摘要:

SummaryThe discovery of T helper type 1 (Th1) and T helper type 2 (Th2) phenotypes within the CD4+T-lymphocyte population has allowed for further elucidation of the roles the T cells play in regulation of humoral and cellular immunity. It is suggested that differential activation of the CD4+subsets, particularly up-regulation of the Th2 cell and down-regulation of the Th1 cell, may be associated with diseases as diverse as AIDS and asthma. We report herein that by using the polymerase chain reaction to analyze the kinetics of in vivo cytokine- and virus-specific gene expression, we can show that mice infected with the molecularly cloned MAIDS defective virus 1/27/A BM5 exhibit an alteration in cytokine gene expression that closely parallels an increase in spleen cell numbers, an increase in IgM production, a decrease in the stimulation index, and an increase in defective-virus gene expression in these mice. As has been suggested to be true for human AIDS, the observed alteration of cytokine gene expression suggests that a pattern of expression similar to that produced by Th2 cells may also have a role in the development of MAIDS.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe usefulness of traditional methods of HIV plasma titration has been limited by poor detection capacity in the asymptomatic phase of HIV disease. We analyzed plasma samples from asymptomatic seropositive or early symptomatic patients, comparing the classic plasma culture method with the following techniques: phorbol 12-myristate 13-acetate treatment of target cells, centrifugal inoculation of the virus, heat treatment of cultures, addition of monocyte/macrophages to cultures, and polyethylene glycol (PEG) treatment of the plasma. Only PEG treatment significantly increased the percentage of HIV isolation. The increase of HIV isolation after PEG treatment is more evident in patients with higher CD4+cell counts and those without detectable levels of p24 antigen. In the p24-negative samples, HIV was isolated in 17 of 24 (71%) with PEG treatment versus nine of 24 (37%) with the classic method (p < 0.01). A number of discordant samples were found using the classic and PEG methods. Combining the positive results obtained with either technique, we obtained an overall HIV detection rate of 76%. The increased sensitivity of the combination of PEG and classic methods may allow a wider use of plasma viremia as part of the virological evaluation of anti-HIV drug efficacy in asymptomatic patients.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryActivation of T helper cells specific for viral antigens is critical for antibody production and for generation of cytotoxic cells during the immune response to HIV. Since T-cell activation depends on antigen-presenting cells (APCs), it is important to define the cells that have a role in presentation of HIV antigens in general and of gp120 in particular. Peripheral blood mononu-clear cells (PBMCs), adherent monocytes (AMs), dendritic cells (DCs) and Epstein Barr virus-transformed B-cell lines (LCLs) were tested for the capacity to present gp120 to a specific T-cell clone. DCs proved to be the most effective APC. Primary T-cell lines were generated from uninfected and unprimed individuals by using different APCs in the presence of gp120 or an immunodominant peptide. T-cell lines specific for gp120 were obtained with PBMCs or DCs as APCs, but not with AMs or LCLs. The data showed that (a) DCs are the most effective APCs for presentation of gp120 to specific T cells and (b) DCs are necessary for in vitro induction of primary T-cell lines specific for gp120.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummarySeveral fluoroalkylated oligomers were found to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Among the test compounds, bis(perfluoro-1,4,7,10-tetramethyl-2,5,8,11-tetraoxatetradecyl)methacrylic acid oligomer (MAA-HFPO5) emerged as the most potent inhibitor of HIV-1 replication. Its 50% antivirally effective concentration for the IIIBstrain was 2.8 g/ml, whereas the compound did not affect the growth and viability of mock-infected MT-4 cells at concentrations $100 μg/ml. MAA-HFPO5 was also inhibitory to other strains of HIV-1 in various human T-cell systems, including peripheral blood lymphocytes. MAA-HFPO5 inhibited syncytium formation and virus adsorption. The combination of MAA-HFPO5 with either 3'-azido-3'dioxythymidine or dextran sulfate resulted in an additive effect. Thus, fluoroalkylated oligomers are novel HIV-1 inhibitors that warrant further evaluation of their therapeutic potential.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryIn 1990 the results of a placebo-controlled study conducted within the AIDS Clinical Trials Group (ACTG 019) showed that in the short term, Zidovudine was effective in slowing progression to advanced disease in HIV-infected asymptomatic patients with low CD4 cell counts. More recently, the preliminary results of the Concorde Trial suggested that while the data at 1 year agreed with those of ACTG 019, no sustained clinical benefit was detectable at 3 years for early versus deferred therapy. Therefore, the length of the clinical usefulness of zidovudine in this population is still to be determined. We evaluated the 2-year outcome of zidovudine therapy in asymptomatic patients through the prospective follow-up of a cohort of 936 subjects with low CD4+(<500/mm3) counts who strictly satisfied, at enrollment, the inclusion and exclusion criteria of the ACTG 019 trial. The clinical end point of the analysis was the development of AIDS. The majority (72.2%) of the individuals in the cohort acquired HIV infection through intravenous drug use; 26.6% were women. The median baseline CD4 cell count was 308/mm3.At 55 weeks of mean follow-up, the progression rate to AIDS (3.2 events per hundred person-years) appears to be comparable to that already reported at the same mean follow-up time for the ACTG 019 zidovudine-treated asymptomatic patients. After 124 weeks of mean follow-up, the overall rate of progression to AIDS was 5.2 per hundred person-years. The majority of those who progressed had CD4+ counts <200/mm3at enrollment and p24 antigenemia and had been treated with high dosages of zidovudine (median dosage: 1,000 mg per day). The analysis of incidence rates over time according to zidovudine dosage group showed that in the low-dosage group (median: 500 mg per day), the progression rate at 124 weeks remained below the rate observed at 55 weeks for the placebo arm of the ACTG 019 study, suggesting that the effect of zidovudine on clinical progression of asymptomatic patients can be sustained for >2 years.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe radiographic presentation ofPneumocystiscarinii pneumonia (PCP) was studied in 93 consecutive patients to determine the frequency of normal findings on chest roentgenograms and possible correlations with clinical or laboratory findings. The roentgenograms were reviewed by two radiologists in an independent, blinded way and judged with a score distinguishing between none, interstitial, and acinar infiltrates. Discordance mainly between absent versus interstitial and interstitial versus acinar infiltrates occurred in 23% of roentgenograms and was settled by consensus. The majority of patients presented with moderate-to-mild symptoms; the combination of dyspnea, cough, and fever was present in 53%. Lactate dehydrogenase (LDH) was elevated in 63%, hypoxemia (PaO2< 75 mm Hg) was present in 57%. Findings on chest roentgenograms were normal in 39%, whereas 36% showed interstitial and 25% acinar infiltrates. These three radiographic groups represented an increasingly severe PCP, indicated by higher LDH levels and hypoxemia (bothp< 0.05). In a multivariate logistic regression, normal roentgenograms were predicted by low LDH and low peripheral blood granulocytes (p< 0.005). Mortality within 3 weeks was only 4% and correlated with the severity of infiltrates (p< 0.05). Normal roentgenograms thus corresponded to an oligosymptomatic, less severe PCP. In immunodeficient HIV-infected patients, a normal chest roentgenogram does not exclude PCP and should not distract from attaining a definite diagnosis by examination of induced sputum or bronchoalveolar lavage.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryWe compared endocrine function in patients with the HIV wasting syndrome with other HIV-positive patients without wasting to determine associations between endocrine dysfunction and wasting. Sixty-six HIV-seropositive patients were evaluated by thyroid, gonadal, and adrenal function tests. Fourteen of these patients met the clinical definition of wasting. Total and free testosterone levels were significantly lower in patients with wasting compared with patients without wasting with both similar and higher mean CD4 counts. Prolactin levels were significantly higher, and cortisol levels were higher with borderline significance in patients with wasting compared with patients with similar CD4 counts without wasting. These findings suggest that endocrine function in the HIV wasting syndrome differs from that of HIV-infected patients without wasting, which may have implications about the pathogenesis and treatment of the HIV wasting syndrome.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryChronic refractory severe pain in HIV-infected patients is a common and often neglected problem. Little data exist evaluating its epidemiology, clinical features, and treatment. Our study assessed all HIV-infected inpatients referred to the pain control service over a 2-year span. All (24) inpatients with HIV infection with chronic refractory severe pain referred to the pain control service (PCS) over a 2-year period were prospectively followed daily by trained specialists who graded the pain, recommended appropriate therapy, and assessed outcome. Ten surviving patients had further long-term outpatient follow-up. The patients included 14 intravenous drug abusers, five of whom were on methadone maintenance. Localized lower-extremity pain was present in 58%. Pain had been present for ≥1 month in 21 (88%) and for ≥6 months in 12 (50%). No patient had been on pain control around the clock. After PCS consultation, all surviving patients (21 of 21, 100%) had partial or total pain relief within 2 weeks (eight within 1 week) using around-the-clock opioid analgesia adjusted daily as necessary. No differences were seen between substance abusing/methadone patients and others. No significant adverse reactions or new addiction problems were found. Our conclusion is that effective pain control can be achieved using around-the-clock opioid analgesia in terminal HIV-infected patients with severe, chronic, refractory pain even if the patients are substance abusers.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe hippocampus is a major center for the regulation of the hypo-thalamic-pituitary-adrenal axis. There is experimental evidence that chronic exposure to high levels of glucocorticoids may be toxic to the hippocampus. We observed elevated mean basal and 60-min cortisol (F) levels in response to adrenocorticotropin stimulation (0.25 mg cortrosyn, i.v. bolus infusion) in 15 children with HIV infection. Furthermore, in eight of the children for whom data was available, in addition to high peripheral cortisol levels, neurologic dysfunction and hippocampal atrophy were noted on CT scan. These preliminary data suggest that in HIV-infected children an altered cortisol secretion may be associated with specific central nervous system damage.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryMaternal antibodies against the V3 loop principal neutralizing domain (PND) have been reported to protect against perinatal HIV-1 transmission. To study this association in an African city with a long-standing HIV epidemic and no established “consensus sequence” for the V3 loop region of gp120, we determined the DNA sequence for the V3 region of HIV-1 from 13 HIV-1-infected residents of Kinshasa, Zaire, and developed peptide enzyme immunoassays (EIAs) reflecting the V3 loop PND for those HIV-1 strains. Using the most broadly reactive locally derived V3 loop peptide in a limited-antigen EIA, there was no significant difference in the perinatal HIV-1 transmission risk between 64 women with anti-V3 loop antibody (transmission risk, 30%) and 104 women without anti-V3 loop antibody (transmission risk, 25%;p= 0.5); this finding was unchanged after we controlled for maternal AIDS and low birth weight. Although we used assays for V3 loop antibody based on local HIV-1 strains and evaluated a large number of mother-child pairs, we found no evidence that maternal anti-V3 loop PND antibody protects against perinatal HIV-1 transmission.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID