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Biomedical subjects

V Deutsch

Publications and source records attributed to V Deutsch.

At least 19 recordsLinked to original sources

Genetic evidence for multiple functions of the matrix protein of vesicular stomatitis virus.

TsO82, a spontaneous temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV) isolated in chick embryo fibroblasts (CEFs), complements the five prototype ts mutants of the virus. The data presented here indicate that the defect in tsO82 is localized in the M gene. The mutation changed a methionine to an arginine at position 51 of the M protein. Only true revertants could be isolated, and their frequency was low, perhaps due to the type of substitution required to return to the wild-type phenotype. TsO82 does not exhibit hypertranscription, in contrast to the data reported for all of the other ts mutants affected in the M protein. Moreover, tsO82 is conditionally ts, since it grows normally in BHK-21 cells at all temperatures. It exhibits no c.p.e. at the non-permissive temperature in CEFs. Our data argue for multiple functions of the M protein of VSV, the domain affected by the tsO82 mutation possibly being implicated both in the shut-off of cellular RNA synthesis, and for the recognition of a cellular factor required for efficient viral RNA synthesis.

Animals

Modulation by all-trans retinoic acid of glycoprotein glycosylation in murine melanoma cells: enhancement of fucosyl- and galactosyltransferase activities.

beta-All-trans retinoic acid (RA) treatment of murine S91-C2 melanoma cells decreases in vitro growth and modulates the glycosylation of specific cellular and cell-surface glycoproteins. The effect of RA treatment on [3H]fucose, [3H]galactose, and [3H]glucosamine incorporation was investigated by metabolic labeling followed by analysis of labeled cellular glycoproteins using polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS-PAGE) and fluorography. RA treatment dramatically increased the incorporation of the labeled monosaccharides into one glycoprotein of Mr 160,000 (gp160), which has been previously implicated in the growth-inhibitory effect of RA on these cells. Following RA treatment, cell-surface sialic acid residues on gp160 were also more intensely labeled by NaIO4 oxidation and subsequent NaB[3H]4 reduction than were those on gp160 of untreated cells. The activities of fucosyl- and galactosyltransferase increased about 1.5 to 1.9 times after RA treatment. These results suggest that the increased activities of the two glycosyltransferases is responsible for the increased incorporation of fucose and galactose into gp160.

Animals

Megakaryocyte function and dysfunction.

More than a hundred years have passed since platelets were recognized as cells and their haemostatic functions discovered. However, the process of platelet production is still not understood. The location, the mechanism and the regulation of thrombopoiesis remain elusive. Megakaryocytes are known to be the source of platelets. Investigations of megakaryocytes have revealed their normal functions and some of the abnormalities present in various diseases which affect platelets. In recent years, new techniques of cell isolation and tissue culture have been developed and have made possible advances in characterizing megakaryocyte precursors and differentiation. The primary function of megakaryocytes is to synthesize and assemble platelet components and organelles. Although debated for a long time, new data seems to indicate that the lung may be a central locus of platelet production. The new techniques for megakaryocyte investigations have barely begun to be of use in the study of abnormal platelet production in disease.

Animals

Growth inhibition of murine melanoma cells by antibodies to a cell surface glycoprotein implicated in retinoic acid action.

Previous studies have shown that treatment of S91-C2 murine melanoma cells with beta-all-trans-retinoic acid (RA) results in growth inhibition, enhanced activity of sialyltransferase, and increased glycosylation of a Mr 160,000 cell surface sialoglycoprotein (gp160). None of these effects could be detected in mutant clones (e.g., S91-C154) selected from the S91-C2 cells for resistance to RA-induced growth inhibition. These findings suggest that modulation by RA of gp160 might be related causally to growth inhibition. In this study we examined the possible role of gp160 in growth regulation using specific antibodies to this glycoprotein. Metabolic labeling of S91-C2 cells with either [3H]glucosamine or [35S]methionine revealed that the cells shed into the growth medium a gp160-like glycoprotein, in addition to several other macromolecules. The gp160-like glycoprotein was isolated from concentrated conditioned medium after preparative polyacrylamide slab gel electrophoresis in the presence of sodium dodecylsulfate by excision of the corresponding protein band. Rabbits were immunized with this material and immunoblotting revealed that their sera contained antibodies that bound specifically to gp160 in extracts of untreated or RA-treated S91-C2 cells. Indirect immunofluorescence staining followed by fluorescence-activated cell sorter analysis demonstrated that the anti-gp160 antibodies bound to the surface of both untreated and RA-treated S91-C2 cells and that the treated cells bound more of the antibodies than untreated ones. In contrast, these antibodies bound to the same extent to untreated and RA-treated resistant S91-C154 cells. The growth of S91-C2 cells in the presence of anti-gp160 antibodies in semisolid medium as well as in monolayer cultures was inhibited in a dose-dependent fashion. Fifty % growth inhibition was obtained at an immunoglobulin concentration of 10 micrograms/ml. The growth of cells exposed concurrently to RA and anti-gp160 antibodies was also inhibited strongly in semisolid medium, but the antibodies caused only a small increase in the inhibitory effect of RA in monolayer cultures. No inhibition by the antibodies of either anchorage-independent growth or anchorage-dependent growth of S91-C154 cells, grown in the absence or presence of RA, was observed. These results support the suggestion that cell surface gp160 might be involved in growth regulation in the S91-C2 cells.

Animals

Inactivation of influenza and vesicular stomatitis virion RNA polymerase activities by photoreaction with 4'-substituted psoralens.

Irradiation of purified influenza virus and vesicular stomatitis virus (VSV) with long-wavelength UV light in the presence of 4'-substituted psoralens inactivated the virion-associated RNA polymerase activity. Inactivation was apparently due to psoralen modification of the viral genome RNAs, since cations that decrease psoralen binding to nucleic acids had a protective effect, and reconstitution of VSV RNA polymerase activity was inhibited by photoreaction of nucleoprotein cores but not by pretreatment of soluble fraction from dissociated virions. Partially inactivated viral particles synthesized reduced amounts of full-length RNA products in vitro without an increase in prematurely terminated transcripts. VSV leader RNA formation was relatively resistant to psoralen photoinactivation, and sequential transcription was maintained by photoreacted VSV. The all-or-none psoralen effect on virion-associated RNA polymerase activities may be due to a differential photosensitivity of promoter sites or to structural changes in modified viral genome RNAs that prevent formation of new mRNA chains.

DNA-Directed RNA Polymerases

Right aortic arch with left descending aorta (circumflex aorta). Roentgenographic diagnosis.

Right aortic arch with retroesophageal segment is a rare anomaly with distinctive roentgenographic features. We present 2 patients, who on the barium oesophogram had an additional finding which has not previously been described. The typical features include an indentation on the right upper barium filled oesophagus (in the antero-posterior view), an oblique indentation descending from right to left (caused by the retroesophageal segment) and the left descending aorta. The oblique identation has not previously been described. The embryology and incidence of the lesion are briefly discussed.

Aorta, Thoracic

Cerebral arteriovenous fistula causing congestive heart failure in infancy.

The case of a newborn female in congestive heart failure due to a cerebral A-V fistula is presented. The cardiac manifestations in the presence of this condition are described, and the diagnostic importance of auscultation of the skull is stressed. Because of the precarious condition of most of these neonates, diagnostic procedures should be minimized if the clinical picture is compatible with this diagnosis, and cerebral angiography should be performed before any heart studies are undertaken.

Female

Arteriosclerotic aneurysm of the coronary artery.

The findings in a patient with an angiographically proven aneurysm of the coronary artery are described. The case is reviewed in the light of 115 similar cases reported in the literature. The patient had had numerous episodes of variant angina, a feature not previously described in coronary arterial aneurysms, which may be related to embolic showers originating from the aneurysm.

Adrenergic beta-Antagonists