摘要:

Background:Human herpesvirus type 8 (HHV-8) has been associated with Kaposi's sarcoma, body cavity-based lymphoma (BCBL), and multicentric Castleman's disease through DNA,in situhybridization, and serologic studies. HHV-8 has been visualized only in HHV-8-positive/Epstein-Barr virus (EBV)-negative/cytomegalovirus (CMV)-negative BCBL cell lines, but not in HHV-8-positive/EBV-negative/CMV-negative Kaposi's sarcoma lesions.Design:Kaposi's sarcoma of the skin, lymph node, and spleen from three patients with AIDS were analysed for HHV-8, EBV and CMV DNA by polymerase chain reaction (PCR), for HHV-8 RNA (T1.1 riboprobe) byin situhybridization (ISH), for viral inclusions by light microscopy, and for herpesviruses by transmission electron microscopy (TEM). Sections were also labeled with T1.1 counterstained with CD34, an endothelial cell marker.Results:The skin lesion was DNA PCR-positive for HHV-8 and CMV (nested, but not single PCR), the lymph node was positive for HHV-8 and EBV, and the spleen was positive for only HHV-8. TEM revealed infection by a virus displaying the typical morphology and cytopathicity of herpesviruses. Hexagonal nucleocapsids and mature enveloped virions were present in vasoformative spindle cells and mononuclear cells, often resembling lymphocytes. Extrapolating from TEM to standard light microscopy on hematoxylin and eosin-stained paraffin sections, eosinophilic, targetoid intranuclear inclusions were identified within spindle cells which often lined vascular lumina. The T1.1-riboprobe labeled CD34+ spindle cells containing intranuclear inclusions, as well as mononuclear cells within Kaposi's sarcoma and residual lymphoid tissue.Conclusion:The herpesvirus visualized in Kaposi's sarcoma lesions has morphologic and cytopathic features typical of human herpesviruses, productively infects vasoformative spindle cells and mononuclear cells, and is consistent with HHV-8. It can also form intranuclear inclusions that are identifiable by light microscopy in hematoxylin and eosin sections and by ISH.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To test, in AIDS patients, a previously proposed hypothesis of clonal population structure inLeishmania infantum, the agent of visceral leishmaniasis.Design:Forty-three stocks ofL. infantumisolated from AIDS patients in Spain were analysed by multilocus enzyme electrophoresis.Methods:The results were analysed in terms of population genetics according to previously described statistical methods. Departures from panmixia were examined by linkage disequilibrium analysis.Results:As previously shown in HIV-negative patients, classical manifestations of clonality were shown, namely strong linkage disequilibrium, over-representation of genotypes and overall lack of genotype diversity. The same dominant clonal genotype (MON1) was recorded in both HIV-positive and HIV-negative patients. Frequency of this dominant genotype was not statistically different in HIV-positive and HIV-negative patients.Conclusions:The parasite population under survey appears to be clonal; parasite genotypes can therefore be equated to natural clones, stable in space and time, which can be used as multilocus epidemiological markers. Nevertheless, additional studies are required to better estimate the long-term stability of these clonal genotypes and the possible interference of gene exchange at an evolutionary scale.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To assess the role of RANTES, macrophage inflammatory protein (MIP)-1α and MIP-1β in modulation of HIV-1 long terminal repeat (LTR)-mediated gene expression and determine whether these chemokines share identity with CD8+ T-lymphocyte-derived HIV-1 LTR-suppressive factors.Design:HIV-1 LTR-directed reporter gene expression is a model for transcription that is susceptible to inhibition by factors produced by CD8+ lymphocytes of HIV-1-infected individuals. The effect of recombinant chemokines on LTR-directed gene expression was examined. The ability of chemokines found to be present in CD8 supernatants to suppress HIV-1 LTR-mediated gene expression was determined by antibody inhibition assays.Methods:The concentrations of RANTES, MIP-1α and MIP-1β in a panel of CD8+ T-lymphocyte-derived supernatants were determined by enzyme-linked immunosorbent assay. Recombinant chemokines were added to freshly transfected (pLTR-CAT and pSV40-tat) human Jurkat T cells. Excessive polyclonal neutralizing antibodies to these chemokines were added to transfected Jurkat T cells cultured in the presence of strongly inhibitory CD8+ T-cell-derived supernatants with known chemokine concentrations.Results:The concentrations of RANTES, MIP-1α and MIP-1β in a panel of CD8+ lymphocyte-derived supernatants were found to correlate with their relative ability to suppress the LTR-mediated gene expression (r = 0.679, 0.764 and 0.48, respectively). The addition of recombinant CC chemokines had no effect over a broad range of doses on HIV-1 LTR-mediated gene expression. The CD8-suppressive effect on HIV-1 LTR-driven gene expression was not abrogated by a combination of antibodies to RANTES, MIP-1α and MIP-1β.Conclusions:RANTES, MIP-1α and MIP-1β do not alter HIV-1 LTR-directed gene expression at doses up to 100 ng/ml. Although present in varying concentrations in supernatants derived from CD8+ lymphocytes from HIV-positive individuals, these chemokines are not responsible for the powerful CD8-derived suppressive effect on HIV-1 LTR-mediated gene expression observed in our system.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:To determine the associations between the suppression of HIV-1 long terminal repeat (LTR)-mediated gene expression by CD8+ T-cell supernatants and clinical correlates of well-being, including CD4+ and CD8+ T-cell counts, β-chemokine production and clinical stage of disease.Methods:Culture supernatants of activated CD8+ T cells derived from a panel of HIV-1-infected subjects were assessed for their ability to suppress HIV-1 LTR-mediated chloramphenicol acetyl transferase (CAT) expression. The percentage suppression of gene expression was correlated with CD4+ and CD8+ T-cell counts and clinical stage of infection. Some individuals within this group were followed at 2–3 month intervals over time to assess the consistency of the suppression. Selected CD8+ T-cell culture supernatants of diverse suppressive ability were screened for the levels of the β-chemokines macrophage inflammatory protein (MIP)-1α, MIP-1β and RANTES.Results:The ability of CD8+ T cells of HIV-1-infected subjects to suppress HIV-1 LTR-mediated gene expression did not show a dependence upon high CD4+ T-cell counts or on the clinical stage or duration of infection. The ability to suppress gene expression did show a relationship with higher CD8+ T-cell counts and correlated with the levels of β-chemokines in the culture supernatants. In contrast, strong suppression was mediated by CD8+ T-cell supernatants from some subjects with very low CD8+ T-cell counts and relatively low chemokine levels.Conclusions:Although the suppression of gene expression by CD8+ T-cell culture supernatants showed statistical correlation with β-chemokine levels and with higher CD8+ T-cell count, no correlation could be found with correlates of clinical well-being.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:To construct retroviral vectors expressing sense or antisense RNA targeted at HIV reverse transcription intermediates, and to test the anti-HIV properties of these constructs in transduced T cells.Design:Five double-copy retroviral vectors were constructed, in which the expression of the sense or antisense RNA corresponding to HIV minus- or plus-strand strong-stop DNA was driven by the human tRNAmetpromoter.Method:The templates for the sense or antisense RNA were polymerase chain reaction-cloned from HIV pNL43 into a murine leukaemia virus-based vector and corresponding defective virions were packaged in PA317 cells. Human Jurkat T cells transduced with these vectors were challenged with HIV and monitored for viral RNA, viral DNA and p24 production for 23 weeks.Results:Intracellular expression of HIV sense RU5 sequences (RNA complementary to minus-strand strong-stop DNA) enhanced HIV replication in T cells. Expression of HIV sense or antisense U3RU5 sequences (identical or complementary to plus-strand strong-stop DNA) conferred long-term inhibition of HIV replication, despite continuous presence of viral challenge in the transduced cell cultures.Conclusion:Plus-strand strong-stop DNA as an intermediate in the early process of viral reverse transcription can be explored as an additional target for anti-HIV gene therapy.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:Hepatitis B virus (HBV) and HIV infections share risk factors; therefore, coinfection is common. Interactions have been reported but controlled studies have been limited. Our objective was to study the effect of HIV infection on the natural history of chronic HBV infection and the reverse effect of the HBV carrier state on HIV infection.Design:Prospective observational cohort study.Setting:Open-access outpatient HIV/genitourinary medicine clinic at a Central London hospital.Patients:Total of 152 untreated homosexual male HBV carriers and 212 HBV surface antigen-negative controls (41.4 and 70.3% HIV-seropositive, respectively).Outcome measures:The rate of loss of serum HBV e antigen (HBeAg) and its reappearance in HIV-infected and HIV-uninfected HBV carriers; serum HBV DNA levels (measured by dot-blot hybridization assay), HBV DNA polymerase activity and liver transaminase activities; the progression of HIV infection to symptomatic disease or AIDS in HIV-infected compared with HBV-HIV coinfected patients.Results:In HIV-infected HBV carriers, serum HBV DNA polymerase activity was higher, alanine aminotransferase was lower and loss of serum HBeAg (mean follow-up, 2.8 years) occurred at a lower rate when compared with HIV-uninfected HBV carriers (estimated relative hazard, 0.39; 95% confidence interval, 0.161–0.942). Concomitant chronic HBV infection had no detectable effect on the rate of progression of HIV disease after correction for lead-time bias.Conclusion:This study strengthens the evidence for a significant effect of HIV infection on the natural history of chronic HBV infection, which by prolonging the period of infectivity could have an important impact on the epidemiology of HBV infection in regions, or patient groups, with high HIV seroprevalence. There was no evidence of an important effect of HBV carriage on HIV disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To evaluate the circulation of a new human herpesvirus (HHV), HHV-8 or Kaposi's sarcoma (KS)-associated herpesvirus in a geographical area where a high incidence rate of classical KS was already present before the appearance of the AIDS epidemic.Design and methods:The study was carried out by analysing: (i) bioptic samples from classic, AIDS-associated KS, and controls; (ii) peripheral blood mononuclear cells (PBMC) from classic KS, HIV-positive subjects with and without KS and healthy HIV-negative individuals; (iii) semen samples from heterosexual HIV-positive and HIV-negative individuals affected or not by KS; and (iv) cervical swabs from HIV-negative healthy heterosexual females. All specimens were tested for the presence of HHV-8 DNA sequences by a two-step polymerase chain reaction.Results:Positive results were obtained in 90% of bioptic samples of classic KS and in 100% of AIDS-associated KS. Viral sequences were also present in 50% of PBMC of subjects with classic KS and AIDS-associated KS, in 10% of AIDS patients without the angiosarcoma, and in 11% of healthy HIV-negative individuals. Finally, HHV-8 DNA was detected in 13% of semen of HIV-negative heterosexual individuals and in 10% of AIDS patients without KS. Both PBMC and ejaculates from the same individual gave positive results. No HHV-8 sequences were found in cervical swabs.Conclusions:HHV-8 is widespread in the general population in Sicily since it was detected in PBMC and semen of heterosexual HIV-negative individuals and is not found only in high-risk groups. The viral load appears to be more elevated in a high-risk population and it may be ascribed to a viral reactivation. The higher incidence rates of KS in Sicily compared with northern Italy and other European countries might be related to the presence of HHV-8 in the general population.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To examine the associations between serum vitamin A and E levels and risk of progression to three key outcomes in HIV-1 infection: first AIDS diagnosis, CD4+ cell decline to < 200 cells × 106/l, and mortality.Design:Non-concurrent prospective study.Methods:Serum levels of vitamins A and E were measured at the enrollment visit of 311 HIV-seroprevalent homo-/bisexual men participating in the Baltimore/Washington DC site of the Multicenter AIDS Cohort Study. Cox proportional hazards models were used to estimate the relative hazard of progression to each outcome over the subsequent 9 years, adjusting for several independent covariates.Results:Men in the highest quartile of serum vitamin E levels (≥ 23.5 µmol/l) showed a 34% decrease in risk of progression to AIDS compared with those in the lowest quartile [relative hazard (RH), 0.66; 95% confidence interval (CI), 0.41–1.06)]. This effect was statistically significant when comparing the highest quartile of serum vitamin E to the remainder of the cohort (RH, 0.67; 95% CI, 0.45–0.98). Associations between serum vitamin A levels and risk of progression to AIDS were less clear, but vitamin A levels were uniformly in the normal to high range (median = 2.44 µmol/l). Similar trends were observed for each vitamin with mortality as the outcome, but neither vitamin was associated with CD4+ cell decline to < 200 cells × 106/l. Men who reported current use of multivitamin or single vitamin E supplements had significantly higher serum tocopherol levels than those who were not taking supplements (P = 0.0001). Serum retinol levels were unrelated to intake of multivitamin or single vitamin A supplements.Conclusions:These data suggest that high serum levels of vitamin E may be associated with slower HIV-1 disease progression, but no relationship was observed between retinol levels and disease progression in this vitamin A-replete population.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To compare the progression and non-progression of HIV infection among 418 injecting drug users (IDU) and 422 homosexual men with documented dates of HIV seroconversion from 12 cohorts.Methods:Seroconversion dates were calculated for each subject using a cohort-specific estimate of the cumulative HIV seroincidence over calendar time. In survival analysis, we studied the progression from seroconversion to AIDS and death by risk group. We compared non-progression between both risk groups by evaluating annual CD4 decline over the 7 years following seroconversion among AIDS-free subjects.Results:The relative hazard (RH) of AIDS for homosexual men compared with IDU was 1.54 before, and 1.21 after, adjusting for age at seroconversion and year of seroconversion. The risk of death from any cause for homosexual men compared with IDU increased over time since seroconversion. Fifty IDU died prior to AIDS, compared with seven homosexual men (unadjusted RH for homosexual men 0.10). Ignoring this pre-AIDS mortality, the crude RH of death for homosexual men compared with IDU was 2.05. After adjusting for age at seroconversion and year of seroconversion in multivariate analysis, the RH became 1.42. No differences in progression between subgroups aged 24 years or older could be demonstrated, but subjects < 24 years were found to be at a decreased risk. Proportions of nonprogressors based on CD4 slope ≥ 0 at 7 years following seroconversion were higher for IDU than for homosexual men. No differences were found in the proportion (≈ 5%) classified as non-progressors by criteria of both slope ≥ 0 and absolute CD4 counts > 500 cells × 106/l, even if pre-AIDS deaths and losses to follow-up were included.Conclusions:We found little evidence for an effect of risk group on progression and non-progression. Pre-AIDS mortality was much higher among IDU than homosexual men. Pre-AIDS mortality and a nonlinear age effect should be considered in planning interventions as well as studies comparing risk groups and modelling the epidemic.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID