Biomedical subjects

Robert Carr

Publications and source records attributed to Robert Carr.

5 recordsLinked to original sources

PubMed2006

Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics.

OBJECTIVE: Our objective was to learn whether genetic polymorphisms of metabolic enzymes or transport proteins provide a mechanistic understanding of the in vivo disposition of atrasentan, a selective endothelin A receptor antagonist. METHODS: Atrasentan uptake was measured in HeLa cells transfected to express major alleles of organic anion transporting polypeptide 1B1 (OATP1B1). The results were used to classify individuals as extensive, intermediate, or poor OATP1B1 transporters according to their SLCO1B1 genotypes. Analysis of covariance including genotype, study, age, weight, sex, and ethnicity was used to identify factors influencing atrasentan single-dose (n = 44) and steady-state (n = 38) pharmacokinetic parameters. Genotypes for cytochrome P450 3A5, uridine diphosphate-glucuronosyltransferase (UGT) 1A1, UGT2B4, UGT2B15, adenosine triphosphate-binding cassette subfamily B (ABCB) 1, solute carrier organic anion transporter (SLCO) 1B1, and solute carrier family 22 (SLC22) A2 were each assessed. RESULTS: Single-dose atrasentan exposure (P = .0244), steady-state atrasentan exposure (P = .0108), and maximum postdose plasma concentration (P = .0002) were associated with OATP1B1 activity classified by SLCO1B1 genotype. No other tested genotypes were observed to be associated with both single-dose and steady-state atrasentan pharmacokinetics. CONCLUSIONS: OATP1B1 is a meaningful factor for atrasentan disposition. Individuals may be classified as having extensive, intermediate, or poor OATP1B1 transport phenotypes according to SLCO1B1 genotypes. Increased exposures of OATP1B1 substrates might be expected in individuals who have the poor transporter phenotype or are treated with an OATP1B1 inhibitor.

Adult↗

PubMed2005

Caribbean: birth of a regional network responding to HIV/AIDS and vulnerability.

In December 2004, representatives from 30 Caribbean NGOs met in Kingston, Jamaica to form a regional network of organizations working with populations most vulnerable to HIV/AIDS--the Caribbean Vulnerable Communities (CVC) Network. In this article, two Caribbean researchers and activists situate this vulnerability and the civil society response in their specific socio-historical context.

HIV Infections↗

PubMed2004

1001 optimal PDB structure alignments: integer programming methods for finding the maximum contact map overlap.

Protein structure comparison is a fundamental problem for structural genomics, with applications to drug design, fold prediction, protein clustering, and evolutionary studies. Despite its importance, there are very few rigorous methods and widely accepted similarity measures known for this problem. In this paper we describe the last few years of developments on the study of an emerging measure, the contact map overlap (CMO), for protein structure comparison. A contact map is a list of pairs of residues which lie in three-dimensional proximity in the protein's native fold. Although this measure is in principle computationally hard to optimize, we show how it can in fact be computed with great accuracy for related proteins by integer linear programming techniques. These methods have the advantage of providing certificates of near-optimality by means of upper bounds to the optimal alignment value. We also illustrate effective heuristics, such as local search and genetic algorithms. We were able to obtain for the first time optimal alignments for large similar proteins (about 1,000 residues and 2,000 contacts) and used the CMO measure to cluster proteins in families. The clusters obtained were compared to SCOP classification in order to validate the measure. Extensive computational experiments showed that alignments which are off by at most 10% from the optimal value can be computed in a short time. Further experiments showed how this measure reacts to the choice of the threshold defining a contact and how to choose this threshold in a sensible way.

Algorithms↗

PubMedDate not supplied

Homosexuality and HIV/AIDS stigma in Jamaica.

This paper reports on a study of the relationship of homophobia to HIV/AIDS-related stigma in Jamaica. Ethnography, key informant interviews and focus groups were used to gather data from a sample of 33 male and female adults during the summer of 2003. The sample included health and social service providers, HIV positive men and women, and men and women with same sex partners in urban and rural Jamaica. A strong and consistent relationship between homophobia and HIV/AIDS-related stigma was reported, but the relationship varied according to geographic location, social class, gender, and skin colour (complexion)-to the extent that this coincided with class. Stigma against people living with HIV/AIDS and homosexuality was implicated in low levels of use of HIV testing, treatment and care services and the reluctance of HIV positive people to reveal their serostatus to their sexual partners. Data reveal a pressing need for anti-stigma measures for both homophobia and HIV/AIDS, and for training for health and human service professionals.

Adult↗

PubMedDate not supplied

Sexual stigma and sympathy: attitudes toward persons living with HIV in Jamaica.

As the number of persons living with HIV continues to increase in Jamaica, attitudes and values become more important. This study aimed to examine the attitudes of university students in Jamaica toward persons living with HIV, including homosexual men, heterosexual men, women sex workers, other women, and children. One thousand two hundred and fifty-two students were surveyed between June 2001 and February 2002 using a 193-item questionnaire measuring a variety of HIV-related knowledge, attitudinal and behavioural items. Less than half of students reported sympathetic attitudes toward homosexual men or women sex workers living with HIV while a majority reported generally sympathetic attitudes toward heterosexual men and non-sex worker women living with the disease. Predictors of sympathy varied by target group. Male students were significantly less likely to report sympathy for homosexual men than for any other group. Spirituality was associated with sympathy for homosexual men and women sex workers, but not for the remaining two groups. Findings suggest that levels of negative attitudes are high in Jamaica and warrant attention to both individual and societal-level actions and interventions. In addition, messages and interventions must be targeted, recognizing both the differences in level of sympathy expressed toward different groups and predictors of sympathy across the groups.

Cultural Characteristics↗