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Biomedical subjects

B Frazier

Publications and source records attributed to B Frazier.

8 recordsLinked to original sources

Patients with HIV/AIDS: physicians' knowledge, attitudes, and referral practices.

BACKGROUND: This study investigated Massachusetts family physicians' current care and referral practices with respect to HIV/AIDS patients and examined actors that might influence family physicians in referring these patients to specialists. Educational opportunities for physicians with regard to HIV were also examined. METHODS: In 1994, a 2-page survey was mailed to the 468 members of the Massachusetts Academy of Family Physicians. The survey questionnaire examined such factors as whether the respondents were teaching or nonteaching, rural or urban; number of years since medical school or residency training; and knowledge and attitudes with regard to HIV/AIDS patients. The data were analyzed using Student's t test, chi-square, and correlation analysis. RESULTS: Usable responses were returned by 281 (60%) of the physicians surveyed. Of these, 65% reported having HIV patients in their practice, and 46% reported having AIDS patients was being managed alone by 53% of these physicians, and 11% managed their patients with AIDS. Physicians providing care for HIV/AIDS patients were more likely to be practicing in urban locations, have three or more HIV/AIDS patients in their practice, or recently graduated from residency. Additionally, they were more likely to be involved in residency teaching programs. Those who did not care for HIV/AIDS patients felt less knowledgeable about HIV/AIDS care, and felt that they had no time in their practice to care for this population of patients. Physicians with HIV patients learn more about HIV care from their colleagues than those without HIV patients. CONCLUSIONS: Family physicians are increasingly seeing HIV/AIDS patients in their offices. The majority are continually caring for these patients, either by themselves or co-managing their care with a specialist. Local CME programs relying on colleagues and community resources to discuss management of these patients may be one of the best ways of ensuring that increasing numbers of family physicians obtain the appropriate knowledge to care for these patients within their own communities.

Acquired Immunodeficiency Syndrome↗

Genetic and linguistic differentiation in the Americas.

The relationship between linguistic differentiation and evolutionary affinities was evaluated in three tribes of the Pacific Northwest. Two tribes (Nuu-Chah-Nulth and Bella Coola) speak Amerind languages, while the language of the third (Haida) belongs to a different linguistic phylum--Na-Dene. Construction of a molecular phylogeny gave no evidence of clustering by linguistic affiliation, suggesting a relatively recent ancestry of these linguistically divergent populations. When the evolutionary affinities of the tribes were evaluated in terms of mitochondrial sequence diversity, the Na-Dene-speaking Haida had a reduced amount of diversity compared to the two Amerind tribes and thus appear to be a biologically younger population. Further, since the sequence diversity between the two Amerind-speaking tribes is comparable to the diversity between the Amerind tribes and the Na-Dene Haida, the evolutionary divergence within the Amerind linguistic phylum may be as great as the evolutionary divergence between the Amerind and Na-Dene phyla. Hence, in the New World, rates of linguistic differentiation appear to be markedly faster than rates of biological differentiation, with little congruence between linguistic hierarchy and the pattern of evolutionary relationships.

Alaska↗

Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization, and viral infection.

The structure of CR2, the human C3d,g/EBV receptor (CR2/CD21) consists of 15 or 16 60-70 amino acid repeats called short consensus repeats (SCRs) followed by a transmembrane and a 34-amino acid intracytoplasmic domain. Functions of CR2 include binding the human complement component C3d,g when it is covalently attached to targets or cross-linked in the fluid phase. In addition, CR2 binds the Epstein-Barr virus (EBV) and mediates internalization of EBV and subsequent infection of cells. In order to explore functional roles of the repetitive extracytoplasmic SCR structure and the intracytoplasmic domain of CR2, we have created truncated CR2 (rCR2) mutants bearing serial deletions of extracytoplasmic SCRs and also the intracytoplasmic tail. We then stably transfected these rCR2 mutants into two cell lines, murine fibroblast L cells and human erythroleukemic K562 cells. Phenotypic analysis of these expressed mutants revealed that 1) The C3d,g- and EBV-binding sites are found in the two amino-terminal SCRs of CR2, 2) expression of SCRs 3 and 4 is further required for high affinity binding to soluble cross-linked C3d,g, 3) the intracytoplasmic domain of CR2 is not required for binding C3d,g or EBV but is necessary for internalization of cross-linked C3d,g as well as for EBV infection of cells, 4) monoclonal anti-CR2 antibodies with similar activities react with single widely separated epitopes, and 5) no functional roles can yet be clearly assigned to SCRs 5-15, as rCR2 mutants not containing these SCRs show no major differences from wild-type rCR2 in binding or internalizing cross-linked C3d,g or mediating EBV binding and infection.

Animals↗

Analysis of epitope expression and the functional repertoire of recombinant complement receptor 2 (CR2/CD21) in mouse and human cells.

We transfected human complement receptor 2 (CR2/CD21) cDNA containing eukaryotic expression constructs into CR2-negative mouse L cells and human K562 erythroleukemia cells. We subsequently selected stably transformed cells that expressed human CR2, as assessed by flow microfluorimetry analysis and immunoprecipitation of 125I-labeled surface membranes using the monoclonal anti-CR2 antibody, HB5. Utilizing flow microfluorimetry analysis, epitopes recognized by anti-CR2 mAb HB5, OKB7, B2, and four other anti-CR2 antibodies were detected on CR2 expressing transfectants but not parental cells. In addition, CR2 expressing transfected cells efficiently formed rosettes with sheep erythrocyte intermediates bearing human C3bi and C3d, but not C4b or C3b, consistent with the known ligand specificity of CR2. CR2 containing transfectants were also demonstrated to specifically bind EBV. Infection with EBV of CR2 expressing L cells and K562 cells resulted in mean expression of Epstein-Barr nuclear Ag (EBNA) at 48 h in 0.35% of CR2 expressing L cells and 3.7% of CR2 expressing K562 cells. Parental L cells and K562 cells did not express EBNA after EBV infection. These results indicate that CR2 alone is sufficient to transfer both C and EBV receptor functions to heterologous cells. In addition, expression of EBNA was found to be significantly higher in human K562 than mouse L cells, both expressing the same recombinant receptor. These results suggest that mechanisms other than CR2 binding lead to inefficient EBV infection and/or EBNA synthesis in mouse fibroblasts.

Animals↗

Genomic organization and polymorphisms of the human C3d/Epstein-Barr virus receptor.

The human C3d/Epstein-Barr virus receptor (CR2/CD21) is a 145-kDa protein primarily expressed on mature B lymphocytes. CR2 is a member of the regulators of complement activation (RCA) gene family found on band q32 of chromosome 1. The RCA proteins are characterized by the presence of 60-70 amino acid short consensus repeats (SCR). A full length CR2 cDNA was cloned and used to identify overlapping cosmid genomic clones. Analysis of CR2 exon-intron junctions revealed the presence of three types of exons in the short consensus repeat region of CR2. First, four exons each of which encodes two SCR are present. Five exons encode a single SCR. Six exons encode SCRs which are split in identical positions. The order of these types of exons is in a repeated array of four SCRs, indicating that the contemporary CR2 gene likely evolved from a more primitive gene containing four SCRs. The CR2 full length cDNA clone was used to find restriction fragment length polymorphisms (RFLPs). Restriction enzyme TaqI generated 2.55- and 2.10-kilobase (kb) polymorphic bands. This RFLP was mapped near the exon containing the first two SCRs. HaeIII digestion generated polymorphic bands of 1.45, 1.55, and 1.75 kb. The HaeIII 1.45-kb RFLP band maps near the exon containing the 15th SCR. The TaqI and HaeIII RFLPs will provide tools for the genetic analysis of CR2. The organization of the CR2 gene provides insights into the evolution of human CR2 and the RCA gene family.

Amino Acid Sequence↗