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The human CYP2A subfamily comprises three genes, CYP2A6, CYP2A7, and CYP2A13. CYP2A6 is active toward many carcinogens and is the major coumarin 7-hydroxylase and nicotine C-oxidase in the liver, whereas CYP2A7 is not functional. The function of CYP2A13 has not been characterized. In this study, a CYP2A13 cDNA was prepared by RNA-PCR from human nasal mucosa(More)
The metabolic activation of two known olfactory mucosal (OM) toxicants, acetaminophen (AP) and 2,6-dichlorobenzonitrile (DCBN), was examined with mouse liver and OM microsomes and purified, heterologously expressed mouse CYP2A5 and CYP2G1. In reconstituted systems, both isoforms were active in metabolizing DCBN and AP to metabolites that formed protein(More)
Limited success of somatic cell nuclear transfer is attributed to incomplete reprogramming of transferred nuclei. The objective was to determine if 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A (TSA) promoted reprogramming and improved development. Relative to untreated controls, treatment of donor cells, cloned embryos, and continuous treatment of(More)
The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and(More)
OBJECTIVE To develop a rapid, nonradioactive test using the polymerase chain reaction (PCR) capable of detecting full fragile X mutations, premutations, and resolving normal alleles and to apply this to prenatal diagnosis and carrier screening of pregnant women at risk for fragile X carrier status. DESIGN Prenatal and blood sample PCR analysis with(More)
In normal subjects and diabetic patients, insulin suppresses whole body proteolysis suggesting that the loss of lean body mass and muscle wasting in insulinopenia is related to increased muscle protein degradation. To document how insulinopenia affects organ weights and to identify the pathway for accelerated proteolysis in muscle, streptozotocin-treated(More)
Previous work has shown that lacZ fusions to the cysK, astD, tnaB, and gabT genes in Escherichia coli are activated by self-produced extracellular signals. Using a combination of ethyl acetate extraction, reversed-phase C(18) chromatography, and thin-layer chromatography, we have purified an extracellular activating signal from E. coli supernatants. Mass(More)
Acetaminophen (AP) is a widely-used analgesic agent that has been linked to human liver and kidney disease with prolonged or high-dose usage. In rodents, the target organs that are affected include liver, kidney, and the olfactory mucosa. AP toxicity requires cytochrome P450(CYP)-mediated metabolic activation, and the isozymes CYP1A2, 2E1, and 3A are known(More)
BACKGROUND Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common. OBJECTIVE To report the identification of a mutation in the human CRYGS gene. SUBJECTS AND METHODS A large six generation family affected by progressive polymorphic cortical cataract(More)
Coumarin was previously found to cause tissue-selective toxicity in the olfactory mucosa (OM) of rats and mice, with rats being the more sensitive species. The aim of this study was to explore the role of target tissue biotransformation in OM-selective toxicity and the metabolic basis of the species differences in coumarin toxicity. At least six coumarin(More)