The interactions of ticlopidine and aspirin in normal subjects. This trial was performed on 24 health volunteers in order to study the possible interactions between aspirin and ticlopidine. The results confirm the inhibitory activity of aspirin on collagen-induced aggregation and that of ticlopidine on ADP-induced aggregation. If aspirin does not modify the inhibitory effect of ticlopidine on ADP-induced aggregation, ticlopidine on the other hand potentiates the effect of aspirin on collagen-induced aggregation.


Tinidazole and metronidazole in the treatment of amoebic liver abscess. Tinidazole, a new drug effective against E histolytica, was studied in patients with amoebic liver abscess proved by aspiration of pus. A preliminary open evaluation in fourteen patients provided a cure in all cases. A subsequent comparative study against metronidazole in another twenty-two patients led to a cure in all eleven patients treated with tinidazole and in ten out of eleven patients treated with metronidazole. The response was faster in patients treated with tinidazole. Tinidazole was totally free from side-effects. Tinidazole is a noteworthy addition to anti-amoebic therapy.


A comparison of a short course of single daily dosage therapy of tinidazole with metronidazole in intestinal amoebiasis. Sixty patients with symptomatic intestinal amoebiasis were treated for 3 days with a single dose of 2 g of either tinidazole or metronidazole respectively by random order. Tinidazole cured 90% of patients (27/30) an metronidazole cured 53.3% of patients (16/30). The difference was significant (p less than 0-01). Mild side-effect were reported by 26-7% of patients (8/30) in the tinidazole group as compared to mild to moderated side-effects reported by 53.3% of patients (16/30) in the metronidazole group. The difference was statistically significant (p less than 0-05). As the average patient has only a limited understanding and toleration of extended treatment courses, the advantages of a short course employing a single daily dose are obvious. With such a regimen, tinidazole was found to be superior to metronidazole in intestinal amoebiasis.


Single-dose treatment of trichomonal vaginitis: a comparison of tinidazole and metronidazole. A randomized, comparative trial was carried out in 100 patients with trichomonal vaginitis to compare the efficacy and toleration of a single 2 g dose of tinidazole and metronidazole. Tinidazole produced parasitological cure in 94% of patients (47/50) and a satisfactory clinical response in 96% of patients (48/50); for metronidazole the figures were 64% (32/50) and 72% (36/50) respectively. Side-effects were reported by 52% of patients (25/50) on tinidazole and 82% of patients (41/50) on metronidazole. Severity of side-effects and their frequency per patient were significantly less (p less than 0-045 to 0-01) with tinidazole than with metronidazole. Statistical evaluation of the results showed that tinidazole was significantly better than metronidzole with respect parasitological cure (p less 0-01) and clinical improvement (p less than 0-01) and also with regard to the incidence and intensity of side-effects (p less than 0-01).


The use of loperamide for treatment of "difficult to manage" chronic diarrhoea in adults. An open study of loperamide in seven chronic diarrhoea patients who were inadequately controlled by previous anti-diarrhoeal therapy is reported. All patients were well controlled by small amounts of loperamide and most could not eat a normal diet. No side-effect were reported.


Once daily administration of pindolol in the treatment of hypertension. An open study was carried out in general practice on patients with mild to moderate essential hypertension to assess the effectiveness of treatment with pindolol on a single daily dose regimen. In twenty-two previously untreated cases given a single daily dosage of pindolol (mean 13-0 mg, range 5 mg- 30 mg), adequate blood pressure control was achieved within five weeks and maintained in the nineteen patients examined at Week 25. Of eleven previously treated patients whose blood pressure was adequately controlled by divided daily doses of pindolol, a change-over to a single daily dosage of pindolol (mean 13-2 mg, range 10 mg-20 mg) did not result in any loss of control over a twenty-five week study period. Few side-effects were reported, and only one patient was withdrawn from the study.


Standards of cleansing and sterilization of infant feeding utensils in the home. Microbiological standards achieved by mothers when sterilizing babies' feeding utensils in the home were studied in the Slough area in England. Results indicated a marked improvement in this aspect of baby hygiene when compared to results of a similar survey conducted in the town of Reading, England, in 1970. Previously, 78% of bottles and 70% of the teats were recorded as being satisfactorily sterilized. During this study the number of sterile bottles had risen to 98.1%, sterile teats to 90-6%. These improved standards may be an indication of better education of mothers.


Efficacy, side-effects, plasma and blood levels of maprotiline (Ludiomil). Two trials of maprotiline (Ludiomil) were performed in general practice. In the first study depressed patients were given either 75 mg of maprotiline in a single dose or 25 mg three times daily. Assessments of the severity of depression and of side-effects were made initially and following 1, 2 and 4 weeks' treatment. At each assessment measurements of plasma levels of maprotiline were made. A second trial was performed in which some patients receiving 75 mg single dose of maprotiline had whole blood levels of maprotiline assayed. Steady-state levels of maprotiline were achieved after one week but these levels showed considerable individual variability. No clear correlation emerged between clinical response, side-effects and plasma or blood levels. Some of the factors which may be responsible are discussed.


The treatment of Depression comparing divided and single doses of maprotiline (Ludiomil). A clinical trial of seventy-five patients suffering from depressive illness and treated with maprotiline (Ludiomil) is reported. Twenty-eight patients were given a single nightly dose of 75 mg and twenty-six patients were treated with 25 mg three times daily. Twenty-one patients withdrew from the trial. It was found that those patients on the nocte regime made greater improvement than those on the divided dosage. Sleep disturbances and mood swings were significantly improved on the nocte dosage. Both regimes were equally well tolerated. Special care was taken in recording any adverse drug effects in order to distinguish these from pre-existing symptoms of the illness.


Maprotiline (Ludiomil) in depression: a report of a monitored release study in general practice. In a three-week study of 10,000 general practice patients with depressive illness, a once nightly dose of maprotiline 75 mg (Ludiomil) was effective therapy in three-quarters of the patients who completed the study. At this dose the drug was well tolerated, and troublesome side-effects presented in only a small percentage of patients. Drowsiness was the most commonly reported side-effect, and the main reason for stopping treatment. The drug was acceptable to most physicians, and in this study was used in a wide age range of patients and over a broad spectrum of depressive illness.


Maprotiline (Ludiomil) in depression: a multicentre assessment of onset of action, efficacy and tolerability. Although open studies have a built-in bias of optimism the results from this study, made valid by the large numbers of patients involved, support the findings reported with smaller numbers in controlled series of studies showing an early onset of action with maprotiline (Ludiomil). The method used in this study to detect unwanted effects indicates that maprotiline is well tolerated. In summary, the efficacy of once daily dosage, the good response in differing types of depressive illness, the early onset of effectiveness without serious side-effects in a wide age range of patients suggests that this drug will be a useful addition for the treatment of depressive illness in general practice.


A comparison of Ludiomil, Tryptizol and Lentizol. One hundred and seventy-six patients were admitted to an open, multicentre, comparative trial of Ludiomil, Tryptizol SR and Lentizol, each administered in a dose of 75 mg at night. Fifty-seven patients received Tryptizol SR, 60 received Lentizol and 59 received Ludiomil. Nine patients on Tryptizol SR, 10 patients on Lentizol and 6 patients on Ludiomil dropped out for a variety of reasons. A seventeen-symptom rating scale was used and the symptoms analyzed individually. A greater response in the severity and number of symptoms was seen in the first week of treatment on Ludiomil though the differences rarely reached the acceptable level of statistical significance. Global assessments did not reveal any differences between the groups. Side-effects were also similar. Only dry mouth and drowsiness were persistent problems.


Synthesis and release of gonadotropins and their subunits by long-term organ cultures of human fetal hypophyses. From weeks 13 to 26 of fetal life human hypophyses disclosed a constant content of radioimmunoassayable FSH. Although present already before this period, LH content increased considerably at week 17, along with the appearance of free beta-LH. In long-term organ culture experiments such early differentiating pituitaries proved to be endowed with autonomous synthesis and release of FSH and of free alpha-subunit, while LH, beta-LH and TSH declined to very low levels within a few weeks. Supplementation of the medium with LH-RH (12 ng/ml) significantly increased FSH synthesis and release but was not sufficient to sustain production of beta-LH and LH. It is suggested that other factors than LH-RH are required for differentiation of beta-LH biosynthesis and thus for production of LH.


Separation of non-melatonin antiovulatory substances from bovine pineal powder by ultrafiltration. An attempt was made to partially separate substances which inhibit the induced ovulation by PMS and hCG in immature mice from the sodium borate buffer extract of bovine pineal powder by means of ultramembrane filtration. The antiovulatory activities were concentrated in fractions which possess materials of a molecular weight greater than 10,000 and also in fractions containing substances of a molecular weight less than 1000. The proteinaceous large inhibitor was thermostable while the small inhibitor, which is different from melatonin or arginine vasotocin, was inactivated by heating.


Biological and immunological characterization of human luteinizing hormone: II. A comparison of the immunological and biological activities of pituitary extracts after electrofocusing using different standard preparations. The profile of immunologically active human luteinizing hormone (hLH) was determined in aqueous pituitary extracts after electrofocusing using two radioimmunoassay systems and the estimates for each fraction were compared to those obtained by an in vitro bioassay method. Similar biological and immunological profiles were obtained in the pH 7.0-9.0 region, where most of the biological activity was present. Biological to immunological (B/I) ratios ranging from 0.6 to 1.7 (mean ratio 1.01; n = 21) were found in the major biologically active fractions of this pH region when a highly purified human pituitary LH preparation (68/40) was used as standard in both types of assays. The close proximity of these ratios to unity indicates a similar composition of biological and immunological activities in all these fractions in relation to that of the highly purified standard. However, marked discrepancies were observed in the pH region 3.0-7.0 where the B/I ratios ranged from 0.1 to 0.9, indicating the presence of immunological activity associated with relatively little biological activity. When impure human LH preparations of pituitary (69/104) and urinary (hMG 2nd IRP) origin were used as standards for the bioassay and radioimmunoassay of the hLH present in the major fractions of the pH region 7.0-9.0, significantly higher B/I ratios were obtained than with the use of the highly purified standard (68/40). These elevated B/I ratios are attributed to the presence in the impure standard preparations of immunological activity, which is associated with little or no biological activity. These observations may provide an explanation for the differences in B/I ratios which were reported for hLH in plasma, using different standard preparations.


Diabetes mellitus in an urbanized, isolated Polynesian population. The Funafuti survey. An epidemiologic study of diabetes in the urbanized Polynesian population of Funafuti has established a prevalence of 8 per cent in subjects aged 10 years and over. Of these, 0.9 per cent were known diabetics, and the remainder were diagnosed on the basis of a plasma glucose level of at least 160 mg./100 ml. two hours after a 75 gm. glucose load. A further 5.9 per cent had borderline diabetes as judged by a two-hour postload plasma glucose of 140-159 mg./100 ml. In those aged 20 years and over, the prevalence of diabetes was 10.1 per cent, similar to that reported in other acculturated Polynesian groups. The prevalence of both borderline diabetes and frank diabetes was twice as high in the females as in males. This difference appeared to be related to the greater degree of obesity in the females, but the prevalence was not related to parity. The increase in frequency of diabetes among these islanders coincides with a change of traditional island life style to that of urbanized Western populations. The results suggest that there may be 10 times the actual number of known diabetics in some Pacific populations.


Insulin and brain metabolism. Absence of direct action of insulin on K+ and Na+ transport in normal rabbit brain. In fed, unanesthetized rabbits, regular zinc insulin, 50 U./kg. intravenously, decreased plasma glucose levels 52 per cent, p = 0.002, 35 minutes after injection. In 15-hour-fasted, unanesthetized animals, the same dose of insulin decreased plasma glucose levels 68 per cent, p less than 0.001. Plasma K+ concentration was not affected by insulin injection in the fed animals; in fasted rabbits, plasma K+ levels fell 26 per cent, p = 0.006. Despite this unequivocal evidence of insulin action in both sets of animals, there was no change in the K+, Na+, or H2O content in the brains of the same animals 35 minutes after insulin injection. These results, which give no evidence of a direct effect of insulin on electrolyte transport in brain, are in sharp contrast with those found in anesthetized rabbits, which suggested that insulin affects brain potassium and water content before any change in plasma glucose occurs.


Bone mass and bone density in maturity-type diabetics measured by the 125I photon-absorption technique. Bone mineral content (BMC) and bone density (BMC/W) of the radius were measured in 138 maturity-type diabetics with the Norland-Cameron bone mineral analyzer and compared with the results of age- and sex-matched controls. In some age groups the mean cortical and trabecular bone mass and density seemed to be significantly higher among diabetic patients, especially in those treated with oral antidiabetic agents. Individual analysis reveals the existence of two distinct diabetic populations--a small group with a tendency to bone loss and a large group with bone gain--when compared with nondiabetic subjects. The higher body weight in the second group can be the origin of this difference. A survey of the already published papers on this subject shows that comparison of the results is impossible because of the heterogeneity in the methodology of material and methods used by the different authors.


Autonomic neuropathy and painless myocardial infarction in diabetic patients. Histologic evidence of their relationship. Myocardial infarction is considered the prime cause of death among adult diabetic patients. In a great number of cases, during myocardial infarction the patients don't feel pain or it is atypical. Diagnosis can be neglected, and mortality increases. In search of an explanation for the absence of pain in these patients, the authors studied the autonomic nerve fibers of the heart muscle with argentic and combined techniques, looking for lesions in the sympathetic or parasympathetic nerve fibers that conduct pain. In the five cases of painless myocardial infarction studied, the nerve fibers showed typical lesions of diabetic neuropathy: beaded thickenings, spindle-shaped thickenings, fragmentation of fibers, and diminution of the number of fibers in the nerves. The patients in the control group (five diabetics with painful infarction, five diabetics with infarction, five nondiabetics with painful infarction, and five nondiabetics without infarction) had no lesions. These facts led us to assume that the absence of pain in diabetics with myocardial infarction could be due to a lesion of the afferent nerves that conduct pain.


Postprandial plasma-glucose and -insulin responses to different complex carbohydrates. We have studied the effects of dextrose, rice, potato, corn, and bread on postprandial plasma glucose and insulin responses in 16 subjects. All carbohydrate loads were calculated to contain 50 gm. of glucose. The data demonstrate (1) that dextrose and potato elicited similar plasma glucose responses whereas rice, corn, and bread elicited lower responses; (2) similarly, dextrose and potato elicited similar and greater plasma insulin responses than rice and corn, with the response to bread being intermediate; (3) when the study group was divided in half, on the basis of each subject's one-hour plasma glucose response to dextrose, the differences in the plasma glucose and insulin responses were greater in the subjects with the highest glucose response to dextrose than in the low responders. In conclusion, there is a range of plasma-glucose and insulin responses to different complex carbohydrates, with rice and corn producing the lowest response curves. Furthermore, these differences are accentuated in patients with reduced glucose tolerance.


Deranged insulin-secretory dynamics in offspring of two diabetic parents after double stimulation with intravenous glucose. Nine offspring of two diabetic parents and 18 normals were studied with two intravenous glucose loads (o.5 gm./kg. body weight), 60 minutes apart. By thus stressing the beta cell, subtle defects could be identified in the prediabetics: (1) An inverse relationship between insulin peak response and insulin concentration 60 minutes postglucose was seen, a phenomenon exactly the opposite to that seen in normals. (2) Insulin peak response was delayed slightly after the first pulse and significantly after the second. (3) A less effective handling of the glucose load when compared with normals was brought out by the second stimulation. (4) There was a significant reduction in the insulin response per unit change in glucose after the first glucose pulse that was accentuated after the second pulse. This double-stimulation technique amplifies previously detected slight but significant defects in insulin secretion that might help to identify a diabetes-prone population.


The monocyte as a model for the study of insulin receptors in man. We have characterized the cellular composition of preparations isolated from peripheral blood by Ficoll-Isopaque gradient centrifugation. 125I-insulin binding to every cell type was measured. A highly significantly positive correlation between specific cell binding fraction and the monocyte concentration of the heterogeneous cell suspension was demonstrated. Depletion of monocytes reduced the insulin binding approximately 80%, which confirms previous findings by other investigators. The granulocytes possessed the second highest binding ability, but only one fourteenth of that of monocytes. Compared to the lymphocyte the monocyte had about 25 times greater insulin binding. Also thrombocytes bound insulin and contamination with these meant that their contribution to the total specific cell binding was not negligible. A reduction in these contaminants is essential. We found that insulin binding to erythrocytes was insignificant. A method of calculating the specific insulin binding to monocytes alone is introduced. The monocyte-insulin-receptor possesses specificity. Only an insignificant degradation of receptor bound insulin could be shown. Evidence of negative cooperativity between receptors was found. Consequently monocytes are considered a useful model for insulin receptor studies in man.


Receptor binding and biological effect of insulin in human adipocytes. The binding of 125I-labelled insulin to human adipocytes was studied at 37 degrees C. The precipitability of the 125I-labelled insulin preparation (0.03 nmol/l) in trichloroacetic acid and the concentration of biologically active insulin (7.5 nmol/l) remained constant in buffer incubated with human adipocytes (100 microliter cells/ml suspension) for 30--60 minutes at 37 degrees C, whereas more than half of the insulin was inactivated by rat fat cells under the same conditions. A constant level of binding of 125I-labelled insulin (0.03 nmol/l) to human adipocytes was obtained after 45 minutes. The apparent dissociation constant of receptor binding was about 0.2 nmol/l as compared to about 2 nmol/l for rat adipocytes. Conversion of [UP14C]glucose to lipids was stimulated half-maximally by about 0.05 nmol/l of insulin (similar to rat adipocytes). Thus, half-maximal stimulation of human adipocytes was obtained with a recptor occupancy of about 20--30 per cent.


Streptozotocin-induced diabetes in the Chinese hamster. Biochemical and endocrine disorders. Streptozotocin treatment (125 mg/kg) in the Chinese hamster induced hyperglycaemia, hypoinsulinaemia, hyperglucagonaemia and changes in body, liver, pancreas, stomach, kidney and adipose tissue weights. The pancreatic reserves of insulin and glucagon in the diabetic animals were low, but stomach glucagon high. These animals showed high levels of phosphoenolpyruvate carboxykinase and low levels of glucokinase, hexokinase, isocitrate dehydrogenase and malic enzyme, but normal levels of pyruvate kinase in the liver. Increases in lactate dehydrogenase subunit B and isozymes 2, 3 and 4 were also observed in the liver, but not in the epididymal fat pad, of the diabetic animals. N-Acetyl-beta-D-glucosaminidase was elevated in plasma, liver and heart, but not in the kidney of the treated animals. Renal alpha-galactosidase and beta-glucosidase were depressed, whereas beta-galactosidase and alpha-glucosidase remained essentially normal. These features indicated that there were considerable differences between the biochemical disorders associated with streptozotocin-diabetes in the Chinese hamster and the published observations in the rat.


The effects of energy and carbohydrate restriction in patients with chronic diabetes mellitus. Thirty-five freshly presenting, diabetic patients received 5 hour, 100 g oral glucose tolerance tests when first seen and after a period of carbohydrate and energy restriction. After treatment, the significant improvement in glucose tolerance was accompanied by increased insulin secretion and lower concentrations of blood ketone bodies, lactate, glycerol, FFA, triglycerides, cholesterol and pre-beta lipoprotein. There were no significant changes in serum growth hormone or blood pyruvate concentrations. Improvement in glucose tolerance was greater in patients who were obese (greater than 115% of desirable body weight for height) on presentation and was related to the improvement in insulin secretion and the diminished lipolysis. An hypothesis to explain the changes in insulin secretion is prosposed. Eleven out of the 35 patients showed sufficient improvement in glucose tolerance to require no treatment other than diet.


Effect of insulin on glycogen and protein synthesis in monolayer cultures of hepatocytes from normal and alloxan diabetic rats. The effects of insulin on net glycogen synthesis and amino acid incorporation into protein were studied in cultured hepatocytes from adult normal and alloxan diabetic rats. Insulin stimulated glycogen synthesis in monolayer cells throughout a four day culture period and enhanced leucine incorporation into protein more effectively in normal cells with high glycogen levels than in cultured diabetic cells. These differences correlate well with the observed cellular ultrastructures which were maintained much better in the presence of insulin. Restoration of the morphological changes of alloxan diabetic hepatocytes to normal liver cell structures can be observed at any time during the culture period by giving insulin continuously.


Hypoglycin stimulates insulin secretion. Hypoglycin A(0.01--1.0 mmol/l) stimulated insulin release from pieces of rabbit pancreas in vitro in the presence or absence of extracellular glucose. The relevance of this finding to the hypoglycaemia of Jamaican vomiting sickness is discussed.


DNA synthetic capabilities of differentiating sperm cells. Spermatogenic cells separated by velocity sedimentation were analysed by a micro-procedure for differentiation-associated changes in DNA synthetic capabilities. DNA-dependent DNA polymerase activity is maximal in premeiotic and meiotic cells, sequentially declines in progressively more differentiated spermiogenic cells to a minimum value in testicular spermatozoa which is 1/14 of the maximum. No further decrease of activity is observed during the subsequent process of sperm cell maturation and, at the end-differentiated state, the potential of sperm cells for DNA synthesis is demonstrated by the presence of substantial activities of thymidine and thymidylate kinases as well as DNA polymerase activity, as determined by in vitro assay, are polymerase. Although levels of DNA polymerase activity, as determined by in vitro assay, are negatively correlated with the state of differentiation, the findings support the hypothesis that, in this cell system, DNA synthetic enzymes may not be limiting factors in the control of DNA synthesis.


Studies on the action of the nuclear factor promoting actinomycin D-binding capacity of chromatin. It is well known that actinomycin D binds to C-G pairs of DNA. The amount of actinomycin D bound to chromatin thus depends directly on the demasked sites of chromatin DNA. The actinomycin D binding of rat liver chromatin, obtained by the method of Dingman and Sporn, was studied in the presence and absence of liver and kidney nuclear extracts (NE). The actinomycin D binding of liver chromatin increases greatly under the action of liver nuclear extract. No changes occur in liver chromatin actinomycin D binding capacity after the action of kidney NE. The removal of protein or RNA from liver NE removes its ability to change the actinomycin D binding capacity of the liver chromatin. According to the obtained results it may be assumed that the nuclear extract contains the factor which plays a role in controlling cell differentiation.


Perturbance analysis of nuclear determination in Tetrahymena I: background, rationale, and illustrative example, employing temperature responses. A model based on comparative considerations, is presented for the nuclear determination of mating type in Tetrahymena thermophila. The model proposes a system of three binary control elements, each capable of stable persistence in one of two states. A general method is proposed for evaluating the model and for assigning particular mating types to particular compound states. Preliminary assignments of mating types are made from the responses of nuclei to temperature differentials.


Modification of pigmentation patterns in allophenic mice by the W gene. Mouse embryos heterozygous at the W locus were combined with embryos which were wild type at this locus but homozygous for albino. The resulting allophenics displayed an unusual pigmentation phenotype consisting of entirely white fur and ruby-coloured eyes. Microscopic examination showed the eye pigment to be located exclusively in the retinal epithelium, which was a mosaic of black and white sectors. This ruby-eyed white pattern corresponds to what would have been expected for WWCC in equilibrium wwcc mosaics but not for WwCC in equlibrium wwcc mice. WW mice are black-eyed whites, but Ww mice have black eyes and black fur, except for a small ventral white spot. These results suggest that melanocytes of the Ww genotype, although capable of producting normally pigmented fur in Ww animals, fail to populate hair follicles when the competition with wwcc (albino) melanocytes that are wild type at the W locus. The genotype of these WwCC in equilibrium wwcc alophenes was proved by progeny testing. This is apparently the first report of a single gene change affecting the competitive ability of cells in allophenic mice, and suggests that such changes may play a significant role in the clonal selection of embryonic cells during development.


Fertilization and preimplantation development in vitro of mouse eggs obtained following stimulation with different doses of pregnant mare serum: a comparison of the responses in two strains. Unfertilized eggs were recovered from TO and (C57BL/10 X CBA)F1 females, induced to ovulate with 0.75--10.0 IU PMS and 5.0 IU HCG/mouse, and mixed with TO sperm in vitro. Among the groups of F1 eggs, there were no significant differences in either fertilization or development to the blastocyst stage in vitro. With TO eggs, however, there was significantly lower fertility in the 0.74 and 1.5 IU PMS groups than in the higher PMS dose groups. Conversely, preimplantation development was significantly better withe low doses. To determine whether polyploidy migh affect viability in vitro, digynic polyploidy was experimentally induced in both F1 and TO eggs with cytochalasin B. Development of polyploid F1 X TO embryos to the blastocyst stage did not differ significantly form that of untreated embryos. Development of polyploid TO X TO embryos obtained from eggs stimulated with 1.5 IU PMS was still higher than that for eggs stimulated with 7.5 IU PMS. This suggests that cytoplasmic inadequacies, rather than genome imbalance, are responsible for the reduced ability of the eggs stimulated with high doses of PMS to reach the blastocyst stage in vitro.


Effect of methylnitrosocyanamide on cultured mammalian cells. Effect of methylnitrosocyanamide (MNC) on a cultured mammalian cell line was examined in comparison with that of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). It was observed that MNC was about 3 times more potent than MNNG in the experiments on toxicity and inducibility of chromosome aberration and mutation. An increase in toxicity of MNNG was observed by minimizing the elevation of pH, while toxicity of MNC was more potent in the serum-free condition than in the presence of serum. Further, MNC was shown to be extremely rapid-acting, that is, 10 min was enough to exert its toxic effect.


Protective effect of syngeneic antitumor serum on mammary tumor in a syngeneic host. The possibility of passive immunotherapy was examined using syngeneic antitumor serum, which could lyse tumor cells in co-operation with immune or activated macrophages. Intraperitoneal injection of syngeneic antiserum into mice soon after inoculation of MM46 tumor cells clearly suppressed peritoneal or subcutaneous tumor growth. However, the antiserum did not suppress an established tumor. The tumor-specific synantibody responsible for the protection was shown by gel filtration to be in the IgG fraction, not the IgM fraction.


Passive immunotherapy of established tumors with syngeneic antitumor serum in combination with immunopotentiators. The possibility of passive therapy of 6 approximately 8-day established tumors with syngeneic antitumor antiserum was tested using (1) combination  of the antiserum and immunopotentiators, (2) combination of the antiserum and inflammatory agents, and (3) repeated injections of antiserum. Therapeutic effect on an ascites tumor was seen using antiserum in combination with BCG or lipopolysaccharide, or less clearly with carrageenan. Combinations of antiserum and PS-K, histamine, or croton oil did not have a synergistic therapeutic effect, but repeated injection of a small amount of antiserum did have a therapeutic effect on established peritoneal and subcutaneous tumors.


Carcinogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine and fission neutron irradiation in rats. Examinations were made on the carcinogenic effects of a chemical compound, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and a physical carcinogen, whole-body irradiation with fission neutrons, on the gastrointestinal tract of male albino Sprague-Dawley rats. The carcinogens were used singly and together in order to investigate their possible synergistic effects on the induction of adenocarcinomas of the stomach and small intestine. Of the 13 animals treated with the chemical, MNNG, and living more than 9 months, 9 showed gross tumors (5 gastric and 4 duodenal), confirming the high incidence of gastrointestinal carcinomas induced by MNNG in the rat. There were no gastrointestinal tumors found after neutron exposure. When the 2 carcinogens were combined, no additivity or synergism occurred. After neutron irradiation, a dental syndrome with loss of incisor teeth was observed. The effect of neutron irradiation on subgingival pathology of the teeth is being investigated.


Isozymic changes of acid phosphatase and esterase in regenerating rat liver after partial hepatectomy in relation to cell differentiation. Activities and isozyme patterns of acid phosphatase and esterase were studied in rat liver at different intervals after partial hepatectomy to clarify the grade of immaturity of normal regenerating liver cells as a control for the unlimited proliferation of hepatoma cells. Acid phosphatase and esterase activities in the liver were elevated during a 12-hr period after hepatectomy, while their isozyme patterns did not change from those of immature liver. Similar findings were also observed in the liver of sham-operated rats. Eighteen hours after the operation, at the S phase before cell division, the isozyme pattern of these enzymes began to shift from an adult liver-type to an immature one resembling those of the infant liver 3 weeks after birth rather than those of newborn or fetal liver. Two or three days after partial hepatectomy, the isozymes characteristic of an immature liver type were more apparent. Although enzyme activities mostly returned to the normal adult level one week after the operation, the isozyme patterns did not completely return to those of an adult liver. These results indicate that despite the rapid proliferation of liver cells, the grade of cell differentiation of the regenerating liver after partial hepatectomy is much nearer to that of the normal adult liver rather than that of the fetal liver.


Induction of rectal carcinoma in mice by local x-irradiation. The pelvic region of random bred female ICR-JCL mice and CF1 mice was irradiated with various doses of X-rays at 1-week intervals to determine the relationship between the X-ray dose and induction of rectal carcinoma. The incidence of rectal carcinoma in ICR mice was zero after a single dose of 2,000 rad of X-rays, but 31% after a single dose of 3,000 rad, 6% after 2 doses of 1,500 rad, 25% after 3 doses of 1,500 rad, 42% after 2 doses of 2,000 rad, and 95% after 3 doses of 2,000 rad. This cancer developed in 70% of CF1 mice exposed to 2 doses of 2,000 rad. No case of this tumor was observed in the control animals not exposed to X-rays. The development of this tumor was found to depend on the X-ray exposure dose. Local X-irradiation of the pelvic region is one of the effective methods for inducing rectal carcinoma in mice. Rectal cancers induced by X-irradiation were adenocarcinoma of the tubular, papillary, and mucinous type, and frequently showed invasive growth into the deep layers of the rectal wall.


