Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera from 98 patients were examined for antinuclear antibodies (ANA). The patient population has been previously identified clinically as having the following diseases: systemic lupus erythematosus, scleroderma, dermato or polymyositis, discoid lupus, rheumatoid arthritis, Raynaud phenomena only, undifferentiated connective tissue disease, and psoriasis. All sera samples were tested using both HEp-2 cells and rat kidney tissue as substrates and were stained with both fluorescein-conjugated antihuman antibody and glucose oxidase-conjugated antibody to human IgG. Each serum was initially tested at a screening dilution of 1:40 with PBS. Positive sera were serially diluted until an end point was observed. The number of dilutions for each specimen in all four combinations was compared mathematically using the Pearson product moment correlation. Using this method, glucose oxidase- and fluorescein-conjugated antinuclear antibody (FANA) techniques appear to have a high positive correlation (r = 0.92 kidney, r = 0.95 Hep-2) in this patient population. In our experience, the glucose oxidase technique offers comparable results to FANA and is ideally suited for the hospital laboratory, especially facilities without the benefit of a fluorescent microscope.
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PMID:A comparative study of glucose oxidase versus FITC-labeled antibody techniques for the detection of antinuclear antibodies. 643 30

Anti-SSB antibodies were measured by ELISA in patients with various kinds of connective tissue diseases using SSB antigen purified from fresh rabbit thymus. The SSB antigen reacted with anti-SSB standard serum, and the positive rates in SS, SLE, RA, PBS and MCTD were 55.1%, 48.3%, 32.8%, 30.8% and 26.3%, respectively. The titers of anti-SSB antibodies were higher in SS and SLE patients than in other connective tissue disease patients. However, 10% of normal individuals were found to have anti-SSB antibodies with low titers. The anti-SSB antibodies detected were mainly of IgG isotype. Preliminary analysis of clinical data showed no relationship between anti-SSB and systemic involvement in SS.
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PMID:Detection of anti-SSB antibodies in patients with rheumatic diseases. 827 26

Scleroderma is a connective tissue disorder with unknown etiology. Myofibroblasts appear during fibrotic processes such as scleroderma, hypertrophic scarring, and wound healing. We previously established a mouse model for scleroderma by local injections of bleomycin. To determine the phenotype of the fibroblasts in sclerotic skin after bleomycin treatment, we examined the expression of alpha-smooth muscle actin (alpha-SMA), a marker for myofibroblasts, in lesional skin as well as in fibrous lung in this model. Dermal sclerosis was induced by daily local injections of bleomycin (100 microg/ml) for 3 weeks in C3H mice. Immunohistochemical examination showed that alpha-SMA-reactive cells were detectable on fibroblastic cells in bleomycin-injected skin at 1 week. There was a significant increase in the immunoreactive fibroblastic cells for alpha-SMA in lesional skin in parallel with the induction of dermal sclerosis. After 3 weeks' treatment with bleomycin, the number of alpha-SMA-reactive fibroblasts showed an 11-fold increase compared with that in control PBS-treated mice. alpha-SMA-positive cells were also detected in lung parenchyma after bleomycin treatment. Following concomitant treatment with anti-transforming growth factor-beta (TGF-beta) antibody with bleomycin, the number of alpha-SMA-positive fibroblastic cells was significantly reduced up to 50%, along with the reduction of dermal sclerosis. To confirm the protein level of alpha-SMA, immunoblotting was carried out. Results showed an increase of alpha-SMA expression in lesional skin at 3 weeks of bleomycin treatment, which was reduced following anti-TGF-beta antibody treatment. These data suggest that fibroblastic cells are phenotypically altered into myofibroblasts during the fibrotic process in the experimental model of bleomycin-induced scleroderma, which was considered mediated, for the most part, by TGF-beta. Blockade of TGF-beta may be a therapeutic intervention for scleroderma.
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PMID:Animal model of sclerotic skin. V: Increased expression of alpha-smooth muscle actin in fibroblastic cells in bleomycin-induced scleroderma. 1178 Oct 70

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis and excessive collagen deposition in the skin and various internal organs. In early stages of SSc, the dermis reveals infiltration of inflammatory cells associated with increased collagen synthesis. SKL-2841 was initially synthesized as a novel small molecule antagonist of MCP-1. In this study, we indicated that SKL-2841 also exerts anti-chemotactic activity for MIP-1 beta in mouse spleen cells. In the early stages of bleomycin-induced skin lesions, immunohistochemical analysis showed the expression of both MCP-1 and MIP-1 beta in dermal inflammatory cells. Moreover, intraperitoneal administration of SKL-2841 suppressed the infiltration of inflammatory mononuclear cells and polymorphonuclear cells in the acute phase and also significantly suppressed fibrillization in the chronic phase in bleomycin-induced scleroderma, compared with PBS treatment. These findings suggest that SKL-2841 has potential as a compound for the treatment of conditions associated with skin fibrosis such as SSc.
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PMID:SKL-2841, a dual antagonist of MCP-1 and MIP-1 beta, prevents bleomycin-induced skin sclerosis in mice. 1714 81

Systemic sclerosis (SSc) is a connective tissue disorder of great clinical heterogeneity. Its pathophysiology remains unclear. Our aim was to evaluate the relative roles of reactive oxygen species (ROS) and of the immune system using an original model of SSc. BALB/c and immunodeficient BALB/c SCID mice were injected s.c. with prooxidative agents (hydroxyl radicals, hypochlorous acid, peroxynitrites, superoxide anions), bleomycin, or PBS everyday for 6 wk. Skin and lung fibrosis were assessed by histological and biochemical methods. Autoantibodies were detected by ELISA. The effects of mouse sera on H(2)O(2) production by endothelial cells and on fibroblast proliferation, and serum concentrations in advanced oxidation protein products (AOPP) were compared with sera from patients with limited or diffuse SSc. We observed that s.c. peroxynitrites induced skin fibrosis and serum anti-CENP-B Abs that characterize limited SSc, whereas hypochlorite or hydroxyl radicals induced cutaneous and lung fibrosis and anti-DNA topoisomerase 1 autoantibodies that characterize human diffuse SSc. Sera from hypochlorite- or hydroxyl radical-treated mice and of patients with diffuse SSc contained high levels of AOPP that triggered endothelial production of H(2)O(2) and fibroblast hyperproliferation. Oxidized topoisomerase 1 recapitulated the effects of whole serum AOPP. SCID mice developed an attenuated form of SSc, demonstrating the synergistic role of the immune system with AOPP in disease propagation. We demonstrate a direct role for ROS in SSc and show that the nature of the ROS dictates the form of SSc. Moreover, this demonstration is the first that shows the specific oxidation of an autoantigen directly participates in the pathogenesis of an autoimmune disease.
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PMID:Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse. 1938 Aug 34