Rise and fall of cyclic AMP required for onset of lymphocyte DNA synthesis. The adenosine 3',5'-monophosphate (cyclic AMP) levels of mouse lymphocytes rose and fell sharply 10 hours after stimulation with concanavalin A. Treatment of the cells with indomethacin reversibly prevented the increase in cyclic AMP and the subsequent onset of DNA synthesis. When the heightened cyclic AMP before S phase was maintained by either inhibiting phosphodiesterase or by adding the 8-bromo derivative of cyclic AMP, DNA synthesis was also blocked. Both the increase and decrease in cyclic AMP appear to be required for progression of lymphocytes into the S phase of growth.


Acute effects of alcohol on auditory brainstem potentials in humans. Auditory brainstem potentials were recorded from human subjects before and after an intoxicating dose of alcohol. Following alcohol ingestion there were significant, progressive increases in the latencies of brainstem potential peaks III through VII. No changes in peak amplitudes were found. The results indicate that alcohol has a depressive effect on neural transmission within the primary auditory brainstem pathway.


Pressure-adaptive differences in lactate dehydrogenases of congeneric fishes living at different depths. The muscle-type (M4) lactate dehydrogenases of Sebastolobus altivelis, a deep-water scorpaenid, and S. alascanus, a shallower species, are electrophoretically indistinguishable, yet differ in pressure sensitivities. The lactate dehydrogenase of S. altivelis exhibits lower pressure sensitivities of substrate and coenzyme binding and catalytic rate. Such apparently pressure-adaptive kinetic properties may be important for establishing species depth zonation patterns in the ocean.


Enzyme-linked immunosorbent assay for identification of rotaviruses from different animal species. Rotaviruses cause gastroenteritis in man and a wide variety of animal species. They cross-react in many immunologic tests and have a similar appearance by electron microscopy, making differentiation among them difficult. Rotaviruses derived from different host species were distinguished by postinfection serum blocking virus activity in an enzyme-linked immunosorbent assay (ELISA). Thirty-three rotavirus isolates from children living in three different parts of the world could not be differentiated by this technique, but they were distinct from four strains recovered from calves, and a series of strains isolated from piglets, foals, monkeys, and infant mice. The four bovine strains were similar, but they could be differentiated from the other animal strains, each of which exhibited a distinct pattern when tested by the ELISA blocking technique.


Chemical evolution from hydrogen cyanide: photochemical decarboxylation of orotic acid and orotate derivatives. Irradiation of solutions at pH 7 to pH 8.5 of orotic acid, orotidine, and orotidine 5'-phosphate with light at 254 nanometers yields the corresponding uracil derivative via the singlet excited state. This reaction completes a plausible prebiotic synthesis of uracil and its derivatives starting from HCN as the only carbon source.


Retrograde amnesia produced by several treatments: evidence for a common neurobiological mechanism. This experiment examined the effects on memory of various amnestic treatments in animals earlier treated with the alpha-adrenergic antagonist phenoxybenzamine (PBZ). Thirty minutes before being trained in a one-trial inhibitory (passive) avoidance task, animals received an injection of PBZ or saline. Immediately after training, each animal received one of the following amnestic treatments: stimulation of the frontal cortex or amygdala, pentylenetetrazol, diethyldithiocarbamate, or cycloheximide. In control animals, each treatment produced retrograde amnesia. However, PBZ-treated animals did not develop amnesia. These findings suggest that there may be a common neurobiological mechanism underlying the amnesias produced by many treatments.


Prostaglandin restoration of the interferon response of hyporeactive animals. Virus-infected animals and those bearing various types of malignancies progressively lose the ability to respond to interferon inducers. The interferon response of virus-infected animals could be restored to normal levels when inducers were administered with certain prostaglandins. This suggests that prostaglandins may enhance the therapeutic efficacy of interferon inducers as antiviral and antineoplastic agents.


Higher order structure of simian virus 40 chromatin. Simian virus 40 nucleoprotein complexes undergo an ionic strength-dependent structural transition. At moderate ionic strength they contain histone H1 as well as the nucleosomal histones and have a compact conformation with globular subunits 190 angstroms in diameter. At high ionic strength histone H1 is released, and the structure unfolds into chains with an average of 24 nucleosomes. The extended viral chromatin converts to the compact form by the addition of histone H1. Transcriptionally active simian virus 40 chromatin undergoes the same structural transitions. The higher order structure of viral chromatin may be analogous to the compact state of cellular chromatin fibers observed at physiological ionic strength.


Virus-induced diabetes mellitus: reovirus infection of pancreatic beta cells in mice. Reovirus type 3, passaged in pancreatic beta-cell cultures, produced an insulitis when inoculated into 1- to 2-week-old mice. By means of a double-label antibody technique, in which we used fluorescein-labeled antibody to reovirus and rhodamine-labeled antibody to insulin, reovirus antigens were found in beta cells. By electron microscopy, viral particles in different stages of morphogenesis were observed in insulin-containing beta cells but not glucagon-containing alpha cells. The infection resulted in destruction of beta cells, reduction in the insulin content of the pancreas, and alteration in the host's capacity to respond normally to a glucose tolerance test.


[Thrombocytosis and cancer. Apropos of a chronological series of 100 patients]. The authors report a personal chronological series of 100 cancer patients submitted to an analytical study, and noted thrombocytosis in 18% of cases. They attempt to draw up a correlation between the presence of increased platelets, and the site of the primary tumour, its spread, the state of anemia or iron deficiency in these patients. During a general review of the literature, they compare their results with those of various american and german series and report the various pathogenic hypotheses suggested upto date. They emphasise the fact that routine platelet counts may be of great interest in the detection of certain early carcinomas in spite of the generally moderate levels of thrombocytosis observed. They therefore have a place in routine health checks.


[Primary "muscle" tumors or tumors with a myosarcomatous component of the central nervous system. General review and attempt at classification based on 2 anatomo-clinical observations]. The authors report the first two French cases of primary rabdomyosarcoma of the central nervous system. They then review the literature on muscle tumours or primary myosarcomas of the nervous system of which 29 cases have now been published. From the point of view of morphology and classification, one should distinguish firstly, purely mesenchymatous tumours (rhabdomyosarcomas, leiosarcoma, mesenchymoma) and secondly, composite tumours of connective tissue or spino-epithelial tumours (medullomyoblastomas, neuromyoblastomas, gliomyosarcomas). Their histogenesis occurs from the ectomesenchyme of the neural crests.


[Post-meningococcal rheumatism].

[Post-meningococcal rheumatism]. Two cases of post-meningococcal inflammatory arthritis with a relapsing course in one case are reported. The authors then recall the characteristics of the joint manifestations during meningococcal infections in the light of other cases in the literature. These arthropathies are generally aseptic and their resistance to antibiotics is remarkable, whilst non- steroid anti-inflammatory drugs, even used alone as in one of the cases reported here, are remarkably effective. The pathogenesis of these cases of arthritis is not clear: it seems however according to Greenwood and Whittle that they are manifestations of immuno-allergic type. This "post-meningococcal rheumatism" may be compared to the gonococcal rheumatism of certain cases of Reiter's syndrome.


[Rupture of the rotator tendon].

[Rupture of the rotator tendon]. The authors report 25 cases of rupture of the rotator tendons operated on at the Stephanie Hospital in Strasburg, and discuss the surgical indications. Debeyre's technic was used with satisfactory overall results both on pain and function.


Rupture of a parasellar aneurysm with a coexisting pituitary tumor. The unusual occurrence of a pituitary tumor and a parasellar aneurysm is reported. The aneurysm ruptured and mimicked spontaneous infarction of the pituitary tumor. The importance of performing cerebral angiography before emergency surgical decompression of a presumed pituitary tumor infarction is emphasized.


Adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma of the breast. We have presented a case of adenoid cystic carcinoma of the breast and reviewed the literature, with emphasis on the behavior of this rare neoplasm and the fact that its prognosis appears to be more favorable than that of other more common histologic types of breast cancer. The accumulated information about adenoid cystic carcinoma of the breast that exists to date is insufficient to allow dogmatic statements, but one can conclude that total mastectomy seems to be the treatment of choice in selected cases.


Granular cell tumor of the abdominal wall musculature. Granular cell tumor (myoblastoma) is a relatively frequent neoplasm found in many different anatomic locations. This is a case of such a tumor arising in the abdominal wall musculature, an extremely unusual site of occurrence. Excision with generous margins is required to prevent recurrence.


Biomedical survey in Irian Jaya (West Irian), Indonesia. A biomedical survey was conducted in several areas of Irian Jaya, Indonesia in July 1972 in association with an investigation of reports of a cholera outbreak. Stool specimens, blood smears and sera were collected and examined for evidence of parasitic as well as other infectious diseases. A total of 114 stools were examined and the most commonly found intestinal parasites were Trichuris trichiura (94%), Ascaris lumbricoides (74%), hookworm (58%), Entamoeba coli (15%), Endolimax nana (8%), Entamoeba histolytica (7), Entamoeba hartmanni (4%), Giardia lamblia (3%) and Chilomastix mesnili (3%). A total of 513 blood smears were examined and Wucheria bancrofti microfilariae were detected in 4% and malaria in 4% (Plasmodium falciparum 3%, Plasmodium vivax 2%). The malaria and filarial positive individuals lived in Beeuw, Waigeo and Arar, Sorong. These parasitic infections were not detected in people from Biak City and Sburia, Biak. Sera were collected from 357 persons and significant antibody titers were found for Entamoeba histolytica (4%) Toxoplasma gondii (7%), Influenza A2 Hong Kong 68 (65%), Influenza B Taiwan 68 (78%), Japanese encephalitis virus (87%) and Dengue 1 virus (79%).


A mammalian cell mutant with temperature-sensitive thymidine kinase. We have isolated a mutant clone from mouse FM3A cells with temperature-sensitive defects both in cytokinesis and in thymidine kinase enzyme activity. The clone, designated tsCl.B59, was isolated after mutagenesis at 33 degrees C followed by exposure to cytosine arabinoside at 39 degrees C. It was derived from a thymidine kinase deficient, 5-bromodeoxyuridine-resistant clone (S-BUCl.42) which was originally derived from wild-type clone H-5 of FM3A cells. The temperature-sensitive mutant clone grows normally at 33 degrees C, but not at 39 degrees C, where it exhibits an increased frequency of multinucleate cells due to defective cytokinesis. Unlike the parental S-BUCl.42 cells, which have negligible thymidine kinase activity and are unable to incorporate 3H-thymidine, the mutant in corporates substantial amounts of 3H-thymidine at 33 degrees C, although its thymidine kinase activity remains lower than that of wild-type H-5 cells. When cultures of tsCl.B59 cells are transferred to 39 degrees C, incorporation of 3H-thymidine decreases markedly. The decrease has been shown to be due to thermolability of the thymidine kinase in tsCl.B59 cells.