Differentiation by colchicine and vincristine sulphate of regenerative hepatocellular mitosis and tumour-associated hepatocellular mitosis. Colchicine and vincristine sulphate differentiate sharply between hepatocyte mitosis associated with the Ehrlich ascites tumour, and regenerative (post-CCl4 necrosis) hepatocyte mitosis. In the former case there is a gross depression of prophase index and a marked lowering of the overall mitotic index. In the latter, although a degree of prophase depression is evident, this is insufficient to prevent an overall substantial elevation of mitotic index due to accumulation at metaphase. Very low doses of colchicine claimed to be effective in stathmokinesis of hepatocytes under influence of hepatomitogenic tumour brei and tumour extracts, produced no discernible effect on the mitotic pattern of hepatocytes in Ehrlich ascites tumour-bearing mice nor in post-CCl4 regenerating livers. The results are discussed in the context of known features of tumour-associated hepatocellular mitosis.


Radioactive components in the acid-soluble fraction of mouse liver cytosol after dimethylnitrosamine[methyl-14C] administration. The acid-soluble components of mouse-liver cytosol, prepared at time intervals after intragastric administration of a single carcinogenic dose of 14C-dimethylnitrosamine, were separated by column chromatography. The columns were calibrated with known in vitro metabolites of the nitrosamine, and the elution profiles were compared with those of the mouse-liver system. The results suggest that the 14C-methyl label is transferred to many of the same compounds as identified in vitro, but that numerous other labeled compounds are also present. The possible significance of these metabolites to the pathogenic processes induced by dimethylnitrosamine has yet to be determined.


Antitumor effect of combined use of OK-432 and yeast cell wall with mitomycin-C in mice. Tumor-inhibitory effect of combined use of mitomycin-C and streptococcal preparation (OK-432) or yeast cell wall (YCW) was examined. Twenty-four hours after intraperitoneal inoculation of Ehrlich carcinoma cells, combination therapy was carried out and tumor growth was observed for 40 days. About one-half of mice treated with yeast cell wall at a single dose of 1 mg survived free of tumor. Mitomycin-C at a single dose of 2 microgram was not effective. However, in combination with yeast cell wall, tumor suppression was observed in 70% of the mice. This tumor-inhibitory effect was enhanced by subsequent treatment with OK-432 or yeast cell wall. When these materials were injected separately or in combination with mitomycin-C, the number of peritoneal exudate cells increased about 3 to 6 times after 3 days and these cells exhibited cytotoxic effect on tumor cells. Hemagglutinating antibody to sheep erythrocytes was hardly affected by the combination therapy.


Reappraisal of cholesterol solubilization in bile salt-lecithin solution and the stability of bile. On the basis obtained in a preceding study, cholesterol solubilization in aqueous bile salt-lecithin solution was investigated. The alteration of mixing sequence was found to yield differences not only in the rate but also in the magnitude of cholesterol solubilization. Both the rate and the magnitude were remarkably bigger in the system solubilizing cholesterol and lecithin mixture by bile salt than that solubilizing cholesterol crystal by bile salt with solubilized lecithin. A linear relation between the quantity of solubilized cholesterol and the concentration of bile salt except for lower concentration range was obtained for every bile salt-lecithin system. Values of k, the slope of the partial straight line, determined for cholate, chenodeoxycholate, deoxycholate and equimolar cholate-deoxycholate systems were 5.85 X 10(-2), 7.60 X 10(-2), 9.50 X 10(-2) and 7.17 X 10(-2), respectively. Cholesterol solubilizing power of bile salt was thus enhanced by the addition of lecithin. Since the solubilizing power could be given by the ratio of the solubilizate to the solubilizer, it was expressed graphically by the ratio of cholesterol to bile salt as ordinate and the concentration of bile salt as abscissa. The saturability of cholesterol solubilization in bile was purposefully exhibited in this graph by plotting assayed data of biliary lipid components.


Diagnosis of pancreatic cancer by endoscopic retrograde cholangiopancreatography and pancreozymin secretin test. Eighy cases with carcinoma of the pancreas were divided into 10 groups according to the location and size of the tumor. Drip infusion cholangiography, percutaneous transphepatic cholangiography, hypotonic duodenography and endoscopic retrograde cholangiopancreatography were employed for this classification. Comparison of cholangiopancreatograms (ERCP) with results of the biliary and pancreatic secretory function assessed by pancreozymin secretin test (PS test clarifies secretory capacity of the exocrine pancreas. But combination of ERCP and PS test with cytology is necessary for the correct diagnosis of the pancreatic cancer and it is hoped that the combination may excavate the disease in the early stage.


Serum amylase isozymes in patients with chronic pancreatitis with hyperamylasemia. In order to clarify the relationship between hyperamylasemia and clinical states in chronic pancreatitis, serum amylase isozymes were studied in 39 cases of chronic pancreatitis including 13 cases of alcoholic pancreatitis. Hyperamylasemia in chronic pancreatitis is generally due to high pancreatic type isoamylase (P-amylase) activity in acute exacerbation, sometimes accompanied by a transient elevation in salivary type isoamylase (S-amylase). On remission, however, hyperamylasemia due to high S-amylase activity has been found. These were cases of advanced alcoholic pancreatitis, which exhibited a characteristic pattern of low serum P-amylase and high serum S-amylase activities while the clearance ratio (Cam/Ccr) was normal despite high S-amylase activity. It should be noted that hyperamylasemia in chronic pancreatitis may be caused by high S-amylase activity in addition to high P-amylase activity, especially in alcoholic pancreatitis.


An extraluminal force transducer for recording contractile activity of the gastrointestinal smooth muscle in the conscious dogs: its construction and implantation. An extraluminal strain-gauge force transducer has been developed for recording contractile activity of the gastrointestinal smooth muscle. The details of its construction and implantation were described. The transducer unit allows for continuous long-term recordings (more the 5 months) from conscious experimental animals. It could be constructed in any laboratory and easily implanted in animals if it is done in aseptic technique. Since it is sutured onto the outside of the gut, it does not interfere passage of the contents. The only disadvantages are that it only measures muscle contractions and it is hard to determine movements of intraluminal contents especially in the digestive state.


Inhibitory effect of pentagastrin and feeding natural and motilin-induced interdigestive contractions in the stomach of conscious dogs. The interaction between motilin, pentagastrin and feeding was investigated during the interdigestive gastric motor state in 4 healthy conscious dogs. We confirmed previous reports that an i.v. infusion of synthetic motilin always induced a pattern precisely like that of the naturally-occurring interdigestive contractions of the stomach. Pentagastrin inhibited the occurrence of the interdigestive contractions at dose between 0.2-1.6 microgram/kg-hr; this inhibition had a dose-related relationship to the occurrence of the motilin-induced contractions. The ingestion of food strongly inhibited the occurrence of not only the natually-occurring contractions but also the motilin-induced contractions in the stomach and changed the motor pattern to the digestive one. These findings strongly support our hypothesis that the interdigestive contractions in the dog are, at least in part, under the control of motilin. Furthermore, it should be emphasized that pentagastrin not always stimulates gastric motor activity but conversely, in the interdigestive state it inhibits movements characteristic of that condition and replaces them with the digestive pattern.


Congenital dilatation of the biliary tract; new classification and study with particular reference to anomalous arrangement of the pancreaticobiliary ducts. Yotsuyanagi's theory is often quoted in the discussion of the etiology of congenital dilatation of the biliary duct (CDBD), but there has been no established etiology as yet. With particular reference to the relationship between anomalous arrangement of the pancreaticobiliary ducts and CDBD, Babbit collected 19 cases of CDBD. The authors also observed the anomalous arrangement in 10 of 24 cases of CDBD (42 percent). Analysis of 570 CDBD cases collected in Japan disclosed that the anomalous arrangement was present in 183 of them (33 percent), dilation of the intraheptic bile ducts in 236 (42 percent), and narrowing and malformation of the bile duct in the hepatic hilum in 58 (10 percent). The authors have proposed a new classification, including these morphologic anomalies of the whole pancreaticobiliary ductal system. This classification provides useful indices in selecting the surgical procedures. The effect of the anomalous arrangement was pathophysiologically studied on dogs. The static internal pressure of the dog pancreatic duct was 14.6 + or - 5.5 cm H2O, and that of the dog bile duct, 8.9 + or - 3.4 cm H2O. Puppies were then operated on by shunting the pancreaticobiliary ducts. As the result, the biliary  tract was devastated by pancreatic juice, giving rise to similar pathologic changes to those clinically observed.


Ultrastructure of botryoid sarcoma of the common bile duct. A case of botryoid sarcoma of the common bile duct in a 4-year-old girl was reported. Electron microscopic examination disclosed that the neoplasm consisted of three types of cells: polygonal, elongated, and small cells. The former two contained moderate to large amounts of poorly developed myofibriles in the cytoplasm with occasional A, I and Z-bands. The small cells contained mitochondria and dilated rough endoplasmic reticulum but few myofilaments. Deposits of glycogen granules were constant components of the neoplastic cells. Mitosis was striking in the small cells. Abnormal multilaminar endoplasmic reticulum was observed in the small cells in the mitotic stage.


Duplication cyst of the duodenum in the adult. A duodenal duplication cyst in a 45-year-old male is reported. A hypotonic duodenography showed a smooth spherical defect in the descending portion of the duodenum. A fiberoptic duodenoscopy disclosed a smooth well-defined tumor which was located orally from the ampulla of Vater. A retrograde pancreatocholangiography indicated the tumor was not in communication with the pancreatic duct or biliary tract. At operation, a cystic spherical mass, 3 cm in diameter, was located in the posterior wall of the duodenum corresponding to the above described diagnosis. The combination of a greater awareness of this condition as well as improved X-ray and endoscopic techniques has made preoperative diagnosis more accurate.


Acute obstructive suppurative cholangitis in a man with an enlarged inferior pancreaticoduodenal lymphnode. A case report of a 55-year-old male, who was seen with epigastric pain and hyperamylasemia, is to be presented. He failed to respond to the intensive antibiotic therapy, and subsequently acute obstructive suppurative cholangitis fully developed. At laparotomy, an inflammatory enlarged inferior pancreaticoduodenal lymphnode, which apparently compressed the common bile duct, was found. To our knowledge, no prior case of acute obstructive suppurative cholangitis provoked by an enlarged lymphnode has been reported. A plea is made for attention to lymphnodes involved by inflammatory or neoplastic disorders, as well as common provoking agents such as calculi.


