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Biomedical subjects

J Silver

Publications and source records attributed to J Silver.

At least 379 records · Page 21Linked to original sources

Deformation of isolated rat hepatocytes by a peptide hepatotoxin from the blue-green alga microcystis aeruginosa.

The effect of the peptide hepatotoxin from the bloom-forming blue-green alga Microcystis aeruginosa was investigated on isolated rat hepatocytes. When toxin was added to hepatocyte suspensions it produced deformation of the cells, as shown by scanning electron microscopy. This was apparent within 5 min of addition of toxin to the cells and the response was dose dependent: 30 ng of toxin was sufficient to cause deformation in 58 +/- 9% of 1.4 x 10(6) hepatocytes/ml of incubation. The deformation did not lead to cell death as measured by Trypan blue uptake within 120 min. Deoxycholate, cholate bromosulphophthalein, and rifampicin were found to prevent the deformation of hepatocytes by Microcystis aeruginosa toxin in a dose dependent manner, analogous to the effect of these agents on the response of hepatocytes to added phalloidin. This suggests that Microcystis aeruginosa toxin is transported into hepatocytes in the same way as phalloidin; namely sharing a transport system for bile acids on the hepatocyte plasma membrane.

Animals↗

Small subunit of I-A subregion antigens determines the allospecificity recognized by a monoclonal antibody.

The murine major histocompatibility complex (MHC) codes for three groups of identifiable cell-surface proteins, the K, D molecules, the I-A subregion antigens and the I-E subregion antigens. All three groups of molecules display a high degree of serologically detectable polymorphism and consist of two noncovalently associated polypeptides. Amino acid sequence and peptide comparisons among allotypes of K, D and I-E molecules reveals that one polypeptide is relatively constant, whereas the other is highly variable. Thus, it is likely that only one of the two polypeptides, the variable component, determines the antigenic specificities recognized by alloantisera. In contrast to the K, D anad I-E molecules, both subunits of I-A molecules display substantial structural differences when comparisons among allotypes are made. Therefore, we have investigated whether one or both subunits of I-A molecules determine their alloantigenic specificities. Our results, presented here, indicate that only one of the two subunits determines a particular allospecificity recognized by a monoclonal antibody.

Animals↗

A mechanism for the guidance and topographic patterning of retinal ganglion cell axons.

Three dimensional reconstruction, with the use of serial, 1-micrometer sections, has revealed a system of oriented intercellular spaces within the undifferentiated optic cup. These large openings appear in the marginal zone of the primitive retina and optic stalk prior to the formation of the first retinal ganglion cell axons. The spaces at the region of the optic disc form sets of long, interconnecting tunnels oriented in the direction of the stalk. The spaces at the back and rim of the cup form blind, radially arranged pockets. The extracellular tunnels of the optic disc region strictly maintain their positions in relation to the optic fissure and, thus, discrete portions of the retina become connected by continuous openings with equivalent regions in the stalk. The path taken by the earliest outgrowing optic fibers is identical to the one previously established by the intercellular tunnels. We propose that the tunnel and pocket layout may provide directional and topographic information to the first forming optic axons.

Animals↗

A novel molecule expressing HLA-DR antigenic determinants.

Our previous studies suggested that the polymorphism of HLA-DR antigens (the human equivalent of murine I-E antigens) was a result of structural variation in the small (beta) subunit. In order to more accurately define this polymorphism we have expanded these studies to include HLA-DR antigens isolated with monoclonal cells derived from genotypically HLA-homozygous DRw2, DR2w5, and DRw7 lymphoblastoid cells derived from offspring of consanguineous relationships. Our results indicate the large (alpha) subunits of DRw2 and DRw7 antigens are nearly identical, while their beta subunits show many differences. In contrast, both the alpha and beta subunits of the DRw5 antigen differ strikingly from the respective subunits of the DRw2 and DRw7 antigens. The significance of the variability of the DRw5 alpha subunit is in question at this point. One intriguing possibility is that DRw5 actually represents the human counterpart of the mouse I-A subregion antigen and that the monoclonal antibody is reacting with a determinant which is shared by the human equivalents of murine I-A and I-E antigens.

Amino Acid Sequence↗

Clindamycin unresponsive anaerobic osteomyelitis treated with oral metronidazole.

A diabetic patient with peripheral neuropathy and a foot ulcer developed osteomyelitis of the foot. Antibiotic therapy of the aerobes isolated from the ulcer resulted in no clinical improvement. Intravenous clindamycin therapy of the anaerobe isolated (Bacteroides fragilis) was associated with an incomplete and temporary response, but there was a dramatic response to oral metronidazole with healing of the ulcer and osteomyelitis. One year later there were no signs of recurrence.

Administration, Oral↗

Malabsorption following aorto-femoral bypass.

A case of malabsorption which developed after aortofemoral bypass surgery is described. Barium enema showed ischemic changes, and postoperative arteriography revealed marked reduction of the peripheral vascular bed of the mesenteric arteries. Malabsorption probably developed as a consequence of mesenteric ischemia, aggravated by the surgical procedure, the so-called aorto-iliac steal syndrome.

Aged↗

Structural polymorphism of human DR antigens.

DR ANTIGENS are polymorphic cell surface molecules whose expression is controlled by a locus closely linked or identical to the D locus of the major histocompatibility complex (MHC) of man (for reviews see refs 1, 2). They are functionally and structurally homologous to the murine la antigens determined by the I-E subregion of the MHC, a region which has been implicated in the genetic control of immune responses(3,4). Both sets of antigens are mainly expressed on cells associated with immune function (for reviews see refs 1, 2, 5), and are involved in mediating T-cell, B-cell and macrophage interactions required for the generation of immune responses(6-9). In addition, both consist of two non-covalently associated polypeptides, designated alpha and beta, with molecular weights of 34,000 and 28,000, respectively(10). The association of some DR antigens with increased susceptibility to certain diseases (for review see ref. 1) and the genetic restrictions imposed on cellular interactions by the HLA-D region(9,11) may represent the effects of structural variability among DR antigens. The aim of the studies reported here was to examine the nature and degree of structural variation among DR antigens isolated from cultured lymphoid B cells with different DR phenotypes. Such information may provide an understanding of the molecular mechanisms by which DR antigens mediate their function.

Journal Article↗

Structural polymorphism of I-E subregion antigens determined by a gene in the H-2K to I-B genetic interval.

THE generation of immune responses in mice is influenced by Ir genes located in the I region of the major histocompatibility complex (MHC)(1). In some instances maximum responses require complementation by two genes, one in the I-A or I-B and the other in the I-E or I-C subregion(2,3). The effects of these genes are thought to be mediated by Ia alloantigens, which are cell surface molecules whose expression is controlled by the I region(4). This is based on the observations that anti-Ia sera inhibit in vitro immune responses(5,6), and soluble factors that enhance in vitro immune responses express Ia alloantigenic determinants(7,9). Jones et al.(10), using two-dimensional gel electrophoresis, observed that the expression of I-E subregion antigens is controlled by two genes, one in the I-A subregion, the other in the I-E subregion, and that the polymorphism of these antigens is influenced by an I-A subregion gene. As an explanation, the authors proposed that only one of the two polypeptide chains present in I-E immunoprecipitates is an I-E subregion product, the second being a product of the I-A subregion. Antisera obtained by cross-immunisation of I-E subregion-disparate strains of mice immunoprecipitates a molecular complex consisting of two chains, designated alpha and beta, with molecular weights of 32,000 and 29,000 respectively(11-14). Previous studies suggested that I-E antigens isolated from B10.A(5R) and B10.D2 mice had identical alpha-chains but different (beta)-chains(15). However, as these mice differed at multiple genetic regions, it was not possible to show which I subregion(s) determined the polymorphism of the E(beta) chain. Therefore, we investigated the effects of the I-A subregion on the polymorphism of I-E subregion antigens. We have now shown by peptide mapping that the I-E subregion polymorphism which Jones et al. found to be controlled by the I-A subregion probably reflects structural polymorphism of beta-chains controlled by an I-A subregion gene.

Journal Article↗

A method for studying plasma transport of vitamin D applicable to hypervitaminosis D.

In man, vitamin D is normally transported on a specific binding globulin (DBP) and on lipoproteins. In addition, binding to albumin occurs in the presence of vitamin D excess. Agarose gel electrohoresis was used to study the binding of radioactive vitamin D to plasma proteins in lipoprotein-free plasma (d greater than 1.21 g/ml). This method completely separates DBP from albumin and thus enables the quantification of vitamin D bound to these proteins in various clinical and experimental conditions. The same method can be used to study the transport of other vitamin D metabolites.

Biological Transport↗

A route for direct retinal input to the preoptic hypothalamus: dendritic projections into the optic chiasm.

With the use of Golgi, horseradish peroxidase, and electron microscopic techniques, neurons within a broad region of the preoptic hypothalamus of the mouse were shown to have dendrites that projected well into the depths of the optic chiasm. Further experimental and ultrastructural investigation demonstrated synapses between these dendrites and retinal axonal boutons within the chiasm. All synapses located in the chiasm were classified as Gray's type I. The possible function of these dendritic projections is discussed.

Animals↗

The effect of DDT on vitamin D metabolism and calcium binding activity in the chick.

The mechanism of DDT impaired calcium absorption was studied in control, DDT fed and starved chicks. The metabolism of [3H]cholecalciferol was the same in the 3 groups, but the DDT fed and starved chicks had less intestinal calcium binding activity than the control chicks. These results suggest that DDT impaired calcium absorption and intestinal calcium binding activity may be a result of DDT induced anorexia.

Animals↗