Publications

OBJECTIVE

To identify current colorectal cancer (CRC) screening practices and barriers to screening in the Latino, Vietnamese, and non-Latino white populations.

METHODS

We conducted a telephone survey of Latino, non-Latino white, and Vietnamese individuals living in San Jose, California. We asked about demographics, CRC screening practices, intentions to be screened, and barriers and facilitators to screening.

RESULTS

Seven hundred and seventy-five individuals (40% white, 29.2% Latino, and 30.8% Vietnamese) completed the survey (Response Rate 50%). Overall, 23% of respondents reported receipt of fecal occult blood test (FOBT) in the past year, 28% reported sigmoidoscopy (SIG) in the past 5 years, and 27% reported colonoscopy (COL) in the past 10 years. Screening rates were generally lower in Latinos and Vietnamese. Vietnamese were less likely than whites to have had SIG in the past 5 years (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09 to 0.72), but ethnicity was not an independent predictor of FOBT or COL. Only 22% of Vietnamese would find endoscopic tests uncomfortable compared with 79% of whites (P <.05). While 21% of Latinos would find performing an FOBT embarrassing, only 8% of whites and 3% of Vietnamese felt this way (P <.05). Vietnamese were more likely than whites to plan to have SIG in the next 5 years (OR, 2.24; 95% CI, 1.15 to 4.38), but ethnicity was not associated with planning to have FOBT or COL.

CONCLUSIONS

Rates of CRC screening are lower in ethnic minority populations than in whites. Differences in attitudes and perceived barriers suggest that culturally tailored interventions to increase CRC screening will be useful in these populations

The mechanism of AF remains controversial as support still exists for multiple wavelets, "mother rotor," and focal sources. These mechanisms need not be mutually exclusive. For example, the mother rotor hypothesis may not be distinct form the focal AF, if the rotor is of small size (ie, microre-entry). With the development of several animal models to study AF, along with improving technologies and mapping techniques, a further understanding of the pathophysiology of AF is being gained. Each animal model has unique electrophysiological and structural abnormalities, and one may not be able to generalize from one model to the next. It is likely that there is not one mechanism for all AF, but that there are substrate-specific mechanisms, and that AF may be comprised of several different mechanisms.

The binding of bacteria and platelets may play a central role in the pathogenesis of infective endocarditis. Platelet binding by Streptococcus gordonii strain M99 is predominantly mediated by the 286-kDa cell wall-anchored protein GspB. This unusually large protein lacks a typical amino-terminal signal peptide and is translocated from the cytoplasm via a dedicated transport system. A 14-kb segment just downstream of gspB encodes SecA2 and SecY2, two components of the GspB-specific transport system. The downstream segment also encodes several putative glycosyl transferases that may be responsible for the posttranslational modification of GspB. In this study, we compared the abilities of M99 and two GspB(-) mutant strains to bind various lectins. GspB was found to have affinity for lectins that bind N-acetylglucosamine. We also examined variant forms of GspB that lack a carboxy-terminal cell wall-anchoring domain and thus are free of covalent linkage to cell wall peptidoglycan. Like native GspB, these truncated proteins appear to be heavily glycosylated, as evidenced by migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass >100 kDa in excess of the predicted mass, negligible staining with conventional protein stains, and reactivity with hydrazide following periodate oxidation. Furthermore, analysis of the carbohydrate associated with the GspB variants by high-pH anion-exchange chromatography revealed the presence of approximately 70 to 100 monosaccharide residues per GspB polypeptide (primarily N-acetylglucosamine and glucose). Analysis of GspB in protoplasts of secA2 or secY2 mutant strains, which do not export GspB, indicates that GspB is glycosylated in the cytoplasm of these strains. The combined data suggest that the native GspB is a glycoprotein and that it may be glycosylated prior to export.

