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Carrier-mediated transporters play a critical role in xenobiotic disposition and transporter research is complicated by species differences and their selective tissue expression. The purpose of this study was to generate a comprehensive data set of xenobiotic transporter gene expression profiles in humans and the pre-clinical species mouse, rat, beagle dog(More)
Microarray technology, which allows one to quantitate the expression of thousands of genes simultaneously, has begun to have a major impact on many different areas of drug discovery and development. The question remains of whether microarray analysis and gene expression signature profiles can be applied to the field of toxicology. To date, there are very(More)
To examine species-specific aspects of the induction of absorption, distribution, metabolism and excretion (ADME)-related genes, we used 25 000 gene oligonucleotide microarrays to construct a rodent gene-response compendium that compared hepatic gene expression profiles and developed consensus aryl hydrocarbon receptor (AhR), constitutive androstane(More)
The biological effects of staphylococcal enterotoxins (SE), potentiated by bacterial lipopolysaccharide (LPS), were studied with mice. Control animals survived the maximum dose of either SE or LPS, while mice receiving both agents died. SEA was 43-fold more potent than SEB and 20-fold more potent than SEC1. The mechanism of toxicity was further examined(More)
PURPOSE To describe outcomes in patients undergoing percutaneous biliary drainage to reduce total serum bilirubin level for administration of chemotherapy. MATERIALS AND METHODS A total of 647 consecutive patients underwent percutaneous biliary drainage between September 2001 and December 2008. In 168, the indication for biliary drainage was to decrease(More)
The development of new protein subunit vaccines has stimulated the search for improved adjuvants to replace traditional aluminum-containing products. We investigated the adjuvant effects of a synthetic Toll-like receptor 4 (TLR4) agonist on vaccine efficacy in an experimental model of toxic shock syndrome. The TLR4 agonist E6020 has a simplified structure(More)
Oligonucleotide microarrays were used to study the variability of pharmacokinetics and drug metabolism (PKDM)-related gene expression in 75 normal human livers. The objective was to define and use absorption, distribution, metabolism and excretion (ADME) gene expression variability to discern co-regulated genes and potential surrogate biomarkers of(More)
Staphylococcal exotoxins are virulence determinants in Staphylococcus aureus arthritis and septicemia. To assess the utility of enterotoxins as vaccine candidates for these diseases, a genetically modified staphylococcal enterotoxin A (SEA) that lacks superantigenic properties was used. Mice immunized with recombinant (r) SEA had significantly longer(More)
All bacterial superantigens use common structural strategies to bind to major histocompatibility complex class II receptors, while binding the T cell antigen receptor in different ways. Overstimulation of the immune response is responsible for the acute pathological effects, while reactivation of developmentally silenced T cells might result in autoimmune(More)