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

The Authors discuss the etiologic, pathogenetic and immunopathologic aspects of Heymann nephritis, in order to compare the numerous acquisitions concerning this nephropathy with the scanty knowledge of human membranous nephropathy, of which it represents the experimental counterpart. This rat disease can be obtained by inoculation of tubular brush border preparations (active form) or of the relevant antibodies (passive form); after an initial hypothesis of glomerular deposition of circulating immune complexes, studies on its pathogenetic mechanisms, instead demonstrated that in situ immunoaggregates, caused by an interaction between circulating antibodies and fixed glomerular antigens, are formed. Recent investigations have led to the identification of a major nephritogenic antigen (gp330), which is a tubular brush border glycoprotein expressed by coated pits located at the glomerular epithelial cell surface. Studies on antigen-antibody interactions at this level have demonstrated that there is a quick redistribution and accumulation of the so-formed immune complexes, and when polyclonal antibodies were utilized, growth of subepithelial electron dense deposits was observed. Although other tubulo-glomerular antigens, which can also be expressed by endothelial cells, play an uncertain role, they seem to favour transmembrane passing of anti-gp330 antibodies. Immune complex formation gives rise to the onset of proteinuria through complement system activation, without leukocyte involvement: in particular a MAC and C9 fraction lytic effect was demonstrated on cultured epithelial cells. In conclusion, studies on Heymann nephritis contribute to our understanding of the etiopathogenetic mechanisms regarding human membranous nephropathy, and emphasize a possible role played by tubular antigens and in situ formed immune complexes.
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PMID:[Etiopathogenesis of membranous nephropathy: is there a correlation between experimental and human pathology?]. 248 93

The excretion profiles of the following marker proteins of glomerular and tubular origin were studied in patients suffering from chronic renal disease (GN, N = 36, GFR: 8 to 120 ml/min/1.73 m2): angiotensinase A (ATA), a glomerular endothelial glycoprotein, tubular ala(-leu-gly)-amino-peptidase-M (APM), gamma-glutamyl transpeptidase (GGT), and the major brush border surface glycoprotein (SGP-antigen) of 240 kD. In addition, urinary excretion of proteins from kidney tissue and serum from 30 patients undergoing chronic hemodialysis (RCDT) were analyzed. Compared to the controls, ATA, APM and GGT activities were significantly higher in urine specimens of patients with GFR greater than 25 ml/min, whereas the urinary APM, GGT and SGP concentrations were decreased, and correlated with the GFR. Urinary GGT activity was negatively correlated with ATA activity but positively correlated with the decrease in GFR. Urine ATA activity of RCDT patients was higher compared to normal controls (2P = 0.001). Urinary excretion of serum proteins of RCDT patients, as assessed by SDS-polyacrylamide gel electrophoresis, disclosed heavy tubular proteinuria, indicating predominant tubular rather than glomerular alterations in handling of proteins. Histochemical evaluation of kidney sections from RCDT patients revealed clusters of hypertrophic nephrons with increased glomerular and tubular concentration of immunoreactive membrane proteins. However, there was a general decrease in renal cell-marker concentrations as observed by quantitative image analyses. These results indicate that renal injury is associated with a modulation in the synthesis of tubular and glomerular cell markers.
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PMID:Glomerular and tubular membrane antigens reflecting cellular adaptation in human renal failure. 263 72

Advances in biomedical technology have contributed effectively to the resolution of basic and clinical problems in Nephrology. Most of our insights on glomerular diseases come from animal models. Antibodies against components of the extracellular matrix have been shown to induce glomerular changes in vivo and the non-collagenous NC1 domain of type IV collagen has been demonstrated to contain the Goodpasture antigen. New pathogenetic mechanisms of glomerular injury are suggested by studies on the interaction of antibodies with glomerular cell surface antigens. Gp330, a glycoprotein expressed at the surface of glomerular visceral epithelial cells, has been recognized to be the most relevant antigen of Heymann nephritis. Antibodies able to crosslink gp330 bind to the antigen at the base of foot processes and the resulting immune complexes are shed into the subepithelial space where they form electron dense deposits. The complement membrane attack complex (C5b-9) is likely to be directly responsible for epithelial cell injury and proteinuria in this model. Other cell surface antigens of the glomerular capillary wall, such as dipeptidyl dipeptidase IV, podocalyxin, podoendin, have been characterized. A novel model of glomerular injury comes from the demonstration that a non-complement fixing monoclonal antibody to a surface sialo-glycoprotein (SGP-115/107) binds to glomerular visceral epithelial cells and causes morphological changes which appear epitope-specific and complement and leukocyte-independent. The mechanisms responsible for the progression of renal disease to glomerular sclerosis have been extensively explored in the last years. Among the hemodynamic factors intraglomerular hypertension has been established to play an important part, at least in some models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Nephrology]. 269 52

Our previous paper showed that the glycoprotein of Mr 108,000 (gp108) is one of the major components of rat renal tubular brush border antigens and that an injection of anti-gp108 antiserum in rats induces passive Heymann nephritis with acute and severe proteinuria. In this study, gp108 was identified as a monomer of dipeptidyl peptidase IV (DPP IV). The anti-gp108 antibody was shown to immunoprecipitate DPP IV from Triton-extract of renal tubular membrane fractions. DPP IV was co-purified with gp108 from the Triton-extract by columns of DEAE-cellulose and Bio-gel A-1.5 m. The ratio of DPP IV activity and gp108 content was nearly constant throughout the purification steps. The final purified gp108 showed a high specific activity of DPP IV, comparable to that reported for purified rat DPP IV. These results indicate that gp108 is a monomer of DPP IV.
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PMID:Identification of gp108, a pathogenic antigen of passive Heymann nephritis, as dipeptidyl peptidase IV. 289 1

Urinary trypsin inhibitory capacity is mainly due to the excretion of a glycoprotein which is immunologically related to the inter alpha-trypsin inhibitor and may be a proteolytic degradation product of that substance. It was tested in 133 subjects divided into 7 groups: 24 healthy controls (group A), 21 patients with bacterial infection (group B), 37 with bacterial infection under antibiotic therapy (group C), 25 with connective tissue disease (group D), 8 with infected connective tissue disease (group E), 14 with cancer (group F) and 4 with infected cancer (group G). Urinary trypsin inhibitory capacity level was very low in controls (3.32 +/- 0.8 U/g urinary creatinine), but it was dramatically increased when infection was present (149.67 +/- 23.6 U/g urinary creatinine). This test appeared to be more effective than serum C-protein measurement simultaneous carried out in the same patients. Urinary trypsin inhibitory capacity is not related to the degree of proteinuria in the urine sample, but it is increased in patients with chronic renal failure excluded from this study. Thus, its measurement is a sensitive, easy and useful test for detecting and monitoring infections. The return to its physiological value is a very good argument in favour of therapeutic effectiveness.
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PMID:[Clinical value of the determination of urinary antitrypsin activity]. 296 52

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a well-defined inborn error of metabolism, where the enzymatic deficiency (LCAT) has been clarified and also the chromosomal defect (chromosome 16q22) is localized. The disease is to-day known all around the world and 50 patients from 26 families are known to-day. Corneal opacities have been found in all patients and appear early in life. The opacities have a characteristic appearance which makes it rather easy to get the correct diagnosis of this disease. Near the limbus, a pronounced opacity of annular shape resembling a marked arcus lipoides senilis occurs. The opacities are composed of numerous minute grayish dots and are localized to the parenchyma and evenly distributed in all layers of the stroma. In polarized light, crystals that may be cholesterol have been seen in both cornea and the fundus. Excess unesterified cholesterol and phospholipid has been found in cornea. The disease is also characterized by slight anemia and proteinuria and sometimes lipemic plasma, but patients without anemia and proteinuria have also been described. All lipoproteins are abnormal in familial LCAT deficiency. The individual lipoprotein fractions are all heterogeneous and characterized by a higher amount of free cholesterol than normal. Rapidly developing renal insufficiency in adult age often appears in this type of familial renal disease. Kidney transplantation may be necessary. LCAT has now been characterized as a glycoprotein with 416 aminoacids + hydrophobic leader sequence of 24 aminoacids and an apparent Mr of 63 kD. Plans exist to proceed with genomic cloning of the LCAT gene from normal DNA and from various patients.
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PMID:Familial lecithin: cholesterol acyltransferase (LCAT) deficiency. An updated review Spring 1988. 306 99

Antibodies directed against tubular brush border antigens (RTE) are used to induce heterologous immune-complex nephritis. Among these antigens a glycoprotein with a molecular weight of 330 kilodaltons (gp330) has been shown to be of pathogenetic significance. We investigated whether antibodies other than those directed against gp330 are present in anti-RTE and whether they play a pathogenetic role. By using enzyme-linked immunosorbent assay techniques and Western blotting, we investigated polyclonal antibodies directed not only against crude RTE but also against RTEgp, a purified glycoprotein fraction of RTE, with respect to activity against glomerular basement membrane (GBM) components laminin, fibronectin, and type IV collagen. Both antibody preparations showed reactivity predominantly to the 220 kilodaltons subunit of laminin. Lower but nevertheless distinct reactivity to fibronectin and type IV collagen was also found. The antibody fraction directed against components of the GBM, which was isolated from anti-RTE IgG by affinity chromatography, showed linear binding to the GBM in indirect immunofluorescence studies. Injection of these antibodies into the renal artery also led to linear binding to the GBM with linear deposition of complement factors 3 and 9 and induced a weak and transient proteinuria. Immunoelectron microscopy revealed binding of the antibodies to glomerular epithelial and endothelial cell surfaces adjacent to the GBM. Injection of anti-RTE antibody absorbed to GBM components resulted in binding of antibodies and complement factors 3 and 9 in a fine granular pattern along the GBM, whereas injection of unabsorbed anti-RTE led to a course granular pattern. We conclude that the presence of antibodies (cross-)reacting with laminin, fibronectin, and type IV collagen in anti-RTE antibody has pathogenetic effects and could explain differences in pathogenicity between monospecific anti-gp330 antibody and polyclonal anti-RTE antibody.
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PMID:Antibodies to purified renal tubular epithelial antigens contain activity against laminin, fibronectin, and type IV collagen. 327 61

Heymann nephritis (HN) is an experimentally induced glomerulonephropathy of the rat characterized by subepithelial immune deposits and proteinuria. Immunization with a complex multimeric glycoprotein, gp600, comprising four subunits gp330, gp140, gp110, and gp70 has been shown to induce the complete form of the disease including proteinuria. Examination of three different batches of heterologous anti-gp600 antisera by immunoblot technique showed that the reactivity toward gp70 was dominant and common to all three antisera. gp70 was isolated from Triton X-100-solubilized Fx1A by lectin Lens culinaris affinity chromatography, and the purity was confirmed by SDS-PAGE. Ten rats were actively immunized with 200 micrograms of gp70. All 10 animals developed circulating brush border antibody and typical granular IgG deposits in the glomerulus but only 1/10 animals developed abnormal proteinuria. A potent antiserum against gp70 was prepared in the rabbit. It reacted strongly to the glomerular capillary wall and the proximal tubular brush border by immunofluorescence. By Protein A immunogold technique using anti-gp70, gold particles were found associated with the glomerular basement membrane (GBM)-endothelial region. By immunoblot analysis of rat GBM using the same anti-gp70 antiserum, a 70-kDa cross-reactive antigen was demonstrated in GBM preparations. These results show that the smallest subunit, gp70 of the complete HN antigen, gp600/Fx1A can independently induce the lesion of HN, but without proteinuria. The presence of gp70 on the endothelial side of the GBM is consistent with a role for in situ antigen-antibody reactions at sites other than the subepithelial region in the pathogenesis of HN.
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PMID:Nephritogenicity and immunocytochemical localization of the 70-kilodalton glycoprotein subunit (gp70) of Heymann antigen. 328 3

Passive Heymann nephritis (PHN) is an animal model of immune-complex-induced renal disease resembling human membranous glomerulonephritis. It was induced in rats by injecting rabbit antiserum directed against glycoprotein antigens isolated from rat embryonic visceral yolk-sac microvilli (VYS-MV). The glycoprotein antigens were isolated by extracting the VYS-MV with detergent Nonidet P-40 followed by gel filtration in Sephacryl S-300 and finally by lectin affinity chromatography with Ricinus communis agglutinin I. In vitro immunofluorescent localization studies demonstrated that the nephritogenic antibodies were localized along the apical region of the visceral yolk-sac endodermal cells and the brush border of the proximal tubular cells of the kidney. Rats injected with a single dose of the antiserum manifested proteinuria. Indirect immunofluorescent studies showed that the injected rabbit IgG was localized in vivo along the capillary walls of the glomerulus in a granular fashion. Electron microscopic examination of the same kidney glomeruli revealed numerous electron-dense deposits along the lamina rara externa of the glomerular basement membrane. Fusion of the epithelial foot processes was also present. These findings represent the typical immunopathological characteristics of Heymann nephritis. Furthermore, with the aid of Ouchterlony analysis, the antiserum against the isolated VYS antigens exhibited an immunoprecipitin band which was in common with that formed by the antiserum against the homogeneous nephritogenic antigen (gp330) of renal brush border origin. Thus, the nephritogenic antigens which have been found to be associated with the brush border of the renal proximal tubules may also be present or cross-reacted in the microvilli of the rat embryonic visceral yolk-sac.
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PMID:Passive Heymann nephritis induced by rabbit antiserum to membrane antigens isolated from rat visceral yolk-sac microvilli. 330 94

We recently reported that an injection of antibody raised against renal brush border glycoprotein, gp108, in rats induced passive Heymann nephritis with acute and severe proteinuria. In this study, the distribution of gp108 in various rat tissues was investigated. On enzyme immunoassay, anti-gp108 antibody reacted to extracts of small intestine, lung, spleen, thymus, liver, epididymis, stomach, pancreas and heart. It also reacted to sera and extracts of peripheral blood cells, especially lymphocytes. These antigens, which are cross-reactive to kidney gp108 have similar biochemical properties: a molecular weight of about 108,000 and an isoelectric point of 4.8-5.4. These results show that immunologically and biochemically related antigens to renal glycoprotein, gp108, are present in various rat tissues.
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PMID:The detection and characterization of renal brush border antigen (gp108) in various rat tissues. 330 35


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