Tumor imaging with x-rays using macrophage uptake of radiopaque fluorocarbon emulsions. Radiopaque fluorocarbon (RFC) emulsions were prepared with small particle size and high concentration of the fluorocarbon. When RFC emulsions were injected intravenously in hamsters, rats, and mice with eight types of malignant tumors, the tumors became radiopaque, except in the mice with spontaneous teratoma of the ovaries. Tumors as small as 3 to 4 mm could be defined radiographically using routine x-ray techniques. The tumors remained radiopaque for days to weeks after injection. Light and electron microscopy revealed characteristic fluorocarbon vacuoles primarily in the tumor macrophages. Thus RFC emulsions may be useful in detection of malignant tumors.


Thermal transformation of cholecalciferol between 100--170 degrees C. Cholecalciferol is transformed, irreversibly, to pyrocholecalciferol and isopyrocholecalciferol. The rate constant, as a function of temperature, for this transformation from the equilibrium mixture of cholecalciferol and precholecalciferol has been determined for temperatures between 100--170 degrees C and is slower than the precholecalciferol-cholecalciferol interconversion. The ratio of rates of production of pyro to isopyro derivatives is 2:1 throughout.


Further characterization of the effects of hypophysectomy, FSH and estrogen on LH stimulation of testosterone production in Leydig cells isolated from immature rats. Hypophysectomy of immature rats results after 5 days in a loss of LH responsiveness of Leydig cells. LH responsiveness can be partly maintained by treatment with FSH for 5 days. When estradiol benzoate was administered together with FSH to hypophysectomized rats the maintenance of LH responsiveness was not observed. The loss in LH responsiveness after hypophysectomy in terms of testosterone production could not be explained by either a change in the amount of Leydig cells present in the Leydig cell preparation or to a higher conversion of testosterone. The LH-stimulated cAMP production in cells from hypophysectomized rats was very low compared to cells from intact rats. There was no difference between cAMP production of Leydig cells from untreated, FSH-treated or FSH plus estradiol benzoate treated hypophysectomized rats. During the first 2 days after hypophysectomy LH responsiveness in both untreated and FSH-treated rats showed a comparable decrease. From day 2 after hypophysectomy LH responsiveness remained at a constant level in cells from rats treated with FSH, but declined further in cells from untreated rats. A single injection of estradiol benzoate to hypophysectomized rats treated with FSH counteracted the effect of FSH on LH responsiveness, but only when estradiol was administered at that time after hypophysectomy, when the effect of FSH on LH responsiveness was clear.


Direct radioimmunoassay of specific urinary estrogen glucosiduronates in normal men and nonpregnant women. Direct radioimmunoassay are described for the measurement of each of three specific estrogen glucosiduronates: estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate and estriol-16 alpha-glucosiduronate in urine. Each assay utilizes a specific antiserum prepared by complexing the carboxylic acid group of the appropriate glucosiduronate to the epsilon-amino group of lysine in bovine serum albumin or bovine thyroglobulin. The antisera showed little or no cross reactivity toward other estrogens that might be present in significant amounts in urine. These antisera were used for the direct assay of the conjugates in urine from normal men and nonpregnant women without prior extraction or chromatography. The values were similar to those obtained after extraction, chromatographic purification on DEAE-Sephadex and subsequent immunoassay; The following mean values +/- SE (microgram/g creatinine) were obtained: estrone glucosiduronate, male 10.1 +/- 0.6, follicular phase female 17.3+/- 1.6, luteal phase female 31.8 +/- 2.5; 17 beta-estradiol-17-glucosiduronate, male 1.7 +/- 0.3, follicular phase female 2.4 +/- 0.1, luteal phase female 4.2 +/- 0.4; estriol-16 alpha-glucosiduronate, male 1.8 +/- 0.2, follicular phase female 4.7 +/- 0.9, luteal phase female 10.0 +/- 1.6.


Steroidogenic activity of hACTH and related peptides on the human neocortex and fetal adrenal cortex in organ culture. Explants prepared from the neocortex and the fetal zone of the human fetal adrenal (gestational age 13 to 18weeks) were maintained under conditions of organ culture for 7 to 9 days during which time they were exposed to hACTH and various related peptides. Corticotrophic activity was monitored by the daily release of dehydroepiandrosterone sulfate (3beta-hydroxy-5-androsten-17-one, 3-sulfate; DHA-S) and cortisol as quantified by radioimmunoassay, hACTH (2.2 x 10(-9) - 2.2 x 10(-8)M) was the most active in sustaining steroidogenesis by both neocortical and fetocortical cells. alpha-MSH possessed similar properties but not at concentrations lower than 10(-6)M, whereas CLIP (4.4 x 10(-9) - 1.1 x 10(-7)M), the 18-39 C-terminal moiety of ACTH, was devoid of activity. Corticotrophic activity with respect to fetocortical explants appeared to be that of maintenance of function best illustrated by dehydroepiandrosterone sulfate biosynthesis, while enhancement of steroidogenesis was observed in the neocortex as manifested by cortisol release. Although not eliminating the possible existence of a specific fetal corticotrophin related to ACTH1-39, the data indicate that hACTH is capable of regulating steroidogenesis in the fetal zone which is primarily geared to the formation of dehydroepiandrosterone sulfate.


Separation of estrogen conjugates by high pressure liquid chromatography. High pressure liquid chromatography using a prepacked commercial strong anion exchanger column (mu Partisil 10 SAX, 25 cm x 4.6 mm) was used to separate a mixture of eight estrogen conjugates. Chromatographic conditions using a 0.01 M potassium phosphate or 0.1 M NaCl as solvent in the isocratic mode are described for the separation of estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate, estriol-3-glucosiduronate, estriol-16alpha-glucosiduronate, estriol-17-glucosiduronate, estrone sulfate and 17beta-estradiol-3-sulfate. This system gives high resolution of the estrogen conjugates in small eluent volumes in less than 30 min. The advantages of this high pressure liquid chromatographic system over other methods of separation are discussed.


Serological evidence of the occurrence of bluetongue in Iraq. Precipitating antibodies against bluetongue were detected in sheep and goat serum samples collected from animals slaughtered in Baghdad abattoir. Out of 294 sheep serum samples and 110 goat serum samples examined, 28 and 18 samples respectively showed precipitating activity. In addition, examination of sheep serum samples collected from localities where clinical cases similar to bluetongue were previously reported revealed the presence of bluetongue precipitating antibodies in 101 sera out of 198 samples examined. This is the first report confirming the occurrence of bluetongue in Iraq.


[Inhibition of alkaline phosphatase I of Pichia guilliermondii yeast in vitro and in vivo]. The rate of p-nitrophenyl phosphate and flavin mononucleotide (FMN) hydrolysis by the partially purified preparation of alkaline phosphatase I of Pichia guilliermondii flavinogenic yeast was studied as affected by different substrates and inorganic ions. Their Km was established to be 2.0 X 10(-4) m and 2.5 X 10(-4) M, respectively. Dephosphorylation of p-nitrophenylphosphate and FMN was inhibited competitively by beta-glycerophosphate (Ki = 3.1 X 10(-3) M, respectively). The presence of inorganic phosphate ions in the reaction mixture decreases or removes inhibition of these compounds hydrolysis by other substrates of alkaline phosphatase I. The activity of alkaline phosphatase I increases in the presence of Mg2+ and was strongly inhibited in the presence of Be2+, Cu2+, Zn2+, Cd2+ and inorganic phosphate, the mixture of Be2+ and F- being the most effective. This mixture inhibited the phosphatase activity of the partially purified preparation of alkaline phosphatase I of the cell-free extract as well as of intact cells in both the alkaline and acid zones of pH (8.6 and 5.5, respectively). Incubation of the washed iron-deficient P. guilliermondii cells in the presence of Be2+ and F- did not result in accumulation of FMN in the yeast culture. A possible role of nonspecific phosphomonoesterases in hydrolysis of FMN in vivo is discussed.


[The content of thiamine, its coenzyme form and activity of thiamine diphosphate-dependent enzymes in ontogenesis]. In experiments on rats of different age it is shown that the lowest content of thiamine and its phosphoric ethers in the liver is typical of the early periods of embryonal development and the highest one of the first days after birth. A direct dependence is established between the content of thiamine, its coenzyme form, enzyme of thiamine diphosphate synthesis (thiamine pyrophosphokinase) and thiamine diphosphate-containing enzyme (transketolase) in the rat liver in different periods of ontogenesis.


[Effect of ions on determination of 3',5'-AMP by the method of saturation]. The effects of La2+, Pb2+, Ba2+, Zn2+, Ca2+, Mg2+, Mn2+, NH+4 in concentrations of 10(-7), 10(-5), 10(-3) M were studied as applied to the protein binding of cyclic 3' : 5' = AMP. It is shown that Ba2+, La2+, Pb2+ increase the binding, while Zn2+ has no effect, and Mn2+, NH+4 decrease the binding of 3' : 5' = AMP. The effects of Ca2+ and Cd2+ were dependent on the concentration. The maximal binding in the presence of Ca2+ and Cd2+ was observed at a concentration of 10(-5) M and 10(-3) M, respectively. It is suggested that Mg2+ and Ca2+ take part in the regulation of cyclic AMP binding with proteinkinase in vivo.


[Adenosine triphosphatase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity of pancreas of thyroidectomized rats]. Activity of enzymes catalizing bioenergetic processes of substance transport through cell membranes, adenosine triphosphatase and para-nitrophenyl phosphates, activity of certain enzymes of carbohydrate metabolism, lactate dehydrogenase and glucose-6-phosphate dehydrogenase, as well as to 5'-nucleotidase taking part in nucleic metabolism were determined in the pancreas of thyreoidectomized rats. Simultaneously the content of lactic acid, phosphorus, potassium and sodium, which immediately related to activation of the mentioned enzymes, was determined in the pancreas. In thyroidectomized rats the activity of Mg2+, Na+, K+-ATPase, Na+, K+-ATPase and lactate dehydrogenase in the pancreas increases, that of glucose-6-phosphate dehydrogenase, para-nitrophenylphosphatase and 5-nucleotidase decreases, the content of lactic acid, potassium, sodium and phosphorus increases.


Fluorometric microassays of adenylate kinase, an enzyme important in energy metabolism. The adenylate kinase system offers a mechanism for the rapid provision of energy by catalysing the production of ATP from ADP. Fluormetric micromethods were developed for determination of the activity of this enzyme using either formation of ADP or ATP, in each case measured by coupling to suitable dehydrogenase reactions. Both procedures yielded results in good agreement, but when ADP formation was measured an interfering phosphatase splitting of ATP had to be corrected for. Therefore, ADP was preferred as the substrate and its conversion to ATP was determined in a coupled hexokinase-glucose-6-phosphate dehydrogenase reaction yielding stoichiometric amounts of NADPH which were measured by the native fluorescence of this form of the nucleotide. The sensitivity and reproducibility of our micro-method permitted assay of small samples (50-500 ng) such as a layer of cerebellar cortical nerve cells and of insulin producing cells from the islets of Langerhans. Although not reaching the high values in muscle, these cells showed significantly higher activities than parenchymatous cells from the liver and the exocrine pancreas. The sensitivity attained is more than required for assay of clinical fine needle biopsies and is quite satisfactory for detection and estimation of adenylate kinase contaminants in enzyme preparations.


Altered in vitro adrenergic responses of dog detrusor msucle after chronic bladder outlet obstruction. Muscle strips from the bladder body and dome of normal and control dogs usually demonstrate a relaxing (beta-adrenergic) response to norepinephrine. After bladder outlet obstruction was caused by urethral constriction, all body muscle strips from 7 of 12 dogs (58 per cent) demonstrated contractile (alpha-adrenergic) responses to norepinephrine. Bladder base muscle strips continued to show alpha-adrenergic responses. Desensitization or decreased beta-adrenergic receptor activity may play a part in causing the low compliance and detrusor instability seen in patients with bladder outlet obstruction.


Mediastinal extragonadal germ cell tumors. Mediastinal germ cell tumors are a rare primary malignancy. An overview of the presenting clinical symptoms, radiographic appearance, patterns of extention and metastasis, and autopsy findings are presented. The difficulty in totally excluding an occult gonadal primary lesion in noted. The theories of the genesis of these tumors are briefly reviewed.


Ultrastructure of malignant paraganglioma of organ of Zuckerkandl. Electron microscopic study of a malignant paraganglioma of the organ of Zuckerkandl revealed similarities between the tumor and the normal paraganglia. The well-differentiated portion of the tumor recapitulated the structure of the basic functional units of the paraganglion. In addition there signs of anaplasia both at the histologic and ultrastructural level. Large neurosecretory granules were noted in some of the tumor cells, but most of the cells were agranular. Crystaloids resembling those seen in alveolar soft part sarcoma were also noted. The study supports the theory on the common origin and histogenesis of paragangliomas and alveolar soft part sarcomas.


[Isolation and detection of avian adenoviruses on cell cultures]. It is important, from the hygienic and epizootological view-point, to detect the presence of various microbiological agents in birds. The authors present the results of the virological examination of poultry, avian adenoviruses being the main object of investigation. Ninety-eight virus strains were isolated from chickens of different age categories and were included in the group of avian adenoviruses according to the form of cytopathic changes on the cell cultures of hen kidneys, according to the need for adaptation passages, chloroform, thermal, and pH resistance, character of nucleic acid, formation of intranuclear inclusions, and joint precipitation antigen, shared with the reference virus.


[Immunofluorescence with the PI-3 virus--study of various working conditions for the detection of viral infection using immunofluorescence on various types of cell cultures]. We used the fluorescence method for the investigation of the sensitivity of several kinds of cell cultures to the infection with the parainfluenza virus 3 (PI-3). Cultures from calf kidneys were the most sensitive while we did not determine any differences between primary cultures and cultures of the first and second subpassages and/or freshly cultivated or incubated cultures over seven days at a temperature of 37 degrees C. Equal values of infection titres like on the cultures of calf kidneys were determined by immunofluorescence also on the kidney cells of lambs though the presence of  the infection was not accompanied by cytopathic changes. Infection of pig kidney cells appeared only after the inoculation of 10(3) TKID50 and higher doses of the virus, the infection having a very slow course of development without detectable cytopathic changes. Fluorescent findings were identical in different tissues. Antibodies present in the culture medium stopped the spreading of the infection by neutralizing the virus released from the cells, however, not the primary infection. The increase in the content of antibodies in the medium led - by inhibiting the intercellular virus - to the slowing down of the growth of primary fluorescent lesions.


Comparative study of experimental inclusion body hepatitis of chickens caused by two serotypes of avian adenovirus. Twenty 1-day-old specific-pathogen-free chickens each were given an intraabdominal inoculation of either a type-8 avian adenovirus, [AMG 5 (2a], or a type-5 avian adenovirus, inclusion body hepatitis virus (IBHV). The diseases produced were similar. High (60-100%) mortality and statistically significant depression of body weights occurred in both infections. There were necrotizing hepatitis and pancreatitis, lymphoid depletion in the spleen, bursa of Fabricius and thymus, hydropericardium, nephritis and enteritis. Intranuclear inclusions occurred in affected organs. Fluorescent-antibody staining, the Feulgen reaction for deoxyribonucleic acid and electron microscopic studies, as well as studies from the literature, indicated that basophilic inclusions consisted of assembled adenovirions.


Pathological changes in the small intestine of neonatal calves naturally infected with reo-like virus (rotavirus). Nine calves, of which six had been challenged with an enteropathogenic strain of Escherichia coli, were found to be naturally infected with rotavirus. Rotavirus was recovered from the faeces of six calves and rotavirus antigen was detected in the intestinal mucosa of all calves. Stunting and fusion of villi were seen principally in the proximal and middle small intestine, where rotavirus antigen was detected by immunofluorescence. Typical lesions of enteric colibacillosis were found in the distal ileum of the challenged calves, associated with adhesion of the challenge strain of E coli to the mucosa. All samples were removed from the intestine under general anaesthesia and denudation of villi was not observed. However, following exsanguination and resampling at the same site in the small intestine of one calf, denudation was a constant feature.


[Intracristal linear inclusions in mitochondria of human rhabdomyoma cells (author's transl)]. Electron microscopic study of a rhabdomyoma of the soft palate of a 50-year-old woman revealed linear structures within the intracristal spaces of mitochondria. In the center of most cristae, an electron-dense line was found located in parallel arrangement to the limiting cristal membrane. The linear inclusion was separated from the cristal membrane by a narrow space of lower electron-density. Thus, when sectioned longitudinally, the abnormal cristae exhibited a pentalaminar appearance. Additionally, they were characterized by a greater diameter than that of normal cristae and a "rigid" configuration. Higher magnification showed that the intracristal line consisted of a row of periodically arranged, electron-dense dots. Sometimes, these seemed to be connected with the wall of the intracristal space by fine, electron-dense cross-striations. In some mitochondria of rhabdomyoma cells, crystals with a linear substructure were observed in both intra- and extracristal spaces. The crystalline bodies located within cristae had probably been formed by accumulation of linear inclusions. The extracristal bodies seemed to have arisen from fusion of pentalaminar cristae. It is supposed that the intracristal linear inclusions in mitochondria of rhabdomyoma cells represent crystallized proteins of mitochondrial enzymes.


Chemodectoma of the larynx. A clinico-pathological study. The present case report is concerned with a clinico-pathological study, including ultrastructural investigation, of a rare and uncommon laryngeal tumour, a chemodectoma, in a 62 year old patient. There have been 23 cases of laryngeal chemodectomas reported in the literature, and only three of them, including our own report, were investigated by electron microscopy. The tumours arise from the superior and inferior larynegeal nonchromaffin paraganglia or possibly from Kultschitzky-cells of the normal bronchial mucosa. Ultrastructurally they have all the characteristics of apudomas whose parent cells (APUD-cells), usually show endocrine function and probably have their origin in the neural crest. The tumours show an aggressive type of behaviour, despite usually benign histological features when compared to chemodectomas at other sites in the head and neck region. Surgery is thus the therapy of choice.


Androgen producing adrenocortical carcinoma. Two cases of androgen secreting adrenocortical carcinoma have been described by light and electron microscopy. The histological and ultrastructural features of the tumour cells were similar to those of compact cells of zona reticularis and to those described in virilizing adenomas. They possess numerous mitochondria with lamellar and tubular cristae, abundant smooth endoplasmic reticulum, lipofuscin bodies and scanty lipid. Irregularly shaped, crenated mitochondria, with outpouchings of the outer limiting membrane have also been observed. The clusters of neoplastic cells were surrounded by basement membrane which demonstrated a focal discontinuity, probably reflecting malignancy of the tumours. Hyperplasia of smooth endoplasmic reticulum and the presence of outpouchings of the mitochondrial outer limiting membrane might be the morphological manifestation of endocrine activity of the tumours.


Deviated formation of intestinal glycocalyx in human stomach cancer cells. Another type of signet ring cell. The process of glycocalyx formation by the trilaminar membrane was investigated at the subcellular level by use of cultivated cancer cells derived from a human stomach adenocarcinoma. Glycocalyx was apparently synthesized on the characteristic trilaminar membrane of Golgi-derived vesicles which gave rise to cytoplasmic vacuoles which, in turn, fused to form an intracytoplasmic cyst. Characteristic microvilli similar to those of intestinal epithelium extended from the membrane lining the intracytoplasmic cyst. These ultrastructural features agree with earlier histochemical findings in suggesting intestinal metaplasia in the origin of the gastric tumor. The morphologic features of the cancer cells clearly indicated that glycoprotein is first synthesized in the Golgi complex and fully formed mucoprotein then emerges as membrane-bound glycocalyx in the vesicles budding from the Golgi stacks. The glycocalyx layer is an integral part of the external leaflet of the characteristic trilaminar membrane. Abundant deposits of glycocalyx in the intracytoplasmic cyst constituted the ultrastructural basis for a distinctive type of signet ring cell that differed from mucous signet ring cells derived from goblet cells.


Anterior polar cataract and lysosomal alterations in the lens of rats treated with the amphiphilic lipidosis-inducing drugs chloroquine and chlorphentermine. Chronic treatment of rats with the amphipilic drugs chloroquine and chlorphentermine caused prominent anterior polar cataracts in virtually all rats. The basic pathologic changes underlying these cataracts were: (a) degeneration of anterior polar and sutural endings of cortical lens cells and (b) multilayered proliferation and invasion of epithelial cells into the anterior polar cortex. Ultrastructurally cortical lens cells displayed various patterns of degeneration, finally undergoing complete liquification. Liquified lens substance was phagocytosed by invading epithelial cells. Cortical lens cells and epithelial cells contained numerous lipidosis-like (lamellated) inclusions, which possessed cytochemical acid phosphatase activity. The present drug-induced lenticular alterations are interpreted as the direct or indirect consequences of a drug-induced disturbance of polar lipid metabolism in the lens.


[Effect of the prolonged administration of the atherogenic fractions of lipoproteins on the blood and myocardial lipid picture in rabbits]. Homologous total fraction of pre-beta and beta-lipoproteins, isolated from intact animal blood and administered intravenously into rabbits within 1.5-2 months, caused distinct alterations in lipid spectra of rabbit-recipient blood serum. The phenomenon was manifested as an increase in concentration of all the lipid components in blood plasma, elevation in content of pre-beta and beta-lipoproteins in blood and decrease in content of alpha-lipoproteins. The alterations were apparently related not only to excessive administration of atherogenic lipoproteins but to impairments in lipid metabolism, similar to lipoproteinemia, reproduced in other experiments.


[Effect of psychotropic preparations on cyclic AMP phosphodiesterase activity in the rat cerebral cortex]. Effect of various psychotropic preparations on cAMP phosphodiesterase was studied. Almost all the psychotropic drugs studied were shown to inhibit the enzymatic activity. Neuroleptics--derivatives of phenothiazine and butyrophene--caused the strongest inhibitory effect.


[Enzymatic mechanisms for antimicrobial protection of the oral cavity]. Data on the role of oral lysozyme, ribonuclease, deoxyribonuclease and peroxidase in antimicrobial defense of the macroorganism are reviewed. The biochemical and physiological properties of the enzymes secreted by salivary glands and released from emigrating leukocytes are discussed. Spectra of antimicrobial action of the enzymes and participation of these enzymes in maintaining the stability of oral biocenosis are described as well as the regulation of these enzymatic activities and the pathogenetic significance of impairments in their secretion. The most perspective aspects of the problems discussed are outlined for further investigation.


[Thymidine phosphorylation with the participation of rat thymic and hepatic thymidine kinase in the presence of a factor from Cl. perfringens (welchii)]. Factor CPW, isolated from Cl. perfringens/welchii was shown to activate latent thymidine kinase (factor N) from liver tissue of rats beginning from 42 days age. CPW factor activated 3.5-fold also thymidine kinase from rat strumous gland; the enzyme was observed during involution of the tissue. The data suggest that increase in thymidine kinase activity in proliferating tissues is related to activation of latent enzymes.


[Reactions of tumor and organs of tumor-bearing animals to administration of a synthetic antioxidant]. Alterations of lipid antioxidative activity in liver and tumor as well as change in weight of spleen and tumor were studied in mice with hepatoma-22 after administration of synthetic antioxidant 4-methyl-2,6-ditertbutylphenol (ionol) at doses 30 mg/kg and 100 mg/kg during the 6th day of growth of the tumor. Lipid antioxidative activity was shown to respond similarly to administration of ionol in liver tissue of both the intact and tumor-bearing animals. The antioxidative activity was increased after administration of these doses of the antioxidant, then the antioxidative activity was decreased down to the initial level when the dose 30 mg/kg was used and below this level--at the dose 100 mg/kg. Both doses of the drug increased the lipid antioxidative activity in tumor. The dose 30 mg/kg of ionol stimulated the growth of the tumor and increased the weight of spleen in tumor-bearing animals and the dose 100 mg/kg--inhibited these parameters. Regulation of oxidation of the lipids in tumor appears to be impaired or altered to another level as compared with the oxidation of lipids in normal tissues or in the tissues of tumor-bearing animals.


[Characteristics of L-threonine- and L-serine dehydratases from mouse liver and spontaneous hepatomas]. High activities of L-threonine and l-serine dehydratases were maintained in spontaneous hepatoma of mice strain CBA as distinct from transplantable hepatoma. The initial rate [v] versus substrate concentration [S]0 curves had complex shapes for the enzymes from the liver tissue of healthy animals (especially after extraction of the enzymes by means of buffers with low concentration of K+). Kinetic patterns of l-threonine and L-serine dehydratases from hepatoma were distinct from those of normal mice liver tissue. The shape of [v] versus [S]0 plots was altered in response to AMP (1.10(-3) M). Contrary to the enzymes from normal tissue, dehydratases from hepatoma did not alter the shape of [v] versus [S]0 curves in response to AMP. The enzymes from hepatoma were apparently desensitized with respect to their possible allosteric effector. Threonine dehydratases of normal mice liver were also dissimilar as compared with the enzymes from hepatoma in the affinity of the apoenzyme to pyridoxal 5'-phosphate. This affinity was 3-fold lower for threonine dehydratase from hepatoma as compared with the enzyme from liver tissue.


[Method of preparing a radioactive collagen substrate from chick embryo tendons for determining the activity of collagenases of animal origin]. A method, described for obtaining of 14C-collagen from chicken embryo tendons, permitted to isolate the highly purified native substrate with high specific radioactivity applied to estimation of animal collagenases activity. The method is relatively simple, reproducible, does not require large amount of labelled amino acids; it shortens the course of protein purification.


[Electron-autoradiographic and biochemical study of the role of foam cells in low density lipoprotein metabolism]. Participation of foam cells in metabolism of lipoproteins of low density (LPLD) was studied by biochemical methods and by electronic autoradiography. The foam cells were isolated from atherosclerotic rabbit aorta after perfusion with 12I-LPLD within 6 hrs. Metabolic activity of foam cells was evaluated by the ratio of radioactivity in lipid and protein components of cells as well as by distribution of reduced argentum granules among the subcellular structures on autoradiogram. The biochemical studies showed that the lipid components of LPLD were preferably accumulated in foam cells. Electronic-autoradiography demonstrated that protein from the lipoprotein particles was also distributed intracellularly in various cytoplasmic structures. Foam cells appear to capture intact lipoprotein particles by pinocytosis with subsequent splitting of protein component by cellular lysosome apparatus.


[Lymphography and the possibility of tumor cell dissemination]. It is concluded that endolymphatic infusion of X-ray contrast substance in the presence of migrating tumor cells in lymphatic routes is inherent in a potential danger of tumor dissemination. Although getting of tumor cells in blood does not always result in metastases, nevertheless, a due account should be taken of the fact that lymphography is frequently performed in poor immunological resistance patients, preliminarily subjected to chemo- and radiotherapy. The decrease of immune resistance of the organism, in which the lymphatic system is of primary importance, is known to contribute per se to generalization of the tumor process. Another important conclusion is that the principal mass of tumor cells is ejected in the immediate period after endolymphatic injection of X-ray contrast substance. Thus, the cannulation of the thoracic duct during this period may prevent or reduce getting of massive amounts of tumor cells into the total blood flow.


[Treatment of phylloid tumors of the breast]. Phylloid fibroadenoma of the mammary gland is a comparatively rare lesion--0.3% of all breast affections, its clinical course is generally known to be characterized by both the possibility of recurrences development after non-radical treatment and its transition into mammary gland sarcoma. The authors report the data on 56 cases of phylloid fibroadenoma of the mammary gland treated at the N.N. Petrov Research Institute of Oncology of the USSR Ministry of Health during the period of 1926 to 1973. Fifty one of these patients showed benign tumors, 5--malignant tumors. The clinical diagnosis of the tumor is rather complicated (the correct preoperative diagnosis was established only in 27.5% of cases). The use of non-contrast mammography and trepanbiopsy failed to appreciably improve the diagnosis. The differential diagnosis between the benign and malignant forms seems to be mostly difficult. Only surgery is advocated. The extent of surgical intervention depends on morphological features of the tumor, its size, rate of growth and the breast size. Among benign forms recurrences were noted in three patients (6.3%). Of 5 patients with malignant phylloid fibroadenoma two patients died due to metastases during two postoperative years.


[Nature of the lipoprotein antigen responsible for the development of resistance to experimental atherosclerosis following its use in immunization of newborn rabbits]. In order to develop a tolerance to experimental atherosclerosis newborn rabbits were immunized with various fractions of atherogenic lipoproteins (lipoproteins of low density, lipoproteins of very low density and total fraction of these lipoproteins), isolated from blood serum of adult rabbits with experimental hypercholesterolemia. The tolerance to atherosclerosis proved to be achieved in immunization with lipoproteins of very low density. The lesser effect was observed using the total fraction of lipoproteins. The tolerance was not developed in immunization with lipoproteins of low density.


[Comparative lecithin-cholesterol-acyltransferase deficiency in the blood of newborn infants. Comparison of the esterifying activity of neonatal and maternal blood]. On the basis of data obtained in studies on the accumulation of cholesterol in erythrocytes of newlorns, the hypothesis is advanced on the deficiency of lecithin-cholesterol-acetyl transferase (LCAT) in the newborn children. A decrease in the rate of the LCAT-reaction was shown in funic blood using the specially developed system "LP-infranatante", the constituents of which were isolated from blood plasma of both newborns and of their mothers by ultracentrifugation at a density 1.21 g/ml and 40.000 rpm. The following factors were considered as possible determinants of the decrease in the rate of cholesterol esterification in blood plasma of newborns: 1) insufficiency in LCAT, 2) alteration in the composition of the substrate lipoproteins (lipoproteins of high density).


[Synthesis of RNA fractions in rat liver during single and multiple stimulation of the hypothalamus]. Specific radioactivity of RNA from rat liver tissue, labelled with 14C-orotic acid and fractionated using thermic phenol method, was altered dissimilarly. In single stimulation of hypothalamus the specific radioactivity of nuclear RNA was increased in RNA-40 degrees fraction than in RNA-55 degrees and RNA-63 degrees ones. A decrease in synthesis of nuclear RNA fractions followed the phase of activation in repeated stimulation of hypothalamus. The distinct increase in specific radioactivity was observed in cytoplasmic RNA (RNA-4 degrees) both in single and repeated stimulation of hypothalamus. The stimulating effect of the prolonged hypothalamus irritation on synthesis of the RNA fractions and on activity of glucose-6-phosphatase and fructose-1,6-diphosphatase disappeared more rapidly than this effect in long-term administration of hydrocortisone. The data obtained suggest that sensitivity of tissue-targets to prolonged hormonal stimulation is distinctly higher than the ability of hypothalamus to activate the synthesis of RNA and enzymatic proteins.


[Effect of rations with an increased sunflower seed oil level on the rate of very low-density lipoprotein formation in the liver, secretion into the blood and composition in the blood]. Feeding of rats on a ration with an excessive content of sunflower-oil (60 per cent of the total calorific value of the ration) for a period of 30 days resulted in lowering the rate of the apoproteins, prolipoproteins synthesis in the liver and in their loading with triglycerides and cholesterol. As a consequence of this it diminished secretion of endogenously formed tryglycerides and cholesterol from the liver into the blood and a changed lipid composition of lipoproteins of a very low density in the blood.


