ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The first step in the replicative cycle of human immunodeficiency virus type 1 (HIV-1) is binding of the virions to the cellular CD4 receptor. This process may be considered as an important target for chemotherapeutic agents against acquired immune deficiency syndrome (AIDS). A method has now been devised whereby virion binding to the cell membrane was visualized by an indirect immunofluorescence assay using human anti-HIV-1 serum, rabbit anti-human-IG-F(ab')2-fluorescein isothiocyanate, and flow cytometry. Heparin, dextran sulfate, and pentosan polysulfate suppressed HIV-1 binding to MT-4 cells at concentrations that protected the cells against HIV-1 cytopatho-genicity. Dextran and dermatan sulfate, two compounds that are inactive against HIV-1, had no inhibitory effect on the binding of HIV-1 to the cells. The potent and selective HIV-1 inhibitor azidothymidine (AZT) did not affect virus binding to the cells, whereas suramin partially blocked HIV-1 binding to the cells at concentrations that fully protected MT-4 cells against destruction of HIV-1. Our immunofluorescence assay thus demonstrated that suramin not only acts as an inhibitor of reverse transcriptase but also interferes with virus-cell binding. Also, Evans blue, an anionic dye structurally related to suramin, partially inhibited HIV-1 attachment to the cells. The present method permits a quantitative determination of the inhibitory effect of anti-HIV-1 agents on virion-cell binding.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Eleven povidone-iodine-containing products (Betadine) and chlorhexidine gluconate solution were tested for their ability to inactivate human immunodeficiency virus (HIV) in a cell culture system. All Betadine products completely inactivated the virus at povidone-iodine concentrations of ≥0.5% (10− to 20-fold dilutions of stock) except for Betadine Lubricating Antiseptic Gel, which required 2.5% for efficacy (1:2 dilution). Chlorhexidine gluconate completely inactivated HIV at concentrations of ≥0.2% (1:100 dilution of laboratory stock; 1:20 dilution of commercial stock). Betadine douche and medicated douche did not inactivate HIV at the concentrations recommended for clinical use (0.33% and 0.25%, respectively) but were effective at povidone-iodine concentrations of 0.5%. Inactivation appeared to be immediate since no difference in efficacy based on length of exposure to the microbicide was detected. Thus, both microbicides are highly effective at killing HIV in vitro.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Following computer-assisted analysis of the amino acid sequence of various HIV-1 isolates, we synthesized a series of oligopeptides derived from variable and conserved regions of the envelope protein complex gp120/gp41. The peptides were used in ELISA tests for their reactivity with human antisera from HIV-1 positive individuals; patients with clinically manifested AIDS showed only a rather limited reaction, predominantly with two peptides (p102–112, p316–326), which is in contrast to sera from HIV-1 positive asymptomatic individuals, whose sera were reactive with almost all peptides. Using consecutive sera of the same patients, decreasing antibody titers to defined epitopes could be shown to occur during the development of AIDS. Cellular immune response recognition was analyzed in T-cell proliferation assays by [3H]thymidine incorporation. One peptide localized in a conserved region clearly induced proliferation of T-cells. Those data were combined to a map of the functions localized in the various regions of the HIV-1 envelope proteins.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

HLA-A, -B, -C, -DR, and -DQ antigens were determined by serology and in cases of severe lymphopenia by RFLP-DNA typing in 51 Caucasians with a diagnosis of AIDS (32 with opportunistic infections and 19 with secondary cancers). In addition, 86 HIV-1 seropositive and 39 HIV-1 seronegative drug abusers and 148 healthy controls were also studied. No significant differences in HLA antigen frequencies were found in comparison of HIV-1 seropositive and HIV-1 seronegative drug abusers with controls, suggesting that HLA polymorphism does not represent a genetic risk for infection with HIV-1. In contrast, a significant increased frequency of B35 (p< 0.01) and CW4 (p< 0.01) was observed in both groups of AIDS patients as compared to controls. Moreover, DR2 was increased in frequency in patients with opportunistic infections (p< 0.01) and DR3 was completely absent in patients with secondary cancers (p< 0.05). In the latter group, the DR5 frequency was increased, although nonsignificantly. These findings provide strong evidence for the existence of HLA-linked factors of susceptibility and host resistance to AIDS.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Antibody-dependent enhancement (ADE) of human immunodeficiency virus type 1 (HIV-1) infection in vitro has been described recently and was shown to occur by two mechanisms: either participation of the alternative pathway of complement or to involve an Fc receptor-mediated, complementindependent mechanism. Complement-mediated ADE results in an accelerated cytopathic effect in target cells that can abrogate the protective properties of neutralizing antibodies. This study characterizes the surface antigens of MT-2 cells using flow cytometric analysis and shows that these cells express high levels of both CD4 and complement receptor type 2 (CR2) while several CD4+cell lines that do not demonstrate complement-mediated ADE lack high levels of complement receptors. Further, utilizing MT-2 cell cultures, it is demonstrated that complement-mediated ADE of HIV-1 infection is conferred by the sera from more than 80% of HIV-1 antibody-positive individuals (N= 85). Complement-mediated ADE of HIV-1 infection causes an acceleration of several parameters indicative of HIV-1 infection in vitro including increased HIV-1 antigen synthesis as detected by indirect immunofluorescence, RNA accumulation as measured by a solution hybridization protocol, reverse transcriptase release, and progeny virus production.It was shown in this study that the majority of HIV-1 antibody-positive individuals have antibodies in their serum that combine with complement to enhance HIV-1 infection in vitro. Previous work had shown that such ADE of HIV-1 infection accelerated the appearance of viral-induced CPE (1–3) in MT-2 cells and increased reverse transcriptase release from peripheral blood mononuclear cells infected with HIV-1 in vitro (4). In the study reported here, it was shown that the rate of HIV-1 infection was accelerated by all parameters of HIV-1 infection as indicated by increased antigen synthesis, RNA synthesis, reverse transcriptase release, and progeny virus synthesis at all time points. Finally, the presence of complement receptors on MT-2 cells offers good supportive evidence that complement is involved in ADE of HIV-1 infection in vitro. From these data, it is proposed that ADE of HIV-1 infection requiring complement be referred to as complement-mediated, antibody-dependent enhancement of HIV-1 infection. This complement-mediated ADE of HIV-1 infection is distinct from the complement-independent, Fc receptor-dependent enhancement described (5,6).

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

People with human immunodeficiency virus disease (HIVD) frequently present to surgical services for consideration of surgical therapies. They may be counseled by physicians who introduce into the decision-making process their personal fear of contagion, uncertainty about potential therapeutic benefits of surgery for people with HIVD, and anecdotal impressions that the immunodeficiency of HIVD might be accelerated by surgical and anesthetic interventions. However, there are no studies that have investigated immunomodulating effects of surgery and anesthesia in people with HIVD. Also, clinical studies of surgical interventions in populations of people with HIVD do not clearly demonstrate adverse outcomes attributable to surgery alone. Review of immunomodulating effects of surgical procedures in populations of people without HIVD reveals that multiple alterations of immune parameters may occur in response to all phases of anesthesia, surgery, and postoperative recovery. These alterations often depend upon the type of anesthesia used and the degree of surgical trauma. Most notably, the alterations are transient and rarely correlated with adverse clinical outcomes. These facts mitigate against the current preconceived notion that surgery will superimpose a sustained and clinically significant detriment to the immunologie competence of people with HIVD. A proposal for rational exploration and study of this issue is presented.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Tumor necrosis factor (TNF) has demonstrated antitumor activity against a variety of tumors and is particularly cytotoxic to capillary endothelial cells, which are the presumed cell of origin of Kaposi's sarcoma. We evaluated the toxicity and clinical antitumor and antiretroviral effects of recombinant TNF administered at a once weekly dose of 100 μ/m2intravenously for 8 weeks in five men with AIDS-related Kaposi's sarcoma and without prior opportunistic infection. One patient was removed from study at week 4 due to rapid progression of Kaposi's sarcoma, another patient with stage IV disease and a pretreatment CD4 count of 11 developed fever, hypotension, and pneumonia at week 7 and died 8 days after discontinuing recombinant TNF. No pathogenic organisms were isolated. He had marked eschar formation of his Kaposi's sarcoma lesions, particularly in areas previously exposed to radiation therapy. Uniform toxicities included fevers, rigors, and headaches during drug infusion that were ameliorated by prophylactic meperidine hydrochloride and acetaminophen. All experienced fatigue and three had arthralgias. One patient had transient hypotension which corrected with i.v. fluids. No significant hematologic, hepatic, or renal toxicities were seen. All patients had some progression of their Kaposi's sarcoma on study. There was no change in CD4 or CD8 count or in CD4:CD8 ratios. Serum human immunodeficiency virus (HIV) p24 antigen levels increased >50% in three patients. We conclude that, as a single agent, at a dose of 100 μ/m2recombinant TNF by i.v. infusion has no obvious antitumor or antiretroviral effects in patients with AIDS-related Kaposi's sarcoma.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Fusidic acid has previously been noted to prevent syncytial formation by human immunodeficiency virus (HIV) in vitro. Since this drug is a cheap, usually well-tolerated substance with known toxicity profile, an open, uncontrolled trial was undertaken to evaluate its possible efficacy in HIV disease. Twenty HIV antibody positive patients (10 with AIDS and 10 with ARC) were treated with sodium fusidate 500 mg every 8 h for up to 3 months. One patient died during therapy and six ceased treatment due to adverse events. Rash, nausea, diarrhea, and/or abdominal pain caused difficulties in all patients. There was no significant improvement in clinical state or T-helper cell levels, and no observed decrease in HIV p24 antigen during treatment. We conclude that in this open trial, sodium fusidate had no observable beneficial clinical, virological, or immunological effects.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

CD4 and CD8 T lymphocytes of three groups of men infected by the human immunodeficiency virus (HIV) were examined twice yearly for 36 months to elucidate the temporal trends in T lymphocytes during infection. The three groups were 37 HIV seroconverters, 304 prevalent HIV seropositives remaining free of the acquired immunodeficiency syndrome (AIDS), and 69 men who developed AIDS during observation. Six months before seroconversion, CD4 levels were similar among HIV seroconverters and 356 seronegative controls. Within 18 months of seroconversion, mean CD4 levels fell to the level of the prevalent seropositives at study entry. From there, the rate of decline slowed. CD8 lymphocyte counts rose dramatically at seroconversion. Among AIDS-free prevalent seropositives, CD4 levels fell steadily over 36 months of observation. By contrast, CD8 cell levels rose slowly. Among men who developed AIDS, mean CD4 levels fell more rapidly again during the 18 months prior to diagnosis. CD8 cell levels remained elevated until 6–12 months before diagnosis, when they began to fall.

ISSN:0894-9255    

出版商:OVID    

年代:1989

数据来源: OVID