Effects of dibutyryl cyclic-AMP on cardiac output and myocardial contractility in dogs. Dibutyryl cyclic-AMP was administered to a group of anesthetized dogs at the doses of 5, 10, 20 and 40 mg/kg, and changes in stroke volume, cardiac output and myocardial contractility were observed. Also, effects of this substance on contractile performance of isolated cardiac muscle were investigated in another group of dogs. Results were as follows: 1) Dibutyryl cyclic-AMP increased heart rate, stroke volume and cardiac output in a dose-related manner in the range from 5 to 40 mg/kg. 2) As indices of myocardial contractility, Vmax and maximum dF/dt were examined. These also showed a dose-dependent increase in response to dibutyryl cyclic-AMP. In isolated dog hearts, dibutyryl cyclic-AMP raised the maximum velocity of shortening (V'max) dose-dependently. 3) Total peripheral resistance declined in a dose-related way. On the other hand, mean arterial pressure and CVP dropped slightly without showing dose-dependence. These results show that dibutyryl cyclic-AMP produces positive inotropic and chronotropic effects and cause dilatation of the peripheral vessels in dose-dependent manners.


[Effects of methylcyclopentadienyl manganese tricarbonyl (MMT) on rat liver mitochondria. II. Activity-structure relation (author's transl)]. The action of various manganese organic compounds, which are structural analogs of methylcyclopentadienyl manganese tricarbonyl (MMT), was investigated. Only the cyclopentadienyl manganese tricarbonyl compounds are effective inhibitors of mitochondrial respiration, but only when associated with NAD+-linked substrates. The manganese tricarbonyl group is required for this mitochondrial respiration inhibition. The substitutions operated on the cyclopentadienyl cycle also interfere and increase the inhibitory effect. Meanwhile, the benzoyl and thenoyl groups are more effective than the methyl group. The effects of the various compounds result from their special electronic configuration.


Effects of cobalt-60 gamma-irradiation in association with prostaglandin E1 treatment on the cyclic AMP levels of some radiosensitive tissues. The amounts of cyclic AMP in brain, liver and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole-body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation in association with a preliminary intraperitoneally treatment with prostaglandin E1 (5 microgram/100 g body weight/day) during five days. The amounts of tissular cyclic AMP in these two experimental groups were compared with those obtained from control groups identically irradiated or treated with prostaglandin E1. The effects of gamma-irradiation and prostaglandin E1 treatment on the cyclic AMP levels were found to be quite specific in these organs, suggesting that they contain different adenyl cyclase-cyclic AMP-phosphodiesterase systems: a cerebral system which is influenced by both gamma-radiation and prostaglandin E1, a hepatic system which is "radioresistant" and an intestinal system which is not influenced by prostaglandin E1. When associated with gamma-radiation, this prostaglandin is capable, on the one hand, to annul the "radioresistance" of the hepatic cyclic AMP system and, on the other hand, to annul the "radiosensitivity" of the intestinal cyclic AMP system.


Progesterone interaction with estrogen and antiestrogen in the rat uterus--receptor effects. Daily injections of estradiol or the antiestrogen tamoxifen initially stimulate uterine weight increase and progesterone receptor synthesis, though continued tamoxifen fails to maintain the increased weight. The stimulatory actions of both estradiol and tamoxifen are inhibited or reversed by a single injection of progesterone. It has been hypothesized that progesterone antagonizes estrogen action by reducing estrogen receptor levels, but in the present experiments neither cytoplasmic nor nuclear estrogen receptor was affected. We conclude that progesterone acts at a point beyond estrogen receptor availability or translocation to antagonize estrogen action.


Effect of estrogens on the acitivities of cholesteryl ester synthetase and cholesteryl ester hydrolases in pigeon aorta. This study is the first to report the effect of conjugated equine estrogens on the acitivity of cholesteryl ester synthetase and cholesteryl ester hydrolases in the aorta. In spontaneously atherosclerosis-susceptible White Carneau pigeons, estrogens significantly decreased (P less 0.01) the activity of cholesteryl ester synthetase and increased (P less than 0.01) the cholesteryl ester hydrolase activity in the microsomal fraction of the aorta. There was no effect on the cholesteryl ester hydrolase activity in the supernatant fraction. The inhibition of cholesteryl ester synthesis and the stimulation of cholesteryl ester hydrolase might be responsible for the decreased content of cholesteryl esters noted in pigeon aorta after estrogen treatment.


[Antigenic rearrangement in the liver of mice and rats as a result of simultaneous effect of the carcinogens]. The antigenic structure of the livers of mice and rats after a single hepatocarcinogenic treatment was investigated using the immunodiffuse and immunofluorescent methods. The next day after carcinogen application changes characteristic of hepatocellular tumors were observed: decrease in the synthesis of organospecific antigens and intensification of the synthesis of heteroorganic antigens.


[Effect of thyroxine, insulin and cholesterol on the amount of cyclic adenosine monophosphate in normal and oncornavirus infected cells]. The intracellular concentration of cyclic AMP in normal cells and in cells infected with the Rous sarcoma virus (chicken fibroblasts) was determined by the method of saturation analysis (method of concurrent binding with protein). Thyroxine (2 mcg/ml) increased the level of cyclic AMP both in normal and infected cells, insulin (2 mcg/ml) decreased the concentration of cyclic AMP in infected cells, but cholesterol (5 mcg/ml) exerted no effect on this parameter in infected cells. The data are discussed from the point of view of a possible influence of hormones on the cholesterol accumulation in cells and on the adenylatecyclase activity in cell membranes.


[Migration of transformed fibroblast-like cells on substrates with patterned relief-work (quantitative study)]. The quantitative estimation of migration ability of transformed fibroblast-like cells of various epecies (mouse , rat, hamster, man) cultured on the substratum with grooves of various depth (5--40 mcm) was performed. Of the majority of 11 cell lines examined, a reduced migration capacity up to its total disappeanance was registered as compared with the homological normal embryonic cells. A  more pronounced reduction of migration ability was shown in mouse and rat transformed cells and less in human ones. Migration of transformed hamster cells was just equal to the weak migrtion of normal hamster embryonis cells. These data shown a weak response of the analysed transformed cells to the relief of underlying substratum.


[Spatial-temporal organization of mitochondria in nerve cells during rest and excitation]. Spatial reorganization of mitochondria in the nerve cell reflects, at the microstructural level, the control of its respiration and oxidative metabolism. During the first two minutes of excitation no changes are observed in the degree of mitochondrion aggregation, while cytochrome oxidase activity in them sharply increases. When the frequency of pulse activity stabilizes, mitochondria aggregate, cytochrome oxidase activity decreases, mainly in the aggregated mitochondria.


Antigenic proteins of nucleolar chromatin of Novikoff hepatoma ascites cells. Nucleolar chromatin of Novikoff hepatoma ascites cells contains an antigen (no-Ag1) detected with antinucleolar antibodies by the immunodiffusion technique. This antigen was distinguished from the previously reported nuclear chromatin antigen NAg-1 (19) by the findings that tumor nucleolar antibodies which formed immunoprecipitin bands with no-Ag1 did not do so with NAg-1 and that tumor cytosol, which contains NAg-1, formed immunoprecipitin bands with tumor chromatin antibodies but not with antibodies to tumor nucleoli. Tumor nucleolar chromatin contains both NAg-1 and no-Ag1, but only no-Ag1 formed bands with tumor nucleolar antibodies, no-Ag1 is a component of tumor nucleolar chromatin that was not soluble in 0.075 M NaCl-0.025 M EDTA, pH 8, and only slightly soluble in 0.01 M Tris-HCl, pH 8. NO-Ag1 was not found in liver nucleoli. Antibodies to liver nucleoli formed immunoprecipitin bands with liver nucleolar antigens but none were confluent with those formed between tumor nucleolar antibodies and antigens of tumor nucleolar chromatin. Absorption of the tumor nucleolar antibodies with whole tumor cells or whole liver pressate did not alter band formation with no-Ag1. Three antigens in liver nucleoli were not found in tumor nucleoli.


A melanotic neuroectodermal tumor of infancy arising from the anterior fontanel. A case of local recurrence of melanotic neuroectodermal tumor of infancy (MNT), arising from the anterior fontanel in a 6-month-old female, is presented. The follow-up of 48 months after surgery confirms the benign nature of this tumor despite its local recurrence. Clinical and histopathologic chracteristics of this rare tumor are discussed. A review of 12 cases of MNT involving the skull is given. It is emphasized that this entity should be kept in mind in the differential diagnosis of a mass in the craniofacial structures in infancy.


The ultrastructure of malignant fibrous histiocytoma (case report). A soft tissue malignant fibrous histiocytoma was studied by light and electron microscopy. The presence of fibroblast-like cells, histiocyte-like cells, undifferentiated stem cells, and xanthomatous cells was confirmed. Fibroblast- and histiocyte-like multinucleated giant cells were also observed. The observation of lysosomes in some fibroblast-like cells, the features of undifferentiated stem cells, and the presence of cells and intermediate characteristics common to xanthomatous, histiocytic, and stem cells suggest a strict relationship among these cellular types.


[Content of free amino acids in rabbit tissues as affected by adrenalectomy and administration of hydrocortisone and ACTH]. Adrenalectomy is accompanied by a decreased content of free amino acids in muscules and blood plasma by an increased content of certain amino acids in the liver. A single injection of hydrocortisone to adrenalectomized animals increases the content of amino acids in muscles and lowers their total content in the liver; a single injection of ACTH lowers the total content of amino acids in the liver and blood plasma "Substitutive therapy" by hydrocortisone essentially increases the content of amino acids in the liver, muscles and blood plasma. Under conditions of the experiment the least changes in the content of amino acids were found in the brain tissue.


An Italian case of nasopharyngeal carcinoma correlated with Epstein-Barr virus specific antigens. An Italian case of nasopharyngeal carcinoma was studied clinically; the immunologic study showed the correlation with the Epstein-Barr virus specific antigen.