Conceptual framework shifts in immunogenetics. II. Some notes on the Ag system. Two Caucasian population materials totalling 530 individuals and 3,180 typing results are analyzed with regard to various combinations of the Ag(x, y, a1, d, c, g) factors. Superficially, both materials appear well aligned to each other and the contemporary (simple-complex) framework. However, when the same set of data are structuralized within a new (complex-simple) framework, the typing results for 12 of 362 or 3.3% of the Swiss and no less than 19 of 168 or 11.3% of the English samples are not compatible with the new framework specifying that the various anti-Ag reagents can be arranged in two 'inclusion groups'--the anti-Ag (y greater than d greater than c) and the anti-Ag (g greater than a1 greater than x) series.


[Foamy viruses in baboons and macaques]. The occurrence of foamy viruses among baboons and macaca monkeys in Sukhumi monkey farm was investigate;. The monkeys were shown to be carriers mainly of foamy virus type II. The frequency of virus isolation increased with the age of the animals and reached 88.8-100% in adult specimens. The virus behaviour in cell cultures is described. The morphological characteristics of the virus are based on electron microscopic examinations of ultrathin sections of primary and inoculated cell cultures.


[Enzymatic activity of the lymphocytes in gnotobionts in adenovirus infection]. The cytochemical activity of succinate dehydrogenases, alpha-glycerophosphate (mitochondrial and hyaloplasmic), lactate, glycose-6-phosphate, glutamate, beta-oxibutyrate, NADP-H2- and NAD-H2 diaphorases and acid phosphatase was studied in lymphocytes of gnotobiotic guinea-pigs infected with human adenovirus type 1. The analysis of transgression of distribution of the values in the experimental and control groups revealed a high informative diagnostic value of acid phosphatase and lactate dehydrogenase of lymphocytes.


[Use of the monkey pox virus for evaluating the intensity of the immunity against smallpox in experiments on M. rhesus]. Monkeypox virus causing in M, rhesus upon aerogenic infection a disease similar to human varioloid was used to evaluate the intensity of immunity against smallpox in immunized M. rhesus monkeys. Postvaccination immunity was solid in all the animals vaccinated intradermally or orally. In 2 out of 14 monkeys immunized orally, however, the immunity was partially overcome. Neutralizing antibody titers in these two monkeys were 1:5 and 1:25, respectively. This agreed with the observations made in Pakistan indicating the possibility that some humans having serum neutralizing antibody titers up to 1:32 could contract smallpox and develop the disease.


[Effect of inactivated Sendai virus on polyomavirus adsorption and penetration]. The quantitative study of adsorption, elution, and penetration of oncogenic polyoma virus (PV) labeled with 3H-thymidine under the influence of beta-propiolactone-inactivated Sendai virus (SV) was carried out in a permissive culture of mouse embryo fibroblasts and in two nonpermissive cultures of human embryo and chick embryo fibroblasts. In adsorption of PV on permissive and nonpermissive cells SV was found to reduce the amount of the adsorbed virus if used before the adsorption and to have no effect on adsorption upon reverse order of treatment of the cells with the two viruses. SV facilitates elution with 5 mM EDTA of PV adsorbed on both permissive and nonpermissive cells. Under the influence of SV, PV could be eluted from the surface of the permissive cells within 1 hour after adsorption and from the surface of the nonpermissive cells within 5-6 hours. Three hours after PV adsorption on permissive cells, both treated and untreated with SV, most of PV DNA (approximately 60%) was found in the nuclear fraction. At the same time, in the nuclear fraction of nonpermissive cells, treated or untreated with SV, the amount of PV DNA was insignificant (about 13%). The fraction containing large granules isolated from the cells which had been in contact with SV was found to contain approximately 50% of 3H-thymidine label.


[Cryotherapy of the cylindroma syndrome]. Two patients with dermal Cylindromas were successfully treated with a special cryoapplicator. This small cryosurgical unit consists of a copper core of 645 g with a 1,5 cm insulating styropore body. At the one end, the cylindrical core has a projection bearing the therapeutic surface, at the other a thread, which takes up a manipulator. This serves the purpose of transfering the core into liquid gas and, after throughout cooling, into the styropore body. After half an hour of therapeutic use, the warmed core requires new cooling in liquid nitrogen or liquid air.


[Rapid diagnosis of infections caused by the chickenpox-herpes zoster viruses]. A diagnostic preparation for the indirect hemagglutination test (IHA) was obtained by sensitization of fixed tannin-treated sheep erythrocytes with IgG-fractions from human herpes zoster convalescent sera. A high specificity of the preparation was established in comparative experiments. It could detect the varicella-herpes-zoster virus antigen in 100% of specimens from patients. The IHA test with this erythrocyte diagnostic preparation is simple, economic, gives the results within 1-1 1/2 hours after the specimens arrive in the laboratory. A great advantage of this test ipesviruses.


Uptake of polynucleotides by mammalian cells. XV. Properties and function of a DNA-protein complex situated in the outer membrane of Ehrlich ascites tumor cells. 1) DNA-protein complexes are supposed to be original constituents of the membrane of Ehrlich ascites tumor cells. These complexes can be attacked at the surface of viable cells by DNase or protease. The DNA is partially embedded in protein structures. 2) The net charge of this complex is of major importance for the RNA uptake capacity of the cells. Negatively charged DNA which is situated at the surface hinders RNA uptake. This is the explanation for the stimulation of RNA uptake by DNase or the decrease in RNA uptake after protease treatment. 3) Upon treatment of DNA-deficient complexes with homologous or heterologous DNA the original RNA uptake capacity of the cells is restored but the original conformation of the complex cannot be regained. 4) The DNase action on the complex is temperature dependent in a sigmoidal fashion. It is markedly slowed down at temperatures below 12 degrees C. This implies that structural changes in the complex occur at this transition temperature which make surface DNA susceptible to DNase. This effect can only be observed in original structures but not in reconstituted ones. 5) Polyanion treatment of the cells [poly(L-lysine)] which increases their RNA uptake capacity, most probably does not interact with the DNA-protein complex. Poly(L-lysine) appears to act at other membrane sites. 6) The DNA-protein complex has been investigated entirely in situ, i.e. situated in the membrane of viable cells.


Further investigations on the p-nitrophenylphosphatase activity of intact Ehrlich ascites tumor cells. The substrate specificity and the effects of nucleotides and SH-blocking agents on the p-nitrophenylphosphatase activity of intact Ehrlich ascites tumor cells (EAT) cells were studied. DL-beta-Glycerophosphate, o-phosphoethanolamine, cholinephosphate, glucose-6-phosphate, o-carboxyphenylphosphate,, phosphoenolpyruvate and AMP were not attacked by intact cells. ATP is greater than GTP is greater than UPT is greater than PPi is greater than pNPP were cleaved with decreasing velocity. A stimulation of the cleavage of p-NPP by the following nucleotides was observed with decreasing effectivity: ATP is greater than ADP is greater than GTP is greater than UTP; AMP was ineffective. The phosphatase activity was not affected by malate, tartrate and glutathion disulfide. The SH blocking agents diamide and thimerosal were more effective inhibitors of the pNPPase than of the ATPase activity, whereas the hydrolysis of ATP is more affected by the ATP analog adenylylimidodiphosphate. The present data are best compatible with a double headed enzyme: Both active sites interact with ATP, only one is active against p-NPP and sensitive against SH-blocking agents.


[Urogenital tuberculosis within the scope of general tuberculosis situation. Ambulatory management and care]. On the basis of two differential graphs the development of the general situation concerning tuberculosis in the GDR for the years 1962 to 1976 is described. Particularly taken into consideration were the new cases of urogenital tuberculosis which were compared with the rates of new cases in other countries. A significantly higher morbidity of tuberculosis was found in members of certain risk groups (so-called "gesunde Befundträger" [healthy persons not yet suffering from tuberculosis]). Regulations of the law for prevention of and combat against tuberculosis, principles of the continued ambulant treatment and the importance of the dispensary care were discussed. The success of treatment in the Berlin district, especially in the combat against urogenital tuberculosis, which refer to a more than 12 years observation period, are traced back to a continuity of initial stay in an urological clinic in connection with special procedures, following continued ambulant treatment and final after-care.


Grave cranio-cerebral trauma 30 years ago as cause of the brain glioma at the locus of the trauma particulars of the case. A glioblastoma multiforma developed 30 years after a penetrating craniocerebral injury in the left parietal region caused by fragments of an artillery projectile. The 3 cm large bone defect was located directly above the tumour. There were close scarry connections between dura, brain and tumour. Partial removal could not prevent the lethal exitus. Causal connection with the accident is assumed to exist.


[Rational method of obtaining sera with a high titre of virus-neutralizing antibodies. Report 2]. In addition to report I (ZHMEI, 1977, No. 1) a study was made of 9 more schemes of rabbit immunization with the poliomyelitis virus, type I, for the purpose of obtaining the neutralizing sera of high titre. Vitamins A and C were used in the experiments in the capacity of the activators of the organism reaction; Freund's adjuvant of different make was tested; different reimmunization periods and different amounts of the adjuvant were administered. Titration of rabbit sera in the process of immunization and reimmunization showed immunization into the lymph nodes with the subsequent single reimmunization in one month to be the most effective and economical method of obtaining high effective sera.


[Protoplast fragmentation as one of the possible mechanisms of L-transformation of bacteria (Clostridium perfringens)]. As revealed, the action of lysozyme on the cells of Clostridium perfringens BP-6K led to the formation of not only typical spheroplasts, but also of cells whose peripheral parts of the cytoplasm were fragmented by membrane component. Small bodies framed by the membrane proper and containing granular and fibrillar components were formed. They were polymorphic in osmium treatment, and had smooth contours in preliminary use of aldehyde fixation. In the latter case a dense lumpy material analogous to the one which fills the periplasmic zone and serves as a rigid wall component formed at the surface of the protoplasm and bodies-fragments. In case of escape of the bodies into the external environment through the perforations in the cell wall the principal mass of the protoplast remains intact. The morphology of the bodies-fragments indicated a principal possibility of their autonomic existence. It is supposed that the phenomenon described could serve as one of the mechanisms of L-cell formation.


[Homogeneous Cl. perfringens alpha-anatoxin: its physicochemical and immunogenic properties]. The authors present a method of obtaining relatively homogeneous preparations of alpha-toxoid of Cl. perfringens, type A, including the primary conception of the alpha-toxin proteins, their chromatography on DEAE-cellulose, fractionation with (NH4)2SO4, detoxication, with the subsequent gel-filtration through sephadex and isoelectric focussing. Sedimentation coefficient of the preparation proved to be 3.8 S, isoelectric point-4.83 +/- 0.07. In studying the immunogenic properties of alpha-toxoid in experiments on guinea pigs and rabbits their high immunogenicity, exceeding that of the industrial toxoid 8- and 6-fold, respectively, was established. Homogeneous preparations of alpha-toxoid provided intense anti-microbial immunity. Interlinear differences in the levels of the immune response of inbred mice, highly-reactive (BALB/c) and low-reactive (C57BL/6) to alpha-toxoid, reached 20-fold; in combination with the high immunogenicity of this antigen for mice this permits to recommend it for immunogenic studies.


[Comparative study of phospholipids in the neurons and glial cells of the brains of mammals, birds and reptiles]. Studies have been made on total content of phospholipids and relative content of various phospholipid families in neuronal and glial fractions obtained from the brain cortex of albino rat and brain hemispheres of the pigeon Columba livia and tortoise Testudo horsfieldi, as well as in oligodendroglial fraction of centrum semiovale and corpus callosum of the brain of rabbits. It was shown that in all the animals studied, the total glial fraction is approximately twice as rich in phospholipids as the neuronal one. With respect to the quantity of phospholipids, glial fraction is similar to the homogenate. Relative content of various phospholipid families in the homogenate and the cellular fractions is approximately identical. Yet, some differences were found between various fractions, as well as between the homologous fractions obtained from representatives of different classes. In all animals investigated, the neuronal fraction exhibits higher phosphatydylinositol content than the glial one. Pigeon neurons have higher level of phosphatydylinositol and lower level of phosphatydyl serine, as compared to rat and tortoise neurons. Glial fraction of rats contains significantly less sphingomyelin, than that of pigeons and tortoises. With respect to phospholipid composition, oligodendroglial fraction differs from total glial one and from neuronal fraction, being also different from the myelin.


[Cyclic 3--5-adenosine monophosphate metabolism in patients with Duchenne myodystrophy]. The state of metabolism of cyclic adenosinmonophosphate was studied. It was established that the concentration of nucleotides was distinctly lower in patients with this disease. The activity of adenilacyclose did not differ from normal rates. The enzyme to a large degree lost its capability of reacting to hormones, which made the metabolism in tissues to a certain extent autonomous. These data permit to rise the question of conducting a correcting treatment. In other forms of progressive muscular dystrophy the level of cyclic adenosinmonophosphate did not differ significantly from normal indices.


Hormonal activation of adenylate cyclase and its role in cyclic AMP mediated regulation of RNA synthesis in the mouse mammary gland. The activity of adenylate cyclase (EC 4.6.1.1) in the mouse mammary gland increases during late pregnancy and reaches its maximum value at one day pre partum. In the mouse mammary gland explant culture the adenylate cyclase activity is stimulated by a cooperative action of insulin, prolactin and hydrocortisone. The effect of these hormones can be demonstrated in intact cells, but not in a cell-free system. In the explants, RNA synthesis is stimulated by dibutyryl cyclic AMP, insulin and prolactin. The effects of both protein hormones and cyclic AMP are additive. The results obtained suggest that insulin and prolactin in cooperation with hydrocortisone are involved in the regulation of RNA synthesis in the mammary gland by activation of the adenylate cyclase system, independently of their effect on this process not mediated by cyclic AMP.


Disappearance of the cyanide-insensitive pathway of oxidation in mitochondria of MI-1 mutant of Neurospora crassa in vitro. Oxidation of exogenous NADH in mitochondria isolated from wild type and mi-1 mutant of Neurospora crassa decreases rapidly in vitro. In mi-1 mutant mitochondria the inactivation concerns the alternate pathway of oxidation whereas in the wild type it involves an unknown component of the respiratory chain. The activity of the primary NADH dehydrogenase is constant within the time of the experiments (2-4 h). NADH oxidase is not inactivated if oxygen is removed from the incubation medium by nitrogen bubbling. Succinate oxidase does not show any remarkable changes in activity within 2-3 h. In fresh mitochondria of the mi-1 mutant reduced ubiquinone is completely reoxidized by cytochrome oxidase but only 80% reoxidized by the alternate oxidase. In aged mitochondria of the mi-1 mutant in the presence of cyanide, ubiquinone is reduced to the level characteristic for fresh mitochondria in which respiration is completely inhibited by cyanide plus salicylhydroxamic acid. In these mitochondria the reoxidation of the reduced ubiquinone proceeds only via the cytochrome pathway. It is supposed that a labile component(s) of the respiratory chain present in the mi-1 mutant and the wild type mitochondria may, in mi-1 mutant, act as an alternate oxidase.


Alpha- and beta-adrenergic receptor stimulation in cultures of beating rat heart cells and its effect on automaticity and cyclic AMP levels. Positive chronotropic responses were elicited in rocker cultures of beating ventricle cells of 1 to 4-day old rats by both alpha- and beta-adrenergic receptor stimulation. Only the beta and not the alpha-adrenergic receptor-mediated increase in automaticity was associated with a rise in the level of cyclic AMP in the cultures.


Brain acetylcholine, adenine nucleotides and their degradation products after intraperitoneal and intracerebral adenosine administration. The paper describes adenosine effects on the acetylcholine synthesis and the profiles of adenine nucleotides, adenosine, inosine, and hypoxanthine in the rat brain in vivo after intracerebral (intraventricular) and intraperitoneal administration of adenosine. Intracerebral as well as extracerebral adenosine injection caused a dose- and time-dependent increase of the cerebral acetylcholine level, which was not accompanied by an equal development of the contents of adenine compounds and their degradation products. However, a considerable turnover of adenosine was observed in the brain after both routes of administration concerning the nucleotide as well as the degradation pathway. The kinetics of the purified enzymes of choline acetyltransferase and acetylcholinesterase were not influenced by adenosine. By this, the adenosine-caused increase of the cerebral acetylcholine cannot be explained by a direct molecular attack of adenosine on the enzymes of the synthesis or degradation of acetylcholine. An indirect mechanism which includes cAMP was discussed as a possible interpretation at present.


[Inhibition of 3-H-noradrenalin uptake in synaptosomes by substance P]. The uptake kinetics of DL-[3H]-norepinephrine into synaptosomes from rat brain hypothalamus can be described as a two stage process with uptake constants of Km = 0.9 micron and Km = 0.06 micron, respectively. Substance P exerts an inhibiting influence on both uptakes. The possible importance of this inhibition for the regulation of noradrenergic transmission is discussed.


Partial gonadotrophin-resistance in pseudohypoparathyroidism. A patient with classical Albright's pseudohypoparathyroidism was investigated because of oligomenorrhoea. Hypo-oestrogenism was associated with elevated basal gonadotrophin values [mean basal serum LH and FSH were 272 +/- 84 (SD) ng/ml and 593 +/- 83 ng/ml, resplectively (normal less than or equal to 220 and less than or equal to 400, respectively)]. The response to gonadotrophin releasing hormone (Gn-RH) was exaggerated, with maximal LH and FSH increments of 1688 and 458 ng/ml, respectively. These results and the findings on ovarian biopsy were compatible with partial ovarian resistance to gonadotrophins. This resistance could be overcome by administration of human menopausal gonadotrophins. This is the first evidence for gonadotrophin resistance in pseudohypoparathyroidism. The plasma cyclic adenosine-3',5'-monophosphate response to glucagon administration by two different protocols was about 70% that of normal control subjects. Other endocrine glands whose responses to hormones are mediated via the adenylate cyclase system evidenced minor abnormalities of questionable significance. This indirect evidence is compatible with a more extensive defect in the adenylate cyclase system in pseudohypoparathyroidism than has hitherto been suspected.


In vitro effects of theophylline and aminogluthetimide upon basal and ACTH induced cAMP levels and steroid output by the normal human adrenal gland. The in vitro effects of theophylline and aminogluthetimide upon basal and ACTH stimulated cAMP, cortisol and aldosterone responses of normal human adrenocortical tissue were evaluated. Theophylline increased basal cAMP levels and cortisol output, however, basal aldosterone output was depressed. Theophylline in concert with ACTH depressed cortisol and aldosterone output. Aminogluthetimide alone did not affect basal cAMP levels, however, the normal cAMP response to ACTH was delayed in aminogluthetimide pre-treated adrenals. Aminogluthetimide also depressed basal and ACTH stimulated cortisol and aldosterone output with the latter being more sensitive. The findings indicate that both theophylline and aminogluthetimide produce effects upon the adrenal in addition to inhibition of phosphodiesterase and cholesterol side-chain cleavage, respectively. Further, theophylline depression of ACTH stimulated steroid output may be helpful in understanding the interplay between a number of factors in the control of adrenal steroid biosynthesis and release.


Coincidence of dystrophia myotonica and pleomorphic adenoma of the parotid gland. Two patients with dystrophia myotonica and pleomorphic adenoma of the parotid gland are described. The probability that this coincidence could be due to chance is less than 1 to 1,000 (P less than or equal to 0.001). There are several reports in the literature of the association of myotonic dystrophy with neoplasia. The reason for their association is not understood.


Syndrome of Dejerine's Fourth Reich.

Syndrome of Dejerine's Fourth Reich. Dejerine's (1914) precise description of the human corticobulbar tracts is now doubted and forgotten for want of clinical significance. He described them as five bundles of aberrant pyramidal fibres which separate out as leashes from the corticospinal fibres at different levels and each had its territory of bulbar nuclei (like the Reich which is the territory of the German empire of which there were only three). Five cases are described who presented with uppermotor neurone lesion of the 7th, 10th and 12th cranial nerves without evidence of involveement of the pyramidal fibres to the limbs. It is postulated that this is caused by a lesion of the 4th Reich described by Dejerine.


Cryptophthalmos, dyscephaly, syndactyly and renal aplasia. Report of a case. A danish girl with incomplete, bilateral cryptophalmos together with assoicated craniofacial malformations, laryngeal hypoplasia, syndactyly, unilateral renal aplasia and slight external genital abnormalities is reported. Chromosomal abnormalities or metabolic disorders were not demonstrated. As the condition is extremely rare, some clinical and pathological fingings previosuly described in analogous cases are mentioned, together with a few pathogenetic mechanisms. Finally, a discussion regarding the aetiology of the condition is presented. Most authors are convinced that the malformative pattern is a syndrome with an autosomally recessive genetic basis. Added envronmental influence explains the wide range of manifestations and the varying gene expressivity.


[Intracellular cAMP concentration in isolated cells of white blood cell series of peripheral blood and bone marrow in healthy subjects and patients with different proliferative syndromes]. The level of cAMP was determined in isolated cells from bone marrow and peripheral blood of healthy subjects and patients with proliferative syndrome (acute and chronic myeloid leukaemia and chronic lymphatic leukaemia). In the investigations tritiated cAMP (3H-cAMP) was used and for binding of endogenous as well as exogenous cAMP protein isolated from bovine muscles was used. The mean cAMP level in peripheral blood granulocytes of healthy subjects was 27.90+/-3.82 pmol/10(7) cells and in normal lymphocytes it was from 11 to 18 pmol/10(7) cells. Much higher concentrations of cAMP: 56.4+/-16.25 and 52.7+/-11.02 pmol/10(7) cells were observed in myelocytes and metamyelocytes isolated from the bone marrow of healthy subjects. Lowering of cAMP concentration (below 4 pmol/10(7) cells) was observed in the lymphocytes of patients with chronic lymphatic leukaemia, while a higher cAMP concentration (above 90 pmol/10(7) cells) was found in the myeloblasts of patients with acute myeloid leukaemia.


