PubMed Health⌕ Search

Biomedical subjects

M Book

Publications and source records attributed to M Book.

22 records · Page 2Linked to original sources
PubMed1991

Expression and functions of very late antigen 1 in inflammatory joint diseases.

In the human immune system, very late antigen 1 (VLA-1), a putative collagen receptor, is expressed on the surface of T lymphocytes that have undergone mitogenic or antigenic stimulation. A new VLA-1-specific monoclonal antibody, 1B3.1, was used to probe the expression and function of VLA-1 on T lymphocytes in patients with arthritis. Synovial mononuclear cells from the joints of patients with rheumatoid arthritis or other joint diseases contained 32.9 +/- 13.8% 1B3.1-positive cells (42.8 +/- 10.4% in patients with rheumatoid arthritis and 28 +/- 12.6% in non rheumatoid patients). In the peripheral blood, patients with active rheumatoid arthritis expressed VLA-1 on 11.7 +/- 6.0% of their mononuclear cells, compared to 1.9 +/- 1.5% in controls (P less than 0.001). Using dual fluorescence analysis, virtually all the 1B3.1-positive synovial cells were CD3+ T lymphocytes and included both CD4+ and CD8+ T cells. When 1B3.1-expressing synovial mononuclear cells or in vitro activated T lymphocytes were triggered with anti-CD3 antibodies, marked augmentation of their proliferation occurred if they were simultaneously cross-linked with mab 1B3.1. Collagen type IV, a putative ligand of VLA-1, also augmented T-cell proliferation to anti-CD3. The data suggest that the VLA-1 molecule could play an important role in the pathophysiology of arthritis by modulating T-cell activation in these diseases.

Antigens, Differentiation, T-Lymphocyte↗
PubMedDate not supplied

-308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter.

Tumor necrosis factor (TNF) is recognized as a central mediator of sepsis, septic shock, and multiple organ failure. These host reactions are associated with increased TNF levels in circulation, presumably due to increased TNF production. A previously described nucleotide variation at position -308 in the promoter region of the human TNF gene was shown to be associated with the clinical outcome of malaria. In this study we addressed the relevance of the -308 polymorphism for expression of the human TNF gene in response to bacterial endo- toxin in vivo and in vitro. First, we typed 80 patients suffering from severe sepsis and 153 healthy individuals and found no association of the -308 variation with incidence of the disease. In contrast, the NcoI marker in the closely linked lymphotoxin-alpha (LT-alpha) gene showed association with survivaL This discrepancy can be explained by the linkage of the TNFB2(NcoI) allele to the common TNF1 (-308) allele. Second, we generated reporter gene constructs with the promoter deletions and with both -308 variation in the context of the extended human TNF promoter region. Although such constructs were highly inducible by lipopolysaccharide (LPS) in transient transfections into a macrophage cell line, the -308 variation had no significant effect on transcription, consistent with the promoter deletion study. We conclude that the functional consequence of the -308 polymorphism may be unrelated to transcriptional response of the TNF gene to bacterial endotoxin.

Adult↗