Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following a small dose of nephrotoxic serum (NTS) WKY rats demonstrated crescentic glomerulonephritis, which was characterized by the early infiltration of CD8 positive cells in glomeruli. In vivo depletion of CD8 positive cells from WKY rats completely prevented proteinuria (4.6 +/- 4.8 mg/day vs. 105.3 +/- 11.6 mg/day on day 10; N = 19, P less than 0.001) and crescent formation (2.7 +/- 2.9% vs. 94.3 +/- 2.6%; P less than 0.001). Immunofluorescence revealed complete inhibition of the influx of CD8 positive cells and subsequent reduction of the infiltration of macrophages in the glomeruli. Glomerular binding of 125I-anti-rat glomerular basement membrane antibodies, host anti-rabbit IgG production and the C3 level in the circulation were the same as in the control. These data indicate that CD8 positive cells play a key role in glomerular injury and crescent formation. This model provides a useful system for studying the cellular mechanisms that lead to glomerular injury and subsequent crescent formation.
 ...
PMID:Depletion of CD8 positive cells in nephrotoxic serum nephritis of WKY rats. 150 8

Heymann's nephritis (HN), a rat model of the membranous glomerulonephritis in man, is thought to be mediated by auto-Ig with subsequent activation of C. Whether T cell mechanisms are involved in the mediation of HN, apart from CD4+ cells providing help for auto-Ig production, was examined by treatment with mAb specific for T cell subsets for 6 weeks after immunization to induce HN. Anti-CD4 mAb therapy totally prevented proteinuria, in that at 6, 8, and 12 week treated rats had less than 15 mg/day of protein compared to controls that all had greater than 260 mg/day. Ig and C deposition in the glomerulus was significantly less and auto-Ig titers in serum were partially suppressed by anti-CD4 therapy. Anti-CD8 mAb therapy markedly reduced proteinuria at all time points, for example at 6 weeks there was 51 +/- 40 mg/day compared to 183 +/- 120 mg/day (P = 0.0003), but had no effect on auto-Ig titers or on Ig and C deposition in the glomerulus. A non-specific effect of high dose mouse mAb therapy was excluded by the findings that a mAb that did not bind to rat cells had no effect on the induction of HN and that serum C was not depleted in any of the mAb treated animals. A role for T effector mechanisms was further supported by the finding that therapy with mAb to T cell receptor alpha/beta chain or with cyclosporine also markedly delayed the onset of proteinuria. Examination of renal biopsies showed a T cell infiltrate in glomeruli and the interstitium of the untreated HN controls that was not present in MRC Ox35 or MRC Ox8 treated groups. This infiltrate included CD4+ and CD8+ T cells and macrophages. These results suggest induction of proteinuria in HN was totally dependent upon CD4+ T cells, and that CD4+ and CD8+ cells may have a direct role in the mediation of glomerular dysfunction in HN.
 ...
PMID:The role of T cells in the mediation of glomerular injury in Heymann's nephritis in the rat. 159 Dec 15

The effects of biweekly intravenous injections of Staphylococcus Enterotoxin B (SEB) into autoimmune MRL-lpr/lpr (MRL/lpr) mice were investigated. Rather than causing the expansion of V beta 8+ T cells, SEB administration resulted in the reduction V beta 8+, CD4-CD8- "double-negative" (DN) T cells. This was shown by FACS analysis as this putative pathogenic population was diminished in both spleen and lymph node. The symptoms of systemic lupus erythematosus (SLE) in MRL/lpr, which include high titers of anti-DNA antibodies and circulating immune complexes and proteinuria, were reduced in SEB-treated mice in a dose-dependent manner. The clinical parameters of SLE in MRL/lpr, which include lymph node hyperplasia and necrotic vasculitis, were suppressed in 50-micrograms SEB-treated mice. T cells bearing V beta 6 T cell receptor, which does not interact with SEB, were not reduced with SEB administration. Thus, disease suppression was associated with a specific reduction in the number of V beta 8+, DN T cells. These results implicate a possible therapeutic role of superantigen-based immunotherapy in V beta-restricted, T cell-dominated clinical syndromes.
 ...
PMID:Reduction of lupus nephritis in MRL/lpr mice by a bacterial superantigen treatment. 174 80

To study immune reactive and thrombotic mechanisms involved in chronic renal allograft rejection, Lewis rat kidneys were transplanted into bilaterally nephrectomized Brown Norway recipients tolerant of LEW erythrocyte antigens. Such BN rats fail to produce anti class I MHC alloantibodies after insertion of a LEW kidney. The LEW renal allografts experience a transient rejection episode without proteinuria followed by the development of chronic rejection, clinically characterized by glomerular proteinuria in the presence of stable renal function. Immunohistological studies of such chronically rejected LEW renal allografts showed the occurrence of glomerular and interstitial infiltration of predominantly monocytes and T cells. CD4-positive T cells dominated over CD8-positive T cells in the chronically rejected LEW renal grafts. IgG deposition was found deposited throughout the renal vasculature--this in contrast to IgM, which was observed only in the glomerular vasculature. Glomerular antibodies were not directed to endothelial class II MHC antigens, and showed only weak complement fixation as demonstrated by C3 staining. Selective glomerular IgM deposition was associated with vascular (platelet-containing) thrombi, and focal and segmental fibrinoid necrosis. In contrast, acutely rejected LEW renal grafts in unmodified BN recipients showed IgM deposition as well as thrombus formation throughout the entire renal vasculature. The results demonstrate that the antibody response to endothelial--and, in particular, glomerular endothelial non-MHC antigens--may bring about chronic vascular renal allograft rejection. How the formation of glomerular thrombotic lesions may be assisted by endothelial reactivity to cytokines from local immune reactive cells is discussed.
 ...
PMID:Chronic renal allograft rejection. Selective involvement of the glomerular endothelium in humoral immune reactivity and intravascular coagulation. 187 89

The effects of mAb therapy to CD4 or CD8 on induction of unresponsiveness to Heymann's nephritis by preimmunization with renal tubular antigen in IFA. Anti-CD4 mAbs (MRC Ox35) given for 2 weeks after RTA/IFA completely prevented the induction of resistance to HN, all rats developing proteinuria as well as high titers of autoantibody and Ig and C deposits in glomeruli. Anti-CD8 mAbs (MRC Ox8) did not prevent induction of unresponsiveness, even though it totally depleted CD8+ cells. In control rats not preimmunized with RTA/IFA, mAb therapy did not suppress disease induction, but in the case of anti-CD4 therapy enhanced the severity of disease. Persistent depletion of T cell subsets or complement components did not explain the effects of mAb therapy. These studies suggest that CD4+ cells are critical for the induction of unresponsiveness to HN and that therapy with mAb to CD4 can prevent induction of tolerance to an antigen, which has implications for its use in the induction of tolerance.
 ...
PMID:Induction of unresponsiveness to Heymann's nephritis: inhibited by monoclonal antibody to CD4 but not to CD8. 190 70

We examined several immunological parameters such as the number of T cells with CD4 antigen and the receptor for the Fc portion of IgA (T alpha cells), in vitro immunoglobulin production by peripheral blood lymphocytes with or without pokeweed mitogen and serum levels of immune complexes in 19 healthy family members of patients with IgA nephropathy (IgAN). It was shown that the levels of serum IgA, T4 cells, CD4/CD8 ratio of T cell subsets, T alpha cells, IgA circulating immune-complexes and spontaneous synthesis of immunoglobulins were significantly increased in family members of patients with IgAN. No family members had proteinuria or hematuria. It was concluded that immunological abnormalities, including abnormalities of T cells and B cells, were found not only in patients with IgAN but also in their healthy family members. It was suggested that some factors in addition to these immunological abnormalities may be involved in the development of IgAN.
 ...
PMID:Immunological abnormalities in family members of patients with IgA nephropathy. 198 51

In Brown-Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti-glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B-cell polyclonal activation probably due to frequent anti-class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti-class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgCl2 provokes the appearance of non-antigen-specific CD8+ T cells responsible for a depression of T-cell functions. The aim of this work was to test the effect of treatment with an anti-CD8 monoclonal antibody (MoAb) in both BN and LEW rats. Anti-CD8 MoAb-treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury-induced autoimmunity were modified in BN rats. Mercury-induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats the appearance of rare anti-class II T cells showing that these cells are normally present in that strain but negatively controlled by suppressor T cells.
 ...
PMID:Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat. 213 55

A 40-day-old male infant suffered from generalized anasarca, proteinuria and hematuria. Serologic study revealed marked elevation of antibody titer against Treponema pallidum, the same serologic finding was also noted in both his parents. Two weeks of treatment with penicillin was given. The edema subsided 7 days later, and proteinuria and hematuria disappeared 20 days after the initiation of penicillin treatment. At the age of 60 days, all the clinical symptoms and signs vanished; urinalysis and renal function were all within normal limits and renal biopsy was performed. Pathologic study revealed membranous glomerulonephritis with deposition of IgG, IgM and complement C3, C1q, C4 and treponema antigen in the subepithelial area of the glomerular basement membrane. These phenomena suggest that treponemal antigen-antibody complexes were deposited in the glomeruli and activated the classic pathway of complements, leading to an immune complex nephritis. Immunologic study revealed that the patient had high circulating helper T cells (CD4 cells), low level of suppressor T cells (Leu2+15+ cells) with high CD4/CD8 ratio. It was accompanied by detectable circulating immune complex and high titer of T. pallidum hemagglutinin antibody titer. This change suggests that abnormal immune regulation may play an important role in the development of syphilitic glomerulonephritis.
 ...
PMID:Persistent histological and immunological abnormalities in congenital syphilitic glomerulonephritis after disappearance of proteinuria. 325 30

Groups of female MRL/MpJ-lpr/lpr mice received either saline or FK506 (tacrolimus; 2 mg/kg intraperitoneally) three times weekly, cyclophosphamide (CY; 20 mg/kg) once monthly, or both drugs from 8 weeks of age. Median survival for untreated and CY-treated mice was 26 weeks, and for FK506- and FK506 + CY-treated groups was > or = 44 weeks. Severity of skin lesions and lymph node hyperplasia was markedly reduced by the drug combination, whereas either drug alone was less effective. FK506 or CY alone delayed the onset of proteinuria, but by 24 weeks all of these animals were positive. In contrast, drug combination reduced the prevalence of proteinuria to < or = 60% throughout the 44 weeks of study. Sequential monitoring of peripheral blood lymphocytes revealed that combination therapy but not monotherapy markedly reduced the proportion of atypical CD3+ B220+ and CD3+CD4-CD8- T cells. Neither FK506 nor CY affected the reduction in IL-2 and IL-4 mRNA levels observed in lymph nodes of diseased animals compared with normals. Although the drug combination also did not affect IL-2 mRNA levels, IL-4 mRNA transcripts were increased six-fold compared with saline-treated controls. IL-10 and interferon-gamma (IFN-gamma) mRNAs were induced by FK506, CY and by the drug combination. Serum levels of anti-dsDNA antibodies were reduced in all treatment groups. These data demonstrate improved efficacy of combined T and B cell-directed immunosuppression in murine lupus, associated with marked inhibition of atypical T cells and selective augmentation of IL-4 within the affected lymphoid tissue.
 ...
PMID:Combined effects of FK506 (tacrolimus) and cyclophosphamide on atypical B220+ T cells, cytokine gene expression and disease activity in MRL/MpJ-lpr/lpr mice. 753 8

To investigate the beneficial effects of food restriction on systemic lupus erythematosus in NZB x NZW F1 mice, we separated the mice into three groups. One was fed a diet in which total food intake was reduced to 60% of normal from age 2 mo onward, while the animals were still healthy (group 2R). A second group was selected at age 7 mo based on a positive lupus nephritis (proteinuria) and fed the 40% restricted diet thereafter (group 7R); a third group was allowed to consume food ad libitum (control). All control mice died of renal disease by age 14 mo, whereas all mice in group 2R and 80% of those in group 7R were living at that age. Measurements of anti-double stranded DNA antibody concentrations in sera and in supernatants of in vitro spleen cell cultures revealed that the production of the immunoglobulin G, but not immunoglobulin M, class of antibodies was markedly and significantly reduced in food-restricted mice. Age-associated changes in lymphocyte subsets seen in control mice, i.e., increases in B:T and CD4:CD8 T cell ratios, decreases in NTA260+ T cell subsets, and increases in aberrant activated NTA204+CD4+ T cells and cycling cells, were all significantly lessened in underfed mice. Food restriction did not suppress the secondary acquired antibody responses to a foreign antigen. Thus, the beneficial effects of food restriction in these mice may be related to the lessening of the age-related onset of T cell subset abnormalities, including activation of autoreactive T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Food restriction inhibits an autoimmune disease resembling systemic lupus erythematosus in (NZB x NZW) F1 mice. 766 48


1 2 3 4 5 6 7 8 9 10 Next >>