Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Total body x-irradiation has been utilized in the treatment of several human diseases, including leukemia, where it is followed by bone marrow transplantation, and in some autoimmune disorders. Recently, it was reported that total body irradiation appeared useful in the treatment of Friend leukemia virus infection in mice. In this report, the effect of x-irradiation on the replication of human immunodeficiency virus (HIV) in vitro in CD4+ cells was examined. MT-4 cells and HIV strain human T cell lymphotropic virus Type IIIB were used to conduct this study. Infected MT-4 cells were irradiated at the time of infection or following infection with x-ray doses of 25-300 cGy. Doses of 50, 150, and 300 cGy enhanced HIV replication by 1.6-, 2-, and 4.8-fold, respectively. Irradiating the cells prior to infection also resulted in similar enhancement of HIV replication. This phenomenon was also observed with wild-type HIV isolates grown in peripheral blood mononuclear and in HIV chronically infected cells. In addition, the enhancement was associated with a radiation-induced increase in intracellular levels of cAMP. The use of the cAMP-dependent protein kinase A inhibitor, H-8, inhibited HIV replication by 65%. These data suggest that in vitro exposure to low doses of x-ray enhances HIV replication partially via a cAMP-dependent pathway.
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PMID:X-irradiation enhances in vitro human immunodeficiency virus replication correlation with cellular levels of cAMP. 135 47

2',3'-Dideoxyuridine (ddUrd) exhibits poor if any anti-human immunodeficiency virus (HIV) activity in ATH8 and MT-4 cells. This is in agreement with the failure of ddUrd to be efficiently anabolized intracellularly to its 5'-triphosphate metabolite. However, 2',3'-dideoxyuridine-5'-triphosphate (ddUTP) proved to be a potent and selective inhibitor of the reverse transcriptase of HIV (Ki, 0.05 microM) and avian myeloblastosis virus (Ki, 1.0 microM). Bacterial DNA polymerase I, mammalian DNA polymerase alpha, terminal deoxyribonucleotidyl transferase, and Moloney murine leukemia virus reverse transcriptase were resistant to ddUTP. ddUTP is incorporated into the growing DNA chain principally at dTTP sites and inhibits further elongation. The potential of ddUTP as an anti-HIV therapeutic agent merits further investigation. However, to achieve this goal, it will be necessary to resort to techniques capable of delivering preformed phosphorylated ddUrd to the susceptible cells.
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PMID:Potent DNA chain termination activity and selective inhibition of human immunodeficiency virus reverse transcriptase by 2',3'-dideoxyuridine-5'-triphosphate. 168 52

While human T-lymphotropic virus type I (HTLV-I) proviral genome is readily detected in leukemic lymphocytes from adult T-cell leukemia patients, viral antigens or viral RNA are not expressed unless these cells are cultured. To address the problem of possible restriction mechanism of HTLV-I replication, we studied the methylation state of provirus in four HTLV-I transformed cell lines. These cell lines are chronically infected with HTLV-I and carry several copies of proviruses but are characterized by different viral expression. Molecular analysis showed that in MT4 cell line, which expresses a low level of viral RNA and proteins, not only are the HTLV-I proviruses heavily methylated but methylation also involves large regions around and within the long terminal repeats. MT4 cells treatment with 5-azacytidine led to an increase in both total viral RNA and p24 gag protein expression. These findings indicate that proviral methylation is responsible for the low viral expression in MT4 cells and also suggest that this phenomenon may be relevant to HTLV-I in vivo latency.
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PMID:Human T-lymphotropic virus type I transcriptional regulation by methylation. 169 63

Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.
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PMID:Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme. 189 2

A series of 3'-deoxy-3'-fluoro- and 2'-azido-2',3'-dideoxy-3'-fluoro-D-ribofuranosides of natural heterocyclic bases have been synthesized with the use of universal carbohydrate precursors, viz., 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-D-ribofuranose and methyl 2-azido-5-O-benzoyl-2,3-dideoxy-3-fluoro-beta-D-ribofuranoside, respectively. The cytostatic and antiviral activity of the compounds was evaluated against a variety of tumor cell lines and DNA/RNA viruses, respectively. As the most active compound, from both a cytostatic and antiviral activity viewpoint, emerged 3'-deoxy-3'-fluoroadenosine. It inhibited the proliferation of some tumor cell lines (i.e. murine leukemia L1210 and human T-lymphocyte MT-4) at a concentration of 0.2-2 micrograms/mL, and proved inhibitory to the replication of positive-stranded RNA viruses (i.e. polio, Coxsackie, Sindbis, Semliki forest), double-stranded RNA viruses (i.e. reo), and some DNA viruses (i.e. vaccinia) at a concentration of 1-4 micrograms/mL, which is well below the cytotoxicity threshold (40 micrograms/mL).
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PMID:Synthesis and antiviral and cytostatic properties of 3'-deoxy-3'-fluoro- and 2'-azido-3'-fluoro-2',3'-dideoxy-D-ribofuranosides of natural heterocyclic bases. 206 92

The effects of somatic components of Lactobacillus casei (L. casei) were studied on cell growth in vitro. L. casei was able to suppress the growth of MT-2, MT-4 cells from adult T-cell leukemia, Molt-4 cells from acute lymphoblastic leukemia and U-937 cells from promonocytic leukemia. This effect was obviously different from the cytotoxicity of Vinbrastin, an anti-cancer drug. Flow cytometric experiments employing BrdU-anti BrdU antibody demonstrated an increase of cells in G1 + G0 phases (pre-DNA synthesis phases) by the treatment of L. casei, therefore L. casei maybe acts as a low grade inhibitor of the protein synthesis. PC-treated L. casei had no more inhibition on cell growth than the non-treated one.
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PMID:[The antitumor activity of Lactobacillus casei--the direct effects of L. casei to human tumor cell lines]. 212 56

Human T-cell leukemia virus type I (HTLV-I) encodes a 40-kDa nuclear protein, Tax, which stimulates transcription from three 21-base pair (bp) repeats in its U3 region. Tax trans-activation is mediated via cellular factors that interact with the TGACGT motifs in the 21-bp repeats. Gel mobility shift assay and UV cross-linking analysis show that two proteins of 52 and 46 kDa in size bind the 21-bp repeat specifically. Base substitutions in the TGACGT motif which abolished Tax trans-activation abrogated factor binding whereas the repeats containing mutations that did not affect Tax trans-activation supported factor binding as the wild-type repeat. The 52- and 46-kDa factors are present in human T-cell lines Jurkat and MT4 (HTLV-I transformed) and in HeLa cells but are undetectable in a human placental cell line JEG-3, which gave a reduced level of trans-activation. JEG-3 extracts contain a distinct DNA binding activity that shows analogous sequence requirements as the 52- and 46-kDa proteins in interacting with the various 21-bp repeats. c-Jun and CREB (cAMP-responsive element binding factor) can stimulate transcription from HTLV-I long terminal repeats in JEG-3 cells. At least two copies of the 21-bp repeats are required for optimal trans-activation by c-Jun and CREB. Most single point mutations in the TGACGT motif that abolished Tax trans-activation, however, did not affect c-Jun- or CREB-directed transcriptional enhancement. These data indicate that many transcription factors including c-Jun and CREB exert stimulatory effects on HTLV-I transcription although they do not directly respond to Tax. The 52- and 46-kDa cellular proteins most likely are involved directly in Tax-mediated trans-activation, and they are tentatively named Tax activation factors I and II, respectively.
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PMID:Cellular factors involved in transcription and Tax-mediated trans-activation directed by the TGACGT motifs in human T-cell leukemia virus type I promoter. 224 93

3'-Azido-2',3'-dideoxythymidine (AZT) and 2',3'-didehydro-2',3'-dideoxythymidine (D4T) are potent and selective inhibitors of human immunodeficiency virus replication in MT-4 and ATH8 cells. They are also inhibitory to the replication of murine retroviruses, i.e. Moloney murine sarcoma virus-induced transformation of C3H cells. In MT-4 cells AZT is readily phosphorylated to its 5'-monophosphate, while the 5'-di- and 5'-triphosphates are generated to a 200-600-fold lower extent than the 5'-monophosphate. D4T is phosphorylated in MT-4 cells to its 5'-monophosphate at a 300-600-fold lower extent than AZT. The phosphorylation of AZT in the thymidine kinase-deficient cell line (Raji/TK-) is severely depressed, while D4T phosphorylation is only slightly diminished in Raji/TK- as compared to Raji/0 cells. D4T has a 10-fold lower affinity for phosphorylation by crude MT-4 cell extracts than AZT (Km, 142 and 14 microM, respectively), and the Vmax for phosphorylation of D4T is only 5% that of AZT. D4T is phosphorylated by MT-4 cell extracts about 180-fold less efficiently than AZT (Vmax/Km, 0.06 for D4T, as compared to 11 for AZT), and this is consistent with the differences found in the amounts of phosphorylated products of D4T and AZT formed in intact MT-4 cells. The 5'-triphosphates of AZT and D4T are equipotent in their inhibitory effects on the reverse transcriptases from human immunodeficiency virus and Moloney murine leukemia virus.
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PMID:Differential patterns of intracellular metabolism of 2',3'-didehydro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. 253 71

Unstimulated human leukemia T-cell lines (MOLT-4, MT-4) were tested for their susceptibility to herpes simplex virus type 2 (HSV-2) infection. Permissive infection of MT-4 cells was demonstrated by growth curve and infectious center assays. In growth curve experiments new progeny virus replication was detected by 24 hrs and maximum titers of HSV-2 replication were measured by 72 hrs after infection of MT-4 cells, whereas, MOLT-4 cells did not produce detectable infectious HSV-2 in growth curve experiments. It may be that a T-cell subset is involved with infectious HSV-2 production, since 5.7% of MT-4 cells were scored as infectious centers after HSV-2 infection compared to only 0.06% of MOLT-4 cells. Furthermore, HSV-2 infected MT-4 (45% of cells) and MOLT-4 cells (30% of cells) expressed viral induced antigen(s) detected by immunofluorescence assays. These data provide the first evidence of infectious HSV-2 replication in T-cells not prestimulated in vitro with mitogens, pharmacologic agents or growth factors. The establishment of T-cell systems that permit rapid and efficient replication of HSV-2 could greatly facilitate studies on interactions between human herpesviruses and AIDS retroviruses since recent published evidence indicates possible synergistic interactions between these virus groups.
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PMID:Herpes simplex virus type 2 infection of unstimulated human T-lymphocytes. 254 23

The human T-cell lines MT-2 and MT-4 carry the human T-cell leukemia virus type I (HTLV-I). When MT-2 and MT-4 were infected with HTLV-III, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS), rapid cytopathogenic effects and cytotoxicity were observed that made it possible to titrate the biologically active virus in a plaque-forming assay. The cytopathogenic effects were preceded by the rapid induction and increase of HTLV-III antigens as revealed by immunofluorescence and immunoprecipitation. Activities of HTLV-III were neutralized by the human antibodies against the virus when immunofluorescence and plaque assays were used. Essentially the same results were obtained with the lymphadenopathy-associated virus (LAV1).
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PMID:Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. 299 81


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