A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines.

Hepatitis B virus (HBV) infection-related hepatocellular carcinoma (HCC) represents a major health problem worldwide. HBV X (HBx) protein is the most common open reading frame that may undergo mutations, resulting in the development of HCC. This study aimed to determine specific HBx mutations that differentiate the central- and para-tumor tissues, and identify their association with HCC development.

Pooled Nucleic Acid Testing to Detect Antiretroviral Treatment Failure in HIV-Infected Patients in Mozambique.

Background: In resource-limited settings, viral load monitoring of HIV-infected patients receiving antiretroviral therapy (ART) is not readily available because of high costs. Here, we compared the accuracy and costs of quantitative and qualitative pooled methods with standard viral load testing.

Methods: Blood was collected prospectively from 461 patients receiving first-line ART in Mozambique who had not been evaluated previously with viral load testing.

Genetic attributes of blood-derived subtype-C HIV-1 tat and env in India and neurocognitive function.

Genetic elements in HIV-1 subtype B tat and env are associated with neurotoxicity yet less is known about other subtypes. HIV-1 subtype C tat and env sequences were analyzed to determine viral genetic elements associated with neurocognitive impairment in a large Indian cohort. Population-based sequences of HIV-1 tat (exon 1) and env (C2-V3 coding region) were generated from blood plasma of HIV-infected patients in Pune, India.

A synthetic bivalent ligand of CXCR4 inhibits HIV infection.

G-protein-coupled receptors (GPCRs) are cell membrane protein receptors that transduce signals across the cell membrane and are important targets for therapeutic interventions. As members of the GPCR superfamily, chemokine receptors such as CXCR4 play critical roles in normal physiology as well as the pathology of many human diseases including cancer, inflammation, autoimmune diseases, and human immunodeficiency virus (HIV) infection. Here we report the discovery and study of a novel peptide ligand of CXCR4 using d-amino acids and bivalent ligand approach.

The relatedness of HIV epidemics in the United States-Mexico border region.

Phylogeography can improve the understanding of local and worldwide HIV epidemics, including the migration of subepidemics across national borders. We analyzed HIV-1 sequences sampled from Mexico and San Diego, California to determine the relatedness of these epidemics. We sampled the HIV epidemics in (1) Mexico by downloading all publicly available HIV-1 pol sequences from antiretroviral-naive individuals in GenBank (n = 100) and generating similar sequences from cohorts of injection drug users and female sex workers in Tijuana, Mexico (n = 27) and (2) in San Diego, California by pol sequencing well-characterized primary (n = 395) and chronic (n = 267) HIV infection cohorts.

Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization.

5-Hydroxytryptamine (5-HT)(2C) receptor agonists hold promise for the treatment of obesity. In this study, we describe the in vitro and in vivo characteristics of lorcaserin [(1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3 benzazepine], a selective, high affinity 5-HT(2C) full agonist. Lorcaserin bound to human and rat 5-HT(2C) receptors with high affinity (K(i) = 15 +/- 1 nM, 29 +/- 7 nM, respectively), and it was a full agonist for the human 5-HT(2C) receptor in a functional inositol phosphate accumulation assay, with 18- and 104-fold selectivity over 5-HT(2A) and 5-HT(2B) receptors, respectively.

Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity.

The synthesis and SAR of a novel 3-benzazepine series of 5-HT2C agonists is described. Compound 7d (lorcaserin, APD356) was identified as one of the more potent and selective compounds in vitro (pEC50 values in functional assays measuring [(3)H]phosphoinositol turnover: 5-HT2C = 8.1; 5-HT2A = 6.

Characteristics of recently HIV-infected men who use the Internet to find male sex partners and sexual practices with those partners.

Objective: To examine (1) characteristics of recently HIV-infected men who have sex with men (MSM) who find sex partners through the Internet and (2) differences in characteristics of and sexual behaviors practiced with Internet partners as compared to other partner types.

Methods: From May 2002 to 2005, a computer-assisted self-interview was administered to 194 recently HIV-infected MSM in southern California. MSM who used the Internet to find sex partners were compared with those who did not report Internet use, and partners found from the Internet were compared with those who were found from other venues using chi analyses, t tests, logistic regression, and generalized estimating equations.

Synthesis and SAR of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones related to licostinel (Acea 1021) as NMDA/glycine site antagonists.

A series of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones (QXs) related to licostinel (Acea 1021) was synthesized and evaluated as antagonists for the glycine site of the N-methyl-D-asparate (NMDA) receptor. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [(3)H]-5,7-dichlorokynurenic acid ([(3)H]DCKA) in rat brain cortical membranes. Structure-activity relationship studies indicate that a cyano group is a good replacement for the nitro group in the 5-position of licostinel while 5-carboxy, 5-ester, 5-ketone and 5-amide derivatives showed reduced potency.