[Properties and action specificity of carboxycathepsin (peptidyl dipepsidase) from bovine kidneys]. Carboxycathepsin from bovine kidney split the dipeptide fragments from the C-terminal part of peptides of different structure. Peptides containing the proline residue at the second position from the C-terminal amino acid residue and also peptides with substituted terminal alpha-carboxyl group were not hydrolyzed by carboxycathepsin. The enzyme was activated by Cl, Zn2+, Co2+ and Mn2+. The substances which formed the chelate complexes with ions of two-valent metals and also heavy metal ions, inhibited the enzymatic activity. Diisopropyl fluorophosphate did not inhibit carboxycathepsin. The homogeneous preparation of carboxycathepsin converted angiotensin 1 into angiotensin 11 and hydrolyzed bradikinine, splitting off C-terminal dipeptides consequentially.


[Effect of amizil on phospholipid metabolism in different parts of the brain]. Effect of central M-cholinolytic amizyle on incorporation of 2-14C-acetate in phospholipids of big hemispheres, cortex of big hemispheres, cerebellum and stem was studied. In administration of amizyle the most distinct alterations were observed in cortex of big hemispheres and cerebellum. In cortex of big hemispheres the specific activity of inosine monophosphate and phosphatidyl choline were increased by 77% and 97%, respectively; the specific activity of phosphatidic acid was decreased by 63%. In cerebellum the specific activity of inosine monophosphate was decreased by 52.5% and of phosphatidyl serine was increased by 95%. Distinct alterations were not observed in the intensity of incorporation of labelled precursor into phospholipids of stem. In big hemispheres the specific activity of the only inosine monophosphate was decreased by 57%.


[Comparison of lipoprotein spectrum and lipids in maternal blood and in umbilical cord blood of newborn infant]. Content of beta- and pre-beta-lipoprotein fractions, total cholesterol and triglycerides was distinctly lower in blood serum of infant than in maternal one. In serum of funicular blood content of free fatty acids was 2.5-fold higher than in maternal blood serum; in erythrocytes of infant content of cholesterol was found to be higher by 40%, as compared with maternal erythrocytes. In blood serum of infant content of free cholesterol amounted to 28% of the total cholesterol at the same time in maternal blood it was equal to 37%. The highest proportion of cholesterol was found in alpha-lipoproteins of infant, in mother it was observed in beta-lipoproteins. In blood of infant and mother the same types of lipoproteins were present but their quantitative ratio was different. The main lipoproteins of infant were shown to be alpha-lipoproteins. Relationship between the content of cholesterol in pre-beta-lipoproteins (correlation coefficient 0.64) was noted in blood of mother and infant.


[Nutrition and state of health of older persons during physiologic aging]. Features peculiar to actual nutritional pattern (in family) of persons of advanced and old age in physiological ageing were studied. According to a fairly broad range of characteristics (cardio-vascular function, blood coagulation system, lipids metabolism parameters, body weight, general clinical diagnosis, etc.) their health status was determined. The alimentation of the examined is shown to be characterized by marked individual peculiarities. On the whole it conforms to the existing recommendations, although there is noted a certain deficiency of proteins, vitamins and mineral elements. Differences in the nutrition of males and females were established. The calorific value of the nutrition declines parallel with the increasing age. Its comparison with the health characteristics of the examined testifies to the presence of a close relationship between them. More favourable indices of the bioelectric activity of the heart, myocardial contractility, the trends in the lipids metabolism, body weight, the blood clotting activity were registered in persons with reduced calorific value of the alimentation.


[HCO3- -stimulated ATPase of rat kidneys]. In homogenate and mitochondria of cortex and medulla of rat kidney a stimulating effect of different concentrations of bicarbonate on the ATPase activity was studied. By the rate of inhibition of Mg2+-ATPase and HCO3-ATPase, thiocyanate, perchlorate and azide were distributed as follows: N3 greater than CNS greater than ClO4. Thiocyanate inhibited non-competitively the HCO3-stimulated ATPase activity. The similarity was observed between HCO3-stimulated ATPase from rat kidney and bicarbonate-stimulated ATPase from other cells.


[New concepts on central regulation of the blood pressure. Mode of action of clonidine and alpha-methyl DOPA (author's transl)]. A review is presented of several reports which strongly indicate that the reaction pattern of "cardiovascular depression" (decrease in blood pressure, heart rate and cardiac output) is triggered off by the stimulation of alpha-adrenoceptors in the brain. The efferent information is mediated by an inhibition of the sympathetic and by an activation of the cardiac vagal system. The central alpha-adrenoceptors, which are localized within the medulla, are stimulated by the antihypertensive agents clonidine and alpha-methyl-DOPA, and also by central administration of other sympathomimetic drugs such as naphazoline, oxymetazoline, amphetamine and others. It can be assumed  that these drugs mimic the action of endogenous nor-adrenaline, which is present in considerable amounts in the brain stem, and which might, under physiological conditions, mediate the pattern of cardiovascular depression.


[Mutual stimulation of oncornavirus and herpetic infections in experiments in vivo and in vitro]. The evidence of mutual stimulation of herpes simplex virus (HSV) and oncornaviruses (OV) reproduction was obtained. HSV titers in mice pre-infected with Rauscher leukosis virus (RLV) were 2.25-3.0 lg LD50 higher than in mice of the same batch but without RLV infection. The continuous HEp-2 culture chronically infected with oncornaviruses was found to be more sensitive to the cytopathic effect of HSV strains, types 1 and 2, and in the culture fluid HSV accumulated to a greater titer than in primarily trypsinized culture of chick embryo fibroblasts. Electron microscope examinations of the continuous J-96 cell culture chronically infected with OV and HSV simultaneously revealed an 8.3-fold increase in the number of oncornavirus particles as compared to the control culture, infected with OV alone.


[Effect of a new food product--cryl paste--on chemical carcinogenesis]. The influence of a new food product obtained from oceanic shrimp--the cryl on the development of tumours under the effect of chemical carcinogens was investigated. DAB (n-dimethylaminobenzene) induced tumours of the liver in 90.8% of the test rats against the background of a caseine-rich diet and in 21.7% of the animals receiving the cryl paste as a part of their alimentation. With the diethylnitrosamine (DENA) induced tumours the lowest percentage (43) and inhibited development were noted with the rats fed on the cryl paste, and the highest--when feeding the animals of beef (74), whereas in the case of a caseine-rich diet--tumours developed in 50% of the animals. Features specific for morphogenesis of tumours induced with DENA with the animals kept on a diet containing different types of protein and also histo- and biochemical changes in the liver in carcinogenesis were studied.


[Effect of Cu++ ions on the morphological, cytological, and physiological state of Candida utilis cells in continuous culture]. Cells of Candida utilis grown in continuous culture under the influence of rather high concentrations of copper ions have been studied biochemically, morphologically, and cytologically. Although under these conditions a new steady state has been adjusted, the population is much more differentiated than under control conditions. With regard to their size, structure, and viability the cells have been arranged into 4 groups. Generally, the "copper cells" in comparison with the "normal cells" are more voluminous (average: 2.5 times; maximum: 4 times) and of altered structure. The appearance of dense particles ("copper containing particles"), globules ("lipid globules"), vacuoles, and the thickening of the cell wall, as well as the disappearance of the mitochondrial cristae have been shown as characteristic indications for damage in the cell substructure caused by the influence of copper ions. Occasionally abnormal cell shapes can be observed. A permanent influence of copper ions in the concentration used was followed also by striking disturbances of the cell metabolism. The cells take up more carbon, phosphorus, and nitrogen, whereas protein synthesis and respiratory activity decrease. Both the synthesis of lipids and polysaccharides and the phosphohydrolase activity increase. A discussion of the experimental data is presented.


Antiviral activity of certain hetarylhydrazones in Mengo virus infected mice. Out of a series of eleven related hetarylhydrazones four derivatives (ZIMET 124/73, ZIMET 38/74, ZIMET 44/69, and IMET 98/69), after subcutaneous administration (0.5 mmole/kg per injection), were found to possess significant antiviral activity against rapidly progressing and highly lethal Mengo virus encephalitis in mice. After peroral administration (2 mmole/kg per injection) only with IMET 98/69 significant protection was achieved. Drug treatments were given twice daily for 5 days. The effectiveness of compounds was evidenced by significant "rates of protection". Possible relationships between the antiviral activity and the structure of compounds are discussed.


[Antibodies to Epstein-Barr virus in the sera of children with different neoplasms]. The presence of antibody to virus capsid antigen (VCA) of Epstein-Barr virus (EBV) was determined in sera from children with various forms of neoplasia by the indirect immunofluorescence procedure of Henle. Eighty-one sera from children with Wilms tumor, teratoblastoma, reticulosarcoma, neuroblastoma, soft tissue sarcoma, as well as from children with benign tumors were examined. The controls included sera from normal children of the same ages. The test cells synthesizing VCA were suspension cultures of P3HR-1 cells which are one of the clones of Burkitt lymphoma. The studies showed no increase in the content of antibody to EBV in any of the groups of children with tumors as compared with the controls. It was also found that the percentage of EBV infection in various groups of sick and normal children varied from 82 to 100.


[Oncogeny of herpes simplex viruses and lupidon]. The part of the herpes simplex virus type 2 in the development of the cervex carcinoma of women is still an open question. After the serological findings that patients with cervix carcinoma have a higher rate of antibodies against type 2 than healthy women, which were initially published with great expectation, the molecular-virological examinations which were meanwhile carried out by several work groups to find traces of the herpes simplex virus type 2 in the carcinoma cells were negative, except some few but not confirmed cases. Hitherto but the results of transformation of embryonic hamster cells by UV-inactivated virus were the strongest indication for the herpes simplex virus possibly having oncogenic power, although one of the most important demonstrations, i.e. that of the virus DNA, is still lacking even for these transformed cells, which induce fibrosarcoma if injected to newborn hamsters. Possibly the transformation of the normal hamster cell into a tumor cell requires but such a small quantity of the herpes simplex virus DNA that it cannot be traced with the present methods. In connection with the question of the herpes simplex virus being oncogenic also LUPIDON which contains heat-inactivated herpes simplex virus, was examined. For this purpose extended transformation experiments in vitro and animal experiments with new-born hamsters were carried out. All these experiments had a negative result. There is thus no indication for LUPIDON having oncogenic properties.


[Epidemiology of herpes simplex diseases]. The epidemiological principle of the herpes simplex virus (HSV) infections is to have the affected host survive, to persist in it and thus to make it to be a life long starting point for new infection chains. There is an accurately tuned correlation between virus and host organism, in which the persistence of the virus as a latent infection in the ganglion cells of sensory neurones is of central importance. In this state the virus cannot be attacked by the defensive power of the body. When changing from latency in the ganglion cell to activity in the periphery it utilizes the nerve conduction. It has not yet been cleared which factors are responsible for the change-over from the productive, cytocide infection to the latent infection, how the latency is being stabilized and how the reactivation to the herpes recidivans takes place. The organ and tissue specifity of both the HSV types 1 and 2 seems to be bound to the entire pathogenetic complex so that inspite of occasional reverse infections HSV type 1 remains epidemiologically the facial virus type and HSV type 2 the genital one. Apparent and inapparent rimary infections and relapes lead to numerous uncontrolled contacts so that the rate of infection is 50% until the age of puberty and 80% in middle-age adults. The contamination with the mainly venerically transmitted HSV type 2 starts with the age of puberty and reaches abt. 10 to 15% of our population. In patients suffering from cervix carcinoma antibodies against herpes simplex virus type 2 are more frequently demonstrated. Comparative examinations have shown that an increased exposition cannot be the sole cause for this prevalence. The kind of relationship between herpes genitalis and cervix carcinoma remains, however, unclear.


[Histochemistry of the carbohydrate metabolism in cysts of Toxoplasma gondii (author's transl)]. Mice were infected with cysts of the ALT strain Toxoplasma by intraperitoneal injection. After 2-8 weeks disseminated cysts could be demonstrated in the brain tissue. All cysts showed identical histochemical characteristics, independent of their sizes or their cell number. The encysted organisms were intensely stained after the PAS-reaction. This polysaccharide is highly diastase and acid resistant. Glycogen synthetase activity could not be demonstrated, but phosphorylase activity was very high. The energy metabolism was characterized by a high lactate dehydrogenase activity, whereas the reaction for succinate dehydrogenase activity only leads to sparse deposits of reaction products. The carbohydrate content is interpreted to be not only a store of energy substrate but also a store of biosynthetic substrate. It is assumed that a part of the liberated glucose at high activities of G-6-P-DH and 6-P-G-DH is metabolized by the hexose monophosphate shunt, the pentoses of which may contribute to nucleic acid synthesis which is necessary for the proliferation of the encysted organisms.


[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. III. Occurence of diphosphatases in muscular tissue (authors' transl)]. After a review on the present knowledge of the occurence of diphosphatases in muscular tissue own data of the diphosphatase acitivity in the bovine longissimus muscle of nine animals are reported. Remarkable differences between animals were observed, the diphosphatase activity being much lower than the tripolyphosphatase activity.


[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. IV. Change in the tripolyphosphatase activity of muscle post mortem (author's transl)]. The triphosphatase (TPase) activity of minced bovine muscle increased during storage of the intact muscle post mortem; after development of rigor mortis it remained constant. The TPase activity of porcine muscle is influenced by the rate ofpost mortem glycolysis.


Production of aflatoxin B1 and G1 by Aspergillus parasiticus on silica gels. Silica gels were prepared by acidifying alkaline silicate solutions with phosphoric or tartaric acid. Various combinations of glucose, sucrose, yeast extract, and salts were included in the gels an nutrients. Maximum production of aflatoxins B1 and G1 occurred when silica gel (0.4 to 0.5 cm deep in a petri dish) containing 20% sucrose and 2% yeast extract, and gelled with tartaric acid, was inoculated with approximately 120 to 12000 spores of Aspergillus parasiticus per plate; and plates were incubated at 28 degrees C for 10 days.


[Genetical investigation of adenylate kinase in the population of the Lübeck area using agarose-thin-layer electrophoresis (author's transl)]. Adenylate kinase phenotypes were determined in a sample of 604 persons in the vicinity of Lübeck by means of thin-layer agarose-electrophoresis: A gene frequency of 0,9577 was estimated for AK1 and 0.0423 for AK2.


[Use of the passive hemagglutination test for the purpose of determining antibody levels following animal immunization with Cl. perfringens toxoid]. Data are presented on the study of possibilities of the application of the passive hemagglutination test for titration of the blood sera of mice, guinea pigs and rabbits immunized with Cl. perfringens toxoid. A diagnostic agent obtained by the sensitization of formalin- and tannin-treated sheep erythrocytes with the serologically pure toxoid, and homologous sera (as standard) were used in this test. A high immune response of BALB/c and C3H mice to the Cl. perfringens toxoid permits to suggest inbred mice as a model for the immunological and immunogenetic studies connected with this toxoid.


[Epidemiologic features of acute viral respiratory infections in familial foci]. A study was made of the epidemiological peculiarities of viral respiratory infections of various etiology in the familial foci with the use of a methodical approach permitting to detect the true spread of infection in the familial foci, with consideration to the subclinical forme fruste of the disease and "carrier state". It appeared that in the familial foci the infectiousness of the majority of respiratory viral infections was greater than in the closed collective bodies uniting persons of the same age. The age composition of the family influences the manifestness (particularly in parainfluenza infection) and the intensity of the epidemic process characterized by the coefficient of the secondary affections. The type of the apartment, the floor on which it is located, and the number of persons residing in it had no significant influence on the spread of the viral infections in the familial foci. A definite role in this process is played by the level of specific serum antibodies in the members of the family surrounding the patient. The association of morbidity level with the antibody level proved to be the most distinct in children with influenza and adenoviral infection; this association was less significant in adults.


Proteolytic activity of subcellular fractions from Streptomyces griseus no. 45-H. Subcellular fractions were prepared from Streptomyces griseus No. 45-H at different stages of life cycle, and their proteolytic activity was examined. The highest proteolytic activity was found in the 24- and 72- h-old vegetative hyphae, the lowest in the resting spores. Spores contained about 9--30% of the proteolytic activity of vegetative cells. At the age of 16 h about 80%, at 26 h 70%, at 72 h 40%, and in spores about 60% of the proteolytic activity was particulate. The greatest part of the proteolytic activity could be inhibited by EDTA, lower levels of serine and sulfhydryl protease activities were detected in the cell-free extracts of vegetative cells.


Cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. Hemorrhagic shock was induced in rats by bleeding to 35 mmHg for a period of 4 h. Plasma glucose increased rapidly following the onset of bleeding and reached twice the control value after 30 min. After 2 h hypotension the liver content of glycogen was depleted and subsequently the rats became hypoglycemic. The rise in plasma glucose was accompanied by a rise in plasma cyclic AMP, which was 10-fold after 1 h, but returned towards control values at the end of the hypotensive period. There were no corresponding changes in the cyclic AMP contents of liver, heart or adipose tissue. Blood lactate was increased 10-fold and the lactate/pyruvate ratio was more than doubled, suggesting an increased anaerobic metabolism. Plasma FFA levels fell significantly, while plasma glycerol was unchanged during the hypotensive period. In this hemorrhagic shock model there is an initial phase of glucose mobilization from the liver, which is accompanied by elevated plasma cyclic AMP. This phase is followed by a period of depressed levels of glucose as well as FFA and thus a lack of metabolizable substrates in plasma.


[Functional state of the adrenal cortex in patients with Parkinsonism before and after surgical treatment]. The results of biochemical examinations of the hormonal function of the adrenal cortex in 22 patients with Parkinson's disease are presented as seen prior and following stereotaxic operations on the ventro-lateral nucleus of the thalamus. It was found that parkinsonics have a decreased androgenic, glucocorticoid and mineralocorticoid function of the adrenal cortex. Long history and growing severity of the disease manifest themselves in a distinct inhibition of the adrenal cortex function. The importance of the changes in the functional state of the hypothalamo-hypophyseal system in the revealed disorders in the hormonal activity is emphasized. Along with a beneficial clinical effect surgery brings about an improvement of the functional state of the adrenal cortex.


Urinary aldosterone excretion rate and plasma aldosterone concentration in the rat: effect of ACTH, DOC, furosemide and of changes in sodium balance. In rats kept under standard conditions urinary aldosterone exretion rate (UAER) and plasma aldosterone concentration (PAC) showed a circadian rhythm with peak values at the beginning of the dark perioith a single dose of DOC (2 mg/kg sc) or given saline as drinking water UAER and PAC decreased to very low levels. Restriction of dietary sodium for 5 weeks increased UAER and PAC 60-fold and 100-fold, respectively. Treatment with ACTH (250 or 500 microng/kg iv) stimulated UAER 8 h following injection and PAC 1 h after injection. In rats treated with a single dose of furosemide (25 mg/kg sc) PAC increased to maximal values within 90 min and reached control values within 24 h. Twenty-four hours-UAER also increased after furosemide treatment. UAER paralleled PAC under all experimental conditions tested. Therefore, our results suggest that UAER is a reliable index of the activity of the renin-angiotensin-aldosterone system in rats under conditions of low and high aldosterone secretion. Measurement of UAER is a useful tool for studies on aldosterone levels in rats over a long period of time.


Effect of local or parenteral application of ACTH or hydrocortisone on bovine corpus luteum function. Studies were conducted to determine the effect on corpus luteum (CL) function of ACTH or hydrocortisone administered by ovarian perfusion on day 11 of the oestrous cycle or by carotid infusion on days 2-9 of the oestrous cycle. No significant local effects on CL function were observed during the ovarian perfusion study. Continuous carotid infusion of ACTH or hydrocortisone on days 2-9 resulted in a decreased slope of the progesterone increase during the infusion period. However, no difference in plasma progesterone level on days 9-11 between control and treated cycles was detected and there was no difference between treated and control CL at day 11 with regard to CL weight or progesterone content. The data suggest a possible direct effect of hydrocortisone on either the hypothalamus or pituitary which results in decreased progesterone secretion but not CL development. No residual effect was observed.


Clinical and virological findings in patients with cytologically diagnosed gynecologic herpes simplex infections. Amoung 57,117 routinely collected Papanicolaou smears from the female genital tract there were 90 slides (0.16%) from 85 patients on which a cytologic diagnosis of herpes simplex virus (HSV) infection was made. The characteristic cytologic changes occurred predominantly on the ectocervical part of the smears. The changes were transient but occasionally remained detectable on the corresponding histologic specimens up to 2.5 months. Viral isolation was successful in a majority of cases when performed simultaneously with or less than a week after the cytologic diagnosis. The rate of success rapidly decreased thereafter. Positive fluorescent antibody assays of viral antigens on cytologic smears behaved similarly. Cases with apparent primary infection as well as with secondary infection (recurrences) were included in the material but no differences in the morphology of virally altered cells and be found, indicating that primary and secondary infections could not be distinguished on this basis. There were significantly more cytologic dysplastic changes as well as assorted micro-organism infections in the HSV group as compared to the controls.


