摘要:

In a previous paper, we determined that treatment of lymphocytes with nonviable preparations of human immunodeficiency virus type 1 (HIV-1) results in an impairment of the phosphatidylinositol/protein kinase C pathway, most likely due to an inhibition of the cleavage of phosphatidylinositol bisphosphate into inositol trisphosphate and diacylglycerol, mediated by phospholipase C. Here we show that one consequence of these changes is a reduced phosphorylation of nuclear matrix-associated DNA topoisomerase II, resulting in an inhibition of the activity of this enzyme. Antibodies to the viral proteins suppressed the inhibitory effects caused by the HIV-1 preparation. Furthermore, the phytohemagglutinin A-caused augmentation of nuclear matrix-associated DNA polymerase α and β activities was found to be abolished by coincubation with the HIV preparation or with the HIV-1 gp120. The phytohemagglutinin A-enhanced matrix association and processivity of DNA polymerase α was determined to be reduced if the lymphocytes were in contact with HIV-1 preparation. These results suggest that the reduced proliferative response of lymphocytes to phytohemagglutinin A in the presence of disrupted HIV-1 preparation is due to inhibition of at least two, perhaps separate, pathways, one involving protein kinase C resulting in a reduced phosphorylation of DNA topoisomerase II and the other changing the state of matrix association of DNA polymerase α and β.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

