David R. Jones

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NF-kappaB is responsible for upregulating gene products that control cell survival. In this study, we demonstrate that SIRT1, a nicotinamide adenosine dinucleotide-dependent histone deacetylase, regulates the transcriptional activity of NF-kappaB. SIRT1, the mammalian ortholog of the yeast SIR2 (Silencing Information Regulator) and a member of the Sirtuin(More)
This review concentrates on the physiological responses, and their control, in freely diving birds and mammals that enable them to remain submerged and sometimes quite active for extended periods of time. Recent developments in technology have provided much detailed information on the behavior of these fascinating animals. Unfortunately, the advances in(More)
An in vitro model is proposed to account for the clinically observed inhibition of cytochrome P450 (CYP) 3A that results from administration of clarithromycin, fluoxetine, or diltiazem. Rates for loss of CYP3A4 enzymatic activity resulting from metabolic intermediate complex formation and the concentration dependencies thereof were determined in vitro for(More)
POSSUM, a Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, is described. This system has been devised from both a retrospective and prospective analysis and the present paper attempts to validate it prospectively. Logistic regression analysis yielded statistically significant equations for both mortality and(More)
We used human liver microsomes (HLMs) and recombinant cytochromes P450 (P450s) to identify the routes of efavirenz metabolism and the P450s involved. In HLMs, efavirenz undergoes primary oxidative hydroxylation to 8-hydroxyefavirenz (major) and 7-hydroxyefavirenz (minor) and secondary metabolism to 8,14-dihydroxyefavirenz. The formation of(More)
OBJECTIVE To assess the relative contribution of intestinal and hepatic CYP3A inhibition to the interaction between the prototypic CYP3A substrates midazolam and clarithromycin. METHODS On day 1, 16 volunteers (eight men and eight women; age range, 20 to 40 years; weight range, 45 to 100 kg) received simultaneous doses of midazolam intravenously (0.05(More)
The capabilities of cytochrome P4503A4 (CYP3A4), CYP3A5, and fetal hepatic microsomes containing CYP3A7 to metabolize midazolam were investigated using human hepatic microsomes and purified CYP3A4 and CYP3A5. Under initial rate conditions and high substrate concentration (400 microM midazolam), variability among eighteen human liver microsomal samples was(More)
The human cytochromes P450 (P450) CYP3A contribute to the biotransformation of 50% of oxidatively metabolized drugs. The predominant hepatic form is CYP3A4, but recent evidence indicates that CYP3A5 contributes more significantly to the total liver CYP3A than was originally thought. CYP3A7 is the major fetal form and is rarely expressed in adults. To(More)
Heart rates of northern elephant seals diving at sea and during apnoea on land were monitored to test whether a cardiac response to submergence is an important factor in their ability to make repetitive, long-duration dives. Seven juvenile northern elephant seals were captured at Año Nuevo, CA, instrumented and translocated to release sites around Monterey(More)
Verapamil inhibition of CYP3A activity results in many drug-drug interactions with CYP3A substrates, but the mechanism of inhibition is unclear. The present study showed that verapamil enantiomers and their major metabolites [norverapamil and N-desalkylverapamil (D617)] inhibited CYP3A in a time- and concentration-dependent manner by using pooled human(More)