A simple and rapid method to measure non-protein-bound fractions of cortisol, testosterone and oestradiol by equilibrium dialysis: comparison with centrifugal filtration. A simple method for measuring the free, non-protein-bound steroid fraction in plasma by equilibrium dialysis is described. The alteration occurring in the volume of the inner phase (undiluted plasma) is corrected by the difference in weight before and after dialysis. Total cortisol was determined by radioimmunoassay. Although it is not possible to differentiate between values for total cortisol after ACTH stimulation (242.2+/-shing's syndrome (n: 15)), and women treated with oestrogens (211.8+/-42.0 ng/ml (n: 20)), there were significant differences for free cortisol (ACTH stimulation: 29.3+/-5.6 ng/ml; Cushing's syndrome: 31.5+/-8.6 ng/ml; women under increased oestrogenic activity: 10.0+/-2.1 ng/ml; pregnant women: 13.7+/-5.1 ng/ml plasma). Compared with normal values for healthy women and men (9.3+/-1.4 ng/ml), women with increased oestrogenic activity showed slight elevations of free cortisol. Compared to cortisol, the percentage of dialysable testosterone and oestradiol was lower in women than in men (1.57 vs. 2.08% for testosterone and 1.68 vs. 2.15% for oestradiol). In healthy men the concentration of free steroid was 13.1+/-1.0 ng free testosterone/100 ml plasma (0.44+/-0.045 pg free oestradiol/ml plasma), in healthy women 0.64+/-0.07 ng/100 ml (0.98+/-0.10 pg/ml) and in women receiving oestrogens 0.37+/-0.04 ng/100 ml (0.01+/-0.015 pg/ml). When the method described here for determing the free fractions of cortisol (n: 45), oestradiol (n: 18) and testosterone (n: 18) at 37 degrees C is compared with the method of centrifugal filtration, the correlation was r: 0.80 r: 0.86 and r: 0.91, respectively. In practice, equilibrium dialysis with undiluted plasma is simple, fast and can be applied to all steroid hormones. It allows direct measurements of non-protein-bound steroids under nearly physiological conditions.


Triodothyronine and thyroxine nuclear receptors in lyphocytes from normal, hyper- and hypothyroid subjects. In an investigation of thyroxine (T4) and triiodothyronine (T3) receptors in humans, the lymphocyte was chosen as the target cell. This study was performed to elucidate whether T3 and T4 bind to different receptors, if T4 is bound only after conversion into T3, and whether there is any modification of the receptors in hyper- and hypothyroidism. Lymphocytes were found to possess a high-affinity, limited-capacity bindings sites for both T4 and T3. The mean equilibrium affinity constant (Ka) was 2.28-10(10 +/- 0.21 m-1 for T3, and 0.98 - 10(10) +/- 0.16 m-1 for T4. The mean number of saturable binding sites was 115 for T3, and 102 for T4. The binding capacities and affinities also determined in the lymphocyte nuclei isolated after incubation of the intact cell, were similar to those observed in the intact cells. In competition experiments, labelled T4 was as readily displaced by T3 as by T4 itself, whereas labelled T3 was displaced only by a 40 times higher concentration of T4 than T3. These observations suggest identical receptors for the two hormones and a binding of T4 as such, provided it is not in competition with T3. In lymphocytes from hyperthyroid patients, receptor affinities and numbers remained unchanged. In lymphocytes from hypothyroid patients, the affinity was normal, but the mean number of T3 binding sites was increased to 310 (P less than 0.0001), to return to normal after a few months of treatment.


Significance of 17alpha OH progesterone assay in the evaluation of ovarian and adrenal function. Plasma 17alpha OH progesterone was assayed radioimmunologically, using an anti-17-OH-progesterone BSA antiserum as specific binding antigen. The method consisted in extracting steroids with ethyl ether from 1 ml plasm (to which 17alpha OH progesterone-1,2-3H had been added for the assessment of losses); the extract was then submitted to chromatography on a Sephadex LH-20 column, antiserum was added and the free steroid was separated from the bound form by Charcoal-dextran. Average recovery of 17alpha OH progesterone-1,2-3H was 75+/-5%. Minimum sensitivity of the method oscillated about 7-10 pg. MIF (Method Interfering Factors) were evaluated. The method was used for the assay of 17alpha OH progesterone plasma levels during normal menstrual cycles, in women undergoing ovarian stimulation with HMG and HCG in the follicular and luteal phase respectively. Finally, changes of plasma 17alpha OH progesterone levels were assessed during adrenal stimulation and suppression in various stages of the menstrual cycle.


Neither cyclic AMP nor cyclic GMP appear to mediate antral gastrin release in the dog. To evaluate whether cyclic nucleotides play a role as mediators in antral gastrin release, the following in vivo experiments were performed in dogs. An antral pouch was constructed and the rest of the stomach, the pancreas and small and large intestine were resected. A gastric artery supplying the pouch was cannulated, and after a basal period with saline infusion either dibutyryl cyclic 3',5'-adenosine monophosphate (cyclic AMP, 0.2 mg per kg per min), dibutyryl cyclic 3',5'-guanosine monophosphate (cyclic GMP, 0.05 mg per kg per min) or saline were infused over a period of 60 min. To prove the viability of the pouch and to show its ability to release gastrin with proper stimulation, bethanechol chloride (urecholine) was infused into the gastric artery at the end of the experiment. Blood samples were taken from the portal vein and assayed for gastrin. Neither cyclic AMP nor cyclic GMP infusion was found to increase portal gastrin concentration to a significant degree. A marked increase in portal gastrin concentration however, was observed when bethanechol chloride was infused. These studies lend no support to the thesis that cyclic nucleotides mediate gastrin release in the dog.


The effect of ACTH and cortisone on the behaviour of arylsulphatases in the salivary glands of white rat. Many reports show (DAVIDOFF 1973, HOOK et al. 1970, KOSTULAK 1974, MILSOM 1970, THYBERG 1972) that arylsulphatases are widely present in the tissues of many animals, and a high activity has been observed, among other things, in secretory epithelia (HSU and TAPPEL 1965, KOSTULAK 1975, MAKITA and SANBORN 1971). The occurrence of these enzymes some authors connect with the metabolism of sulphated polysaccharides (DOGSON 1968, MARTIN et al. 1969, MEYER 1969). However, although the specificity and intracellular localization of these enzymes in different tissues have been described perviously, there are only a few reports about their localization in the salivary gland, and the functional role of arylsulphatases in the physiological function of the salivary glands. The observations reported by numerous authors (KOZLOWSKA 1973, KYAW and MELLORS 1972, SACHS and DE DUVE 1962), and in ours studies (KOSTULAK 1975) indicate that the activity of lysosomal enzymes, including arylsulphatases, is modified by steroid hormones. Moreover, it is known that these hormones have an influence on the composition and nature of the carbohydrate-protein complexes produced by the salivary glands (KOFOED et al. 1973, KOSTULAK et al. 1972). Therefore it seemed interesting to examine the behaviour of arylsolphatases in the salivary glands after treatment with large doses of ACTH and cortisone, and find if there is any correlation between the activity of these enzymes and the changes of sulphated polysaccharides observed previously in the cell of the salivary glands after applying ACTH and cortisone.


Infantile chronic peripheral neuropathy with giant axons. Report of a case. An 8-year-old boy with a slowly progressive motor neuropathy is described. The first signs appeared at the age of 3 years. Histological examination of the sural nerve showed the presence of numerous segmental axonal swellings and features of demyelination as well as remyelination. These enlargements were filled with irregularly orientated 10 nm filaments. The case resembled the previously described cases of giant axonal neuropathy but differed from them in absence of kinky hair.


Department of Neurology, Northwestern University Medical School, Chicago, Illinois. A case of non-progressive congenital myopathy is described in which there was absence of muscles and scapulo-peroneal distribution of weakness. The muscle biopsy showed preferential atrophy of Type I fibers and subsarcolemal bodies. These bodies were composed of an acidic protein with sulphahydryl groups which showed acid stable adenosine triphosphatase activity. The possibility of a maturational arrest as a cause is presented.


Filamentous and multilamellated cytoplasmic inclusions in progressive multifocal leukoencephalopathy. Inclusions identical to those described in multiple sclerosis (MS) brain by Prineas (1975) have been seen by ultrastructural study of cerebral tissue in two elsewhere reported cases of Progressive Multifocal Leukoencephalopathy (PML). The meaning of these formations, which have been suggested to be related to a special process of demyelination in MS, is discussed in the light of the hypotheses concerning the demyelination mechanism in  PML. Whatever might be their significance, these cytoplasmic non viral inclusions are not specific for MS.


Microprobe scanning of normal and pathological human peripheral nerve. The localization of calcium (Ca) and phosphorus (P) by scanning with the electron microprobe of Casting, provides a morphological outline of the normal nerve which can be used qualitatively and quantitatively for comparison with abnormal nerves. The normal saphenous nerves of eight cadavers and the abnormal saphenous nerves of two cases of diabetic neuropathy, were scanned and the results compared.


The role of the subependymal plate in avian sarcoma virus brain tumor induction: comparison of incipient tumors in neonatal and adult rats. F-344 rats were inoculated intracerebrally at 1 and at 133 days of age with the Bratislava-77 strain of avian sarcoma virus. Groups of rats were sequentially sacrificed following inoculation so that early stages of microtumor formation could be evaluated. In neonatally inoculated rats incipient tumors developed in the subependymal region of the lateral ventricles in close juxtaposition to clusters of poorly differentiated germinal cells. Among these animals microtumors were detected as soon as 2 weeks after inoculation; by 4 weeks post-inoculation all rats inoculated at 1 day of age had tumors. In contrast among rats inoculated as adults incipient tumors developed in the cerebral cortex away from the subependymal region but adjacent to the locus of inoculation. Incipient tumors were uncommon in rats inoculated as adults during the first 2 months after inoculation.


[Electron microscopic study of nerve, muscle and skin lesions induced by perhexiline maleate (author's transl)]. The pathological findings in four nerves and muscles and in one skin biopsies from four patients treated with perhexiline maleate for angina pectoris are reported. In every case, a muscular denervation atrophy and a decrease in the large diameter myelinated fibers were observed. Only one case showed a decrease of the total number of myelinated fibers, on quantitative studies. The electron microscopic study of each nerve displayed findings consistent with a predominant schwannian degeneration, associated with a few onion bulbs formations and, in two cases, with a mild wallerian degeneration. The most striking finding consisted in  the presence of polymorphous membrane-bound inclusions reminding the morphology of lysosomal complex lipids. These structures were very abundant in Schwann cells, but they were seen also in fibrocytes, endothelial and pericytic cells. Similar inclusions were present in the single muscle and skin biopsies studied by electron microscopy. In the muscle, they were seen in muscular cells as well as in endothelial and pericytic cells. In the skin, similar inclusions were observed in endothelial, smooth muscle and sweat gland cells. These inclusions were difficult to identify in one micron thick sections, emphazing the need of ultrastructural study for diagnostic purposes.


I-cell disease (mucolipidosis 11). Pathological and biochemical studies of an autopsy case. An autopsy case of I-cell disease was examined by histological, histochemical, ultrastructural and biochemical methods. Cultured fibroblasts contained numerous PAS- and oil-red O positive granules consistent with lysosomes. The beta-galactosidase activity was specifically low in liver of the patient. The fiboblast-like cells including the cardiac valves, periosteum and stromal cells of the organs were closely similar to those found in mucopolysaccharidoses histochemically as well as ultrastructurally. Lipid-like materials were observed massively in the myocardium and in the neurons of spinal ganglia, and from these organs excessive amount of ceramide tri-hexosides (CTH) was extracted. In a few hepatocytes the dense membrane-bound bodies suggestive of lipids were found by electron microscopy. Swollen glomerular epithelium contained strongly colloidal-iron positive material, but the amount of mucopolysaccharides in kidney was not elevated. In this paper, the relationship among the morphology, the material stored and the enzymes was discussed.


Immunohistological study on the ACTH producing islet cell carcinoma of the pancreas. ACTH producing cells in islet cell carcinoma associated with Cushing's syndrome were studied by an improved immunoperoxidase as well as immunofluorescence technique. The cells which contained ACTH antigen were distributed throughout the tumor tissue of both primary and metastatic lesions in rather small numbers. In the small cancer nests they were present in an irregular or mosaic pattern and, on the contrary, they tend to line along the margin in the larger nests. The intracytoplasmic localization of the ACTH antigen was characteristically demonstrated in the infranuclear area of the tumor cells, closely simulating that of the argentaffin granules of the enterochromaffin cells. The electron microscopic observation identified membrane enclosed, cored granules, 200-300 nm in diameter, present in clusters in the infranuclear area of some tumor cells, which were considered corresponding well to the ACTH positive cells in immune staining.


Viral placentitis - a case report.

Viral placentitis - a case report. A case of viral placentitis, in a 20 year-old pregnant woman suffering from chronic glomerulonephritis, was presented. In light microscopic findings of the placenta, many necrotic foci with intranuclear inclusion - bearing cells revealed in chorionic villi and by electron microscopy numerous immature and mature virus particles, probably herpes simplex were proved in intranuclear inclusion-bearing cells.


Demonstration of host antigens in the myxovirus memebrane: lysis of virus by antibody and complement. Complement-mediated lesions developed in myxovirus membranes in the presence of antibody to host antigens. Intact virions reacted with antibody to the keratosulphate-like host antigen present in the spike layer. Spike-deprived influenza virus reacted in the same way when an antiserum to the Forssman glycolipid was used. The holes in the membrane varied considerably in size, but were otherwise similar to those found in erythrocyte membranes. This immune electron microscopy method proved useful for the localization of host material in viral membranes.


Classification of coagulase-negative staphylococci in the diagnostic laboratory. One hundred and ninety-eight coagulase-negative staphylococci isolated from urines, blood cultures, and pus samples were classified by means of two identification schemes, and their wall teichoic acids were determined serologically. S. epidermidis, S. saprophyticus, and S. cohnii were identified reliably by the use of five criteria: acid aerobically from sucrose, trehalose, and mannitol, phosphatase production, and sensitivity to novobiocin. Further species, notably S. haemolyticus and S. hominis, could be identified when haemolysis on blood agar plates was included in the criteria group. The investigation shows, that a considerable number of coagulase-negative staphylococci isolated from human specimens belong to species other than S. epidermidis and S. saprophyticus. These staphylococci can cause human infections and should be identified in the diagnostic laboratory. S. epidermidis and S. saprophyticus were found to contain the teichoic acids previously identified in these species. S. cohnii contained the same teichoic acids as S. saprophyticus. No characteristic teichoic acid was demonstrated in the other species, but several strains contained poly C (beta-N-acetylglucosaminylglycerol teichoic acid).


Alpha-receptor subsensitivity of isolated atria from rats following physical training or repeated ACTH-injections. Decreased chronotropic and inotropic sensitivity of isolated atria to phenylephrine but not to isoprenaline was found in rats following repeated physical training by swimming or repeated ACTH-injections. These changes were induced within a week of subjection of animals to these treatments. It is concluded, that these effects are mediated by increased adrenergic activity which results in this subsensitivity of alpha-receptors.


Effects of ACTH 4-10 on ECT-induced memory dysfunctions. Double-blind studies of ACTH 4-10 and placebo were conducted in psychiatric patients receiving bilateral ECT to determine whether the polypeptide exerted anti-amnesic effects. Observations after a single ECT were suggestive of some positive effects, but studies between seizures after five or six ECTs showed no significant drug-placebo differences. Although the findings were largely negative, they do not rule out positive effects of ACTH 4-10 on memory. Possibly the designs and timing of the experiments and/or the dosages of ACTH 4-10 employed were unsuitable for demonstrating such influences.


Electron microscopic studies of various cells in the alveolar wall of mice with special reference to spheroid alveolar epithelial cells after intravenous injection of squid-ink (sepia-melanin) solution. The effect of an intravenous injection of squid-ink (sepia-melanin) solution on adult mouse spheroid alveolar epithelial cells was observed by the electron microscope. Sepia-melanin particles were seen in all alveolar wall cells examined that seems to suggest the entrance of sepia-melanin particles into the spheroid alveolar epithlial cells from the alveolar blood capillary. In cases of large penetrations of sepia-melanin particles into spheroid alveolar epithelial cells, a greater increase was found in the intramitochondrial granules. In addition, the so-called inclusion body believed to be formed by the degeneration of mitochondria had very high electron density and its quantity was abundant. On the contrary, in cases where the quantity of sepia-melanin entrance into the spheroid alveolar epithelial cell was small, neither an increase of intramitochondrial granules, an increase of the electron density nor an increase in the quantity of specific inclusion body was found.


Tissue localization of C1q in HBs antigen positive liver disease patients by direct immunofluorescent technique. Tissue localization of a subcomponent of the first component of complement (CLq) was examined in one postmortem case of HBs antigen (HBs Ag) positive hepatocellular carcinoma and in six cases of chronic hepatitis from liver biopsy specimens. The direct immunofluorescent method was used after fixation with 2% para-formaldehyde in concentrated ammonium sulfate. CLq localization was found in collagen fibers and the cytoplasm of fibroblasts in the connective tissues of specimens examined. The localization was particularly marked in the region of the fundal glands of the gastric wall. Apart from collagen fibers, other sites of localization included the surface membrane of lymphocytes, especially those cells of the mesenteric lymph nodes. In HBs Ag positive specimens, immune deposit-like substances appeared localized intra-hepatically and in the renal glomeruli. Since C3 and C4 were identified concomitantly, it indicates that these substances were indeed immune diposits. Despite the finding that C3 and C4 were identified together in the hepatic cell cytoplasm, C1q itself was not demonstrated in all hepatic cell cytoplasms.


After-care services for schizophrenic patients. The multi-dimensional therapeutic requirements of an aftercare programme for schizophrenic patients are emphasized. The manipulation of a single variable, e.g. a drug, without paying attention to the social, demographic and ecological context of the programme, may lead not only to disappointing results but to non-valid comparisons of effectiveness between results in different centers. In face of the multiple contraints, the after-care of the schizophrenic patient will long remain a task of therapeutic skill.


Use of elution marker for the intratypic characterization of poliovirus strains. Elution marker was used for intratypic characterization of poliovirus strains with Al(OH)3 gel as adsorbent. The virion suspensions to be tested were partially purified by chromatography and labelled with 32P. In the labelled preparations of wild virus strains practically all radioactivity was found in virus-specific bond, whereas in those of the vaccine strains and isolates of vaccine origin a considerable, but variable, proportion of the activity was bound to residual cell components. For this reason, the EC50 value (i.e. the phosphate molarity corresponding to the 50% adsorption equilibrium of virions), for the vaccine and vaccine-like strains showed a wide scattering. The activity bound to cell components was removable from the gel with 0.005 M phosphate buffer, whereas the elution maxima for all the poliovirus strains examined so far were over 0.02 M. The elution marker was calculated for 25 type-2 and 30 type-3 strains, all isolated during or soon after vaccination periods from cases suspect of poliomyelitis, both with and without taking into account the cell-bound activity. In the latter case, the EC50 values agreed with that for the corresponding reference vaccine strain much better than in the former; furthermore, the type-2 reference vaccine strain and the type-2 isolates, indistinguishable from the wild reference strain by the original method, could easily be differentiated on the basis of the corrected EC50 value. The possibility that the lack of an appreciable proportion of cell-bound radioactivity may reflect the pathogenicity of poliovirus strains is discussed.


Studies on the regulation of the biosynthesis of myocardial adenine nucleotides. 1) Changes in the rates of biosynthesis of adenine nucleotides in rat hearts under various experimental conditions are paralleled by corresponding alterations in the concentration of cyclic AMP. 2) Pentoses and pentitols cause an acceleration of the de novo synthesis of adenine nucleotides in the normal heart and a further amplification of the increase of adenine nucleotide synthesis in isoproterenol-stimulated hearts. 3) The enhancement of de novo synthesis of adenine and nucleotides induced by isoproterenol as well as by pentoses and pentitols appears to be causally related to a greater availability of 5-phos-phoribosyl-1-pyrophosphate.


Immunological aspects of purine metabolism. The development of our knowledge of the immune system has been reviewed and evidence presented of the need for a rapid rate of purine synthesis de novo for the proliferative events in this process. The mechanism of the inhibition of the immune system in a model of ADA deficiency has been studied intensively and considerable indirect evidence obtained of adenosine toxicity as a possible mediator of a reversible inhibition of proliferation of T-cells and to a slightly lesser extent B-cells. A secondary inhibition of ADA by inosine accumulation in PNP deficiency is proposed as a unifying hypothesis in which a somewhat lesser adenosine toxicity would inhibit proliferation only only of T-cells. The correction of the immune response by addition of ADA both in vitro and in vivo provides strong evidence in favor of this view. In HPRT deficiency no evidence was found of a gross impairment of the immune system; however, the HPRT enzyme is required for inhibition of the immune response by 6MP in a variety of systems using different mitogenic stimuli.


