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

The intracellular precursor polyproteins of simian sarcoma-simian-associated virus [SiSV(SiAV)] were compared to the intracellular proteins of the human retrovirus isolates. HL23V, HEL12V and A1476V, by radioimmunoprecipitation followed by SDS-polyacrylamide gel electrophoresis and tryptic peptide analysis. Cells infected with SiSV(SiAV) were characterized by polyproteins Pr200gag-pol, gPr80env, Pr80gag, Pr60gag and Pr40gag. Identical intracellular precursor polyprotein profiles were obtained from cells infected with HL23V, HEL12V and A1476V. Tryptic digest mapping of peptides containing [3H]leucine showed the structural composition of Pr60gag to be the virus core proteins, p28, p15/p12 and p10. The SiSV(SiAV) envelope precursor, gPr80env, contained the structural determinants of mature viral gp70 and a non-glycosylated protein termed p15E. The homology of the human isolate viruses, HL23V, HEL12V and A1476V, to the SiSV(SiAV)/GaLV (gibbon ape leukaemia virus) family of viruses was confirmed by mapping studies. Both gPr80env and Pr60gag of SiAV were identical by tryptic peptide mapping to the respective proteins from the three human retrovirus isolates examined. The potential significance of these results to considerations of the origins of SiAV and the SiAV-like human isolates is discussed.
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PMID:A comparison of the intracellular precursor polyproteins of simian sarcoma-associated virus [SiSV(SiAV)] and three human virus isolates: HL23V, HEL12V and A1476V. 629 May 96

Human blood plasma from patients with myeloid leukemias, potentially preleukemic disorders and healthy individuals contains antibodies which react with purified glycoproteins of the baboon endogenous virus and the gibbon ape leukemia virus. Experiments are presented which illustrate characteristic distributions of antiviral antibodies in the plasma of different investigated groups. The presence of high-titer antibodies is associated with remission of acute myeloid leukemia and longer survival of patients with preleukemia.
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PMID:Studies on antibodies reactive with glycoproteins of primate type C viruses in patients with myeloid leukemias and with potential preleukemia. 629 Sep 14

Closed circular unintegrated DNA of the SEATO strain of gibbon ape leukemia virus (GaLV-S) was isolated from canine thymus fibroblasts after cocultivation with chronically infected bat lung fibroblasts. Restriction endonuclease HindIII cleaves GaLV-S DNA once, thus allowing isolation and cloning of HindIII-digested unintegrated DNA in a permitted form. Two clones isolated in the vector, Charon 21A, were nearly identical by restriction enzyme mapping to each of the two types of GaLV-S previously observed. These two types differ at a single SalI site. Unlike previous maps of GaLV-S proviral DNA, however, both clones lack SstI sites in the long-terminal-repeat units. Both the GaLV-S clones and the major species of GaLV-S proviral DNA contain an EcoRI site in the long-terminal-repeat units. The presence of this EcoRI site and the absence of an SstI site in the GaLV-S long-terminal-repeat units differentiate it from all other known GaLV strains and from the closely related nononcogenic simian sarcoma-associated virus. Heteroduplex comparisons of each of the two clones to clones of simian sarcoma-associated virus show no obvious deletion or substitution loops. This suggests that the ability of GaLV-S to induce myeloid leukemia in gibbon apes in not due to an acquired onc gene.
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PMID:Molecular cloning of circular unintegrated DNA of two types of the SEATO strain of gibbon ape leukemia virus. 629 90

Cytotoxicity of lymphocytes or antibodies against autologous tumor cells could be demonstrated very frequently in patients with chronic myeloid leukemia, whereas the presence of such cytotoxic activities was very rare in patients with acute myeloid leukemia. Lymphocytes and antibodies cytotoxic against autologous granulocytes were found in persons with potentially preleukemic cytopenic disorders. Control subjects with nonpreleukemic hematological disorders and healthy persons exhibited no cytotoxic activity. In the majority of cases the lymphocyte- or antibody-mediated cytotoxicity could be blocked with gp70 antigen of gibbon ape leukemia virus and baboon endogenous virus.
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PMID:Cytotoxicity of lymphocytes and antibodies against autologous tumor cells in patients with myeloid leukemias and preleukemic disorders. I. Blocking activity of gp70 antigens of primate type C viruses. 630 27

Mouse monoclonal antibody to HTLV p19 was used to locate HTLV p19 on the surface of cells and virions by immunofluorescence microscopy (IFM) and immunoelectron microscopy (IEM). When HTLV-producing cells HUT 102 (B2 clone), MT-2 and strain A were used as target cells, HTLV p19 was detected on the surface of cells and virions as spots or small sectors by both IFM and IEM. Cells infected with animal type-C retroviruses, e.g., gibbon ape leukemia virus, simian sarcoma virus, feline leukemia virus, and Gross murine leukemia virus, were completely negative for HTLVp19 expression. Other human T cells not producing HTLV, including HUT78 and HSB2-0, immature or pre-T cells (Molt-3) derived from leukemia patients, and fresh peripheral blood T cells from healthy persons, were also negative. In addition, B cells including Rob-B, IM-9, Raji, and BT-1 did not react with the monoclonal antibody to HTLV p19. In the light of the presence of HTLV p19 in the periphery of acetone-fixed HTLV-producing cells as shown by IFM, it seems most likely that HTLV p19 is an internal antigen of HTLV with part of its structure protruding out of the viral and cell membrane. The monoclonal antibody to HTLV p19 did not lyse HTLV-producing cells in the presence of complement, as expected, because the antibody is an IgG1. Antibody-dependent cell-mediated cytotoxicity was also studied by the 51Cr-release assay. No cytotoxicity was observed. Although HTLV p19 does not contribute to the destruction of malignant T cells for treatment and/or virions for prophylaxis, this protein is an important marker for diagnosis of HTLV infection. The patterns of HTLV p19 expression described above were exactly the same for American HTLV-producing HUT 102 (B2 clone), for strain A cells and for Japanese HTLV-producing MT-2 cells. These results further substantiate the close relationship of the Japanese and American HTLV isolates.
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PMID:Location of human T-cell leukemia virus (HTLV) p19 antigen on virus-producing cells. 631 98

Gibbon ape leukemia virus, SEATO strain (GaLV-SEATO), a virus that induces myeloid leukemia in gibbon apes, and GaLV, San Francisco strain (GaLV-SF), a virus associated etiologically with lymphocytic leukemia in gibbon apes, have been molecularly cloned. The complete nucleotide sequence of the large terminal repeats (LTRs) of both viruses are reported and compared to the previously published nucleotide sequence of the LTR of another member of the same virus group, the simian sarcoma virus (SSV). Substantial homology is evident among all three LTR sequences. The most striking feature of the GaLV-SEATO LTR is the presence of a 45-bp tandem direct repeat in the U3 region, an area likely to contain transcriptional enhancers. Both GaLV-SEATO and GaLV-SF contain a deletion in U3 when compared to SSV. Each of the three LTRs differ from the other two by short deletions in R-U5 and short additions in U3, as well as by numerous point mutations. The possibility that the structural changes observed in the LTR contribute to the differences in the pathogenic effects of these viruses is discussed.
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PMID:Nucleotide sequence of the large terminal repeat of two different strains of gibbon ape leukemia virus. 647 32

Circulating immune complexes were isolated from sera of 8 patients with acute myeloid leukemia (AML) in relapse, and 20 healthy blood donors. F(ab')2 fragments were prepared from the isolated complexes. Using a radioimmunoassay (RIA), these F(ab')2 fragments, the undigested complexes and the original sera were examined for the presence of antibodies against a panel of primate retrovirus antigens: gp70, p15 and p30 of gibbon ape leukemia virus (GaLV) and baboon endogenous virus (BaEV). F(ab')2 fragments derived from the immune complexes of all patients reacted with one or more of the antigens tested, whereas no antibody activity was found in the sera or undigested immune complexes of the same patients. By a competitive RIA, antigens related to GaLV and/or BaEV were found in the serum of 7 out of 8 patients. No markers of these retroviruses were detected in the F(ab')2 preparations, in immune complexes or in sera of any of the 20 control subjects. Our results indicate that a part of the circulating immune complexes in AML contain antigens related to primate retroviruses and specific antibodies to these antigens.
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PMID:Antibodies to primate retrovirus antigens in circulating immune complexes of patients with acute myeloid leukemia. 659 12

Young gibbons that were experimentally inoculated with cell-free gibbon ape leukemia virus (GaLV) and developed peristent viremia subsequently developed chronic granulocytic leukemia (CGL) with associated multifocal bone lesions and metastases. An 8-month-old gibbon inoculated with 10(5) tissue culture infectious virus (TCIV) developed acute myeloproliferative disease with associated bone lesions after a latency of 5 months, while a 9-month-old gibbon inoculated with 10(3) TCIV developed CGL after and 11-month latency. The clinical symptoms associated with the onset of leukemia were an increased number of leukocytes which were predominantly mature granulocytes, development of anemia, and multifocal bone lesions. Terminally, the animals had elevated immature granulocytes in the blood, cellular bone marrow with a predominant number of immature granulocytes, and hepatosplenomegaly. The gibbon with CGL had metastatic growth in the spleen and lung. Two 14-month-old gibbons that were inoculated with 10(3) TCIV and developed persistent neutralizing antibody to the virus infection remained free of hematopoietic disease, as did uninoculated animals. The fact that only animals with persistent viremia developed leukemia supports the oncogenicity of GaLV in gibbons.
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PMID:Oncogenicity of gibbon type-C myelogenous leukemia virus. 676 82

Retrovirus-like particles have been isolated from normal fetal human plasma and from different embryonic organs collected from late first-trimester fetuses. The majority of the virus-like particles banded at a density region of of 1.19-1.22 g/ml, although lighter particles having a density of 1.15-1.17 g/ml were observed in some fetal tissues. The particles appeared similar to retroviruses when viewed electron-microscopically. They contained reverse transcriptase (RT) which accepted oligo (dG)-poly(C) in Mn+2 over other synthetic template-primers and transcribed heteropolymeric RNAs primed with oligo (dT). The enzyme was partially (40%) inhibited by the antiserum against RT of feline endogenous virus (RD114) and not at all by the antisera against RT of avian myeloblastosis virus (AMV), spleen necrosis virus (SNV) and gibbon ape leukemia virus (GALV). The simultaneous detection test in the presence of actinomycin D revealed that the particles contained high mol. wt. (70 S and 35 S) RNAs. The single-stranded DNA complementary to RNA of the human fetal particle hybridized to DNA obtained from different tissues of human adults, showing that the nucleic acids of the virus-like particles were endogenous. The particles could be isolated only from the embryonic organs during differentiation. This suggests that the retroviral gene expression is correlated with embryonic differentiation. These particles could not be induced and as yet infectivity has not been demonstrated, therefore, they are at present described as retroviral elements, not as retroviruses.
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PMID:Isolation and characterization of retrovirus-like elements from normal human fetuses. 712 78

Retroviral-mediated gene transfer is the most attractive modality for gene transfer into hematopoietic stem cells. However, transduction efficiency has been low using amphotropic Moloney murine leukemia virus (MoMLV) vectors. In this study, we investigated modifications of gene transfer using amphotropic MoMLV vectors in cell-free supernatant for their ability to increase the currently low transduction of both committed hematopoietic progenitors, granulocyte-macrophage colony-forming units (CFU-GMs), and their precursors, long-term culture-initiating cells (LTC-IC). First, based on the observation that bone marrow cells express more gibbon ape leukemia virus (GALV) receptor (Glvr-1) than amphotropic receptor (Ram-1), PG13/LN, which is a MoMLV vector pseudotyped with the GALV envelope, was compared with the analogous amphotropic envelope vector (PA317/LN). Second, progenitor cell transduction efficiency was compared between CD34 enriched and nonenriched progenitor populations. Third, the duration of transduction in vitro was extended to increase the proportion of progenitor cells that entered cell cycle and could thereby integrate vector cDNA. In 20 experiments, 1 x 10(6) marrow or peripheral blood mononuclear cells (PBMCs)/mL were exposed to identical titers of pseudotyped PG13/LN vector or PA317/LN vector in the presence of recombinant human interleukin-1 (IL-1), IL-3, IL-6, and stem cell factor (SCF; c-kit ligand) for 5 days. 50% of fresh vector supernatant was refed daily. Hematopoietic progenitor cells as measured by G418-resistant granulomonocytic colony (CFU-GM) formation were transduced more effectively with PG13/LN (19.35%) than with PA317/LN (11.5%, P = .012). In 11 further experiments, enrichment of CD34 antigen positive cells significantly improved gene transfer from 13.9% G418-resistant CFU-GM in nonenriched to 24.9% in CD34-enriched progenitor cells (P < .01). To analyze gene transfer after extended growth factor-supported long-term culture, 1 x 10(6) marrow cells/mL were cultured with IL-1, IL-3, IL-6, and SCF (50 ng/mL each) for 1, 2, and 3 weeks. Fifty percent of PG13/LN supernatant with growth factors was refed on 5 days per week. Five percent of marrow CFU-GM and 67% of LTC-IC were G418 resistant at 1 week (n = 4), 60% of CFU-GM and 100% of LTC-IC were resistant at 2 weeks (n = 2) and 74% of CFU-GM (n = 4) and 82% of LTC-IC (n = 2) were resistant at three weeks.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector. 752 56


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