Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the cellular adhesion molecules ICAM-1, VCAM-1, E-selectin and PECAM in human kidney allografts was assessed by immunoperoxidase labelling of cryostat sections. Biopsies from 10 kidneys immediately prior to transplantation and 58 biopsies from 51 kidney transplants with graft dysfunction were studied. Allograft dysfunction was due to acute tubular necrosis (n = 5), acute rejection (n = 30), cyclosporin A (CyA) nephrotoxicity (n = 6), acute pyelonephritis (n = 3), recurrent glomerulonephritis (n = 4) and chronic rejection (n = 10). There was variability in the distribution of ICAM-1, VCAM-1 and E-selectin expression in pretransplant kidneys but the principal observation was a marked increase in the expression of ICAM-1 and VCAM-1 by the renal vasculature and the proximal tubules during acute rejection. By contrast, grafts with dysfunction not attributed to rejection showed a pattern of ICAM-1 and VCAM-1 expression similar to that observed prior to transplantation. E-selectin was expressed only weakly by occasional intertubular capillaries during acute rejection but the three grafts with pyelonephritis displayed strong expression of E-selectin on intertubular capillaries. There was no change in the pattern of PECAM expression following transplantation. The induction of ICAM-1 and VCAM-1 during rejection may contribute to the recruitment of mononuclear cells and render endothelial and tubular renal cells more susceptible to cell-mediated injury.
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PMID:Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human kidney allografts. 752 37

Vascular endothelial cells express membrane bound adhesion molecules which play a direct role in the localization and subsequent movement of leucocytes from the blood into sites of inflammation. E-Selectin is a cytokine induced adhesion molecule, known to be expressed by endothelial cells in inflammatory conditions, which binds to various leucocyte subpopulations. In a prospective study we have investigated the expression and distribution of E-selectin on renal allograft needle biopsies taken from 16 pretransplant kidneys and 119 post-transplant kidneys. Post-transplant biopsies were taken at times of graft dysfunction and at times of normal graft function. Formal histology was also performed and assessed independently. E-Selectin was found predominantly on the intertubular endothelium and on the endothelium of larger vessels. E-Selectin was present, at low intensity, in some pretransplant biopsies and also some post-transplant biopsies which were reported histologically as normal. In post-transplant biopsies taken for dysfunction E-selectin was present in the majority of cases. Expression was strong in biopsies showing acute cellular rejection and this was associated with a CD4 positive cellular infiltrate. Biopsies showing other causes of dysfunction, in particular acute tubular necrosis, also were E-selectin and CD4 positive with lower intensity than those with acute cellular rejection. These results suggest that E-selectin is a good marker for endothelial activation in renal transplant biopsies. Its presence in histologically apparently normal biopsies suggests that its in vivo kinetics may differ from previously reported in vitro kinetics. E-Selectin may be a potential target for therapeutic intervention.
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PMID:The importance of E-selectin as a marker for renal transplant rejection. 753 43

E-Selectin is a 115-kDa cell surface glycoprotein transiently expressed on vascular endothelium in response to interleukin-1 and tumour necrosis factor-alpha with a peak in expression at four hours. Its distribution in transplant biopsies has been associated with inflammatory events such as allograft rejection. Recently, a soluble isoform of E-selectin has been detected in the culture medium of cytokine activated endothelial cells by an ELISA method. In this study soluble E-selectin levels in renal allograft recipients were compared with the incidence of rejection, acute tubular necrosis (ATN), cyclosporin A (CyA) toxicity, and use of orthoclone OKT3 (muromonab-CD3) to establish whether early endothelial activation and inflammatory damage could be detected. The mean soluble E-selectin level in normal volunteers was 89 ng/ml serum compared to 120 ng/ml for a group of chronic renal failure patients. Soluble E-selectin levels declined upon transplantation but this was not significant, nor was the difference in samples from patients experiencing rejection, ATN or CyA toxicity. A dramatic and sustained rise in soluble E-selectin levels was found within 24 hours of the first dose of OKT3 treatment. This study shows that soluble E-selectin does not provide early unequivocal indication of pathological sequelae in renal transplantation, although extensive endothelial activation can be demonstrated with OKT3 treatment.
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PMID:Lack of correlation of soluble E-selectin level with renal transplant rejection. 755 79

Ischaemia followed by reperfusion (I/R) can induce inflammation and injury and is a risk factor for delayed graft function and rejection of transplanted kidneys. Inflammation is regulated by NF-kappaB transcription factors which induce pro-inflammatory molecules in endothelial cells (EC). We examined whether A20, a negative regulator of NF-kappaB, can protect kidneys from I/R injury. To mimic the fluctuations in endothelial oxygenation that occur during I/R we exposed cultured human umbilical vein EC (HUVEC) to hypoxia (1% O(2) for 4 h) followed by re-oxygenation (21% O(2) for 1 h-24 h). We observed transient expression of pro-inflammatory molecules (E-selectin, VCAM-1 and IL-8) and sustained expression of A20 in HUVEC exposed to hypoxia/re-oxygenation. The effect of A20 on endothelial responses to hypoxia/re-oxygenation was assessed. We observed that pre-treatment of HUVEC with an adenovirus containing A20 (Ad-A20) suppressed activation of NF-kappaB and induction of pro-inflammatory molecules by hypoxia/re-oxygenation, whereas a control adenovirus had little or no effect. Thus the induction of A20 may form a negative feedback loop in pro-inflammatory signalling in cells exposed to hypoxia/re-oxygenation. To validate our cell culture experiments we examined the role of A20 in renal responses to I/R. We observed that A20 was induced in rat kidneys exposed to I/R. Moreover, pre-treatment of animals with Ad-A20 significantly reduced acute tubular necrosis, renal expression of VCAM-1 and NF-kappaB activation in response to I/R, whereas pre-treatment with control adenovirus did not. Our observations suggest that A20 maintains physiological homeostasis in kidneys exposed to I/R by protecting them from inflammation and injury.
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PMID:The A20 gene protects kidneys from ischaemia/reperfusion injury by suppressing pro-inflammatory activation. 1894 30