[Demonstrating the localization of hemoproteins by an electron cytochemical method]. The dynamics of division and interphase cell size in the growing ovule of Pinus silvestris was studied on histological slides in the year of fertilization. A constant extension in size of dividing cells of the endosperm was shown which, in this respect, do not differ much from the interphase ones. Cell division and elongation in this tissue occur simultaneously to be completed only with the transition of cell to differentiation. The size extention of the dividing cell does not influence the frequency of cell division. In the integument and the nucleus, the value of dividing cells is relatively constant. At the transition of these cells to elongation their mitotic activity decreases shaply to stop completely after-wards. Cell division and elongation are divided here in time.


[Analysis of substances issuing from Zajdela ascitic hepatoma cells following exposure to UV radiation of different wavelength. II. Proton release]. The release of protein from the Zaidela ascitic hepatoma cells following irradiation with physiological doses of short-wave (254 nm) and long-wave (300--380 nm) UV light (far and near UV radiation) has been investigated. The amount of protein increases with dose making, upon the maximal radiation damage, 180 and 2 per cent of the protein against, resp., the protein amount releasing from non-treated cells and the total protein of the intact cell. The far UV light is by one order more efficient than the near UV light. Irradiation of cells with the former and the latter results in the release of high and low molecular proteins, resp. The near UV irradiation brings about heavier releasing of proteins than does the far UV light.


Report of Joint Committee for Stroke Resources. IV. Brain edema in stroke. A classification of brain edema is provided as well as an extensive review of the animal models from which we have derived most of the basic information we have about the formation and resolution of edema. The clinical aspects of cerebral edema in stroke are discussed and also modern methods for identifying cerebral edema in the human. Attention is given to computed tomography and enhanced CT and advances in their application to this condition. Treatment of cerebral edema in the stroke patient using glycerol, dextran 40, mannitol, steroids, and other drugs is discussed and the need pointed out for controlled clinical trials of the therapeutic effectiveness of these agents.


[Prospects for use of the anterior chamber of the eye for studying proliferation, differentiation and hybridization of tumor cells]. The anterior chamber of mammalian eye (ACE) is one of the places of organism privileged immunologically that permits to use it for transplantations of allogenic tissues. Besides, the medium filling the chamber, provides an excellent growth of transplants there, whereas the transparent cornea allows to control the growth. The analysis of results obtained with this method shows its acceptibility both for heterotransplantations of tumors including human tumors, and for homotransplantations with the aim to study the progression of tumors and the selection of constant tumor lines. The ACE is easily applicable for studying morphogenetic potentialities of tumor cells, as well as their ability to differentiation and normalization, because its medium has the quality of "differentiating" for many tissues. Cytological heterogeneity, revealed during tumor transplantations, allows to study the spectrum of cytological variability and transgression of tumor characters at different stages of their progression. The ACE can be used for estimation of tumor formation ability of tumor cells by determining TD50 (tumor dosis 50) which is important for estimation of different kinds of damage (X-rays, chemotherapy etc.). According to authors' point of view, it is very perspective to use the anterior chamber of eye for elaboration of effective methods of hybridization tumor cells with normal ones.


[Effect of colchamine on the morphology of transformed fibroblast-like cells in culture]. Colcemid-induced changes in the morphology of cultured transformed fibroblast-like mouse cells were studied using scanning electron microscope. Colcemid interferes with the normal cell polarization so that all the cell edges became active. Colcemid-treated normal cells remained well spread over the substrate. Transformed cells lost their polarization after colcemid treatment--the long, narrow, poorly attached processes of different form appeared along all the cell periphery. As in the case of the absence of colcemid, transformed cells remained less spread and worse attached to the substrate than normal ones. It is suggests that a) the same colcemid-sensitive structures are responsible for the polarization of transformed and normal cells; b) morphological differences between transformed and normal cells are determined mainly by structures different from colcemide-sensitive ones.


Allelic structural genes for the expression of mature of immature endogenous type-C virus in C57BL/he and C57BL/6J mice. Type C particles produced in a great amount by the exocrine pancreas of normal C57BL mice have been found by electron microscopy to retain their immature morphology in C57BL/6J mice and to develop into the mature form in C57BL/He mice. Examining F1, F2 and BC1 hybrids between the 2 strains, evidence of a dominant allelism for the immature phenotype was found.


[Quaternary structure of NAD-kinase from rabbit skeletal muscles]. The quaternary structure and some kinetic properties were studied for NAD-kinase from the rabbit skeletal muscles. The molecular weight of the 150-300-fold purified enzymic preparation was determined by separation in the Sephadex G-200 thin layer, by means of Sephadex G-200 column gel-filtration and by the method of electrophoresis in the gradient of polyacrylamide gel concentration. Some molecular forms of NAD-kinase with a molecular weight of 31000-305000 are found in the enzymic preparation and possibility to change from one form to another is shown. On the basis of the established quaternary structure and complex kinetic characteristics of the enzyme a conclusion is drawn on the existence of the rabbit skeletal muscle NAD-kinase as an equilibrium system of the oligomeric forms possessing different catalytic activity and consisting of different combinations of subunits with a molecular weight of 31000.


[Relation between catecholamines metabolism and CoA content in rat tissues]. The content of CoA in the liver, heart, kidneys and brain of rats was studied as affected by ACTH, melipramine and prednisolone. After ACTH administration the content of CoA in the liver increases. When blocking "capture" and "reverse capture" of catecholamines by melipramine the content of CoA in the kidneys lowers. Administration of melipramines causes no changes in the content of CoA in the tissues. Under the effect of prednisolone there is a tendency to the CoA content decrease in the kidneys. In the other tissues the subcutaneous administration of the preparations does not effect the content of CoA. Possible mechanism of the studied pharmacologic substances effect on the content of CoA in the tissues is under discussion.


Granular myoblastoma: perineal neoplasm of probable neural origin. A seventy-year-old man with a painless, perineal neoplasm was found to have a granular cell myoblastoma densely adherent to the bulbar urethra. This case represents the fourth known perineal neoplasm of neural origin.


[Differences in transcription of nuclear RNA from rat liver with normal and malignant growth]. Total nuclear RNA was isolated under conditions of actinomycin D blocking ion-exchange chromatography on kieselguhr columns with methylated albumin detected differences in transpiration of rat liver nuclear RNA with intensive normal and malignant growth. Actinomycin D in doses blocking the appearance of peculiar proteins in the blood serum of rats with the regenerating liver and RS-1 hepatoma produces a different effect on the biosynthesis of nuclear DNA-like RNA of the rat liver. 24h after a partial hepatectomy the antibiotic inhibits considerably the biosynthesis of nuclear DNA-like RNA which is eluated during chromatographying with 0.2% solution of sodium dodecyl sulphate at 70 degrees C. With RS-1 hepatoma the actinomycin D effect is most pronounced with respect to nuclear DNA-like RNA of rats with a tumour which is washed off from the column with a 0.2% solution of sodium dodecyl sulphate at 37 degrees C.


[Peptide hydrolase activity in rabbit brain subcellular fractions under conditions of adrenalectomy and administration of hydrocortisone and ACTH]. Adrenalectomy and administration of hydrocortisone and ACTH are shown to induce no changes in the total activity of neutral peptide-hydrolase in both homogenates and brain subcellular fractions. The absence of adrenalectomy and hormone administration effect on the total peptide-hydrolase activity in homogenates is established simultaneously with its essential changes in the brain subcellular fractions. A decrease in the enzymic activity of the mitochondrial-lysosomal fraction (MLF) following adrenalectomy is observed side by side with its increase in a soluble fraction. Hydrocortisone and ACTH administration cause an increase in the acid peptide-hydrolase activity in MLF and its decrease in the brain soluble and microsomal fractions of adrenalectomized rabbits. The degree of solubilization of MLF acid and neutral peptide-hydrolase by detergent triton X-100 after adrenalectomy is increased. Hydrocortisone and ACTH administration, on the contrary, decrease a degree of solubilization of the brain MLF peptide-hydrolase in adrenalectomized animals.


A jugular foramen schwannoma simulating an acoustic tumor with recovery of retrolabyrinthine cochleovestibular function. Our literature review has tabulated 33 jugular foramen neuromas that appeared either as a neurologic "syndrome of the jugular foramen" like a glomas tumor, or similar to an acoustic tumor. The few posterior fossa tumors involving the eighth nerve or encroaching upon it that have been removed and resulted in cochleovestibular preservation or recovery have been reviewed. A rare case of jugular foramen schwannoma with cochleovestibular preservation after total removal has been extensively studied with preoperative and postoperative cochleovestibular tests.


[Use of inactivated vaccine against infectious rhinotracheitis--pustular vulvovaginitis (IBR-IPV) in calves and pregnant cows]. A total of twelve batches of an inactivated vaccine against IBR--IPV, obtained by the authors, were tested in the practice. Vaccinated were 212 calves and 1172 cows and heifers on five dairy farms in different communities. On the basis of virologic, serologic, clinical and epizootiologic investigations the conclusions were drawn that the vaccine is harmless and highly immunogenic. In subcutaneous application at the rate of 3 cm3, twice, it renders protection against IBR--IPV infection (respiratory diseases and abortions) to calves aged more than 30 days for at least 6 months and 8 months for pregnant cows and heifers. On farms with a record of active IBP--IPV infection it is suggested to treat both the diseased and apparently (clinically) normal calves, either therapeutically or prophylactically, with a hyperimmune serum, and after the disease has receded--to resort to vaccination. In comparison with the live vaccines the tested one has been shown to provoke no postvaccinal accidents, eliminating the possibility of maintaining and widening the active infection foci, at otherwise almost comparable immunogenic properties as regards the titers of the virus-neutralizing antibodies produced after the vaccination.


Ultrasonic evaluation of salivary glands. Diagnostic ultrasound was used to study 40 patients undergoing excision of a major salivary gland for various disease entities. Findings were as follows: Malignant lesions showed low reflectivity and attenuation with poorly outlined or diffuse borders. Inflammation demonstrated high reflectivity and attentuation with diffuse borders. Echographic patterns from mixed tumors showed either high or medium to low reflectivity; all demonstrated low to medium attenuation and were well outlined. It appears that various diseases of the major salivary glands have different echographic patterns. An attempt to correlate the echographic patterns with the histology of the disease process was made.


Microscopic and pulse cytophotometric investigation of a carcinoma of the jejumum in a seven year old child. In a seven year old boy with acute abdominal pain and intestinal bleeding, laparotomy revealed an invaginated carcinoma adenomatosum cylindrocellulare in the distal part of the jejunum. Histological and pulse cytophotometric investigations support the diagnosis of a highly differentiated but locally destructive and malignant tumor.


Interaction between ceruloplasmin and Sendai virus envolpe components. Note IV. Effect of ceruloplasmin on the hemagglutinin and neuraminidase activities of Tween 20-solubilized envelope components separated by adsorption--elution on RBC. Ceruloplasmin inhibits the hemagglutinin (HA) and neuraminidase (N-ase) activities of envelope fragment populations isolated from Sendai virus disrupted by alkali--Tween 20 treatment. The inhibition induced differs according to adsorption--elution characteristics, value and ratio of HA and N-ase activities and sterical configuration of the envelope fragments.


[Effect of 5-fluorouracil and thiophosphamide on the activity and fractional content of phosphatases of Zajdela hepatoma]. The administration of different types of antitumor drugs is found to lead to a decrease in total activity of phosphatases in mitochondrial, lysosomal and microsomal fraction of Zajdela hepatoma cells, the free activity being enhanced. The isoenzyme pattern of phosphatases in soluble fraction is influenced too. The results suggest that different antitumor drugs cause a uniform response in tumor cells, manifested in disorders in the protein synthesizing system and membranes of subcellular particles involved.


[Influence of diets with a high content of qualitatively different carbohydrates on the metabolism of blood lipoproteins]. The feeding of rats for a space of 30 days on diets with elevated content of starch or saccharose (71 per cent of the total calorific value) was followed by an accelerated synthesis and secretion into the blood of pre-beta-lipoproteins. The ration with succharose, however, produced a much greater effect on the rate of synthesis of pre-beta-lipoproteins than did the one containing starch. The action of both carbohydrate-rich rations was noted to be attended by a growing rate of the apoproteids and glycerides exchange in the low-density lipoproteins. The feature distinguishing the effect produced by the ration with saccharose, as compared with that containing starch, was an accelerated etherification of cholesterol in the blood.


[Several virologic and biochemical aspects of vaccination with antipoliomyelitis vaccine. Fate of the parent virus]. In the present study we attempted to follow the fate of the parental poliomyelitis virus of immunological type II labeled with 3H-uridine in vaccinated animals. For this purpose, 3H-uridine labeled purified and concentrated virus was inoculated intramuscularly into cotton rats (sensitive to poliomyelitis virus) and guinea pigs (insensitive to poliomyelitis virus). The controls consisted of two groups of the same animal species: the animals of the first group were inoculated intramuscularly with pure 3H-uridine of known high activity while the animals of the second group were inoculated also intramuscularly with pure 3H-uridine and in another leg 0.5 ml of standard poliovirus vaccine of type II. Since poliomyelitis virus replicates in the cytoplasm, we studied cytoplasmic extracts of various organs (the brain, spinal cord, lungs, and spleen) of cotton rats and guinea pigs at different intervals after virus inoculation (1, 4, and 15 days). The experimental results showed the attenuated type II poliomyelitis virus to be able to persist for long periods in animals in the form of subviral particles with a higher buoyant density in cesium chloride gradient.


[A simple micro-procedure in virological and serological diagnosis]. The author reports on a micro-neutralization test which makes it possible to detect the antibodies against 7 different respiratory viruses (adeno and parainfluenza viruses) using only 0.080 ml of serum from patient. Swaged PVC foil used for packing pharmaceuticals, also known here as strip packing or press-through packing for pills and dragees was employed as plates for the cultures. This material is not toxic for the cell cultures, it is cheap and suitable also for other microbiological work in the field of serology.


[Several virologic and biochemical aspects of vaccination with antipoliomyelitis vaccine. Characteristics of intracellular virus-specific structures]. The data are presented concerning infectious potentials of subvirus particles isolated from cytoplasmic extracts of various organs of cotton rats and guinea pigs inoculated intramuscularly with purified and concentrated poliomyelitis virus type II. As described earlier, from various organs of the animals (the brain, spinal cord, lungs, and spleen) subvirus particles were isolated which in cesium chloride gradient had a density higher by 0.05-0.1 g/ml than that of the intact virus. Determinations of the infectious titre of these subparticles in susceptible cells showed their infectivity to be lower by 4-5 lg than that of the infact virus. When DEAE-dextran was used, a titre of both subvirus particles isolated from cytoplasmic extracts of various organs of the immunized animals and of the original poliomyelitis virus increased by 3-4 lg. The subvirus particles were sensitive to pancreatic RN-ase and to the antiserum against poliovirus type II. All the foregoing permits a conclusion that attenuated type II poliovirus or a portion of its population after inoculation into the living body is capable of long-term persistence there in the form of subviral particles with high buoyant density values.


[Antiviral activity of experimental combination of 5-iodo-2-deoxyuridine with 6-azauridine and its effectiveness in the treatment of herpetic infection with lesions of the skin and mucous membranes]. The use of the combination of 5-iodo-2-dioxyuridine (IUDR) and 6-azauridine drugs differing in their mechanisms of action in an experimental herpetic infection demonstrated its definite antiviral activity, not only not inferior to the effect of each of the drugs alone, but also remaining sufficiently high when the concentration of IUDR was decreased 2-fold. In clinical trials in relapsing genital herpes all the drugs under study showed statistically significant therapeutic activity. The combined use of the drugs exerted a certain synergistic effect.


Carcinogenicity of nitrosoazetidine and tetradeuteronitrosoazetidine in Sprague-Dawley Rats. Nitrosoazetidine was fed to rats in drinking water at three different concentrations. At 2 mmol (10 mmol total dose) all of the rats died with hepatocellular carcinomas by the 62nd week. This was a greater response than to an equivalent dose of nitrosopyrrolidine. At 0.67 mmol, 6 of 21 rats developed liver tumors, and at 0.17 millimolar 2 of 30 animals had liver tumors. The comparable responses to feeding of nitrosoazetidine-2,2,4,4-d4 were 3 of 21 rats with liver tumors at 0.69 millimolar and 3 of 30 rats with liver tumors at 0.17 mmol. These results show only a small deuterium isotope effect in liver carcinogenesis with nitrosoazetidine.


Mechanism and control of fluid secretion. Fluid secretion and reabsorption by a variety of plant and animal tissues appear to be accomplished by osmotic coupling between solute transport and water movement. The local osmosis model suggests that active accumulation of solutes within narrow folds at the cell surface may produce the local gradients that generate water flow. Both micropuncture techniques and electron-probe X-ray microanalysis have established that local osmotic gradients occur in absorptive epithelia, but they have not as yet been detected in secretory tissues.Hormonal control of secretion involves stimulation of solute pumps and adjustments of permeability to non-transported solutes. Since hormone receptors and pumps are often located on opposite surfaces of the cell, intracellular second messengers convey the secretory signal through cytoplasm. Much has been learned by study of insect tissues that are anatomically simple and that function for long periods in vitro. Aspects of hormone-receptor interaction have been explored, including the action of halluninogenic molecules. In insect salivary glands cyclic AMP appears to stimulate cation transport, while calcium increases anion permeability. The various second messengers probably interact with each other in complex feedback loops that stabilize the system and make it quickly responsive to hormone. Cyclic AMP may stimulate release of calcium from mitochondria. Unresolved is the way second messengers alter properties of the cell surface.


[Proximal ureteral atresia in childhood]. A rare cause of the congenital hydronephrosis is the proximal atresia of the ureter. With the help of 6 own cases morphology, clinic and therapy of this clinical picture are discussed. The differentiation from Wilms's tumour renders differential-diagnostic difficulties. It seems that a clinical description of this picture of a disease is hitherto not yet existing.


[Malignant mixed tumor of the liver in an adult (author's transl)]. A malignant mixed tumor of the liver was observed in a 55 years old woman. The tumor was composed of an adenocarcinoma, a haemangioendothe liosarcoma, and a chondrosarcoma.


[Mortality rate after lung resection for bronchial carcinoma (author's transl)]. 1351 patients with lung resection were analyzed. Lethality during hospital treatment was 6.2%. 11 patients, who died during the 6 first weeks after the resection, had occult metastases. The causes of death among these 6.2% were pulmonary embolism (40.5%), insufficiency of the bronchial stump and following complications (17.9%), pneumonia (10.7%), cardiorespiratory failure (9.5%) and intraabdominal complications (8.3%). Improving these figures should begin with reducing the cases with pulmonary embolism.


[Immunological characteristics of the 2-stage method of smallpox vaccination]. As a result of observations carried out on children the authors present immunological characteristics of two-stage smallpox vaccination at different intervals (1 to 60 days) between the injection of inactivated and live vaccine. There proved to be acceleration and intensification of antibody formation after two-stage immunization in comparison with the rutine vaccination. A seven-day interval between the injection of the inactivated and live preparations was recommended on the basis of the data obtained.


[Immunochemical study of the antigenic structure of microbes of the genus Bordetella. 5. Fractionation of the extracts of the parapertussis microbes and the study of the immunochemical and biochemical properties of the isolated fractions]. Fractions responsible for the main part of the serological and immunogenic activity differing by the set of antigens were isolated from the salt extracts of parapertussis microbes by gel-filtration on Sephadex G-100, ion exchange chromatography on DEAE-cellulose, and preparative electrophoresis in agar. Fractions, disclosing a sufficiently high serological activity and possessing the immunological properties, but containing the minimal set (2--3 out of 7) antigens, which were included in the initial extract, were isolated in the agar gel in the use of the preparative electrophoresis method.


[Characteristics of the immunologic response of animals to Clostridium perfringens anatoxin]. Experiments were conducted on guinea pigs, rabbits and mice (mongrel and inbred); immunogenic properties of Cl. perfringens toxoids of different purity were studied. Toxin neutralization and passive hemagglutination tests were used to determine the antitoxic immunity level. It appeared that in the immunization of guinea pigs and rabbits the degree of immunogenicity of the preparations increased with the elevation of their specific activity. Under the same conditions both the mongrel and the inbred mice displayed the maximum immune response in the immunization with the least purified preparations, and the minimum after the injection of a highly purified antigen.


[Glucose-6-phosphatase activity of the pia mater of several representative vertebrates]. Studies have been made on the glucose-6-phosphatase activity in the pial matter of the lamprey Lampetra fluviatilis, carp Cyprinus carpio, frog Rana temporaria, tortoises Emys orbicularis and Testudo horsfieldi, hen, rabbit and cat. The data obtained not only confirmed earlier observations on extremely high activity of the enzyme in lamprey's brain, but also demonstrated high activity of glucose-6-phosphatase in the pial matter of other vertebrates, especially in tortoises.


[Intracellular analysis of the effects of micro-application of several amino acids on lumbar motor neurons of Rana ridibunda frogs]. Intracellular recordings were made from lumbar motoneurones of the isolated spinal cord of the frog while glutamate, GABA or glycine were applied iontophoretically through the extracellular microelectrode. Glutamate had depolarizing excitatory effects and caused slight (if any) increase in membrane conductance. Responses to BABA and glycine were inhibitory regardless of the sign of membrane potential shift as revealed by conductance measurements and the dependence of anti- and orthodromically induced potentials on their application. Blocade of synaptic transmission by reducing extracellular Ca++ and increasing Mg++ concentrations did not alter the effects of application indicating the immediate activation of the postsynaptic membrane. These results are in agreement with the possible role of GABA and glycine as transmitters in inhibitory as transmitters in inhibitory synapses. The function of glutamate remains uncertain.


[Obtaining group-specific fluorescent immunoglobulin for diagnosis of adenovirus infection]. The authors present the results of a comparative study of several schemes of rabbit immunization with mixtures consisting of 4 and 7 (mixture No. 1) nad 2, 4, and 7 (mixture No. 2) adenovirus types for the purpose of obtaining group-specific fluorescent immunoglobulins. Since a direct correlative dependence of the activity of fluorescent immunoglobulins on the antibody level to the adenoviruses of homologous type was revealed in the immune sera a combined scheme of mixture No. 2 administration was elaborated for the immunization of animals.


[Effect of thymus histones on the RNAase, ATPase and phosphatase activity of staphylococcal cells]. It was shown that the representatives of different strains of Staphylococcus genus were characterized by a differential histone sensitivity. The membrane permeability increased in case of the bacterial contact with histones, and the degrading of the sum total cell RNA occurred in the contact of bacteria with histones. The RNA-ase, phosphatase, and the ATP-ase activity increased in the cells after their treatment with histones. The extent of expression of all these processes in the representatives of different strains correlated with their sensitivity to individual histone fractions. The problem that all the phenomena described indicated both the inhibitory effect of histones and some metabolic changes (permitting the cells to preserve their viability under unfavourable conditions) is discussed.


[Obtaining spheroplasts from the agents of glanders and melioidosis and separation of membrane structures from them]. Spheroplasts were obtained from the causative agents of glanders and melioidosis under the effect of lysozyme and antibiotics. In the capacity of an inducing agent lysozyme was effective in high concentration only (0.4%); preliminary washing and incubation in sucrose were necessary to obtain glanders spheroplasts. Of the antibiotics studied penicillin was more useful for obtaining melioidosis spheroplasts and ampicillin--for glanders spheroplasts. Membrane preparations were derived from the spheroplasts of glanders and melioidosis causative agents.


[Jugular and tympanic glomus tumors with intracranial growth]. The authors studied 9 patients with an intracranial growth of a glome tumour. Clinically it was characterized by tumorous symptoms of the middle ear or of the jugular fossa. These signs were accompanied by a cerebral hypertensive syndrome and by symptoms related to the influence of the tumour on the brain stem, cerebellum and III--IV cranial nerves. Radiotherapy was performed in 7 cases and combined therapy in 2 cases. Clinical remission in 2 patients following radiotherapy was seen during II and 3 years. After combined therapy 2 patients (during 9 and 1 year) did not demonstrate any clinical signs of tumour growth. Three patients died due to persistent growth. The fate of 2 patients is unknown.


[Disorders in lipoprotein metabolism indices in cerebral atherosclerosis, their importance for diagnosis and medical-occupational expertise]. Using a wide complex of biochemical indices 166 patients with cerebral atherosclerosis were examined. It was shown that in this disease regardless of the period of acute stage a deficiency of the brain circulation of physicochemical changes of the serum proteins, lipoproteins and an oppression of the process of cholesterol exterfication precede quantitative accumulation of total cholesterol in the blood, beta-lipoproteins, a decrease of the lecethin level and changes of protein fractions. Heparin treatment along with improvement of the patients' clinical state, indices of general and brain hemodynamics decreased a free cholesterol level, increased the strength of cholesterol and apoprotein relationship and phosphorolipid content in the blood. In the author's opinion one of the leading causes of lipoprotein metabolic disorders in atherosclerosis can be a change of hormonal regulation of the activity in proteins enzymes of the organs and tissues, including the enzymes regulating an oxidation-reduction process in the organism. The significance of the studied indices for diagnosis and medical labour examination is considered.


[Pathogenesis of creatinuria and aminoaciduria in neuromuscular diseases]. By introducing inhibitors of phosphodiestherase and adenylacyclase the authors studied the role of cyclic AMP in the pathogenesis of creatinuria and aminoaciduria in neuro-muscular diseases. It was demonstrated that in patients with Duchenne myopathy creatinuria and aminoaciduria were possibly due to a deop of nucleotide level in the muscles. And on the contrary in cases of Erb's and Landouzy-Dejerine myopathy the changes of nitrogen metabolism are due to an increased content of cyclic AMP. These data may be used for differential diagnosis of myopathy.


[Electron-cytochemical study of nervous tissue at different periods after death]. Using electron cytochemistry the authors studied the brain frontal cortex and hypothalamus in rats and humans in different periods following death. With the aid of 3,3'-diaminobenzidin, cytochrome C which was located inside the crystal and between the external and internal membrane of the mitochondria was detected. ATP-ase and acid phosphatase was revealed by the lead method. The activity of acid phosphotase was demonstrated in the nucleoli, along the membrane of the cytoplasmatical reticulum, in the symaptical terminals and in the circulatory capillaries. It was established that in the human brain it is possible to study the localization of the cytochrome C up to 24 hours, ATP-ase up to 15-20 hours and acid phosphatase up to 12 hours following death.


Pituitary adrenal system hormones and behaviour. Neuropeptides related to ACTH, MSH and LPH are involved in acquisition and maintenance of conditioned behaviour. These peptides affect the behaviour by a temporary selective increase in the state of arousal in limbic midbrain structures, thereby increasing the motivational influence of environmental stimuli. Steroids of adrenal origin affect conditioned behaviour in a way opposite to that of ACTH and related peptides. Such steroids alter the arousal level in limbic midbrain structures to enhance discrimination and consequently the elimination of non relevant behaviourla responses. Neuropeptides related to ACTH play a basic role in motivational, learning and memory processes, while the pituitary-adrenal system through the secretion of corticosteroids has a secondary modulationg function.


Histochemical features of C-cell thyroid carcinoma. Six cases of C-cell carcinoma of thyroid gland were studied applying histologic and histochemical methods as well as electron microscopy technique. A histologic feature of the carcinoma pattern was the diversity of pictures. Amyloid was commonly found in the carcinoma stroma. In some cells glycogen was present. Histochemically the carcinoma cells were marked by a strong activity of oxidative enzymes (GDH, SDH, LDH and MAO) as well as hydrolitic one (G-6-P and non specific enterases). Serotonin was found in two cases. An ultrastructural feature of carcinoma cells was the presence of cytoplasmic electron-dense, specific "endocrine type" secretory granules.


Antibodies against herpes simplex virus type 1 subunit antigens in patients with trigeminal neuralgia and controls. Serum IgG antibody levels against herpes simplex virus (HSV) type 1 subunit (capsid, envelope, and excreted) antigens detected with radioimmunoassay were compared in 25 patients with trigeminal neuralgia and their age- and sex-matched controls. No significant differences were found between the patients and controls, either in the distribution of the antibody titers or in the mean titers against any of the subunit antigens tested. In 6 patients HSV antibody titers were tested before and after trigeminal root section; no significant changes were observed.


Characteristic residual neuropathological features of Japanese B encephalitis. Characteristic residual (12-67 years) neuropathological features of 4 verified or suspected cases of Japanese B encephalitis (JBE) are reported. These features are summarized as: 1. unique distribution pattern of the main lesions, i.e. combination of lesions in the thalamus, substantia nigra and Ammon's horn. Lesions in the thalamus consistently involved, in a linear fashion, lamina medullaris medialis with nucleus intralaminalis and adjacent portions of the nucleus lateralis thalami. Lesions in the substantia nigra usually occupied the middle parts of zona compacta. These lesions were usually symmetrical, though unequal in extent. 2. Unique nature of the lesions, especially those in the thalamus and substantia nigra. Characteristic "light circumscribed foci (LCF)", which consisted of small rarefied areas, with few cellular and fibrous elements, surrounded by dense gliomesenchymal scarring, were observed there and occasionally in cerebral cortices. Lesions were thought to be vestiges of "circumscribed necrotic foci" reported in the CNS of acute stage of JBE. Additional characteristic features in the thalamic lesions were calcified and binucleated nerve cells. Alzheimer's neurofibrillary tangles were not found. Authors consider that the distribution and nature of the lesions are of diagnostic value.


Ultrastructure of muscle and sensory nerve in Fabry's disease. A study of a muscle biopsy has provided evidence of storage involvement of the skeletal muscle fibres in Fabry's disease. In the endothelial cells of the capillaries, the inclusions were more abundant and pleomorphic. Muscle satellite cells were spared. In the sensory nerve biopsy, the perineurial and endothelial cells contained lamillar bodies, but not the Schwann cells. There was a slight reduction of the number of the small myelinated fibres and of the unmyelinated fibres. An electron microscopic study of a muscle biopsy can be helpful in the diagnosis of the disease. The physiopathology of the pain attacks is still a matter for discussion.


Anterior horn cell degeneration and Bunina-type inclusions associated with dementia. The ultrastructural features of Bunina type inclusions in the anterior horn cells of a patient dying of amyotrophic lateral sclerosis with dementia appear unique. The Bunina-type inclusions are electron dense aggregates containing, and surrounded by organelle-like membranes. These inclusions appear to be a special type of autophagic vacuole, possibly arising from altered mitochondria.


Acid hydrolase and cytochrome oxidase activities in nitrosourea induced tumors of the nervous system. Nitrosourea induced tumors of the nervous system in rats have proven useful for biochemical studies combined with morphological approaches. The pattern of enzyme activities for acid hydrolases and cytochrome oxidase resemble those previously observed in spontaneous nervous system tumors of man. The activities of 4 acid hydrolases were generally high in the gliomas. This could not be attributed solely to zones of regression or necrosis but was a general characteristic of the neoplasms. The activities were predominantly particulate and most likely lysosomal in localization. In schwannomas a similar increase in hydrolases was found in comparison with normal neural tissues but aryl-sulfatase was not increased. Cytochrome oxidase activities were markedly reduced in all tumors studied. The proportionate reduction with respect to normal brain was comparable to that noted in man. No differences were found with respect to fairly well differentiated gliomas.


