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)

Immune deposits in the glomerular mesangium were induced in rats by injection of rabbit antibodies to rat plasma fibronectin (FN). By direct immunofluorescence and electron microscopy, deposits of immunoglobulins were detected in the mesangium of all rats injected with anti-FN IgG but not of control rats injected with normal rabbit IgG. By light microscopy, kidneys obtained 20 days after the antibody injection appeared to be normal. No proteinuria was detected during the experiment. Tissue uptake studies combined with direct immunofluorescence examination suggest that the initial accumulation of rabbit immunoglobulins in the glomerular mesangium is probably due to direct local binding of anti-FN antibody rather than trapping of immune complexes formed in the circulation. Quantitation of the direct binding using an in vivo perfused kidney system indicate that only a small fraction of the injected antibodies (less than 1 microgram/kidney) could bind. These studies indicate that (1) mesangial immune deposits may be induced by injection of antibodies to a glycoprotein, fibronectin, which is a normal structural component of the mesangium; (2) the initial accumulation of immunoglobulins in the mesangium is probably related to an in situ binding; and (3) mesangial antigens might be involved, in certain cases, in autoimmune reactions.
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PMID:Mesangial immune deposits induced in rats by antibodies to fibronectin. 637 May 24

This longitudinal study compared the renal morphologic changes and hemostatic defects of FH/Wjd rats at different ages. A second aim was to determine whether the bleeding tendency becomes intensified in older animals by the concomitant renal disease. Results indicated that reduced capacity for platelet 14C-serotonin release (P less than 0.01) was found for each age group studied in comparison with Wistar controls. The nephropathy of old FH/Wjd male rats was more severe than that in either FH/Wjd females or age-matched Wistars of both sexes. The mesangial lesions showed abundant deposits of factor VIII-related antigen, fibronectin, and immunoglobulins, but not C3, along with tightly packed or loose electron-dense material. Polyethylene glycol precipitation and platelet aggregation tests detected small amounts of circulating immune complex-like material. Old FH/Wjd rats did not develop edema, and the glomerular filtration rate remained normal despite the persistent proteinuria, hematuria, and arterial hypertension characteristic of this strain. Our data indicated that the congenital platelet dysfunction does not become more severe in older animals and that the nephropathy seems unrelated, does not appear to be mediated by immune complexes, and, in contrast to the focal segmental glomerulosclerosis of persons, the lesions progress without a parallel impairment of renal function.
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PMID:Age-related renal, hematologic, and hemostatic abnormalities in FH/Wjd rats. 638 48

The kidneys of four human fetuses aged 18 to 20 weeks of gestation with congenital nephrosis of the Finnish type (CNF) were studied by immunohistochemistry and electron microscopy to elucidate the pathogenesis of the disease. The immunohistochemical stainings for laminin, type IV collagen, fibronectin, brushborder antigens (BBA), Tamm-Horsfall protein (TH), and binding of wheat germ agglutinin (WGA) did not reveal changes as compared to the age-matched control kidneys. Proximal tubules of the CNF kidneys showed excessive accumulation of coarse granular alpha fetoprotein (AFP) and large absorption droplets with paracrystalline and membraneous structures were seen in electron microscopy. The dilated tubules were both of proximal and distal origin as judged from the BBA and TH stainings. It is suggested that the formation of the dilated tubules results from degeneration caused by obstruction and excessive protein loading of the tubular epithelium. Demonstration of the coarse granular AFP in the proximal tubular epithelium and lumina indicates heavy fetal proteinuria and serves as an additional diagnostic marker for prenatal CNF.
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PMID:Pathology of fetal congenital nephrosis: immunohistochemical and ultrastructural studies. 638 19

This report describes a patient with thrombocytopenia, microangiopathic hemolytic anemia, proteinuria, and microscopic hematuria that could be transiently improved by the infusion of plasma or various plasma components. An increase in platelet count following the transfusion of normal plasma was predictable and reproducible. In therapeutic trials with commercially available plasma components, factor VIII preparations were effective for inducing an increase in the platelet count and improving hemolytic anemia, but albumin, gamma-globulin, factor IX, and fibronectin preparations were ineffective. Serum from normal donors also relieved the symptoms of this condition in our patient. Partial plasma exchange (1,000 ml/m2 of body surface area) was performed with albumin instead of normal plasma, but there was no significant effect on platelet count or anemia. Large, multimeric von Willebrand factor components of the factor VIII complex (VIII/vWF) were found in the patient's plasma when his platelet count was normal, but their levels were reduced when the platelet count was decreased. The multimers of the patient's plasma were larger than those in normal plasma, but smaller than those in normal platelet lysate. Although the pathogenesis of this disease remains unknown, we conclude that transfusions of normal plasma, serum or factor VIII concentrate provide a factor that causes significant improvement in the thrombocytopenia and hemolytic anemia. Furthermore, large VIII/vWF multimers are possibly directly involved in pathogenesis of this disease.
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PMID:Efficacy of several plasma components in a young boy with chronic thrombocytopenia and hemolytic anemia who responds repeatedly to normal plasma infusions. 643 3

In nine patients with nephrotic syndrome the behaviour of plasma fibronectin was studied. Of nine patients seven showed elevated plasma fibronectin levels while the plasma fibrinogen level was increased in eight of the nine investigated patients. A positive correlation was found between plasma fibronectin levels and fibrinogen (P less than 0.01), cholesterol (P less than 0.01) and proteinuria (P less than 0.05). The results indicate that elevated plasma fibronectin levels could be an additional factor responsible for hypercoagulability in nephrotic syndrome.
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PMID:Elevated plasma fibronectin levels in nephrotic syndrome. 647 78

We measured plasma fibronectin levels in 21 patients with severe proteinuria secondary to primary renal disorders and compared those results with values obtained in 77 healthy volunteers and 15 patients with chronic renal disease but minimal proteinuria. Seventeen of the 21 patients with proteinuria (81%) demonstrated plasma fibronectin concentrations greater than 2 SDs above control values. Fibronectin levels in the group with chronic renal disease did not differ from normal values. In the group with proteinuria, plasma fibronectin levels were inversely correlated with total serum protein and serum albumin concentrations but were not correlated with the degree of proteinuria, serum creatinine level, or histologic diagnosis of kidney disease. The possible relevance of these findings to the hypercoagulable state of the nephrotic syndrome is discussed.
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PMID:Abnormal plasma fibronectin levels in patients with proteinuria. 650 99

A newly recognized type of familial glomerulopathy observed in patients of both sexes in six families is reported. Proteinuria, often within the nephrotic range, microscopic hematuria, hypertension and a slowly decreasing renal function over several years were common. No underlying systemic diseases were identified. Generally, light microscopy showed enlarged glomeruli with minimal hypercellularity and with extensive deposits in the mesangium and subendothelial space. By electron microscopy, granular deposits with some admixture of fibrils were most common. In one family, the deposits were predominantly fibrillary. Immunoglobulins and complement factors were inconstant or lacking. A main finding was a strong immune reactivity to fibronectin, corresponding to the distribution of the deposits. In one patient, the deposits recurred in a renal transplant. There was no indication of systemic deposition. Abnormalities in the metabolism of circulating fibronectin may play a pathogenetic role in this disease of probably autosomal dominant inheritance.
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PMID:Glomerulopathy associated with predominant fibronectin deposits: a newly recognized hereditary disease. 756 73

The present study was carried out to test whether transforming growth factor beta (TGF beta) plays a pathological role in the induction or progression of glomerulonephritis in a murine model of systemic lupus erythematosus (SLE), and whether dietary supplementation with fish oil (FO) can modulate the expression of TGF beta. Weanling female (NZB x NZW) F1 (B/W) mice were divided into three groups. One group was fed an unmanipulated diet (lab. chow; LC) and the other two groups were fed a nutritionally adequate semipurified diet supplemented with 10% CO or FO. Both water and food were provided ad libitum. Proteinuria and serum anti-dsDNA antibody levels were measured to assess disease progression. Mice were killed at 3.5 and 6.5 months of age and renal mRNA levels for TGF beta isoforms, fibronectin-1 (FN-1) and intercellular adhesion molecule-1 (ICAM-1) were studied by Northern blot analysis. TGF beta 1 protein levels were also examined in kidneys by Western blot analysis. Our results indicate that at 3.5 months of age, when urinary protein levels were undetectable and very low levels of anti-dsDNA were detected, no mRNA signal could be detected for TGF beta isoforms, ICAM-1 and FN-1 in either dietary group. However, at 6.5 months, the FO-fed mice, compared to LC and CO, had [1] greatly reduced proteinuria (LC: 2-3+, CO: 2-3+; FO: trace -1+) and serum anti-dsDNA antibodies; [2] improved survival (CO: 100% death (15/15) occurred by 8 months; FO: 50% were alive at 12 months (8/15) and [3] reduced renal TGF beta 1 mRNA and protein levels. TGF beta 2 and beta 3 were not significantly affected by FO diet. Similarly, lower levels of renal FN-1 and ICAM-1 mRNA were observed in FO fed mice. These data indicate that in B/W mice on a FO diet, prolonged survival and amelioration of renal disease may be attributed at least in part to lower levels of TGF beta 1 mRNA and protein in the kidneys.
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PMID:Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression. 757 99

We have studied the sequential morphological changes that took place in the kidneys of 8 rats with nephrotoxic serum nephritis (NTN). Rats underwent kidney biopsies at different time intervals (days 7, 15, 30, 90 and 120). The tissues were processed for light microscopy as well as immunohistochemistry for inflammatory cellular infiltrate as well as for the components of the extracellular matrix (ECM) and myofibroblasts (cells expressing alpha-smooth muscle actin, alpha-SMA). Nephrotic rats developed severe proteinuria, impaired renal function as well as progressive renal scarring. However, the natural history of NTN was heterogeneous with some rats recovering (n = 5) and other progressing to end-stage renal failure (n = 3). The heterogeneous nature of the glomerulonephritis has established that those with a good outcome had a stabilisation, with some resolution, of the deposited ECM and of the scarring process. By contrast, rats with a poor outcome had a progressive increase in glomerular as well as interstitial ECM. Cells expressing alpha-SMA (myofibroblasts) were detected in the glomeruli as well as in the interstitium of nephritic rats. Changes in the expression of cells expressing alpha-SMA paralleled those of the components of the ECM in particular fibronectin. alpha-SMA immunostain was the best predictor of progression. Early glomerular alpha-SMA immunostain (days 7 and 30) was a strong predictor of the subsequent development of glomerulosclerosis and renal dysfunction. The predictive value of interstitial alpha-SMA immunostain on days 7 for subsequent tubulo-interstitial scarring and renal insufficiency was also strong and exceeded that of other histological or immunohistochemical parameters of scarring. This study establishes the natural history of experimental renal scarring and identifies a renal cell type, the myofibroblast, as a useful marker of progression. It also suggests a role for myofibroblasts in the progression of glomerulosclerosis and tubulo-interstitial fibrosis.
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PMID:Myofibroblasts and the progression of experimental glomerulonephritis. 758 53

Human mesangial cell (HMC) cultures synthesize cellular fibronectin (FN), which is secreted and incorporated into a fibrillar extracellular matrix (ECM). The anticancer drug adriamycin (ADR) induces changes in extracellular FN deposition. As revealed by immunofluorescence staining, a 24 h incubation of the cells with 2 micrograms ADR/ml resulted in a marked expansion of the pericellular FN fibers, which may be due to either an increased synthesis or a decreased FN degradation. The effects of ADR on FN mRNA were analysed by northern hybridization and in vitro translation. Steady-state FN mRNA levels were significantly increased by 60% following ADR administration. However, yields of radioactivity incorporated into FN by cell-free translation remained constant (2.3 +/- 0.7%, n = 24, vs controls 2.2 +/- 0.8% of total radioactivity, n = 23). The quality of translation products was not affected by the drug, whereas translation efficiency of total RNA from ADR-treated HMC was only 75% of controls. The data presented suggest a negative feedback control of FN expression on the level of translation. Extracellular FN accumulation in the experimental model of ADR-induced progressive glomerulopathy therefore cannot be explained by an increased FN synthesis, but is rather regarded a consequence of proteinase inhibition. This assumption is compatible with a diminished number of FN fragments recently demonstrated in the culture medium of ADR-treated HMC, and is further corroborated by the loss of urinary FN degradation products accompanying the onset of proteinuria in ADR-treated rats.
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PMID:Fibronectin expression in human mesangial cell cultures and its alterations by adriamycin. 760 Feb 59


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