[Evolutionary myology as a research method in the morphological evolution of human muscles]. The author presents the evolutionary myology as a complex research method by which the morphological transformation of human muscles could be proved. This process of muscle transformation is elucidated by 3 investigation types: 1. Morphological macroscopic investigation of the variations of certain human muscle. 2. Comparative anatomic investigation of the same muscle. 3. Muscle organogenetic study of human embryos and fetuses. The macroscopic morphological investigation of the variations of any human muscle enables the examination of the variability in its complete versatility and volume if a sufficient number of preparations are investigated. A line of successive muscle variations could be composed from the established variants, arranged one after another. Furthermore, the frequency of each variation could be determined in per cents. The material for comparative-anatomic investigation must be selected according to the contemporary zoology. The variation line of human material can be properly directed due to that examination. Now it is possible to understand which is the initial form, the transitional forms and the final form of the transformation process. Thus the direction of transformation process could be understand. The muscle organogenetic investigation must be carried out on human embryos and fetuses of different ages. In this way muscle and tendion primordium could be observed directly and in the same time the important factors about the primordium maturity and its eventual shifting could be established. The example described refers to the transformation of m. abductor pollicis longus. It reveals how the evolutionary myology can be used to prove the morphological evolution of any muscle.


[An algol program for the computation of empiric regressions]. An explanation is given about the meaning of empirical regression and on the domain of application of this biomathematical-statistical procedure. It may be helpful in data handling after the measurements and in a first stage of data processing especially if there is a large amount of datas. An empirical regression can provide the basis for a functional relationship analysis by giving hints for the choice of empirical mathematical functions. This will be useful and necessary in such cases where the measured values have a greater dispersion and one wants to get an analytical expression for the course of measured points. In the appendix a program listing of the ALGOL-program for empirical regression is presented. Detailed remarks are made in the text concerning the program structure, the data input and output resp. the program control parameters to enable the biological or medical user to adapt the program to their special problems without the help by a mathematician, and neither with deeper knowledge of mathematics nor with detailed insight to computer technical aspects of data processing.


Observations on the lateral-line sense organs of the Salamander Neurergus crocatus crocatus Cope (Amphibia: Urodela). The lateral-line system of the subadult and adult Neurergus crocatus crocatus Cope is retained throughout the life. It is constructed of pear-shaped sense organs or neuromasts which in the subadults are confined entirely to the epidermis with their apices opening distally to the exterior at the general level of the epidermal surface whereas in the adults they are embedded proximally more than halfway in the dermis with their distal apices opening into shallow grooves slightly below the regular epidermal surface. Dimensional differences are also observed between these organs in both stages. The neuromasts are constructed of 4 distinct cell types: sense cells, basal cells, sustentacular cells and mantle cells. These cells differ morphologically, structurally, topographically and functionally. The sense cells are clup-shaped, sensory, central in position and couched among the extremely elongated supporting basal and sustentacular cells, all of which are covered laterally by the extremely slender protective mantle cells. In both the mature and larvae, differences are observed among these cells in their size, number, location and arrangement. The sense organs are richly-supplied and well-nourished with vascular and nervous supplies.


A new sequence-specific endonuclease (Bsp) from Bacillus sphaericus. A new restriction endonuclease has been isolated from Bacillus sphaericus R. The purification procedure includes Bio-Gel filtration, (NH4)2SO4 fractionation and phosphocellulose chromatography. After the phosphocellulose step the enzyme preparation is free of non-specific nucleases. Bsp cleaves double-stranded DNA with the same specificity as Bacillus subtilis (Bsu) and Haemophilus aegyptius (HaeIII) restriction endonucleases, as concluded from digests and double-digests of phiX174 replicative form DNA with Bsu and Bsp. The 5'-terminal nucleotide of the cleavage products was shown to be C. Bacillus sphaericus R produces Bsp in extremely large quantities and the enzyme can be easily purified in high yield.


Chemical synthesis of two deoxyribododecanucleotides for the attachment of restriction termini to an artificial minigene. In order to permit in vivo cloning of an artificial minigene designed to code for a modified S-peptide, the phosphodiester method for the chemical synthesis of two dodecadeoxyribonucleotides is described. Each of the latter possesses antiparallel complementarity to one of the two minigene strands and to the single-stranded EcoRI-generated end. They can thus serve as cohesive termini ("splints") for polynucleotide ligase joining.


Distamycin A and its analogs as agents for blocking of endo R. EcoRI activity. Distamycin A (Dst) and its analogs protect the lambda phage DNA from cleavage with endoR. EcoRI and show selective affinity for different recognition sites of endoR. EcoRI on this DNA producing enlarged DNA fragments of various composition and length. The affinity of the antibiotic for DNA is influenced by the number of pyrrol carboxamide units in Dst molecule and does not strongly depend on the substitution of the N-methyl group by the N-propyl one. Since in the complex with DNA the antibiotics of the Dst type are localized in its minor groove a conclusion can be made that the minor groove of DNA is needed for the interaction of the restriction endonuclease with DNA.


Correlation of variations in intraluminal pressure and potential differences in the perfused colen. To investigate the nature of variations in the large intestine potential differences, a continuous perfusion of isotonic saline was carried out in the colon of 14 rats. Intraluminal pressure and potential differences between the lumen and the peritoneal cavity were continuously and simultaneously recorded, while impedance of the system and respiration were also constantly monitored. To obtain a quantitative evaluation of the data, Fast Fouier Transform was performed on the signals and their derivatives which were auto- and cross-correlated. While there was no obvious relation between pressure and potential in the unperfused colon, there was clear visual qualirative evidence that, during steady state conditions of perfusion, an increase in intraluminal pressure was accompanied by a decrease in potential differences, while impedance of the recording system remained unchanged. Computer analysis disclosed four narrow ranges of stable frequencies for both pressure and potential. They were centred around 0-3, 1-75, 10-7, and 75 cycles per minute, the latter being synchronous with respiration. It is concluded that the variations of potential differences recorded during perfusion, a well-know phenomenon, are not electrical artefacts: the fast rhythm is probably induced by respiration, which increases intracolonic pressure and that, in turn, reduces the absolute value of potential differences, which remain negative mucosa versus serosa. The slower rhythms are synchronous for pressure and potential. Mechanisms responsible for the decrease in potential related to the increase in pressure remain unknown.


Use of an elemental diet (Vivonex) in the management of bile acid-induced diarrhoea. The effect of a low fat containing elemental diet (Vivonex) on faecal bile acid excretion was studied in six patients with cholerheic diarrhoea, two normal controls, and four patients with non-cholerheic diarrhoea. The total faecal bile acid excretion for the patients with bile acid-induced diarrhoea was significantly reduced fron 6-37+/- 1-64 mmol/24 h (mean +/- SEM) to 2-70 +/- 1-12 mmol/24 h during Vivonex treatment (p less than 0-05). A marked improvement in the diarrhoea of these patients occurred; the number of stools per day decreased and there was less urgency associated with the diarrhoea. No significant reduction in faecal bile acid excretion was observed for the control and non-cholerheic diarrhoea groups. An elemental diet of this type may be of value in the management of patients with bile acid-induced diarrhoea unresponsive to other forms of therapy, and may be of particular value in patients with Crohn's disease.


Stagnant loop syndrome in patients with continent ileostomy (intra-abdominal ileal reservoir). Intestinal absorption and bacteriology of the ileal contents were compared in seven patients with continent ileostomy and seven patients with conventional ileostomy. The absorption of vitamin B12 was reduced in five patients with continent ileostomy and subnormal in two patients with conventional ileostomy. Steatorrhoea was present in four patients with continent and one patient with conventional ileostomy. Increased concentrations of total anaerobic bacteria and Bacteroides were found in the ileum of the patients with continent ileostomy. After an oral dose of (1-14C) glycocholic acid there was no difference in the faecal excretion of radioactivity, whereas the 14CO2-expiration was increased in two patients with continent ileostomy. In four patients with continent ileostomy and malabsorption of B12, there was evidence of a stagnant loopsyndrome as oral lincomycin treatment resulted in increased absorption of B12 decreased excretion of faecal fat, and decreased concentrations of Bacteroides in the ileum.


Jejunal villous atrophy and granulomatous inflammation responding to a gluten--free diet. A 48 year old female patient with intestinal malabsorption and subtotal to total jejunal villous atrophy also had granulomatous inflammation characterised by numerous epitheloid and giant cell granulomas in the stomach, the jejunum, and the liver, On a gluten-free diet a complete remission was achieved that included disappearance of the granulomatous inflammation. It is suggested that the granulomas in this case were manifestations of the gluten intolerance.


Effects of long chain fatty acids on solute absorption: perfusion studies in the human jejunum. Perfusion studies were performed in healthy volunteers to test the hypothesis that net fluid secretion induced by fatty acids is accompanied by parallel reduction in solute transport. Ricinoleic acid provoked a marked net secretion of fluid and concomitantly inhibited the absorption of all solutes tested; these included glucose, xylose, L-leucine, L-lysine, Folic acid, and 2-mono-olein. Oleic acid also reduced net fluid and solute transport, but was less potent in reducing solute absorption than was ricinoleic acid. When fluid secretion was induced osmotically with mannitol, glucose and xylose absorption was not affected. The mechanism for this generalised effect of fatty acids on solute absorption is uncertain, possibly nonspecific, and might be related to mucosal damage and altered mucosal permeability induced by these agents.


Gastric epithelial cell turnover, mucus production, and healing of gastric ulcers with carbenoxolone. Nineteen healthy subjects were studied and 17 patients with gastric ulcer before and after ulcer healing with carbenoxolone. Gastric deoxytibonucleic acid (DNA) loss was measured as an index of epithelial cell turnover, and N-acetylneuraminic acid (NANA) content of gastric juice as an index of mucus secretion. In normal subjects there was a negative correlation (p less that 0-025) between gastric DNA loss and NANA secretion; the lower the cell turnover the higher the NANA production. In gastric ulcer patients DNA loss or turnover was significantly (p less than 0-01) higher than normal, and fell significantly (p less than 0-01) after four weeks' treatment with carbenoxolone when 16 of the 17 ulcers had healed. At the same time NANA output increased significantly (p less than 0-01). It is suggested that patients with gastric ulcer lose cells at a high rate, a state of affairs which is returned towards normal by carbenoxolone, thus allowing the epithelial cells to mature within the mucosa and produce more mucus.