An adult case of canine neuronal ceroid-lipofuscinosis. Intraneuronal accumulation of cytosomes with the fluorescent and tinctorial properties of ceroidlipofuscin occurred in the C.N.S. of a fully matured dog with signs of slowly progressive cerebellar disease. Ultrastructural study revealed various membrane-bound inclusions in addition to typical lipofuscin granules. The clinicopathologic findings in this case were contrasted with those occurring in English Setters with juvenile neuronal ceroid-lipofuscinosis, and compared with those reported in Kufs' disease in man.


Radiation-induced nerve root degeneration and hypertrophic neuropathy in the lumbosacral spinal cord of rats: the relation with changes in aging rats. Three-month-old WAG/Rij rats were irradiated with 300 kV X-rays on the lumbar region of the spinal column with doses below the level for causing paralysis due to radiation radiculomyelopathy. 8--9 months after irradiation, degeneration of predominantly the ventral nerve roots of the cauda equina was boserved. Three stages were distinguishable: I) Demyelination and proliferation of Schwann cells; II) Local swelling of ventral nerve roots, with concentric layers of Schwann cells resembling hypertrophic neuropathy; III) Malignant Schwannoma, invading roots and spinal cord. It is concluded that the degenerative and proliferative lesions represent a continuous series of stages of slowly progressive lesions. The ventral nerve root degeneration (1st stage) is similar to that observed in aging, unirradiated rats, normally developing at the age of 18--20 months.


Dense core vesicles around the Lewy body in incidental Parkinson's disease: an electron microscopic study. In a case of Lewy body disease incidentally found at autopsy, numerous dense core vesicles 80--200 nm in diameter, were seen in the neuronal perikarya of the locus caeruleus. They were particularly numerous in the vicinity of the Lewy bodies. The change seems to occur at the early stage of Lewy body production and may represent an additional morphologic clue to abnormal catecholamine metabolism in Parkinson's disease.


Infection of cultivated CNS tissue with herpes virus, HSVII. A reappraisal. Organized cultures of newborn rat and hamster cerebellum were infected with herpes virus type II, after 7 and 14 days "in vitro". 48 h after the infection, electron microscopic examination of the cultures showed that astrocytes contained numerous intranuclear and intracytoplasmic viral particles, while neurons remained apparently intact. The specificity of the infection for a given cell type is discussed.


Carbamyl-phosphate-synthetase deficiency with neonatal onset of symptoms. The clinical course and biochemical findings in a case of carbamyl-phosphate-synthetase deficiency are described. The patient, a boy, presented 48 h after birth with rapidly developing hypotonia and hypothermia. Pulmonary haemorrhage, melaena and haematemesis ensued and despite ventilatory assistance and peritoneal dialysis the patient died on the fifth day. A virtual absence of carbamyl phosphate synthetase I (N-acetylglutamate dependent) was proved by analysis of tissue samples removed post mortem. Other urea cycle enzymes were normal.


Oculodentodigital dysplasia syndrome. Report of four cases. Four cases of oculodentodigital dysplasia are reported. Three cases are from the same family, father and two daughers. These three cases have the characteristics typical of this disorder: narrow nose, hypoplastic alae nasi, microphthalmia, defects of the teeth, syndactylyl of the IV and V fingers, and skeletal anomalies. The fourth case differs from the earlier reported cases; he has all the typical findings of oculodentodigital dysplasia but in addition he shows features not previously reported, namely exceptionally poor vision, mental retardation, monilethrix and pili annuli changes of the hair.


Primary carcinoma of the liver. A histological study of 27 cases of primary carcinoma of the liver from Malawi. Liver biopsies from 27 Bantu patients with primary carcinoma of the liver from Malawi were examined histologically. All the biopsies showed hepatocellular carcinoma (HCC). Structurally the tumours consisted of trabeculae or groups of such, separated by a variable amount of connective tissue which in a few cases was so pronounced that the tumour had a scirrhous character. Evaluation of the grade of differentiation showed 3 cases to be of grade I, 10 of grade II, 5 of grade III, and 8 of grade IV. The grade could bary in tumour tissue from the same patient, but never extremely so. The histological structure did not differ significantly from that found in other African and Caucasian series. The reticulin structure of tumour tissue was found distinctly different from that of benign tissue and thus an important tool in the differential diagnosis between HCC grade I and normal or cirrhotic liver tissue. Out of 15 patients 12 had cirrhosis which was of the postnecrotic type.


Scanning electron microscopic surface morphology of isolated hepatocytes from normal and premalignant rat liver. Scanning electron microscopy was performed on hepatocytes isolated after collagenase perfusion of livers from rats fed 2-acetylaminofluorene (AAF) in the diet for 6--8 weeks and on hepatocytes from control rats. The premalignant AAF-cells showed a greater variation in cell size and shape. They also exhibited a reduced number of microvilli and more blebs and other protrusions on the surface than hepatocytes from control animals.


Gastric carcinoma I. The reproducibility of a histogenetic classification proposed by Masson, Rember and Mulligan. The purpose of the present paper has been to examine the reproducibility of the classification of gastric carcinomas, as proposed by Mulligan and Rember. Two microscopic slides from each of one hundred randomly selected specimens of gastric carcinoma, obtained by gastrectomy or gastric resection, were classified independently by both authors. Neither of the authors knew which slides originated from the same specimen. The inter-examiner reproducibility rate was 79 per cent. The reproducibility rates of the diagnoses with two independent slides from the same tumour was 74 per cent with examiner I and 80 per cent with examiner II.


Gastric carcinoma 2. An analysis of morphological and prognostic parameters correlated to the classification proposed by Masson, Rember and Mulligan. One-hundred and fifteen gastric adenocarcinomas were classified according to Mulligan and Rember into one of the following types: Intestinal cell carcinoma (IC), pyloro-cardiac gland carcinoma (PC), mucous cell carcinoma (MC) and unclassified. The tumour type was correlated to the growth pattern and inflammatory reaction at the margin of the tumour, invasion of the veins and nerve sheaths, Dukes' stage, intra- and extracellular mucous production, and occurrence of intestinal metaplasia in the non-tumour bearing parts of the gastric mucosa. MC was the only type of tumour producing the macroscopic picture "linitis plastica". PC was the type of tumour that dominated in the cardiac region. The following parameters showed no relation to tumour type: Sex and age, size of tumour, invasion of lymphatic vessels. This study suggests that the three types of tumour are different entities, MC being the most aggressive and IC the least aggressive of the types of tumour.


Cytochemical electron microscopy on polysaccharide granules in the endogenous forms of Eimeria brunetti. The endogenous stages in the life cycle of Eimeria brunetti were tested for polysaccharide material by electron microscopical cytochemistry using the periodic acid-thiocarbohydrazide-osmium tetroxide (PATO)-method. The parasites were observed within the epithelial cells of the small intestine of infected domestic fowls. Two types of granules reacted positively for polysaccharide. The first was large, approximately 500 nm by 250 nm. These granules had an appearance similar to the polysaccharide granules reported for other coccidian parasites. They were observed in mature merozoites, macrogamonts, and developing oocysts. The second type of granule was smaller (15-30 nm in diameter) and was only observed at the periphery of the residual cytoplasmic mass of mature microgamonts. It was more similar in appearance to metazoan glycogen than the former. However, since the PATO-method does not differentiate between different polysaccharides it can not be proven if these granules in fast contain glycogen. The WFBI of the macrogamete and the outer layer of the oocyst wall gave a slight positive reaction but after examination of the controls it appeared that this was not a specific reaction for polysaccharides.


Thermostable Neisseria gonorrhoeae antigens examined by a bacterial agglutination test. Rabbit antisera against three different N. gonorrhoeae isolates agglutinated heated gonococci (100 degrees C, 2 h) before and after treatment with periodate or pronase, but this was not the case with gonococci exposed to the combined action of the reagents. All agglutinins could be removed by absorption of antiserum with untreated or heat-treated gonococci or with a heat extract of the bacteria. Antiserum absorbed with the lipopolysaccharide still agglutinated the heated gonococci both before and after exposure of the bacteria to periodate or pronase. The results of cross-absorption experiments indicated strain variation of thermostable antigenic determinants involved in the agglutination reaction.


Studies on the mechanism of flush induced by nicotinic acid. Flush is a common side effect of nicotinic acid therapy in patients. The effect is present as long as the level of nicotinic acid increases in the plasma. The mechanism of flush after nicotinic acid has been studied in the ears of guinea-pigs in vivo. The threshold dose of nicotinic acid (1-3 mg/kg) to raise the skin temperature of the ears and to increase the cyclic AMP level of this tissue was similar. Indomethacin and acetylsalicylic acid which inhibit the synthesis of prostaglandins markedly reduce the duration and intensity of the flush. In isolated slices from guinea-pig ears, nicotinic acid increased the level of cyclic AMP; this effect was inhibited by indomethacin. The stimulating action of prostaglandin E1 on the cyclic AMP level of the ear slices was not inhibited by indomethacin. Since administration to man of both cyclic AMP and prostaglandin E1 produces flush it is suggested that nicotinic acid may induce flush by the formation of some prostaglandin which then increases the formation of cyclic AMP.


Cyclic AMP and Ca-binding in microsomal fractions isolated from rabbit colon smooth muscle. From a homogenate of rabbit colon muscle two ATP dependent Ca-accumulating microsomal fractions were isolated by differential centrifugation on a sucrose density grandient at 35% and 35-45% sucrose. Adenylate cyclase and phosphodiesterase activities were found in the fractions. The Ca-accumulation and the ATPase activity of these fractions were stimulated by cyclic AMP (10(-5)M) at an ATP concentration of 0.35 mM ATP. In the presence of higher concentrations of ATP (5 mM) cyclic AMP had no effect on the Ca-binding. The higher concentration of ATP markedly increased the cyclic AMP formation in relation to the activity found at the lower concentration of ATP. Isoprenaline (2 X 10(-6)M) stimulated the Ca-accumulation in the 35-45% fraction and increased the hydrolysis of ATP. These effects were absent in the fraction isolated at 35% sucrose. In the former fraction isoprenaline also stimulated the adenylate cyclase activity at 0.35 mM but not at 5 mM ATP. Both the effect of isoprenaline on the Ca-binding and the adenylate cyclase activity were inhibited by the adrenergic beta-receptor blocking agent sotalol. In the 35-45% fraction papaverine (1 X 10(-3)M) stimulated the Ca-accumulation and inhibited the phosphodiesterase activity. It is suggested that cyclic AMP and agents which influence the cyclic AMP metabolism in the microsomes may have a regulatory role on the Ca-binding of the microsomes.


Studies on the phosphodiesterase in various organs of rats and guinea-pigs of different ages and different sex. The method of Butcher and Sutherland is used to determine the phosphodiesterase activity of various organ homogenates from rats and guinea-pigs of different age and sex. The different rat organs manifest great differences in their phosphodiesterase activity. Especially high phosphodiesterase activity is found in the adrenal gland and in the brain cortex. Sex is not found to be related to definite differences in the activity of the enzyme. In some organs age differences are established both in the phosphodiesterase activity and in the degree of its inhibition or activation by inhibitors and stimulators of the enzyme. It is assumed that in some organs age conditions changes not only in the general phosphodiesterase activity, but also in the ratio between its isoenzymes.


Effects of volleys in cortico-spinal tract fibres on ventral spino-cerebellar tract cells in the cat. Both excitation and inhibition has been found in cells of origin of the ventral spino-cerebellar tract (VSCT) to be evoked by volleys in cortico-spinal fibres. The earliest EPSPs and IPSPs had features of disynaptically evoked postsynaptic potentials; these were, however, found only in a small proportion of cells and polysynaptic EPSPs and IPSPs were dominating . Postsynaptic potentials evoked in VSCT cells from primary afferents were effectively facilitated by cortico-spinal volleys. The cortico-spinal effects on VSCT cells may thus well be mediated by the same interneurones which mediate their excitation or inhibition from the periphery and which could evoke similar postsynaptic potentials in motoneurones. Generally all the observation are in keeping with the hypothesis (Lundberg 1971) that VSCT cells monitor transmission through interneurones interposed in various reflex paths to motoneurones.


Sleep and behavioral changes possibly reflecting central receptor hypersensitivity following catecholamine synthesis inhibition in man. This paper reports a marked decrease in total hours of sleep in depressed and manic patients on days 3 and 4 following discontinuation of alpha-methyl-para-tyrosine (AMPT), a specific inhibitor of the synthesis of the neurotransmitters, norepinephrine and dopamine. Discontinuation of two precursors of biogenic amines, L-dopa and L-tryptophan, produced no changes in total sleep. It is suggested that the decrease in sleep following AMPT may result from catecholamine neuronal receptor hypersensitivity induced during AMPT treatment. Animal data consistent with this hypothesis are reviewed. The importance of studying rebound phenomena following psychoactive drugs and the practical therapeutic implications of these findings are discussed.


Search for virus specific DNA sequences and viral particles in mitochondria of avian leukemic myeloblasts. The intracellular localization of the avian myeloblastosis virus (AMV) genome was studied. Nuclear and mitochondrial DNAs from myeloblasts were examined by hybridization with 32P labeled AMV-RNA of high molecular weight for the presence of virus specific DNA sequences. Nuclear DNA (nDNA) from myeloblasts specifically hybridized with viral RNA, whereas purified closed circular mitochondrial DNA (mtDNA) did not hybridize with viral RNA. It was therefore concluded that viral genome was present in nuclear DNA and not in mitochondrial DNA. Likewise, in normal chick cells, nDNA but not mtDNA hybridized with viral RNA.


Morphological studies of Gross virus-induced lymphoblasts by scanning electron microscopy. The surface of Gross virus-induced murine lymphoblasts and C-type virus particles budding from these cells were investigated under the scanning electron microscope (SEM). The cells appeared spindle-shaped or roughly-rounded with extensive surface features consisting of microvilli, blebs and ruffled membranes. C-type virus particles were detected on the cell membrane as small spherical particles, distinguishable from the microvilli. Clustered virions were observed in some cases. However, the distribution of virions appeared to be random. The surface of the virion was smooth and had no globular units at high magnification. These morphological observations were confirmed in ultrathin sections.


Urinary cyclic AMP: relation to calcium balance and comparison of assay methods. Urinary adenosine 3',5'-monophosphate (cyclic AMP, cAMP) has been determined in 84 males. Two protein-binding assays were used: the method of Gilman and the Amersham assay kit. The results were in close agreement. The excretion of cAMP was nor correlated to urinary calcium or to estimated calcium intake.


The effect of glucagon on plasma cyclic AMP and glucose concentrations in patients with alcoholic cirrhosis. Glucagon was infused intravenously into four patients with alcoholic cirrhosis and five healthy subjects and serial measurements were made of plasma cyclic AMP and glucose concentrations. The results in the cirrhotic patients did not differ significantly from those in healthy subjects.


Effects of dexamethasone, desoxycorticosterone, and ACTH on serum concentrations of thyroxine, 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine. The effects of a pure glucocorticoid, dexamethasone, and a pure mineralocorticoid, desoxycorticosterone, on the serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (reverse T3, rT3) were compared both in healthy subjects and in athyreotic T4-substituted patients. In addition, the effect of exogenous ACTH was examined in healthy subjects. Both in healthy subjects and in T4-substituted athyreotic patients, administration of a single oral dose of dexamethasone caused a rapid and sharp decrease in the serum concentration of T3, and a corresponding increase in the serum concentration of rT3. The T4 concentration was not changed. A single oral dose of desoxycorticosterone evoked no significant changes in the serum concentrations of T3, rT3, or T4 either in healthy subjects or in T4-substituted athyreotic patients. Like dexamethasone, ACTH (two i.v. injections of 60 IU each, at a 6-hour interval) evoked a serum T3 reduction and a serum rT3 increase. Hence, it appears that both endogenous and exogenous glucocorticoids, but not mineralocorticoids, may partially divert the deiodination of T4 from the activating (T4 lead to T3) to the inactivating (T4 leads to rT3) pathway.


The empty sella syndrome analysis of 10 cases. Ten cases of the empty sella syndrome are presented. In four a pituitary adenoma had been treated by surgery with or without radiotherapy. In three women there was a close relation pregnancy, and two boys had congenital malformations. Five cases presented with appearances of pseudotomour, and the remainder had cerebrospinal fluid (CSF) fistula. Four fistulas were spontaneous, one was post-traumatic aggravated by the intrasellar implantation of YT-90. Two were occult CSF fistulas causing recurrent meningitis. Gamma cisternography and iodocisternography proved to be good diagnostic tests, both for the empty sella and for CSF fistulas. Nine cases were operated on. In four na intrasellar cyst was present. In the other five an empty sella with deficient or absent diaphragm was found. Treatment of most cases consisted of covering the floor of the sella with lyophilized dura, which was fixed in place with biological glue.


Effect of vitamin D3 and 1,25-dihydroxyvitamin D3 on intestinal transport of phosphate. Dietary variations (low calcium, low calcium, low phosphorus, or high strontium) change phosphate transport by the jejunum according to their respective ability to increase or block the synthesis of 1,25-dihydroxyvitamin D3, suggesting that the action of this active sterol underlies the response of intestinal phosphate absorption to vitamin D. 1,25-(OH)2D3 stimulates the active entry of Pi at the mucosal border by its action on protein synthesis. It is attractive to speculate that 1,25-(OH)2D3 might induce the synthesis of a "phosphate carrier" protein in the plasma membrane. The interpretation that the enhancement of the maximal velocity of the "phosphate pump" by vitamin D is due to the creation of new pump sites would be consistent with this hypothesis.


Effects of neomycin on polyphosphoinositides in inner ear tissues and monomolecular films. The effect of neomycin on polyphosphoinositides was studied in vivo and in vitro. In vivo, the incorporation of 32Pi into phosphatidylinositol phosphate and phosphatidylinositol diphosphate was measured in inner ear tissues. Concentrations of neomycin which decreased the electrophysiological response of the chochlea to sound stimulation also decreased labeling of phosphatidylinositol diphosphate. In vitro experiments with brain tissues and polyphosphoinositide extracts indicated a direct interaction between the lipids and neomycin. Neomycin interacts strongly with monomolecular films of polyphosphoinositides. The interaction appears to be complex and is a function of neomycin concentration in the subphase and surface pressure of the film. Condensation of the polyphosphoinositide film is favored at low neomycin concentrations and low film pressures while expansion of the film is favored at high neomycin concentrations and high film pressures. The interactions of neomycin with other negatively charged films (phosphatidyl inositol and phosphatidyl serine) are much weaker, particularly at low neomycin concentrations. The metabolic and physiological consequences of the neomycin/polyphosphoinositide interaction are discussed in regard to the ototoxicity of the drug.


Cell membranes in cytotoxicity.

Cell membranes in cytotoxicity. Silica particles are cytotoxic for macrophages because they damage the membranes around secondary lysosomes in which the particles are engulfed. Hydroxyl groups of silicic acid on the surface of the particles form hydrogen bonds with phosphate ester groups of phospholipids and disrupt a variety of natural and artificial membranes. Asbestos fibers induce secretion of hydrolytic enzymes from cultured macrophages. Magnesium hydroxide groups of chrysotile asbestos interact ionically with ionized sialic acid residues of membrane glycoproteins, increase passive cation flux and produce osmotic lysis. The terminal components of complement (C5b-C9) when inserted into the bilayer structure also increase passive cation flux and produce osmotic lysis. The small complement cleavage product C3a is lytic for several cell types, especially malignant cells. The mechanism by which specifically sensitized thymus-derived (T)-lymphocytes kill tumour cells is discussed. Plasma membranes from effector lymphocytes possess considerable cytolytic potential, which is dependent on the activity of a membrane-associated proteinase.


Lead actions on sodium-plus-potassium-activated adenosinetriphosphatase from electroplax, rat brain, and rat kidney. Inorganic lead ion, in micromolar concentrations, reversibly inhibits the sodium-plus-potassium-activated adenosinetriphosphatase (ATPase) and potassium-activated p-nitrophenylphosphatase (NPPase) activities of microsomal fractions from electric organ, rat kidney, and rat brain. In the presence of 3 mM MgC12 and 3 mM ATP, the concentrations of PbC12 producing half-maximal inhibition of the ATPase from these tissues are 4 X 10(-6) M, 20 X 10(-6) M, and 55 X 10(-6) M, respectively. The corresponding values for inhibition of the NPPase are 10(-6) M, 53 X  10(-6) M, and 22 X 10(-6) M. PbC12 also stimulates the phosphorylation by [gamma-32P]ATP of a microsomal protein from all three tissues in the absence of added sodium ion. This reaction was extensively studied with electroplax microsomes. In common with the well-known Na+-dependent phosphorylation of (Na+ + K+)-ATPase, the Pb2 -dependent reaction is inhibited by ouabain, specific for ATP, dependent on Mg2+, and yields and acid-stable phosphoprotein with a molecular weight of 98,000 in sodium dodecylsulfate. The Pb2+-dependent phosphoprotein, however, is not sensitive to K+. These observations are pertinent to the biochemistry and toxicity of inorganic lead in tissues and to the molecular mechanism of the cation transport enzyme.


Investigations into the cardiac effects of tolazoline in guinea pig atria and ventricular strips. The positive inotropic, chronotropic and cyclic AMP producing effects of tolazoline were studied on atrial and ventricular preparations obtained from guinea pig heart. (1) The direct positive inotropic effects of tolazoline on the paced left atrial preparation from the guinea pig hearts was blocked by promethazine, but not by burimamide. Tolazoline did not elevate cyclic AMP levels in this preparation. (2) Tolazoline produced a positive chronotropic effect which was blocked by burimamide and not by promethazine and caused a 2-3 fold elevation of cyclic AMP in spontaneously beating right atria. (3) Burimamide antagonized the inotropic and cyclic AMP increasing effects of tolazoline on electrically driven ventricular strips. (4) The effects of tolazoline were unchanged by reserpine pretreatment of the guinea pigs or by prior exposure to phentolamine or propranolol. (5) These results suggest that tolazoline can activate both H1 and H2 receptors in the guinea pig heart. Furthermore the data suggests that H2 receptors are present in right atria and ventricle and that such receptors are associated with cyclic AMP. H1 receptors are present in the left atria and are not associated with the cyclic nucleotide.


Human synovial fibroblasts: the relationships between cyclic AMP, bradykinin, and prostaglandins. Human synovial fibroblasts in culture respond to bradykinin (8 X 10(-9) M) with an increment in intracellular cyclic AMP concentration. These bradykinin (BK) concentrations are comparable to levels of the nonapeptide found in pathological synovial effusions. The cyclic AMP response to BK is enhanced by a heat stable factor(s) in fetal calf serum (FCS) and by the addition of arachidonic acid (AA) to monolayer cultures incubated in serum-free media. Synovial fibroblasts initially treated with BK are refractory to rechallenge with this agent as measured by the absence of an increment in cyclic AMP. These BK refractory cells do respond with significant increment in cyclic AMP to challenge with prostaglandin E1 (PGE1). Cells that have become refractory to PGE1 stimulation respond to BK. this suggests that a receptor or activator system different from the one for PGE1 and PGE2 exists for BK. When both BK and PGE1 are incubated together with synovial fibroblasts, the cyclic AMP response elicited is more than additive as compared to the response of each hormone separately. Indomethacin (IM) inhibits the BK evoked cyclic AMP response unless cell cultures are pretreated with PGE1. The PGE1 analog, 7-oxa-13-prostynoic acid, is a better inhibitor of the cyclic AMP response induced by BK than by PGE1. BK does not elicit a cyclic AMP response solely by elaborating PGE1, yet the prostaglandin pathway and its products seem to have a role in the degree of the cyclic AMP response to BK challenge.


Multiple symmetrical fractures of bone of unresolved etiology. The clinical, laboratory, and radiologic picture of a unique patient with symmetrical fractures of the anterior tibial midshafts, dorsal ulnar cortices, and lateral metatarsals is presented. The findings are not compatible with a diagnosis of osteogenesis imperfecta or osteomalacia despite osseous fragility. The elevated serum pyrophosphate and low urine phosphate content suggest that abnormalities in phosphate metabolism may have contributed to the formation of bone which is biochemically and structurally deficient.


"Hot spot" on hepatic scintigraphy and radionuclide venacavography. Seven patients showing a localized area of increased uptake (hot spot) on 99mTc sulfur colloid liver scans are described. Four also had dynamic studies. In five patients the hot spot was associated with superior vena caval obstruction, in one it was associated with inferior vena caval obstruction, and in one with a hepatoma. Although a hot spot on static liver images usually indicates superior vena caval obstruction, the addition of radionuclide venacavography is recommended to confirm the diagnosis. A hot spot in the liver area in a radionuclide venogram of the lower limbs suggests inferior vena caval obstruction with collaterals via the liver.


Angiographic observations on chemodectomas of the head and neck. Angiographic experience with chemodectomas in 21 patients is reviewed. Arterial supply was identified from the vertebral artery, the internal carotid artery, and branches of the external carotid artery. A striated cephalad extension from a cervical chemodectoma (five patients) is believed to represent arterial supply to tumor in vein. In two patients, internal and external carotid arteriograms did not opacify important arteries originating near the carotid bifurcation. Retrograde filling of sigmoid sinus (four patients), tumor mass in jugular vein (two patients), and arteriovenous shunting (nine patients) were observed during the venous phase. Thorough angiogra phy is essential for evaluation of chemodectomas of the head and neck.


Hand radiographic measurements in growth hormone deficiency before and after treatment. Hand radiographs in 10 male patients (eight white, two black) with isolated growth hormone deficiency were studied before and after treatment. The length of the second metacarpal was the most significantly depressed measurement when considered by chronologic age and responded most to treatment with human growth hormone. All patients had osteoporosis even when evaluated by height age. The bone mass improved with treatment by subperiosteal new bone apposition. Skeletal maturation was retarded with the carpals showing more severe retardation than the tubular bones and responding more dramatically to treatment. The depression in height age and carpal age was very similar, indicating that the carpal age may have the greatest correlation with height. The greater sensitivity of the carpal age deficiency of growth hormone and its greater response to treatment suggest that the carpal age and the phalangeal-metacarpal age should be considered independently during evaluation of skeletal maturation.


Toxicological evaluations of some brominated biphenyls. Extensive toxicological studies were carried out to define the probable hazard of octabromobiphenyl (OBB) to workers, users, and the environment. OBB had low acute toxicity in mammals and birds by various routes of administration. It was essentially non-irritating to rabbit eyes, non-irritating to human skin and caused only mild skin irritation and no sensitization in the guinea pig. OBB caused equivocal effects in the rat fetus. OBB was stored in the body fat of rats and caused liver enlargement at high single doses or low repeated doses. The studies indicate probable low safety factors in application and use and probable bioaccumulation. Hexabromobiphenyl (HBB) was more acutely toxic than OBB by skin absorption in the rabbit and caused liver enlargement at lower single doses.


Application of counterimmunoelectrophoresis in rapid detection of cytomegalovirus antibodies. Determination of cytomegalovirus antibodies by counterimmune-electrophoresis correlated well with results of complement-fixation antibody studies. The sensitivity and specificity of the counterimmunoelectrophoresis method (vs. complement fixation) was 88.9%. Fourfold antibody increases detected by complement fixation were also detected by counterimmunoelectrophoresis. In addition, no cross-reaction was observed in the counterimmunoelectrophoresis assay between other DNA viral antisera and cytomegalovirus antigen (Ad-169).


Multiple apocrine fibroadenomas of the anal skin. The authors describe an apocrine sweat gland tumor that resembles intracanalicular fibroadenoma of the breast. Three of these tumors were present in the anal skin of their patient.


Atypical fibrous histiocytoma of the humerus: a light and electron microscopic study. A unique osseous tumor, which arose in the humerus of a 44-year-old white man, is reported. The lesion was designated atypical fibrous histiocytoma because of the absence of atypical mitoses despite prominent nuclear pleomorphism of tumor cells. The tumor was composed mainly of spindle cells, tightly packed in a storiform pattern. Clear histiocytes and tumor giant cells were occasionally seen. Toward the proximal and distal ends, the tumor showed increasing fibrogenesis, and the ends were composed of areas of packed clear histiocytes and acellular myxoid matrix with focal calcification. Ultrastructurally, five cell types comprised the tumor, but fibroblast-like cells predominated. Histiocyte-like, xanthomatous, giant and undifferentiated cells were observed only occasionally. The patient has been followed for five years after disarticulation without developing evidence of distant metastasis.


Hepatoma presenting as lower gastrointestinal bleeding. A 61-year old white male, known to have alcoholic cirrhosis, presented with massive fresh bleeding per rectum. Various investigations failed to ascertain the cause of bleeding. Hepatoma of the liver was revealed by selective hepatic and superior mesenteric angiography. Massive lower gastrointestinal bleeding occurred again one month later and was rapidly followed by death from hepatic coma. An extensive hepatoma infiltrating the adjacent hepatic flexure of the colon was found at autopsy, the colonic infiltration explaining the lower gastrointestinal hemorrhage.


Effects of progesterone on some enzymes of fat and carbohydrate metabolism in rat liver. The known effect of progesterone on carbohydrate metabolism prompted a study of some of the hepatic "lipogenic" and "gluconeogenic" enzymes in rats treated with progesterone. Several enzymes providing lipid precursors (phosphofructokinase, malic enzyme, glucose-6-phosphate dehydrogenase, and citrate cleavage enzyme) showed increased specific activity. These changes may represent insulin effects. Specific activity of phosphoenolpyruvate carboxykinase, usually associated with control of gluconeogenesis, was also increased. The latter is compatible with increased capability for glycogenesis, which is recognized as a progesterone effect.


Ocular findings associated with encephalomyelitis caused by Herpesvirus simiae. A 29-year-old monkey handler developed acute encephalomyelitis with serological evidence of Herpesvirus simiae infection. He had sudden unilateral loss of vision on the 32nd day of illness caused by vitreous hemorrhage. This cleared gradually, revealing chorioretinal scarring and a gliovascular vitreous band which eventually caused local tractional retinal detachment.


Pseudotumoral aspect of posttraumatic digital synovitis. A case of posttraumatic subacute synovitis with pseudotumor of the digit with bone lesions on plain film is reported. Arteriography showed a pattern of hypervascularity  that did not appear malignant and evoked a benign tumor of the synovial. Biopsy helped establish diagnosis of common subacute synovitis. Swelling disappeared spontaneously during subsequent months. Diagnosis of villonodular synovitis is difficllt when proliferation of histiocytes is present.


