Active transport by membrane vesicles from anaerobically grown Escherichia coli energized by electron transfer to ferricyanide and chlorate. Active transport of amino acids by membrane vesicles from Escherichia coli, grown anaerobically on glucose in the presence of nitrate, can be energized under anaerobic conditions by electron transfer in the nitrate respiration system with formate as electron donor and nitrate as acceptor. A high rate of amino acid transport is also obtained under anaerobic conditions by electron transfer from formate to the nitrate analogue chlorate or to the membrane-impermeable electron acceptor ferricyanide. Electron transfer from formate to nitrate results in the generation of an electrical potential as is indicated by the uptake of the lipophilic cation triphenylmethylphosphonium. Ferricyanide accpets electrons from at least two sites of the nitrate respiration system. One of these sites appears to be nitrate reductase, because cytochrome b, reduced by formate, is completely reoxidized by ferricyanide and glutamate transport energized by formate plus ferricyanide and formate plus nitrate are affected by the same electron transfer inhibitors. A second site of electron transfer to ferricyanide appears to be located prior to nitrate reductase in the nitrate respiration system, since formate is oxidized at a higher rate in the presence of ferricyanide than with nitrate while formate/ferricyanide energizes transport of amino acids at a lower rate than formate/nitrate. Moreover, electron transfer inhibitors block electron transfer from formate to nitrate to a significantly higher extent than from formate to ferricyanide. The effects of irradiation of the membrane vesicles with near ultra-violet light suggest that quinones play an essential role in the electron transfer from formate to nitrate or ferricyanide. Irradiation blocks completely formate-dependent nitrate and ferricyanide reduction and active transport driven by formate/nitrate and formate/ferricyanide, but has hardly any effect on the activity of formate dehydrogenase and on ascorbate/phenazine methosulphate/oxygen-driven transport. Similar effects of ferricyanide have been observed in membrane vesicles from E. coli, grown anaerobically in the presence of fumarate. In these membrane vesicles a high rate of lactose and triphenylmethylphosphonium uptake under anaerobic conditions is obtained by electron transfer from glycerol 1-phosphate to fumarate and also to ferricyanide and evidence has been presented for the involvement of cytochromes in these electron transfers.


Heart failure in experimental refractory shock. Severe haemorrhagic shock was studied in a series of animal experiments. Reduction in myocardial oxygen and substrate utilisation in association with cardiac failure was demonstrated when the duration of shock was prolonged. The probable aetiological factors included ischaemia and the presence in the blood of certain vasoactive and metabolic depressant substances. It was concluded that the process leading to irreversible shock was multi-factorial in origin but failure appeared to play an important role.


The effect of a progressive decrease in the circulating blood volume of the dog on the transthoracic impedance. The correlations between the haemodynamic and transthoracic electrial impedance changes resulting from a progressive reduction in the circulating blood volume were studied in four intact mongrel dogs artificially ventilated with a mixture of halothane in nitrous oxide-oxygen. The cardiac output of the dogs was measured by both the electrical impedance and the fibre optic dye dilution techniques. It was found that significant correlations existed between the blood lloss and the arterial blood pressure, the maximum first derivative of the transthoracic impedance, the Heather Index, the transthoracic impedance, the maximum rate of change of aortic pressure and the cardiac stroke work. There was also a good correlation between the dye and impedance cardiac output values, the impedance value always being higher than the corresponding dye value. The correlation between the Heather Index and the PEP/LVET ratio and 1/PEP2 varied markedly from dog to dog.


The use of nasal CPAP in newborns with respiratory distress syndrome. The efficiency of applying continuous positive airway pressure (CPAP) by the nasal route was retrospectively nalyzed in 32 newborns with RDS (23 uncomplicated HMD with additional cardiac or pulmonary complications and 7 RDS of non-hyaline membrane etiology) who underwent nasal CPAP treatment at the Kinderspital Zurich from 1972--1974. 16 of the 23 infants with uncomplicated HMD were successfully treated with CPAP. They showed a significant rise in PaO2 as well as a significant drop in respiratory frequency during nasal CPAP application, the PaCO2 did not change significantly. The remaining 7 infants in this group (7/23) had to be intubated and mechanically ventilated owing to a persistent high FIO2 (4 infants), technical difficulties (1) or nasal hypersecretion (2). Two of these 23 infants died, one of meningitis, one of cerebral hemorrhage. The two infants with HMD and additional cardiac or pulmonary complications and 3 of 7 infants with RDS of non-hyaline membrane etiology had to be intubated and mechanically ventilated after failure of nasal CPAP. All 9 infants in these two groups survived. The nasal CPAP system as described is a simple, inexpensive and effective method of applying CPTPP in newborns with uncomplicated HMD, except radiological stage IV. In HMD with additional cardiac or pulmonary complications and in RDS of non-hyaline membrane etiology the results of nasal CPAP treatment were not convincing.


Correlation of PPD and BCG-induced leukocyte migration inhibition, delayed cutaneous hypersensitivity, lymphocyte transformation in vitro and humoral antibodies to PPD in man. In a study of healthy human individuals a complete lack of correlation between the results of the agarose leukocyte migration inhibition (LMI) test, using purified protein derivative (of tuberculin) (PPD) and Bacillus Calmette Guérin (BCG) as antigens, and delayed cutaneous hypersensitivity and lymphocyte transformation in vitro to PPD was found. There was a reasonable correlation between PPD- and BCG-induced LMI. Antibodies to PPD proved to have no influence on PPD-induced LMI. Purified polymorphonuclear leukocytes, whether derived from donors sensitive to PPD in the agarose LMI test or from nonsensitive donors, did not show migration inhibition to PPD. It was concluded that polymorphonuclear leukocytes and lymphocytes need to be present simultaneously for migration inhibition of peripheral blood leukocytes by PPD. Furthermore, because a consistent relation with conventional parameters of cell-mediated immunity was lacking, it is doubtful whether the agarose LMI test can be considered as an alternative parameter of this kind of immunity.


Selective breeding of mice for antibody responsiveness to flagellar and somatic antigens of salmonellae. Selective breeding has been performed in mice for their high or low antibody responsiveness to Salmonella antigens (Ag). Two noncross-reacting Salmonellae (S. typhimurium and S. oranienburg) have been alternately used to immunize successive generations in order to avoid interference of maternally transmitted antibody. Both Salmonellae carry two independent antigens: flagellar (f) and somatic (s). Two two-way selections were carried out: one for agglutinin response to fAg and the other for agglutinin response to sAg (Selection Ags). The agglutinin response to the other independent Ag was also measured (Associated Ags). The phenotypic character chosen for selection is the maximal agglutinin titer in response to optimal immunization. In both selections, high and low responder lines diverged progressively. There was a 27-fold interline difference in the F13 generation of selection for fAg response and a 38-fold one in the F11 generation of selection for sAg response. This divergence and the continuous distribution of phenotypes in the foundation population indicate that the quantitative character investigated is subject to polygenic regulation. The realized heritability (h2) of the character, measured from the interline divergence, was 0.18 +/- 0.06 in both f and s selections. This means that about 20% of the phenotypic variance of the foundation population is additive. The modification of immune responsiveness to the selection Ag produced by selective breeding was accompanied by a parallel and equivalent effect on immune responsiveness to the noncross-reacting Associated Ag. This effect is therefore entirely nonspecific. A small but definite sex effect in favor of female antibody responsiveness was demonstrated. The results are discussed in comparison with other selection experiments made in mice for quantitative antibody response to other antigens.


Dual pathway of B lymphocyte differentiation in vitro. Direct visualization of the events resulting from LPS stimulation of mouse spleen cells in vitro was achieved by characterizing the cells during four days of culture for morphology, Ig and theta surface markers and autoradiography after [3H] thymidine uptake. The changes observed were related to biochemical parameters such as incorporation of [3H] thymidine into DNA, Ig biosynthesis and secretion. Two pathways of B lymphocyte differentiation were observed: a) the generation of a large number of small B lymphocytes with high density of surface Ig but no internal pool detectable by immunofluorescence, and b) the maturation of a very small proportion of cells with a large intracellular pool and the ability to secrete Ig. Both cell types arise from dividing blast cells, either physically separated or traced by pulse chase experiments with [3H] thymidine. We discuss whether this duality is caused by the triggering of different B cell subpopulations at different developmental stages, preprogramed to one or the other pathway or whether the final direction of development depends on the microenvironment of individual dividing cells.


Control mechanism of lymphocyte traffic. Altered distribution of 51Cr-labeled mouse lymph node cells pretreated in vitro with lipopolysaccharide. The effect of in vitro treatment of mouse lymph node cell populations with lipopolysaccharide (LPS) on their migration in syngeneic recipients was studied. LPS-exposed cells had a decreased lymph node localization and an increased spleen distribution when compared to control untreated cells, after intravenous injection into syngeneic recipients. This effect of LPS on cell traffic was maximal at 24 h and could not be detected at either 1 or 72 h after cell transfer. These changes induced on cell distribution by LPS treatment are interpreted as the consequence of a modified interaction between the circulating lymphocytes and the resident cells within the spleen of the recipients.


Reduction of trapping of aggregated human IgG in germinal centers by mitogens. The effect of nonspecific mitogens on the trapping of 125I-labeled aggregated human IgG (125I-AHGG) in germinal centers (GC) of mouse spleens has been investigated by both radioactivity uptake and immunofluorescence. Phytohemagglutinin and concanavalin A (Con A) significantly decreased trapping. Lipopolysaccharide produced less inhibition, and pokeweed mitogen had no significant effect. The maximum inhibition occurred with 250--500 mug Con A. This had no effect on 125I-AHGG uptake in liver kidney and blood. No differences were found between i.p. and i.v. routes of Con A injection. The effect of mitogens on the 125I-AHGG trapping in GC is due more likely to modification of the migratory properties of lymphocytes brought about by surface binding, than to their mitogenic properties, since Con A decreased 125I-AHGG localization in thymectomized, x-irradiated and bone marrow-reconstituted animals.


Effects of morphine on the turnover of brain catecholamines and serotonin in rats-acute morphine administration. Morphine increased the rate of brain dopamine (DA) depletion when given before alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide, but not when given after AMT. No effect of morphine was found on the rate of depletion of brain noradrenaline (NA) or serotonin (5-HT) after the two synthesis inhibitors. The accumulation of homovanillic acid and 5-hydroxy-indoleacetic acid induced by probenecid was significantly increased by morphine pretreatment, whereas the accumulation of 3-methoxy-4-hydroxy-phenylglycol sulphate was not changed. These findings can be best explained by the hypothesis that morphine increases the non-functional intraneuronal catabolism of newly synthesized DA and 5-HT, without much effect on the monoamines already taken up in the synaptic vesicles. NA turnover does not seem to be changed by acute morphine administration.


Effects of morphine on the turnover of brain catecholamines and serotonin in rats-chronic morphine administration. The turnover of brain monoamine was studied in rats in which different degrees of tolerance to and dependence on morphine were induced by pellet implantation. The degree of tolerance to morphine was assessed by measuring the increase in effective dose for an antinociceptive effect (vocalization test). The rate of depletion of brain dopamine (DA) and serotonin (5-ht) after alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide (dopacetamide) was not changed by chronic morphine treatment. In contrast, the accumulation of brain homovanillic acid HVA) and 5-hydroxyindoleacetic acid (5-HIAA) after probenecid was significantly increased, but there was no correlation between the biochemical changes and the degree of tolerance/dependence of the animals; at a very high degree of dependence 5-HIAA accumulation even became normal. In rats in which smaller amounts of morphine were repeatedly injected every 8 hr for 1 week the increased accumulation of HVA and 5-HIAA persisted in spite of complete tolerance to the antinociceptive effect. The rate of depletion of brain noradrenaline (NA) after AMT or dopacetamide was not changed and the accumulation of brain 3-methoxy-4-hydroxy-phenylglycol sulphate (MHPG-SO4) after probenecid was not affected in most chronic morphine groups. In the group with the highest degree of tolerance/dependence NA depletion after AMT was even retarded. The results suggest that chronic morphine treatment increases the synthesis and the intraneuronal destruction of newly synthesized DA and 5-HT without changing the rate of functional utilization of the monoamines. It is unlikely that the changes in monoamine metabolism are causally related to processes leading to morphine tolerance/dependence.


A comparison of the abilities of typical neuroleptic agents and of thioridazine, clozapine, sulpiride and metoclopramide to antagonise the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems. Dopamine injected directly into the caudate--putamen, nucleus accumbens or tuberculum olfactorium of rat brain, following a nialamide pretreatment, caused dose-dependent hyperactivity. The hyperactivity was more intense after injections into the nucleus accumbens, but was limited by the development of stereotyped biting when larger doses of dopamine were injected into the caudate--putamen or tuberculum olfactorium. Haloperidol, fluphenazine and pimozide were shown to antagonise, in a dose-dependent manner, the hyperactivity induced by dopamine from all 3 areas. Pimozide appeared equieffective against the 3 hyperactivity mediated from the mesolimbic areas, the nucleus accumbens and tuberculum olfactorium. Sulpiride, clozapine and thioridazine also caused dose-dependent reductions in the hyperactivity induced by dopamine injections into the caudata--putamen, nucleus accumbens and tuberculum olfactorium, although the doses required to effect this inhibition were notably larger than for the typical neuroleptics. Generally, these atypical agents were also least effective as antagonists of the hyperactivity following intrastriatal dopamine. Metoclopramide differed from all other agents tested in failing to antagonise the hyperactivity induced by dopamine injections into the nucleus accumbens. However, the responses to dopamine from the caudate-putamen and tuberculum olfactorium were both antagonised by metoclopramide, the striatal response  being the least sensitive. The alpha- and beta-adrenergic blocking agents, aceperone and propranolol, failed to reduce the hyperactivity induced by dopamine injections into the caudate-putamen, nucleus accumbens or tuberculum olfactorium. The abilities of the agents tested to antagonise a hyperactivity induced by dopamine in the striatum or in the mesolimbic areas, the nucleus accumbens and tuberculum olfactorium, are compared with the potential of these agents to induce extrapyramidal side effects and to exert an antipsychotic action in man.


Ultrastructural features of proliferating fibroblasts in inflammatory granulomas. Proliferating fibroblasts in subcutaneous connective tissue of rats after injection of peanut oil or implantation of an almost insoluble synthetic material (silicap) were characterized electron microscopically. In tissue samples of both the foreign body granulomas typical fibroblasts with abundant rough endoplasmic reticulum and a peculiar cellular modulation resembling histiocytes concerning their organelle composition were found. The morphological picture of the latter cells does not allow the conclusion that their function must be a merely phagocytic one. True myofibroblasts as detected in other stages of connective tissue proliferation are not present. The capillary vessels show a clear proliferation of their vascular cells and migration of these cells with assumption of fibroblastic features is suggested basing on morphological observations.


Effects of antithymic reticuloepithelial cells serum on the levels of circulating thymic factor and on the sensitivity to azathioprine of spleen spontaneous rosette-forming cells. Swiss mice treated with an antithymic reticuloepithelial cells serum (ATRES) showed a drastic and prolonged depression of the serum thymic factor. A similar but less pronounced effect was also observed following the administration of the antithymocyte (ATS) and the antilymphocyte (ALS) sera. Conversely, the azathioprine sensitivity of spleen spontaneous rosette-forming cells was highly modified by the ATRES but not by the ATS or the ALS. The probable mechanisms of such effects are discussed.


Enrichment in spontaneous and complement dependent rosette forming cell populations using Ficoll-Hypaque gradient centrifugation. Peripheral blood human T (TL) and B (BL) lymphocytes were separated by continuous Ficoll-Hypaque (FH) gradients. BL were found at the 1050 density interfase (70.5% EAC rosettes) with no TL (0% EAC rosettes); while at the 1068 density interfase there was an enrichment of TL (68% E rosettes) with very few BL (8.5% EAC rosettes).


Recent advances in the metabolism of organophosphorus insecticides. Rat metabolism studies were conducted with three organophosphorus ester insecticides: [phenyl- or ethoxy-14C]Dyfonate, O-ethyl S-phenyl ethylphosphonodithioate; [phenyl-14C]Trithion, S-[(4-chlorophenylthio)methyl]O,O-diethylphosphorodithioate; and [phenyl-14C]R-14805, 4-[O,0-diethyl phosphorothioyl)]-acetophenoneoxime-N'-methylcarbamate. Compounds were administered orally to rats at 2 to 8 mg/kg, and biotransformation pathways were established from identified metabolites. Metabolites were isolated from O-96 hr urine and identified by using one or more methods including thin-layer chromatography, radio-gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance. Each of these model insecticides displayed a distinct bioactivation and detoxification pathway. Conversion to potent acetylcholinesterase inhibitors resulted from desulfuration of Dyfonate, desulfuration and thioether oxidation of Trithion, and desulfuration and a variety of modifications of the leaving group of R-14805. The compounds were deactivated primarily via cleavage of an organophosphorus ester group. All three compounds and their metabolites were rapidly excreted primarily in urine without any bioaccumulation in tissues.


Quantitative characteristics of antibody forming cells in partial tolerance. Direct PFC to SRBC were enumerated simultaneously by the LHL and LHG in the spleens of partially tolerant and control rats. The sensitivity of LHL was higher than that of LHG, but the factor by which the number of PFC was higher in LHL than in LHG was in the two groups similar (1.44 in tolerant and 1.47 in control group). When the plaque size distribution was studied in the LHL, a significant increase in small size plaques was observed in tolerant rats. The findings are discussed and the conclusion is reached that the decrease in AFC number and not in antibody production by individual PFC is the main factor responsible for partial tolerance.


Analysis of different survival of weakly incompatible allografts of skin from the ear and back. A comparison of the survival of skin grafts across the H-barrier presented by the male-specific antigen in mice was made with grafts of skin from different sources, namely from the back or from the ear. Their survival was roughly similar provided the ear skin was depleted of the subepidermal connective tissue with the cartilage. With this layer intact, the ear skin grafts had a prolonged survival and some of them even took permanently. A local administration of a mucolytic agent to the normal grafts from the back accelerated their rejection. The factors of the subepidermal connective tissue which might be responsible for the effect on the survival of weakly incompatible skin grafts and in this connection the role of the source of the skin are discussed.


A method of orientation of embedded bacterial colonies prepared for ultrathin sections. The described method of embedding of bacterial colonies into media used for electron microscopy allows the precise orientation of the material for the preparation of ultrathin sections. The colonies are covered by a strip of agar joined to the agar-layer with the cultivated colonies by means of a heated razor-blade. This method is especially useful for ultrastructural studies of L-colonies.


Is mycosis fungoides an "immunoma'?

Is mycosis fungoides an "immunoma'? New knowledge of the function and biological behaviour of the cells of the lymphocytic system justifies a critical reappraisal of the nature and origin of mycosis fungoides (MF). The fact that in MF the immune response remains active during the whole course of the disease distinguishes it from other malignant processes. On the basis of the well-known fact that chronic stimulation of the immunological system may lead to tumour formation, the hypothesis is stressed that MF may be an "immunocytoma' or 'immunoma'. New findings indicate that immunological stimulation of lymphocytes may lead to the formation of endogenous oncogenic viruses. All these questions should be investigated in as many centres as possible.


Interactions between econazole, a broad-spectrum antimicrobic substance, and topically active glucocorticoids. Econazole is a broad-spectrum antimicrobic substance which acts by permeabilizing the cell membranes. Glucocorticoids by their surface activity may counteract this effect by protecting the cell membranes. In fact, a protective action of glucocorticoids in high concentrations against econazole nitrate could be demonstrated in yeasts, not in staphylococci. The techniques applied were the Warburg assays (resting yeasts, resting and proliferating bacteria). The elicitation of a blanching reaction on human skin by triamcinolone acetonide was not altered in the presence of econazole nitrate. The data collected in this study were discussed in regard to the combined use of antimicrobic drugs and glucocorticoids in topical therapy.


Dihydroxyacetone naphthoquinone protection against photosensitivity. 30 patients with multiple types of sunlight sensitivity were treated successfully with DHA/lawsone sunscreen. This sunscreen was able to protect all patients even though their photosensitivities were in different parts of the ultraviolet and visible spectrum. About 80% of the patients experienced sufficient protection during the summer months to lead a virtually normal life-style while participating in all kinds of outdoor activities.


[Diagnostic problems associated with the coincidence of bullous dermatosis and lupus erythematosus visceralis. Demonstration of a case with Duhring's dermatitis herpetiformis in association with visceral lupus erythematosus]. This report describes a patient, whom we observed for 3 years, exhibiting a coincidence of dermatitis herpetiformis Duhring and systemic Lupus erythematosus. The difficulties involved in demarcating bullous lupus erythematosus from the more rare association of bullous pemphigoid or dermatitis herpetiformis with systemic lupus erythematosus are discussed in connection with differential, histological, direct and indirect immunofluorescence diagnostic aids.


Relationship of subepidermal immune complex to renal deposits in the (NZB X W)F1 mouse. In an attempt to correlate the presence of subepidermal and renal glomerular deposits in murine lupus, skin and kidney tissue from 67 (NZB X W)F1 mice was examined by direct immunofluorescence and the results tabulated. Between 36 and 43 weeks of age, deposits in both locations were detected in only 50.5% of the mice, and between 44 and 52 weeks, in only 79.0%. The titer of antibody to DNA did not correlate with the presence of subepidermal deposits even though DNA was demonstrated at the epidermal-dermal interface. It is concluded that the absence of immunoglobulin in the subepidermis does not preclude the presence of renal deposits, and it is hazardous to attempt to predict underlying glomerular deposition by performing immunofluorescence examination of skin in murine lupus.


[Insulin receptors-a review (author's transl)]. The first step in insulin action is interaction of the hormone with specific receptors on the plasma membrane of target cells. The receptor site is defined by its functional properties: it binds insulin with a high degree of specificity and affinity; the specific binding sites are finite in number; hormone binding is rapid and reversible; the binding sites are, or predominate, on the plasma membrane; hormone binding can be related to biological effects. The use of biologically active monoiodoinsulin permits direct study of the binding of 125I-insulin to receptor in isolated cells or in cell membranes. The binding of 125I-insulin is highly specific and strictly dependent on the biologically active structure of the insulin molecule. Both the rate and the amount of binding are time and temperature-dependent. The insulin--receptor interaction is a complex reaction, whose quantitative analysis requires consideration of, in addition to hormone binding to receptor, degradation of the hormone and of the receptor. By measuring binding at steady state, one can determine both the apparent insulin--binding capacity and the apparent dissociation constant of the insulin--receptor complex. Scatchard analyses of these data reveals heterogeneity of the binding sites with respect to equilibrium constant, a result which is also compatible with negative cooperativity between the receptor sites. Studies of insulin--receptor interactions have led to a variety of applications, two of which are of special interest from pharmacological, pathophysiological and clinical viewpoints. One is concerned with the use of insulin--receptor binding systems to study hormone structure--activity relationships and to analyze endogenous forms of insulin. These studies have shown that, in every instance, the binding affinity of an insulin or insulin analogue is in direct proportion to its biological potency. No antagonist of native insulin has been found thus far, including data obtained with proinsulin, proinsulin intermediates and Non-Suppressible Insulin-Like Activity (NSILA) or somatomedin (s). These studies have also revealed that proinsulin reacts only with insulin receptors in contrast to NSILA which, inaddition to reacting with insulin receptors, also possesses its own specific receptor sites. The other application deals with studies of receptor alteration in pathological states. This investigation has been well documented in the obese hyperglycemic (ob/ob) mouse which exhibits a receptor defect in the liver, fat, thymic lymphocyte and myocardium. The defect essentially involves a decrease in the number of binding sites and selectively affects the insulin receptor. A variety of data, both in vivo and in vitro, indicate an inverse relationship between the concentration of insulin and the number of insulin receptors, and suggest a negative feedback effect of the hormone on its own receptor...


Kinetics of the early insulin response of the perfused rat pancreas to various metabolites and tolbutamide. The collection every 15 seconds of the portal effluent of the isolated and perfused rat pancreas permitted the following observations: while the insulin response to tolbutamide (250 or 125 mug/ml) occurred immediately, that to glucose (15 mM), or to 1-leucine (15 mM) was delayed by 60-90 seconds. The response to d-glyceraldehyde occurred slightly but significantly more quickly than that of glucose. The response to alpha-keto-isocaproate was an intense and immediate one. Isovalerate elicited no insulin discharge. These results suggest that d-glucose and l-leucine have to be metabolized to stimulate insulin secretion and that alpha-keto-isocaproate seems to be a direct and specific signal.


[Diabetes mellitus secondary to liver diseases. A review (author's transl)]. Diabetes mellitus is more frequently found in pateints with hepatic cirrhosis (about 10%) than in subjects without liver disease. Cirrhosis has been the main subject of interest in this respect. Very few studies have been made in viral hepatitis or steatosis. In about 40% of cases, the diabetes is identified before the cirrhosis. More often (in about 60% of cases) the diabetes is discovered at the same time as or after the finding of cirrhosis. This "post-cirrhosis diabetes" shows no clinical peculiarity. In about 80% of patients with liver cirrhosis when fasting blood glucose is normal, abnormalities of carbohydrate metabolism are to be found by the oral glucose tolerance test. Approximately 50% show an abnormal response to intravenous glucose and 30% to intravenous tolbutamide. The "mechanism" of these metabolic abnormalities in liver cirrhosis is unknown. The following abnormalities are observed: 1) With similar glycaemic response to a glucose challenge, plasma insulin levels are higher than in patients without liver disease, suggesting insulin unresponsiveness. Resistance to exogenous insulin can be demonstrated. 2) Plasma free fatty acid levels are often elevated. 3) Plasma growth hormone levels are often raised. 4) Plasma glucagon levels are high when porto-caval shunting is present. 5) Potassium is often depleted. These metabolic abnormalities, in association with porto-caval shunting and hepatocyte insufficiency may explain the insulin resistance which characterises liver cirrhosis, and the diabetes which it may precipitate in predisposed persons.


[The role of glucagon in hyperglycemia. A review (author's transl)]. Glucagon is secreted not only by A2-cells of the pancreatic islets but also by A cells in the gastric fundus and duodenum. Several reports have demonstrated that the glucagon plasma concentration is increased in genetic diabetes as well as in many conditions associated with a decreased glucose tolerance such as hepatic cirrhosis, myocardial infarction, infectious diseases, burns, taumatic shock, glucagonomas, acute pancreatitis, acromegaly, pheochromacytoma and Cushing's syndrome. Hyperglucagonemia is particularly important in diabetic ketoacidosis and in non-ketotic hyperosmolar coma. The mechanisms responsible for the diabetic's hyperglucagonemia remain controversial. According to several authors, the increased glucagon secretion is, for its main part, secondary to a prolonged defect in insulin secretion and thus relatively insensitive to an acute insulin administration. According to others, the A cell abnormality is of primary origin, independant from insulin deficiency and its effects are cumulative with those of the insulin lack. Several reports dealing with induced or spontaneous experimental diabetes are in favor of the first or the second hypothesis. It appears likely that glucagon plays a role in the metabolic derangments of diabetes. Indeed, hepatic glucose production is closely related to the ratio of molar concentrations of insulin and glucagon. Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy. These results illustrate the contribution of glucagon in the pathogenesis of hyperglycemia and ketosis. Several arguments have been accumulated in favor of the following concept: diabetes hyperglycemia results both from glucose under-utilization secondary to insulin lack and from hepatic glucose over-production due to glucagon excess. Although controversial, the role of glucagon in ketogenesis appears likely.


Calcium antagonists and islet function. VIII. The effect of magnesium. Mg2+ in high concentration (10 to 20 mEq/l) caused a dose-related inhibition of glucose-induced 45calcium net uptake and subsequent insulin release in isolated islets. Experiments performed with the isolated perfused pancreas indicated that the inhibitory effect of Mg2+ upon insulin secretion was rapid and reversible. Although excess Mg2+ reduced lactate production by the islets, the process of glucose recognition by the B-cell was apparently unaltered as judged by the inhibitory effect of the hexose upon 45calcium efflux from perifused islets and the resultant accumulation of 45calcium in the islets. Mg2+ in high concentration failed to facilitate 45calcium efflux from the islets, whether in the presence or absence of glucose. These data suggest that the major effect of Mg2+ upon islet function is to inhibit Ca2+ entry in the B-cell.


The breakfast tolerance test: a return to physiology. The effects of a standardized breakfast on blood glucose, plasma free fatty acid and alpha-amino nitrogen levels, plasma insulin, glucagon and cortisol concentrations as well as serum growth hormone circulating levels are described in a group of six healthy, young, male volunteers. It is suggested to the clinician to use this "breakfast tolerance test" or B.T.T. as a simple means to reconsider on physiological grounds some widely accepted pathophysiological concepts derived from highly unphysiological procedures such as the oral glucose tolerance test or O.G.T.T.


Cellular interrelationships during in vitro granulopoiesis. Long-term production of fully differentiated granulocytes can be maintained in vitro in a liquid system of cultured bone marrow. Marrow is cultured in medical flasks and allowed to form an adherent layer over a three-week period, and then recharged with fresh marrow resulting in continued mature granulocyte production for several months. During the initial establishment of the adherent layer, three attached populations become apparent: phagocytic monocytes, an attached epithelial cell type, and aggregations of epithelial cells swollen to enormous proportions by the presence of numerous lipid-containing vacuoles. Without the formation of these aggregations, granulocyte production is not maintained beyond an initial period and the culture converts to phagocytic mononuclear cell production alone. Thus not only is the presence of the fat-containing aggregations necessary to continued granulopoiesis, but cultures in full granulocyte production show a characteristic clumping of granulocytes around these aggregates. Electron microscopy has shown that the epithelial cells from the adherent layer form a layer covering some of the attached cells in these areas and thus may provide the necessary in vitro microenvironment for granulopoiesis to occur. Pinocytotic vesicles and gap junctions have been observed between the adjacent membranes of the undifferentiated granulocytes (possibly stem cells) and the epithelial cells themselves.