Maximum acid output to graded doses of pentagastrin and its relation to parietal cell mass in Chinese patients with duodenal ulcer. In groups of Chinese patients with duodenal ulcer and controls, increasing the dose of pentagastrin from the standard dose of 6 ug/kg or 12 ug/kg did not result in any change in the maximum acid output (MAO). Comparison of the MAO thus obtained with that reported in series of Occidental subjects suggested that the Chinese subjects had smaller MAO. Using the method of Card and Marks (1960), the parietal cells of resected stomachs were counted in a group of Chinese patients with duodenal ulcer. It was found that the parietal cell mass (PCM) correlated with the MAO, both PCM and MAO were significantly small in the Chinese series as compared with the Scottish series, but the acid output per unit parietal cell mass (MAO per 10(9) parietal cells) was not different in the two groups. These observations suggested that the Chinese patients with duodenal ulcer had smaller parietal cell mass compared with the Westerners.


Effect of cigarette smoking on the lower oesophageal sphincter. Observations on the effect of smoking on lower oesophageal sphincter pressure (LOSP) are based on station pull-through techniques of eosophageal manometry and recent studies have suggested that these techniques are inaccurate. Reproducible measurements of LOSP may be achieved with a rapid pull-through (RPT) method of manometry. This method was used to determine the effect of cigarette smoking on LOSP in 10 asymptomatic volunteers and in a group of 10 patients with symptoms of gastro-oesophageal reflux. Basal LOSP measurements in the two groups were not significantly different but LOSP was reduced by 19% in asymptomatic subjects (p less than 0-01) and by 21% in symptomatic patients (p less than 0-02) during cigarette smoking. The results suggest that smoking should be avoided in the clinical management of gastro-oesophageal reflux.


Electron probe microanalysis in the study of gallstones. Detailed information on the structure and composition of gallstones was obtained using an electron probe microanalyser in conjunction with the other methods. Gallstones were studied layer by layer without greatly disturbing the arrangement of the materials present. Elements, including trace elements such as copper, iron, and manganese, were identified and their distributions mapped. The range of the method was extended to determine the character and distribution of certain chemical groups present by treating sections of gallstone with reagents which contained easily detected elements. The nature of the bonding of the sulphur in the stones was studied by examining the sulphur-X-ray spectrum. Pigmented sulphur-containing deposits were found to contain sulphur in a low valence state but taurine conjugates and the sulphate groups of mucosubstances were not detected. Microcrystalline apatite present in the stones contained some manganese and seemed to be implicated in the absorption of the low valence sulphur compound and in the nucleation of some stones.


Mechanism of hypogonadism in cirrhotic males. Men with chronic liver disease frequently develop clinical signs of hypogonadism and overt feminisation. Associated with these features, they have been found to have a reduced production of testosterone with low plasma concentrations, but only a minority of cirrhotic men would seem to have a marginal increase in circulating biologically potent oestrogens. Furthermore, this latter finding does not correlate with the presence of clinical feminisation. The original hypothesis to explain these changes now seems less likely to be true and no other single hypothesis has, on its own, been found to provide an adequate explanation for all the clinical and biochemical features found in cirrhotic men. It may be that the pathogenesis of endocrine changes in cirrhotic men is multifactorial--for instance, a combination of decreased hepatic clearance of some oestrogenic compounds, an autoimmune mediated primary testicular defect, and a specific potentiation effect by alcohol. Alternatively, it may be that none of these suggested mechanisms is of importance and that the endocrine changes are mediated instead by other mechanisms which remain, as yet, undiscovered or unconsidered. The fascination which this problem has held for clinicians and biochemists for many years seems likely to persist for some time to come.


Anatomy and radiology of the areae gastricae. The anatomy and radiology of the areae gastricae were studied in human and pig specimens and it was shown that the double contrast barium meal demonstrates a true picture of the undulating gastric mucosa, which is distinctive in appearance in the antrum body and fundus of the pig stomach. The importance of the type of barium used and the thickness of barrier mucus in the demonstration of the areae pattern is emphasised and the high incidence of duodenal ulcer in the grade 4 pattern and the low incidence in the non-coater is described. A knowledge of the anatomy and radiology of the areae gastricae pattern is central to the interpretation of the double contrast barium meal.


Unstirred layer and kinetics of electrogenic glucose absorption in the human jejunum in situ. Using an electrical technique we estimated the thickness of the unstirred layer in the human jejunum during kinetic studies of electrogenic glucose absorption. The unstirred layer in seven healthy volunteers (632 +/- 24 mum: mean +/- SEM) was significantly thicker than in 10 patients with active coeliac disease (442 +/- 23 mum) but not significantly different in seven patients who had responded to treatment by gluten withdrawal (585 +/- 49 mum). There were similar differences in the values of ;Apparent Km' for electrogenic glucose absorption between healthy control subjects (36 +/- 6 mM) active coeliac patients (11 +/- 1 mM) and treated coeliac patients (31 +/- 5 mM). The changes in PDmax however, showed a different pattern. The PDmax in the active coeliac group (6.8 +/- 0.7 mV) was lower than in controls (7.6 +/- 0.6 mV) but not significantly so, while the PDmax in the treated coeliac group (10.6 +/- 0.9 mV) was significantly higher than in both the active coeliac and control groups. It should be noted that both operational kinetic parameters obtained in the present study are much lower than those obtained previously (Read et al., 1976b) because of the use of siphonage. Analysis of the results using a computer simulation indicates that the reduction in Apparent Km in active coeliac disease can be caused by the interaction of the decreased maximal absorption rate for glucose (Jmax) with the attenuated unstirred layer. In these circumstances it is not necessary to postulate any change in the affinity of the transport mechanism for glucose (;Real Km'). It is remarkable that the disease process produces an Apparent Km which is much closer to the Real Km than that found in health.


Role of gastrointestinal hormones in the response to massive resection of the small bowel. Hypersecretion of gastric acid and accelerated intestinal transit are largely unexplained consequences of massive resection of the small bowel; several postulated humoral mechanisms remain unsubstantiated. The purpose of the study was to investigate the effects of 75% resection of the distal small bowel in dogs on circulating levels of a range of gastrointestinal hormones. Basal and meal-stimulated concentrations of insulin, secretin, gastrin, pancreatic glucagon, and total glucagon-like immunoreactivity (GLI) were measured by radioimmunoassay techniques. After resection, significant depletions of basal and stimulated total GLI (p less than 0.05 -- p less than 0.001) and a significant rise of stimulated gastrin (p less than 0.05) were discovered. These hormonal alterations may produce an important imbalance of humoral influences on gastrointestinal function. It is suggested that these changes may hold a key to the aetiology of the complications of massive resection of the small bowel.


Increased tissue concentrations of 5-hydroxytryptamine in the duodenal mucosa of patients with coeliac disease. Tissue concentrations of 5-HT have been measured in the duodenal mucosa of adults and children with coeliac disease and were found to be significantly higher than those from a control group. This finding may be associated with hyperactivity or hyperplasia of enterochromaffin (EC) cells in the duodenum of patients with coeliac disease and could also be directly related to described abnormalities of 5-HT metabolism in this disease.


Nippostronglylus brasiliensis infection in the rat: effect of iron and protein deficiency and dexamethasone on the efficacy of benzimidazole anthelmintics. Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities.


Platelet function in fulminant hepatic failure and effect of charcoal haemoperfusion. In 34 patients with fulminant hepatic failure, platelets, in addition to being reduced in numbers, were smaller than those of healthy controls. In keeping with this, capillary bleeding times were significantly longer than could be accounted for by reduction in numbers alone. In a small group of these patients use of charcoal haemoperfusion for temporary liver support produced a doubling of the capillary bleeding time despite only a small drop in arterial platelet counts. This disproportionate prolongation of bleeding time was almost certainly caused by the loss of larger platelets in the charcoal columns during perfusion, as the mean median volume also fell during perfusion. Rises in screen filtration pressure of blood leaving the columns were found during some perfusions and thought to be indicative of platelet aggregates. Release of vasoactive substances from platelets could account for the hypotension often found at this time.


Association of abnormal fibrin polymerisation with severe liver disease. The frequent occurrence of abnormal fibrin polymerisation in patients with liver disease has recently been reported. To investigate this further, fibrin polymerisation was studied in 68 patients with cirrhosis or chronic active liver disease. Thirty-three of these patients demonstrated impairment of this phase of blood coagulation. When other tests of liver function were compared in patients demonstrating this abnormality and those in whom fibrin polymerisation was normal, it was found that the former group demonstrated significantly reduced albumin concentrations (p less than 0.0002), raised bilirubin and aspartate aminotransferase levels (p less than 0.0006 and less than 0.003 respectively), and greater prolongation of the one-stage prothrombin time (p less than 0.001) with more marked reduction in factor VII levels (p less than 0.002) compared with the latter patients. It is concluded that defective fibrin polymerisation occurring in patients with liver disease indicates the presence of severely impaired hepatocellular function. This might account for the grave prognosis reported in cirrhotic patients with abnormal fibrin polymerisation who also suffer bleeding from gastro-oesophageal varices.


Serum bile acids in the diagnosis of hepatobiliary disease. The value of serum bile acids (SBA) in the diagnosis of hepatobiliary disease has been investigated. A modified GLC method was used, with an overall coefficient of variation of +/- 11% in the control range. Serum was obtained after a 12 hour fast, and two hours after a fatty meal from 73 patients and 14 control subjects. In controls the total fasting SBA of 2.17 +/- 0.86 mumol/l increased significantly (p less than 0.001) to 3.81 +/- 1.14 mumol/l after a meal. All icteric patients had raised SBA, but in 23 anicteric patients there was no significant difference in the detection of chronic liver disease by fasting SBA, postprandial SBA, AST, or gamma GTP. Compared with controls, serum in patients contained proportionately less deoxycholic acid (p less than 0.001), there was proportionately more cholic acid in extrahepatic obstruction (p less than 0.001), and proportionately more chenodeoxycholic acid in patients with cirrhosis, viral hepatitis, and neoplasia (p less than 0.001). In control subjects, the fasting cholic:chenodeoxycholic acid ratio ranged from 0.5-1.0, and differed significantly (p less than 0.001) from patients with extrahepatic obstruction 0.96-3.6, and cirrhosis 0.1-0.5. It is concluded that serum bile acids measured by sensitive methods can provide useful diagnostic information.


Device for obtaining multiple simultaneous samples of intestinal contents during perfusion studies in man. A system is described for obtaining frequent simultaneous samples from three jejunal sites. It can be easily made from materials ordinarily available in any laboratory.


Identifying the sexually abused child in a medical setting. From January to April 1975, 40 patients treated for gonorrhea in a Pediatric Emergency Clinic were studied to explore the problem of sexual abuse of children. Presented in this article is a review of that study and the resulting method for identifying sexually abused children in the medical setting.


Children in limbo: a study of New York City "boarder babies". Some children not in need of medical care are living on hospital wards-some spend a few days, some, many years. This article presents the findings of a pilot study made to find out who these children are and why they are there. It suggests that stigmatizing labels as well as bureaucratic indifference may contribute to the denial of alternate care for these children.


Lawyer and social worker as collaborators in the medical setting. Part of the role of the social worker in a medical setting should be to determine if a patient has reviewed his legal status concerning wills, insurance, and estate planning. If not, the worker should encourage the patient and his family to seek legal advice so that the patient can receive medical treatment free of legal and financial concerns.


Consumer participation in Health Maintenance Organizations. Recent health legislation, particularly the Health Maintenance Organization Act, appears to invite the participation of consumers in the governance of health care programs. This represents an opportunity for the community organizer to influence the role of the consumer in health care systems. This paper examines federal policy relating to consumer participation, discusses resulting issues and dilemmas, and offers suggestions for programs to strengthen consumer participation in HMOs.


Sexuality in the aging woman.

Sexuality in the aging woman. The sexuality of the older woman is often ignored by therapists, families, and even the woman herself, but studies have shown that menopause does not signal the end of sexuality. In practice with older women, the social worker must take into account their continuing need for intimacy.


Treatment for adults with psychosomatic symptoms. Patients frequently ask their physicians to advise them about problems that are psychological in origin and would, in fact, be more appropriately treated by a social worker. This article presents a model of cooperation between a family physician and a social worker that enabled the two to provide effective counseling services to adults with psychosomatic symptoms and their families.


A study on long-term prognosis of epilepsy. Of 631 epileptic patients examined in our seizure clinic in the period between January 1961 and December 1966, 97 (15.4%) have been treated until September 1976, when the long-term prognosis was evaluated. The "good prognosis (completely controlled)" were found in 59% of grand mal, in 55% of focal motor seizure, in 42% of psychomotor and in 33% of the mixed seizure in which more than two types of seizures were combined; in 49% (48 cases) on the average. Seventy-nine percent of the cases of the mixed seizure were combined with psychomotor seizures. In the psychomotor and the mixed seizure groups, the presence of personality disorders tended to lead them to "poor prognosis" which meant that the seizures were not well controlled. Twelve cases manifested psychotic (paranoid) state: a schizophrenic, a case with chronic paranoid-hallucinatory state, and 10 patients with episodic paranoid state, whose episodes may be identified with the paranoid reactions. Out of the 49 "poor prognosis" cases, 17 (35%) had had seizure-free periods for more than three years in the past course of their treatment.


A retrospective study on the prognosis of aged patients with epilepsy. A retrospective follow-up study on the prognosis of 90 patients with epilepsy above 40 years of age has resulted in: 1. In the aged patients, the duration of epilepsy (mean: 23 years) was longer than the period of treatment they underwent (mean: 14 years). The delayed commencement and/or interrupted medication along with the patients' incompliance of taking drugs accounted for the main reasons for at least 70% of the patients. 2. The partial epilepsy (80%) especially with complex symptomatology (55%) were predominating in the aged group. And also, that the tonic-clonic seizures were liable to convert to the complex partial seizures in their thirties and forties, was found in this study. 3. Although almost all the patients (97%) had more or less clinical attacks even at the time of survey, 75% or more decrease in seizure frequency have been exerted for one and a half year, regardless of the seizure types in the majority of the patients (81%). This seems to offer an explanation that an appropriate sociomedical strategy is necessitated for patients with long-standing epilepsies.


Electroclinical studies of seizures in the newborn. Electroclinical features of neonatal seizures were studied in 215 neonates who developed seizures during the first three weeks of life. In 62 of them, clinical fits occurred during the actual polygraphic recording. The electro-clinical correlations were very variable, although there were some statistically significant associations between certain types of seizures and electrical discharges. The relation between seizures and sleep states was investigated in 40 infants who had more than three fits during the recording. The state in which more than 70% of seizures occurred was active sleep in 28% of the cases, quiet sleep in 13%, indeterminate sleep in 8%, and wakefulness in 8%. In 50%, seizures did not tend to occur in a given state. The authors thank Professor Suzuki for his continued interest and encouragement.


The studies of the attacks of abnormal eye movement in a case of infantile spasms. We observed the attacks of nystagmus in a case of infantile spasms and carried out overnight sleep polygraphy. The following findings were obtained: (1) Awake time was prolonged to 56% of TIB, while sleep time was markedly shortened to 44% of TIB. Also REM sleep time was reduced to 20% of SPT and deep slow sleep (stage N3) was absent. (2) Attacks of nystagmus were observed only during wakefulness. At first, fast wave bursts appeared in the right occipital area, and were followed by left-upward deviations of eyeballs, and then the attacks of counterclockwise right-downward rotatory nystagmus. Also the fast wave bursts were succeeded by spreading of fast waves to adjacent areas. At the same time, EMG exhibited elevated muscle action potentials of mentalis and biceps femoris. During the attacks of nystagmus, there was alteration of respiratory movements. In NREM sleep, both fast wave bursts and the attacks of nystagmus were not observed. In REM sleep, the fast wave bursts and eye movements were observed but the attacks of nystagmus did not appear. During the fast wave bursts, alteration of respiratory movements were observed. From the results of this study, it was presumed that the brain lesions of this case were extended with severe degree of damage in the great parts of brain containing cerebral cortex and brain stem.


Ictal clinical patterns and ictal EEG in a case of partial seizures of frontotemporal origin associated with complex symptomatology. The patient was a 35-year-old, unmarried male whose epileptic psychomotor fits persisted since the age of 13. The author has observed the case for about 12 years, so that incomplete information concerning epileptic symptoms was considered to be compensated considerably by longitudinal observation, including ictal seizure and ictal EEG's. In this patient seizure with impaired consciousness which correspond rhythmic slow waves of EEG tracing might be a nuclear sign; several kinds of automatism then might be considered as postictal phenomenon. The most important of all was tonic seizure of psychomotor epilepsy particularly in the face which was not seen in the petit mal epilepsy. With observation of ictal period as well as ictal EEG, differential identification of centrencephalic epilepsy and psychomotor epilepsy may not be totally impossible. The case also showed a typical productive psychotic episodes of Landolt, which could be treated favorably by 10 mg of intravenous Haloperidol. This method, named as "pathologization" of Helmchen, was found by the present author as a useful treatmental means of choice.


A case of musicogenic epilepsy.

A case of musicogenic epilepsy. 1) A case of musicogenic epilepsy or psychomotor seizures supervening whenever the patient hears a certain tume has been presented. 2) The EEG features of the seizure are such as are often seen in psychomotor seizures. 3) Auditory evoked response may be left out of consideration. 4) There is no appreciable relationship between the disease and the life history of the patient. The attempt of our patient to cure herself by making use of conditioned reflex proved to be a failure. The patient is more liable to the disease when she is on the strain while hearing a tune. 5) Our consideration of the mechanism of the disease has led to the presumptive conclusion that hyperacusis, conditioned reflexes and the impact of life history may be involved, and the fragility of the memory function of the temporal lobe underlie the genesis of the disease.


Brain catecholamine concentrations and convulsions in E1 mice. Brain dopamine and norepinephrine concentrations of "stimulated" E1 mice were lower than those of "non-stimulated" control E1 mice. Furthermore, the pre-convulsive stage showed lower concentrations of these catecholamines than the resting stage.


Functional changes in the caudate and accumbens nuclei during amygdaloid and hippocampal seizure development in kindled cats. Electroencephalographic changes were examined in the caudate nucleus and accumbens nucleus during limbic seizure development in eight kindled cat preparations. The emergence of self-sustained after-discharge and interictal discharge was demonstrated in the accumbens nucleus during limbic seizure development. This finding suggests secondary epileptogenic functional alterations in the mesolimbic dopamine neuron systems. Moreover, the epileptiform responses triggered from the accumbens and caudate nuclei increased markedly with progressive limbic seizure development. These results suggest that a limbic seizure could produce a secondary functional reorganization of the brain dopaminergic neuron systems, especially of the mesolimbic dopamine neuron systems that has been reported to play an important role in the manifestation of psychotic symptom.


A method for provoking EEG abnormalities by administration of nialamide. Nialamide, a kind of monoamine oxydase inhibitor, was used for provoking centrencephalic EEG abnormalities and 6-14 Hz positive spikes. It was assumed that these EEG abnormalities have close relationship with dysfunctions of the brainstem which is rich in monoamines and monoamine oxydase. The nialamide provocation was carried out on 49 inpatients who had centrencephalic discharges in their EEG reports. These patients consisted of four cases of epilepsy, one case of anorexia nervosa, two cases of narcolepsy and 42 cases of diencephalosis. Another series of 22 patients suffering from other diseases, in whome EEG no centrencephalic EEG abnormallities were detected, were examined with nialamide. Out of the 49 patients, 35 cases (71.4+) showed increased EEG abnormalities following the administration of nialamide. It was noteworthy that this drug had provocative effect not only for EEG abnormalities, but also for the symptoms from which patients were suffering. In 26 out of 49 patients, both EEG abnormalities and clinical symptoms were provoked by nialamide. And the nialamide administration resulted in negative on all 22 patients who did not register centrencephalic EEG abnormalities. The mechanism and characteristics of this provocative procedure by the use of nialamide were evaluated.


