Daniel H Rogers

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3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, E.C. 1.1.1.34), the major rate-limiting enzyme of the sterol biosynthetic pathway, was studied in ileal epithelial cells isolated in a villus-to-crypt gradient according to Weiser (Weiser, M. M. 1973. J. Biol. Chem, 248:2536-2541). Alkaline phosphatase (E.C. 3.1.3.1) served as a marker for(More)
Clinical studies suggest that carcinoma of the pancreas may be more common in patients with chronic diabetes mellitus. To examine the effect of diabetes on growth of pancreatic carcinoma, 5 X 10(5) cultured hamster H2T pancreatic carcinoma cells were implanted into the cheek pouches of streptozocin-diabetic and nondiabetic Syrian hamsters. Tumor size and(More)
3-Hydroxy-3-methylglutaryl-CoA reductase (NADPH) was solubilized with polyoxyethylene ether (Brij) W-1 from a heavy-membrane fraction, sedimented at 16000 X g from a cell-free homogenate of four-day-old, dark-grown radish seedlings (Raphanus sativus L.). Approximately 350-fold purification of the solubilized enzyme activity was achieved by (NH4)2SO4(More)
Sodium/chloride cotransport carrier is known to be involved in transepithelial fluid absorption and secretion in various tissues. Recent studies indicate that Na,K,2Cl cotransport carrier also exists in the choroid plexus cells and inhibition of the carrier alters ionic composition of the choroidal tissue. In this study, we report the effects of large dose(More)
Squalene synthase (SQase) catalyzes the condensation of two molecules of farnesyl diphosphate (FPP) to form presqualene diphosphate (PSPP) and the subsequent rearrangement and NADPH-dependent reduction of PSPP to squalene (SQ). These reactions are the first committed steps in cholesterol biosynthesis. When recombinant SQase was incubated with FPP in the(More)
Adenocarcinoma of the exocrine pancreas in man is associated with a high incidence of diabetes mellitus. Hyperglycemia in humans with pancreatic cancer is presumed to be caused by destruction of islets of Langerhans with a resultant impairment in pancreatic insulin secretion. This hypothesis was tested in an animal model of exocrine pancreatic cancer.(More)
Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as novel inhibitors of raf kinase, a key mediator in the ras signal transduction pathway. Structure-activity relationships were established, and the potency of the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial synthesis approach enabled the identification(More)