UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased endotoxin sensitivity during pregnancy occurs in many animals, including rats. The mechanism of this phenomenon is not understood. In the present study it was investigated whether this increased sensitivity is reflected by an altered inflammatory pattern. Inflammatory cell influx, the O2(-)-producing potential of these cells, and expression of adhesion molecules was studied in the glomeruli of pregnant and cyclic rats at various intervals after low dose endotoxin infusion. Kidney sections were stained for monocytes and adhesion molecules (ICAM-1, VCAM-1, LFA-1, and VLA-4) using monoclonals, while potentially O2(-)-producing neutrophils (ie, activated neutrophils) were quantified using immunohistochemical methods. The results show early glomerular influx of activated neutrophils, maximally 4 hours after endotoxin. Both absolute neutrophil counts and relative numbers of activated neutrophils were significantly increased in pregnant versus cyclic rats. In contrast to cyclic rats, showing transient monocyte influx, in pregnant endotoxin-treated rats monocyte influx reaches a maximum at t = 168 hours. These cell kinetics were paralleled by expression of the various adhesion molecules. It was concluded that pregnancy profoundly influences not only the inflammation kinetics after endotoxin, but also the violence of the reaction, reflected by activated neutrophils. This altered glomerular inflammatory pattern may help to explain why low dose endotoxin infusion induces pre-eclamptic-like symptoms (such as an intraglomerular prothrombotic microenvironment and proteinuria) exclusively in the pregnant rat.
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PMID:Glomerular inflammation in pregnant rats after infusion of low dose endotoxin. An immunohistological study in experimental pre-eclampsia. 748 13

Rat kidneys were perfused with anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibody prior to allotransplantation. In the two strain combinations examined, LEF-to-WKAH transplants resulted in accelerated graft loss, and no prolongation of graft survival. The accelerated graft loss was the result of frequent occurrence of necrotizing arteritis within the grafts. In contrast, TO-to-WKAH transplants resulted in no change in graft survival and no arteritis. Necrotizing vasculitis in the LEJ-to-WKAH grafts was characterized by fibrinoid necrosis, collection of cellular infiltrates and serum macromolecular protein entrapment. The F(ab1)2 form of anti-ICAM-1 antibody partially preserved the antibody's capacity to accelerate graft loss. Therefore, although endothelial injury by Fc-mediated cytotoxicity may be involved in vascular damage, other mechanisms also come into play. The amount and distribution pattern of ICAM-1 antigen were identical in both TO and LEJ strains. Intravenous anti-ICAM-1 antibody administration combined with lipopolysaccharide, Poly(I)-Poly(C), warm ischemia to the kidney, or subcutaneous immunization with allogeneic spleen cells, but without renal transplantation, did not generate necrotizing vasculitis or proteinuria. These observations plus our previous data on the rat liver transplantation model clearly show that graft perfusion with anti-ICAM-1 monoclonal antibody invokes extensive vascular damage within allografts by Fc-mediated and Fc-independent mechanisms, depending on the donor-to-host combination.
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PMID:Strain combination-dependent genesis of necrotizing arteritis in anti-ICAM-1 antibody-perfused renal allografts in the rat. 778 89

