摘要:

A high frequency of autoantibodies to brain proteins has been reported in HIV-l-positive patients. However, the specificity of this response has not been characterized. Using; homogenized tissue from three normal brains, the presence of autoantibodies to human brain proteins was analyzed in 16 HIV-l-positive patients with AIDS dementia complex (ADC). 10 HIV-I-positive patients without ADC. 10 patients with multiple sclerosis. 10 patients with juvenile rheumatoid arthritis, and 10 normal controls. Although antibodies to various brain proteins were detected in sera from one-third of HIV-1 infected individuals with or without ADC. the proteins recognized were different among different brains. Only one ADC patient had consistent seroreactivity to a 50-kDa brain-specific protein. Our results indicate that autoantibodies to brain proteins are infrequently present in patients with ADC.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Expression of tumor necrosis factor α (TNIα). interleukin 1β(II.-1α). and interleukin 6 (II.-6) was evaluated in unstimulated peripheral blood monocytes obtained from human immunodeficiency virus-positive (HIV+) individuals using a reverse transcription-polymerase chain reaction (RT-PCR) method. In all. 40 subjects were included—13 asymptomatic. II with ARC. seven with AIDS, and nine HIV controls. Of the asymptomatic individuals. 85% were positive for TNFα and ILβ compared with only 27% of the ARC and 42% of the AIDS patients. Expression of IL-6 message was observed in lesser proportions, with no significant differences among disease states. Quantitation of IL-lβ and TNFα mRNA from the positive samples fell into two categories, low responders (six of 17). with 5,000 copies of II.-1β and TNFα mRNA. and high responders ( II of 17). with 5.000 copies per 10 pg of total cellular RNA. There was no correlation of mRNA detection or concentration with CD4 cell number or β-microglobulin levels. However, the levels of mRNA. but not its presence alone, were positively correlated with neopterin levels. The data show differential cytokine regulation in monocytes, observed as an increase in the expression of TNFα and II.-lβ compared with Il.6 in HIV patients. Our report also emphasizes the utility of an RT-PC'R system in analyzing multiple cytokine transcript levels in small amounts of clinical materials.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-1). In this study we found that pseudotypes allow penetration of HIV particles into CD-I-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could he blocked with anti-HTLV-l serum hut failed to be significantly inhibited with anti-HlV serum or a V,-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility for pseudotypes to escape neutralization by the immune system in vivo. Pre vious reports have suggested that carbohydrate structures may be conserved neutralization epitopes on retroviruses. In this study, the neutralizing capacity of lectins and anti-carbohydrate monoclonal antibodies was found to block infection by cell-free pseudotypes in CD-I-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo. HIV and HTLV-1 seem to induce common carbohydrate neutralization epitopes.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

It has been hypothesized that the progressive deletion of CD4+T cells in the course of infection due to human immunodeficiency virus (HIV) may be mediated in part by interaction with a superantigen inherent in an HIV protein. Consequently, selective loss of CD4+cells with a T cell receptor Vβ-chain capable of interaction with superantigen would produce a CD4 population less or totally unresponsive to superantigen such as staphylococcal enterotoxins B and A (SHU and SEA respectively), but not to other mitogens such as concanavalin A. anti-CD3 (OKT3). or pokeweed mitogen. We tested this hypothesis by comparing the proliferative response of SEB and SEA with the other mitogens for 25 controls. 20 HIV+. and 15 donors with acquired immune deficiency syndrome (AIDS). We found that peripheral blood mononuclear cells, as well as the CD4+and CD8+subsets from both HIV+and AIDS sources, the degree of suppression of mitogenesis for SEB and SEA was approximately equal to or less than that of the other mitogens. Moreover. suppression of HIV+CD4+and CDS T cell responses to SEB and SEA was equal (26%). If HIV superantigens exist, our data suggest that they are not responsible for the selective depletion of the CD4+T cell subset as evaluated by SEB and SEA specificity.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Phenylalanine-containing peptides from CD4 were synthesized based on chemical similarity with active CD4(81–92)-benzylated peptides. The synthetic peptide FYIFFVEDQKEEDD) blocked the binding of gp120 to CD4 and inhibited 50% μ human immunodeficiency virus (HIV)-induced syncytia formation at a concentration (1C50) of 40–50 μM and HIV p17 expression with an 1C50of 67 μM. The peptide is not toxic to cells in vitro. Moreover, acute toxicity studies carried out in Swiss mice showed the peptide to be nontoxic at a dose of 2.000 mg kg. This phenylalanine-substituted CD4 peptide may prove to be useful in the treatment of AIDS.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To ascertain whether combination therapy with zidovudine (AZT) and zaleitabine (ddC) delayed the emergence of AZT resistance, isolates of human immunodeficiency virus (HIV) were evaluated from 15 previously untreated patients with advanced HIV disease who received combination therapy. Eighteen sequential viral isolates were available from 15 patients who received −6 months of combination therapy. Isolates from eight (73% of 11 patients obtained between 24 and 48 weeks of therapy were AZT resistant [50% inhibitory concentration (1C50)of 40–45 μM range. 0.45–2.0 μM]. Four of these eight patients yielded virus isolates that were highly AZT resistant (IC50(μM). NO changes in ddC susceptibility were discerned. The median IC50, for ddC was 0.2 μM and ranged from 0.07 to 0.5 μM. The CD4 cell counts of patients with AZT -sensitive virus tended to have higher median areas under the curve (AUC) and greater increases compared with patients who had AZT-resistant virus. They also had higher means and ranges of the average CD4 154 cell counts at week 36 (p 0.01) and week 48 (p - 0.04). These data would indicate that the previously described more sustained CD4 cell responses conferred by the addition of ddC to AZT therapy cannot be ascribed to delayed emergence of AZT resistance with combination therapy.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We conducted a double-blind. randomized phase II study to evaluate the safety and activity of combination therapy with N-deoxynojirimycin (SC-48334) (an α-glucosidase I inhibitor) and zidovndine versus zidovudine alone. Patients with 200 to 500 Cl)4 cells mm3who tolerated −12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h and zidovudine ( 100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58. zidovudine and placebo. Twenty-three patients (38%) and 15 (26%). in the combination and zidovudine groups, respectively. discontinued therapy (p - 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μ.g ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells mm3and 52.4 cells mm3for the combination and zidovudine groups, respectively (p - 0.36). lor patients with prior zidovudine therapy. the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells mm3and 4.9 cells mm3at week 8 and 6.8 cells mm3and 45.1 cells mm3at week 16. respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p - 0.10) and five (45%) and two (14%) at week 24 (p - 0.08). respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Of 170 Western Australian patients who had their first A1DS-defining illness between 1 January 1983 and 31 December 1991. 61 (36%) were of unknown HIV antibody status (AIDS presenters), while 109 (64%) were of known HIV antibody status (HIV presenters). Pneumocystis carinii pneumonia (PCP) was less common as the AIDS-defining illness in HIV presenters (41% versus 62%. p 0.005). In this study of 70 patients with PCP as the index AIDS diagnosis. 36 were HIV presenters and 34 were AIDS presenters. Ten HIV presenters were taking prophylaxis at the time PCP manifested. The duration of symptoms of cough or dyspnea before the diagnosis of PCP was shorter, and the arterial Po2. measurement on admission was higher in those on prophylaxis, and a lower proportion of patients on prophylaxis required hospital admission (p - 0.05 for all comparisons). Furthermore. the CD4 counts at diagnosis of PCP were lower in patients taking PCP prophylaxis (mean 26 - 106L) than in patients who were not (mean 94 - 106L. p - 0.007). Of seven patients who died of PCP. none were receiving treatment for HIV disease before AIDS presentation. These findings suggest that PCP is prevented or deferred in patients receiving care for HIV disease and is less severe as a result of early diagnosis and treatment.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The objective of this study was to determine the dam. fetal, and infant toxicity of zidovudine (AZT) administered to pigtailed macaques during pregnane). Pregnant macaques were administered AZT (1.5 mg kg dose every 4 hl or water via gastric catheter throughout pregnaney, AZT concentration and hematological changes were monitored in the dam. and fetal growth was monitored via ultrasound. Infant hematocrit was assessed at birth. and the neurological, perceptual, and motor development of the offspring were assessed for 9 to 10 months. Twelve pregnancies were brought to term. Mean plasma concentrations of AZT were comparable to those in human studies. Hemoglobin dropped significantly in pregnant dams and remained low. whereas platelets increased during treatment but returned to normal before the end of the study. There were no significant differences in any ultrasound measure of fetal growth, and AZT -exposed infants exhibited little behavioral delay or impairment. We predict no significant toxic effects of prenatal AZT exposure at this dosage in humans.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A prospective study of persistent arthralgia was carried out on 331 consecutive female patients admitted to the Department of Internal Medicine of the Centre Hospitalier de Kigali in Kigali. Rwanda. The aim of this study was to determine its association with HIV-I infection and to describe its clinical characteristics, Ten additional HIV-l-seropositive patients with this condition attending the outpatient clinic were also included in the clinical study. Persistent arthralgia was significantly more common in HIV-1 -seropositive hospitalized patients (14 of 209.6.7%) than in HIV-1-seronegative hospitalized patients (one of 122. 0.8%p - 0.02) and had a specificity and a positive predictive value for HIV-I infection of 99.1% and 43.3';, respectively. HIV-1-related persistent arthralgia, studied in 24 patients in early as well as late stages of HIV-I infection, commonly affected several and mainly large joints. was mostly distributed symmetrically. and was usually relieved with nonsteroidal antiinflammatory drugs. Recurrencies were noted in eight patients. In areas highly endemic for HIV-1, persistent arthralgia should be considered a probable manifestation of HIV-1 infection, and although it is uncommon, it can be regarded as a predictor of HIV-I infection.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID