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)

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.
 ...
PMID:Nephropathies and exposure to perchloroethylene in dry-cleaners. 135 33

A postulated mechanism of immune glomerular injury is a direct interaction between antibody and glomerular epithelial cell (GEC) surface antigens. To explore this hypothesis, we examined the interaction of the noncomplement-fixing gamma 2-subclass of sheep anti-rat nephrotoxic serum (NTS), which causes immediate complement- and neutrophil-independent proteinuria in vivo, with rat GECs in culture. Reactivity of NTS with GEC surface antigens was determined by positive immunofluorescence of GEC plasma membranes and by the ability of NTS-coated tissue culture wells to provide an adhesive substrate for GECs. NTS immunoprecipitated two proteins (135 and 118 kDa) from surface-labeled GECs. Proteins of similar molecular mass were precipitated by a polyclonal rabbit antibody that identifies the beta 1-integrin chain of the mouse fibronectin receptor (anti-FnR). In addition, NTS identified similarly sized bands on Western blot analysis of cell membranes from isolated rat glomeruli. Similar reactivity was eluted from the glomeruli of proteinuric rats injected with NTS. NTS significantly inhibited GEC adhesion to laminin, types I and IV collagen, and fibronectin and prevented GEC spreading on types I and IV collagen. Anti-FnR similarly inhibited GEC adhesion. Cell viability was not affected. These results show that NTS recognizes a pair of GEC surface proteins that have the characteristics of an alpha- and beta 1-integrin and, at low concentrations, disrupt cell-matrix interactions.
 ...
PMID:Nephrotoxic antiserum identifies a beta 1-integrin on rat glomerular epithelial cells. 137 74

In order to investigate the renal change in preeclampsia, molecular weight and specific protein analyses in unconcentrated urine were performed by the immunoblot method. Urine samples were taken from 34 preeclamptic cases (pure type), including 20 severe cases. Polypeptide profiles of urine consisted of four patterns: low MW (L) pattern (tubular damage), high MW (H) pattern (glomerular damage), high and low MW (HL) pattern, and middle MW (M) pattern. The incidences of the HL, H, L, and M patterns were 26.5%, 14.7%, 11.8%, and 47.1%, respectively. The HL pattern was found more frequently in severe proteinuria than in mild proteinuria. High incidences of the HL and H patterns were found in the hypertensive group. Larger amounts of IgM, fibronectin, IgG, and beta 2 microglobulin in urine were confirmed using specific antibodies. Our results suggest that the immunoblot method makes it possible to differentiate glomerular and tubular damages and to evaluate the severity of renal damage in preeclampsia using unconcentrated urine.
 ...
PMID:Analysis of urinary protein by immunoblot method using unconcentrated urine in preeclampsia. 138 Feb 35

Chronic progressive membranous nephropathy (MN) in humans is characterized by thickening of the glomerular basement membrane (GBM) with formation of spikes which contain laminin and other extracellular matrix (ECM) proteins. We have utilized two models of MN in the rat (active and passive Heymann nephritis, AICN, PHN) to define the sequential changes in composition of GBM as they relate to changes in glomerular gene expression for ECM components, altered permeability and morphological changes. Renal biopsies obtained during the course of AICN and PHN were immunostained for various ECM proteins and total glomerular RNA was hybridized with cDNA probes specific for laminin B2-chain, s-laminin, and types I and IV collagen. In addition, the ability of anti-glomerular epithelial cell (GEC) antibody and complement on rat GEC in culture to induce laminin release or laminin and s-laminin mRNA expression was determined. The results demonstrate that at weeks 12, 16, and 20 of AICN, immunostaining for laminin, s-laminin, fibronectin, entactin, and heparan sulfate proteoglycan increased in the GBM in a spike-like pattern. Concomitantly, glomerular mRNA levels of laminin B2-chain and of s-laminin increased. Type IV collagen protein and gene expression remained unchanged or decreased. No glomerular immunostaining for type I collagen occurred during AICN despite increased expression of mRNA for this collagen type. In contrast to AICN, in PHN no pronounced changes of the glomerular ECM occurred, except for transient expression of type I collagen mRNA in whole glomerular RNA and type I collagen protein the GEC cytoplasm. Stimulation of GEC in culture with anti-GEC antibody and complement also failed to induce transcription of laminin or s-laminin mRNA or the release of laminin protein. These findings suggest that the polyantigenic expansion of GBM which occurs in chronic experimental MN may be stimulated by factors different from the C5b-9 mediated processes that cause the initial proteinuria.
 ...
PMID:Altered glomerular extracellular matrix synthesis in experimental membranous nephropathy. 138 96

The pathogenesis of diabetic nephropathy relative to the changes in the glomerular extracellular matrices was investigated. Renal tissues from 10 diabetic patients were immunostained with antibodies directed against heparan sulfate proteoglycans (HS-PGs), laminin, type IV collagen and fibronectin. Seven patients were nephrotic and had advanced glomerulosclerosis with nodular lesion, while the other 3 had no renal manifestations or minor glomerular tissue alterations. Controls included kidneys removed from patients with renal tumors and specimens obtained by renal biopsy from patients with IgA nephropathy. Relationships among proteinuria, intensity of fluorescence and glomerular changes were studied. In diabetes 3 patients with minor glomerular lesions were found to have no changes in various components of extracellular matrices. A marked reduction in the intensity of staining with anti-HS-PG antibodies was observed in renal specimens from patients with nodular glomerulosclerosis and proteinuria, while a mild decrease in the intensity of fluorescence was observed in tissues stained with antilaminin antibodies. An increase compared to normal control sample findings in type IV collagen and fibronectin was observed in the mesangium of sclerosing glomeruli. No loss of HS-PG was observed in patients with IgA nephropathy. These results indicate that glomerular extracellular matrix HS-PG is lost in association with diabetic nephropathy; this loss results in alteration of the charge-selective properties of glomerular capillaries. This alteration may, in part, be the cause of the proteinuria associated with diabetic nephropathy.
 ...
PMID:Heparan sulfate proteoglycans are lost in patients with diabetic nephropathy. 150 38

The present study describes the development of membranous glomerulopathy (MGP) with high proteinuria in DZB rats exposed to mercuric chloride (HgCl2). IgG1 and IgG2a antibodies, eluted from glomeruli with subepithelial immune deposits, bind to the interface of the GBM and epithelial cells. High reactivity to GBM was demonstrated by ELISA and Western blotting, which could be absorbed for 30% by laminin or laminin-associated extracellular matrix components. No reactivity was found with type IV collagen, fibronectin, heparan sulfate proteoglycans, or tubular brush border antigens. Absorption to GBM removed the reactivity to renal antigens. Passively transferred eluted antibodies bind in a predominantly linear pattern along the GBM, causing focal ultrastructural transformations of the podocytes. These results suggest that this type of HgCl2-induced MGP, associated with epithelial cell injury and proteinuria, is caused by autoantibodies to basement membrane components which are located at the epithelial cell-basement membrane interface and may be involved in cell-matrix binding.
 ...
PMID:Antigenic specificities of glomerular-bound autoantibodies in membranous glomerulopathy induced by mercuric chloride. 159 88

After immunization of mice with partially-purified heparan sulfate proteoglycan (HSPG) isolated from rat glomeruli, a monoclonal antibody (mAb JM-403) was obtained, which was directed against heparan sulfate (HS), the glycosaminoglycan side chain of HSPG. In ELISA it reacted with isolated human glomerular basement membrane (GBM) HSPG, HS and hyaluronic acid, but not with the core protein of human GBM HSPG, and not with chondroitin sulfate A and C, dermatan sulfate, keratan sulfate and heparin. Furthermore, it did not bind to laminin, collagen type IV or fibronectin. Specificity of JM-403 for HS was also suggested by results of inhibition studies, which found that intact HSPG and HS, but not the core protein, inhibited the binding of JM-403 to HS. In indirect immunofluorescence on cryostat sections of rat kidney, a fine granular to linear staining of the GBM was observed, along with a variable staining of the other renal basement membranes. Pretreatment of the sections with heparitinase completely prevented the binding of mAb JM-403, whereas pretreatment with chondroitinase ABC or hyaluronidase had no effect. The precise binding site of mAb JM-403 was investigated by indirect immunoelectron microscopy. It revealed a diffuse staining of the whole width of the GBM. One hour after intravenous injection of JM-403 into rats, the mAb was detected along the glomerular capillary wall in a fine granular pattern, which shifted towards a more mesangial localization after 24 hours. No binding was observed anymore by day 15. Intravenous injection induced a dose-dependent, transient and selective proteinuria that was maximal immediately after the injection.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. 159 46

The changes in glomerular extracellular matrices components in diabetic nephropathy were investigated. Indirect immunofluorescence staining, using polyclonal antibodies to heparan sulfate proteoglycan (HS-PG), laminin, type IV collagen, and fibronectin was carried out on renal specimens obtained by needle biopsy. Immunofluorescence intensity and distribution were observed. HS-PG and laminin decreased in the capillary walls; on the other hand, type IV collagen and fibronectin tended to increase in the mesangial area. HS-PG and laminin decreased in inverse proportion to sclerosis grades and proteinuria. These changes seemed to play an important role in progression of diabetic glomerulosclerosis.
 ...
PMID:Changes in glomerular extracellular matrices components in diabetic nephropathy. 177 41

Immunohistochemical and light microscopic examinations were carried out to assess the correlation between the progression of glomerular lesions and changes in the intensity of glomerular extracellular components such as type IV and I collagens, laminin and fibronectin, and of IgA deposits in repeated renal biopsies of patients with IgA nephropathy. By light microscopy, the percentage of glomeruli showing glomerular mesangial expansion or sclerosis was found to be significantly higher in the second renal biopsy. Type IV collagen, laminin and fibronectin were also marked in the expanded glomerular mesangium in the second biopsy. Although these components were not observed in the global sclerotic glomeruli, type I collagen was detected in such areas of patients with IgA nephropathy. Patients who revealed high percentages of glomerular sclerosis associated with marked type IV collagen, laminin, fibronectin and/or type I collagen, had high levels of proteinuria and progressive deterioration of renal function. It is concluded that hyperproduction of the above extracellular components mainly in the glomerular mesangium is closely linked to the progression of glomerular lesions in patients with IgA nephropathy.
 ...
PMID:Immunohistochemical studies of glomerular extracellular components in repeated renal biopsies of patients with IgA nephropathy. 177 39

Plasma fibronectin (Fn) levels and activities of antithrombin III (AT-III) function were determined in 219 cases, including 61 cases of pregnancy-induced hypertension (PIH) and 127 normal pregnant women and 31 normal nonpregnant women as controls. The plasma Fn levels of PIH patients were significantly increases to 539.04 +/- 256.3 mg/L, while the plasma AT-III activities were significantly lowered to 76.1 + 13.9%. There was a negative correlation between plasma Fn and AT-III in PIH patients (r = -0.377, P less than 0.01). High plasma Fn and low plasma AT-III in PIH were related to proteinuria. Plasma AT-III decreased as PIH became more severe. The results suggested that the high plasma Fn with low AT-III levels may serve as an indicator of the severity of PIH.
 ...
PMID:[Changes of plasma fibronectin and antithrombin III in pregnancy-induced hypertension]. 200 75


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