UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interest has recently increased in the role of alloantigen-independent factors in chronic rejection. In this context, we examined the long-term effects of reduced functioning kidney mass in a F344-->LEW allograft (A) model. Animals were divided into three groups depending upon the amount of retained kidney. Renal arterial branches in the hilus were ligated so that one-third or two-thirds of the graft remained viable (1/3 and 2/3 groups, respectively); organs were left intact in the third (3/3) group. Urine protein concentrations were determined 4, 6, 8 and 10 weeks after engraftment and organs (five/group/time) were harvested and examined morphologically and immunohistologically. Proteinuria increased progressively in all 1/3, 2/3 and 3/3A animals, but faster in those with reduced kidney mass. This functional decline correlated well with increasing numbers of macrophages followed by interstitial fibrosis and glomerular sclerosis, which had become prominent by week 6 in group 1/3A and by 8 weeks in groups 2/3A and 1/3I (I, isografted), with animals beginning to die. IL-1, IL-6 and TNF production correlated well with the location and number of macrophages in all groups. These results suggest that kidney mass exerts a significant alloantigen-independent influence on chronic rejection. Allogenicity of the graft accelerates and amplifies the process.
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PMID:The relationship between reduced functioning kidney mass and chronic rejection in rats. 1127 Dec 43

Systemic lupus erythematosus (SLE) is inherited as a complex polygenic trait. (New Zealand Black (NZB) x New Zealand White (NZW)) F(1) hybrid mice develop symptoms that remarkably resemble human SLE, but (NZB x PL/J)F(1) hybrids do not develop lupus. Our study was conducted using (NZW x PL/J)F(1) x NZB (BWP) mice to determine the effects of the PL/J and the NZW genome on disease. Forty-five percent of BWP female mice had significant proteinuria and 25% died before 12 mo of age compared with (NZB x NZW)F(1) mice in which >90% developed severe renal disease and died before 12 mo. The analysis of BWP mice revealed a novel locus (chi(2) = 25.0; p < 1 x 10(-6); log of likelihood = 6.6 for mortality) designated Wbw1 on chromosome 2, which apparently plays an important role in the development of the disease. We also observed that both H-2 class II (the u haplotype) and TNF-alpha (TNF(z) allele) appear to contribute to the disease. A suggestive linkage to proteinuria and death was found for an NZW allele (designated Wbw2) telomeric to the H-2 locus. The NZW allele that overlaps with the previously described locus Sle1c at the telomeric part of chromosome 1 was associated with antinuclear autoantibody production in the present study. Furthermore, the previously identified Sle and Lbw susceptibility loci were associated with an increased incidence of disease. Thus, multiple NZW alleles including the Wbw1 allele discovered in this study contribute to disease induction, in conjunction with the NZB genome, and the PL/J genome appears to be protective.
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PMID:A novel susceptibility locus on chromosome 2 in the (New Zealand Black x New Zealand White)F1 hybrid mouse model of systemic lupus erythematosus. 1188 77

Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine and has multiple physiological function. Its binding to specific receptors produced the reactions of TNF. In sera and urine of healthy persons and diseased patients two soluble types of TNF receptors--p55--sTNF I and p 75--sTNF RII have been detected. They can protect cells against excessive cytotoxic activity TNF-alpha in vitro and in vivo. The aim of the work was to investigate the prognostic significance and role of sTNF R in various types of glomerular diseases. We studied 49 patients with primary glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FS; 4 membranous nephropathy--MN; 12--mesangial proliferative GN--MesPGN; 18 IgA nephropathy--IgAN; and 6 membranoproliferative GR--MPGN) and 10 healthy persons. Renal biopsies were evaluated by light and immunofluorescence microscopy. sTNF RI and sTNF RII concentrations were measured by ELISA (BIOSOURCE International kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days) followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide 0.6 g/l m2/month. The study groups showed a significantly higher concentration of sTNF RI and sTNF RII in their sera and urine compared with the control. In patient groups serum Cr showed significant correlations with interstitial volume in renal biopsy, correlation serum Cr with serum sTNF RI, serum sTNF RI with serum sTNF RII and with urinary sTNF RI, serum sTNF RII with urinary sTNF RI and with urinary sTNF RII. The ratio of serum sTNF RI to serum sTNF RII in patients was unchanged compared to the controls but ratio urinary sTNF RI to sTNF RII was higher in all patient groups except patients with MC. In patients with renal sufficiency (Cr < 1.3 mg%) and reduction of proteinuria > 50% after 1 year treatment urinary secretion of sTNF RII was higher before treatment than in patients with protein reduction < 50%. In patients with renal insufficiency and reduction of proteinuria > 50% urinary excretion of sTNF RI was lower than in patients with lower reduction of proteinuria (< 50%) after 1 year treatment. These results suggest that serum sTNF R could be useful as indicator of clinical disease activity but urinary excretion permits prediction of reduction in proteinuria.
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PMID:[Serum levels and urinary excretion of soluble receptors for tumor necrosis factor (sTNF R) in patients with primary glomerulonephritis]. 1210 79

About half of all the patients with CHF are anemic (they have a hemoglobin of < 12 g%). The prevalence and severity of this anemia increase with increasing severity of the CHF. The anemia is caused by a combination of poor nutrition, associated renal insufficiency causing inappropriately low Erythropoietin (EPO) levels, bone marrow depression and EPO resistance caused by excessive TNF alpha and other factors, gastrointestinal blood loss caused by aspirin, ACE inhibitors, EPO loss in the urine with proteinuria, and hemodilution caused by the excessive plasma volume. Studies have shown that the anemia is an independent risk factor for death in CHF, almost doubling the mortality rate. Correction of the anemia with subcutaneous EPO and IV iron improves cardiac function and functional capacity, helps prevent the progression of renal failure, markedly reduces hospitalization and diuretic doses, and improves self assessed quality of life. This so-called Cardio Renal Anemia Syndrome is very common in CHF. Its successful treatment demands close cooperation between cardiologists and nephrologists.
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PMID:The importance of anemia and its correction in the management of severe congestive heart failure. 1245 37

The objective of the paper was compare the effects and tolerability of combined therapy of multiple intravenous infusions of anti-tumour necrosis factor-alfa (TNF-alfa) monoclonal antibody (Remicade) with methotrexate versus treatment with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis (RA). We investigate also the interval necessary to obtain the improvement in both treatment groups. 36 patients commencing intramuscular sodium aurothiomalate therapy with intramuscular depot methylprednisolone acetate at weeks 0, 4, 8 and 12 in addition to chrysotherapy were compared in retrospective analysis with 32 patients starting with multiple intravenous infusions of infliximab, anti-TNF-alfa monoclonal antibody (Remicade) and methotrexate at a stable dose. Patients were assessed by composite clinical score (DAS 28) and C-reactive protein during 22 weeks of therapy. At week 2 and 6 a significantly greater percentage of infliximab-treated than gold-treated RA patients achieved improvement in each clinical measurement of disease activity. At 22 week of treatment moderate and good response according to EULAR criteria was achieved in 91% of infliximab-treated patients and 58% gold treated patients (p < 0.001). Adverse events were more frequently observed in infliximab-treated patients, but only gold-treated patients discontinued treatment because adverse events (2 patients due to proteinuria, 2 patients due to mucocutaneous changes and one patient due to leucopenia). The higher percentage of adverse events in infliximab-treated patients was caused mainly by the occurrence of infusion reactions (23 reactions out of 160 infusions); most of them were mild (somnolentia and headache) and transient. Viral infections (including herpes simplex and zoster) were more common in patients treated with infliximab and methotrexate. Combination therapy of infliximab and methotrexate is more effective in reducing clinical and biochemical disease activity than gold with methylprednisolone treatment in RA patients during 22 weeks of treatment, especially in the first 6 weeks.
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PMID:[Analysis of efficacy and safety of multiple intravenous infusion of anti-tumor necrosis factor-alpha monoclonal antibody (Remicade) combined with methotrexate compared with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis]. 1268 46

