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)

Tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels are elevated among patients with human immunodeficiency virus (HIV) infection. TNF-alpha is known to lower NO production. In this study we used a TNF-alpha inhibitor, pentoxiphylline, to treat patients with HIV infection who were free of opportunistic infections and see if NO production was altered with this drug. NO production was determined by spectrophotometric analysis using nitrite and citrulline as surrogate markers and TNF-alpha levels were determined by ELISA before and after 4 weeks of the treatment. Nineteen patients (ten males, mean age 36.6+/-5.2 years) and 16 age and sex matched healthy controls were studied. Mean CD4 counts of patients were 206.5 mm(3). Nitrite level among patients at recruitment was 99.7+/-26.5 nmol/ml (range 50-167 nmol/ml) and was significantly higher than 46.4+/-16.2 nmol/ml; the value of healthy controls (P<0.05). Patient levels declined significantly to 44. 2+/-19.7 nmol/ml (range 10-106.6 nmol/ml) following 4 weeks of therapy (P<0.01). Citrulline level at recruitment was 810.8+/-425.8 nmol/ml (range 366.6-1888.7 nmol/ml), which was significantly higher than 488.6+/-224.5 nmol/ml, the level of controls (P<0.01). There was a statistically significant decrease in these levels among patients to 533.6+/-299.5 nmol/ml (range 250-163.4 nmol/ml) after 4 weeks of therapy (P<0.01). TNF-alpha levels showed a significant decline in the OD values from 0.34+/-0.22 at the start of therapy to 0.24+/-0.18 (P<0.05). We conclude that the use of pentoxiphylline is associated with decrease in TNF-alpha levels and NO production.
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PMID:Pentoxiphylline reduces nitric oxide production among patients with HIV infection. 1099 87

Defining the source of HIV-1 RNA in cerebrospinal fluid (CSF) will facilitate studies of treatment efficacy in the brain. Four antiretroviral drug-naive adults underwent two 48-hr ultraintensive CSF sampling procedures, once at baseline and again beginning on day 4 after initiating three-drug therapy with stavudine, lamivudine, and nelfinavir. At baseline, constant CSF HIV-1 RNA concentrations were maintained by daily entry of at least 10(4) to 10(6) HIV-1 RNA copies into CSF. Change from baseline to day 5 ranged from -0.38 to -1.18 log(10) HIV-1 RNA copies/ml in CSF, and from -0.80 to -1.33 log(10) HIV-1 RNA copies/ml in plasma, with no correlation between CSF and plasma changes. There was no evidence of genotypic or phenotypic viral resistance in either CSF or plasma. With regard to pharmacokinetics, mean CSF-to-plasma area-under-the-curve (AUC) ratios were 38.9% for stavudine and 15.3% for lamivudine. Nelfinavir and its active M8 metabolite could not be accurately quantified in CSF, although plasma M8 peak level and AUC(0-8hr) correlated with CSF HIV-1 RNA decline. This study supports the utility of ultraintensive CSF sampling for studying HIV-1 pathogenesis and therapy in the CNS, and provides strong evidence that HIV-1 RNA in CSF arises, at least in part, from a source other than plasma.
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PMID:Evidence of a source of HIV type 1 within the central nervous system by ultraintensive sampling of cerebrospinal fluid and plasma. 1105 62

Although many HIV-positive individuals use alternative medicine, little is known about user characteristics. In this study, the prevalence of alternative medicine use in a sample of 70 HIV-positive gay men is assessed and characteristics of alternative medicine users are identified. Seventy-one per cent (50/70) of the sample used at least one alternative therapy since HIV serostatus notification, alone or in combination with traditional medicine. A logistic regression was used to identify those measures which are characteristic of alternative users. It revealed that the typical user is a person with symptomatic HIV disease (Wald = 6.18, p = 0.01), who reports little or no pain (Wald = 10.01, p < 0.01) and actively tries to cope with disease-specific problems (Wald = 7.35, p = 0.01) while expressing his feelings about them (Wald = 7.66, p = 0.01). In the sub-set of subjects using antiretroviral medication, those also using alternative medicine reported using more antiretrovirals and better adherence to them, than those not using alternative medicine.
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PMID:Use of alternative medicine in a sample of HIV-positive gay men: an exploratory study of prevalence and user characteristics. 1109 76

The main goal of this study was to investigate a novel approach for an efficient and reproducible production of Virus-Like Particles (VLPs) expressing multiple HIV-1 epitopes. The HIV-1 Pr55(gag)-based VLPs have been produced in a Baculovirus expression system, using a transfer vector able to support the independent expression of different open reading frames (ORFs). In this regard, the gp120 derived from 94UG018 HIV-1(A) isolate, previously studied in our laboratory, has been packaged into the VLPs together with nef and pol ORFs. In particular, the gp120(UG) sequence shows a 90% homology in the V3 region compared to African HIV-1 strains of the A-clade. This novel approach is extremely effective for the production of VLPs expressing all the epitopes, as confirmed by Western Blot characterization. Furthermore, the resulting HIV-VLP(A)s show the expected density (1.14--1.18 g/ml) on a 10--60% sucrose gradient and the morphology of an immature virion at standard transmission electron microscopy. Our results demonstrate that this strategy is highly efficient for expressing a balanced amount of multiple epitopes and their packaging in VLP structures, without affecting the Pr55(gag) autoassembling capacities. Furthermore, the genetic transposition performed in a modified E. coli represents a methodological improvement, allowing a faster and more reproducible identification of recombinant Baculovirus DNA molecules.
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PMID:High efficient production of Pr55(gag) virus-like particles expressing multiple HIV-1 epitopes, including a gp120 protein derived from an Ugandan HIV-1 isolate of subtype A. 1116 59

Hepatitis C virus (HCV) is the major cause of chronic liver disease in hemophiliacs. To determine the effect of human immunodeficiency virus (HIV) on the natural history of HCV infection, we evaluated end-stage liver disease (ESLD) in 157 hemophiliacs (85 HIV positive and 72 HIV negative) with HCV infection for an average of 24 years. After adjusting for age at HCV infection, past or current hepatitis B surface antigen positivity, and history of alcohol abuse, we determined that the rate of ESLD was significantly greater among HIV-positive than among HIV-negative hemophiliacs (relative risk [RR], 3.72; 95% confidence interval [CI], 1.25-11.09), as was the adjusted RR for death due to ESLD (RR, 3.81; 95% CI, 1.19-12.16). Among HIV-positive hemophiliacs, crude RR for ESLD was lower, but not significantly so, with antiretroviral treatment (RR, 0.19; 95% CI, 0.03-1.14; P=.069) and increased with each decade of HCV infection (RR, 2.26; 95% CI, 1.42-3.59; P=.0006) and HIV infection (RR, 2.18; 95% CI, 1.36-3.49; P=.0013). These findings suggest that HIV accelerates HCV disease progression.
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PMID:Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection. 1123 38

Lower baseline antipneumolysin antibody (alpha-PLY) levels have been found in populations with a higher incidence of pneumococcal infections. To determine whether predisease alpha-PLY titer is associated with invasive pneumococcal disease in HIV-seropositive injection drug users (IDU), we utilized a prospective cohort of IDU in Baltimore to compare alpha-PLY titers before bacteremia in 28 HIV- seropositive IDU cases with alpha-PLY titers in 56 matched (CD4 and seroconversion date) HIV-seropositive IDU control subjects and 28 matched (calendar time) HIV-seronegative IDU control subjects remaining free of pneumococcal disease. We also compared the postinfection fold-rise of alpha-PLY titers in cases relative to the change in alpha-PLY titers in control subjects during the same interval; alpha-PLY titers were measured using quantitative ELISA, and functional activity was assessed using antihemolysin assays. Predisease alpha-PLY titer did not differ between cases (66 units) and HIV-seropositive control subjects (70 units, p = 0.56) or HIV-seronegative control subjects (80 units, p = 0.10). There was a significant difference in fold-rise of alpha-PLY titers postdisease between cases (1.18) and HIV-seronegative control subjects (0.76), p = 0.03. Baseline alpha-PLY titers do not differ significantly between HIV-seropositive IDU who develop pneumococcal bacteremia from HIV-seropositive and HIV-seronegative IDU control subjects remaining free of severe pneumococcal disease.
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PMID:Antipneumolysin antibody titers in HIV-seropositive injection drug users before and after pneumococcal bacteremia. 1125 23

Questions exist about whether testing of preventive human immunodeficiency virus (HIV)-1 vaccines, which will require rapid recruitment and retention of cohorts with high HIV-1 seroincidence, is feasible in the United States. A prospective cohort study was conducted in 1995-1997 among 4,892 persons at high risk for HIV infection in nine US cities. At 18 months, with an 88% retention rate, 90 incident HIV-1 infections were observed (1.31/100 person-years (PY), 95% confidence interval (CI): 1.06, 1.61). HIV-1 seroincidence rates varied significantly by baseline eligibility criteria--1.55/100 PY among men who had sex with men, 0.38/100 PY among male intravenous drug users, 1.24/100 PY among female intravenous drug users, and 1.13/100 PY among women at heterosexual risk-and by enrollment site, from 0.48/100 PY to 2.18/100 PY. HIV-1 incidence was highest among those men who had sex with men who reported unprotected anal intercourse (2.01/100 PY, 95% CI: 1.54, 2.63), participants who were definitely willing to enroll in an HIV vaccine trial (1.96/100 PY, 95% CI: 1.41, 2.73), and women who used crack cocaine (1.62/100 PY, 95% CI: 0.92, 2.85). Therefore, cohorts with HIV-1 seroincidence rates appropriate for HIV-1 vaccine trials can be recruited, enrolled, and retained.
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PMID:Are US populations appropriate for trials of human immunodeficiency virus vaccine? The HIVNET Vaccine Preparedness Study. 1128 87

Both human immunodeficiency virus (HIV) infection and certain malignancies including breast cancer occur predominantly in premenopausal women in an African population. Cancers that are associated with HIV infection are Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) and invasive cervical carcinoma. Recently, cases of breast cancer have been reported in patients with HIV infection but an association between breast cancer and HIV infection has yet to be determined. The present study investigated for association between HIV infection and breast cancer. Among the 101 patients studied, 50 were cases with breast cancer while the remaining 51 were referents with conditions other than mammary cancer. Patients with breast cancer 30 years of age and below recorded in the Cancer registry during 1974-1987 constituted 8% while those recorded during the ongoing AIDS epidemic amounted to only 2%. When a similar comparison was undertaken among patients below 50 years there was also an overall decrease in the proportion of patients from 76.1 to 58.0%. Conversely, in the age groups above 50 years the breast cancer cases increased from 33.9 to 42% respectively (chi2=1.83 on 1df, p=0.18). The overall prevalence of HIV infection among the control group was 35.5% (95% CI=22.2-48.4) while among breast cancer patients it was 6% (95% CI=0.6-12.6). Women below 50 years of age with breast cancer were less likely to be HIV positive; OR=0.18: (95% CI=0.04-0.76) chi2=5.95; p=0.01. However, there is no basis to suggest that HIV infection is protective against this malignancy. AIDS associated mortality commonly occurs in the second and third decades of life and probably these deaths have changed the demographic of the disease in an African population. The impact of AIDS associated mortality on cancer registries needs attention.
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PMID:Breast cancer during the HIV epidemic in an African population. 1129 98

High concentrations of salts dramatically affect the interaction of small ligands with HIV-1 protease. For instance, the Km and kcat values for Abz-Thr-Ile-Nle-p-nitro-Phe-Gln-Arg-NH2 (S) increased 120-fold and 3-fold, respectively, as the NaCl concentration in the assay decreased from 4.0 to 0.5 M. The Kd value for the competitive inhibitor amprenavir increased 12-fold over this concentration range of NaCl. The bimolecular rate constant for association of enzyme with amprenavir was independent of NaCl concentration, whereas the dissociation rate constant decreased with increasing NaCl concentration. Polyanionic polymers such as heparin or poly A substituted for NaCl. For example, the value of kcat/Km for S was 0.18 microM(-1) x s(-1) when the enzyme (<10 nM) was assayed in the standard buffer supplemented with 5 mM NaCl. If 0.01% poly A were included, the value of kcat/Km increased to 8.6 microM(-1) x s(-1). A DNA oligomer (23-mer) with an hexachlorofluoresceinyl moiety linked to the 5' end was studied as a model polyanionic polymer. The enzyme bound HF23 (Kd < 1 nM) with concomitant quenching of the hexachlorofluoresceinyl fluorescence. The stoichiometry for binding was 3 mol of enzyme per mol of oligomer. The hydrolytic activity of the enzyme with this oligomer was similar to that observed with poly A or high salt concentration when the molar ratio of oligomer to enzyme was greater than one. The results presented herein demonstrate that polyanionic polymers substitute for salts as effectors of HIV protease.
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PMID:Effectors of HIV-1 protease peptidolytic activity. 1155 Dec 11

This paper examines the association between traditional practices of female genital cutting (FGC) and adult women's reproductive morbidity in rural Gambia. In 1999, we conducted a cross-sectional community survey of 1348 women aged 15-54 years, to estimate the prevalence of reproductive morbidity on the basis of women's reports, a gynaecological examination and laboratory analysis of specimens. Descriptive statistics and logistic regression were used to compare the prevalence of each morbidity between cut and uncut women adjusting for possible confounders. A total of 1157 women consented to gynaecological examination and 58% had signs of genital cutting. There was a high level of agreement between reported circumcision status and that found on examination (97% agreement). The majority of operations consisted of clitoridectomy and excision of the labia minora (WHO classification type II) and were performed between the ages of 4 and 7 years. The practice of genital cutting was highly associated with ethnic group for two of the three main ethnic groups, making the effects of ethnic group and cutting difficult to distinguish. Women who had undergone FGC had a significantly higher prevalence of bacterial vaginosis (BV) [adjusted odds ratio (OR)=1.66; 95% confidence interval (CI) 1.25-2.18] and a substantially higher prevalence of herpes simplex virus 2 (HSV2) [adjusted OR=4.71; 95% CI 3.46-6.42]. The higher prevalence of HSV2 suggests that cut women may be at increased risk of HIV infection. Commonly cited negative consequences of FGC such as damage to the perineum or anus, vulval tumours (such as Bartholin's cysts and excessive keloid formation), painful sex, infertility, prolapse and other reproductive tract infections (RTIs) were not significantly more common in cut women. The relationship between FGC and long-term reproductive morbidity remains unclear, especially in settings where type II cutting predominates. Efforts to eradicate the practice should incorporate a human rights approach rather than rely solely on the damaging health consequences.
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PMID:The long-term reproductive health consequences of female genital cutting in rural Gambia: a community-based survey. 1155 30


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