摘要:

SummaryDNA integration appears to be an obligatory step for the efficient replication of retroviruses. Studies of the integration reaction for the avian and murine C-type retroviruses have defined the importance of: i) LTR terminal sequences, which are joined to host DNA, and ii) the activity of the retroviral integration protein (IN). The specific requirements for the integration of HIV DNA have not yet been defined. In this review, we survey studies pertinent to this reaction for HIV and extrapolate a mechanism for HIV DNA integration based upon knowledge of the integrative recombination reaction of the C-type retroviruses.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryThe termini of integrated retroviral DNAs are characterized by highly conserved dinucleotide sequences: 5'TG...//...CA3'. For the avian and murine C-type retroviruses, the dinucleotide sequences reside two deoxynu-cleotides (usually AA and TT) from the LTR ends of unintegrated viral DNA (5'AATG...//...CATT3'). The number and identity of terminal deoxynucle-otides in unintegrated HIV-1 linear DNA that extend beyond the conserved dinucleotides have not been determined. However, they had been presumed to consist of a single nucleotide (5'CTG...//...CAG3') on each end, based on inspection of the nucleotide sequence between the end of the supposed primer sites for retroviral DNA synthesis and the conserved proviral termini. We have utilized the polymerase chain reaction (PCR) to amplify segments representing the joined ends of linear DNA present in covalently closed circular HIV-1 DNA molecules isolated from infected T cells. These fragments were cloned and the nucleotide sequence of the LTR-LTR circle junction of several independent clones determined. Based upon the results, we predict that, like the avian and murine viruses, HIV-1 linear DNA contains two nucleotides beyond the conserved dinucleotides: 5'ACTG...//...CAGT3'. Models for the origin of these termini and other observed junction sequences are proposed.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryThe 177 N-terminal amino acids of CD4, the receptor of the human immunodeficiency virus (HIV), have been expressed in Escherichia coli as genetic fusions to the periplasmic maltose-binding protein (MalE) from this organism. A large fraction of the hybrid proteins can be released from the periplasm by osmotic shock and purified in one step on a cross-linked amylose column eluted with maltose under mild conditions. One hybrid protein binds HIV envelope protein gp 160 and neutralizes the virus in vitro. This provides the first example of the production and one-step purification of an active form of an eukaryotic protein by fusion to MalE. The use of this system for mass screening of CD4 mutants, high-scale production of the hybrid protein for structural studies on CD4, testing antiviral compounds, and therapeutic assays is discussed.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryWe investigated serum neopterin, tryptophan, and kynurenine concentrations in 23 HIV-1 seropositive patients (Walter Reed Stage 4–6). Ten patients presented with polyneuropathy and three with dementia, one of the patients with dementia also had polyneuropathy and dementia. We found significant associations between lower tryptophan concentrations and neurologic/psychiatric symptoms. The negative correlation of tryptophan with kynurenine and neopterin concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO) in patients. IDO can be induced by cytokines such as interferon-γ and therefore low tryptophan levels may result from chronic immune stimulation in HIV-1 seropositives.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryTo determine the compliance and tolerance with zidovudine (azi-dothymidine or AZT) therapy among poor, minority, and intravenous drug-using patients, data were collected on all AIDS and ARC patients followed for at least 4 weeks in a New York City Human Immunodeficiency Virus clinic. Ninety-nine patients received zidovudine, of whom 75% were males, 92% were minorities, and 59% had a history of intravenous drug use. Of the 99 patients, 72 had AIDS and 27 had ARC with T-helper (CD4) lymphocytes ≤ 500 mm3. Eighty-seven of the 99 patients (88%) were compliant with zidovudine therapy. Fifty-seven percent of these had at least one adverse drug reaction requiring dose reduction (44%) or cessation (13%). Adverse reactions were similar to those reported in other populations with HIV-related illness, although headache and nausea were less common. Twenty opportunistic infections (OIs) or HIV-related malignancies occurred in 15 of 82 (18%) patients who were on zidovudine for at least 4 weeks (7.6 OIs/1,000 patient weeks). Seven of the 82 died (9%), compared to 9 of the 17 patients (53%) who did not complete 4 weeks of zidovudine therapy (p< 0.05). There were no significant differences in any of these measures when intravenous drug users were compared with other risk groups. We conclude that zidovudine can be administered to intravenous drug users and others in an inner city clinic with acceptable compliance and tolerance.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryA double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin and placebo was conducted at four medical centers. One hundred sixty-four adult men with lymphadenopathy were enrolled over a 2-month period and randomized to receive ribavirin 800 mg (53 subjects), ribavirin 600 mg (55 subjects), or placebo (56 subjects). Active treatment was administered for 24 weeks followed by a 4-week washout period. Nine subjects receiving placebo, four receiving ribavirin 600 mg, and none in the 800 mg group developed AIDS during the 24 weeks of active treatment. One patient randomized to the 800 mg group had Kaposi's sarcoma at study entry and was included in the intent-to-treat analysis. An overall significant difference in progression to AIDS was observed among the three treatment groups (p= 0.028) with patients randomized to receive 800 mg having a significantly longer time to AIDS than placebo patients (p= 0.012; relative risk, 9.0; 95% confidence interval, 1.1 to 70.8). There was no significant difference between the 600 mg and placebo groups (p= 0.15; relative risk, 2.3; 95% confidence interval, 0.7 to 7.6). Baseline CD4 cell count and hematocrit made independent contributions and formed a multivariate prognostic set for these progression data. The significant treatment superiority of 800 mg compared to placebo remained after adjustment for these factors (p= 0.019). After deletion of patients with major protocol violations at entry, the difference between the 800 mg and placebo treatment remained significant (p= 0.021). Reduction in CD4 counts was noted over the 24-week treatment period in both active treatment groups relative to placebo (600 mg vs. placebo,p= 0.018; 800 mg vs. placebo,p= 0.042). CD4 counts returned toward baseline levels in the two treatment groups during the subsequent 4-week washout period, while CD4 counts dropped during this same period in the placebo group. Functional lymphocyte measurements or delayed cutaneous hypersensitivity were not enhanced. Ribavirin was well tolerated and all clinical and hematologic adverse reactions were reversible following 24 weeks of active therapy.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Editors' NoteA certain degree of controversy has surrounded the multicenter dose comparison clinical trial of oral ribavirin for patients with HIV-related lymphadenopathy since its inception in 1987. TheJournal of Acquired Immune Deficiency Syndromespresented in this issue the peer-reviewed data as it was collected, analyzed, and summarized by a team of researchers headed by Richard B. Roberts, Vice Chairman and Professor of the Department of Medicine, Cornell University Medical College, New York, NY. Herewith is presented an invited Editorial Commentary in response to those clinicians who suggested that an opposing point of view should be heard in the interest of fairness.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryWe investigated the relationship of human papillomavirus (HPV) infection of the female genital tract, cervical cytology, and human immunodeficiency virus (HIV) infection in 67 women. Forty-eight women had a history of intravenous drug use, 18 were heterosexual partners of HIV-infected intravenous drug users, and one was a transfusion recipient. Patients received a Pap smear, cervicovaginal lavage for HPV determination by Southern blot, HIV serum antibody by enzyme immunoassay with Western blot confirmation, and thorough screening for other sexually transmitted diseases. Seventeen of the 35 (49%) women seropositive for HIV had HPV infection, compared with 8 of 32 (25%) seronegative women (p< 0.05). Fourteen of 35 (40%) HIV-positive women had squamous intraepithelial lesions (SIL) on cervical cytology, compared with three of 32 (9%) HIV-negative women (p< 0.01). Of 22 women with symptomatic HIV infection, 11 (50%) had SIL on cytology; 10 of these 11 were HPV-positive. Among 13 asymptomatic HIV-positive women, only three (23%) had such cytological lesions. Our findings strongly suggest that HIV-induced immunosuppression exacerbates HPV-mediated cervical cytologic abnormalities.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryIt is important in planning to meet resource needs and financing of care of people with acquired immune deficiency syndrome (AIDS) to determine the effect of the use of azidothymidine (AZT) on overall medical care costs. This study compares the medical care costs of people with AIDS (PWAs) who received AZT with those of PWAs not receiving it. Seven of the nine PWAs who were on the AZT arm of the phase II drug trial of AZT at San Francisco General Hospital (SFGH) in 1986 and a matched sample of PWAs at SFGH who were eligible for the trial but did not participate in it were included in the study and followed for 12 months. It was found that costs in the first 12 months and especially in the first 6 months were lower for persons using AZT, primarily because of significantly lower use of hospital services. However, costs began to rise in the second 6 months for those using AZT. The authors therefore doubt that the lifetime costs of PWAs are lowered by the use of AZT and conclude that they are likely to be the same as those of PWAs not using the drug. If this is indeed the case, the use of the drug is likely to be relatively cost-effective.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

SummaryBetween 1985 and 1987, examinations for human immune deficiency virus (HIV) antibody were done on 25,392 prostitutes working in 64 cities throughout the Philippines. The country-wide seropositivity rate among prostitutes based on this sample was 0.8/1,000. Of the HIV cases, 85% were working in just two cities whose prostitute populations comprised 50% of the total sample. The average incidence rate for the same two cities after 1 year was 2.3/1,000. HIV antibody-positive women were enrolled in a case-control study to determine demographic and epidemiologic risk factors. This study involving 34 HIV-positive prostitutes and 61 randomly selected negative control prostitutes did not reveal any risk factors related to sexual or other types of behavior. A history of genital warts, a history of abnormal vaginal discharge, and cytomegalovirus antibody were significantly more frequent in the HIV-positive cases than in the controls; however, by logistic regression analysis, only an abnormal vaginal discharge was independently associated with HIV infection. Absence of any evidence of transmission by blood transfusion or i.v. drug abuse suggests that HIV was introduced by the heterosexual route.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID