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)

Sera of patients with different types of leukemia and acquired immune deficiency syndrome (AIDS) have been examined for the presence of the anti-DNA antibodies. DNA-hydrolyzing activity of antibodies was detected in the sera of patients with chronic lymphoid leukemia (CLL), pre-B-cell acute lymphoid leukemia (pre-B-All), acute myeloleukosis (AML), and AIDS in stages III and IV of the disease. In immunofluorescence tests, the DNA-hydrolyzing antibodies reacted preferentially with proliferating cell nuclei compared with resting cells. A 35-kDa factor was identified as the target for the DNA antibodies in the cell nuclei. The DNA-hydrolyzing antibody fraction from the serum of an AIDS patient crossreacted with HIV I virus proteins gp160, gp120, and p65.
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PMID:DNA-protein complexes. Natural targets for DNA-hydrolyzing antibodies. 794 45

The human immunodeficiency virus type-1 (HIV-1) encoded Vpu protein facilitates the release of budding virions from the surface of infected cells and delays the rate of syncytium formation of the virus. Furthermore, Vpu induces rapid degradation of nascent CD4 molecules that are retained in the endoplasmic reticulum by the formation of gp160-CD4 complexes. Currently, little is known of the precise mechanism(s) by which Vpu function. Whether or not these different events are related remain unclear. In this report, we describe our recent structure/function studies on vpu suggesting that the protein may have independent biological activities during the HIV-1 infection.
Leukemia 1994 Apr
PMID:Mutational analysis of the HIV-1 Vpu protein. 815 84

In contrast to animal retroviruses such as murine leukemia virus, HIV-1 is not lysed by human complement. Nevertheless, HIV-1 activates complement via the classical pathway independently of antibody. Evidence is provided for activation of the reconstituted C1 complex by the virus, resulting from direct interaction between C1q and the external part of the viral transmembrane envelope protein (sgp41). Using C1q fragments and synthetic peptides covering the putative interaction regions in C1q and sgp41, we obtain evidence that the C1q/HIV-1 interaction involves: A site on C1q that appears to be located in the intermediary region between the collagen-like and the globular regions of C1q, and which may be conformational, involving two or more C1q chains. A site on gp41 located between residues 601 and 613 (gp160 nomenclature), i.e. within the immunodominant domain of HIV-1. This site shares homology with the corresponding region of HIV-2.
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PMID:Interaction of C1 with HIV-1. 817 63

The murine B-lymphocyte differentiation antigen BP-1/6C3 has been identified as glutamyl aminopeptidase (E-AP), formerly known as aminopeptidase A, the new gene symbol for which is ENPEP. In mice, the enzyme is found on early B-lineage cells and certain stromal cells of the bone marrow and thymus. This ectopeptidase is also expressed by capillary endothelial cells, placenta, and epithelial cells of the intestine and proximal renal tubules. Here we have used a mouse E-AP cDNA to identify the human counterpart in a kidney library. Sequence comparison of the human and mouse cDNAs reveals approximately 80% homology at both nucleotide and predicted amino acid levels. The nucleotide sequence of human E-AP predicts a type II integral membrane protein of 957 amino acids with an 18-amino-acid aminoterminal intracellular domain, and a 22-amino-acid transmembrane domain. The large extracellular carboxyterminal domain contains the zinc-binding motif typical of zinc-dependent metallohydrolases. When the human E-AP cDNA was placed downstream of the SR alpha promoter in an expression vector and transfected into COS-7 cells, the transfected cells exhibited cell surface E-AP activity. A 4.1-kb transcript could be detected in a variety of human tissues, including heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas. However, in representative lymphoid leukemias, E-AP transcripts were restricted to pre-B leukemia and were not found in T- and B-cell leukemias. The cDNA cloning and successful expression of human E-AP will allow more precise analysis of its physiological role(s).
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PMID:cDNA cloning and expression of human glutamyl aminopeptidase (aminopeptidase A). 824 82

The major envelope glycoproteins gp120 and gp41 of human immunodeficiency virus type 1, the causative agent for human AIDS, contain numerous N-linked oligosaccharides. We report here our discovery that N-acetylglucosamine residues within the complex-type N-linked oligosaccharides of both gp120 and its precursor, gp160, are sulfated. When human Molt-3 cells persistently infected with human T-cell leukemia virus IIIB were metabolically radiolabeled with 35SO4, gp160, gp120, and to some extent gp41 were radiolabeled. The 35SO4-labeled oligosaccharides were quantitatively released by N-glycanase treatment and were bound by immobilized Ricinus communis agglutinin I, a lectin that binds to terminal beta-galactosyl residues. The kinetics of release of sulfate upon acid hydrolysis from 35SO4-labeled gp120 indicate that sulfation occurs in a primary sulfate ester linkage. Methylation analysis of total glycopeptides from Molt-3 cells metabolically radiolabeled with [3H]glucosamine demonstrates that sulfation occurs at the C-6 position of N-acetylglucosamine. Fragmentation of the gp120-derived 35SO4-labeled glycopeptides by treatment with hydrazine and nitrous acid and subsequent reduction generated galactosyl-anhydromannitol-6-35SO4, which is the expected reaction product from GlcNAc-6-sulfate within a sulfated lactosamine moiety. Charge analysis of the [3H]galactose- and [3H]glucosamine-labeled glycopeptides from gp120 and gp160 indicates that approximately 14% of the complex-type N-linked oligosaccharides are sulfated.
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PMID:Complex-type N-linked oligosaccharides of gp120 from human immunodeficiency virus type 1 contain sulfated N-acetylglucosamine. 841 50

Vpu is a 16-kDa membrane-associated phosphoprotein that is expressed from the same, singly spliced message as the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor, gp160. Previous studies suggest that Vpu functions in the late stages of viral replication, possibly in virus egression from the cell. Recently, it has been demonstrated that Vpu functions to allow gp160 to be more efficiently processed by disrupting CD4-gp160 complexes generated by transfection of HeLa cells. We show here that the lack of expression of intact Vpu results in a 90% reduction in infectious virus produced over a single round of replication from HeLa cells in the absence of CD4 expression. This reduction persists when HIV-1 particles are pseudotyped with the HIV-2 or amphotropic murine leukemia virus envelope glycoprotein. Pulse-chase analysis of HIV-1 capsid protein (p24) in the absence of CD4 and envelope glycoprotein demonstrates that the rate of virus release is reduced when Vpu is not expressed. Our findings indicate that Vpu has a function involving particle release not dependent on CD4 or envelope glycoprotein expression.
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PMID:Human immunodeficiency virus type 1 Vpu has a CD4- and an envelope glycoprotein-independent function. 851 Feb 20

The use of Moloney murine leukemia virus (Mo-MLV)-based vectors to deliver therapeutic genes into target cells is limited by their inability to transduce nondividing cells. To test the capacity of HIV-based vectors to deliver genes into nondividing cells, we have generated replication-defective HIV type 1 (HIV-1) reporter vectors carrying neomycin phosphotransferase or mouse heat stable antigen, replacing the HIV-1 sequences encoding gp160. These vectors also harbor inactive vpr, vpu, and nef coding regions. Pseudotyped HIV-1 particles carrying either the ecotropic or the amphotropic Mo-MLV envelope proteins or the vesicular stomatitis virus G protein were released after single or double transfections of either human 293T or monkey COS-7 cells with titers of up to 10(7) colony-forming units per milliliter. A simple ultrafiltration procedure resulted in an additional 10- to 20-fold concentration of the pseudotyped particles. These vectors along with Mo-MLV-based vectors were used to transduce primary human skin fibroblasts and human peripheral blood CD34+ cells. The HIV-1 vector system was significantly more efficient than its Mo-MLV-based counterpart in transducing human skin fibroblasts arrested at the G0/G1 stage of the cell cycle by density-dependent inhibition of growth. Human CD34+ cells were transduced efficiently using HIV-1 pseudotype particles without prior stimulation with cytokines.
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PMID:Transduction of nondividing cells using pseudotyped defective high-titer HIV type 1 particles. 898 99

Fusion of viral and cellular membranes by the envelope glycoprotein gp120/gp41 effects entry of HIV-1 into the cell. The precursor, gp160, is cleaved post-translationally into gp120 and gp41 which remain non-covalently associated. Binding to both CD4 and a co-receptor leads to the conformational changes in gp120/gp41 needed for membrane fusion. We used X-ray crystallography to determine the structure of the protease-resistant part of a gp41 ectodomain solubilized with a trimeric GCN4 coiled coil in place of the amino-terminal fusion peptide. The core of the molecule is found to be an extended, triple-stranded alpha-helical coiled coil with the amino terminus at its tip. A carboxy-terminal alpha-helix packs in the reverse direction against the outside of the coiled coil, placing the amino and carboxy termini near each other at one end of the long rod. These features, and the existence of a similar reversal of chain direction in the fusion pH-induced conformation of influenza virus HA2 and in the transmembrane subunit of Moloney murine leukaemia virus (Fig. 1a-d), suggest a common mechanism for initiating fusion.
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PMID:Atomic structure of the ectodomain from HIV-1 gp41. 916 13

A rapid (within 1 h) and profound cytotoxic cell death of immature TdT+CD4+CD8+ and/or TdT+CD4+ thymic T cell type leukemia cell lines, and of normal thymocyte populations rich in TdT+CD4+CD8+ cells was induced by contact with some human immunodeficiency virus type-1 (HIV-1) carrier T cell clones. This cytotoxic reaction, without requiring a complete viral replication cycle in the thymic T cells, did not occur in any mature CD4+CD8+ and/or CD4+ T cells which are otherwise permissive for virus infection. Although it was not an antigen-specific cytotoxic reaction, the rapid and profound thymic T cell destruction was shown, at the individual clonal level, to be triggered specifically by the binding of CD4 molecules on thymic T cells with gp120/gp160 on HIV-1 carrier clones. The present study suggesting direct elimination of immature T cells by contact with some HIV-1-infected T cells, may provide a novel insight into the mechanism responsible for the mature CD4+ T cell depletion in HIV-1 infection.
Leukemia 1997 May
PMID:In vitro study using leukemia cell line panel to demonstrate rapid thymic T cell death due to contact with HIV-1 carrier cell clones. 918 Feb 97

Oxathlin carboxanilide analogs (UC) and alpha APA, compounds recognized as nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI), were evaluated for activity against the human immunodeficiency virus (HIV-1) and drug-resistant variants. These NNRTIs are structurally diverse but potent inhibitors of HIV-1 with efficacy in the nanomolar to low micromolar concentrations. They interact at a specific site in the pain domain of the p66 subunit of RT. Treatment of HIV-1 infected cell cultures with UC compounds resulted in the selection of drug-resistant viruses bearing specific amino acid changes at 100, 101, 103, 106, and/or 181. Since Y181C and L1001 are the most commonly observed resistance-engendering mutations, RT enzymatic analysis was correlated with molecular modeling to glean information on the structural interactions between these NNRTIs and RT. Information derived from these studies will facilitate rational drug design and the selection of complementary anti-HIV drugs for combination therapy.
Leukemia 1997 Apr
PMID:Cross-resistance analysis and molecular modeling of nonnucleoside reverse transcriptase inhibitors targeting drug-resistance mutations in the reverse transcriptase of human immunodeficiency virus. 920 8


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