In vitro activation of adenylate cyclase by parathyroid hormone and calcitonin during normal and hydrocortisone-induced cleft palate development in the golden hamster. An adenylate cyclase highly responsive to stimulation by parathyroid hormone (PTH) and calcitonin (CT) in vitro was observed at certain times during normal prenatal development of the maxillary-palatal process complex in the golden hamster. Responses of the enzyme to these hormones were barely detectible at the earliest stage examined (day 10/20). The enzyme became extremely sensitive to activation by either hormone during the time of rapid growth of the palatal processes (day 11/20) and during fusion between the palatal processes (day 12/20). Thereafter, responses were greatly diminished and little or no activation of adenylate cyclase was observed until birth. Adenylate cyclase from fetuses in which clefts of the secondary palate were induced by maternal treatment with hydrocortisone (50 mg) on day 11/3 also displayed an enhanced sensitivity to PTH and CT  on day 11/20, but the sensitivity of the enzyme was greatly decreased from that in normal animals during the normal time of palatal fusion (day 12/20) and was barely detectible or absent at the remaining time periods studied (days 13/20 and 14/20). Addition of hydrocortisone to the incubation mixture, either separately or in combination with PTH or CT, did not remarkably affect the response of adenylate cyclase to these hormones. Moreover, the appearance of the adenylate cyclase sensitive to hormonal activation did not result from changes in phosphodiesterase activity during palatal maturation.


Dishabituation of mesencephalic reticular neurons by anesthetics. To determine whether neuronal firing is affected by anesthetics, the behavior of neurons in the mesencephalic reticular formation in response to repetitive somatosensory stimulation at 2/sec was studied during wakefulness and during nitrous oxide, halothane, and thiopental anesthesia in the cat. With clinical doses of the three anesthetics there were simultaneous blockades of both initial facilitation (28 of 32) and subsequent habituation (31 of 32) of the evoked responses in a majority of the mesencephalic reticular formation neurons. This dishabituation phenomenon was most prominent with thiopental and least prominent with nitrous oxide. Thus, it is suggested that progressive inactivation of not only the facilitatory process but also the inhibitory process in the neuronal activities of the mesencephalic reticular formation is associated with the so-called "anesthetic state" produced by these three anesthetics.


[Enzymatic determination of blood ethanol with centrifugal analyser]. An automated method for ethanol determination on Gemsaec centrifugal fast analyser is described. The measurements have been done by a non linear two-point kinetic method during 10 minutes. The suitability of the proposed method has been evaluated by determination of the detection limit and the recovery. The method is applicated to whole blood and to plasma with and without initial perchloric acid deproteinization. Similar results are obtained for the different samples.


Neurologic manifestations in sarcoidosis: review of the literature, with a report of 23 cases. Nervous system involvement by sarcoidosis has been considered rare, yet more than 400 cases have been reported. We present 23 additional cases here, including 14 with autopsies, and we review the literature. The overall frequency of neurologic involvement is 5%. Patients usually have other stigmata of sarcoidosis; however, neurologic dysfunction is frequently the presenting finding. The protean manifestations of central nervous system (CNS) involvement usually occur in the early phase of the disease, while those of peripheral nervous system and skeletal muscle involvement are characteristically seen in the chronic stages. Basal granulomatous meningitis causes most of the CNS manifestations either by infiltration or compression of adjacent structures. Steroids are the mainstay of therapy, and the overall response is quite variable. The course is also variable, being transient in some and chronic in others. The prognosis is better with peripheral than with central nervous system involvement.


The effect of a topical anesthetic on the recovery of Herpes simplex virus. The effect of proparacaine hydrochloride (Ophthaine), a commonly used topical ocular anesthetic, on the recovery of types 1 and 2 herpes simplex virus (HSV) was studied in vitro and in vivo. In the in vitro studies, the titers of both virus types were significantly lower after exposing them to Ophthaine than after exposing them to a control solution. but in the recovery of virus from corneal scrapings from HSV-infected rabbit eyes, collected on the third and seventh days of clinical disease, there was no significant difference between the Ophthaine-treated eyes and the controls. We explored the possible reasons for the disparity between these in vitro and in vivo results.


[Detection of small amounts of viruses (enteroviruses) in drinking water (author's transl)]. A simple detection method of enteroviruses and adenoviruses in drinking water has been performed, using adsorption-elution on to cellulose nitrate membranes. Average of enteroviruses recovering is varying from 23 to 80% when 30 liters of water containing 60 PFU are monitored. Only 10% of adenoviruses are recovered in the same conditions. This method allowed us to detect 12 PFU of enteroviruses in 120 liters of water. Recovering of 1 PFU in 10 liters when examining more than 100 liters is reproducible.


Prolactin content of the pituitary gland in response to hypertonic saline medium, antithyroid drugs, methallibure and thyroxine in a freshwater teleost Heteropneustes fossilis. Variations in the prolactin content of the pituitary gland in response to different treatments were studied in a freshwater catfish, H. fossilis. One week of saline (1% NaCl medium) treatment reduced the pituitary prolactin content but enhanced the serum prolactin level showing release of prolactin from the pituitary gland. Two weeks of saline treatment reduced pituitary as well as serum prolactin content presumably a result of reduced prolactin synthesis in the pituitary gland. This reduction of synthetic activity in this species is probably due to a drop in prolactin requirement. All the antithyroid durgs tested as well as L-thyroxine decreased the pituitary prolactin content. Methallibure administration induced the release of prolactin from the pituitary as evidenced by the lowered prolactin level in this gland and a simultaneous increase in the prolactin content of the serum.


[Vip in human neonates and infants. As measured by radioimmunoassay and radioreceptorassay (author's transl)]. The Vasoactive Intestinal Peptide (VIP) was assayed in the gut of human neonates and premature infants immediately after death or surgery. In these conditions, values ranged between 150 and 740 ng/g of bioled tissue. The implication of VIP in Vermer-Morrison syndrome is further assessed by the correlation between clinical symptomatology and plasma VIP levels. The immunoassayable VIP (IA-VIP) extracted from normal gut or tumor is shown to fully interact with specific receptor for VIP in liver. This fact suggests the biological potency of IA-VIP.


[Islet cell tumor with diarrhea and diabetes (glucagonoma?) associated with hyperparathyroidism. Long-term results of local-regional treatment with streptozotocin]. A case report of endocrine pancreatic tumour associated with diabetes and hyperparathyroidism is presented. Some arguments are in favour of a glucagonoma. Despite the absence of beta-cells in tumour, an exceptional result was obtained by use of Streptozotocin. This case brings up the relations between endocrine pancreatic tumours and parathyroid, and may be included in polyglandular adenoma syndrome.


Subacute sensory neuropathy: a remote effect of carcinoma. Seven patients with subacute sensory neuropathy are described and the findings in 29 previously reported patients are reviewed. The presence of this characteristic neurological disorder strongly suggests an accompanying neoplasm. Five of 7 patients had cancer, and 4 died. Autopsy was performed on 3, and pathological analysis revealed inflammation and degeneration of dorsal root ganglia and degeneration of posterior roots and posterior columns of the spinal cord. The dorsal root ganglion was biopsied in 4 patients and showed similar inflammatory lesions. Electron microscopical studies showed inflammation and neuronal degeneration. No viral particles were seen. Viral cultures of the biopsied ganglia from 4 patients were negative. Antineuronal antibodies were not detected in 2 patients. The cause of this syndrome is unknown, and no treatment has been successful.


[Radio-receptor assay for thyrotropin releasing hormone (author's transl)]. The high affinity receptor for TRH of a rat pituitary GH3 strain in culture (Km: 4 X 10(-9) M) was found suitable to design a radio-receptor assay for TRH. Attached GH3 cells were incubated for 30 min at 37 degrees C in presence of a tracer amount of 3H-TRH (200 pg/ml, 0.54 nM) and increasing quantities of cold synthetic TRH. After extensive washings, the radioactivity associated with the cells was counted, and the log-logit transformation was applied to the results expressed as % binding (100%: binding in absence of unlabelled TRH). The standard curve is linear between 200 pg/ml and 5 ng/ml TRH. Hypothalamic or thyroid hormones were tested for their competitive effect with 3H-TRH towards the GH3 cells receptor. None of them interfered. TRH analogs were also assayed for their competition with TRH towards the receptor. Only compounds methylated on Prolineamide or Histidine could compete with TRH, but these derivatives have never been shown to occur in vivo. Because of this high specificity, we applied this radioreceptor assay to biological samples, once extracted by acidic methanol and purified by CMC column (following a technics designed by K Bauer, Berlin).


Polymyxin and related peptide antibiotics. The general mechanism for the antibiotic activities of the polymyxins and octapeptins has been elucidated by research using a broad range of experimental techniques. However, this phenomenon has not been described in detailed molecular terms, and this must be one of the major goals for future research in this area. Since 1947, when polymyxin was first isolated, there have been tremendous advances in our knowledge of membrane structure. The application of biophysical technology such as NMR, ESR, fluorescence spectroscopy, differential scanning calorimetry, and electron microscopy has been particularly valuable for studying model and biological membrane structures. It is these techniques which will provide a detailed molecular mechanism for the effects of these peptide antibiotics on membrane structure. In addition, the large number of antibiotic derivatives available should be exploited more extensively for structure-function correlations. The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions.


Specificity of isoniazid on growth inhibition and competition for an oxidized nicotinamide adenine dinucleotide regulatory site on the electron transport pathway in Mycobacterium phlei. The mechanism of action of isoniazid (INH) on saprophytic and atypical mycobacteria is thought to be different from that on Mycobacterium tuberculosis because higher concentrations are required to be effective in these species. In this investigation, M. phlei was inhibited by INH at a concentration of 25 mug/ml. Benzoic acid hydrazide (BZH) and nicotinic acid hydrazide (NAH) were inhibitory at levels of 300 and 500 mug/ml, respectively. Inhibition by these compounds was not inoculum dependent. An isolated M. phlei mutant resistant to 100 mug of INH per ml (Inh(r)) was inhibited by INH only at concentrations about equal to those inhibitory for BZH and NAH. When NAH and BZH were below their minimal inhibitory concentrations, INH inhibition was antagonized. Hence, there appears to be a single target site for INH in mycobacteria with different affinities for various hydrazide analogs of INH. The increased inhibitory levels required for the atypical and saprophytic species are due to a decreased affinity of the target site for INH in these species. INH also inhibited both the oxidized nicotinamide adenine dinucleotide (NAD(+)) and adenosine 5'-monophosphate stimulation of reduced NAD (NADH) oxidase activity associated with the M. phlei and M. tuberculosis H(37)R(a) electron transport particles. INH did not reverse the NAD(+) stimulation of oxidase activity in the Inh(r) strain of M. phlei. No direct inhibitory effect of INH on NADH oxidase activity was observed. Incubation of M. phlei electron transport particles at 0 degrees C with INH resulted in a dramatic loss of oxidase activity which could have been prevented if NAD(+) were present. However, INH had no effect upon the NADH oxidase when stored with electron transport particles isolated from the Inh(r) strain. Therefore, INH inhibition of regulation and/or stabilization of the electron transport pathway by NAD(+) or adenosine 5'-monophosphate may account, in part, for the lethal action of the drug on mycobacteria.


Antiviral activity of arabinosylthymine in herpesviral replication: mechanism of action in vivo and in vitro. 1-beta-d-Arabinofuranosylthymine (ara-T), a metabolite of the sponge Tethya crypta, has shown selective activity against herpes simplex virus (HSV) replication (G. A. Gentry and J. F. Aswell, Virology 65:294-296, 1975). Analysis of HSV-infected and uninfected cell lysates by CsCl isopycnic centrifugation showed that ara-T blocked the incorporation of [(3)H]hypoxanthine into viral deoxyribonucleic acid and, to a large extent, into host deoxyribonucleic acid of infected (but not uninfected) cells. Additional experiments with [gamma-(32)P]adenosine 5'-triphosphate as a radiophosphate donor demonstrated that ara-T is phosphorylated by extracts of HSV-infected BHK cells and not by those of uninfected cells. At an ara-T concentration that almost completely inhibited the growth of LM cells, which had been transformed to a pyrimidine deoxyribonucleoside kinase(+) (dPyK(+)) phenotype by ultraviolet-inactivated HSV-1, the growth of uninfected LM cells was not affected. These results indicate that the viral dPyK is responsible for the selective antiviral activity of ara-T. This conclusion was further supported by experiments that showed that the replication of a variety of dPyK(-) mutants of HSV-1 and HSV-2 were not affected by ara-T and that ara-T inhibited the phosphorylation of deoxycytidine and deoxythymidine by HSV-1 dPyK, but not by host deoxycytidine and deoxythymidine kinases, respectively. Ara-T also selectively inhibited the replication of equine herpesvirus type 1 (EHV-1) in vitro and was effective against EHV-1 infection in vivo in hamsters. Further, EHV-1 was inhibited by ara-T and by bromodeoxyuridine in LM cells lacking a cytosol thymidine kinase, suggesting that EHV-1 induces a dPyK. Finally, spectrophotometric assay for thymine suggested that ara-T is not a substrate for nucleoside phosphorylase of hamster liver, and a microbiological assay indicated that substantial amounts of ara-T were excreted in the urine of uninfected hamsters that had received a single injection of 5 mg of ara-T, the amount given in each injection in the in vivo experiments with EHV-1.


Hypothalamic hypopituitarism after pituitary apoplexy in acromegaly. Pituitary apoplexy in acromegaly is an uncommon event having been recorded approximately 30 times in the English literature. This report records two additional cases that included growth hormone measurements and an assessment of pituitary function. The apoplectic event developed spontaneously in one, and in the other it developed within two weeks of completing a course of radiotherapy to the pituitary gland. Autocure of the acromegaly was apparent. Basal levels of growth hormone were in the normal range but failed to change with provocative stimuli. Luteinizing hormone and follicle-stimulating hormone titers, although detectable, were inappropriately low for the degree of hypogonadism. Pituitary insufficiency was associated with a significant thyroid-stimulating hormone response to protirelin in one patient tested. It is suggested that these experiments of nature lend credence to the proposal that the hypothalamus may play a critical role in the perpetuation of growth hormone hypersecretion in some patients with acromegaly.


[Relationship between the limbic system and gonadal function. 2. Quantifiable prepuberal differentiation of medial cortical amygdaloid nuclei]. In juvenile female rats beteen the 21st and 26th days of age, the neurons of the medial and cortical amygdaloid nuclei undergo a highly significant karyovolumetrically measurable activation which, however, partially declines almost immediately. Such prepuberal variation of activity was found to be correlated with age-dependent effects of direct interventions with these nuclear regions upon the hypothalamy-pituitary-gonadal axis, e.g. implantation of oestradiol benzoate, stimulation or lesioning. This basically, is a quantitatibe-morphological confirmation of an assumption that had been derived earlier from experimental studies, according to which the mediocortical part of the amygdala undergoes in the prepuberal period a functional muteration or differentiation which is specific and related to puberty and gonadal functions (Döcke, 1976a, b; Döcke et al., 1976).


Follow-up of adolescents treated in a psychiatric hospital. Predictors of outcome. In the context of a long-term follow-up of 60 hospitalized adolescent psychiatric patients (26 months to four years after discharge), we examined correlates of outcome. The variables were as follows: (1) severity of psychopathology; (2) onset of symptomatology (process or reactive); (3) type of hospital treatment termination; (4) continuation of individual psychotherapy following discharge; (5) physically destructive behavior before hospitalization; and (6) energy level. Follow-up was by personal clinical interview exploring the expatient's current living conditions, peer relationships, current psychopathology and drug or alcohol use, legal difficulties, academic and work functioning, subjective contentment, and plans for the future. An evaluation was also obtained from parents and/or spouse. Statistical analyses of the interrelationships among the predictor variables and outcome demonstrated the importance of a multivariate approach.


News on psychiatric research. Two recent advisory reports. Two recent reports have rendered psychiatric research a great service in acknowledging the serious problem under which this research has been laboring and by making recommendations for improved functioning. The President's Biomedical Research Panel is the first high-level government body to take note of what it has felicitously called the "precipitous decline" in research support of the National Institute of Mental Health. Its recommendations of a greatly strengthened research advisory capability of the Alcohol, Drug Abuse, and Mental Health Administration Institutes effectively complements its recommendations for increased funding of these institutes. The Committee on Biomedical Research in the Veterans Administration, noting the "severely limited" support of research on the VA's massive problem of mental illness, proposed a series of specific recommendations for an improved and expanded research effort.


Wilms' tumor with acute abdominal pain.

Wilms' tumor with acute abdominal pain. Acute abdominal pain is the presenting manifestation in approximately 30% of all patients with Willms' tumor. In a small proportion of these patients this pain is significant enough to engender a diagnosis of an acute surgical abdomen. Six of 38 patients with Wilms' tumors treated between the years 1965 and 1975 at the Shands Teaching Hospital of the University of Florida Medical Center have had significant pain. Our experience with these patients emphasizes the importance of thoroughly palpating the abdomen of any child with a suspected acute surgical condition, following induction of anesthesia and prior to initiating the operation. In the absence of any evidence of an acute surgical problem at the time of the exploratory laparotomy, it is also imperative that a careful intra-abdominal examination be performed to exclude the presence of conditions, such as Wilms tumor of the kidney, that may occasionally present in this manner.


[Chromatin fibril. Structure and relationship to the nuclear membrane]. Literature for the recent years on chromatin fibrilla structure is reviewed in the work. Ultrastructural and molecular organization of the elementary chromatin subunits--nucleosomes, discovered in 1974 is discussed and their relation to other discrete chromatin particles is analyzed. The author represents his own data on electron microscopic studies of the cell nucleus after certain experimental effect demonstrating a complex structure of chromatin particles. The scheme of chromatin fibrilla structure is given; morphologic and functional aspects of its connection with the nuclear membrane are considered.


[Quantitative histoenzymologic characteristics of the human submandibular salivary glands]. Quantitative activity of oxidative-reductive and hydrolytic enzymes obtained during operation was investigated in different parts of the human submandibular salivary glands. Quantitative estimation of enzymic activity was done by photometry of the negatives prepared on MY-phi-6. Comparative examination of enzymatic activity made it possible to state that according to the peculiarities of metabolic processes, the cells of striated and intralobular secreting ducts are similar to the cells of the secreting terminal parts. A high activity of NADP-diaphorase, G-6-PhDG and acid phosphatase in the epithelium of the secreting ducts, and parallelism, stated between histoenzymatic and morphologic criteria of functional activity proved the participation of these structural-functional units in secret-producing processes. A high activity of NAK-diaphorase, LDG and acid phosphatase in all the parts and in the secreting ducts system, in particular, ensures, besides the processes of protein secret formation, an active transport of natrium and potassium, formation of final saliva and its discharge.


[Differential diagnosis of ulcerogenic tumors, insulomas and carcinoid tumors]. The ultrastructural intactness of secretory granules in the cells of ulcerogenic tumours, insuloma and carcinoid were demonstrated in the operation material embedded in paraffin. Feature of similarity and differences in the tumours under study with respect to the size and shape, and distribution of granules in the cells were established.


[Effect of drugs on electroclinical types of epileptic seizures in Lennox-Gastaut syndrome]. The therapeutics results with the use of different drugs (diazepam, nitrazepam, clonazepam, diphenylhydantoin, barbiturates--phenobarbital and primidone--, sodium dipropylacetate and ACTH) in twenty-nine patients with Lennox--Gastaut syndrome are carefully analysed. The effect of each drug on seizures (tonic, tonic-clonic, clonic, myoclonic or myoclonic-atonic, atonic and atypical absences) during the first month of each treatment is discussed. The "specific" use of each drug on the various forms of epileptic seizures is determined and the possibility of crisis control with reduction of the drugs dosage is verified.


Antibiotic therapy of experimental Pseudomonas keratitis in guinea pigs. Antibiotic therapy of experimental Pseudomonas keratitis was evaluated quantitatively by determining numbers of viable bacteria in the cornea of guinea pigs. Topically applied carbenicillin disodium, gentamicin sulfate, and tobramycin sulfate were often significantly more effective than topically applied polymyxin B sulfate. Intramuscular therapy with tobramycin was as effective as topical therapy, and the results exhibited less variability. Topical tobramycin every 30 minutes was significantly more effective than topical therapy every 60 minutes. No combination of antibiotics was significantly better than a single effective drug. The concentration of tobramycin in the aqueous correlated  more closely to therapeutic efficacy than did the concentration in the cornea. Although all antibiotics reduced numbers of bacteria in the cornea by more than 99% in the first 24 hours of therapy, none was able to sterilize the cornea in four additional days of continuous therapy. Persistence of organisms despite apparently adequate topical therapy may explain some reported cases of relapse in humans.


Laryngeal carcinoma associated with multiple additional primary tumors. Immunologic studies. Four malignant tumors and one benign in a 76-year-old man appeared. Three of the neoplasms were in the respiratory system, and one was a bladder carcinoma; all were linked to heavy smoking habits. The patient underwent immunologic investigations consisting of in vivo testing for cutaneous reactivity, in vitro lymphocyte blastogenesis studies, T- and B-cell level studies, and serum immunoglobulin level studies. The studies have demonstrated anergy to recall antigens, decreased lymphocyte responses to phytohemagglutinin, and low levels of peripheral T-lymphocytes. The serum immunoglobulins were at the upper limit of the normal. The relationship between the patient's immunologic status and the occurrence of multiple primary neoplasms is discussed.