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)

Eukaryotic DNA polymerase beta and the reverse transcriptases are the most inaccurate of the known DNA polymerases. We report here mutagenic replication in vitro past intrastrand N(7)G-N(7)G chelates of the cis-diamminedichloroplatinum(II), the major DNA adduct of the antitumor agent cisplatin by calf thymus DNA polymerase beta and human immunodeficiency virus type I reverse transcriptase (42% and 26% mutations, respectively). The most frequent modifications generated by both enzymes were one-base frameshift deletions. Only one mutational hot spot opposite the platinated guanines was observed with human immunodeficiency virus type I reverse transcriptase, while two hot spots were generated by DNA polymerase beta, one at the base situated 5' to the lesion and the other situated 4-6 nucleotides 5' to the adduct. An unusual mutagenic event, tandem replication of a 12-base pair sequence, was observed with DNA polymerase beta. The mutational spectra of the two DNA polymerases suggest that template slippage occurred with higher frequency in the presence of the more distributive DNA polymerase beta.
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PMID:In vitro bypass replication of the cisplatin-d(GpG) lesion by calf thymus DNA polymerase beta and human immunodeficiency virus type I reverse transcriptase is highly mutagenic. 866 82

Autoantibodies against both striated muscle proteins, particularly titin, and the acetylcholine receptor are a hallmark of thymoma-associated myasthenia gravis. However, the stimulus for these responses remains enigmatic as whole titin is not detectable in these tumors. This study reports that in thymomas with cortical differentiation many of the neoplastic epithelial cells expressed low and medium molecular weight neurofilaments detected with several antibodies (on selections and blots) and at the RNA level (by reverse transcriptase polymerase chain reaction). Moreover, higher molecular weight forms sharing at least one epitope with titin were detectable slightly less frequently, as were the more strongly phosphorylated epitopes. In stark contrast, in medullary and mixed thymomas, and especially in the normal thymus, immunoreactivity with anti-neurofilament antibodies was rare. This aberrant overexpression of a titin epitope by epithelial cells with antigen-presenting phenotype in an inappropriate cortical microenvironment suggests that they might autosensitize maturing T cells there and so initiate anti-titin autoimmunity in these patients.
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PMID:Expression of neurofilaments and of a titin epitope in thymic epithelial tumors. Implications for the pathogenesis of myasthenia gravis. 866 70

Granulomas form in the liver and intestines of mice infected with the parasite Schistosoma mansoni. Vasoactive intestinal peptide (VIP) is a neurokine that can modulate aspects of the immune response by acting through receptors within the granuloma. Cloned are two novel VIP receptor (VIPR) mRNAs (VIPR1 and VIPR2) that also bind a second neurokine called pituitary adenylated cyclase-activating polypeptide (PACAP). The objective of this study was to determine if granulomas express either VIPR1 or VIPR2. Using a radioligand-binding assay, it was established that PACAP is as effective as VIP at displacing radiolabeled VIP from splenocytes and granuloma cells, and that most if not all VIPRs in the spleen and granulomas bind PACAP. PCR amplification of reverse transcribed RNA determined that granulomas express both VIPR1 and VIPR2 mRNAs. Gel electrophoresis and nucleotide sequencing confirmed the authenticity of the PCR products. Also, both receptor subtypes were amplified from several granuloma CD4+ T cell lines; yet reverse transcribed RNA from T cell-depleted, dispersed granuloma cells had only VIPR1 RNA. It is notable that reverse transcriptase-PCR detected only VIPR1 in the thymus and spleen, which are organs rich in T lymphocytes. Thus, the granulomas and spleens from mice with schistosomiasis contain cells that display authentic VIP/PACAP receptors. Moreover, these data suggest that T cells in different compartments vary in VIPR subtype expression. VIPR1 and VIPR2 may have different physiologic roles in inflammation.
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PMID:T cell vasoactive intestinal peptide receptor subtype expression differs between granulomas and spleen of schistosome-infected mice. 868 24

Congenic PVG.RT1u rats rapidly reject Aa class I-disparate kidney allografts from recombinant PVG R8 donors and we recently demonstrated that anti-class I MHC alloantibody plays a critical role in effecting acute rejection in this experimental model. In this article, we show that PVG.RT1u recipients can be rendered permanently and specifically tolerant to R8 kidney allografts by administration of four weekly donor-specific transfusions (DST) combined with a 7-day course of cyclosporine given with the first DST. Tolerance induction correlated with abrogation of a cytotoxic alloantibody response by thymus-independent, i.e., peripheral mechanisms; IgM and all IgG subclasses of anti-class I alloantibody were abolished. In contrast, nonrejecting kidney allografts in tolerant rats and rejecting grafts from unmodified recipients were similarly infiltrated by mononuclear cells, and intragraft transcripts for interleukin (IL)-2, interferon-gamma, and IL-13 were readily detected by reverse transcriptase polymerase chain reaction with no apparent quantitative difference between the two groups. Messenger RNA for IL-4 and IL-10 was present in rejecting grafts but barely detectable in grafts from tolerant animals. These results suggest that tolerance induction by DST and cyclosporine is, in this experimental model, associated with a selective impairment in humoral alloimmunity.
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PMID:Alloantibody and intragraft cellular response to MHC class I-disparate kidney allografts in recipients tolerized by donor-specific transfusion and cyclosporine. 869 38

In order to define more accurately the initial events that take place during rabbit haemorrhagic disease virus (RHDV) infection, different organs of experimentally infected rabbits were analysed for the presence of the virus and correlated with histopathological observations. A total of 24 rabbits were intranasally inoculated with a viral suspension, and tissue samples were taken from the liver, spleen, kidney, lung, thymus, lymph node and tonsil at different intervals post-inoculation (2, 4, 6, 12, 18, 24, 30, 36, 48, 50, 51, 70 and 72 h). Histopathological observations revealed the presence of the first significant lesions at 30 h post-inoculation (p.i.) in the liver. Using an ELISA and a haemagglutination test (HAT), the virus was detected in the liver at 36 h p.i. The reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the RHDV RNA was present as early as 18 h p.i. in the liver and spleen, whereas thymus, kidney, tonsil and lymph node were found to be positive after more than 36 h p.i. The lungs presented a variable positivity between 0 and 36 h p.i., but remained positive after this time.
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PMID:Early stages of rabbit haemorrhagic disease virus infection monitored by polymerase chain reaction. 869 42

The SUP T1 lymphoblasts express an original subtype of VIP receptors characterized by a high affinity for the VIP analogue from lizard venom named helodermin, a preference for the neuropeptide PACAP-38 over PACAP-27 and VIP, and an extremely low affinity for secretin. The molecular cloning of that receptor revealed its identity with the VIP2 receptor subtype first cloned in rat and mouse tissues. The access to selective probes permits the detection of the mRNA coding for the VIP2 receptor by Northern blot, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization. These highly selective and sensitive techniques identify the cell types that are equipped to synthesize the receptor but do not prove that the receptor is indeed efficiently expressed at the cell surface. VIP2 mRNA was detected in selected areas of the brain different from that expressing the classical VIP1 receptor, in pituitary, in pineal, in pancreatic islets, in testes and ovary. It was also detected in the stomach, in the thymus and in spleen and in T lymphoblastic cell lines. A systematic screening of the immunocompetent cells must still be performed.
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PMID:Characterization of the VIP receptor from SUP T1 lymphoblasts. 879 Jul 81

Several 2'-deoxythymidine 5'-triphosphate and 3'-azido-2', 3'-dideoxythymidine 5'-triphosphate analogs containing a hydrophobic phosphonate group instead of the gamma-phosphate were synthesized and evaluated as substrates for human immunodeficiency virus (HIV) and avian myeloblastosis virus reverse transcriptases, human placental DNA polymerases alpha and beta, and calf thymus terminal deoxynucleotidyl transferase. They were efficiently incorporated into the DNA chain by the retroviral enzymes but were not utilized by the mammalian ones. Also, some gamma-ester and gamma-amide derivatives of dTTP and 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP) were synthesized and studied. They proved to be substrates for both the retroviral and mammalian enzymes under study. The Km values for incorporation of the dTTP derivatives into the DNA chain were close to those for dTTP and AZTTP. The Km for the AZTTP derivatives were one order of magnitude greater than those for dTTP and AZTTP. The results obtained indicate that HIV and avian myeloblastosis virus reverse transcriptases have no sterical obstacles for binding the triphosphate fragment bearing a bulky substituent at the gamma-position. Modification of the gamma-phosphate in AZTTP increased the selectivity of HIV reverse transcriptase inhibition versus DNA polymerase alpha. gamma-Methylphosphonate and gamma-phenylphosphonate were dephosphorylated in human serum much less rapidly than AZTTP. Besides, they were shown to be markedly more hydrophobic than AZTTP. Thus, replacement of the gamma-phosphate in AZTTP with gamma-phosphonate markedly alters its substrate properties toward some cellular DNA polymerases and blood dephosphorylating enzymes but does not change its substrate activity with respect to HIV reverse transcriptase.
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PMID:Gamma-phosphate-substituted 2'-deoxynucleoside 5'-triphosphates as substrates for DNA polymerases. 879 94

The role of the p53 tumor suppressor gene in bovine lymphosarcomas, a fragment of about 100 bp corresponding to approximately 97% of the open reading frame of the p53 gene was first amplified from single-strand cDNA originated from calf thymus by polymerase chain reaction PCR) and sequenced to obtain the bovine wild-type p53 gene. At the amino acid level, the omologies of the bovine p53 gene with the human, mouse, chicken and cat p53 genes were 0.9%, 72.8%, 52.7% and 82.3%, respectively. Moreover, eight bovine leukemic cells lines were studied for alterations in the p53 gene. These lines showed no significant somatic alterations in southern blot analysis, and expressed 2.5 kb p53-specific transcripts in Northern blot analysis. In mutation analysis using the reverse transcriptase-PCR technique, we detected three missense point mutations in four of these bovine leukemic cell lines. These mutations occurred in the 'hotspots' of the p53 gene. Thus p53 mutations predominantly occur in BLV-transformed cell lines and seem to be necessary for development of enzootic bovine leukosis (EBL).
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PMID:Predominant p53 mutations in enzootic bovine leukemic cell lines. 880 76

We have developed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the quantitation of 1D mRNA, which encodes a 64-kDa protein associated with thyroid-associated ophthalmopathy, in preparations of total RNA from a variety of human tissues. This competitive RT-PCR assay is based on coamplification of competing 1D cDNA internal control template (pGEM-1D') and target cDNA template. 1D-specific mRNA was quantified in 10 human tissues. The level of 1D transcript expression in these tissues decreased in the following order: thyroid (5 pg/mg total RNA) > eye muscle (3.2 pg/mg) > skeletal muscle (2.4 pg/mg) > ovary (2 pg/mg) > cerebellum (0.4 pg/mg), kidney (0.33 pg/mg), pancreas (0.27 pg/mg), spleen (0.22 pg/mg), and thymus (0.19 pg/microgram) > retina (0.016 pg/mg). Graves' disease may be a multisystem autoimmune disorder of the connective tissue and skeletal muscle (and thyroid) that is mainly localized in the orbit and skin. One mechanism for this localization may be increased expression of target autoantigens, of which the 64-kDa protein 1D is a candidate, in the involved tissues. The higher expression of the 1D molecule in thyroid and eye supports this hypothesis.
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PMID:Tissue distribution and quantitation of a gene expressing a 64-kDa antigen associated with thyroid-associated ophthalmopathy. 881 Oct 43

The gamma common (gamma c) chain is a partner in several interleukin receptor complexes, including the interleukin-2 receptor (IL-2R), IL-4R, and IL-7R. Mutations in the gamma c gene are associated with X-linked severe combined immunodeficiency (SCID). Using reverse transcriptase-PCR, we examined the level of mRNA-encoding gamma c and its partners in mouse pluripotent hematopoietic stem cells (PHSCs), which repopulate both bone marrow and thymus. We also assayed developing lymphocytes to define which, if any, IL-R complexes are expressed at the earliest stage of T and B lymphocyte maturation. RNA extracted from bone marrow-derived PHSCs did not contain detectable levels of mRNA-encoding IL-7R alpha. However, the most primitive (CD4- CD8-) T cells from the thymus and the most primitive (c-kit+ B220+) B cells from bone marrow contained high levels of IL-7R alpha mRNA. There were no detectable differences between PHSCs and primitive or more mature T and B cells for expression of gamma c mRNA. We conclude that the onset of IL-7R formation occurs at the earliest stage of differentiation of T and B lymphocytes. Our findings are consistent with the hypothesis that the absence of an intact IL-7R (IL-7R alpha and gamma c) may be a critical loss that interrupts lymphopoiesis.
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PMID:Interleukin-7R alpha mRNA expression increases as stem cells differentiate into T and B lymphocyte progenitors. 909 Dec 97


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