[Diffuse poliencephalitis and visceral neoplasm (author's transl)]. A case of diffuse polioencephalitis associated with non-differentiated bronchial carcinoma is reported. Clinically the patient presented mental distrubance and an extra-pyramidal syndrome. Anatomopathological investigation revealed inflammation of the cerebral hemispheres and the brain stem. Similar involvement of others regions of the central nervous system has been reported in the literature, probably indicating various locations of a single nosological entity. A viral origin is probable but not yet established.


Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22--65 years. Biopsies for histochemical and biochemical analyses were taken from the vastus lateralis muscle of 55 untrained, healthy male subjects from 22 to 65 years of age. Fibre type distribution changed towards a decrease in the percentage of type II fibres, both in type IIA and type IIB fibres, whereas type IIB/IIA fibre ratio and type IIC percentage did not change with increasing age. It was found that the type IIB/IIA fibre ratio was inversely related to type I fibres, i.e. subjects rich in type I fibres had a relatively smaller proportion of type IIB fibres. Fibre area determinations revealed a selective decrease in type II fibre area. Consequently, the type II/I fibre area ratio and relative type II fibre area decreased. No changes in the specific activities of Mg2+ stimulated ATPase and myokinase were observed, while the activity of lactate dehydrogenase (LDH) was higher in the youngest groups than in the oldest. LDH isozyme pattern shifted towards a decrease in percentage distribution of the muscle specific isozymes and a corresponding decrease in muscle specific activity while the activity of the heart specific isozymes did not change.


Conversion of the electrophoretic pattern of type IV hyperlipidaemia to type III by intravenous heparin. Heparin was given i.v. to subjects with type IV hyperlipoproteinaemia who had only ordinary pre-beta lipoproteins and no late pre-beta lipoproteins (LP-beta) in their very low density lipoproteins (VLDL, d less than 1.006) upon agarose gel lipoprotein electrophoresis. Within 15 min the electrophoretic pattern of VLDL had changed completely. The normal pre-beta lipoproteins had disappeared and a discrete LP-beta lipoprotein had appeared. This new electrophoretic pattern, induced 15 min after heparin, is similar to that diagnostic of type III hyperlipoproteinaemia. It is suggested that the LP-beta lipoproteins represent an end stage in the catabolism of VLDL.


Myocardial scintigraphy with 99mTc-pyrophosphate in patients with unstable angina pectoris. A total of 400 patients, aged 25-82 years, admitted to the Coronary Care Unit due to clinical suspicion of acute myocardial infarction, were examined with 10 mCi 99mTc labelled to pyrophosphate. The examinations were carried out 4-120 hours post onset of symptoms, with a mobile gamma camera. Scintigrams were evaluated with regard to presence, localization and intensity of an uptake. Among 249 patients with a verified acute myocardial infarction, uptake was found in 237. Sixty-two of 85 patients with unstable angina showed a diffuse uptake with low intensity. Scintigraphy could not be used as a prognostic index of which patients would later develop an infarct. However, the scintigraphic pattern was useful as an aid in the differential diagnosis between acute myocardial infarction and unstable angina.


The reliability of computer tomography for the diagnosis and differential diagnosis of meningiomas, gliomas, and brain metastases. The CT characteristics were studied in a series of 90 tumours, and the diagnostic criteria were determined for meningiomas glioblastomas, other gliomas and metastases. These criteria were then employed in another group of 46 tumours in which the histological diagnosis was not known at the time of examination. The over-all diagnostic accuracy was 85%, and it was largely the same for the various sub-groups. Careful combination of the CT characteristics, perfect techniques, and increased experience may further improve the diagnostic accuracy.


The effects of amphiphilic compounds on phosphatidate metabolism. Amphiphilic cations interact with phosphatidate and thereby change its physical properties. This interaction can redirect phospholipid metabolism. In the presence of Mg2+ amphiphilic cations inhibit the activity of phosphatidate phosphohydrolase and stimulate that of phosphatidate cytidylyltransferase. Increasing the concentration of Mg2+ further, or adding Ca2+ have similar effects, except that Ca2+ does not stimulate phosphatidate cytidylyltransferase activity. Amphiphilic anions reverse the effects caused by the amphiphilic cations. The implication of these results are discussed in relation to the pharmacological effects of amphiphilic cationic drugs.


Studies of rat brain choline ethanolamine phosphotransferases using labeled alkylacylglycerol as substrate with evidence for reversibility of the reactions. Cholinephosphotransferase activity in brain microsomes may be assayed with labeled alkylacylglycerols or with CDP-choline with label in the phosphocholine with nearly identical results. The direct linear plot method was used for evaluation of Michaelis-Menten kinetic parameters. Most of the cholinephosphotransferase activity is in microsomes and a stimulatory factor seems to be present in the cytosol. Incubation of microsomes with labeled alkylacylglycerols and CDP-choline, in the initial absence of CDP-ethanolamine, produced labeled ethanolamine glycerophospholipids as well as labeled choline glycerophospholipids. Since the labeling of ethanolamine glycerophospholipids was increased by the addition of CMP, the labeling was probably due to the reversal of ethanolamine phosphotransferase to yield CDP-ethanolamine produced by the choline phosphotransferase reaction. Cholinephosphotransferase was reversed more readily than ethanolaminephosphotransferase in brain as it is in liver (Kanok and Ohno, 1973). Only trace quantities of plasmalogens were formed with labeled alkylacylglycerols. Previous results of plasmalogen labeling from labeled CDP-nucleotides were apparently due to reversal of phosphotransferase reactions. Alkylacylglycerophospholipids are not good substrates for plasmalogen formation, even when they are incorporated into microsomes.


Adsorption and activation of pancreatic lipase at interfaces. The first step of the lipase-catalyzed hydrolysis of insoluble long chain triglycerides is the adsorption of the enzyme to the interface. This adsorption, which is spontaneous when the interface is hydrophobic, is hindered by bile salts. Under these conditions, a small protein cofactor designated colipase adsorbs first and then anchors lipase at the interface. Interfacial adsorption enhances lipase activity, due, at least in part, to an acceleration of the rate-limiting deacylation step of the reaction. In this respect, lipase appears to be a most interesting model of an enzyme being activated by the presence of a lipid. The 3 steps of the heterogeneous catalysis induced by lipase, interfacial adsorption, interfacial activation and catalysis proper are under the control, respectively, of a serine hydroxyl group, a carboxyl and a histidine imidazole.


Effect of adenosine and catecholamines on cyclic AMP levels in guinea pig heart. Adenosine has been shown to stimulate cyclic AMP accumulation in guinea pig atrial and ventricular slice preparations in a rapid and dose-dependent manner. Response to adenosine was inhibited by therophylline, potentiated by several other phosphodiesterase inhibitors and unaffected by alpha- or beta-adrenergic blocking agents. Agonist action required free hydroxyl groups at 2', 3', and 5' positions on the ribosyl moiety, retention of one proton on the 6-amino group, N at position 7, and unsubstituted C at position 8 on the purine moiety. The combined action between adenosine and isoproterenol was the sum of the individual stimulations. The alpha-agonist action of epinephrine and norepinephrine reduced cyclic AMP levels stimulated by beta-agonist or by adenosine; this action was mimicked by methoxamine. The effect of an alpha-agonist was particularly pronounced when cyclic AMP levels were elevated by adenosine.


Cyclic AMP-dependent phosphorylation of the actin-binding protein filamin. Filamin is a high molecular weight protein that binds to actin filaments in cells. It is found in large amounts in several different cells and tissues, including smooth muscle, fibroblasts, platelets, and macrophages. It is immunologically related to the previously described macrophage high molecular weight actin-binding protein but clearly different from erythrocyte spectrin. Filamin is a phosphoprotein; it is phosphorylated in vivo in intact tissues and cells. It can be phosphorylated in vitro with endogenous kinases; cyclic AMP stimulates this phosohorylation. Furthermore, the purified protein can be phosphorylated by purified cyclic AMP-dependent protein kinase. In smooth muscle homogenates, the stimulation of filamin phosphorylation by cyclic AMP is specific. Cyclic GMP and Ca2+ do not increase its phosphorylation, although they do stimulate phosphorylation of other proteins.


Mechanisms of catecholamine actions on liver carbohydrate metabolism. Epinephrine rapidly activates phosphorylase in hepatocytes, mainly by a mechanism(s) involving alpha-adrenergic and not beta-adrenergic receptors. The alpha-adrenergic mechanism does not involve accumulation of cAMP or activation of cAMP-dependent protein kinase. It is impaired when hepatocytes are depleted of calcium by EGTA treatment and is rapidly restored by readdition of calcium. Basal phosphorylase is also lowered by calcium deficiency and rapidly increased by calcium but not other divalent cations. The divalent cation ioniphore A23187 increases phosphorylase a levels in hepatocytes in a calcium-dependent manner. Calcium deficiency does not modify the effects of glucagon, cAMP, or beta-adrenergic activation on phosphorylase. Activation of alpha-adrenergic receptors rapidly increases 45Ca fluxes in hepatocytes. Glucagon produces similar effects, but supraphysiological concentrations are required. The hypothesis is advanced that alpha-adrenergic activation of phosphorylase involves alterations in cell calcium such that there is an increase in cytosolic Ca2+ concentration leading to increased phosphorylase kinase activity. Epinephrine induces greater cAMP accumulation in calcium-depleted cells than in normal cells. The effect is mediated by alpha-adrenergic and not beta-adrenergic receptors. Calcium deficiency also cuases cAMP accumulation in hepatocytes incubated with phenylephrine but does not modify the responses of the cells to isoproterenol, glucagon, or cAMP. Low concentrations of calcium rapidly reverse alpha-adrenergic receptor-mediated cAMP accumulation in calcium-depleted cells. The hypothesis is advanced that calcium normally exerts an inhibitory effect on a linkage between alpha-adrenergic receptors and adenylate cyclase in hepatocytes.


