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Biomedical subjects

V Kempf

Publications and source records attributed to V Kempf.

4 recordsLinked to original sources

Antibiotic treatment to prevent urinary tract infections after urodynamic evaluation.

The aim of the study was to determine the efficacy of cotrimoxazole administration after urodynamic testing to prevent urinary tract infections. In a single-blind prospective randomized study 94 women who attended for urodynamic evaluation were included. After multichannel urodynamic testing, including two catheterizations, the women received a single dose of cotrimoxazole or placebo. A clean-catch urine specimen was tested for infection after 1 week. Seventy women returned a urine specimen after 1 week: 2/37 (5.4%) in the treatment and 2/33 (6.1%) in the placebo group had acquired a new urinary tract infection after urodynamics. One major and one minor adverse reaction to cotrimoxazole were reported. The power of the sample size was unfortunately too small to draw conclusions as to the efficacy of prophylaxis.

Adult↗

A novel monospecific IgG2/lambda-autoantibody with specificity for a mitochondrial antigen: evidence for an antigen-driven pathogenetic B-cell response in rheumatoid synovial tissue, induced by tissue alteration.

To elucidate the pathogenic role of synovial B cells in rheumatoid arthritis (RA), nine human IgG/lambda-secreting B-cell hybridomas from rheumatoid synovial tissue of a patient with definite RA were screened by enzyme-linked immunosorbent assay and indirect immunofluorescence on tissue cryosections for detection of antibodies against autoantigens. One IgG2/lambda monoclonal antibody (mAb) from the B-cell hybridoma ELG211/15/63 (= hybr63) exhibited intense immunofluorescence reactivity in the cytoplasm of chondrocytes and epithelial cells of the gastrointestinal tract, especially in parietal cells of gastric mucosa (human and mouse tissue), representing a mitochondrial pattern. This result was confirmed by morphometric analysis of immunoelectron microscopy data, exhibiting a significantly higher labeling density in mitochondria (p < or = 0.001) than in the cytoplasmic background, with predominant staining in the inner mitochondrial membrane and mitochondrial matrix (p < or = 0.05). Immunoblotting experiments carried out with gastric mucosa, and a mitochondrial protein preparation revealed two major proteins of 38 and 50 kd under reducing conditions. The analysis of the IgV(H) genes from this B-cell hybridoma showed highest homology to the human germline gene DP53 (96%). The IgV(L) region gave highest homology to the human germline gene DP5 (93%). In the complementarity-determining regions, residues of the H- and L-chain variable regions replacement mutations only indicated that this B-cell clone had been antigen-selected for its affinity (ratio of replacement to silent mutations: > or = 7). To analyze the in vivo expansion of the B-cell clone, primers specific for the V(H) to D to J(H) rearrangement of this B-cell hybridoma were used. Specific amplifications could be detected within part of the synovial tissue but not within the cells of the synovial fluid and peripheral blood of the patient. The ability of the IgG2/lambda mAb to induce an inflammatory reaction was tested by intraperitoneal application in severe combined immunodeficiency (SCID) mice, which resulted in an inflammatory, predominantly granulocytic infiltration of the peritoneum. Consequently, intrasynovial cell death or cartilage destruction seems to be a possible source of liberation of mitochondrial antigens, inducing a local, antigen-driven IgG2/lambda B-cell response with the ability to induce an inflammatory reaction. These data suggest that tissue destruction may serve as a source of arthritogenic antigens that perpetuate and amplify the local pernicious inflammatory process in RA synovialitis.

Amino Acid Sequence↗

Defense mechanisms in Peyer's patches and mesenteric lymph nodes against Yersinia enterocolitica involve integrins and cytokines.

Adhesion molecules and cytokines are involved in regulation of cellular host responses in infection processes. In this study the roles of the integrins Mac-1 and VLA-4, as well as those of the cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), in defense mechanisms against Yersinia enterocolitica in Peyer's patches (PP) and mesenteric lymph nodes (MLN) were investigated by blocking these molecules with antibodies in vivo prior to orogastric Yersinia infection. Intestinal Yersinia infection caused abscesses composed of polymorphonuclear (Mac-1+ VLA-4+ Pgp-1+ ICAM-1-) and mononuclear (Mac-1+ VLA-4+ Pgp-1+ ICAM-inhibited phagocytosis of yersiniae by macrophages, (ii) reduced Yersinia-specific proliferation and IFN-gamma production of T cells from PP and MLN, and (iii) caused increased bacterial growth in PP and MLN followed by profound tissue destruction. Neutralization of TNF-alpha or IFN-gamma had comparable effects, suggesting that cell-mediated host responses including activated macrophages are required for control of yersiniae in intestinal tissues. The number of Mac-1+ cells in PP and MLN increased after yersinia infection, and recruitment of these cells was not blocked by administration of anticytokine or anti-integrin antibodies. While anti-VLA-4, -TNF-alpha, or -IFN-gamma antibody treatment caused an increased dissemination of yersiniae from PP to the spleen systemic dissemination was reduced by anti-Mac-1 antibodies. The results of this study suggest that the cytokines IFN-gamma and TNF-alpha as well as the integrins Mac-1 and VLA-4 are involved in protective cellular host defense mechanisms in PP and MLN against Y. enterocolitica, the latter probably being involved in both cell-cell and cell-pathogen interactions.

Animals↗