[Effect of carbostimulin and vitamin D3 on activity of glycolytic enzymes of rabbit bones, regenerates and muscles]. Activity of glycolysis enzymes such as: phosphofructokinase, aldolase, phosphoglucomutase, was determined in the regenerate of a bone, bone fragments, native bone and, for the sake of comparison, in the animal muscles after the radius resection and feeding of carbostimulin and its mixture with vitamin D3 for 10 days. On the 12th day after the radius resection the phosphofructokinase activity in rabbits increases in the native and operated bones as compared to that in bones of nonoperative animals. In the group of rabbits which were fed on the mixture of carbostimulin and vitamin D3 the phosphofructokinase activity is 7-2 times as high. In the regenerate of these animals the activity becomes 12 times as high as that in the regenerate of the control rabbits. An analogous increase in the aldolase and phosphoglucomutase reaction rate is observed in the bones of the animals which received carbostimulin and vitamin D3 (4.5 and 7.5 times, respectively). The same tendency to the increase in the activity of these enzymes is observed in the regenerate tissue. In the muscular tissue at this stage of regeneration the activity of the studied enzymes which is usually high in norm decreases.


[Adenylate cyclase system and its interrelation with muscle function]. The article deals with the data of the recent years on localization, structural organization and function of the adenylate cyclase system enzymes. They are mainly membrane-linked enzymes responsible for perception, transformation and transmission of signals of nervous and humoral systems from the cell surface to its internal part, right up the genetic apparatus. The enzymes are characterized catalyzing formation and transformation of cAMP-adenylate cyclase, phosphodisterase and enzymes by means of which intracellular metabolism is regulated with participation of cAMP-protein kinases and phosphoproteinphosphatases. The data are systematized as to possible interrelation of the adenylate cyclatase system function with calcium ion exchange. Attention is concentrated on the system possible role in the transport of this important cation, particularly in ensuring the function of the organism contractile systems.


[Study of cytoplasmic RNA in tissues of the rat, regenerating liver and in liver of rats with hepatoma PC-1]. Cytoplasmic RNA of the rat regenerating liver and liver of rats with hepatoma PC-1 is separated into five fractions on the column of kieselgur with methylated albumin (MAK). Studies in the nucleotide composition showed that certain fractions of cytoplasm RNA are ribosomal and messenger RNA. The highest amount of radioactive precursor is incorporated into messenger RNA of the rat regenerating liver and liver of the rats with hepatoma PC-1 which is eluated from the column by 0.2% solution of sodium dodecyl sulphate at 37 degrees C (third fraction). Actinomycin D in doses inhibiting appearance of characteristic proteins in the blood serum of rats with the regenerating liver and heaptoma PC-1 blocks almost completely biosynthesis of ribosomal RNA eluated from the MAK column in the gradient of sodium chloride (second fraction), and that of messenger RNA, eluated by sodium dodecyl-sulphate at 37 degrees C (third fraction).


Pathology of adenoviral infection in turkeys (Meleagris gallopavo) with respiratory disease and colisepticemia. Nuclear inclusion bodies typical of the adenovirus group were widespread in in the spleen and other tissues of 8-week-old turkeys with severe respiratory disease and concomitant evidence of colisepticemia. Adenoviral virions were seen in affected nuclei of splenic tissue and in negatively stained preparations of ground spleen. In splenic tissue, inclusions were most prominent in reticular cells and macrophages in the periarterial lymphoid sheaths, the red pulp and the marginal zones of the periarteriolar reticular sheaths. Marked reticuloendothelial hyperplasia, lymphoid atrophy and granulocytic splenitis characterized the splenic changes. There were inclusions in the respiratory tract, intestinal tract, liver, kidney and pancreas. Inoculation of young turkeys, especially when immunosuppressed, resulted in evidence of infection and respiratory disease. The viruses produced cytopathic changes in primary turkey kidney cell cultures but did not affect embryonating chicken eggs. Concentrated viral suspensions induced precipitin lines in agar gel immunodiffusion tests with known antisera against known turkey adenoviruses but did not show an antigenic relationship to chicken adenoviruses.


Primary renal neoplasms of the dog.

Primary renal neoplasms of the dog. Of 48 canine primary renal neoplasms found in the files of the Armed Forces Institute of Pathology, 36 were of tubular cell origin (five adenomas and 31 carcinomas), six of transitional cell origin (two papillomas and four carcinomas), two were nephroblastomas and four were nonepithelial. With the exception of nephroblastomas, renal neoplasms occurred in dogs older than 5 years and were most common in males. No breed predilection was apparent. Eight of the neoplasms were classified by histologic criteria as benign and 40 as malignant. Seventeen of the malignant neoplasms had metastasized. The neoplasms of tubular cell origin contained solid, tubular and papillary patterns, often mixed within the same tumor.


[Pathomorphology of infectious bursitis in chicks]. Morphologic studies were carried out on birds aged 17 to 90 days, affected with Gumboro disease and occasionally died from the same disease (infectious bursitis). Established were hemorrhages in the leg and breast musculature, substantial enlargement of the bursa of Fabricius, and lesions in the kidneys. In some cases hemorrhages were also found on the serous membrane of the parenchymal organs. The histologic investigation of the involved parenchymal organs revealed necrobiotic changes (karyopycnosis, karyorrhexis) in the cellular elements, which were evaluated as a possible diagnostic symptom. Discussed is the problem of the dynamics of the morphologic changes observed in the bursa of Fabricius in view of their differential-diagnostic value.


[RNA-synthesizing complex of the Sendai virus in the nucleoli of infected Erlich ascitic carcinoma cells]. A virus-specific complex with sedimentation constant of 250S and buoyant density 1.35 g/cm3 in cesium chloride density gradient is formed within 20--24 hours after infection in nucleoli of Ehrlich ascitic carcinoma cells infected with Sendai virus. The complex contains a rapidly sedimenting RNA (70--90S) which is about 50% stable to RN-ase. The complex has RNA-polymerase activity in a cell-free system; the product of the RNA-polymerase reaction is a RNA with sedimentation constant 50S. It is suggested that the virus-specific structure with sedimentation constant 250 S found in nucleoli is the Sendai virus replicative complex.


[Study of Sendai virus proteins: the proteolytic activity in the composition of the viral particles]. Disruption of virions with non-ionic detergent induced cleavage of virus proteins in purified preparations of Sendai virus. The proteolytic activity was detected in fraction of both the soluble proteins and subvirus particles. In the fraction of soluble proteins which initially had contained glycoproteins of the viral external envelope--HN and F--, both proteins were cleaved at a different relative rate. In parallel with polypeptide cleavage, the hemagglutinating and neuraminidase activity of the analysed specimens decreased. In the fraction of subvirus particles, sequential cleavage of inner virion proteins, P, m1, M, and NP, was observed, and also the formation of certain classes of intermediate products which had two typical features; (1) the products retained their connection with subvirus particles, and (2) the products of hydrolysis of the major structural proteins of the internal virus ribonucleoprotein, --P and NP--, had the electrophoretic motility similar to that of minor components, m2--m5. These observations demonstrate the principal possibility of the origin of some minor Sendai virus proteins as a result of degradation of major virus proteins.


[Long-time follow-up of rare liver tumours in infancy (author's transl)]. Two rarely-observed tumours of the liver are discussed: firstly, primary liver carcinoma in a 5-month-old infant, and secondly, myxoma in a newborn infant. Both tumours were removed surgically. The child with primary liver cell carcinoma was treated for 2 1/2 years with cyclophosphamide. She has been followed-up for 8 years and can be assumed to be cured. Both children developed normally. The pathogenesis of liver tumours at this early age is discussed.


[Reproduction, morphogenesis and immunobiological properties of Aujeszky's disease virus commercially cultured in a suspension of poultry embryo explants]. The results of the study of reproduction, morphogenesis, and immunogenic properties of Aujeszky's disease virus (ADV) cultivated on an industrial scale in chick, duck and quail embryo explant suspensions are presented. A method for production of vaccine and virulent ADV strains with the activity of at least 7.5 log TCD50/ML in tanks of 5, 50, and 100 1 capacity was developed. A relationship between virion morphology and duration of cultivation was established. For ADV cultivated for 70 hours, a direct relationship between infectivity and immunogenicity was demonstrated.


[Importance of the results of a virological examination of sewage. A comparison of the series of enteroviruses isolated from sewage and from the feces of virus excreters]. Simultaneous examinations for the presence of enteroviruses were carried out on sewage of the central aeration station, periferal collectors of the most populous institutions, preschool children's institutions as well as feces of children attending these institutions in a community of urban type. A high degree of coincidence of spectra of enteroviruses isolated from sewage of the central station, periferal collectors, sewage of children's institutions, and from the feces of most virus excretors was demonstrated. No enteroviruses found in occasional virus excretors were detected in sewage. Enteroviruses were regularly found in sewage of periferal collectors if approximately 10% of children excreted a certain virus type simultaneously.


[Collagenase activity in an animal and a human carcinoma (author's transl)]. High amounts of collagenase were found in chemically-induced carcinomas of the mouse skin and in carcinomas of the human urinary bladder. Part of the total enzyme activity was detected in the supernatant after sedimentation of the tumour homogenate at 6000 x g and dialysis for 48 hours. The remainder was extracted from the pellet by the use of 5 M urea. Though the localization of enzyme production and regulation of enzyme activity is still unclear, the collagenases may be implicated in the breakdown of collagen structures during tumour invasion.


[Herpes simplex virus (hsv-1 and hsv-2) infection: its clinical and oncogenic properties (author's transl)]. The epidemiology and clinical features of diseases caused by the herpes simplex virus, are reviewed and recent results are discussed which give an insight into the complex mechanism of primary and chronic, recurrent HSV-1 infections. Immunological reactions in HSV infection and data concerning the oncogenic potential of HSV-1 and -2 are dealt with. Furthermore, current therapeutic possibilities are outlined.


[Importance of the results of a virological examination of sewage. A quantitative evaluation of the finding of enteroviruses in sewage]. In order to evaluate quantitatively the effectiveness of virological examinations of sewage, a labeled virus in a dose of 7.5X10(9) PFU was introduced into the canalization system of a community. Such an amount of virus could be found in the canalization system if 5--10% of the residents would excrete it simultaneously. The labeled virus was selectively detected in the community sewage. This procedure has demonstrated that the routine methods for sewage collection, specimen treatment, and virus isolation permit virus detection when 5--10% of this virus excretors are available. The labeled virus entered the canalization system most actively within the first 2 hours after administration, then its amount declined, and within 24 hours ceased. The labeled virus was found on all swabs which were in the sewage flow since the time of administration to the 7th day. The maximum amount of virus was found on the swab which was in the sewage flow for the first 2 hours after virus administration. By 7 days the amount of labeled virus on swabs decreased 10-fold. Under experimental conditions, in sewage kept at 25 degrees C enteroviruses of the group of poliomyelitis, ECHO, and Coxsackie had approximately similar inactivation rate (0.16--0.22 Ig TCD50 per day) and the half-life period (1.3 days), that is, in 7 days the virus titer on a swab should decline by 1.0--1.5 Ig TCD50.


[D-thyroxin in the therapy of type IIa and IIb hyperlipoproteinemias]. 21 patients with hyperlipoproteinaemias of type IIa and IIb were treated with D-thyroxin (4 mg/die) after a placebo phase. The observed changes of the cholesterol and triglyceride level in the serum are described. Hypermetabolic and cardiac side effects did not appear in the patients. The possible sites of action of D-thyroxin in the intermediary lipid metabolism are discussed.


[Methods for the rapid diagnosis of herpes simplex using the indirect hemagglutination reaction]. A method for preparation of an erythrocyte immunoglobulin herpes preparation for the indirect hemagglutination test (IHA) is described. A high specificity and sensitivity of this test and the preparation has been demonstrated. The results of the use of IHA with this preparation for the detection of herpes simplex virus in specimens from patients are presented.


[Tracer kinetic studies of the cholesterol metabolism in patients with hypercholesterolemia]. For the examination of the cholesterol metabolism in patients with normal and increased serum cholesterol the 3H-cholesterol was used. The tracer-kinetic investigation programme consisted of the examination of the serum for free and esterified cholesterol as well as the separation in VLDL-, LDL- AND HDL-fractions. The establishment of the content of radioactivity of the individual samples was carried out in the LSC-nitrobeta 1210. Specific activity-time-curves were established and fitted according to a mathematical programme. The most essential findings of the evaluation of these curves resulted in a clearly changed turnover of the LDL-fraction. Possible causes for the disturbed LDL-turnover were discussed.


Virion antigens introduced exogeneously into the cell membrane render syngeneic target cells susceptible for T cell-mediated cytolysis. Non-infectious sendai virus renders H-2 matched target cells susceptible to the lytic effect of sendai virus immune cytotoxic T lymphocytes. This observation suggests that exogeneous insertion of virion antigen in the membrane of the target cell is sufficient for T cell cytotoxicity. The finding is incompatible with the concept that H-2K or H-2D gene products of the target cells must be altered in their primary structure (pretranslational effect of the virus infection) for T cell-mediated cytolysis to occur.


Enzyme histochemistry of cultured ovarian cells. II. Histochemistry of porcine theca interna cells in tissue culture. By means of histochemical technique the activities of delta53beta-, 17beta-, 20alpha-hydroxysteroid dehydrogenases and glucose-6-phosphate dehydrogenase, as well as alkaline and acid phosphatase were investigated in monolayer cultures of theca interna cells, isolated from preovulatory porcine ovarian follicles. It was found that theca interna cells exhibited high and constant activity of delta53beta-hydroxysteroid dehydrogenase and G6P-DH, whereas activities of both 17beta- and 20alpha-hydroxysteroid dehydrogenase were lower and showed some fluctuations during in vitro culture. Addition of LH to the medium brought about the increase of all studied dehydrogenases. FSH was less effective. Estradiol showed quite and inhibiting effect. All the hormones mentioned above caused the increase of alkaline and acid phosphatase activity in cultured porcine theca interna cells.


[Size, structure, and dynamics of bile salt/lecithin mixed micelles (author's transl)]. The structure and size of lecithin/sodium glycocholate mixed micelles was investigated by quasi-elastic laser light scattering and spin label techniques. The investigations are in accordance with a bilayer model for these micelles. The order parameter and the phase transition enthalpy of the micellar bilayer were determined. The lateral and rotational diffusion constants of label molecules are compared with the corresponding diffusion constants in liposomes.


P1, P5-Bis-(5'-adenosyl)pentaphosphate: is this adenylate kinase inhibitor substrate for mitochondrial processes? 1. P1, P5-Bis-(5'-adenosyl) pentaphosphate (AP5-A) inhibits "soluble" adenylate kinase even when this enzyme is an integral part of the complete mitochondrion. The Ki is 10(-5) M, i.e. about two orders of magnitude higher than the inhibitor contants determined for the purified adenylate kinase of rabbit muscle and an enzyme preparation separated from the mitochondrial intermembrane space. The weaker inhibitory effect is due to a lower accessibility of the enzyme. 2. as to be expected Ap5A which is of the "multisubstrate analogue"-type does not affect mitochondrial nucleoside diphosphate kinase. 3. Though Ap5A owns the structural elements of both ATP and ADP it is not a substrate of the adenine nucleotide carrier, i.e. neither it is exchanged across the inner mitochondrial membrane nor speicifically bound. 4. Ap5A is not metabolized by rat liver mitochondria.


Chirality of the Hydrogen transfer to NAD catalyzed by (3R) hydroxybutyrate dehydrogenase from Pseudomonas lemoignei. The chirality of the hydrogen transfer from (3R) hydroxybutyrate to NAD catalyzed by (3R)hydroxybutyrate dehydrogenase (E.C. 1.1.1.30, D-3-hydroxybutyrate : NAD oxidoreductase) from Pseudomonas lemoignei was investigated. [4(-3)H] NAD was enzymatically reduced to (4R) [4(-3)H]NADH with (3RS) hydroxybutyrate. This observation was confirmed since NAD could be reduced to (4S) [4(-3)H] NADH with (3RS) [3(-3)H] hydroxybutyrate and (3R) hydroxybutyrate dehydrogenase. From these experiments it can be concluded that (3R) hydroxybutyrate dehydrogenase from P. lemoignei should be classified as an B or (S) type dehydrogenase.


[Serum-treatment in the rubella hi-test by menas of silicic acid (author's transl)]. The serum treatment for the removal of nonspecific inhibitors in the Rubella HI-test with silicic acid was investigated by means of isolated lipoproteins and after a micromethod by means of Sindbis-virus. Reduction of the three classes of lipoproteins after treatment with silicic acid was good. In the Sindbis HI-test only 2% of the sera showed low titers after treatment. The method proved to be a reliable tool as removal of unspecific inhibitory activity is concerned.


[Plastic reorganization of the activity of sensorimotor cortex neurons during elaboration of a cellular analog of a temporary connection]. A study of plastic reorganizations of neuronal responses in the rabbit sensorimotor cortex was made on a cellular analogue of conditioned connection where stimulation of the ventrobasal thalamic complex (VBC) was used as a conditioned stimulus, while polarization of the cell through a recording microelectrode, as an unconditioned one. The responses of 60% of the studied neurones to the stimulation of the VBC showed significant plastic changes after the pairing of thalamic stimulation with polarization. The changes obtained met the criteria of identification of conditioned reactions. One of the possible mechanisms of the recorded plastic reorganizations of neuronal reactions consists in a selective increase in the effectiveness of excitatory synapses, whose subthreshold activation coincided with the cell activation. These data may be regarded as manifestation of a hypothetic reverse influence of neuronal discharges on the effectiveness of the synaptic transmission.


[Ultrastructural study of lipopolysaccharide and of polymyxin B-induced changes of the outer membrane of Serratia marcescens (author's transl)]. Electron micrographs of lipopolysaccharide (LPS) from Serratia marcescens which have been extracted with phenol/water, suspended in dist. water and subsequently negatively stained reveale round to ovoid particles besides singular ribbon-like structures. These structures are interpreted as collapsed LPS-strands of the outer membrane (OM). Fine structure investigations were carried out on strand-like structures which had been obtained by light alcalization of the particle suspension. Partial denaturation of LPS in ethylene-diaminotetracetic acid with polymyxin B (PB) gave rise to broad bends with periodic 180 degrees-torsions, indicating a helical structure. Chemically fixed LPS in phosphate buffer which were only partial transformed into LPS-strands, additionally revealed that a given LPS-strand consists of two electron-microscopic identical sub-strands which form a double helix. After short times of exposure to PB, negatively stained cells of Serratia marcescens show strand-like cell wall components on the cell surface consisting of longitudinal fibrils. In a further stage of denaturation, the strand-like structures form "projections" of the OM or are completely loosened. Based on a helical arrangement in the negative staining preparations as well as in the thin sections, they are identified as LPS-strands. Presumably, the LPS in the OM exists as contiguous strains. The development of the "double track"-aspect of the LPS in thin sections may be explained as a result of the projections of the helical longitudinal fibrils into the image plane.


Cytomegalovirus hepatitis (diagnosis and differential diagnosis). In a 12-year-old female patients with HBAg phi hepatitis a differential diagnosis of the diseases has been considered. The CMV etiology of the hepatitis was suspected on the basis of a persistent temperature, hepatomegaly, a mild icterus, enlarged glands in the neck, predominantly mononuclear cells in the peripheral blood, a negative Paul-Bunnell test, and insufficiently characteristic biochemical analyses for virus A hepatitis. The CMV etiology of the disease was virologically confirmed. On the basis of the clinical picture without virological results, the diagnosis could not have been made with certainty.


Effect of salicylates on cyclic AMP in isolated rat gastric mucosa. Studies on the cyclic AMP content of isolated rat gastric mucosa have been conducted with sodium salicylate and lysine-acetylsalicylate singly and combined with gastric secretagogues and their antagonists. Both salicylates at a concentration of 1.66 X 10(-2) M increased the amount of cyclic AMP. The increase of gastric mucosal cyclic AMP produced by sodium salicylate was diminished by prostaglandin E1 (10(-5) M), atropine (10(-6) M) and the H2-antihistamine metiamide (2 X 10(-4) M). Theophylline 3 X 10(-3) M), histamine (10(-3) M) and pentagastrin (10(-6) M) did not enhance the cyclic-AMP-response to salicylate or lysine-acetyl-salicylate.


[Nasopharyngeal angiofibroma. Histochemical observations and hormone therapy (author's transl)]. There were carried out substrate- and enzymhistochemical reactions of the typical nasopharyngeal angiofibroma in 6 cases. In the environs of the vessels there were mainly neutral mucopolysaccharides, in the left intercellular substance and in the fibroblasts and most cells acid carbohydrates were found. The protein reactions pointed out a conspicouos strong contents of alkaline proteins in fibroblasts, mast cells and vessel environs. In the mast cells and fibroblasts tryptophan was found plentifully, in fibroblasts and vessel environs a lot of tyrosin was provable. The alakline phosphatase was traceable in fibroblasts and mast cells with great intensity. Strong reactivities of the acid phosphatases in all of the cells of the tissue refer to intensive lysosomal activities and considerable secretion transactions. The reaction of LDH as a representative of energy metabolism settles down in all of the cells and vessel environs in a strong way. The histochemical examination of a preparation of the naso-pharyngeal angiofibroma after hormone therapy showed a falling out of all the enzyme activities. The reduction of the acid phosphatases seems to be of special importance. Substrathistochemically there weren't any clear modifications concerning quality and quantity. A comparatively examined separation of an ordinary fibroma of the nasopharynx indicated similar enzymhistochemical pictures disregard the intensive reaction of the unspecific esterase, which doesn't appear concerning the nasopharyngeal angiofibroma. The carbohydrate reactions demonstrated some differences to the typical nasopharyngeal angiofibroma.


Dry weight, triglycerides content and glucose-6-phosphatase activity of hepatocytes separated by sedimentation. 1) Isolated rat-hepatocytes were subfractionated by isopycnic or velocity sedimentation, and dry mass, triglycerides content and Glucose-6-Phosphatase activity of different subpopulations were determined. 2) Distribution of the cell dry masses and dry mass per average cell were substantially similar in all the fractions separated by isopycnic sedimentation. Velocity sedimentation allowed a satisfactory separation of cells of different dry mass. 3) Triglycerides content and Glucose-6-Phosphatase activity of cells of the different fractions obtained by isopycnic sedimentation showed no statistically significant difference. Subpopulations fractionated by velocity sedimentation differed in both triglycerides content and Glucose-6-Phosphatase activity, which were substantially parallel to the cell dry mass.


Fine structural localization of glucose-6-phosphatase activity in the pancreatic islets of two amphibian species (Salamandra salamandra L. and Rana esculenta L.). The ultrastructural distribution of glucose-6-phosphatase activity has been investigated in the salamander and frog pancreas. In the pancreas of salamander the enzyme was located in the A-cells, while in frog it occurred in all main types of islet cells B-, A-, and D-cells). As a rule, the reaction intensity was higher in the frog islet cells. No reaction was recorded in the exocrine pancreatic tissue of both species. The glucose-6-phosphatase activity was constantly detected in the lumen of rough endoplasmic reticulum and between the nuclear envelopes. Other enzyme localizations, observed especially in the A-cells of the salamander pancreas, were considered possible diffusion artifacts ro remnants of other phosphatase activity. The enzyme distribution in different types of islet cells, as well as its functional significance are discussed in relation to the findings of other authors.


The potency ratio of galanthamine and neostigmine on the reversal of the tubocurarine block in the isolated rat diaphragm. The potency ratio of galanthamine and neostigmine was studied on the rat phrenic nerve-diaphragm preparation. This ratio appeared to be about 18 on a weight base. The potency ratio in man in vivo, is about 20. Hence we concluded that this potency ratio might mainly be due to the difference in potency on the neuromuscular transmission and not to kinetic differences.


Demyelination in allergic and Marek's disease virus induced neuritis. Comparative electron microscopic studies. Patterns of demyelination were studied in sciatic nerves, spinal roots and ganglia of chickens afflicted with either Marek's disease (MD) or experimental allergic neuritis (EAN). MD was induced in susceptible chicks after hatching by inoculation of the JM strain of MD Herpes virus. Tissues from these chickens were examined 7-83 days after infection. EAN was studied 10-21 days after sensitization of 4 week old chickens to emulsions containing human peripheral nerve with complete Freund's adjuvant. In both conditions lesions were encountered which consisted of perivenular infiltrates of mononuclear cells that penetrated the basal lamina of the neurolemmal sheath, displaced Schwann cells, lysed and stripped myelin lamellae without damage to axons. Other lesions in MD were characterized by lymphomatous infiltrates that contained necrotic cells and disintegrating axons. The similarity of the demyelinating process in MD to that seen in EAN suggests that MD virus infection activates lymphocytes sensitized to peripheral nerve myelin. The findings are discussed with reference to acute idiopathic polyneuritis (Guillain-Barré syndrome) in patients with preceding or concurrent Herpes virus infections including those known to cause lymphoproliferative disorders.


Seitelberger's connatal form of Pelizaeus-Merzbacher Disease. Case report, clinical, pathological and biochemical findings. A case of Seitelberger's connatal form of Pelizaeus-Merzbacher disease is reported. He lived to the age of 13 and was able to recognize persons. Both is unusual in this disease. Some of the few myelin sheaths had two different periodicities (150 and 90 A). Intranuclear inclusions similar to Hirano's cytoplasmic eosinophilic rodlets were observed. The findings of connatal form of Pelizaeus-Merzbacher disease are compared with those of dysmyelinating mice (Jimpy and Quacking) and of manipulated myelinating tissue cultures. The possibility is considered, that the alterations in these dysmyelinating human and animal conditions are caused by extraneural circulating factors.


Core/targetoid fibres and multiple cytoplasmic bodies in organophosphate neuropathy. From correlated histochemical and ultrastructural investigations of biopsy specimens of a rare case with delayed-onset neuropathy due to organophosphate (Dipterex) intoxication, several pathological characteristics were recognized in the muscle fibres. Most striking was concurrence of core/targetoids and multiple cytoplasmic bodies in the same fibres. Foci of markedly reduced or absent oxidative enzyme activity were revealed in 71.6% of type I fibres and in 3.4% of type II fibres. Most of those foci were two-zoned core/targetoids. Cytoplasmic bodies were also revealed selectively in type I fibres contrary to the previous reports. Targets, targetoids, cores and multicores were suggested to be strongly related to each other pathogenetically and to be due to the disturbance of some neurotrophic influences. In the biopsy specimen taken 220 days after exposure to the drug, numerous sarcoplasmic masses were revealed, and they were very likely to represent special forms of regeneration.


Pathology of acute ischemic myocardium. Special references to (I) evaluation of morphological methods for detection of early myocardial infarcts, and (II) lipid metabolism in infarcted myocardium. Morphological changes of early myocardial infarction within 24 hours after the onset of the acute attack were described together with a review of the literatures. For the practical purpose in detecting very early infarcts, enzymatic histochemistry is the most reliable method. Other methods previously reported such as wavy pattern of the muscle fibers and fuchsinophilia are still controvertial. Lipid metabolism in the infarcted myocardium of dogs was studied both morphologically and biochemically. Up to 3 hours, after the coronary ligation, the tissue lipids accumulated in the necrotic areas with a rise of triglyceride, but later than 6 hours the lipids decreased and were lost from the necrotic tissue, while the surrounding living cells were accumulated with neutral lipids. Serum free fatty acids were elevated in the coronary sinus blood in 6 hours after the ligation. Linolic acids were contained in high proportion in both coronary venous blood after 6 hours, and normal myocardial phospholipid. These results may lead to another possible factor in addition to catecholamine activity to elevate serum FFA in acute myocardial infarction that fatty acids may be released partly from tissue phospholipid and once ever accumulated triglyceride.


Ultrastructural study of thyroid medullary carcinoma. This study deals with 11 cases of thyroid medullary carcinoma of which 7 were familial cases including 3 cases of Sipple's syndrome and 4 cases of sporadic cases. There were also 2 cases of Cushing's syndrome. In addition to the previously described English literatures about human medullary carcinoma of the thyroid, the rod-shaped body with cristae and an abundant glycogen particles in the cytoplasm, nuclear inclusion bodies of cytoplasmic invagination and microvilli at the surface membrane of gland formation were found in our cases. The mean and mode diameters of secretory granules of all familial cases with only calcitonin secretion were larger than those of the sporadic cases with ectopic ACTH and beta-MSH in addition to calcitonin secretion. Ultrastructural study on non-cancerous follicles of grossly normal thyroid of two cases of early familial medullary carcinoma disclosed apparently increased C-cells which were not intrathyroidal metastases. It is supposed that the increased C-cells in the thyroid of the familial cases are multicentric C-cell hyperplasia.


Histological studies on the effect of ACTH and flavin adenine dinucleotide on the rat adrenal cortex atrophied by hypophysectomy. The present study describes the morphological changes in the adrenals of hypophysectomized rats injected 0.03 mg of ACTH and/or 10 mg of FAD intraperitoneally for 5 successive days starting 24 hrs after the operation. The administration of only FAD to intact or hypophysectomized rats showed no morphological change in the adrenal cortex. Simultaneous administration of FAD and ACTH to the hypophysectomized rats is more effective for preventing the atrophy induced than the administration of only ACTH. In these animals, similar morphological observations to those in the control, such as the increased nuclear volume, an increase of clear cells, diminuted numbers of lipid droplets and frequent occurrence of various types of granules, were obtained. FAD seems to be effective, through coexisting with ACTH, for preventing atrophy of the adrenals induced by hypophysectomy.


Electron microscopic studies on the effect of ACTH and flavin adenine dinucleotide on adrenocortical atrophy of hypophysectomized rat. Electron microscopic observation was made on the outer fasciculata cells in the adrenal cortex of hypophysectomized rats receiving 10 mg of FAD and/or 0.3 mg of ACTH intraperitoneally once a day for 5 consecutive days from 24 hours after hypophysectomy. The simultaneous administration of FAD and ACTH to the hypophysectomized rat was more effective for preventing adrenocortical atrophy induced than the administration of ACTH alone. This effect appeared as clear cells with low electron density. While the characteristics induced by hypophysectomy were the decrease in number of smooth-surfaced endoplasmic reticulum (SER) and mitochondria and also crista of mitochondria being tubular. The clear cells showed a less degree of their characteristic. From this fact, it is considered that the external FAD acts against fasciculata cells in the adrenal cortex of hypophysectomized rats as a coenzyme for flavin enzyme under ACTH and decreases oxidation-reaction in mitochondria and oxidative phosphorilation reaction in SER, being induced by hypophysectomy.


Differentiation of human neuroblastoma cells in vitro--morphological changes induced by dibutyrl cyclic AMP. Differentiation ability of neuroblastoma cells was studied in vitro, light and electron microscopically using three continuously cultured cell lines (NB-1, GOTO, and YT-nu) of human origin. The cells ordinarily cultured appeared to differentiate along directions of both ganglionic and paraganglionic characterized by cytoplasmic catecholamine granules measuring 150 to 250 treatment with But2cAMP in NB-1 and YT-nu cells, but GOTO cells revealed only one-directed differentiation along ganglionic cell regardless of But2cAMP conditioning. Morphological and functional differentiation of mouse and human neuroblastoma cells in vitro, conversion of rat phenochromocytoma cells into sympathetic neurons in vitro, and ultrastructural differentiation of human neuroblastoma in vivo were discussed. In conclusion, neuroblastoma might be derived from a primitive stem cell of neural crest origin which possesses the pluripotency to be capable of differentiating along the sympathetic, parasympathetic, and other neural crest derivatives under certain conditions.


