摘要:

Summary:Kaposi's sarcoma (KS) is a multifocal vascular lesion characterized by abnormal proliferation of endothelial-like KS cells linked to a pronounced leukocyte infiltration. KS lesions contain novel herpes-like DNA sequences, KSHV, hypothesized to originate from the viral pathogen for KS. Using cultured KS cells that retain the KSHV sequences, diverse signals, including tumor necrosis factor alpha, interleukin (IL) 1β, polyinosinic acid/polycytidylic acid, and lipopolysaccharide, induced the expression of the cytokine IL-6 and cellular adhesion molecules involved in leukocyte recruitment, including vascular adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). The thiol-antioxidant pyrrolidine dithiocarbamate (PDTC) selectively inhibited >90% of the activation of nuclear factor κB-like DNA binding activity in KS cells. PDTC also reduced by >85% induced levels of VCAM-1 and IL-6 at the mRNA, protein, and functional levels in KS cells. In contrast, PDTC did not inhibit the induced expression of either ICAM-1 or E-selectin. These studies show that PDTC differentially modulates the expression of inflammatory response genes in KS cells that contain KSHV, suggesting that reduction-oxidation-sensitive events are involved in the regulation of these genes. These studies also suggest that thiol-antioxidants such as PDTC may play a potentially therapeutic role in the treatment of KS by preventing induction of specific inflammatory response genes that may be involved in the pathogenesis of KS.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Chimpanzees infected with human immunodeficiency virus type 1 (HIV-1) are used to model acquired immunodeficiency syndrome (AIDS). Since the central nervous system (CNS) is involved in AIDS, we performed an immunovirological study in 18 chimpanzees inoculated up to 87 months prior to the study (mean, 45 months) with HIV-1 and 8 uninfected controls. Serum and cerebrospinal fluid (CSF) IgG and albumin levels of infected chimpanzees never exceeded those of controls. The CSF/serum albumin ratio was elevated in 1 of 18 infected chimpanzees compared to controls; however, all animals had an elevated ratio indicating a more open blood-brain barrier relative to humans. The intrathecal IgG production index was elevated in only 1 of 18 infected chimpanzees compared to controls. Identical serum and CSF IgG bands were found by isoelectric focusing in 2 of 8 controls and in 1 of 18 infected chimpanzees. None of these bands reacted with recombinant HIV-1 p24gag or gp120env. HIV-1 was isolated from the peripheral blood of 4 of 18 infected chimpanzees but never from the paired CSF samples. Anti-HIV-1 antibody was detected by a enzyme-linked immunosorbent assay in 18 of 18 paired serum and CSF samples and by Western blot in 18 of 18 serum and 13 of 18 CSF samples from infected chimpanzees without a difference in pattern. Polymerase chain reaction analysis on brain tissue of one animal was negative for HIV-1 sequences. Our results demonstrate that, unlike human infection, chimpanzees inoculated with HIV-1 show no evidence of isolatable virus in the CSF and no evidence of intrathecal anti-HIV-1 antibody synthesis up to several years after experimental infection. The lack of CNS involvement may contribute to the delay or suppression of clinical disease in infected chimpanzees.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Phagosome-lysosome fusion is critical for intracellular killing of most organisms and is inhibited by some viruses, notably influenza. We explored the effects of infection in vitro with HIV-1 (IIIB or Ada-M) on phagosome-lysosome fusion in blood monocyte-derived macrophages. After 8 days of infection, fusion was assessed from the fluorescence change occurring up to 2 h after labeling the lysosome compartment with acridine orange and loading of phagosomes with opsonized yeast. Compared with mock-infected control macrophages, the proportion of cells showing fusion after infection was reduced from a mean of 70% to a mean of 47% (p = 0.0001). Inhibition was seen with heat-killed HIV-1 IIIB but not virus-free filtrate. It was mimicked by recombinant gp120 and blocked by soluble CD4 or antibody to CD4 but not by a neutralizing antibody to the V3 loop of gp120. The inhibitory effect was seen 8 days after the original, transient exposure to gp120. These results suggest that a lasting abnormality of phagosome-lysosome fusion results from interaction between gp120 and CD4, contributing, perhaps, to the increased susceptibility to opportunistic infections of people infected with HIV.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

SummaryWe examined the effect of bacterial pneumonia on the magnitude of circulating plasma HIV RNA in HIV-infected patients. Serum samples from 13 adult HIV-infected patients (median CD4 count = 83 cells/μl) were assayed for HIV RNA using the reverse transcriptase polymerase chain reaction assay (a) before bacterial pneumonia, (b) during the acute phase, and (c) after the recovery from the disease. Patients remained on constant antiretroviral therapy; HIV RNA was detected in all samples tested. The medians before, during, and after bacterial pneumonia were 60,000 copies per ml, 245,000 copies per ml, and 84,000 copies per ml, respectively. All 13 patients had increased HIV RNA levels on developing pneumonia. There was a decline in the level of HIV RNA with recovery from pneumonia in 12 of 13 patients. The difference between the HIV RNA levels before and after pneumonia was not significant, nor was there significant difference in the CD4 counts before and after pneumonia. In conclusion, bacterial pneumonia is associated with a consistent, transient increase in HIV RNA of variable magnitude in AIDS patients. Interpretation of HIV RNA changes for clinical management of AIDS patients must take into account this reversible elevation during infections.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:DisseminatedMycobacterium aviumcomplex (MAC) infection is common in persons with advanced HIV infection and can be prevented by prophylactic use of rifabutin; however, routine prophylaxis is costly and incompletely effective. Chronic anemia is a common manifestation of MAC infection. We conducted a retrospective population study of the annual incidence of MAC bacteremia and blood transfusion for anemia in a regional HIV-positive population before and after the introduction of rifabutin to determine the effect of MAC prophylaxis on the incidence of transfusion-requiring anemia. The HIV-infected patient populations in 1992 and 1993 were comparable in number, severity of immunodeficiency, and zidovudine (ZDV) use. The use of rifabutin for MAC prophylaxis for those with CD4 T-lymphocyte counts <100/μl increased from 17.2% in 1992 to 33.7% in 1993 (p< 0.001), whereas diagnostic surveillance for MAC bacteremia was stable. In 1993, there was a decrease in the number of HIV-infected persons from whom MAC was isolated (10 vs. 26,p= 0.004), and a significant decrease in the number of patients transfused for anemia (15 vs. 35,p= 0.002), number of transfusion episodes, and numbers of units transfused, associated with significant cost and resource savings. Adoption of MAC prophylaxis was followed by a significant decrease in the number of diagnosed MAC infections and in transfusion requirements in an HIV-positive population with sustained surveillance and similar levels of immunodeficiency, which may represent a health and economic benefit of defective MAC prophylaxis in a population at risk.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To examine the prevalence of stool viruses and their role in the pathogenesis of diarrhea in HIV infection, we evaluated biopsies and repeated stool samples of 256 HIV-infected patients undergoing diagnostic endoscopy because of diarrhea (n = 136) or other symptoms (n = 120) for bacterial, protozoal, and viral enteropathogens. In 70% of the patients with diarrhea, at least one potential enteropathogen was detected. Stool virus was detected by electron microscopy in 17% (44 of 256), adenovirus in 6.6% (17 of 256), and coronavirus in 11.3% (29 of 256) of the patients. Adenovirus and coronavirus were detected more frequently in patients with diarrhea than in patients without diarrhea [adenovirus 10% (13 of 136) vs. 3.3% (4 of 120),p= 0.0129; coronavirus 15% (21 of 136) vs. 6.6% (8 of 120),p= 0.0142]. Sixty-one percent of patients harboring stool virus were coinfected by another enteropathogen. Pathogens other than stool virus were detected more frequently in patients harboring adenovirus (82%) than in patients without stool virus (48%,p< 0.025). Adenovirus and coronavirus are frequently detected in stools of HIV-infected patients and may contribute to diarrhea. Adenovirus infection may facilitate the occurrence of other intestinal pathogens. Due to frequent coinfections, detection of stool viruses reduces the rate of diarrhea of unknown origin only by ≈5%.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:We wished to establish the feasibility of fine needle aspiration of lymph nodes as a noninvasive method for measuring subsets of immune cells and viral load in HIV-infected patients. Twenty-five patients (CD4+T cell range 4-760/μl, median 362) were selected. Lymph node aspiration was attempted in 21 patients. Lymph node cells (LNC), ranging from 6 × 103to 2 × 106(median 6 × 105) were obtained in 17 subjects, and compared with peripheral blood mononuclear cells (PBMC) obtained simultaneously. Immunophenotype could be determined by flow cytometry in 9 patients. Mean percent of CD4+CD3+T cells in LNC and PBMC and 23.2 and 14.6. Mean percent of CD8+CD3+T cells in LNC and PBMC was 23.1 and 45.0, respectively. Therefore, CD4+/CD8+ratios were much higher in LNC (mean ± SD: 1.06 ± 0.31) than in PBMC (0.35 ± 0.13). The amount of HIV DNA (11 patients) and RNA (8 patients) was determined in the plasma, LNC, and PBMC by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). The number of copies of viral DNA/105cells was higher in LNC than in PBMC (LNC/PBMC ratio range: 0.54-25, median 3.4). The number of copies of unspliced viral RNA/105cells was much higher in LNC than in PBMC (LNC/PBMC ratio range 65-1, 159, median 435). The plasma RNA copy number, a measure of circulating cell-free virus, was correlated with the RNA copy number in PBMC, but not in LNC. A RT-PCR system specific for spliced transcripts was also used to assess the level of transcripts independent of genomic RNA. This assay also detected more signal in LNC than in PBMC. The level of spliced transcripts in LNC and PBMC correlated with the amount of full-length RNA detected by competitive PCR. A semiquantitative coculture assay with lymphoblasts from healthy donors was used to assess the infectivity of LNC as compared with PBMC in 14 patients. The minimum number of LNC necessary to cause a positive coculture ranged from 103to >105(median 104); the corresponding number for PBMC ranged from 103to >106(median 5 × 105). In most patients selected for palpable lymph nodes, LNC could be obtained by fine needle aspiration, thus allowing noninvasive monitoring of viral burden in lymphoid tissue. The present study also suggests that both T-cell subsets and viral load differ in the blood and lymphoid tissue, which raises the question of whether the study of the lymphoid tissue would yield better prognostic markers of disease course.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The Bronx, New York, has a large, inner-city, AIDS population which contains a greater proportion of women and intravenous drug users and a lower percentage of homosexuals than the U.S. AIDS population overall. Because this population is reflective of the evolving trends in the national AIDS population, our objective was to gain an understanding of patterns of infections, malignancies, and cause of death among these individuals. All autopsies (252) performed on patients with AIDS at two hospitals affiliated with a major academic center in the Bronx between 1982 and 1995 were reviewed. Cytomegalovirus (CMV) as an infection or as a cause of death (COD) occurred more commonly among patients who had been infected with HIV through sexual relations (p= 0.0002 andp= 0.0011, respectively). Bacterial pneumonia was the most common source of pulmonary infection, althoughPneumocystis cariniipneumonia was more often a cause of death. A higher frequency of aspergillus infection in female subjects was also noted (p= 0.010). These and other observations may have ramifications for treatment and prevention in analogous AIDS inner-city populations.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Twenty-seven HIV-1-infected patients, 16 at early stage of disease and without concomitant antiretroviral therapy and 11 at more advanced stage of disease receiving antiretroviral therapy, have been followed since their enrollment, November 1992 and July 1993, respectively, in phase I/II studies to evaluate safety and immunogenicity of an anti-interferon-α (IFN-α) vaccine, aimed at modulating the impaired cytokine network in AIDS patients by counteracting IFN-α overproduction. We compared clinical, virological, and immunological markers of disease progression, including circulating IFN-α levels in a 24- to 30-month follow-up period with those of 62 patients fulfilling the same enrollment criteria and comparable for sex, risk factor, and age, regularly followed at our center. Anti-IFN-α immunization consisted of four-six intramuscular injections 1 month apart of a water-in-oil emulsion of 500 μg formalin-inactivated recombinant IFN-α-2b (iIFN-α) followed by intramuscular injections of 250 μg iIFN-α adsorbed onto calcium phosphate every 3 months. Neither clinical deterioration nor a CD4+cell count decrease from pretreatment values was observed in IFN-α-immunized patients in the follow-up period, whereas clinical and immunological disease progressions were observed among open-comparison patients. Furthermore, statistical analysis showed a strong association between occurrence of clinical manifestations and high circulating IFN-α titers, while nonprogression of IFN-α-immunized patients was associated with decreased levels of circulating IFN-α.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:An extensive collaboration of laboratories and investigators has been developed to define the seroprevalence of human T-cell leukaemia/lymphoma virus type I and II (HTLV-I and -II) infection in Europe. An algorithm for serological screening for HTLV-I and -II infection has been established by consensus. Data from screening almost 4 million subjects, including many unpublished studies, which conform to this algorithm are presented. In extensive studies the seroprevalence of HTLV-I/II in blood donors is low, ranging from <1 in 100,000 to 30 in 100,000 donors and is due predominantly to HTLV-I. In antenatal clinics in France and the United Kingdom the seroprevalence of HTLV-I is >0.2%, but surveillance in this setting has been limited and extensive study of the seroprevalence of HTLV-I/II infection in pregnant women in Europe is urgently required to determine the need for HTLV-I/II antenatal screening. HTLV-I is present in populations who have immigrated to Europe from endemic areas and is spreading into indigenous European populations, particularly through sexual transmission to females. HTLV-II infection is present predominantly amongst IVDU and is usually a coinfection with HIV-1. There are considerable regional differences in HTLV-II seroprevalence.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID