Prevalence and correlates of HIV infection among young injection drug users in San Francisco

OBJECTIVE: We assessed the prevalence of HIV infection and associated risk behaviors among street-recruited young injection drug users (IDUs) in San Francisco. METHODS: In a cross-sectional study, 304 young (age <30 years) IDUs with a history of injecting in the previous 30 days were interviewed and tested for antibodies to HIV. Analyses assessing independent associations with HIV infection were limited to males only, due to the low number of infections in women. RESULTS: The prevalence of HIV infection was 5.3% overall but was highly stratified by gender and sexual preference (15.6% among homosexual/bisexual men vs. heterosexual men) and recruitment neighborhood (18% in the Polk Street area). Of 16 HIV infections, 14 (88%) were in males. Factors independently associated with HIV infection in males included sexual preference (homosexual/bisexual vs. heterosexual: adjusted odds ratio [AOR], 7.5; 95% confidence interval [CI], 1.5-36.6), recruitment neighborhood (Polk Street neighborhood vs. other neighborhoods: AOR, 4.8; 95% CI, 1.4-16.7), and duration of residence in San Francisco (>or=1 year vs. <1 year: AOR, 11.8; 95% CI, 1.4-95.8). CONCLUSIONS: The prevalence of HIV infection was highest among male IDUs who have sex with men. The strong associations between HIV infection and sexual orientation and HIV infection and recruitment locale suggest that risk may be attributable largely to sexual risk. In addition to successful prevention efforts aimed at reducing needle-associated risk, current intervention models aimed at young IDUs should target high-risk neighborhoods and emphasize sexual risk reduction measures, in particular among men who have sex with men.     

Interleukin-1 and tumor necrosis factor receptor signaling is not required for bacteria-induced osteoclastogenesis and bone loss but is essential for protecting the host from a mixed anaerobic infection

Bacterial infection causes significant morbidity, mediated in part by the up-regulation of inflammatory cytokines. Cytokine induction is thought to stimulate osteolysis in conditions such as periodontal disease and otitis media. To establish the relative importance of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in mediating the response to a mixed anaerobic infection, we used an in vivo model in which the dental pulp was inoculated with six anaerobic pathogens, in mice with functional deletions of receptors to IL-1 (IL-1RI(-/-)), TNF (TNFRp55(-/-)-p75(-/-)), or both (TNFRp55(-/-)-IL-1RI(-/-)). Polymorphonuclear and mononuclear phagocyte recruitment occurred to the greatest extent in TNFRp55(-/-)-IL-1RI(-/-) mice, and to a lesser extent in IL-1RI(-/-) or TNFRp55(-/-)-p75(-/-) mice, and the least in wild-type mice, demonstrating that recruitment of these phagocytes is not dependent on IL-1 or TNF receptor signaling. A similar pattern was observed for bacterial penetration into host tissue. Because it had recently been reported that TNF played a critical role in mediating lipopolysaccharide-induced bone loss, we anticipated that mice with targeted deletions of TNFRp55(-/-) would have reduced osteoclastogenesis. Surprisingly, osteolytic lesion formation was greatest in animals lacking TNF and/or IL-1 receptors. These results indicate that IL-1 or TNF receptor signaling is not required for bacteria-induced osteoclastogenesis and bone loss, but does play a critical role in protecting the host against mixed anaerobic infections.     

Monocyte chemoattractant protein 1 and interleukin-8 production in mononuclear cells stimulated by oral microorganisms.

Chemokines are a family of low-molecular-weight proinflammatory cytokines that stimulate recruitment of leukocytes. The chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) are relatively specific chemoattractants for neutrophils and monocytes, respectively. Chemokine expression contributes to the presence of different leukocyte populations observed in normal and pathologic states. In the present studies, peripheral blood mononuclear cells (PBMC) were stimulated by microbes (Candida albicans, Streptococcus mutans, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) selected based upon their importance as oral pathogens. IL-8 and MCP-1 gene expression and protein release were determined by Northern blot (RNA blot) analysis and enzyme-linked immunosorbent assay. C. albicans, P. gingivalis, and A. actinomycetemcomitans induced high levels of production of both MCP-1 and IL-8. S. mutans was a strong inducer of MCP-1, but it did not stimulate significant production of IL-8. C. albicans, S. mutans, and A. actinomycetemcomitans were 500 to 5,000 times more potent than P. gingivalis in terms of MCP-1 production. In general, the microbe-to-PBMC ratios required for maximum gene expression of MCP-1 were lower than those for IL-8. However, for actual protein release of MCP-1 versus IL-8, differences in the effects of various microbe concentrations were observed only for A. actinomycetemcomitans. These results demonstrate that different oral pathogens induce specific dose-dependent patterns of chemokine gene expression and release. Such patterns may help explain the immunopathology of oral infections, particularly with regard to inflammatory leukocyte recruitment.     

Serum creatine kinase activity following forearm flexion isometric exercise

Summary The purpose of this study was to 1) compare serum creatine kinase (CK) activity following two forearm flexion isometric exercise regimens differing in work to rest ratio, and 2) examine the CK response to a repeated bout of isometric exercise. Eleven males were tested on two sessions (bouts) spaced 1 week apart. For bout 1, five subjects (group A) performed a forearm flexion isometric exercise consisting of 40 10-s maximal contractions with 20-s inter-trial rests (1020), while six (group B) performed 40 maximal 10-s contractions with 5-s inter-trial rests (105). The increase in serum CK activity following the 1020 exercise (143%) was significantly greater than that following the 105 exercise (52%). The 1020 exercise was also associated with greater tension generation over trials. One week later, both groups performed a bout of 1020 exercise. A substantial reduction in the serum CK response was found following this second bout. The data suggest that for bout 1 the isometric exercise associated with the greater overall tension levels resulted in the greater CK response. However, when the 1020 exercise was repeated 1 week later, a substantial reduction in the CK response was found which was unrelated to the tension generated.This study was supported by a University Faculty Research Grant No. 2-03021     

A microsatellite-based,physically anchored linkage map for the gray,short-tailed Opossum (<Emphasis Type="Italic">Monodelphis domestica</Emphasis>)

The genome of the gray, short-tailed opossum, Monodelphis domestica, will be the first of any marsupial to be fully sequenced. The utility of this sequence will be greatly enhanced by construction and integration of detailed genetic and physical maps. Therefore, it is important to verify the unusual recombinational characteristics that were suggested by the ‘first-generation’ M. domestica linkage map; specifically, very low levels of recombination and severely reduced female recombination, both of which are contrary to patterns in other vertebrates. We constructed a new linkage map based on a different genetic cross, using a new and much larger set of map markers, and physically anchored and oriented the linkage groups onto chromosomes via fluorescence in-situ hybridization mapping. This map includes 150 loci in eight autosomal linkage groups corresponding to the eight autosome pairs, and spans 86–89% of the autosomal genome. The sex-averaged autosomal map covers 715 cM, with a full-length estimate of 866 cM; the shortest full-length linkage map reported for any vertebrate. The sex-specific maps confirmed severely reduced female recombination in all linkage groups, and an overall F/M map ratio =  0.54. These results greatly extend earlier findings, and provide an improved microsatellite-based linkage map for this species. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.