Epstein-Barr virus and cytomegalovirus antibodies in infectious mononucleosis. A method has been evolved for the demonstration of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in 83 cases of infectious mononucleosis. Serum samples were tested for EBV IgM, anti-VCA IgG, anti-EBNA, CMV IgM and CMV IgG antibodies. An acute-phase sample (or samples) and a convalescence sample were examined in each case, and in 44 cases an additional samples was examined 5-12 months after the illness. Since the different antibodies showed characteristic differences in both titre and persistence, a reliable serodiagnosis has become possible. Acute EBV infection is characterized by the presence of EBV-VCA IgG and EBV IgG antibodies and the lack of anti-EBNA. The latter becomes demonstrable as late as the 4th to 5th month after infection. Mean age of the patients was 19 years. EBV infection was demonstrated in 65%, CMV infection in 18% of the cases. In 12% double infection seemed to be probable.


Cytomegalovirus-induced membrane antigens in productively infected cells. Adsorbed but not penetrated virus can be removed from the CMV-infected cell membrane by digestion with cystine-activated papain. Membrane antigens appear on 80-90% of the infected cells 14-20 hr after infection as a result of de novo protein synthesis. Antigen synthesis can be blocked with inhibitors of protein synthesis, but not with DNA inhibitors. In the early stage of infection, pooled human convalescent serum reacted well with the membrane antigen, whereas pooled antiserum of rabbits immunized with CMV virion suspension gave a positive reaction with a small proportion of the cells. After the 48th hr, both the human and the rabbit serum pool reacted with the membrane of the infected cells. Absorption with cell cultured for 24 hr after CMV infection reduced the neutralization titres of the antisera only slightly but the titre reduction was considerable when absorption was performed with cells cultured for more than 48 hr after infection. It is concluded that on the membrane of cells productively infected by CMV at least two membrane antigens are present, one coded for by the DNA of the parent virus and another which is the product of the DNA of the virus progeny. The two antigens can be differentiated serologically.


L-dopa-induced hypotension: depression of spinal sympathetic neurons by release of 5-hydroxytryptamine. In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these affects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory.


Bradykinin action in the rat duodenum through the cyclic AMP system. Activators of the adenylate cyclase or inhibitors of the cAMP-phosphodiesterase, respectively, potentiate the bradykinin-induced relaxation of the rat duodenum, whereas imidazole as a stimulator of the cAMP-phosphodiesterase reduces the relaxation. The experiments indicate a linkage between the adenylate cyclase system with the biological action of bradykinin on the rat duodenum. In contrast, no similar effect has been observed on the rat uterus.


Familial hypo-beta-lipoproteinemia: a family detected by cord blood tests. A family with low-density lipoprotein (LDL) deficiency was detected during the course of screening cord blood samples. The initial diagnosis in the proband was based on the cord blood LDL cholesterol and lipoprotein electrophoretic pattern, and was confirmed by repeated studies at the age of 8 months. The infant had none of the clinical abnormalities previously ascribed to the condition. Further investigation did not disclose any other significant biochemical or histological abnormalities. Hypo-beta-lipoproteinemia was found to exist in the proband's mother and only sibling. Hence the diagnosis of familial hypo-beta-lipoproteinemia is possible by unselected cord blood LDL cholesterol measurement and lipoprotein electrophoresis in conjunction with kindred studies.


Viral hepatitis: enzyme assays and serologic procedures in the study of an epidemic. An epidemic of viral hepatitis beginning in late 1975 in a residence for multiply handicapped children, recognized very early in its course, was investigated prospectively to permit comparison of enzymatic and serologic tests. Thirty-three residents of the institution and 46 full- and part-time employees were studied by the immune adherence hemagglutination procedure for antibody (anti-HAV) to hepatitis A virus (HAV). Of these, 31 residents and 37 staff members were susceptible at the beginning of the epidemic. Nineteen and six, respectively, had anti-HAV seroconversion indicating HAV infection. Thus, 12 children (39%) and 31 staff members (81%) of presumed susceptibles did not have serologic evidence of infection. The subclinical/clinical ratio for the children was 1.1:1; for personnel, it was 1:1. Serum alanine aminotransferase (ALT) levels compatible with viral hepatitis occurred in 21 persons (84%) who had anti-HAV seroconversion; conversely, there were 10 persons who had ALT abnormality without detectable anti-HAV in late specimens among the total of 68 susceptibles. There was no evidence the latter could be attributed to hepatitis B virus infection; therefore, they may represent the endemic occurrence of non-A, non-B agent(s).


Corticosteroid-responsive skeletal muscle disease associated with partial carnitine deficiency: studies of liver and metabolic alterations. A patient with progressive skeletal muscle weakness had lipid-containing vacuoles in type I muscle fibers and partial carnitine deficiency of skeletal muscle. Results of certain liver function tests were abnormal, marked morphologic abnormalities of liver were detected, and a reduced cyclic adenosine 3',5'-monophosphate response to glucagon was present. After the oral administration of prednisone the patient exhibited gradual but striking clinical improvement, skeletal muscle fiber vacuoles could no longer be demonstrated, and the glucagon-provoked cyclic AMP response reverted to normal, but liver abnormalities persisted. At the same time utilization by skeletal muscle of long-chain fatty acids, pyruvate and beta-hydroxybutyrate was depressed. It is possible that the involvement of skeletal muscles was due to an inability of carnitine to attach to or to penetrate the sarcolemmal membrane. Some of the derangement, perhaps related to liver malfunction, was apparently corrected by the oral administration of prednisone although skeletal muscle metabolism remained impaired.


Growth characteristics of populations of Tibetan origin in Nepal. Previous growth studies of highland-dwelling populations in the ecologically diverse areas of Peru and Ethiopia have yielded highly varied results: the retarded growth of the Peruvian sample was attributed to the effects of hypoxia, while the increased height and weight of the highland Ethiopian sample could be traced to better health conditions in the highland village than in the lowland village studied. In an attempt to provide a basis for evaluating studies of growth at high altitude, the present study compared Sherpa children living in the Everest region of Nepal with Tibetan children living in Kathmandu. It was found that: (1) the growth of Sherpa and Tibetan children is considerably retarded compared to other high altitude populations; (2) despite conditions favorable for optimum growth among the Tibetans, their growth resembled that of the Sherpas and (3) increased chest circumference, which seems to reflect a developmental acclimatization to hypoxia among Peruvian high-altitude natives, was not seen among the Sherpas.


The application of EEG sleep for the differential diagnosis of affective disorders. On the basis of two EEG sleep criteria, REM latency and REM activity, the authors achieved 81% accuracy in distinguishing between 47 patients with primary depression and 48 patients with secondary depression using discriminant analysis. Sleep efficiency, the percentage of delta sleep, and the percentage of REM sleep discriminated between psychotic and nonpsychotic subgroups in the group with primary depression with 75% accuracy. REM activity and intermittent nocturnal awakening accurately discriminated two subtypes of patients with secondary depression at a level of 81%. These results suggest  that EEG sleep measurements can yield significant data to aid in differential diagnosis in psychiatry.


Comparison of intestinal (Illinois strain) and cell culture-adapted (M-HP strain) viral populations of transmissible gastroenteritis of swine. Intestinal and cell culture-adapted viral populations of transmissible gastroenteritis (TGE) of swine were compared by means of sucrose gradient centrifugation, immunnofluorescence, electron microscopy, immune electron microscopy, statistical analysis of the number of plaque-forming units, and ultraviolet sensitivity. Results indicated that the size range and general coronavirus morphologic characteristics were shared by both viral populations. Marked morphologic variations existed among particles from both populations. Unlike the cell culture-adapted virus, the Illinois virus of intestinal origin was infractions representing 2 bands of infectivity which were isolated by the sucrose gradient centrifugation method. The intestinal and cell culture-adapted TGE viruses were similar in antigenicity and in sensitivity to ultraviolet irradiation. There was no indication of a 2nd virus in addition to the coronavirus described as the cause of TGE.


Clinical and immunologic responses of cattle to infectious bovine rhinotracheitis virus after infection by viral aerosol or intramuscular inoculation. Aerosol or intramuscular exposure to infectious bovine rhinotracheitis virus elicited generally comparable levels of serum antibody in cattle, but not measurable nasal secretion antibody. Aerosol-exposed cattle developed signs of mild clinical disease, fever, and leukopenia and shed virus from their nasal passages. Cattle exposed by intra-muscular inoculation developed a brief febrile response and leukopenia but did not shed virus. After an aerosol challenge exposure, cattle in each group developed detectable nasal secretion antibodies, but no clinical signs of disease.


Vaccination of cattle and sheep with a combined Clostridium perfringens types C and D toxoid. Cattle and sheep (30 each) were vaccinated with a combined Clostridium perfringens type C and C perfringens type D toxoid. Vaccination and blood sample collections were made every 2 weeks over a period of 8 weeks. Increases in antitoxin titers occurred after the 2nd administration of the 2.0-ml combined product. Highest titers were recorded when the 2nd vaccinal dose was given 2 weeks after the first. This confirms reports that response to clostridial antigens is greater when the 2nd immunizing dose is delayed 2 to 6 weeks after the initial dose.


Platelet affinity for burro aorta collagen. Despite ingenious concepts, there are no unequivocal clues as to what, when, and how some undefined biochemical factor(s) or constituent(s) that localizes in the arterial wall can precipitate a thromboatheromatous lesion or arterial disease. The present study focused on the extraction, partial purification, and characterization of a collagen-active platelet stimulator from the aortas of aged burros. The aggregator moiety in the aorta extracts invariably had a higher affinity for platelets in citrated platelet-rich plasma of human beings than for platelets of homologous burros. The platelet-aggregating factor(s) in the aorta extract was retained by incubation with alpha-chymotrypsin. Platelet-aggregating activity was rapidldy abolished after incubation with collagenase, as determined by plateletaggregometry tests. Evidence based on light microscope and polysaccharide histochemical reactions indicates a probability that the intracellular amorphous matrix (PAS-positive) and filamentous components (PTAH-positive) expelled from smooth muscle cells disrupted during homogenization of the aorta may be a principle source of a precursor collagen species which is a potent inducer of platelet aggregation.


Detection of inapparent Aleutian disease virus infection in mink. The normal serum gamma-globulin centration of mink from the Ontario Veterinary College field station was 13.2 +/- 2.6% of total serum proteins. Mink serum gamma-globulin concentrations above 21%, which represented 3 standard deviations above the normal mean, were considered to be hypergammaglobulinemic. About 39% of pastel mink infected naturally with Aleutin disease virus (ADV) exhibited an inapparent or nonprogressive infection. These nonprogressivley infected mink had serum gamma-globulin values below 21% andhad antibody titers less than 256 if tested by the couterimmunoelectrophoresis technique. Mink maintained inapparent infection for at least 10 months after infection with ADV. Neither gross nor histopathologic changes were present in the mink with inapparent ADV infection. The virus persisted in blood, mesenteric lymph nodes, kidney, liver, and spleen of mink with non-progressive infection, although the amount of virus present probably was small.


Characterization of herpesviruses isolated from lactating dairy cows with mammary pustular dermatitis. Herpesviruses serologically indistinguishable from the DN599 strain of bovine herpesvirus were isolated from 2 separate enzootics of mammary pustular dermatitis in lactating Holstein-Friesian cows.


Plasma adrenocorticotropin levels in normal dogs. Plasma concentrations of adrenocorticotropin (ACTH; corticotropin) were measured in 31 normal dogs (house pets) at rest. The mean concentration was 45.77 pg/ml of blood, with individual values ranging from 17 to 98 pg/ml of blood. The measurement of this hormone secreted by the anterior lobe of the pituitary gland (adenohypophysis) may aid in the diagnosis of spontaneous canine adrenal cortical disorders, both primary and secondary.


Bluetongue in cattle: effects of vector-transmitted bluetongue virus on calves previously infected in utero. Three of 7 principal calves, after a challenge of immunity exposure by bites of bluetongue (BT) virus-infected Culicoides variipennis, became latently infected with BT virus. These calves were born to heifers infected with the homologous virus by bites of C variipennis at 60 or 120 days' gestation. Latent BT virus infection was detected by isolation of BT virus from washed erythrocyte samples obtained from the calves at 57, 100 to 102, 200 to 202, 300 to 302, and 400 to 402 days after challenge of immunity and from 1 of the calves over 5 years after challenge of immunity. The 3 latently infected calves were healthy; 2 were immunologically competent and 1 was immunologically incompetent to develop detectable BT virus antibodies in their blood. Bluetongue virus infection was detected (by viral isolation) in 2 other principal calves during the challenge of immunity, but they were not considered latently infected. The latter 2 calves were immunologically incompetent to develop detectable BT virus antibodies.


Bluetongue in cattle: repeated exposure of two immunologically tolerant calves to bluetongue virus by vector bites. A heifer and steer that were immunologically tolerant to bluetongue (BT) virus became immunologically competent after repeated exposures by bites of BT virus-infected Culicoides variipennis. Immunologic tolerance ended in the heifer at 25 months of age, after the 2nd exposure to the virus, and in the steer at 22 months, after the 4th exposure. High hemic concentrations of BT virus were detected in both animals after they became immunologically competent, but neither developed an overt BT clinical response. The steer died suddenly and extensive pathologic changes were observed at necropsy.


Susceptibility of bovine macrophage and tracheal-ring cultures to bovine viruses. Cultures of macrophages initiated from peripheral blood monocytes and organ cultures of tracheal rings were tested for their susceptibility to bovine viruses. With several notable exceptions, viruses cytopathogenic for bovine embryonic lung cultures were cytopathogenic for macrophages. Although cowpox virus replicated in macrophages, pseudocowpox did not, and although pseudorabies virus replicated within macrophages, infectious bovine rhinotracheitis and DN-599 herpesviruses did not. Bluetongue virus established an interesting relationship with macrophages. Whereas bluetongue virus was initially cytopathogenic for macrophages, it lost its cytopathogenicity on repeated passage, although it was capable of continued replication in macrophages. When subsequently passaged onto bovine embryonic lung cultures, it regained its cytopathogenicity. Parainfluenza-3, bovine viral diarrhea, and infectious bovine rhinotracheitis viruses readily destroyed ciliary activity in tracheal-ring cultures, as contrasted with the inability of bovine respiratory syncytial virus to destroy ciliary activity, even though bovine respiratory syncytial virus was able to replicate within ciliated epithelial cells of tracheal rings.


Investigation of causative agents of bovine respiratory tract disease in a beef cow-calf herd with an early weaning program. Serum samples were collected from early weaned fall calves shortly after the onset of respiratory tract disease. Antibody titers to infectious bovine rhinotracheitis (IBR) virus, parainfluenza type 3 (PI-3) virus, bovine viral diarrhea (BVD) virus, bovine adenovirus type 3 (BAV-3), and bovine respiratory syncytial virus (BRSV) were determined on paired (acute and convalescent) serums. Seroconversion rate (a fourfold or greater rise in antibody titer) for IBR virus was 4.3%, PI-3 virus--16.3%, BVD virus--9.6%, and BAV-3--2.2%. Seroconversion for BRSV was 45.4%. An increased rate of seroconversion for IBR, PI-3, and BVD viruses and BAV-3 was observed in the presence of BRSV seroconversion. These results suggest that BRSV may facilitate infection by other viruses. Results of virus isolation procedures from these calves were negative.


Occurrence of cross reactions to foot-and-mouth disease virus in normal swine sera. Sera from 101 swine never exposed to foot-and-mouth disease virus were tested by the plaque-reduction neutralization (PRN) and radial immunodiffusion techniques for cross-reactions to 5 types of foot-and-mouth disease viruses. Depending on the group of sera and the virus used, the percentage of sera cross-reacting at low levels varied from 0 to 50% with the PRN technique and 0 to 20% with the radial immunodiffusion technique. 5erum-neutralization tests in mice support the finding of neutralizing antibody by the PRN technique. Ultracentrifugation and 2-mercaptoethanol studies indicate that the cross-reactions are the result of immunoglobulin M or similar macroglobulins.


Cell culture propagation of porcine rotavirus (reovirus-like agent). Two isolates of porcine rotavirus (reovirus-like agent) were isolated and passaged in primary procine kidney cell cultures. Viral infectivity for cells was monitored by immunofluorescence because viral cytopathic effect was moderate. Successful passage of virus in cell culture required that viral suspensions obtained from infected cell cultures be treated with pancreatin prior to inoculation onto cell monolayers. Porcine rotavirus passage in cell culture also was accomplished, using trypsin treatments in lieu of pancreatin treatments. Porcine rotavirus passaged 10 times in cell culture infected gnotobiotic pigs and caused diarrhea. Gnotobiotic pigs that recovered from this infection were resistant to challenge exposure with porcine rotavirus but were susceptible to challenge exposure with transmissible gastroenteritis virus. As determined by immunofluorescent cross reactions, porcine rotavirus was found to be antigenically related to the human and bovine rotaviruses but not to reovirus type 3 or to transmissible gastroenteritis virus.


Adenosine 3',5'-monophosphate in plasma, urine, and native and isoproterenol-stimulated leukocytes of dogs. Adenosine 3',5'-monophosphate (cAMP) was determined by means of a commercial kit in urine and plasma from 40 hospitalized dogs and in native and isoproternol-stimulated leukocytes from 30 of these animals. Mean urine and plasma concentrations were 6.1 micron and 14 nM, with 95% tolerance limits ("normal values") ranging from 0.0 to 12 micron and 0.21 to 27 nM, respectively. The plasma concentration was approximately half the value previously reported for experimental dogs. The median cAMP content in native leukocytes was 5.9 pmol/10(7) cells. The mean response to isoproterenol was 0.85 pmol/10(7) cells, much less than in human leukocytes. The response was statistically significant (P less than 0.01), but was so small that it is unlikely to be measurably affected in atopic dogs.


Bovine leukemia virus-associated antigens in lymphocyte cultures. Short-term lymphocyte cultures from bovine leukemia virus (BLV)-infected cattle were tested for BLV-associated antigens at various times after incubation. Several immunologic methods were used, including fluorescent antibody tests, immunodiffusion, and radial immunodiffusion. Antigens were not detected in uncultured lymphocytes. The BLV-associated antigens were detected as early as 3 hours, with maximum antigen production occurring at 18 to 24 hours after incubation. These results indicate that culturing of lymphocytes in vitro is necessary for the expression of the virus.


Effect of estrogens and calcium carbonate on bone loss in postmenopausal women. Sixty postmenopausal women were placed in three groups--control, sex hormone-treated, and CaCO3-treated--and followed for 2 years. Skeletal mass decreased by 1.18%/year in the control group, 0.15%/year in the hormone group, and 0.22%/year in the CaCO3 group by radiogrammetry; and 2.88%/year in the control group, 0.73%/year in the hormone group, and 1.83%/year in the CaCO3 group by photon absorptiometry. The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group. Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics, resorption more so than accretion. We conclude that [1] these techniques are sufficiently sensitive to detect age-related bone loss; [2] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover, resorption more than accretion; and [3] calcium supplements produce the same effect but at the dose we used were slightly less effective.


Swine influenza and the news media.

Swine influenza and the news media. Press coverage of the swine influenza inoculation campaign was generally superficial and marked by a "body count" mentality, but it was rarely inaccurate or sensationa, as has frequently been assumed. A study of coverage in 19 daily newspapers, the three television networks, and a wire service shows that the best work was done by science and medical writers on major metropolitan newspaper. Television newsmen and wire reporters were unprepared for a story of such complexity. A weak press relations effort by the Center for Disease Control and other public health agencies contributed to the public's confusion and upset professionals in the press. A better understanding by doctors of how the press works and closer relations between the medical community and the press can improve coverage of future public health programs.


Blood chemistry and lipid profiles of elite distance runners. In summary, we conclude that the analysis of the blood profiles of elite runners offers no explanation for their superior fitness of physical ability when compared to the good runners. Selected enzymes related to cellular or tissue damage may be elevated in distance runners and could be classified as abnormal on routine clinical evaluation if unaware of their physical lifestyles. It is also important to note that certain blood profile parameters, especially the hematocrit, could be classified as abnormally low. Finally, the high degree of daily physical activity performed by the elite runners and good runners appears to be associated with a lipoprotein profile consistent with a low risk for development of coronary artery disease manifestations. These profiles persist despite increasing age in active running males.


Plasma lipoprotein distributions in male and female runners. Recent studies have shown a consistent association between relatively low plasma concentrations of high-density lipoprotein (HDL) cholesterol and increased risk of coronary heart disease. A cross-sectional comparison was made of the distribution of plasma lipids and lipoproteins in groups of 41 male and 43 female long distance runners versus larger control groups matched for age and sex, randomly selected from northern California towns. The runners showed modestly lower total cholesterol concentrations, while their triglyceride levels were only 50% of control. HDL-cholesterol was higher in runners than controls (75 +/- 14 vs 56 +/- 14 mg/100 ml for women; 64 +/- 13 vs 43 +/- 10 for men), while low-density lipoprotein cholesterol was lower (113 +/- 33 vs 124 +/- 34 for women; 125 +/- 21 vs 139 +/- 32 for men). All differences were statistically significant (p less than 0.05), and only partially attributable to known factors other than high physical activity level. Since the runners were predominantly normotensive, relatively lean, and exclusively nonsmokers, they appear to constitute a remarkably favored group with respect to risk of cardiovascular disease.


[The value of therapeutic arteriography in the treatment of tympano-jugular glomus tumours (author's transl)]. In this article, the authors stress three fundamental points in the diagnostic and therapeutic angiographic study of tympano-jugular glomus tumours. The first basic concept is the need for complete right, left, internal carotid, vertebral and external carotid angiographic examination. The latter must be selective, regardless of the information provided by common carotid arteriography. This implies prior knowledge of the different arteries which may "supply" the gloumus tumour. The second basic point is the concept of vascular compartment, , often mutually independent and vascularised by a single pedicle. The juxtaposition of the different vascular compartments gives the exact size of the tumour. The third important point concerns embolisation carried out at the same time as diagnostic angiography. This is invariably indicated on a pre-operative basis, except in two circumstances: --when the glomus, tumour is small and situated close to the drum of the tympanum, its surgical excision posing no problem of haemostasis under these circumstances: --when radiotherapy is envisaged as treatment of the glomus tumour when surgery is impossible. In this case, embolisation is contraindicated for two reasons: -radiotherapy is more effective when blood flow is preserved; -the risks of necrosis are increased.


Skeletal maturation of Hong Kong Chinese children in the first five years of life. This report describes the skeletal maturity during the first five years of life of 492 Chinese children in Hong Kong in a longitudinal study. Hand-wrist radiographs taken half-yearly were assessed by the Tanner-Whitehouse method and rated according to the TW1 20-bone self-weighting maturity score. Skeletal age was in advance of chronological age in both sexes, but significantly more so in females, especially between 18 months and three years. The relationship of the skeletal maturation of these children to various socioeconomic factors is discussed, including the effect of preferential child rearing in favour of males.


Skeletal maturity of the hand and wrist in Japanese children by the TW2 method. The skeletal maturity of Japanese children aged 0--18 years in Tokyo was compared with that of British children by the TW2 method. The skeletal age was the same as or less than the chronological age until 8 years. Thereafter, it was in advance of chronological age until 18 years in boys and 15 years in girls. The hand and wrist bones completed maturation about the same time in both Japanese and British children, at the age of 18 years in boys and 16 years in girls.


Polymyxin B and rifampin: new regimen for multiresistant Serratia marcescens infections. Polymyxin B and rifampin were given to 12 patients with multi-drug-resistant nosocomial Serratia marcescens infections. Eight cures were achieved; drug hepatotoxicity occurred once; one fatal suprainfection was encountered; and two patients died during therapy of causes related to severe underlying illnesses. Polymyxin B and rifampin were uniformly synergistic in vitro against the infecting strains and against 40 additional clinical isolates of S. marcescens.


Inactivation of enteric viruses in wastewater sludge through dewatering by evaporation. The effect of dewatering on the inactivation rates of enteric viruses in sludge was determined. For this study, water was evaporated from seeded raw sludge at 21 degrees C, and the loss of viral plaque-forming units was measured. Initial results with poliovirus showed that recoverable infectivity gradually decreased with the loss of water until the solids content reached about 65%. When the solids content was increased from 65 to 83%, a further, more dramatic decrease in virus titer of greater than three orders of magnitude was observed. This loss of infectivity was due to irreversible inactivation of poliovirus because viral particles were found to have released their RNA molecules which were extensively degraded. Viral inactivation in these experiments may have been at least partially caused by the evaporation process itself because similar effects on poliovirus particles were observed in distilled water after only partial loss of water by evaporation. Coxsackievirus and reovirus were also found to be inactivated in sludge under comparable conditions, which suggests that dewatering by evaporation may be a feasible method of inactivating all enteric viruses in sludge.


Agar plate screening procedure for cyclic adenosine 3',5'-monophosphate and inhibitors of cyclic nucleotide phosphodiesterase. A procedure is described for the semiquantitative measurement of cyclic adenosine 3',5'-monophosphate (cAMP) and detection of inhibitors of cAMP phosphodiesterase by an agar plate test. The assay organism was an adenyl cyclase-deficient mutant derived from Escherichia coli HfrH. In the presence of an acid base indicator, acid production from barbohydrate metabolism was observed as a yellow zone around filter paper disks containing cAMP. Since yellow zone formation reflects the presence of cAMP, a phosphodiesterase inhibitor can be detected indirectly by the presence of a yellow zone on assay plates from a reaction mixture of an inhibitor, phosphodiesterase, and cAMP. Three known cyclic nucleotide phosphodiesterase inhibitors were active against beef brain phosphodiesterase in this system.


Fatal cytomegalic inclusion disease. Associated skin manifestations in a renal transplant patient. A case of cytomegalovirus-induced vasculitis led to skin ulcerations in a renal transplant patient. Light and electron microscopy revealed inclusion bodies and viral particles, respectively, characteristic of cytomegalovirus. To our knowledge, this is the first report of cytomegalovirus-induced vasculitis producing skin ulcerations, and it illustrates another of the protean manifestations of cytomegalovirus inclusion disease that may have important clinical implications.


DNA-binding proteins of psoriatic scales. I. Isolation by affinity chromatography and characterisation by SDS slab gel electrophoresis. DNA binding proteins (DBP) are shown to be engaged in the regulatory functions of the genome. Since the accelerated epidermopoesis in psoriasis indicates changed gene activities, the examination of DBP possible could help to clarify the pathological processes. Psoriatic scales were used to elaborate the method. DBP was isolated from a protein extract by affinity chromatography with DNA-cellulose according to Alberts et al. About 3-5% of postribosomal crude protein (PCP) extract had an affinity to DNA. The separation of DBP on SDS polyacrylamide slab gels showed a characteristic spectrum of proteins with molecular weights from 12.7 to 150 X 10(3) daltons. The protein band spectrum of the concentrated DBP fraction was different from that of the crude extract. These observations show the isolated DBP to represent an own group of water soluble proteins with DNA binding abilities.


DNA-binding proteins of psoriatic scales. II. DNA-Affinity of the three characteristic proteins increased in the water soluble extract of psoriatic scales. The disc-electrophoretic pattern of a water soluble protein extract of psoriatic scales contains three characteristic proteins. They appear in higher amounts in psoriatic scales compared to normal human stratum corneum. Assuming that these proteins have any functional implication at DNA, their possible correlation to DNA-binding proteins (DBP) of psoriatic scales was examined. The disc-electrophoretic spectrum of DBP was compared with the protein profile of crude extract. However, no protein of DBP fraction correlated with one of the three characteristic proteins present in a water soluble extract. This signifies these proteins to be more a metabolically enriched product than proteins of chromosomal origin.


Peripheral vascular actions of alpha-methyldopa in the dog. The aim of these study was to investigate peripheral vascular actions of alpha-methyldopa. The following experimental procedures were used: hind-limb of the dog perfused with the animals own blood or with Krebs solution; nictitating membrane of the dog; isolated and perfused segments of the saphenous vein of the dog; superfused strips of the saphenous vein of the dog. In these preparations, effects of alpha-methyldopa on responses elicited by electrical stimulation and on release of 3H-noradrenaline were studied. In dogs pretreated with alpha-methyldopa (200 mg/kg, i.v., 36, 24 and 4 hr before the experiment) contractions of the nictitating membrane caused by cervical sympathetic electrical stimulation were markedly reduced: however, the frequency--response curve to stimulation in the hind-limb and responsiveness to noradrenaline were not significantly different of controls. Perfusion of the hind-limb with Krebs containing alpha-methyldopa (2.2 mM) resulted in a significant reduction of perfusion pressure responses to lumbar sympathetic electrical stimulation with augmented responsiveness to exogenous noradrenaline. Similar results were obtained in in vitro experiments. Effects of alpha-methyldopa were not prevented by cocaine nor by inhibition of decarboxylase by Ro 4-4602 (D,L-serine,2-(2,3,4-,trihydroxybenzyl) hydrazine hydrochloride). Alpha-methyldopa depresses the release of tritiated compounds evoked by electrical stimulation, in saphenous vein strips. This suggests that inhibition of transmitter release could be an important factor to understand peripheral actions of alpha-methyldopa.


Norepinephrine-stimulated cyclic AMP accumulation in brain slices in vitro after serotonin depletion or chronic administration of selective amine reuptake inhibitors. These experiments demonstrate that altering serotonin availability in vivo does not influence the interaction of norepinephrine with adenylate cyclase in vitro. Neither reducing serotonin levels (parachloroamphetamine) nor increasing the availability of serotonin by blocking its reuptake (fluoxetine) affect the norepinephrine-induced elevation of cyclic AMP in slices of the limbic forebrain of rats. However, increasing norepinephrine availability by chronic administration of desipramine, a norepinephrine reuptake inhibitor, reduces cyclic AMP synthesis in the limbic forebrain. However, it is doubtful that blockade of norepinephrine reuptake alone accounts for the reduction in receptor sensitivity produced by desipramine since chronic administration of a new norepinephrine reuptake inhibitor, nisoxetine, does not decrease cyclic AMP accumulation.


Isoprenaline-induced release of cyclic adenosine 3',5'-monophosphate by the left ventricle in the anaesthetized intact dog. The ability of the heart to release cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the coronary venous blood was examined in closed-chest anaesthetized dogs before and during an infusion of isoprenaline. Before the infusion, no difference was observed between the cyclic AMP plasma levels in the aortic and coronary sinus blood. During the infusion, significant coronary veno-arterial differences in nucleotide concentration were observed despite a considerable elevation of the cyclic AMP plasma level in the aortic blood.


A unique multisystemic syndrome of unknown origin. A unique multisystemic syndrome of polyneuropathy, anasarca, polycythemia, pigmentation, and endocrinopathy that occurred outside of Japan is reported, along with the results of postmortem examination. A review of the literature on this syndrome is presented, and the possible etiological considerations are discussed.


Effect of phosgene on rat lungs after single high-level exposure. Rats were exposed under static conditions to phosgene at concentrations within the LCt50 range and above. Lungs were removed at various postexposure intervals. Degrees of pulmonary edema were estimated by increases in percentage of water in the lungs of exposed groups as opposed to control animals. Lungs were fractionated into four major subcellular organelle fractions: nuclear debris, mitochondrial-lysosomal, microsomal, and soluble (cytoplasmic). Activities of p-nitrophenyl phosphatase, cytochrome C oxidase, ATP'ase, and LDH within these fractions were decreased after phosgene exposure. There was a concomitant increase in serum LDH levels. One possible mechanism that may play a role in phosgene damage can be associated with either inhibition or loss of enzyme activities from the lung.


[Ultrastructural-morphometric investigations on liver biopsies--the influence of oral contraceptives on the human liver (author's transl)]. Liver biopsies from 12 healthy women were investigated morphometrically--according to the methods of Weibel (1969). All women had taken an oral contraceptive agent during 2 til 76 months. The evaluated stereological datas were compared with base-line dates for normal human liver biopsies, which were elaborated in a previous investigation (Roessner et al., 1977). Statistical analysis was performed on an IBM 360/50 computer system, including F- and student's t-test. In the liver biopsy-specimen from the women, which were on oral contraceptives, the volume-density of lysosomes per ml hepatocytes shows a pronounced, significant (p less than 0.001) increase. A moderate increase of cytoplasm is combined with decrease of nuclei-volume. The surface-densities of the rough and smooth endoplasmatic reticulum do not differ significantly from the datas calculated from normal human liver biopsies. All other datas too demonstrate that there are no striking changes in the ultrastructure of human liver, caused by oral contraceptives. Functional alterations however can not be excluded.


[Association between HSV 2 antigen and colpocytologic finding (author's transl)]. Prophylactic gynecologic examinations were performed in 1440 women using colposcopy and vaginalcytology. A search for HSV antigen in cervical cells was performed HSV antigen was found in 12% of Pap I--II smears, in 41% of Pap III smears and in all cases of Pap IV--V. It is suggested that there is a probable association between HSV 2 and cervical cancer.


[Hyperparathyroidism in deficiency rickets. Changes after vitamin therapy]. The study concerned 16 cases of deficiency rickets observed over 3 years. The level of serum parathyroid (IPTH) hormone was always increased in the late stages of rickets, but was normal in 3 cases of early rickets with hypocalcaemia and monophosphataemia. There was no statistical correlation between the level of IPTH and monophosphataemia. There was no statistical correlation between the level of IPTH and calcaemia. After vitamin D-therapy, the levels if IPTH returned to normal in 5 to 21 days in most cases. No obvious difference was noted in this evolution between children treated by vitamin D2 and 25 OH D. The excretion of urinary cyclic adenosine monophosphate decreases in parallel with blood IPTH.


[Neurogenic stomach neoplasms induced by nitrosomethylures in Syrian hamsters]. In the experiment with inoculation of N-nitroso-N-methylurea (a maximum total dose of 7.5 mg) to Syrian hamsters, tumors developed in 20 out of 25 animals surviving the time of the occurrence of the first tumor (31 weeks). Out of 35 tumors 17 developed at the site of inoculation: in the left cheek pouch (of them 12 embryonal rhabdomyoblastomas), 11 in the stomach (of them 6 neurogenic), and 7 in other organs (skin, liver, adrenals, hemopoietic system). The paper describes the histological pattern of 6 neurogenic tumors of the stomach in which all the elements of the nervous system have been found: ganglionic cells, neuroglia, and nerve stems. On the basis of some signs the authors classify these tumors as malignant.


[Papillomatosis of the distal part of the common bile duct associated with adenomatosis of its wall]. A case of papillomatosis of the distal part of the common bile duct in combination with adenomatosis of its wall in a patient aged thirty nine is described. On the basis of data from the literature and their own observations, the authors present different opinions concerning the mechanism of the development of bile duct papillomatosis.


Hallervorden-Spatz syndrome.

Hallervorden-Spatz syndrome. Two siblings with Hallervorden-Spatz syndrome showed striking homotypism and homochronism. Neuropathologic examination and electron microscopic studies were done; neutron activation analysis showed an increase in the uptake of iron in the basal ganglia. Of particular relevance is the application of radioactive iron studies in the clinical course of this syndrome. These studies disclosed an increase in the uptake of iron in the area of the basal ganglia in one sibling and in another isolated patient. This procedure will be helpful toward the clinical diagnosis.


Demonstration of hormonal activity of a glomus juglare tumour by catecholamine determination. For the first time the hormonal activity of a glomus jugulare tumour, clinically manifest by intermitting hypertension, could be demonstrated by catecholamine level determination in blood. Endocrinological and diagnostic aspects concerned to the differential diagnosis of the hypertension in these patients are discussed.


[Clinical and morphological findings in Tangier disease (hypo-alpha-lipoporteinaemia) and its ENT-significance (author's transl)]. The report deals with the first three cases of Tangier disease (Hypo-alpha-Lipoproteinaemia) observed in Germany. This rare metabolic disorder is distinguished by a diminution of HDL-Lipoproteins in serum and a lipid storage in histiocytes. The prominent symptom is the orange yellow discolouration of hyperplastic tonsills and adenoids; further symptoms of the disease generally are various, the development is little typical. The morphological substrat of the deranged fat metabolism is cholesteryl ester storage in the reticuloendothelial system, smooth muscle cells, pericytes and Schwann cells of peripheral nerves. M. Tangier can be differentiated from other lysosomal defects by ultrastructural and chemical parameters, it seems to have a autosomal recessive inheritance. It is the ENT-specialist, who can establish an early diagnosis of this disease, provided he is aware of its clinical features.


Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects. The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids.


Alterations of pulmonary vascular resistance and pulmonary cyclic nucleotide metabolism in the hypoxic pig. Hypoxia leads to an elevation of the pulmonary vascular resistance (pvR) in pigs. This alteration of the hemodynamic was accompanied by a slight increase of intraparenchymatous concentrations of cyclic GMP (cGMP), while cycle AMP (cAMP) levels were not different from values, measured during normoxia. beta-adrenergic agents are potent inhibitors of the hypoxia induced vasoconstriction. This effect was associated with an increase of intraparenchymatous cAMP-concentrations and a decrease of cGMP-levels. The regression analysis between pvR versus the ratio cGMP/cAMP revealed a significant linear correlation. These data may indicate, that cAMP and cGMP are involved in hypoxia induced vasoconstriction and its pharmacological inhibition.


A comparison of cAMP phosphodiesterases in normal, malignant, and somatic cell hybrids. Hybrids (PCM) between a malignant mouse lymphoma suspension cell line (P388F-36) and a normal Chinese hamster fibroblastic cell line (Ch23) have already been isolated in this laboratory. Investigations were carried out on the cAMP phospodiesterases of the parents and two of these hybrids--PCM2 and PCM3. PCM3 shows a rather unusual growth characteristic in that a considerable proportion of the cells exist at any one time either in suspension or only loosely attached to the substratum, the remaining cell population existing in a monolayer form. It was found that each cell line exhibited multiple forms of the enzyme with varying affinities for cAMP. Both parents, although different, contained high-, low-, and extra-high apparent Km forms of the enzyme. The hybrids exhibited characteristics of both parental systems but were different from each other. Neither hybrid exhibited a high-Km enzyme, but both exhibited two low-Km forms. There was also a slight variation between monolayer and suspension cells of PCM3 hybrid. An attempt has been made to explain these phenomena with respect to hybridization and the growth characteristics of the cells.


An investigation of the homology of guanylate kinase isozymes in mammals and further evidence for multiple GUK gene loci. Guanylate kinase in the red cells of 63 different mammalian species was studied by electrophoresis and multiple molecular forms of the enzyme were found in all species. Two species were investigated in more detail. Using molecular weight estimates as a criterion of homology, the fallow deer and the Chinese hamster were found to have isozymes that corresponded to isozyme e, f, and g of man. Variation in the guanylate kinase isozymes was detected in a small population of orangutans. Results suggested that isozymes a and b were monomeric and that they were the products of a gene locus, GUK1, different from the locus GUK3 which coded for isozymes e, f, and g. Products c and d of the presumptive GUK2 locus were not found in the orangutan.


The reactions of 1,10-phenanthroline with yeast alcohol dehydrogenase. Freshly prepared samples of yeast alcohol dehydrogenase (EC 1.1.1.1) were inhibited by 1,10-phenanthroline at pH 7.0 and 0 degrees C in a two-stage process. The first step appeared to be slowly established, but was rendered reversible by removal of reagent or by addition of excess Zn2+ ions. The second step was irreversible and was associated with the dissociation of the tetrameric enzyme. The presence of saturating concentrations of NAD+ or NADH promoted and enhanced inhibition by the slowly established reversible process, but prevented dissociation of the enzyme. For the incubation mixtures containing NAD+, removal of the 1,10-phenanthroline resulted in virtually complete recovery of activity, whereas, for the incubation mixtures containing NADH, removal of the reagent gave only partial re-activation. The presence of NAD+ and pyrazole, or NADH and acetamide, in incubation mixtures with the enzyme gave rise to ternary complexes that gave protection against both forms of inactivation by 1,10-phenanthroline. The results support the view that at least some of the Zn2+ ions associated with yeast alcohol dehydrogenase have a catalytic, as opposed to a purely structural, role.


Electron-paramagnetic-resonance studies on a photochemically produced species of horseradish peroxidase compound I. Strong electron-paramagnetic-resonance signals in the g = 2.00 region were detected after irradiation of horseradish peroxidase Compound I at temperatures of 10 and 100 K. These signals establish the presence of new free-radical species in the peroxidase system. The new species are interpreted in terms of a haem-photosensitized oxidation of the protein's peptide groups close to the Compound I radical site. On warming to room temperature, the radicals decayed irreversibly to a species having a weak asymmetric electron-paramagnetic-resonance signal at 100 K, which could still be observed after incubation at room temperature for more than 1 h.


Hydroxylation of aromatic compounds by reduced nicotinamide-adenine dinucleotide and phenazine methosulphate requires hydrogen peroxide and hydroxyl radicals, but not superoxide. 1. A mixture of NADH and phenazine methosulphate hydroxylates aromatic compounds at acidic pH values. 2. Hydroxylation is inhibited by catalase and by scavengers of the hydroxyl radical (-OH) but not by superoxide dismutase. 3. It is concluded that neither O2 leads to nor HO2- is sufficiently reactive to hydroxylate aromatic rings.