Fluorescence histochemical study of the pancreas in the cat. The exocrine and endocrine pancreas was investigated according to the fluorescence histochemical method of Flack and Hillarp. 1) Green fluorescent adrenergic fibers were regularly seen associated with arteries and arterioles in the exocrine pancreas. 2) Cholinergic fibers as shown by cholinesterase activity, were also found in the parenchyma of pancreas. 3) Yellow fluorescent cells scattered in the exocrine parenchyma and localized to a population of pancreatic islet cells with a characteristic distribution at the islet periphery was found. 4) By the fluorescence microscopic observation, inter-or intralobular pancreatic ducts, involving the zymogen granules, can also be seen after treatment with HCL vapor. 5) Yellow fluorescent cells, beta-cells containing insulin, remained at the Islet periphery. At present, the above mentioned yellow fluorescent cells are identified as containing HPP (Human pancreatic polypeptide) according to the immunofluorescence technique. With the use of the Falck and Hillarp histochemical technique ethionine induced pancreatitis in cats has been investigated. 1) After seven days of ethionine (5 mg/kg BW oral ad.) treatment, pancreas showed histochemical changes such as hemorrhage, fat necrosis, destruction of acinar cells and degranulation of zymogen from the parenchyma of pancreas. 2) Oral administration of ethionine for ten days induced severe degranulation, rupture of vessels, especially of veins and venules and later influenced arteries or arterioles. 3) Necrosis and fibrosis began to appear in the spaces between the cellular debris and marked pancreatic atrophy could be found. 4) The destruction of Islets of Langerhans can be found in the ethionine induced pancreatic parenchyma. On the other hand, an increased number of Islets of Langerhans was also observed in the site of lobule. 5) The presented findings may also suggest that the duration of administration of ethionine is more important factor than graded doses of ethionine in the production of ethionine is more important factor than graded doses of ethionine in the production of ethionine induced pancreatitis in cats.


Extrahepatic malignancy in chronic liver disease: report of six cases. Six patients are described with chronic liver disease, 3 with primary biliary cirrhosis and 3 with chronic active hepatitis, all of whom developed malignant disease in organs other than the liver. Two malignancies were mixed histiocytic-lymphocytic lymphomas. All patients had received corticosteroid or azathioprine therapy. Specific lymphocyte counts and immunoglobulin and antibody determinations failed to reveal a consistent pattern of abnormality to recognize the patient at risk. Several diseases in which the immune responsiveness is disturbed seem to have this potentiality in common, especially if therapy that further alters immunological reactivity is given.


[Contribution to the diagnosis of gonorrhea (author's transl)]. The culture is the optimal procedure for the diagnosis of gonorrhea in the female and should be used in every suspicious case. The percentage of loss through use of a transport medium (Stuart) and by submitting the specimen to a central laboratory for examination affects the results. For this reason a simple procedure was tested based on Chapin's candle-flame method and using Martin and Thayer's selective culture medium. This method can be used in every laboratory. The described procedure requires little more work than Gram's method. In our test series, a higher percentage of positive results were obtained with this method than with the microscopic diagnosis and the transport medium.


[Oral immunization of rabbits against enteropathogenic serotypes of E. coli. II. Production of circulating and fecal antibodies induced with monovalent and polyvalent vaccines]. Oral vaccination of rabbits with killed polivalent E. coli vaccines (enteropathogenic strains) induced the production of circulating and fecal antibodies to the large majority of serotypes present in the vaccines. The production of specific IgA immunoglobulins in the intestine was also detected. The titres were in general of the same height as those obtained when individual vaccines were administered singularly.


[Cultural, biochemical, cytochemical, pathogenic and morphological aspects (as seen with the scanning microscope) of pathogenic strains of Candida albicans treated with pyrrolnitrin]. The author has analyzed the pyrrolnitrine activity on eighty strains of Candida albicans isolated from hospital patients. On these various strains the M.I.C., the enzymatic activity, the pathogenicity on rabbits, the ability to form clamydospores were determined. Also cytochemical tests, tests on chorioallantoic membrane, absorption tests and morphological analysis at the scanning microscope were performed on these strains. The various findings obtained have shown a strong activity of pyrrolnitrine on the different biological activities of Candida albicans strains used in the present work.


A study of the transmission and structure of double stranded RNAs associated with the killer phenomenon in Saccharomyces cerevisiae. Killer strains contain two double stranded RNAs, L and M. The M dsRNA appears to be necessary for production of a toxin and for resistance to that toxin. Mutant strains have been found that are defective in their ability to kill and in their resistance to toxin. These sensitive, non-killer strains have altered dsRNA composition. One class has no M dsRNA. Another class of sensitive, non-killers called suppressives has no M dsRNA but instead has smaller dsRNAscalledS. Indiploidsresulting from a cross of a wild-type killer by a suppressive the transmission of the M dsRNA is suppressed by the S dsRNA. When a suppressive is crossed by a strain with no M dsRNA, the diploids and all four meiotic spores have the S dsRNA characteristic of the parental suppressive strain. Suppressive strains do not suppress each other. Intercrosses between two different suppressives yields diploids with both parental S dsRNAs. These two S dsRNAs are transmitted to all 4 meiotic progeny. Another class of mutants has been found which is defective for one of the traits but retains the other. One type, temperature-sensitive killers, has a normal dsRNA composition but is unable to kill at 30 degrees. The other type, immunity-minus, has a complex dsRNA pattern. The immunity-minus strain is extremely unstable during mitotic growth and segregates several different types of non-killers. Analysis of the dsRNAs from wild type and the mutants by electron microscopy shows that the L, M, and S dsRNAs are linear. All strains regardless of killer phenotype appear to have the same size L dsRNA.


Depilated (dep), a mutant gene that affects the coat of the mouse and acts in the epidermis. Depilated is a recessive mutation on Chromosome 4 in the position b-1.93+/-0.51-dep-3.45+/-0.68.-Pt. It causes severe abnormalities of hair structure. The site of action of dep was investigated by the method of dermal-epidermal recombination. Skins from 14-day mutant and normal mouse embryos were separated into dermal and epidermal components, recombined, and grown in histocompatible mouse testes for 20 days. The recombinations made were +/+ epidermis with +/+ dermis, +/+ epidermis with dep/dep dermis, dep/dep epidermis with +/+ dermis and dep/dep epidermis with dep/dep dermis. Grafts that contained mutant epidermis as one of the components produced hairs that were similar to those found in depilated mice. There was no observable effect of the dermis on hair types produced in this experiment.


Theoretical modifications of reciprocal recurrent selection. Reciprocal recurrent selection (RRS), which assumes overdominant loci to be important, alters two genetically different populations to improve their crossbred mean. Individual plants from two populations (A and B) are selfed and also crossed with plants from the reciprocal female tester population (B and A, respectively). Selection is based on the mean of crossbred families, and the selected individuals are randomly mated within A and B to form new populations.--We propose two alternatives to RRS. The first (RRS-I) uses, as the tester of population A, a population (LB) that is derived from population B by family selection for low yield. The second (RRS-II) is similar to RRS-I, but also uses, as the tester of B, a population (LA) that is derived from population A by family selection for low yield.--The expected crossbred means of RRS, RRS-I, and RRS-II were compared, assuming equal sigmaP, at several cycles of selection for incomplete and complete dominance, and for several cases of overdominance (depending on the gene frequencies in A and B, and on the equilibrium gene frequency).--The choice of selection method depends on the importance of the effects of overdominant loci compared to loci exhibiting incomplete or complete dominance. If overdominance is unimportant, RRS-II is the best selection method, followed by RRS-I and RRS. If overdominance is important, both RRS and RRS-I are superior to RRS-II; RRS is preferred to RRS-I if the effects of overdominant loci are sufficiently important. If the genetic model is a mixture of levels of dominance at different loci, a combination of selection systems is suggested.


[Radiosensitive mutants of Escherichia coli with disrupted cell membrane permeability]. Membrane proteins and cell permeability of Escherichia coli B/r and different substrains of B/r containing mutations of loci uvrB, exrA, lon and suppressors of that mutations were studied. Membrane proteins were found to be modified only in E. coli B/r exrA. The content of 40 000--70 000 D polypeptides was increased and the content of 80 000--100 000 D polypeptides was decreased. Alteration of membrane proteins in E. coli B/r exrA was associated with the impaired permeability of cell membrane.


Human umbilical vessel diameters and bloodgas tensions in the first two minutes after delivery. Human umbilical vein and artery diameters reduce significantly during the first 2 min after delivery, whereas blood gas tensions do not change significantly. Gas tension changes, therefore, cannot account for the reduction in the umbilical vessel diameters which occurs during this time.


[Thumb reconstruction by means of transposition of a damaged little finger and interposition splint after an explosion injury to the hand]. This case report concerns the loss of the thumb, the middle and ring fingers as well as the distal phalanx of the little finger as a result of an explosion. A combined procedure for the reconstruction of a thumb was performed employing interposition lengthening of the first metacarpal by an iliac crest bone graft followed by the transposition of the distal part of the remainder of the little finger. The proximal portion of that digit was preserved in order to obtain better span grasp.


Professional review of health care services. The question of professional accountability has frequently been raised with regard to the provision of health care services. Various systems, among them peer review, utilization review, and the PSRO, have accordingly been introduced to monitor the quality and the cost of health care. Social workers will have increased opportunities to participate in these review systems and, thus, to improve health care delivery.


Oxygen transfer rate, respiration and yields in batch and chemostat cultures of Klebsiella aerogenes. The effect was studied of oxygen supply on the changes in total and specific rate of oxygen consumption by the cells, oxygen transfer rate, saturation concentrations of dissolved oxygen and the yields of batch and continuous cultivations. Experiments were done on the microorganism Klebsiella aerogenes CCM 2318 growing on synthetic glucose medium. Continuous cultivations were carried out at dilution rates of 0.96 and 0.178 h-1. The rate of oxygen transfer was determined by the sulphite method and the coefficient KLa was assessed using the dynamic method with a correction for changes in the saturations of dissolved oxygen. A lowered oxygen supply in batch cultivations caused deformations in the course of cell respiration. Comparison of results of batch and continuous cultivations showed that the highest yields Y X/S and Y X/O are attained at low dilution rates without oxygen limitation. Batch cultivations, on the other hand, exhibit the lowest yields and the highest cell respiration levels. In both types of cultivations, a respiration peak was ascertained under the conditions of growth limitation by oxygen.


Simultaneous and gradual induction of beta-galactosidase and tryptophanase synthesis in an Escherichia coli batch culture. beta-Galactosidase and tryptophanase can be induced in Escherichia coli simultaneously or gradually during a batch cultivation. In the strain Escherichia coli K 12 and ML 30, in which the synthesis of the two enzymes was induced simultaneously, only the synthesis of tryptophanase partially decreased, whereas the synthesis of beta-galactosidase was not influenced. In the strains B 28 and ATCC 9637 the synthesis of both enzymes was partially decreased. On a gradual induction of these enzymes in the strain Escherichia coli K 12 only the synthesis of tryptophanase decreased. Thus, the results obtained here resemble those observed during the simultaneous induction. In addition, it was found that it is not important which of the two enzymes is induced as the first one.


Biosynthesis of yeast mannan. Characterization of mannan-synthesizing enzyme systems from mutants defective in mannan structure. The yeast Saccharomyces cerevisiae X2180-1A (wild) and its mutants X2180-1A-4 (mnn 1) and X2180-1A-5 (mnn 2) defective in mannan biosynthesis were used as enzyme sources to catalyze in vitro mannosyl transfer from GDP-[14C-U]-mannose to endogenous glycoproteins as well as to exogenous, low-molecular weight acceptors. While the enzyme preparation from the wild strain exhibited all mannosyl transferase activities involved in mannan biosynthesis by catalyzing the synthesis of characteristic mannoprotein, the enzyme from mnn 1 mutant failed to catalyze the synthesis of alpha(1 leads to 3) mannoside linkages both with endogenous as well as with exogenous acceptors. The enzyme preparation from the mnn 2 mutant catalyzed the formation of mannoprotein very similar to that obtained with the enzyme from the wild strain. The most important difference was the formation of a higher number of unsubstituted mannosyl units in the alpha(1 leads to 6) linked mannan backbone. The observed results support the hypothesis that in the mnn 1 the mutation has altered the structural gene involved in biosynthesis of an alpha(1 leads to 3) mannosyl transferase catalyzing the addition of alpha(1 leads to 3) linked mannosyl units to alpha(1 leads to 2) linked mannotrioses in the polysaccharide side chains and in the oligosaccharides attached to serine and/or threonine in the protein part of mannan molecule. The mnn 2 mutant represents most probably a kind of regulatory mutation where the activity of an alpha(1 leads to 2) mannosyl transferase adding the mannosyl units directly to alpha(1 leads to 6) linked backbone in the outer region of polysaccharide part of yeast mannan is repressed in vivo but becomes significant in vitro.


A morphological study on vascular changes in the surgically resected tissues of temporal lobe epilepsy-with a special reference to the etiology. (1) Twenty-one out of 23 cases surgically resected specimens of TLE presented the common histological findings; sclerotic changes of the tissues. And the other two cases encountered the small tumors which might be called "cryptic". (2) Since circulatory disturbance is generally accepted to explain the cause of TLE we reexamined vascular behaviors in detail and found the quantitative and qualitative abnormaltities which reached the high rate of 71% (17 out of 21 cases) except two cases of small tumors. Moreover, it is remarkably noteworthy that these vascular changes adjoin the sclerosed parenchymal tissue. (3) It may be said that vascular changes have exerted some influences on the formation of inferomedial temporal sclerosis from the standpoint of the histological findings, though they are alone not fully sufficient to explain the etiology of TLE.


[Reconstruction of nasal defects using local flaps]. Of the various procedures available for the reconstruction of nasal defects, examples of local flaps are demonstrated. These local flaps preserve the aesthetic and function of the nose since they prevent ugly scar retractions. An early surgical intervention minimizes the extent of the operation although radically performed and gives optimal results.


[Contact- and suture-free hemostasis on the kidney parenchyma by means of a new infrared radiation instrument (MICOR)]. A new industrial instrument named MICOR (prototype), which means "Melting with Infrared Concentrated Radiation", is used on the dog kidney. We compare haemosytpiss after partial resection by scalpell using convential sutures (16 dogs) and MICOR (17 dogs);the dog kidneys are single organs. The results show, that MICOR--without touching kidney--is very effective and as effective as parenchym--sutures. Comparing examinations of morphology and kidney function show no essential difference between both methods. By renal clearance techniques an advantage MICOR could be shown. We expect better results by imporvement of the MICOR and hope for a helpful use in human surgery.


[Alrheumum in the daily practice].

[Alrheumum in the daily practice]. The new antirheumatic drug Ketoprofen (Alrheumun) has been tested by an open trial in 100 out-patients and the activity and tolerance have been evaluated under practice conditions. A daily dose of 3 capsules Alrheumun proved to have a good activity in patients with rheumatoid arthritis, osteoarthrosis and soft tissue conditions. 80% of all patients did not show to have any side-effects. Among all groups of patients, treatment had to be interupted because of side-effects in two patients only. A negative influence on any of the laboratory tests used was not found.


[Euphylline suppositories in the treatment of obstructive respiratory tract diseases in childhood]. In the present uncontrolled study the effectiveness and tolerance of aminophylline suppositories were assayed in 79 children of varying age, based on clinical and chemical laboratory findings. Results as well as specific dosage problems are discussed. Special emphasis is laid on the advantages provided by the application of suppositories in the treatment of small children.


[The neurobiology of the successive stages of life (author's transl)]. The neurobiological sciences deal with morphological, physiological, biochemical, and pharmacological investigations of neurobiological processes and mechanisms. In addition, they are interested in living organisms as action systems, with their forms of motion, types of behavior, and means of adapting to the environment. The topic "The Neurobiology of the Successive Stages of Life" covers the entire span of life, from the induction of the neural tube to senescence and death, i.e. the sum total of all continuous changes which are described by such terms as development, differentiation, specialization, individuation, functional maturity, and ageing. The following gives a survey from a special neurological-neuroanatomical point of view, it deals with the early development of prenatal activities, forms of movement, and refled differentiation cycles in regard to neurofibrillation, myelination, and cytological-cytoarchetectonic structures. Paul Yakovlev's and Peter Kuzmich Anokhin's interpretations of such selective morphological-functional maturation processes inherent in the system are discussed. There follows a brief survey of varying metabolic systems in close connection with the differentiation of nerve and glia cells and capillarization processes. The subject of early programmed cell death, nerve-cell degeneration, and heterotopia during the development, differentiation, and maturation of the central nervous system leads to a discussion of the likewise selective system-bound processes that take place during senescence of the central nervous system.


Localization of seminal plasma proteinase inhibitors in human spermatozoa as revealed by the indirect immunofluorescence technique. Acidic extracts of washed, ejaculated human spermatozoa contain, besides acrosin, two proteinase inhibitors, a trypsin-chymotrypsin (elastase) inhibitor (HUSI-I) and a trypsin-acrosin inhibitor (HUSI-II). Using the indirect immunofluorescence technique these inhibitors could be localized in the spermatozoa. Ejaculated spermatozoa were treated with monospecific antibodies raised in rabbits against HUSI-I and HUSI-II, respectively, and with fluorescein-labeled IgG from goat directed against the rabbit IgG. If acetone-fixed spermatozoa were used, fluorescence appeared only in a small ring near or at the equatorial segment of the spermatozoa. After prefixation of washed spermatozoa with 0.36% formaldehyde, however, distribution of both inhibitors in the region of the acrosomal caps could clearly be demonstrated. Present results suggest that they are attached at the plasma membrane. Obviously, in the case of human spermatozoa the inhibitors are relatively easily detached together with the membrane so that prefixation is necessary to achieve proper localization.


Isolation and characterization of CNBr derived peptides of the alpha1 (III) chain of pepsin-solubilized calf skin collagen. Fetal calf skin was solubilized by limited pepsin digestion and type III collagen separated from type I collagen by fractional salt precipitations. Cleavage of the type III collagen with CNBr gave rise to ten peptides, which were isolated by molecular sieve and ion exchange chromatography. The peptides were characterized by determination of their molecular weights and amino acid compositions. Together they account for all the amino acids and total molecular weight of the alpha1 (III) chain. Six of the peptides contain more hydroxyproline than proline residues. The two cysteinyl residues of the alpha1 (III) chain which provide sites for interchain disulfide bonding were localized in the C-terminal CNBr peptide. In addition to the ten CNBr peptides, three double peptides were isolated which still contained one methionine residue. About 0.1 residue Gal-Hyl monosaccharide and 0.8 Glc-Gal-Hyl residue disaccharide were found per alpha1 (III) chain. Almost all hydroxylysine-bound carbohydrate was located on peptide 7.


Isolation and structure of the amino-terminal cross-linking region in insoluble type III collagen. A collagenous peptide T1X was isolated from a tryptic digest of the insoluble matrix of calf skin. The peptide consists of two identical polypeptide chains each with a length of 72 amino acid residues joined by a cross-link. Absorption spectra obtained from hydrazone and azine derivatives of T1X indicated that the peptide contains an aldol-type of cross-link (X). The sequence of 23 amino acid residues in the amino-terminal region was determined as Glx-Tyr-Glu-Ala-Tyr-Asp-Val-X-Ser-Gly-Val-Ala-Gly-Gly-Gly-Ile-Ala-Gly-Tyr-Hyp-Gly-Pro-Ala. This sequence overlaps the previously described amino-terminal sequence of alpha1 (III) chain obtained from pepsin treated, insoluble type III collagen. Thus, the present data demonstrate a nonhelical segment of 14 amino acid residues in type III collagen important for cross-linking.


Localization of catalase A in vacuoles of Saccharomyces cerevisiae: evidence for the vacuolar nature of isolated "yeast peroxisomes". The subcellular distribution of catalase A in the yeast Saccharomyces cerevisiae has been investigated. The enzyme was found to be bound to large particles, whereas most of the activity of catalase T was located in a 38 000 X g supernatant. Under various isolation conditions catalase A always showed a distribution among subcellular fractions virtually identical to that of two markers for vacuoles, proteinase B and alpha-mannosidase. More than 80 percent of the catalase A activity of a crude vacuole fraci-onercent of the catalase A activity of a crude vacuole fraction has been detected in purified vacuoles. Malate synthase, isocitrate lyase and glyoxylate reductase (NADP), three peroxisomal markers, showed a subcellular distribution significantly different from that of catalase A. It is concluded from these results that catalase A is specifically associated with the vacuoles of yeast. Like vacuoles, "peroxisomal" fractions isolated from yeast spheroplasts as described by Avers[1] contain only one catalase protein, catalase A. It could be shown by isopycnic and sedimentation velocity separations of crude mitochondrial fractions that catalase A in "peroxisomal" fractions is accompanied by considerable activities of proteinase B and alpha-mannosidase. From all our results it seems that the catalase-active particles isolated under such conditions are not typical peroxisomes but vesicles formed from vacuoles during the isolation procedure.


Estimation of polygenic recurrence risk for cleft lip and palate. Data on cleft lip with or without cleft palate are utilized to evaluate a new method for estimating recurrence risk under the polygenic threshold model. The influence of critical factors on the accuracy of the estimated risks are evaluated. The model is relatively sensitive to the estimate of heritability employed and relatively robust to the population prevalence estimate and to family size. The calculated risks for cleft lip with or without cleft palate are contrasted with the empiric figures from studies on Caucasians and Japanese populations.


E rosette formation by human t lymphocytes: a spontaneous cell mediated cytotoxic phenomenon. The nature and significance of spontaneous association between unsensitized human T lymphocytes and sheep erythrocytes has been studied in relation to a possible cytotoxic reaction. Human lymphocytes and 51Cr labelled sheep erythrocytes when mixed in ratios of 5 or 10:1 released 70-100% of 51Cr into the supernatants. This suggests that E rosette formation may be the first step in a spontaneous T cell mediated cytotoxic reaction to sheep erythrocytes.


Unification and technical aspects of total t, active t and b lymphocyte rosette assays. Conditions for rosette formation of human adult T and B lymphocytes with unsensitized and complement coated SRBC respectively, have been examined in this collaborative study. Modified procedures for identifying, by rosette formation, the total T, active T and B-RFC lymphocytes are described. The procedures reported here yielded results for the percent of peripheral blood lymphocytes forming total T, active T and B-RFC for control individuals that are comparable with those previously reported. The advantage of the procedures described here are that they are 1) easy to perform; 2) highly reproducible; 3) allow for the preparation of a single lymphocyte concentration and common reaction mixture volume to be used in all three rosette assays and 4) allow for the removal of non-lymphocytic cells which would interfere with the determination of B-RFC. The use of these procedures would allow other laboratories to obtain similar values so results for controls and various types of patients could be compared.


Effect of immunosuppressive drugs on an in vito correlate of cell-mediated immunity. The migration inhibition test. The effect of a number of immunosuppressive drugs on the migration-inhibition test was studied. These drugs could be divided into four categories: (1) drugs influencing both the MIF production and MIF effect on macrophages (amethopterin, azathioprine); (2) drugs influencing MIF production (puromycin, actinomycin D); (3) drugs influencing the effect of MIF on macrophages (hydrocortisone); (4) drugs without any influence.


B lymphocyte subpopulations in the mouse spleen. A study of the differentiation pathway using free flow electrophoretically separated subpopulations of direct PFC progenitor cells. Free-flow electrophoretic separation of mouse spleen cells provides three distinct progenitor cells of direct PFC, showing high, medium and low electrophoretic mobility. All progenitor cells possess surface immunoglobulin and mouse B-lymphocyte specific antigen. The progenitor cells of high electrophoretic mobility show high cycling turnover, a spleen seeking capacity of 16%, provide PFC with a maximum 8 days after transfer and reveal an isometrical increase of the PFC dose response line as a function of the graft size. The progenitor cells of medium electrophoretic mobility are low cycling, 16% home to the spleen, a maximum of PFC is developed eight days after transfer and the PFC dose response line increases allometrically. The progenitor cells of low EPM show low cycling activity, 20% home to the spleen, a maximum of PFC is attained six days after transfer and the PFC dose response line rises isometrically. These results suggest that the electrokinetically different PFC progenitors represent biologically distinct subsets. In double transfer experiments, some evidence was obtained that progenitor cells of low electrophoretic mobility are derived from progenitors of higher electrophoretic mobility. The same observation accounts also for the formation of B lymphocytes of low EPM. Since it seemed likely that the PFC progenitor cells represent virgin cells of a single lineage, the results were discussed in the terms of differentiation pathways of B lymphocytes. A model is considered in which a progenitor of medium electrophoretic mobility provides those of high electrophoretic mobility which after passing a transient cycling stage finally produce mature resting B lymphocytes of low electrophoretic mobility.


Reduced humoral immune activity in long-lived old mice: an approach to elucidating its mechanisms. Spleen cells from young (3-5 months) and old (22-27 months) mice were assessed in cultures, both in vivo and in vitro, for their anti-sheep RBC response separately and in mixtures. Pooled young spleens, pooled old spleens, and individual old spleens were analysed. The response of pure young spleen cells was always higher than that of pure old spleen cells (approximately 30 times). The responses of mixtures were either less than (i.e. reduced; frequency approximately 65%), comparable to (i.e. additive; frequency approximately 10%), or greater than (i.e. elevated; frequency approximately 30%) the sum of the responses given by equivalent numbers of pure young and pure old spleen cells. The reduced response was observed in mixtures containing cells from histologically normal old spleens, old spleens with tumours and old spleens with atrophic follicles. Additive and elevated responses were observed only in mixutres containing cells from histologically normal old spleens. The reduced response is explicable in terms of excessive numbers of suppressor cells in old spleens that can prevent young immunocompetent cells from responding maximally to the test antigen. The additive response can be accounted for by a reduction in number of immunocompetent cells in old spleens and/or a decrease in their functional efficiency. The elevated response can be explained by a reduction in number of at least one type of immunocompetent cell in old spleens that exists in excess in young spleens. These results indicate that there are several types of cellular changes responsible for the decrease in humoral immune activity in old mice. Pooling of old spleens, as was commonly done in the past, should therefore be discouraged. Not only might it selectively favour the expression of old spleens with an excess of supressor cells but it conceivably could result in an elevated response.


Assay of Escherichia coli enterotoxins by in vivo perfusion in the rat jejunum. Assay of Escherichia coli enterotoxins by in vitro perfusion in rats was evaluated by examining the effects of variously prepared fractions of heat-labile (LT) and heat-stable (ST) toxins on water transport in this system. The assay was found to respond equally well, in a dose-related manner, to both LT and ST; it was sufficiently sensitive to detect the toxigenic effect of concentrations as small as 1 ng/ml. With the assay, it was found that LT is produced in cultures grown under aerobic, but not anaerobic, conditions; in contrast, ST is elaborated in stationary aerobic and anaerobic broth cultures but not in those grown under agitated aerobic conditions. Both toxins can be precipitated by either ammonium sulfate or acetone. The two toxin forms were completely separated from each other by sequential ultrafiltration. LT alone (thermolabile after exposure to 100 degrees C for 30 min) was retained by a PM-30 membrane, and ST alone was present in UM-2 retentates; ST was retained more effectively by a UM-05 membrane, with a 1,000-fold increase in activity over that of the UM-2 retentate. Washed ultrafiltration retentates containing either LT or ST derived from the proper culture conditions all induced water secretion at concentrations of 100 ng or less per ml. These results indicate that in vivo perfusion in rats is a sensitive, duplicable assay for both the LT and ST forms of E. coli enterotoxin.


Cyclophosphamide pretreatment and protection against malaria. Mice pretreated with cyclophosphamide were able to overcome infection from a lethal malarial strain. The development of resistance was preceded by increased hypersensitivity to malarial antigens. Hypersensitivity was demonstrable by a delayed footpad swelling technique.


Association of viable and inactivated Salmonella typhimurium 395 MS and MR 10 with HeLa cells. The mouse-virulent Salmonella typhimurium 395 MS, containing a complete lipopolysaccharide (LPS) structure with S-specific repeating units, and the nonvirulent, LPS-defective mutant 395 MR 10 (chemotype Rd), derived from it, were studied for their tendency to interact with HeLa cells. In the definition of interaction no distinction has been made between intracellular and cell membrane-attached bacteria. R10 bacteria were found to have a greater tendency to interact than MS bacteria. This difference was seen as early as 1 h after the start of incubation, but it became more pronounced beyond 3 h. Heat-killed and ultraviolet-killed R10 bacteria interacted with HeLa cells less than living ones. Killed MS bacteria interacted to an extent similar to that of living ones. These results are discussed in relation to the susceptibility of the bacteria to phagocytosis by professional phagocytic cells and to the physiochemical properties of the bacteria as measured by their distribution in a two-polymer, aqueous-phase system.


In vitro growth inhibition of mastitis-causing coliform bacteria by bovine apo-lactoferrin and reversal of inhibition by citrate and high concentrations of apo-lactoferin. Bovine apo-lactoferrin (apo-Lf) was added to in vitro cultures of eight strains of coliform bacteria associated with bovine mastitis. As little as 0.02 mg of APO-Lf per ml resulted in marked inhibition of growth of all coliforms. Growth inhibition was lost if saturated Lf or iron plus apo-Lf was added to the synthetic medium. The inhibition of growth increased as the concentration of apo-Lf increased from 0.02 to 0.2 mg/ml for Klebsiella pneumoniae (OARDC-A1), Klebsiella spp. (K1-21), and Aerobacter aerogenes (55-12222) and 2 mg/ml for A. aerogenes (76-2414-1), Escherichia coli (60-Lilly), E. coli (66-S16), and Klebsiella spp. (K6-24). As the concentration of apo-Lf was increased above 0.2 or 2 mg/ml, there was less inhibition of growth except for E. coli (33-C4). Apo-Lf at 20 mg/ml was bactericidal for E. coli (33-C4). Results are compatible with the hypothesis that coliform bacteria respond to low-iron environments by production of iron-sequestering agents that complete effectively with apo-Lf for free iron. Addition of apo-Lf plus citrate resulted in loss of growth inhibition. The molar ratio (citrate to apo-Lf) was found to be more important than the absolute concentration of either component. A ratio of 75 resulted in 50% growth inhibition, whereas ratios of 300 and greater resulted in less than 10% growth inhibition. These results suggest that the ratio of citrate to Lf would be important in evaluating Lf as a nonspecific protective factor of bovine mammary secretions.


T cells and protective immunity to Plasmodium berghei in rats. Experiments were carried out in which unfractionated spleen cells, and T lymphocyte subpopulations characterized by certain experimental criteria, were isolated at various times from rats infected with Plasmodium berghei. By adoptive transfer it was shown that unfractionated spleen cells, and T cells alone, could transfer protection to syngenic recipients as early as 11 days after infection of the cell donors. The protection conferred by T cells increased with the duration of the infection in the donors, at least up to 100 days. The additional presence of B cells in transferred lymphocyte populations enhanced their protective capacity over that shown by T cells alone. The role of T cells in protective immunity to malaria is discussed.


A less radical surgical approach to the solution of prosthetic problems. Pre-prosthetic surgery is but an aid to good prosthetics and patients requiring it are often elderly and/or infirm. Prosthetic requirements should govern both the design and the amount of surgery undertaken to facilitate the insertion of a satisfactory and successful denture. The manner in which the author relates his practice to these concepts is described.


Selective inhibition of T lymphocyte repopulation of lymphoid organs as a mechanism of immunosuppression in tumor-bearing mice. The mechanism of selective suppression of T-cell activity in Ehrlich tumor-bearing mice was investigated in an adoptive cell transfer system of secondary antibody responses to haptens. The induction of secondary antidinitrophenyl (DNP) antibody response after stimulation with DNP-homologous carrier (TD) of thymus-dependent DNP-carrier (TD)-primed spleen cells was markedly inhibited in tumor-bearing recipient mice, whereas the response to thymus independent DNP-carrier (TID) was intact as compared to that seen in normal recipients. However, if tumors were induced in the DNP-TD-primed donor mice and the spleen cells were assayed for responsiveness to DNP-TD in normal recipients, they generated a normal anti-hapten antibody response. After the DNP-TD-primed cells had been transferred into normal recipients and tumors had been induced in the recipients before DNP-TD-stimulation, the cells in tumor-bearers responded normally. These results indicate that the tumor-bearing state neither directly suppresses the responsiveness of primed cells nor interferes with the mechanism for antigen stimulation of primed cells. Direct measurement of recovery of transferred primed T and B cells from the spleen of tumor-bearing recipients revealed that the net recovery of T-cell activity markedly decreased, whereas the recovery of B cells in the spleens of tumor-bearing hosts was not affected or was even higher than the normal. Prevention of repopulation by T lymphocytes of lymphoid organs due to a postulated change in the microenvironment is suggested as a mechanism for the selective suppression of T-cell activity in Ehrlich tumor-bearing animals.


Influence of cell-free tumour-associated antigen preparations on the development of immunity to chemically induced rat tumours. Inbred rats were treated with extranuclear tumour membrane fractions or 3 M KCl-solubilized extracts of two antigenically distinct 3-methylcholanthrene-induced sarcomas, Mc7 and Mc57. The rats developed tumour-specific humoral antibody responses, but were not immune to tumour challenge. Moreover, they were unresponsive to subsequent immunization with irradiated tumour grafts, this effect being immunologically specific for the tumour from which the cell-free extracts was derived. In vitro studies revealed a depressed state of cell-mediated tumour immunity in animals inoculated with cell-free tumour extracts, and this was associated with the presence of serum inhibitory factors and suppressor lymphoid cells which abrogated the cytotoxic effect of sensitized lymphoid cells in vitro. It is postulated that the development of an inappropriate immune response due to the effect of tumour antigen during the induction phase of tumour immunity may be relevant to the immunobiology of tumour-bearing hosts.


Desoxymethasone: a new topical corticosteroid. In a double-blind controlled trial, desoxymethasone was compared with betamethasone valerate in 50 patients with bilateral acute dermatitis using a "within patient" type of comparison. The topical efficacy of desoxymethasone was somewhat greater than that of betamethasone valerate. It was well tolerated and produced no local side effects.


Epidemics of Mycoplasma pneumoniae infection in Denmark from 1958 to 1974. The study is a retrospective and prospective serological investigation of the incidence of Mycoplasma (M.) pneumoniae infection in Denmark during a 17-year period. By least square multiple regression analysis it was shown that four major outbreaks or epidemics had occurred which culminated at regular intervals of four and a half years. The study was based on cold agglutinin (CA) positive sera tested for antibodies to  M. pneumoniae by an indirect immunofluorescence (IF) test, an indirect haemagglutination (IHA) test or a complement fixation (CF) test. By the criteria chosen for a positive test, the CF test was found to detect more cases than the IF or IHA tests. A shift during the study from the latter two tests to the CF test influenced the incidence, but not the periodicity of epidemics. The consequence of including only CA positive sera in the study was investigated.


Time-blind analysis of TV-stored interviews. An objective method to study antidepressive drug-effects. A new method of evaluating the time course of an antidepressive drug effect is described. It has the advantage that the rater is "blind" as to the duration of the treatment (time-blind analysis). TV-stored tapes of interviews recorded during the drug trial were presented in a randomized sequence to raters who ranked each patient's tapes in terms of the degree of depression shown during the interview. Patients treated with Amitriptyline showed a continuous amelioration of depression throughout the drug trial while those treated with Mianserin showed an amelioration of depression that was not constant in time.


Immunofluorescent studies on the trabecular meshwork in open-angle glaucoma. The trabecular meshwork of eyes with open-angle glaucoma has been demonstrated to have an increase in gamma globulin and plasma cells, raising the question of an immunogenic mechanism in this disorder. In the present study, however, immunofluorescence assays on the trabecular meshwork of eyes with open-angle glaucoma were negative for specific immunoglobulins and for complement components that would result specifically from an antigen-antibody reaction. The study fails to provide any evidence in support of an immunogenic mechanism in open-angle glaucoma.


The role of denervation in renal transplantation on renal function in the dog. The role of denervation in renal transplantation on renal function in the dog was assessed in a controlled study. There was no significant difference between innervated and denervated kidney with regard to effective renal plasma flow, glomerular filtration rate, and urinary potassium excretion. However, urinary sodium excretion was elevated, and a significant increase in urinary bicarbonate excretion was observed in the in situ denervated or autotransplanted kidney compared with the innervated control kidney. Denervation rather than either tubular damage from the transplantation procedure or a decreased glomerular filtration rate probably is responsible in part for the observed posttransplant urinary sodium and bicarbonate loss and its associated metabolic problems.


[Herpes gestationis. Immunopathologic studies in mother and child]. Herpes gestationis is a nosologically undefined uncommon bullous disease in pregnancy. In a patient with herpes gestationis C3, C5 und C9 deposits could be demonstrated by immunohistological methods at the epidermal basement membrane (BM). Deposits of immunoglobulins, properdin and C3PA were absent. Autoantibodies against BM were found in the serum of the mother by using rabbit oesophagus but not with normal human skin as antigen. In the sera of mother and child a factor could be demonstrated which in vitro leads to complement fixation in human epidermal BM. Immunopathological findings may speak in favor of a nosological entity of herpes gestationis with respect to dermatitis herpetiformis and bullous pemphigoid.


[Comparative studies of human finger and nail imprints on pottery fragments of the late copper period]. The author has established on the basis of comparative investigations--called "archeodactyloscopy"--that in the past 4,500 years, which corresponds to 214 generations, the appearance of the fingertips (dactylogram) did not change. The making of pottery found at Salgotarjan-Pecsko's excavation was supposedly the task of men, while the nail-impressions on two torsos could have been left by women or by children.


References to dentistry in the Bible and Talmud. References were brought from the Bible and Talmud which prove that distinctions--morphological and functional--were recognized between incisors, canines, and molars. Diseases of the gums and pains originating from the teeth were cited from the Talmud. Examples were brought which show a clear distinction between a physician and a technician and also forms of healing and tooth-restoration were described. It is interesting that throughout most of these examples the dental patient is invariably a woman. Little has changed in this respect up to the present day, and, the woman still remains the dentist's most frequent patient.


[IgE and the significance of the radio-allergo-sorbent-test (RAST)]. In 1966 a new immunoglobulin was found in persons with allergies and in non-typical myeloma proteins. Normally this immunoglobulin E is present only in nanogramms and rests with predilection on the membrane of mast-cells. There is a reaginic-anaphylactic reaction after re-exposure of antigens to the antigen-antibody reaction followed by denudation of mediators of the anaphylactic reaction. With the Radio-Immuno-Sorbent-Test (RIST) the IgE can be quantitatively determined. Elevated IgE-blood levels are typically found in atopic eczema. With the Radio-Allergo-Sorbent-Test (Rast) the allergen specific IgE can be defined. A conformity with appropriate patchtests can be achieved in 60-80% of the cases. In this review advantoses and problem of RIST- and RAST-diagnoses are described. RAST represents a valuable aid in diagnosis of allergies beeing not burdensome and risky, as it is easy to perform and bears no risk to the patients. At the present time, however, patch tests are necessary in the diagnosis of allergies.


Ultrastructural localization of adenyl cyclase activity in the pancreas of two amphibian species (Salamandra salamandra L. and Rana esculenta L.). The distribution of adenyl cyclase activity in the pancreas of one species of urodeles and anura has been investigated using electron microscopy. In both islet and acinar tissues the reaction product was located at the outer cell surfaces, while in nerve bundles it occurred in the cleft between axolemma and Schwann cell-extensions. The functional signification of the enzyme localization is discussed in relation to the findings of other authors.


Immunofluorescent localization of hepatitis B antigens in chimpanzee tissues. Three chimpanzee chronic carriers of hepatitis B surface antigen (HBs Ag) were examined by immunofluorescent techniques to determine the localization of HBs Ag and hepatitis B core antigen (HBc Ag) in their tissues. All specimens were quick-frozen in liquid nitrogen and stored at -70degrees until sectioned. Frozen sections were prepared and stained for examination by fluorescent microscopy. For staining, anti-HBs and anti-HBc labeled with fluorescein isothiocyanate were used. HBs Ag was found in the liver of all three animals. In two animals which were necropsied, HBs Ag was detected in other tissues, e.g., lymph nodes, spleen, and kidney. Specificity of these tests was demonstrated by blocking with purified HBs Ag. Examination of various tissues revealed HBc Ag only in the liver. 32 samples of liver, from different sites from one chimpanzee, were examined and all were positive for both HBs Ag and HBc Ag. The finding of HBc Ag only in the liver further supports the assertion that the liver is the sole site of replication of hepatitis B virus in chronic carriers.


Light- and electron-microscopic studies on the formation of "dark" variants of chromaffin cells in the rat adrenal medulla. "Dark" cell formation has been studies in the adrenal medulla with combined light- and electron-microscopic methods. Correlation between light- and electron-microscopic appearance has been demonstrated. It has been pointed out that the formation of "dark" cell artefact can be prevented during immersion fixation and can be produced also during perfusion fixation by appropriate physical conditions. "Dark" cell formation was elicited by prefixation cooling and/or by increased tissular pressure. The nature of the underlying physicochemical change was interpreted as a uniformly distributed sol-gel transition of cytoplasmic macromolecules. The formation of cytoplasmic gel structures can be considered an endothermic process which involves volume increase (+ deltaV) - as may be inferred by their susceptibility to solation by high pressure and low temperature.


Histochemical lectin affinity technique by means of FITC-labeled serum protein fractions. A two-step affinity technique is described for light microscopic demonstration of the Concanavalin A, Agaricus bisporus lectin and Ricinus communis lectin binding sites by means of various FITC-labeled human and rabbit serum protein fractions. Experiments for the visualization of the Lens culinaris lectin and the Pisum sativum lectin binding sites gaves negative results. The technique consist of two reaction steps which involve the incubation of tissue sections in the lectins followed by the visualization of receptor-bound lectins with FITC-labeled serum protein fractions basing on their carbohydrate content. The specificity of the technique could be demonstrated by the addition of the hapten or by incubation in the FITC-labeled serum protein fractions only. In contrast to the direct or indirect staining methods only very small amounts of purified lectins are necessary.


A historical note on the iodine-sulphuric acid reaction of amyloid. The historical development of the iodine-sulphuric acid reaction for amyloid is described. The reaction dates back to 1814 when Colin and Gaultier de Claubry, and independently Stromeyer, introduced the iodine reaction for starch. A variant of the acidified iodine reaction appears to have been used for printing paper by Gmelin in 1829, and in 1838 Schleiden used the iodine-sulphuric acid test on plants to demonstrate what he considered to be a transformation of the plant material into starch. Shortly afterwards Payen (1839) defined "cellulose", and the iodine-sulphuric acid reaction became a standard procedure used by botanists to demonstrate this plant component. In 1853 Virchow used Harting's (1847) procedure to demonstrate the reaction of Purkynĕ's corpora amylacea to this test, on the assumption that they might be cellulose derivatives, and applied it to what appeared to be similar corpuscles in a "waxy" spleen. The first histochemical reaction for amyloidosis had thus been introduced into pathology, and continued to exert from that time on an important influence on amyloid research, whose impact is felt to the present day.


Pancreatic APUD cells in older chick embryos, with special reference to their identity. Pancreatic APUD cells showing formaldehyde-induced fluorescence in Black Australorp chick embryos of nine to eighteen days of incubation, proved, on subsequent staining and silver impregnation, to be A, B, D and, from sixteen days, enterochromaffin (EC) cells. EC and D cells were scattered in the exocrine parenchyma, the latter cells increasing with time. Some group of B cells were associated with large A islets from the ninth day of incubation onwards. The composition of A islets (A and some D cells) and B islets (B and some D cells) and the distribution attained (A islets in the splenic and third lobes; B islets in all lobes), accords with the situation reported for adults.


Enterochromaffin cells as the endocrine source of gastrointestinal substance P. Immunoreactive Substance P is localized in the intramural neural plexuses of mammalian intestine, and in endocrine cells in the intestinal mucosa which have now been identified as enterochromaffin (EC). The presence of a neurotransmitter peptide in these cells favours the hypothesis of their neuroectodermal origin.


[The operative management of laryngo-tracheal stenosis (author's transl)]. The different types of laryngo-tracheal stenoses are grouped by etiology and operative procedures for correction. The operations used are described in detail, and our experiences analysed.


[Reconstruction of the nose by forehead skin flaps (author's transl)]. On introduction the advantages and disadvantages of forehead skin in reconstructive rhinoplasty are presented. The median frontal flap described by Kazanjian, a horizontal or slightly oblique frontal flap, the frontotemporal flap described by Schmid and the scalp flap described by Converse are discussed. After detailed description together with illustration of various techniques it is shown that each method can be used for specific indications. The choice of method by the less experienced is therefore facilitated. A. The median frontal flap is especially indicated for the grosser perforating defects of the external nose. B. The fronto-temporal flap is especially indicated for subtotal or total defects of the nasal alae, tip and columella of the younger patients who expects a good cosmetic result. C. The horizontal or slightly oblique frontal flap is especially indicated for subtotal or total defects of the nasal alae or tip of the older patient, who cannot undergo repeated surgery or prolonged hospitalisation. D. The frontal scalp flap is especially indicated for the grosser subtotal defects of the external nose.


Structure-activity relationships among negamycin analogs. Various negamycin analogs were examined for (1) miscoding activity and (2) inhibition of the termination of protein synthesis. Since properties (1) and (2) do not correlate for the investigated compounds they may depend on different structural features of negamycin analogs. The results of biochemical and antimicrobial studies indicate that (a) the natural configuration of the carbon atom carrying the beta-amino group is essential, (b) the delta-hydroxyl group is unnecessary, and (c) the acylation of the epsilon-amino group causes loss of activity.


Integration of chemoreceptor stimuli by caudal pontile and rostral medullary sites. Ventilatory regulation by pontile pneumotaxic and apneustic centers and by rostral medullary sites was evaluated in intercollicular decerebrate cats. Following pneumotaxic center ablation, PAco2 was significantly elevated. Moreover, in response to hypercapina or hypoxia, frequency responses were significantly diminished whereas tidal volume responses were unchanged or elevated. Interruption of apneustic center function by caudal pontile transection or radiofrequency lesions in the caudal pons and/or rostral medulla resulted in significant decreases of tidal volume responses and significant elevations of frequency responses to both hypercapnia and hypoxia. Neither minute volume responses nor the PAco2 level was altered. It is concluded that the apneustic center exercises a primary role in the brainstem definition of tidal volume responses for both peripheral and central chemoreceptor afferent stimuli. The apneustic center is also considered to exert an impoetant function in the definition of respiratory frequency. A medially placed pathway in the rostral medulla is proposed to interconnect the apneustic center with the medullary respiratory nuclei.


Impedance cardiography for determination of stroke index. Stroke index obtained by impedance cardiography was compared with values obtained by dye-dilution technique in 17 subjects in 122 determinations made within 2 min of each other. Fifty of these determinations were done after drug administration, postural change, or saline infusion. All values obtained by both methods correlated significantly, but with wide scatter (r=0.49, n = 122, P less than 0.001). The series of determinations within each subject, however, correlated only in one subject significantly; thus any changes of stroke index measured by both techniques were not commensurate. In addition, the impedance stroke index values were significantly lower than the dye-dilution technique, impedance cardiography presently does not determine reliably absolute values of stroke index and is not suitable to evaluate changes of stroke index.


Colorimetric method for the determination of ethylene dibromide residues in grains and air. A method based on the hydrolytic debromination of ethylene dibromide (EDB) in the presence of an oxidizing agent has been developed. Bromine liberated from inorganic bromide is used to brominate p-rosaniline. The intensity of the resulting violet-red bromo compound in chloroform is measured at 580 nm. The relationship between absorbance and concentration of EDB is linear in the range of 5-60 mug. The method is very sensitive and as little as 0.50 ppm unchanged EDB residue in a 20 g sample of fumigated grain and 1 ppm EDB in a 10 ml air sample can be detected.


The genetics, if any, of infantile autism and childhood schizophrenia. A critical examination of the data for and against genetic factors in early infantile autism and childhood schizophrenia is presented. The extreme rareness of both disorders made analysis difficult. No strong evidence exists implicating genetics in the development of childhood psychoses that begin before the age of 5. Family pedigree data fail to support psychogenic transmission because very few siblings of early onset cases are affected. Biological but not genetic etiological agents are more likely. Genetic factors are implicated in the development of psychoses that begin near pubescence and such factors appear to overlap with those for adult schizophrenia. Reevaluation of the minimum age of onset for adult-type schizophrenia is suggested.


Control of replication and segregation of R plasmid Rts1. A mutant plasmid, pTW2, which was derived from the integrated Rst1 genome in the Escherichia coli chromosome, was studied as to its mode of replication at 30 degrees C. When Proteus mirabilis Pm17 harboring pTW2 was grown in broth at 30 degrees C, a considerable number of R- segregants (approximately 40%) were consistently observed. This indicates that pTW2 is unstable even at the permissive temperature for the replication of Rts1. The pTW2+ cells in a culture were heterogeneous with respect to the level of kanamycin resistance, ranging from 500 to 4,000 mug of the drug per ml. The amount of pTW2 deoxyribonucleic acid (DNA) relative to the Pm17 chromosomal DNA was about fivefold as large as that of Rts1 DNA in an exponentially growing culture. In addition, pTW2 in P. mirabilis continued to replicate after the chromosome had ceased to replicate, which was shown in the study of the inhibition of protein synthesis. Contrary to pTW2, the parent plasmid Rts1 is highly stable, and the relative percent Rts1 DNA is maintained at approximately 7% in any cultural conditions at a permissive temperature. These results suggest that copies of pTW2 may not segregate evenly into the host progeny upon cell division and that the replication of pTW2 does not coordinate with that of the chromosome. A remarkable instability of pTW2 as well as an increase in the relative percent pTW2 DNA was also shown when E. coli were used as the host cells. These results suggest the possibility that there is a gene or a gene cluster on the Rst1 genome responsible for the control of both replication and segregation of Rts1.


lacY mutant of Escherichia coli with altered physiology of lactose induction. A mutant of Escherichia coli is described that grew on lactose only in the presence of isopropylthiogalactoside. This cell contained a defect in the lacY gene that resulted in the formation of a transport system with a poor affinity for lactose. The inability to grow on lactose alone was due to the failure of induction by this disaccharide. This failure of inducation was presumably due to a defect in lactose accumulation which resulted in significant reduction in the formation of allo-lactose, the true inducer of lac operon. These results are consistent with the view that the capacity to accumulate lactose plays an important physiological role in the induction of the enzymes necessary for its utilization.


Chromosome segregation in Escherichia coli B/r at various growth rates. Chromosome segregation was analyzed in three substrains of Escherichia coli B/r growing at various rates. The cultures were pulse labeled with [14C]thymidine and bound to the bottom surface of a nitrocellulose membrane filter, and the radioactivity in newborn cells released from the surface during continuous elution with growth medium was measured. Since there was a fixed orientation in the release of newborn cells, the time course of the change in radioactivity per effluent cell could be used to investigate the orientation of chromosome segregation. If the radioactive deoxyribonucleic acid strands were partitioned at random between the progenies remaining attached to the membrane filter and those released into the effluent, the radioactivity per cell would decrease twofold after each generation of elution. The decrease in radioactivity was less than twofold at C + D min of elution and larger than twofold one generation later, indicating that chromosome segregation was nonrandom.