Thomas F. Kalhorn

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Therapy for advanced prostate cancer centers on suppressing systemic androgens and blocking activation of the androgen receptor (AR). Despite anorchid serum androgen levels, nearly all patients develop castration-resistant disease. We hypothesized that ongoing steroidogenesis within prostate tumors and the maintenance of intratumoral androgens may(More)
We have investigated the formation of 4-hydroxycyclophosphamide (HCY) and deschloroethylcyclophosphamide (DCCY) from cyclophosphamide (CY) in human liver microsomes. For HCY, the estimated values (mean +/- SD; n = 3) of Km1 and Km2 were 0.095 +/- 0.072 and 5.09 +/- 4.30 mM, and the estimated values of Vmax1 and Vmax2 were 0.138 +/- 0.070 and 1.55 +/- 0.50(More)
BACKGROUND CYP2E1, 1A2, and 3A4 have all been implicated in the formation of N-acetyl-p-benzoquinone imine (NAPQI), the reactive intermediate of acetaminophen (INN, paracetamol), in studies in human liver microsomes and complementary deoxyribonucleic acid-expressed enzymes. However, recent pharmacokinetic evidence in humans has shown that the involvement of(More)
The character of reactive metabolites formed from carbamazepine (CBZ) was sought in incubations of [14C]CBZ in hepatic microsomes prepared from adult female mice of a strain (SWV/Fnn) susceptible to CBZ-induced teratogenicity. The formation of radio-labeled protein adducts was used as an index of reactive metabolite exposure. A dependence on cytochrome P450(More)
BACKGROUND Soy foods may have various health benefits, but little is known about the patterns and correlates of soy consumption among postmenopausal women in the United States. OBJECTIVE We assessed the reliability and validity of a soy food-frequency questionnaire (FFQ) and examined demographic, lifestyle, and dietary correlates of plasma isoflavone(More)
OBJECTIVE To validate assessment of soy intake using food frequency questionnaires (FFQs) compared with plasma isoflavone (genistein and daidzein) concentrations. DESIGN Cross-sectional analysis of soy isoflavone intake and plasma analysis of isoflavones. SUBJECTS 77 men and women, age range 20 to 40 years, recruited from the Seattle metropolitan area.(More)
The time course of excretion of acetaminophen and its metabolites in urine was determined in eight healthy adults (seven men and one woman) who ingested 1 gm of the drug and collected timed urine samples for 24 hours. The mean time of peak excretion rate was 1.3 to 3.7 hours for acetaminophen, its glucuronide, sulfate, cysteine, mercapturate, and methoxy(More)
Dapsone toxicity is putatively initiated by formation of a hydroxylamine metabolite by cytochromes P450. In human liver microsomes, the kinetics of P450-catalyzed N-oxidation of dapsone were biphasic, with the Michaelis-Menten constants of 0.14 +/- 0.05 and 0.004 +/- 0.003 mmol/L and the respective maximum velocities of 1.3 +/- 0.1 and 0.13 +/- 0.04 nmol/mg(More)
Omeprazole, a widely used and potent gastric proton pump inhibitor, induces cytochrome P450 (CYP) 1A2 in humans. Induction is most pronounced in slow metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is responsible for the elimination of omeprazole. Acetaminophen (INN, paracetamol), a widely used and effective analgesic and(More)
Impacts of trace concentrations of estrogens on aquatic ecosystems are a serious environmental concern, with their primary source being wastewater treatment facility effluents. Increased removal of 17alpha-ethinylestradiol (EE2) has been reported for activated sludge treatment with long enough solids retention time for nitrification. Previous work based on(More)