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At least 1,441 records · Page 80Linked to original sources
PubMed1993

Development and preliminary application of a simple assay of S-mephenytoin 4-hydroxylase activity in human liver microsomes.

We have developed a simple HPLC assay to measure the activity of S-mephenytoin 4-hydroxylase in human liver microsomes, and have assessed its practical applicability by determining the kinetic parameters of the enzyme in 10 different human liver samples. The recovery of 4-hydroxymephenytoin and phenobarbital (the internal standard) after the precipitation of microsomal protein was almost complete, and the coefficients of variation for the intra- and interassay measurement of S-mephenytoin 4-hydroxylase activity were < 6.4 and 8.0%, respectively. Eadie-Hofstee plots for the formation of 4-hydroxymephenytoin gave a straight line for all of the 10 samples studied. There was large interindividual variability in the kinetic parameters estimated: 4.6- (36 to 166 microM), 11.8- (0.9 to 10.6 nmole/mg protein/h) and 30.1- times (0.10 to 3.01 microliters/mg protein/min) for Km, Vmax and Vmax/Km, respectively. The mean (+/- SD) Km, Vmax and Vmax/Km were 72.4 +/- 40.4 microM, 4.23 +/- 2.88 nmole/mg protein/h and 1.33 +/- 1.02 microliters/mg protein/min, respectively. Thus, the assay was sufficiently accurate and reproducible to permit estimation of the kinetic parameters of S-mephenytoin 4-hydroxylase in human liver microsomes, and it appears to be applicable to an in vitro study of the possible involvement of S-mephenytoin-type oxidation polymorphism in drug metabolism.

Aryl Hydrocarbon Hydroxylases↗
PubMed2003

Analysis of higher-order neuronal interactions based on conditional inference.

Higher-order neural interactions, i.e., interactions that cannot be reduced to interactions between pairs of cells, have received increasing attention in the context of recent attempts to understand the cooperative dynamics in cortical neural networks. Typically, likelihood-ratio tests of log-linear models are being employed for statistical inference. The parameter estimation of these models for simultaneously recorded single-neuron spiking activities is a crucial ingredient of this approach. Extending a previous investigation of a two-neuron system, we present here the general formulation of an exact test suited for the detection of positive higher-order interactions between m neurons. This procedure does not require the estimation of any interaction parameters and additionally optimizes the test power of the statistical inference. We apply the approach to a three-neuron system and show how second-order and third-order interactions can be reliably distinguished. We study the performance of the method as a function of the interaction strength.

Action Potentials↗
PubMed1986

Compartment model approaches for estimating the parameters of a chronic disease process under changing risk factor exposures.

Compartment model approaches have been proposed for the analysis of the age incidence of specific types of cancer. These models represented the age increases in incidence as the result of a compound hazard function where individual level risks were described by the Weibull hazard function and where the population level hazard rate is a continuous mixture of the Weibull hazards. These formulations assumed that the mixing function, which described differences in risk due to different exposure histories, was constant after the age at which the model was first applied. In this paper we show how the mixing distribution can be allowed to change with time reflecting changing exposures. The model is fitted to U.S. lung cancer mortality data where for recent male cohorts there appear to be changing patterns of exposure possibly related to recent declines in male smoking. The implications for future lung cancer mortality trends in the United States are discussed.

Adult↗