not differ
from plasma ultrafiltrate in cl and k concentra-
tion but contained higher na, markedly
higher mg, and lower ca concentrations
than the ultrafiltrate.  cisterna magna
fluid differed from the ultrafiltrate with
respect to all 5 electrolytes, containing
higher concentrations of cl, na, and mg
and lower concentrations of k and ca.
it differed from choroid plexus fluid in con-
taining a higher concentration of cl but
lower concentrations of k, ca, and mg.
hco3-concentration, calculated on the
basis of the charge balance, was 7 mm/kg
h2o higher in choroid plexus fluid than
in cisterna magna fluid, suggesting an ele-
vated ph at the former site.  without
measurement of the potential difference be-
tween the csf and plasma, definitive
conclusions could not be drawn as to which
cations were actively transported.  the fact
that the distribution ratio between cerebro-
spinal fluid and ultrafiltrate of one divalent
cation was in the opposite direction
from that of the other, and that this was
also true of the monovalent cations, was
taken as evidence that the mechanisms
involved in cation transfer are quite selec-
tive.  though not proven, active transport
was considered the most likely explana-
tion of these findings.  the data suggest
that these specific transfer mechanisms
subserve a homeostatic function with
regard to mg and k in the cerebrospinal fluid.
.I 292
.W
3230. cerebral hemodynamics, blood gases, and electrolytes
during breath-holding and the valsalva maneuver
continuous recordings of arterial and
internal jugular blood oxygen tension, oxy-
gen saturation, carbon dioxide tension,
ph, sodium and potassium, together with
peco2, blood pressure, and
electroencephalogram were obtained to compare the
effects of inspiratory and expiratory
breath-holding and the valsalva maneuver on
the cerebral circulation and cerebral
oxygen availability in man.  during the inter-
val of tolerated breath-holding for
69 seconds or less, jugular venous oxygen tension
was increased owing to increased
cerebral blood flow resulting from an increase
of arterial carbon dioxide tension.
there was a statistically significant correlation
between changes in jpo2 and paco2,
which proved to be more or less linear for
both increases and decreases of paco2 4 mm.
above and below control levels.  no
threshold was found for changes in paco2
altering effective cerebral perfusion and
cerebral venous po2, extremely small
changes in paco2 (less than 1 mm. hg)
altered cerebral oxygen availability within
10 to 20 seconds.  during the valsalva
maneuver a consistent reduction of jugular
oxygen tension was found associated
with the sudden fall in arterial blood
pressure and reduction of arterial carbon
dioxide tension.  the rapid changes in
cerebral hemodynamics and cerebral oxy-
gen availability during the procedure
are briefly discussed.
.I 293
.W
2344. respiratory and cardiovascular changes during rapid spon-
taneous variations of ventricular fluid pressure in pa-
tients with intracranial hypertension
in patients with intracranial hypertension
the ventricular fluid pressure (vfp)
curve is characterized by 3 main forms
of spontaneous variations.  two of these
forms are of a rhythmical nature, and
are here called 1-per-minute waves and 6-
per-minute waves, respectively, in
accordance with the dominating frequency.
the third form - irregularly appearing
waves of large amplitude and duration -
is called plateau waves in accordance
with the usual shape of the fluctuations.
respiratory and cardio-vascular changes
accompanying these variations of the vfp
were studied by simultaneous recording,
in various combinations, of the vfp, the
pulmonary ventilation, the pco2 of the
expiratory air, the arterial and the venous
blood pressure, and the pulse frequency.
it was found that the rhythmic vfp vari-
ations of the 1-per-minute type occurred
synchronously with the respiratory peri-
ods in cheyne-stokes breathing.
synchronously appearing variations in systemic
blood pressure, in pulse frequency,
as well as in consciousness and in muscular
tone of the limbs were also noted.  the
respiratory midposition shifted towards the
inspiratory side during the periods of
hyperpnoea.  the 6-per-minute waves were
entirely synchronous with variations
in the systemic arterial blood pressure of the
traube-hering-mayer type.  long
sequences of these waves were observed only
when the vfp level was considerably
elevated.  the plateau waves were not accom-
panied by corresponding elevations of
the arterial or venous systemic blood pres-
sure.  simultaneously with the crests
of the plateau waves sudden changes often
occurred in the pulse frequency (from
bradycardia to tachycardia), and in the res-
piratory pattern, sometimes also in the
degree of consciousness and in the muscu-
lar tone.  there were also long sequences
of 6-per-minute waves.  the deep, irre-
gular breathing seen in this stage induced
a considerable hypocapnia preceeding
the final critical fall in the vfp ending the
plateau wave.  in most instances, how-
ever, this fall did not begin until several
minutes after the appearance of the hypo-
capnia.
.I 294
.W
82. central nervous system lesions in rats
exposed to oxygen at high pressure
adult female rats paralyzed by repeated exposures
to oxygen at high pressure were found to have cns le-
sions of 2 types  (1) focal necrosis of individual neurons
within certain nuclear groups, and (2) complete or partial
necrosis of nuclear groups with frequent damage to mye-
lin, axons, and glia in the area involved.  both types
were usually bilateral and symmetrical.  lesions of the
first type were found consistently in the superior olivary
complex, ventral cochlear nuclei, and nuclei of the spinal
tract of cranial nerve v.  lesions of the second type were
found consistently in the substantia nigra and globus pal-
lidus, were frequent in the rhinencephalon, and never
occurred in the neocortex.
.I 295
.W
747. electrode size and tissue po2 measurement in rats exposed
to air or high pressure oxygen
a comparison has been made of values of
po2 recorded in several rat tissues with
60-u or 330-u flexible gold electrodes.
although qualitatively both sizes of elec-
trodes give similar results, the quantitative
values of po2 differ.  such large differ-
ences as are found in some cases between
electrodes varying only in physical di-
mensions are thought to reflect the amount
of trauma caused in the tissue under in-
vestigation due to electrode insertion.
errors in po2 estimations due to tissue da-
mage are considered to outweigh any other
errors such as those due to electrode
calibration.  soft, highly vascular tissues,
such as liver, kidney and spleen, which
show macroscopic bruising over quite a
large area when electrodes are inserted,
show the greatest difference in estimations
of the po2 value.  recordings of tissue
po2 were made while animals breathed air
and when compressed to 4 or 5 atm. in
pure oxygen, and the pattern of response of
tissue po2 to such exposure of the ani-
mal to high pressures of oxygen is described.
.I 296
.W
3384. adrenergic effects in splenic po2 of rats in air or oxygen
at 5 atmospheres
oxygen tensions have been measured
in the spleens of rats breathing air and during
exposure of the animals to 5 atm abs
of oxygen (hpo).  the response of splenic po2
to compression was complex, usually
reaching a peak value immediately after com-
pression, then falling to a lower value.
this form of response has been termed a
hump response.  after adrenalectomy
or bretylium tosylate injection the hump res-
ponse of po2 after compression was
almost abolished, and the values of splenic po2
at 5 atm were considerably higher
than in control animals.  a combination of adrena-
lectomy and bretylium tosylate also
markedly reduced the number of hump responses,
but unexpectedly significantly lowered
splenic oxygen tensions, both when the ani-
mals were under ambient conditions
or at 5 atm of oxygen.  cardiac rate and blood
pressure were studied in an attempt
to find the explanation of this latter effect, and
while blood pressure was the same
in adrenalectomized rats and control rats after
bretylium injection, adrenalectomy
potentiated the bradycardia produced by brety-
lium tosylate.
.I 297
.W
10642. the effects of antioxidants on high pressure oxygen toxicity
several commonly used antioxidants have
been tested for their effect against poison-
ing due to high pressures of oxygen (ohp).
the tests used were preconclusive pe-
riod and survival time of mice at 5 atm
absolute oxygen, lung damage in rats ex-
posed to 5 atm oxygen for 1 hr., and post
ohp paralysis in rats following deep
pentobarbital-na anesthesia and ohp at 4
atm for 30 min.  2,5-bis (1,1-dimethyl-
propyl) hydroquinone gave excellent
protection against ohp toxicity in all tests,
and several other antioxidants also
protected against ohp toxicity but their potency
and effectiveness varied for the
different criteria of oxygen poisoning tested in the
experiments.
.I 298
.W
3716. glycolytic control mechanisms. i. inhibition of glycolysis
by acetate and pyruvate in the isolated, perfused rat heart
acetate or pyruvate had similar effects
on the over-all metabolism of glucose.  gly-
colytic flux was decreased in both the
presence and absence of insulin, glucose
oxidation was greatly decreased, and
the conversion of glucose to glycogen and lac-
tate was promoted.  glucose phosphorylation
was decreased in the presence but not
in the absence of insulin.  hexokinase,
phosphofructokinase, glyceraldehyde phos-
phate dehydrogenase, and pyruvic kinase
are far displaced from equilibrium, while
the other enzymic steps of glycolysis
are maintained either at equilibrium or fairly
close to equilibrium.  in different metabolic
situations, glycolytic flux may be affec-
ted by those steps which are far displaced
from equilibrium.  increased levels of
the hexose monophosphates, and decreased
levels of the other glycolytic inter-
mediates between fructose 1,6-diphosphate
and pyruvate after the addition of 10 mm
acetate indicate that glycolytic flux was
decreased by inhibition of phosphofructo-
kinase.  after the addition of 10 mm pyruvate,
fructose 1,6-diphosphate, and triose-
phosphate accumulated as a result of an
inhibition of either glyceraldehyde phosphate
dehydrogenase or phosphoglyceric kinase.
acetate had little effect on the total con-
tent of oxidized or reduced di- or
triphosphopyridine nucleotides, but slightly de-
creased the ratio of nad to nadh2
in the cytoplasm, as estimated from the ratios
of lactate to pyruvate and a-glycerophosphate
to dihydroxyacetone phosphate.  pyru-
vate increased the total content of nadh2
and nadph2 as shown both by an increase
of fluorescence in the intact heart, and by
tissue analyses, but the ratio of nad to
nadii2 in the cytoplasm was greatly
increased.  these results demonstrate com-
partmentation of pyridine nucleotides
between cytoplasm and mitochondria in the
intact cell.  after the addition of acetate,
citrate was the only intermediate of the
citric acid cycle which increased greatly
in amount, while oxaloacetate levels de-
creased.  after the addition of pyruvate,
the levels of citrate, a-ketoglutarate, ma-
late, and oxaloacetate were all greatly
elevated.  the glutamic-oxaloacetate trans-
aminase reaction as measured from the
total contents of the reactants in the tissue
remained close to equilibrium.  changes
in the concentrations of the adenine nu-
cleotides were insufficient to account for
the inhibition of phosphofructokinase, but
the results are consistent with control at this
step being mediated by citrate.
.I 299
.W
244. oxygen tension in human malignant disease under hyperbaric
conditions
oxygen tensions were recorded continuously
in tumours and normal tissues of 34 pa-
tients pressurized in pure oxygen to 4 atmospheres
absolute.  mean rises to 620 mm.
hg and 320 mm. hg for tumours and normal tissues
respectively were recorded.
with patients breathing air at atmospheric
pressure 22/90 (24%) of tumour elec-
trodes registered po2values of less than 4 mm. hg
compared to only 2/39 (5%) of normal
tissue electrodes.  the results obtained
suggest that oxygen polarography as a meth-
od for determining po2 in 'solid' tissues
in vivo is complicated by many artefacts -
particularly tissue damage due to electrode
trauma - which reduce its value to clin-
ical research concerned with accurate
information of absolute po2 values in intact
tissues.
.I 300
.W
7839.cortical ph and the blood-brain barrier
a method was described for measuring
the ph, dc and ac potentials concurrently
on the cerebral cortex of the adult cat,
under conditions of controlled ventilation.
kittens and rabbits were also studied.
the cortical ph response to i.v. nahco3
was acidic and was accompanied by a
dc negativity, while the blood became alkaline.
such an acidic response was present in
the rabbit and kitten.  it was not present
in a number of other tissues in the cat,
including the dura.  the cortical acidic
response was not affected, qualitatively,
by i.v. acetazolamide, prolonged hypoxia
or 10% (v/v) co2.  it was reduced reversibly
by 20% (v/v) co2.  it was not affected
by removal of the arachnoid membrane.
the cortical ph response to an i.v. nh4+
salt solution was complex.  nh4c1 did not
produce an alkaline response.  the cortical
ph response to an alkaline or an acidic
sodium phosphate solution was augmented
but not changed in its direction following
treatment of the cortex with n-butanol.
the results were interpreted in terms of
a restriction of hco3- by the blood-brain
barrier, through which co2 can pass.  this
restriction is probably non-specific for
inorganic ions, and perhaps for other
substances.  it does not appear to be related
to a low cerebral extracellular space,
and is independent of substantial oxidative metabolism.
.I 301
.W
7083. brain damage and paralysis in animals exposed to high pressure oxygen -
pharmacological and biochemical observations
single exposures of high pressure oxygen
(ohp) at 30-66  gauge pressure caused
cns damage and paralysis in rats and mice
but guinea-pigs, rabbits, and man did
not show such sequelae.  the cns damage
in rats was greatly increased by cns-de-
pressant drugs (pentobarbital, paraldehyde,
n2o and phencyclidine) given before ex-
posure to ohp.  the cns lesions were also
potentiated by raised respired pco2, by
acetazolamide and by nh4c1, whilst protection
was afforded by methaemoglobinae-
mia by tham, by 2 4-dinitrophenol and by
serotonin against the barbiturate and
co2 potentiation of ohp brain damage.
ohp-induced brain damage was not modified
by hypothermia (cp2), electroconvulsive
shock treatment during ohp, cerebral x-
irradiation, adrenalectomy or cortisone,
slow decompression rates, spinal block
with local anaesthetic, 'conditioning' of
rats to ohp, hyper- and hypoglycaemia, or
alterations in tissue histamine levels.
the results are discussed in relation to pos-
sible biochemical mechanisms and
theories of oxygen poisoning.
.I 302
.W
8914. the effect of hypoxia on oxygen consumption of cerebral
cortex, liver slices and of diaphragm in vitro during post-
natal development of the rat
oxygen consumption of slices from the liver
and cerebral cortex and of the cut dia-
phragm was determined in rats aged 5, 10,
14, 20 and 25 days and in adult animals.
under hypoxic conditions (gas phase 10%
oxygen, 90% nitrogen) oxygen consumption
of liver slices and diaghragm is decreased
by about 25% in all age groups.  hypoxia,
however, did not affect oxygen consumption
of slices of the cortex from 5-day-old
rats and its inhibitory effect only appeared
later as the normal oxygen consumption
started to rise.  the inhibitory effect of
hypoxia was greatest in adult animals.
.I 303
.W
5407. hypoxic-hypercapnic interaction in subjects with bilateral
cerebral dysfunction
to analyze cerebral influences modifying
autonomic respiratory responses, the
authors compared normals and patients
with bilateral pyramidal tract disease for
their ventilatory response to hypoxia and
hypoxia-hypercapnia.  during eucapnia,
the 2 groups showed similar hypoxic
responses.  during hypercapnia, the ventilatory
response to hypoxia was greater in the
brain-damaged subjects.  this apparent aug-
mentation, however, was due entirely
to anoxia interacting with an abnormally fa-
cilitated carbon dioxide sensitivity
compared with normals, brain-damaged patients
at pao,90-100 mm hg showed an 85%
greater co2 response, and at pao,50mm hg
showed a 79% greater co2 response.
since cerebral dysfunction facilitated the ven-
tilatory response to hypoxia-hypercapnia
combined but not the response to hypoxia
alone, the results imply that the 2
respiratory stimuli interact centrally rather than
peripherally.
.I 304
.W
3917. plasma free fatty acid and blood sugar levels in newborn
infants and their mothers
simultaneous plasma free fatty acid (ffa)
and blood sugar levels were determined
for fasting newborn infants during the first
24 hours of life, for their cord bloods,
and for their mothers at delivery.  the
following observations were made.  in con-
trol infants the mean ffa level rose about
three times the cord level after birth
and was accompanied by a 25% drop in the
mean blood sugar level.  thereafter, the
mean blood sugar level remained relatively
constant, but the mean ffa level varied
from 2.5 to 3 times the cord level.  there
was no significant correlation between the
length of maternal fasting prior to delivery
and the infant ffa level; there was,
however, a significant negative correlation
between the length of maternal fasting
prior to delivery and the infant blood sugar
level at 24 hours of age.  high ffa levels
occurred in the infants of obese mothers
and low levels were observed in infants with
delayed respirations, in infants of preeclamptic
mothers, and in infants of diabetic
mothers.
.I 305
.W
2933. the essential fatty acid requirement of infants and the
assessment of their dietary intake of linoleate by serum
fatty acid analysis
the content of polyunsaturated fatty acids
in serum total fatty acids was related
to the dietary intake of linoleate in 243 infants
two to four months of age and in 197
infants eleven to twelve months of age.  the
curves relating triene tetraene ratio
to dietary linoleate indicated approximately
1 per cent of total calories as minimal
linoleate requirement.  the exponential
equations relating dienoic, trienoic and
tetraenoic acids to dietary linoleate were
derived by computer methods.  these
yielded constants from which the minimal
nutrient requirement could be calculated.
the best estimates were obtained from the
triene and tetraene data for two to four
months' old infants and were found to be
approximately 1.4 per cent of the caloric
intake.  the nutritive status with respect to
linoleate may be estimated by means
of logarithmic regression equations.  the
equation for two to four months' old infants
is  log 10 dietary linoleate = -1.087 + 0.0432
(di - tri + tetra).  the data for eleven to
twelve months' old infants were found to have
greater scatter and give lower triene
tetraene ratios at comparable linoleate intakes.
the scatter and displacement are
considered to be due to supplements of solid food
to the basic diet not considered in
the calculated dietary linoleate.
.I 306
.W
74. analytic study of the a- and b-lipoprotein micellar groups
and of nonesterified fatty acids of the plasma in normal pregnancy
an analytical study has been made on 39
patients, using a chemical method which
allows the simultaneous detailed evaluation
of the lipidic and a- and b-liproproteinic
fractions of the plasma.  in addition the
non-esterified fatty acids have been titrated,
the b-proteins and the uric acid assayed,
and numerous indices and deducible ratios
made from the data obtained.  the existence
of quantitative dyslipidemia has been
proven, starting gradually, especially in the
4th-5th month of pregnancy, and most-
ly regarding the b-lipoproteins, prevalently
the slow subfractions, greater increase
of glycerides than phosphatides and cholesterol,
but with a non-proportional in-
crease of b-proteins (lower proteinic content).
it has, moreover, been noted that
there is a prevalent rise of free cholesterol in
the fraction of b-lipoproteins with
a reduction of the total esterification coefficient.
the morphological picture of the
lipidic rate in pregnancy shows characteristics
which, according to the authors,
are like those to be seen in the lipidic rate of
male presenility.
.I 307
.W
75. behavior of polyunsaturated fatty acids in physiological
pregnancy
by the enzymatic lipoxidase method of
macgee et al., the author measured polyun-
satured fatty acids (p.f.a.) in healthy
pregnant women at full term of pregnancy.
before labour there are in the blood 75-95
mg.% of p.f.a., i.e. 10-15% more
than in non-pregnant women; during labour
p.f.a. increase very much, 100-137
mg.%, about 50% more than before labour.
.I 308
.W
5196. effects of nutritional deficiency of unsaturated fats on
the distribution of fatty acids in rat liver mitochondrial phospholipids
the fatty acid composition of liver mitochondrial
phospholipids from rats rendered
deficient in essential unsaturated fatty acids
has been determined, and compared
with that of rats fed a diet containing corn oil.
in addition to marked reductions in
the amounts of linoleic and arachidonic acids
esterified at the b-position of ethanol-
amine-, inositol-, and choline glycerophosphatides,
the deficiency resulted in ex-
tensive changes in the distribution of saturated
acids at both the a- and b-positions.
palmitoleic and oleic acids were increased in
amount in fat deficiency, and large
amounts of docosatrienoic acids appeared in
these 3 phospholipids.  the fatty acids
of the sphingomyelins were not altered as a
result of essential fatty acid deficiency.
the data demonstrate that each phospholipid
is unique in the way in which its fatty
acid moieties change in response to feeding
a fat deficient diet.
.I 309
.W
3204. interventricular septal defects with aortic insufficiency
sanchez f.-villaran e.
the coincidence of these 2 malformations
permits their diagnosis provided that a
careful evaluation is made of the hemodynamic
and oximetric data, on the basis of
specific auscultatory features.  even then, a
differentiation from other cardiopathies
patent ductus arteriosus with/without pulmonary
hypertension, aortopulmonary sep-
tal defect, interventricular communication,
truncus arteriosus, aneurysm of the
sinus aortae ruptured into right cavities - is
not simple.  for this an analysis of the
course of the syndrome together with the
information supplied by phonocardiography,
catheterization, angiocardiography, radiology
and ecg (in this order of importance)
are indispensable.  an analysis is made of 5 cases
in which, in the absence of ana-
tomical confirmation, concrete data were obtained
on which to base the diagnosis.
.I 310
.W
2579. measurement of aortic regurgitation by upstream sampling with continuous
infusion of indicator
a direct and theoretically valid method
for the measurement of aortic regurgitation
involves the recording of indicator concentrations
from the left ventricle and a down-
stream site during aortic root injection.  however,
this method has yielded erratic
results when applied to man in the authors'
laboratory when using the sudden in-
jection technique.  therefore, the upstream
sampling method, using continuous in-
fusion of indicator, was evaluated in 18 patients
with aortic regurgitation during
retrograde aortic and transseptal left ventricular
catheterization.  the continuous
infusion technique was compared with the technique
of sudden injection in 10 patients
and with aortic valvulography in 14 patients.
measurements of forward flow obtained
with continuous infusions into the aortic root
were not significantly different from
measurements obtained with sudden injections
into the pulmonary artery.  recordings
of indicator concentrations from the left ventricle,
during continuous infusions into
the aortic root, demonstrated readily evident
equilibrium plateaus.  the resultant
measurements of regurgitant flow were highly
reproducible and not impaired by
nonsimultaneity of upstream and downstream
sampling.  the percentage error of
estimate at 95% confidence limits was 22% of
the measurement for regurgitant flow,
13% for total flow, and 9% for the regurgitant
fraction of total flow.  the correspond-
ing errors of estimate for the sudden injection
technique were 4 times larger.  re-
gurgitant flow by the continuous infusion method
ranged from 0.8-30.0 l/min, total
flow from 3.0-36.0 l/min, and the regurgitant
fraction of total flow from 12-86%.
ranking of patients by the magnitudes of regurgitant
and total flow did not correspond
to ranking by angiographic criteria of severity.
however, an excellent correlation
prevailed between angiographic grade and the regurgitant
fraction of total flow,
demonstrating that this variable is the most meaningful
expression of severity.  the
correlation (0.997) between the angiographic grade and
the regurgitant fraction
measured by the continuous infusion technique was
clearly superior to that obtained
with the sudden injection technique (0.894).  mild
regurgitation was equivalent to
a regurgitant fraction of <25%, moderate
regurgitation to a fraction of 25-50%,
moderately severe regurgitation to a fraction
of 50-75% and severe regurgitation to
a fraction of >75%.  it is concluded that the
upstream sampling method during con-
tinuous infusion of indicator, because of its
sensitivity, reliability, applicability to
multiple measurements, and validity in the
presence of mitral regurgitation is the
most useful method for quantifying aortic
regurgitation in man.
.I 311
.W
2950. aortico-left ventricular tunnel.  a cause of massive aortic regurgitation
and of intracardiac aneurysm
the clinical, roentgenographic, hemodynamic
and pathologic findings in a 14-year-
old boy with aortico-left ventricular tunnel are
presented.  the accessory channel
between the aorta and left ventricle resulted in
massive aortic regurgitation, and
the portion of the tunnel which traversed the
ventricular septum was aneurysmal,
displaced the posterior wall of the right
ventricle and caused severe obstruction
to right ventricular outflow.  the presence
of associated cardiovascular anomalies,
in this and previously reported cases,
suggests that the malformation is congenital
rather than acquired.  the clinical and
hemodynamic manifestations of aortico-left
ventricular tunnel are indistinguishable
from those observed with the more common
forms of aortic regurgitation, and the
correct diagnosis can be established only by
thoracic aortography.  the malformation
is usually recognized in childhood; since
aortic regurgitant flow can be abolished by
simple closure of the aortic ostium,
and without aortic valve replacement, the
indications for operative treatment
differ from those which apply in aortic
regurgitation due to a valvular anomaly.
.I 312
.W
502. the haemodynamic implications of the bisferiens pulse
a bisferiens carotid arterial displacement pulse
was recorded in 10 patients with
severe aortic valvular disease.  the braunwald
test indicated that moderately severe,
severe, or gross aortic regurgitation was present
in each.  the absence of a peak
systolic aortic pressure gradient in certain cases,
particularly in those with the
most severe regurgitation, suggested their freedom
from an element of stenosis.
the anacrotic wave and the peak of the aortic
pressure pulse were found to coincide
with the percussion and the tidal waves of the
simultaneously recorded carotid ar-
terial displacement curves.  it is suggested that
amplitude of the peak of the anacro-
tic wave is proportional to the rate of change of
momentum of the ejected blood, and
that the amplitude of the corresponding percussion
wave of displacement is modified by
the distensibility of the artery.  the depth and shape
of the trough between the two
peaks is thought to depend upon the magnitude and
slope of the two waves rather than
upon a venturi effect.  it is suggested that the condition
of the arterial wall, the dia-
stolic blood pressure, and the stroke volume can
influence the pulse sufficiently to
preclude its use as a simple guide to the nature of
the aortic valve lesion.
.I 313
.W
2753. left ventricular function following replacement of the
aortic valve.  hemodynamic responses to muscular exercise
evaluations of left ventricular myocardial
function were carried out in 14 patients
4-16 mth after stenotic or regurgitant
malformations of the aortic valve had been
corrected by valve replacement.  the
circulatory responses to exercise, judged by
the increases in cardiac output in relation
to the increases in oxygen consumption,
were normal or only mildly reduced in 12
patients.  in 5 patients the relationships
between the change in the left ventricular
end-diastolic pressure and the alteration
in the stroke volume were also normal, a
fall or an increase in left ventricular
end-diastolic pressure of less than 3 mm
hg being accompanied by an increase in
stroke volume.  in 8 patients, however,
abnormal increases in the left ventricular
end-diastolic pressure occurred during
exercise, and in 4 the left ventricular end-
diastolic pressure was increased to levels
above 12 mm hg.  variable alterations in
the stroke volume accompanied these increases
in end-diastolic pressure.  it is
suggested that in the 3 patients who exhibited
simultaneous increases in left ven-
tricular end-diastolic pressure and stroke
volume, the changes were either a mani-
festation of the frank-starling mechanism,
or primarily the result of a positive
inotropic influence.  in the 5 patients who
exhibited increases in left ventricular
end-diastolic pressure, but no change or a
fall in stroke volume, it is proposed
that a distinct depression of left ventricular
performance was present.  thus, while
the cardiac output response was adequate to
meet the stress of exercise in the
majority of the patients studied following aortic
valve replacement, determination
of the relationship between the left ventricular
end-diastolic pressure and the stroke
volume permitted the detection of abnormalities
in the function of the left ventricle.
.I 314
.W
2497. pulmonary atresia with intact ventricular septum
when the pulmonary valve is atretic and
the ventricular septum intact, the right
ventricle usually consists of a small chamber
with a very thick wall capable of de-
veloping high pressure.  this pathologic picture
is associated with clinical findings
similar to those in tricuspid atresia-cyanosis,
decreased pulmonary flow, left ven-
tricular preponderance on the electrocardiogram,
and early death.  the diagnosis
may be confirmed by heart catheterization and
selective angiocardiography with in-
jection into the right ventricle, but the risk is
great.  surgery has never been suc-
cessful in the past; but because of the equally
hopeless prognosis on medical treat-
ment, attempts should continue to be made.
anastomosis of the superior vena cava
to the right pulmonary artery appears to offer
hope of success in the future.
.I 315
.W
1635. intra-atrial pressure measurement and electrocardiography in the
detailed diagnosis of atrial septal defect
after discussing the possibilities and
limitations of different methods for identifying
the anatomical type of atrial septal
defect, the authors suggest a more useful new
method.  this consists in simultaneous
recording of both the pressure curve and
endocavitary electrocardiogram during
withdrawal of the catheter from the left into
the right atrium.  in the ostium primum
type, the septal foramen has no infe-
rior margin, and the point of the catheter
during retraction (unlike in the ostium
secundum type) rests on the intermediate
section of the atrioventricular septum.
the endocavitary electrocardiogram in the
zone of passage between the two atria
shows the typical pattern of the intermediate
section of the atrioventricular septum;
the pressure curve may show a pattern of the
atrial of intravalvular type.
.I 316
.W
1636. ventricular septal aneurysms.  a report of two cases
two cases of ventriuclar cuptal aneurysm
are reported, one in the membranous and one
in the muscular portion.  the diagnosis was
made by selective left ventricular angiogra-
phy.  it is suggested that these cases represent
spontaneous closure of a ventricular septal
defect with weakness and aneurysmal formation
due to the high left ventricular pressure.
both are asymptomatic and hemodynamically
within normal limits.  surgical repair
of the aneurysms is not considered necessary.
.I 317
.W
1642. electrode catheters and the diagnosis of ebstein's anomaly
of the tricuspid valve
the successful surgical treatment of ebstein's
anomaly calls for accurate pre-ope-
rative assessment of the nature and severity of
the tricuspid valvular lesion.  the
increased risk of cardiac catheterization in this
condition has been matched by in-
creased experience of intracardiac techniques,
and provided the examination is in
skilled hands, patients with ebstein's anomaly
should be investigated in the same
way as those with any other serious congenital
heart lesion for whom surgery is con-
templated.  the diagnostic value of electrode
catheters is discussed, and the intra-
cardiac electrocardiographic features of ebstein's
anomaly are illustrated.  false
positive and false negative records are demonstrated
and the mechanism of their
production is explained.  it is concluded that, though
helpful, intracardiac electro-
cardiographic evidence should be regarded as confirmatory
rather than diagnostic.
records made with electrode catheters during cardiac
catheterization should be con-
sidered only along with the other clinical,
electrocardiographic, and radiological
features of the case, and should not be relied upon
as the definitive method in the
diagnosis of ebstein's anomaly.
.I 318
.W
3326. unusual aneurysm of the membranous interventricular septum
the case of a patient with a huge aneurysm of the
membranous interventricular
septum is presented.  this is believed to be the
first such patient to have undergone
successful resection.
.I 319
.W
934. laevocardia with situs inversus.  a case report and a review of literature
a case of levocardia, with
inversion of the cham-
bers of the heart and
transposition of the great vessels
and situs inversus, has been described.
gross cyanosis
and clubbing were present and were due
to a veno-arteri-
al shunt through a right-sided superior
vena cava open-
ing into the arterial atrium and
passage of venous blood
into the aorta through a ventricular
septal defect.  the
case was complicated with right-sided
hemiplegia and
with the development of a liver abscess.
a review of the
literature with prognosis and possible
etiology of the
condition has also been made.
.I 320
.W
1831. postoperative aneurysm of the right ventricle
twelve patients with postoperative aneurysm
of the right ventricular outflow tract
after corrective surgery for pulmonic valvar
stenosis, ventricular septal defect and
tetralogy of fallot are reported.  the literature
is reviewed and the pathogenesis is
discussed.  different diagnostic tests are evaluated
stressing the role of roentgen
examinations and the importance of careful follow-up
by intercalative chest roent-
genography.
.I 321
.W
1991. ventricular septal defect with aortic regurgitation.
medical and pathologic aspects
thirty-four patients with ventricular septal defect
and aortic regurgitation, repre-
senting less than 5% of the patients with ventricular
septal defect, are discussed.
a loud, systolic murmur, characteristic of ventricular
septal defect, is noted dur-
ing infancy, whereas evidences of aortic regurgitation
(protodiastolic murmur and
wide pulse pressure) does not usually appear until some
time between 2 and 10
years of age.  clinical and catheterization data indicate
that the principal hemody-
namic load is aortic regurgitation, whereas the
ventricular septal defect does not
usually result in a large pulmonary blood flow or
high pulmonary arterial pressure.
in about 50% of the patients, a significant pressure
gradient across the right ven-
tricular outflow tract exists.  detailed pathologic
studies indicate that the ventricular
septal defects are high and anterior and encroach
to a greater or lesser degree on
the membranous bulbar septum.  the right coronary
cusp is the one most severely
involved, and, by its prolapse, causes aortic
regurgitation; the noncoronary cusp
is always less severely affected.  the anatomic basis
of the pressure gradient ob-
served across the right ventricular outflow tract is
not always clear.
.I 322
.W
2431. the natural history of arrhythmias following septal defect reapir
the repair of 191 atrial and ventricular septal
defects between 1955 and 1961 was
reviewed to determine the incidence and prognosis
of arrhythmias related to operation.
cases included 90 ventricular septal defects, 61
atrial defects of the ostium secundum
type, and 40 of the ostium primum variety.
nodal rhythms, second degree blocks,
complete heart block, and flutter or fibrillation that
persisted after completion of operation
were analyzed, while intermittent ectopic beats,
sinus tachycardia, and bundle branch
blocks were excluded.  fifteen per cent of the
patients with ventricular defects, 17%
with ostium primum defects, and 35% with ostium
secundum defects developed abnormal
rhythms associated with repair.  of 18 patients whose
arrhythmias began during operation,
there were 8 deaths; no fatalities occurred in the 24
patients who developed arrhythmias
in the postoperative period.  seven deaths were
associated with complete heart block and
one with second degree block.  although only one
half of the patients who developed
arrhythmias had pulmonary artery pressure greater
than 30 mm. hg systolic, all fatalities
occurred in this group.  four of the deaths followed
surgery with the use of the pump
oxygenator in children under 30 months of age.
thirty-eight per cent of the abnormal
rhythms that began in the postoperative period
were nodal.  flutter and fibrillation
were common following repair of atrial secundum
defects in patients over 15 yr. of age
but did not occur in younger patients.  deaths from
heart block occurred in the first 30 days
following operation except one, 5 months later.
survivors of complete heart block reverted
to a less serious arrhythmia or normal rhythm
within 3 months.
.I 323
.W
1021. left ventricular angiocardiography in the study of ventricular
septal defects
sixty-five cases of ventricular septal defect
were studied by left angiocardiography.
the left ventricle was entered by retrograde
arterial catheterization with a catheter
having a j-shaped tip.  this procedure appears
to be little, or no more, hazardous
than right-sided angiocardiography.  ventricular
septal defects may be divided into
5 types, depending on their location in the ventricular
septum.  the anatomic and
radiological features of the septum and septal defects
are described.  selective in-
jection of contrast material into the left ventricle
opacifies the blood passing through
the defect in the septum and permits preoperative
localization of the defect in rela-
tion to identifiable anatomic landmarks.  multiple
defects of the septum are well de-
monstrated.  such information may be of
considerable value to the surgeon under-
taking repair of the septum.  left ventriculography,
often combined with supraval-
vular aortography, has been used, when indicated,
to differentiate between mitral
insufficiency and ventricular septal defect and in
the detection of other cardiac ano-
malies whose manifestations are marked by those
of the septal lesion.  this tech-
nique is well suited to the postoperative study of
patients following repair of the
septal defect and for follow-up studies in patients
not operated upon to clarify the
natural history of defects in different portions of
the ventricular septum.
.I 324
.W
4105. free fatty acid metabolism in chinese hamsters
in normal chinese hamsters (cricetulus
griseus) the mean concentration of free
fatty acids (ffa) in serum varied from
group to group, but was (1) consistently 4
to 9 times greater than in rats, dogs,
or man; (2) slightly higher than in syrian
hamsters; (3) two- to four-fold higher
than in fasting or alloxan-diabetic rats.  the
epididymal adipose tissue of the chinese
hamster (1) had initial concentrations of
ffa comparable to those in the rat and
syrian hamster; (2) released, in the same
time interval, 8- to 10-fold more ffa
in vitro than this tissue of the rat; (3) had
higher concentrations of ffa after incubation
than the incubated tissue of the rat.
the retroperitoneal (perirenal) adipose tissue
of the chinese hamster was less ac-
tive in release of fatty acids in vitro than the
epididymal, but was, however, more
active than the epididymal adipose tissue of
the rat.  these characteristics of ffa
metabolism in the chinese hamster were
apparently attributable to species, not to
age, diet, or sex.  in the chinese hamster,
the weight of the epididymal adipose tis-
sue per gram of body was relatively high.
it appears that in this species the rate of
release of fatty acids from adipose tissue
is great, leading to high ffa concentra-
tions in serum.  in chinese hamster and rat
adipose tissues in vitro, glucose and in-
sulin (separately) reduced the rate of release
of ffa and the amount of ffa in the
tissues, but glucose and insulin together
produced the greatest reduction.  the net
reduction in ffa release by glucose and
insulin in vitro was greater in tissue from
the chinese hamster.  insulin markedly
increased glucose uptake by the adipose tis-
sues of both species.  the possible relation
of the results to spontaneous diabetes in
the chinese hamster is discussed.
.I 325
.W
95. changes in serum non-esterified fatty acid levels in spon-
taneous and in oxytocin induced labour
the nonesterified fatty acid (nefa)
concentration of serum rises progressively
during the course of normal labor.
the rise appears to be related to the duration
of labor.  the use of oxytocin to induce
and stimulate labor does not alter the normal
pattern of rise in nefa provided it is
given in physiologic dosage.  the levels of
nefa in the umbilical vein and the
umbilical artery at delivery are comparable and
always significantly lower than the
maternal level.  the maternal/fetal ratio varies
between 1.7 1 and 3.9 1 in this series.
following delivery the nefa levels begin
to fall almost immediately.  the rate
of fall is 10-30% of the delivery value in the 1st
hour, 30-50% within 18 hr. and 50-70% within 36 hr.
.I 326
.W
1545. the effect of combined glucose and insulin infusions on
the lipoid and carbohydrate metabolism of the parturient
woman and of the fetus
the infusion of glucose with insulin during delivery
was used by the authors pri-
marily in order to determine, whether the utilization
of glucose can be enhanced
under these conditions.  they wanted to investigate,
whether the increase of unesteri-
fied fatty acids in the cord blood which takes place
after a sole glucose infusion in
the mother, could be caused by the low capability
of glucose utilization in the fetus.
the infusion during delivery which consisted of the
application of 500 ml of 10%
glucose and 16 u of insulin over a period of 30 min.
brought about a greater decrease
of unesterified fatty acids in the parturient woman
as compared with the infusion of
glucose exclusively.  the reason for this result
is thought to be due to a better utili-
zation of glucose which is favorably influenced
by insulin.  during the infusion of
glucose with insulin, an increase in the values
of lactic and pyruvic acid took place
in the parturient women; this was probably due
to an accelerated glycolysis and an
increased production of lactic acid, but not
caused by a higher share of the anaerobic
metabolism.  in the cord blood, there were
likewise increased values of lactic and py-
ruvic acid as a reflection of the higher values
of these substances in the mother.  the
formation of these products of metabolic
breakdown by the fetus, however, was not
significantly increased.  after infusion of
glucose with insulin, the other investigated
parameter values, including those of the levels
of unesterified fatty acids are found
in the cord blood in similar amounts as after
infusion of glucose alone.  these re-
sults cannot reliably prove the passage of
insulin through the placenta especially
after a continued study of the metabolic values
in newborns.  as a proof of the passage
of insulin through the placenta could not be
established, it is possible that after an
intake of insulin the increase of unesterified
fatty acids in the cord blood could be
caused by a relative insufficiency of the insular
apparatus of the fetus.  the most
probable reason for the increase of unesterified
fatty acids is the different depo-
sition and metabolization of unesterified fatty
acids in the course of intrauterine
life.
.I 327
.W
1547. glucose and nonesterified fatty acid levels in maternal
and cord plasma
the authors established in 44 healthy women
at the moment of delivery the contents
of glucose and free fatty acids in the blood
of the mother and of the umbilical cord.
the concentration of both substances was
significantly higher in the mother than in
the infant.  the relation for free fatty acids
was 1.7 1, that for glucose 1.3 1.  the
relation glucose fatty acids in the mother was
significantly different from that in the
infant.
.I 328
.W
3294. epinephrine infusions in normal and toxemic pregnancies.
ii. plasma glucose, nonesterified fatty acid, and epineph-
rine-norepinephrine alterations
seven controls and 9 preeclamptic patients
were infused with different amounts of
epinephrine.  plasma nefa, glucose and
catecholamines were determined before,
during and after epinephrine infusion.  the
toxemic patient responds to the metabolic
effects of infused epinephrine in a manner
similar to that of the normal pregnant
patient.  the increased levels of nefa in
pregnant patients are explained by a com-
plicated biochemical mechanism involving
an increased availability of cortisone-like
steroids, slightly increased amounts of thyroid,
hormones, etc., resulting in an
alteration of carbohydrate utilization.  the study
leads to the conclusion that epi-
nephrine is not an etiologic agent in toxemia of pregnancy.
.I 329
.W
766. a lipid-mobilizing substance in the serum of pregnant wo-
men, of probable placental origin
a substance capable of inducing free fatty
acid (ffa) release was found in the sera
of 12 from 13 pregnant women.  the rat
epididymal fat pad was used for bioassay.
this substance circulates in late pregnancy
and disappears within 5 days post partum.
it is present in crude placental extracts and
is removed by their deproteination.  it
is nondialyzable.  application of pituitary
extraction procedure to placentae yielded
active fractions where pituitary growth
hormone is usually found.  in accordance with
these facts a hypothesis concerning a part
of metabolic changes occurring during preg-
nancy was pronounced as follows.  the
described substance diminishes maternal glu-
cose consumption through the elevation of
plasma free fatty acids, or by direct in-
hibition of glucose uptake, or both.  this
permits a preferential shunting of glucose
to the fetus.  at the same time, increased
plasma free fatty acid levels would serve
as the alternative maternal energy substrate.
elevated maternal insulin levels during
late pregnancy stabilize the degree of maternal
lipid mobilization.  the contrainsulin
properties of a substance capable of mobilizing
free fatty acids and inhibiting mater-
nal glucose utilization would pose a diabetogenic
challenge, and in the face of com-
promised maternal insulin reserves, provoke
overt or worsen existing diabetes
mellitus.
.I 330
.W
3682. metabolism of free fatty acids during perinatal life of lambs
there is a rapid rise of free fatty acids
in blood plasma after birth in newborn
lambs.  this study confirms this rise,
caused by an augmented mobilization of these
acids from the tissues.  norepinephrine
easily mobilizes free fatty acids in adult
ewes.  in newborn lambs this special effect
is lacking, though cardiovascular re-
sponses are clearly demonstrable.  blocking
the sympathetic nervous system in
newborn lambs inhibits the rapid rise of free
fatty acids after birth.  this is com-
patible with the concept, that increased activity
of these sympathetic nerves after
birth is an important factor for free fatty acids
mobilization.  during intrauterine
life there is an ample study of carbohydrates
and the organism uses them as an
energy source.  hypoglycaemia resulting from
sudden carbohydrate deprivation at
birth, demonstrates with rising free fatty acids
the change-over to (tissue) fat as
main source of energy.
.I 331
.W
1163. the effect of glucose infusions on the lipoid and the
carbohydrate metabolism of the parturient woman and
the fetus
in 20 parturient women who were given glucose
infusions during the expulsive stage
of labor, the authors were able to observe an unusual
hyperglycemia and a decrease
in unesterified fatty acids (uefa).  the uefa-level
usually increases regularly
during delivery.  likewise, the values of esterified
fatty acids (efa) showed an in-
crease above the normally present levels in women
who had received a glucose in-
fusion during the expulsive stage of labor.  the
results show that during delivery
both hyperglycemia and the increase in lipoids
are predominantly due to the energy
demands of the organism.  however, there is also
evidence that other, hitherto un-
known factors may play a role.  in the fetus,
the infusion of glucose leads to an in-
creased glucose retention.  the infusion, however,
does not bring about a decrease,
but, contrary to the expectations, an increase
in the uefa-values.  in general,
such a reaction is not found in any of the
subsequent periods of life.  further inves-
tigations were conducted in order to find an
explanation for the paradox uefa-
reaction.  as shown by an analysis of the lactic
acid and the pyruvic acid values, the
increase in the uefa can most probably not be
attributed to an impairment in the
fetal metabolic conditions.  the administration
of physiological saline infusions to
10 parturient women under equal conditions
revealed that the cause for the uefa-
increase can apparently neither be found in
hemodynamic changes due to the infusion
nor in changes of the electrolyte balance, but
rather in an adaptation insufficiency
of the fetal islet cells, respectively in a different
fat mobilization or fat deposition.
.I 332
.W
1320. the plasma free fatty acid composition and blood glucose
of normal and diabetic pregnant women and of their new-
borns
the blood glucose and plasma ffa content
and composition of the newborns of
normal women, gestational diabetics, and
insulin-dependent diabetics were analyzed.
normal maternal ffa levels were twice the
fetal values; by 2 hr of age ffa in-
creased 4-fold over initial values in normal
infants, while infants of gestational
diabetics had a 3-fold rise, and those of
insulin dependent diabetics only 2-fold.
blood sugar at the same time decreased and
there was an inverse relationship be-
tween blood glucose in the normal infants and
ffa.  this relationship is altered in
the infant of the diabetic mother.  gas
chromatography of plasma indicated a higher
ratio of unsaturated to saturated ffa in
mothers compared to infants.  no pattern
differences were noted between the normal
and diabetic mothers, except that the
latter had higher oleic acid.  in the initial 2
hr of life, the patterns changed, although
no differences were noted between infants
of diabetic mothers and normals.  the
observations suggest  (1) the metabolic
interrelationships of glucose and ffa in
the normal infant are different from those
in the infant of the diabetic mother, the
latter infant having a state of physiologic
hyperinsulinism; (2) plasma ffa in the
fetus is derived from both fetal fat synthesis
as well as placental transfers; (3) the
infant of the diabetic mother does not differ
from the normal as regards ffa com-
position.
.I 333
.W
3107. lipids of human placenta
the chloroform-methanol-soluble
components of 4 human placentae were isolated
by rubber membrane dialysis and gas
chromatography, and analysed.  two thirds
of the total lipids consisted of phosphatides
with lecithin as the main component
(22.5%), colamine cephalin (13%)
and sphingomyelin (7.5%).  free cholesterol form-
ed 14% of the total lipids, while
cholesterol esters accounted for 6% and trigly-
cerides for 13%.  investigation of
the phosphatide fatty acids by gas chromatography
showed a content of 60% saturated,
27% simple unsaturated and 12% polyunsaturated
acids.  the fatty acids of the triglycerides
consisted of about 50% saturated and
25% each of simple and polyunsaturated
acids.  the polyenoic acids (30%) of the
cholesterol fatty acids had a high content
of linoleic acid, about one quarter that
of the total acids.
.I 334
.W
377. experimental study of sensitization to nickel
sensitization was effected by epicutaneous
application of nickel sulfate in
15 guinea-pigs.  it was confirmed by the
appearance of eczematiform lesions in
skin tests with nickel sulfate.  for maintenance
of the animals in good general
condition it was necessary to add vit. c and
antiinfective agents to the diet.
for this reason the allergenicity of the ni
salt had to be augmented by the use
of adjuvants (freund's complete adjuvant or alum).
such adjuvants act by
stimulating the res.  the method for
sensitization of guinea-pigs to metal salts
having been worked out, it is now proposed
to study the mechanism of such
sensitization, the biological disturbances
involved and the possible existence
of cross-sensitizations.
.I 335
.W
2285. some remarks on the nickel dermatitis
by non-occupational contact
this dermatitis represents 2% of the
skin diseases observed at the
allergologic outpatients department of
the dermatological clinic of milan.
the disorder is more frequent in women
and prefers the thighs (girdles, keys)
and the wrist (watch); its incubation
period is generally long and a peculiar
papulo-vesicular follicular and lichenoid eruption often follows.
.I 336
.W
3200. studies on the binding of protein by nickel.
with special reference to
its role in nickel sensitivity
the reaction between nickel and proteins
was studied using the technique of
equilibrium dialysis.  in most of the experiments
crystalline bovine serum
albumen was used.  the nickel-protein complex
was of low stability, the quantity
of nickel bound by the protein being dependent
on the concentration of free
nickel ions, the ph, and the particular protein used.
the sites of binding of
the nickel ions were primarily carboxyl and amino
groups.  the author concluded
that it was unlikely that nickel behaved as a
hapten capable of initiating an
allergic response.
.I 337
.W
2596. experimental nickel contact sensitization in man
in 16 of 172 male prisoners contact-type
delayed hypersensitivity was induced
experimentally by repeated application of
25% nicl2 in a 0.1% sodium lauryl
sulphate solution on the skin.  test reactions
with 5% nicl2 with occlusion
were found to be irritating.  no experimentally
sensitized subject demonstrated
clinical sensitivity to the metal in his environment.
.I 338
.W
1013. hand eczema
the clinical aspects of 106 cases of hand
eczema are reviewed.  the clinical
types are defined  nummular eczema, nickel
allergy, atopic dermatitis,
hyperkeratotic dermatitis of the palms, hand
eczema post partum, mycotic eczema,
contact dermatitis, occupational eczema and
idiopathic eczema.  the results
of the patch tests, the influence of
psychological and psychiatric factors,
the effect of water and cleansers, the
diagnosis, treatment and prognosis are
discussed.  in 39% no significant causative
factor could be found.  in
many cases where causative factors could
be identified these were probably
no more than contributory, superimposed
upon an underlying idiopathic eczema.
.I 339
.W
670.  steroid aerosol spray in contact dermatitis.
prophylactic use with
particular reference to nickel hypersensitivity
proper use of topical aerosol dexamethasone
(decadron) spray affords complete
protection to patients with nickel sensitivity.
this clinical result is
confirmed by the results of patch testing
nickel-sensitive patients with a
5% nickel sulfate solution and nickel coins.
a combination of dexamethasone and
an isopropylmyristate film is necessary
for successful prophylaxis; the
individual components alone do not protect
these patients.  clinical and patch
test results indicate that a moderate degree
of protection is afforded to
patients with paraphenylenediamine sensitivity.
patch test results indicate
that the spray does not protect against
poison ivy and ragweed oleoresin,
potassium dichromate, certain rubber accelerators,
and monobenzyl ether of
hydroquinone.  it affords a moderate protection
against formaldehyde.  no tests
were done with patients with formaldehyde
hypersensitivity.  a fair degree of
protection was obtained by the use of the spray
in housewives eczema presumably
due to irritants present in soap and detergents.
.I 340
.W
2078. the pathogenesis of contact eczema due
to detergents for domestic use
the thesis is maintained that eczema due
to household detergents is
pathogenically linked with allergic contact
sensitization to metallic salts,
especially chromium and nickel.  in a series
of 20 cases of contact eczema
attributable to detergents, the existence of
sensitization to these metals was
demonstrated by the patch test.  likewise,
in the analysis of 9 samples of
different detergents used for washing,
in all of them chromium and nickel were
found to be present in a proportion which,
for either of these metals, varied
between 1 and 5 p.p.m.
.I 341
.W
4010. studies of nickel carcinogenesis.
the subcellular partition of nickel
in lung and liver following inhalation of nickel carbonyl
wistar rats were exposed by inhalation to
nickel carbonyl either once only
at a concentration of 80 ppm for 60 minutes
(0.60 mg ni(co)4/l.air), or
repeatedly at 4 ppm (0.03 mg ni(co)4/l. air)
for 30 minutes 3 times weekly
for 1 year.  they were killed 24 hours after
(the final period of) exposure.
nuclear, mitochondrial, microsomal and supernatant
fractions were isolated
from lung and liver homogenates and measurements
of the nickel, nitrogen
and rna-content of each subcellular fraction
were made.  the greatest ratios
of nickel to nitrogen were in the nuclear
fractions of both liver and lung,
but increased amounts of nickel were also found
in the microsomal and
supernatant fractions of both liver and lung
and in the mitochondrial
fraction of lung.
.I 342
.W
188. studies of nickel carcinogenesis;metastasizing pulmonary tumors in rats
induced by the inhalation of nickel carbonyl
in a combined series of studies, 6 out of 409 rats (n.b. only 195 survived for
more than 3 wk.) exposed to nickel carbonyl developed pulmonary carcinoma
with metastases.  the lesions included the common types of pulmonary cancer,
squamous cell carcinoma, adenocarcinoma and anaplastic carcinoma.  all of
the pulmonary lesions were found between 24 and 27 mth. after the initial
exposure to nickel carbonyl.  the amount of nickel found capable of inducing
lung cancer in the rat was comparable to the amount of nickel inhaled by
persons smoking less than 15 cigarettes per day for a period of a year.  the
mean weight of rats chronically exposed to nickel carbonyl was found to be
consistently less than that of the control rats throughout the entire 3-year
period of study.
.I 343
.W
189. influence of age, sex and glandular extirpation on muscle carcinogenesis
in rats
the carcinogenic effect of a single intramuscular injection of nickel sulphide
in an aqueous suspension to which penicillin g had been added was compared
in male and female castrated, hypophysectomized or intact, rats of different
ages.  the response seemed most marked in intact females injected when 2 mth.
old.  castrated or hypophysectomized 2-month old females were less
responsive.  one-month old intact males were more responsive than 2-month or
3-month old intact males, 1-month old castrated males, or 1-month old
intact females.  more data would be required before firm conclusions could be
drawn from these results.
.I 344
.W
3176. studies of trace metal metabolism  electron paramagnetic resonance of
manganese in ribonucleic acids
the electron paramagnetic resonance spectrum pattern of manganese was
readily detected in all of the samples of rna.  the resonance patterns
indicate that manganese is present in rna in a divalent state and suggest
that manganese is located at the center of a distorted octahedron of oxygen
atoms.  from the intensity of nominally forbidden resonances, the crystal
field splitting parameter d was estimated to be 0.02 cm -1.
.I 345
.W
4790. metal chelates as potential reactivators of organic phosphate poisoned
acetylcholinesterase
as part of a study to investigate metal chelates as possible reactivators
of phosphate poisoned acetylcholinesterase, it is shown that chelates act
as inhibitors of the enzyme.  in addition, copper and nickel chelates of
2-pyridinealdoxime catalyze the decomposition of dfp and sarin.  compared to
2-pam, however, these chelates are very poor reactivators, probably because
of an improper alignment of the oxine oxygen in the chelate-enzyme complex.
.I 346
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3446. effect of nicl2 on an isolated ranvier node
an attempt was made to explain the extreme prolongation of the nodal
potential by 0.1-1.0 mm nicl2 in terms of the ionic theory.  the effects of
nicl2 at room temperature are similar to those of temperature reduction
decreased maximum rate of rise of the action potential, lengthened action
potential duration, elevated threshold, increased tendency for repetitive
activity; in addition, the amplitude of the action potential is slightly
increased.  the long-lasting plateaus of the responses obtained under the
combined influence of nicl2 and temperature reduction are shortened by cathodal
polarization, strong anodal polarization and decrease of (na)0.  the plateau
can be prematurely terminated by short anodal pulses of critical amplitude;
short cathodal pulses reduce the duration of the plateau gradually with
increasing pulse strength.  increased (k)0 prolongs plateau duration; the
steep repolarization phase which normally terminates the plateau is
replaced by a long lasting after-depolarization with stepwise potential
decline.
the amplitude of k-depolarization is not influenced by nicl2 or temperature
reduction.  1.0 mm nicl2 changes the relation between maximum rate of
rise and steady-state polarization; the potential change required for 50%
sodium inactivation is +8mv in normal ringer's solution and +16mv in the
presence of 1.0 mm nicl2 (22 c.).  1.0 mm nicl2 increases the time constant
of delayed rectification as measured in na-poor solutions at 4 c. by a factor
of about 2.  the decrease of action potential under cathodal polarization is
slightly delayed by nicl2.  it is concluded that prolongation of the nodal
action potential by nicl2 is due to delayed and reduced inactivation of na
permeability and delayed increase of k permeability; part of the nicl2-effect
could be explained by assuming competition between ni++ and ca++ for specific
sites at the membrane.
.I 347
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2302. the carcinogenic activities of n-hydroxy-2-acetylaminofluorene and its
metal chelates as a function of retention at the injection site
the carcinogenic activities of s.c. administered
n-hydroxy-2-acetylaminofluorene
(n-hydroxy-aaf) and a variety of its metal chelates indicate that greater
activity locally is associated with a longer retention of the chelates at the
site of injection with a slow release of n-hydroxy-aaf to the surrounding
tissue.  no tumors were obtained at the sites of 4 injections of n-hydroxy-aaf
(3.2 mg. /injection), but 4 and 16 of 20 rats developed sarcomas at the
sites of 8 and 16 injections, respectively.  the nickelous, cobaltous, ferric,
or cupric chelates induced moderate to high incidences of sarcomas with 1 or 4
injections; in these cases one-half of the administered n-hydroxy-aaf was
retained at the injection site for 4-50 days.  the manganous and zinc chelates
and the potassium salt were less active at the injection site; the
half-retention times for these ranged from 2.5 hr. to 2.5 days.  the comparable
half-retention time for n-hydroxy-aaf was about 2 hr.  injection of the metal
derivatives s. c. with short half-retention times resulted in higher incidences
of mammary tumors than injection of the derivatives with half-retention
times of 4 or more days.  when administered in the food the cupric chelate
of n-hydroxy-aaf induced the same spectrum of tumors as n-hydroxy-aaf,
but the incidences were lower.  while the prolonged retention of the material
at the injection site may account for the greater carcinogenic activities of
the metal chelates, serious consideration must also be given to the possible
importance of chelation of carcinogens or their metabolites to cellular
constituents.
.I 348
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12083. generation of action potentials in single ranvier's nodes of isolated
frog nerve fibres under the influence of nickel and cadmium ions (russian)
by experimenting on single ranvier's nodes of frog isolated nerve fibres it
was shown that, along with a marked prolongation of the repolarization
phase of the action potential (ap), ni and cd ions also caused a rise of
the critical membrane depolarization level and an increased ap amplitude
with somewhat reduced steepness of its ascending phase.  ni and cd ions
restored the ap generation in the nodes of ranvier altered by a 0.01% procaine
solution, by an excess of potassium ions 00mm/1. of kcl) or by slight
mechanical injury during dissection.  it was only with a reduced na
concentration in the medium that the restoration of ap could be achieved.
ni and cd ions considerably slowed down and weakened the cathodal rise of the
critical level and the ap reduction.  cysteine (10 -2 to 10 -3 m)
eliminated all the effects of the mentioned ions.  a suggestion is made that by
binding the sh-groups of the nerve fibre proteins, nickel and cadmium reduce
the rate of inactivation and the increase of potassium permeability in
depolarization and also weaken the initial inactivation and the increase of
potassium permeability in depolarization, as well as weaken the initial
inactivation of the membrane (i-h), whenever this happened to be raised by
previous influences.
.I 349
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1287. agnostic alexia and constructive apraxia with regressive evolution in
a child of 12 yr. of age
after an acute encephalopathy, the etiology of which could not be determined,
a boy of 11 yr. and 10 mth. of age developed a syndrome of agnostic alexia
and constructive apraxia which was remarkably pure.  the intellectual
functions were normal as determined by iq tests, speech was not disturbed
either.  the child could not read or copy a text, but was fully able to write
(both freely and dictated).  the patient could not read what he had written.
this shows the characteristic features of agnostic apraxia.  motor activity and
performance were normal, but the child had extreme difficulty in constructing
geometric forms, even elementary, either spontaneously or by copying.
this remarkable syndrome disappeared, and during its involution it was
followed up.
.I 350
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1288. the symptomatology of the parietal cerebral syndrome of the dominant
hemisphere.  parietal dyslexia and conduction aphasia
this is a very comprehensive study on a patient.  in the beginning there was
a pronounced gerstmann's syndrome, with autotopagnosia for parts of the face,
dyspraxia and constructive apraxia and dyslexia.  the autotopagnosia and mild
left-right disturbances showed marked regression.  actual hemianopsia was
not observed, but tachistoscopy revealed that perception of the right field of
vision was poor.  audiometric examination showed a conduction deafness and
disturbed binaural word synthesis.  the disturbances were examined
meticulously and tested for symptom relationships, which became evident
in the various factors concerned with creative ability.
.I 351
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4544. observations on colour agnosia
a 56-year-old right-handed man, following the formation of a left posterior
subdural hematoma developed 'spelling dyslexia' and impaired picture
interpretation, which resolved, and color agnosia, which persisted.  the latter
impaired the use both of color information and of the names of the colors.
this may be explained as a disorder impairing the recollection and formation
of associations between color names and other types of information, with
resulting interference in any task in which colors or their names have
to be placed in a specific context.  the alternative views of willbrand (1887)
that here a limited dysphasia, and of sittig (1921) that a recognition defect
is simultaneously present, cannot be excluded.  in the present and in
previously reported cases the causative lesion seems to have been posteriorly
located in the dominant hemisphere, in the borderland between the area
receiving visual input and the language or verbal recording area.
.I 352
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652. bitemporal hemianopia
two stages can be distinguished in the development of bitemporal hemianopia
in hypophyseal tumors.  the first stage is the consequence of direct pressure
of the tumor on the lower side of the chiasma.  hence its start with upper
quadrantic field defects.  in this stage the visual disorder is amenable to
prompt and complete restoration.  with progressing growth of the tumor the
second stage follows as consequence of constriction by the circle of vessels.
in this stage nerve fibers are being destroyed.  therefore, after pressure
relieving operation no restoration occurs, or to a limited extent only.
.I 353
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387. ophthalmic manifestations of bilateral non-occipital cerebral lesions
twelve patients are described with neuro-ophthalmic symptoms resulting from
bilateral cerebral lesions in areas other than the occipital lobes.  the
symptoms and signs are categorized as follows  group i  those showing
predominant disturbances in visual object recognition (visual agnosia) and
disturbances of visual spatial localization.  group iia  those having defects
in voluntary control of eye movements (ocular motor apraxia).  group iib  those
with persistent palsies of conjugate gaze.  although these symptoms may be
present to some extent with unilateral lesions, they are much more profound
and less able to be compensated with bilateral lesions.  the evidence in the
present cases suggests a biparieto-temporal localization for the lesions
causing visual agnosia, disturbances of spatial localization, and ocular motor
apraxia, and a more frontal localization for the lesions causing prolonged
paralysis of conjugate gaze.
.I 354
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1774. the speed of reading.  basis for a clinical function test
as an easily comprehensible measure for the capability of reading, the author
recommends the determination of the reading speed for supplementation of the
ocular function tests.  the method in question constitutes a senso-motor
efficiency test which is of value in the appraisal of haemianopias, paracentral
and central defects of the visual field, in squint amblyopias and in
spontaneous nystagmus.
.I 355
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1303. the problem of visual agnosia
this is a critical assessment of the ancient and modern theories on visual
agnosia.  an original description of the subjective world of these patients is
also given.  visual agnosia is a rare disorder, but it has led to comprehensive
discussions, for instance, by the fact that the problem of normal visual
perception is always involved.  bay's view, which denies the existence of
agnosia as a separate phenomenon in perception disorders, is especially dealt
with.  it is affirmed that no case has been described in the literature
in which visual agnosia is decidedly a pure and isolated phenomenon.
mostly there are also disturbances in the intellectual interpretation of visual
data.  often there is metamorphopsia or asthenopia.  there is no localized
prestriate gnostic center for visual impressions.  the older concept of higher
and lower levels of perception and perception disorders is also criticized.
visual perception is not a passive, but a very active process, in which
neurophysiological and psychological aspects are involved.
each of these can be
disturbed, leading to various degrees of visual perception disturbance.
.I 356
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2496. dysbarism among hyperbaric personnel
a survey of the effects of hyperbaric exposure on 62 medical personnel exposed
to 1,516 compressions and decompressions revealed no case of permanent ill
effect.  pain in the ears or sinuses was the most common symptom but could
often be ameliorated or avoided by the valsalva technique of forced
insufflation with the nostrils occluded.  the most serious symptoms
encountered were 3 episodes of transient homonymous hemianopsia.  the
classic symptoms of decompression sickness
extremity pains (the 'bends'), pulmonary or
substernal distress (the 'chokes'), and skin dysesthesias occurred only rarely,
and were so mild or so fleeting as to require no treatment.  a further
reduction in symptoms without increase in decompression time may be
obtained by the inhalation of 100% oxygen during decompression stops at
pressures below 26.8 pounds per square inch gauge (psig).
.I 357
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2996. visual static agnosia with special reference to literal agnosic alexia
this is a report of 2, right-handed adults who had 'visual agnosia (with
predominance of literal alexia)'.  recognition of letters was poor or
nonexistent when the patient simply viewed the material (static method) but
if the letter was slowly developed for them, they were able to identify it
(dynamic method).  one patient had vascular pathology which was considered
to involve both occipital lobes and the 2nd patient had the surgical removal of
the left occipital lobe for an angioma.
.I 358
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1388. optic agnosia  semeiological and pathogenetic aspects
the authors discuss the classical concept of agnosia and make a survey of
pathogenetical factors which determine its phenomenology.  the original and
traditional concept of such a term implied the loss of the capacity to
recognize objects, when the functions of sense organs are undamaged.  the
psychological studies on perception and the modern physiology of
vision allow to avoid the dichotomy between sensation and perception and
to affirm their identity.  cortex and recptors are closely bound and
function in unison.
every cortical alteration is thus reflected in sensorial functions; it is
therefore that on practical semeiological grounds it is possible to obtain a
congruous information of the corresponding cortical functionality through an
exploration of sense organs carried out by suitable means.  since we are
confronted with functional changes, exploration methods must be fit to evaluate
dynamic aspects of perception in connection with the temporalization and
spatialization of stimuli.  such methods are now quite numerous and often
complex  a particular stress is laid on local adaptation, flicker fusion, and
tachistoscopy on account of their significance and suitability.  by such
methods it is possible to show those functional deficits or pathological
disturbances of sensorial functions which are also behind the pathology of
visual recognition.  fluctuation, extinction, alteration in the perception of
movement, both real and apparent, changes in adaptation to light and
darkness are all phenomena which can be detected instrumentally and which,
at the same time, may be of determinant importance for the onset of 'agnosic'
behaviour.  the complexity of the latter, on the other hand, cannot always
be explained by sensorial disturbances only  other mechanisms, with a function
complementary but not less indispensable to the dynamics of perceptive
processes, may intervene and interfere in it.  on the basis of the latest
neurophysiological data the attention is called to ocular motility and
proprioceptivity, centrifugal innervation of sensorial receptors, and
vestibular afferences.  a particular clinico-pathogenetical significance is
attached by the authors to the association of lateral visual disturbances with
altered proprioceptive and kinesthetic information from the corresponding
half-body  such association in fact is nearly always present among the factors
responsible for the most strictly 'spatial' errors of 'agnosic' pathology.  in
the light of these pathogenetical considerations as well as of suitable
semeiological findings, the authors deem it convenient to divide their cases
into 3 categories with distinct clinical features  (a) cases in which altered
visual behaviour may be related to changes of the visual function and of its
complementary mechanisms; (b) cases in which hemianopia is associated with
a homolateral deficit of somatic proprioceptivity; (c) cases in which the
changes in behaviour are chiefly, but not only, due to a dissolution
of the symbolic sphere.
.I 359
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2568. clinical observations on hemianopia (japanese)
the clinical findings in 19 cases of hemianopia were analyzed.  hemianopia was
caused most frequently by vascular lesions of the central nervous mianopsia,
and by tumors.  wilbrand's prism sign, which is generally taken as evidence
of an optic tract lesion, was positive in one case with a parietal lesion.  no
case showed a cogwheel movement of the eyeball.  optokinetic nystagmus was
positive in 3 cases, one of which proved to have a parieto-occipital aneurysm.
the etiological factor could not be identified in the remaining 2 cases.
macular sparing was found to be symptomatic of an occipital lobe lesion.
incongruity of the 2 fields was observed in 2 cases with an occipital lobe
lesion.  as for the prognosis, hemianoptic field defects remained stationary in
cases of vascular lesions.  on the other hand perfect recovery of the visual
field defect occurred in cases with an occipital lobe tumor and in hypophyseal
hypertrophy caused by pregnancy.  the visual acuity of hemianoptic patients was
fairly good and no deterioration occurred during the observation period of
about 4 years.  only one patient out of the present series died.  these results
suggest that a favorable vital prognosis can be accorded to hemianoptic
subjects.
.I 360
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1384. importance of campimetry and carotid and vertebral angiography in
thrombosis of the posterior cerebral artery
the authors report a case of thrombosis of the posterior cerebral artery which
presented only lateral homonymous hemianopia and stress the importance of
campimetry and of carotid angiography beside vertebral angiography.
.I 361
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375. hemianopsia and glaucoma
after a discussion of the bibliographic references to the few observations on
the simultaneous occurrence of hemianopsias and glaucoma the author states on
the basis of his experiences the following points  homonymous hemianopsias
occasionally take place in glaucoma, although no direct relation can be
established between the former and the glaucoma.  it has to be pointed out,
however, that in other older patients, for example in those with retinal
detachment, neuritis, etc. who are likewise subjected to repeated and exact
perimetry, such hemianopsias do not occur, or are to be found at a lesser rate
than in glaucoma.  a homonymous hemianopsia has to be taken into consideration
also in the event of a sudden impairment of the visual field in a glaucomatous
patient or when the hemianopic defect supervenes in addition to the visual
field defect due to glaucoma.  in cases of binasal hemianopsia, the
simultaneous presence of glaucoma is not a rare incident.  whether the
binasal hemianopsia is the result of the gradual development of a
glaucomatous visual field with nasal defects or whether it constitutes an
independent symptom to a certain extent, cannot always be clarified
in the individual case.  obviously the condition of the basal cerebral
vessels plays a certain role in the development of glaucoma, even if
this role cannot be clearly defined as yet.  in cases of
binasal hemianopsia, a glaucoma has to be ruled out before radical diagnostic
and therapeutic measures are carried out.
.I 362
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1131. disorders of oculomotor functions in lesions of the optic pathway at the
parieto-occipital level and their significance in topical diagnosis
paresis of ocular movements to the hemianopic side is described in 9 patients
with acute vascular lesions in the parieto-occipital region.  in 7 cases the
paresis was of the dissociated type with inability to follow the moving finger,
while ocular movement in a verbally stated direction was quite normal.  in the
remaining 2 patients in whom the oedema extended into the frontal region there
was complete paresis of all conjugate movements.  conjugate paresis receded
hand-in-hand with the parietal symptomatology even if the hemianopia
persisted.  the oculomotor disorders referred to have never been observed in
lesions which did not extend beyond the occipital region.  conjugate
paresis has in all cases drawn attention to the presence of hemianopia
unobserved by the patients and this has led to a more accurate topical
diagnosis.
.I 363
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2333. binocularity in anomalous retinal correspondence
patients with anomalous retinal correspondence demonstrate complete bitemporal
or binasal hemianopia when tested for binocular vision; exotropes have a
binasal suppression and esotropes a bitemporal suppression.  this is contrary
to the prevailing concept of the function of the peripheral retina in
anomalous retinal correspondence.  6 references.
.I 364
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2120. thioguanine in the treatment of certain autoimmune, immunologic and
related diseases
the therapeutic effectiveness of 6-thioguanine has been evaluated over the past
3 years in 19 patients with diverse syndromes.  only patients with severe
debilitating disease unresponsive to conventional therapy were treated.
remissions occurred in 2 of 5 patients with systemic lupus erythematosus, in 1
patient each with dermatomyositis and necrotizing angiitis, 2 patients with
psoriasis and 2 of 4 patients with atopic disease.  improvement occurred in
other patients with these diseases and in 2 of 4 patients with
neurodermatitis.  two patients with scleroderma experienced only
equivocal benefit.  significant toxicity attributable to the drug
was observed in 5 patients.  assessment of the eventual value of
these agents in therapy requires further study.  hypotheses regarding the
mechanism of action of these agents and the significance of clinical
response are discussed.
.I 365
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2469. the nature of collagen disease, particularly of systemic lupus
erythematosus (sle), with special reference to renal lesions (japanese)
from the results of examination of 161 autopsy cases of collagen diseases,
rheumatic fever and polyarteritis nodosa (pn) are considered as diseases of
hyperergic nature, showing pronounced specific manifestation in particular
organs.  as the reactivity becomes lower, this specific localization becomes
less significant and many organs become affected in sle.  it may accordingly be
supposed that sle is not a disease of hypersensitivity but one occurring in
a state of exhaustion of reactability after prolonged sensitization.  moreover,
a sle-like syndrome arises not only in the end stage of parasepsis, nephritis,
nephrosis and some cases of prolonged sensitization by myco.tb but also in
pn,pss,dm and rheumatism.  it may therefore be conceivable that sle is
a syndrome rather than a separate entity.  it is most important to consider
whether sle-like symptomatology may be regarded as a process equal to
an auto-immunization and whether the key to morphological elucidation of the
auto-immune phenomenon may lie hidden in this problem.
.I 366
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420. therapy of lupus nephropathies by 6-mercaptopurine
corticosteroid therapy improved the general prognosis of sle, but has no
detectable effect on the nephropathy and this is actually the main cause of
death.  a new therapeutic method is presented using 6-mp purinethol (leupurin)
which produced 2 remissions in 6 consecutive cases total and in 4 cases
with severe nephropathy definite remission.  it should be emphasized that 5 of
the cases reported had definite npn elevation, accordingly they are considered
hopeless.
.I 367
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2475. lupus erythematosus with fatal hemorrhage into the liver and lesions
resembling those of periarteritis nodosa and malignant hypertension.
immunocytochemical observations
a firmly established case of lupus erythematosus with histologic
characteristics of periarteritis nodosa and fatal hemorrhage is presented.
immunocytochemical studies were done to explore the possibility of the vascular
lesions being immunological in type.  by immuno-fluorescent techniques
y-globulin, human serum complement, albumin and fibrinogen were demonstrated in
the vascular lesions.  y-globulin in the renal glomeruli was associated only
with complement.  the conclusion is that lupus erythematosus is primarily an
immunological disease with complex auto-immune mechanisms operative.
.I 368
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198. early experiences with azathioprine in ulcerative colitis.  a note of
caution
azathioprine was administered to 10 patients with ulcerative colitis classified
as 'very severe' in 2,'moderately severe' in 7 and 'relatively mild' in 1
patient, in conjunction with 'standard' therapy and adrenal corticosteroids in
8 of the 10 patients.  the possible beneficial therapeutic effects of
azathioprine in this small series cannot be evaluated definitively because of
the concurrent medication and the preliminary uncontrolled observations.
however, clinical improvement was apparent in 8 of the 10 patients; and in 2
patients, the favorable course occurred in the absence of steroid therapy.  in
2 additional patients, the favorable course was maintained during the
administration of azathioprine following the discontinuance of prolonged
steroid therapy.  in 1 patient, the administration of azathioprine was
associated with amelioration of an arthritis and pyoderma gangrenosum which did
not respond to the use of steroids and other medication.  immuno-suppressive
observations were limited.  the established delayed hypersensitivity response,
as reflected in various skin tests, was unchanged during the administration of
azathioprine.  azathioprine had no discernible toxic effects upon the kidneys
or the liver in 2 patients, 1 with postnecrotic cirrhosis and the other with
serum hepatitis.  gastro-intestinal symptoms (anorexia, epigastric discomfort,
and nausea) occurred in 8 patients.  mild to moderate leukopenia developed in 8
patients and, in 2 individuals, was accompanied by thrombocytopenia.  temporary
alopecia occurred in 1 woman.  the hematopoietic effects developed within 2 or
3 wk of therapy with azathioprine at a dosage level of 4-6 mg/kg/day.
azathioprine does not exert the rapid beneficial effect in ulcerative colitis
noted with corticotropin and adrenal corticosteroids.  therefore, its use in
severe ulcerative colitis requiring intensive therapy probably is undesirable.
azathioprine, on the basis of these initial observations, may be considered for
moderately severe ulcerative colitis, under circumstances permitting controlled
and prolonged therapeutic trial as adjunct medication, but with careful
supervision for prevention of toxicity, especially leukopenia.
.I 369
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1281. effect of fluoropyrimidines on delayed cutaneous hypersensitivity
the ability to express delayed cutaneous hypersensitivity was assessed in 51
patients with carcinoma.  evidence is presented that 5-fluorouracil and
5-fluoro-2'-deoxyuridine paradoxically potentiate this parameter of immune
responsiveness.
.I 370
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248. data on etiology, pathogenesis, treatment results and survival period in
560 patients with cirrhosis of the liver
statistics were compiled from a total of 560 cases chosen at random, of
cirrhosis of the liver.  the figures refer to the age and sex of the patients,
as well as to the etiology and the hepatic morphology.  as the date of death of
304 of the subjects was known, it was possible to calculate the survival time
after the diagnosis was made.  only 36% survived the time of diagnosis by 1
year, 16% by 3 years, and 8% by 5 years.  these figures show that modern
therapy of liver cirrhosis has up to now not succeeded to prolong the life of
the majority of the victims.  in many cases, however, it is possible to a large
extent to relieve the patients' suffering by improving the appetite and the
general condition and by eliminating ascites and periods of hemorrhage and
stupor.  particular attention should be paid to the prophylaxis of the disease
and, by studying the survival time assessments and therapeutic reports, to the
method of selection of the subjects.
.I 371
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897. chronic renal diseases and pregnancy  a review
a review is given of the reciprocal relationships between chronic renal disease
and pregnancy.  after a short review of the most important changes in renal
function due to normal pregnancy, the diagnosis of chronic renal disease is
discussed.  subsequently, the following complications of pregnancy are
discussed individually  chronic pyelonephritis, chronic glomerulonephritis,
lupus erythematosus, the nephrotic syndrome, diabetic nephropathy and
polycystic disease of the kidney.  the paper is concluded by a discussion on
the influence of pregnancy on the different renal affections.
.I 372
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4193. the occurrence to cytomegalovirus infections in childhood leukemia.
report of three cases
cytomegalic inclusion disease (cmid) presented the following clinical findings
in three children with acute leukemia  persistent high temperature, cough,
vomiting, diarrhea, hepatosplenomegaly, rales, and terminal icterus.
pancytopenia was present in all, including two children in leukemic remission.
roentgenographic evidence of pneumonia did not appear until the third week
after the onset of symptoms.  abnormalities in liver function tests were late
findings.  intranuclear inclusions were seen in urine sediments of two
patients.  in neither of these patients were intranuclear inclusions
demonstrable in the sputa.  virus culture from urine was done in one of these
patients and cytopathogenic changes characteristic of cytomegalovirus (cmv)
were demonstrated.  cmid was the cause of death in these three children, all
of whom had received chemotherapy with agents known to have immunosuppressive
properties.
.I 373
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   . on chorea, lupus erythematosus, and cerebral arteritis
a woman aged 33 developed chorea 10 yr after the onset of systemic lupus
erythematosus (sle).  she had experienced an asymptomatic interval of
8 yr.  the abnormal movements persisted for 5 mth, but then subsided
after short-term administration of 6-mercaptopurine.  there are 11 previous
descriptions of chorea patients with sle.  in 3 out of 4 autopsied cases,
extensive cerebral lesions due to diffuse arteritis were found.  the cns
changes were quite similar to those found in chorea minor.
.I 374
.W
1878. pharmacologic actions on cellular immunity
the following chapters of interest in the field of drugs and immunity processes
are included  manifestations of cellular immunity.  states of reduced
immunologic reactivity.  present status of pharmacologic immunosuppression.
tests for susceptibility of tuberculin reactions to pharmacologic action.
tests for susceptibility of transplantation immunity to pharmacologic action.
comparative susceptibilities of tuberculin and skin homotransplantation
reactions to pharmacologic action.
.I 375
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2625. chromosome aberrations in human cells following treatment with imuran
five women with various collagen diseases were studied.  bone marrow aspirates
were obtained from each patient before and 12 to 24 days after start of imuran
(azothioprine) therapy.  fifty metaphases from each sample were counted.  in
patients nos. 1 and 2 the increase in cells with structural abnormalities
during therapy is significant.  the aberrations found were mostly breaks of the
chromatid and chromosomal type.  a few abnormal chromosomes were seen,
among which a ring chromosome.  in patient no. 1 chromatid exchanges were
seen in three cells.
.I 376
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3645. autoimmune hepatitis
in 30% of 301 patients with cirrhosis, the cause was uncertain.  of these 90
cases the clinical picture of active chronic hepatitis could be recognized in
69, and 26 of these were characterized as lupoid hepatitis.  the relationship
between active chronic hepatitis, lupoid hepatitis and sle was studied in 3
groups of 25 cases each.  a comparison was then made between the possible
etiological factors, the systemic manifestations, the survival rate, the
histological appearances, the biochemical tests, the autoimmune reactions
and the results of the immunosuppressive drugs.  from this study a concept
emerged according to which a proportion of cases of cirrhosis occurring in
adequately nourished individuals can be attributed to the end result of an
autoimmune reaction.
.I 377
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766. a comparison of the effects of selected cytotoxic agents on the primary
agglutinin response in rats injected with sheep erythrocytes
a comparative study was made of the effects of several cytotoxic agents, given
at maximally tolerable doses, on the primary agglutinin response in rats
immunized with sheep erythrocytes given intraperitoneally.  antigen was given
before, at the beginning, or in the middle of a 5-day course of drug
treatment.  chlormethine (mechlorethamine), 5-fluorouracil, and
5-fluoro-2'-deoxyuridine did not suppress the primary response
significantly.  methotrexate, 6-mercaptopurine, 6-mercaptopurine roboside
and 2-amino-6-((1-methyl-4-nitro-5-imidazolyl) thio) purine
prolonged induction time and suppressed peak titer maximally
when immunization was performed one to three days prior
to drug treatment.  vinblastine did not affect peak titer, but did prolong
induction time when antigen was given 2 days prior to drug treatment.
cyclophosphamide markedly prolonged induction time and suppressed peak titer
irrespective of the time of antigen administration.  the antimetabolites
appeared to suppress maximally the intermediate stage of the primary response.
cyclophosphamide appeared to suppress all stages.
.I 378
.W
1959. analysis of mechanism of immunosuppressive drugs in renal
homotransplantation
dammin g. j.
a long-term study of the mechanism of action of immunosuppressive drugs has
been completed in bilaterally nephrectomized dogs with kidney homotransplants.
over 1,000 test animals with 24 different drug protocols have been analyzed.
increasing numbers of long surviving animals have posed many questions
regarding the status treated host.  the current drug protocol of azathioprine
and diazoacetylserine ('azaserine') has produced 90% 50-day survivors and 50%
100-day survivors.  the following observations have been documented  all
animals on prolonged drug therapy are immunologically competent; drug therapy
can be stopped successfully in some but not all animals; long surviving kidneys
apparently are protected in some way in the new environment because a
second donor kidney can be rejected while the first survives; retransplantation
of a long surviving kidney back to its original host did not lead to a decrease
in renal function; long surviving kidneys successfully retransplanted back
to their original donors are rejected when transplanted to third party,
non-drug treated recipients; immune paralysis does not account for the
prolonged survival because the second donor kidney which constitutes a double
dose of antigen is rejected while the first continues to survive; absorption or
metabolism of the drug does not account for the variation in results because
two kidneys, each from separate donors, can be rejected differentially in the
same drug treated host; and all hosts are sensitized against the recipient and
this sensitization continues even in those animals successfully weaned from
drugs.  additional analyses of the relationship of skin homografts and kidney
homografts reveal the following  skin homografts are universally rejected
within 20 days by hosts treated with the drug regimen which protects kidney
homografts sometimes permanently.  when skin and kidney homografts from the
same donor are placed simultaneously skin survival is prolonged while kidney
survival is shortened.  this paradoxical effect probably is explained by the
production of antibodies by skin which are absorbed by the rejecting kidney.
additional observations indicate that drug-treated animals, male and female,
are fertile and that multiple rejection processes can produce generalized
immunological picture in the host similar to an autoimmune disease process.
.I 379
.W
3083. myocardial toxicity of contrast agents used in angiography
the myocardial toxicity of many current and
some experimental contrast agents
has been studied in dogs, by use of a previously
unreported method of occlusion
retrograde coronary venography as well as the
familiar technique of selective
coronary arterial catheterization.  the following
conclusions appear justified in
the light of the experiments   not only the
iodine-containing radicals with which the
contrast agents are so often identified (acetrizoates,
diatrizoates, iothalamates,
etc.), but also the final salification products appear
to be responsible for the widely
divergent degrees of myocardial toxicity of contrast
agents, to the point that differ-
ent salts of the same compound behave as entirely
different agents both chemically
and biologically.  the results seem to indicate the
dominance of sodium ion and/or
the protective effect of methylglucamine salts with
respect to the myocardial toxi-
city of current radiopaque media.  reported,
yet unexplained, electrocardiographic
changes occurring within one to two seconds
from the beginning of massive caval
high-pressure injections appear to find a
causal relationship in the myocardial ir-
ritability induced by the distention of the
coronary veins and the myocardial infiltra-
tion which is intentionally enhanced with
our retrograde injection techniques.  a pe-
culiar trait, shared in varying degrees by
all radiopaque agents tested, is their
ability to increase coronary blood flow.
the clinical significance of this phenome-
non, however, remains to be established.
these studies re-emphasize the limita-
tions of the standard toxicity studies conducted
in animals.  it should be clear from
the results reported that agents to be
administered into the coronary circulation
demand investigation in regard to their
potential toxicity by the methods described
herein or variations thereof.  in fact,
similar tests should be carried out for all or-
gans to be subjected to radiographic
examination via the vascular bed.  the authors
hope that this presentation will stimulate
renewed investigation, particularly in view
of the growing clinical applications of
selective cardiovascular opacification tech-
niques.
.I 380
.W
2476. studies on cardiac dimensions in intact,
unanesthetized man. i. description of techniques and their
validation. ii. effects of respiration. iii. effects of
muscular exercise
a method is described which permits
measurement of relative changes in the exter-
nal dimensions of individual cardiac
chambers throughout the cardiac cycle in intact,
unanaesthetized man.  it consists of
suturing multiple radiopaque silver-tantalum
clips to the surface of the heart at the
time of cardiac operations.  in the postopera-
tive period, cineradiograms are
obtained and the distances between clips are mea-
sured on each individual frame.
this technique has been found to be safe and has
been employed in 68 patients without
any complications.  as a result of studies in 8
patients utilizing biplane serial exposures,
the effects of rotation of the heart in the
sagittal plane during the cardiac and
respiratory cycles were determined precisely.
if clips were properly placed on the heart,
the possible errors resulting from such
rotation were found to be quite small.
during inspiration right ventricular dimen-
sions increased, while the opposite occurred
during expiration and during the val-
salva manoeuvre.  left ventricular dimensions
exhibited little change during normal
respiration.  during deep, slow inspiration,
the changes in dimensions of the left
ventricle lagged behind those of the right
ventricle by 1 to 5 (generally 2 or 3) car-
diac cycles; the magnitude of the changes in
the dimensions of the left ventricle was
smaller than that which occurred in the right
ventricle.  the effects on ventricular
dimensions of light muscular exercise performed
in the supine position were studied
in 9 patients.  the end-diastolic dimensions
decreased by an average of 6.0% of con-
trol in the right ventricle, and by an average of
5.1% in the left ventricle.  end-sys-
tolic dimensions decreased by an average of 5.6%
of control in the right ventricle
and by an average of 6.5% in the left ventricle.
these decreases are considered to
approximate one-half of the resting stroke volume.
in the 4 patients in whom the
rate of right ventricular pressure rise was determined
continuously, exercise re-
sulted in an elevation of dp/dt while ventricular
end-diastolic dimensions decreased.
these data are interpreted to indicate that an
increase in myocardial contractility
occurs during muscular exercise in man.
.I 381
.W
3765. radioactive isotope determination of myocardial blood
flow by surface counting and ratio formula
wilkinson d.
the results presented here have a large
scale error and a large scatter, so that
the authors recommend that further clinical
use of this method should not be at-
tempted.  if the coronary portion of the flow
rate curve exists, then a change in the
present instrumentation is needed to allow
use of the technique of sevelius and
johnson in defining a coronary portion of the
flow rate.  an attempt is made to
evaluate the possible source of errors.
.I 382
.W
1379. risa-ventriculography and risa-cisternography
some general experience of the authors with
risa-ventriculography and risa-cis-
ternography is related.  they conclude that the
former technique may be particularly
useful in detecting intraventricular tumors and
internal hydrocephalus as well as
assessing the efficiency of surgical shunts; the
latter technique may be useful in
the study of normal csf circulation as well as
in cases of csf leaks, arachnoiditis
and external hydrocephalus.
.I 383
.W
3485. measurement of the cardiac output and ventricular
volumes by radiocardiography
cardiac output was measured by external
counting after injection of radioisotopes
(rihsa and erythrocytes-cr51).  the results
in 113 subjects, including 16 normals,
are presented and compared with the results
by other methods.  cardiac output at
rest and after exercise was compared in 65 subjects.
the principle of ventricular
volume measurement by radioisotope-cardiography is
discussed.  the results of
measurement of the ventricular volume in 17 normal
subjects and 90 patients, and
of measurement of the ventricular volume in 57 patients,
are presented.
.I 384
.W
3762. aberrant left coronary artery
five cases of aberrant coronary artery are
presented, with emphasis on the angio-
graphic features and differentiation from
endocardial fibroelastosis.  clinical and
electrocardiographic features may suggest
the proper diagnosis, but only angio-
graphy can conclusively demonstrate the
continuity between the pulmonary artery
and the left coronary artery.  in these cases,
blood flow was from the pulmonary
artery to the coronary artery (forward) in 2
cases, and from the coronary artery
to the pulmonary artery (retrograde) in the
other 3.  when the diagnosis of aberrant
coronary artery is suspected, selective
left-sided angiocardiography should be the
angiographic procedure of choice.  the differentiation
from endocardial fibroelas-
tosis and other myocardiopathies is usually not a
problem with such a study, but
may be more difficult with intravenous angiocardiography.
with this latter type of
study, the coronary arteries are not generally visible,
but a persistently thin la-
teral aspect of the left ventricular wall should suggest
the proper diagnosis.  sub-
sequent confirmation by a left-sided injection is advisable.
.I 385
.W
4159. detection of heart shunts by means of i 125
external scintillation detection of a pure dilution
curve originating in the right ven-
tricle has been pursued by investigators for many
yr.  the use of the soft photons
of 125 i offers an improved method of determination
by allowing excellent collimation
through 2 mechanisms  (1) a small half value layer
of 2 cm in tissue, and (2) uni-
directionality, in part due to all-or-none photoelectric
absorption of these photons
as compared with the pluridirectionality due to compton
scatter in the case of 131 i.
in 30 normal individuals, externally detected dilution
curves from the right heart
ventricle and arterial dilution curves obtained by arterial
puncture are compared.
five hundred microcuries of 125 i are injected into an
antecubital vein.  the amount
of radiation absorbed from a 500 uc dose in an adult of
70 kilos is 1000 to 2000
mrads when injected in the form of 125 i iodide.  the use
of 125 i orthoiodohippu-
rate is advised due to its short biological half-period and
the integrated whole-body
radiation exposure is decreased 100-fold in comparison
with the 125 i iodide.  the
shape of the right heart curve is very similar to the arterial
dilution curve with a
13   5% excess of counts originating outside the right ventricle
area.  the descending
segment of the right ventricle curve has a minimum count rate
of only 12   2% of the
peak of the curve as compared with the arterial curve of 10
   2.5%.  a mean t 1/2
of the descending down slope of the right ventricle is 1.52
   0.45 sec. for the right
heart curve and 2.4   0.65 sec. for the arterial curve.
the clinical usefulness of this
procedure in 20 patients with atrial septal defects and 9
patients with ventricular sep-
tal defects is analyzed.  it seems possible to perform selective
right-heart radiocardio-
graphy by means of external precordial detection of 125 i.  the
method is simple and
reproducible.
.I 386
.W
4160. clinical applications of quantitative radiocardiography. i.
results in normal subjects and changes with age
a technique is described for routine determinations
at the bedside of blood volume,
cardiac output and pulmonary blood volume by means
of the method of quantitative
radiocardiography.  the instrumentation is simple,
the technique is easy to perform
and causes little trouble to the patients, only one
injection of about 50 uc of rihsa
being needed.  thirty-nine patients aged 17-83 yr.,
free of cardiovascular or re-
spiratory disorders, were studied.  the results
obtained are in close agreement with
previous reports.  only the cardiac index showed a
significant decrease with age,
while the reduction of blood volume and of pulmonary
blood volume was slight.  a close
statistical correlation was found between pbv and sv,
and was interpreted as a
dependence of pbv on sv.
