Michael Ching

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Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving(More)
The inhibitory effects of dihydroquinidine, quinidine and several quinidine metabolites on cytochrome P450 2D6 (CYP2D6) activity were examined. CYP2D6 heterologously expressed in yeast cells O-demethylated dextromethorphan with a mean Km of 5.4 microM and a Vmax of 0.47 nmol/min/nmol. Quinidine and dihydroquinidine both potently inhibited CYP2D6 metabolic(More)
The majority of studies of fetal hepatic elimination have concentrated on the expression and activity of the metabolizing enzymes, but the unique physiologic milieu of the fetal liver should also be considered. The basic structure of the liver is formed by the end of the first trimester. The fetal hepatic circulation differs substantially from that of the(More)
1. Little is known about the comparative plasma protein binding of the antimalarial agents quinine (QN) and its isomer quinidine (QD). We have examined the in vitro binding of QN and QD to albumin, alpha 1-acid glycoprotein, normal human plasma, and maternal and foetal umbilical cord plasma. 2. QN was more avidly bound than QD, and binding of both drugs was(More)
We describe a cooperad structure on the simplicial bar construction on a reduced operad of based spaces or spectra and, dually, an operad structure on the cobar construction on a cooperad. We also show that if the homology of the original operad (respectively, cooperad) is Koszul, then the homology of the bar (respectively, cobar) construction is the Koszul(More)
Maternal and fetal disposition of the beta adrenoceptor blocking drug, propranolol was examined in the pregnant sheep from day 95 to day 140 (term, 145 days) of gestation. Propranolol was administered to the mother (bolus dose, 1.5 mg/kg followed by an infusion of 1.2 mg/kg/hr over 3 hr) to achieve an average steady-state maternal total drug concentration(More)
It is unclear if reduced hepatic drug elimination in congestive heart failure is primarily due to impairment of enzyme function as a result of tissue hypoxia, to the direct effects of hepatic congestion, or to changes intrinsic to the liver, such as reductions in enzyme content and activity. We therefore compared propranolol clearance in perfused rat livers(More)
We have studied the enantioselectivity and regioselectivity of ring-hydroxylation and N-desisopropylation of R(+)- and S(-)-propranolol in microsomes from yeast expressing cytochrome P4502D6 (CYP2D6), using both NADPH and molecular oxygen (NADPH/O2) and cumene hydroperoxide-supported reactions. With NADPH/O2-supported reactions, CYP2D6 catalyzed 4- and(More)
The transfer of cimetidine across the isolated perfused human placenta was examined. Placentas obtained at cesarean section were perfused for 2 hr from both maternal and fetal sides in constant flow recycling systems. Cimetidine was administered as a bolus dose to either the maternal circuit alone (n = 4) or to both maternal and fetal circuits(More)