Gene/Protein Disease Symptom Drug Enzyme Compound
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 48,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors examined the relation between dietary and supplemental micronutrient intake and subsequent mortality among 281 human immunodeficiency type 1 (HIV-1)-infected participants at the Baltimore, Maryland/Washington, DC, site of the Multicenter Acquired Immunodeficiency Syndrome Cohort Study. Subjects completed a semiquantitative food frequency questionnaire at their baseline visit in 1984. Levels of daily micronutrient intake were examined in relation to subsequent mortality over the 8-year follow-up period by using multivariate Cox models, adjusting for age, symptoms, CD4+ count, energy intake, and treatment. The highest quartile of intake for each B-group vitamin was independently associated with improved survival: B1 (relative hazard (RH) = 0.60, 95% confidence interval (CI) 0.38-0.95), B2 (RH = 0.59, 95% CI 0.38-0.93), B6 (RH = 0.45, 95% CI 0.28-0.73), and niacin (RH = 0.57, 95% CI 0.36-0.91). In a final model, the third quartile of beta-carotene intake (RH = 0.60, 95% CI 0.37-0.98) was associated with improved survival, while increasing intakes of zinc were associated with poorer survival. Intakes of B6 supplements at more than twice the recommended dietary allowance were associated with improved survival (RH = 0.60, 95% CI 0.39-0.93), while intakes of B1 and B2 supplements at levels greater than five times the recommended dietary allowance were associated with improved survival (B1: RH = 0.61, 95% CI 0.38-0.98; B2:RH = 0.60, 95% CI 0.37-0.97). Any intake of zinc supplements, however, was associated with poorer survival (RH = 1.49, 95% CI 1.02-2.18). These data support the performance of clinical trials to assess the effects of B-group vitamin supplements on HIV-1-related survival. Further studies are needed to determine the optimal level of zinc intake in HIV-1-infected individuals.
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PMID:Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. 865 Dec 23

The construction, expression, and purification of an active Fv fragment of the 0.5beta monoclonal human immunodeficiency virus type 1 (HIV-1) neutralizing antibody is reported. The interaction between the Fv fragment and the RP135 peptide derived from the V3 loop of gp120 from HIV-1IIIB was studied by varying the salt concentration and by mutating arginine residues in the peptide. The mutations R4A, R8A and R11A (which correspond to residues 311, 315, and 318 in gp120 of HIV-1IIIB) reduce the binding free energy by 0.22 (+/- 0. 20), 4.32 (+/- 0.16), and 1.58 (+/- 0.17) kcal mol-1, respectively. The salt-dependent components of their contributions to binding are 0.02 (+/- 0.22), -0.55 (+/- 0.18), and -0.97 (+/- 0.19) kcal mol-1, respectively. The magnitudes of the mutational effects and the extent of shielding by 1 M NaCl suggest that Arg-8 is involved in a buried salt bridge in the peptide-Fv fragment complex, whereas Arg-11 is involved in a more solvent-exposed electrostatic interaction.
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PMID:Contribution of arginine residues in the RP135 peptide derived from the V3 loop of gp120 to its interaction with the Fv fragment of the 0.5beta HIV-1 neutralizing antibody. 866 80

The aim of the study was to estimate the prevalence of hepatitis C infection among attenders of several high-volume needle exchanges in southeast Queensland, and to compare the prevalences among the needle exchanges. Clients at four needle exchanges were surveyed over a five-day period by means of a self-administered questionnaire. A high proportion of respondents (76 per cent) reported having been tested for hepatitis C antibodies and the overall prevalence of reported hepatitis C infection was 34 per cent. Thirty-one per cent of the respondents were amphetamine injectors, among whom there was a lower prevalence of reported hepatitis C infection than among opioid injectors (odds ratio 0.18, P < 0.01). There were some differences in the respondents' characteristics and in hepatitis C prevalence between different needle exchanges. The reported prevalence of HIV infection was 2 per cent. This study highlights the importance of surveying a range of needle exchanges to obtain a representative sample of needle-exchange clients overall. The low prevalence of hepatitis C in some groups of injecting drug users suggests that it is possible to prevent hepatitis C transmission among injecting drug users, and points to the opportunity for aiming hepatitis C prevention strategies at these groups.
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PMID:Reported prevalence of hepatitis C among clients of needle exchanges in southeast Queensland. 879 69

This study examined the incidence of infectious and neoplastic diseases among 222 HIV-seronegative gay men who participated in the Natural History of AIDS Psychosocial Study. Those who concealed the expression of their homosexual identity experienced a significantly higher incidence of cancer (odds ratio = 3.18) and several infectious diseases (pneumonia, bronchitis, sinusitis, and tuberculosis; odds ratio = 2.91) over a 5-year follow-up period. These effects could not be attributed to differences in age, ethnicity, socioeconomic status, repressive coping style, health-relevant behavioral patterns (e.g., drug use, exercise), anxiety, depression, or reporting biases (e.g., negative affectivity, social desirability). Results are interpreted in the context of previous data linking concealed homosexual identity to other physical health outcomes (e.g., HIV progression and psychosomatic symptomatology) and theories linking psychological inhibition to physical illness.
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PMID:Elevated physical health risk among gay men who conceal their homosexual identity. 881 70

Results of a prospective HIV testing and questionnaire response study of 1607 male factory workers in Harare, Zimbabwe, were used to identify demographic and behavioral characteristics associated with HIV seroconversion. Specifically, the objectives of this study were to estimate HIV seroincidence, identify behavioral and biological determinants of infection, and evaluate the impact of current AIDS prevention intervention programs presented in the workplace. This male cohort was followed from a pre-intervention program phase through the establishment of a workplace/post-intervention program. Results were compared. Correlates of HIV seroconversion were identified using Cox regression analysis. There were 51 (3.2%) seroconversions among the 1607 HIV-negative participants following 1738 person-years (PY) of observation (seroincidence, 2.93/100 PY; 95% confidence interval (CI), 2.18-3.86). The HIV prevalence in the cohort was 19.1%. HIV seroincidence was significantly increased among men who were younger (hazard ratio (HR) per year, 0.96; 95% CI, 0.93-0.99), were single (HR, 3.29; 95% CI, 1.56-6.96), were married but resided separately from their wives (HR, 2.18; 95% CI, 0.99-4.80), reported having an STD (HR, 3.00; 95% CI, 1.53-5.86), reported having a genital ulcer (HR, 4.87; 95% CI, 2.18-10.91), and reported paying for sex (HR, 2.01; 95% CI, 1.06-3.77). Seroincidence also increased with the number of sex partners reported from the preceding calendar year (HR per partner, 1.10; 95% CI, 1.01-1.21). The authors conclude that innovative and sustained workplace-based interventions are needed to address the high risk of HIV infection in this economically productive segment of the Zimbabwe population. The risk factors and predictors of HIV seroconversion described in this study underscore the great need for public health efforts designed to address the biological, socioeconomic, cultural, and behavioral factors surrounding the spread of HIV and STDs.
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PMID:HIV seroincidence and correlates of seroconversion in a cohort of male factory workers in Harare, Zimbabwe. 882 47

In a prospective, randomized, controlled, three-arm study, the pharmacokinetics of hydroxyurea administered as an antiviral agent in patients infected with human immunodeficiency virus type 1 (HIV-1) were evaluated. The three arms of the study consisted of azidothymidine (AZT) 250 mg twice daily, hydroxyurea 500 mg twice daily, or a combination of the two. Nine patients receiving hydroxyurea in monotherapy (n = 4) or in combination with AZT (n = 5) agreed to undergo multiple venipunctures for pharmacokinetic analysis. Sample collection was performed at steady-state conditions and serum concentration-time data for hydroxyurea were fitted using a one-compartment model. Mean (+/- standard deviation) peak concentration (Cmax) was 0.135 +/- 0.06 mmol/L and mean trough level (Cmin) was 0.0085 +/- 0.003 mmol/L. Mean concentration at steady state was 0.045 +/- 0.006 mmol/L. Apparent clearance (Cl/F) was 0.18 +/- 0.005 L/hr/kg, and half-life (t1/2) was 2.5 +/- 0.5 hours. Hydroxyurea given orally to patients infected with HIV-1 was well absorbed from the gastrointestinal tract, with a tmax of 0.85 to 0.96 hours after ingestion. Serum levels of hydroxyurea ranged from 0.01 to 0.13 mmol/L. These values are similar to the concentrations (between 0.01 and 0.1 mmol/L) demonstrated to inhibit HIV-1 in vitro. Our data show that hydroxyurea given at a dosage of 500 mg twice daily is sufficient to yield serum concentrations potentially useful for in vivo inhibition of HIV-1.
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PMID:Pharmacokinetics of hydroxyurea in patients infected with human immunodeficiency virus type I. 885 87

A cross-sectional study was designed to determine whether plasma concentrations of glutathione and cysteine in HIV-infected hemophiliacs vary according to the progression of the disease and to compare them with those obtained in HIV negative hemophiliacs. Cysteine, total glutathione and glutathione disulphide were measured in plasma of HIV-infected hemophiliacs at different stages of HIV infection and in plasma of HIV-negative hemophiliacs. CD4 and CD8 T-cell counts, leukocyte and lymphocyte counts, beta 2-microglobulin and p24 antigen values were recorded for HIV positive hemophiliacs at the time of the study. The hemophiliac HIV-positive group showed a decrease in total glutathione levels (-18%) and an increase of glutathione disulphide (8.18 vs. 14.90%) compared to the HIV-negative group. The cysteine levels found in HIV-positive hemophiliacs were not different from those found in the HIV-negative group. There were no differences with statistical significance in total glutathione, glutathione disulphide and cysteine among HIV-infected hemophiliacs according to the different clinical stage of the disease (AIDS vs. non-AIDS). The interest of evaluating plasma concentrations of glutathione and cysteine in HIV-infected patients is limited from the point of view of considering them as markers of progression of the disease. Interest in a therapeutic strategy designed to replenish or normalize glutathione plasma levels is also limited.
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PMID:Glutathione and cysteine in HIV-infected hemophiliacs. 889 10

This study explored the variability of zidovudine concentrations with computer simulations and measured concentrations. A one-compartment oral absorption model was selected to characterize zidovudine disposition. Mean (+/-standard deviation) values for the pharmacokinetic parameters were taken from the literature. Five different Monte Carlo simulations (50 each) were performed of zidovudine concentrations following repetitive administration of 100-mg oral doses 6 times/day in patients weighing 45-85 kg. A sixth simulation considered a weight-adjusted regimen. Predicted concentrations were compared with those measured in 30 HIV-infected persons receiving 100 mg/dose. Predicted concentrations 1 hour after 100 mg was administered fell in the range of 0.52-5.18 microM; measured values in 30 patients were 0.54-3.07 microM. This study confirms substantial variability in zidovudine serum concentrations. The simulation study of a weight-adjusted regimen suggests one possibility to reduce this variability. These observations provide a basis to explore dosing strategies that control for pharmacokinetic and perhaps pharmacodynamic sources of interpatient variability.
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PMID:Variability in zidovudine serum concentrations. 894 89

Cigarette smoking has been associated with impaired immune defenses and an increased risk of certain infectious and neoplastic diseases in HIV-1 seronegative populations. We examined the relationship between cigarette smoking and clinical outcome in a prospective cohort of 3221 HIV-1-seropositive men and women enrolled in the Terry Beirn Community Programs for Clinical Research on AIDS. Differences in clinical outcomes between never, former, and current cigarette smokers were assessed using proportional hazards regression analysis. After adjustment for CD4+ cell count, prior disease progression, use of antiretroviral therapy, and other covariates, there was no difference between current smokers and never smokers in the overall risk of opportunistic diseases [relative hazard (RH) = 1.05; 95% confidence interval (CI) 0.90-1.23; p = 0.52] or death (RH = 1.00; 95% CI 0.86-1.18; p = 0.97). However, current smokers were more likely than never smokers to develop bacterial pneumonia (RH = 1.57; 95% CI 1.14-2.15; p = 0.006), oral candidiasis (RH = 1.37; 95% CI 1.16-1.62; p = 0.0002), and AIDS dementia complex (RH = 1.80; 95% CI 1.11-2.90; p = 0.02). In addition, current smokers were less likely to develop Kaposi's sarcoma (RH = 0.58; 95% CI 0.39-0.88; p = 0.01) and several other non-respiratory tract diseases. If confirmed by other studies, these findings have important clinical implications.
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PMID:Cigarette smoking, bacterial pneumonia, and other clinical outcomes in HIV-1 infection. Terry Beirn Community Programs for Clinical Research on AIDS. 894 77

The structure of a complex between a hexapeptide-based inhibitor, MVT-101, and the chemically synthesized (Aba 67,95,167,195; Aba: L-alpha-amino-n-butyric acid) protease from the human immunodeficiency virus (HIV-1), reported previously at 2.3 A has now been refined to a crystallographic R factor of 15.4% at 2.0 A resolution. Root mean square deviations from ideality are 0.18 A for bond lengths and 2.4 degrees for the angles. The inhibitor can be fitted to the difference electron density map in two alternative orientations. Drastic differences are observed for positions and interactions at P3/S3 and P3'/S3' subsites of the two orientations due to different crystallographic environments.
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PMID:Analysis of the structure of chemically synthesized HIV-1 protease complexed with a hexapeptide inhibitor. Part I: Crystallographic refinement of 2 A data. 906 82


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