Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mercuric chloride (HgCl2) induces in Brown Norway (BN) rats an autoimmune disease characterized by a biphasic glomerulonephritis (GN). A transient nephrotic syndrome occurs during the third and fourth weeks after the first HgCl2 injection. Related to nephrotic syndrome, an hypercoagulable state develops with decreased factor XII and anti-thrombin III (AT III) levels and increased factor V activity and fibrinogen concentration. Moreover, during the same period, most of the rats were found thrombocytopenic. The presence of soluble fibrin monomer complexes and of fibrin degradation products (FDP) in the plasma of these rats associated with fibrin thrombi in glomerular capillary lumen proved the occurrence of disseminated intravascular coagulation (DIC). DIC was responsible for the death of several rats but most of these survived and clotting abnormalities were no longer found. Numerous factors can explain the occurrence of DIC in this model: anti glomerular basement membrane antibodies, circulating immune complexes, complement activation and/or glomerular endothelial cell detachment. The HgCl2 induced autoimmune disease appears as a good experimental model to study the relation between coagulation process and glomerulonephritis.
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PMID:Involvement of hemostasis during an autoimmune glomerulonephritis induced by mercuric chloride in brown Norway rats. 622 1

In Brown-Norway (BN) rats, oral administration of mercuric chloride (HgCl2) induced morphological lesions of the ileum and, in lesser degree, of the colon, with abnormal deposits of IgA in the basement membranes of intestinal glands and of IgG in the basement membranes and in the lamina propria. IgG reactive with renal and intestinal basement membranes and in the lamina propria. IgG reactive with renal and intestinal basement membranes and with the lamina propria of a normal BN rat was found in the serum and IgG deposits were present in renal glomeruli of BN rats receiving HgCl2. Thus, it is conceivable that the deposits of IgG present in the intestine resulted from local fixation of circulating autoantibodies. In contrast, IgA with basement membrane reactivity was not detected in the sera nor in the renal glomeruli, suggesting that the intestinal deposits of IgA were formed in situ. This IgA-IgG intestinal disease inducible in BN rats may provide a model for the study of alterations of the secretory IgA system, as well as for testing the possibility that abnormal deposits IgA-IgG in the intestinal structures are associated with local functional changes.
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PMID:IgA-IgG disease in the intestine of Brown-Norway rats ingesting mercuric chloride. 623 Jan 86

Mercuric chloride injections in the Brown Norway rat induce the transient formation of anti-glomerular basement membrane (GBM) autoantibodies. Transfer of spleen cells from convalescent animals, after circulating anti-GBM autoantibodies are no longer detectable, inhibits reinduction of the disease by HgCl2 in naive recipients. This inhibition is significantly less when the T suppressor cell population is depleted by the monoclonal antibody, MRC OX8 , before transfer. Our studies suggest a role for T suppressor cells in autoregulation in this animal model of autoimmune nephritis and may form a basis for the design of specific therapy for anti-GBM disease in man.
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PMID:Autoregulation of autoantibody synthesis in mercuric chloride nephritis in the Brown Norway rat. I. A role for T suppressor cells. 623 59

Plaque-forming cell (PFC) assays were used to investigate in vitro the immunoregulatory mechanism operating in the self-limiting anti-glomerular basement membrane (GBM) autoantibody response of Brown Norway (BN) rats given HgCl2. The peak splenic PFC response occurred at day 9; thereafter the response fell sharply and was rarely detected after day 12. In specificity studies, incorporation of soluble GBM in the PFC assays of animals at day 9 had two distinct effects. In some animals the PFC response was inhibited in a dose-dependent fashion; however, in others an augmented number of PFC was observed. Furthermore, addition of GBM to the PFC mixture from certain animals studied at day 12 (or after) revealed large numbers of GBM-specific PFC when originally no GBM-specific PFC had been observed in the standard PFC assay. Sera from such animals, with and without antigen-augmentable PFC, were incorporated in the PFC mixture containing cells taken from day 9 animals. Sera from animals with revealed plaques could inhibit the GBM-specific PFC response of day 9 animals, whereas sera from animals without revealed plaques could not. Thus sera, from BN rats whose own antibody levels were falling, could inhibit the GBM-specific plaque-forming capability of cells from animals at an earlier stage of the autoimmune response and showed the potential importance of humoral factors, putatively antiidiotypic antibodies, in effecting autoregulation of autoantibody formation in this model.
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PMID:Autoregulation of autoantibody synthesis in mercuric chloride nephritis in the Brown Norway rat. II. Presence of antigen-augmentable plaque-forming cells in the spleen is associated with humoral factors behaving as auto-anti-idiotypic antibodies. 623 60

Transpositional mutagenesis of the mer operon of the IncFII plasmid, R100, has revealed a second, trans-acting positive regulatory function. Mutants in this function do not synthesize any of the three small mer operon peptides and have no inducible Hg(II) uptake activity. This second regulatory function is part of complementation group B and so depends upon the activity of the previously described trans-acting positive regulatory function merR. All mutants in this new function map in the amino-terminal 20 kDal of the Hg(II) reductase, suggesting either that this enzyme is also a regulatory protein or that there is a distinct protein whose reading frame is superimposed on that of the Hg(II) reductase. While we have only seen the five previously described mer operon peptides of 69, 66, 15.1, 14 and 12 (13) kDal encoded in minicells by single-copy plasmids, we have observed two new HgCl2-inducible polypeptides of approx. 20 kDal in minicells carrying a multicopy derivative of the mer operon of R100. Sequence data for the Hg(II) reductase region of the related mer operon of the transposon, Tn501 [Brown, N.L., Ford, S.J., Pridmore, R.D. and Fritzinger, D.C., Biochemistry 22 (1983) 4089-4095], shows a second reading frame very rich in cysteine and arginine which overlaps the amino-terminal 20 kDal of the Hg(II) reductase structural gene. We believe that this reading frame is the structural gene for this new regulatory function and propose the name merC (for control).
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PMID:A second positive regulatory function in the mer (mercury resistance) operon. 631 37

Susceptibility to HgCl2-induced glomerulonephritis was transferred to resistant Lewis (LEW) rats, irradiated and reconstituted with (LEW X BN)F1 hybrid immunocompetent cells. This glomerulonephritis was similar to that observed in Brown-Norway (BN) rats with a first stage characterized by anti-glomerular basement membrane antibodies and a second stage with immune complex-type deposits in the glomerular tufts and in the small renal arteries.
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PMID:Induction of susceptibility to HgCl2 immune glomerulonephritis in the Lewis rat by immunocompetent cells from susceptible F1 hybrids. 644 8

The present study demonstrates that mercuric chloride (HgCl2) induces a striking increase of total serum IgE in Brown Norway (BN) rats. Values up to several milligrams of IgE per milliliter of serum were observed. No antibody specificity was demonstrated for these IgE. Mercuric chloride also potentiated a specific anti-ovalbumin IgE response when the rats were immunized with ovalbumin. The kinetics of the response to HgCl2 was different from that to an antigenic stimulus alone: total IgE increased together with the potentiated anti-ovalbumin IgE antibody response to reach maximum values about 14 days after initiation of HgCl2 injections. The potentiated IgE antibodies represented only an insignificant fraction of total IgE. All these findings were observed in BN but not in Lewis rats. These data show analogies with those reported after parasitic infection in the rat and suggest similar mechanisms of action.
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PMID:Induction of IgE synthesis and potentiation of anti-ovalbumin IgE antibody response by HgCl2 in the rat. 700 42

Recent data has suggested a role for nitric oxide (NO) both in the induction of immunity and as an effector of tissue injury in experimental models of inflammation. In this study, we have tested the efficacy of two inhibitors of NO synthase, NG-monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG), to modify the autoimmune leucocytoclastic necrotizing vasculitis which develops following the administration of mercuric chloride (HgCl2) to the Brown Norway rat. Neither agent affected the induction of autoimmunity as judged by plasma IgE titres or the degree of tissue neutrophil infiltration; however, L-NMMA did significantly attenuate tissue injury scores. We conclude that inhibition of NO synthase does not influence the induction of autoimmunity by HgCl2, but that NO does contribute to the development of tissue injury in this experimental model.
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PMID:Nitric oxide contributes to tissue injury in mercuric chloride-induced autoimmunity. 750 30

CHIP28 is a major water transporting protein in erythrocytes and kidney which forms tetramers in membranes (Verbavatz, J. M., Brown, D., Sabolic, I., Valenti, G., Ausiello, D. A., Van Hoek, A. N., Ma, T., and Verkman, A. S. (1993) J. Cell Biol. 123, 605-618). To determine whether CHIP28 monomers function independently, chimeric cDNA dimers were constructed which contained wild-type CHIP28 in series with either wild-type CHIP28, a non-water transporting CHIP28 mutant (C189W), or a functional but mercurial-insensitive CHIP28 mutant (C189S). Transcribed cRNAs were injected in Xenopus oocytes and plasma membrane expression was assayed by quantitative immunofluorescence. Water channel function was measured by osmotically induced swelling. CHIP28 homo- and heterodimers were targeted to the oocyte plasma membrane and functioned as water channels. Relative osmotic water permeability (Pf) values (normalized for plasma membrane expression of monomeric subunits) were: 1.0 (CHIP28 monomer), 0.0 (C189W), 1.07 (C189S), 1.10 (CHIP28-CHIP28 dimer) and 0.52 (CHIP28-C189W). The increase in oocyte Pf was linearly related to plasma membrane expression of wild-type CHIP28 and C189S subunits. HgCl2 (0.3 mM) inhibited channel-mediated Pf in oocytes expressing wild-type CHIP28 monomers and dimers by 85-90%, but did not inhibit Pf in oocytes expressing C189S. HgCl2 inhibited Pf in oocytes expressing CHIP28-C189S dimers by 44 +/- 7%, consistent with one mercurial-sensitive and one insensitive subunit in the heterodimer. These results indicate that despite their assembly in tetramers, monomeric CHIP28 subunits function independently as water channels.
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PMID:Functional independence of monomeric CHIP28 water channels revealed by expression of wild-type mutant heterodimers. 751

The phosphodiesterase inhibitor oxpentifylline (OXP) has a number of potentially important immunomodulatory actions which include a selective inhibition of the Th1 subset of CD4+ cells in vitro and inhibition of tumor necrosis factor (TNF)-alpha mRNA transcription. In vivo, it has a dramatic protective effect against experimental allergic encephalomyelitis. In this animal model, tissue injury is associated with both a Th1 response and with TNF-alpha production, either of which could be targets for the protective action of OXP. In an attempt to clarify the relative importance of the Th cell subsets and TNF-alpha in pathogenesis, we investigated the effect of OXP on a Th2 model of T cell-dependent disease, mercuric chloride (HgCl2)-induced autoimmunity in the Brown Norway rat. The effects of OXP on the Th1:Th2 response, TNF-alpha mRNA transcription in spleen and ankle joints, and on the incidence and severity of arthritis and cecal vasculitis have been examined and the effects in vivo have been compared with those of a soluble TNF receptor-IgG1 fusion protein (sTNFR) that neutralizes rat TNF-alpha. In two separate experiments, OXP significantly enhanced unstimulated levels of splenic interleukin-4 (IL-4) mRNA (median 62%, of an artificial IL-4 mRNA construct, vs. 36.5% in controls) and in one experiment, exaggerated the total IgE response to HgCl2. OXP inhibited HgCl2-induced TNF-alpha mRNA transcription in spleen and ankle joints. In three separate experiments, OXP had a significant protective effect against arthritis, with the mean incidence reduced from 100% to 30% and mean peak score reduced from 7.2 to 2.59 (experiments 1 and 2). The protection against arthritis was indistinguishable from that produced by sTNFR. There was no such protection against cecal vasculitis with either OXP or sTNFR. These results demonstrate that OXP induces a shift towards a Th2 response, inhibits TNF-alpha mRNA transcription locally in joint and systemically in spleen, and has a protective effect against arthritis similar to that produced by sTNFR in the HgCl2-treated BN rat. We conclude that TNF-alpha is a critical cytokine in the pathogenesis of arthritis but not cecal vasculitis in this model, and that inhibition of TNF-alpha transcription is the most important mode of action of OXP in this situation. OXP may be a potential therapeutic agent in the treatment of other arthritides, such as human rheumatoid arthritis, in which TNF-alpha has been implicated in pathogenesis.
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PMID:Oxpentifylline inhibits tumor necrosis factor-alpha mRNA transcription and protects against arthritis in mercuric chloride-treated brown Norway rats. 758 90


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