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)

Mouse myeloid leukemic cells which differ in their competence to be induced to differentiate by the normal macrophage- and granulocyte-inducing protein MGI have been used to study the relationship between type C RNA virus production and myeloid cell differentiation. Clones which can be induced by MGI to form Fc and C3 rosettes, to synthesize and secrete lysozyme and to differentiate to mature macrophages and granulocytes (MGI+D+) were induced by MGI to produce higher amounts of type C virus. Clones (MGI+D-) that were less inducible by MGI for Fc and C3 rosettes and lysozyme and were not induced to from mature cells were also less inducible higher virus production. In both types of clones, the increased virus production induced by MGI preceded the induction of rosettes and lysozyme. Clones that were not induced by MGI for rosettes or lysozyme (MGI-D-) showed little or no enhancement of virus production. MGI did not affect virus production in erythroleukemic cells, and erythropoietin did not affect virus production in the myeloid leukemic cells. Dexamethasone, lipopolysaccharide, dimethylsulfoxide and low concentrations of actinomycin D can induce some differentiation-associated properties in some of the clones. With these compounds, there was also a direct relationship between the enhancement of virus production and induction of differentiation-associated properties. Virus released from the three types of clones before or after treatment with MGI or dexamethasone was identified as N-tropic. The enhancement of virus production, as measured by reverse transcriptase activity, was accompanied by an increase in the amount of the viral protein p30, and interferon, which idd not inhibit the induction of differentiation in the myeloid leukemic cells, also did not prevent the increase in the amount of p30. After the early enhancement of virus production associated with the induction of differentiation, a shut-off of virus production occurred in the mature cells induced by MGI in MGI+D+ clones, whereas clones that did not differentiate to mature cells continued to produce virus. The results indicate that enhancement of virus production appears to be an early step in the induction of differentiation. Once induction has occurred, the lack of virus production in the mature cells suggest that a subsequent shut-off of virus production may be required for the completion of differentiation to mature cells. This relationship between cell differentiation and virus production suggests that type C virus has a regulatory role in myeloid cell differentiation.
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PMID:Co-regulation of type C RNA virus production and cell differentiation in myeloid leukemic cells. 8 97

Strains of Friend leukemia virus (FLV) that are associated with polycythemia contain the defective spleen focus-forming virus (SFFV). To determine whether the transforming ability of FLV was affected by the presence of this second agent, DBA/2J mouse bone marrow cells were infected in vitro. Criteria for transformation were the establishment of permanent lines, growth on semisolid agarose, and the production of tumors at the site of inoculation in syngeneic hosts. Two lines of immature hematopoietic cells that grow in suspension originated from the infected cultures. Each has an almost diploid karyotype (38-39 chromosomes) and 3-4 metacentric chromosomes. These transformed cells express gp71 viral envelope glycoprotein and p30 viral core protein antigens. Virus production was measured by reverse transcriptase (RNA-dependent DNA polymerase) activity of the virions released into the medium. The virus, assayed in vivo for infectivity, has SFFV activity but is attenuated for leukemogenicity. The stimulation of hemoglobin synthesis in the cells grown in medium supplemented with dimethyl sulfoxide or hexamethylene bisacetamide indicates that the cells are erythroid in origin. SFFV may have a function analogous to erythropoietin in influencing the process of transformation by FLV.
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PMID:In vitro transformation of mouse bone marrow cells by the polycythemic strain of Friend leukemia virus. 8 91

