Precision-cut tissue chips as an in vitro toxicology system.

Precision-cut tissue slices mimic specific organ toxicity because normal cellular heterogeneity and organ architecture are retained. To optimize the use of the smaller tissues of the mouse and to establish easy assays for tissue viability, a tissue chip based system was used to generate large numbers of samples from a single organ. Iodoacetamide (IAM) was used as a model toxicant and assays for intracellular potassium (normalized to DNA content) were used to establish viability and toxicant susceptibility. Thereafter, assays that were more rapid and specific were pursued. Lysates from tissues incubated in 6-carboxyfluorescein fluoresced proportionately to concentrations of IAM, indicating disruption of cellular membranes. Similarly, FURA-2, a probe applied to lysates to measure calcium levels, fluoresced proportionately to IAM dosage. Monobromobimane, a fluorescent sulfhydryl probe, displayed a decrease in fluorescent intensity at higher IAM challenge-a finding confirmed with an absorbance assay with Ellman's reagent. Importantly, the number of samples per organ/mouse was increased at least threefold and a significant time reduction per analysis was realized.

High-risk sexual behavior and knowledge of HIV antibody status in the San Francisco City Clinic Cohort.

To evaluate the effectiveness of human immunodeficiency virus (HIV) testing and counseling among homosexual and bisexual men participating in the San Francisco City Clinic Cohort, compared behavioral data from 181 men who learned their HIV antibody status between 1985 and 1987 with data from 128 men who were tested but declined to receive their results. Overall, significant declines in risk indices for unprotected receptive and insertive anal intercourse occurred between 1983-1984 and 1986-1987, but these declines were independent of both knowledge of HIV status and actual serostatus. Those who chose to learn their HIV status were also no more likely to report depression or to learn their HIV status were also no more likely to report depression or anxiety subsequent to testing. Regression analyses showed no relationship between length of time since learning one's HIV status, mental health symptoms, and the persistence of high-risk behavior in 1986-1987. Although these results do not negate the value of HIV testing and counseling, they suggest that other motivating factors such as frequent access to risk-reduction information may provide sufficient impetus for behavioral change.