LC-HR/MS offers unique opportunities for time-sensitive clinical analysis of blood samples from intoxicated patients and for comprehensive screening in a wide range of situations and materials. While the identification is not as definitive as that obtained by conventional fragmentation MS, the presumptive identification can be confirmed later with standards and spectral library matches. Optimum utilization of the presumptive diagnosis requires close collaboration between the laboratory analysts and their clinical counterparts.

Existing amphetamines immunoassays unevenly detect amphetamine-like drugs, particularly in the 2C, piperazine, and β-keto classes. Computational similarity methods perform well in predicting cross-reactivity and can help prioritize testing of additional compounds in the future.

Abstract-To investigate the molecular mechanisms involved in the estrogen-dependent control of plasminogen activator inhibitor-1 (PAI-1) gene expression in vascular cells, we compared the transactivation properties of estrogen receptors (ER␣ and ER␤) in regulating the activity of a human PAI-1 promoter reporter construct in transfected bovine aortic endothelial cells (BAECs). ER␣ increased PAI-1 promoter activity in BAECs by an estrogen-dependent mechanism, whereas ER␤ suppressed PAI-1 promoter activity by an estrogen-independent mechanism. The suppressive activity of ER␤ was dominant over the inductive activity of ER␣. Mutation of a putative estrogen response element (ERE) located at position Ϫ427 in the proximal promoter abolished the ER␣ action without influencing the suppressive effects of ER␤. Mutation of either AP1-like site did not eliminate the ER␣ or ER␤ actions at the PAI-1 promoter, suggesting that other promoter elements are involved in these responses. These mutations significantly reduced the Ϫ3.4kbp PAI-1 promoter response to serum. We concluded that ER␣ and ER␤ exert differential effects on the PAI-1 promoter activity in transfected BAECs. ER␣ activated the PAI-1 promoter through a proximal ERE (Ϫ427) and possibly additional EREs located within the PAI-1 promoter, whereas ER␤ suppressed the promoter construct via an unidentified mechanism. This is the first demonstration of the differential regulation of a vascular gene promoter by ER␣ and ER␤. Key Words: estrogen receptors Ⅲ plasminogen activator inhibitor-1 promoter Ⅲ estrogen response element Ⅲ bovine aortic endothelial cell