A histochemical study of mucosubstances in the bovine respiratory tract with special reference to cuffing pneumonia. The mucosubstances of the bronchial epithelial goblet cells in non-pneumonic calves were almost exclusively sulphomucin; neutral mucin, sialomucin and sulphomucin were produced by the submucosal glands. Calves with lesions of cuffing pneumonia from which M. dispar was frequently cultured had increased numbers of epithelial goblet cells extending into the peripheral airways as far as the bronchioles. These pneumonic animals had epithelial goblet cells, some of which contained sialomucin, while in the gland a switch from neutral to acid mucosubstance in the form of increased sulphomucins and sialomucins was detected.


The immune response of the chicken to vaccination against Newcastle disease with live virus and killed emulsified virus in relation to the length of time between two vaccinations. Chicks with no specific antibodies were initially y vaccinated against Newcastle disease at 21 days old with the live 'La Sota' strain or beta-propiolactone-killed virus emulsified in mineral oils. After a second vaccination 15 or 21 days later with the live "La Sota' strain, the interference produced by the first vaccination on the antibody production induced by the second vaccination was investigated. It was found that the live virus vaccine used for the second immunization was affected by the antibodies induced by the first vaccination, as shown in previous work utilizing 1-day-old chicks.


Ultrastructural studies of some organs from pigs with swine fever. Six pigs were experimentally infected with swine fever (SF) virus and their organs (tonsils, spleen, pancreas, kidneys and popliteal lymph nodes) were examined by electron microscopy. The study was designed to detect the presence of SF virus in the tissues examined. Particles that were probably SF virus were demonstrated. Paracrystalline aggregates and microtubular structures were also found.


[Acute injuries to peripheral nerves. 1. Diagnosis and principles for therapy]. A simple scheme for the identification of the most frequent lesions of single peripheral nerves is given. The scheme is based on a few--mostly two--characteristic features of each lesion. The significance of the degree of the nerve lesion for the choice of therapy is stressed.


[Diagnostic measures in bronchial asthma]. The diagnostic steps for in five groups divided forms of bronchial asthma are listed and are discussed. The diagnosis includes: 1. the anamnesis. 2. the clinical examination including X-ray, lung function tests, bronchologic inspection a.s.o., 3. special examinations for allergy including skin tests, provocation tests and pharmacodynamic tests, 4. serological-immunological methods of examination including determination of total IgE, specific IgE and several serum proteins.


[Beta-sitosterin in the treatment of essential type II hyperlipoproteinemias]. The effect of Beta-Sitosterol (Sitosterin Delalande) on plasma lipids in 20 pretreated patients with type IIa and IIb familial hyperlipoproteinemia is reported. 6-18 g of the drug were given for a time of two to twelve months. In 11 patients the plasma cholesterol level decreased between 10 and 30%. Since Beta-Sitosterol has no effect on plasma triglycerides, an additional hypertriglyceridemia must be taken care of and treated if necessary. Beta-Sitosterol can be called an effective substance in the treatment of hypercholesterinemia. In addition the diet cure becomes easier.


[CEA blood level in patients with Crohn's disease with reference to localization, duration and severity of the disease]. CEA-serum-levels were determined in 24 patients with Crohn's disease over a period up to 35 months. 13 patients showed elevated CEA-Levels (greater than 3 ng/ml). A positive correlation between the extent of the lesion and the CEA-serum-level could be demonstrated. This correlation could not be demonstrated in regard to the duration of the disease. The attempt to utilize CEA-serum-levels for the estimation of the activity of Crohn's disease showed a good correlation between the activity and CEA-levels in a few cases; the activity was measured by means of the Crohn's Disease Activity Index (CDAI), which was recommended in the National Crohn's Disease Study in the United States.


[Community psychiatry. An empirical study]. Aim of the present study was the analysis of the situation of fulltime and partime stationary psychiatric services, as well as clinic-administered out-patient services for a geographically defined population group in a large city (Hannover) over a period of serveral years. For this purpose an analysis was made of the clinical, social and demographic characteristics of all patients from a particular part of the city (sector), which had been admitted for treatment into the psychiatric hospitals of Wunstorf, Ilten, the municipal clinic in Hannover-Langenhagen and the psychiatric department of the Medical University of Hannover.


Failure of exogenous insulin to inhibit insulin secretion in man. In order to explore whether or not the negative feedback mechanism of insulin per se on insulin secretion exists in man, changes in plasma C-peptide immunoreactivity (CPR), as an index of pancreatic B cells secretory function, were studied in 6 nonobese healthy volunteers in the presence of high circulating levels of exogenous insulin. 10% glucose was infused concurrently so as to maintain blood sugar at the basal level. The insulin-glucose infusion was maintained for 120 minutes, achieving mean plasma levels of 140-180 mu1/ml. After this period, the insulin infusion was continued at the same rate for an additional 10 minutes while the glucose was omitted. Despite the elevated level of circulating insulin, no significant change in plasma CPR concentration was observed so long as the blood sugar was maintained at the basal levels. Following cessation of the glucose infusion, the plasma CPR levels declined with a decrease in blood sugar level. Under the conditions of the present study, no inhibitory effect of exogenous insulin on the secretory function of the B cells was noticed.


A possible role for gut GLI: an inhibitor of lipolysis. Duck gut GLI was incubated a) alone and b) with the lipolytically active duck pancreatic GLI and the intestinal factors peak 2 and 3, and the glycerol released from duck adipocytes measured. Intestinal GLI was non-lipolytic, but not inert: it reduced the lipolysis induced by pancreatic GLI and peak 2.


Decreased sensitivity to insulin in white adipose tissue from adrenalectomised rats. The ability of insulin to increase both [14C]-glucose incorporation into fatty acids and pyruvate dehydrogenase activity in incubated rat epididymal adipose tissues was considerably lessened after adrenalectomy. Insulin antagonism of adrenaline-stimulated lipolysis in isolated fat cells was abolished after adrenalectomy. Percentage stimulation of lipolysis above basal by adrenaline was not appreciably altered by adrenalectomy.


Effect of metoclopramide on prolactin secretion in man. Prolactin (PRL) secretion was studied after i.m. administration of Metoclopramide (alone or with a pretreatment with 5-Br-2alpha-ergo-cryptine) and after i.m. administration of Sulpiride. The results obtained evidenced a considerable hPRL increase after Metoclopramide administration, similar to that observed with Sulpiride, completely abolished by 5-Br-2alpha-ergocryptine. On the basis of these data it seems evident a strong and specific effect of Metoclopramide on hPRL secretion, probably more potent than Sulpiride.


Effects of aldosterone on the urinary excretion of total and non-dialyzable hydroxyproline. In order to explore the role of mineralocorticoids on collagen metabolism, the effects of aldosterone on the urinary excretion of total and non dialyzable hydroxyproline (HYPRO) was studied in rats. The administration of aldosterone in sesame oil, 75 microgram/100 g body weight to adrenalectomized rats maintained on 1% NaCl solution as drinking fluid and 1 mg of cortisone subcutaneously daily, provoked elevation of total and non dialyzable HYPRO in urine (P less than 0.001), when compared to similarly treated adrenalectomized rats receiving sesame oil but no aldosterone. Both groups showed a normal growth curve and had similar urinary excretion of creatinine. The effects of aldosterone are opposed to the known lowering effects of glucocorticoids on HYPRO excretion and may suggest an effect of aldosterone on collagen turnover. Alternatively, aldosterone may modify the metabolism or excretion of HYPRO in an opposite manner to that of glucocorticoids.


Hormonal regulation of the number and activity of ribosomes in mammary gland explants of mice. Possible effects of insulin, hydrocortisone and prolactin on the number and activity of ribosomes enganged in protein biosynthesis in mammary gland explants were explored. The rate and extent of [3H]-puromycin attachment to nascent peptides was used to assess, respectively, the activity and number of ribosomes engaged in protein biosynthesis. None of the hormones altered the number of ribosomes engaged in protein biosynthesis. In addition, of the hormones tested, only insulin appeared to accelerate the rate at which ribosomes carried out the translocation process. The early (1 hr) effect of insulin on protein biosynthesis in the mammary gland would therefore appear to occur via an activation of ribosomal activity. In contrast, the early (6 hr.) effect of prolactin on protein biosynthesis would appear to be exclusively via an RNA-DNA dependent mechanism.


Isolation of a protease inhibitor from tissues resistant to tumor invasion. We have purified to homogeneity the major trypsin inhibitors from both bovine cartilage and aorta, two tissues reported to be highly resistant to invasion. The two inhibitors appear to be identical and they resemble the Kunitz inhibitor with respect to molecular weight, amino acid composition, range of susceptible proteases, and antigenicity. Each of these inhibitors accounts for 100% of the antitrypsin activity found in extracts of bovine cartilage and aorta.


Glutamate-glyoxylate aminotransferase in rat liver cytosol. Purification, properties and identity with alanine-2-oxoglutarate aminotransferase. After cortisone injection, virtually identical increases in rat liver cytosol alanine-2-oxoglutarate aminotransferase and glutamate-glyoxylate aminotransferase activities were observed. The two activities were co-purified to homogeneity from rat liver cytosol. The purified enzyme was specific for L-alanine with 2-oxoglutarate as amino acceptor. With glyoxylate, however, the enzyme utilized various L-amino acids as amino donors in the following order of activity: glutamate greater than alanine greater than glutamine greater than methionine. The ratio of alanine-2-oxoglutarate aminotransferase activity to glutamate-glyoxylate aminotransferase activity remained constant during purification and was unchanged by a variety of treatments of the purified enzyme. These results suggest that glutamate-glyoxylate aminotransferase is identical with alanine-2-oxoglutarate aminotransferase. Evidence was obtained that the two enzyme activities in the cytosol of dog, cat and human liver are also properties of the same protein.


Preparation of highly purified human somatotropin (growth hormone). A method for preparation of highly purified human somatotropin on large-scale basis is described. Starting from deep-frozen pituitary gland, less time is needed to obtain highly purified hormone than with other published methods for preparation of human somatotropin. The hormone obtained in this fasion is chromatographically and electrophoretically homogeneous; it shows high biological and radioimmunological growth hormone activity and is free of other pituitary hormone activities. The effects of various experimental conditions upon aggregation of somatotropin are critically evaluated.