Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impact of cold storage of cardiac allografts on expression of major histocompatibility complex antigens and vascular adhesion molecules is not known. We obtained serial endomyocardial biopsy specimens at harvest, on implantation, and approximately 15 minutes after reperfusion from six consecutive human cardiac allografts stored in University of Wisconsin solution. Cold ischemia time was 187 +/- 45 minutes. A fourth endomyocardial biopsy specimen was obtained from the recipients of cardiac allografts 1 week after operation. Expression of major histocompatibility complex antigens and vascular adhesion molecules was studied by immunohistochemistry. The intensity was scored blindly by a semiquantitative method. On vascular endothelial cells, the expression of major histocompatibility complex class I and II antigens was strong; ICAM-1 expression was moderate, and expression of VCAM-1 and ELAM-1 was weak to absent. The expression of these antigens on vascular endothelial cells did not change in sequential biopsy specimens. The expression of major histocompatibility complex class I antigens on myocardial cells was weak and remained unchanged. Myocardial cells did not express major histocompatibility complex class II antigens, ICAM-1, VCAM-1, or ELAM-1 on serial examinations. During cold storage of cardiac allografts in University of Wisconsin solution, the expression of major histocompatibility complex antigens and vascular adhesion molecules on endothelial cells and myocardial cells remains unchanged.
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PMID:Expression of major histocompatibility antigens and vascular adhesion molecules on human cardiac allografts preserved in University of Wisconsin solution. 750 49

Recent studies suggest that graft microvascular endothelia may play an important role in the regulation of rejection. Alloantigen-dependent changes in microvascular endothelial phenotype may be associated with differences in infiltrate function in allografts vs. isografts, as reflected in alloantigen-specific CTL accumulation and cytokine production. To correlate cytokine production with differences in microvascular endothelial phenotype during allograft inflammation, we used PCR to identify cytokine mRNAs isolated from pooled cardiac isografts and allografts on days 1, 3, and 5 after transplantation. Graft microvascular endothelia express an inflamed phenotype associated with wound healing and the repair of tissue damage due to mechanical trauma, ischemia, and/or reperfusion injury--i.e., high levels of ICAM-1 expression and MECA-32 mAb reactivity. By day 1 in both isografts and allografts, mRNAs for the cytokines IL1 alpha, IL6, TNF, LT, and TGF beta are upregulated or induced. By the third day in cardiac allografts, an antigen-dependent endothelial phenotype is expressed, characterized by the presence of cell surface VCAM-1. Concomitantly, mRNAs for the lymphokines IL2 and IFN gamma are detected, followed by IL4 mRNA by day 5. The expression of VCAM-1 by allograft endothelia may influence the inflammatory process, by physically recruiting specific T cell subpopulations into the response and/or by delivering additional signals to the infiltrating cells. Eventually, these and other regulatory events occurring at these early times initiate a process that later results in alloreactive tissue destruction.
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PMID:Alloantigen-dependent endothelial phenotype and lymphokine mRNA expression in rejecting murine cardiac allografts. 847 68

Transplantation-related pathogenic factors such as ischemia or allograft-directed inflammation are associated with oxidative changes that might lead to cellular oxidative stress. The aim of this study was to investigate the impact of oxidative stress on: (1) CMV replication in cultured human endothelial cells and (2) the stimulation of endothelial cells by proinfiammatory cytokines. Both pathomechanisms are known to contribute to graft rejection crises in vivo. Oxidative stress was induced in endothelial cell cultures with 10-200 microM buthionine sulfoximine. Western blotting showed a significant increase in the production of CMV-specific immediate early and late proteins in buthionine sulfoximine-treated cultures. Immunocytochemical staining suggested that this effect was caused by increased numbers of CMV antigen expressing cells (66% immediate early; 78%, late). Quantitative polymerase chain reaction for CMV-specific DNA and virus titration revealed that enhanced viral replication levels correlated with increased virion production. As a measure for the endothelial cell activation status, the surface expression of HLA-ABC and HLA-DR and adhesion molecules (ICAM-1, ELAM-1, VCAM-1) was quantified by fluorometric methods. Whereas oxidative stress alone did not modulate any surface molecule expression, the IFN-gamma-mediated expression of HLA-ABC and HLA-DR and the IL-1-mediated expression of ICAM-1, but not of ELAM-1 and VCAM-1 (IL-1 + TNF-alpha), was amplified. Interestingly, the amplification of HLA molecule expression was even higher in CMV-infected endothelial cells. This study provides evidence that oxidative stress contributes to the regulation of CMV replication, virus shedding, and the activation of endothelial cells by proinflammatory cytokines as it is observed in transplant recipients.
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PMID:Impact of oxidative stress on human cytomegalovirus replication and on cytokine-mediated stimulation of endothelial cells. 868 57

Neutrophil adhesion to the vascular endothelium is enhanced during tissue ischemia and/or inflammation, conditions that are associated with tissue acidosis. This study examined the effects of hypercarbic acidosis (10 or 20% CO2) and of hypocarbic alkalosis (0% CO2) on human neutrophil CD18 and human aortic endothelial cell intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin expression quantified by flow cytometry. Acidosis with 20% CO2 for 4 h decreased ICAM-1 to 60.6 +/- 9.7% of control. In contrast, alkalosis with 0% CO2 for 4 h enhanced ICAM-1 expression to 143.8 +/- 10.1% of control. There was no pH dependence of VCAM-1 or E-selectin expression. Tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml) increased endothelial ICAM-1, E-selectin, and VCAM-1; under these conditions, acidosis with 20% CO2 blunted both ICAM-1 and E-selectin surface expression compared with 5% CO2-, TNF-alpha-treated cells. Hypercarbic acidosis with 20% CO2 increased neutrophil CD18 expression and enhanced neutrophil adhesion. This latter effect was inhibited by neutrophil pretreatment with an anti-CD18 monoclonal antibody. In contrast, when only endothelial cells were preincubated with the hypercarbic buffer, neutrophil adhesion diminished to 55.6 +/- 7.8% of control. The results suggest that acidosis generated during tissue ischemia/inflammation may induce CD18-mediated neutrophil adhesion despite a decrease in ICAM-1 expression.
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PMID:pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression. 884 27

In this study we used nonradioactive in situ hybridization for the cellular localization of vascular cell adhesion molecule-1 (VCAM-1) mRNA in immune-mediated, ischemic and degenerative diseases of the rat nervous system. In the acute phase of experimental autoimmune encephalomyelitis and neuritis VCAM-1 mRNA was expressed not only on the luminal surface of inflamed vessels but also in perivascular cells suggesting a functional role of VCAM-1 in both endothelial adhesion and local restimulation of autoantigen-specific T cells. Accordingly, perivascular T cell accumulation was most pronounced at sites of local VCAM-1 mRNA expression. In addition, VCAM-1 mRNA was detected in the border zone around photochemically induced cerebral infarcts which is the predeliction site of T cell infiltration and expression of immune activation markers during the first week after ischemia. VCAM-1 mRNA was absent from the center of the infarcts as well as axotomized central and peripheral nerves undergoing Wallerian degeneration. These data indicate that VCAM-1-mediated adhesion processes are involved in immune-mediated and ischemic diseases of the nervous system but not in T cell-independent macrophage recruitment during Wallerian degeneration.
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PMID:Vascular cell adhesion molecule-1 mRNA is expressed in immune-mediated and ischemic injury of the rat nervous system. 886 37

Secondary ischemic brain injury has been shown to develop as a consequence of inflammation and vasogenic brain edema. In this study we show that inflammatory cytokines and simulated in vitro ischemia stimulate the surface expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) in human cerebromicrovascular endothelial cells (HCEC) in culture. The levels of all three adhesion molecules were dramatically (3 to 10-fold) up-regulated by 4-24 hour exposure to the inflammatory cytokines. IL-1 beta (10-200 u/ml) or TNF alpha (50 200 u/ml), and by a 4 hour exposure to "simulated" in vitro ischemia, as determined by immunocytochemistry and ELISA. Following 24 hours of subsequent reperfusion, the expression of ICAM-1 and VCAM-1 was maintained at ischemia-induced levels, whereas E-selectin was no longer detectable. Both the cytokine- and ischemia-induced up-regulation of adhesion molecules were completely abolished by the transcriptional inhibitor, actinomycin D (10 micrograms/ml), and inhibited by the cycloxygenase (COX) inhibitor, indomethacin (300 microM). These findings implicate HCEC in the processes of leukocyte adhesion and recruitment in the brain during stroke in vivo.
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PMID:Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults. 941 64

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.
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PMID:Soluble adhesion molecules in CSF are increased in children with severe head injury. 981 34

There is recent evidence that angiotensin-converting enzyme (ACE) inhibition reduces postischemic injury and angiotensin II receptor inhibition may have similar effects. We therefore further characterized the role of ACE- vs. AT1-receptor inhibition on cell injury and temporal association of leukocyte endothelial interaction in response to ischemia-reperfusion. A combined in vivo and in vitro study comparing the ACE inhibitor enalapril and the AT1-receptor antagonist losartan was performed. The extent and temporal correlation of cellular damage (propidium-iodide staining), microvascular perfusion failure and leukocyte-endothelial interaction (leukocyte adherence) were investigated by means of intravital microscopy, after the application of hemodynamically ineffective doses of enalapril and losartan (5 mg/kg). A hamster dorsal skinfold model with a 4-h tourniquet ischemia was used. In vitro, the effect of enalapril and losartan on polymorphonuclear cell (PMN) adherence, as well as adhesion molecule expression (ICAM-1, VCAM-1), on hypoxia- or IL-1beta-stimulated endothelial cells (HUVEC) was assessed using a PMN-adhesion assay and flow cytometry, respectively. Ischemia-reperfusion responses revealed a biphasic pattern, comprised of an early phase (30 min) of acute cellular damage and microvascular perfusion failure, followed by a late increase (240 min) in leukocyte adherence in vivo. Enalapril significantly reduced early cellular damage, microvascular perfusion failure, and leukocyte adherence in response to ischemia-reperfusion. Conversely, AT1 receptor inhibition with losartan proved to be ineffective at attenuating postischemic microcirculatory disorders (leukocyte-endothelial interactions, microvascular perfusion failure) and aggravated cellular injury. In vitro, enalapril reduced PMN adherence and ICAM-1 and VCAM-1 expression, while losartan was ineffective in the same respect. Following ischemia-reperfusion injury, ACE- versus AT1-receptor inhibition induce differential effects concerning the extent and temporal association of cell injury and leukocyte-endothelial interaction. The use of enalapril combines the beneficial effects of preventing cell and vascular injury immediately after reperfusion, with a delayed inhibition of the inflammatory response. Since the AT1-receptor inhibitor losartan did not mimic effects obtained with ACE inhibition, it is conceivable that the responses in ischemia-reperfusion are mediated by a non-angiotensin II-AT1 receptor-dependent mechanism.
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PMID:Differential effects of short-term ace- and AT1-receptor inhibition on postischemic injury and leukocyte adherence in vivo and in vitro. 1071 75

Monocyte influx secondary to ischemia-reperfusion conditions the renal allograft to rejection by presentation of antigens and production of cytokines. Monocyte influx depends on NFkappaB-dependent transcription of genes encoding adhesion molecules and chemokines. Here we demonstrate that cationic liposomes containing phosphorothioated oligodeoxynucleotides (ODN) with the kappaB binding site serving as competitive binding decoy, can prevent TNF-alpha-induced NFkappaB activity in endothelial cells in vitro. In an allogenic rat kidney transplantation model (BN to LEW), we show that perfusing the renal allograft with this decoy prior to transplantation abolishes nuclear NFkappaB activity in vivo and inhibits VCAM-1 expression in the donor endothelium (P<0.05). At 24 h postreperfusion, periarterial infiltration of monocytes/macrophages was significantly reduced in decoy ODN-treated allografts compared to control allografts (3.7+/-0.7 vs. 9.2+/-1.2 macrophages/vessel; P<0.01). At 72 h, there was a reduction of tubulointerstitial macrophage infiltration in decoy ODN-treated kidneys compared to controls (75.6+/-13.9 vs. 120.0+/-11.2 macrophages/tubulointerstitial area; P<0.05). In conclusion, perfusion of the renal allograft with NFkappaB decoy ODN prior to transplantation decreases the initial inflammatory response in a stringent, nonimmunosuppressed allogenic transplantation model. Therefore, the NFkappaB decoy approach may be useful to explore the role of endothelium and macrophages in graft rejection and may be developed into a graft-specific immunosuppressive strategy allowing reduction of systemic immunosuppression on organ transplantation.
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PMID:NFkappaB decoy oligodeoxynucleotides reduce monocyte infiltration in renal allografts. 1074 38

Induction of NF-kappaB-dependent gene expression plays an important role in a number of biological processes including inflammation and ischemia-reperfusion injury. However, few attempts aimed at selective regulation of this transcription factor have been successful. We report here that a naturally occurring antibacterial peptide PR39 reversibly binds to the alpha 7 subunit of the 26S proteasome and blocks degradation of NF-kappa B inhibitor I kappa B alpha by the ubiquitin-proteasome pathway without affecting overall proteasome activity. I kappa B alpha phosphorylation and ubiquitination occur normally after PR39 treatment, and binding of valosin-containing proteins is not impaired. The inhibition of I kappa B alpha degradation abolishes induction of NF-kappa B-dependent gene expression in cell culture and in mouse models of acute pancreatitis and myocardial infarction, including upregulation of endothelial adhesion proteins VCAM-1 and ICAM-1. In the latter model, sustained infusion of PR39 peptide resulted in significant reduction of myocardial infarct size. PR39 and related peptides may provide novel means to regulate cellular function and to control of NF-kappa B-dependent gene expression for therapeutic purposes.
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PMID:Inhibition of ubiquitin-proteasome pathway-mediated I kappa B alpha degradation by a naturally occurring antibacterial peptide. 1093 Apr 47


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