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)

We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a female patient with nervous system disease, the biological characteristics of CM-1 cells was studied in this paper. Another T lymphocytes, such as peripheral T lymphocytes donated by a male patient with multiple sclerosis, could be transformed into a malignant lymphoma line by using filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line was established. The CM-1 and CM-2 cells were transplanted by subcutaneous inoculation into nude mice, and could cause the occurrence of typical malignant lymphoma. The observation of electron micrographs suggested the existence of virions in the CM-1 and CM-2 cells, and these virions were similar to retrovirus in the ultra-structure characteristics. It was found that this virus possesses reverse transcriptase activity. Results obtained from serological assay, molecular hybridization and PCR excluded the existence of other human viruses, which were commonly used in our laboratory. The unknown virus possesses strong transformation activity, and probably is a new retrovirus. Meanwhile, the work on the clone and sequence analysis of this virus are being carried out.
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PMID:Establishment of a human malignant T lymphoma cell line carrying retrovirus-like particles with RT activity. 751 81

The relationship between clinical and molecular characteristics of 45 treated individuals with histologically-documented human immunodeficiency virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to determine whether differences in molecular features of lymphoma were associated with differences in clinical outcome. Tissue specimens from these tumors were evaluated for evidence of Ig heavy-chain gene rearrangements using both Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Lymphomas were also evaluated for the presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gene rearrangements. Twenty-five lymphomas were characterized as polyclonal and 20 as monoclonal. PCR amplification of expressed Ig variable (V)-region genes confirmed polyclonality in three extensively studied polyclonal lymphomas. The median CD4 count was significantly higher in the group with polyclonal disease (277/microL) than in the group with monoclonal disease (123/microL), P = .04. The complete response rate to therapy was significantly higher in patients with polyclonal disease (78%) and CD4 greater than 200/microL (81%) than in those with monoclonal disease (31%) and CD4 less than 200/microL (33%). CD4 count, clonality, and presence of EBV DNA sequences were the most important predictors of survival. Both Kaplan-Meier and Cox proportional hazards analyses showed a markedly prolonged survival in those patients with both CD4 > or = 200/microL and polyclonal disease. Histologically the polyclonal lymphomas were high grade in appearance and contained prominent macrophages. All seven surviving patients were in this group. Median survival for those individuals whose tumors contained EBV sequences was only 3.2 months (range, 0.4 to 19.5), whereas those with EBV- tumors survived for a median of 9.0 months (range, 0.7 to 65.2), P = .0007. These data indicate that molecular features of HIV-associated lymphomas may be important predictors of clinical outcome. These characteristics define a distinct subset of patients with polyclonal EBV- tumors and CD4 counts greater than 200/microL that appear to have a less aggressive clinical course.
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PMID:Influence of molecular characteristics on clinical outcome in human immunodeficiency virus-associated non-Hodgkin's lymphoma: identification of a subgroup with favorable clinical outcome. 753 86

Isoforms of the transmembrane glycoprotein CD44, generated by alternative RNA splicing, have been correlated to tumor dissemination. For evaluation of the potential role of CD44 variant isoforms in non-Hodgkin's lymphoma (NHL), the presence of CD44 isoforms was analyzed in a large panel of reactive and neoplastic lymphoid tissues by immunohistochemical staining, as well as detection of CD44 variant RNAs by the reverse transcriptase-polymerase chain reaction. Whereas the CD44 standard or hematopoietic isoform (CD44s), devoid of the variant regions, was expressed in all leukocyte subpopulations, the variant isoforms (CD44v) showed a highly restricted pattern of expression, mainly observed in epithelial layers of lymphoid tissues and subpopulations of leukocytes after stimulation. In addition to a strong expression of CD44s, variant isoforms containing CD44-6v in combination with other variant exons were observed predominantly in aggressive lymphoma and were associated with a shorter overall survival of patients (n = 138; P < .0001). Moreover, multivariate analysis indicated CD44-6v as a new independent prognostic parameter in high grade NHL in comparison with the risk groups defined by the International NHL Lymphoma Prognostic Factors Project (N Engl J Med 329:987, 1993).
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PMID:CD44 variant isoforms in non-Hodgkin's lymphoma: a new independent prognostic factor. 753 83

Oltipraz, an inhibitor of human immunodeficiency virus type 1 replication in vitro (ED50 approximately 10 microM), undergoes extensive metabolism in vivo. Most of the orally administered drug undergoes opening of the dithiolethione ring, reduction, recyclization, and methylation to form 7-methyl-6,8-bis(methylthio)pyrrolo[1,2-a]pyrazine ("metabolite III"). We report here that metabolite III inhibits viral replication in vitro (ED50 approximately 25 microM) in acutely infected H9 and CEM T cell lymphoma cell lines. Although both metabolite III and oltipraz were able to inhibit phorbol-12-myristate-13-acetate-stimulated viral replication in the chronically infected U1 promonocytic leukemia cell line, only metabolite III was able to inhibit phorbol-12-myristate-13-acetate-stimulated viral replication in chronically infected ACH-2 T cell lymphoma cells. The results with ACH-2 cells suggest that oltipraz inhibits an early stage of the viral life cycle, whereas metabolite III affects human immunodeficiency virus type 1 replication at a step distal to viral integration. This is consistent with the finding that oltipraz inhibits reverse transcriptase, whereas metabolite III does not. Although the mean ED50 for metabolite III in acutely infected peripheral blood mononuclear cells was 18 microM, the ED50 was below 5 microM in three of eight independent experiments. Studies of metabolite III in combination with oltipraz in acutely infected peripheral blood mononuclear cells demonstrated significant antiviral synergy. These results raise the possibility that the in vitro potency of oltipraz may underestimate its antiretroviral activity in vivo. Based on these results, the pharmacokinetics of oltipraz and metabolite III will be compared with the pharmacodynamic effects of orally administered oltipraz in a forthcoming phase I/II trial of oltipraz in patients with p24 antigenemia.
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PMID:Inhibition of human immunodeficiency virus type 1 replication by 7-methyl-6,8-bis(methylthio)pyrrolo[1,2-a]pyrazine, an in vivo metabolite of oltipraz. 754 38

Some Brazilian regions are considered to be endemic for human T-cell leukemia/lymphoma virus type I (HTLV-I) infection. Several studies have shown a high prevalence of HTLV-I infection among different groups such as blood donors, hemophiliacs and patients suffering from hematological and neurological diseases. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) have already been described in Brazil. We report the isolation of an HTLV-I strain from cultured lymphocytes of a TSP/HAM patient. An IL-2-dependent HTLV-I-infected T-cell line (ROB) expressing viral antigens was established and reverse transcriptase activity could be detected in the culture supernatant. Ultrastructural analysis showed immature and mature HTLV retrovirus particles. Finally, HTLV-I provirus type I was demonstrated by the polymerase chain reaction. This is the first isolation completely carried out in Latin America. The molecular analysis of viral strains, now in progress, should clarify the molecular epidemiology of HTLV-I in Brazil.
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PMID:Detection and isolation of human T-cell leukemia/lymphoma virus type I (HTLV-I) from cultured lymphocytes of a Brazilian TSP/HAM patient. 758 Oct 28

Cytokine expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) in a retrospective sampling of 16 AIDS-associated large cell lymphomas (LCL). IL-6 receptor (IL-6R) and IL-10 expression was detected in a majority of the tumor specimens tested, IL-6 expression was detected in 5 of 16 lymphomas that also expressed IL-6R, suggestive of an autocrine mechanism of disease. A subset of tumor samples described as mixed immunophenotype contained large numbers of infiltrating T lymphocytes and macrophages. Immunoperoxidase staining of a representative tumor of mixed immunophenotype demonstrated the presence of HIV-infected macrophages that also stained with anti-IL-6. This finding suggests that IL-6 produced by nonlymphoid cells may act as a paracrine growth factor for tumor cells that express IL-6R. Although earlier studies of AIDs burkitt's lymphoma cell lines suggested that IL-10 expression required EBV infection, 7 of 12 AIDS LCLs that expressed IL-10 did so in the absence of EBV by EBER in situ hybridization. Because AIDS LCLs frequently express cell surface CD5, we speculate that IL-10 may act as an autocrine or paracrine growth factor for this class of lymphoma. These studies suggest that IL-6 and IL-10 are involved in the pathogenesis of AIDS-associated large cell and mixed immunophenotype lymphoma.
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PMID:Cytokine expression in large cell lymphoma associated with acquired immunodeficiency syndrome. 758 73

In this paper we describe a patient with bcr/abl positive acute undifferentiated leukemia (AUL) derived from acquired sideroblastic anemia secondary to ifosphamide treatment given for the preceding non-Hodgkin lymphoma of the lung. Cytogenetically, Philadelphia chromosome was not detected through the whole course in this patient, and multiple chromosomal abnormalities including 5q- and monosomy 7 were found at the stage of sideroblastic anemia. The reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed no bcr/abl fusion transcript at the diagnosis of malignant lymphoma. The mRNA encoding the major bcr/abl fusion protein then appeared in the stage of sideroblastic anemia. Finally, the mRNA encoding both major and minor bcr/abl was detected in the stage of AUL transformation. MLL gene rearrangement was not found by RT-PCR analysis at any stage of the disorder. These results may be direct evidence for the induction of the bcr/abl fusion gene by treatment with an alkylating agent (ifosphamide).
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PMID:Detection of major and minor bcr/abl fusion gene transcripts in a patient with acute undifferentiated leukemia secondary to treatment with an alkylating agent. 759 51

Temperature elevation constitutes a beneficial component of the host defence against viral pathogens. However, heat treatment may be detrimental to HTLV-I-infected cells by increasing virion and oncoprotein production. We investigated the effects of thermal elevation on the in vitro replication of HTLV-I (human T-cell leukaemia/lymphoma virus type I) in MT-2 cells, an HTLV-I-transformed lymphoid cell line. We found that HTLV-I replication in MT-2 cells was markedly increased as demonstrated by a nearly 2-fold increase in detection of viral p24 antigen and a 20-fold increase in reverse transcriptase activity during up to 5 h of heat treatment at 42 degrees C. The results suggest that physiologic thermal elevations may induce viral production in HTLV-I-infected individuals.
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PMID:In vitro thermal enhancement of human T-cell leukaemia/lymphoma virus type I (HTLV-I) in HTLV-I-transformed cells. 768 46

The interaction between lymphoma cells and vascular endothelial cells (EC) is the first critical step in the invasion of lymphoma cells. We found that invasive human CCRF-CEM T lymphoma cells (CEM) released a factor that upregulates the expression of adhesion molecules on vascular EC. The supernatant of CEM (CEM-SUP) increased the expression of both ICAM-1 and ELAM-1 in time- and dose-dependent manners as shown by cell enzyme-linked immunoabsorbent assay (ELISA). In contrast, the induction of VCAM-1 on EC with CEM-SUP was relatively weak. No activity for interleukin-1 alpha (IL-1 alpha), IL-1 beta, interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha), which are known to augment ICAM-1 expression, was detected in CEM-SUP by ELISA. In reverse transcriptase polymerase chain reaction (RT-PCR) assay, CEM expressed a minimum amount of TNF-alpha mRNA, but absolutely no IL-1 beta or IFN-gamma mRNA. In addition, antibodies for cytokines did not inhibit the upregulatory effect of CEM-SUP. Semipurified CEM-SUP further increased the cellular binding between CEM cells and EC in vitro. This factor was stable to heat (65 degrees C, 30 minutes) and labile to acid (pH 2.0). Gel filtration and chromatofocusing estimated its molecular weight at 50 kd, with an isoelectric point of pH 7.2. Production of this factor might contribute to the invasive character of CEM through upregulation of adhesion molecules on EC.
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PMID:Invasive human T lymphoma cells produce a novel factor that upregulates expression of adhesion molecules on endothelial cells. 769 38

Interleukin 10 (IL-10) is a strong B-cell-activating factor. Since murine Ly1-positive peritoneal or lymphoma B cells strongly express IL-10, we examined malignant cells from patients with acute and chronic leukemias by reverse transcriptase polymerase chain reaction (RT-PCR) for the expression of IL-10 mRNA. High expression was found in three out of four samples from CD10+, CD5- common acute lymphoblastic leukemia (cALL) cells, whereas T-ALL samples generally did not contain IL-10 mRNA. In contrast to the murine system, only low levels of IL-10 expression were seen in 10 out of 11 samples from patients with CD5+ CLL. Myeloid derived cell lines were negative for IL-10. Epstein Barr virus (EBV) positive and negative Burkitt's lymphoma (BL) cell lines showed heterogenous IL-10 expression: BL cell lines with a nonactivated germinal center phenotype (CD10+, CD77+, CD23-, CD30-, CDw70-) expressed little or no IL-10, whereas EBV-positive and negative BL cell lines with an activated phenotype (CD77-, CD23+, CD30+, CDw70+) expressed easily detectable amounts of IL-10 mRNA. The highest expression of IL-10 was found in EBV-immortalized lymphoblastoid cell lines (LCL). Upon superinfection with non-defective EBV, the EBV-negative cell line BL 41 up-regulated IL-10 expression. Thus, in vivo IL-10 expression is not restricted to cells showing a specific (CD5+) phenotype. IL-10 may play an important role in c-ALL. The expression of IL-10 in BL cell lines is correlated to an activated phenotype in vitro and is independent of the EBV carrier status. EBV can induce IL-10 expression.
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PMID:Expression of interleukin 10 in B lymphocytes of different origin. 769 7


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