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  • 1
    ISSN: 1437-160X
    Keywords: bcl-2 ; Lymphocyte subsets ; Synovial inflammation ; Rheumatoid arthritis ; Germinal center
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We used a double-immunostaining technique to analyze the distribution of bcl-2+ B and T lymphocytes within the synovial membranes (SM) of 13 patients with rheumatic diseases: 11 with rheumatoid arthritis (RA), 1 with ankylosing spondylitis (AS), and 1 with osteoarthritis (OA). A high proportion (up to 50%) of the lymphocytes belonged to the B cell subset. Most of both T and B lymphocytes were positive for the bcl-2 protein. In germinal centers B lymphocytes were also negative for bcl-2 protein expression, comparable to the situation in germinal centers of secondary lymphatic organs. We conclude that bcl-2+ B lymphocytes are submitted to antigen selection in the inflamed SMs while bcl-2+ protein expression provides survival signals for their persistence in the infiltrates. The expression of bel-2 may be an important factor in protecting lymphocytes in SM from apoptosis by glucocorticoids, cytostatic drugs, and irradiation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1437-160X
    Keywords: IgA ; Rheumatoid factor ; Monoclonal antibodies ; Immunoglobulin genes ; cDNA clones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A human hybridoma stably secreting IgA rheumatoid factor (RF) was produced by cell hybridization with peripheral blood lymphocytes of a patient with rheumatoid arthritis. The RF was of the IgA1 isotype with ϰ-light chains and was useful for standardization or specificity controls in class-specific RF assays. RF activity was detected only when the IgA molecular were in a polymeric state, and could be measured by enzyme linked immunosorbent assay as well as in conventional agglutination based tests. The RF had the modified Ga fine specificity described previously for several RFs and for protein A. The immunoglobulin V genes used were isolated and sequenced. The light chain was encoded by the VkIV gene rearranged to Jk2; compared to the published VkIV germ line gene there was 90% nucleotide homology. The heavy chain gene used belonged to the VHI family and was rearranged to JH4. Comparisons with published sequences revealed 90% homology with the recently characterized VH gene expressed by RF-TS3, a rheumatoid synovia RF hybridoma.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1437-160X
    Keywords: Key words VH gene repertoire ; Immunoglobulin gene rearrangements ; Rheumatoid arthritis ; Somatic mutation ; Memory B cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The VH gene (Variable gene segments of the heavy chain locus) repertoire can be investigated by DNA analysis of rearranged immunoglobulin VH genes, which also allows for an indirect estimation of antibody selection by analysis of somatic mutations. Using a polymerase chain reaction (PCR) it is also possible to analyse these genes in small numbers of cells or even single cells. This approach was chosen to investigate germinal centre like lymphocyte follicles in the synovial membranes of two patients with rheumatoid arthritis (RA) in order to analyse the local humoral immune response in RA. Individual B-cell aggregates of synovial membrane of two patients with RA were isolated by micromanipulation from microscopic slides. VH-DH-JH (variable, diversity, and joining segments of the heavy chain locus) rearrangements in all possible VH-JH combinations were amplified from these B cell foci, cloned and subjected to sequence analysis. Sequence analysis revealed that most of the rearranged VH genes were somatically mutated with at least 1% (range 1.3 – 14.9%) somatic mutations and therefore were derived from antigen-selected memory B cells. Intraclonal diversity in one-third of the clones indicated the generation of memory B cells in the synovial membrane and characterized the synovial membrane as lymphatic tissue where secondary immune responses to an as yet unknown antigen take place.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Der Gynäkologe 33 (2000), S. 326-327 
    ISSN: 1433-0393
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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