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)

Urinary proteins from 50 patients with multiple myeloma (37 Ig G, 6 Ig A, 7 Bence Jones) were investigated by discelectrophoresis in polyacrylamidgels containing sodium dodecylsulfat. All samples were also characterized by immunelectrophoresis. Quantitatively and qualitatively normal proteinuria was found in 13 patients (26%). 22 patients (44%) had monoclonal free light chains in the urine, kappachains were eliminated mainly in the monomeric form, lambdachains in all samples in the dimeric form. In 2 patients were found to exist light chains as monomers and dimers. 11 other patients (22%) had peaks of monoclonal Ig G or Ig A in the urine, always associated with the elimination of other nonmonoclonal proteins. Non-specific proteinuria was found in the remaining 4 patients. The clinical validity of the findings is discussed.
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PMID:[Analysis of urinary proteins from 50 patients with multiple myeloma by discelectrophoresis (author's transl)]. 43 51

The origin and mechanism of renal clearance of urinary 'fibrin-fibrinogen degradation products' (FDP) were studied in patients with renal glomerular diseases associated with heavy, non-selective proteinuria and high levels of urinary FDP. The results indicated that the urinary FDP arose primarily by the filtration of unaltered plasma fibrinogen through a damaged and abnormally permeable glomerular basement membrane and that a variable degree of lysis of the filtered fibrinogen occurred in the urine. The lysis of cross-linked fibrin in intraglomerular deposits, as evidenced by the presence of dimeric fragment D in the urine, appeared to contribute only a small amount to the total urinary FDP excretion.
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PMID:Origin of urinary fibrin-fibrinogen degradation products in renal glomerular disease. 45 Jan 68

The chemistry of low-osmolality contrast agents is reviewed, the effects of these agents on vascular and organ physiology are compared with the effects of conventional ionic contrast media, and guidelines for intravascular use of the low-osmolality agents in selected high-risk patients are presented. Three low-osmolality contrast agents, the nonionic media iohexol (Omnipaque, Winthrop-Breon) and iopamidol (Isovue, Squibb) and the dimeric medium ioxaglate meglumine-sodium (Hexabrix, Mallinckrodt) have recently been introduced into the contrast-media market. Compared with conventional ionic contrast media, these new agents demonstrate approximately one third of the osmolality per given iodine concentration (degree of roentgenographic opacification). Therefore, the risks of hyperosmolarity-induced reactions to contrast media are lower with the new agents. The low-osmolality agents may be associated with a reduced incidence of contrast-media-induced hypersensitivity reactions. Because of their lower osmolality, these agents produce less vessel dilation, vascular endothelial damage, and associated pain and discomfort than equi-iodine concentrations of the conventional ionic media. They also demonstrate a reduction in the incidence and severity of contrast-media-induced renal vasoconstriction and proteinuria, hemodynamic alterations, negative chronotropic effects, depression of myocardial contractility, and neurotoxicity in the presence of an altered blood-brain barrier. These low-osmolality agents produce fewer undesirable physiological effects than conventional contrast agents, but the cost of the new products can be more than 10 times as great. Therefore, the new products should be used selectively in patients known to be at increased risk for reactions to intravascular contrast media. A scoring system was developed to permit rapid recognition of documented single or multiple risk factors and subsequent determination of whether to administer a low-osmolality agent.
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PMID:Evaluation of intravascular low-osmolality contrast agents. 378 Jan 59

Urinary proteins were studied by quantitative and electrophoretic methods in 6-month-old spontaneously hypertensive rats and normotensive controls. Protein analysis was carried out before and after adrenalectomy and during gluco- or mineralocorticoid treatment. Urinary protein excretion was significantly diminished after adrenalectomy both in the hypertensive and control groups. The original level of protein excretion was restored only by glycocorticoid treatment. Normal or pathologic electrophoretic pattern of urinary proteins was not influenced by the experimental procedure. Moderately non-selective glomerular proteinuria persisted in the spontaneously hypertensive rats referring to a definitely damaged glomerular barrier. One protein fraction of about 130,000 dalton molecular weight disappeared from the urine of hypertensive animals after adrenalectomy and reappeared after glucocorticoid treatment only. This fraction probably represents the dimeric form of albumin. Quantitative changes of urinary protein excretion can be explained by haemodynamic factors.
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PMID:The effect of adrenalectomy on the proteinuria of spontaneously hypertensive rats and normotensive controls. 381 95

Samples of the urine of 10 myeloma patients with proteinuria were examined by SDS-PAGE. Light chain proteins of Bence Jones (B.J.) type were excreted by 7 patients as monomer (m.w. 20--26.5 x 10(3) Dalton, by 2 patients as a mixture of monomer and dimer and by one patient as dimer. By two-dimensional electrophoresis in SDS-PAG and subsequent electrophoresis in agarose containing kappa and lambda chain specific antibodies the immunological identity of monomeric and dimeric B.J. protein of one patient has been shown. The two-dimensional analysis has been proven a valuable procedure in cases with the excretion of complete monoclonal protein and B.J. protein at the same time.
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PMID:Study of uroproteins in myeloma patients by sodium dodecyl sulfate-polyacrylamide gel electrohporesis (SDS-PAGE). 739 39

Apolipoprotein (apo) D is a glycoprotein that contains at least one free cysteine. This allows the formation of disulfide linked dimers of apoD, a phenomenon that could interfere with the study of the isoforms of apoD. Consequently, it is important to consider the effects of hetero- and homodimer formation on the molecular heterogeneity of apoD as well as on the evaluation of the specificity of antibodies to this glycoprotein. The identification of apoD in urine has provided a potential new marker of tubular proteinuria. Thus, we have studied the specificity of our polyclonal antibodies to apoD against the proteins present in normal urine, and at the same time, the existence of dimeric species of apoD linked by disulfide bonds in urine. The specimens were obtained from apparently healthy individuals and analyzed by Western blot. The results showed that apoD in urine exists as a mixture of monomers and dimers, the latter having apparent molecular weights different from those occurring in plasma. Only monomeric apoD was observed under reducing conditions, proving the monospecificity of the polyclonal apoD antibodies.
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PMID:Disulfide linked dimers of apolipoprotein D in urine. 812 62

The intravenous use of roentgen contrast media (CM) is associated with a low incidence of renal impairment. This paper considers the intravascular handling and retention of CM in relation to effects on renal function - specifically the ability of the kidney to reabsorb and catabolise low molecular weight proteins. Renal morphology following experimental administration of a high dose of an isotonic dimeric CM (iodixanol at 3 g I/kg) in rats showed numerous, large, protein-containing vacuoles or droplets in the cells of the proximal convoluted tubule. These were fully formed within 3.5 hours. The process of vacuole-formation involving the uptake of CM appears to be analogous to dextran uptake that occurs via fluid phase endocytosis. These vacuoles or CM droplets are abundant for 7 days but then slowly decline over several weeks. The quantitative recovery of (14)C iodixanol (3g I/kg) from the kidneys between 3.5 hours to 7 days after administration was about 1% of the dose, with some 0.2% of the original dose still present at 28 days. Subcellular analysis to determine the site of the radiolabel showed that the (14)C was associated with lysosomal marker enzymes. The CM-induced vacuoles/droplets are most probably giant lysosomes, which contain the intracellularly retained CM. Co-administration of tracer doses of (125)I-labelled cytochrome C with iodixanol showed some impairment of low molecular weight protein reabsorption, but remarkably this process was not effected when the vacuoles were fully formed. The conspicuous morphology of the vacuoles, the CM retention and the transient proteinuria and enzymuria cannot presently be associated with any functionally significant impairment of tubular or cellular processes.
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PMID:Biochemical and morphological effects of contrast media on the kidney. 861 May 15

The effects of the new nonionic dimeric hexa-iodinated contrast media (CM) iodixanol on renal function and morphology were investigated in 7 independent studies in rats, rabbits and monkeys and compared with other iodinated CM. No significant effect on serum creatinine levels was seen at doses up to and including 5 g I/kg in rats and 10.5 g I/kg in rabbits. An immediate and transient increase in proteinuria was found in rabbits when 10.5 g I/kg was administered as a bolus, and when 12.5 g I/kg was administered as a slow infusion in a comparative study with several CM. Increased serum elimination half-life was shown by measuring serum iodine concentrations after the infusion of 12.5 g I/kg. The effect of a high dose of iodixanol on proteinuria and elimination half-life were in this study in the same range as those of the monomeric nonionic CM, but less pronounced than those of the monomeric ionic CM. Reduced renal capacity was induced in male rats by performing unilateral nephrectomy 4 weeks before i.v. injection of iodixanol or iopamidol (2g I/kg). The administration of CM did not affect renal function monitored as serum concentrations of creatinine and urea. The vacuolation of renal proximal tubular cells and kidney iodine retention were investigated in rats 48 hours after administration of different doses of iodixanol or iotrolan. The no-effect level for vacuolation was 0.5 g I/kg for both CM. Iodine retention was higher in male than females rats, and was higher for iodixanol than iotrolan at the 2 highest dose levels (3 and 5 g I/kg). No difference in iodine retention was found at the other dose levels (0.25-1g I/kg). The reversibility of renal proximal tubular vacuolation after administration of iodixanol was studied in male rats (1.2 g I/kg) and monkeys (1.2 and 3.6 g I/kg). The vacuolation was more pronounced in rats than in monkeys. Vacuolation was completely reversed in all rats 3 weeks after dosing, and 2 of 3 monkeys 3 days after a dose of 1.2 g I/kg. The degree of vacuolation evident in renal percutaneous biopsy specimens from monkeys 14 days after i.v. administration of iodixanol at a dose of 3.5 g I/kg was not significantly different to that in control animals. In conclusion, iodixanol affected renal function to the same degree as did the nonionic monomeric and dimeric comparative media, but to a lesser degree than the ionic monomers. The degree of renal proximal tubular cell vacuolation induced by iodixanol seems to be species-dependent, being less pronounced and more quickly reversed in monkeys than rats.
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PMID:Renal effects of iodixanol in experimental animals. 861 May 17

IgA nephropathy (IgAN) is a chronic form of glomerulonephritis (GN) characterized by the deposition in the glomerular mesangium of mainly IgA. An experimental form of mesangial proliferative GN can be induced in rats by either polyclonal or monoclonal antibodies against Thy-1.1, a glycoprotein present on the surface of MC. The IgG-mediated renal inflammation is complement dependent and associated with influx of platelets and monocytes. In the present study we switched an IgG2a anti-Thy-1.1 (ER4G) producing hybridoma to an IgA anti-Thy-1.1 (ER4A) producing clone and analyzed the effects of IgA anti-Thy-1.1 in rats. FPLC analysis by gel filtration revealed that the IgA produced by the hybridoma cells was mainly dimeric and polymeric. Infusion of rats with purified ER4A (1 mg/kg) resulted in the deposition of IgA in a mesangial pattern in the glomeruli, similar to that found with ER4G. While administration of ER4G resulted in proteinuria, no significant urinary protein excretion was found in rats treated with ER4A. However, significant microhematuria was observed in rats receiving either ER4A or ER4G. Furthermore, the administration of ER4A was not accompanied by activation of complement, and no significant influx of monocytes or polymorphonuclear leukocytes was observed in contrast to the rats receiving ER4G. We conclude that microhematuria is selectively induced in Wistar rats by mouse IgA anti-Thy-1.1 without detectable complement-mediated injury to MC. These studies may be of importance in understanding the mechanisms leading to IgAN in patients.
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PMID:Induction of microhematuria by an IgA isotype switch variant of a monoclonal anti-Thy-1.1 antibody in the rat. 891 28

To investigate the relationship between high serum levels of IgA and glomerular lesions, selective mating was performed in high serum IgA ddY mice, a murine model of spontaneously developing mesangioproliferative glomerulonephritis mimicking human IgA nephropathy. The selection and mating of high IgA ddY mice were accomplished when the mice were three to four months old. In the 12th generation of high IgA ddY (HIGA) mice, significantly higher levels of serum IgA from 10 age weeks to 60 weeks (P < 0.0002 to 0.0001) were observed in comparison with BALB/c mice. Relatively high proteinuria was observed at 40 weeks of age, although hematuria was consistently negative. Microscopic observations of renal tissue disclosed a marked glomerular mesangial matrix increase and a reduction of cell proliferation with age by both semiquantitative and morphometric analyses with moderate tubulointerstitial damage. These mesangial matrices were stained markedly by antisera for collagen type IV and by fibronectin, but not by collagen type I. Localization of TGF-beta protein was also detected in the mesangium of the HIGA mice. The positive mesangial IgA deposition was maintained consistently by this mating procedure and became more marked with age. Size analysis of IgA from ten pooled HIGA mice aged 50 to 60 weeks revealed dominant polymeric IgA in sera and dimeric IgA in glomerular eluates. Clonal analysis of serum IgA disclosed heterogeneous spectrotypes in a wide pH range (4.5 to 6.5), in contrast to very limited spectrotypes in the acidic pH range (4.5 to 5.2) of IgA in the glomerular eluates from these mice. The analyses of retroviral gp70 antigen involvement in the HIGA mice disclosed a significant increase of serum levels of gp70 anti-gp70 immune complexes with age, with no relationship to the severity of glomerular gp70 deposition. Northern blot analysis of renal tissue revealed markedly high mRNA expression of collagen type I, IV, fibronectin and TGF-beta even in 10-week-old HIGA mice in comparison with BALB/c mice. The expression became more significant in 60-week-old animals. The genetic background required to induce the expansion of IgA-producing B-cell clones is suggested to be closely related to the increased gene expression of TGF-beta, which induces enhanced glomerular extracellular matrix (especially fibronectin) accumulation in HIGA mice, being possibly mediated by the mesangial deposition of dimeric and highly acidic IgA. This newly established strain may provide a model for investigating the relationship between progressive glomerular sclerotic lesions and the induction of pathogenic IgA in human IgA nephropathy.
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PMID:Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice. 894 78


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