Biomedical subjects

J B Weitzman

Publications and source records attributed to J B Weitzman.

22 records · Page 2Linked to original sources

PubMed1993

The function and distinctive regulation of the integrin VLA-3 in cell adhesion, spreading, and homotypic cell aggregation.

To assess directly the functional role of the integrin VLA-3 (alpha 3 beta 1), we transfected human alpha 3 cDNA into erythroleukemia (K562) cells and rhabdomyosarcoma (RD) cells. The resulting transfectants (KA3 and RA3) expressed alpha 3 beta 1 on the cell surface as confirmed using a panel of nine anti-alpha 3 monoclonal antibodies. Neither of the transfected cells exhibited increased adhesion to the extracellular matrix proteins fibronectin, laminin, and collagen. However, the KA3 transfectants did bind strongly to the extracellular matrix deposited by epidermal and carcinoma cell lines, allowing the cells to attach and spread. Binding to this cell-deposited ligand, probably containing epiligrin/kalinin, was specific to VLA-3 and could be inhibited by anti-alpha 3 antibodies and by EDTA, but not by RGD peptides. In marked contrast to other integrins (VLA-2 and VLA-4), VLA-3 showed high constitutive activity in K562 cells, but was minimally active in RD cells. Also contrasting with other beta 1 integrins, VLA-3 was minimally stimulated by the anti-beta 1 monoclonal antibody TS/216 under normal conditions. VLA-3-mediated adhesive function was well supported by either Mg2+ or Mn2+, but was almost completely abolished by the presence of 1 mM Ca2+. Surprisingly, this negative Ca2+ effect was completely overcome by the addition of the stimulatory anti-beta 1 monoclonal antibody TS2/16. Together, these results point to markedly distinct regulation for VLA-3 function compared to other beta 1 integrins. Also, all anti-VLA-3 antibodies were able to induce temperature-dependent homotypic cell aggregation of KA3 cells, but not K562 cells. However, this aggregation did not appear to be directly mediated by VLA-3 since it was not inhibited by EDTA. In addition, no enhancement of heterotypic cell-cell adhesion was observed in alpha 3-transfected cells.

Animals↗

PubMed1992

Very high values of serum high-density lipoprotein cholesterol.

Little is known about individuals who have very high values of serum high-density lipoprotein cholesterol (HDL-C) with the exception of those who have very rare genetic conditions, eg, familial hyperalphalipoproteinemia or hypobetalipoproteinemia. During a period of 60 months of testing for HDL-C, we found 46 individuals (of whom 43 were women) who had an HDL-C level equal to or higher than 2.58 mmol/L (greater than or equal to 100 mg/dL) (range, 2.58 to 6.15 mmol/L [100 to 238 mg/dL]). Sixteen of these individuals were treated with estrogens or ranitidine or were alcoholic, and several had evidence of coronary heart disease. We conclude that very high values of HDL-C can be found in the general population mostly in women, and this is often related to environmental causes, eg, the use of H2-blockers, estrogens, and alcohol. The finding of very elevated HDL-C levels in serum is probably not always due to a genetic condition and does not always signify absence of coronary heart disease and increased life expectancy.

Adult↗

PubMed1991

The gene organisation of the human beta 2 integrin subunit (CD18).

We have studied the gene of the human beta 2 integrin subunit (CD18) and found it to be organised into 16 exons spanning a region of about 40 kb. All exon/intron boundaries conform to the GT/AG splicing consensus. The exons coding for the cysteine-rich region, which has been postulated to consist of 3 or 4 repeating elements, are not organised correspondingly. Transcription of the gene initiates from multiple sites which may be due to the absence of an upstream TATA box. The polyadenylation site is also heterogeneous. Five different sites were identified over a stretch of 10 bases.

Amino Acid Sequence↗

PubMedDate not supplied

Potent inhibitors of glucagon-stimulated adenylate cyclase associated with serum lipoprotein particles.

Lipoprotein fractions from some individuals have inhibitory effects on rat liver adenylate cyclase. Precipitation of the lipoprotein fractions with acetone released an inhibitory factor, which was soluble in acetone-H2O (3:1, v/v). The inhibition was greater against glucagon-stimulated activity than against basal activity. Acetone extraction increased the potency of inhibition. All three lipoprotein fractions, i.e., very low, low, and high density lipoproteins, released some inhibitory component after acetone extraction. The inhibitor was concentrated in the lipoprotein fractions, since acetone extraction of plasma did not release an inhibitor. The acetone extract from the very low density lipoprotein was the most inhibitory. This material was further purified and partially characterized. The inhibitor had a molecular mass of about 500. It was inhibitory at micromolar concentrations. The material was sufficiently hydrophobic to migrate in normal-phase thin-layer chromatography (TLC). Nuclear magnetic resonance results indicated that it was not a polar lipid. There were several different inhibitory factors that were separable by TLC. The sequestration of these inhibitors into lipoproteins reduced their effectiveness in inhibiting the action of counter-regulatory hormones, such as glucagon.

Adenylyl Cyclase Inhibitors↗