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)

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)
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PMID:A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. 159 46

Investigations of glomerular anionic charge status in human renal biopsies have previously been restricted, by the techniques and markers used, to staining of sites in pre-embedded tissue. The introduction of a novel marker, cationic colloidal gold, which demonstrates fixed anionic sites in hydrophilic resin (LR Gold)-embedded, ultrathin tissue sections, has now enabled glomerular charge to be evaluated in routine biopsy material. The cationic gold marker detects components which express anionic charge under different pH conditions. The patterns of staining in tissue showing minor glomerular pathology and low proteinuria, together with enzyme-digestion studies indicate that anionic sites are normally associated with heparan sulphate proteoglycans, glycocalyx sialoproteins, hyaluronic acid, and other GBM components which have not yet been characterised. Several charge aberrations involving different pathological mechanisms have been identified using cationic gold. These aberrations may be categorised according to the pathological basis of the charge pattern defect, rather than glomerular disease classification, as a prelude to the precise identification of the anionic sites and their functional importance in relation to the glomerular charge selectivity barrier. The categories which have been defined are: (1) 'Normal', (2) interrupted, (3) neutralised, (4) structurally disorganised, and (5) depleted. As sites are further characterised sub-categorisation is likely. We anticipate that this approach will help to elucidate both the participation of charged components in disease pathogenesis and their role in relation to glomerular proteinuria.
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PMID:Cationic colloidal gold--a novel marker for the demonstration of glomerular polyanion status in routine renal biopsies. 172 90

Alterations in the permeability of the glomerular basement membrane (GBM) towards native ferritin (NF) and iodinated albumin (125I-BSA) following removal of the major glycosaminoglycans (GAGs) of the GBM, heparan sulfate (HS) and hyaluronic acid (HA), were assessed utilizing the techniques of routine electron microscopy and autoradiography, respectively. Kidneys were incubated with heparinase (to degrade the GAGs of the GBM) and subsequently perfused with either NF or 125I-BSA. Control kidneys, which were not treated with heparinase, showed a low permeability to both tracers, with NF being confined to the lamina rara interna and 125I-BSA exhibiting a low level of passage into the urinary spaces (as indicated by a low density of autoradiographic grains over the urinary spaces). After heparinase treatment there was an increase in the permeability of the GBM such that both NF and 125I-BSA passed through the GBM in larger quantities and entered the urinary spaces. Perfusion of cationized ferritin (CF) into control kidneys revealed this probe to bind to the HS-rich anionic sites present within the GBM. Treatment with heparinase resulted in an abolition of the CF binding thereby indicating that the sites are composed mainly of HS and that HS plays a key role in establishing the permeability properties of the GBM. The changes in the pattern of distribution and density of the anionic sites of the GBM following induction of nephrosis was also studied. Animals were rendered nephrotic by subcutaneous injections of an aminonucleoside of puromycin and their kidneys subsequently perfused with either CF or cationized cytochrome c. No difference in either the pattern of distribution on density of the anionic sites in the GBM of nephrotic kidneys was observed when compared to nonnephrotic controls; thus indicating that the proteinuria associated with aminonucleoside nephrosis might be due to changes in components of the glomerular capillary wall other than the anionic sites.
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PMID:Glycosaminoglycans of the glomerular basement membrane in normal and nephrotic states. 730 62

The mechanism of edema, proteinuria, hypertension (EPH)-gestosis-associated premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs) in the umbilical cord arteries is not known. It may result from altered biosynthesis, a different degradation rate or a combination of both phenomena. In order to solve this problem, it was decided to evaluate the biosynthesis and degradation of newly synthesized GAGs in the umbilical cord arteries of control newborns and those delivered by mothers with EPH-gestosis. Incorporation of radioactive precursors ([14C]glucosamine and [35S]sulphate) into GAGs and degradation of newly synthesized GAGs using the pulse-chase experiment were evaluated. We found that the investigated tissue slices incorporated distinctly less [14C]glucosamine into hyaluronic acid in comparison to controls. In contrast to that, the biosynthesis of sulphated GAGs did not change significantly. However, the degradation of newly synthesized sulphated GAGs was distinctly slower than in control tissues. It may be concluded that an EPH-gestosis associated decrease in hyaluronic acid content in the umbilical cord artery is a result of decreased biosynthesis of this substance, whereas an increase in sulphated GAGs-content is rather a result of slower degradation of newly synthesized GAGs.
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PMID:Glycosaminoglycan-biosynthesis in the wall of the umbilical cord artery and its alteration in EPH-gestosis. 907 17

Edema, proteinuria, hypertension (EPH) gestosis is accompanied by an increase of collagen content and premature replacement of hyaluronic acid by sulfated glycosaminoglycans both in the umbilical cord arteries and in Wharton's jelly. The effect of EPH gestosis on elastin content and metabolism in the umbilical cord arterial wall was the aim of this work. Studies were performed on normal umbilical cord arteries and those taken from newborns of mothers with EPH gestosis. Elastin was isolated from the arterial wall and quantified by a dye-binding method. Biosynthesis and degradation of this protein was evaluated by a pulse-chase experiment with the use of 14C-proline. It was found that EPH gestosis is associated with a significant reduction of elastin content in the umbilical cord arteries as a result of decrease in elastin biosynthesis rate and accelerated degradation of this protein. The replacement of elastin by collagen, and hyaluronate by sulfated glycosaminoglycans, may decrease the hydration of arterial wall and reduce its elasticity. Such rearrangement of extracellular matrix of the umbilical cord arteries may affect mechanical properties of these vessels and disturb fetal blood circulation.
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PMID:Elastin of the umbilical cord arteries and its alterations in EPH gestosis (preeclampsia). 985 59

It was found that hyaluronic acid is the most abundant glycosaminoglycan (GAG) both in the umbilical cord arteries and in the umbilical cord veins. Chromatographic and as well as electrophoretic studies demonstrated that EPH-gestosis (Edema-Proteinuria-Hypertension), the most common pathological syndrome occurring in pregnancy, is accompanied by premature replacement of hyaluronic acid by sulphated GAGs in the investigated arteries but not in the veins. Such a replacement is a characteristic feature of the ageing process. One may conclude that EPH-gestosis is associated with a "premature ageing" of the umbilical cord arterial walls. The mechanism and possible role of this phenomenon in pathology are discussed.
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PMID:Electrophoretic and chromatographic patterns of glycosaminoglycans of the umbilical cord vessels and their alteration in EPH-gestosis. 991 8

Edema, proteinuria, hypertension (EPH)-gestosis is associated with a premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs), both in the umbilical cord arteries (UCAs) and in Wharton's jelly. This phenomenon may be considered as a sign of premature ageing of the umbilical cord tissues. The decrease in hyaluronic acid content in the UCA was found to be the result of reduced biosynthesis of this substance, whereas an increase in sulphated GAGs-content is rather a result of slower degradation of newly synthesised GAGs. In this study the activities of GAGs-degrading enzymes in normal umbilical cord arteries and those taken from newborns delivered by mothers with EPH-gestosis were compared. It was found that EPH-gestosis results in a significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated glycosaminoglycans (with the exception of heparan sulphate). The activities of exoglycosidases also decrease but to a lesser degree. These alterations are thought to be responsible for EPH-gestosis-associated accumulation of sulphated glycosaminoglycans in the extracellular matrix of the arterial wall. Such remodelling of the arterial wall may affect foetal blood circulation. The significance of these phenomena in the pathological mechanism of EPH-gestosis is discussed.
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PMID:The activities of some glycosaminoglycan-degrading enzymes in the wall of the umbilical cord artery and their alteration in edema, proteinuria, hypertension (EPH)-gestosis. 1036 12

Oedema, proteinuria, hypertension (EPH)-gestosis (pre-eclampsia) is associated with a premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs), both in the umbilical cord arteries and in Wharton's jelly. It may be concluded from our previous report that such a phenomenon may be the result of reduction in degradation of these compounds. In order to support such a conclusion the activities of GAG-degrading enzymes in normal umbilical cord arteries and those taken from newborns delivered by mothers with EPH-gestosis were compared. It was found that EPH-gestosis results in a significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated GAGs (except keratan sulphate). In the case of acidic endoglycosidases, no characteristic alterations have been found. Only the activity of heparan sulphate-degrading endoglycosidase significantly decreased. In contrast to the above-mentioned endoglycosidases, the activities of arylsulphatase B and 6-sulphatase distinctly increased. The decrease in the activities of endoglycosidases are thought to be responsible for EPH-gestosis-associated accumulation of sulphated GAGs in extracellular matrix of Wharton's jelly. This leads to the suspicion that EPH-gestosis-induced changes in the GAGs composition may alter the fibrillogenesis conditions in Wharton's jelly. The sulphated GAGs accumulated in Wharton's jelly may interact with some growth factors which modify the myofibroblasts' proliferation, gene expression, protein biosynthesis and other processes. A significance of EPH-gestosis-induced alteration in Wharton's jelly is discussed.
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PMID:Activities of some glycosaminoglycan- degrading enzymes in Wharton's jelly and their alteration in EPH-gestosis (Pre-eclampsia). 1046 Sep 52

Edema, proteinuria, hypertension (EPH)-gestosis, known also as preeclampsia, is the most common, pregnancy-associated pathological syndrome. It is accompanied by a significant increase in collagen content in the umbilical cord arteries and premature replacement of hyaluronic acid by sulfated glycosaminoglycans both in these arteries and in Wharton's jelly. This remodelling of the umbilical cord tissues is accompanied by a distinct increase in insulin-like growth factor-I (IGF-I) concentration in the umbilical cord serum. Such a serum introduced into the culture medium of fibroblasts growing in vitro strongly stimulated the incorporation of radioactive proline into collagen (hydroxyproline-containing and collagenase-sensitive protein). Biosynthesis of noncollagenous proteins was not stimulated. Since IGF-I is known as a stimulator of collagen and sulfated glycosaminoglycan biosynthesis, the high concentration of this growth factor in the umbilical cord plasma may be an agent responsible for preeclampsia-associated remodelling of the umbilical cord, which results in dysfunction in fetal circulation.
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PMID:Stimulation of collagen biosynthesis by the umbilical cord serum of newborns delivered by mothers with EPH-gestosis (preeclampsia). 1107 61

An important function of CD44 is to act as a cellular receptor for hyaluronic acid and osteopontin. Cell-matrix interactions mediated by the CD44/hyaluronic acid receptor-ligand pair are involved in the regulation of leukocyte migration and activation. Osteopontin is a molecule associated with cell adhesion and migration and functions through binding to CD44. This study examined whether CD44, hyaluronic acid and osteopontin participate in the progression of IgA nephropathy. CD44 was expressed in mesangial cells, crescents, tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. Hyaluronic acid was deposited in the capillary tuft of adhesion, crescents and the periglomerular area, and around damaged tubules. Osteopontin was expressed in tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. The glomerular and interstitial deposition of hyaluronic acid correlated with the glomerular and interstitial expression of CD44. The interstitial expression of CD44 correlated with the interstitial expression of osteopontin. The expression of both CD44 and osteopontin in the interstitium correlated with the extent of tubulointerstitial damage. The expression of CD44 in the interstitium correlated with the severity of chronic glomerular lesions. The glomerular and interstitial CD44 and hyaluronic acid expression correlated with proteinuria, and interstitial CD44 and hyaluronic acid expression correlated with creatinine clearance rate. In summary, this study suggests that CD44 participates in the progression of IgA nephropathy by binding hyaluronic acid and osteopontin.
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PMID:Localization and roles of CD44, hyaluronic acid and osteopontin in IgA nephropathy. 1172 Nov 59


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