2019
Developmental Expression of the Cytosolic Sulfotransferases in Human Liver
Dubaisi S, Caruso J, Gaedigk R, Vyhlidal C, Smith P, Hines R, Kocarek T, Runge-Morris M. Developmental Expression of the Cytosolic Sulfotransferases in Human Liver. Drug Metabolism And Disposition 2019, 47: dmd.119.086363. PMID: 30885913, PMCID: PMC6505379, DOI: 10.1124/dmd.119.086363.Peer-Reviewed Original ResearchConceptsMRNA levelsLiver specimensHuman liverReverse transcription-quantitative polymerase chain reactionTranscription-quantitative polymerase chain reactionProtein levelsRT-qPCR analysisHuman liver cytosolHuman liver samplesQuantitative polymerase chain reactionCytosolic sulfotransferasesRNA sequencingHepatic sulfotransferasesPolymerase chain reactionDrug eliminationPredominant organInfant liverLiverLiver samplesChain reactionLiver cytosolForeign chemicalsImportant metabolic roleInfantsAdditional findings
2016
Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny
Giebel N, Shadley J, McCarver D, Dorko K, Gramignoli R, Strom S, Yan K, Simpson P, Hines R. Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny. Drug Metabolism And Disposition 2016, 44: 1027-1037. PMID: 26921389, PMCID: PMC4931893, DOI: 10.1124/dmd.116.069344.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBinding SitesChildChild, PreschoolChromatinChromatin Assembly and DisassemblyCytochrome P-450 CYP3AGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGestational AgeHepatocytesHistonesHumansInfantLiverMiddle AgedNucleic Acid ConformationPromoter Regions, GeneticProtein ConformationStructure-Activity RelationshipTranscription, Genetic
2015
Ontogeny of plasma proteins, albumin and binding of diazepam, cyclosporine, and deltamethrin
Sethi P, White C, Cummings B, Hines R, Muralidhara S, Bruckner J. Ontogeny of plasma proteins, albumin and binding of diazepam, cyclosporine, and deltamethrin. Pediatric Research 2015, 79: 409-415. PMID: 26571224, DOI: 10.1038/pr.2015.237.Peer-Reviewed Original ResearchConceptsTotal proteinBinding of diazepamUnbound diazepamAlbumin levelsStandard dosesPlasma levelsDrugs/chemicalsPediatric databasePlasma bindingAge groupsMaturational changesAdult levelsCyclosporineDiazepamPlasma albuminThree- to fourfoldPlasma samplesFree drugNeonatesPlasma proteinsPyrethroid insecticidesAge bracketDrugsAlbuminRisk
2012
Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes
Sharma S, Ellis E, Gramignoli R, Dorko K, Tahan V, Hansel M, Mattison D, Caritis S, Hines R, Venkataramanan R, Strom S. Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes. Drug Metabolism And Disposition 2012, 41: 296-304. PMID: 23129211, PMCID: PMC3558857, DOI: 10.1124/dmd.112.044891.Peer-Reviewed Original ResearchMeSH Keywords17 alpha-Hydroxyprogesterone CaproateAdultAge FactorsAgedBiological TransportCells, CulturedCold TemperatureCyclosporineFemaleGestational AgeHepatocytesHumansHydroxyprogesteronesKineticsMaleMembrane Transport ProteinsMiddle AgedMultidrug Resistance-Associated Protein 2RifampinRNA, MessengerTaurocholic AcidVerapamilYoung AdultConceptsHuman hepatocytesFetal human hepatocytesFetal human liverConcentration-dependent inhibitionAdult human hepatocytesBile acid transporterFetal circulationPlacental barrierRecurrent miscarriageSpontaneous abortionProgesterone metabolitesTaurocholate effluxAdult hepatocytesTherapeutic levelsLower mRNA levelsHepatobiliary dispositionHepatic transportersActivity of transportersActive efflux mechanismHuman liverHuman fetalAdverse effectsRole of transportersEfflux mechanismMRNA levels
2011
Prenatal and Postnatal Expression of Glutathione Transferase ζ 1 in Human Liver and the Roles of Haplotype and Subject Age in Determining Activity with Dichloroacetate
Li W, Gu Y, James M, Hines R, Simpson P, Langaee T, Stacpoole P. Prenatal and Postnatal Expression of Glutathione Transferase ζ 1 in Human Liver and the Roles of Haplotype and Subject Age in Determining Activity with Dichloroacetate. Drug Metabolism And Disposition 2011, 40: 232-239. PMID: 22028318, PMCID: PMC3263939, DOI: 10.1124/dmd.111.041533.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAmino Acid SubstitutionAntineoplastic AgentsChildCytoplasmDichloroacetic AcidDrugs, InvestigationalFemaleGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGlutathione TransferaseHalogenationHumansLiverMaleMiddle AgedMitochondria, LiverPolymorphism, Single NucleotideSubstrate SpecificityYoung AdultConceptsGSTZ1 activityHuman liverProtein expressionAge 74 yearsInfluence of haplotypeAge 7 yearsAge-dependent mannerAge-related increaseRole of haplotypesWeeks' gestationHuman liver developmentNeonatal onsetAge-related differencesLactic acidosisInvestigational drugsSolid tumorsGSTZ1 protein expressionPostnatal expressionSubject ageLevel of expressionFetal liverLiverGSTZ1 expressionExpression levelsTyrosine catabolism
2008
Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein β (C/EBPβ) liver inhibitory and liver activating proteins
Klick D, Shadley J, Hines R. Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein β (C/EBPβ) liver inhibitory and liver activating proteins. Biochemical Pharmacology 2008, 76: 268-278. PMID: 18555208, DOI: 10.1016/j.bcp.2008.05.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBase SequenceCCAAT-Enhancer-Binding Protein-betaCell Line, TumorCells, CulturedDNAEmbryo, MammalianFemaleHepatocyte Nuclear Factor 3-betaHepatocytesHumansInfantLiverMaleMiddle AgedMolecular Sequence DataMutagenesis, Site-DirectedOxygenasesPromoter Regions, GeneticProtein Structure, TertiarySequence AlignmentSequence Analysis, DNAConceptsNuclear proteinsLiver nuclear proteinsSpecific DNA/protein interactionsPromoter activityDNA-protein binding studiesDNA/protein interactionsDNA-protein interactionsTransient expression experimentsCell nuclear proteinsDNA methylase inhibitorCCAAT enhancer-binding proteinGene regulation studiesEnhancer-binding proteinNuclear protein extractsOxidative xenobiotic metabolismHepG2 cellsFMO3 expressionTranscriptional machineryChromatin immunoprecipitationProtein interactionsPromoter functionExpression experimentsMethylase inhibitorTransient expressionDNA hypermethylation
2007
Mechanisms Regulating Human FMO3 Transcription
Klick D, Hines R. Mechanisms Regulating Human FMO3 Transcription. Drug Metabolism Reviews 2007, 39: 419-442. PMID: 17786630, DOI: 10.1080/03602530701498612.Peer-Reviewed Original ResearchConceptsGC-box binding proteinsHepG2 cellsPromoter characterizationLiver nuclear proteinsNuclear proteinsTransient expressionFMO enzymesDevelopmental expressionBinding proteinTranscriptionAdult regulationProteinSpecific mechanismsEnzymeExpressionCellsNFYMajor roleYY1USF1Oxidative drugsHeterodimersMonooxygenasesReporterIsoforms
2006
Population-Based Analysis of Methadone Distribution and Metabolism Using an Age-Dependent Physiologically Based Pharmacokinetic Model
Yang F, Tong X, McCarver D, Hines R, Beard D. Population-Based Analysis of Methadone Distribution and Metabolism Using an Age-Dependent Physiologically Based Pharmacokinetic Model. Journal Of Pharmacokinetics And Pharmacodynamics 2006, 33: 485-518. PMID: 16758333, DOI: 10.1007/s10928-006-9018-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAnalgesics, OpioidArea Under CurveBiological AvailabilityChild, PreschoolComputer SimulationHumansHydrogen-Ion ConcentrationInfantInfant, NewbornMaleMethadoneMiddle AgedModels, BiologicalMonte Carlo MethodProtein BindingRegression AnalysisStereoisomerismTissue DistributionConceptsInter-individual variabilityPediatric populationPharmacokinetic modelMethadone kineticsPopulation-based analysisPopulation-based pharmacokineticsMetabolism of methadoneMethadone distributionMethadone metabolismMethadone pharmacokineticsOpioid abstinencePediatric patientsClinical effectsPD relationshipBlood concentrationsPlasma concentrationsLimited pharmacokineticsPharmacodynamic dataOrosomucoid concentrationPK parametersPK dataMethadonePharmacokineticsClearance kineticsPBPK model
1990
Expression of CYP1A1 Gene in Patients With Lung Cancer: Evidence for Cigarette Smoke-Induced Gene Expression in Normal Lung Tissue and for Altered Gene Regulation in Primary Pulmonary Carcinomas
McLemore T, Adelberg S, Liu M, McMahon N, Yu S, Hubbard W, Czerwinski M, Wood T, Storeng R, Lubet R, Eggleston J, Boyd M, Hines R. Expression of CYP1A1 Gene in Patients With Lung Cancer: Evidence for Cigarette Smoke-Induced Gene Expression in Normal Lung Tissue and for Altered Gene Regulation in Primary Pulmonary Carcinomas. Journal Of The National Cancer Institute 1990, 82: 1333-1339. PMID: 2380990, DOI: 10.1093/jnci/82.16.1333.Peer-Reviewed Original ResearchConceptsNormal lung tissuesLung tissueLung cancerFormer smokersCigarette smokersCYP1A1 gene expressionCYP1A1 geneActive cigarette smokersPrimary pulmonary carcinomasHuman pulmonary tissueMessenger RNA expressionPulmonary carcinogenesisCigarette smokingPulmonary carcinomaTime-dependent decreasePulmonary tissueGene expressionSmokersCarcinoma tissuesPatientsCancerTumorsRNA expressionMRNA levelsCYP1A1 mRNA