No immunosuppression agent is as yet available that prevents the process of chronic allograft rejection, the most critical cause of late organ allograft loss. RS61443 (mycophenolate mofetil) inhibits de novo DNA synthesis as well as diminishes expression of cell surface molecules and antibody production. As these factors seem important in the pathophysiology of the chronic phenomenon, we investigated the effects of the agent in an established model of chronic rejection of kidney allografts in a F344-to-Lewis rat strain combination. All recipients were treated for the first 10 days after engraftment with low-dose cyclosporine (1.5 mg/kg/day) to reverse an initial acute rejection episode. Since functional and morphological changes do not become manifest in this model until after 12 wk, treatment with RS61443 (15 mg/kg/day, p.o.) was either initiated at the day of grafting (Gp 1) or 8 wks thereafter (Gp 2), and continued throughout the follow-up period. Non-RS61443-treated allografted rats receiving vehicle only (Gp 3) developed progressive proteinuria after 12 wk. Peak cellular infiltration (particularly macrophages in glomeruli and perivascular areas) at 16 wk was associated with densely expressed adhesion molecules (ICAM-1 on endothelium), cytokines and growth factors (TNF-alpha and TGF-beta in glomeruli and PDGF on arterial smooth muscle cells). Interstitial fibrosis, with tubular atrophy, glomerulosclerosis, and varying degrees of intimal proliferation and luminal obliteration of vessels, progressed thereafter. In vitro binding of MNC from naive animals to chronically rejecting allografted kidneys generally confirmed the immunohistological observations, peaking at 12 wk; this binding was significantly inhibited by mAbs against specific adhesion molecules (CD11a, CD18, and ICAM-1). Serum-allospecific IgG and IgM peaked at 1-2 wk after engraftment in the control recipients, decreasing thereafter. Although IgM declined to baseline after 12 wk, low levels of allospecific IgG persisted throughout the follow-up period. In contrast, recipient treatment with RS61443 (both Gp 1 and Gp 2) allowed the allografts to function normally throughout follow-up period. Proteinuria was virtually absent, and morphological and immunohistological manifestations of the chronic process were markedly diminished. In addition, treated recipients developed no significant side effects, including leukopenia, anemia, thrombopenia, nephrotoxicity, and hepatotoxicity. It appears that this agent can safely prevent the changes of chronic rejection of kidney allografts in this rat model.
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PMID:Effects of RS61443 on functional and morphological changes in chronically rejecting rat kidney allografts. 787 46

Puumala hantavirus-induced nephropathia epidemica (NE) is an important cause for an acute reversible renal failure in Scandinavia, European Russia, and the Balkans. The characteristic histopathological renal finding is an acute tubulointerstitial nephritis. Mild to massive proteinuria, hematuria, and a rise in the serum creatinine level are typically seen. The pathogenetic mechanisms of NE kidney failure are incompletely understood. Therefore we studied the infiltrating cell populations and local expression of cytokines and growth factors in the kidney during the acute disease. Results of the histological and immunohistological studies of eight kidney biopsies show mild to moderate interstitial infiltration of lymphocytes, plasma cells, monocytes/macrophages, and polymorphonuclear leukocytes, mainly eosinophilic granulocytes and neutrophils. An increased expression of the cytokines tumor necrosis factor-alpha, transforming growth factor-beta, and platelet-derived growth factor was seen at the same sites mainly in the peritubular area of the distal nephron. Concomitantly also at the same locations expression of the endothelial adhesion molecules ICAM-1, VCAM, and PECAM was seen. Light microscopic changes in tubuli were common. Interestingly, despite the often massive transient proteinuria, no marked changes were seen in the glomeruli of NE kidneys. No evidence of Puumala virus was found in the kidney biopsies.
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PMID:Cytokines, adhesion molecules, and cellular infiltration in nephropathia epidemica kidneys: an immunohistochemical study. 859 83

We studied the expression of adhesion molecules on infiltrating leukocytes and tubular cells in chronic tubulointerstitial nephritis associated with puromycin aminonucleoside (PA) nephrosis. Rats received injections of PA (2 mg/100 g body wt) weekly for the first 3 weeks and every other week thereafter. Rats were killed at 0, 3, 5, 8, and 12 weeks after the start of injections. From the third to the fifth week, the initial infiltrating cells in interstitial tissue were mainly CD4+ T lymphocytes. At the fifth week, ICAM-1, CD44, and hyaluronate were expressed on infiltrating cells in interstitial tissue. At the eighth week, the number of infiltrating cells reached a peak and consisted of T lymphocytes (CD4, CD8) and macrophages (ED1, MHC class II, CD11b, and CD18). The severity of interstitial infiltration was correlated with the degree of proteinuria and with ICAM-1 expression. Our results suggest that CD4+ T lymphocytes may contribute to the production of initial tubular injury. Expression of ICAM-1 helps mononuclear cells migrate to the interstitium. In addition, expression of CD44 and hyaluronate may play important roles in the chronicity of tubulointerstitial nephritis.
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PMID:The relationship of adhesion molecules and leukocyte infiltration in chronic tubulointerstitial nephritis induced by puromycin aminonucleoside in Wistar rats. 863 80

We investigated whether acteoside can inhibit mesangial matrix expansion or mesangial cell proliferation in mesangioproliferative anti-Thy 1 nephritis. Untreated control rats were compared to the rats treated with acteoside either during early (day 1 to 8) or late (day 4 to 12) period after the induction of anti-Thy 1 nephritis. The result showed that acteoside and prednisolone treatments (in either early or late period) significantly reduced proteinuria, mesangial matrix expansion (the index of matrix expansion) and mesangial proliferation as determined by the number of proliferating nuclear cell antigen (PCNA)-positive cells. Acteoside also reduced glomerular macrophage infiltration and ICAM-1 expression in glomeruli of anti-Thy 1 nephritic rats. Furthermore, acteoside treatment markedly increased the activities of matrix metaloproteinases (MMP) in glomeruli. These results suggest that acteoside can inhibit mesangial cell proliferation and extracellular matrix overproduction by either inhibiting ICAM-1 expression or increasing activities of MMP.
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PMID:Effect of acteoside on mesangial proliferation in rat anti-Thy 1 nephritis. 869 10

Glomerular expression of intercellular adhesion molecule-1 (ICAM1) (CD54) and membrane cofactor protein (MCP; CD46) and positive infiltrating cells in leukocyte function associated antigen-1 (LFA1)alpha (CD11a) and C3bi receptors (CR3/CD11b, CR4/CD11c) were examined by the indirect immunoperoxidase method on 43 sets of repeated renal biopsy specimens from patients with immunoglobulin A nephropathy. Twenty-four-hour urine protein at the time of renal biopsy was also evaluated. Glomerular infiltration of LFA1alpha+ cells was significantly correlated with glomerular expression of ICAM1 (r = 0.494, P < 0.0001). Glomerular complement receptor type 4 (CR4)+ cells were significantly correlated with glomerular expression of MCP (r = 0.405, P < 0.0001). The glomerular expressions of ICAM1 and MCP were significantly correlated with each other (r = 0.700, P < 0.00001). The glomerular infiltrations of LFA1alpha+ and CR4+ cells were highly correlated with each other (r = 0.884, P < 0.00001), and both cell types were significantly correlated with urine protein (respectively, r = 0.426 and 0.478, P < 0.001 and 0.0001). When the change in these parameters between the time of the initial and follow-up biopsies was evaluated, there was a significant correlation between the change in glomerular expression of ICAM1 (DeltaICAM1) and MCP (DeltaMCP) as well as between the change in glomerular infiltration of LFA1alpha+ cells (DeltaLFA1alpha+) and CR4+ cells (DeltaCR4+). Both DeltaLFA1alpha+ and DeltaCR4+ were significantly correlated with the change in urine protein. These findings suggest that ICAM1/LFA1 interaction and MCP-mediated C3bi/C3biR interaction cooperate and participate in persistent glomerular infiltration of immune cells in immunoglobulin A nephropathy, and that these LFA1alpha+ and C3biR+ cells contribute to the induction of proteinuria.
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PMID:Intercellular adhesion molecule-1/leukocyte function associated antigen-1-mediated and complement receptor type 4-mediated infiltration and activation of glomerular immune cells in immunoglobulin A nephropathy. 871 20

We conducted an immunohistological investigation on the pathogenesis of interstitial foam cell formation in patients with idiopathic membranous nephropathy (MN). The patients were divided into two groups: Group I consisted of 23 MN patients with interstitial foam cells; Group II consisted of the other 159 patients without foam cells. Age at renal biopsy, duration of proteinuria, blood pressure and other clinical parameters were not significantly different between the two groups. The proportion of nephrotic patients in Group I was 52.2% (12/23), and was not significantly different from that in Group II (48.4%, 77/159). Renal biopsy specimens were examined by immunoperoxidase studies using monoclonal antibodies. The interstitial foam cells were positive for EBM11 (CD68) and 25F9, which are markers of macrophage (M phi) and mature M phi, respectively, but did not express markers of T cells. In interstitial infiltrating cells, both M phi and T cells were observed, but mature M phi were seldom seen. Furthermore, LFA-1 and ICAM-1, but not ICAM-3 (the third ligand for LFA-1) were observed in the interstitial foam cells. LFA-1 and ICAM-3 were observed mainly in interstitial infiltrating cells, but ICAM-1 was observed to a much lesser extent in these cells. These results suggest that interstitial foam cells in MN may be independent of severe hyperlipidemia and proteinuria, and that there may be different mechanisms underlying the accumulation of interstitial foam cells and infiltrating m phi s. Further investigations are required to clarify the pathogenesis of interstitial foam cells in renal tissue.
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PMID:[Clinicopathological study of interstitial foam cells in idiopathic membranous nephropathy. Consideration of the appearance of interstitial foam cells in renal tissue]. 871 10

Intercellular adhesion molecule-1 (ICAM-1, CD54), an adhesion molecule of the immunoglobulin superfamily, is an endothelial cell surface ligand for such leukocyte integrins as lymphocyte-function-associated molecule 1 (LFA-1, CD11a/CD18), Mac-1 (CD11b/CD18) and CD43. These molecules mediate adhesive interactions between leukocytes and endothelial cells and are critically involved in infiltration of leukocytes into inflammatory lesions. We examined the expression of ICAM-1 in renal tissues of Masugi nephritis rats and directly examined the role of ICAM-1 by administration of neutralizing monoclonal antibodies (MAbs) to rat ICAM-1, LFA-1 alpha-subunit (LFA-1 alpha), beta-subunit (LFA-1 beta) and Mac-1 alpha-subunit (Mac-1 alpha). Within 3 h after injection of nephrotoxic serum, increased expression of ICAM-1 was detected in the glomeruli by in situ hybridization and an immunofluorescence study. Proteinuria was significantly suppressed by the MAbs against ICAM-1, Mac-1 alpha and LFA-1 beta. Neutrophil infiltration into the glomeruli was significantly prevented by injection of the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta. These results indicate that both ICAM-1/LFA-1 and ICAM-1/Mac-1 pathways are involved in neutrophil infiltration into the glomeruli. On the other hand, monocytic infiltration was prevented by the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta but not by anti-Mac-1 alpha MAb. Due to these results, ICAM-1 is considered to be a critical molecule involved in the pathogenesis of the leukocyte infiltration into the glomeruli in the heterologous phase of Masugi nephritis. Anti-ICAM-1 antibody may be beneficial in the treatment of leukocyte-mediated glomerular diseases.
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PMID:The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats. 877 54

DOCA-NaCl treatment causes hypertension, accelerates development of proteinuria, and leads to glomerulosclerosis in rats with autoimmune Heymann nephritis. To study the mechanisms of kidney injury induced by renal haemodynamic load in chronic nephritis, we studied by immunohistochemistry the local expression of various cytokines, growth factors and adhesion molecules in the kidneys of Heymann nephritic rats with or without DOCA-NaCl-induced hypertension. The DOCA-NaCl-nephritis group developed hypertension and marked renal enlargement as compared with the nephritis group, the DOCA-NaCl group, and the controls. Albuminuria appeared earlier and was heavier in the DOCA-NaCl-nephritis group compared with the nephritic rats without DOCA-NaCl. Expression of IL-6, TNF-alpha, GM-CSF, b-FGF, NGF, TGF-beta, and ICAM-1 was enhanced in the kidneys of the DOCA-NaCl-nephritis group as compared with other groups, localized mainly in the glomerular mesangium (IL-6, GM-CSF, TGF-beta), glomerular and peritubular endothelium (ICAM-1), and collecting ducts (TNF-alpha, b-FGF, NGF, TGF-beta), possibly associated with the observed tubulointerstitial mononuclear cellular infiltration. Thus in autoimmune Heymann nephritis, DOCA-NaCl treatment causes hypertension and increased renal mass together with upregulation of local cytokine and growth factor production, which may further aggravate hypertension and accelerate progression of renal damage.
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PMID:Increased renal expression of cytokines and growth factors induced by DOCA-NaCl treatment in Heymann nephritis. 880 10

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