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Principal components analysis (PCA) is a classic method for the reduction of dimensionality of data in the form of n observations (or cases) of a vector with p variables. Contemporary datasets often have p comparable with or even much larger than n. Our main assertions, in such settings, are (a) that some initial reduction in dimensionality is desirable(More)
Identifying selective inhibitors of cytochrome P450 isoforms is a useful tool in defining the role of individual cytochrome P450s in the metabolism process. In this study, nine chemical inhibitors were selected based on literature data and were examined for their specificity toward cytochrome P450-mediated reactions in human liver microsomes. Furafylline(More)
N-acetyl-p-benzoquinone imine (NAPQI) has been proposed as the toxic metabolite of acetaminophen for the past 10 years, although it has never been detected as an enzymatic oxidation product of acetaminophen. We report (i) direct detection of NAPQI formed as an oxidation product of acetaminophen by cytochrome P-450 and cumene hydroperoxide and (ii) indirect(More)
The cytochrome P450s (CYPs) constitute a superfamily of isoforms that play an important role in the oxidative metabolism of drugs. Each CYP isoform possesses a characteristic broad spectrum of catalytic activities of substrates. Whenever 2 or more drugs are administered concurrently, the possibility of drug interactions exists. The ability of a single CYP(More)
One third of the world's hip fractures are said to occur in Asia, mostly in China. However, there have as yet been no validated studies of hip fracture rates in China. The authors estimated the incidence of hip fractures in Beijing, People's Republic of China, and took several steps to validate the estimates. All 76 Beijing hospitals reported all 1988-1992(More)
Principal components analysis (PCA) is a classical method for the reduction of dimensionality of data in the form of n observations (or cases) of a vector with p variables. Contemporary data sets often have p comparable to, or even much larger than n. Our main assertions, in such settings, are (a) that some initial reduction in dimensionality is desirable(More)
Testosterone, terfenadine, midazolam, and nifedipine, four commonly used substrates for human cytochrome P-450 3A4 (CYP3A4), were studied in pairs in human liver microsomes and in microsomes from cells containing recombinant human CYP3A4 and P-450 reductase, to investigate in vitro substrate-substrate interaction with CYP3A4. The interaction patterns(More)
Previous studies from our laboratories have shown that the metabolism of the cholesterol-lowering drug lovastatin by rat and human liver microsomes occurs primarily at the 6'-position, giving 6' beta-hydroxy- and 6'-exomethylene-lovastatin and that these oxidations are catalyzed by cytochrome P450-dependent monooxygenases. In the present study, the specific(More)