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)

Recently there has been much interest in using immunohistology with monoclonal antibodies (MABs) against different cells of the immune system in lymph nodes (LNs) of patients with HIV infection. The panel of these MABs is becoming increasingly extensive. In this study we report on our finding that by using a limited number of properly chosen MABs, diagnostically and prognostically relevant parameters can be acquired. One hundred and twenty-one LN biopsy specimens from patients with HIV infection were reviewed and classified according to our expanded working classification and a fifth main type of LN lesion, the small lymphocyte follicular type, was added to our earlier classification. We propose that this new type represents a transitional form between the mixed follicular type and the follicular depleted type. In the follicular type of LN lesion there is no marked change in the number of CD4 cells within the follicles and in the extrafollicular parenchyma. The reaction against the major core proteins of HIV is always positive and the number of proliferating cells is very high. The positivity is weaker in the earlier cases and stronger in the older ones. The follicular dendritic cell (FDC) network shows degenerative changes. In the hypervascular follicular type the reaction pattern with these selected MABs is very similar to the one in the follicular type. In the mixed type there are hyperplastic follicles and regressively transformed follicles in the same node. The hyperplastic follicles show a pattern similar to those in the follicular type. However, the reaction with MABs against core proteins of HIV is often markedly stronger. The number of proliferating cells is decreased markedly. Some follicles show extensive FDC network destruction. CD4 cells within the follicles and in the extrafollicular parenchyma are decreased. The regressively transformed follicles contain very few proliferating cells and the reaction with MABs against core proteins is variable, being strong in some follicles and weak in others. The small lymphocyte type contains follicles consisting mainly of small lymphocytes. These lymphocytes are of the same phenotype as those in the primary follicles. In contrast to these, however, the numbers of CD4 and Leu 7+ cells are much decreased. The reaction with MABs to core proteins is weak and limited to the germinal centres (GCs). The number of proliferating cells is strongly diminished. The FDC network, however, is well developed in most follicles. In the follicular depleted LNs there are no follicles; however, in some LNs remnants of FDC can be seen.
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PMID:Monoclonal antibodies to human immunodeficiency virus: their relation to the patterns of lymph node changes in persistent generalized lymphadenopathy and AIDS. 313 85

The fact that patients with hemophilia treated with clotting factor and HIV 1-seronegative subjects with congenital anemias given repeated blood transfusions both have decreased ratios of T4/T8 lymphocytes and diminished NK cell activity indicates that these immunological abnormalities can be due to repeated exposure to blood and blood products, and are not necessarily indicative of HIV 1 infection. To search for an immunological change specific for HIV 1 infection we tested 36 hemophiliacs (22 HIV 1-seropositive, 14 HIV 1-seronegative), and 27 normal subjects for peripheral blood lymphocytes which coexpress Leu 2, a marker associated with suppressor/cytotoxic cells, and Leu 7, an NK cell marker. Compared to normal subjects, seropositive hemophiliacs showed a 2.5-fold increase in Leu 2+ Leu 7+ cells. No increase in this population was seen in the seronegative hemophiliacs. An increase in the percentage of Leu 2+ Leu 7+ cells is therefore an immunological alteration associated with HIV 1 infection but not blood product exposure per se.
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PMID:Increase in Leu 2+ Leu 7+ lymphocytes in HIV 1-seropositive patients with hemophilia repeatedly treated with clotting factor concentrates. 325 29

Two color cytofluorometric analyses of CD3-, CD16+, Leu 19+ natural killer cells (NK) were assessed in HIV seropositive patients, high-risk seronegative homosexuals, and healthy heterosexuals. A selective depletion of lymphocytes bearing NK phenotypes was found among HIV-positive infected patients. When the CD16+ lymphocyte compartment was further dissected, lymphoid cells bearing simultaneously low cell-surface density CD8 and CD16 (Leu 11a or Leu 11c) or Leu 19 epitopes were selectively and significantly decreased. This important depletion of CD8+ NK cells, which in most cases are CD3-, accounts for the decline in low-density CD8+ lymphocytes in HIV positive group, while a significant increase occurs in their CTL pool. Furthermore, in HIV negative high-risk homosexuals, a less profound but significant reduction of this lymphocyte subset was also found. Whether the involvement of the NK compartment, especially NK cells expressing the CD8 marker, may influence the outcome of individuals infected with HIV is still an open question.
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PMID:Selective depletion of low-density CD8+, CD16+ lymphocytes during HIV infection. 325 41

Cytotoxic T lymphocyte (CTL) responses to HLA alloantigens are unexpectedly weak compared to the CTL response to influenza virus. Allogeneic CTL activity was increased dramatically by removal of a Leu M3+ cell with adherence properties. The Leu M3+-enriched population was capable of suppressing the allogeneic-CTL response. Precultured cells suppressed both allogeneic and influenza-specific CTL responses. Inactivation of suppression was achieved by addition of influenza virus to the cultures in which suppressor activity was generated. A high proportion of asymptomatic HIV-seropositive and AIDS patients, as well as one high-risk group appear to have lost suppressor-cell activity. These findings are discussed with respect to the possible role of this suppressor system in transplantation immunology and the T cell-immune abnormalities observed in development of AIDS.
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PMID:Suppression of human cytotoxic T lymphocyte responses by adherent peripheral blood leukocytes. 326 71

Serum and CSF from 32 patients with idiopathic ALS, 30 age-matched controls and 30 MS patients were investigated regarding immunoglobulin concentration and virus-specific antibodies, the lymphocytes in the peripheral blood and lymphocyte subsets were also investigated. ALS patients' results were compared with findings in MS and controls. The ALS patients had significantly higher IgG concentration in serum than the controls, marked lymphopenia, reduction of CD2, CD8 and Leu 7 positive cells and increase of the CD4/CD8 ratio and of SIg-positive lymphocytes. Compared with the MS patients, the ALS patients showed similarity in T-subset distribution with a lower standard deviation. No HTLV-I and HIV antibodies were found in any group and no significant differences in antibody distribution to Toxoplasma G, herpes simplex, cytomegalovirus, measles and mumps viruses were evident. All ALS patients were investigated at an early disease stage, therefore, our findings seem to support the conclusion that the immune alterations are related to the mechanisms of the disease and not to complications of its evolution.
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PMID:Immunity assessment in the early stages of amyotrophic lateral sclerosis: a study of virus antibodies and lymphocyte subsets. 326 63

An antibody detection procedure based on agglutination of autologous red cells has been developed for samples of whole blood. A nonagglutinating monoclonal antibody to human red blood cells conjugated to a synthetic peptide antigen (in this case residues 579 to 601 of the HIV-1 envelope precursor, Arg-Ile-Leu-Ala-Val-Glu-Arg-Tyr-Leu-Lys-Asp-Gln-Gln-Leu-Leu-Gly-Ile-Trp- Gly-Cys - Ser-Gly-Lys) permitted the detection of antibodies to the human immunodeficiency virus type 1 (HIV-1) in 10 microliters of whole blood within 2 minutes. Agglutination was specifically inhibited by addition of synthetic peptide antigen but not by unrelated peptides. The frequency of false positive results was 0.1% with HIV-1 seronegative blood donors (n = 874). The false negative results were approximately 1% (n = 81). The autologous red cell agglutination test is potentially suitable for simple, rapid, qualitative screening for antibodies to a variety of antigens of medical and veterinary diagnostic significance.
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PMID:Autologous red cell agglutination assay for HIV-1 antibodies: simplified test with whole blood. 341 97

Forty-nine percent of homosexual/bisexual men were positive for antibody to the human immunodeficiency virus (HIV) in a population-based probability sample of 1034 single men recruited from San Francisco. All heterosexual men were negative. Among seropositive men, marked lymphadenopathy was present in 29%, and 16% had at least two other symptoms or signs suggestive of HIV infection. However, lymphadenopathy alone failed to indicate severity of immune impairment. The occurrence of two or more clinical signs and symptoms, except for marked lymphadenopathy, correlated with HIV infection, diminished skin test reactivity, and reduction in Leu 3a T cells. Twenty-nine percent of seropositive men had fewer than 400 absolute Leu 3a T helper cells per microliter (less than 0.4 X 10(9)/L). Seronegative homosexual/bisexual men did not differ from heterosexual men in any clinical or laboratory variables except for increased numbers of suppressor Leu 2a T suppressor cells per microliter.
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PMID:Clinical, immunologic, and serologic findings in men at risk for acquired immunodeficiency syndrome. The San Francisco Men's Health Study. 349 10

A monoclonal anti-idiotypic (anti-Id) antibody, HF1.7, was generated against anti-Leu-3a, a mouse monoclonal antibody (mAb) specific for the CD4 molecule on human helper/inducer T lymphocytes. The anti-Id nature of HF1.7 was demonstrated by the following properties. (i) It reacted in a solid-phase immunoassay with anti-Leu-3a and not with a panel of irrelevant mouse mAbs. (ii) It partially inhibited the binding of anti-Leu-3a to CD4+ T cells. (iii) It detected a common idiotype present on various anti-CD4 mAbs. Because the CD4 molecule represents the receptor site for human immunodeficiency virus (HIV), the etiologic viral agent of acquired immunodeficiency syndrome, we examined the ability of the anti-mAb HF1.7 to mimic CD4 and bind HIV. This anti-Id mAb reacted with HIV antigens in commercial HIV ELISAs and recognized HIV-infected human T cells but not uninfected cells when analyzed by flow cytofluorometry. Attesting further to the HIV specificity, the anti-Id mAb reacted with a recombinant gp160 peptide and a molecule of Mr 110,000-120,000 in immunoblot analysis of HIV-infected cell lysates. The anti-Id mAb also partially neutralized HIV infection of human T cells in vitro. These results strongly suggest that this anti-Id mAb mimics the CD4 antigenic determinants involved in binding to HIV.
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PMID:Monoclonal anti-idiotypic antibody mimics the CD4 receptor and binds human immunodeficiency virus. 349 1

The dipyridodiazepinone Nevirapine is a potent and highly specific inhibitor of the reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1). It is a member of an important class of nonnucleoside drugs that appear to share part or all of the same binding site on the enzyme but are susceptible to a variety of spontaneous drug-resistance mutations. The co-crystal-structure of HIV-1 RT and Nevirapine has been solved previously at 3.5-A resolution and now is partially refined against data extending to 2.9-A spacing. The drug is bound in a hydrophobic pocket and in contact with some 38 protein atoms from the p66 palm and thumb subdomains. Most, but not all, nonnucleoside drug-resistance mutations map to residues in close contact with Nevirapine. The major effects of these mutations are to introduce steric clashes with the drug molecule or to remove favorable protein-drug contacts. Additionally, four residues (Phe-227, Trp-229, Leu-234, and Tyr-319) in contact with Nevirapine have not been selected as sites of drug-resistance mutations, implying that there may be limitations on the number and types of resistance mutations that yield viable virus. Strategies of inhibitor design that target interactions with these conserved residues may yield drugs that are less vulnerable to escape mutations.
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PMID:Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. 751 27

Multimerization of the human immunodeficiency virus type 1 (HIV-1) Rev protein is believed to be critical to its biological activity. However, the precise protein sequence requirements for Rev multimerization in vivo, and whether multimerization is facilitated by specific RNA binding or vice versa, has remained controversial. In this report, we describe a sensitive in vivo assay for the multimerization of HIV-1 Rev on its cognate RRE primary RNA binding site. Using this assay, we demonstrate that an intact Rev arginine-rich domain, while critical to specific RNA binding, is dispensable for multimerization on the RRE. Mutations introduced into Rev sequences that flank this basic domain produce a partial multimerization phenotype in vivo even though these mutations are known to block Rev multimerization in vitro. Similarly, mutations introduced into the leucine-rich activation domain of Rev, which appear to have no effect on in vitro multimerization, also markedly inhibit multimerization of Rev on the RRE in vivo. Overall, these data appear consistent with the hypothesis that in vivo formation of the multimeric Rev:RRE ribonucleoprotein complex is facilitated by both the RRE RNA substrate and, as first proposed by Bogerd and Greene U. Virol. 67, 2496-2502, 1993), by bridging by a cellular cofactor for Rev that likely interacts with multiple Rev activation domains.
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PMID:Sequence requirements for Rev multimerization in vivo. 751 96


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