H1 - and H2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscles from guinea-pig hearts. On guinea-pig heart we investigated whether cyclic AMP serves as a messenger for H1 - and/or H2-mediated responses to histamine. (1) On papillary muscle histamine elicited positive inotropic responses which were antagonized by burimamide but not by promethazine. The stimulation of H2-receptors was not only associated with an increase in contractility but also with an increase in cAMP. As shown by the time course of effects for 10(-5) M histamine, the maximal increase in cAMP preceded the maximum in contractility. The mechanical and biochemical responses to histamine were potentiated by the phosphodiesterase inhibitor papaverine, but antagonized by burimamide. (2) On the left guinea-pig atrium containing H1-receptors the inotropic response to histamine (10(-5) M) was not accompanied by increases in cAMP at stimulation frequencies of 0.5 and 2 Hz, respectively. In addition, in the presence of papaverine (3 X 10 (-5) M) no change in the cyclic AMP level occurred after application of histamine. Papaverine by itself, however, concomitantly increased contractility and cyclic AMP at a stimulation frequency of 0.5 Hz. In contrast, at 2 Hz papaverine increased only cAMP leaving the contractility unchanged. At this frequency the well-known Ca2+-antagonistic effect comes into prominence, thus masking the positive inotropic effect attributable to the inhibition of the phosphodiesterase. (3) On the right guinea-pig atrium the mediation of the positive chronotropic response to histamine by H2-receptors which is partly involved in the inotropic effect via the frequency-force relationship does not lead to a concomitant increase in cAMP. Also, in the presence of papaverine, histamine had no influence on the cAMP. However, papaverine potentiated the cardioacceleration produced by histamine. Although it is very likely that the cAMP in the sinus node rises, we were not able to detect an increase in cAMP in the whole atrial tissue. From the present results the conclusion can be drawn that the mediation of the inotropic effect due to stimulation of H2-receptors by histamine is associated with an increase of cyclic AMP, whereas that of H1-receptors is not. The view that cAMP may be the second messenger in the chronotropic action of histamine needs further elucidation by experiments on sino-atrial cells.


Role of phosphate, pyrophosphate, adenine nucleotides and sulfate in activating production of the superoxide radical by macrophages, and in formation of rat paw edema. The presence of anions of phosphate (Pi), pyrophosphate (PPi), adenine nucleotides and sulfate greatly enhanced the production of superoxide radical (-O-2) by isolated guinea-pig macrophages. These anions, however, failed to enhance the production of -O-2 by the xanthine oxidase system, suggesting that they serve only as activators of -O-2 generating enzyme(s) located on the macrophage cell membrane. Many other common anions  were ineffective in the macrophage system. In the presence of concentrations of Pi, PPi, adenine-5'-triphosphate (ATP) reported to be in the synovial fluid, -O-2 was produced efficiently and was inhibited by diclofenac sodium. These anions induced rat paw edema, maintained the swelling at least up to 6 h. The edema was suppressed partially by repeated injection of superoxide dismutase (SOD). High doses of sodium chloride and nitrate failed to maintain the swelling.


A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis. The acute inflammatory response to calcium pyrophosphate dihydrate crystals follows the meeting of neutrophils and crystals. The ensuing phagocytosis leads to the generation of a glycoprotein chemotactically active for neutrophils and to the release of lysosomal enzymes. Indomethacin and phenylbutazone, at therapeutic concentrations, impaired phagocytosis of the crystals and generation of chemotactic factor activity. Colchicine had no effect upon phagocytosis but significantly impaired the appearance of chemotactic factor activity.


Primary adrenocortical insufficiency (Addison's disease). In the United States the etiology of most cases of adrenal gland atrophy or destruction is unknown. Autoimmune processes may be responsible. With rare exceptions, all three zones of the adrenal cortex are destroyed and there is reduced glucocorticoid, mineralocorticoid and androgen secretion. Although the deficiency of glucocorticoid is probably the most severe threat to life, treatment is available to correct all the deficiencies. Patient education and preparedness can prevent serious complications.


Significance and treatment of nocturnal angina preceding myocardial infarction. The presence of nocturnal angina and congestive heart failure within the month prior to admission was evaluated in the 174 patients with acute myocardial infarction. Heart size was evaluated radiographically at the time of admission. Twenty-three patients (13 per cent) experienced nocturnal angina. The incidence of nocturnal angina was significantly higher in those with anterior myocardial infarction (p less than 0.005) and subendocardial infarction (p less than 0.02) when compared with patients with inferior MI. Congestive heart failure was more common prior to admission in those with nocturnal angina (9/23) as opposed to those without (3/141) (p less than 0.001). Cardiomegaly was seen in 9/23 patients with nocturnal angina and 22/141 without (p less than 0.02). We conclude that the presence of nocturnal angina in those who develop MI increases the likelihood that the infarction will be either anterior or subendocardial rather than inferior. The association of nocturnal angina and congestive heart failure to anterior myocardial infarction is probably due to more severe and probably significant left coronary artery disease.


Morphological and histochemical organization of the flexor carpi radialis muscle in the cat. Most studies concerning the structure and function of skeletal muscle have utilized the hind limb of the experimental animal. However, it has been shown that the number of behavioral tasks performed by the cat's forelimb is greater than that of the hind limb. In addition, the forelimb muscles exhibit a functional complexity not observed in hind-limb musculature. The purpose of this study was to investigate the distribution of fast-twitch and slow-twitch muscle fibers and muscle spindles in the flexor carpi radialis muscle (FCR) and to correlate the distributional patterns in these structures with muscle tendon architecture and muscle function. It was found that the FCR, a wrist flexor, contains 37% slow-twitch fibers and 63% fast-twitch fibers. However, the slow-twitch fibers were concentrated in the deep region located between the tendons of origin and insertion, while the fast-twitch-glycolytic fibers were concentrated more peripherally. Muscle spindles were associated with the slow-twitch region and were never found in the region containing high concentrations of fast-twitch-glycolytic fibers. Fast-twitch-oxidative-glycolytic fibers were uniformly distributed throughout the muscle. It is proposed that the association of muscle spindles with slow-twitch fibers and the differential distribution of muscle fibers into slow-twitch and fast-twitch regions might allow these regions to function independently of one another when called upon to perform complex behavioral tasks.


Plasma triglyceride lowering by exercise despite increased food intake in patients with type IV hyperlipoproteinemia. Exercise can lower fasting triglyceride levels (TG). This study was undertaken to determine whether the exercise-induced decrease in TG is the result of a negative caloric balance. Five subjects with primary type IV hyperlipoproteinemia were given diets comparable in composition to their usual diets. During one experimental period the subjects exercised while maintaining their usual caloric intakes. During another experimental period their caloric intake was increased to compensate for the exercise-induced increase in energy expenditure. The exercise, which consisted of 30 min of treadmill walking per day for 4 days, resulted in a progressive decrease in TG. The reduction in TG, which averaged 120 mg/100 ml, occurred regardless of whether or not the increase in caloric expenditure was compensated for by an increase in food intake. The decrease in TG was limited to the very low density lipoprotein fraction. No significant changes occurred in total plasma cholesterol concentration or in the distribution of cholesterol between the lipoprotein fractions. Fasting plasma glucagon concentration was constant for each individual and was unaffected by the exercise. The finding that exercise induces a decrease in TG despite increased food intake indicates that the TG lowering effect of exercise is not mediated by a negative caloric balance.


The "post-heparin pattern" in routine serum protein immunoelectrophoresis. For some time following intravenous administration of heparin to non-fasting normal subjects, routine immunoelectrophoretic preparations show characteristic changes in serum lipoproteins. These alterations are of two types: (1) marked anodal mobility increase, the alpha-2 (beta) component locating in the alpha-1 region while the alpha-1 appears as a pre-albumin; (2) conformational alterations of the immunoprecipitin arcs comprising elongation of the alpha-2 (beta) arc, and splitting of the alpha-1 arc into two distinct entities. Familiarity with these patterns should minimize the possibility of interpretative errors with specimens from patients receiving heparin.


Anti-"i" antibody and hemolytic anemia associated with spontaneous cytomegalovirus mononucleosis. Hemolytic anemia occurred in a 23-year-old woman with spontaneous cytomegalovirus mononucleosis who had not received a blood transfusion. The patient's serum gave positive reactions in Coombs' antiglobulin test with human cord erythrocytes but did not react with adult "O" cells. Complement-fixation antibody titers against cytomegalovirus and levels of activity against cord erythrocytes increased as the anemia worsened and remained at high levels when recovery from the anemia occurred.


Bordetella parapertussis. Recent experience and a review of the literature. During 1974, eight of 37 (22%) Bordetella organisms isolated from patients in Cincinnate were Bordetella parapertussis. This is in contrast to other experience in the United States where parapertussis has comprised less than5% of the Bordetella species isolated and suggest that B parapertussis infection may be more common in this country than generally recognized. The failure to appreciate the presence of this infection may result from the lack of cultures taken from children with mild disease and the failure todistinguish B parapertussis from B pertussis. Ccultures were obtained from family members of three of the children with B parapertussis, and  B pertussis was isolated from members of two families, including the mother and sister of a child who died of pneumonia and encephalopathy. These cases suggest that patients with severe disease associated with B parapertussis should be carefully evaluated for the possibility of dual infection caused by b pertussis.


Multicystic cerebral degeneration in neonatal herpes simplex virus encephalitis. Typical herpetic papulovesicular skin lesions developed in an apparently normal infant at 12 days of age and were followed within 48 hours by signs and symptoms of acute encephalitis. Herpes simplex virus type 2 was cultured from the intact skin vesicles, and a fourfold increase in complement fixation titer to herpes simplex virus type 2 was found over the ensuing 24 days. The infant survived her acute illness, but was left with severe neurologic sequelae manifested as microcephaly with multicystic cerebral degeneration. The short-term and convalescent course is documented by serial, clinical, and EEG examinations, and the nature of the cerebral damage is demonstrated by computerized transaxial tomography.


Cancer in chronic ulcerative colitis. Diagnostic role of segmental colonic lavage. Saline colonic lavage in 74 patients with chronic ulcerative colitis was performed utilizing a commercially available dental irrigating unit through a polyethylene catheter in the biopsy channel of a colonoscope or through a sigmoidoscope via a lavage-aspirating double-lumen probe. Six patients were found with colonic carcinoma. Two diagnoses of malignancy were established by cytologic smears and cell block alone. Two patients had positive mucosal biopsies and cell block. One patient with a hepatic flexure carcinoma and a second patient with a malignancy proximal to the left colon stricture were missed by these techniques. Considering the established proclivity for carcinoma in these patients, it is felt that segmental lavage in areas of stricutre, grossly dostorted mucosa, or endoscopically inaccessible areas represents a valuable adjunct in the diagnosis of carcinoma in chronic ulcerative colitis.


Early acquisition of cytomegalovirus and Epstein-Barr virus antibody in several isolated Melanesian populations. Significant differences among diverse human populations have been found in the seroepidemiology of cytomegalovirus (CMV) and Epstein-Barr virus (EBV). The present report documents a very high rate of early acquisition of antibody to CMV and EBV among three remote populations living in the Eastern Highlands of Papua New Guinea, the Solomon Islands, and the New Hebrides, respectively. These three genetically distinct populations, living in widely different ecologies and social settings, each had the same pattern of early acquisition of infection with both viruses. It is suggested that spread of CMV and EBV is determined by patterns of interpersonal contact as well as by the prevalence of virus-shedders. The large number of handlers of each infant in these studied groups appears directly related to the early acquisition of these viruses.


High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Lipid and lipoprotein values, including fasting triglycerides and high density lipoproteins (HDL), low density lipoproteins (LDL) and total cholesterol levels, were obtained on 2,815 men and women aged 49 to 82 years chiefly between 1969 and 1971 at Framingham. In the approximately four years following the characterization of lipids, coronary heart disease developed in 79 of the 1,025 men and 63 of the 1,445 women free of coronary heart diseases. At these older ages the major potent lipid risk factor was HDL cholesterol, which had an inverse association with the incidence of coronary heart disease (p less than 0.001) in either men or women. This lipid was associated with each major manifestation of coronary heart disease. These associations were equally significant even when other lipids and other standard risk factors for coronary heart disease were taken into consideration. A weaker association with the incidence of coronary heart disease (p less than 0.05) was observed for LDL cholesterol. Triglycerides were associated with the incidence of coronary heart disease only in women and then only when the level of other lipids was not taken into account. At these ages total cholesterol was not associated with the risk of coronary heart disease.


The influence of ovarian denervation and nerve stimulation on ovarian contractions. Two techniques were used to study the neuromuscular control of rabbit ovarian contractions. First, the ovary was denervated by stripping its artery. Spontaneous contractions were noted, as was a normal response to exogenously administered adrenergic agents. Second, the ovarian nerves were electrically stimulated in an in vitro perfused ovary system. Inhibition of ovarian contractions was noted, and the additive effects with adrenergic agents suggested a betamimetic effect of nerve stimulation in the estrous rabbit. After administration of exogenous human chorionic gonadotropin, the response was reversed. The significance of the contribution of a neuromuscular mechanism to the control of ovulation is discussed.


Cyclic 3',5' -adenosine monophosphate in umbilical cord and maternal plasma before and after the onset of parturition. Significant arteriovenous differences in cord cyclic 3',5'-adenosine monophosphate (cAMP) levels and between the maternal plasma (MP) and each cord vessel (mean umbilical artery [UA] greater than umbilical vein [UV] greater than MP) was observed. cAMP levels were significantly higher in the umbilical cord vessels and maternal plasma after vaginal delivery than they were following delivery by elective cesarean section before the onset of labor. The higher mean cAMP levels observed after parturition appeared to be more pronounced in the fetoplacental unit than in the maternal compartment. A significant positive correlation in cAMP levels between the UA and UV was also observed.


A comparison of two methods for the microscopic determination of age at death. The precision and accuracy of the Kerley and Ahlqvist-Damsten microscopic methods of age determination are compared. Both methods were applied to the same sample of 40 femoral thin sections of documented age at death. The results indicate that (1) both methods can be used with equal precision, as suggested by comparable observer errors; and (2) the Kerley method produces overall more accurate age estimates. The low previously published standard error of the Ahlqvist-Damsten method (6.71 years) apparently results from the uneven age distribution and small size (20) of their sample.


Cortical bone measurements in Turner's syndrome. Cortical bone width measurements taken at midshaft on the second metacarpal were obtained from 156 hand X-rays of 80 karyotypically documented individuals with Turner's syndrome age 1 to 25 years. Total shaft width, medullary width, cortical width and percent cortical area were grouped by bone age and compared with normal female standards. Total width was significantly and increasingly below normal; medullary width was not consistently different from normal; cortical width was significantly lower from normal from age 14 onward, although it did rise at age 17 (adult bone age); percent cortical area was significantly below normal at ages 14 and 15, but was normal by adulthood. Values for percent cortical area did not indicate severe or widespread osteoporosis. Within the Turners sample cortical bone measurement were not significantly decreased in the presence of the XO sex chromosome constitution compared with other sex chromosome variants. Nor were the measurements decreased in the presence of positive metacarpal sign or a combination of typical Turner stigmata (web neck, low posterior hairline, shield chest). There was evidence that cortical width and percent cortical area increased significantly following estrogen treatment or spontaneous menarche.


Radiological anthropometry of the hand in Turner's syndrome. Metacarpal-phalangeal (M-P) lengths, metacarpal sign, and carpal angle were studied using 142 pairs of hand X-rays from 81 individuals with Turner's syndrome age 6 to 25 years. Left M-P lengths, grouped by bone age, were compared with normal female standards and Z-score pattern profiles calculated for each bone age. Differences between Turners and normals in most M-P lengths increased with age, particularly after puberty. Calculation of inter-individual and intra-individual variability yielded good evidence for a M-P pattern profile typical of Turner's syndrome, with increasing growth deficiency from distal to proximal and lateral to medial. The incidence of positive metacarpal sign was 33.8%, with no significant difference between XO and non-XO Turners. It did not appear that M4 ceased growth prematurely, suggesting that short M4 is not the result of early epiphyseal fusion. Carpal angle, reported to be abnormally decreased in Turners, was not found to differ from normal. There was no difference between right and left sides or between XO and non-XO Turners, but carpal angle did decrease significantly with both decreasing ulnar deviation in positioning of the hand and increasing age. In the latter respect Turners differ from normals who show an increase in carpal angle with age.


Response of mitochondria of different types of skeletal muscle to thyrotoxicosis. To determine the effect of long-term thyrotoxicosis on muscle mitochondria, we measured representative mitochondrial enzymes from three different types of skeletal muscle (fast-twitch red and fast-twitch white from the quadriceps, and slow-twitch red from the soleus) in rats given 3 mg L-thyroxine and 1 mg triiodo-L-thyronine per kilogram of diet for 12 wk. Marker enzymes of the electron transport chain and citric acid cycle (cytochrome oxidase, cytochrome c, and citrate synthase) increase approximately twofold in soleus muscle in response to this treatment. The fast-twitch muscles exhibit no more than 44% increases in these enzymes in response to the same treatment. Relative to initial concentration, 3-hydroxybutyrate dehydrogenase increased to the same extent in fast-twitch red muscle as it did in the soleus (70%). Mitochondrial alpha-glycerophosphate dehydrogenase increased 76% in red quadriceps and 170% in soleus, but did not change in white muscle in the thyrotoxic rats. This differential sensitivity of the three types of muscle provides a tool for studying the mechanisms underlying the action of thyroid hormones on muscle mitochondria.


Thyroid hormone control of Na+-K+-ATPase and K+-dependent phosphatase in rat heart. To assess the possible role of the Na+ pump in mediating physiological responses to thyroid hormone in the rat myocardium, we examined the effects of L-3,5,3'-triiodothyronine (T3) on the activities of the closely associated enzymes, Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) and K+-dependent p-nitrophenyl phosphatase (K-dep-pNPPase). In hypothyroid rats, administration of T3 (50 microng/100 g body wt) resulted in significant increases (greater than 50%) in Na-K-ATPase and K-dep-pNPPase activities in both crude homogenates and microsomal fractions of the rat ventricle. Significant effects on Na-K-ATPase activity were also attained with low doses (1 microng/100 g body wt) of T3. A method was developed for assaying K-dep-pNPPase activity in cardiac slices. With this technique, enhancement in K-dep-pNPPase activity of 89.2% was found in ventricle slices after treatment of hypothyroid rats with T3 (50 microng/100 g body wt), implying that augmentation of the capacity of the Na+ pump is achieved in vivo. The potent analogue, L-3,5-diiodo-3' isopropyl thyronine (isopropyl T2) had the same effects on cardiac growth and Na-K-ATPase as T3, in hypothyroid rats. In contrast, the relatively inactive isomer, L-3,3',5'-triiodothyronine (reverse T3) had no significant effect on the heart weight-to-body weight ratio or on ventricular Na-K-ATPase activity.


Evidence for interference of 25 (OH) vitamin D3 with phosphaturic action of calcitonin. The present study evaluated the effect of 25(OH)vitamin D3[25(OH)vit D3] on the phosphaturic action of calcitonin in anesthetized parathyroidectomized rats. In group 1, calcitonin was given intravenously over six clearance periods. In group 2, after three periods of calcitonin given intravenously, 25(OH)vit D3 was added and given together with calcitonin for three additional periods. During calcitonin infusion, Cp/CIn 0.18 +/- 0.02 (mean +/- SE) in group 1 was not different from the corresponding Cp/CIn 0.18 +/- 0.03 in group 2; but when 25(OH)vit D3 was added, Cp/CIn 0.12 +/- 0.01 in group 2 was lower (P less than 0.001) than the corresponding Cp/CIn 0.26 +/- 0.02 in group 1. With intravenous calcitonin the urinary excretion of cycle AMP (UcAMP) 97 +/- 29 in group 1 did not differ from the corresponding UcAMP 86 +/- 27 pmol/min in group 2, but when 25(OH)vit D3 was added UcAMP 41 +/- 12 in group 2 was lower (P less than 0.001) than the corresponding UcAMP 131 +/- 14 pmol/min in group 1. This study demonstrated that 25(OH)vit D3 blocks the phosphaturic action of calcitonin. The associated fall in Uctamp suggests that25 (OV)vit D3 acts possibly by inhibiting the calcitonin-induced activation of adenylate cyclase in the kidney. However, other alternative mechanisms of action have not been excluded.


Dependence of tonin activity in rat submaxillary gland on growth hormone and testosterone. Tonin, an enzyme present in rat submaxillary gland, converts angiotensin I to angiotensin II and is able to form angiotensin II directly from renin substrates. This enzyme was previously shown to be different from renin, tissue isorenins, and angiotensin I converting enzyme. The specific activity of tonin in rat submaxillary gland increases with the age of the animal and is much higher in male than in female rats; this sex difference is apparent from 60 to 70 days of age. There is a sharp drop of tonin activity in hypophysectomized animals, whereas adrenalectomy, thyroidectomy, and gonadectomy have have little effect. The marked increase in tonin activity was observed in animals bearing MtT-F4 transplantable tumors known to produce ACTH, prolactin, and growth hormone. Tonin specific activity in hypophysectomized male rats is restored to control levels by combined treatment with growth hormone and testosterone. Prolactin alone or in combination with testosterone, as well as transplanted pituitaries, has no effect in hypophysectomized animals. There is a significant specific binding of 125I-labeled growth hormone to isolated membranes of rat submaxillary gland.


Depriving rats of REM sleep: the identification of a methodological problem. Several studies that used Jouvet's platform-in-the-water technique to deprive rats of REM sleep are reviewed. It is observed that a consistent feature of the design of these studies was to ignore the ratio between the size of the animal and the diameter of the platform when the REM deprivation was manipulated. Some contradictory studies are considered, and it is shown that the discrepant outcomes in the literature could be the result of inattention to that ratio.


Subselective angiography in localizing insulinomas of the pancreas. Preoperative angiography was performed on 10 patients who had insulin-producing islet cell adenomas. Eight of the 10 islet cell tumors were localized. Seven of the eight adenomas were demonstrated only on subselective injections into the small intrapancreatic arteries, and one was demonstrated by a selective injection into a large artery. Failure to localize two islet cell adenomas was probably caused by the inability to subselect the small intrapancreatic arteries supplying the tumor. One tumor was seen only with subtraction techniques, which were used in all cases. Localization was not related to vascularity, size of tumor, or location within the pancreas. Vasoconstrictive pharmacoangiography was not helpful; magnification was helpful but not essential. The most important factor in localizing islet cell tumors is demonstrating the complete pancreatic blood supply with subselective injections into the small intrapancreatic arteries supplying the tumor (inferior and superior pancreaticoduodenal and dorsal arteries).


Antimicrobial systems of the surgical wound. I. A comparison of oxidative metabolism and microbicidal capacity of phagocytes from wounds and from peripheral blood. Oxygen consumption glucose oxidation via the hexose monophosphate shunt, and superoxide production by resting and stimulated leukocytes derived from rabbit blood and from experimental rabbit wounds five to seventeen days old were measured and compared. In vitro killing of staphylococci by blood and wound leukocytes was also measured. In all of these studies there were no significant functional differences between blood and wound cells. The data presented suggest that under the same in vitro conditions, blood and wound leukocytes are functionally equivalent, that tissue mobilization does not cause alteration of wound leukocytes, and that aging of the wound does not impair the microbicidal capacity of wound leukocytes.


Cytochemical localiztion of nucleoside diphosphatase and thiamine pyrophosphatase activities in the rabbit corneal endothelium. Localization of NDPase and TPPase activities in the rabbit corneal endothelium was investigated by cytochemical methods. After incubation at both pH 7.0 and 8.0, the NDPase activity was detected in cisternae of ER, nuclear envelope, and Golgi saccules, while the TPPase activity was demonstrated only in Golgi saccules. The reaction products of both enzymes were decreased when incubated at pH 8.0. The NDPase activity was inhibited by uranyl nitrate but not by sodium fluoride, while the TPPase was inhibited by fluoride but not by uranium.


[The origin of histological changes in amebiasis]. On microscopic examination of histological specimens from an autopsy case with severe amoebiasis, extensive ulcerative-necrotic lesions in the colon were found associated with an amoebic peritonitis and severe degenerative lesions of the ganglion-cells of the plexus myentericus induced by Entamoeba histolytica. There was also an infiltration of a mesenteric lymphnode by amoebae carried by the lymph through the vasa afferentiae lymphaticae. In the liver several granulomas (amoebic granulomas) and numerous small necrotic areas, surrounded by a dense leucocytic infiltration, were observed. The origin of the lesions in the colon could be attributed to the motility of the amoebae and the secretion of lytic substances (ferments) by the amoebae, whereas the lesions in the liver (amoebic granulomas and necrotic areas) must be considered as the residues of the destroyed amoebae which were brought by the circulation into the liver parenchyma. These lesions are similar to those seen in experimentally produced amoebiasis.


Decreased granulocyte response to isoproterenol in asthma during upper respiratory infections. Isoproterenol inhibits zymosan-stimulated release of lysosomal enzymes from granulocytes. Using this as an in vitro cell model to study beta-adrenergic response, granulocyte reaction to isoproterenol was examined in asthma. There was a significantly decreased response to isoproterenol (10(-7) to 10(+-5) M) in patients with mild asthma who had not taken bronchodilators for 2 weeks before study and also in patients with severe asthma requiring bronchodilators and corticosteroids. During respiratory infections that provoked an attack of asthma, the granulocyte response to isoproterenol was further decreased. The change in granulocyte response to isoproterenol may reflect a similar change in beta-adrenergic tone of the airways and provide one explanation for asthma during colds.


The activity of some nucleolytic enzymes in semen and in the secretion of the male reproductive tract. The activity of 5'-nucleotidase (EC 1.3.5), cyclic nucleotide phosphodiesterase (EC 2.1.4.17), non-specific phosphodiesterase (EC 3.1.4.1) and ribonuclease (EC 1.7.7.16)has been investigated in the seminal plasma of whole semen and in the secretions of the seminal vesicle, prostate and epididymis of the bull, boar, ram, stallion, jackass, rabbit and man. Bull seminal plasma showed the highest activity for 5'-nucleotidase, cyclic nucleotide phosphodiesterase and ribonuclease; in contrast, stallion and jackass semen were very poor in these enzymes. Ram, rabbit and boar seminal plasma showed intermediate levels for all enzymes studied. In the bull and ram, nucleolytic enzymes were found to be secreted by the seminal vesicles but in the boar, rabbit and stallion they originate mostly from the epididymis. In human seminal plasma all of the enzymes studied exhibited activity but the levels were generally lower than those recorded for the other species.


[Etiology of acute respiratory infection in hospitalized children (author's transl)]. Incidence of respiratory tract infection represents 23% of the total number of admissions between 1-24 months of age, during a period of 18 months. The diagnosis were: bronchiolities, 143 cases; bronchopneumonia, 134 cases; tracheobronchitis, 50 cases; laryngitis, four cases, and bacterial pneumonia, 61 cases. Monthly incidence was maximal in December of each year. From the total group, 144 cases were included in the present study to determine etiology of the infection. In 19% of the cases a serological diagnosis was posible. The adenovirus group was the most frequently found, followed by mycoplasma pneumoniae, parainfluenza 2, RS virus and M. parotiditis. RS virus was associated with a clinical picture of bronchopneumonia, mycoplasma pneumoniae with one of bronchiolitis and adenovirus was indistinctly associated with features either bronchopneumonia or bronchiolitis. In two cases it was detected a mixed infection by two virus: influenza 2 and mycoplasma pneumoniae. In four cases a bacterial surinfection was demonstrated: in two cases with coagulase-positive staphilococus and other two with klebsiella pneumoniae.


Gonadotrophin levels in male rats following impairment of Leydig cell function by ethylene dimethanesulphonate. The effects of the antispermatogenic compound, ethylene dimethanesulphonate on anterior pituitary and serum FSH, LH and prolactin levels in male rats were investigated. A rapid and sustained rise in serum LH, reaching castrate levels, indictated a normal pituitary response to androgen deprivation. Whilst no change in prolactin was observed, serum FSH showed a biphasic increase which is discussed in relation to the spermatogenic process.


Subcellular localization of enzymes.

Subcellular localization of enzymes. Localization of enzyme activity at the subcellular level requires techniques that have been essentially developed for the conventional light microscopic histochemistry and modified to fulfull the requirements of high resolution. Such procedures are manipulated in a certain sequence that starts with a short period of fixation, capture of the enzyme activity, postosmication and then dehydration followed by embedding of the specimen in a suitable plastic medium. References for the study of some selected enzymes pertinent to the hepatocytic organelles and their response under varied conditions are given as an example of the various procedures applied. Absence of glucose-6-phosphatase activity is currently used as a marker for the detection of early formation of preneoplastic cells in the liver of experimental animals treated with hepatocarcinogens and other agents.


[Massive tumours of the parotid. A description of 12 cases (author's transl)]. A number of useful conclusions can be drawn from this research involving twelve personal cases. In the southern half of Madagascar, malignant tumours of the parotid are much more frequent than mixed tumours. This appears to be true whatever the age or sex of the patient or the clinical characteristics encountered. The absence of facial paralysis and adenopathy should never be considered to invalidate this theory. Mixed tumours exist but in about the same proportion as other tumours (cysts or vascular tumours) which are to be found here. When faced with any large latero-cervical tumour with no O.R.L. entrypoint or homo- or contro-lateral adenopathy, where there is no arteriography or extemporaneous biopsy available, the parotid should always spring to mind, and when surgery is carried out, the cervico-facial branch of the VIIth nerve at the lower pole or at the lower external face of the tumour should first be singled out.


Cytomegalovirus (CMV) in the compromised host(s). Cytomegalovirus infection in compromised hosts occurs most frequently as asymptomatic shedding of a reactivated virus. Reactivation occurs when cellular immunity is compromised owing to either immune-deficiency disease or iatrogenic intervention. When intervention is modest, most antibody-positive patients do not shed virus (19); when the group is treated with a higher mean dose of cytotoxic agents, almost all antibody-positive patients shed virus (6). In the instance where the chemotherapeutic program includes massive doses of these agents, as in heart or marrow transplantation, or when dysfunction of all cellular activity is extreme, as in the case of severe combined immune deficiency and far-advanced neoplasia, dissemination of infection with multiple-organ involvement ensues (17, 20-22). Primary infection may occur in some patients with neoplasia or in marrow-transplant recipients from either blood transfusions or from marrow, although data are insufficient to be certain (22). It has been conclusively shown, however, that seronegative renal-allograft recipients usually develop primary infection when they acquire a kidney from a seropositive donor. Clinical illness related to virus infection in the first few months after transplantation occurs in almost all patients with primary infection and seldom in those with reactivation infection (6, 25, 26). Three very intriguing observations have been made that should suggest avenues for future research: (a) Since illness occurs more closely related to development of antibody than it does to onset of virus shedding, this suggests that host response plays an important role in the disease that is obviously caused by a virus; a definition of the mechanism of this interaction could lead to an understanding of host-induced disease processes in man; (b) Graft-versus-host disease in marrow transplantation; and (c) allograft rejection in renal-graft recipients correlate with development of CMV infection (16, 22, 24, 26). Taken together, these observations are consistent with the hypothesis that virus antigens interrelate with most antigens in such a way as to lead to immune response to both antigens. Exploration of this clinical observation could lead to a greater understanding of the function of the HL-A system in man.


Enzymes in amniotic fluid.

Enzymes in amniotic fluid. The determination of enzyme levels in cell-free amniotic fluid has proven useful in assessing fetal maturity and fetal well being, and is being utilized for the prenatal diagnosis of genetic disorders. The activities of amylase, alpha-galactosidase, phosphatidic acid phosphohydrolase, lysozyme and heat-stable alkaline phosphatase in amniotic fluid increase with gestational age and have an established relationship to fetal maturity. The ratio of amniotic fluid diamine oxidase activity to maternal serum activity (amniotic DAO/serum DAO) may be used as an indicator of the degree of rhesus isoimmunization after 28 weeks gestation. Creatine phosphokinase in amniotic fluid is elevated in cases of in utero fetal death and is of diagnostic significance. The prenatal diagnosis of Tay-Sachs disease, Sandhoff's disease, fucosidosis, GM1-gangliosidosis and I-cell disease have been made from the analysis of appropriate enzymes in cell-free amniotic fluid.


Diagnosis of hyperparathyroidism.

Diagnosis of hyperparathyroidism. States of hypersecretion of PTH may occur primarily, or in response to other physiologic abnormalities. Primary hyperparathyroidism must be considered in the differential diagnosis of hypercalcemia, nephrolithiasis, metabolic bone disease, and pancreatitis and peptic-ulcer disease. The clinical manifestations of this disease have become more subtle with improved detection. The serum calcium level is almost always elevated, and when it it accompanied by relatively high serum PTH levels or increased urinary cAMP excretion, the diagnosis is usually secure. Findings of hypophosphatemia, decreased renal tubular reabsorption of phosphorus, hypercalciuria, and characteristic roentgenographic changes support the diagnosis of hyperparathyroidism, but are not prerequisites for that diagnosis. Most cases will come to operation, and experienced intraoperative assessment is necessary for the correct distinction between multiglandular disease and that involving only a single gland. We expect that a clearer understanding of the histopathologic features of these diseases, and improvement in the methods for measurement of PTH will be the main areas of advancement in the diagnosis of hyperparathyroidism in the next few years.


Pathophysiology of psoriasis.

Pathophysiology of psoriasis. Psoriasis is a disease characterized by benign but unrestricted epithelial growth. The molecular pathophysiology of this unregulated growth has been discussed. A better understanding of the role of the cell surface, cyclic nucleotides, arachidonic acid-prostaglandin metabolism, and polyamines in psoriasis may clarify our understanding of this disease and produce clues pertinent to a general understanding of growth regulation.


Surgical adjuvant chemotherapy.

Surgical adjuvant chemotherapy. The evidence that the principles of surgical adjuvant chemotherapy developed in experimental animal systems also apply to a variety of neoplastic diseases in man has been clearly demonstrated. Micrometastatic disease can be eradicated with effective chemotherapy in several diseases. Prolongation of disease-free interval, if not cure, is now possible in diseases in which curative surgery alone or in combination with radiotherapy does not achieve these goals. The previously fatal childhood solid tumors--Wilms', Ewings' sarcoma, embryonal rhabdomyosarcoma--are curable in a high percentage of patients appropriately treated with combinations of surgery, radiotherapy, and chemotherapy. The prolongation of the disease-free interval in osteogenic sarcoma has permitted consideration of entirely new surgical approaches for this tumor in which radical amputation has traditionally been employed. The spectacular results achieved in the treatment of Stage II breast cancer may potentially save hundreds of thousands of lives in the coming decade. Clinically recognizable metastatic disease is rarely curable by any currently available treatment modality. The prolongation of disease-free intervals and production of cures when surgical adjuvant chemotherapy is employed may be partly explained by relatively more circulation, and thus drug delivery to each tumor cell, more favorable cellular kinetics, and a healthier and more immunocompetent host who is better able to withstand drug effects on normal tissues, and to participate in tumor destruction. Cures of certain patients with neoplastic diseases using surgical adjuvant chemotherapy has increased the incentive to learn more about new and old drugs and their effective use alone and in combination. Chemotherapy, in appropriate combinations with surgery, radiotherapy, and immunotherapy, may well be more efficacious in many clinical situations than the traditional use of single-modality treatment. The data presented in this paper relate solid evidence that the possibility of cure in a variety of neoplastic diseases is real.


Cytochemical and biochemical studies of yeasts after in vitro exposure to miconazole. Yeast cells exposed to different doses of the antimycotic agent miconazole revealed important cytochemical changes in the topographic distribution of the phosphatases. A strong effect was observed on the behavior of oxidative and peroxidative enzymes. Decreased cytochrome c oxidase and peroxidase activity and increased catalase activity were seen after treatment with a fungistatic dose of miconazole, whereas a complete disappearance of these enzymes was observed after treatment with a minimal fungicidal dose of miconazole. This was in complete agreement with the quantitative biochemical data. A hypothesis is advanced concerning the possible involvement of peroxidase and catalase in the mechanism of action of this drug.


Inhibition of cellular and viral protein synthesis by 3-methyleneoxindole. The effect of 3-methyleneoxindole (MO) on mengovirus and L-cell protein synthesis was investigated. MO was found to inhibit mengovirus multiplication and the incorporation of radioactive amino acids into both viral and cellular proteins. These results suggest that the antiviral effect of this compound is not specific but rather stems from its inhibition of the cellular translational machinery upon which mengovirus depends. We have also found that MO inhibits natural messenger ribonucleic acid (mengovirus and globin messenger ribonucleic acid) translation in cell-free extracts from Ehrlich ascites tumor cells but has no significant effect on polyuridylic acid translation. Additional data which suggest that MO inhibits protein synthesis at the level of initiation are shown.


Comparison of the effects of mecillinam and 6-aminopenicillanic acid on Proteus mirabilis, Escherichia coli, and Staphylococcus aureus. Single strains of Proteus mirabilis, Escherichia coli, and Staphylococcus aureus were grown on filter membranes placed on agar containing concentration series of mecillinam (FL 1060), 6-aminopenicillanic acid (6-APA), or ampicillin. P. mirabilis and E. coli were also exposed to combinations of mecillinam or 6-APA with ampicillin. Colony-forming units were counted, and cells were examined by interference phase-contrast and transmission electron microscopy. Mecillinam and 6-APA were very effective in reducing the viability of the two gram-negative species, but they were less effective against S. aureus. Combinations of mecillinam and 6-APA with ampicillin acted synergistically against the gram-negative bacilli. When the antibiotics were presented consecutively, their effects on viability were usually no greater than the effects of the individual antibiotics acting alone. When P. mirabilis and E. coli were exposed to mecillinam alone or in combination with ampicillin, the cells became rounded. 6-APA alone or in combination with ampicillin produced elongated polymorphic cells in these species. The most unusual morphological effects were ultrastructural. Mecillinam and, to a lesser extent, 6-APA produced inward growth of numerous pairs of trilamellar membranous structures within the cells. It is possible that these membranes represent the growth initiation of aberrant cross walls. Both mecillinam and 6-APA produced multiple, thick cross walls in S. aureus.


Susceptibility of clinical isolates of cytomegalovirus to human interferon. Human cell culture-derived interferon was shown to inhibit human cytomegalovirus in vitro. A prototype strain, Davis, and six clinical isolates of cytomegalovirus were tested. All six isolates showed uniform susceptibility to interferon, exceeding that of the Davis strain by two- to fourfold. The latter virus was found to be 32 to 4 times less susceptible than the sensitive indicator, vesicular stomatitis virus. However, the laboratory finding of susceptibility to an antiviral material may not relate to its clinical effectiveness.


Susceptibility of Clostridium perfringens isolated from human infections to twenty antibiotics. The proper choice of antibiotic for Clostridium perfringens infections in patients allergic to penicillin is not clear; the usual recommendations and recent in vitro studies disagree. We tested the susceptibility of 57 strains of C. perfringens to eight penicillins, seven cephalosporins, two tetracyclines, clindamycin, chloramphenicol, and rifampin by the agar dilution method. All strains were inhibited by (per milliliter) 4 mug or less of any of the penicillins, chloramphenicol, or clindamycin and 8 mug or less of any of the cephalosporins tested. Penicillin G and amoxicillin inhibited all strains at 0.12 mug or less per ml. Only 54% of the strains were inhibited by 1 mug of tetracycline per ml. Penicillin G remains the drug of first choice for infections with C. perfringens; it need not be added to a regimen containing a penicillinase-resistant penicillin given parenterally in high doses. The cephalosporins should be considered as alternative drugs for penicillin-allergic patients. Clindamycin and chloramphenicol are also effective. Tetracyclines cannot be depended upon in clostridial infections without in vitro testing, which is impracticable for initial empirical therapy.


(3H)-isoproterenol binding to subcellular fractions of mouse parotid: relationship to cyclic nucleotide formation and the stimulation of DNA synthesis. (3H) Isoproterenol binding to subcellular fractions of mouse parotid: Relationship to cyclic nucleotide formation and the stimulation of DNA synthesis. (Unión the (3H) Isoproterenol a fracciones subcelulares de parótida de ratón y su relacón con la formacón de nucleótidos cíclicos y la estimulación de la síntesis de DNA). Arch. Biol. Med. Exper. 10: 105-114, 1976. Tritiated isoproterenol binds to all subcellular fractions of mouse parotid but 70% of the binding is to the nuclear fraction. Binding to other mouse tissues was less than to the parotid. The patterns of binding did not correlate with the distribution of adenylate cyclase, guanylate cyclase or catechol-O-methyl transferase among the fractions or tissues nor with the extent of response in stimulation of DNA synthesis among the tissues. Inhibition of (3H) Isoproterenol binding to parotid fractions by catecholamine analogs was studied. There was no correlation between their ability to inhibit binding and the ability of the analogs themselves to raise cyclic AMP levels or stimulate DNA synthesis.