Regulation of aldosterone secretion: current concepts and newer aspects. Four humoral factors have been shown to play important roles in the regulation of aldosterone secretion. These are ACTH, potassium, sodium and angiotensin II. ACTH appears to play little or no role in the maintenance of adrenal zona glomerulosa cells in response to specific stimuli. However, there is evidence to show that physiologic levels of ACTH regulate the  minute-to-minute fluctuations of plasma aldosterone. In man and in experimental animals, alterations in potassium balance as well as acute increments in serum potassium can stimulate aldosterone production. The importance of potassium ion in the control of aldosterone secretion can be fully appreciated by the demonstration that aldosterone responses to other stimuli are subnormal in the presence of potassium depletion. Changes in dietary sodium can alter the aldosterone response to a number of acute stimuli. Sodium deprivation enhances aldosterone responses to ACTH infusion, potassium loading and angiotensin II administration. Enhanced conversion of corticosterone to aldosterone (due to sodium depletion) coupled with an acute stimulus acting at an earlier step in aldosterone biosynthesis probably explains the sensitizing effect of dietary sodium restriction. In recent years, indirect evidence has emerged to suggest that the COOH-terminal heptapeptide fragment of angiotensin II may mediate the aldosterone-stimulating activity of the renin-angiotensin system. The evidence has been derived from in vivo and in vitro studies indicating that angiotensin II and the heptapeptide stimulate aldosterone production equally well and that their relative binding potencies to adrenal zona glomerulosa cells are identical. In addition, heptapeptide antagonists are potent and specific inhibitors of angiotensin II-induced aldosterone biosynthesis. However, the data do not preclude the possibility that angiotensin II could stimulate aldosterone production without prior conversion to the heptapeptide.


Serological studies in the elderly.

Serological studies in the elderly. Sera from 108 elderly patients in psychiatric and general hospitals were tested for antibodies to seven viruses. Measles virus antibody levels were significantly higher in patients from the psychiatric hospital, regardless of diagnosis, than in those from other hospitals. Demented patients, regardless of their hospital, had significantly higher levels of antibody to adenovirus than control patients.


Receptor dysfunction and hormone resistance in human diseases--a review. Studies of the hormone-receptor interaction have introduced a new chapter in endocrine and metabolic disorders. Receptor (R) dysfunction in human diseases, due either to an alteration in the number or affinity of the R, or to antibodies against the R, is reviewed and classified in the first part of this paper. Disorders where hormone resistance has been implicated, but where R studies are still unavailable are also presented.


A comparison of the adrenal responses to hypoglycemia, metyrapone and ACTH. The adrenal responses to insulin-induced hypoglycemia and the rapid adrenocorticotropic hormone (ACTH) stimulation test were compared in 24 healthy volunteers, 18 of whom also underwent a rapid oral metyrapone test. The cortisol levels after hypoglycemia (18.0-30.0 microgram/100 ml) were similar to and directly related to the levels after ACTH (21.0-31.0 microgram/100 ml). The levels after both stimuli were independent of age, sex, height, and weight. The 11-deoxycortisol response to the metyrapone test was less than the cortisol response to hypoglycemia and metyrapone administration was associated with more unpleasant side effects. In a group of 69 control subjects, the post-ACTH cortisol levels were 15.0 to 80.0 microgram/100 ml while in seven patients with Addison's disease they were less than 1-4.5 microgram/100 ml. In 44 control subjects, the posthypoglycemia cortisol levels were 18.0 to 30.0 microgram/100 ml compared with less than 1.0-9.0 microgram/100 ml in 22 patients with hypopituitarism. The absolute poststimulation cortisol levels provided better separation of control subjects from patients with adrenal or pituitary insufficiency than either the increment in cortisol levels or the 11-deoxycortisol response to metyrapone.


Intermittent occlusion of the hepatic artery and infusion chemotherapy for carcinoma of the liver. Twenty-nine patients with hepatocellular or metastatic colon carcinoma were included in the present study. A system of staging the extent of disease was developed to provide a guideline for patient selection and evaluation of the results of therapy. Sixteen patients received intraarterial infusion chemotherapy only and thirteen were treated by a combination of intermittent occlusion of the hepatic artery and infusion chemotherapy. In this latter group intermittent occlusion of the hepatic artery was employed as an alternative to hepatic artery ligation. Patients in either group having disease confined to the liver experienced good response to treatment, had a low incidence of drug-related complications, and survived for relatively long periods. The study confirmed that intermittent occlusion of the hepatic artery is a safe procedure and that it is not accompanied by an increase in morbidity or mortality. The rationale for using this technic and the advantages it has over hepatic artery ligation were presented. The procedure is currently being utilized with increasing frequency in patients in relatively early stages of the disease. Accumulation of more material and longer periods of follow-up are required to determine the therapeutic advantages of the new method over infusion chemotherapy alone.


Antibiotic-induced paralysis of the mouse phrenic nerve-hemidiaphragm preparation, and reversibility by calcium and by neostigmine. Certain antibiotics can induce neuromuscular paralysis, but the mechanism of this action is largely unknown. The purpose of this study was to compare the neuromuscular blocking potencies and reversibilities of 16 antibiotics in the isolated mouse phrenic nerve-hemidiaphragm preparation. The antibiotics tested were five aminoglycosides (neomycin, gentamicin, streptomycin, dihydrostreptomycin and kanamycin), tetracycline and oxytetracycline, polymyxins B and E, penicillins G and V, cephradine, cephaloridine, erythromycin, lincomycin, and clindamycin. Reversibility of the muscle paralysis by calcium and neostigmine was assessed. All the aminoglycosides resembled magnesium in blocking neuromuscular transmission, the neuromuscular blockade being almost completely reversed (to 64-77 per cent of control) by calcium but only poorly reversed by neostigmine (to 20-67 per cent of control). Neuromuscular blockade produced by the tetracyclines was also reversed by calcium (44-104 per cent) but not by neostigmine (0-15 per cent). Neuromuscular blockade produced by the polymyxins or by lincomycin was only partially reversed by calcium (0-34 per cent). Penicillin V, erythromycin, clindamycin, polymyxin B and the tetracyclines could also produce muscle paralysis by decreasing muscle contractility. This effect on contractility was irreversible by pharmacologic means. Penicillin G, cephradine and cephaloridine possessed negligible paralyzing effects on the nerve-muscle preparation. It is concluded that the different groups of antibiotics tested act by different mechanisms and that only the calcium-induced reversal of aminoglycoside block is predictable.


Chromatographic analysis of multiple tracer inert gases in the presence of anesthetic gases. A gas chromatographic method for simultaneous analysis of multiple tracer inert gases in blood and expired gas samples is described. The method enables determination of the distribution of ventilation-perfusion ratios in the lungs during anesthesia with nitrous oxide and halothane. In addition, simultaneous analysis of anesthetic gas concentration in blood permits calculation of the amount of uptake or elimination of anesthetic gases from the Fick principle.


A comparison of a theophylline-ephedrine combination with terbutaline. In a single-blind, crossover study 10 adult asthmatic patients received a theophylline-ephedrine combination tablet (theophylline 90 mg, ephedrine 16 mg and phenobarbital 25 mg in an immediate release layer and theophylline 90 mg and ephedrine 32 mg in a sustained release layer) twice daily or terbutaline 5 mg three times daily for two weeks. There was no significant difference in bronchodilator response to a single dose of the study drugs on either the initial day of treatment or after two weeks of continuous therapy. Mean increases in serum cyclic-AMP levels produced by both drugs were not significantly different. Mean peak plasma theophylline levels were 2.9 +/- 1.3 microgram/ml following the initial dose and 7.3 +/- 3.4 microgram/ml after two weeks of continuous dosing with the combination drug. No adverse effects on blood pressure or pulse rate were observed to either drug. Overall, the incidence and severity of reported side effects (tremor, nausea and nervousness) were less with the theophylline-ephedrine combination.


Protides of the Mustelidae: immunoresponse of mustelids to Aleutian mink disease virus. Members of North American Mustelidae were tested for their response to inoculation with 10(6) infective doses of Aleutian disease virus. In subfamily Mustelinae, 3 species in the genus Mustela (M vision, M erminea, and M putorius) and 2 species in genus Martes (Ma pennanti and Ma americana) responded immunologically with some features resembling Aleutian disease in mink. In subfamily Mephitinae, only Mephitis mephitis responded, and others of the subfamily did not, nor did members of subfamilies Melinae and Lutrinae. The responses observed ranged from development of detectable antibody levels determined by counterimmunoelectrophoresis to histopathologic changes typical of Aleutian disease.


Maintenance of foals with combined immunodeficiency: causes and control of secondary infections. Sixty-six cases of combined immunodeficiency (CID) in foals were studied to determine the most prevalent causes of infection and death. Lesions of the respiratory system were observed in 59 of the foals and were attributable to infection with equine adenovirus. Pneumocystis carinii, and bacteria. Significant lesions were also observed in liver, pancreas, intestines, heart, and kidneys. Maintenance of foals with CID for experimental purposes is directed at the prevention and control of these secondary infections. Adenovirus can be controlled by administration of horse plasma containing high titers of antiadenovirus antibody. Bacteria are controlled by appropriate antibiotic therapy. Pneumocystis carinii infection remains a significant problem in the maintenance of foals with CID.


Equine grass sickness: serologic evidence of association with Clostridium perfringens type A enterotoxin. Clostridium perfringens type A enterotoxin seroneutralization was carried out on sera from 50 horses recovered from grass sickness and from 100 other horses with no record of having had the disease. Of the affected horses, 70% had seroneutralizating titers higher than 1:64, half of these being equal or higher than 1:128. More than 88% of the horses with no record of grass sickness had titers lower than 1:64. These data support the theory of association between C perfringens type A toxins and grass sickness.


Intrafetal inoculation of swine with transmissible gastroenteritis virus. Fetuses in 3 sows were inoculated (intramuscularly) with transmissible gastroenteritis (TGE) virus on 95th, 77th, and 74th days of the gestation. At 15, 14, and 37 days later (or days when pigs were obtained by hysterectomy), there was evidence of intestinal localization of virus, with villous atrophy and subsequent repair. All intrafetal-inoculated pigs became serologic-positive for TGE. A noninoculated pig shown to be seropositive for TGE at 15 days of age (after hysterectomy) was resistant to challenge exposure with virulent TGE virus given on the 32nd day, in contrast to 3 seronegative littermates that developed typical disease when challenge exposed.


Distribution of Bovid herpesvirus 2 in calves inoculated intravenously. The behavior of Bovid herpesvirus 2 in the skin, lymph nodes, and nervous system of calves injected intravenously with the virus was studied. After a latent phase that lasted up to 40 hours after inoculation, the virus produced a systemic infection which was characterized by primary localization of virus in the skin, lymph nodes, and nervous system. Between postinoculation days 7 and 12, the infection tended to persist in the skin only. The finding of intranuclear inclusions in the pyramidal cells of the cerebral cortex and in the neurons of the superior cervical and stellate ganglia supports the hypothesis that the virus might utilize the structures of the nervous system for its replicative cycle in the calf.