Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum antibody to p24 (anti-p24) and p24 antigen, alone and in combination with CD4+ lymphocyte number, were evaluated as predictors of progression of human immunodeficiency virus type 1 (HIV-1) infection. Two hundred six HIV-1-prevalent seropositive men in the Multi-center AIDS Cohort Study since 1984-1985 were studied cross-sectionally and 84 seroconverters were evaluated longitudinally. Cross-sectional analyses revealed significant associations among titer of anti-p24, CD4+ cell count, disease status (Centers for Disease Control class), and progression to AIDS. A high titer of anti-p24 was associated with lack of p24 antigenemia. Longitudinal studies of seroconverters demonstrated that a low titer of anti-p24, low CD4+ cell count, and detection of HIV-1 p24 antigen are individually strong predictors of AIDS, but only low CD4+ cell count retains its independent predictive value in multivariate analysis of the three markers during the period immediately after infection with HIV-1.
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PMID:Association of antibody to human immunodeficiency virus type 1 core protein (p24), CD4+ lymphocyte number, and AIDS-free time. 135 85

435 hemophiliacs are usually being attended in the La Paz hemophilia Center (Madrid, Spain). 257 (59%) of these patients have been infected by the human immunodeficiency virus (HIV-1) because of human plasma derivate substitution therapy. The infection has been more frequent among the severely affected patients and among the most treated patients. 82% of the infected patients are between 14 and 40 years old. By December 1991, 95 (37%) of 257 seropositive patients have developed full-blown AIDS. The most frequent opportunistic infection they had suffered was esophageal candidiasis. Looking for an evolution marker, we can point that the patients older than 35 years with CD4 levels below 200/mm3 had the worst prognosis. There was no difference in the evolution among the patients aged below 17 and those aged between 17 and 35 years. The amount of concentrate used between 1980 and 1984 did not hold any relation to the evolution. 49 patients (51%) of the 95 suffering from AIDS had died by December 1991. The evolution to the death was unrelated to the patient age, CD4 lymphocyte levels, and amount of substitution therapy. In our opinion, the most valuable marker could be the kind of opportunistic infection or tumor the patient suffers from. Finally, Retrovir has demonstrated to be useful in increasing the survival rate of the patients, but after 36 months of treatment, only 33% of those AIDS patients who began taking it remained alive. Retrovir was also used in asymptomatic patients, and during an average period of time of 15 months, a lesser bone marrow toxicity and a stabilization in CD4 lymphocyte levels could be observed, but this was unable to modify the disease progression in those patients who presented circulating p24 antigen.
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PMID:AIDS and hemophilia: experience in the La Paz Hemophilia Center. 136 77

A semimicromethod was established for isolating human immunodeficiency virus (HIV) in plasma using 48-well plates and a pool of peripheral blood mononuclear cells (PBMC) from several donors as targets for infection, which increases the efficiency of isolation by reducing the effect of variability due to diverse donor cell susceptibility to HIV infection. The addition of H9 cells to the PBMC cultures did not affect measurable titers. Nevertheless, it potentiated strongly virus replication in terms of p24 production in the supernatant of the wells with HIV isolates, thus facilitating interpretation of the results. The titration of a virus strain of a known titre and reverse transcriptase activity in parallel provided a constant parameter of efficiency and reproducibility within each experiment, permitting comparison with results from other laboratories. The reproducibility of the method was highly significant (r = 0.97, P < 0.001); 68% of the 22 plasma samples from HIV-infected individuals tested by this method were positive. The presence of plasma HIV titer correlated well (P < 0.02) with the low count of CD4+ cells of less than 300/mm3, but not with the presence of the p24 antigen in the serum.
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PMID:Efficient and reproducible new semimicromethod for the detection and titration of HIV in human plasma. 136 19

Contact of human immunodeficiency virus (HIV)-infected MOLT-4 lymphocytes with epithelial cells derived from small intestine (I407; Intestine 407) resulted in a rapid polar budding of viral particles into an enclosed space formed by interdigitating microvilli of the contacting cells. Electron microscopy showed that released HIV was taken up into the mucosal cell via three independent mechanisms: (1) phagocytosis, (2) coated pits, and (3) direct fusion. Morphological evidence suggests that internalized HIV may escape into the cytoplasm of the target cell by uncoating at the endosomal membrane. Based on CD4 antibody binding and CD4 antibody blocking experiments, HIV entry does not appear to be mediated by a viral CD4 receptor. Productivity of I407 infection was confirmed by virus isolation from cocultured MT-4 lymphocytic cells, reverse transcriptase assay, p24 antigen ELISA, in situ HIV mRNA hybridization, and Southern dot blot analysis. Contrary to infection with free virus, the cell-to-cell infection was not blocked by anti-gp120 or antiviral serum from HIV-positive individuals. It appears that HIV transmission within the confined space between contacting cells enables HIV to evade immune protection provided by neutralizing antibodies. Our results reveal a mechanism of HIV infection of epithelial cells which is triggered by cell-cell contact. Furthermore, these observations offer an insight into the cellular sequence of events which may take place during sexual transmission of HIV across an intact epithelial barrier.
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PMID:Mechanism of HIV spread from lymphocytes to epithelia. 137 Jan 28

The association between viral activity and antibody profiles was investigated in 202 individuals infected by the human immunodeficiency virus (HIV) grouped according to their Walter Reed clinical stage. Each study group was subdivided into subjects positive or negative for markers of active viral replication: presence of serum p24 antigen and viral culture. In Western blots using recombinant antigens, sera of HIV-positive individuals with positive viral markers had a significantly lower antibody reactivity to several viral proteins than did individuals without viral markers. Noticeably, proteins of the gag (p24, p17) and env (gp120, COOH-terminal part of gp41) open-reading frames revealed a decreased reactivity. The antibody response to the regulatory proteins revealed no or poor association with viral activity in the host. The results suggest that seroreactivity is mainly influenced by factors reflecting the viral activity of an HIV-infected individual, while the clinical stage of the patient is less important. Especially, reductions in antibodies against gp120 and p17 were useful markers associated with increased viral activity.
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PMID:Viral culture and p24 antigenemia of human immunodeficiency virus (HIV)-infected individuals correlated with antibody profiles determined with recombinant polypeptides of all HIV-1 open-reading frames. 137 34

2',3'-Dideoxyuridine (ddU) is ineffective at controlling human immunodeficiency virus type 1 (HIV-1) infection in human T cells, because it is not biotransformed to the active 5'-triphosphate. The metabolic block resides in the poor substrate affinity of ddU for cellular nucleoside kinases. This problem cannot be overcome by supplying the preformed nucleotides, because such compounds are unable to penetrate cells. To circumvent the requirement of ddU for enzymic phosphorylation, we have prepared bis(pivaloyloxymethyl) 2',3'-dideoxyuridine 5'-monophosphate (piv2 ddUMP), as a potential membrane-permeable prodrug of ddUMP, and investigated its metabolism and anti-HIV activity in two human T cell lines, one with wild-type thymidine kinase activity (MT-4) and the other deficient in thymidine kinase activity (CEM-tk-). The 5'-mono-, di-, and triphosphates of ddU were formed in both cell lines after exposure to piv2-ddUMP. In contrast, phosphorylated metabolites were not observed in cells treated with ddU or ddUMP alone. piv2-ddUMP also reduced the cytopathic effects of HIV-1 in MT-4 cells (ED50, 4.75 microM) and inhibited virus production in culture fluid (ED50, 20 microM). In addition, piv2-ddUMP protected CEM-tk- cells from HIV-1 infection, as demonstrated by inhibition of intracellular p24 antigen levels (ED50, 3 microM) and reverse transcriptase activity in culture medium (Ed50, 2.5 microM). Based on these findings, we propose that the "masked nucleotide" strategy may make available for development nucleoside analogues hitherto considered inactive because of failure to undergo biotransformation to the corresponding 5'-monophosphates. Moreover, by circumventing metabolic dependency on nucleoside kinases, the strategy may overcome acquired resistance to nucleoside analogues caused by the loss or depletion of nucleoside kinases.
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PMID:Membrane-permeable dideoxyuridine 5'-monophosphate analogue inhibits human immunodeficiency virus infection. 137 82

The majority of lymphomas in the setting of acquired, iatrogenic, or congenital immunodeficiencies are B-cell lymphoproliferations. We describe a rare T-cell lymphoma in a fulminantly ill patient infected with human immunodeficiency virus type 1 (HIV-1). The T-cell nature of the process was defined genotypically (monoclonal T-cell receptor beta-chain [CT beta] rearrangement) and phenotypically (CD45RO+, CD4+, CD5+, CD25+, CD8-, CD3- and negative for a variety of B-cell and monocyte markers). The CD4+, CD25+ (interleukin-2 receptor [IL-2R]) phenotype with production of IL-2 and IL-2R RNA is analogous to human T-lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATLL); however, no HTLV-1 could be detected. Southern blot analysis did demonstrate monoclonally integrated HIV-1 within the tumor genome. Furthermore, the tumor cells were producing HIV p24 antigen as shown by immunohistochemistry. This is the first case of acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's lymphoma in which HIV-1 infection may have played a central role in the lymphocyte transformation process.
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PMID:Acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human immunodeficiency virus type 1-associated T-cell transformation. 137 87

In this report the role played by human immunodeficiency virus type-1 (HIV-1) in the pathogenesis of HIV-1-related thrombocytopenia was investigated. CD34+ hematopoietic stem/progenitor cells were purified from the bone marrow (BM) of HIV-1(+) thrombocytopenic patients, HIV-1(+) nonthrombocytopenic individuals, HIV-1(-) patients with immune thrombocytopenic purpura, and HIV-1(-) normal donors. CD34+ cells from HIV-1(+) thrombocytopenic individuals alone showed a reduced capacity to give rise to megakaryocytic colonies (CFU-Meg) and also a progressive and significant decline in cell number when placed in liquid culture containing recombinant human interleukin-3 (rIL-3). This decline involved not only megakaryocyte but also erythroid and granulocyte/macrophage progenitors. The defects in megakaryocyte colony formation and CD34+ cell growth did not result from a productive HIV-1 infection of CD34+ cells. Moreover, HIV-1 DNA was absent from CD34+ cells in 10 of 12 thrombocytopenic patients examined. On the other hand, the decreased survival/proliferation of CD34+ cells in liquid culture, within the HIV-1(+) thrombocytopenic patients, was correlated with the presence of HIV-1 p24 antigen in BM plasma. These results demonstrate an impairment of CD34+ cells in HIV-1(+) individuals presenting thrombocytopenia as the only hematologic manifestation. Furthermore, these findings suggest that increased viral replication in the BM microenvironment may cause this impairment and possibly contributes to HIV-induced thrombocytopenia.
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PMID:Impaired in vitro growth of purified (CD34+) hematopoietic progenitors in human immunodeficiency virus-1 seropositive thrombocytopenic individuals. 137 10

A number of non-human-immunodeficiency-virus (HIV) type 1 disorders are associated with CD4+ T-cell deficiency and dysfunction. However, the etiopathogenesis of CD4+ T-cell immunodeficiency in these disease states remains unclear. Human intracisternal retroviral (HICRV) particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from a patient with severe CD4+ T-cell deficiency without risk factors for HIV infection. Ultrastructurally, the HICRV is distinct from HIV-1, HIV-2, human T-lymphotropic virus (HTLV) type I, and HTLV-II. Supernatants of activated mononuclear cells showed significant reverse transcriptase activity that was predominantly Mn2+ dependent. The patient's mononuclear cells were negative for HIV-1, HIV-2, HTLV-I, and HTLV-II proviruses as demonstrated by the lack of amplification by PCR. Also, the patient's serum was negative for antibodies to HIV-1, HTLV-I, and HTLV-II and for HIV-1 p24 antigen; however, serum was positive for antibodies against the HICRV as demonstrated by Western blot. Similar HICRV particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from the patient's daughter, who showed CD4+ T-cell dysfunction. The HICRV may be associated with CD4+ T-cell immunodeficiency and dysfunction in patients without risk for HIV-1, HIV-2, HTLV-I, and HTLV-II.
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PMID:Detection of a human intracisternal retroviral particle associated with CD4+ T-cell deficiency. 138 Jan 69

Down-regulation of Epstein-Barr virus (EBV) induced transformation of human lymphocytes in vitro by dehydroepiandrosterone (DHEA), a naturally occurring human steroid secreted by the adrenal gland has been demonstrated. This article reports on the effects of DHEA and its novel synthetic analogs 16 alpha-fluoro-5-androsten-17-one (8354) and 3 beta-hydroxy-16 alpha-fluoro-5 alpha-androstan-17-one (OH8356) on human immunodeficiency virus (HIV-1) replication. Treatment with DHEA, 8354, or OH8356 resulted in a modest down-regulation of HIV-1 replication in phytohemagglutinin-stimulated peripheral blood lymphocytes as measured by syncytia formation, release of p24 antigen, and accumulation of reverse transcriptase activity. DHEA and 8354 also reduced syncytia formation in HIV-1-infected SupT1 lymphoblasts. DHEA and synthetic analogs of DHEA, which have been shown previously to have antiproliferative effects, now are shown to reduce HIV-1 replication. DHEA or synthetic analogs of DHEA could provide an alternative and/or adjuvant for HIV-1 infection.
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PMID:Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication. 138 Dec 6


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