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)

We administered a 12-week course of cyclosporine (CsA) (4 to 6 mg/kg/24 h) to nephrotic patients with membranous glomerulopathy (MG). Nephrotic patients with minimal change nephropathy (MCN) served as a comparison group. We evaluated the effects of CsA on proteinuria, glomerular function, and the release of cytokines by peripheral blood mononuclear cells in culture. Proteinuria was restored to normal levels within 2 to 4 weeks in MCN. Proteinuria declined from nephrotic to subnephrotic levels (< 3,500 mg/24 h) in 10 of 14 patients with MG, also within 2 to 4 weeks of onset of therapy. The four nonresponders exhibited a rapidly progressive and presumably irreversible form of MG culminating in renal failure. On average, fractional clearances of albumin and IgG declined by 59% and 73% in MG (P < 0.005); corresponding declines in MCN were by 99% (P < .0001). Corresponding rates of glomerular filtration in each glomerular injury remained unchanged. A strong trend for proteinuria to relapse after CsA was withdrawn was evident in both disorders. The release of tumor necrosis factor (TNF)-alpha by mononuclear cells in culture was enhanced in each glomerular injury, both before and after the course of CsA. We conclude that the proteinuria in most cases of MG exhibits a responsiveness to CsA that is qualitatively similar to, but less complete than, that in MCN. The rapidity with which barrier function improves suggests a possible role for cell-mediated immune injury in MG.
 ...
PMID:Short-term responsiveness of membranous glomerulopathy to cyclosporine. 848 28

To investigate the role of dietary components in immunoglobulin A mesangial nephropathy (IgAGN), this study focused on gliadin, based on the reported association between coeliac disease and IgAGN as well as the pilot observation that a gluten-free diet was able to reduce the levels of circulating IgA immune complexes (IgAIC). IgA mesangial deposits in mice were induced by oral immunization with gliadin and in rats by inducing alcoholic liver cirrhosis, which increased the levels of IgA against dietary antigens (Ag). Gliadin was able to bind to cultured mesangial cells by a lectinic bond, which was reversed by competitive sugars. Binding increased mesangial cell tumor necrosis factor synthesis and decreased prostaglandin E2 production. Several gluten lectinic fractions modulate leukocyte oxidative metabolism, cytotoxicity, and chemotaxis. In IgAGN patients, serum IgA to dietary Ag were sporadically positive and IgAIC containing IgA to dietary components were significantly increased. The affinity of serum IgA to various lectins was increased in some patients. Conversely, no substantial deposition in renal tissue of dietary Ags was observed by immunofluorescence. A gluten-free diet, given to IgAGN patients with high levels of circulating IgAIC and positive antigliadin IgA, was followed by a decrease in the mean levels of both IgAIC and IgA to various dietary Ag, parallel to a reduction in proteinuria. These data suggest that dietary components, such as Ag or lectins, may play a role in IgAGN by promoting IgAIC formation and perhaps favoring mesangial localization via lectinic interactions.
 ...
PMID:Dietary antigens and primary immunoglobulin A nephropathy. 160 Jan 33

The production of tumor necrosis factor (TNF) by nephritic glomeruli and glomerular macrophages was studied in antiglomerular basement membrane antibody induced glomerulonephritis (anti-GBM GN) in rabbits. Autologous phase injury was associated with glomerular macrophage infiltration and augmented TNF production by isolated nephritic glomeruli (day 8, 1.15 +/- 0.10 ng/10(3) glomeruli/24 hours; normal, 0.01 +/- 0.01 ng/10(3) glomeruli/24 hours; p less than 0.05). In contrast, during the heterologous phase, in which macrophages were not prominent, injury was not associated with augmented glomerular TNF production. Glomerular TNF bioactivity had a molecular weight and isoelectric point consistent with rabbit TNF and was inhibitable by an anti-TNF antibody. TNF was also identified in nephritic glomerular supernatants by Western blotting. Macrophages isolated from glomeruli of rabbits developing autologous phase anti-GBM GN produced significantly more TNF (0.14 +/- 0.02 ng/10(3) macrophages/24 hours) than blood monocytes (0.03 +/- 0.02 ng/10(3) monocytes/24 hours, p less than 0.05) from the same rabbits. Macrophage depletion of rabbits with autologous phase anti-GBM GN significantly reduced proteinuria, prevented glomerular macrophage accumulation, and blocked augmentation of glomerular TNF production. These studies demonstrate the association of glomerular TNF production with the development of glomerular macrophage infiltration and injury in anti-GBM GN and suggest that infiltrating glomerular macrophages are the major source of glomerular TNF.
 ...
PMID:Tumor necrosis factor production by glomerular macrophages in anti-glomerular basement membrane glomerulonephritis in rabbits. 189 Aug 5

Phytohemagglutinin (PHA), a leukocyte mitogen, induces a lymphocyte and blast cell glomerulonephritis in rat renal allografts (Cell Immunol 13:146, 1974). The aim of this study was to assess whether PHA similarly enhances rabbit monocyte-dependent experimental, acute immune complex glomerulonephritis, and whether this effect is associated with local release of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Rabbits with experimental acute serum sickness (AcSS: Group I) had focal proliferative and exudative glomerulonephritis with immune deposits, scattered subepithelial electron-dense deposits (humps), mild and transient proteinuria, normal creatinine clearance and slightly increased production of IL-1 and TNF from isolated glomeruli. Rabbits with AcSS and injected with PHA (Group II) developed severe lymphocyte and blast cell glomerulonephritis with diffuse endothelial damage; immune deposits were significantly reduced, focal subepithelial electron-dense deposits were absent, proteinuria was increased, creatinine clearance was decreased and production of IL-1 and TNF was markedly augmented as compared to rabbits in Group I. Rabbits with AcSS and injected with IL-1 beta and TNF alpha (Group V) had lesions comparable to those seen in Group II. These results show that PHA, IL-1 and TNF enhance the severity of acute immune complex glomerulonephritis, presumably by activating glomerular endothelial and mesangial cells and resident or infiltrated leukocytes.
 ...
PMID:Effect of leukocyte stimulation on rabbit immune complex glomerulonephritis. 215 83

OK-432 (a streptococcal preparation) has been widely used for cancer immunotherapy in Japan. It is a potent immunostimulator, activating macrophages and T lymphocytes, and increasing the production of TNF and several other cytokines in both humans and animals. In the present study, we evaluated the prophylactic effect of OK-432 on the development of autoimmune kidney disease in NZB/W F1 (BWF1) mice. The mice were given 0.5 or 2.0 KE ('klinische Einheit'; clinical unit) of OK-432 intraperitoneally every week from 21 weeks of age to the time of death. The control group received the same volume of saline (vehicle). OK-432 delayed the development of proteinuria and prolonged the survival of these mice dose dependently. At 49 weeks, 33.3% of control mice were alive, whereas 55.6% in the 0.5-KE- and 75% in the 2.0-KE-treated mice were alive. In the control group, the serum cholesterol level increased due to the development of glomerulonephritis. In contrast, mice treated with OK-432 had significantly lower levels of serum cholesterol. The serum levels of anti-DNA and anti-TNP antibodies were not affected by OK-432 administration. OK-432 induced the production of tumor necrosis factor (TNF)-alpha in the peritoneal fluid in the BWF1 mice. These results indicate that the effect of OK-432 in preventing the development of autoimmune disease in the mice may result from the stimulation of the endogenous TNF-alpha production.
 ...
PMID:The biological response modifier OK-432 (a streptococcal preparation) inhibits the development of autoimmune kidney disease in NZB/W F1 hybrid mice: possible involvement of tumor necrosis factor. 280 78

We investigated the effect of the potent immunosuppressive agent, FK506, on experimental glomerular thrombosis in rats by combined injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS). Either FK506 or placebo was administered intramuscularly three hours prior to injection of NTS that was followed one hour later by LPS. Rats were killed five hours after the LPS injection. Compared with placebo, FK506 pretreatment significantly reduced thrombosis formation, in a dose-dependent manner. FK506 also reduced proteinuria and the rise of serum creatinine level. Early infiltration of polymorphonuclear leukocytes into the glomeruli after LPS injection was significantly suppressed in the FK506 group compared with the placebo group. We also measured serum tumor necrosis factor (TNF) activity by using an L929 fibroblast cytotoxicity assay. Peak serum TNF activity was observed one hour after LPS injection, and FK506 significantly suppressed the elevation. Thrombosis was also developed in athymic nude rats, suggesting thrombosis formation is T cell independent. These data suggest that the FK506 has inhibitory effects on non-lymphocytes and possesses an anti-inflammatory effect in vivo.
 ...
PMID:FK506 inhibits renal glomerular thrombosis induced in rats by nephrotoxic serum and lipopolysaccharide. 752 50

In the present study, urinary tumor necrosis factor-alpha (TNF) levels in nonproliferative glomerulopathies [minimal change disease (n = 4), focal glomerulosclerosis (n = 4), membranous glomerulonephritis (GN) (n = 1), and in patients with chronic glomerulopathies (n = 4)] were compared to proliferative ones [a rapidly progressive GN patient and 8 patients with mesangial proliferative GN and membranoproliferative GN (MPGN) who had clinically active disease]. The mean urine TNF levels of the proliferative group were significantly higher than both the nonproliferative GN and 4 controls, whereas the mean value of the nonproliferative group was not significantly different than the controls. The urine TNF levels in 4 MPGN patients with chronic disease and in 2 who entered remission were also very low. In the patients with active renal disease and cellular proliferation there were significant correlations between the urinary TNF levels and both proteinuria and the clinical activity scores. We suggest that in human proliferative glomerulopathies TNF may be implicated in the glomerular inflammation.
 ...
PMID:Urinary tumor necrosis factor levels in primary glomerulopathies. 819 Jan 81

We studied mRNA and protein expression of interleukins (IL) and tumor necrosis factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis. Immunofluorescent staining with antibodies to IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which were dual-stained with an anti-monocyte-macrophage antibody. In addition, moderate immunofluorescence for TNF-alpha, and weak staining for IL-1 alpha and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1 alpha, IL-6, and TNF-alpha mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta were also observed in the interstitium. Most of these cells were also labeled with the anti-monocyte-macrophage antibody. The number of IL-1 alpha, IL-6, and TNF-alpha-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1 alpha, IL-6, IL-8, and TNF-alpha was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1 alpha, IL-6, and TNF-alpha expression in glomeruli or interstitium and serum or urinary levels of the respective cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:In situ expression of cytokines in IgA nephritis. 825 57

Cell-mediated immunity and monocyte infiltration is a prominent histologic feature of several different types of glomerulonephritis. Monocyte influx to the glomerulus correlates with glomerular hypercellularity and proteinuria. Glomerular mesangial cells, in addition to being targets for inflammatory stimuli, are also effector cells that actively participate in glomerular pathology. Mesangial cells release monocyte chemotactic protein (MCP-1). In the present article, we characterized and studied the regulation of MCP-1 released by cultured human mesangial cells. Serum-deprived mesangial cells constitutively release chemotactic activity that is neutralized by specific anti-MCP-1 antibody. An antibody to baboon MCP-1 recognized 16, 15, and 11 kd proteins from concentrated conditioned medium that were consistent with the presence of different forms of MCP-1. Gamma interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1) markedly stimulate the release of MCP-1 as measured by a specific and sensitive radioimmunoassay. The release of MCP-1 in response to these cytokines is at least partially dependent on de novo synthesis of the protein because all three cytokines markedly stimulate the expression of MCP-1 mRNA. These data demonstrate that human mesangial cells synthesize and release at least three different forms of MCP-1 and that IFN-gamma and other cytokines regulate the secretion of MCP-1. IFN-gamma and MCP-1 may play a major role in the recruitment and activation of monocytes to the inflamed glomerulus.
 ...
PMID:Gamma interferon stimulates monocyte chemotactic protein (MCP-1) in human mesangial cells. 830 Dec 5

Interferon-inducible protein (IP)-10 is a small glycoprotein member of a family of chemotactic cytokines structurally related to interleukin-8. We have recently described the induction of IP-10 mRNA in mouse mesangial cells stimulated with lipopolysacharide, interferon-gamma, and tumor necrosis factor-alpha. To further evaluate a possible role for this chemokine in renal injury, we have studied IP-10 in an experimental model of nephrosis induced in rats by adriamycin. High levels of glomerular IP-10 mRNA expression and glomerular and tubulointerstitial IP-10 protein were seen on day 21, coinciding with maximal proteinuria, glomerular tumor necrosis factor mRNA expression, and interstitial cellular infiltrates. Maintenance on a low protein diet not only delayed the appearance of proteinuria and interstitial cellular infiltrate but also decreased glomerular IP-10 mRNA expression. Isolated normal glomeruli and cultured glomerular epithelial and mesangial cells from normal rats expressed IP-10 mRNA upon stimulation with 100 U/ml interferon or 1 microgram/ml lipopolysaccharide for 3 hours. IP-10 mRNA expression was also inducible by lipopolysaccharide and cytokines in NRK 49F renal interstitial fibroblasts and, to a lesser extent, in NRK 52E tubular epithelial cells. Furthermore, IP-10 protein was inducible in murine mesangial cells. We conclude that IP-10 is highly inducible in vitro and in vivo in resident glomerular and tubulointerstitial cells. IP-10 may participate in the modulation of renal damage in experimental nephrosis.
 ...
PMID:Interferon-inducible protein-10 is highly expressed in rats with experimental nephrosis. 854 19


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