摘要:

Summary:Immunoaffinity enriched spleen follicular dendritic cells (FDCs), lymphocytes, and macrophages from SIV sm-inoculated cynomolgus monkeys (Macaca fascicularis) at different stages of disease were compared for latent and productive SIV infection. Analysis of FDCs by in situ hybridization, electron microscopy, and coculture assays indicated that comparatively high levels of virus were associated with the FDC fraction. Polymerase chain reaction (PCR) and RT-PCR results revealed that the levels for SIV pol DNA did not correlate with the level ofenvmRNA in the various cell subsets, suggesting differences in latency. Limiting dilution assays for spliced env mRNA showed a 10-100-fold higher amount ofenvmRNA in FDCs than in other spleen cell subsets early during SIV infection. At late stages of disease, the number of productively infected FDCs significantly decreased in parallel with a marked reduction of the FDC network and follicular involution. Our findings indicate that destruction of FDCs probably reflects a cytopathic effect of SIV and/or the activity of specific antiviral cytotoxic T lymphocytes.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The molecular basis for cross-reactive antibody binding to human T cell leukemia virus type I (HTLV-I) p19 core protein and human thymic epithelium has been defined with two monoclonal antibodies (mAbs), 12/1-2 and 13B12, raised to HTLV-I p19. The mAb 12/1-2 has previously been shown to react with HTLV-I p19, HTLV-II p22, and antigens of normal human thymic epithelium, placenta, and foreskin, whereas mAb 13B12 binds only to the carboxyl terminus of HTLV-I p19. In the present study, mAb 12/1-2 bound to a subset of Triton X-100-insoluble intermediate filaments in human thymic epithelium also recognized by antikeratin antibodies AE1 and AE3. The mAb 12/1-2 also reacted in Western blot assays with proteins of 54, 46, and 40 kDa present in extracts of human thymic epithelium and with hexameric peptides containing overlapping sequences of HTLV-I p19 with the amino acids IPP (amino acids 117-119). In contrast, the HTLV-I-specific mAb 13B12 did not bind to human thymic epithelium and reacted with a single hexameric peptide containing the carboxy-terminal HTLV-I p19 sequence IPPPYV (amino acids 117-122). Binding of mAb 12/1-2 to thymic epithelium could be inhibited by adsorption with peptide SP-79 containing aC-terminal sequence (amino acids 112-125) of p19. The crossreactive IPP site is within a region of p19 that has been previously shown to be highly immunogenic in HTLV-I-infected individuals and that is also encoded by genes or mRNA of human cytokeratin 17, keratin 4, epidermal cytokeratin 2, and 50-kDa type I epidermal keratin. Thus, our studies define the sequence of a cross-reactive antigen on HTLV-I p19 that is also associated with keratin intermediate filaments from human thymic epithelium and other normal human tissues and that could serve as a focus of an autoimmune response during HTLV-I infection.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Recombinant wild type (wt) and T215Y HIV-1 reverse transcriptase (RT) were isolated using three methods designated A, B, and C. The three samples of wt RT were kinetically indistinguishable with respect to dTTP turnover on poly(rA) · p(dT)10. However, whereas the kinetic constants for dTTP and AZTTP for both T215Y B and T215Y C were similar to those of wt protein, T215Y A exhibited a twofold increase inKmvalue for dTTP and a 13-fold increase inKivalue for AZTTP with respect to wt protein purified in the same manner. We further investigated this observation by studying the denaturation of wt RT by urea. The urea denaturation curves monitored by fluorescence and circular dichroism spectroscopy were not coincident with the denaturation curve monitored by enzyme activity and yieldedCmvalues (the concentration of urea at which 50% of the protein is denatured) of 4.1 and 2.0Murea, respectively. The noncoincidence of the transition curves reflects two separable, sequential, noncooperative conformational changes in the molecule: (a) from a catalytically active to an inactive conformation, and (b) from a catalytically inactive to a denatured, unfolded conformation. We therefore used denaturation as detected by changes in enzyme activity to compare the conformational stability of the three samples of wt and T215Y RT A, B, and C. TheCmvalues for T215Y RT did not differ from those of the respective wt; however, differences inCmvalues were noted depending on how the protein was isolated. This suggested that the heterogeneity of the recombinant RT was due to small differences in conformation at or near the active site.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Human antibody variable region gene usage during human immunodeficiency virus type 1 (HIV-1) infection is examined in the following review, and several hypotheses are presented to account for the distinct patterns of antibody gene expression associated with infection. Evidence supporting qualitatively biased antibody gene expression has been derived from analysis of the human humoral immune response by isoelectric focusing (IEF) and serological and molecular studies of immunoglobulin (Ig) from different lymphoid compartments of HIV-1-infected patients. Preferential usage of heavy-chain variable region (VH) gene families 1 and 4 is supported by serological studies of serum Ig and molecular characterization of anti-HIV-1 human monoclonal antibodies derived from infected patients. Negative biases against VH3 family gene usage are detected by polymerase chain reaction (PCR) studies of peripheral blood lymphocytes from AIDS patients but not by combinatorial phage display library techniques. Biased antibody gene usage and expression during HIV-1 infection may be related to HIV-1 pathogenesis by limiting the available HIV-1 neutralizing repertoire. Further molecular characterization of anti-HIV-1 antibodies and in vivo expression of V-region genes during HIV-1 infection should provide important information regarding antibody gene expression and its relationship to HIV-1 pathogenesis.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The aim of the study was to describe the epidemiology of AIDS dementia complex (ADC) in Europe and to assess the possible role of zidovudine therapy in preventing or delaying its occurrence. We used an inception cohort, with data collected retrospectively from patients' clinical records from 52 clinical centers in 17 countries across Europe. The subjects were 6,548 adult people with AIDS consecutively diagnosed from 1979 to 1989. The main outcome measures were codiagnosis of ADC at the time of AIDS diagnosis and ADC-free time after AIDS diagnosis. ADC was reported in 295 patients (4.5%) at the time of AIDS diagnosis and during follow-up in a further 402 of the 5,160 patients (7.8%) who were diagnosed with AIDS based on diseases other than ADC. Whether at the time of AIDS diagnosis or later, the occurrence of ADC was significantly associated with age, transmission category, and CD4+cell counts. The risk was greater in older patients (14 and 19% greater, at AIDS diagnosis and after, respectively, for a 5-year difference in age), in i.v. drug users than in homosexual and bisexual men (89 and 60% greater, at AIDS diagnosis and after, respectively), and for people with lower CD4+cell counts (14 and 30% greater for a reduction of 1 on the natural log scale). Risk was almost double for women than for men. A significant reduction, of ≈40%, was found in the risk of developing ADC after AIDS diagnosis for patients receiving zidovudine therapy, but this effect was present only during the first 18 months of treatment, irrespective of whether treatment began before or after AIDS diagnosis. In conclusion, an increase in the risk of developing ADC either at the time of AIDS diagnosis or thereafter is associated with increasing age, i.v. drug use, and decreased CD4+cell count. Women tend to have a higher risk of ADC at the time of AIDS diagnosis. Zidovudine therapy appears to have a definite, but time-limited, effect of protecting patients against ADC development after AIDS diagnosis.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The objective of this study was to determine whether HIV patients' subjective tolerance of zidovudine differs by racial or ethnic grouping by conducting a post hoc analysis of reported symptoms in two multicenter, placebo-controlled trials of zidovudine monotherapy for early HIV disease. Ratios of rates of developing new or worsening symptoms as reported by patients assigned to active drug or placebo were compared in groups of white/non-Hispanic, black, or Hispanic origin. Patients were included in the study if they had asymptomatic HIV disease and entry absolute CD4 lymphocyte counts below 500 cells/μL and were enrolled in National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group (ACTG) protocol 019 or had mild symptoms of HIV disease, were enrolled in ACTG protocol 016, met protocol eligibility criteria for the respective trial, and were categorized at entry as white/non-Hispanic (N = 1801), black (N = 195), or Hispanic (n = 214). The primary outcome measure was development of a new or worsening symptom of any severity. Among patients treated with zidovudine compared with placebo, the estimated risk for developing a new or worsening symptom was not significantly greater for blacks or Hispanics than for white/non-Hispanics for any of the most frequently reported symptoms (p> 0.05 after adjustment for the multiple comparisons performed). Our analysis of 195 black and 214 Hispanic patients did not reveal a significantly increased risk of subjective zidovudine intolerance compared with white/non-Hispanic subjects. If there is an increased risk of such intolerance in minority groups compared with white/non-Hispanics, it is not likely to be clinically important.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To describe the characteristics of mycobacterial infection in Mexico, we reviewed records from patients who were seen at the AIDS Clinic of the National Institute of Nutrition in Mexico City from 1983 to 1992. Of 460 AIDS patients, 118 (25.6%) were found to have mycobacterial infections by positive Ziehl-Neelsen stain, culture, or both. Cultures were completed for 66 of the 118 stain-positive specimens.Mycobacterium tuberculosiswas the most common species found (n = 13), followed byM. aviumcomplex (n = 12); 21 infections were identified a nonspecific mycobacteria other than tuberculosis (MOTT) and 20 infections were from species other than tuberculosis. Susceptibility testing was performed in only two tuberculosis cases, with one strain showing multidrug resistance. We conclude that mycobacterial infection is common among our AIDS population, and MOTT may be at least as common asM. tuberculosis. Previous reports of the rarity of MOTT could be related to the lack of adequate diagnostic methods in developing countries.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:In vitro experiments have suggested that interleukin (IL)-6 may contribute to human immunodeficiency virus (HIV) burden and to immunological abnormalities in HIV-infected patients. We had the opportunity to directly address this question in vivo through the virological and immunological monitoring of HIV-infected patients treated with an anti-IL-6 monoclonal antibody (mAb) for a lymphoma (ANRS 018 trial). Sixteen courses of anti-IL-6 mAb administration, performed in 11 patients, were studied. All patients were at a late stage of HIV infection. The HIV load and the immunological status were determined at the initiation of each course and at its end, 21 days later. The mAb induced no significant change of HIV load, as evaluated by p24 antigenemia, plasma viremia, and quantification of circulating HIV RNA by reverse transcriptase-polymerase chain reaction and branched DNA techniques. The anti-IL-6 mAb also did not affect CD4+, CD8+, and CD19+circulating cell counts, nor the serum concentrations of sIL-2R and of sCD8. In contrast, the mAb completely abrogated acute-phase reaction, as demonstrated by the normalization of C-reactive protein and fibrinogen circulating levels (p = 0.013 and p = 0.008, respectively). It increased serum albumin concentration. The latter effect was restricted to patients with a spontaneously low albuminemia (p = 0.01). It decreased B-lymphocyte hyperactivity, as reflected by decreased IgG and IgA serum levels (p = 0.008 and p < 0.001, respectively), and by a decreased production of IgG in vitro (p = 0.017). In contrast, the IgM hyperproduction was not affected by the mAb. Therefore, increased IL-6 production in HIV-infected patients at a late stage of the infection may not stimulate HIV replication in vivo, but it may represent a key mechanism contributing to the metabolic and immunological dysbalance of the disease.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:In this study we estimated past human immunodeficiency virus (HIV) incidence in 19 nations in the primarily English-speaking Caribbean and projected the course of the epidemic to the year 1999. We compared the results obtained from several different models of HIV incidence and different assumed incubation distributions. Linear and nonlinear optimization methods were used to fit several models (power, logistic, spline, and step) to adult (age 15 years or older) AIDS incidence data derived from our existing surveillance system. All four models tested gave good fits to the data, with estimates of cumulative HIV incidence in 1993 ranging from 16,504 to 21,732. An increase in the assumed median of the AIDS incubation distribution by one year increased the estimates of current cumulative adult HIV incidence by approximately 12%; these estimates varied by as much as 6% between models. An adjustment of the data for possible reporting delay increased the estimates by approximately 7% and for underreporting by 25%. Despite their sensitivity to underlying assumptions, back-projection estimates provide useful insights into the patterns of HIV and AIDS incidence. The models indicate that HIV and AIDS incidences in the English-speaking Caribbean have been rising steadily, with adult HIV prevalence in the general population still less than 1%.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Survival from the time of AIDS diagnosis to death was determined retrospectively among Thai patients (≥13 years old) who attended a public tertiary care infectious disease hospital in a suburb of Bangkok, Thailand, from February 1987 through February 1993. An AIDS diagnosis was based on the 1987 Centers for Disease Control (CDC) definition, exceptPenicillium marneffeiinfection was included as an AIDS-defining condition. Of 329 AIDS patients, 152 (46.2%) had died. The median age at diagnosis was 31.5 years (range, 18-74) 306 patients (93.0%) were males. Reported risk categories were heterosexual contact (55.2%), injecting drug use (IDU, 22.6%), male homosexual or bisexual contact (9.5%), and unidentified risk or other (12.7%). Median survival time (Kaplan-Meier) for all patients was 7.0 months; 1-year survival probability was 39.2% (95% confidence interval [CI] = 31.5-46.9%). Cox's proportional hazards model showed three factors associated with survival: age, reported risk category, and presenting diagnosis. Patients aged 26 to 35 years survived longer (median survival time, 10.6 months; relative hazard [RH] = 0.61, 95% CI = 0.44-0.85, referent: others), as did patients in sexual risk categories (median survival time, 7.3 months; RH = 0.59, 95% CI = 0.40-0.78, referent: IDU and other categories). A single presenting diagnosis of extrapulmonary tuberculosis was also associated with longer survival (median survival time, 19.9 months, RH = 0.55, 95% CI = 0.35-0.86, referent: other diagnoses). AIDS patients in the early phase of the epidemic in Bangkok have much shorter survival times than patients in developed countries, in part perhaps because they are often diagnosed late in the course of HIV infection. Increased attention should be given to the early diagnosis and treatment of these patients.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID