Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using differential mRNA display to uncover potential mediators associated with chronic rejection, we identified a cDNA fragment induced in Lewis to F344 rat cardiac allografts with arteriosclerosis but not Lewis syngrafts. The full-length cDNA (1.4 kb) isolated from a rat cardiac allograft cDNA library was 99% identical to galactose/N-acetylgalactosamine (Gal/GalNAc) macrophage lectin, a cell-surface receptor. This cDNA hybridized in Northern analysis with total RNA from eight cardiac allografts but not with host hearts, syngrafts, or other organs. There was a significant allograft-specific increase in transcript levels measured by reverse transcriptase PCR at days 7, 14, 28, and 75 in comparison with paired F344 host hearts (subject to same circulation but histologically normal), day-0 hearts, and syngrafts (P < 0.008, n = 4 at each time). Transcript levels in cardiac allografts were higher than those in paired host spleens (a major source of inflammatory cells) (P < 0.0001), indicating the localized nature of Gal/GalNAc lectin induction. By in situ hybridization and immunostaining, Gal/GalNAc lectin expression localized to a subset of inflammatory cells in cardiac allografts. These findings link Gal/GalNAc macrophage lectin to the chronic rejection process, as a possible mediator of macrophage infiltration.
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PMID:Identification and upregulation of galactose/N-acetylgalactosamine macrophage lectin in rat cardiac allografts with arteriosclerosis. 804 Mar 27

Blocking CD28-B7 T-cell costimulation by systemic administration of CTLA4Ig, a fusion protein which binds B7 molecules on the surface of antigen-presenting cells, prevents rejection and induces tolerance in experimental acute allograft rejection models. We tested the effect of CTLA4Ig therapy on the process of chronic renal allograft rejection using an established experimental transplantation model. F344 kidneys were transplanted orthotopically into bilaterally nephrectomized LEW recipients. Control animals received low dose cyclosporine for 10 days posttransplantation. Administration of a single injection of CTLA4Ig on day 2 posttransplant alone or in addition to the low dose cyclosporine protocol resulted in improvement of long-term graft survival as compared with controls. More importantly, control recipients which received cyclosporine only developed progressive proteinuria by 8-12 weeks, and morphological evidence of chronic rejection by 16-24 weeks, including widespread transplant arteriosclerosis and focal and segmental glomerulosclerosis, while animals treated with CTLA4Ig alone or in addition to cyclosporine did not. Competitive reverse transcriptase-PCR and immunohistological analysis of allografts at 8, 16, and 24 weeks showed attenuation of lymphocyte and macrophage infiltration and activation in the CTLA4Ig-treated animals, as compared with cyclosporine-alone treated controls. These data confirm that early blockade of the CD28-B7 T-cell costimulatory pathway prevents later development and evolution of chronic renal allograft rejection. Our results indicate that T-cell recognition of alloantigen is a central event in initiating the process of chronic rejection, and that strategies targeted at blocking T-cell costimulation may prove to be a valuable clinical approach to preventing development of the process.
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PMID:Blockade of T-cell costimulation prevents development of experimental chronic renal allograft rejection. 890 33

Accurate diagnosis and prevention of graft arteriosclerosis, known as chronic rejection, is critical to the success of cardiac transplantation, but often is difficult to attain. Expression of cell division cycle (cdc) 2 kinase, which plays a critical role in cell transition through the G2/M phase, is critical to the proliferation of vascular smooth muscle cells. To evaluate the usefulness of cdc2 kinase expression for pathophysiological analysis of chronic rejection, heterotopic cardiac transplantation was performed in Japanese monkeys (n = 7). Standard reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ RT-PCR were performed to evaluate the expression. In the coronary arteries of chronically rejected allografts, enhanced cdc2 kinase expression was observed in thickened intima and media, while none was expressed in native hearts. The cdc2 kinase was also expressed before the intimal thickening occurred. These results indicate that enhanced expression of cdc2 kinase is a sensitive indicator for chronic cardiac rejection; targeting cdc2 kinase may be a viable gene therapy for prevention of this vasculopathy.
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PMID:Expression of cell division cycle 2 kinase transcription in chronically rejected cardiac allografts of nonhuman primates. 986 Jan 94

Epidemiological studies have shown that chronic exposure to arsenic can result in liver injury, peripheral neuropathy, arteriosclerosis, and an increased incidence of cancer of the lung, skin, bladder, and liver. The overexpression of inducible cyclooxygenase-2 (Cox-2) has been associated with vascular inflammation and cellular proliferation. However, the effect of arsenite on Cox-2 gene expression in endothelial cells was left to be investigated. Western Blot analysis of HUVECs revealed a two-fold induction of Cox-2 protein by arsenite. This induction was associated with a two-fold increase of prostaglandin E2 in the media. Furthermore, the level of Cox-2 mRNA was correspondingly elevated as demonstrated by both Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Transfection of an immortalized human endothelium cell line (ECV304) with Cox-2 reporter gene constructs demonstrated that the transcription of Cox-2 gene was enhanced by arsenite. This induction was attenuated by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFkappaB. In addition, electrophoretic mobility shift assays indicated that NFkappaB activity was induced by arsenite. The kinase activity assay also indicated that IkappaB kinase (IKK) activity was induced by arsenite. These findings indicated that the induction of Cox-2 gene transcription by arsenite was through the stimulation of NFkappaB activity. Arsenite could induce IKK activity, which leads to the phosphorylation and degradation of IkappaB in ECV304 cells. Therefore, it appears that IKK signaling pathway is involved in arsenite-mediated Cox-2 expression.
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PMID:Arsenite stimulates cyclooxygenase-2 expression through activating IkappaB kinase and nuclear factor kappaB in primary and ECV304 endothelial cells. 1183

Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals, respectively, at baseline. HIV infection was independently associated with carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was independently associated with age, years of smoking, and exposure to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5 cases/100 patients, respectively. Carotid atheromatosis progression was significantly associated with NNRTI exposure. People living with HIV infection exhibited high prevalence and incidence of subclinical arterial damage and site-specific predilection for the carotids. These investigations may help optimize HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis, emphasizing the need to consider the atherogenic potential of antiretroviral drugs in management strategies.
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PMID:Prevalence, Incidence, and Contributors of Subclinical Atheromatosis, Arteriosclerosis, and Arterial Hypertrophy in HIV-Infected Individuals: A Single-Center, 3-Year Prospective Study. 3044 34