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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histochemical and functional properties of mast cells (MC) in Brown Norway rats recovering from chronic treatment with the MC secretagogue compound 48/80 were examined. In the skin, treatment for 5 days with compound 48/80 resulted in a marked decrease in MC subpopulations defined by differential alcian blue/safranin staining. Both safranin-positive connective tissue MC and alcian blue staining MC were reduced in number. This was accompanied by significant decreases in skin histamine and rat MC serine protease I contents and a loss of specific IgE-mediated passive cutaneous anaphylaxis (PCA) activity. The PCA reaction did not return to normal before 2 months after stopping treatment and only when the numbers of safranin-positive connective tissue MC and skin histamine content reached pretreatment levels. The subepidermal alcian blue staining MC not eliminated by the compound 48/80 treatment were formalin resistant (unlike alcian blue staining mucosal MC of the intestine) and apparently played no role in the PCA response. MC numbers, histamine levels, and rat MC serine protease I content of the tongue were similarly decreased by compound 48/80. In contrast, mucosal MC of the gut were unaffected by the secretagogue treatment.
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PMID:Mast cell recovery following chronic treatment with compound 48/80. 752 91

Gram-negative septic episodes are a potential risk of small-bowel transplantation; bacterial translocation through the graft is considered the mechanism. As a measure to prevent this complication, we evaluated postoperative selective bowel decontamination (SBD) in the rat model of orthotopic small-bowel transplantation [Lewis (LEW) and Brown-Norway (BN) rats as donors and recipients]. For 4 days after transplantation we gave FK 506, 2 mg/kg, which prevents rejection and results in indefinite recipient survival. For SBD, 24 mg/kg/day polymyxin E and 20 mg/kg/day tobramycin were administered via orogastric gavage to allograft recipients, both with and without FK 506 therapy. On Day 9, all rats were sacrificed, the peritoneal cavity was swabbed, and mesenteric lymph nodes (MLN), spleen, liver, and ileum were harvested for microbial qualitative and quantitative analysis. Animals with positive peritoneal swab cultures were excluded. SBD resulted in a significant reduction of the quantitative gram-negative bacterial flora in the ileum and cecum and of bacterial translocation to the MLN [0% versus 50% (no FK 506 therapy) and 8% versus 50% (FK 506 treated)]. In the allograft groups not treated with FK 506, SBD failed to significantly prolong survival, suggesting that acute rejection is not hastened by infection (bacterial translocation). We conclude that SBD in small-bowel-graft recipients prevents bacterial translocation by reducing intestinal gram-negative bacterial flora; this may reduce local and systemic infections by gut-derived organisms.
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PMID:Postoperative selective bowel decontamination prevents gram-negative bacterial translocation in small-bowel graft recipients. 753 86

Mercuric chloride (HgCl2) induces an autoimmune syndrome in the Brown Norway (BN) rat which includes widespread tissue injury. There is necrotizing leucocytoclastic vasculitis in the gut with maximal injury occurring 2 weeks after the start of HgCl2 injections. There is evidence that disease is driven by Th2-like cell (CD4+CD45RClow) activity and that Th1-like cells (CD4+CD45RChigh) may be protective. Using the established protocol of five injections of HgCl2 over 10 days, we have studied in greater detail the presence and extent of vasculitis and changes in T cell subsets from 12 h to 20 days after the first injection. Animals were killed at various time points and necropsies performed. Tissue injury was scored both macroscopically and histologically, with immunohistochemistry for T cell subsets. Flow cytometry was used to determine T cell subsets in peripheral blood, mesenteric lymph node (LN) and spleen. Tissue injury was seen as early as 24 h after the first injection of HgCl2. The size of lesions and extent of vasculitis increased over the next two weeks with partial resolution at day 20. We confirmed that of peripheral blood T cells in the BN rat, less than 20% were CD8+ and a similar proportion were CD4+CD45RChigh, but found that less than 75% of CD8+ T cells were CD45RChigh (in other strains of rat more than 90% CD8+ T cells are CD45RChigh). Within 48 h, HgCl2 caused a rise in the proportion of CD4+ T cells in spleen, LN and peripheral blood which then fell towards normal at peak tissue injury. The proportion of CD4+CD45RClow T cells rose in the first week, but subsequently fell, with reciprocal changes in CD4+CD45RChigh T cells. There was an increase in CD8+ T cells towards peak disease. The speed of onset of tissue injury suggests that cells other than T cells may be involved in the primary induction of vasculitis, although Th2-like cells may be important in further tissue injury and in B cell activation. The rise in CD8+ and Th1-like cells towards peak disease supports the hypothesis that they are involved in disease regulation.
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PMID:The time course and characterization of mercuric chloride-induced immunopathology in the brown Norway rat. 761 48