.I 387
.W
2725. demonstration of myocardial infarction by photoscans of
the heart in man
intravenously injected radioiodinated oleic acid
was incorporated into heart muscle
in sufficient concentration to permit recording photoscans
of the heart in man.  in
3 fatal cases of massive septal myocardial infarction,
injection of the radioiodin-
ated fatty acid (rifa) was made during life; at necropsy
photoscans of the excised
heart showed a discrete area of absent radioactivity
corresponding to the infarcted
interventricular septum.  photoscans of the heart were
made during life in 42 pa-
tients, 9 of whom had suffered recent myocardial infarction.
there were definite
areas of deceased radioactivity corresponding to the location
of the infarction,
judged by the electrocardiogram, in 4, and probable areas of
decreased radioactivity
in 2, of the 9 cases of myocardial infarction.  the technic as
presently employed
just approaches the limits of definition of infarction in acute
cases.  modification of
the biochemical principles or further development of the
y-camera may bring the
method to a level of diagnostic usefulness.
.I 388
.W
2716. y-angiocardiography
recordings were made, simultaneously with
the y-cardiogram, of a pulmonary an-
giogram by means of a collimator placed in
the left scapular region and of carotid
angiogram by a collimator centered on the axis
of the external auditory canal.  the
3 curves yielded very interesting information on
the chronology of the various car-
diac cycles.  the pattern of the pulmonary and
carotid y-angiograms was valuable
in several pathologic conditions.  it is more logical
to measure the cardiac output
on the carotid curve than on the y-cardiogram,
especially if there are shunts.  the
pulmonary curve allows rectification of the time
constant of emptying of the left
cavities of the heart.  as regards chronologic
information on cardiac cycles, atten-
tion is drawn to the fact that in the pulmonary
circulation long and short circuits
can be demonstrated.  the characteristic times
can be measured.  between the time
that the radioactive material appears in the left
cavities and the time that it leaves
the carotid, there is an interval of 3-4 systoles,
which represents the time neces-
sary for left circular filling.  the validity of
calculation of the cardiac output with
the stewart-hamilton formula is discussed.
this is valid if the collimator covers
a small volume of the principal channel.  it remains
to be shown if such a calculation
is valid for larger cavities, or for 2 cavities, through
which the radioactive material
passes successively, and which have different c (t)
functions as well as for all tissue
'seen' by the collimator, some of which are not yet
irrigated with the radioactive
blood, while in other areas recirculation has already
started.  these aspects, and
their application to the pulmonary angiogram, are
discussed in detail.  with the
authors' technique, y-angiogram is
especially valuable, as correc-
tion for the time constant of the decrease of the left
peak is based on the lengthening
of this curve.  this again serves as a basis for
determining the left ventricular
volume.
.I 389
.W
2717. the value of quantitative radiocardiography in the study
of hemodynamics
six normal subjects and 7 patients with mitral
stenosis were studied.  quantitative
radiocardiographic investigations (rihsa) were
performed according to donato's
method.  the stroke volume as well as the cardiac
output were found to be decreased
in mitral stenosis, the right ventricular evacuation
ratio diminished, and the pul-
monary circulation time prolonged.  the results
pertaining to diastolic right ventricu-
lar capacity, right ventricular resting blood volume
and pulmonary blood volume
proved inconclusive.
.I 390
.W
3056. the localization of aortic shunts developed by a precordial
registration of i 131 injected into the aorta at different levels
a technique for localizing shunts of aortic origin
is described, based on the analysis
of precordial records of i 131 injected at different
aortic levels.  seven patients with
patent ductus arteriosus (pda), 1 with a
coronary av fistula, 2 with ventricular
septal defect (vsd), 1 with atrial septal defect
(asd), 3 with mitral regurgitation,
2 with aortic regurgitation and 2 with systemic
hypertension were studied.  retro-
grade arterial catheterization by seldinger's
technique was performed in all the
patients, as well as right-sided catheterization
in those with congenital cardiopathies,
and transseptal catheterization in those with
valvulopathies.  a dose of 5-15 uc of na
i 131 was injected at the levels of the aortic root,
the ascending aorta, the aortic arch,
the origin of the left subclavian artery (ductus
level) and the descending aorta (post-
ductus level).  precordial curves were obtained by
means of a 2-inch thallium-acti-
vated nai crystal focused over the 3rd left intercostal
space at the sternal margin.
the shunt outlet can be detected by obtaining
simultaneous venous dilution curves
from the right chambers and the pulmonary artery.
the latter technique was used
in 2 patients with pda, 1 with coronary av fistula
and 1 with vsd.  these curves
were obtained by continuous withdrawal of blood which
had flowed through a well
scintillation counter.  the crystal pulses were carried
to ratemeters which worked
with the following time constants  0.01-0.15 sec for the
precordial curves and 0.5
sec for the venous curves.  a direct recorder with a
5-mm/sec paper speed was
used.  normal precordial curves after injecting above
the aortic valve were obtained
in patients with arterial hypertension, mitral regurgitation
and asd and vsd.  a
swift downslope which fell down near the baseline level and
the recirculatory area
was observed.
.I 391
.W
1671. the use of 99m tc pertechnetate in cardiac scanning
technetium 99m pertechnetate has been utilized
in the aas' laboratory for scanning the
cardiac blood pool.  the delineation of the heart
pool and surrounding vasculature
is comparable to that obtained with the standard
131 i compounds now in use.  in the
authors' hands 99m tc had the following advantages
since they routinely utilized
99m tc for brain and thyroid scans, it is available,
eliminating the purchase and
shelf decay of other materials.  three to 5 mc quantities
may be administered
with relatively low patient radiation dosage.  the
associated high count rate permits
rapid scanning.  the identification of pericardial effusions
is enhanced by the radio-
activity in the stomach which in some cases becomes
abnormally separated from
the cardiac blood pool.
.I 392
.W
2012. the use of technetium 99m as a clinical tracer element
the physical properties, metabolism and
radiation dose of tc 99m are discussed and
compared with those of i 123, i 125, i 131 and i 132.
it is shown that with tc 99m the highest
'in vivo' counting rates are obtained for a
given internal radiation dose, so that mea-
surements of high statistical accuracy may
safely be made.  the y-ray energy is near
optimum for scanning and the observation of
transients allowing light-weight collima-
tors to be used.  while tc 99m tagged albumin
is considered superior to risa for ap-
plications such as brain scanning, placentography
and the measurement of cardiac
output, i 123 if it becomes available will be preferable
for thyroid scanning.
.I 393
.W
2626. a study of central arteriovenous shunts by
precordial recording of radioalbumin dilution curves
precordial dilution curves of 185 patients were
studied, 56 of them without cardio-
vascular disease, 48 with central arteriovenous
shunts and 45 with various cardiac
diseases.  collimation was not used, allowing only
minimal quantities of radioactive
material (0.5-2.2 uc. of i 131-tagged albumin) to be
utilized.  the precordial focusing
zone was a critical factor in this technique.  the
application of different discrimina-
tion factors, among them the ratio between the
minimal concentration and the latter
-an index proposed here - made possible the
diagnosis in 46 of the 48 patients with
shunts.  this method was shown to be as sensitive
as classical oximetry done during
cardiac catheterization.  the curves in pure valvular
stenosis do not show similar
changes to the shunts.  on the other hand, these
changes are shown in certain val-
vular regurgitations.  this fact becomes the most
important limiting factor in the
diagnosis of central arteriovenous shunts.  cardiac
failure does not preclude the
diagnosis, providing one can exclude valvular
regurgitation by other means.  the
method is thus, in spite of its limitations, of extreme
value in diagnosing central
arteriovenous shunts, especially when the results are
analyzed together with clinical
.I 394
.W
information.
2724. primary epidermoid cancers of the lung.  electron micro-
scopic study
an electron microscopic study was made
of 8 squamous cell, 3 undifferentiated,
and 3 alveolar carcinomas of the lung on
biopsy specimens embedded in methacryl-
ate.  the squamous cell carcinomas were
found to contain cylindrical cells with
glycogen granules, scanty mitochondria,
a reticular endoplasm which was chiefly
vesicular, numerous free ribosomes,
and bundles of confluent fibrils in the desmo-
somes.  the authors also observed in
the center of the tumor nodes, cells richer
in tonofibrils which enveloped the
nucleus, and cells in which all the cytoplasmic
organelles had almost disappeared
except for tonofibrils or cells packed with
keratohyalin and even lipid granules
sometimes arranged in lamellar formations
of the myelin type.  the picture as a
whole was that so often seen in the optic
microscope tumor foci formed of
slightly differentiated cells at the periphery
which became more differentiated
as one approaches the center.  the undifferenti-
ated cells resembled more the
intermediate bronchial cells than the basal cells.
the paper does not describe the
undifferentiated and alveolar carcinomas.
.I 395
.W
1375. loss of neoplastic properties in vitro. ii. observations on
kb sublines
ten sublines of the kb cell line obtained from
a number of different laboratories
were reexamined with respect to chromosome
number and heterotransplantability
to the syrian hamster cheek pouch.  twelve
clonal cultures derived from 2 of these
sublines were similarly examined.  three
sublines differed from one another and
from the kb cell line originally studied,
which was heterotransplantable with inocula
of circa 10 cells.  only 2 of the sublines
could be heterotransplanted with inocula
of less than 10 4 cells; 5 were heterotransplantable
with inocula of 10 4-10 6 cells; and
2 failed to heterotransplant, even with
inocula of 10 6 cells.  similar differences in
heterotransplantability were observed
among the clonal derivatives of 2 of these
sublines.  although the modal numbers of
these sublines and clonal derivatives were
basically similar, ranging from 73 to 80,
a few lines had a chromosome of sufficient-
ly distinctive morphology to serve as a
marker.  there was, however, no apparent
correlation between these minor karyotypic
differences and heterotransplantability.
possible differences between non-heterotransplantable
and heterotransplantable
sublines with respect to the pattern of
variability in cytoplasmic protein and cyto-
plasmic ribonucleic (rna) content per cell
remain to be studied in detail.  for i of this
series of articles see exc. medica cancer, 1965, abstr. no. 2378.
.I 396
.W
1377. establishment of a tissue culture strain jtc-14 from actino-
mycin-induced ascites sarcoma, and its biological characters
cell line jtc-14 has been maintained for more
than 2 yr. and subcultured 93 times.
cells from the 10th subculture on subcutaneous
injection into mice produced tumors
identical with those produced by the original
cells.  judged by the time taken to kill
mice on intraperitoneal injection the tissue
culture cells were not as malignant as
the original tumor cells.  after passage in
animals the cells were easily re-established
in culture in vitro.
.I 397
.W
1378. microcinematographic study of the mechanism of cancerous
invasion in cultures of normal tissue combined with malignant cells
normal myocardium of newborn c3h mice was
cultivated in vitro in contact with
homologous sarcomatous cells (strain n1 and
strain nctc) and studied by micro-
cinematography for 22 days.  it was found that
the tumor cells tend to move apart,
and with more vigorous and rapid movements
some of them called 'commando's'
make their way into the group of normal
cells but are arrested wherever they meet
a compact group of these cells.  this then
demonstrates, on the one hand, direct
aggresivity of the tumor cells and, on the
other, the 'group' defence of the normal
cells.
.I 398
.W
2413. the presence of lymphocytes in long term cultures of
newborn mouse thymic epithelium
thymic epithelial cells derived from newborn
mouse thymic fragments were cultured
in vitro for over 22 mth.  subcultures were
started by transferring minute cell
sheets obtained by mechanical scraping of
the original culture when it was 14 mth
old or older.  lymphocytes, many of them
with the morphological appearance of
plasma cells, were seen in the subcultures.
intact lymphocytes, as well as mitotic
figures were seen within cytoplasmatic vacuoles
of the epithelial cells.  the possible
bearing of these observations on the origin of the
thymic lymphocytes is briefly
discussed.
.I 399
.W
3748. four separate tumour clones derived from a transplantable pleo-
morphic carcinoma of the lung in a heterozygous mouse
a metastasising pleomorphic adenocarcinoma
in the lung of an untreated hetero-
zygous male mouse was successfully
transplanted to 4 brothers by the 'plating'
technique of henderson and rous.  by
'plating' multiple small grafts in air bells in
the subcutaneous tissues of the new hosts
it was possible to select 4 different clones
of transplantable tumour for further study.
the histological peculiarities of
different parts of the original tumour
were reproduced in the different clones a i,
ii, iii, and b.  retrospective study
of the primary tumour and of its metastases
provided some interesting clues to routes
of metastasis and the selective survival of
malignant cells.  it is concluded that by
the cloning of transplantable cells, at the
first serial passage, valuable information
about the histogenesis and potential
malignancy of the primary tumour can be
obtained.  lastly, the highly malignant
character of 4 clones of tumour cells apparently
derived from the familiar clinically
benign adenoma of the mouse lung may
be of some interest, from the point of
view of prognosis based on histology.
.I 400
.W
2379. in-vitro culture of pulmonary tumors in hamsters caused by adenovirus 12
it is known that the adenoviruses 12 and
18 provoke malignant tumors in the
new-born hamster.  the authors made a study
of the histogenesis of these tumors and
examined the specific changes brought about
in the cells by the virus infection
malignancy, presence of viral antigen, reactions
to superinfection.  when new-born
hamsters were inoculated in the chest with
adenovirus 12, malignant tumors
developed in one or two months, in 16 animals
out of 22.  these tumors presented
an epithelial aspect and were of bronchiolo-alveolar
origin.  they were transplant-
able in vivo; if they were cultured in vitro,
they consisted in the first few cultures of
macrophages, fibroblasts and epithelium.
in subsequent passages, there was a
progressive disappearance of the macrophages
and fibroblasts.  in some cases, the
culture after seven passages was of a purely
epithelial nature, and when it was
reimplanted into hamsters at this time it
gave rise to the rapid development of an
epithelial tumor.  in the tumor cultures,
no adenovirus could be demonstrated.
nor could cultures of the pulmonary tumors,
or cultures of normal hamster lung be
infected with adenovirus.  it appears that the
lung of the hamster in an organotyp-
ical culture constitutes a means of choice
for the malignant transformation of
adenovirus 12.
.I 401
.W
133. demonstration, purification, and partial characterization of ab-
normal (hsl) antigens in stable human cell lines
the existence of abnormal human stable
line (hsl) antigens common to a
number of stable human cell lines, but
absent from normal human tissues and
normal human diploid cell strains in tissue
culture, was demonstrated by agar gel
microimmunodiffusion.  hsl was detected
in hela-sj, hela-mba, hela-s3,
chang conjunctiva, syverton's embryo
esophagus, chang liver, and j-iii.  it
was not detected in henle's human intestine
or detroit-6.  it was absent from two
normal diploid strains, wi-38 and sj-dhl,
and was not found in a variety of
concentrated extracts of fresh human
organs.  hsl was not associated with
contamination by pleuropneumonia-like
organisms (pplo) of cell lines.  the
purest hsl preparations obtained from hela-sj
by ammonium sulfate fractiona-
tion yielded absorption spectra characteristic of
protein and were inactivated by
trypsin.  sephadex chromatography indicated a
particle weight of approximately
150,000; hsl was not sedimented at 125,000 x g.
in 0.02 m po4 buffer, activity
was virtually completely eliminated after 2 minutes
at 50 c., 8 minutes at 45 c.,
or 80 minutes at 40 c.  preliminary studies with
fluorescent anti-hsl globulin
indicated that hsl was not a surface antigen;
rabbit antisera to purified hsl
fractions were not cytotoxic to hela cells.
the best preparations of hsl still
contained a trace of common human antigen
and appeared to consist of multiple
components active in immunoprecipitation.
electrophoresis indicated the in-
homogeneity of this material.
.I 402
.W
1696. further comparative studies on two isogenic cell lines of autologous
origin, one of which is tumor-producing
a single explant of normal lung tissue
from an adult female mouse c57bl provided
2 cell lines.  one remained normal
and is referred to as pg, the other became
malignant and is designated as pt.
with successive in vitro passages by tryp-
sinization the tumour-inducing capacity
of the pt line considerably decreased its
tumour-producing capacity as well
as its acrobic glycolysis coefficient, while the
pg line showed no appreciable
change.  results of chromosome studies are de-
scribed, but proved inconclusive.
similar experiments were also carried out on
cell lines derived from the pt line
and their results are discussed.
.I 403
.W
1202. characteristics of human adenovirus type 12 induced hamster tumor
cells in tissue culture
characteristics of a human adenovirus
type 12 induced hamster tumor serially pro-
pagated in vitro are described.  these
include small cell size, epithelioid appear-
ance, rapid growth rate, resistance to
superinfection with a-12, and transplant-
ability to weanling hamsters.  these cells grew
either as monolayers or as balls of
aggregated cells detached from the glass,
depending on whether calf serum or horse
serum was added to the eagle's medium.  attempts
to demonstrate virus activity by
subculture of supernatant fluids and lysed cells into
hela cells, mixed culture with
human and hamster cells, electron microscopy,
and inoculation of newborn
hamsters with irradiated tumor cells were negative.
.I 404
.W
142. trials of heterotransplantation of human cancer in rabbits
and kleisbauer a.
trials of transplantation of human
tumours (some 20, almost all carcinomas) in
the pleural cavity of large rabbits
(6 months old flanders, weighing 3 kg.) gave
negative results also when cortisone
treatment was associated with it, though in
the cortisone treated animals the
necrosis of the tumours was less massive.
examination of the grafted tumour
was carried out at different times (from 8 to
365 days after transplantation) and
was also controlled by radiographic examina-
tions.  detailed description of the
giant cell reactions around the tumours and in
the adjoining lung.
.I 405
.W
1207. solitary mast cell granuloma (histiocytoma) of the lung.
a histopathologic, tissue culture and time-lapse cinemato-
graphic study
a pulmonary histiocytoma in a 57-year-old
woman was studied intensively histo-
pathologically and by other techniques.
abundant mast cells were found within the
lesion, a previously unreported finding.
tissue culture studies suggested that the
process is reactive rather than neoplastic.
some plasma-cell granulomas of the
lung may be mast cell histiocytomas.
.I 406
.W
2773. the value of fluorescence cytology for the cytodiagnosis
of pulmonary cancer
the paper discusses the test results
of 527 tissue samples sent in for the cytodiag-
nostics of lung cancer and compares
the method of ao-fluorochromation with other
methods of preparation.  by means of
applying ao-fluorochromation, the rate of er-
roneously positive findings could be
reduced.  the rate of erroneously negative find-
ings was somewhat higher but the total
diagnostic precision of 93% was 3% higher
than in all other methods applied.
.I 407
.W
2774. pitfalls in the clinical and histologic diagnosis of broncho-
genic carcinoma
a necropsy study of 380 cases of extrathoracic
carcinoma revealed that pulmonary
metastases occurred in almost 50% of the
cases and bronchial metastases in over
25%.  there were 39 cases (10.3%) in the
series with clinical features simulating
bronchogenic carcinoma and in 24 (62%)
of these cases there was cytologic and/or
histologic confirmation.  carcinomas of
the pancreas presented the greatest source
of diagnostic error accounting for more
than one-third of the 39 cases; the primary
site second in frequency was carcinoma
of the kidney.  bronchial metastases were
chiefly responsible for the clinical,
cytologic, and histologic findings compatible
with the diagnosis of bronchogenic
carcinoma.  secondary growths in the lungs may
present roentgenologically as solitary
tumors indistinguishable from primary lung
cancer.  metastatic lesions in lymph
nodes, bronchi, and lung may exhibit pleomor-
phic features simulating squamous
cell carcinoma.  the diagnosis of bronchioloalveo-
lar carcinoma in resected lung tissue
is a presumptive conclusion inasmuch as the
identical morphological features may
be reproduced by metastases from duct or
glandular carcinomas.  the simulation
of bronchogenic carcinoma by metastatic tum-
ors occurs with sufficient frequency to
challenge the diagnostic accuracy of deaths
certified as bronchogenic carcinoma
with necropsy exclusion of other primary sites.
.I 408
.W
4396. effects of arginine deprivation, ultraviolet radiation,
and x-radiation on cultured kb cells.  a cytochemical and
ultrastructural study
cultured kb cells (derived from a
human oral carcinoma) grown in monolayers
were injured by one of three agents
starvation by arginine deprivation or treatment
with high doses of either ultraviolet
radiation or x-radiation.  the different agents
produced changes in nucleolar structure
and varying accumulations of triglyceride
and glycogen.  all three agents produced
an increase in number and size of lyso-
somes.  these were studied in acid
phosphatase preparations, viewed by both light
and electron microscopy, and, occasionally,
in vital dye, esterase, and aryl sul-
fatase preparations.  ultrastructurally,
alterations in lysosomes suggested that
'residual bodies' developed in a variety
of ways, i.e., from the endoplasmic retic-
ulum, multivesicular bodies, or autophagic
vacuoles.  following all three agents,
the endoplasmic reticulum assumed
the form of 'rough' or 'smooth' whorls, and,
after two of the agents, arginine
deprivation or ultraviolet radiation, it acquired
cytochemically demonstrable acid
phosphatase activity.  near connections between
the endoplasmic reticulum and lysosomes
raise the possibility that in kb cells, at
least when injured, the endoplasmic
reticulum is involved in the formation of
lysosomes and the transport of acid
phosphatase to them.
.I 409
.W
1106. the simultaneous use of extracorporal circulation and hypothermia in the
surgery of the heart
the operative technique of cardiac
surgery under conditions of deep hypothermia with
simultaneous use of a pump oxygenator
and cardiopulmonary bypass is described.  in
the majority of cases the patients were
cooled with water at 2 c. and the perfusion
volume was reduced by more than 50%
during hypothermia.  in others, a gradient of
10 c. between blood and water was
maintained and the perfusion volume was reduced
by less than 50%.  the data presented
show that neither technique leads to hypoxic
changes in the cerebrum and internal
organs, provided the mean arterial pressure
is kept between 70 and 90 mm. hg during perfusion.
the overall mortality in the
authors' 168 cases - most of which
had congenital heart disease - was 14.8%.  in 53
cases of tetralogy of fallot - most
of them cyanotic - the vsd was closed by taking
a flap of tissue from the crista supraventricularis.
in this group mortality was 24.5%.
.I 410
.W
464. cardiac performance in hypothermia.  an experimental study of left
ventricular power, oxygen consumption, and efficiency in dogs
multiple cardiac parameters have been measured
in 30 dogs cooled to 20 c. aortic
blood temperature.  the parameters have been
expressed both as absolute values
and as percentages of normothermic values.
at normothermia, dogs with closed
chest had an ascending aorta flow of 154%
and a left ventricular external power of
183% of the corresponding values for dogs
with open chest.  both ascending aorta
flow and left circumflex coronary artery flow
were reduced to 25% of normothermic level
at 20 c.  aortic arch mean pressure was
reduced to 50% of normothermic level
at 20 c.  total peripheral resistance was
increased to 205% of normothermic level
at 20 c.  left ventricular external power
was decreased to 11% of normothermic
level at 20 c.  left ventricular oxygen
consumption was decreased to 31% of nor-
mothermic level at 20 c.  mechanical
efficiency of the left ventricular myocardium
was decreased to 39% of normothermic level at 20 c.
.I 411
.W
3270. tolerance of dogs to deep hypothermia.  controlled and maintained with a
pump oxygenator
the advantages of hypothermia of below 10 c for 2 hr,
induced and maintained by
extracorporeal circulation of 200 min.,
were compared to partial bypass of the
same duration during normothermia.
in the normothermic group 9 dogs out of 12
lived.  in the hypothermic group 6 dogs
out of 15 (40%) survived when perfused at
the high flow of 55 cc/kg/min.  eleven
dogs out of 15 (70%) survived when the flow
rate was reduced to 25 cc/kg/min when
the temperature was below 10 c.  the death
in the high flow group were due mainly
to postperfusion lung changes even when low
pulmonary venous pressure was assured
by venting in the left atrial chamber.  me-
tabolic acidosis occurred in all groups;
though greater in the high flow, with the
low flow intermediate between the former
and the normothermic group.  this change
to a great degree, can be explained by the lung changes.
.I 412
.W
1593. bleeding tendencies associated with profound-hypothermia technics in
neurologic surgery
forty-three patients with bleeding intracranial
aneurysms were operated on under
deep hypothermia and with the aid of extracorporeal
circulation.  the open-thorax
method was used in 18 cases and the closed-thorax
method in 25.  the following
points are made  (1) the closed-thorax method
is considered superior to the open-
thorax method in several respects; (2) meticulous
hemostasis is essential to control
the oozing that occurs during extracorporeal
circulation under profound hypothermia
until the heparin antagonist can become
effective and body temperature can return
to normal; (3) significant thrombocytopenia
may develop during extracorporeal cir-
culation, and inhibition of the thrombin-fibrinogen
reaction by factors other than
heparin may cause a major coagulation defect
and may also, by mimicking the he-
parin effect, lead to the excessive use of
heparin antagonists; (4) pathologic changes
in microcirculation during extracorporeal
circulation may be determinants of a
hemorrhagic tendency.
.I 413
.W
4088. the use of hypothermia and dehydration in the treatment of severe
cerebral hypoxia
the rational for using hypothermia or
cerebral dehydration is to suppress or re-
verse progressive or delayed cerebral
damage after hypoxia.  it is suggested that
damage of this nature results from injury
to the astroglia and oligodendroglia,
especially the former.  experimental and
clinical evidence favors lowering of the
body temperature immediately after any
episode of hypoxia accompanied by impor-
tant damage to the brain.  the rational
for using dehydration is insecure and its
results are uncertain.  this treatment
should probably be reserved for cases in
which a raised cerebrospinal fluid pressure
has been proved, and in which other
measures, especially hypothermia,
are either not available or have failed.
.I 414
.W
7828. selective cerebral hypothermia  physiology and technic
a safe, suitable technique for producing
selective brain cooling by a perfusion
method is described.  of 15 dogs, 7 survived.
the salient features aiding survival
are discussed.  the use of a direct vasodilator
(papaverine) in the perfusate to
relieve vasospasm markedly reduced cooling time
and represented the most signi-
ficant technical advance over previously
described methods.  an acid base analysis
utilizing the siggaard-andersen curve nomogram
was performed on 4 dogs and no
significant acidosis noted during selective brain
cooling.  a definite arteriovenous
lactic acid difference developed at hypothermic
temperatures indicating the brain
may metabolize this substance in preference to
glucose at lowered brain tempera-
tures, the reasons for which were discussed.
the rate of disappearance of physi-
cally dissolved oxygen (po2) was measured
in the brain following ischemia at dif-
ferent temperatures.  the average rate of
disappearance at 20 c. was 40% of the
rate at 37 c.  the discrepancy between this
finding and the in vitro oxygen utili-
zation rate at the same temperature was discussed.
.I 415
.W
948.cardiac activity in cranio-cerebral hypothermia
the onset of hypothermia rarely alters the heart
rate.  as it deepens to 35-32, the
rate slows, and at the level of 30-29 it usually
amounts to only half its original va-
lue.  at 28 or below, the development of
bradycardia is observed.  after warming
to 32 the normal heart rate is restored.
during operations on the abdominal organs
the heart rate is only slightly modified.
the appearance of solitary extrasystoles is
rare and is usually associated with stimulation
of the diaphragm.  the most marked
changes in the heart rate are observed during operations on the heart,
especially if
it is excluded from the circulation.  an
idioventricular rhythm may develop before
the heart stops beating.  after removal of the
ligatures from the venae cavae the nor-
mal rhythm is restored.  as the temperature
falls, the excitability of the myocardium
increases.  conduction is more resistant.
areflexia continues even during direct sti-
mulation of reflexogenic zones.  in the surgical
stage of cranio-cerebral hypothermia
it is clear that no significant degree of energy
or hemodynamic insufficiency deve-
lops, whether in experimental conditions or
during operations on patients.  at opera-
tion a well-marked stabilization of the contractile
power of the myocardium may be observed.
.I 416
.W
946. respiration in hypothermia.  i. respiratory pattern and
acid-base balance in the blood
mongrel dogs, under light pentobarbital anesthesia,
were made hypothermic by im-
mersing them in ice water and then normothermic
in warm water.  in the course of
cooling, the respiratory rate and pulmonary
ventilation, after an initial increase,
were reduced as the rectal temperature fell,
and spontaneous respiration was ar-
rested at rectal temperatures of 21-25 c.
alveolar pco2 was increased, after an
initial slight lowering, with the progress of
hypothermia.  arterial ph and standard
bicarbonate (jorgensen and astrup) decreased,
and the alkalinity of the blood coh/
ch (winterstein) decreased markedly during hypothermia.
these findings suggest
both respiratory and metabolic acidosis as the
mechanisms concerned.  in the course
of rewarming all these changes disappeared rapidly
and completely though the venti-
latory stimulation observed as an initial transitory
phenomenon during cooling failed to occur.
.I 417
.W
896. studies on blood viscosity and its significance in anesthesia
the principles for measuring blood viscosity
have been discussed.  although blood
does not behave in a newtonian manner,
the data obtained in in vitro measurement
are useful.  a modified simple method for
measuring blood viscosity relative to nor-
mal saline has been described.  there is
essentially no difference in viscosity be-
tween fresh blood and heparinized blood and between plasma and serum.
viscosity varies with the quantity and nature of proteins
in plasma and the cellular concentra-
tion.  halothane and thiopental sodium reduce
blood viscosity and seem to be indicat-
ed in conditions in which there is hemoconcentration
and a tendency for red blood
cells to aggregate.  cyclopropane, hypothermia,
and norepinephrine tend to raise
blood viscosity and would seem to be contraindicated
when the microcirculation is failing.
.I 418
.W
4612. flow considerations in regional cerebral hypothermia
it is suggested that low flows are dangerous
and may cause anoxia either directly
or by interfering with cooling.  sixty dogs
have been subjected to local cerebral
hypothermia by the method of femoral to
carotid cooling of arterial blood with per-
fusion at a predetermined pressure rather
than predetermined flow rate.  the cir-
cuit is described and its advantages for
clinical use mentioned together with its in-
accuracies as a method of scientific investigation.
these are chiefly concerned
with maintenance of systemic blood pressure
which may require the injection of
pressor agents.  evidence for reduction in flow
at low temperatures is discussed
and evidence presented that this is not only due
to increase in viscosity but that
there is an active spasm, manifested by
'rewarming humps' which occur in the
cooling graphs.  mean carotid flow rates
were determined by a revolution counter
attached to a pump of fixed stroke volume,
the output of which was linked to the per-
fusion pressure and thus determined by the resistance.
the place of added co2
is discussed particularly in relation to the fall
in partial pressure which accompa-
nies the cooling of the blood.  the addition of 5% co2
did not increase total carotid
flows.  halothane had been used as an anesthetic
because of its sympatholytic ac-
tion.  it has increased flows by 37% and
abolished 'rewarming humps'.  rheomacro-
dex used as a priming fluid instead of blood
produced increased flow averaging 75%
but did not abolish spasm.  it is suggested that
cooling faster than 1 c. per minute
is not intrinsically dangerous if spasm is prevented
and high flow maintained by the methods described.
.I 419
.W
4613. selective brain cooling produced by cerebral ventricular perfusion
hypothermic cerebral ventricular perfusion
was applied to dogs.  shivering appear-
ed to be directly related to the cns temperature
rather than the peripheral body
temperature.  selective heating of the brain-stem
produced panting.  rewarming
of the body was retarded by the initiation of heat
loss mechanisms controlled cen-
trally when hyperthermic perfusion was used.
shivering disappeared but panting
was unaffected by pentobarbital anesthesia.
cooling of one or both frontal areas and
the anterior part of the third ventricle did not
significantly affect the respiratory
or circulatory systems but brain-stem hypothermia
produced distinct respiratory
and circulatory reactions.  it is suggested that
cooling of the 3rd and 4th ventricu-
lar areas may be utilized for anesthetic purposes.
.I 420
.W
1139. optimal coronary flow in the bypassed normothermic and hypothermic heart
a series of experiments were conducted in dogs
in which bypass flow, temperature,
and direct coronary perfusion pressure were varied.
coronary flow, coronary ven-
ous saturation, myocardial oxygen consumption (mvo2),
and coronary vascular re-
sistance were assayed.  coronary flow as a percentage
of total bypass flow did not
vary appreciably at varying levels of bypass flow.
induction of hypothermia, when
total bypass flow is constant, results in decreasing
coronary flow.  induction of hy-
pothermia when maintaining a constant bypass pressure
results in an increasing
coronary flow with temperatures down to 22 c.
further cooling causes a reduction
in flow.  using isolated coronary perfusion at 100 mm. hg,
coronary flow fell and
resistance rose during the first 15 min. of bypass.
using isolated coronary perfu-
sion at 100 mm. hg, induction of moderate hypothermia
(25 c.) caused an increase
in coronary flow and venous saturation and a decrease
in cardiovascular resistance
and mvo2.  under the same conditions, induction of
hypothermia to 18 c. produced
similar changes but caused myocardial hemorrhage
and ventricular fibrillation.  pro-
found hypothermia probably leads to excessive
fragility of the capillary bed.  reduc-
tion of perfusion pressure to 50 mm. hg at near
normothermia reduced coronary
flow and slightly reduced venous saturation
and mvo2.  the same reduction of perfu-
sion pressure at 18 c. produced similar but
less marked changes.  reduction to 25
mm. hg at 18 c. markedly reduced coronary flow,
venous saturation, and mvo2
initially, but with partial recovery later.  from this
data of acute experiments in
dogs, coronary perfusion using moderate hypothermia
(about 31 c.) and 50 mm.
hg, slightly pulsatile mean pressure appears optimal.
.I 421
.W
974. extracorporeal hypothermia without thoracotomy.  an ex-
perimental study in the use of cold for neurosurgery and
cancericidal perfusions
this paper includes minor clinical notes
on open heart surgery and cancer perfusion
but contains no experimental information
on neurosurgery or cancer perfusions.  a
method of closed-chest hypothermic perfusion
in 30 dogs is reported.  the authors
utilize drainage of superior and inferior cavae
by gravity.  the volume of venous
drainage sometimes enhanced by transfusions
or 12.5% low molecular weight dex-
tran determined the flow rate.  cooling was
maintained for quite variable periods
apparently generally to an unspecified
esophageal temperature.  perfusion time va-
ried from 30 min. to 4 hr.  animals with
low flows were perfused longer, had a high-
er incidence of ventricular fibrillation,
and a very low survival rate.  eleven ani-
mals survived.  all had pre-cooling flow
rates above 40 ml./kg./min., good flow
rates during the perfusion, and only 3 had
ventricular fibrillation.  flow rates and
survival were increased in animals receiving
low molecular weight dextran.  four-
teen of 15 animals with ventricular fibrillation
were defibrillated electrically, 8 re-
gained 'adequate' cardiac function, but only 3
survived.  some interesting data on
regional cooling of the lower half of the body
is presented.  the authors conclude
without sufficient evidence that the most
important factor in the mortality in hypo-
thermic perfusion is the ability to maintain
'a flow rate approaching the estimated
normothermic cardiac output of the animal'
.I 422
.W
2406. profound hypothermia
the aim of hypothermia is protection of vital
cerebral structures from hypoxia
during aneurysm repair; profound hypothermia
is also valuable in operating on
certain cardiac defects which cannot be repaired
even with whole body perfusion.
since the time needed for aneurysm repair often
exceeded the safe limit of 8 to 12
minutes without circulation afforded by surface
hypothermia of 29  to 30  c., the
authors have investigated the drew (open-chest)
technic, the closed-chest method,
and isolated cerebral perfusion.  the drew technic
consists of substituting two
pumps for the heart while the patient's lungs act
as the oxygenator.  because of its
disadvantages (the large amounts of blood needed
and the morbidity due to intra-
cardiac cannulation and median sternotomy), a
closed-chest method was developed,
using a mayo-gibbons vertical-sheet pump-oxygenator
to provide the perfusion and
extracorporeal cooling without requiring thoracotomy.
in cerebral perfusion, blood
is taken from one artery, pumped through a heat
exchanger, and returned to another
artery.  the authors describe anesthetic technics,
offer comparisons of the three
methods, give instructions pertaining to the production
of hypothermia, and list the
problems encountered in the management of these cases.
.I 423
.W
3194. systemic hypothermia via gastric cooling
eight dogs underwent gastric cooling for
systemic hypothermia.  each dog was cooled
with the balloon filled with a 'safe' volume
based on weight (20 ml/kg) and subjected
to cooling with the balloon filled maximally,
but safely to a pressure of 10 mm hg.
consistently, the latter procedure was far
more efficient, averaging 2.6 times as
rapid for all degrees of hypothermia.  a
decrease in core temperature by 7 c re-
quired an average of only 28.4 minutes.
on comparison with clinical reports of hy-
pothermia induced by the usual gastric
cooling, an improved efficiency of two-fold
to three-fold is still noted.
.I 424
.W
3820. the dubious haemopoietic
stem cell function of the lym-
phoid cells of the blood.
autoradiographic studies on
dogs
the migration, fate and turnover of
lymphoid cells in blood and bone marrow of
irradiated and non-irradiated dogs were
studied by serial autoradiography with co-
ping of the hind legs during the plasma
clearance time of h3-thymidine injected into
an anterior vein.  in irradiated dogs,
the h3-thymidine injection procedure was car-
ried out during the early recovery phase
following 250 r whole body x-irradiation.
conclusive evidence of transformation of
hematogenous bone marrow lymphoid cells
into hemopoietic precursors was not found.
however, in the light of the individual
grain counts transformation of a few lymphoid
cells into hemopoietic cells cannot be
ruled out.  the data obtained from a dog in the
very early recovery phase following
whole body irradiation strongly indicate such
a transformation.
.I 425
.W
3927. studies on growth and cytomorphosis
in the thymo-lympha-
tic systems - with special
reference to the influence of
the thymus and the thyroid
in guinea-pigs
migratory streams of lymphocytes between
different parts of the thymo-lymphatic
system were evaluated by comparisons between
lymphocyte populations in thoracic-
duct lymph and arterial and venous blood,
especially thymic venous blood.  by re-
cording organ weights in sham-operated and
thymectomized guinea-pigs, treated
with thyroxin or untreated, the importance
of the thymus and the thyroid for growth
and regeneration in the thymo-lymphatic
system was studied.  the main results are
as follows.  there is a considerable venous
output of lymphocytes with low mito-
chondrial content (small lymphocytes) from
the thymus in normal young guinea-pigs.
this explains the much higher incidence of
small lymphocytes in blood than in tho-
racic-duct lymph.  neonatal thymectomy
causes lymphatic hypotrophy with defi-
ciency of lymphocytes and pyroninophilic
cells in relation to reticular ones.  body
growth and survival of the animals are not
affected.  in the thymus, exogenous
thyroxin most probably promotes differentiation
of large basophilic cells to small
lymphocytes, resulting in an increased output of
small lymphocytes.  in the lymph
nodes, thyroxin promotes differentiation of large
pyroninophilic cells ('transitional
cells') into immature and mature plasma cells.
the effects of thyroxin on dif-
ferentiation are followed by an increased growth
of the thymo-lymphatic organs,
characterized by an increased incidence of large
basophilic cells and increased weight
of the lymphatic organs.  growth of the thymus and
lymph nodes precedes that of
the red splenic pulp.  this delayed splenic response
is not due to a transformation
of an increased number of immigrated thymic
lymphocytes, as neonatal thymectomy
does not prevent the thyroxin-stimulated
occurrence of large basophilic cells in the
red splenic pulp.  the thyroxin-stimulated
growth of the lymphatic system is ac-
companied by an increased output of larger
lymphocytes through the thoracic
duct, resulting in an increased number of
larger lymphocytes in the blood.  in
postnatally thymectomized animals, having a
normal (or above normal) amount of
circulating small lymphocytes, thyroxin produces
a drastic decrease in the number of
small blood lymphocytes, indicating a decreased
delivery and/or increased disappear-
ance of these cells to and from the blood, respectively.
this decrease in number of small
lymphocytes is not seen in sham-operated animals.
as judged by studies of organ
weights, the thyroxin-stimulated growth and
regeneration of the lymphatic tissue
are influenced antagonistically by thymectomy
and synergistically by local factors
in involuted tissue.
.I 426
.W
815. the origin of macrophages
from bone marrow in the rat
skin windows' and subcutaneous coverslips
were applied to rats in a study designed
to identify the tissues in which the precursors
of macrophages proliferate.  lympho-
cyte-depletion by either chronic drainage from
the thoracic duct or 400 rads of x-
irradiation failed to suppress the emigration of
macrophages or to reduce the pro-
portion of them which became labelled after an
injection of tritiated thymidine.  x-
irradiation with 750 rads suppressed
the emigration and the labelling of the exudate
macrophages.  both were restored to
normal when the tibial marrow was shielded
during irradiation.  radioactively-labelled
cell suspensions obtained from thoracic
duct lymph, lymph nodes, thymus, spleen
and bone marrow were transfused into
syngeneic recipients.  the emigration of
labelled macrophages on to coverslips
could be demonstrated only in recipients
of labelled bone marrow and spleen cells.
labelled monocytes were found in the blood
of rats which had received injections
of labelled bone marrow.  it was concluded
that in the rat, bone marrow, and to a
lesser extent spleen, are major sources of
the macrophages which emigrate into
foci of acute, non-bacterial inflammation.
.I 427
.W
1786. studies of the
leucocyte compartment
in guinea-pig bone
marrow after acute
haemorrhage and
severe hypoxia  evidence
for a common stem-cell
after a large acute hemorrhage,
the absolute le-
vels of neutrophils, eosinophils, and
basophils in guinea
pig bone marrow are considerably
reduced.  all stages
of differentiation are involved, the
decline in myelo-
blasts and promyelocytes being
particularly marked.
exposure to severe hypoxia also
temporarily depresses
the number of marrow granulocytes.
bone marrow
lymphocytes are only slightly reduced
after a single he-
morrhage but in the later stages of
severe hypoxia their
numbers are greatly reduced.
assuming the supply of
stem cells in the bone marrow
is not unlimited, the de-
crease in marrow granulocytes
and lymphocytes follow-
ing marked erythropoietic stimulation
appears to favor
a monophyletic theory of hemopoiesis;
a heavy demand
for stem cells to differentiate into the
erythron may
temporarily restrict the
number entering the leukon.  the
hypoxic animals showed
a considerable loss of body weight
and the notable reduction
of marrow lymphocytes in the
later stages of hypoxia
may be specifically related to a
generalized atrophy of
lymphoid tissue.  using h3-thymi-
dine there is evidence
of active dna synthesis in guinea
pig metamyelocytes.
although dna-synthesis was found
in metamyelocytes of
normal marrow, after hemorrhage
these cells form a much
larger proportion of the total
synthesizing cells in the
granulocyte compartment and
also the ratio of labeled
metamyelocytes to myelocytes
is considerably increased.
microspectrophotometric
measurements of the feulgen
dna-content of metamyelo-
cytes after hemorrhage show
that there are 2 populations
of these cells.  one group has
values typical of resting or
nonsynthesizing cells but a 2nd
group shows a complete
range of dna-values up to levels
characteristic of those
found in dividing cells.  certain
small mononuclear cells
with minimal but deeply basophilic
cytoplasm are a dis-
tinctive group of dna-synthesizing
cells in marrow af-
ter hemorrhage.  morphologically,
there appears to be a
complete sequence between these
cells and procrythro-
blasts.
.I 428
.W
3831. relative ability of parental
marrow to repopulate lethal-
ly irradiated f1 hybrids
lethally irradiate (c57bl x 101)f1 mice
injected with a mixture of 10 million
c57bl and 10 million 101 bone-marrow
cells were repopulated only by the 101
bone-marrow cells.  experiments with other
cell mixtures indicated that the 101
marrow was relatively nine times as efficient
as c57bl marrow in repopulating
lethally irradiated (c57bl x 101)f1 mice.
results from additional strain combina-
tions suggested that the behavior of the
donor marrows was not determined solely
by h-2 factors.  c57bl marrow, which
frequently regresses in irradiated f1 mice,
has shown to be relatively less capable
of repopulating the recipient than regularly
retained parental marrow.  the differences
in the relative abilities of parental mar-
rows to repopulate f1 mice cannot as yet be
fully explained.  they might be corre-
lated with physiological differences between
the parental marrows or with a micro-
environmental advantage of one hematopoietic
cell type over another in the irradiated
recipient.  immunological and physiological factors
that might favor this selective
growth are discussed.
.I 429
.W
3832. pluripotent stem cell function
of the mouse marrow
'lymphocyte'
bone marrow from normal and polycythemic
mice was filtered through glass wool
columns to remove cells other than 'lymphocytes'.
for a given number of nucleated
cells, filtered marrow was more efficient than
the original marrow in repopulating
the spleen of an isogenic recipient previously
exposed to lethal irradiation.  the
proliferative capacity of both the filtered and
unfiltered marrow suspensions ap-
peared to be a constant function of the number
of small and medium 'lymphocytes'
present and not of any other cell type.
.I 430
.W
2045. the effect of
unilateral limb shield-
ing on the haemopoietic
response of the
guinea-pig to gamma
irradiation
guineapigs were exposed to
150 r  -irradiation
whilst approx. 1/5 of the total bone
marrow was protect-
ed by shielding 2 limbs.  quantitative
cell counts of both
the shielded and irradiated marrow
were combined with
observations on the thymus, spleen
and blood during the
recovery period, and compared
with the effects of whole-
body irradiation.  following
whole-body irradiation
(150 r) the thymus shows a
delayed secondary cellular
depletion coinciding with a
marked splenic hyperplasia.
both phenomena were eliminated
by limb shielding.  the
lymphocytes in the irradiated
marrow of partially shiel-
ded animals continued to show
both the overshoot and the
secondary fall in numbers which
characterize recovery
from whole-body irradiation
(150 r).  after an initial fall
in numbers of erythroid and
granulocytic precursors,
the shielded marrow showed
a temporary increase in
granulocytopoiesis coinciding
with an abortive phase of
granulocytopoiesis in the irradiated
marrow.  there was
no evidence of any effective colonization
of irradiated
marrow by cells from the shielded marrow.
the signi-
ficance of these findings is discussed.
.I 431
.W
4311. studies on intravenous transfusion
of thymus cells and
lymphnode cells.  iii. influence of
transfused thymus cells
and lymphnode cells on the bone
marrow
in rabbits transfused with thymus cells and
lymphnode cells the peripheral blood and
bone marrow were studied.  the transfusion
of thymus cells caused a peripheral
lymphocytosis and a diminution of lymphoid
cells in the bone marrow of both young
and adult rabbits.  the transfusion of lymphnode
cells resulted in a peripheral lympho-
penia, and an initial increase and a subsequent
diminution of lymphoid cells in the
bone marrow.  it is suggested that lymphoid cells
in the bone marrow may be lympho-
cytes which are stored or discharged according
to a variety of conditions.  further-
more, thymus cells are thought to mobilize
lymphocytes from the bone marrow to
the peripheral blood.
.I 432
.W
5041. studies on hypoxia.  iii. the
differential response of the
bone marrow to primary and
secondary hypoxia
twenty-five adult male guinea pigs were
placed in a decompression chamber, at a
simulated altitude of 14,000 feet for 5 days,
then kept in ordinary air for 5 days,
and finally returned to the decompression
chamber to be subjected to hypoxia a
second time, for periods ranging from 1
to 5 days.  during this period of secondary
hypoxia quantitative studies were made
of the changes in the blood and bone marrow.
in secondary as in primary hypoxia there
is a significant increase in the nucleated
red cells of the marrow.  in secondary
hypoxia, however, there is a very marked
increase in the marrow lymphocytes,
whereas in primary hypoxia the lymphocytes
fall.  the marrow reticulocytes remain
at a fairly constant level despite marked
fluctuations in erythropoiesis.
.I 433
.W
1044. an investigation of lymphocyte
production in guinea-pig
bone marrow
evidence from a variety of experiments indicates
that lymphocytes are produced in
guinea-pig bone marrow.  under certain conditions
the numbers produced appear to
be considerable.  during recovery from irradiation
there are numerous telophases
in marrow smears which appear to be forming small
lymphocytes.  moreover, many
lymphocytes are still found in shielded bone marrow
after the rest of the body, in-
cluding the conventional lymphoid tissues, has
received lethal or supra-lethal irra-
diation.  almost 50% of these cells are formed
after the irradiation.  finally, when
bone marrow is cultured in the peritoneal cavity
of a host whose own lymphocyte
production has been suppressed by irradiation,
small percentages of newly-formed
small lymphocytes are found in this marrow.
.I 434
.W
103. repopulation of bone marrow
in mice  number and type of
cells required for
post-x-irradiation protection
fractionation of cells from mouse bone
marrow and autologous mouse spleen indi-
cates that the cell responsible for bone
marrow repopulation and x-irradiation
protection resembles the small lymphocyte.
experiments with injection of different
numbers of bone marrow and spleen cells
and observations on survival obtained by
fractional irradiation of the entire body and
of extirpation of the shielded spleen
after irradiation indicate that approximately
3 x 10 4 cells of this type are required
to provide 50% survival, and that approximately
this number migrates from the
shielded extremity or spleen of a mouse per hour
(slightly faster for spleen and slower for bone marrow).
.I 435
.W
104. hyperbasophilic cells as an
indication of proliferation of
bone marrow transplanted to
irradiated dogs
a study was made of hyperbasophilic cells
which appeared following transplantation
of bone marrow to 20 irradiated mongrel
dogs of both sexes.  in the main series of
experiments the animals were irradiated
with a dosage of 600 r., using a four-tube
rum-3 x-ray machine  voltage 200 kv,
current 10 ma, filters 0.5 cu mm + 1.0
mm.al, target distance 60 cm., rate
18-22 r./min.  at 1-2 days after irradiation,
a suspension of bone marrow cells in a
dosage of 10 9 - 5 x 10 9 nuclear cells was
administered i.v.  the marrow was
obtained by aspiration from various skeletal
bones or by compression from the
sternum, ribs and other bones.  a study was made
of the morphological composition
of the blood and bone marrow before irradiation
and at 1-5, 10, 15, 20, 25 and 30
days after irradiation and transfusion of bone mar-
row, and thereafter at 10-15 days
intervals.  smears of blood and marrow were
stained with azure-ii-eosin.  it was
found that distinctive cells with basophilic proto-
plasm and frequent incidence of an
immature nucleus were present in the blood of
dogs following irradiation with 600 r.
and transplantation of bone marrow.  hyper-
basophilic cells appeared in the blood
at 2 - 4 days after transplantation and attained
a maximum 14 - 21 days later; thereafter
their number diminished rapidly.  the
trend of number of hyperbasophilic cells
coincided with that of other donor elements
(leukocytes, erythrocytes).  hyperbasophilic
cells were not found during acute radia-
tion sickness in dogs which were not given
injections of bone marrow.  they were
found 3 mth. after transplantation of bone
marrow to nonirradiated puppies at 2-3
days of age.  when the irradiation dosage
was increased to 800-1,000 r., the number
of hyperbasophilic cells increased and
attained a peak sooner than after the 600 r.
dosage.  such cells were formed from
the donor cells.
.I 436
.W
172. autoradiographic
studies of lymphoid
cells in blood and
bone marrow of nor-
mal and irradiated
dogs
the migration, fate, and
turnover of lymphoid
cells in blood and bone marrow
of 4 irradiated and 4 non-
irradiated dogs were studied
by serial autoradiography
with clamping of the hind legs
during the plasma clear-
ance time of h3-thymidine
injected into an anterior
vein.  in irradiated dogs, the
h3-thymidine injection pro-
cedure was carried out during
the early recovery phase
after 250 r of whole-body
x-irradiation.  the results on
2 irradiated and 2 normal
dogs were described in de-
tail.  migration of lymphoid
cells from blood to marrow
parenchyma was confirmed
in the irradiated dogs.  con-
clusive evidence of transformation
of these cells into
hemopoietic precursors was not
found.  the relative
number of large lymphoid cells,
the labeling index of
the whole population of lymphoid
cells, and that of small
lymphoid cells were increased
in irradiated marrow;
few initially labeled small
lymphoid cells could also be
observed.  these data indicate
that the pattern of pro-
liferation of lymphoid cells is
changed in irradiated re-
generating bone marrow.
.I 437
.W
175. lysozyme in bone
marrow and periph-
eral blood cells
by means of an indirect
histochemical technique,
the intracellular lysozyme of
the formed elements of the
peripheral blood and bone marrow
was estimated.  evi-
dence is presented that monocytes,
as well as mature
neutrophils and their precursors
extending back to the
progranulocyte, contain significant
amounts of this en-
zyme.  a rare mature eosinophil
demonstrated a trace
of lysozyme activity.  there was
no evidence of lyso-
zyme activity in basophils,
erythrocytes, megakaryo-
cytes, platelets, plasma
cells, tissue mast cells or
bone marrow
reticuloendothelial cells.
.I 438
.W
1770. proliferative activity of the
lymphatic tissues of rats as
studied with tritium-labelled
thymidine
cytokinetic data are presented, employing
quantitation of h3dna in the lymphatic
tissues of normal rats serially sacrificed
after h3tdr administration.  a marked
difference in the patterns of initial labeling
and label loss was observed between the
thymus and peripheral lymphatic tissue.
the data are compatible with other indica-
tions of rapid cell renewal in the thymus.
there is suppression of initial uptake of
h3tdr into the dna of each large lymphocytic
progenitor cell in the thymus, appa-
rently because of a feedback of thymidine
containing material from small lympho-
cytes in the thymus.  depletion of the thymus
of small cells, as by operative stress
or whole body x-ray, leads to a marked
increase in the uptake of h3tdr into the
dna of large thymocytes.  this finding,
which is in agreement with the previous
findings of sugino et al. suggesting transfer
of thymine nucleotides from small thy-
mus lymphocytes to precursor cells, may or
may not be related to the apparent
transfer of dna label between thymic cells.
the evidence for the latter consists of
the curvilinear dilution of the dna label in
the thymus proliferating cell population
and the relationship between the rate of dna
label dilution in large cells and the
dna in the small cells in the thymus.  after
the dna label in progenitor cells in
the thymus and lymph nodes has entered the
small cell population, the subsequent
dilution of grains in these dividing cells follows
the same slope as the loss of radio-
activity from the entire lymph node.  there is a
long retention of some h3dna label
in the dividing lymph node cell population.  this
suggests that the loss of radioacti-
vity from the dividing cells and from the small
cell population as a whole occurs e-
qually.  this pattern prevails regardless of
whether the percentage of large and
small cells is altered experimentally.  these
findings can be explained by an inter-
change of the dna nuclear label between small
lymphocytes and large lymphocytes.
this could occur by some process such as
phagocytosis or pinocytosis, or by trans-
formation of the small lymphocyte into a large,
dividing cell.  the data fit best with
the latter possibility.  all or any of these
mechanisms would lead to an equilibration
of the dna label between large and small
cells.  this finding prevents the assign-
ment of a finite life span to lymphocytes on
the basis of dna labeling kinetics.  ne-
vertheless, there appear to be at least two
different types of lymphocytes.  one,
the 'thymus-type' lymphocyte, is found in the
thymus cortex, bone marrow and ger-
minal centers of lymphoid follicles.  the other
type, found abundantly in the wide-
spread peripheral lymphatic tissue, shows a
very prolonged retention of dna la-
bel and is believed to be recirculating,
'immunologically committed' cells described
by others.  these cells do not appear to
enter the thymus cortex.
.I 439
.W
6674. the free and glucuronic acid-bound
17-hydroxy-corticosteroids in the
plasma of patients with cancer of the
breast on i.v. infusion of acth
seventeen patients with advanced mammary
cancer were given an infusion with
3 u. of acth in 5 hr. and 6 others an infusion
of 25 u.  determinations were made
of the plasma 17-hydroxy-corticosteroids,
free and bound to glucuronic acid both
before and after the infusion.  in rapidly
growing carcinomas, high initial values
were found for the free corticosteroids
(more than 20 ug./100 ml. of plasma).
the ratio of free to bound corticosteroids is
for stage iv patients 1.8 on the average,
and approximately 1 for the mixed
forms stage iv + m.  these ratios are not
altered by acth.  shifts in the ratio
of free to bound corticosteroids with acth
treatment can be seen, depending on
the initial value of the free corticosteroids.
the administration of 3 u. is enough
and the 5 hr. value is some 70%, related to a
maximal stimulation with 25 u.
.I 440
.W
4179. reduced estriol excretion in patients
with breast cancer prior to endocrine
therapy
the urinary quotient of estriol/estrone +
estradiol-17b(eq) was measured chemically in
women with and without breast cancer, as an in-
dex of the ratio of noncarcinogenic impeded es-
trogens to mammary carcinogenic estrogens.  in
34 controls, the median eq was 1.3 before and 1.2
after menopause, with only 21% of the patients sub-
normal.  in 26 breast cancer patients without endo-
crine treatment or recent surgery, the median eq
was 0.5 and 0.8 respectively, with 62% of the pa-
tients subnormal.  after major surgery or hormo-
nal therapy, only 23% of 53 patients were subnor-
mal, no remissions being observed unless the eq
rose toward normal.  matching of 24 controls and
patients in pairs by age and ovarian status in the
wilcoxon test indicated that the decreased eq ex-
creted in untreated cancer was significant at the
0.2% confidence level.  the marked increase in eq
induced by castration and androgen, estrogen, and
corticosteroid therapy suggests that normaliza-
tion of a precancerous metabolic imbalance be-
tween impeded and active estrogens derived from
ovarian and adrenocortical sources contributed to
arrested growth of estradiol-dependent metastases.
.I 441
.W
1107. urinary excretion of estrone,
estradiol and estriol by pa-
tients with breast cancer and
benign breast disease
premenopausal patients with breast cancer
and benign breast disease appear to ex-
crete a significantly lower percentage of
the total estrogen as estrone and a signifi-
cantly higher percentage as estriol than
women in the premenopausal control group.
there was no significant difference in the
excretion of total estrogen between cancer
groups and controls in good health.
postmenopausal patients with cancer excreted
higher levels of estriol than postmenopausal
control groups.  the increase in estriol
excretion cannot be explained by debilitation.
.I 442
.W
5323. systemic effects of androgenic
and estrogenic hormones in advanced
breast cancer
the systemic effects of diethylstilbestrol
(45 patients), testosterone propionate
(48 patients), and both hormones (22 patients)
were studied during the treatment
(six weeks to over three months) of advanced
breast cancer in postmenopausal
women.  serious complications included
induced hypercalcemia and fluid re-
tention.  physiologic effects such as
urinary incontinence (diethylstilbestrol),
virilization (testosterone), or nausea and
vomiting did not necessitate disconti-
nuance of treatment.  androgenic therapy
stimulated erythropoiesis.  observa-
tions on the systemic reactions to these
hormonal agents definitely contribute to
the evaluation of sex steroid therapy.
.I 443
.W
3478. the effect of dehydroepiandrosterone
on the 17-hydroxycorti-
costeroids in the plasma in various stages
of cancer and other diseases of
the breast
the reducing effect of dehydroepiandrosterone
on the plasma corticosteroids is
on the average shortened in advanced
(stage iv) cases of breast cancer.  in 3
groups of patients, the lowest corticosteroid
levels were found up to 6 hr. after
infusion of dehydroepiandrosterone-phosphate.
in patients with mastopathy the
effect was still detectable 12 hr. later; in patients
with breast cancer in stage iv the
initial levels were reached at that time.  in
cases with stages i and ii lesions, the
findings were intermediate.  the shortening
is attributed to a more intensive
transformation of dehydroepiandrosterone in
advanced cases of breast cancer.
.I 444
.W
5274. urinary excretion of estrone,
estradiol and estriol by patients with
prostatic cancer and benign prostatic
hypertrophy
and hopkins c.e.
urinary estrone, estradiol, and estriol
fractions excreted by 21 patients with
prostatic cancer, 17 patients with benign
hypertrophy, and 59 clinically well
subjects were assayed to determine whether
differences exist.  absolute levels of
estrone, estradiol, and estriol fractions were
not significantly different.  the
excretion of relatively lower levels of estrone
and estradiol, and relatively higher
levels of estriol by patients with prostatic
cancer compared to clinically well
subjects resulted in significantly lower
proportions of the total estrogen being
excreted as estrone and estradiol.  differences in
the proportions of estrogen frac-
tions between patients with benign hypertrophy
and clinically well subjects were
not significant.  with the exception of a significantly
higher percentage of the total
estrogen being excreted as estrone by the patients
with benign hypertrophy,
differences between that group and the cancer
group were also not significant.
clinical variations between the 3 groups, and
within the cancer and hypertrophy
groups, preclude assignment of significant
differences to prostatic dystrophies
alone.  cancer patients experiencing inanition
due to a loss of appetite excreted
significantly lower levels of estrone than patients
who reported no loss of appetite.
significantly lower levels of estrone were excreted
by patients with benign hyper-
trophy hospitalized 6 days or more compared to
patients hospitalized 5 days or less.
a significantly higher urinary estrone-androsterone
ratio was present in the cancer
group than in the clinically well group.  it is not
believed, however, that an arbi-
trary ratio can be used to suggest an internal
estrogen-androgen imbalance.
.I 445
.W
28029 enzymic synthesis of steroid
sulfates.  ii. presence of steroid sulfo-
kinase in human mammary carcinoma
extracts
extracts of human primary and secondary
mammary carcinomas were shown to
contain steroid sulfokinase(s) in every case
examined.  examination of normal
breast tissue surrounding the tumors revealed
very weak steroid sulfokinase
activity in some instances.  this was thought to
be due to the fibrous nature and
poor cellularity of the normal breast tissue.
normal ovarian tissue specimens,
obtained from cancer patients undergoing
oophorectomy, did not generally
contain the enzyme, but trace levels were detected
in 1 of 5 specimens examined.
steroids, without necessarily showing conversion
to steroid sulfate, were observed
to increase the incorporation of s35-sulfate into
one of the products formed enzy-
mically on incubating breast tissue extracts
with s35-adenosine-3'-phosphate-5'-
phosphosulfate.
.I 446
.W
3752. steroid excretion in early breast cancer
patients with advanced breast cancer
who subsequently fail to respond to adrenalec-
tomy or hypophysectomy have been
found to excrete abnormal amounts of the
urinary metabolites of androgen and
cortisol.  when similar measurements are
carried out on patients with early breast
cancer, it is found that approximately half
the cases presenting for mastectomy are
also excreting abnormal amounts of these
steroids.  subsequent follow-up shows that
these cases tend to have a poor progno-
sis, and a trial had therefore been started
in which the abnormality is being cor-
rected.  in addition, it seems possible that
the deficiency in adrogen excretion may
precede the onset of the disease.  this
problem is being investigated in a trial
involving urinary steroid estimations in
5000 normal women.  the measurements
are being compared with the subsequent
development of breast cancer.
.I 447
.W
2365. the excretion of oestrone, pregnanediol
and pregnanetriol in breast
cancer patients.  i. excretion after spontaneous
menopause
the urinary excretion of oestrone, pregnanediol and
pregnanetriol was determined
in a series of postmenopausal breast cancer patients
receiving no endocrine treat-
ment.  the steroid excretion was studied
both in relation to the age of the patients
as well as in relation to the time elapsed
since the last menstrual cycle.  the results
indicate that after an initial slow decrease
from the age of the menopause onward,
the excretion of oestrone and preganediol
increases again.  a new maximum was
found in the group 10-15 yr. after the
menopause.  the excretion of pregnanetriol
however, remains relatively constant
after a more rapid fall during the first few
years after the menopause.
.I 448
.W
2366. the excretion of oestrone,
pregnanediol and pregnanetriol in breast
cancer patients.  ii. effect of ovariectomy,
ovarian irradiation and corticos-
teroids.
the urinary excretion of oestrone,
pregnanediol and pregnanetriol was determined
in breast cancer patients at different
stages of their endocrine treatment.  the
results demonstrate that corticosteroids
in substitution doses (cortisone 50 mg. daily
or prednisone 10 mg. daily, divided in 4
daily doses) are very effective in depressing
the excretion of all 3 steroids in postmenopausal
patients.  this is in agreement with
the clinical impression that these easily tolerated
small doses of corticosteroids have
the same therapeutic effect as adrenalectomy in
patients with breast cancer.  the
results indicate that the ovaries may contribute
to the production of oestrogens for
many years after the menopause, and that this
production is depressed by ovarian
irradiation.  this is in agreement with the clinical
observation that ovarian irra-
diation has a therapeutic value in postmenopausal
women with breast cancer.
.I 449
.W
414. estimation of the urinary
17-ketosteroids in the diagnosis of car-
cinoma of the prostate
in 33 patients with histologically
confirmed carcinoma and in 37 patients with
confirmed benign hyperplasia of the
prostate the amount of neutral 17-ketosteroids
was estimated in 24-hr. samples of
urine.  the results revealed that, contrary to
reports in the literature, this diagnostic
method is quite unreliable.  raised
17-ketosteroid levels were found also in
a high percentage of control subjects.
moreover, the estimation of 17-ketosteroids
is a very laborious biochemical
method and involves a relatively great
experimental error.
.I 450
.W
2820. influence of small doses of corticosteroids
on the excretion of pregnanetriol and oestrone
in a series of patients with breast cancer
excretion of oestrone and pregnanetriol
was determined.  with administration of
corticosteroids oestrone excretion in
postmenopausal women diminished   67%.
a decrease of pregnanetriol ex-
cretion values was observed as well.  evidently
a low oestrone excretion in patients
subjected to corticosteroid therapy is due to a
depression of the adrenal function.
.I 451
.W
5062. urinary ii-deoxy-17-oxosteroids
in british and japanese women with
reference to the incidence of breast cancer
japanese women excrete more andosterene
(5a) relative to aetiocholanone (5b)
than do british women living in tokyo.  the
mean 5a/5b ratio in the former is 1.3
and in the latter 1.0, and these means differ
significantly.  the ratio is markedly
affected by thyroid function, and thyroid
disease has been reported to affect the
incidence of breast cancer which in japan is
only one eighth of that in white women
in north america or great britain.
.I 452
.W
5318. the plasma 17-ketosteroids and
17-hydrocorticosteroids in women
with breast cancer
in 100 women in the menopause with breast cancer
the mean level of plasma 17-
ketosteroids (17-ks) and 17-hydroxycorticosteroids
(17-ohcs) was significantly
higher than in normal women of equivalent age.
in 67 young women only the
level of the plasma 17-ohcs was significantly higher
than normal.  in menopausal
women with breast cancer whether treated or not
there is no correlation between
the level of the plasma 17-ks and that of 17-ohcs.
.I 453
.W
5319. urinary porter-silber chromogens
following intravenous metho-
pyrapone and acth in patients with breast cancer
urinary porter-silber chromogens have been
measured in 2 groups of patients
with breast cancer before, during and after
intravenous methopyrapone and
acth administration.  the control group
consisted of females free of disease
5 years or more following mastectomy while
the study group had documented
metastatic disease.  no significant difference in
the urinary porter-silber chromo-
gens was found between the 2 groups on any day
during the course of the study and
were within the range of normal as measured
in this laboratory.  it is concluded
that the functional reserve capacity for both
pituitary acth secretion and adreno-
cortical steroidogenesis in patients with
advanced metastatic breast cancer is rela-
tively normal.
.I 454
.W
2349. amyloidosis in the autopsy material of the pathology department of
tuberculosis institute, warsaw, in 1945-1962
the autopsy material of the pathology
department of the tuberculosis institute, in
1945-1962, included 1218 postmortem
examinations of patients who died from tuberculo-
sis.  in 111 cases tuberculosis was
complicated by amyloidosis.  in 1945-1957 amy-
loidosis accounted for 8.7% of the cases;
in 1958-1962 this percentage was 10.8.
there was no difference in the incidence
between men and women, the only difference
between the two sexes was that the peak
tuberculosis fatality curve in men was in
the 40-60 years age group, and that of
amyloidosis at the 20-30 age group, while in
women the greatest number of death from
tuberculosis was in the 20-30 age group,
and from amyloidosis in the 30-40 age group.
.I 455
.W
766. certain features of the haemogram in patients with pulmonary tuberculosis
complicated by amyloidosis (russian)
regression of amyloidosis in the early stages
seems possible and for this reason
russian clinicians are exploring the possibilities
of finding means of early diagnosis
of this complication.  the author studied 300
complete clinical blood analyses made
in 60 patients, viz. 30 with chronic fibrocavernous
and cirrhotic forms of tb com-
plicated by amyloidosis and 30 with the same forms
of tb without amyloidosis.  from
detailed serial study of the haemogram in patients
with pulmonary tb it is possible
to diagnose associated amyloidosis of the internal
organs in its initial stage.  the
presence of amyloidosis of the internal organs can
be inferred from the following
changes in the blood picture  (a) the appearance of
normochromic and hypochromic
anaemia in patients with various forms of tb (with
the exception of tb of the kidneys,
intestinal tract or larynx, and of caseous lymph
nodes), (b) progressive increase
in the leucocyte count with a neutrophil shift to
the left not corresponding with a
phase of quiescence of the main disease, (c) consistently
high esr in the absence
of an active process, (d) thrombocytosis in the phase of
subsidence of a flare-up,
and also changes in the thrombocytic formula tending
towards the appearance of de-
generative forms and old and mature thrombocytes.
.I 456
.W
1319. diffuse tracheo-bronchial amyloidosis  a rare variant of a protean disease
a patient with diffuse tracheo-bronchial
amyloidosis is described; brief clinical
details supplement those published in a
previous report (prowse,1958) and are
followed by an account of the necropsy
findings and the histological appearances
at the site of amyloid deposition.  the
literature is reviewed and arguments are
advanced in favour of a common aetiology
for amyloidosis in all its forms.  if this
acts through the immunity mechanism, it is
suggested that variations in the site,
strength, duration, and frequency of the
antigen stimulus and the antibody response
may determine the nature and distribution
of the amyloid deposits.
.I 457
.W
2091. modern methods of treatment of visceral amyloidosis in patients with
pulmonary tuberculosis (russian)
the immediate and long-term results of
treatment during 1945-1962 of 414 patients
with pulmonary tuberculosis complicated
by amyloidosis were studied.  hormonal
(corticosteroid) therapy is the pathogenetic
treatment for visceral amyloidosis and
is indicated in the proteinuric and early
edema-hypotonic phase of amyloidosis when
the functional capacity of the kidneys and
the liver is still adequate.  in the azotemic
phase of amyloidosis, hormonal (corticosteroid)
therapy is not indicated, since it
leads to rapid deterioration in the patient's
condition.  since hypoxemia is one of the
main factors in the pathogenesis of amyloidosis,
oxygen therapy is rational patho-
genetic therapy for patients with pulmonary
tuberculosis complicated by hypoxemia
and with symptoms of the proteinuric or
edema-hypotonic phase of amyloidosis
(without ascites), in the form of
subcutaneous introduction of oxygen or oxy-
geno-peritoneum.  in patients with
pulmonary tuberculosis surgical interven-
tion on account of the main process
is indicated only in the early stages of amyloi-
dosis when pronounced functional
disorders of the kidneys and liver are absent.  co-
joint therapy using protein vitamins
(particularly ascorbic acid), hormonal (corticos-
teroid) preparations, oxygen and
desensitizing agents and elimination of all foci of
infection is indicated in treatment
of pulmonary tuberculosis with even the earliest
signs of amyloidosis.
.I 458
.W
2317. the use of needle biopsy of the liver in the diagnosis of visceral
amyloidosis in patients with pulmonary tuberculosis (russian)
the results of 86 puncture biopsies of the
liver in 84 patients with pulmonary tuber-
culosis (55 men and 31 women aged from
18 to 73 yr.) for the purpose of diagnosing
amyloidosis are reported.  puncture was
performed when amyloidosis was suspected
on the basis of the case history (destructive
process of more than 2-3 years' duration),
clinical signs in the form of enlargement of
the liver and spleen, edema, changes
in the blood picture and blood protein formula,
and changes in the urine (proteinuria,
cylindruria, isohyposthenuria).  amyloidosis
was diagnosed or its presence surmised
before puncture in 23 patients; the puncture
biopsy confirmed the diagnosis in 14
and refuted it in 9 of them.  in 8 patients without
clinical symptoms, amyloidosis
was diagnosed on the basis of the puncture biopsy
alone.  in 9 cases with fatal out-
come, the post-mortem findings coincided with
the results of the bioptic puncture.
of the 62 patients in whom amyloidosis was not
detected by biopsy, 31 had moderate
dystrophic changes and 9 had marked dystrophic
changes while in 22 cases no patho-
logical changes were found; 6 of these patients
later developed amyloidosis.  these
findings supported the contention that liver
amyloidosis is linked with dystrophic
changes in the epithelial cells.  marked
dystrophic changes can precede amyloidosis
or may occur simultaneously with it.  moderate
dystrophic changes are quite common
in patients with an exacerbating tuberculous
process in the lungs.  the wide applica-
tion of bioptic puncture of the liver in indicated
cases can increase our knowledge
of the morphological changes taking place in the
liver in tb.
.I 459
.W
2701. the role of certain additional factors in the development of amyloidosis,
and its prophylaxis in patients with pulmonary tuberculosis (russian)
in patients with chronic fibrocavernous
tuberculosis of the lungs, any toxic-aller-
gic side reactions to antibacterial therapy,
chronic foci or infection and diseases
with an allergic component can contribute
to the development of amyloidosis.  the
early detection and clearing of chronic
foci of infection and effective measures
against even mildly pronounced toxic-allergic
side reactions are of prime impor-
tance in the prevention of amyloidosis.  the
unsystematic and prolonged administra-
tion of antibacterial preparations, along with
their toxic side effects, tends to in-
crease the incidence of amyloidosis in patients
with chronic fibrocavernous pulmon-
ary tb.  individual constitutional factors are
of great importance in the development
of side effects.  side reactions to chemopreparations,
in cases of hypofunction of
the liver and kidneys and autonomic
dysfunction promote the development of dys-
trophic processes, as is confirmed
by the high frequency of toxic-allergic reac-
tions in patients with fibrocavernous
pulmonary tb who later develop amyloidosis.
the administration of desensitizing drugs
to patients showing side reactions there-
fore helps to prevent amyloidosis in cases
of chronic fibrocavernous tb, and chemo-
therapy should be automatically combined
with the administration of desensitizing
and stimulatory drugs in this class of case.
.I 460
.W
1835. the decrease of the steroids in the urine in the course of lung tb.
(the therapeutic value of their increase after calciferol)
quantitative determination of the urinary
steroids in 38 patients with extensive ul-
cero-caseous pulmonary tb confirmed
that the 17-ketosteroids are always decreased
in these cases.  calciferol, in the form
of one ampoule of vit.  d2 of 600,000 u.
every 10 days, in combination with active
tuberculostatic drugs, in the majority of
the cases leads to an increase of the
urinary 17-ketosteroids from 50 to 100% in 2
mth.  it appears that the calciferol
exerts its action through proteolysis; it stimulates
the liquefaction and evacuation of the
caseous material.  this proteolytic effect is
related to that of the mineralocorticoids,
which are phlogistic and proteolytic sub-
stances.  calciferol offers the advantage
over these substances that it does not affect
the electrolytes and is well tolerated by
the organism.  for this reason, good results
may be expected from its administration
in cases of extensive pulmonary tb, in
which the myc. tuberculosis has remained
sensitive to the administered tuberculostic
drugs but nevertheless does not proceed
towards recovery because of the marked caseous
lesions.  in such cases calciferol treatment
leads to a rapid and pronounced decrease
of the radiological shadows, improves the
general condition and also modifies the
steroid metabolism rendered abnormal by the disease.
.I 461
.W
1837. development of amylosis in less than 2 months in the course of a primary
tb infection
the case is reported of a previously healthy
young north-african male, in whom
a post-primary ulcero-infiltrative tb in less
than 2 mth. led to the development of
visceral amyloidosis, which could be confirmed
by biopsies of the kidney and liver.
during treatment with antibiotics,
the hepatic amyloidosis regressed parallel with
the improvement of the tb, and the
biological signs of the renal amyloidosis dis-
appeared with the exception of a
pronounced proteinuria, the persistence of which
renders the long-term prognosis highly doubtful.
.I 462
.W
2216. the relations between lupus erythematosus and diseases of the
lympho-reticular system
a case report of a patient with led
(aged 48 years), who developed secondarily
a lymphoblastic sarcoma.  when the
sarcomatous degeneration of the lympho-
reticular system became apparent,
the serological and immuno-hematological tests,
typical for led, were negative.  to
interpret the observation, 62 further patients
with lymphogranuloma, lymphosarcoma,
leukemias, other malignant tumors, sar-
coidosis, and tuberculosis were investigated
serologically and immunohematolo-
gically.  antinuclear factors were found in
serum of 4 patients with lymphogranulo-
ma, one patient with anaplastic carcinoma,
and one patient with metastasizing
mixed parotid-tumor.  the identity of the
antinuclear antibodies with those found in
led could not be proved by different methods.
the importance of certain diseases
of the lympho-reticular system for the production
of antinuclear factors was dis-
cussed.
.I 463
.W
4417. value and significance of the prednisolone test in diseases of the kidney
twelve normal subjects, 18 cases of
tubulo-interstitial nephropathy, 12 cases of
glomerular nephropathy and 17 cases
of other renal disorders were investigated.
all patients were given a prednisolone
test, with urine culture before and after the
test, and in many instances determination
of the urinary osmolarity; the urinary
sediment was examined with the sternheimer
and malbin staining technique and
with the peroxydase stain to investigate the
urinary cytology.  with the criteria
adopted, the test was negative in the normals
and was positive in 61.1% of the cases
of chronic pyelonephritis and in 12.1% of the
remaining cases of unequivocally non-
infectious renal disease.  the increase of the
urinary bacterial count after cortico-
steroid administration, and investigation of the
various components of the urinary
sediment also supplied useful diagnostic
information.  on the contrary, the stern-
heimer-malbin stain for the urinary
sediment proved of little use.
.I 464
.W
564. tumoral amyloidosis of the lung
an incidental finding at necropsy on a woman
aged 95 was a tumor-like mass, 8.5
x 6.5 x 6 cm., in the lower lobe of the left lung.
the detailed structure of this
may suggested angioma of hamartoma; the stroma
and some vessels contained
amyloid.  amyloid is not uncommon in the stroma
of tumors.  a summary of 17
tumoral amyloid cases reported by others is included.
.I 465
.W
7364. experimental amyloidosis in immunity
much of interest in the mechanism of
experimental amyloidosis as a result of the
parenteral introduction of foreign protein
has been centered around the nature of
the links leading to cytological and biochemical
changes in tissues and body fluids.
some of the authors suggested that such links
may be of immunological nature.
there is however, no clear-cut proof either
in favor of or against the theory of an
immunological origin of amyloid.  since
injection of proteins during the perinatal
period prevents an immune response when
the animal is subsequently challenged
with the same antigen, the authors studied
amyloidosis caused by casein in mice
treated after birth with this protein.  mice
exposed soon after birth to casein ac-
quire an immune tolerance to this antigen.
this was demonstrated by the absence
of circulating antibodies as measured by the
disappearance of i-labeled casein
from the circulation and by means of passive
hemagglutination tests with ascitic
fluids.  both tolerant and control animals
developed amyloidosis to the same extent.
the results imply that the pathogenesis of
amyloidosis does not rest upon a classic
immunological basis; they do not exclude
the possibility, that the disease may be
due to some auto-immune process.
.I 466
.W
3535. electron microscopic study of six cases of human renal amyloidosis
this study is particularly concerned
with  (a) the basal membrane in the different
stages; and (b) the intercapillary spaces
in the early stages.  the conclusions may
be put as follows  (1) the amyloid substance
seems to have a fibrillar structure
from the start.  (2) when the walls of the
peripheral capillary loops are thickened
by voluminous amyloid deposits, the
hyaline aspect of the primitive basal membrane
persists, but its structure is altered by
the presence of multiple amyloid fibrils.
(3) on the other hand, in the initial stages,
amyloid fibrils cannot be seen in the
'lamina densa' of the basal membrane; they
only appear on the epithelial and endo-
thelial surfaces of the membrane.  this suggests
that amyloidosis represents an
abnormal precipitate of extrinsic origin, rather
than a transformation 'in situ'
of the basal membrane.  (4) in the very early stages
of amyloid infiltration into the
glomeruli the fibrillar substance is found first in
the intercapillary spaces, only
later does it reach the peripheral capillary walls.
.I 467
.W
3544. morphology and development of infectious-toxic affections of the kidneys
in pulmonary tuberculosis (russian)
the kidneys of 75 patients dead from tb of
the lungs and of 30 rabbits with pulmonary
tb were examined.  the first lesions develop
in the glomeruli, followed by changes
in the stroma and tubules.  infectious-toxic
affection of the kidneys is a complex and
prolonged process involving organic immune
reactions, lymphostasis, venous stasis
and finally nephrosclerosis.  infectious-toxic
lesions were found in one third of the patients
who died of pulmonary tb.  these changes had
produced clinical manifestations, on the
basis of which the following affections had been
diagnosed  nephritis, nephrosis, amyloi-
dosis.  antibacterial therapy of the pulmonary
process reduced the renal lesions.  how-
ever, severe infectious-toxic affection of the kidneys
may develop after recovery from
pulmonary tb.
.I 468
.W
3553. diffuse nodular amyloidosis of the lungs
in a 59-year-old man, who 12 yr. previously
had ceased working in an aluminium
factory and who had died from respiratory
insufficiency, the postmortem examination
revealed disseminated nodules in the lungs.
the nodules were sharply defined, of
a greyish color and of a doughy consistency
and could easily be removed from their
capsules.  the diagnosis of amyloidosis was
made on the basis of the histological
findings, the staining qualities of the material,
its intraseptal and periarteriolar
localization, and the existence of plasmocytic
infiltrates and foreign-body giant-cell
granulomas.  amyloid deposits were also found
in the spleen, kidney and some
coronary branches.  in regard to the pathogenesis,
it is suggested that the exposure
to aluminium products for more than 10 yr. might
have constituted a predisposing
factor.
.I 469
.W
3724. the bacterial induction of homograft sensitivity. ii. effects of
sensitization with staphylococci and other microorganisms
heat-killed strains of staph. aureus and staph.
albus can induce in guinea pigs a
state of altered reactivity to skin homografts
which is indistinguishable from that
which results from sensitization with homologous
tissues or group a streptococci.
challenge of suitably prepared recipients
with 1st-set skin homografts obtained
from unrelated randomly selected donors
elicits white graft reactions or accelera-
ted rejections of such grafts.  other bacteria
tested included lancefield streptococcal
groups b, c, d, e, g, h, l, and o,
pneumococcus types ii, iii, xiv and a rough
strain, c. xerosis, b. subtilis, e. coli,
a. aerogenes, s. typhimurium, pr. vul-
garis, n. catarrhalis, h. influenzae, and
2 human virulent strains of myc. tuber-
culosis.  none of these microorganisms was
active in the induction of homograft
sensitivity in the guinea pig.  pretreatment of
recipients with gram-negative bac-
terial suspensions was associated with a slight
increase in the mean survival time
of 1st-set skin homografts.  results of this study
suggest the presence in staphylo-
cocci, as well as in group a streptococci, of antigens
related in their biologic ef-
fects to tissue transplantation antigens.
.I 470
.W
6590. structure and function of cross-linked dna. i. reversible denaturation and
bacillus subtilis transformation
reaction of nitrous acid with dna
results in covalent linkage of complementary
polynucleotide strands.  the resulting
material denatures reversibly and retains
biological activity in bacterial transformation.
.I 471
.W
4958. the mechanism of messenger-rna replication in bacteria
the transformation of bacillus subtilis
sb25 his-tryp-by two linked genetic mar-
kers under the action of hybrid molecules
of dna was investigated.  the molecular
hybrids were obtained by thermal denaturation
and annealing of a mixture of two
dna's, each one extracted from a single
auxotrophic strain (h25 his-and 168 tryp-).
the formation of the heterozygous dna
double helices was proved by special experi-
ments.  the transformation procedure
excluded dna synthesis by recipient cells
prior to the formation of enzymes for
histidine and tryptophane synthesis.  it was
found that heterozygous molecules of
dna are able to transform in these conditions
the double auxotrophic cells to prototrophic
ones.  this means that both strands of
the dna double helix can serve as templates
for the m-rna synthesis.  the possi-
bility of a secondary replication of m-rna
outside the chromosome under the action
of rna-polymerases, using rna as a primer,
is discussed.
.I 472
.W
2567. the molecular basis of histidase induction in bacillus subtilis
bacillus subtilis growing at 37  on
glutamate, as only carbon source, is induced
to form histidase by l-histidine.  this
enzyme, converting histidine to urocanic
acid, was isolated in a purified form.
a highly sensitive and convenient assay for
the induced enzyme is described and
applied to show that histidase appears in the
cell 5 min. after addition of the inducer.
histidase-synthesizing capacity appears
after 2 min. and decays exponentially after
addition of actinomycin (an inhibitor
of dna-dependent rna synthesis).  the
half-time value of histidase-synthesizing
capacity of 2.4 is high, compared with the
half-time value of messenger rna.
the histidase formation after addition of
actinomycin was not only due to protein
synthesis directed by accumulated m-rna
but also by conversion of an enzymatical-
ly inactive protein, present on the moment
of actinomycin addition and product of
the specific m-rna, to the active enzyme.
the existence of this enzyme pre-
cursor was shown by means of experiments
performed in the presence of chlor-
amphenicof.  finally, numerical values for
the steady state of histidase synthesis,
reached 9 min. after addition of the inducer,
are calculated, on the basis of ki-
netics of histidase synthetic capacity, precursor
and enzyme formation  the cell
contains sufficient precursor to form
approximately 100 molecules of histidase.
the cell produces approximately 50
molecules histidase per min.  the cell ac-
quires and loses, every minute, the
capacity to make 15 molecules of histidase
per minute.  the maximal enzyme
level is 15,000 molecules per cell.
.I 473
.W
2542. symposium on the fine structure and replication of bacteria and their
parts. ii. bacterial cytoplasm
comparison of the fine structure of the
cytoplasm of the bacterial cell with that of
the 'cell in general' reveals important
differences leading to the conclusion that, in
the bacterial cytoplasm, there is little
differentiation into separate functional en-
tities.  there is no nuclear membrane, and
fine fibrils appear to extend from the nucleo-
plasm into the cytoplasm where they may
expand in all directions.  the cytoplasm is not
necessarily intersected by membranous
profiles of special configuration, as is borne
out by e. coli b and other gram-negative
organisms.  when membranous profiles
of special configuration are present, as
in the gram-positive b. subtilis, these
do not appear differentiated into clearly
definable endoplasmic reticulum, golgi
substance, microbodies, etc., and mitochondria.
as for kinetosomes, the presence
of centrioles is perhaps not very likely.  the
experiments in which tellurite is re-
duced in the cells suggest that there are
structures at the base of the flagella with
reductive capacity.  however, upon application
of the tetranitro-blue tetrazolium
technic to b. subtilis, these are not stained.
they are presumably identical with
basal granules.  the membranous structures
in b. subtilis are called chondrioids
by the author because probably one of their
functions is that they are the sites of
the respiratory enzyme chain.  in the
gram-negative p. vulgaris, the probable site
of the respiratory chain has a structure
very different from that in the bacillus; it
is not clear whether membranes are
involved in their structure.  morphologically,
even in b. subtilis chondrioids differ
fundamentally from the mitochondria in that
they are not built up from composite
membranes, they are extensions of the plasma
membrane, and they may not be completely
closed systems.  regarding this last
point, it was observed that chondrioids may
possibly stand in open connection with
the cell's environment, since its lumen is not
separated from the cell wall by a
plasma membrane.  although as yet nothing is
known about this, it does not seem to
be precluded that these membranous organelles
may function also as intracellular
transport systems.  contrary to porter's ideas
about er, the chondrioids are not
extensions of a nuclear envelope, but of the
plasma membrane.  on the other hand,
they are in the nuclear area, in direct contact
with the nucleoplasm, and therefore,
perhaps, they need not carry in their interior
some dna, as is now becoming known
for ordinary mitochondria.  the chromatophore
vesicle is of a simple structure and
in connection with the plasma membrane.  it is
covered by a single membrane and
thus resembles the granum disc, but it is much
smaller.  in tissue cells, an im-
portant function of the er is the support of protein
synthesis by ribosomes bound
to their surfaces.  evidence is now accumulating
that the active complexes for poly-
peptide synthesis in bacteria are also membrane-bound
and are series of 70s ribo-
somes using the same messenger rna molecule.
it remains a contradictory situ-
ation that the particles obtained here through release
of cytoplasm from protoplasts
in diluted, rather crude fixing media, and identified
as ribosomes, could not be
recognized as such in thin sections of the ryter-kellenberger
fixed protoplasts.
this point is much in need of clarification.  but
even if the cytoplasm in the thin
sections of the protoplasts is in a state of
dispersion brought about artificially, it
is still apparent from the various micrographs
that basically the cytoplasm is a
network of presumably linear arrays, with many
interconnections due to fibrillar
systems.  fibrils from the nucleoplasm penetrate
deeply into the cytoplasm.  the
presence of fine fibrils of various thicknesses,
electron densities, and orientations
makes high-resolution study of the cytoplasmic
details an intriguing prospect from
which much fundamental information can be
gained.  the organizational pattern on
the ultrastructural level in bacteria reveals
fundamental similarities and divergen-
cies from that in the 'cell in general'.
.I 474
.W
906. molecular mechanism of genetic recombination in bacterial transformation
the mechanism of dna incorporation into
the recipient cell chromosome was in-
vestigated in a b. subtilis transformation
system.  the recipient cells were auxo-
trophic for 2 linked markers.  hybrid dna
used for transformation was heterozy-
gous for one of these markers.  no differences
in transformation activity were found
when the effect of native and hybrid dna was
compared.  according to the authors
this observation is easily explained if we accept
that each of both complementary
strands of the donor dna can be incorporated
into the recipient chromosome with
equal probability.  the results on the segregation
of genetic characters in the pro-
geny of transformed cells are also consistent
with the model of independent incorpo-
ration of both dna strands.  some calculations
were done on the probability of the
integration of a single dna strand carrying a
particular genetic marker, and on the
probability of recombination leading to double transformants.
.I 475
.W
1520. multiplication of bacteriophages
the reproduction of bacteriophages requires
the participation of bacterial metabol-
ism.  synthesis of the viral protein components
is accomplished by the same me-
chanism as ordinarily produces bacterial
proteins; however, for the synthesis of
nucleic acids (dna or rna) enzymes may
be required which are not present in non-
infected bacteria; their formation is then
induced by the virus itself.  the fundamental
biological processes of replication, transcription
and translation are discussed in
this context.
.I 476
.W
1361. the mechanism of histidase induction and formation in bacillus subtilis
the role of the inducer, l-histidine, in the
synthesis of histidase (l-histidine am-
monia lyase) in b. subtilis was investigated.
it was found that induced cells poisoned
with actinomycin, an inhibitor of rna synthesis,
lose their capacity for the forma-
tion of a protein precursor of histidase at a rate
which is independent of the presence
or absence of the inducer.  these results show
that the inducer does not increase
the intracellular level of histidase-specific
messenger rna by preventing the des-
truction of the major portion of this material,
the fraction that is engaged in pro-
tein synthesis.  the possibility has not been
excluded that the inducer exerts its
effect by bringing about the stabilization of
the messenger rna that is still attached
to dna or has not yet become attached to
ribosomes.  alternatively, the inducer may
actually stimulate the synthesis of
histidase-specific messenger rna.  the conver-
sion of the precursor to active enzyme
appears to involve polymerization of mono-
mers, rather than the release of
ribosome-bound inactive enzyme.
.I 477
.W
1362. the synthesis of phage and host dna in the establishment of lysogeny
a method of extraction is described which
prevents excessive fragmentation of bac-
terial dna.  the larger bacterial dna can
then be separated from the phage dna
on sucrose gradients.  the relative amounts
of phage and host dna made at various
times during infection of s. typhimurium
with phage p22 leading to lysogeny have
been determined.  phage-specific dna
synthesis begins at about 4 min, continues
to increase for 2-4 min, and then decreases
until complete repression is attained
at 16 min.  autonomous phage dna synthesis
remains repressed from then on.  bac-
teria-specific synthesis proceeds at a
decreasing rate until about 16 min, when
almost complete inhibition is reached.
when dna synthesis recovers in the in-
fected cells, only host-specific material
is made.  a new species of dna, which is
made only when phage dna is synthesized,
has been detected.  the possible implica-
tions of these findings in the understanding
of the lysogenic interaction is discussed.
.I 478
.W
438. lag period characterizing the entry of transforming deoxyribonucleic acid
into bacillus subtilis
the kinetics of appearance of transformants
as a function of time of exposure to
dna has been studied.  a short lag period
of approximately 1 min at 37 c is evi-
dent when the transformation is terminated
with deoxyribonuclease.  the length of
this lag is independent of the genetic trait
transferred.  moreover, the lag is unaf-
fected by transforming dna concentration,
by the presence of homologous unmarked
dna, and by shearing and cross-linking of
the transforming dna.  the lag shows
a strong inverse temperature dependence.
the energy of activation is 13.9 kcal.
the lag is abolished when the transformation
is terminated by washing instead of
by addition of deoxyribonuclease.  these results
are taken to indicate an immediate
adsorption of dna to cells, followed by a
deoxyribonuclease-sensitive period of
1 min, during which time the genetic trait
is entering the cell.  these results make
feasible an investigation of the configuration
assumed by the dna molecule during
entry into the cell.
.I 479
.W
439. configuration of transforming deoxyribonucleic acid during entry into
bacillus subtilis
a correlation was obtained between map
distance and the length of the lag period
preceding the appearance of pairs of genetic
traits after the addition of dna to a
competent culture of b. subtilis.  the results
are taken to indicate that dna enters
competent cells in lengthwise fashion.
the smallest length of transforming dna
which can participate in a recombination
event, and the number of nucleotide pairs
which enter the cell per unit time, have
been estimated.  the evidence indicates
that only part of the lag period is devoted
to the transport of dna into the cell.
the significance of these results with
respect to the mechanism of entry of dna
into the cell is discussed.
.I 480
.W
2564. chemical inactivation and reactivation of transforming dna (russian)
the kinetics of the inactivation of linked
and unlinked genetic markers by means
of hno2 or uv light was studied.  closely
linked markers are inactivated simul-
taneously, unlinked markers are inactivated
independently.  it seems that the
chemical attack on dna impairs a large part
of macromolecule, including many
cistrons.  it was shown by genetic experiments
that chemical inactivation prac-
tically does not influence the process of dna
inclusion into competent cells.  by
means of viscosity measurements it was
shown that the molecular weight and
macromolecular properties of dna do not
significantly change during chemical
inactivation by means of hno2.  two explanations
for the inactivation of trans-
forming activity of dna are discussed  (1) structural
deteriorations, preventing
integration of dna molecule into the genome of
recipient cell, or (2) deletion of
a chain unit out of dna chain resulting in wrong
reading of code triplets.  it was
previously described in the literature that extensive
inactivation leads to a state
of dna, apparently more resistant than the initial one.
inactivation does not con-
firm to exponential kinetics.  the authors discuss the
coding mistake hypothesis
as an explanation for this remarkable fact.  extensive
hno2 or uv light action re-
sults in multiple lesions in the dna molecule and
leads to reactivation because
the deletions restore correct reading of the code
in a large part of dna molecule.
on the basis of this explanation reactivation of
chemically injured dna by means
of fusion and annealing with homologous but
genetically inactive dna, or by slight
fragmentation of dna by means of ultrasonic
vibrations may be expected.  attempts
to achieve reactivation by both methods gave
positive results.
.I 481
.W
2565. separation of the transforming and viral deoxyribonucleic acids of a
transducing bacteriophage of bacillus subtilis
the authors used the transducing b. subtilis
phage ps 10 and present the fol-
lowing experimental data  dna isolated from
ps 10 is effective for transformation
of competent b. subtilis cells.  ps 10 dna is
distinguishable from b. subtilis dna
by its higher density in a cs2so4 gradient and
its lower thermal denaturation
temperature.  the transforming activity present
in dna from ps 10 denatures at
a temperature characteristic of b. subtilis dna
rather than of viral dna.  the
transforming activity of ps 10 dna bands in a
cs2so4 gradient with bacterial dna.
this data indicated that bacterial dna is
incorporated into phage ps 10 without
being integrated in the viral dna.  this incorporated
bacterial dna is involved
in transduction.
.I 482
.W
2529. repair of damage induced by a monofunctional alkylating agent in a
transformable, ultraviolet-sensitive strain of bacillus subtilis
a uv sensitive, transformable strain of
b. subtilis (uvr-) was unable to carry out
host cell reactivation of the virulent
bacteriophage spo1.  the ratio of the slopes
(kuvr-/kuvr+) of the uv inactivation curves
was 6-8 for cells or for whole phage, and 2
for indole+ transforming dna or for
spo1 phage dna measured in a transforming
system.  whole phage inactivated with
nitrogen mustard showed greater survival on
uvr+ cells than on uvr-; there was no such
difference for whole phage inactivated with
methyl methanesulfonate.  whole uvr+ cells
recovered from uv induced damage, as
determined by an increase in extractable
transforming activity during a period of
incubation in which net dna synthesis did
not occur.  uvr- cells were unable to reco-
ver from uv induced damage but they did
recover from methyl methanesulfonate
induced damage in similar experiments.
density labeled (h2n15) methyl methanesul-
fonate treated uvr+ cells incubated in (h1n14)
medium containing (h3) thymidine show-
ed a 3-fold increase in extractable transforming
activity, with no formation of new
dna molecules as determined by pyknometric
analysis.  the repair of damage in-
duced by uv irradiation differs by at least one
step from the repair of damage in-
duced by methyl methanesulfonate.
.I 483
.W
1451. the biosynthesis of 5-hydroxymethyldeoxyuridylic acid in
bacteriophage-infected bacillus subtilis
when phage  e, which contains
5-hydroxymethyluracil in its dna in place of thymine,
infects b. subtilis, enzyme changes
occur in the host organism which can account
for the synthesis of the abnormal base.
deoxycytidylate deaminase increases at
least 90-fold and the product of its action,
deoxyuridylic acid, is converted directly
into the deoxynucleotide of 5-hydroxymethyluracil
by a hydroxymethylase enzyme.
the activity of thymidylate synthetase, which also
uses deoxyuridylic acid as
substrate, decreases rapidly after phage infection.
.I 484
.W
5574. death anxiety in children with a fatal illness
the author reports studies of a series
of 50 children hospitalized because of fatal
illness due to leukemia or some other
form of cancer.  it was postulated that the
younger children would experience
separation anxiety while the older children
would be more likely to experience
death anxiety.  in general the hypothesis
was supported by the results of the study.
there was some evidence to indicate that
the younger children perceive death
anxiety but deal with it in more symbolic form.
in older children, it was felt that boys
tended to react to death anxiety by acting out
behavior while girls tended to become depressed.
.I 485
.W
1209. the theory and practice of the family diagnostic.  ii. theoretical
aspects and resident education
family intervention and observation have proved
useful in 3 areas.  the 1st of these is observation of the
psychosocial context in the patient.  on admission to a
mental hospital the phenomenon of extrusion and separ-
ation from the family is evident, and the need for study
of the interaction between the patient and his family
milieu is vital.  the 2nd area where the family inter-
view has a major role is resident education.  the tra-
ditional medical education of the ill prepares the stu-
dent for consideration of the multifactorial problems of
emotional disorder in which balances between mem-
bers of a group may be the issue rather than external
pathogenes.  the family interview offers a unique point
of observation of factually evident and emotionally con-
vincing group data.  in addition to the observation of
family phenomena, mutual understanding of others'
problems is created.  finally, the family interview
serves as an instrument for data collection and hypo-
thesis seeking in relating individual psychopathology
to family adaptations.  the patient and his family at
the time of admission are dealing with a crisis.  some-
times this is traumatic, such as the unexpected loss
of a young marital partner, an unexpected illness, or
a financial reverse.  more commonly, however, it is
developmental being a natural part of the life cycle.
characteristically, the developmental task involved
in dealing with the crises has been postponed so that
one does not see the family at the age specific and ap-
propriate time for this task.  the crisis emerges dis-
ruptively because of inevitable biological maturation,
personal decision, or social expectation.  a primary
concern of the leader is to determine what life task is
being faced.  families have a mentally ill member not
merely because they are dealing with the vicissitudes
of life.  they are unable to cope with the crisis, be-
cause of the feelings which are aroused.  each life cri-
sis leads to a particular constellation of effects in any
given family.  these include primarily, sadness, anger,
and guilt, but there may well be specific affective con-
stellations appropriate to different developmental tasks.
the patient's inability to cope with a life crisis is due
to his particular adaptation of a style of dealing with
feelings that is employed by other members of the family.
.I 486
.W
265. studies in personality.  ii. a bio-psychological and experimental
approach to problems of human adaptation in modern society
experimentally determined fixation-ambivalence
measures are related to some anxiety estimates obtain-
ed from a projective test in a group of male adolescents.
it is shown that (1) fixation increases with increase in
corporal injury anxiety when ambivalence is kept con-
stant, (2) ambivalence increases with increase in separa-
tion anxiety when fixation is kept constant, (3) extremely
hetero-fixated subjects show presence of intense guilt
and absence of aggression towards the mother; one ef-
fect of this system of organizers seems to be
suicidal
tendencies, (4) extremely ambivalent subjects have in-
tense separation anxiety; one effect seems to be suicidal
tendencies combined with high ambition and impaired
cognitive capacity.
.I 487
.W
2837. early indicators of outcome in schizophrenia
the case material of 50 persons who
were seen at a child guidance center in child-
hood or adolescence and were later
hospitalized with schizophrenia were examined
intensively.  the study concentrated
especially on the differences associated with
chronicity vs. hospital release.  the
following 12 factors were significantly related
to chronicity  (1) psychotic or schizoid
pathology in the mothering person, (2) no se-
paration of any kind from the pathogenic
families, (3) pre-illness history of poor so-
cial and sexual adjustment, (4) failure
to continue in treatment (during childhood)
for at least 3 mth., (5) less acting out
in the community, (6) neither disorientation
nor confusion on admission, (7) no
symptoms of depressive psychosis, (8) premor-
bid schizoid personality, (9) no clear
precipitating events, (10) no concern with dying
during the acute phase of the illness,
(11) length of onset over 6 mth., and (12) schi-
zophrenic reaction in patients' heredity.
items 1, 2, and 5 were derived from early
life history data and are thought to be
new to the literature of prognosis in schizo-
phrenia.  the remaining 8 factors can be
scored from hospital data alone, and have
been cited in previous prognostic studies.
.I 488
.W
4854. on the formation of object-relations and identifications of the
kibbutz child
some of the issues relevant to the early
stages of object relation formation and
identification of kibbutz children are
discussed.  for this purpose the child rearing
milieu of the kibbutz child is described
and some clinical illustrations are given.
the relationship to the mother is seen
as the main object-relation and those to the
educators as transient-interchangeable
need-satisfying relationships.  on the basis
of retrospective analytical material it
appears that in the course of development
the two relations as well as the two
respective, originally distinct, object represen-
tations are synthetised into one.  the
conditions of communal education, character-
ised by double object-relation formation
from birth on, are seen as factors that in-
tensify the 'normative crisis of infancy',
especially the transition from the symbio-
tic to the separation-individuation stage
of object-relation development.
.I 489
.W
4846. the meaning of crying
the multiple meanings of crying are
reviewed and, in particular, stress is laid
on tears as a response to some type of separation loss.
.I 490
.W
2953. the death of a parent
in the case of depressive illnesses the death
of either parent prior to the child reach-
ing the age of 15 seemed to be correlated
as a significant contributory factor.  with
this exception, statistical studies suggest
that it is the death of a mother in the first
7 yr. of a child's life, as opposed to that
of a father, that is potentially an etiologi-
cal factor for the future development of
psychoses, delinquency and psychoneuroses.
the case histories of 6 boys who had lost
their fathers were given.  in each instance
there was distinct evidence that the psychological
symptoms and behavioral disturb-
ances were to be attributed in large measure
to the effect of the death upon the child,
and that in some cases the symptom choice was
to be correlated with specific cir-
cumstances surrounding the death of the father.
in some cases it was the unresolved
grief reaction in the mother which helped to
perpetuate the disorder in the child.  re-
solution of this in the mother during therapy
led to improvement in the child's func-
tioning.  in other instances improvement
occurred especially when the child ceased
to be preoccupied with a close identification
with the dead father.  those boys who
were involved most closely in their mother's
grief reactions were the ones who were
most disturbed.  the brief treatment given
these boys and their mothers appeared
to be responsible for the considerable
amelioration of symptoms that resulted.  ther-
apeutic intervention is worthwhile,
especially in those instances where there is an
unresolved grief reaction in the mother.
.I 491
.W
1848. the child's concept of death
in this translation of a paper, which first
appeared in 1912, it is shown, according
to freud, how far a child's appreciation
of being dead differs from its true signifi-
cance.  death means a reversible decrease
in life functions, that can be interrupted
at any time, like sleep.  at other times it
may mean a temporary separation; but
always it is in man's power to change it.
in this concept, the child's unconscious
finds license for his sadism.  cruelty to
animals and death wishes against persons
close to him appear, in overcompensation, as
exaggerated pity for dead creatures
and the belief in man's power over life and death.
.I 492
.W
1849. mother child interaction during separation individuation
after a stage of normal autism during the
1st weeks of extrauterine life, the infant
passes into a symbiotic phase, gradually
emerging from this stage of dual unity at
the end of the 5th mth and during the 6th mth.
just before this, the next phase
separation individuation begins.  four
characteristic subphases of this separation
individuation process are described
differentiation, the practicing period, association
and a stage, characterized by unfolding
of complex cognitive functions.  the relation
of mother and child throughout these
subphases are studied and illustrated by clinical
material.  a poor relation between mother
and child in 1 subphase does not necessarily
or usually preclude impressive changes
for the better in the next subphase.
.I 493
.W
2736. the emotional needs of children in hospital
hospitalization of a child for physical
reasons brings with it separation from pa-
rents, siblings and familiar surroundings,
as well as the probability of subjection
to frightening and painful procedures.
unless steps are taken to prevent or modify
the resultant stress, behavioral
disturbances may arise and may result in per-
manent damage to the developing personality.
.I 494
.W
2906. early childhood separations
every child in this long-term study of child
rearing showed significant reactions to
ordinary separations by about 1 yr. of age.
the similar pattern of response in this
group of children suggests a biologically
determined cause.  the clinging reaction
appeared when the child became mobile and
able to move away from his mother re-
gardless of the frequency or duration of his
separations.  the majority of the mothers
did not understand this natural phenomenon
and regarded the clinging and crying of
the 1-year-old as evidence of spoiled or
regressed behavior.  the pediatrician can
be helpful to a mother by anticipating and
explaining separation responses, by indi-
cating their universality, and by giving
specific recommendations for gradual changes
to modify these reactions.
.I 495
.W
9787. changes in developmental quotient under two conditions of maternal
separation.
developmental scales were
administered to 2 groups of infants during and sub-
sequent to a temporary period of institutionalization.
although both groups experienced maternal separa-
tion, only 1 group was subjected to deprivation, in
that it received very much less stimulation than the
other.  results from a longitudinal testing program
show that the scores of the deprived group during
the period of separation were significantly lower than
those of the nondeprived group, no progressive de-
terioration of scores took place in the course of
institutionalization, immediately following return
home, while the scores of the nondeprived group re-
mained constant, those of the deprived infants jumped
to the level of the other group.  3 theories regarding
the mechanism underlying the association between
deprivation and developmental retardation are exam-
ined and it is suggested that an explanation in moti-
vational terms best fits the results obtained.
.I 496
.W
1808. separation anxiety  a factor in the object relations of
schizophrenic patients.
the thesis is advanced that
special vulnerability to separation anxiety is a crucial
factor in the schizophrenic's difficulty in establishing
and maintaining satisfactory interpersonal relationships.
2 major reasons for this are lack of autonomy and lack
of object constancy.  without a stable autonomous
capacity for self-regulation and adaptation, he is inordi-
nately dependent upon others for help, protection, and
direction.  without object constancy, he is unable to
maintain a stable representation of the needed person in
the latter's absence.  evidence is presented from the
intensive psychotherapy of schizophrenic patients.
many of the vicissitudes of the doctor-patient relation-
ship center about the patient's separation anxiety and
his attempted defenses against it.  these include clinging,
perceptual and cognitive distortions designed to deny
separation, and recourse to substitute objects.  promi-
nent in many of these efforts is the attempt to reverse
passive victimization into active mastery.  the practical
implications of this thesis for the treatment of schiz-
ophrenic patients are discussed.
.I 497
.W
9101. separation experiences and health records in a group of normal adults.
about 25% of 455 ostensibly normal ss
reported a recent "separation experience" as defined
in this study.  the frequency of visits to the dis-
pensary for symptomatic complaints was not signifi-
cantly higher among those who reported separation
than among those who did not.  the data suggest
that an apparent association between relatively high
cornell medical index score and history of separation
experience may be understandable in terms of a cause-
effect relationship between separation experience and illness.
.I 498
.W
11306. separation and attempted suicide.
of 3 groups of psychiatric patients-at-
tempted suicides, those with suicidal urges, and non-
suicides-there were significantly more attempted
suicides among patients with a history of childhood and
antecedent separation than controls.  in childhood the
significant difference was found primarily in the period
from birth to 7 yr.  there was no significant interaction
between childhood and antecendent separation and
suicide attempt or suicide urge.
.I 499
.W
1463. investigations of lens protein and microelectrophoresis of
hydrosoluble protein in senile cataract
the investigations on lens protein and
on agar-microelectrophoresis of hydro-
soluble protein in normal lenses and in those affected with senile cataract re-
vealed the following facts  (1) in opaque
lenses, a diminution of the total protein
and the soluble protein takes place, as
well as an increase in the amount of in-
soluble protein.  the decrease in the
quantity of soluble protein is higher than the
increase of insoluble protein which does
not only point to a transformation of the
soluble protein into the insoluble variety,
but also to the disappearance of a protein
fraction from the lens.  changes in the
quantity of soluble protein are accompanied
by the decrease of protein in slow fractions
of the electropherogram and even by
the disappearance of these fractions and
the increase of the amount of protein in
fractions of medium velocity.  with the
development of cataract and the mature
phase of cataract, all these processes
become more and more distinct.  in this
respect, a strong parallelism exists between
the protein changes and the clinical
picture of senile cataract.  (2) qualitative
and quantitative changes which occur in
the protein of normal lenses with advancing
age show a character similar to those
in senile cataract, however, they are less
pronounced.  in this instance, the de-
crease in the quantity of soluble protein is
likewise closely associated with the
diminution of the protein content in the slow
fractions of the electropherogram.
(3) the changes in the soluble protein content
of the lens and the alterations of
the protein amounts in the slow fractions which
always accompany the former,
play the principal role in the aging process
of the lens and in the development of
senile cataract.  (4) the investigations
seem to indicate that the aging processes,
of lenses as well as the development of
senile cataract are of a similar character,
but of different intensity.  (5) undoubtedly,
the processes of transition from slow
fractions of soluble protein into faster ones
and the transformation of part of the
soluble protein into insoluble protein which is
likely to be associated with these
processes as well as the partial disappearance
of total protein from the lens seem
to play a very important part in the mechanisms
pertaining to the development
of cataract.
.I 500
.W
1949. studies on the soluble proteins of bovine lens.  immuno-
chemical analyses of protein fractions
the lyophilized soluble lens proteins
were dissolved in 0.005 m phosphate buffer
at ph 6.8 and the solution was subjected to
column chromatography on deae (die-
thylamino ethyl) cellulose.  elution was
accomplished by changing the ph and ionic
strength of the eluting buffer.  the components
were fractionated by stepwise elu-
tion.  the lens proteins were separated into
17 fractions by column chromatogra-
phy.  these fractions were compared with
a, b and y crystallines for electrophore-
tic mobility, and the antigenic purity of each
fraction was examined immunochemi-
cally.  the results showed that while the
fractions were not completely pure they
were purer than the a, b and y crystalline
fractions, and that f-1-a, b, c and d
corresponded to y crystalline, while
f-2-a, b, c, d, e and f corresponded to b
crystalline and f-3, 4, 5, 6, 7, 8 and
9 to a crystalline.
.I 501
.W
3107. studies on y-crystallin from calf lens.  ii.  purification and
some properties of the main protein components
four proteins belonging to the y-crystallin group
were purified by chromatography
on sulphoethyl-sephadex and phosphate-cellulose
columns.  the proteins were homo-
geneous in gel and immunoelectrophoresis
experiments and could be crystallized.
their molecular weights, n-terminal amino
acid sequences and antigenic structures
were all similar, but their amino acid
compositions and the sulphydryl groups con-
tained showed certain dissimilarities.  it
is probable that the 4 proteins possess
small differences in their primary structure,
which are not associated with the
antigenic sites and which may have arisen
from mutations during evolution.
.I 502
.W
3105. studies on the subunits of a-crystallin and their recombi-
nation
earlier investigations have shown that, in
the presence of high concentrations of
urea, a-crystallin from bovine lens is split
into a number of subunits with apparent-
ly different electrophoretic mobilities but
similar molecular weights.  the recom-
bination of these subunits after removal of
the urea has been studied by ultracentri-
fugation and immunoprecipitation techniques.
it was found that maximal recombina-
tion was obtained when the ionic strength
during the removal of the urea was high
(>0.2), whereas at low ionic strengths a
molecule with only half the molecular weight
of native a-crystallin and a much lower
sedimentation coefficient was obtained.  a
complete recovery of the structure of
native a-crystallin was never obtained, even
at high ionic strengths, as was evident
from electrophoretic and quantitative preci-
pitin analyses.  the subunits were
fractionated by chromatography on deae-cellu-
lose in the presence of 7 m urea.
the purification was followed by polyacrylamide-
gel electrophoresis.  after removal of
the urea at high ionic strength, 2 of the
fractions obtained showed reactions of
only partial identity with native a-crystallin
in immunodiffusion tests, but all other
fractions showed complete identity.  the
differences in the electrophoretic
mobilities of the fractions in the presence of
urea persisted after removal of the urea.
all fractions had much higher sedimen-
tation coefficients in the absence of urea
than in its presence, although the values
for urea-treated unfractionated a-crystallin
obtained after removal of the urea
were not reached even at high ionic strengths.
the amino acid composition of the
fractions was found to differ.  these
observations suggest that a-crystallin is com-
posed of a number of chemically different,
but related, subunits of approximately
the same size, which are bound together
by nonspecific, noncovalent bonds, pos-
sibly hydrophobic bonds.  moreover,
when isolated, these subunits have the ability
to associate and form molecules of
high molecular weight.
.I 503
.W
3106. fractionation of b-crystallin from calf lens by gel fil-
tration
b-crystallin was isolated from calf lenses
by a combination of gel filtration on
sephadex g-75 and vertical-column zone
electrophoresis.  it was subdivided into
4 fractions by subsequent gel filtration on
dextran gels with low cross-linkage.
each fraction showed only 1 major peak in
the ultracentrifuge, the sedimentation
coefficients of which were 13.6, 9.6, 4.9 and
4.2 s for fractions i-iv, respectively.
however, all 4 fractions contained some
additional minor components, as revealed
by sedimentation and immunoelectrophoretic
analyses.  the fractionation procedure
may be of value as a first step in the isolation
of individual proteins of the b-crystal-
lin group.
.I 504
.W
195. properties of a cold-precipitable protein fraction in the
lens
a soluble protein fraction which precipitates
in aqueous solutions at temperatures
below 10  c has been isolated from the rat
lens.  this fraction appears to be re-
sponsible for the reversible 'cold cataract'
which has been seen to develop when
young mammals are exposed to temperatures
below 10  c.  as the rat ages, the
concentration of this protein fraction
decreases, but the fraction does not com-
pletely disappear, even from the lenses
of 3-year-old rats.  although the molecular
species comprising this fraction appear to
be homogeneous in the ultracentrifuge,
disc electrophoresis and immunodiffusion
have shown that they are a heterogeneous
mixture of a-, b- and y-crystallin subunits.
the ability of the cold-precipitable
protein (ccp) fraction to precipitate in the
cold depends upon its concentration and
the ionic strength and ph of the solvent.  in
solutions of ph 4.0, some aggregation
of the 4 s cpp occurs to form a 17 s component,
which no longer precipitates in
the cold.  the ability of this protein fraction to
precipitate in the cold may depend
on hydrophobic bonding and its influence on the
conformation of the protein.
.I 505
.W
773. the effect of radiation on lenticular epithelial enzymes
in young rabbits
the mitochondrial fraction and the soluble
fraction of the epithelial cells of the lens
from 6-week-old new zealand white male
rabbits, exposed to 800 r of whole-head
x-irradiation, were evaluated for glucose
6-phosphate dehydrogenase, isocitrate
dehydrogenase, malate dehydrogenase,
glutathione reductase, glyceraldehydephos-
phate dehydrogenase, purine nucleoside
phosphorylase, nadph2 diaphorase, and
nadh2 cytochrome c reductase activities.
increased enzyme activities were noted
in the irradiated lenticular tissues for
purine nucleoside phosphorylase, nadph2
diaphorase and nadh2 cytochrome c
reductase.  decreased activities for glucose
6-phosphate dehydrogenase, malate
dehydrogenase, glutathione reductase and gly-
ceraldehydephosphate dehydrogenase
were observed in the lenticular tissues of ir-
radiated animals.  the activity of isocitrate
dehydrogenase was the same in the ir-
radiated and in the control animals.
.I 506
.W
465. conversion of a-crystallin of bovine lens into insoluble
protein in vitro
a-crystallin can be converted into an insoluble
form by treatment with alloxan and
to a very small extent with iodoacetate.
other reagents such as hcl, naoh, reduced
glutathione, hydrogen peroxide,
mercaptoethanol, were not able to convert a-crys-
tallin into an insoluble form.  the
alloxan treated insoluble a-crystallin could be made
soluble by treatment with 7 m urea.
the product thus made soluble had the same
electrophoretic mobility as a-crystallin,
but showed cross reaction with a-crystallin
in ouchterlony plate and did not have
proteolytic activity.  alloxan was effective in
producing cataract of rabbit lens when very
small amounts were injected into the
aqueous.
.I 507
.W
1972. structural studies of a-crystallin
a-crystallin has been isolated from the cortex
of ox lens by isoelectric precipitation
followed by chromatography on deae-cellulose.
the amino acid composition is in
agreement with that reported for a-crystallin
prepared by a different method.  there
is one thiol group/20,000g. of protein
(20,000 is the order of magnitude of the sub-
unit molecular weight), and disulphide
bonds are absent.  the thiol group has been
alkylated with radioactive iodoacetate
in the presence of urea.  partial acid hydroly-
sis of the alkylated protein gives,
according to the conditions, mainly 3 radioactive
peptides or nearly exclusively one
radioactive dipeptide.  the dipeptide is n-seryl-
(s-carboxymethyl) cysteine, ser-cmcys.
the 2 other peptides are probably the tri-
peptides related to ser-cmcys.  the
simplest interpretation of these results is that
the sequence around the cysteine residue
is a common structural feature of the sub-
units of a-crystallin.
.I 508
.W
1751. on the subunits of a-crystallin
a-crystallin was isolated from total
water-soluble lens extract by preparative zone
electrophoresis on starch or pevikon
c870 blocks and purified by density gradient
centrifugation and sephadex chromatography.
these preparations were treated with
urea or sodium dodecyl sulphate and
submitted to electrophoresis on polyacrylamide
gels containing either urea or sodium
dodecyl sulphate.  whereas in 7 m urea a large
number of zones was detected, only
three bands were observed in 1% sodium dodecyl
sulphate.  on the other hand, the
sedimentation coefficient had the same value in both
media.  the authors re-investigated the
n-terminal amino acid content in the starch block
preparations and compared the result
with that obtained from the preparations isolated
according to their new procedure.  the
concentration of dinitrophenyl-glutamic acid
was lower in the purified samples.
urea-treated samples had the same concentration
of n-terminal glutamic acid whereas
the concentration of the 'trace' end-groups did
not change.  sedimentation-diffusion
equilibrium in the analytical ultracentrifuge
revealed a slight heterogeneity in the
purified samples.  electron micrographs of
electrophoretic and of further purified
samples were very similar.  at neutral or
slightly alkaline ph they showed almost
uniform spherical aggregates in which a
substructure was observed.  at acid ph,
coiled filaments rather than small globules
could be demonstrated.
.I 509
.W
1752. separation of the soluble proteins of bovine lenses on
polyacrylamide gels
the soluble proteins of bovine lenses were
separated by gel filtration on polyacryl-
amide gels.  the presence of ethylenediaminetetra-
acetate in the buffer was found
to be essential for achieving a good separation
of the lens homogenate into four
fractions - a, b, c and d.  ultracentrifugal,
electrophoretic and immunochemical
analyses were used to compare these fractions
with the soluble crystallin fractions
of the lens.  fraction a was compared
with a-crystallin, fractions b and c with
b-crystallin and fraction d with y-crystallin.
the distribution of these four protein
fractions in the nuclear and cortical parts
of calf and cow lenses was determined.
the oxidation-sensitive protein fraction of
the calf lenses was separated from
fraction b on an se-sephadex column.
.I 510
.W
1745. the deaggregation of bovine lens a-crystallin
sedimentation equilibrium studies of lens
a-crystallin at neutral ph indicate that
this material is composed of a number
of different sized species.  a study of the
effect of alkali upon a-crystallin indicates
a progressive deaggregation of the ma-
terial with increasing ph.  sedimentation
equilibrium studies were performed at ph
12.8 as well as in guanidine hydrochloride,
7 m urea, and with succinylated material.
under all of these conditions a molecular
heterogeneity was observed.  the data
indicate that independent species coexisted
under most dissociating conditions.  the
weight average molecular weights of the
succinylated, and of the alkali-, urea-,
and guanidine hydrochloride-treated
material were found to have an integral relation-
ship of 8 4 2 1, respectively.  since a
constant ratio of m2 mw was found, it was
concluded that the same spread of
distribution of molecular species occurred for
each of the deaggregating conditions.
the results in guanidine hydrochloride could
not be evaluated in this manner because
of a small concentration dependence.  these
conclusions imply that not only the
weight average molecular weight in 7 m urea
but the actual molecular weight of
each individual species in urea was one-half of
the value to be found in alkali and
one-quarter that of the succinylated material.
.I 511
.W
1747. the problem of albuminoid
albuminoid is the main constituent of the
insoluble fraction of the lens proteins.
albuminoid from the cortex of ox lens has
been fractionated on deae-cellulose in
7 m urea; peptide maps of the fractions
are very similar to those from the corre-
sponding fractions from a-crystallin.
albuminoid can be regarded as an insoluble
a-crystallin.  an undiluted ground lens
is clear but becomes turbid on dilution.  if
albuminoid is present in the normal lens,
it does not cause turbidity even when the
cellular structure is disrupted.  it is
perhaps more likely that the albuminoid is
formed on dilution of the lens mush.
the high concentration of proteins in the lens,
especially in the nucleus, entails a high
degree of order, which will be destroyed
on dilution  this phenomenon may well be
connected with the precipitation of the
albuminoid.
.I 512
.W
787. further autoradiographic studies of the lens epithelium.
normal and x-irradiated rat eyes
cell proliferation and migration in
the lens epithelium of normal and x-irradiated
rat eyes were studied by means of
autoradiography after labelling with tritiated
thymidine.  cells of the normal lens
epithelium require 16 hr. to pass from the
beginning of the synthesizing period
to the completion of mitosis.  this interval is
partitioned as follows  s period,
approximately 10 hr.; g2, slightly less than 5 hr;
and mitosis, 72 min.  following division,
labelled daughter cells migrate from the
germinative zone to the postequatorial
rows, and by 2 weeks after tracer injection
many radioactive nuclei are found in the
lens bow.  epithelial cells irradiated while
in the dna synthesis phase undergo
degeneration beginning approximately 8 hr.
after exposure.  the onset of cell death
corresponds to the time at which these cells
would normally be preparing for mitosis
indicating that they die in abortive divisions.
a small percentage of the originally
labelled cells survived until 3 days after irradi-
ation, but by 2 weeks this number fell
almost to zero.  the loss of radioactive cells
occurred most rapidly in the equatorial zone.
.I 513
.W
2627. chicken lens development  epithelial cell production and
migration
in the earliest stages of chicken lens
development, cell division occurred over the
entire lens.  cell division first stopped
in the posterior side of the lens vesicle, as
the cells differentiated into primary lens
fibers.  after the annular pad developed,
cell division occurred, for the most part,
in the anterior surface epithelial cells.
shortly after hatching and thereafter, a
germinative zone, consisting of a narrow
band of epithelial cells adjacent to the
annular pad developed.  the cells from the
germinative zone migrated slowly and
differentiated first into annular pad cells and
then into lens cortex fibers over an
estimated 2-year period.  this slow migration
of cells in the lens is discussed in
relation to the failure of the adult chicken to de-
velop radiation cataracts.
.I 514
.W
1494. selenium content of fish flour in relation to kwashiorkor and dental
caries
the fact that fish flour was shown to be a rich source of
dietary selenium (169 p.p.m. may have important implications (i.e. deleterious
effect on teeth) in the treatment and prevention of protein malnutrition.  it
indicates that some disease syndromes in man may be a manifestation of selenium
deficiency.  it is recommended that the role played by selenium in protein
malnutrition should be given serious consideration by research workers.
.I 515
.W
2192. selenium content of fresh eggs
during a study of effects of traces of se on dental caries the authors
determined this element in eggs.  whole egg contains appreciable
amounts of se; this is found chiefly in the yolk (mean value 0.324
0.039 p.p.m.) with only 0.051 0.029 p.p.m. in the white.
.I 516
.W
1541. selenium content of human milk  possible effect on dental caries
selenium appears to be a factor capable of increasing susceptibility to
dental caries in children and rats.  in an area considered to be
nonseleniferous, milk collected from 15 mothers (17-44 yr. old) of low
socio-economic class had a mean selenium content of 0.021 p.p.m.
(standard error  0.003).
.I 517
.W
1577. mode of action of selenium in relation to biological activity of
tocopherols
dietary selenium at levels below 1 ppm has a partially beneficial effect
upon nutritional muscular dystrophy but is ineffective or detrimental
at higher levels.  the role of selenium in improving the effectiveness of
vitamin e is due at least in part to the fact that dietary selenium increases
the retention of the a-tocopherols, especially d-a-tocopherol.  this has been
shown by chemical determination of plasma tocopherols and also by tracing the
activities of tritiated tocopherols and selenium75 in serum and in various
fractions of serum proteins in chicks receiving these nutrients alone and in
combination.  se75 and h3-a-tocopherol activities followed each other very
closely in the serum proteins.  these studies indicated that vitamin e may be
carried by a selenolipoprotein fraction associated with serum y-globulin.  thus,
one biological role of selenium appears to lie in a selenium-containing
compound which acts as a carrier of vitamin e and which may function in
absorption, retention, prevention of destruction, and perhaps transfer across
cell membranes of d-a-tocopherol, thereby enhancing its biological activity
in the blood and perhaps in cells throughout the body.
.I 518
.W
3123. effect of sodium selenate on acute poisoning with thallium
experiments were performed on wistar rats weighing 150-200 g.  thallium was ad-
ministered s.c. in doses of 20 mg/kg and 30 mg/kg.  sodium selenate was
given per os in doses of 10 mg/kg 2 hr after poisoning and 5 mg/kg daily
for the next 2 days.  results indicate that sodium selenate protects the
animals from death.  it binds the thallium ions and increases their deposition
in organs.  comparison of the level of thallium in organs of treated rats
shows that selenate increases in liver by 290.6%, in kidneys by 326.8% and in
bones by 210.0%.  no influence of selenate on excretion of thallium in the
urine was found, but fecal excretion of thallium increased by an average of
45% of the treated animals.
.I 519
.W
2281. inhibition of active transport of sugars through rat intestine in vitro.
ii. action of mepacrine, atractyloside and selenite
it is shown that mepacrine, atractyloside and selenite, which had been regarded
as inhibitors of intestinal absorption of glucose, are inhibitors of active
transport of sugars in sacs of everted jejunum of rat (wilson and wiseman's
method).  mepacrine 5 x 10 -3 m and 10 -2 m inhibit, by 85% and 100%
respectively, the active transport of galactose.  with atractyloside 10 -5 m
and 10 -3 m, the inhibitions were 77% and 100% and, with selenite 10 -4 m and
10 -3 m, about 70%.  in general the inhibitors are effective within orders of
magnitude which are similar in vivo and in vitro.  atractyloside is rather more
effective in vitro than in vivo, and mepacrine rather less.  it is easier to
achieve total inhibitions of the active transport of sugars in vitro than of
intestinal absorption from isotonic solutions in vivo.
.I 520
.W
2284. analogs parasympathetic neuroeffectors.  ii. comparative pharmacological
studies of acetylcholine, its thio and seleno analogs, and their hydrolysis
products
acetylthiocholine and acetylselenocholine exert acetylcholine-like effects on
the guinea-pig ileum and frog rectus abdominis preparations.  with the
latter preparation, responses to acetylthiocholine and acetylselenocholine,
in contrast to that to acetylcholine, are not enhanced by the addition of an
anticholinesterase.  this is attributable to the relatively high activity of
the hydrolysis products, cholinethiol and cholineselenol; acetylthiocholine
and acetyselenocholine undergo enzymatic hydrolysis at approximately the same
rate as does acetylcholine.  the hydrolysis products of acetylthiocholine and
acetylselenocholine, which have effects on the guinea-pig ileum comparable
to those of the parent esters, are readily oxidized in air to the relatively
inactive choline disulfide and choline diselenide, respectively.  these
observations are helpful in explaining many of the apparently contradictory
statements in the literature regarding the actions of acetylthiocholine.
.I 521
.W
3604. cytotoxicity of organophosphorus compounds.  comparative activities of
trimethyl derivatives of thiophosphoric and selenophosphoric acids on vegetable
(pisum root) and human (hela) cells
of the 4 compounds studied, the seleno compounds were more cytotoxic for
hela cells than their thio analogues, whereas the activities on pisum
root cells were equal.  the parent phosphoric acid derivatives have a
wider activity range on hela cells than the seleno and thio derivatives.
further studies are in progress.
.I 522
.W
3640. poisoning with sodium selenite
chronic poisoning with na selenite (in the drinking water) causes hepatic
cirrhosis, usually of atrophic type, in rats.  in rabbits there seems to be a
definite diabetogenic action, while attempts to demonstrate such action in
dogs have so far given inconclusive results.  the difference between these
2 species is perhaps due to the technique used (different spacing of injections
for practical reasons).  the action of selenite on the pancreas is discussed
and it is pointed out that se can replace s in sh groups, thus rendering the
latter ineffective.  both in effects on the liver and in those on the pancreas
se seems to resemble alloxan.
.I 523
.W
2552. the tissue distribution of se75 -selenouracil and se75 -selenourea
when selenium analogues of thiouracil and thiourea labelled with se75 were
injected into rabbits, high radioactivity appeared in lung, liver and kidney.
the animal's lungs could be visualised by photoscanning, but quality was
poor, and neither compound is recommended for trial for lung or
adrenal scanning in man.
.I 524
.W
1142. sodium selenate toxicosis  pathology and pathogenesis of sodium
selenate toxicosis in sheep
the pathogenesis of selenium toxicosis was studied in 30 ewes fed subtoxic to
toxic levels of sodium selenate for 1 to 5 mth.  seventeen of the 30 died of
selenium toxicosis.  the most severe and consistent pathologic changes were
found in the myocardium and lungs.  myocardial alterations were focal to
diffuse degeneration, necrosis and early replacement fibrosis.  pulmonary
changes, consisting of edema and interstitial hemorrhages, were typical of the
degenerative processes which characterize passive congestion of the lungs
resulting from left ventricular insufficiency.  atrophy of lymphoid centers
in the spleen and lymph nodes was common.  degenerative changes were
occasionally found in liver, kidneys, and gastrointestinal tract.
.I 525
.W
1143. sodium selenate toxicosis  the distribution of selenium within the body
after prolonged feeding of toxic quantities of sodium selenate to sheep
the distribution of selenium in the body tissues of adult sheep fed subtoxic to
toxic quantities of sodium selenate daily for 1 to 5 mth. varied with the
tissue
type and with the level and duration of selenium consumption.  selenium
concentration was highest in the liver, followed by (in descending order)
the kidneys, lungs, spleen, myocardium, skeletal muscles, and brain.
.I 526
.W
1172. studies on selenium toxicity and chondroitin sulfate and taurine
biosynthesis in the chick embryo
fourteen-day-old chick embryos were used in in vivo experiments.  a toxic
selenite treatment did not cause a reduction in the extent of sulfate-s
incorporation into chondroitin sulfate or into taurine or a reduction in the
observed tissue levels of these metabolites.  rather, the taurine level was
significantly greater with the embryos which received selenium.  the extent of
the incorporation of selenite-se into the metabolites was low or not
significant.
.I 527
.W
843. reactions of seleno- and sulfoamino acids with hydroperoxides
reactions of methionine, cystine and their selenium analogues with
hydrogen peroxide and organic peroxides have been studied.  methionine reacts
most rapidly with hydrogen peroxide but selenocystine causes the most
decomposition; both react much more slowly with organic peroxides.  the results
suggest that selenocystine may act as a biological antioxidant.
.I 528
.W
2127. selenium toxicity in domestic animals
the article, with an extensive bibliography, is a compendium of available
information on selenium toxicity in domestic animals.  literature reveals
evidence of organically bound se being more biologically active, when given
orally to domestic animals, than inorganic se salts.  there is also variation
in toxicity of organic se analogs.  when exposed to ruminal digestion, there is
considerable reduction of se salts to the relatively biologically inactive
elemental se; which may result in fecal excretion of se, as such, to as much
as 40% of a single oral dose.  fluorine, molybdenum, chromium, vanadium,
cadmium, zinc, cobalt, nickel and uranium increase se toxicity.  arsenic and
tungsten give some protection against it.  bromobenzene, benzene, and
napthalene
mobilize tissue se and stimulate its excretion.  since se preparations designed
for topical application in treatment of skin disease have been available for
use
in both man and dogs, the literature has reported cases of poisoning from
misuse
of such preparations.  selenium, properly used, can be a valuable therapeutic
agent, though certain salts of se must be regarded as potentially toxic.
however, there is considerable latitude between therapeutic and/or nutritional
and toxic doses of these salts.
.I 529
.W
1845. further studies on specific transplantation antigens in rous sarcoma of
mice
mice allografted with different sarcomas, induced by the schmidt-ruppin variant
of rous sarcoma virus (rsv-sr), showed a resistance against subsequent
isografting of 9 different rous sarcomas.  transplantation
resistance could also be induced by
rous mouse tumor cells x-irradiated with 8000 r
or with cell-free tumor extracts,
containing no demonstrable virus.  no
transplantation resistance could be demon-
strated after allograft pretreatment with
various polyoma tumors or non-viral tu-
mors.  allograft pretreatment with rous
tumors induced no demonstrable resistance
against isografting of polyoma tumors.
inoculation of rsv-sr or rous chicken sar-
coma suspension into adult mice gave
no clear cut resistance against isograft-
ing of mouse sarcomas.  neither after
allografting of rous tumors nor after virus
or chicken sarcoma inoculation into adult
mice could virus-neutralizing activity be
demonstrated in the sera.  the results
demonstrate the presence of common, speci-
fic transplantation antigen(s) in different
rous sarcomas in mice and speak against
an identity between the transplantation
antigen(s) and viral antigen(s).
.I 530
.W
1846. anaphylactic tests in model tumour antigen investigations
the efficacy of anaphylactic tests in detecting
'tumor' antigen in serum was investi-
gated.  a simple model of a tumor-antigen
study was carried out using rat tissue
and rat serum, with bovine y-globulin (byg)
acting as a mock cancer antigen.  it
was found that if byg (absolute dosage 100
ug.) had formed 1/6 of the antigen mix-
ture used for sensitization it was readily
detected when present in a concentration
of 10-3 in the serum used for challenge,
but not invariably detected in a concentra-
tion of 10-4.  if byg (absolute dosage 50
ug.) had formed approximately 1/50 of the
sensitizing mixture, it was infrequently
detected even when present in the challeng-
ing serum in a concentration of 10-2.  it
is concluded that anaphylactic tests used in
this context do not have a very high
sensitivity or discriminatory capacity.
.I 531
.W
1066. the effect of lymphoid cells from
the lymph of specifically immunised sheep
on the growth of primary sarcomata in
rats
the growth of primary fibrosarcomata induced in
rats with 3:4-benzpyrene was retarded by the injection
of lymphocytes obtained from the efferent duct of a
lymph node in a sheep immunized with a piece of the
tumor to be treated.  the action of the heterologous lym-
phocytes was specific to the particular tumor used for
immunization suggesting that reaction against tumor-
specific antigens is involved.  the cells responsible are
believed to be medium-sized pyroninophilic lymphocytes
which may stimulate the immune system of the host to
react against the autochthonous tumor.
.I 532
.W
2570. treatment of canine neoplasms with autogenous vaccinial preparations
inbred mice with transplantable sarcoma
and carcinoma were treated with im-
plants of their tumours which had been
grown in strains of mice normally resistant
to the tumours.  complete regression of
transplantable tumours was noted in 22%
of the treated mice and 78% had life
spans double that of untreated controls.
one dog with spontaneous scirrhous
mammary carcinoma and another with
lymphosarcoma were treated with implants
of their own tumours after growth in
cortisone-treated mice.  regression of the
spontaneous neoplasms followed in both
cases.  it is suggested that growth of a
neoplasm in a foreign host alters the mole-
cular structure of the neoplasm, making it
antigenic when returned to the original
host.  antigens produced are also effective
against the original lesions.
.I 533
.W
744. studies on protein and nucleic acid metabolism in virus-in-
fected mammalian cells.  the formation of a virus-specific
antigen in krebs ii ascites-tumour cells infected with ence-
phalomyocarditis virus
krebs ii mouse ascites-tumor cells infected
with encephalomyocarditis virus were
found to contain, in addition to mature virus,
a virus-specific protein antigen.  an
assay, based on the ability of this antigen
to block the neutralization of purified virus
by its specific antiserum, was developed.
this antigen was present both in the cul-
ture fluid 17 hr. after the infection of cells
with virus and intracellularly, where its
titer increased at a time when viral capsid
protein was being synthesized.  within the
cell, it was mostly localized in the soluble
cell sap.  in contrast with virus, the anti-
gen did not agglutinate sheep erythrocytes,
and its immunological properties were
destroyed by digestion with trypsin.  ribonucleic
acid was not detected in concentrat-
ed preparations of the antigen, nor was the titer
of antigen affected by ribonuclease.
the antigen had a sedimentation coefficient (20 )
of approx. 14s, and its diffusion co-
efficient, determined by the method of allison and
humphrey (1960), was 3.2 x 10-7
sq. cm. sec.-1.  the particle weight of the antigen
was hence 420,000   40,000.  the
capsid protein from purified encephalomyocarditis
virus could be degraded by treat-
ment with ethanolamine into a protein of sedimentation
coefficient (20 ) of approx. 4s.
the 14s antigen, when similarly treated, yielded
a protein of similar size.  however,
no such smaller antigen was detected in virus-infected
cells.  it is concluded that the
non-hemagglutinating antigen represents a polymeric
form of the basic viral capsid-
protein molecule and that it is synthesized in the
cytoplasm of infected cells.  it may
be either an intermediate or a by-product in the
process of viral capsid-protein syn-
thesis.
.I 534
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1368. immunologic competence and induction of neoplasms by
polyoma virus
thymectomy at 3 days of age in several
inbred strains of mice and in an f1 hybrid
resulted in a strikingly increased frequency
of neoplasms following infection with
polyoma virus.  age susceptibility was extended
to at least 30 days of age in highly
resistant c57bl mice.  the usual stigmata
associated with thymectomy at birth were
not found in the 3-day thymectomized mice.
nonetheless the methods used to restore
immunologically deficient thymectomized
neonates were also effective in restoring
the capacity to resist polyoma virus tumor
induction: adult syngeneic spleen cells,
thymus tissue in millipore diffusion chambers
and syngeneic thymus grafts.  growth
curves of polyoma virus in kidney, salivary
glands and liver were quite similar in
thymectomized and intact litter mates.
hemagglutination-inhibition antibodies deter-
mined periodically up to 30 days after
infection were also similar in both groups.
these results are discussed in terms of
a concept involving virus-specific 'tumor'
antigens and the immunologic status of the animal.
.I 535
.W
1848. antigen analysis of sera from patients with malignant
tumors by immunodiffusion methods
immunoelectrophoresis and ouchterlony's
method were used for the antigen analy-
sis of sera from 320 cancer patients; 250
normal or non-tumorous cases served as
controls.  immunoelectrophoresis showed
abnormal precipitin lines which could not
be demonstrated in normal sera.  most of
the abnormal antigens were demonstrated
in the a2- and b1-globulin fractions.  the
distribution of these antigens differed in
individual cases and was not related to the
histopathological classification and site
of the tumors.  however, these antigens
increased in parallel with growth of the
tumors and disappeared or markedly
decreased after surgical removal of the tumor
tissue.  almost all sera of patients with
myeloma, leukemia, and malignant lymph-
oma formed one characteristic line in
the b2-globulin region and they could be dif-
ferentiated from the patterns in cases of carcinoma.
.I 536
.W
2354. isoantigenic properties of tumors transgressing histocompatibility
barriers of the h-2 system
sublines capable of transgressing h-2 histocompatibility
barriers have been derived
from strictly strain-specific tumors by 1) passage
through newborn hosts of a
foreign genotype; 2) passage through adult h-2
incompatible recipients pretreated
with isoantisera directed against the tumor cells.
the nonspecific character induced
by these procedures was usually expressed in a
number of different h-2 incompa-
tible recipients.  the changes responsible for
the conversion to nonspecific growth
appeared to proceed in a stepwise fashion.
expression of the nonspecific character
required exposure to the foreign host environment
for more than 30 days.  at this
stage and during the subsequent 3 transfer
generations, reversion to strain-specific
growth occurred on back-transfer to the
strain of origin; after 4 passages in the
foreign hosts the nonspecific character was
permanently established, however, and
could not be reverted by prolonged passage
in the original host genotype.  the
growth rate of strain-specific tumors and
their nonspecific sublines was compared
in the strain of origin.  no difference was
found with one tumor, while the strain-
specific line grew better than the nonspecific
sublines with another.  this difference
was detected in the homozygous strain of
origin and in different semi-isologous f1
hybrids.  all lines grew better in the
homozygous strain than in the f1 hybrids,
however.  a comparison was made
between the concentration of h-2 isoantigenic
surface determinants in strain-specific
tumors and their nonspecific sublines by a
quantitative absorption technique in
vitro.  all nonspecific sublines had a lower
concentration of h-2 isoantigens than
the strain-specific tumors.  this suggests
that nonspecific tumors develop as a result
of immunoselection of variants resistant
to the homograft reaction and are characterized
by a lowered concentration of
h-2 antigens.
.I 537
.W
2371. participation of 7s and 19s antibodies in enhancement and
resistance to methylcholanthrene-induced tumours
serum factors responsible for enhancement
and resistance to methylcholanthrene-
induced tumors in a syngeneic system in mice
were studied.  they were found to be
part of the serum immunoglobulin system.
the active components of specific anti-
tumor serum were always contained in the
7s (y-2) and 19s (y-1m) fraction, while
no activity was detected in the 4s fraction.
in sera which in the given dose enhanced
growth of the tumor graft, enhancing activity
was present in both the 7s and 19s
fraction of the serum and was higher in the
former.  in sera which in the given dose
influenced the interaction of the organism with
the tumor by producing resistance
to the tumor graft, both fractions were again
active, the activity of fraction 19s
being higher than that of fraction 7s.
.I 538
.W
2372. the effect of immunity against sex-antigen on a tumour
graft containing sex-antigen
the tumor bp 1 induced by benzpyrene in c57bl
male mice contains sex-antigen.
sex-antigen is not lost during growth of tumor
against immunity directed against
this antigen.  the tumor, however, becomes
more resistant to immunity and the
content of sex-antigen is decreased.
.I 539
.W
2373. factors influencing the induction of enhancement and re-
sistance to methylcholanthrene-induced tumours in a syn-
geneic system
active immunological enhancement of the
growth of methylcholanthrene-induced tu-
mors was demonstrated in a syngeneic
system in mice.  enhancement was detected
3-5 wk. after preimmunization with
irradiated tumor suspension and was succeeded
after the 6th wk. by the development of
resistance to the tumor.  analysis by means
of adoptive and passive transfer showed
these to be true immunological phenomena.
enhancement and resistance were transferred
by serum and by the lymph node cells
of preimmunized mice.  threshold doses of
tumor cells were found to be the most
satisfactory for the detection of resistance
and enhancement in this system.
.I 540
.W
5512. antigenic properties of human tumours
preliminary studies on the antigenic
properties of human tumours have been
carried out using heterologous antisera,
prepared in rabbits, against a number of
different cancerous and normal tissues.
after repeated absorptions, antisera
were obtained which reacted only with
tissue antigens.  some antisera, after ab-
sorption with normal tissues, reacted only
with tumours.  seventy-two tumour and
31 normal tissue extracts were studied
by means of the ouchterlony agar gel
double diffusion technique.  the results
showed the presence of an antigen or
antigens in some human malignant tumours
which were not detectable in normal
tissues, in foetal tissues, or in hela cells.
in addition, there was some loss of
normal tissue antigens from tumours.
attempts are being made to isolate and
characterize these tumour and normal
tissue antigens.
.I 541
.W
5514. the incorporation of sv40 genetic material into adenovirus 7 as
measured by intranuclear synthesis of sv40 tumor antigen
the l.l. strain of adenovirus 7, free of
detectable infectious sv40 virus, induced
sv40 tumour antigen, demonstrable by
fluorescent antibody staining, in green mon-
key kidney, rabbit kidney, hamster embryo
and human embryo kidney cell cultures.
in green monkey and human cell cultures
there was a cytopathic effect and more
cells contained the sv40 tumour antigen
than in the other types of culture.
adenovirus 7 viral antiserum neutralized
the sv40 tumour antigen inducing
ability of the l.l. strain virus but anti-sv40
monkey serum and serum from sv40
tumour bearing hamsters did not.  an
adenovirus 7 preparation propagated
exclusively in human tissue did not induce
the sv40 tumour antigen.  the sv40
tumour antigen was entirely localised within
the cell nuclei and appeared to be
transmitted to daughter cells during mitosis.
.I 542
.W
264. fluorescent antibodies to human cancer-specific dna and
nuclear proteins
specific antigens have been demonstrated
in certain cancers.  in this study they were
obtained from an adenocarcinoma of the
colon and an ewing's sarcoma.  homogenates
were prepared and male rabbits were
immunized.  the animals were bled to death
10 days after the last injection.  testing
included fluorescent antibody methods and
agar-gel horizontal double-diffusion precipitin
test.  the pattern of reaction of these
antibodies against various cancers seems to
be dependent upon the source of the
cancerous dna-bound proteins and the salt
concentration used in their isolation.
human cancer-specific cross nuclear antigens
seem to be cross reacting rather
than identical in structure.  the cancer-specific
antibodies could be removed only
with absorption of the immune globulins with
cancerous tissues.  salt-soluble human
dna-bound proteins from an adenocarcinoma
of the colon and an ewing's sarcoma
induced the formation of cancer specific
antibodies which showed positive fta re-
actions (to a maximum titer of 1/128) against
95% of the cancerous tissues studied.
these cancer-specific antibodies gave
similar fta reactions with cell nuclei of
normal appearing liver parenchyma
adjacent to metastatic carcinoma of colon, nor-
mal appearing colon near to metastatic
carcinoma of the colon, normal appearing
colon near to carcinoma of the colon,
and a long-standing case of chronic ulcerative
colitis.  evidence is shown that this finding
possibly may represent a serological
detection of an early or latent cancerous
change in morphologically normal cells.
these cancer-specific antigens have been
identified as rounded, intranuclear dna-
bodies and nuclear proteins which can be
specifically destroyed by dnase trypsin.
.I 543
.W
266. immunology of the cancer cell: tumour-specific antigens
after a broad historical survey of immunological
studies of cancer, a review is given
of the evidence showing that antigens present in
normal cells are missing from the
malignant cells that arise from the same tissue.
this evidence is considered in con-
junction with the deletion hypothesis of carcinogenesis,
and the author emphasizes,
that in his view, the key event in carcinogenesis
is enzymatic deletion.  antigenic
gain and intensification in the course of spontaneous,
chemical, and viral carcino-
genesis is reviewed, together with experiments
demonstrating the existence of
tumour-specific antigens.  the question is then
posed: if tumours have specific anti-
gens, why is evidence for their rejection so scanty?
the occasional spontaneous re-
gression points to host resistance but its rarity
suggests that tolerance generally
develops.  consideration is given to the
application of immunological methods to
therapy and although current achievement
in this field is limited, new immunological
stratagems might yet transform the picture.
finally a plea is made for the integra-
tion of the disciplines of immunology and
cellular differentiation.  the prospect is
raised that through a synthetic and holistic
approach we might discover the suscepti-
bility of the cancer cell to re-differentiation
and re-recognition.
.I 544
.W
effets de la carence potassique
chez le rat sur le squelette,
le cholesterol plasmatique
l'histologie des surrenales
r. habib, j. lefebvre et p. royer
potassium deficiency in the male rat at the time of weaning,
provokes an increase in the weight of the suprarenals, an
atrophy of the glomerular zone and a lipoid hypertrophy of
the fasciculae.
it causes a rise in the level of the blood cholesterol.  it
reduces the phosphate level in the blood and increases the
phosphate in the urine.
the blood calcium level is not altered but a hypocalciuria is
noted.
it leads to a severe osteopathy which has been investigated
by radiography, microradiography and histological and bio-
chemical study of the skeleton.  the following are the charac-
teristics : arrest of osseous growth, delay of maturation, arrest
of chondrogenesis, formation of dense metaphyseal lines or
lines of arrest, osteoporosis.
these facts are discussed and compared to the analogous
changes found in the syndrome of chronic idiopathic hypo-
kalaemia with hyperkaluria in the infant.
.I 545
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vergleichende renale phosphatelearance-untersuchungen
beim hyperparathyreoidismus und beim sog.  phosphatdiabetes
the analysis of the function of the kidneys give a contribution to
the pathophysiology of two different diseases of general osteopathies
whose pathogenesis or etiology are still not clear in some points.  the
phosphate clearance pre- and postoperative in one patient with hyper-
parathyroidism showed that after the removal of the adenoma of the
parathyroid the renal reabsorption of phosphate improved only tempo-
rary as a secondary form of hyperparathyroidism was already present.
in a patient with a "phosphatdiabetes" the clearance examination showed
that under a high dosage of vitamin d the reabsorption of phosphate did
not increase.  based on these results we have not continued therapy
with vitamin d which is certainly not indifferent.  comparative renal
clearance examinations were carried out in 10 patients which did not
show any disturbances of calcium/phosphate-metabolism.
.I 546
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the unreliability of the titan yellow method
for the determination of magnesium
in patients receiving intravenous
calcium gluconate
gluconate was found to interfere with the determination of magnesium by the
titan yellow method.  with this method, false low results were found in the
serum and urine of patients receiving intravenous calcium gluconate.  the
interference can be prevented by ashing of the specimen.
.I 547
.W
absorption and excretion of toxogonin, an alkyl-phosphate antidote,
after intramuscular injection in man
tolerance, absorption and urinary excretion stu-
dies of toxogonin (bis-(4-hydroxyiminomethyl-
pyridine-1-methyl) ether dichloride), a specific anti-
dote in poisoning by esterase-blocking organic
phosphates, were made on 11 men by intramuscular
injection of 250 mg. (ca. 3 mg./kg.) of the drug,
given by self-injection ampoules.  injections made
with the automatic ampoule autule caused no local
irritation.  certain facial symptoms reported can for
the time being be regarded as resorptive side-effects
of toxogonin.  maximum blood levels of 6 ug./ml.
were recorded within 20 minutes.  even after four
hours the level was still 1-2 ug./ml., a concentra-
tion amply sufficient to ensure reactivation of blood
esterases.  of the injected dose, 52% was excreted
in the urine after two hours, 87% after eight hours.
toxogonin appears to pass through the body un-
changed.
.I 548
.W
the study of osteoporosis
and osteomalacia
radiological evidence strongly suggests that
osteoporosis (with the possible exception of acute
immobilization osteoporosis) may be an irrever-
sible condition.  the changes therefore to be
expected in calcium balance when an osteoporotic
is treated are small compared with those often
seen in osteomalacia.  methods of obtaining more
accurate calcium balances are needed to show
these small changes, especially when a high
calcium intake is used.  the method of continuous
marking of stools with chromium sesquioxide
seems to provide just such a method.  using this
method, it has so far proved impossible to obtain
prolonged large positive calcium balances in
osteoporosis on either high calcium intake,
anabolic hormones, or sodium fluoride.
two alternative therapies to vitamin d have
been explored for use in vitamin d-resistant
osteomalacia.  atp has been found to be inneffective.
intravenous phosphate alone has been ineffective
in producing positive calcium balances, but is
effective as a complement to vitamin d under
certain conditions.
.I 549
.W
the aetiology and treatment of
urinary calculus
investigations in this laboratory have been
based on the hypothesis that calculus formation is
primarily a process of crystallization from super-
saturated solutions rather than one of adsorption
on a specific protein matrix, as has been postulated
by boyce and his colleagues (boyce and king,
1963).  that crystallization is the primary factor
is strongly suggested by the recent studies of
vermeulen, lyon and gill (1964).  these authors
produced artificial concretions which closely
resembled urinary calculi by immersing a rotating
wire loop in normal urine for several days and
slowly adding the appropriate stone-forming
elements.
if the above hypothesis is correct then the
factors of primary interest in urinary stone
formation are those responsible for supersaturation,
nucleation and crystal poisoning.  much remains
to be learnt about these various factors, their
inter-relationships, and their relative importance.
the significance of the urinary colloids (proteins,
muco-proteins and polysaccharides) in calculus
formation is still not clear but it is probable that
they play an important secondary role in binding
crystalline precipitates to form a non-friable
calculus.  since time is an important factor in
crystal growth such non-specific binding by
proteins would increase the chances of stone
growth and retention within the upper urinary
tract.
.I 550
.W
control of idiopathic hypercalciuria
the paper discusses the causes of hypercalciuria and describes
15 cases of different origins all of which presented similarly
with renal stones.  the diagnosis of idiopathic hypercalciuria
was made by exclusion.  the effects of dietary restriction of
calcium, sodium bicarbonate, cortisone, sodium phosphate,
sodium phytate, and cellulose phosphate were demonstrated by
calcium and phosphorus balance techniques.  all were shown
to have some urinary-calcium-lowering effect.  finally, a
chlorothiazide derivative--namely, bendrofluazide--was also
demonstrated to have a hypocalciuric effect, and the mode of
action is discussed.