.I 1 .W 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 . .I 2 .W 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 . .I 3 .W 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 . .I 4 .W 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 . .I 5 .W 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 . .I 6 .W 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 . .I 7 .W 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 . .I 8 .W 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. .I 9 .W 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 . .I 10 .W 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 . .I 11 .W 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 . .I 12 .W 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 . .I 13 .W 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 . .I 14 .W 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 . .I 15 .W 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 . .I 16 .W 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 . .I 17 .W 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 . .I 18 .W 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 . .I 19 .W 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 . .I 20 .W 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 . .I 21 .W fine structure of subtilis phage sp-50 . some structural details and anomalous forms of subtilis phage sp-50 are described . .I 22 .W 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 . .I 23 .W 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 . .I 24 .W 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 . .I 25 .W 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 . .I 26 .W 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 . .I 27 .W 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 . .I 28 .W 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 . .I 29 .W 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 .W 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 . .I 31 .W 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 .W 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 .W 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 .W 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 .W 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 . .I 36 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 . .I 103 .W 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 .W 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 . .I 105 .W 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 . .I 106 .W 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 . .I 107 .W 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 . .I 108 .W 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 . .I 109 .W 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 .W 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) . .I 111 .W 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 .W 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 . .I 113 .W 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 . .I 114 .W 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 . .I 115 .W 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 . .I 116 .W 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 . .I 117 .W 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 . .I 118 .W 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 . .I 119 .W 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 . .I 120 .W 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 . .I 121 .W 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 . .I 122 .W 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 . .I 123 .W 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 . .I 124 .W 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 . .I 125 .W 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 . .I 126 .W 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 . .I 127 .W 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 . .I 128 .W 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 . .I 129 .W 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 .W 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 .W 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 . .I 132 .W 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 . .I 133 .W 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 . .I 134 .W 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 . .I 135 .W 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 . .I 136 .W 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 . .I 137 .W 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 . .I 138 .W 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 .W 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 . .I 140 .W 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 .W 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 .W 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 . .I 143 .W 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 .W 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 . .I 145 .W 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 . .I 146 .W 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 . .I 147 .W 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 . .I 148 .W 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 . .I 149 .W 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 . .I 150 .W 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 . .I 151 .W 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 .W 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 .W 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 . .I 154 .W 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 .W 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 . .I 156 .W 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 .W 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 . .I 158 .W 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 .W 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 .W 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 .W 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 .W 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 . .I 199 .W 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 .I 200 .W 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 . .I 201 .W 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 . .I 202 .W 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 . .I 203 .W 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 . .I 204 .W 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 . .I 205 .W 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 . .I 206 .W 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 . .I 207 .W 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 . .I 208 .W 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 . .I 209 .W 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 . .I 210 .W 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 . .I 211 .W 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 . .I 212 .W 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 . .I 213 .W 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) . .I 214 .W 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 . .I 215 .W 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 . .I 216 .W 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 . .I 217 .W 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 . .I 218 .W 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 . .I 219 .W 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 . .I 220 .W 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 . .I 221 .W 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 . .I 222 .W 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 . .I 223 .W 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 . .I 224 .W 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 .W 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 .W /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 . .I 227 .W 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 .W 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 . .I 229 .W 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 . .I 230 .W 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 .W 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 .W 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 .W 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 . .I 234 .W 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 .W 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 .W 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 . .I 237 .W 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 . .I 238 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 . .I 244 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 . .I 250 .W 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 .W 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 .W 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 . .I 253 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 . .I 260 .W 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 .W 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 .W 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 .W 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 .W 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 . .I 265 .W 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 . .I 266 .W 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 . .I 267 .W 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 . .I 268 .W 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 . .I 269 .W 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 . .I 270 .W 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 . .I 271 .W 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 . .I 272 .W 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 . .I 273 .W 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 . .I 274 .W 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. .I 275 .W 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. .I 276 .W 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. .I 277 .W 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. .I 278 .W 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. .I 279 .W 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. .I 280 .W 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. .I 281 .W 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. .I 282 .W 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. .I 283 .W 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*) .I 284 .W 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 .W 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 .W 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. .I 287 .W 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. .I 288 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W . 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 .W 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 .W 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 .W 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 .W 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 .W 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 .W 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.