Effect of temperature-transfer on growth of laboratory populations of a South American annual fish Cynolebias bellottii.

Previous observation had shown that annual fish living at 15 degrees C grow faster and live longer than those at 20 degrees C. We now demonstrate that when populations of these fish undergo reciprocal transfer between these two temperatures, their growth rates change to that of animals living at the temperature into which they have been transferred. These growth rates do not entirely correlate with the longevity patterns observed in annual fish subjected to temperature-transfer, nor to certain other observations of the relationships among growth, temperature and longevity as reported in the literature.


Stress and fluctuating limb asymmetry in various species of rodents.

Recent studies have shown that the dentition of rodents responds to stress, evidenced by an increase in fluctuating asymmetry. In the present study, three known stressors, noise, cold and behavioral modification, were employed in evaluating the effects of stress on limb asymmetry. None of the stressors employed produced significant increases in fluctuating limb asymmetry except in the humerus. As teeth are highly genetically determined and bone highly responsive to function, these results suggest a stress-related interference in the synchronization of genetically stable structures.


Bone mineral in mentally retarded patients receiving long-term anticonvulsive therapy.

A direct photon absorptiometry method was used to measure bone mineral content in a population of mentally retarded subjects, one half of whom were undergoing long-term anticonvulsant drug therapy. The sample consisted of 134 subjects, 60 males and 74 females. Average ages were 22.5 years for the females and 19.7 years for the males. A multiple regression analysis showed there was no apparent effect on anticonvulsant drug therapy on bone mineral content in this mentally retarded and growth retarded population. A comparison with normal standards indicates that bone mineral values for age for both sexes of mentally retarded subjects were depressed from 15-40 percent relative to white standards. The bone mineral depression closely paralleled the growth depression seen in this population. It is suggested that the inability to detect an overall anticonvulsive drug effect on bone mineral values may be due to the general growth retardation seen in this institutionalized mentally retarded population.


Standards of morphological development of the quail, Coturnix coturnix japonica, embryo.

The morphologic growth of 290 Japanese quail embryos was analyzed to enable an assessment of the developmental status of an organism and permit the evaluation of experimental effects on development. The growth of 36- to 228-hr embryos was analyzed according to Hamburger and Hamilton's (1951) stages of development for the chick; the growth of 240-hr and older embryos was analyzed by correlating age with the length of 5 morphologic structures, toe, leg, beak, wing, and total. A correlation of +.99 was obtained for age-stage relations and a correlation of +.97 was found for age-structure length relations.


Assessment of severity in colitis: a preliminary study.

Clinical features, alone and in combinations of up to five, noted early in patients during 181 admissions to one hospital for treatment of acute colitis over five years, have been correlated with the success or failure of drug treatment as judged by death during medical treatment or the need for urgent surgical treatment. Many of the 56 clinical features studied were of no value in predicting the outcome of the attack. The four features of greatest predictive value were the maximum daily body temperature, the maximum daily pulse rate, the bowel frequency and plasma albumin. The simplest and most discriminating prediction at the end of the first 24 hours in hospital was obtained by combining observations on maximum body temperature and the number of stools passed. Serial observations of temperature or pulse rate over the first four days in hospital gave more prognostic information than observations confined to the first day. The predictive value of certain other features, such as x-ray appearances, is described. A simple classification of severity in acute colitis is proposed from these results as a basis for prospective testing in other hospitals.


The effect of iron stores on iron absorption in the rat: the possible role of circulating ferritin.

Iron absorption in man is inversely related to body iron stores and serum ferritin concentration. A negative correlation between intestinal iron absorption and the amount of storage iron in the body has been confirmed in the rat and the hypothesis that absorption may be regulated through the mediation of ferritin has been tested. There was no difference in mucosal iron uptake or absorption between rats undergoing a jugular infusion of ferritin and those infused with saline despite a hundredfold difference in circulating ferritin concentration.


A structural study of gallstones.

A number of gallstones have been studied using methods which have not previously been applied to gallstones. In particular, the use of scanning electron microscopy and micro-x-radiography have allowed detailed observations to be made on the structure of the stones and the distribution of the various components within the stones. Large differences in structure have been shown to exist between stones having similar overall chemical compositions. In cholesterol gallstones containing calcium carbonate the crystalline nature, distribution and method of deposition of the calcium carbonate was studied and was found to vary from stone to stone. Evidence was found for the presence of fibrous material in the centre of many stones and it is possible that this material acted as a nucleus for the deposition of the other stone components.


The influence of plasma triglycerides on human growth hormone response to arginine and insulin: a study in hyperlipemics and normal subjects.

Human growth hormone (HGH) response to arginine (25 gm IV in 30 min) and to insulin (0.1 U/kg B.W.) was studied in 12 male patients (mean age 36 +/- 2 years), with normal glucose tolerance and normal body weight, affected with Fredrickson's Type IV primary hyperlipemia. The patients were examined both when plasma triglycerides (TG) were elevated and following clofibrate (2 gm/die for 30-60 days) induced TG reduction. No variations in glucose or FFA behaviour or in body weight were observed after clofibrate. HGH response to arginine was absent, while that to insulin was only inhibited, when plasma TG were elevated. A significant increase in HGH peaks after arginine (from 1.99 +/- 0.59 to 9.34 +/- 1.58 ng/ml) and a slight increment in HGH peaks after insulin (from 23.09 +/- 7.19 to 31.46 +/- 7.95 ng/ml) were observed following reduction in plasma TG. Arginine test was carried out in 7 normal subjects during saline infusion and at the 3rd hour of lipid infusion (Intralipid 20%). HGH response to arginine was absent in all of the subjects during lipid infusion. The HGH response to insulin test, carried out in 9 other normal subjects during saline infusion and at the 3rd hour of lipid infusion (Lipiphysan 15%) was significantly inhibited during lipid infusion. Since lipid infusion provoked an increment, not only in plasma TG but also in FFA, the inhibition of HGH release could be correlated with the elevated plasma levels of both TG and FFA. The results obtained in both spontaneous and experimental hyperlipemia not only confirm the role played by FFA in the regulation of HGH secretion, but also support the hypothesis that elevated TG levels could inhibit HGH response to some stimuli.


Blood glucose and serum insulin levels in lean and genetically obese mice.

Fed and 24 hour fasted lean and genetically obese mice (ob/ob) were given a fixed glucose load per gm body weight by intraperitoneal and intragastric administration. Intraperitoneal glucose injection into the obese mice produced a prolonged elevated blood glucose level with a concomitant significant decrease of circulating insulin. Possible interpretations of this observation are discussed. In those obese animals in which glucose was administered intragastrically the fed obese mice had a blood glucose concentration of 450-500 mg% for a period of one hour but there was no increase in circulating insulin, however, in the fasted obese mice in which the glucose concentration was about 350 mg% for one hour, there was a significant increase in the circulating insulin levels. The fed and fasted lean mice showed normal glucose tolerance curves and the expected increase in circulating insulin following either intraperitoneal orintragastric glucose loads. It is concluded that hyperglycaemia in the ob/ob mice is unlikely to be the principal cause of hyperinsulinaemia.


The role of cortisol and growth hormone in the counter-regulation of insulin-induced hypoglycemia.

Four normal volunteers underwent a control insulin tolerance test (ITT) and an insulin tolerance test (ITT) after two days administration of the serotonin antagonist cyproheptadine (Cypro). Cypro administration resulted in an 81 +/- 11.4% (M +/- SEM) reduction in cortisol secretion and a 73 +/- 15.1% reduction in growth hormone (GH) secretion. Despite the reduction in hypoglycemia-induced cortisol and GH secretion, there was a similar decline and recovery of plasma glucose in the control ITT and the ITT after Cypro administration. Although previous studies indicate that normal basal levels of cortisol and growth hormone are needed for normal counter-regulation after insulin-induced hypoglycemia, augmented secretion of these hormones is probably not essential for this response. Hypoglycemia-induced increases in epinephrine and glucagon, secretion may contribute to the restoration of the normal plasma glucose concentration after insulin-induced hypoglycemia.


The effect of insulin on amino acid incorporation into exocrine pancreatic cells of the rat.

The rate of incorporation of radioactive leucine per cell in the acinar pancreatic cells of the rat increases by 50 per cent within one hour after subcutaneous administration of insulin, an effect that lasts for at least one more hour. The rate of incorporation has been measured by quantitative radioautography and by determination of the radioactivity per mug DNA in TCA-precipitable material from tissue homogenates. The capacity for amino acid (leucine and lysine) incorporation as measured by incubating pancreatic fragments in vitro is not enhanced by insulin treatment of the rat in vivo during one or more hours. Insulin was found to lower the serum concentration of most amino acids significantly, leucine by 50 per cent. The apparent effect of insulin on the incorporation of radioactive leucine in vivo can be explained by the difference in the specific radioactivity of the circulating amino acid in the treated rats as compared to the untreated ones. A change in amino acid concentration in the serum may likewise be the explanation of the decrease in amino acid incorporation rate in alloxan diabetic rats. The absence of a short term effect of insulin on the rate of protein synthesis does not exclude a long term effect as suggested by the higher rate of incorporation in the cells of peri-insular acini.


Studies on the different forms of material reacting with antiinsulin antibodies in the fetal and adult rat.

The nature of peak B (MW = 10-12000, proinsulin?) and PEak C (MW = 50-100000, "big big" insulin?) materials detected by the double antibody (DA) procedure in elution profiles of rat sera after Sephadex G 50 or G 100 chromatography (cf. preceding companion paper) is further investigated. Peak B is converted by mild tryptic digestion in an immunoreactive material behaving in rechromatography exactly like insulin monomer. Peak C is less easily detected by the dextran coated charcoal (DCC) method; it resists 8 M urea 37 degrees C for 1 hr, is not an artifact due to the complement system; its relative importance is very much reduced in pancreatic extracts or perifusates. Incubation of biologically active 125I labelled insulin in rat sera results in appearance of labelled material behaving on chromatography like peak C natural material, having the electrophoretic mobility of rat alpha I globulins and albumin, and resisting 8 M urea, acidic pHs and 0.5 M NaCl. Similar incubation in buffer supplemented with bovine albumin results in appearance of a labelled material having the electrophoretic mobility of beef albumin; N-ethyl-maleimide provides against this binding, which might result from (S-S)-(SH) interchanges. Rat alpha globulins and albumin (but not beef albumin) cross-react with the DA procedures; they do not react with the DCC method. Insulin bound to plasma proteins reacts with both methods. It is suggested that peak C material, as detected by the DA method in rat serum, consists both of insulin covalently bound to plasma proteins and of certain plasma proteins; the DCC method detects only bound insulin. In streptozotocin treated rats, peak C material persists after the complete disappearance of insulin and proinsulin, when detected by the (DA) procedure, but disappears when detected by the DCC procedure.


Effect of insulin on human intestinal smooth muscle.

The action of insulin (0.1 U/ml) on the metabolism of human intestinal smooth muscle was studied in vitro. The experiments were performed on the muscle layer of human jujunum obtained from patients undergoing intestinal shunt operations because of obesity. Insulin significantly increased glucose uptake, glycogen content, the membrane transport of alpha-amino-isobutyric acid (AIB), the incorporation of leucine into protein and tended to increase the membrane transport of the nonutilizable model monosaccharide 3-0-methylglucose. The effects of insulin were moderate and appeared after incubation times of 120 to 180 min.


The triglyceride content of adipocytes and plasma of patients with diabetes mellitus.

In two groups of obese diabetic patients closely matched for age, glucose intolerance and indices of obesity, the group with hypertriglyceridaemia was found to have an increased triglyceride content of adipocytes (p less than 0.001) and raised fasting plasma insulin (p less than 0.02). Plasma insulin did not directly relate to the level of plasma triglyceride (r = +0.28, n = 36, p N.S.) but correlated with the triglyceride content of adipocytes (r = +0.59, n = 37, p less than 0.001). The results suggest that raised plasma insulin is not a primary determinant of the level of plasmatriglyceride but that it may be related by its effect on lipogenesis in adipose and other tissues.


Adrenal function and the effect of a high-fat diet on C57BL/6J and C57BL/6J-ob/ob mice.

In C57BL/6J mice and the ob/+ and ob/ob mutants total plasma corticosterone levels were found to be statistically different. In C57BL/6J mice the level was 1.9 +/- 0.2 mug/100 ml plasma, in ob/+ mice 8.6 +/- 1.6 mug/100 ml and in ob/ob mice 13.7 +/- 1.5 mug/100 ml. The percentage of protein-bound corticosterone as well as the free endogenous corticosterone levels were also different. Feeding a high-fat diet to young C57BL/6J and C57BL/6J-ob/ob mice for a period of 4 weeks had no effect upon blood glucose, plasma insulin and plasma corticosterone levels. The significantly higher increase in body weight of the high-fat diet groups of both lines of mice was mainly due to fat cell hypertrophy.


Effects of SH-reagents of different molecular size upon glucose metabolism in isolated rat fat cells.

To study the role of membrane SH-groups in glucose transport of isolated rat fat cells we compared the effects of a small organic mercurial reagent p-CMB with those of a large p--CMB-derivative -- p-CMB-Dextran, MW  10.000 --. It could be shown that both compounds were of almost identical reactivity on fat cell homogenate metabolism. When applied to intact fat cells uncoupled p--CMB showed an (1) insulin like enhancement of 14C incorporation from (U-14C) glucose into CO2 and triglyceride, (2) inhibition of the insulin-stimulatory effect on these parameters and (3) inhibition of basal glucose uptake dependent on the concentrations used. Identical concentrations of p-CMB-Dextran, however, failed to influence basal glucose uptake as well as the insulin mediated increase in glucose metabolism.


Regulation of aldosterone secretion in primary aldosteronism.

Plasma aldosterone, plasma renin activity and plasma cortisol were determined in patients with primary aldosteronism in response to posture and at short-time intervals overnight while the patient were supine. In the 5 patients with an aldosterone-producing adenoma postural changes in plasma aldosterone were paralleled by those in cortisol while plasma renin activity was generally undetectable indicating an ACTH-dependent secretion of aldosterone. This concept was supported by the observation that in 3 of these patients who were tested overnight 1. episodic secretion of plasma aldosterone was paralleled by those of cortisol and 2. episodic secretion of plasma aldosterone could be blunted by dexamethasone. In the patient with idiopathic adrenal hyperplasia concomittant changes in plasma aldosterone and plasma renin activity occurred. The assumption that in this patient the fluctuations in plasma aldosterone were mediated through changes in renal renin secretion was supported by the finding that episodic secretion of plasma aldosterone persisted under suppression of ACTH-secretion by dexamethasone. Our results indicate, that the described procedures may all serve as diagnostic criteria to differentiate between aldosterone-producing adenoma and idiopathic adrenal hyperplasia.


Plasma immunoreactive calcitonin levels in pregnant mares and newborn foals.

Plasma calcium and calcitonin levels were measured periodically during the two last months of pregnancy and at the time of parturition in 9 pregnant mares and their foals. In pregnant animals, there was an increase in plasma calcitonin levels in the days before parturition, which was not due to any change in plasma calcium. This result indicates that in the mare, as in the cow, in the days before parturition CT secretion escapes from its control by plasma calcium. In 0-day and 7-day-old foals plasma calcium levels were significantly higher than in their mothers, but plasma calcitonin levels were not significantly different from those observed in their dams at the time of parturition.


Kinetic study of the enzymatic inactivation of progestogens by rat liver microsomes.

The kinetics of enzymatic hydrogenation of synthetic progestogens by female rat liver microsomes with NADPH as hydrogen donor were investigated by means of an optical test. Steroids with high progestational activity (Clauberg test) showed a low hydrogenation rate (Vmax). There also seemed to be a certain correlation between molecular structure and Vmax. The metabolites from incubation with the progestogens were isolated from the micro-preparations, and identified by infrared spectroscopy. It was found that the hydrogenation of the olefinic and carbonylic groups involved the uptake of hydrogen from NADPH.


Effect of electroconvulsive therapy without anticonvulsive premedication on serum growth hormone in man.

Serum concentrations of human growth hormone (HGH) were measured in psychiatric patients during the first, third and sixth electroconvulsive therapy (ECT) without anticonvulsive premedication. Serum HGH increased 30 min after the application of current and no differences were found between responses to 1st, 3rd, or 6th ECT. Maximal increase of serum glucose was seen after the first ECT and gradual decreases after the 3rd and 6th ECT were observed


Changes in gonadotropin secretion following complete or hemicastration in the adult rat.

The effect of sham castration, hemicastration or complete castration on gonadotropin and testosterone secretion was studied in adult male rats. Untreated control rats were autopsied 1, 10, 20, 30 and 40 days following assignment to treatment groups. Sham-castrated controls were autopsied 1, 2 and 3 days after surgery. Complete and hemicastrates were autopsied 1, 2, 3, 10, 20, 30 and 40 days after surgery. Serum levels of both FSH and LH were elevated by 24 h postcastration and the levels of both gonadotropins continued to rise throughout the course of the experiment. Serum levels of LH rose following hemicastration and remained above control values through day 30. Serum FSH levels were not significantly affected by hemicastration. Compensatory testicular hypertrophy was not observed in hemicastrated rats.


Radioimmunoassay of 17-hydroxyprogesterone in serum with or without thin-layer chromatographic purification.

A radioimmunoassay for the measurement of 17-hydroxyprogesterone (17-OHP) is described. The antigen 11-desoxycortisol-21-hemisuccinate-bovine serum albumin has been used to produce two antisera of different antibody populations in the same animal. The thin-layer chromatographic system described can be used to separate all the cross-reacting steroids investigated from 17-OHP. A simplified method is also presented using preliminary solvent extraction only. The mean 17-OHP levels measured, using this method, were, for normal men, 0.86 +/- 0.19 ng/ml (SD), for normal females 0.30 +/- 0.19 ng/ml in the follicular phase and 1.72 +/- 0.18 ng/ml in the luteal phase of the menstrual cycle, and 0.45 +/- 0.17 ng/ml in normal postmenopausal women.


Thyroxine-induced hyperthyroidism upon the reproductive performance of female rats.

L-Thyroxine (L-T4) was injected into mature rats daily at levels of 0, 3, 6, 12, 24, 48 and 96 mug/100 g body weight through estrous cycling, conception, pregnancy, parturition and 20 days of lactation. Mothers which lactated to 20 days were killed and mammary glands measured for DNA and RNA content. Those which were not able to maintain their pups were killed on the day when all pups died. Estrous cycling and pregnancy were not markedly effected by exogenous L-T4 at levels 3-96 times the normal thyroxine secretion rate in rats. After parturition the mothers on L-T4 above 12 mug did not allow the pups to suckle. As a result the pups died within 2-7 days after birth. Levels of L-T4 from 3 to 12 mug allowed lactation to progress, but survival of pups to day 20 of lactation was significantly lower than in the normal control group. The results of this study indicate that high levels of L-T4 inhibit mammary growth and mild secretion. This, in turn, results in the loss of pups, probably through depletion of prolactin as a result of higher metabolic rate due to hyperthyroidism.


Enzymic activity in rat uterus during early pregnancy.

Total protein, RNA and DNA content and the activity of acid and alkaline phosphatases, 5'-nucleotidase and isocitrate dehydrogenase were studied in rat uterus during the first 8 days of pregnancy. Isocitrate dehydrogenase activity showed marked fluctuations from day to day. Nucleotidase and acid phosphatase activities showed a significant increase on day 8. The most marked change in activity was that of alkaline phosphatase which showed a 10-fold increase between days 6 and 8, due largely to an increase in the activity of this enzyme in the decidual nodule. The rise in alkaline phosphatase activity did not occur in rats ovariectomized on days 1, 2 or 4 of pregnancy and was markedly decreased in those ovariectomized on day 6. [3H]-uridine incorporation into RNA showed a significant increase between days 2 and 6 whereas [3H]-thymidine incorporation into DNA showed a significant increase on day 6.


Utilization of part-time employees can enhance operating efficiency.

Part-time employees offer some distinct advantages in improving hospital efficiency. Part-time employees provide significant scheduling benefits that will enable perceptive supervisors to enhance their department's performance. Desperately needed skills to staff laboratories, nursing units, admissions offices, clinics, and other divisions can be found among housewives and retirees. These benefits can be achieved while cutting the hospital's total labor costs--the most promising dimension of all. It is becoming increasingly important for administrators to discover new methods of achieving their organizations' objectives. With labor costs representing a significant part of operating expenditures, creative manpower innovations hold the potential for major improvements, especially in hospitals.


