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)

Isolated and purified glomerular basement membranes (GBM) of normal and aminonucleoside (PAN) nephrosis rats were observed by electron microscopy after negative staining. Although GBM of normal rats appeared as a molecular sieve with uniform pores, GBM of nephrotic rats showed enlargement and elongation of the pores. For an average of fifty pores, the long dimension was 40.4+/-10.7 A and the short dimension 13.8+/-3.6 A in nephrosis whereas the long dimension was 12.3+/-2.5 A and the short dimension 8.4+/-1.0 A in normal rats. Changes in the pores in GBM were thought to result in increased permeability of serum protein and hence proteinuria.
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PMID:Changes in the molecular sieve of glomerular basement membrane in rats with aminonucleoside nephrosis. 644 42

To establish models of proteinuria in the mouse, BALB/c mice were injected with puromycin aminonucleoside (PAN, 1.5 or 4.5 mg/10 g body weight), adriamycin (AD, 0.2 mg/10 g body weight) intravenously or bovine serum albumin (BSA, 100 mg/10 g body weight) intraperitoneally. Proteinuria was measured as the ratio of urinary albumin (micrograms/ml) to creatinine (mg/dl) and further characterized by isotyping the immunoglobulin. Although not obtained with PAN (followed for 4 weeks), proteinuria was readily attained in the mouse after treatment with AD or BSA. Most AD-treated mice (5/7) developed an abrupt increase of proteinuria at day 2 after injection, with the ratio of urinary albumin to creatinine in the range 0.28-0.45. The degree of proteinuria increased with time and all mice tested (7/7) showed overt proteinuria at day 4. These mice became anuric at day 5 and died at days 6 and 7. For BSA, 4 h after administration, four of seven mice showed enhanced proteinuria, lasting 8 h with urinary albumin and creatinine in a ratio < 0.05. Isotyping of urine samples collected at the time of heavy proteinuria (ratio of urinary albumin to creatinine: > 0.40 for AD-treated mice, > 0.15 for BSA-treated mice) showed that all of the mice (7/7) with AD-induced proteinuria (ADp) and three of four mice with BSA-induced proteinuria (BSAp) revealed urinary IgG2b and IgA, while only one of seven control mice showed IgG2b alone in urine. The mice were sacrificed at the time they presented with heavy proteinura for pathologic and anionic studies on renal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of proteinuria by adriamycin or bovine serum albumin in the mouse. 775 63

Rats receiving a single dose (10 mg/100 g) of aminonucleoside of puromycin (PAN) develop heavy proteinuria and acute interstitial nephritis (AIN). Whole isolated glomeruli from rats injected with PAN secreted both TNF-alpha and IL-1 beta cytokines. TNF-alpha secretion was first and maximally detected on day 3, whereas IL-beta activity was found on day 7, when rats were heavily proteinuric and AIN developed. In vivo treatment with either anti-TNF-alpha or anti-IL-1 beta antibodies produced a drastic and simultaneous reduction in both levels of proteinuria and intensity of interstitial cell infiltrate. These effects improved when both antibodies were administered together. Our studies demonstrate the effectiveness of immunosuppressive therapy against these two cytokines in rats with PAN-induced nephrosis.
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PMID:Passive dual immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta maximally ameliorates acute aminonucleoside nephrosis. 785 Oct 23

Copper (Cu) and zinc (Zn) were measured in urine, serum and tissues from rats with nephrotic syndrome (NS) induced with a single subcutaneous dose of puromycin aminonucleoside (PAN; 15 mg/100 g BW). Control animals were pair-fed. Urine was collected daily, and the rats were sacrificed on day 10. PAN-nephrotic rats had proteinuria (days 3-10), high urinary Cu (days 1, 2, 4-10) and Zn (days 3-10) excretion. On day 10, nephrotic rats had: (a) albuminuria, hypoalbuminemia, hypoproteinemia, high urine and low serum levels of ceruloplasmin; (b) low Cu and Zn serum levels; (c) high clearance and fractional excretion of Cu and Zn, and (d) low kidney and liver Cu content and essentially normal tissue Zn levels. The alterations in Cu metabolism were more intense than those in Zn metabolism. Urine Cu and Zn showed a positive correlation with urine total protein on days 3-10 which suggests that high urinary excretion of Cu and Zn may be due to the excretion of its carrier proteins. In conclusion, these rats did not show a typical Zn deficiency but a clear decrease in Cu in the liver and kidney.
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PMID:Copper and zinc metabolism in aminonucleoside-induced nephrotic syndrome. 810 60

In the present study, two series of experiments were done with PAN nephropathy rats given fibroblast growth factor 2 (FGF2) or FGF2 neutralizing antibodies. In the first series of experiments, a dose of 10 micrograms of FGF2 (FGF2 group), 40 micrograms of an FGF2 neutralizing antibody (Anti-FGF2 group) or an equal volume of physiological saline (Control group) was administered for four days after PAN injection. Urinary protein increased more in the FGF2 group than in the other two groups. PCNA (+) glomerular cells were found in decreasing order in groups FGF2, Control and Anti-FGF2. Most of the PCNA (+) cells were podocytes and epithelial cells of Bowman's capsule. Staining for desmin, a marker of podocyte injury, was significantly reduced in the Anti-FGF2 group. Glomerular adhesive lesions were found in decreasing order in groups FGF2, Control and Anti-FGF2. The second series of experiments was designed to study the effects of FGF2 neutralizing antibody (40 micrograms for 5 days after PAN injection, in MoAb group) on severely damaged podocytes caused by repeated (two courses) injections in the PAN nephropathy rats. The results were the same as those in series 1. An increase in urinary protein excretion was observed in both groups, but on the 40th day, the level of proteinuria in the MoAb group decreased abruptly. It was observed that the MoAb group had few adhesive glomeruli compared to the IgG group (administration of mouse IgG) and the PCNA (+) epithelial cells of Bowman's capsule were also few. It was supposed that FGF2 would promote the formation of adhesive lesions by stimulating the proliferation of podocytes and epithelial cells of Bowman's capsule. Additionally, FGF2 itself was thought to impair podocytes because of the increasing desmin score and proteinuria.
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PMID:Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing antibody in puromycin aminonucleoside nephropathy. 899 47

Rats receiving a single dose (10 mg/l00 g body wt) of PAN develop severe proteinuria and acute interstitial nephritis. To investigate the mechanisms involved in interstitial leucocyte accumulation, we examined the expression of adhesion molecules on kidney tissue sections as well as on endothelial cell cultures. We also performed in vivo treatments with antibodies against adhesion molecules. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) was found on day 7 of the disease, when interstitial nephritis was first detected. Also, rat endothelial cells in culture showed maximal expression of ICAM-1 in the presence of 10(-9) - 10(-11) M PAN. Adhesion of peripheral blood mononuclear cells (PBMC) on kidney sections from PAN-treated rats was highest on day 7 (3.05 +/- 0.7 (mean +/- s.e.m.); controls 0.75 +/- 0.5). Such increased adhesion was notably blocked after PAN-treated rat kidney sections were incubated with anti-ICAM-1 MoAb (0.9 +/- 0.4). In addition, adhesiveness of PBMC to PAN-stimulated endothelial cells in culture was enhanced (25 +/- 2.5%; non-stimulated cells 13 +/- 3.1%). The addition of specific MoAbs against ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) produced a high blockage of adhesiveness induced by exposure to PAN (inhibition 58 +/- 3%; non-stimulated cells 40 +/- 7%). Simultaneous administration to PAN-treated rats of anti-LFA-1 and anti-ICAM-1 MoAbs reduced the number of interstitial cells by 70% compared with the 30% of reduction obtained when anti-very late antigen-4 (VLA-4) MoAb and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies were used. Our results suggest that the LFA-1/ICAM-1 pathway plays a principal role in the interstitial nephritis occurring in rats with PAN-nephrosis.
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PMID:Role of leucocyte adhesion molecules in aminonucleoside of puromycin (PAN)-associated interstitial nephritis. 909 15

Clusterin is a glycoprotein induced after renal tubular cell injury. The purpose of this study was to examine the expression of clusterin in a disease model characterized early in its course by predominant glomerular injury. Male Wistar rats (weighing 251 +/- 16 g) were treated with puromycin aminonucleoside (PAN: 15 mg/100 g body wt, subcutaneously; n = 7) or vehicle (control; n = 8). The kidneys were harvested 6 d after treatment, when rats were nephrotic. Clusterin mRNA was markedly induced in the kidneys of nephrotic rats (8.5-fold versus control). Immunohistochemistry studies demonstrated clusterin primarily in tubules in the cortex and medulla. Many of the tubules staining for clusterin were dilated but had no other differentiating morphologic features. Increased numbers of proliferating tubular cells were seen at 6 d, but there was no correlation between these cells and clusterin staining. In contrast to the extent and pattern of clusterin staining, vimentin was seen in only sporadic, dilated tubules, in addition to its expected glomerular localization. An increase in clusterin mRNA was not seen 1, 2, or 4 d after PAN injection. In conclusion, tubular epithelial cell induction of clusterin occurs in the kidneys of nephrotic rats. The appearance of clusterin precedes the development of tubulointerstitial disease and may be a response to the proteinuria.
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PMID:Induction of clusterin in tubules of nephrotic rats. 944 84

The single dose administration of the aminonucleoside of puromycin (PAN) induces a nephrotic syndrome in rats characterized by massive proteinuria and progressive histologic changes. This model of acute parenchymal nephritis is thought to be mediated by the renal recruitment of monocytes and macrophages. To investigate the role of leukocytes in the experimental nephrotic syndrome model, the effects of two methylxanthines, pentoxifylline (45 mg/kg i.p. twice daily) and torbafylline (5 mg/kg i.p. twice daily) were compared with controls over a 2-week period. Pentoxifylline treatment was associated with 3- and 6-fold reductions in urinary protein excretion at 7 and 14 days, respectively, compared with PAN-treated control animals (p < .01). Similarly, 14-day dosing of torbafylline resulted in a 3-fold decrease in urinary protein excretion. Glomerular filtration and electrolyte excretion rates were similar between all treatment groups. There were significant reductions in glomerular neutrophil and macro-phage counts, but not T-cells (OX19+) or suppressor/cytotoxic T-cells (0X8+), in kidneys of rats given either treatment compared with PAN con-trol rats. In summary, both pentoxifylline and torbafylline attenuated the proteinuria and glomerular macrophage and neutrophil infiltration associated with PAN administration. These data support the role of macrophages and neutrophils in the pathogenesis of acute parenchymal injury and the potential role of pentoxifylline or related analogues in the attenuation of the ensuing renal deficit associated with minimal lesion disease.
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PMID:Role of neutrophils and macrophages in experimental nephrosis of the rat. 950 60

Vasculitis in children is uncommon and hardly any information is available from India. We, at PGIMER, Chandigarh, have diagnosed and followed many children with vasculitis of different types though not all, which occur in children. In this article, we have given an overview of the vasculitides that we have encountered along-with a review of relevant literature. We have described 8 children with classical PAN and have highlighted a higher frequency of CNS involvement in our patients. Amongst the 10 BCPAN children, as many as 8 had peripheral gangrene which resulted in auto-amputation in 7. Gangrene of such severity has not been previously reported in this condition. We have also included 30 children with HSP. Gastrointestinal involvement was noted in 86.7% of children and in one of these, it was severe enough to result in hypovolemic shock. Such severe bleeding is very rare. Two of our patients with HSP came late to us after having been operated for an 'acute abdomen' elsewhere. Although renal involvement was seen less frequently than reported in the literature, the severity of involvement was greater (nephrotic range proteinuria in 62% and azotemia in 50%). We have only limited experience of Kawasaki Disease but it appears that children with this disorder are probably not being diagnosed in the acute stage in our country.
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PMID:Vasculitis in children. 1083 7

Nephrin is a novel transmembrane protein of kidney glomerular podocytes, which appears crucially important for the maintenance of the glomerular filtration barrier. According to its predicted structure, nephrin has additional roles in cell-cell adhesion and/or signal transduction. We have previously cloned the rat homologue of nephrin and described its alternatively spliced transcripts alpha and beta. In this study we examined the alterations in expression and regulation of particularly the major alternatively spliced nephrin-alpha giving rise to a variant lacking the membrane spanning domain in the puromycin nephrosis of the rat. A down-regulation of up to 78% was observed of the full length mRNA after 10 d of PAN treatment. The expression changes of nephrin-alpha followed closely the expression of the full length mRNA. Interestingly, we also found nephrin protein in urine at the peak proteinuria samples of this model. These results suggest that soluble nephrin variants may be important markers for proteinuric diseases.
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PMID:Alternatively spliced nephrin in experimental glomerular disease of the rat. 1110 43


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