摘要:

We have developed an assay, using a biosensor matrix and surface plasmon resonance, that rapidly and reproducibly measures antibody reactivity to human immunodeficiency virus type 1 (HIV-1) gp120 in various structural conformations. In particular, antibodies displaying preferential reactivity to a CD4-binding competent (“native,” rgp120) or CD4-binding incompetent (“reduced,” rcmgp120) monomeric gp120 molecule were distinguished. This technique has advantages over conventional enzyme-linked immunosorbent assay (ELISA) methodology in which it is difficult to control the concentration of protein adsorbed to the ELISA wells and a significant disruption of protein structure occurs on adsorption. A population of gp120 molecules that lacked CD4 receptor binding capacity and bound antibodies specific for reduced gp120 was found in several native gp120 preparations. The relative amount of this CD4-binding incompetent population varied among the various preparations studied. This presence of CD4-binding incompetent molecules within various native recombinant gp120 preparations may have implications for HIV-1 envelope vaccine development. By measuring antibody-binding ratios, several monoclonal antibodies were identified, which, although elicited by immunization with various native gp120 preparations, bound specifically to reduced gp120. The ability to screen antibody specificity against HIV-1 envelope proteins with different conformations will assist in determining the quality of antibodies induced by various HIV-1 envelope vaccine candidates.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: Human immunodeficiency virus type 1 (HIV-1) and HIV-2 encode related transcriptional activators known as Tat-1 and Tat-2, respectively, that are required for efficient viral replication. The Tat proteins have been studied extensively, and it appears that their mechanism of action is unique to the primate immunodeficiency viruses or a few distantly related lentiviruses. Here we describe a collection of 24 wild-type and mutant Tat-1 and Tat-2 proteins that are expressed inEscherichia colias fusions with glutathioneS-transferase (GST). The GST-Tat fusions can be used for biochemical studies after simple purification fromE. colilysates in a single step under nondenaturing conditions. The availability of these GST-Tat fusions should be useful to investigators examining biochemical properties of Tat-1 and Tat-2 proteins.E. colicultures harboring GST-Tat fusions described here are available through the National Institute of Health AIDS Research and Reference Reagent Program.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Eight healthy men infected with human immunodeficiency virus, type 1 (HIV) and eight HIV seronegative age- and sex-matched controls exercised on a bicycle ergometer (75% of VO2max, 1 h). The percentages of CD4+, CD4+45RA+, and CD4+45RO+cells did not change, whereas the absolute number of CD4+cells increased twofold during exercise and fell below prevalues 2 h after. The neutrophil count increase was more pronounced after exercise in the controls compared with in HIV-seropositive subjects. The percent CD16+cells, and the natural killer (NK) and lymphokine activated killer (LAK) cell activity increased during exercise, but this increase was significantly less pronounced in the HIV-seropositive group. The results suggest that in response to physical stress, HIV-seropositive subjects have an impaired ability to mobilize neutrophils, NK and LAK cells to the blood. Furthermore, because the total number of CD4+cells, but not the percentage of CD4+cells, changed in response to exercise, this study further strengthens the idea that the percentage of CD4+cells is preferable to the number of CD4+cells in monitoring patients seropositive for HIV.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Our objective was to determine the yield and cost of standardized laboratory testing of HIV-infected patients entering medical care after testing positive for HIV. An HIV staging and referral clinic in a municipal public hospital was our site for a cross-sectional study, and 308 patients were evaluated in the clinic between February 1, 1990 and October 1, 1991. Patients underwent standardized laboratory testing, including hematologic studies, serum chemistries, infectious disease serologies, and chest radiographs. The percentage of abnormal results for each test was determined. Abnormal results were stratified as mild or severe. They were also examined with regard to whether injection drug users or other patient subgroups had higher percentages of abnormalities. Charges and Medicare reimbursements for the tests were also determined. There were substantial numbers of abnormalities in all types of laboratory testing. Only 3% of patients had normal CD4 lymphocyte counts; 85% had counts of3, and 35% were3. Forty-four percent of patients had at least one abnormal hematologic study; 8% were severe. Nearly 75% had abnormal liver function tests; 20% of these were severe abnormalities. Fifteen percent of patients were PPD-positive, and >50% were anergic. Fourteen percent had a positive nonspecific test for syphilis, and 7% had a positive confirmatory test. Fourteen percent of patients had an abnormal chest radiograph. Injection drug users were more likely to have severely abnormal liver function tests (25.7% vs. 14.7%;p< 0.001), be hepatitis B core antibody positive (88.6% vs. 62.0%;p< 0.001) and have a positive syphilis serology (19.8% vs. 6.8%;p< 0.001) compared with non drug-users. Total average charges for the laboratory panel were ∼422 per person, and Medicare reimbursements were 198. In a municipal public hospital clinic, extensive initial laboratory testing of HIV-infected patients yields a substantial number of abnormalities, many of which are severe and require clinical intervention. Routine laboratory testing of patients like these entering primary care for HIV infection is justified, given the high frequency of abnormalities in all groups of patients.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The efficacy of clarithromycin combined with either pyrimethamine or minocycline for treatment of experimentalToxoplasma gondiiinfection was investigated. Mice were infected intraperitoneally with 2 x 103to 2 x 104T.gondiistrain RH or TS4 tachyzoites. Mortality was recorded for 35 days postinfection. Latency was evaluated by inoculation of brain homogenates from surviving mice into naive untreated mice. The combination of clarithromycin and pyrimethamine therapy caused a significantly greater reduction in mortality than did either drug alone. Similar synergy was observed between clarithromycin and minocycline. A 100% cure rate of active and latent infection was achieved in mice treated with the clarithromycin based combinations. Clarithromycin in combination with either pyrimethamine or minocycline produced efficacy comparable to combined therapy of pyrimethamine with sulfamethoxazole. The in vitro potency of clarithromycin, pyrimethamine, or minocycline againstT. gondiion a mouse macrophage monolayer was not predictive of the in vivo efficacy in mice. Clarithromycin combined with minocycline or pyrimethamine could allow greater flexability for treatment of patients predisposed to the toxicity associated with standard pyrimethamine-sulfonamide or pyrimethamine-nonsulfonamide therapy.This therapy could be especially useful since clarithromycin-based therapy provides safe and effective treatment againstMycobacterium aviumcomplex infections associated with AIDS patients.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We investigated 63 individuals with HIV infection, 34 of whom were asymptomatic (nine had oral candidiasis, four had constitutional signs and symptoms, and 16 had AIDS), for plasma lipids, soluble tumor necrosis factor receptor 75 (sTNF-R75) and other immune activation markers, namely urinary neopterin, β2-microglobulin, and the CD4+T cell count. The median CD4+T cell count was 318 x 106/L. All individuals were allowed to have light breakfast in the morning; the venipuncture for the plasma lipids was done between 11 a.m. and 3 p.m.. Decreased plasma concentrations were found for total cholesterol, and HDL and LDL cholesterol in 3.2%, 46%, and 56% of the subjects, respectively. Plasma triglyceride levels were increased in 31.7% of the study population. The frequency and the extent of the decrease of HDL and LDL cholesterol and the increase in triglyceride levels were greater in those with a CD4+T cell count below the median (p=0.003,p= 0.05, andp= 0.01); when comparing individuals with CD4+T cell counts above and below 500 x 106/L (19 individuals), a difference was only found for HDL cholesterol (p= 0.01). Plasma levels of triglycerides correlated significantly however weakly with serum concentrations of sTNF-R75 (rs= 0.32,p= 0.01) but not at all with urinary neopterin or serum β2-microglobulin. HDL cholesterol correlated inversely with sTNF-R75 (rs= −0.53,p< 0.0001) and to a lesser extent with urinary neopterin (rs= −0.46,p= 0.0003) and β2-microglobulin (rs= −0.34,p= 0.008). When only the individuals with a CD4+T cell count above the median or 500 x 106/L were analyzed, HDL cholesterol correlated with sTNF-R75(rs= - 0.45,p= 0.01 or rs= - 0.38,p> 0.05), but no longer with urinary neopterin and β2-microglobulin. Immune activation in HIV infection is associated with disturbances in lipid metabolism, which may influence biological properties of HIV. HDL cholesterol may also be a useful marker of disease progression.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A prospective follow-up study of the progression of HIV infection, from seroconversion to onset of opportunistic infections (OI) indicative of immune deficiency and to death, was performed in a cohort of 54 HIV-1 antibody positive Filipino female commercial sex workers (FCSW). The cumulative probability of having a CD4+T cell count of3and/or an OI indicative of severe immune deficiency was 52.9% within 5 years and 73.8% within 6 years after seroconversion. The cumulative probability of death was 52.1% within 6.5 years following seroconversion and 52.7% within 1.5 years after a depressed (3)CD4+T cell or onset of an OI. Although several OI associated with immune impairment were observed, a CD4+cell count of3was the initial indicator of a failing immune system in more than 50% of the patients.Mycobacterium tuberculosisor unidentified acid fast bacilli (presumed to beM. tuberculosis) andPneumocystis cariniipneumonia were the initial indictors of immune deficiency in the remaining patients.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A review of the data on infectivity per contact for transmission of the HIV suggests that the infectivity may be on the order of 0.1–0.3 per anal intercourse in the period of the initial infection, 10-4to 10-3in the long asymptomatic period, and 10-3to 10-2in the period leading into AIDS. The pattern of high contagiousness during the primary infection followed by a large drop in infectiousness may explain the pattern of epidemic spread seen in male homosexual cohorts in the early years of the epidemic. Simulations of cohorts of homosexual males, using that range of parameter values, indicate the following: (a) The initial fast rise and then more or less rapid flattening of the incidence curve of seropositives is primarily due to rapid initial spread, yielding a group of infecteds all of whom pass into the low infectivity asymptomatic period at close to the same time. All this occurs only if the basic reproduction number for the primary infection is > 1. (b) The behavioral changes that have been reported all started after the incidence of new infections began to fall, too late to have a major effect on the initial rise. The behavioral changes had a major effect in slowing down the subsequent rise in the number of seropositives. (c) High activity groups play an important role in the early rapid rise of the epidemic. However, it is not likely that the rapid decrease in rate of growth of seropositives is solely due to saturation of these very high activity groups. Although the evidence for this interpretation of the role of the primary infection is not conclusive, its implications for prevention and for vaccine trials are so markedly different from those of other interpretations that we consider it to be an important hypothesis for further testing.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary:By the turn of the century 20–50 million adults are projected to be HIV positive in Asia, and India will have the largest burden of newly infected patients in a single country. To determine the present status of the epidemic, a systematic review of available data in India has been carried out. Regional differences in reported HIV seroprevalence were found, with high levels in western, northeastern, and southern India and lower levels in northern, central, and eastern India. While differences in the temporal introduction of HIV may be partly responsible, the more likely explanation is incomplete data and reporting. In the past 4 years HIV has rapidly increased among commercial sex workers and patients coming to sexually transmitted diseases clinics in western (Bombay) and southern (Madras and Vellore) India. Assessing HIV seroprevalence in the general population is difficult because of limited data, especially from rural areas, where 60% of Indians reside. Heterosexual contact with commercial sex workers is the major reported risk factor, except in eastern India, where intravenous drug use is common. The impact of transfusions or contaminated needles is uncertain, but between 25 and 75% of blood donations are not screened for HIV, and 15% of infected patients had received transfusions. By October 1993, 494 cases of AIDS had been reported, but this number grossly underestimates the real situation since HIV is often unrecognized. Tuberculosis is the major HIV-associated infection. In its efforts to control HIV, India needs to institute a standardized surveillance system to provide data needed to design and implement appropriate interventions.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary:To provide an estimate of the seroprevalence of human immunodeficiency virus (HIV) in a representative sample of the U.S. household population, serum samples from participants in the third National Health and Nutrition Examination Survey (NHANES III) were tested for HIV antibody. The testing was performed anonymously on 5,430 individuals 18–59 years old from phase 1 of NHANES III conducted from 1988 to 1991. Twenty-nine individuals were HIV positive. The total weighted prevalence was 0.39%. The population estimate of infected individuals was 547,000, with a 95% confidence interval of 299,000–1,020,000 infected persons. Black participants were four times more likely to be HIV positive than white/other individuals and three times more likely than Mexican Americans. Men were three times more likely to be infected than women. Higher nonresponse to the survey and to phlebotomy was observed in young white men; therefore these data provide a conservative estimate of HIV infection in the general household population. This estimate does not include individuals who do not live in households and who may be at higher risk of infection, such as persons in penal institutions, the homeless, or certain hospitalized patients.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID