Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CTL and antibody responses to HIV-1 p17 and p24 antigens were monitored from 1986-1991, in 4 hemophiliacs. The patients had been infected with HIV-1 between 1980 and 1984. Two patients have remained asymptomatic while two progressed to AIDS in 1990. CTL were boosted by culturing with peptides from p17 aa 86-115, or p24 aa 265-279; and aa 270-373 or PHA. Lysis was measured on autologous or allogeneic targets pulsed with peptides or infected with recombinant vaccinia virus carrying HIV-1 gag or influenza A matrix genes. Antibodies to p17 and p24 were tested by ELISA using peptides and by Western blotting. High levels of CTL activity to p17 and p24 antigens could be generated only with lymphocytes from the two asymptomatic patients between 1986 and 1989, but these responses were absent in 1990 and 1991. Antibodies to p17 peptides disappeared in parallel with CTL activity. Antibodies to some p24 peptides also declined but most patients retained activity to others. In all patients a > or = 3-fold increase in CD8+ cell numbers occurred over time and accompanied the decline of CTL and antibody responses. The loss of CTL and p17 antibodies occurred irrespective of whether patients remained asymptomatic or progressed to AIDS in the intervening two years.
AIDS Res Hum Retroviruses 1992 Aug
PMID:Decline in CTL and antibody responses to HIV-1 p17 and p24 antigens in HIV-1-infected hemophiliacs irrespective of disease progression. A 5-year follow-up study. 128 55

LP-BM5 murine leukemia virus (MuLV) induces an immunodeficiency syndrome (MAIDS) in C57BL/6 mice which resembles immunological abnormalities observed in early stages of human AIDS. In our study, MAIDS virus-infected mice were exposed to low doses of ultraviolet radiation (UVR) before and after virus inoculation and compared with MAIDS-infected but not UVR-exposed mice. In all tested parameters (blood IgM levels; mitogenic responses to PHA, ConA, LPS and anti-mu; MLR; antigenic response to SRBC; enlargement and histopathologic changes of the spleen) we observed the same trend: changes due to MAIDS infection were more pronounced in the UVR-exposed group than in the unexposed group. Statistically significant differences between these two groups were seen for mitogenic responses at two different time points after virus inoculation. These results demonstrate that in vivo UVR exposure enhances the immunosuppressive effects of a retroviral infection. UVR exposure may affect the progression of AIDS in a similar manner.
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PMID:In vivo exposure to ultraviolet radiation enhances pathogenic effects of murine leukemia virus, LP-BM5, in murine acquired immunodeficiency syndrome. 133 87

(B10.A x A/WySn)F1 mice, infected with the Friend virus (FV) complex, were used as a predictive therapeutic model for AIDS. These infected mice exhibit many of the viral and immunologic manifestations of AIDS. Bropirimine (2-amino-5-bromo-6-phenyl-4[3H]pyrimidinone, ABPP) is an immunomodulating compound which has been shown to inhibit other viral infections. Oral (per os treatment) dosages of ABPP ranging from 50 to 400 mg/kg/day for 3 days resulted in increased numbers of infectious centers in the infected mice and increased splenomegaly and percentage of Ig+ (B cells) in spleens of infected and uninfected mice. Decreased percentages of total Thy-1.2+ (total T) cells and L3T4+ (T-helper) cells were seen in both uninfected and infected mice and a slightly decreased percentage of Ly-2+ (T-suppressor/cytotoxic) cells was observed in spleens of the infected mice. No effect on Ly2+ cells in spleens of uninfected mice was found. Intraperitoneal injection, single or multiple, of 20-200 mg/kg ABPP prior to FV injection resulted in increased spleen weights but had no effect on numbers of infectious centers in the spleens or on FV antibody titers in the plasma. Intraperitoneal treatment of uninfected mice with ABPP resulted in slight or no changes in percentages of Thy-1.2+, L3T4+ and Ly-2+ cells. Mice receiving multiple exposures of ABPP had an increase in percentage of splenic B cells and a depressed response to the T cell mitogen PHA. Treatment with ABPP induced the production of interferon (IFN); however, a state of hyporesponsive IFN production was seen following multiple administrations of ABPP. These data suggest that the immunomodulator ABPP may have an enhancing effect on this retroviral disease.
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PMID:Murine retroviral disease-enhancing effects of a pyrimidinone immunomodulator. 144 28

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study. 156 21

Soluble suppressor factor (SSF), first described in association with HIV-1 infection in vivo, is a molecule(s) capable of inhibiting T cell-dependent immune reactivity. Its relationship to human immunodeficiency virus (HIV) was further defined as supernatants of mononuclear cell cultures from HIV-1-seropositive carriers, CD4+ T lymphocytes infected with HIV-1 in vitro, and a T cell hybridoma incorporating CD4+ lymphocytes from an HIV-1-seropositive individual were shown to elaborate factors with similar activity profiles. These factors were recognized antigenically by certain antibodies directed against epitopes of p15E, a transmembrane protein of murine leukemia virus which shares regions of identity with proteins deduced from human endogenous retroviral envelope transcripts as well as HIV. These reagents precipitated a single-chain, nonglycosylated, nonviral protein of molecular weight 57,000 Da from SSF-producing cells. There was no cross-reactivity with antisera recognizing the IL-2R alpha-chain (CD25) or tumor necrosis factor. This molecule was present in very low levels in PHA-activated T lymphocytes and was upregulated following their infection with HIV-1. Isolation of HIV-linked SSF should permit comparisons with other virion, cellular, and serum inhibitory substances described in AIDS, and perhaps suggest therapeutic strategies.
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PMID:A soluble inhibitor of T lymphocyte function induced by HIV-1 infection of CD4+ T cells: characterization of a cellular protein and its relationship to p15E. 169 8

The constitutively expressed IL-2R beta (p70) chain participates in the formation of high-affinity (h.a.) IL-2R and transduces IL-2-mediated signals to normal cells. Its expression on HIV-infected patients' PBMC was evaluated and was found to be decreased in both nonstimulated CD4+ and CD8+ cells. Mitogenic cell stimulation induced IL-2R beta chain expression on both CD4+ and CD8+ cells from asymptomatic and persistent generalized lymphadenopathy patients but not on those from AIDS patients. Comparison of mean fluorescence intensity of IL-2R beta positively stained cells from normals and patients did not reveal significant differences. Cross-linking of 125I-rIL-2 on patients' PHA-blasts revealed decreased signals corresponding to both IL-2-binding chains and, in some cases, neither IL-2R alpha nor IL-2R beta chains could be detected. Decreased expression of IL-2R beta polypeptide was associated with impaired accumulation of the corresponding mRNA transcripts. Binding experiments with 125I-rIL-2 under h.a. conditions showed a decreased number of IL-2-binding sites/cell which was more pronounced in patients with AIDS than in patients with less advanced clinical stages. In vitro HIV infection of normal PHA-blasts also resulted in a decreased number of h.a. IL-2R/cell. High concentrations of rIL-2 in the absence of other mitogenic stimuli induced a decreased cell proliferation and expression of the IL-2R alpha chain and did not enhance the constitutive NK and the generation of LAK activity in several patients, suggesting an impaired IL-2R beta chain-mediated cell activation.
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PMID:Abnormal expression of IL-2R beta (p70)-binding polypeptide on HIV-infected patients' cells. 173 5

The possible differences in lipid composition between human immunodeficiency virus- (HIV) infected and uninfected PHA-activated human peripheral blood mononuclear cells (PBMC) have been studied. The total fatty acid composition was similar, except for the proportion of arachidonic acid, that was slightly higher in infected than in noninfected cells. No significant differences were obtained in the incorporation of radiolabeled stearic or oleic acids in the different lipid classes. The staining of cells with Nile Red showed similar amounts of intracytoplasmic lipid droplets. On the contrary, the CH/PL ratio, the major factor in determining cell membrane fluidity, was clearly higher in infected than in uninfected cells (0.60 and 0.36, respectively). This fact is discussed in relation with the known high CH/PL ratio (0.95) of the lipid envelope of HIV.
AIDS Res Hum Retroviruses 1991 Sep
PMID:Changes in lipid composition of human peripheral blood lymphocytes infected by HIV. 174 83

This study was conducted to evaluate the in vivo genotoxicity of zidovudine (ZDV) in patients with Acquired Immune Deficiency Syndrome (AIDS). Patients with this disease who were non-smokers and on ZDV (1200 mg/day) as their only medication for 4 weeks to 7 months were studied. Patients with AIDS who had not received ZDV served as a negative control. Whole blood cultures were initiated by conventional methods with PHA 1:50 dilution. In addition, for each culture there was an untreated control and a recombinant interferon-beta (rIFN-beta)-treated culture. The IFN-treated cultures were exposed to 10, 100, 1000, or 10000 units of rIFN-beta for the entire incubation period. The cells were harvested at 72 h and stained with a fluorescence plus Giemsa method which permits the determination of the number of division cycles a cell has completed. One hundred metaphases from first division cells were scored from each culture for chromosome aberrations that were mainly from the chromatid-type, i.e. chromatid, chromosome, and isochromatid breaks. The frequency of breaks in the ZDV and no ZDV group was 8.29 +/- 2.65 and 0.5 +/- 0.29 per 100 cells respectively (P less than 0.05). Cultures from ZDV patients that were incubated with 100 and 1000 units of rIFN-beta, however, showed a frequency of 1.3 +/- 0.71 and 1.9 +/- 1.08 respectively, which was significantly lower than observed in the cultures not exposed to IFN (P less than 0.05). At the highest dose of rIFN-beta utilized no aberrations were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant human interferon beta ser protects against zidovudine-induced genetic damage in AIDS patients. 179 78

We have previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV 1 gp41 (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies raised against synthetic peptides from these homologous regions bound not only to the isolated peptides, but also to "native" HLA class II molecules on cells. Screening of sera from HIV 1 infected individuals revealed high frequency of sera (35%) containing anti-class II crossreactive antibodies (CRAb), not only in AIDS patients, but also in early, asymptomatic patients. The CRAb containing sera caused potent inhibition of normal CD4-bearing cells' proliferative responses to tetanus toxoid in vitro. They could also kill class II bearing cells by ADCC. The possible contribution of these antibodies to the establishment of immunodeficiency state in HIV 1 infected individuals and/or to disease progression, was examined in two clinical studies: I. Asymptomatic patients were tested in parallel for their PBL responses to flu/tetanus, HLA alloantigens, and PHA (proliferation and IL2 production), and for the presence of anti-class II CRAb. About 50% of these patients showed a selective loss of their in vitro responses to recall antigens (flu/tetanus), which depend on CD4+ cells, while still responding to PHA and ALLO. Interestingly, positive correlation was found (P less than 0.001) between patients' lack of responsiveness to flu/tetanus and the presence in their sera of anti-class II CRAb. II. Retrospective study of HIV 1-infected hemophiliacs, suggest that patients with high titers of CRAb early in the disease progressed faster to full blown disease.
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PMID:Common sequence in HIV 1 GP41 and HLA class II beta chains can generate crossreactive autoantibodies with immunosuppressive potential early in the course of HIV 1 infection. 180 76

We evaluated clinical efficacy and tolerability of recombinant alpha 2a interferon (IFN), in a group of 16 patients with AIDS and ARC, including 3 children. All patients were followed up monthly for clinical and immunological studies. The frequency of oportunistic infections (OI) in AIDS, and the following symptoms in all patients were studied: fever, night sweats, fatigue, diarrhoea, weight loss. Immunological parameters (CD3+, CD4+, CD8+ lymphocytes, skin tests to recall antigens, NK activity, lymphoproliferative response to PHA) were also evaluated. Adult patients were treated with 3-6 million IU of r-alpha 2a IFN daily im for 3 months and the 3 times weekly up to 12 months. Pediatric cases were treated with lower doses of 0.5-1.5 million IU using the same time schedule. We observed clinical improvement and reduction of severe infections in 10/15 evaluable patients (4/4 ARC and 6/11 AIDS). Immunological parameters were transiently improved in one third of cases. We observed only mild side effects in r-alpha IFN treatment. We suggest therapy with r-alpha 2a IFN at low dosage should be tried in patients with AIDS for its beneficial effects on OI development.
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PMID:Recombinant alpha-2a interferon treatment in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC): clinical and immunological evaluation. 181 17


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