In sera and urine of healthy and diseased patients two soluble types of TNF receptors--p55--sTNF RI and p75--sTNF RII have been detected. They can protect cells against excessive cytotoxic activity of TNF-alpha in vitro and in vivo. The aim of the study was to investigate the prognostic significance and role of sTNF R in various types of glomerular diseases. We studied 49 patients with primary glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FSGN; 4 membranous nephropathy--MN; 12 mesangial proliferative GN--MSPGN; 18 IgA nephropathy--IgAN; and 6 membranoproliferative GN--MPGN) and 10 healthy persons. Renal biopsies were evaluated by light and immunofluorescence microscopy. STNF RI and sTNF RII concentrations were measured by ELISA (BIOSOURCE international kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days) followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide 0.6 g/1 m2/month. The studied groups showed a significantly higher concentration of sTNF RI and sTNF RII in their sera and urine when compared with the control. In patient groups serum Cr showed significant correlations with volume of interstitial tissue in renal biopsy, correlation of serum Cr with serum sTNF RI, serum sTNF RI with serum sTNF RII and with urinary sTNF RI, serum sTNF RII with urinary sTNF RI and with urinary sTNF RII. The ratio of serum sTNF RI to serum sTNF RII in patients was unchanged compared to the controls but ratio of urinary sTNF RI to sTNF RII was higher in all patient groups except patients with MC. In patients with renal sufficiency (Cr < 1.3 mg/dl) and reduction of proteinuria > 50% after 1 year of therapy urinary secretion of sTNF RII was higher before treatment than in patients with protein reduction < 50%. In patients with renal insufficiency and reduction of proteinuria > 50% urinary excretion of sTNF RI was lower than in patients with lower reduction of proteinuria (< 50%) after 1 year of therapy. Our results suggest that serum sTNF R could be useful as indicator of clinical activity of the disease and urinary excretion of soluble receptors as a predictor of effectiveness of immunosuppressive therapy.
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PMID:[Serum concentration and urinary excretion of soluble receptors for tumor necrosis factor in patients with primary glomerulonephritis]. 1497 72

B cell-activating factor belonging to the TNF family (BAFF) blockade prevents the onset of disease in systemic lupus erythematosus (SLE)-prone NZB/NZW F(1) mice. To determine the mechanism of this effect, we administered a short course of TACI-Ig with and without six doses of CTLA4-Ig to 18- to 20-wk-old NZB/NZW F(1) mice and evaluated the effect on B and T cell subsets and on anti-dsDNA Ab-producing B cells. Even a brief exposure to TACI-Ig had a beneficial effect on murine SLE; CTLA4-Ig potentiated this effect. The combination of TACI-Ig and CTLA4-Ig resulted in a temporary decrease in serum IgG levels. However, after cessation of treatment, high titers of IgG anti-dsDNA Abs appeared in the serum and IgG Abs deposited in the kidneys. Despite the appearance of pathogenic autoantibodies, the onset of proteinuria was markedly delayed; this was associated with prolonged depletion of B cells past the T1 stage, a decrease in the size of the spleen and lymph nodes, and a decrease in the absolute number of activated and memory CD4(+) T cells. TACI-Ig treatment normalized serum levels of IgM that are markedly elevated in NZB/W F(1) mice; this appeared to be due to a prolonged effect on the ability of the splenic microenvironment to support short-lived IgM plasma cells. Finally, a short course of combination TACI-Ig and CTLA4-Ig prolonged life and even reversed proteinuria in aged NZB/W F(1) mice, suggesting that BAFF blockade may be an effective therapeutic strategy for active SLE.
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PMID:Mechanism of action of transmembrane activator and calcium modulator ligand interactor-Ig in murine systemic lupus erythematosus. 1532 17

A persistent proteinuria is commonly observed in nephrotic patient with focal segmental glomerulosclerosis (FSGS) under treatment with prednisolone+/-cyclophosphamide or with vasodilators (ACEI+AII receptor antagonist, calcium channel blocker and antiplatelet agent). Fourteen such patients with persistent proteinuria were subject to be treated with Ganoderma lucidum. Initial study revealed an enhanced endothelial cell cytotoxicity induced by patient's serum, and an altered immunocirculatory balance with predominant proinflammatory cytokine TNF alpha activity in the presence of defective anti-inflammatory cytokine interleukin-10. Treatment with Ganoderma lucidum suppressed endothelial cell cytotoxicity, restored immunocirculatory balance and successfully suppressed proteinuria in all of these 14 patients.
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PMID:Ganoderma lucidum suppresses endothelial cell cytotoxicity and proteinuria in persistent proteinuric focal segmental glomerulosclerosis (FSGS) nephrosis. 1556 96

TNF is essential for the development of glomerulonephritis, an immune-mediated disorder that is a major cause of renal failure worldwide. However, TNF has proinflammatory and immunosuppressive properties that may segregate at the level of the 2 TNF receptors (TNFRs), TNFR1 and TNFR2. TNFR1-deficient mice subjected to immune complex-mediated glomerulonephritis developed less proteinuria and glomerular injury, and fewer renal leukocyte infiltrates at early time points after disease induction, and this was associated with a reduced systemic immune response to nephrotoxic rabbit IgG. However, proteinuria and renal pathology were similar to those in wild-type controls at later time points, when lack of TNFR1 resulted in excessive renal T cell accumulation and an associated reduction in apoptosis of these cells. In sharp contrast, TNFR2-deficient mice were completely protected from glomerulonephritis at all time points, despite an intact systemic immune response. TNFR2 was induced on glomerular endothelial cells of nephritic kidneys, and TNFR2 expression on intrinsic cells, but not leukocytes, was essential for glomerulonephritis and glomerular complement deposition. Thus, TNFR1 promotes systemic immune responses and renal T cell death, while intrinsic cell TNFR2 plays a critical role in complement-dependent tissue injury. Therefore, therapeutic blockade specifically of TNFR2 may be a promising strategy in the treatment of immune-mediated glomerulonephritis.
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PMID:Renal cell-expressed TNF receptor 2, not receptor 1, is essential for the development of glomerulonephritis. 1584 Dec 13

GM-CSF has previously been demonstrated to be important in crescentic glomerulonephritis (GN). As both renal parenchymal cells and infiltrating inflammatory cells produce GM-CSF, their separate contributions to inflammatory renal injury were investigated by creation of two different types of GM-CSF chimeric mice: (1) GM-CSF-deficient (GM-CSF-/-)-->wild-type (WT) chimeras with leukocytes that are unable to produce GM-CSF and (2) WT-->GM-CSF-/- chimeras with deficient renal cell GM-CSF expression. Crescentic anti-glomerular basement membrane GN was induced in WT, GM-CSF(-/-)-->WT chimeras, WT-->GM-CSF-/- chimeras, and GM-CSF-/- mice by planting an antigen (sheep globulin) in their glomeruli. WT mice developed severe crescentic GN, whereas GM-CSF-/- were protected from development of disease. Glomerular T cell recruitment, CD40+ glomerular cells, and renal IFN-gamma and TNF expression were similar in both chimeras and WT mice but significantly reduced in GM-CSF-/- mice, indicating that either leukocyte or renal sources of GM-CSF are sufficient to drive these aspects of the inflammatory response. Restricted expression of GM-CSF revealed a major role for renal cell-derived GM-CSF but a minor role for leukocyte-derived GM-CSF in the formation of cellular crescents; glomerular MHC II expression; serum creatinine; and monocyte chemoattractant protein-1, vascular cellular adhesion molecule, and IL-1beta expression. Glomerular macrophage accumulation, proteinuria, and interstitial infiltrate were equivalent in both chimeric groups but intermediate between WT and GM-CSF-/-, indicating that both sources are required for the full development of glomerular injury in crescentic GN.
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PMID:Granulocyte macrophage colony-stimulating factor expression by both renal parenchymal and immune cells mediates murine crescentic glomerulonephritis. 1603 60

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