The pharmacokinetics, metabolism, and excretion of cobimetinib, a MEK inhibitor, were characterized in healthy male subjects (n = 6) following a single 20 mg (200 mCi) oral dose. Unchanged cobimetinib and M16 (glycine conjugate of hydrolyzed cobimetinib) were the major circulating species, accounting for 20.5% and 18.3% of the drug-related material in plasma up to 48 hours postdose, respectivel...

Abreu-Martin, Maria T., Andrew A. Palladino, Mary Faris, Nelson M. Carramanzana, André E. Nel, and Stephan R. Targan. Fas activates the JNK pathway in human colonic epithelial cells: lack of a direct role in apoptosis. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G599–G605, 1999.—Fas is expressed constitutively by colonic epithelial cells, and its ligand is expressed by intraepithelia...

Jones, Michael K., Rabiha M. Itani, Hongtao Wang, Morimasa Tomikawa, I. James Sarfeh, Sandor Szabo, and Andrzej S. Tarnawski. Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G1345–G1355, 1999.—Our previous studies demonstrated that ethanol injury triggers the angiogenic response in gastric mu...

I Introduction In recent years, specialists in human–computer interaction (HCI) have come to appreciate the importance of understanding the context in which computer-supported activities take place [1]. Such understanding directly affects design and evaluation by revealing what users are up to and how they might most effectively use a technology. The idea is to gain this understanding before th...

Standley, Paul R., Tamar J. Obards, and Cherie L. Martina. Cyclic stretch regulates autocrine IGF-I in vascular smooth muscle cells: implications in vascular hyperplasia. Am. J. Physiol. 276 (Endocrinol. Metab. 39): E697–E705, 1999.—Vascular smooth muscle cells (VSMC) subjected to acute or chronic stretch display enhanced growth rates in vitro and in vivo. Clinical examples of vascular hyperpla...

The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6mediate...

Here we report the development of a gene-synthesis technology, circular assembly amplification. In this approach, we first constructed exonuclease-resistant circular DNA via simultaneous ligation of oligonucleotides. Exonucleaseand subsequent mismatch cleaving endonuclease–mediated degradation of the resulting ligation mixture eliminated error-rich products, thereby substantially improving gene...

JAMES R. GUM, JR.,1,2 JAMES W. HICKS,3 ANNE-MARIE GILLESPIE,4 ELAINE J. CARLSON,4 LAZLO KÖMÜVES,5 SATYAJIT KARNIK,1 JOE C. HONG,3 CHARLES J. EPSTEIN,4 AND YOUNG S. KIM1,3 1Gastrointestinal Research Laboratory, Department of Veterans Affairs Medical Center, San Francisco 94121; and Departments of 2Anatomy, 3Medicine, 4Pediatrics, and 5Dermatology, University of California at San Francisco, Calif...

The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6mediate...