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)

Gene rearrangement during the ontogeny of T- and B-cells generates an enormous repertoire of T-cell receptor (TCR) and immunoglobulin (Ig) genes. Because of the error-prone nature of this rearrangement process, two-thirds of rearranged TCR and Ig genes are expected to be out-of-frame and thus contain premature terminations codons (ptcs). We performed sequence analysis of reverse transcriptase-polymerase chain reaction products from fetal and adult thymus and found that newly transcribed TCR-beta pre-mRNAs (intron-bearing) are frequently derived from ptc-bearing genes but such transcripts rarely accumulate as mature (fully spliced) TCR-beta transcripts. Transfection studies in the SL12.4 T-cell line showed that the presence of a ptc in any of several TCR-beta exons triggered a decrease in mRNA levels. Ptc-bearing TCR-beta transcripts were selectively depressed in levels in a cell clone that contained both an in-frame and an out-of-frame gene, thus demonstrating the allelic specificity of this down-regulatory response. Protein synthesis inhibitors with different mechanism of action (anisomysin, cycloheximide, emetine, pactamycin, puromycin, and polio virus) all reversed the down-regulatory response. Ptc-bearing transcripts were induced within 0.5 h after cycloheximide treatment. The reversal by protein synthesis inhibitors was not restricted to lymphoid cells, as shown with TCR-beta and beta-globin constructs transfected in HeLa cells. Collectively, the data suggest that the ptc-mediated mRNA decay pathway requires an unstable protein, a ribosome, or a ribosome-like entity. Protein synthesis inhibitors may be useful tools toward elucidating the molecular mechanism of ptc-mediated mRNA decay, an enigmatic response that can occur in the nuclear fraction of mammalian cells.
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PMID:A regulatory mechanism that detects premature nonsense codons in T-cell receptor transcripts in vivo is reversed by protein synthesis inhibitors in vitro. 749 32

The 8E5 clonal cell line, derived from HIV-1-infected CEM cells, carries a single, reverse transcriptase (RT)-defective copy of an integrated HIV genome. The absence of RT production is a consequence of a frame shift in the pol gene, due to the addition of a single base at position 3241. We report here that 8E5 cells produce an infectious virus that can be serially passaged on CD4+ lymphoid cells. This virus (8E5R) is RT positive, but displays a slow replication profile, together with a reduced cytopathic effect. The nucleotide sequence of a segment of the pol region produced by PCR amplification of DNA from 8E5R-infected cells shows that the single nucleotide insertion characteristic of the 8E5 genome had been corrected. The same reversion event was also found to occur in most single-cell clones derived from the 8E5 cell line. Because this cell line is used in many laboratories, notably as a standard for PCR quantitation, and is generally considered as unable to produce infectious virus, our findings should prompt investigators to use particular care in the handling of these cells.
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PMID:Reversion of a polymerase-defective integrated HIV-1 genome. 750 52

Disruption of normal p53 expression is the most frequent genetic change occurring in various human solid tumors; it is mostly due to sequence alterations of the p53 coding region by missense mutations or to loss of an entire, functional allele of this gene. In the present study, possible mechanisms resulting in a disruption of regulated expression of wild-type p53 were examined in acute leukemias of either lymphoid (ALL) or myeloid (AML) phenotype. p53 transcript accumulation, nucleotide sequence and gene structure were analyzed in primary leukemic cells from 50 patients. p53-specific transcripts were detected in 26/26 cases of ALL and 16/23 cases of AML using reverse transcriptase (RT)-PCR. Sequencing of transcripts did not reveal any point mutations or deletions. Heterozygosity at a polymorphic Bg/II site within intron 1 was found in 4/28 leukemic samples, and loss of one allele was noted in one of these. In addition, a novel, leukemia-associated structural abnormality located within the 5' flanking region of the p53 gene and associated with the loss of heterozygosity was observed in cells from this patient with ALL. The MDM2 gene which inactivates p53 by binding to it was neither amplified nor rearranged in 28 leukemias studied. Thus, disruption of regulated p53 expression resulting in lack of detectable p53 mRNA even by RT-PCR occurs in about 30% of cases of AML; however, p53 alterations typical for human solid tumors are an infrequent event in most types of human acute leukemias.
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PMID:Mechanisms of p53 alteration in acute leukemias. 752 98

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

A putative retrovirus was isolated from a dog with a severe, acquired immunodeficiency-like syndrome. The haematological abnormalities and immunological deficiencies included anaemia, leucopenia (lymphopenia and neutropenia), thrombocytopenia, decreased humoral immunity, and ineffective T-cell responses in-vitro. The necropsy findings included generalized lymphoid depletion, severe bone marrow hypoplasia, plasmacytic infiltrates in lymphoid and non-lymphoid organs, and severe secondary infections. Supernates of peripheral blood mononuclear cell cultures from the affected dog contained an agent with manganese-dependent reverse transcriptase (RT) activity that sedimented at a density of 1.122 g/ml. RT activity was also found post-mortem in extracts prepared from the bone marrow, lymph nodes, and small intestine. The lymph nodes and small intestine expressed a 3.8 kb mRNA that was recognized by a bovine leukaemia virus (BLV) pol DNA probe by Northern blotting. DNA isolated from the lymph nodes and small intestine from the affected dog showed distinct band patterns by Southern analysis, suggesting an exogenous retrovirus. The retrovirus could be propagated in normal canine peripheral blood mononuclear cells or short-term canine lymphocyte cell lines in-vitro, and was cytopathogenic for cells of canine, but not human, origin. These results suggest the existence of a pathogenic canine retrovirus capable of producing disease of the type associated with retroviruses in other species.
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PMID:Retrovirus-like activity in an immunosuppressed dog: pathological and immunological findings. 753 63

We have analyzed the replication of Nef+ and Nef- isogenic human immunodeficiency virus in CEM, HUT78, MT4 lymphoid, and U937 monocytic cell lines. At each passage of infected cells, we have assessed the relative infectivity of the virus particles released in culture media by measuring the number of infections units per nanogram of p24 protein. Values appeared to be 3- to 10-fold higher for the Nef+ virus than for the Nef- number The positive effect of Nef was observed regardless of the cell line, the multiplicity of infection, and the number of virus replication cycles achieved. We showed, by using cells expressing glycosylphosphatidylinositol-linked CD4, that the enhancement of virion infectivity could be dissociated from the down-regulation of cell surface CD4 also induced by Nef. The gp120-to-p24 ratio and the RNA content of virus particles produced in the presence or in the absence of Nef were equivalent. Virions bound to cell surface CD4 receptors with equal efficiencies. Equivalent reverse transcriptase activities were measured both on exogenous substrate and on particle genomic RNAs. In contrast, reverse transcription in infected cells generated 5- to 10-fold less DNA when the virions were produced in the absence of Nef, indicating that these particles performed reverse transcription in a suboptimal environment. These data suggest that the expression of Nef in virus-producing cells is required for efficient processing of the early stages of virus replication in target cells, including the internalization in an appropriate cell compartment and the uncoating of the particle.
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PMID:Human immunodeficiency virus type 1 Nef increases the efficiency of reverse transcription in the infected cell. 753 5

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

To understand the clinical implications of transcription factors and their biologic roles during cellular differentiation in the hematopoietic system, we examined the expression of GATA-1, GATA-2, and stem cell leukemia (SCL) gene in human leukemia cell lines and various leukemia patients using the reverse transcriptase-polymerase chain reaction. Cell lines exhibiting megakaryocytic or erythrocytic phenotypes had GATA-1, GATA-2, and SCL gene transcripts, while monocytic cell lines had no detectable GATA-1, GATA-2, or SCL gene mRNA. In some myeloid cell lines, GATA-1 expression, but not SCL gene expression, was detected; GATA-1 expression in HL-60 cells was downregulated during the process of monocytic differentiation. We next examined GATA-1, GATA-2, and SCL gene expression in 110 leukemia samples obtained from 76 patients with acute myeloid leukemia (AML), 19 with acute lymphoblastic leukemia (ALL), and 15 with chronic myeloid leukemia in blast crisis (CML-BC). SCL gene expression was usually accompanied by GATA-1 expression and was preferentially detected in patients with leukemia exhibiting megakaryocytic or erythrocytic phenotypes, while patients with monocytic leukemia were clustered in the group with no detectable GATA-1 expression. None of the patients with ALL or CML-lymphoid-BC expressed SCL. De novo AML patients with SCL gene expression had a lower complete remission (CR) rate and had a significantly poorer prognosis. Among the patients with AML not expressing SCL, a high percentage of patients with CD7+ AML and CD19+ AML had detectable GATA-1, while patients with GATA-1-negative AML had the best CR rate (87.5%). Our results suggest that the expression pattern of transcription factors reflects the lineage potential of leukemia cells, and GATA-1 and SCL gene expression may have prognostic value for the outcome of patients with AML.
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PMID:The expression pattern of erythrocyte/megakaryocyte-related transcription factors GATA-1 and the stem cell leukemia gene correlates with hematopoietic differentiation and is associated with outcome of acute myeloid leukemia. 757 12

Anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD) have some pathologic and immunohistochemical similarities, and a histogenetic relationship between them has been suggested by some investigators. By cytogenetic study, the t(2;5)(p23;q35) translocation appears to be unique for ALCL. The breakpoints of the t(2;5)(p23;q35) have recently been cloned and are reported to involve a novel tyrosine kinase gene, anaplastic lymphoma kinase (alk), on chromosome 2 and the nucleophosmin gene (npm) on chromosome 5. Therefore, we studied the frequency of npm-alk translocation in ALCL using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. We also studied HD and a variety of reactive lymphoid lesions since there is contradictory information in the literature on the occurrence of the npm-alk rearrangement in HD. We detected npm-alk hybrid mRNA in 8 of 22 cases of ALCL (36%), but none of the 21 cases of HD or the 11 cases with reactive lesions contained amplifiable template. All positive ALCL had the T or indeterminate phenotype and occurred in young adults or children. There was very good correlation between a cytogenetically detectable t(2;5) and a positive signal by RT-PCR. Our results indicate a selective but relatively infrequent association between the t(2;5) and ALCL of T or indeterminate phenotype, not shared with HD or reactive hyperplasia.
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PMID:Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma, Hodgkin's disease, and reactive lymphoid lesions. 757 58

Germline transcription of the Tcrb-V8.2 gene has been recently shown to occur in a lymphoid precursor cell line and to result in weak expression of an aberrant T-cell receptor (Tcr) beta chain on the cell surface. An investigation into the expression of a similar Tcr structure in normal lymphoid sites has involved antibody staining and sorting to identify a minor subset of Tcr-Vbeta+ Cbeta- cells in mesenteric lymph node and thymus. These cells have been analyzed by reverse transcriptase-polymerase chain reaction for the presence of transcripts encoded by bV8 genes in rearranged vs germline configuration in subsets of cells sorted on the basis of Tcrb-V8 and Tcrb-C gene expression. Germline transcripts were found in the Tcr-Vbeta- Cbeta- subset of cells in bone marrow, thymus, and mesenteric lymph node. They were also found to be present in the Tcr-Vbeta8(+) Cbeta+ subset of cells in thymus and mesenteric lymph node. Cells in the Tcr-Vbeta8(+) Cbeta- subset of mesenteric lymph node contained germline but no rearranged bV8 transcripts. The same thymus subset expressed high levels of both rearranged and germline bV8 transcripts. The presence of germline bV8 transcripts in Tcr-alphabeta- cells in bone marrow and mesenteric lymph node suggests that germline Tcrb-V8 gene transcription is unrelated to the differentiation of mature T cells. The possible function and significance of the expression of a truncated Tcr beta chain is discussed.
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PMID:Germline transcription and expression of Tcrb-V8 genes in peripheral mouse lymphoid tissues. 759 Sep 63


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