Pseudomalignant myositis ossificans. A pathological study of eight cases.

Eight cases of pseudomalignant myositis ossificans are presented. There was a male predominance and four patients were under 20 years of age. There was no history of trauma, but there was evidence of mild local or general inflammation with positive roentgenograms in two cases. Histologically there was active fibroblastic proliferation, appearing to develop essentially in fibrin deposits with metaplasia leading to the formation of an unusual osteoid. The newly formed mass was surrounded by bone and compressed the surrounding muscle fibers, which were either atrophic or trapped therein. The histological criteria distinguishing this disorder from other forms of myositis ossificans are discussed, and comparisons are drawn with nodular fascitis and proliferative myositis. An association with the latter was observed in one case. This nontumourous growth must be distinguished from osteogenic sarcoma of soft tissue. The differential diagnosis is based on careful histological criteria, which must be supported by clinical and radiological data.


Mental retardation, hypotonia, and generalized seizures associated with astrocytic "residual" bodies. An ultrastructural study.

Two siblings suffering since birth from convulsions, hypotonia, and mental retardation are presented. In the older sibling (eight and one-half years of age) frontal lobe biopsy revealed abnormal cytosomes with lamellar profiles in astrocytes, macrophages, and to a lesser degree in neurons. Similar cytosomes have not yet been reported in cases of sphingolipidoses or in late infantile-juvenile amaurotic idiocy. These cytosomes stained intensely with silver proteinate, an ultrastructural cytochemical stain for carbohydrate moieties. In contrast, lipofuscin did not stain with silver proteinate. Multilamellar (crescentic curvilinear) cytosomes from a reported case of late infantile amaurotic idocy (Batten-Vogt-Spielmeyer disease) did not stain with silver proteinate. Abnormal cytosomes were not found in blood cells, liver, and peripheral nerve. In the younger sibling (14 months old) postmortem ultrastructural studies of cerebral tissue showed very few abnormal cytosomes. On the basis of the clinical and ultrastructural findings, we conclude that these two cases can be distinguished from those with multilamellar (crescentic-curvilinear) inclusions and from cases of the so-called "neuronal ceroid-lipofuscinosis" syndrome.


Pathology of high dose intermittent cyclophosphamide therapy.

Pathologic changes induced by high dose intermittent cyclophosphamide therapy are described in 39 patients with solid tumors, lymphohematopoietic malignant disease, and bone marrow transplants. Patients receiving 50 to 120 mg. per kg. daily for one to four days showed transmural bladder injury affecting all component tissue; toxic vasculitis involving small arteries, capillaries, and venules; and interstitial, myocardial, and vascular changes in the heart. Myocardial necrosis with heart failure was the dose limiting factor of very high dose therapy. Patients receiving 15 to 30 mg. per kg. for four days showed variable degrees of bladder injury limited to the mucosa and lamina propria and vascular changes consisting only of telangiectasia. Both groups showed atypia of transitional urinary and esophageal epithelia as well as of mesenchymal cells in the lamina propria of the bladder, persistent and total ablation of spermatogenesis, and long lasting absence of ovarian follicular maturation. Bone marrow hypoplasia and lymphoid depletion developing after cyclophosphamide therapy completely disappeared an average of 3.5 weeks after the last dose.


Pathogenesis of fungal infection on heart valve prosthesis.

Four patients with heart valve prostheses developed Candidate endocarditis. At autopsy the foci of infection were confined to patches of neoendocardium that appeared to have developed as ingrowths of host endocardium onto the sewing cloth of the artificial valve. This suggested that one mechanism of fungal infection is related to the presence of the neoendocardium rather than to the cloth or metallic substances of the valve itself. Future studies might be directed toward inhibiting the development of the neoendocardium or to agents preventing its susceptibility to infection.


Small cell malignant tumors of the thyroid. A light and electron microscopic study.

Three small cell malignant tumors involving the thyroid gland were examined by light and electron microscopy. In each, numerous similarities were presented on light microscopic analysis rendering interpretation difficult. In the first patient the small cells were identified on electron microscopy as moderately well differentiated lymphocytes. This tumor occurred in an elderly woman as a locally invasive thyroid tumor, subsequently involving distant sites, including the liver, spleen, lymph nodes, and soft tissue. The tumor repeatedly regressed following radiotherapy. The patients eventually died with disseminated lymphocytic lymphoma. In the second patient the thyroid tumor, also locally invasive, was composed principally of neoplastic epithelial cells when studied on electron microscopy. This patient responded poorly to radiation and died within a year after diagnosis. The third patient presented with an enlarging thyroid mass, which ultrastructurally was found to be composed principally of well differentiated lymphocytes. Subsequent clinical evaluation established a diagnosis of chronic lymphocytic leukemia. Small cell malignant tumors of the thyroid represent a difficult diagnosis problem for surgical pathologists. Ultrastructural study, we believe, is a useful adjunct in the differentiation of these tumors.


Hematoxylin bodies: their appearance in renal tubular epithelium.

Hematoxylin bodies, the pathognomonic light microscopic feature of systemic lupus erythematosus commonly found in renal glomeruli affected with active nephritis, are described in renal tubular epithelium. Formerly thought to be the result of "L.E. transformation" of these cells, a proposed mechanism of this phenomenon is that hematoxylin space are phagocytosed by tubular epithelial cells. This would explain the observation in the case presented and also that of the single previous report of this unusual feature.


Double aortic arch: report of a case.

Abnormalities of the embryonic development of the aortic arch system and the great vessels produce a multiplicity of anomalies. This discussion deals with an unusual combination of congenital abnormalities of the aortic arch system found at necropsy in a 71 year old woman. The condition had not produced any clinical signs or symptoms and was totally unsuspected.


Arterial dysplasia with ruptured basilar artery aneurysm: report of a case.

An 11 year old girl died unexpectedly as a result of spontaneous subarachnoid hemorrhage originating from a ruptured giant fusiform aneurysm of the basilar artery. The aneurysm had developed as a long standing complication of arterial fibromuscular dysplasia. This discussion describes the light and electron microscopic findings in the aneurysm and the histologic examination of abnormalities in the muscular arteries of the viscera.


Incidence of chromosome aberrations among 11148 newborn children.

Chromosome analysis has been made of 11148 children; 29 had sex chromosome abnormalities (2.60 per 1000) and 64 autosomal abnormalities (5.74 per 1000). The total incidence of major chromosome abnormalities was 8.34 per 1000. The incidence of chromosome variations was 16.8 per 1000. The most common variants were those with variation in size of short arms-satellites in D and G chromosomes and variations in Y chromosome size. So far, very little is known about the significance of such chromosome variations. The incidence of most chromosome abnormalities in liveborn children is well established by now from studies of a total of 54749 consecutively liveborn children in 6 studies as shown in Table 1. More chromosome studies of liveborn children are, however, needed for several purposes such as finding families with chromosome translocations, studying segregation rates and giving genetic advice to families with inheritable chromosome aberrations and an increased risk of getting children with unbalanced chromosome abnormalities, mental retardation and physical abnormalities. One of the main purposes in chromosome examination of newborn children is to study the development of children with different chromosome abnormalities, especially those with sex chromosome abnormalities, and compare then with controls, treat them when needed and give advice to the parents of such children.


Adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase immunoprecipitation reactions in human-mouse and human-hamster cell hybrids.

Male New Zealand White rabbits were immunized with human adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which were purified about 2000-fold and 800-fold, respectively, from erythrocytes by DEAE-cellulose chromatography, ammonium sulfate precipitation and preparative polyacrylamide gel electrophoresis. Specific immunoprecipitations of APRT and HGPRT were achieved with the antisera that were obtained and by using polyethylene glycol as a substitute for goat anti-(rabbit) gamma globulin. The activities of the human forms of these enzymes, whether from red blood cells or from cultured cells, were almost completely eliminated under the conditions of immunoprecipitation used. Little or no reduction of APRT and HGPRT activities from mouse and Chinese hamster cells was observed. This discriminatory capacity of the antisera was successfully used for the identification of human APRT and HGPRT in human-mouse and human-hamster cell hybrids using the immunoprecipitation reaction.


A 6p trisomy detected in a family with a "giant satellite".

A very large (giant) satellite was observed on one of the D-group chromosomes of a malformed and mentally retarded infant and her father. Detailed cytogenetic studies revealed that the giant satellite represented, in fact, a der(15) chromosome of translocation t(6;15)(p21;p12 or 13). The proposita was trisomic for a part of 6p(6pter leads to 6p21). The father was a balanced carrier, however, the deletion of the short arm of a No. 6 was hard to detect in routine karyotype analysis.


Transmission of a t(13q22q) chromosome observed in three generations with segregation of the translocation D1-trisomy syndrome.

A case of an inherited type of D/G translocation D1-trisomy syndrome was described. A female proposita who had the clinical signs of D1-trisomy syndrome was found to have a chromosome complement of 46,XX,--G,+t(DqGq). examination of Q- and G-stained karyotypes revealed that the chromosomes involved in the translocation were members of Nos. 13 and 22, or t(13q22q) with breaks at p12 of both chromosomes. C-stained figures also showed a large heterochromatin block in its centromeric region. The t(13q22q) chromosome was transmitted from the paternal grandmother of the proposita through at least three generations.


Association of pericentric inversion of chromosome 9 and reproductive failure in ten unrelated families.

A pericentric inversion of chromosome 9 has been detected in 10 unrelated families. The break points are identical and the inversions involved the heterochromatic segment. The effects of inversion of chromosome 9 on different aspects of reproductive failure are discussed.


A case of extra small acrocentric bisatellited chromosome in a non mongoloid child.

A mentally retarded child with an extra small bisatellited acrocentric chromosome is described. The patient exhibited rather unspecific clinical signs such as strabismus, marked facial asymmetry, broad and prominent nasal bridge, hypertelorism, Brushfield's spots, malformed ears with atresia of the external auditory canal on the right side. Giemsa banding (R and G methods) did not allow a clear cytogenetic identification of the extra-chromosome. A tentative interpretation of the cytogenetic aberration as a trisomy of the proximal part of the long arm of chromosome 13 is discussed.


A new contribution to the study of 22 trisomy.

The case of a 2 1/2-month-old male child with intrauterine distrophy features and multiple congenital malformations is presented. Cytogenetic studies of the child and his parents, completed with Q- and G-banding techniques led us to conclude that it is a case of 22 trisomy inherited from his mother.


Genetic parameters of dermal patterns of ridge counts.

Dermatoglyphic traits including ridge counts and pattern type counts on fingers were studied in 711 families representing six racial groups in Hawaii. Heritability tesimates were derived from regressions of offspring on father, mother and mid-parent values as well as from full-sib correlations. These estimates varied from 0.23 for radial loops to 0.80 for total ridge count. The heritability estimates were lower for ridge counts of single hands or single digits.


Abnormal hemoglobins, glucose-6-phosphate dehydrogenase deficiency and hereditary ovalocytosis in the Dayaks of Sarawak.

A survey of abnormal hemoglobins, G6PD deficiency and hereditary ovalocytosis was carried out among the Dayaks of Sarawak. The only abnormal hemoglobin found was Hb Co Sp, which occurred in 0.35% of the Land Dayaks and 0.83% of the Sea Dayaks. G6PD deficiency occurred in 5.3% of the male Land Dayaks and 5.0% of the male Sea Dayaks; no electrophoretic variant of G6PD was found in any of the 285 Land Dayaks and 240 Sea Dayaks examined. Hereditary ovalocytosis was found in 12.7% of the Land Dayaks and 9.0% of the Sea Dayaks.


Red cell glutamic-pyruvic transaminase polymorphism in a sample of the Italian population a new variant allele: GPT8.

247 individuals from Northern Italy have been tested for red cell glutamic-pyruvic transaminase (GPT) polymorphism. An abnormal phenotype has been detected. Family data support the hypothesis of the existence of a new variant allele, GPT8, at the GPT locus.


Association between the C3F gene and atherosclerotic vascular diseases.

The C3 phenotype distribution was studied in a group of patients suffering from atherosclerotic vascular diseases. A statistically significant association was found between the presence of the C3F gene and the occurrence of atherosclerosis. A relative risk incidence of the disease of 1.87 was found for the C3F-positive individuals as compared to the C3F-negative ones.


C3 polymorphism in relation to age.

The C3 phenotype distribution was investigated in different age-groups among 2,078 voluntary blood donors between the ages of 20 and 65 years, in a group of unrelated babies and in a group of old healthy persons. A continuous increase in the C3F gene frequency with age was found among the blood donors varying from 0.1780 in the youngest age group (babies: 0.1585) to 0.2516 at the age of 50-55 years followed by a continuous decrease to a level of 0.1700 among the eldest donors (01718 among the old persons). In the age group 45-49 years the C3 distribution differed significantly from that in the adjoining age-groups (C3F = 0.1619). It is believed that the variations are brought about by selection of the blood donor population and a balanced polymorphism for the C3 system, possibly due to differences in the biological efficiency of the C3 variants in the complement sequence.


Plasma cholinesterase studies on south-eastern Bantu of Mozambique.

Blood samples from four Bantu tribes in South-East Mozambique have been phenotyped for the plasma cholinesterase variants of the E1 locus. A control roup of 153 Portuguese residents in Mozambique have also been phenotyped. The frequencies of both the E1a and E1f genes in the Portuguese population is very similar to those in other Caucasian populations. The absence of the E1a gene in the four Bantu tribes provides more evidence of the rarity of this gene in Negroid populations. There is an increased frequency of E1f gene in all tribes as compared with previous surveys. The Ronga and Bitonga tribes have similar E1f frequencies of 0.047 and 0.048, respectively. The Shangana has an E1f frequency of 0.060, and the corresponding figure for the Chopi tribe is 0.089. The latter is the highest recorded frequency for this gene. The results give some support to the doubts concerning the affiliation of the Chopi tribe.


A heterozygot expression of a 'recessive' gene?

An individual affected with severe bone reductions of the upper limbs, apparently due to an autosomal recessive gene, had eight normal children and then a child with absence of the right thumb and the correspondent metacarpal. This is supposed to be the result of a mild expression of the postulated gene in heterozygous state.


Sex-linked hereditary thrombocytopenia with immunological defects.

14 cases of severe thrombocytopenia in one family are presented. Case histories, clinical examination, analyses of platelets, haemoglobin, reticulocytes, leucocytes, eosinophilocytes, differential counts of leucocytes, serum immunoglobulin IgA, IgM, IgG, IgE concentrations, complement fixing platelet antibodies, isohaemagglutinins, colour perception, determination of red cell and serum groups as well as HL-A types were obtained from a total of 59 members of the family. The in vitro blast transformation response of blood lymphocytes was studied in 6 patients and 45 relatives. The pattern of transmission of the disease was in full agreement with X-linked recessive inheritance. Investigation of the immune system revealed impaired responses to microbial antigens in the 6 patients so studied. All relatives examined had normal haematological status, whereas approximately half showed a subnormal response to one microbial extract. The low responders were evenly distributed within the family, and it was not possible to correlate low response and presumed carrier state.


Establishment of heteroploid cell lines from mouse peritoneal exudate cells.

Proliferation was observed during in vitro cultivation of peritoneal exudate cells that had been educed from a C3H mouse with Freund's incomplete adjuvant. These cells were successfully subcultured by release with trypsin-EDTA solution and are now at passage 108 after 22 months in culture. Using this technique, 12 other rapidly growing peritoneal exudate cultures were obtained, whereas 10 cultures not educed with adjuvant did not proliferate. Characteristics of four adjuvant-induced cell lines established in culture include: rapid attachment to glass, doubling time in culture of 18 to 19 hr, phagocytosis of colloidal carbon, enhanced phagocytosis of specifically sensitized bacteria, epithelium-like morphology, and retention of C3H histocompatible specificities. These cell lines had widely varying chromosome distributions with modes from 37.3 +/- 2.4 to 82.6 +/- 2.30, but inoculation of 10(7) cultured cells into syngeneic animals did not produce tumors. Procedures described for the reproducible establishment of peritoneal exudate cell lines did not require use of conditioned media or exogenous viral infection.


Development of an in vitro colony formation assay for the evaluation of in vivo chemotherapy of a rat brain tumor.

An in vitro colony formation assay for the evaluation of in vivo brain tumor therapy has been developed. When plated, disaggregated cells derived from solid tumors proliferated to form relatively homogeneous colonies after a latency period of 2 to 6 days. Increasing concentrations of fetal calf serum enhanced colony-forming efficiency (CFE) with a plateau between 7 and 16%. Supplementation with either irradiated feeder cells (10(3) to 10(5) cells per dish), or medium conditioned by 1 to 3 days of in vitro incubation with the same cell line, doubled the CFE. The density of tumor cells (untreated or previously treated with chemotherapeutic agents) did not affect the CFE when a minimum of 10(4) total cells (tumor plus feeder) were plated. Therefore, in this system the optimal experimental conditions for evaluating chemotherapy and radiotherapy require incubation of disaggregated tumor cells for 12 days in medium containing 10% of fetal calf serum and enough feeder cells to provide a minimum of 10(4) cells per dish. The CFE for untreated tumors was 18 +/- 10% (+/-S.D.), demonstrating that there is significant biological variation. The assay appeared sensitive, with reproducible results, when applied to individual chemically treated tumors. An estimate of the percentage of clonogenic cells affected by in vivo chemotherapy may be obtained by comparing the CFE of cells from treated and untreated tumors. This assay can measure up to a 5 log(10) cell kill, and it should prove to be valuable in developing more effective regimens for the treatment of solid tumors in animals and man.


Technique for cultivation of transitional epithelium from mammalian urinary bladder.

A technique for initiating cultures of epithelial (urothelial) cells from mammalian urinary bladder has been described. Urothelial cells obtained by this method have been used to support replication of viruses and as controls for immunological, biochemical, chromosome, and electron microscopy studies. Both light and electron microscopic studies of cultured cells suggest that they are epithelial and not a mixed culture.


Influence of physical factors on the growth of insect cells in vitro. II. Sodium and potassium as osmotic pressure regulators of moth cell growth.

The tolerance of a cell line (IMC-HZ-1) from a moth, Heliothis zea, for the monovalent cations Na+ and K+ were defined. Cells shifted to media containing more than 70 mM of K+ showed decreased growth rates. No evidence was obtained for Na+ toxicity. The osmotic pressure tolerances were influenced by the K+ concentration of the medium. The richer the medium was in K+, the narrower was the spectrum of osmotic pressure tolerance. Once the limit of K+ tolerance was exceeded, the rate of decline of growth was linear with respect to further increases in K+. This rate of decline was independent of osmotic pressure. The initial responses of cells during one subculture (2 to 4 population doublings) in media differing from the standard medium (used to maintain the cell line) were not reliable indicators of the growth potential of the cells. Continued subculture in such media resulted in an upward trend in population growth rates in most cases.


Collagen synthesized and modified by aging fibroblasts in culture.

Collagen is produced by WI-38 diploid human fibroblast cultures throughout their life cycle. It is examined by a sensitive method based on the analysis of specific peptides obtained after digestion with bacterial collagenase. The production and hydroxylation of the collagen is strongly dependent upon the age (population doublings) of the culture and the presence of ascorbic acid. Young cultures (passage 26) produce large amounts of collagen in the absence of ascorbic acid, and this collagen is about 50% hydroxylated compared to that produced by young cultures in the presence of ascorbic acid. Ascorbic acid reduces to about one-half the amount of collagen produced by these young cultures. The young confluent cultures also depend strongly on ascorbic acid for hydroxylation of proline. The dependence declines rapidly with the age of the culture. The collagen produced by young cultures supplied with ascorbic acid is very similar to the type I collagen produced by normal individuals and has about the same degree of hydroxylation of its prolyl residues. The amount of collagen produced by "older" cultures is unaffected by ascorbic acid, but the degree of hydroxylation is normal only if ascorbic acid is present, and is decreased to about 60 to 70% in the absence of the vitamin. "Senescent" cultures showed little, if any, dependency on ascorbic acid, and the collagen produced, with and without the vitamine, is about 80% hydroxylated. The prolyl hydroxylation system of the WI-38 cells and the various controls on the system are age-dependent.


[Current problems and new developments in therapy of mycoses (author's transl)].

Mycoses for most of them) represent a group of infectious diseases which seem to increase steadily although numerous fungicidal or fungistatic therapeutics are available. A severe problem is provided by the so-called opportunistic fungi which become parasitic only after the host's immunological protection has been impaired by predisposing factors. Therapy resistance and prevention of relapse are problems of a general nature in the therapy of mycoses. As special topics local treatment of dermatophytoses, of Candida mycoses, and new development in systemic treatment of deep mycoses are discussed.


[Mathematical methods to judge the efficiency of protective vaccinations (author's transl)].

The effect, hazards and risk of vaccinations may be calculated by means of special formulas which determine the value for N, Q and D. The formula for N considers the question whether a vaccination is effective, necessary and valuable and may be recommended on epidemiological grounds. Q considers the individual risk (i. e. relation between total risk of unvaccinated and vaccinated persons) and D the yearly difference in risks between unvaccinated and vaccinated members of a community. If p stands for protection rate of a vaccination, t = time for which the vaccination effect is lasting, R = complications of disease under study in a community in which vaccinations against this disease are not in use and r = comparable complications of vaccination, the following formulas are applicable: (see article) A vaccination may be recommended if N and Q greater than 1 and the value for D is positiv. Application of these formulas to special vaccinations lead to the following conclusions: In case of BCG, measles and poliomyelitis (oral vaccination) the above mentioned values exceed at least 10(1)-10(2) (N), 4-5 (Q) or are highly positiv (D). These vaccinations-if performed correctly-are considered valuable and highly recommendable. Vaccination against pertussis is not recommendable beyond the second year of life. According to the present epidemiologic situation in Austria this vaccination is still rectified in children under 2 years. However, values for N, Q and D are near border-line and should be yearly evaluated. Smallpox vaccination in Europe is still recommendable. Similarly, continuous reevaluations are necessary due to low values of N, Q and D. On the other hand, vaccination against tetanus is available and vaccination against influenza may be recommended.


[The diangostic value of skin tests with tissue-extracts, especially in lepra and sarcoidosis (author's transl)].

The immunological aspects of lepra (India, Germany) and Sarcoidosis are presented under consideration of cutaneous reaction to lepromin and Kveim-extracts. Patients with lepra, erythema nodosum, sarcoidosis and different dermatoses have been tested with lepromin, Kveim-Antigen and tuberculin. The specifity of the results has been discussed. Patients with tuberculoid lepra did not react on Kveim-test, but patients with sarcoidosis can give positive reaction on lepromin. Patients with erythema nodosum without clinical signs of sarcoidosis are Kveim negativ and a positive lepromin-test is an exception. The positive Kveim-test is bound to a histological examination. The positive lepromin-test in non lepraendemic countries should be interpreted also by histological examination. Granulomatous dermatoses can show positive lepromin-tests, but the histological picture is different from the lepromin reaction in tuberculoid lepra. The positive reactions on tissue extracts are not combined with positive immunfluorescence results. Intracutaneous injection of lepra-bacilli in lepromin extract can be presented days to weeks after intracutaneous application in biopsies.


[Seroimmunity against rubella 5 years after immunisation with Cendehill vaccine (author's transl)].

The HI-antibodies against rubella of 383 schoolgirls, vaccinated with the Cendehill vaccine between 1969 and 1973 were investigated 8 weeks and 1,9 to 5 years, respectively, after the immunisation. The geometric mean titer of the sera investigated was 1 : 81 in the second sera. 69% of the girls, immunized at the age of 15 to 17 years in 1973 had identical serotiters in the 1st and 2nd serum samples, whilst those vaccinated between 1969 and 1971 had only in 54% constant titers. The geometric mean titer varied between 1 : 91 and 1 : 73. 33% of those vaccinated between 1969 and 1971 and 24% of the vaccinees from 1973 had a fourfold increase in the serotiter in the second postvaccinal serum. A decrease in titer could be demonstrated between 7% to 13% in different periods. Only 1% of the sera investigated became seronegative. The fourfold increases in titers are probably due to inapparent clinical rubella infections, leading to a not undesirable booster of immunity.


[Progresses in the development of antimycotic effective substances (author's transl)].

Comparative review of widely used classic and modern antimycotic agents - Polyene-group, Griseofulvin, Tolnaphthate, 5-Fluorcytosin and the new Imidazolyl-group - in view of antimycotic, pharmacocinetic and therapeutic properties.


Serological study of coronavirus antibodies in Hamburg.

A serological study of coronaviruses with the OC 43 agent (HI-test) was undertaken in 1000 sera from the population of Hamburg. 32,7% of the sera showed HI=titers between 1 : 8 and 1 : 128. The geometric mean titer (GMT) for the whole group was 1 : 16. The frequency of seropositive reactions was highest in 244 individuals 15 to 24 years old (52,8% positive reactions, GMT 1 : 19) whilst in the older age groups (25-59 years and over 60 years old) the precentage of positive reactors was markedly lower (14,4% and 16,8%, respectively, GMT 1 : 12). Among 131 twelve to 17 years old youngsters, a seroconversion was demonstrated in paired sera in 6,8% with a 4- to 8-fold rise in HI-titer within 8 weeks.


[Auto-immune diseases of the skeletal muscle-system. Immune-pathogenetic mechanisms in myasthenia gravis and polymyositis (author's transl)].

Intensive clinical as well as experimental research over the past decade in the pathogenesis of myasthenia gravis suggest the imporatance of involved immunological reactions. The thymus as well as the muscle endplates appeare to be possible target organs of autoaggressive reactions, although the real trigger mechanismus of autoimmune reactivity are not yet understood. Different pathogenetic hypothesis for myasthenia gravis are discussed. Regarding the pathogenesis of polymyositis more direct evidence for the possible involvement of viruses are offered by electronmicroscopy. Beside clinical and neurological findings, immunoserological data provide the most important facts for the diagnosis and differential diagnosis of myasthenia gravis and polymyositis.


[Treatment of chronic active hepatitis--newer aspects (author's transl)].

Recent advances in the treatment of chronic active hepatitis based on several controlled studies indicate that immunosuppressive therapy with corticosteroids alone or in combination with low doses of azathioprine for more than one year is the therapy of choice because of the induction of long lasting remissions. with the combination therapy (10 mg prednisone and 50 mg azathioprine per day) the side effects seem to be less pronounced. Clinical, histological and immunological results indicate that the lupoid form of chronic hepatitis may be differentiated from the HBAg positive one. Although many reports seem to underline that immunosuppressive treatment should be performed in all cases of chronic active hepatitis this conclusion cannot be drawn in general because the controlled studies almost exclusively contained BHAg negative patients. Considering the different conceptions on the aetiology of chronic active hepatitis the possibility has been discussed to influence chronic active hepatitis by active immunotherapy. First results of such a treatment were demonstrated.


A new micromethod for lymphocyte stimulation using whole blood.

A new micromethod for stimulation of human lymphocytes is described. The use of small amounts of whole blood, microtiter plates, 125I-5-iodo-2'-deoxyuridine, 5-fluoro-2'-deoxyuridine and a multiple cell-culture harvester makes the method easy, rapid, reproducible and suitable for routine laboratory use.


Role of the regional lymph node in neoplasia: cellular mediated reactivity in vitro by autologous regional or distant lymph nodes or peripheral blood lymphocytes of dogs with spontaneous neoplasms.

This report concerns the in vitro reactivity of lymphocytes obtained from regional (draining) lymph nodes, distant nodes and peripheral blood against autochthonous spontaneous neoplasms. Tumors, blood and lymph nodes were collected aseptically prior to necropsy. Primary tumor cultures were established. Viable tumor cells were first incubated with media or autologous sera and then various numbers of lymphocytes were added. The mixtures were rotated for 60 minutes and then plated. Two and/or five days later cultures were terminated and viable target cells counted. The results of the tests were similar regardless of the lymphocyte source utilized. In vitro tumor cell cytotoxicity by high numbers (1000:1 lymphocytes to tumor cells) of any autologous lymphocytes and interference of such reactivity by autologous sera were demonstrated. Low numbers (100:1) of any lymphocyte source lead to tumor growth stimulation. Animals with spontaneous neoplasms are probably the best model for the study of human clinical oncology. Our data demonstrate that in these animals lymphocytes obtained from regional nodes were not unique in their reactivity to tumors. It is possible that early in the disease the draining node may play a vital role in initiation of host response; however, later its importance probably diminishes.


Nascent DNA from phytohemagglutinin-stimulated human lymphocytes.

DNA synthesis was studied in human peripheral blood lymphocytes that had been stimulated with phytohemagglutinin. DNA pulse-labeled with [3H]thymidine was fractionated by sucrose gradient centrifugation or by chromatography on hydroxylapatite columns. Nascent DNA was identified as a single-stranded species that sedimented at 4-5S in neutral sucrose gradients and appeared to be precursor to chromosomal DNA in pulse-chase experiments. At least two-thirds of the nascent DNA was released as single strands from high molecular weight DNA without employing a denaturation step. It is concluded that synthesis of DNA by phytohemagglutinin-stimulated lymphocytes involves a low molecular weight, single-stranded, short-lived intermediate similar to that described for other eukaryotic cells.


Amplification of cell-associated immunological memory by secondary antigenic stimulus. Secondary type increase in memory.

In mice primed with a mixture of bovine serum albumin (BSA) and adjuvant (capsular polysaccharide of Klebsiella pneumoniae (CPS-K)) cell-associated immunological memory was increased secondarily after a second injection of BSA alone, whereas a primary injection of BSA alone into normal unprimed mice did not result in detectable memory. The optimum antigen doses for expression of the primary and secondary memories of adoptively transferred cells from unboosted primed donors or boosted donors in in vivo culture systems were very similar, although those observed in intact mice were very different, as reported previously. The size of the secondary memory of adoptively transferred cells from boosted donors was more than ten times greater than that of the primary memory of adoptively transferred cells from unboosted primed donors. The lag period for increase of the secondary memory was shorter than that for the primary memory. Both primary and secondary memories increased during a long period (up to 3 months) after the antigenic stimulus. From the results of this study it was concluded that cell-associated immunological memory could be amplified in a secondary fashion upon contact with a second stimulus.


The effect of cytochalasin B on effector--target cell interaction. Quantitative and ultrastructural study.

Interaction between pokeweed mitogen-stimulated secondary lymphocytes (PWM-lymphocytes) and target fibroblasts resulted in over 80 per cent adherence of the sensitized lymphocytes to the target cells. Adherence is by pseudopod penetration into target fibroblasts. The only lymphocyte cellular components found in the contact region were microfilaments. Cytochalasin B completely inhibited the specific adsorption of the PWM-secondary lymphocytes to the target cells. What adhesion did take place in the presence of cytochalasin B was found to be nonspecific. Ultrastructurally, the contact between lymphocyte and target cells was altered by the drug, when pseudopods were not observed. Possible effects of cytochalasin B on lymphocyte-mediated cytolysis, mainly by its effect on microfilament function, is discussed.


Prevention of spontaneous autoimmunity to DNA in NZB/Swiss mice by treatment with natural double-stranded RNA.

Data are presented demonstrating the prevention of spontaneous autoimmune disease in NZB/Swiss mice treated natural double-stranded RNA. The successful treatment of animals was followed both by improvement in clinical manifestations and by the migration inhibition test performed with DNA as antigen. The reasons for the successful employment of natural double-stranded RNA are thought to be in its physicochemical properties.


Lymphocyte reactivity to influenza virus in man.

Dermal delayed hypersensitivity and in vitro lymphocyte reactivity, both to purified influenza antigens, have been observed in man. A correlation between these two indices of delayed hypersensitivity was found in subjects without known recent exposure to the virus, but neither correlated with levels of circulating haemagglutination-inhibiting (HAI) antibody. Results suggest that in man immunological sensitization of lymphocytes to influenza virus antigen is long-lived.


The role of the macrophage in cutaneous leishmaniasis.

The investigation of the role of the macrophage in cutaneous leishmaniasis has been prompted by observations of the clinical behaviour of the infection. In contrast to the self-healing oriental sore, chronic leishmaniasis is characterized by persistent lesions and leishmania recidiva by lesions that flare up locally long after clinical healing. In both clinical types, the parasite is thought to be maintained inside the macrophages. It will be shown that the normal macrophages of mice and guinea-pigs are parasitized by L. tropica; the parasite is not killed by the macrophages but it multiplies within these cells. Incubation of the macrophages with rabbit or human anti-Leishmania sera on the other hand, leads to the attachment of specific immunoglobulins to the macrophage cell surface and consequently to the prevention of parasitization by L. tropica under the experimental conditions. The parasite appears to be immobilized at the macrophage cell surface. Normal rabbit or human sera did not interfere with parasitization. It is postulated that the parasite specifically immobilized at the cell surface might possibly be better exposed to and affected by the immune response than intracellular parasites. Furthermore, infected parasitized macrophages contribute to the immune response by processing soluble antigens from the intracellular parasites and presenting them on their surfaces, as seen by the greater affinity (higher dilution) of anti-Leishmania antibody for the cell membrane of infected macrophages than for normal macrophages.


Phylogeny of immunoglobulin structure and function. VII. Monomeric and tetrameric immunoglobulins of the margate, a marine teleost fish.

The margate, a marine teleost fish, was found to contain both high (16S) and low (7S) molecular weight antibodies 17 days after initial immunization. The 16S antibodies were detectable with both haemagglutination and antigen-binding assays, whereas the 7S antibodies were only detected by the latter technique. Margate 16S (molecular weight approximately 700,000) and 7S (molecular weight approximately 175,000) immunoglobulins were isolated and shown to be antigenically indistinguishable. They therefore appear to belong to the same immunoglobulin class and to have a tetramer--monomer relationship. Experiments with stored sera indicated the 7S protein is probably not an in vitro degradation product of the 16S molecule.


[Metabolic behavior and utilization of parenterally administered carbohydrates in the postoperative phase].

60 patients who had to undergo the same operation were subdivided at random into five groups. Each group obtained in respect to the part of carbohydrates a different infusion solution (5% glucose, 5% fructose, 5% xylitol, 5% xylitol-glucose-fructose, 5% sorbitol) with an always constant part of electrolytes, the dosage of which was 60 ml/kg body weight on the day of operation and 40 ml/kg body weight during the first 3 postoperative days being continuously distributed over 24 hours. From the day before the operation until the third postoperative day the effects on metabolic parameters (lactate, uric acid, blood glucose and others) as well as the utilization of the different energy carriers were investigated. While after a glucose infusion, due to a reduced utilization, no change of the lactate level could be proved in the postoperative phase, the effect of fructose on the lactate concentration was most evident. The administration of xylitol was followed by a small increase of the serum uric acid on the first and second postoperative day, whereas in the other groups its decrease could be proved - there was no change after the administration of sorbitol. The highest blood glucose levels were found in the group to which glucose and the three-part solution of xylitol-glucose-fructose were administered. About the utilization of the different energy carriers only a limited information could be given. Altogether the results allow the conclusion that a combination of xylitol, glucose, and fructose or alternatively sorbitol can be considered the most favourable carbohydrates for preparing an isotonic base electrolyte solution.


[The complications of the subclavian vein catheter and their prevention].

The subclavian vein catheter as approach to vena cava in emergency cases and intensive care is today approved. However, it is loaded with some troublesome complications. The most important are such in consequence of incorrect puncture like lesions of the pleura or the subclavian artery, complications by catheter embolism, air embolus or thrombosis or infection. Cause and frequency of these complications and possibilities to avoid them are demonstrated. Finally a new set for cannulation and catheterisation of the subclavian vein is presented, which considers the risk of this method in the best way. The advantages of the subclavian catheter in catheterisation of the vena cava are proved. But on account of the demonstrated complications it must be strictly limited to certain indications.


[The effect of potassium chloride and organic potassium salts on the acid-base equilibrium in normo and hypokalemic rats].

The effects of intravenous infusions of potassium chloride, potassium acetate, potassium aspartate and potassium malate on plasma electrolytes and acid-base balance were investigated in normokalemic or hypokalemic alkalotic rats. Animals who obtained equal volumes of isotonic sodium chloride solution served as controls. All of these potassium solutions increased the plasma potassium concentrations to the same extent. Potassium chloride shifted the acid-base balance to acidotic values in normal rats or corrected metabolic alkalosis in hypokalemic rats. The potassium salts of organic acids, however, caused an increase in alkalosis, acetate acting stronger than aspartate and malate. In potassium deficiency combined with metabolic alkalosis the administration of potassium chloride is preferable to the organic potassium salts since it corrects both the electrolyte disturbances at the same time.


Experience with essential amino acids in the treatment of patients with chronic uremia.

Nitrogen balance studies in chronic severe uremia have shown that it is possible to convert the negative nitrogen balance on a protein-poor diet to a positive one when the diet is supplemented with the essential amino acids intravenously or orally. It has been possible to make the diet variable and good tasting. This is a great advance as the patients can remain on the diet for a long time. 15N-studies have shown that this nitrogen balance represents true protein synthesis. These studies have also shown that histidine may be an essential amino acid in chronic severe uremia and further improves the nitrogen balance. During long-term treatment with the diet supplemented with essential amino acids including histidine, no signs of progressive neuropathy, bleeding or muscle wasting have been observed. We think that this diet and amino acid regimen is a feasible way to keep chronic severe uremic patients in fairly good general condition and nutritive state until they can have a renal transplantation or a place in a home-dialysis program.


[Infusion therapy in uretero-enterostomy].

The special problems of the uretero-enterostomy, which is often followed by disturbances of the electrolyte metabolism such as hyperchloremia, metabolic acidosis and hypokalemia with all complications, are dealt with. The pre-operative treatment of the patient and the postoperative infusion therapy are discussed in detail, suggestions as to the infusion, electrolyte and calorie quantity to be administered are made. The postoperative complications are demonstrated on the basis of a special case, the theories on the causes of the electrolyte imbalances are also mentioned.


Amino acid requirements and non-specific nitrogen.

These investigations report on the E/T ratios and the importance of the amino acid histidine. Proteins with high proportions of essential amino acids can be diluted to very low E/T ratios with non-specific nitrogen sources without losing their biological value. Histidine has to be regarded as an essential amino acid because the histidine level in plasma and in the muscles decreased by more than 50% when a histidine-free diet is administered.


[Changes in serum electrolyte concentration and in urinary electrolyte excretion during the infusion of glucose or glucose substitutes].

In groups of volunteers the concentration differences of phosphate potassium and sodium in serum were measured during 48-hour continuous infusion of glucose or glucose substitutes (fructose, sorbitol or xylitol). The dosage was 0.25 g/kg BW/hour. Additionally, the effect of fructose infusion in a dosage of 0.5 g/kg BW/hour was observed. Besides, the urinary excretion of sodium  and of potassium was analysed. In contrast to short-term and high-dosed infusions of glucose or glucose substitutes, the phosphate concentration in serum was scarcely influenced. Only during high-dosed fructose infusion and during infusion of xylitol and sorbitol a small decrease in serum phosphate concentration was noticed. The effect of xylitol is pronounced. Additionally, the sodium concentration in serum was especially decreased during xylitol infusion. With regard to the sodium excretion - and less pronounced with regard to the potassium excretion - a gradual adaptation to the infusion of the electrolyte-free solution is observed. The excretion of the cations is more and more decreased. In particular the excretion of sodium and of potassium is very high in the initial period, i.e. in the course of the first twelve hours of the xylitol infusions. On the other hand, the potassium excretion is very low in the final period of the infusion of xylitol (during 36 hours up to 48 hours) in comparison to the other sugars.


Effects of oral xylitol administration on carbohydrate and lipid metabolism in normal subjects.

Oral tolerance tests with 30 and 50 g of xylitol were performed in 10 normal subjects adapted to taking this pentitol. A 50 g oral glucose tolerance test served as control. Continuous indirect calorimetry was carried out in 7 of these subjects to measure the effects on the metabolic rate and on the oxidation rates of carbohydrate and fat. A small and short rise in serum xylitol and low quantitites of xylitol excretion in urine were observed in both xylitol tests. Xylitol caused a small but statistically significant increase in blood glucose and plasma insulin concentrations. Plasma free glycerol diminished significantly. After xylitol the metabolic rate rose throughout the test period but the total increase was only half of that after glucose administration. There was no significant influence of xylitol on the oxidation rates of carbohydrate and lipids. The total increase in carbohydrate oxidation during 2 1/2 hours amounted to one fourth of that caused by glucose. It is suggested that xylitol, during the first two hours after ingestion, charges the body's metabolism much less than equal amounts of glucose. Therefore, the use of xylitol as a sweetener in the diet of diabetic patients seems to be justified.


[Intranarcotic infusion therapy -- a computer interpretation using the program package SPSS (Statistical Package for the Social Sciences)].

In a retrospective 18-month study the infusion therapy applied in a great anesthesia institute is examined. The data of the course of anesthesia recorded on magnetic tape by routine are analysed for this purpose bya computer with the statistical program SPSS. It could be proved that the behaviour of the several anesthetists is very different. Various correlations are discussed.


[Determination of molecular weight distributions and mean molecular-weight values of clinical dextrans].

Clinical dextrans can be separated in fractions of different molecular size by permeation chromatography on porous glass columns. The apparatus, which is rather simple, is described in detail. The conversion of the elution diagrams in molecular weight distributions is possible if an adequate calibration curve and the magnitude of peak broadening are known. This information can be obtained experimentally. The analysis of the elution diagram is uncomplicated and generally applicable if both the elution curve and the boradening function are approximately Gaussian distributions. Usually this is the case in the systems in question. With the method described clinical dextrans can be characterized as to their molecular weights with high accuracy. The separation method can also be applied to the production of dextran fractions of narrow molecular weight distributions in a preparative scale.


[Heparin therapy in postoperative consumption coagulopathy in childhood].

On the basis of clinical symptoms and the results of coagulation tests, some changes in the blood coagulation similar to a consumption coagulopathy were found in eight children in the postoperative phase. In addition to the postoperative routine basic therapy a "low-dosage heparin therapy" was started. 3-5 IU of heparin/kg body weight/hour were administered in the form of a continuous intravenous infusion. The results are discussed.


[The importance of the carbohydrate portion in a synthetic diet].

The influence of an almost fat-free and carbohydrate-rich diet on different serum parameters was investigated in human volunteers. These studies were supplemented by animal experiments where the effects of different additions of carbohydrates were compared. In human volunteers the fat-free and carbohydrate-rich diet caused a decrease in serum cholesterol concentration. This effect was especially seen when the initial cholesterol values were elevated. Exchange of the glucose carbohydrates (consisting predominantly of oligosaccharides) by frutose or by surose was without an influence on serum concentrations of cholesterol or triglycerides. No signs of carbohydrate-induced hyperlipemia were seen in human volunteers. Only under extreme conditions (60% fructose in the diet) a moderate increase in serum triglyceride concentration was found in animal experiments. However, serum cholesterol was unaltered even under these conditions. Additionally, no significant influence on fat concentration in the liver (triglycerides or cholesterol) was seen. Only using an imbalanced diet (80% glucose or 80% fructose) a slight increase in fat content of the liver and a moderate hypertriglyceridemia were observed. The concentration of serum cholesterol remained unaltered, cholesterol concentration in the liver diminished slightly. These experimental results are considered as evidence that only the extreme situation of a food imbalance (or hypernutrition) can cause a so-called carbohydrate-induced hyperlipemia.


[The effect of various electrolyte solutions on the water and electrolyte balance during the postoperative phase].

Investigations with 3 electrolyte solutions having different qualitative and quantitative compositions were carried out to see their effect on the physiological equilibrium in the pre, intra- and postoperative phases in patients who had to undergo moderately severe surgery. On the basis of electrolyte and osmolarity determinations in serum and 24-hour urine, blood gas analyses, determinations of hemoglobin and hematocrit, 24-hour volume and specific weight of the urine, it was possible to establish an electrolyte administration adapted to the pre-, intra- and postoperative condition of the patients. By the infusion of a solution with this electrolyte content it was possible to keep the measured parameters within the normal range throughout the entire period of measurement before, during and after the operation.


[Clinical experiences with a new ready-made lidocain-electrolyte solution for intravenous permanent therapy of ventricular arrhythmias].

Efficacy, tolerability and adverse effects of a ready-for-use lidocain-electrolyte infusion solution for the therapy and prophylaxis of ventricular arrhythmias were tested in routine clinical use. The solution proved highly efficacious and was well tolerated. Even in long-term administration (mean 5 days), no disturbances of the water and electrolyte homeostasis or any other complications were observed.


[The effect of halothane on the fructose metabolism in the liver].

Glucose production from frutose (2 mmol) and fructolysis was studied in perfused rat liver. In the presence of halothane (0.5, 1.5, and 4.0 vol%) glucose production was inhibited, whereas lactate production was stimulated. Total fructose metabolism was unchanged. Since halogenated hydrocarbon compounds are known to inhibit the mitochondrial respiratory chain, it is concluded that glucose synthesis is inhibited due to decreased supply of energy-rich phosphates from oxidative phosphorylation. On the other hand, this depletion of energy may be partially compensated for by an increased extramitochondrial energy production due to fructolysis.


[Clinical studies on possible side effects of a plasma substitute on the basis of gelatin (in spinal anesthesia)].

In 265 patients who were infused 500 ml of modified gelatin during spinal anesthesia, examinations for adverse effects were carried out. Only in one case a weak reaction (shivering) was observed. Other clinically manifest side effects could not be detected.


[Osmo-oncotherapy in brain edema].

The treatment of cerebral edema must be directed towards improving the volume regulation of the brain cell which is disturbed due to reduced blood flow and hypoxia and towards restoring the disturbed function of the blood-brain barrier. Onco-osmotherapy increases the effective intracranial blood pressure difference and improves cerebral blood supply and oxygen absorption, thus exerting a positive effect on sodium concentration in the brain cell which is responsible for the intracellular corticocerebral edema. After renal excretion of the osmotherapeutic agent, however, water may again flow into the brain cell, depending on the osmotic gradient. When the function of the blood-brain barrier is disturbed, osmotherapy may lead to an undesired increase of the osmotic pressure in the tissue. In spite of this, onco-osmotherapy is one of the most effective measures in the treatment of cerebral edema. Choice of therapeutic agents, dosage, infusion rates, side effects and contraindications are dealt with in detail.


[Knowledge of the damages of wrong nutrition and of the effect of stimulants. (Results of questioning 100 employees of a large industry].

In an unselected collective of 100 employees of a big concern the knowledge with regard to body weight, nutrition and nicotine abuse was studied and the eating habits as well as the principles of education connected with them were ascertained. Nearly all questioned persons knew their body weight. Half of them were able to indicate their ideal weight with a precision of +/- 10%. The rate of the considerably overweight persons in the collective showed a dependence on higher age and female sex. Among the questionees with secondary education more normalweight persons were found. The test persons were well informed about the disadvantages of overweight and controlled their body weight in two thirds of the cases at least once a week. They stated to have met the term "diet" above all in the mass media. About half of them were able to define the term "calorie" approximately precisely. The questionees, however, often underestimated the required caloric quantity, apparently without drawing conclusions. The caloric content of alcoholic drinks was underestimated. Beer ranked first among the consumed alcoholic drinks. Only one fifth of the test persons "reward" their children with sweets and wish that they eat up their dinner. About half of the questionees were smokers. One fourth had never smoked, while another fourth had given up smoking. Mostly cigarettes were consumed, although nearly all test persons regarded inhaling smoking as harmful. The sole knowledge of factors that have a detrimental effect on the state of health (e.g. overweight, smoking) seems to be not sufficient to lead a healthy life. Since the test persons are, however, willing to do something for their health it would be useful to concentrate adipose persons and smokers into groups that should be treated by behaviour therapy and be positively motivated.


[Permanent registration of the energy transformation in patients with skull-brain injuries and brain tumors].

By means of a measuring device based on the principles of indirect calorimetry, long-term recording of energy transformation in patients with cerebral tumours and cerebral traumas is performed. Contrary to the conception that the catabolic state in the postoperative/posttraumatic period corresponds to a negative balance between requirement and enteral/parenteral supply, it appears that, as a rule, the energy requirement is only 1 to 1 1/2 times higher than under normal conditions. During long-term measurement, clinical phenomena that are characterized by increased muscular activity (seizures, extension automatisms, extreme psychomotor excitations) show a daily requirement of maximal 3,500 kcal. Considering the clearly lower requirement, the change of the catabolic state by a high-caloric intake (5,000 and 6,000 calories/day) can only be due to an effect on the regulation of the metabolic processes.


The use of vivasorb in the treatment of enterocutaneous fistulae.

The authors report excellent results with Vivasorb in the treatment of 9 patients with enterocutaneous fistulae. During exclusive alimentation with Vivasorb, there was a spontaneous closure in all 9 cases. With this form of therapy, all the risks of a long-term complete parenteral nutrition can be avoided.


Treatment with elementary diet in gastrointestinal disease.

Experiences with Vivasorb in the treatment of gastrointestinal diseases are reported. The author successfully treated severe cases of Crohn's disease and distal ulcerative colitis. In severe total ulcerative colitis, marked improvement with Vivasorb could be achieved in only one of three cases. The administration also proved successful in one case of agnogenic chronic diarrhea. No effect could be achieved in two patients with internal and external bowel fistulae, nor in three patients with short bowel syndrome in the immediate postoperative phase.


Chemically defined diet in the treatment of kwashiorkor.

The authors report on the treatment of children with kwashiorkor, using Vivonex or Casilan. With Vivonex, all patients were bottle-fed as early as the 2nd or 3rd day, whereas Casilan had to be administered by stomach tube for about a week. Children fed Casilan vomited much more frequently than patients receiving Vivonex. When Casilan was given, the albumin level rose after 8 days, whereas with Vivonex, this did not occur unitl 15 days. On the other hand, only the Vivonex fed children showed an increase of hemoglobin in the first 3 weeks of treatment. With Vivonex, the patients reached their minimum weight much faster and at a lower albumin level than with Casilan. In both groups, the frequency of diarrhea was similar; the relatively high glucose concentration of Vivonex and the disturbance of resorption, even of monosaccharides, which is frequently observed in severe cases of kwashiorkor may be responsible for the diarrhea of the children receiving Vivonex.


[Long term feeding with a chemically defined diet].

The author reports the successful treatment with Vivasorb, the bulk-free, balanced synthetic diet, of patients with severe forms of ulcerative colitis and Crohn's disease, indigenous sprue and condition after small bowel resection, and of one patient with a Cronkhite Canada syndrome. The duration of the treatment was from a few weeks to 34 months. The patients received between 320 and 640 g/day, according to their requirements and their tolerance. Because of the relatively low content of essential fatty acids, long-term exclusive administration of Vivasorb may lead to symptoms of essential fatty acid deficiency, which disappear after the administration of Lipofundin S. The successful treatment of patients with malabsorption syndrome was verified histologically. Particles of mucosa taken from different small bowel sections showed the development of villi after only four weeks of treatment, whereas, before the treatment, subtotal villi atrophy had been observed.


Phagocytosis by macrophages of mycoplasma pneumoniae after opsonization by complement.

Mycoplasma pneumoniae cells are not phagocytized by peritoneal macrophages without opsonization. They are taken up after treatment with complement or antibody.


How infection can trigger autoimmunity.

The role of infection in the development of autoimmunity is discussed in view of recent advances in the field of immunologic tolerance. Infectious agents may directly damage immune function by impairing the mechanisms of discrimination between self and non-self antigens; alternatively they may "deceive" the immune system by presentation of self-determinants in an immunogenic form or by uncovering of normally sequestered antigenic determinants. The first of these two pathogenetic mechanisms may be responsible for generalized and the second for selective autoimmune reactions. Different clinical conditions are evaluated on the basis of these concepts. The interaction of personal factors with infection and autoimmunity is also taken into consideration.


[Experimental study in rats on the renal compatibility of cephalothin and cephalothin-aminoglycoside combinations (author's transl)].

The possible nephrotoxity of cephalothin and the antibiotic combinations cephalotin-gentamicin and cephalothin-tobramycin was investigated in standardized animal experiments. Toxicity parameters were blood-urea concentration, the urinary enzymes GOT, LDH, MDH and the cell excretion rate, supplemented by histological investigations of the kidneys. Compared with other cephalosporine derivates, the antibiotic cephalothin in a toxic threshold-dose of 3000 mg/kg/day proved to be realtively well tolerated by the kidneys. On comparison with the respective monotherapy, the renal tolerance for cephalothin-aminoglycoside combinations was reduced. The clinical value of these findings is discussed.


Familial clustering of hepatitis B antigen and liver diseases in families with a high incidence of viral hepatitis.

In each of 23 families in which two or more cases of acute hepatitis-like jaundice (index cases) occurred, all family members were studied to evaluate HBAg clustering and the incidence of asymptomatic liver disease. There were 49 "index cases" of hepatitis-like jaundice: 38 cases of acute viral hepatitis, 5 of chronic agressive hepatitis and 6 of active cirrhosis. The overall number of members in these families (excluding index cases) was 170 and 155 of which were tested by clinical examination, laboratory tests and needle liver biopsy. In 27 out of the 155 subjects there was evidence of liver diseases (10 non icteric hepatitis cases, 12 CAH cases and 5 cirrhosis cases). HBAg was present in the serum of 19 of these patients, and twof the cirrhotic patients were positive. Furthermore, 33 of the 155 cases were healthy HGAg carriers showing no abnormality in liver function tests. In the majority of these carriers liver histology showed slight damage (pin-head necrosis or portitis) sometimes compatible with resolving viral hepatitis. A long-term follow-up of the HGAg carriers showed that three of these subjects progressed to acute viral hepatitis.


Relationship between the response to complete freund adjuvant, phytohemagglutinin, and subsequent tumor growth in mice.

Groups of inbred C3H mice selected on the basis of strong or weak PPD reactions after sensitization with complete Freund adjuvant had significantly different reactions to PHA. The growth rate of a methylcholanthrene-induced tumor, previously shown to elicit a cell-mediated immune response, was significantly different in these two groups of mice. The basis for the marked variation observed between members of an inbred mouse strain in response to CFA is not understood but may bear an important potential relationship to tumor growth.


In vitro reaction of antibodies to ragweed. I. Radioimmunoassay for measuring antibody levels.

A radioimmunoassay was developed in which human antibodies to ragweed compete with 125I-labeled rabbit anti-ragweed antibodies for the ragweed antigen coupled to cellulose particles. By means of this test, antibodies to ragweed were determined in 96 sera of treated and untreated patients with ragweed allergy and in 32 sera of nonallergic individuals. Within the applied experimental conditions, it was possible to measure antibodies over a range from 0.4 to 200 mug/ml. In patients receiving immunotherapy, the mean value of the antibodies was 7.2 mug/ml, and in the untreated patients 1.8 mug/ml. Antibodies to ragweed were also found in the sera of nonallergic individuals. It is assumed that this test measures 'total' serum antibodies to ragweed.


Experimental osteomyelitis induced by repeated administration of soluble immune complexes: consideration of the fundamental pathogenesis of osteomyelitis.

Morphological changes of blood vessel walls including various kinds of capillaries have been induced by administration of soluble immune complexes. After repeated administrations, those experimental animals who survived the phase of initial anaphylactic shock developed osteomyelitis. In this paper, the formative processes of osteomyelitis will be discussed in relation to Aschoff's definition of inflammation. We will emphasize the importance of the capillarization of the sinusoidal endothelia for the formation of osteomyelitis.


Cellular immune reactivity in vitro and tumor rejection provided by tumor-associated antigens of friend-virus-induced leukemia.

Cell-mediated immunity (CMI) and tumor rejection were studied in the Friend virus leukemia system of C57Bl/6 mice. Mice were immunized with Friend leukemia virus (FLV) or X-irradiated FBL-3 leukemic cells and studied temporally for the development of CMI reactivity by assays of 51Cr release lymphocyte cytotoxicity, lymphocyte transformation, migration inhibition, Winn tumor cell neutralization and transplantation rejection. High levels of specific lymphocyte cytotoxicity were observed by day 7 f0llowing FLV infection; this reactivity reached a peak between 17 and 21 days, and returned to background levels by day 36. Further, positive Winn assays were obtained with spleen cells from mice immunized with FLV at times when the mice resisted live FBL-3 tumor challenge. Positive lymphocyte transformation was obtained with spleen cells from mice immunized with FLV or FBL-3, but not with cells from normal mice or mice immune to a syngeneic methycholanthrene-induced tumor, when cultured with papain-soluble FBL-3 or RBL-5 tumor-cell extracts or mitomycin-C (MMC)-treated FBL-3 or RBL-5 cells. Positive reactivity in the lymphocyte transformation assay occurred after reactivity had peaked in the lymphocyte cytotoxicity test. Similar positive macrophage migration inhibition patterns were also obtained with peritoneal exudate cells (PEC) from FLV-immunized mice using papain-solubilized tumor-associated antigen (TAA) from FBL-3 cells. These data suggest that sequential development and modulation of CMI reactivity occurs as observed in different assays following immunization in this system.


Humoral cytotoxicity in melanoma patients and its correlation with the extent and course of the disease.

Complement-dependent cytotoxicity against melanoma cells was demonstrated with a microassay in sera from melanoma patients. The response was tumor-specific and histologic type-specific since 16 out of 52 (30%) melanoma patient sera taken before surgery reacted against melanoma cells, whereas 3 out of 43 (7%) control sera, collected from patients with unrelated tumors and from cancer-free individuals, were positive. The serum activity correlated with the clinical stage of the disease since it was detected in 15 out of 40 patients with stage I and II tumors and in 1 of the 12 patients in stage III. Twelve melanoma patients, clinically tumor-free for  to 4 years after surgery, showed no humoral cytotoxicity. A follow-up study of 13 melanoma patients revealed that the cytotoxicity appeared 7-10 days after radical removal of the tumor and that it disappeared if there was no recurrence. The histologic type-specificity was further tested by assaying sera from 16 melanoma and 10 breast-cancer patients simultaneously on both melanoma and breast-cancer cells; a positive reaction was observed in 6 cases of melanoma and in 5 of breast cancer on homologous cells only, in 1 case on the opposite type of cells, and in 3 cases on both types of tumor cells.


Combination of C. parvum and specific immunization against artificial pulmonary metastases in mice.

We have studied whether specific immunization administered intraperitoneally can augment the activity of C. parvum (0.25 mg intraperitoneally or intravenously) against intravenously injected cells of a syngeneic fibrosarcoma in C3Hf/Bu mice as expressed by the reduction of pulmonary metastases (nodules, colonies) and/or by the prolongation of the survival of recipients. Combination of specific immunization and C. parvum, applied either before or after IV inoculation of viable tumor cells, was more effective than the single treatments. IV injection of a mixture of heavily irradiated and viable tumor cells gave more tumor nodules in the lungs of normal mice than injection of viable cells alone. The metastasis-enhancing effect of admixed irradiated cells was not found in mice previously treated with C. parvum, and was abolished if the immunostimulant was injected after tumor cells. Generation of lung metastases by IV inoculation of fibrosarcoma cells was reduced in mice already having this tumor in the leg. This concomitant immunity to metastases was increased by treating the recipients with C. parvum, but not with irradiated cells; also, the injection of irradiated cells together with C. parvum did not augment the efficiency of the latter. C. parvum was not as effective in T-cell deprived as in control mice, which suggests that in this system, T-cells are required for optimal anti-tumor activity of this immunostimulant. Specific immunization was not effective in T-cell-deprived mice and did not augment the efficiency of C. parvum.


The effect produced by some carcinogenic nitrosocompounds on organ cultures from human embryonic lung and kidney tissues.

Previous works using organ cultures of lung and kidney tissues of mouse, rat and hamster embryos exposed to transplacental action of some carcinogens showed premalignant growth. This paper presents the results of organ culture of human embryonic lung and kidney tissues. Direct action of some carcinogenic nitrosocompounds (N-nitrosomethylurea, dimethylnitrosamine and orthoaminoazotoluene) resulted in higher survival of the treated organ cultures and induced epithelial hyperplasia. The changes depended directly upon the dose of carcinogen employed.


Isolation of tumor-specific antibodies from effusions of ovarian carcinomas.

Peritoneal effusions of patients with ovarian cancer contain sizable amounts of free and complexed immunoglobulins. By means of salt precipitation procedures, antibodies were recovered that after purification and concentration displayed a high degree of specificity against ovarian carcinoma cells. In indirect immunofluorescence, immunoglobulins recovered from seven different peritoneal effusions showed bright cytoplasmic staining with tissue cultures and fresh suspensions of ovarian carcinoma cells but not of normal ovaries or non-ovarian tumors. Immunoglobulins isolated from fluids of benign ovarian cysts or from effusions of non-ovarian tumors were negative in immunofluorescence tests. Autologous antibodies recovered from peritoneal effusions will be hopefully utilized in sensitive radioimmunoassay tests that are greatly needed for the early detection of ovarian cancer, the leading cause of death from gynecologic neoplasia.