Cells of the monocyte lineage are important targets for the replication of human immunodeficiency virus (HIV). Our group and others have previously shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates HIV replication in monocyte/macrophages, but that it also enhances the anti-HIV activity of 2',3'-dideoxy-3'-azidothymidine (AZT). In the present study, we have explored the effects of other bone marrow stimulatory cytokines on the replication of HIV and on the anti-HIV activity of certain dideoxynucleosides in human peripheral blood monocyte/macrophages (M/M). Like GM-CSF, macrophage CSF (M-CSF) enhanced HIV replication in M/M. In contrast, granulocyte CSF (G-CSF) and erythropoietin (Epo) had no such effects. The anti-HIV activity of zidovudine (AZT) was increased in M/M exposed to GM-CSF. In contrast, the anti-HIV activity of AZT was unchanged in M/M exposed to M-CSF, and the activities of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddl) were unchanged or slightly diminished in M/M stimulated with GM-CSF or M-CSF. These differential activities of AZT and ddC were paralleled by differential effects of the cytokines on the anabolism of these drugs to their active 5'-triphosphate moieties. GM-CSF increased the levels of AZT-5'-triphosphate (at least in part through an increase in thymidine kinase activity) and overall induced an increase in the ratio of AZT-5'-triphosphate/thymidine-5'-triphosphate. In contrast, M-CSF-induced increases in AZT-5'-triphosphate were roughly matched by increases in thymidine-5'-triphosphate. Also, GM-CSF- or M-CSF-induced increases in the levels of ddC-5'-triphosphate were associated with parallel increases in the levels of deoxycytidine-5'-triphosphate (the physiologic nucleoside that competes at the level of reverse transcriptase), so that there was relatively little net change in the ddC-5'-triphosphate/deoxycytidine-5'-triphosphate ratio. Thus, bone marrow stimulatory cytokines may have a variety of effects on HIV replication and on the activity and metabolism of dideoxynucleosides in M/M.
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PMID:Effects of bone marrow stimulatory cytokines on human immunodeficiency virus replication and the antiviral activity of dideoxynucleosides in cultures of monocyte/macrophages. 137 54

We have developed an in vitro transcription system for the erythropoietin (Epo) gene. This system uses a plasmid carrying 0.2 kb of 5'-flanking sequence from the human Epo gene, rNTPs and a nuclear extract from mouse kidney. The transcribed RNA was assayed by primer extension with an end-labeled primer complementary to the sequence of the plasmid, dNTPs and reverse transcriptase. The primer extension product corresponding to the transcript was detected on a sequencing gel. The in vitro promoter activity of the Epo 5'-flanking sequence was observed with a nuclear extract from anemic kidney but not with that from normal kidney.
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PMID:In vitro reconstitution of an erythropoietin gene transcription system using its 5'-flanking sequence and a nuclear extract from anemic kidney. 173 75

The drug 3'-azido-3'-deoxythymidine (AZT), a synthetic thymidine analogue, has been used clinically in the management of acquired immune deficiency syndrome (AIDS). The drug is an effective antiviral agent due to its ability to block reverse transcriptase activity. This action of AZT was demonstrated in the Rauscher leukemia virus (RLV)-induced murine erythroleukemia model system. Unfortunately, associated with AZT has been the development of hematopoietic toxicity manifested by anemia, neutropenia, and overall bone marrow suppression. Hematopoietic growth factors (GM-CSF, erythropoietin), cytokines (interleukin-1), and agents known to potentiate hematopoiesis (lithium) have been demonstrated to modulate drug and/or radiation-induced hematopoietic toxicity. We report the results of further studies designed to investigate the ability of GM-CSF, erythropoietin, interleukin-1, and lithium to modulate AZT toxicity on murine hematopoietic granulocyte-macrophage (CFU-GM), megakaryocytic (CFU-Meg), and erythroid (BFU-E) progenitors cultured from bone marrow and spleen cells from mice infected with RLV. Hematopoietic progenitors from either normal or RLV-infected animals when exposed to AZT demonstrated concentration-dependent toxicity and differed for each progenitor with BFU-E being the most sensitive (ID50 concentration, 5 x 10(-9) M) and CFU-GM the least sensitive (ID50 concentration, 5 x 10(-5) M). As has been previously demonstrated using normal murine hematopoietic progenitors, when cultured with RLV-infected marrow or spleen cells, addition of GM-CSF, Meg-CSF or erythropoietin failed to inhibit AZT toxicity in vitro on CFU-GM, CFU-Meg, and BFU-E, respectively. However, in the presence of interleukin-1 (recombinant human IL-1 alpha, 30 ngm) or lithium chloride (ultra-pure, 1.0 mM), AZT toxicity CFU-GM, CFU-Meg, and BFU-E cultured from RLV-infected marrow or spleen cells was reduced. These results further demonstrate interleukin-1 and lithium are effective in modulating the toxic action of AZT on hematopoietic progenitors and that RLV-infected animals serve as a useful viral model system to study the effect of agents capable of modulating hematopoiesis in the presence of the anti-viral drug AZT.
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PMID:Effect of interleukin-1, GM-CSF, erythropoietin, and lithium on the toxicity associated with 3'-azido-3'-deoxythymidine (AZT) in vitro on hematopoietic progenitors (CFU-GM, CFU-MEG, and BFU-E) using murine retrovirus-infected hematopoietic cells. 194 Jun 11

A 68-year-old man with hepatocellular carcinoma complicated by erythrocytosis showed an increased plasma level of immunoreactive erythropoietin (EPO). Northern blot analysis and RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. Histological and immunocytochemical examination showed that the tumor was a hepatocellular carcinoma with predominant immunostaining for EPO. The erythrocytosis improved and the high serum EPO level decreased after resection of the tumor. This is the first demonstration of EPO mRNA expression in hepatocellular carcinoma tissue by RT-PCR.
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PMID:Gene expression of erythropoietin in hepatocellular carcinoma. 752 23

Mechanisms of helper virus-induced growth factor-independence were examined in FDC-P1 cells and FDC-P1 cells expressing the erythropoietin receptor (FDER cells). Retroviral mutagenesis of FDC-P1 cells led to factor-independent (FI) colonies from which cell lines could readily be established; whereas control cells exhibited at least 20 to 40-fold lower rates of factor-independence. From 44 independent experiments using either FDC-P1 or FDER cells, 205 autonomous cell lines were obtained. Sixteen colonies displayed a novel ("satellite-inducing") appearance in agar and produced up to 4.1 x 10(5) U/mL granulocyte-macrophage colony-stimulating factor (GM-CSF) (some with altered GM-CSF transcript sizes) and/or interleukin-3 (IL-3). Retroviral mutagenesis of FDER cells increased the repertoire of autocrine growth factors now responsible for stimulating autocrine proliferation: 3% of FI cell lines produced erythropoietin (Epo) (0.5 U/mL). Unexpectedly, in every autonomous FDC-P1 cell line, reverse transcriptase-PCR demonstrated expression of a growth factor normally required for proliferation. Thus, a profound selection for cells able to produce growth factors as the mechanism for achieving autonomous proliferation was documented. The ectopic expression of a receptor lacking a cognate ligand ("orphan") followed by retroviral mutagenesis and selection for autocrine mutants may offer an effective method for identifying new ligands.
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PMID:The cytokine receptor repertoire specifies autocrine growth factor production in factor-dependent cells. 772 Aug 17

Although it is well established that homeobox (HOX) genes play a key role in normal human embryogenesis, the expression and function of HOX genes in normal hematopoiesis is largely unknown. We have investigated by reverse transcriptase-polymerase chain reaction the mRNA expression of HOXB cluster genes (3' to 5' position in the cluster: from HOXB2 through B9) in 72% to 88% purified hematopoietic progenitor cells (HPCs) from adult peripheral blood induced in liquid suspension culture to gradual erythroid or granulopoietic (largely eosinophilic) differentiation and maturation by differential growth factor (GF) stimulus (ie, low-dose interleukin-3 [IL-3] and granulocyte-macrophage colony-stimulating factor [GM-CSF] and high-dose erythropoietin, or saturating amounts of IL-3/GM-CSF, respectively). Only B3 is expressed in quiescent HPCs. After GF treatment B3 expression is enhanced in the initial 24 hours and then through differentiation and maturation in erythroid and granulopoietic cultures. HOXB4 and B5 are induced at slightly later times and expressed through maturation in both lineages, whereas B6 is selectively induced in granulocytic differentiation. B2 is transiently expressed at low level in the granulopoietic pathway, whereas it is detected only in advanced stages of erythropoiesis: B7, B8, and B9 are essentially not detected. Functional studies were performed with antisense phosphorothioate oligomers to HOX mRNAs and included control analysis of the targeted mRNA. The results are strictly coherent with the HOX mRNA expression pattern: (1) anti-B3 oligomer (alpha-B3) treatment of purified HPCs induces a striking blockade of both erythroid and granulomonocytic colony formation (similarly, alpha-B3 treatment of K562 cell line causes a significant dose-related inhibition of cell proliferation); (2) alpha-B6 selectively and markedly inhibits granulomonocytic colony formation; (3) alpha-B4 and alpha-B5 cause a significant, less pronounced decrease of both colony types; (4) finally, alpha-B2 and alpha-B7, -B9 exert little and no effect, respectively. These studies provide novel evidence on the coordinate expression of selected HOXB cluster genes in erythropoiesis and granulopoiesis, particularly in the early stages of differentiation: B3 apparently functions as a master gene in early hematopoiesis, whereas B6 exerts a key selective function in the granulopoietic pathway.
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PMID:Key functional role and lineage-specific expression of selected HOXB genes in purified hematopoietic progenitor differentiation. 794 19

The expression and extracellular release of transferrin receptor (TR) was investigated by in vitro model system of erythroid differentiation. Human peripheral blood mononuclear cells were cultured with interleukin-3 (IL-3) for 7 days, and with erythropoietin (EPO) for an additional 8 days. After EPO stimulation, IL-3-stimulated blastic cells were serially differentiated into mature erythrocytes. [3H]-thymidine incorporation of cultured cells increased linearly from day 0 to 5, followed by a decrease. Flow cytometric analysis showed an increase of TR expression from day 0 to 5, followed by a slight decrease. By metabolic labeling with [35S]methionine and immunoprecipitation, the cell lysate exhibited a 95-kD band corresponding to the intact TR on sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography at day 5, when polychromatic erythroblasts had their peak. The culture supernatant solubilized by tween-20 exhibited a 95-kD and an 85-kD band on days 5 and 8, which corresponded to the intact and the truncated forms of TR, respectively. The 95-kD band was more intense at day 5 than at day 8. The reverse transcriptase-polymerase chain reaction assay showed that the receptor-mRNA expression was parallel to receptor synthesis. Thus, the synthesis and expression of TR on erythrocytes is associated mainly with cell proliferation in the early phase, and with both cell proliferation and hemoglobin production in the middle to late phases of maturation. Concomitantly, the extracellular release of TR from erythrocytes occurs in the middle to late phases of maturation. These data suggest that polychromatic erythroblasts release soluble TR as both intact and truncated forms and may be an important source of serum TR implicated as an index for erythropoietic activity in the marrow.
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PMID:Expression and extracellular release of transferrin receptors during peripheral erythroid progenitor cell differentiation in liquid culture. 811 25

A case of hepatocellular carcinoma complicated by erythrocytosis showed an increased level of serum immunoreactive erythropoietin (EPO) and EPO bioactivity. RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. The nucleotide sequences of PCR amplified regions of the EPO precursor mRNA in tumor tissue showed three differences to those of normal EPO cDNA. The deduced amino acid sequence of the coding region also showed three differences from that of normal EPO. The erythrocytosis improved and the high serum EPO immunoreactive and bioactive level decreased after resection of the tumor. This is the first demonstration of mutant EPO mRNA expression and bioactive mutant EPO protein in hepatocellular carcinoma tissue.
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PMID:Gene expression of mutant erythropoietin in hepatocellular carcinoma. 839 23


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