Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The modulatory activity of dextran sulfate with a relative molecular mass of 8 and 500 kDa and pentosan polysulfate with a relative molecular mass of 6 kDa on human T cell surface molecules CD2, CD3, CD4, CD8 and HLA-DR was investigated by analytical flow cytometry. The 500-kDa dextran sulfate induces a complete disappearance of the CD4 and a 50% diminution of CD2 immune reactivity on peripheral blood lymphocytes after a 4-h incubation while the low molecular mass polyanions do not. This modulation of the CD4 immune reactivity includes all CD4 epitopes investigated. It does not correlate with the antiviral effect of polyanions against human immunodeficiency virus infection. The interaction of polyanions with the CD4 presentation is temperature dependent and differs between fresh lymphocytes and immortal cell lines. From our data it can be concluded that mechanisms other than cell surface effects are responsible for the antiviral potency of these drugs. Implications for the modes of antiviral action of sulfated carbohydrates are discussed.
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PMID:Influence of sulfated carbohydrates on the accessibility of CD4 and other CD molecules on the cell surface and implications for human immunodeficiency virus infection. 247 10

Malignant lymphomas occurring in patients with AIDS are usually derived from the B-cell lineage while T-cell malignant lymphomas are very rare in these patients. We report a HIV seropositive 29-year-old homosexual man in whom cervical lymph node biopsy showed an atypical lymphoproliferative process. On morphological and paraffin section immunohistochemical grounds the possibility of Hodgkin's disease (HD) mixed cellularity was initially suggested, but frozen section immunohistochemical studies revealed that the cellular infiltrate exhibited an aberrant pan T immunophenotype and consequently the diagnosis of peripheral T-malignant lymphomas (T-ML) was made. However, genotypic studies would be required to definitely confirm this diagnosis, in such cases. In our case, varying numbers of small and medium-sized cells were positive for both Leu 3/CD4 and Leu 2/CD8 whereas some large cells reacted only with Leu 3/CD4 antibody. Some medium-sized, large and giant cells showed cytoplasmic positivity for Leu M1/CD15. Furthermore, the positivity of many large and giant cells with the activation markers BerH2/CD30, Ki-1/CD30, Tac/CD25 and HLA-DR suggested an activation state for these cells. Our findings emphasize the usefulness of frozen section immunohistochemical methods in order to investigate the spectrum of lymphoid malignancies occurring in HIV seropositive patients, and confirm results of previous studies which stressed the diagnostic difficulties that may appear in distinguishing HD from peripheral T-ML.
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PMID:Peripheral T-cell lymphoma or Hodgkin's disease in a HIV seropositive patient: a histopathological study. 248 99

Peripheral blood monocytes from AIDS patients exhibit defective migratory responses to chemotactic stimuli in vitro and to inflammatory sites in vivo. In studies presented here, normal monocytes were infected with the HIV-1/HTLV-IIIBa-L isolate in vitro and evaluated for chemotactic responsiveness. Within 2 days after viral exposure, but before evidence of virus production in the monocytes, chemotactic activity was significantly impaired. Decreased chemotactic activity was associated with modulation of receptors for the chemotactic ligands, C5a and FMLP, on the monocyte cell surface. In addition to HIV-1, monocytes treated with purified HIV-1 envelope glycoprotein gp120 demonstrated a comparable modulation of chemotactic ligand receptors and migratory function. In addition, the HIV-1 or HIV-1 gp120-treated monocytes were induced to undergo differentiation as monitored by HLA-DR expression. Immunoprecipitation of the gp120 with a specific antibody reversed its effects on monocyte chemotaxis and HLA-DR expression. Taken together, these data indicate that the initial interaction of HIV-1 with the monocyte is not passive, but that the binding of HIV-1 and/or HIV-1 gp120 to the CD4R on monocytes transduces a signal leading to transient monocyte activation.
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PMID:HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes. 254 Dec

Plasma membrane-bound 5'-nucleotidase (5'-NT), gamma-glutamyltransferase (gamma-GT) and soluble deoxynucleotidyltransferase (TdT) were studied in peripheral blood cells (PBMN) of 35 individuals, 26 male and 9 female, with circulating anti-HIV antibodies. Twenty-six were drug abusers, 2 were drug abusers and homosexuals and 4 were homosexuals. Three did not fall into any risk group. The surface immunologic phenotype of cells stained with the fluorescent monoclonal antibodies Leu 5, Leu 3, Leu 2, Leu 12, Leu M3, Leu M1, anti-CALLA and anti-HLA-DR was delineated by flow cytometry. While the gamma-GT activity did not change, the lymphocyte 5'-NT activity was significantly less than normal in anti-HIV positive individuals and in anti-HIV negative drug abusers. TdT activity was detectable in 14 anti-HIV positive patients (40%), who did not have clinical AIDS. Of 8 patients with AIDS, 3 had a low level of TdT activity but 5 had cells completely devoid of TdT and 5'-NT activity. 5'-nucleotidase activity and the frequency of Leu 2 suppressor antigen bearing cells were the only independent variables that correlated with AIDS incidence.
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PMID:Enzymatic imbalance in peripheral blood mononuclear cells isolated from individuals with anti-HIV antibodies. 257 Jun 50

