Publications

Although endothelin-1-stimulated contractile force generation by stellate cells is believed to play an important role in hepatic pathophysiology, the molecular signals that mediate this process are incompletely understood. The aim of this study was to test the hypothesis that myosin mediates the contractile force generated by stellate cells in response to endothelin-1. Contractile force generation by primary and immortalized stellate cells was directly and quantitatively measured. Myosin phosphorylation and reorganization, and actin stress fiber formation were investigated in immortalized stellate cells. Endothelin-1 stimulated a rapid and robust generation of contractile force by primary and immortalized stellate cells with a similar dose dependence. Myosin phosphorylation, actin stress fiber assembly, and reorganization of myosin to stress fibers were induced by concentrations of endothelin-1 that also stimulated stellate cell contraction. BQ-123, a selective endothelin receptor antagonist, inhibited myosin phosphorylation and contractile force generation. Y-27632, which selectively inhibits rho-associated kinase, also blocked endothelin-1-stimulated myosin phosphorylation and contractile force generation with a similar dose dependence. These results suggest that endothelin-1-stimulated contractile force generation by stellate cells is mediated by myosin.

Cannabinoids, including smoked marijuana and delta9-tetrahydrocannabinol (THC) (dronabinol, Marinol), have been used to treat human immunodeficiency virus-1 (HIV)-associated anorexia and weight loss. Concerns have been raised, however, that these compounds might have adverse effects on the immune system of subjects with HIV infection. To determine whether such effects occur, the authors designed a randomized, prospective, controlled trial comparing the use of marijuana cigarettes (3.95% THC), dronabinol (2.5 mg), and oral placebo in HIV-infected adults taking protease inhibitor-containing highly active antiretroviral therapy (HAART). Assays of immune phenotype (including flow cytometric quantitation of T cell subpopulations, B cells, and natural killer [NK] cells) and immunefunction (including assays for induced cytokine production, NK cell function, and lymphoproliferation) were performed at baseline and weekly thereafter. On the basis of these measurements and during this short 21-day study period, few statistically significant effects were noted on immune system phenotypes orfunctions in this patient population.

BACKGROUND

Screening mammogram and Pap smear rates are lower for women in underserved racial and ethnic groups, yet may be overestimated due to reliance on patients' self-reports. The purpose of this study was to determine accuracy of self-reports of mammograms and Pap smears in a multiethnic, multilingual population of African American, Latina, Chinese, Filipina, and White women residing in low-income census tracts of Alameda County, California.

METHODS

Following a baseline telephone survey of 1,464 women regarding receipt of mammograms and Pap smears, we examined computerized and written medical records to validate the dates and locations of tests reported by women.

RESULTS

Of 1,464 subjects, 94.9% reported having had a Pap smear, and 87% reported having had a mammogram. For Pap smears, in a subsample of 448 cases, we validated only 69.4% of the women's self-reports, and for mammography, in a subsample of 846 women, we validated only 75.4% of the self-reports. Validation rates differed significantly by ethnicity and site of care for both Pap smears and mammograms.

CONCLUSIONS

Population estimates of breast and cervical cancer screening rates based upon patient self-reports need to be adjusted downward, by as much as one-quarter to one-third, for low-income, ethnic women.