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Recent studies have demonstrated that the pregnane X receptor (PXR) is a key regulator of cytochromes P450 3A (e.g. CYP3A4 in human) gene expression. As a result, activation of PXR may lead to CYP3A4 protein over-expression. Because induction of CYP3A4 could result in clinically important drug drug interactions, there has been a great interest in reducing(More)
Bradykinin (BK) is an important mediator in several inflammatory and vascular diseases that acts in part via induction of cyclooxygenase-2 (COX-2). The mechanisms involved in BK-mediated COX-2 induction are unclear. Here we characterized the transcriptional mechanisms involved in human pulmonary artery smooth muscle cells. BK stimulated the activity of a(More)
Phospholipase A2 (Naja mocambique) catalyzed release of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) from phospholipids of isolated human platelets. The amount of EETs released by phospholipase A2 measured by gas chromatography/mass spectrometry (GC/MS) was 4.3 +/- 0.9 pmol/10(6) platelets. No EETs were detected when(More)
Despite evidence that DNA topoisomerase I is required to relieve torsional stress during DNA replication and transcription, yeast strains with a top1 null mutation are viable and display no gross defects in DNA or RNA synthesis, possibly because other proteins provide overlapping functions. We isolated mutants whose inviablility or growth defect is relieved(More)
Bradykinin (BK) is a potent neutrophil chemotractant, proinflammatory mediator, and angiogenic factor, which acts through G protein-coupled receptors (GPCRs). Here we studied the mechanisms involved in IL-8 generation by BK in human airway smooth muscle cells focusing on the transcription factors involved and role of endogenous prostanoids in transcription(More)
In search of water-soluble artemisinin derivatives that are more stable than sodium artesunate, over 30 derivatives containing an amino group (compounds 3-5) were synthesized and tested in mice. All products tested (except 5a and 5b) are the beta isomers. These basic compounds combined with organic acids (oxalic acid, maleic acid, etc. ) to yield the(More)
BACKGROUND Platelets (PLTs) stored at 22°C accumulate microparticles and biologic response modifiers (BRMs) that induce inflammatory reactions in transfusion recipients. However, soluble BRMs are fully diluted in the recipient's blood circulation. The mechanisms by which BRMs exert their effects have not been elucidated. The objectives of this study were to(More)
Acute promyelocytic leukemia (APL) is characterized by typical morphological manifestation, t(15;17) translocation and active response to all-trans retinoic acid (ATRA) in the great majority of patients. However, a subset of APL cases may present atypical phenotypic, cytogenetic or molecular features at different stages of the disease. The biological and(More)
Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of(More)
Lung cancer is the leading cause of cancer death worldwide. The majority of patients is diagnosed too late for curative treatment. There is an urgent need for a noninvasive test to identify early lung cancer. Although levels of circulating cell-free DNA in plasma or serum are higher in patients with lung cancer than in healthy controls, it is not yet clear(More)