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)

An involvement of cellular immunity in alveolar echinococcosis is strongly suggested by the intense granulomatous infiltrations observed around the hepatic parasite lesions. However, the basis of cellular immunoregulation in patient with alveolar echinococcosis is poorly understood. The present report shows a comparative analysis of lymphoid cell function in peripheral blood mononuclear cells (PBMC) of 16 patients with alveolar echinococcosis and of healthy individuals. Our in vitro restimulation studies with crude Echinococcus multilocularis antigen demonstrated that PBMC from patients with alveolar echinococcosis were responsive to challenge with parasitic antigen as measured by lymphoid cell proliferation. In this system, we also evaluated cytokine expression at the gene and protein levels after stimulation with E. multilocularis antigen. Analysis of cytokine mRNA expression revealed distinct patterns of cytokine expression in patients and normal donors. By using reverse transcriptase PCR, we could demonstrate that the TH1 cytokine transcripts interleukin-2 (IL-2) and gamma interferon (IFN-gamma) are present in PBMC from patients with alveolar echinococcosis. Moreover, it was found that stimulation with E. multilocularis antigen induced or enhanced the expression of the TH2 cytokine IL-3, IL-4, IL-10, and especially IL-5 mRNAs in PBMC from 13 of 16 patients with alveolar echinococcosis. Two patients who were examined after radical surgery, as well as another patient with a stable course of the disease under continuous chemotherapy, were not able to generate the same pattern of cytokine response and had no evidence of IL-5 mRNA synthesis. In contrast to the frequent expression of TH2 cytokine mRNAs observed in patients with alveolar echinococcosis, PBMC cultures from normal donors showed prominent IL-2 and IFN-gamma mRNA expression but weak IL-3, IL-4, and IL-10 mRNA expression. Most interestingly, IL-5 mRNA was substantially absent in PBMC from healthy individuals. In accordance with the mRNA studies, it was found that E. multilocularis antigen induced the secretion of large amounts of IL-5 and intermediate amounts of IFN-gamma in patients with alveolar echinococcosis, whereas large amounts of IFN-gamma and no or threshold amounts of IL-5 were detected in supernatants from healthy individuals. Collectively, the present study provides the first evidence that a TH2 immune response is gradually activated during the course of E. multilocularis infection, indicating a critical role for IL-5 in the manifestation of human alveolar echinococcosis.
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PMID:Interleukin-5 is the predominant cytokine produced by peripheral blood mononuclear cells in alveolar echinococcosis. 772 73

Bcl-2 protein expression has been found to block apoptosis and its overexpression has been implicated in lymphoid malignancies where the chromosomal translocation t(14;18) is present. In this study we investigated bcl-2 transcription and protein expression in cultured cervical carcinoma cell lines and keratinocytes. Western blotting and immunofluorescence microscopy demonstrated bcl-2 expression in the cytoplasm of 4 out of 5 cervical carcinoma cell lines examined (HeLa, CaSki, C-33A, and HT-3, but not SiHa). Bcl-2 protein expression was undetectable in normal keratinocytes. None of the cell lines examined demonstrated chromosomal translocation or rearrangement at the major breakpoint-cluster region (MBR) of the bcl-2 gene using either Southern blot or polymerase chain reaction (PCR) analyses. Northern blot analysis demonstrated low levels of bcl-2 transcription in HeLa, CaSki, and C-33A cell lines while reverse transcriptase (RT)-PCR demonstrated bcl-2 transcription in all cervical carcinoma cell lines which had bcl-2 protein expression. Thus, these data suggest that bcl-2 expression occurs in cervical carcinoma cell lines in the absence of chromosomal translocation or rearrangement of the bcl-2 gene. However, each of these cervical carcinoma cell lines contains inactive p53, either due to mutation (C-33A and HT-3) or via complexation and degradation with human papillomavirus (HPV) 16/18 E6 protein (HeLa and CaSki). Thus, functional p53, which can induce apoptosis in certain cells, is not present in these cervical cells which have increased bcl-2 expression. Increased bcl-2 expression under conditions of p53 inactivation may provide cells with a selective advantage for survival and consequently play a role in the development of cervical carcinogenesis.
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PMID:Bcl-2 protooncogene expression in cervical carcinoma cell lines containing inactive p53. 776 85

We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and myelodysplastic syndrome (MDS) using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage myelodysplasia, and in 8 (34.8%) of 23 patients with post-myelodysplastic syndrome AML (post-MDS AML). EVI1 expression was also detected in 6 (35.3%) of 17 MDS patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with MDS and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-MDS AML and AML with trilineage myelodysplasia, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-MDS AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-MDS AML and leukemia, with EVI1 expression associated with a 3q26 abnormality.
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PMID:Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression. 778 Jan 55

Prolactin (PRL) is involved in a wide range of physiological effects in several species and its immunoregulatory role has already been well documented. The PRL receptor has been cloned from various species. There are at least two receptor isoforms (short and long) in rats and mice, which differ only in their cytoplasmic domains, generated by alternative splicing of a single gene, although in human only the long form exists. Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we detected transcripts encoding both forms of PRL receptor in all lymphoid tissues examined in human, mouse, and rat, but in mouse and rat the ratio between the two forms was variable from animal to animal. Concerning the transcript encoding the PRL itself, a clear signal was always found in human lymphocytes and occasionally in rat thymus. We also developed a quantitative PCR (Q-PCR) in order to measure the absolute number of transcripts in thymus and spleen from rats at two stages of estrous cycle. The level of expression of the two forms was about equal. Finally, we identified the tyrosine kinase JAK2, which is constitutively associated with the PRLR, using the Nb2 rat lymphoma cell line as a model system with which to study the action of PRL on cell mitogenesis. We also showed that, after stimulation by PRL, the dimerization process is a prerequisite step for the phosphorylation of the PRLR and JAK2, which represents the earliest event in the signal transduction pathway.
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PMID:Prolactin and the immune system. 784 46

We recently identified a gene that is induced by lymphocyte activation (ILA). The sequence of the full-length 1.4-kb cDNA characterized ILA as a new member of the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor family and the human homologue of the murine T-cell-specific receptor 4-1BB. The present study demonstrates ILA mRNA isoforms at 4.4, 4.0, and 1.8 kb in poly-A+ RNA from activated, but not from resting human peripheral blood T lymphocytes. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to study tissue distribution and regulation of ILA expression. The gene was induced in T lymphocytes by phytohemagglutinin (PHA), phorbol myristate acetate (PMA), and antibody to CD3, in B lymphocytes by PMA and antibodies to cell surface Ig, and in blood monocytes by interleukin-1 beta (IL-1 beta), lipopolysaccharide (LPS), and PMA. In T lymphocytes, ILA mRNA was detectable 1.5 hours after stimulation, reached maximal levels at 8 hours, and declined to background levels by 48 hours. Induction of ILA mRNA required protein synthesis and was primarily due to increased transcription. Actinomycin D reduced ILA mRNA levels in activated lymphocytes 50% within 30 minutes, demonstrating a relatively short half-life of this mRNA. Analysis of nonlymphoid cells showed that ILA mRNA was not detectable in resting cells. However, in contrast to the lymphoid-specific expression of the murine 4-1BB gene, ILA was detected in nonlymphoid cells, including epithelial and hepatoma cells after stimulation with IL-1 beta. ILA was not detectable in several brain derived cell lines. The ILA cDNA encodes a 30-kD protein as demonstrated by in vitro translation, and this protein is immunoprecipitated by antisera that were raised against ILA peptides or a glutathione-S-transferase fusion protein. Flow cytometry showed expression of ILA protein on a subset of activated T or B lymphocytes. In conclusion, activation-dependent expression of ILA is found not only in T lymphocytes, but also in B lymphocytes, monocytes, and diverse nonlymphoid cell types.
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PMID:ILA, the human 4-1BB homologue, is inducible in lymphoid and other cell lineages. 784 93

Previous studies have demonstrated that oligodeoxynucleotide phosphorothioates complementary to human immunodeficiency virus type 1 (HIV-1) RNA are more nuclease resistant and are effective inhibitors of HIV-1 replication than their unmodified counterpart. In this study, antisense oligodeoxynucleotide sequences were evaluated for therapeutic potential in the treatment of HIV infections. The use of HIV-infected lymphocytes to test the efficacy of a drug is very complex, and therefore it is difficult to draw conclusions about the mechanism. We used a COS-like Monkey kidney cell line (CMT3) stably transfected with plasmids pCMVgagpol-rre-r (containing gag and pol genes) and pCMVrev (containing the rev gene of HIV-1), derived from cDNA clone BH10, as a model. A biologically active provirus that transcribes and translates their nucleotide sequences into viral proteins p24, p39/41, p55, and p160 was generated. Sequence-specific and dose-dependent inhibition of HIV-1 viral protein synthesis and significant inhibition at the mRNA level were demonstrated by antisense construct GPI2A, directed against a nonregulatory region of the HIV-1 genome. Also, our studies demonstrated enhancement of the antisense effect through encapsulation in a cationic lipid preparation. The observed attenuation of HIV-1 mRNA levels suggests that, at least in part, the mechanism of action of GPI2A was at the transcript level. Further studies have also shown antiviral activity of this construct as determined by the reverse transcriptase assay using acutely and chronically infected cells of lymphoid origin (H9 cells). Toxicological studies involving cell growth characteristics, colony-forming ability, effects on cellular proteins, specific activities of labeled proteins, and DNA synthesis in cell culture showed no cytotoxic effects of GPI2A.
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PMID:Sequence-specific inhibition of gene expression by a novel antisense oligodeoxynucleotide phosphorothioate directed against a nonregulatory region of the human immunodeficiency virus type 1 genome. 785 19

We sequentially analyzed the immunoglobulin heavy chain variable (IgH V) region gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who had three episodes of B-lymphoid crisis after bone marrow transplantation. Southern blot analysis using the JH probe showed different rearranged bands at each crisis, although the same rearranged bands of the BCR gene were observed. We amplified and sequenced the IgH V region gene of the leukemia cells by reverse transcriptase polymerase chain reaction (RT-PCR) using the primers corresponding to the consensus 5'VH and mu constant regions. The dominant leukemia clone at each crisis had a unique VH-D-JH rearrangement; VH4A (V79)-DLR2-J5 (clone-1), VH4B (DP70)-DK4-J6 (clone-2) and VH4A (V79)-DN4-J6 (clone-3) at the first, second and third crises, respectively. Further analysis by PCR amplification using the consensus 5'VH and clone-specific primers revealed that clone-1 underwent VH4-->VH3 replacement at the second crisis, and that clone-3 was already in existence at the first crisis. Moreover, the DN4-J6 joining clone, in which the sequence was the same as that of clone-3, was identified at the first and third crises by PCR amplification using primers corresponding to the region upstream of the DN4 segment and DN4-J6 boundary of clone-3. These observations suggest that multiple clones were generated from the progenitor cells of blast crisis, which were transformed at a very early stage of B-lymphocyte ontogeny, by continuing rearrangement mechanisms of the IgH genes, and that the dominant clone at each crisis was undergoing change.
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PMID:Continuing immunoglobulin heavy chain gene rearrangements in chronic myeloid leukemia with recurrent B-lymphoid blast crises after bone marrow transplantation. 786 62

2',5'-Oligoadenylate synthetase (2-5A synthetase) is an enzyme induced by interferon (IFN) that is considered to play an important role in IFN action. The normal mouse, not treated exogenously with any IFN or IFN inducers, has been shown to have an enhanced level of 2-5A synthetase activity, which is distributed among several lymphoid tissues. In the present report, we investigated the expression of the 42-kD 2-5A synthetase mRNA in the organs of normal mice using RNA blot hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). Among the organs tested, intestinal tissues had the highest levels of this mRNA. Furthermore, the 42-kD 2-5A synthetase mRNA was expressed in intestines from germ-free mice and fetuses. Immunoblotting analysis using a monoclonal antibody against the 42-kD 2-5A synthetase revealed that the 42-kD enzyme as well as a cross-reactive protein of 30 kD were produced in the organs of the normal mouse.
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PMID:Physiological expression of the 2',5'-oligoadenylate synthetase gene in mouse intestine. 793 Jul 58

Defective particles are naturally occurring virus mutants that lack one or more genes required for viral replication. Such viruses may affect positively or negatively the symptoms of the disease. Thus, it is of great interest to measure the role played by defective particles in the process of human immunodeficiency virus (HIV) infection since accumulating evidence indicates that a great proportion of HIV genomes are defective. We used defective particles produced by two stable cellular clones (UHC-8 and UHC-18) to investigate whether they can affect replication of infectious viral particles generated by a human T-cell line transfected with a molecular HIV-1 clone. Progeny virus harvested from UHC-8 cells has no reverse transcriptase and integrase proteins, while UHC-18 has no reverse transcriptase protein. We demonstrate here that coinoculation of a T-lymphoid cell line and of peripheral blood mononuclear cells with defective and infectious particles leads to a dramatic inhibition of virus replication. Defective particles do not interfere with virus production from proviral DNA. Rather, the inhibition of reinfection events seems to be their mechanism of action. This model closely parallels the in vivo conditions and demonstrates that defective particles may limit the spread of infection and progression of the disease by reducing the yield of infectious virus.
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PMID:Homologous interference resulting from the presence of defective particles of human immunodeficiency virus type 1. 798 21

After phosphorylation to the corresponding diphosphates, 2'-azido-2'-deoxycytidine and 2'-difluorocytidine act as powerful inhibitors of ribonucleotide reductase. Phosphorylation requires deoxycytidine kinase, an enzyme with particularly high activity in lymphoid cells. Therefore, the deoxycytidine analogs can be expected to inhibit the reductase with some specificity for the lymphoid system. Pretreatment of human CEM lymphoblasts with the analogs considerably increased the phosphorylation of 3'-deoxy-3'-azidothymidine (AzT). The increased phosphorylation of AzT is caused by a prolongation of the S phase of the cell cycle. Our results suggest the possibility of a combination of 2'-substituted deoxycytidine analogs with AzT in the treatment of AIDS. Gao et al. [Gao, W.-Y., Cara, A., Gallo, R. C. & Lori, F. (1993) Proc. Natl. Acad. Sci. USA 90, 8925-8928] have suggested the use of the ribonucleotide reductase inhibitor hydroxyurea for this purpose, since the resulting decrease in the size of deoxyribonucleotide pools decreases the processivity of the HIV reverse transcriptase. From our results it would appear that the 2'-substituted deoxycytidine analogs might be preferable to hydroxyurea.
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PMID:Inhibition of ribonucleotide reductase by 2'-substituted deoxycytidine analogs: possible application in AIDS treatment. 807 94


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