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)

Antibodies directed against antigens present on renal epithelial cells can cause membranous glomerulonephritis in experimental animals, which closely resembles the human form of this disease. However, most antibodies produced so far fail to cause the persistent and severe proteinuria that is seen in humans. In our search for new antibodies of this kind, we have now produced a monoclonal antibody (mAb) against mouse aminopeptidase A, a hydrolase that is present in the mouse kidney. The mAb (ASD-4) was prepared by fusion of mouse myeloma cells with splenocytes of Lou rats immunized with brush border (BB) membranes from mouse kidneys. ASD-4 is of the IgG1 subclass and reacts with a 140-kD protein as demonstrated by immunoprecipitation on radiolabeled BB membranes. In indirect immunofluorescence and immunoelectronmicroscopy of normal mouse kidneys, ASD-4 was diffusely present on the BB of the S1 and S2 segments of the proximal tubules, and on the cell membranes of the glomerular visceral epithelia. It also bound to cell membranes of nonglomerular endothelia, smooth muscle cells of arteries, and juxtaglomerular cells. After injection of ASD-4 into normal mice, an immediate homogeneous binding to the capillary wall was seen that gradually changed into a fine granular pattern after 1 d. This glomerular binding was followed by binding to the BB and basolateral membranes of the convoluted proximal tubules. Immediately after injection of ASD-4, a dose-dependent albuminuria occurred that lasted for at least 16 d. ASD-4 is thus a new rat mAb against a well-defined renal epithelial antigen that causes not only membranous glomerulonephritis after a single injection in the mouse, but also severe albuminuria.
 ...
PMID:A nephritogenic rat monoclonal antibody to mouse aminopeptidase A. Induction of massive albuminuria after a single intravenous injection. 174 Jun 57

Six welders who had been exposed to high cadmium concentrations were monitored for 5 years after cessation of exposure. Indicators of exposure and effect had shown marked alterations during exposure, with 3 subjects showing low molecular weight proteinuria (beta 2-microglobinuria), one of whom with total proteinuria as well. During the follow-up period, beta 2-microglobinuria increased up to a maximum in 2 subjects; in another subject, after a temporary increase, beta 2-microglobinuria returned to normal levels after 5 years. Urinary enzyme excretion had exceeded normal values during exposure; during the follow-up, brush border enzyme excretion was persistently high (only angiotensin converting enzyme activity showed a progressive reduction), whereas cytoplasmatic enzyme values returned to normal one year after cessation of exposure.
 ...
PMID:[Biological indicators of the renal involvement in workers with previous exposure to cadmium: a 5-year follow up]. 180 16

Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not yet been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent) (15 mg/kg body weight). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of beta 2-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome platers and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chronic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced exposure may produce persistent renal injury. The absence of evidence of chromate-induced chronic renal disease cannot be interpreted as evidence of the absence of such injury. Rather, it must be recognized that no prospective cohort or case-control study of the delayed renal effects of low-level, long-term exposure to chromium has been published.
 ...
PMID:Chromium-induced kidney disease. 193 54

A chelator, dichloromethane diphosphonate (Cl2MDP), used to treat for malignancy-induced hypercalcemia, has nephrotoxic potential. An acute animal model developed to examine the mechanism was used to further characterize the renal effects. NAG enzymuria appears to be an early premonitor of injury. Ultrastructurally, an increase in size and number of protein-containing phagolysosomal reabsorption droplets in proximal convoluted tubules associated with proteinuria precedes advent of tubular cell necrosis indicating these organelles to be a potential target site for Cl2MDP in the kidney. In vitro studies using rabbit cortical tubules and rat brush border membrane vesicle preparations suggest that the renal toxicity is not due to perturbation of phosphate transport or oxidative metabolism. An operational hypothesis emerges indicating that Cl2MDP may be protein bound affecting carrier protein charge facilitating glomerular leakage with tubular accumulation via protein transport. Cl2MDP may induce critical cation perturbation at the subcellular level as the mechanism of cell death.
 ...
PMID:Characterization of the early ultrastructural and biochemical events occurring in dichloromethane diphosphonate nephrotoxicity. 215 Dec 1

Effects of cadmium intoxication on renal transport systems for various amino acids were studied. Subcutaneous injections of CdCl2, at a dose of 2 mg Cd/kg.day for 2 weeks, resulted in polyuria, proteinuria, glycosuria, phosphaturia, and aminoaciduria, as observed in chronic cadmium-intoxicated humans and experimental animals. The nature of aminoaciduria was nonspecific, including iminoacid as well as almost all species of neutral, acidic, and basic amino acids. In renal cortical brush border membrane vesicles isolated from cadmium-intoxicated rats, Na(+)-dependent transport of L-proline, L-alanine, and L-lysine was markedly attenuated, whereas the amino acid transport in the basolateral membrane vesicle was not significantly affected. Similar results were obtained in the normal membrane vesicles directly exposed to inorganic cadmium. These results indicate that cadmium intoxication impairs various Na(+)-amino acid cotransport systems in the renal brush border membrane, which leads to panaminoaciduria.
 ...
PMID:Alteration of renal amino acid transport system in cadmium-intoxicated rats. 225 75

A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal beta-N-acetyl-glucosaminidase (beta-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, gamma-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein 'SGP-240' and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cis-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both 'soluble' and high-molecular-weight membrane particles (vacuolar blebs, greater than 10(6) dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular 'histuria' which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase.
 ...
PMID:Urinary proteins of tubular origin: basic immunochemical and clinical aspects. 225 76

As a contribution to the noninvasive diagnosis of kidney damage, polyclonal antisera specifically directed against brush border surface glycoproteins of the proximal tubule of the human kidney were used in radioimmunoblotting studies for the assessment of kidney-tissue proteinuria. Urine specimens from healthy controls, from patients (n = 41) with various forms of renal involvement and from those suffering from symptomatic HIV-infection (AIDS) but having normal kidney function, were investigated for the excretion of kidney-derived membrane proteins. After SDS-polyacrylamide gel electrophoresis of urine samples and electroblotting of protein bands on nitrocellulose sheets, followed by incubation with the antibody and subsequently with 125I-labelled protein A, 3 major tubular glycoproteins (Mr 240 000, 160 000, 120 000) were revealed by autoradiography. The results indicate and increased shedding of epithelial membrane glycoproteins in the urine of patients with kidney lesions, and they also demonstrate the suitability of radioimmunoblotting for the determination of such tissue-antigens ("brush border-histuria").
 ...
PMID:Tubule-derived membrane glycoproteins in the urine of patients (including those with AIDS) as analysed by radioimmunoblotting. 231 34

The present studies dealt with the pathogenesis of renal involvement in murine chronic graft-versus-host disease, which is a model for human systemic lupus erythematosus. The disease was induced in (C57BL10xDBA/2)F1 hybrids by injection of DBA/2 lymphocytes. The animals developed systemic disease accompanied by deposition of autoantibodies in the glomeruli and a lupus type of nephritis. Antibodies were eluted from glomeruli isolated during various stages of the disease by magnetic extraction from iron-perfused kidneys. For assessment of the specificity of the antibodies, we used indirect immunofluorescence, an enzyme-linked immunosorbent assay, and immunoblotting. In glomeruli from week 4, autoantibodies were found to be directed against several antigens, among which were the glomerular basement membrane component laminin and the glomerular enzyme dipeptidyl peptidase IV, whereas week 8 glomeruli also showed antibodies directed against nuclear antigens. Both laminin and dipeptidyl peptidase IV are known nephritogenic antigens occurring in renal tubular epithelial brush border preparations. Antibodies eluted from isolated glomeruli of diseased animals bound in a granular pattern along the glomerular capillary wall after in vivo transfer. Anti-renal tubular epithelial antibodies in the sera of diseased animals were affinity purified and injected into naive mice, which induced immune complex glomerulonephritis and proteinuria, thus confirming the nephritogenic role of these autoantibodies in this model.
 ...
PMID:Characterization and in vivo transfer of nephritogenic autoantibodies directed against dipeptidyl peptidase IV and laminin in experimental lupus nephritis. 239 30

Effects of cadmium intoxication on renal transport systems for various organic compounds were studied. Subcutaneous injections of CdCl2 (2 mg Cd/kg.day) for two to three weeks induced marked polyuria, glycosuria, and proteinuria without altering glomerular filtration rate. In renal cortical brush border membrane vesicles (BBMV) isolated from cadmium treated rats, Na(+)-dependent D-glucose uptake was markedly attenuated, and this was due to reduction in Vmax and not Km. Likewise, Na(+)-driven L-glutamate transport and H(+)-driven tetraethylammonium transport were significantly reduced. In renal cortical basolateral membrane vesicles (BLMV) of cadmium intoxicated rats, Na(+)-dependent succinate transport was drastically reduced. These results indicate that cadmium intoxication impairs various transport systems for organic compounds in the brush border and basolateral membranes of proximal renal tubules.
 ...
PMID:Transport of organic compounds in renal plasma membrane vesicles of cadmium intoxicated rats. 240 86

The present study was conducted to determine if Fx1A, a renal cortical extract used to induce Heymann nephritis, contains nephritogenic antigens in addition to the brush border-derived glycoprotein gp 330. Of 26 Lewis rats immunized with Fx1A, 24 developed abnormal proteinuria (greater than 20 mg/24 hr) by wk 10, whereas of 15 rats immunized with a partially purified gp 330 preparation (MVH), only one developed proteinuria. Immunofluorescence studies showed that all Fx1A rats developed large, diffuse, granular deposits along the glomerular basement membrane which stained brightly for IgG and C3; only 11 of the 15 MVH rats had definite deposits; in most rats, they were small and stained only moderately for IgG and faintly or not at all for C3. The Fx1A and MVH rats developed comparable levels of antibodies to MVH (gp 330) before the onset of proteinuria in Fx1A rats, after which serum IgG and antibody levels declined. In contrast, antibodies against soluble Fx1A antigens appeared earlier and rose more rapidly in Fx1A than in MVH rats. Larger amounts of IgG could be eluted from the glomeruli of Fx1A rats than from MVH rats. Eluates from the Fx1A rats contained antibodies that reacted with gp 330 and also a 95 kd antigen; the latter reactivity was not demonstrated in eluates of MVH rats. Immunoprecipitation studies showed that both gp 330 and the 95 kd antigen are components of normal glomeruli. The results show that immunization with Fx1A produces a more severe form of Heymann nephritis than does gp 330, and that Fx1A contains at least one nephritogenic antigen in addition to gp 330.
 ...
PMID:Characterization of antigens and antibody specificities involved in Heymann nephritis. 241 95


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