Virions of the type 1 human immunodeficiency virus (HIV-1) can enter target cells by fusion or endocytosis, with sharply different functional consequences. Fusion promotes productive infection of the target cell, while endocytosis generally leads to virion inactivation in acidified endosomes or degradation in lysosomes. Virion fusion and endocytosis occur equally in T cells, but these pathways have been regarded as independent because endocytosis of HIV virions requires neither CD4 nor CCR5/CXCR4 engagement in HeLa-CD4 cells. Using flow cytometric techniques to assess the binding and entry of green fluorescent protein (GFP)-Vpr-labeled HIV virions into primary peripheral blood mononuclear cells, we have found that HIV fusion and endocytosis are restricted to the CD4-expressing subset of cells and that both pathways commonly require the initial binding of HIV virions to surface CD4 receptors. Blockade of CXCR4-tropic HIV virion fusion with AMD3100, a CXCR4-specific entry inhibitor, increased virion entry via the endocytic pathway. Similarly, inhibition of endosome acidification with bafilomycin A1, concanamycin A, or NH(4)Cl enhanced entry via the fusion pathway. Although fusion remained dependent on CD4 and chemokine receptor binding, the endosome inhibitors did not alter surface expression of CD4 and CXCR4. These results suggest that fusion in the presence of the endosome inhibitors likely occurs within nonacidified endosomes. However, the ability of these inhibitors to impair vesicle trafficking from early to late endosomes in some cells could also increase the recycling of these virion-containing endosomes to the cell surface, where fusion occurs. In summary, our results reveal an unexpected, CD4-mediated reciprocal relationship between the pathways governing HIV virion fusion and endocytosis.

PURPOSE OF REVIEW

The prevalence of lipodystrophy in HIV infection reported in the early literature has varied widely due in part to the different methods used in assessing and defining lipodystrophy in studies. There remains a lack of clarity regarding whether the peripheral lipoatrophy and central lipohypertrophy initially described in HIV infection are a result of separate mechanisms or a single mechanism. We review the current methods used to assess and define lipodystrophy in HIV infection; the prevalence and incidence of lipodystrophy reported in the recent HIV literature; and future directions in elucidating the morphologic changes associated with HIV infection.

RECENT FINDINGS

Different methods of assessing and defining lipodystrophy continue to lead to varying prevalence and incidence rates in recent large cross-sectional and prospective studies. Recent studies that include a predominantly HIV-uninfected comparison group and utilize bi-directional surveys to describe fat loss and fat gain in both peripheral and central body sites suggest that there is an HIV-associated lipoatrophy that affects both peripheral and central sites. In one study that used objective measures to quantify fat such as magnetic resonance imaging, HIV-associated subcutaneous lipoatrophy appeared to predominate when compared with a healthy control group.

SUMMARY

Peripheral and central lipoatrophy affecting subcutaneous fat is emerging as the dominant morphologic change associated with HIV infection when compared with those without known HIV infection. Studies of lipodystrophy in HIV infection should focus on lipoatrophy using direct measures of fat when possible.

At birth, human stratum corneum (SC) displays a near-neutral surface pH, which declines over several days to weeks to months to an acidic pH, comparable to that of adults. Recent studies suggest that an acidic pH is required for normal permeability barrier homeostasis and SC integrity/cohesion. We assessed here the basis for postnatal acidification in the neonatal rat, where SC pH, as measured with a flat surface electrode, declines progressively from near-neutral levels (pH 6.63) on postnatal days 0 to 1 to adult levels (pH 5.9) or even below over the subsequent 7 to 8 d. The postnatal decline in SC pH was paralleled by a progressive activation of a pH-dependent hydrolytic enzyme, beta-glucocerebrosidase. Because SC acidification could not be linked to commonly implicated exogenous factors, such as bacterial colonization, or the deposition of sebaceous gland products. We next assessed whether changes in one or more of three endogenous mechanisms demonstrate postnatal activity changes that contribute to the progressive development of an acidic SC pH. Although the histidine-to-urocanic acid pathway has been implicated in acidification of the adult SC, surface pH is completely normal in histidase-deficient (his/his, Peruvian) mice, ruling out a requirement for this mechanism. In contrast, when sodium/hydrogen antiporter-1 (NHE1), which predominantly acidifies membrane domains at the stratum granulosum-SC interface, is inhibited, postnatal acidification of the SC is partially blocked. Likewise, SC secretory phospholipase A2 (sPLA2) activity, measured with a fluorometric assay, is low at birth, but increases progressively (by 66%) over the first 5 d after birth, and inhibition of sPLA2 between days 0 to 1 and days 5 to 6 delays postnatal SC acidification. Together, these results describe a neonatal model, in which the development of an acidic surface pH can be ascribed, in part, to progressive SC acidification by two endogenous mechanisms, namely, sPLA2 and NHE1, which are known to be important for acidification of adult rodent SC. Conversely, the impaired acidification of neonatal SC, which has important functional and clinical consequences, can be explained by the relatively low activities of one or both of these mechanisms at birth.