To investigate the role ofvpr(viral protein R) in the replication and cytopathicity of human immunodeficiency virus type 1 (HIV-1), infectious proviruses were constructed that were isogenic except for the ability to produce the protein product ofvpr. The experiments described here demonstrate thatvprencodes a 96 amino acid 15 kDa protein. Thevprproduct increases the rate of replication and accelerates the cytopathic effect of the virus in T cells.Vpracts intransto increase levels of viral protein expression. The stimulatory effect ofvpris observed to act on the HIV-1 LTR as well as on several heterologous promoters.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Two solid phase, nonradioactive immunoassays were developed and evaluated for the determination of zidovudine (Retrovir, ZDV, AZT) concentrations in serum. The first, an enzyme-liked immunosorbent assay (ELISA), used an anti-AZT monoclonal antibody (MAb) and subsequent alkaline phosphatase second antibody system for the detection method. The second, a time-resolved fluoroimmunoassay (TR-FIA), used a polyclonal anti-AZT antibody followed by a europium-labeled goat anti-rabbit immunoglobulin (IgG) as the fluorescent probe. The ELISA had a detection range from 125 to 4,000 nMand a 50% inhibitory concentration (IC50) of about 500 nM. Development of the TR-FIA was based on a very sensitive detection system of metal chelate chemistry and time-resolved fluorometry. The standard curve in the TR-FIA was from 5 to 4,000 nM with an IC50of 200 nM. Intra- and interassay precision of the ELISA was good, with coefficients of variation from 3.9 to 7.3% and 3 to 17%, respectively, while the same values for the TR-FIA were 6.2 to 10.9% and 5.4 to 19.9%, respectively. The results obtained from each method were compared individually with those of high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). There was good agreement among the results obtained by each method. These two methods enable laboratories not licensed for radioisotopes to analyze potentially infectious samples without aerosol-forming centrifugation.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Eight patients with AIDS or ARC received four single doses of 2′,3′-dideoxycytidine (ddC). The treatments included 0.5 and 5 mg oral tablets, a 0.5 mg oral solution, and a 0.5 mg intravenous infusion. Blood samples were collected for 4 to 6 h after each dose. Plasma concentrations of ddC were determined by a specific gas chromatographic-mass spectrometric (GC-MS) assay. A combination of the low dose and the assay sensitivity of 2 ng/ml limited data treatment and comparison. MeanCmaxof 8.5, 7.6, and 79.0 ng/ml occurred at meantmaxof 1.1, 1.3, and 0.9 h for the 0.5 mg oral solution, the 0.5 mg tablet, and the 5 mg tablet, respectively. A mean clearance of 5.57 ml/min/kg and volume of distribution of 0.64 L/kg were determined from the 0.5 mg intravenous infusion. Half-life values ranged between 0.95 and 2.0 h and appeared to be independent of the dose and route of administration. The bioavailability values calculated for the oral tablets were variable, ranging from 54 to 127%. Single doses of ddC were well tolerated in this population. The results of this pilot study indicate that ddC is rapidly and extensively absorbed when administered as an oral tablet or solution to fasting AIDS or ARC patients. It is also rapidly eliminated with a half-life of 1–2 h. There are no apparent differences in the absorption or elimination of ddC between 0.5 and 5 mg oral doses.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Zidovudine (azidothymidine, AZT) disposition was examined during a hemodialysis session in an HIV-infected male with mesangial proliferative glomerulonephritis. Serum concentrations of zidovudine and its glucuronidated inactive metabolite (G-ZDV) were measured by HPLC. Zidovudine pharmacokinetics were similiar to previous reports in patients with normal renal function, however, G-ZDV concentrations were significantly elevated (23–440 times zidovudine concentration). Hemodialysis did not appreciably reduce zidovudine or G-ZDV levels. Significance of chronically elevated G-ZDV levels is unknown.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The prevalence of retroviral infection in renal transplantation remains poorly defined. We tested retrospectively sera from 224 of 331 patients undergoing renal transplantation between 1979 and 1985. Viral antigen based EIA was used for screening IgG antibodies to human immunodeficiency virus (HIV-1) and human T-cell leukemia virus type I (HTLV-I). Positive El As were confirmed by Western blot. Six patients (2.7%) were found to have retroviral infection, four with HIV-1 and two with HTLV-I. The four patients with HIV-1 infection were negative before and became EIA and Western blot positive following transplantation. All patients had transient HIV-1 antigenemia documented before antibody was detected. One patient died of Kaposi's sarcoma 2 years posttransplantation with a functioning graft. One is alive and asymptomatic 4 years posttransplant, and two rejected their grafts and are asymptomatic on maintenance hemodialysis. Six patients tested positive for HTLV-I by EIA. Only two patients, however, were also positive for HTLV-I by Western blot, RIPA, and p24 antigen RIA, one prior to and one after transplantation. Both had HTLV-I-positive lymphocyte cultures and remain asymptomatic of retroviral infection 3 years after renal transplantation. A third patient, positive for HTLV-I by EIA, had indeterminate Western blot and negative RIPA, RIA, and lymphocyte culture. Intravenous drug use was not a risk factor for retroviral infection in this patient population. It is likely that patients became infected peritransplantation from blood transfusions. Contamination by donor kidneys, however, cannot be excluded.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Thirty-seven HIV-1-positive patients contributed salivary samples from individual major salivary glands. Nineteen patients were unmedicated and asymptomatic, and 18 patients had developed signs of AIDS. Salivas from 15 healthy males served as controls. Levels of four salivary antimicrobial proteins (lactoferrin, lysozyme, secretory IgA, and histatins) were determined, as well as total fluid output of the major salivary glands. Concentrations of all four salivary antimicrobial proteins were found to be increased in the stimulated submandibular/sublingual saliva of all HIV-1-positive patients as well as the subset of unmediated HIV-1-positive patients. Those patients with evidence of oral candidiasis had the highest concentrations of lysozyme and histatins, potent antifungual proteins, in their saliva. Although the etiology of these protein increases is still unknown, these results further document salivary changes following HIV-1 infection.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A simple noniterative method is presented for adjustment of AIDS surveillance data for reporting delays. The method estimates the distribution of reporting delays from a cross-classification of incident cases according to date of diagnosis vs. length of reporting delay. Using the delay distribution, the number of cases reported to have occurred within each period of calendar time is inflated to reflect the actual number of cases diagnosed but not yet reported. The method assumes that the delay distribution is independent of the calendar period of diagnosis, but can readily be modified to account for early departures from the current pattern. The method is illustrated using surveillance data from the northeastern United States.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The simplest models of HIV infectivity treat the HIV transmission process as a series of independent Bernoulli trials over sex acts or sex partners. In this paper, an approximate maximum likelihood estimator of the transmission probability is derived for such models, and applied to two data sets. Nonparametric models of HIV infectivity are constructed as alternatives for comparison to the simple models. The results suggest that while HIV infectivity can be modeled as a Bernoulli process with a constant infection probability per partner, the Bernoulli model may not be appropriate at the level of sexual contacts. Probabilistic arguments consistent with these findings are proposed and discussed.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

One hundred thirty-four homosexual men from a prospective cohort study of AIDS risk from New York City and Washington D.C. and 139 homosexual men from a similar cohort in Copenhagen and Aarhus, Denmark were questioned regarding their sexual practices and knowledge of their human immunodeficiency virus (HIV) status over the previous 12 months. Seventy percent of Danish men and 63% of U.S. men participated in anal intercourse during the previous 12 months. Knowledge of one's own HIV status by itself did not have any significant effect on participation in anal intercourse, partner number, or condom use. Only 23% of U.S. men and 24% of Danish men always asked potential partners about their HIV status. However, men who did ask were very unlikely to choose a partner of opposite HIV status (p< 0.006). Danish men were more likely to practice anal intercourse without a condom than were the U.S. men (p< 0.0001); however, Danes were more likely to be in a concordant monogamous relationship than were the U.S. men (p< 0.001). Fourteen percent of U.S. men and 21% of Danish men were not aware of their own HIV status and 52% of the U.S. cohort and 31% of the Danes had anal intercourse with a man whose status was unknown to them. Overall, only 32% of American and 53% of Danish homosexual men were practicing completely safe sex. We suggest that education to promote the need for awareness of one's own and one's partner's HIV status should be stressed.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID