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Biomedical subjects

J Silver

Publications and source records attributed to J Silver.

At least 433 records · Page 24Linked to original sources
PubMed1973

Osteomalacia after prolonged glutethimide administration.

Vitamin D deficiency is a previously unreported complication of therapy with hypnotics, and we here report a case of osteomalacia associated with long-term glutethimide administration. There was evidence of pronounced hepatic enzyme induction, and the plasma half-time of (3)H vitamin D(3) was decreased by this drug. In addition, raised levels of serum gamma-glutamyl transpeptidase, 5-nucleotidase, and leucine aminopeptidase were observed and the patient excreted large amounts of xylulose. These changes were reversed by stopping the glutethimide.

Cholecalciferol↗
PubMedDate not supplied

CD4+ cell oligoclonality in Crohn's disease: evidence for an antigen-specific response.

To identify disease-specific T cell changes that occur in Crohn's disease (CD) the T-cell receptor (TCR) BV repertoires of lamina propria lymphocytes (LPL) from both disease-active and disease-inactive colonic tissue of three CD patients were compared by a quantitative polymerase chain reaction (qPCR) and CDR3 length analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon of the same individual were different, and most of the differences occurred in CD4+ LPL with very few differences in the CD8+ populations of LPL. Although the pattern of BV segments that was increased in disease-active relative to disease-inactive tissue was different for all three CD patients, there was an increase in the levels of BV11, 13S2, 15, 16, and 17 segments in the disease-active tissue of all three patients. Standard CDR3 length analysis of BV11, 13S2, 15, 16, and 17 segments revealed that in two of the three CD patients there was a striking degree of TCR oligoclonality in the disease-active tissue that was absent from disease-inactive tissue of the same individual. Additional differences between the disease-active and disease-inactive tissues were observed using a more refined method of CDR3 length analysis, which employs BV- and BJ-specific primers. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens.

Adolescent↗
PubMedDate not supplied

The heavy chain of human B-cell alloantigen HLA-DS has a variable N-terminal region and a constant immunoglobulin-like region.

The HLA-D region of the major histocompatibility complex (MHC) of man encodes polymorphic glycoproteins found predominantly on the cell surfaces of B cells and macrophages. These proteins mediate interactions, required for the induction of immune responses, among cells of the immune system and consequently are referred to as Ia (immune-response associated). Two families of Ia molecules, DR and DS (also known as DC), have been defined, the former analogous to the I-E (ref. 1) and the latter to the I-A molecules of the murine MHC. Both DR and DS molecules consist of two noncovalently associated polypeptide chains with molecular weights of 33,000 and 28,000, designated alpha and beta, respectively. The polymorphism of DR molecules is due to structural variation in the small subunit, DR beta, with the large subunit, DR alpha, being constant in structure. In contrast, both subunits DS alpha and DS beta are structurally variable when DS allotypes are compared. We have now isolated a cDNA clone from a DR7 cell line that contains the entire coding sequence for the DS alpha subunit and have compared its predicted amino acid sequence with that previously deduced from a DS alpha cDNA clone isolated from a DR4,w6 cell line. This comparison reveals that 10 of 11 amino acid differences are located within the alpha 1 (N-terminal) domain and that the alpha 2 or immunoglobulin-like domains are identical.

Amino Acid Sequence↗
PubMedDate not supplied

Structural organization of the rat thy-1 gene.

Thy-1 is a differentiation marker expressed predominantly on thymocytes, T cells and brain tissue. Its presence on murine peripheral T cells but not B cells has long been used to distinguish between these two populations of lymphocytes. Although analogues of Thy-1 have been described in several mammalian species, its tissue distribution in different species varies widely, precluding its use as T-cell-specific marker. The Thy-1 molecule is a cell-surface glycoprotein of relative molecular mass 18,000, one-third of which represents carbohydrate; the protein moieties of the rat and murine Thy-1 molecules have been sequenced and found to consist of 111 and 112 amino acids, respectively. An unusual aspect of Thy-1 is the apparent absence of a hydrophobic segment comparable to that observed in other membrane glycoproteins which would allow integration of Thy-1 within the membrane lipid bilayer. This has prompted speculation that Thy-1 is anchored to the cell surface by some other hydrophobic component such as glycolipid. Here we report the structure of thy-1 complementary DNA and genomic clones and describe the exon-intron organization of the gene. More importantly, our data indicate that Thy-1 is initially synthesized as a molecule of 142 amino acids, 31 amino acids longer at the carboxyl end than the Thy-1 molecule isolated and characterized by Campbell et al. An extremely hydrophobic region of 20 amino acids lies within this 31-amino acid stretch and may represent the transmembrane segment responsible for anchoring Thy-1 to the cell membrane.

Amino Acid Sequence↗
PubMedDate not supplied

Regeneration of adult axons in white matter tracts of the central nervous system.

It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons. In addition to physical or molecular barriers presented by glial scarring at the lesion site, it has been suggested that the normal myelinated CNS environment contains potent growth inhibitors or lacks growth-promoting molecules. Here we investigate whether adult CNS white matter can support long-distance regeneration of adult axons in the absence of glial scarring, by using a microtransplantation technique that minimizes scarring to inject minute volumes of dissociated adult rat dorsal root ganglia directly into adult rat CNS pathways. This atraumatic injection procedure allowed considerable numbers of regenerating adult axons immediate access to the host glial terrain, where we found that they rapidly extended for long distances in white matter, eventually invading grey matter. Abortive regeneration correlated precisely with increased levels of proteoglycans within the extracellular matrix at the transplant interface, whereas successfully regenerating transplants were associated with minimal upregulation of these molecules. Our results demonstrate, to our knowledge for the first time, that reactive glial extracellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo, and that adult myelinated white matter tracts beyond the glial scar can be highly permissive for regeneration.

Aging↗