The biologic role and repertoire of cells bearing the gamma delta T cell receptor has not been fully defined. However, their tropism for epithelial microenvironments is recognized and suggests an important role for these cells in immune defense at mucosal tissue surfaces. The study presented below utilizes an experimental model in which repeated exposure of Brown Norway rats to OVA by inhalation induces a state of Ag-specific, IgE isotype-specific "tolerance" via immune deviation. This process seems similar to oral tolerance in the gut. This form of tolerance was adoptively transferred to naive syngeneic recipients by i.p. injection of as few as 10(3) positively selected TCR-gamma delta+ cells from OVA-exposed rats. These TCR-gamma delta+ T-cells are demonstrated to produce high levels of INF-gamma in response to OVA stimulation, and this provides a potential mechanism for the inhibition of Th2 cell proliferation, resulting in suppression of IgE production. The unique potency of these cells in selective suppression of IgE Ab production in response to natural "mucosal" Ag exposure suggests a potentially important role in protection against primary allergic sensitization in vivo.
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PMID:Gamma delta T cells down-regulate primary IgE responses in rats to inhaled soluble protein antigens. 772 96

The plasma level of mucosal mast-cell protease was examined to find whether such measurements could be an indicator of allergic response to beta-lactoglobulin (beta-LG) challenged orally by rats. Brown Norway rats, which had been raised on a bovine milk-free diet, were systemically sensitized on day 0 with a low dose of beta-LG, and then by an oral administration of beta-LG for 3 h on day 14. The oral challenge with beta-LG in saline, when compared to saline alone, resulted in a systemic elevation of rat mast-cell protease II (RMCPII), one of the specific markers for gut mucosal mast-cell secretion. The challenge with beta-LG in a fat emulsion further increased the level of plasma RMCPII. This manipulation, however, was not successful for detecting any significant difference in mucosal leucotriene C4, another allergic mediator. An oral challenge with polymerized beta-LG did not induce any elevation of the protease, but resulted in a lower plasma level of beta-LG-specific IgG. This animal model is thus relevant to investigate the events regulating the mucosal hypersensitivity and humoral immunity to food proteins.
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PMID:Systemic release of mucosal mast-cell protease in primed brown Norway rats after feeding with beta-lactoglobulin. 778 91

Mercuric chloride (HgCl2) induces autoimmunity in Brown Norway (BN) rats, with necrotizing vasculitis in the gut. Circumstantial evidence implicates the Th2 subset of CD4+ T lymphocytes, which produces IL-4. We developed a quantitative polymerase chain reaction (PCR) technique to quantify IL-4 gene expression. A phagemid containing rat IL-4 cDNA was modified to act as the template for a synthetic RNA construct; a known amount of synthetic RNA was added to total RNA from spleen and caecum of BN rats at various times after HgCl2, followed by reverse transcriptase PCR. IL-4 gene expression increased markedly in spleen and caecum after HgCl2. Splenic levels peaked by 10 days at approximately five-times baseline, then returned towards normal as the autoimmune response was spontaneously regulated. Caecal IL-4 expression peaked at 48 h, at which time we observed a previously unreported early phase of tissue injury, with necrotizing vasculitis qualitatively similar to that reported previously in the later phases of the model. These data support a key role for IL-4 in this experimental model of autoimmunity. The quantitative PCR technique can be modified for analysis of other cytokines, allowing further investigation of the role of T cell subsets in this model.
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PMID:Interleukin-4 gene expression in mercury-induced autoimmunity. 787 86

Necrotizing leucocytoclastic vasculitis is the histopathological hallmark of the small vessel systemic vasculitides (SV), a group of human diseases commonly associated with anti-neutrophil cytoplasm autoantibodies (ANCA). Necrotizing vasculitis is seen in a number of experimental systems, but none of these provide an ideal animal model for human SV. Vasculitis occurs in serum sickness reactions; in murine models of systemic lupus erythematosus; in association with infection, particularly chronic viral infections; and after treatment with certain drugs or inflammatory mediators. 'Spontaneous' vasculitis has been reported in specific mouse strains, especially with ageing, and in some larger species. The size of vessel involved and the type of inflammatory cells predominating are variable in these experimental situations, and none of these models feature antibodies analogous to ANCA. We have recently reported that Brown Norway rats treated with mercuric chloride (HgCl2) develop necrotizing leucocytoclastic vasculitis, especially in the gut, and also develop antibodies to myeloperoxidase (MPO) which recognize similar determinants on MPO to those bound by a subset of ANCA. Transfer of serum from HgCl2-treated rats to naive animals does not induce tissue injury. Preliminary experiments using pooled immunoglobulin or an anti-CD4 monoclonal antibody did not show useful therapeutic benefit from these treatments. HgCl2-induced vasculitis has weaknesses as an animal model of human SV, but is the only experimental model in which anti-MPO autoantibodies have so far been demonstrated, and therefore may be of particular relevance to ANCA-associated SV.
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PMID:Animal models of systemic vasculitis. 838 93

Azo dyes, the largest portion of manufactured dyestuffs, are primarily used as colouring substances in food, textiles, and the plastic industry. It has been estimated that 128 tonnes per annum of dyes are released into the environment worldwide [Anliker, 1977]. Certain azo compounds are known to be mutagenic in bacterial tests [Yahagi et al., 1975; Venitt and Bushell, 1976; Brown et al., 1978]. Watersoluble dyes are biotransformed by intestinal micro-organisms in the gastro intestinal tract, and the toxicity, mutagenicity, and carcinogenicity of these dyes in the gut or liver may be attributed to their metabolites. Since it is desirable to have a genotoxic evaluation of a chemical being released into the environment in order to check their indiscriminate use, a project has been initiated to determine the mutagenicity of the azo dyes being used commercially. The present report deals with the results of 13 dyes tested in Salmonella typhimurium with and without metabolic activation.
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PMID:Screening of azo dyes for mutagenicity with Ames/Salmonella assay. 840 79

In the Brown-Norway rat, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by high IgE levels. There is widespread necrotizing leukocytoclastic vasculitis involving lung, skin, mucous membranes, pancreas, liver, and gut, with tissue injury being most marked in the cecum. As in systemic vasculitis in man, there are neutrophils at the site of tissue injury and the animals develop anti-neutrophil cytoplasmic antibodies, which in the Brown-Norway rat are directed against myeloperoxidase. To determine whether neutrophils are involved in the pathogenesis of the vasculitis, we have used a monoclonal antibody that was reported to deplete neutrophils in other rat strains. Rats treated with HgCl2 received antibody by intravenous injection at various time points. Serial blood samples were taken for neutrophil counts and to assay for anti-myeloperoxidase and IgE antibodies. The guts of animals killed after antibody therapy were scored for vasculitic changes and neutrophils infiltrate. RP3 (but not the control antibody MAC6) was shown to bind to Brown-Norway rat neutrophils and to block glycogen-induced influx of neutrophils into the peritoneum. When given at peak disease, RP3 caused a dose-dependent reduction in tissue injury with a marked reduction in circulating blood neutrophil numbers and in tissue neutrophil infiltrate. RP3 treatment did not affect the rise in titer of IgE and anti-myeloperoxidase antibodies. The data presented demonstrate that in this model neutrophils are necessary for the induction of vasculitis and that the degree of vasculitis correlates with neutrophil number. To our knowledge, this study is the first to provide direct evidence for a role for neutrophils in vasculitis. We suggest that antibodies directed against neutrophils, especially if they deplete neutrophils, may be useful in the therapy of vasculitis in man.
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PMID:Role of neutrophils in the pathogenesis of experimental vasculitis. 868 65

The strong association of anti-neutrophil cytoplasmic antibodies with various forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the present study, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats bad developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 micrograms of a human neutrophil lysosomal extract containing 200 micrograms of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and 14 after systemic infection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Control immunized rats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes were found in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associated vasculitides.
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PMID:Systemic injection of products of activated neutrophils and H2O2 in myeloperoxidase-immunized rats leads to necrotizing vasculitis in the lungs and gut. 921 39


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