Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Cellular constituents of heart muscle contain both constitutive and inducible nitric oxide (NO) signaling pathways that modulate the contractile properties of cardiac myocytes. The identities of the inducible NO synthase (iNOS) isoform(s) expressed in cardiac muscle, and of the specific cell types expressing iNOS activity, remain poorly characterized. We amplified a 217-base pair cDNA by reverse transcriptase-polymerase chain reaction from primary cultures of inflammatory cytokine-pretreated adult rat ventricular myocytes (ARVM) that was nearly identical to other iNOS cDNA sequences. Using this 217-base pair cDNA as a probe in Northern blots, we found no evidence of iNOS mRNA in control myocytes, but both interleukin-1 beta and interferon-gamma individually increased iNOS mRNA abundance in primary cultures of ARVM, with maximal expression at 12 h. The half-life of iNOS mRNA in actinomycin C1-treated cells was 4 h. Both dexamethasone and transforming growth factor-beta attenuated the induction of iNOS mRNA abundance and enzyme activity by IL-1 beta and INF gamma. Pretreatment with dexamethasone also abolished the induction of iNOS mRNA, but not the increase in GTP cyclohydrolase mRNA in purified cardiac myocytes from lipopolysaccharide-injected rats. In order to further characterize the specific cell type producing NO, we used a NO-specific porphyrinic/Nafion-coated microsensor to record NO release from a single, isolated ARVM pretreated with IL-1 beta and IFN gamma in L-arginine-depleted medium. NO release could be detected following microinjection of L-arginine in the vicinity of the cell juxtaposed to the NO microsensor, but not following microinjection of D-arginine, and not from ARVM pretreated with L-N-monomethylarginine. Cytokine-pretreated ARVM that had been maintained in L-arginine-depleted medium also exhibited a depressed contractile response to isoproterenol after addition of L-arginine, but not D-arginine. These results indicate that altered contractile function of cardiac myocytes following exposure to specific inflammatory cytokines is due to induction of myocyte iNOS.
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PMID:Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. 752 57

Delavirdine (bisheteroarylpiperazine, U-90152), a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1), was evaluated in a two-drug combination with recombinant human interferon-alpha (IFN-alpha) or the peptidomimetic protease inhibitor U-75875 against HIV-1 replication in vitro. Viral growth was assayed in a CD4+ T cell line (H9) infected with HIVIIIB and in human peripheral blood mononuclear cells infected with the clinical isolate HIVJRCSF. Drug synergy, estimated by the combination index method and the method of Pritchard and Shipman, was observed when delavirdine was combined with U-75875 or IFN-alpha over a range of drug concentrations (delavirdine: 0.001, 0.003, 0.01, 0.03 microM; U-75875: 0.01, 0.03, 0.1, 0.3, 1.0 microM; IFN-alpha: 2, 6, 17, and 50 or 10, 30, 100, and 300 IU/mL). The combinations showed no detectable drug antagonism or cytotoxicity. These in vitro synergy data support the potential use of delavirdine with either a protease inhibitor or IFN-alpha in patients with AIDS.
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PMID:In vitro inhibition of human immunodeficiency virus type 1 by a combination of delavirdine (U-90152) with protease inhibitor U-75875 or interferon-alpha. 752 53

The efficacy of CTLA4Ig in blocking immune activation and allograft rejection (AR) was tested in an aggressive and rapid model of rat lung AR (Brown Norway [BN]-->Lewis [LEW]). CTLA4Ig is a recombinant soluble protein that binds with high affinity to rat B7/BB1 and other surface molecules on APCs, subsequently blocking the binding of B7/BB1 to CD28/CTLA4 on T cells. This interrupts the costimulatory pathway critical for complete T cell activation and completion of the AR process. Left single-lung transplants were performed between BN-->Lew. Five allograft recipients were examined in each group. At transplantation, animals received 250 micrograms of CTLA4Ig or 250 micrograms of control Ig intraperitoneally daily until sacrifice. Animals were sacrificed on days 2, 4, and 7 after transplant. Control (BN-->Lew) grafts show irreversible rejection by day 7. Syngeneic (Lew-->Lew) grafts show no AR on day 7. AR episodes were graded histologically (stages 0-IV) and pathologic intensity of inflammation was graded on percentage of involvement. Cytokine transcript levels were measured in control and CTLA4Ig-treated animals (n = 5 in each group) on day 7 using reverse transcriptase polymerase chain reaction techniques. The most profound differences were found on day 7 after transplant. The degree of lymphocytic infiltration was greater in the CTLA4Ig group (perivascular: 4 +/- 0 vs. 2.6 +/- 0.6, peribronchial: 4 +/- 0 vs. 2.2 +/- 0.4, and peribronchiolar: 3.6 +/- 0.5 vs. 2 +/- 0.3, P < 0.01). However, in striking contrast, the stage of AR (3 +/- 0 vs. 4 +/- 0, P < 0.01), vasculitis (1 +/- 0.7 vs. 2.6 +/- 0.6, P < 0.05), hemorrhage (0.4 +/- 0.6 vs. 3.2 +/- 0.4, P < 0.01), and necrosis (0 +/- 0 vs. 2.4 +/- 0.5, P < 0.005) were significantly reduced in animals treated with CTLA4Ig. Since CTLA4Ig blocks Th1 cell activation in vitro, we compared the levels of Th1 inflammatory cytokines IL-2, gamma-IFN, and TNF-alpha in the two models. The intragraft ratios (CTLA4Ig/control) were IL-2:0.77, gamma-IFN: 1.29, and TNF-alpha:1.33. Thus, CTLA4Ig did not significantly block intragraft production of Th1 cytokines on day 7.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Soluble CTLA4Ig modifies parameters of acute inflammation in rat lung allograft rejection without altering lymphocytic infiltration or transcription of key cytokines. 753 46

The Fas antigen is a transmembrane receptor that can trigger apoptosis in a variety of tumor and hematopoietic cells. Ovarian follicular atresia and luteolysis are thought to occur by apoptosis. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry, we demonstrated that human granulosa/luteal cells express the Fas antigen. An anti-human Fas antigen monoclonal antibody (Fas mAb; clone CH-11), which induces apoptosis in other cell types by binding to the Fas antigen, induced significant cell death (30%) in cultures pretreated with interferon gamma (IFN gamma). This agrees with studies on tumor cell lines showing that IFN gamma enhances cytotoxic effects of Fas mAb. Granulosa/luteal cells exhibited morphological characteristics typical of apoptosis, including membrane blebbing and condensed chromatin. DNA fragmentation into oligonucleosomal units of approximately 180 bp, typical of apoptosis, was detected at elevated levels in Fas mAb-treated cultures via 3' end-labeling and gel electrophoresis. Examination of cultured cells in situ for apoptotic DNA cleavage by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) indicated that more apoptotic death occurred in Fas mAb-treated cultures than in control cultures. Effects of hCG-induced luteinization of cultures on Fas mAb-induced cytotoxicity was examined: combined pretreatment with IFN gamma and hCG induced a synergistic increase in Fas mAb-induced cytotoxicity (40%) over that obtained with IFN gamma-pretreatment alone (15%). In summary, granulosa/luteal cells express the Fas antigen and are sensitive to Fas mAb-induced apoptosis. Human CG synergized with IFN gamma to increase Fas mAb-induced death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fas antigen-mediated apoptosis in human granulosa/luteal cells. 753 48

The distribution of four cytokines was analyzed in the endometrium and trophoblast of the horse between Days 30 and 55 of gestation. Endometrial tissues, invasive trophoblast (chorionic girdle), and noninvasive trophoblast (chorion and allantochorion) were examined separately. Cytokine expression was determined by amplification of specific mRNA via the reverse transcriptase polymerase chain reaction (RT-PCR). Messenger RNA for interleukin 2 (IL-2), interleukin 4 (IL-4), and interferon gamma (IFN gamma) was detected in endometrial tissues, unstimulated peripheral blood lymphocytes, and control kidney tissue, but not in trophoblasts. leukocytes resident in the endometrium or traversing the uterus via blood vessels might be the source of these cytokines. Endometrial tissues and invasive and noninvasive trophoblasts expressed mRNA for tumor necrosis factor alpha TNF alpha). Immuonoreactive TNF alpha protein was detected in different cell types of the endometrium and in the invasive and noninvasive trophoblast. The ubiquitous expression of TNF alpha by the endometrium and trophoblasts suggests that this cytokine might have an important role in regulating placental growth and differentiation or maternal leukocyte responses to trophoblasts. IL-2, IL-4, and IFN gamma might have important immunoregulatory roles within the endometrium.
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PMID:Horse trophoblasts produce tumor necrosis factor alpha but not interleukin 2, interleukin 4, or interferon gamma. 753 96

The expression of the cytokine and IFN-related genes was studied in mouse embryo using RT-PCR method capable of detecting low levels of mRNA. Total RNA was prepared from the days 7 embryos by acid guanidinium thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by M-MLV reverse transcriptase, and amplified using the specific oligonucleotide primers for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, IFN-beta, IFN-gamma, IFN-alpha/beta receptor (IFN-alpha/beta R), IFN-gamma receptor (IFN-gamma R), interferon reguratory factor (IRF)-1, IRF-2 and 2'-5' oligoadenylate synthetase (2-5AS) by PCR method. Although the expressions of IL-1 beta, IL-4, IL-5, IL-6, TNF-alpha and IFN-gamma mRNA were detected in all the embryos tested, the expressions of IL-2, IL-3, IFN-alpha and IFN-beta mRNA were not detected at all. On the other hand, the expressions of IFN-related genes such as IFN-alpha/beta R, IFN-gamma R, IRF-1, IRF-2 and 2-5AS mRNA, were also detected. These results suggest that these cytokine may play an important role in early embryonic development.
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PMID:[Expression of cytokines and interferon-related genes in the mouse embryo]. 754 Jan 2

The expression and function of the FAS antigen was analyzed in 21 patients with B chronic lymphocytic leukemia (CLL) and four with hairy cell leukemia (HCL) using a specific IgM monoclonal antibody and FACS analysis. The FAS antigen was expressed in a minority (5-41%, mean 15.6%) of the CLL cells in 10 of 21 CLL patients and this expression was not modified during spontaneous or hydrocortisone-induced apoptosis of CLL cells. In contrast, culture with gamma-interferon (gamma-IFN) upregulated the expression of FAS in all CLL patients, with 65-100% (mean 84.8%) of the cells being positive after 2 days in vitro culture. Culture with alpha-IFN induced FAS expression in 15 of 19 CLL patients tested, with 15-74% (mean 34%) of the cells being FAS+ after 2 days culture. IL-4 and IL-10, lymphokines that inhibit and promote CLL apoptosis respectively, did not modify the expression of FAS. These results from FACS analysis were consistent with FAS mRNA analysis of fresh and cultured CLL cells, using a semi-quantitative reverse transcriptase (RT)-PCR technique. Although IL-4 and IFNs prevent apoptotic cell death of CLL cells in vitro, the present results show that IFNs induce the expression of the apoptosis-inducing protein FAS. However, FAS+ CLL cells were not killed in the presence of anti-FAS monoclonal antibody (while the FAS+ Jurkat and four lymphoblastoid cell lines were killed). This resistance is not due to a mutated FAS protein, since only wild-type FAS cDNA was demonstrated in the leukemic cells of three CLL patients. In four HCL patients 34-53% (mean 44.5%) of the leukemic cells were FAS+ and they were also resistant to the anti-FAS mediated cytotoxicity. The combination of high bcl-2 protein levels and resistance to anti-FAS mediated cytotoxicity may contribute to the extended in vivo survival of CLL and HCL cells.
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PMID:Expression and function of the FAS antigen in B chronic lymphocytic leukemia and hairy cell leukemia. 754 75

We have reported that patients with metastatic melanoma treated with an autologous, dinitrophenol-modified vaccine develop inflammatory responses at tumor sites. Histologically, these inflamed lesions are characterized by T cell infiltration, which is sometimes associated with tumor cell destruction. We tested biopsy specimens of eight subcutaneous metastases that had developed inflammation following vaccine treatment for expression of mRNA for interferon gamma (IFN gamma), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF alpha), and IL-10. Post-vaccine, inflamed biopsies contained mRNA for IFN gamma (5/8), IL-4 (4/8) or both (3/8), and for TNF alpha (4/7). In contrast, IFN gamma mRNA was detected in only 1/17 and TNF alpha mRNA in 2/16 control specimens (pre-treatment lymph node metastases or non-inflamed subcutaneous metastases). mRNA for IL-10, a cytokine with anti-inflammatory properties, was detected in 24/25 melanoma metastases and was independent of lymphoid content; in situ the reverse transcriptase/polymerase chain reaction confirmed that melanoma cells were the major source. These findings may provide a new parameter by which to measure the effects of cancer immunotherapy.
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PMID:Expression of cytokine mRNA in human melanoma tissues. 755 83

In contrast to therapeutic benefits of interferon-alpha (IFN-alpha) in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the mechanisms underlying its clinical efficacy. To investigate the anti-viral and/or immunomodulatory properties of IFN-alpha in HTLV-I infection, the effects of IFN-alpha on HTLV-I-induced in vitro phenomena were evaluated. In vitro activation of HTLV-I in fractionated CD4+ T lymphocyte-rich cells (CD4+ cells) could be demonstrated by increased thymidine incorporation into the cells, detection of proviral HTLV-I and viral RNA, and by assays of reverse transcriptase activities in culture supernatants. T cell immune responses were evaluated by thymidine incorporation into CD8+ T lymphocyte-rich cells (CD8+ cells) responding to cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens. It could be shown that IFN-alpha suppressed both the in vitro activation of HTLV-I and the CD8+ cell response. Moreover, 1 day supplementation of IFN-alpha as a pretreatment was sufficient for the induction of these properties. These findings, together with the clinical efficacy of IFN-alpha administration in patients with HAM/TSP, support the view that viral activation and T cell responses are critical components in the pathogenic processes involved in HAM/TSP.
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PMID:Anti-viral and immunomodulatory effects of interferon-alpha on cultured lymphocytes from patients with human T lymphotropic virus type I-associated myelopathy (HAM/TSP). 759 57

The in vitro effect of human natural interferon alpha (IFN-alpha) on cell contact-mediated human immunodeficiency virus type 1 (HIV-1) transmission from epithelial cells to lymphocytes was examined. This type of infection is most likely to occur when the mucosal linings of the reproductive or digestive organs serve as latent viral reservoirs and HIV-1 invades the host through the basolateral surface of polarized epithelia upon contact with intraepithelial lymphocytes. The cell-to-cell infection model consisted of target MOLT-4 T lymphocytes exposed for various time periods to chronically HIV-1-infected intestinal monolayers (I407/YH5) in the presence of log10 dilutions of IFN (range 10(5)-10(-2) IU/ml). Concurrent measurements of resulting productive infection from MOLT-4 revealed that complete inhibition of reverse transcriptase activity was prevented by doses starting from 1 IU, whereas the cessation of p24 production occurred at 1000 IU of IFN present at inoculation. The results indicate that IFN can efficiently prevent not only cell-free but also cell-mediated HIV-1 infection--an important means of viral spread in vivo pertinent to HIV-1 transmission resulting from mucosa-lymphocyte interaction.
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PMID:Inhibitory effect of natural interferon alpha on human immunodeficiency virus type 1 transmission from epithelial cells to lymphocytes in vitro. 767 77


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