Monocytes and macrophages play an important role in the pathogenesis of the acquired immunodeficiency syndrome (AIDS). Dysfunction of these cells contributes to the immunocompromised state that characterizes AIDS, and they probably serve as a reservoir for the human immunodeficiency virus (HIV). HIV-infected macrophages may also be responsible for the infection of many CD4-positive lymphocytes by means of cell to cell contact during the initiation of immunological responses. The efficiency of this process would be enhanced by activation of the macrophages, since that is accompanied by increased expression of class II major histocompatibility (HLA-DR) antigen. Using a direct blood antibody marking procedure in conjunction with flow cytometry, we have analyzed the expression of HLA-DR antigen on the surfaces of monocytes present in the peripheral blood of HIV-infected patients. In contrast to the results reported by other investigators who purified the monocytes using Ficoll-Hypaque centrifugation prior to antibody marking, we found that the percentage of monocytes expressing HLA-DR antigen was identical in the patients and normal controls. However, a subpopulation of monocytes was detected in the blood of the majority of the patients that was expressing increased levels of HLA-DR antigen. It was also found that the proportion of monocytes with a high density of HLA-DR antigen on their surfaces negatively correlated with the absolute numbers of CD4-positive lymphocytes present in the peripheral blood of the patient. These findings support the postulated role of monocytes and macrophages in the HIV infection and ultimate destruction of CD4-positive lymphocytes.
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PMID:Increased density of HLA-DR antigen on monocytes of patients infected with the human immunodeficiency virus. 260 May 92

A group of 10 leukocyte and lymphocyte subsets were measured by simultaneous dual immunofluorescence and flow cytometry in a group of homosexual men from the San Francisco General cohort. Absolute numbers and percentages of lymphocytes were determined in 30 individuals who progressed to AIDS and 29 who did not over a 44-month period at annual intervals. At entry into the study, all subjects were asymptomatic, HIV seropositive, and had multiple changes in lymphocyte subsets compared to HIV-negative controls. In progressors, large changes occurred from the first visit to the last visit before progression in both absolute numbers and percentages of CD4 cells. The percentage of HLA-DR-bearing CD8 cells also increased. We utilized a proportional hazards model to assign a predictive value for progression to AIDS to lymphocyte subsets in both univariate and multivariate tests. Increased DR-positive CD8 cells, decreased CD4 cells, and increased CD8-positive, Leu 7-positive cells independently predicted progression to AIDS at P less than 0.006 (relative hazard 5.8-4.0). In a multivariate model, the most useful tests were either increased numbers or percentages of DR-positive CD8 cells. These data suggest parsimonious approaches to following HIV-positive individuals and further support the possibility of autoreactive T cells in the pathogenesis of HIV-associated diseases.
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PMID:Lymphocyte subset analysis to predict progression to AIDS in a cohort of homosexual men in San Francisco. 278 91

We have developed a flow cytometric method for demonstrating cell fusion between human immunodeficiency virus type 1 (HIV-1)- or HIV-2-infected HUT-78 cells and uninfected CD4-bearing MOLT-4 cells. Syncytium formation due to an interaction between the gp120 glycoprotein expressed on HIV-infected HUT-78 cells and the CD4 receptor present on MOLT-4 cells, resulted in an immediate decrease in the number of MOLT-4 cells; after a 24 h incubation period almost all MOLT-4 cells had disappeared from the culture. To show that the target MOLT-4 cells and not the aggressor HUT-78 cells were destroyed, specific monoclonal antibodies (MAbs) that reacted with antigens expressed on either MOLT-4 or HUT-78 cells were used. The formation of giant cells and the concomitant disappearance of MOLT-4 cells was blocked by MAbs specific for OKT4A and Leu3a, and, to a much lower level, by the MAbs specific of OKT4 and gp120. MAbs specific for OKT3, Leu2a, HLA-DR, Leu18 and LeuM3 did not prevent the disappearance of MOLT-4 cells. Sera from two AIDS patients containing antibodies to the HIV envelope glycoproteins did not protect MOLT-4 cells against the destructive effect of the HIV-infected HUT-78 cells. The fusion index, the percentage fusion inhibition and the 50% fusion inhibitory concentration of the MAbs can be accurately determined with the flow cytometric assay. The method can be readily implemented to evaluate any therapeutic treatment by examining its capacity to block cell-to-cell fusion, and hence destruction of the target bystander cells. Five anti-HIV compounds which have been previously shown to interfere with HIV binding to cells (namely pentosan polysulphate, heparin, suramin, aurintricarboxylic acid and Evans Blue) were further evaluated by this new method. With the exception of heparin, all of these compounds were found to inhibit cell-to-cell fusion and the concomitant destruction of the target bystander cells. Azidothymidine failed to inhibit fusion or bystander T cell destruction.
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PMID:Syncytium formation and destruction of bystander CD4+ cells cocultured with T cells persistently infected with human immunodeficiency virus as demonstrated by flow cytometry. 278 68

The histopathological and immunopathological features of peripheral neuropathy were investigated in 21 patients with the acquired immunopathological syndrome (AIDS) or AIDS-related complex (ARC). Clinical syndromes observed in the 11 (52%) symptomatic patients included distal symmetrical polyneuropathy (DSPN) and chronic inflammatory demyelinative polyneuropathy (CIDP). Specimens from 19 of 20 patients (95%), both symptomatic and asymptomatic, had histopathological evidence of moderate or severe demyelination (79%), axonal degeneration (36%), and mononuclear cell inflammation (37%). Nerves from patients with CIDP and DSPN showed similar degrees of demyelination and axonal degeneration, but inflammation was more intense in CIDP. Immunohistochemical staining identified the majority of inflammatory cells as T lymphocytes or macrophages, with a predominance of CD8+ cytotoxic/suppressor cells. Diffuse immunostaining for human leukocyte antigen (HLA)-DR was present on endothelial cells, mononuclear inflammatory cells, and Schwann cells, and variable patchy immunostaining for HLA-DR was present on nerve fibers. Control nerve specimens showed staining for HLA-DR limited to endothelial, and a few mononuclear cells. The patterns of immunostaining were similar for AIDS and ARC patients. Human immunodeficiency virus (HIV) was cultured from peripheral nerve in 3 patients, but HIV antigen was not detected by immunohistochemical staining of 8 specimens. The findings implicate HIV infection in nerve, with T cell- and macrophage-mediated tissue destruction as the pathogenetic mechanism of the AIDS/ARC neuropathy.
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PMID:Peripheral neuropathy in the acquired immunodeficiency syndrome. 283 6

The primary interaction of HIV-1 with the target cell involves the viral large envelope protein (gp120) and the cellular CD4 molecule. mAb reacting with portions of CD4 have been shown to block HIV-1 attachment and infection. In one of the early reports describing HIV-1 cell interaction, some mAb reacting with MHC class II Ag were also found to block infection. To investigate further a possible role for MHC class II in HIV-1 binding, a cultured T lymphocyte cell line (H-9) that expresses MHC class II molecules and PHA-stimulated PBL was exposed for various time periods to concentrated viral particles and individual HIV-1 proteins. A decrease in the ability to detect the CD4a epitope and HLA-DR was observed after the cells were exposed to virus for 15, 30, and 60 min whereas HLA-DP and HLA-DQ Ag increased or remained unchanged. After 120 min of virus exposure, the CD4a epitope remained diminished whereas HLA-DR was detected at levels found on cells not exposed to virus. mAb detecting the CD4a epitope and HLA-DR, as well as alloantisera detecting the specific HLA-DR Ag on the target cell, blocked HIV-1 binding. When immunopurified gp120 was added to PHA-stimulated and unstimulated PBL, the CD4a epitope decreased in the same manner as was observed with whole virus preparations. In contrast to exposure to the intact virus, HLA-DR expression appeared to increase. Other viral proteins, p17, p24, and a portion of the small envelope protein, gp41, had no effect on the ability to detect cell surface Ag. Thus, although CD4 is the primary receptor for HIV-1 binding, HLA-DR appears to be involved in the binding site, probably by virtue of its close proximity to the CD4 molecule on the cell surface.
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PMID:HLA-DR is involved in the HIV-1 binding site on cells expressing MHC class II antigens. 235 80

As part of a larger study to characterize immune alterations in blood donors seropositive for human immunodeficiency virus (HIV), we measured subsets of CD4 (T helper/inducer) and CD8 (T suppressor/cytotoxic) cells by 2-color cytofluorometry. Alterations observed in asymptomatic seropositive donors (ASP) included: 1) decreased mean levels of Leu 8+ CD4 cells, although the proportion of Leu 8+ cells within the CD4 population was unchanged; 2) a selective increase in Leu 8- CD8 and Leu 18- CD8 cell levels; and 3) increased levels of both CD8 subsets defined by Leu 7, Leu 17, or HLA-DR expression. Alterations observed in symptomatic seropositive donors (SSP) were: 1) a further decrease in Leu 8+ CD4 cell levels, with a decrease in the proportion of Leu 8+ CD4 cells; 2) decreased levels of both Leu 18- and Leu 18+ CD4 subsets; 3) selective increases in Leu 8- and Leu 18- CD8 cell levels; and 4) increases in Leu 7+ CD8, Leu 17+ CD8, and HLA-DR+ CD8 subsets but not the reciprocal negative CD8 subsets. Thus, changes merely reflective of HIV infection included decreased levels of Leu 8+ CD4 cells and increased levels of Leu 8- CD8, Leu 18- CD8, Leu 7+ CD8, Leu 17+ CD8, and HLA-DR+ CD8 cells. Development of symptoms were associated with a further, preferential loss of Leu 8+ CD4 cells, proportional losses of both CD4 subsets defined by Leu 18 expression, and a return to normal levels of Leu 7- CD8, Leu 17- CD8, and HLA-DR- CD8 cells.
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PMID:CD4 and CD8 subsets defined by dual-color cytofluorometry which distinguish symptomatic from asymptomatic blood donors seropositive for human immunodeficiency virus. 296 80


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