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
2017
Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages
Song G, Sun X, Hines R, McCarver D, Lake B, Osimitz T, Creek M, Clewell H, Yoon M. Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages. Drug Metabolism And Disposition 2017, 45: dmd.116.074583. PMID: 28228413, DOI: 10.1124/dmd.116.074583.Peer-Reviewed Original ResearchConceptsCYP2C8 expressionOntogeny dataMonths postnatal ageProtein levelsLiver microsomal samplesAge-dependent expressionMultiple cytochrome P450Weeks' gestationPostnatal agePostnatal dayYoung infantsPostnatal samplesFetal samplesMicrosomal samplesCYP1A2 expressionQuantitative Western blottingPyrethroid metabolismCYP2C8Western blottingHealth risk assessmentHuman health risk assessmentRisk assessmentAgeCarboxylesterase enzymesCytochrome P450
2016
Expression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver
Thomson M, Hines R, Schuetz E, Meibohm B. Expression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver. Drug Metabolism And Disposition 2016, 44: 999-1004. PMID: 27098745, PMCID: PMC4931892, DOI: 10.1124/dmd.115.069252.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgingChildChild, PreschoolFemaleGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGlycosylationHumansInfantInfant, NewbornLiver-Specific Organic Anion Transporter 1MaleProtein Processing, Post-TranslationalSolute Carrier Organic Anion Transporter Family Member 1B3ConceptsYears of ageOrganic anion transporting polypeptide (OATP) 1B1Relative protein expressionAge groupsProtein expressionDrug disposition pathwaysMonths of ageDrug-metabolizing enzymesHigh interindividual variabilityStudied age groupsPolypeptide 1B1Appropriate pharmacotherapyPediatric liverChildren 6Children 2Liver specimensInterindividual variabilityFirst monthDrug transportersWestern blottingDisposition pathwaysPreadolescent periodHigh expressionAge rangeMonthsAge-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny
Hines R, Simpson P, McCarver D. Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny. Drug Metabolism And Disposition 2016, 44: 959-966. PMID: 26825642, DOI: 10.1124/dmd.115.068957.Peer-Reviewed Original ResearchConceptsHepatic carboxylesterase 1Weeks of ageCarboxylesterase 1CES2 expressionAge groupsYounger age groupsCES1 expressionLiver diseaseAdverse outcomesMetabolic clearancePmol/Older groupOlder individualsWestern blottingLiver samplesWeeksEnvironmental chemicalsPostnatal ontogenyMicrosomal proteinMedian valueAgeCytosolic fractionGroupExpressionSubjects
2015
Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression
McCullough S, Bowers E, On D, Morgan D, Dailey L, Hines R, Devlin R, Diaz-Sanchez D. Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression. Toxicological Sciences 2015, 150: 216-224. PMID: 26719369, PMCID: PMC4838038, DOI: 10.1093/toxsci/kfv324.Peer-Reviewed Original ResearchConceptsChromatin modificationsH3 lysine 4 trimethylationSpecific chromatin modificationsChromatin modification statesLysine 4 trimethylationUnmodified H3Human bronchial epithelial cellsModification statesTotal H3H3K27 acetylationCellular signalsGene inductionPrimary human bronchial epithelial cellsKey regulatorGene expressionEpigenetic markersBronchial epithelial cellsTraditional toxicological paradigmModification levelsRelative abundanceAir-liquid interface modelTrimethylationEpithelial cellsH3Specific modificationsOntogeny 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
2014
Human Hepatic UGT2B15 Developmental Expression
Divakaran K, Hines R, McCarver D. Human Hepatic UGT2B15 Developmental Expression. Toxicological Sciences 2014, 141: 292-299. PMID: 24980262, PMCID: PMC4271124, DOI: 10.1093/toxsci/kfu126.Peer-Reviewed Original ResearchConceptsUGT2B15 expressionAge groupsHuman hepatic microsomesLate fetal lifeFunctional single nucleotide polymorphismsFetal contentMale genderFetal lifeLate gestationPostnatal samplesLower clearanceOlder individualsWeeks ageHepatic microsomesProtein expressionSingle nucleotide polymorphismsLatter groupImportant drugsMature valuesBisphenol ADevelopmental expressionExpression changesNucleotide polymorphismsGreater rateGroupTolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes
Rudraiah S, Rohrer P, Gurevich I, Goedken M, Rasmussen T, Hines R, Manautou J. Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes. Toxicological Sciences 2014, 141: 263-277. PMID: 24973094, PMCID: PMC4271123, DOI: 10.1093/toxsci/kfu124.Peer-Reviewed Original ResearchConceptsMale C57BL/6J miceAPAP hepatotoxicityFlavin-Containing Monooxygenase 3Protein expressionC57BL/6J miceFemale miceMouse modelMRNA levelsFirst time inductionNovel protective functionSingle doseAPAP treatmentMale miceAPAP cytotoxicityAcetaminophen pretreatmentHepatotoxic doseHigh doseAcetaminophen hepatotoxicityHepatotoxicityMice resultsCell line clonesMRNA expressionFMO3 expressionMiceAPAP
2013
Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants
Sampath V, Mulrooney N, Garland J, He J, Patel A, Cohen J, Simpson P, Hines R. Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants. Journal Of Perinatology 2013, 33: 772-777. PMID: 23867959, PMCID: PMC4465440, DOI: 10.1038/jp.2013.80.Peer-Reviewed Original ResearchMeSH KeywordsBlack or African AmericanFemaleGenetic Predisposition to DiseaseGenetic VariationGram-Negative Bacterial InfectionsHumansImmunity, InnateInfant, NewbornInfant, PrematureInfant, Premature, DiseasesInfant, Very Low Birth WeightInterleukin-1 Receptor-Associated KinasesLeukocyte CountLogistic ModelsMalePolymorphism, Single NucleotideRisk FactorsToll-Like Receptor 4Toll-Like Receptor 5Toll-Like ReceptorsWhite PeopleConceptsWhite blood cellsToll-like receptorsGram-negative infectionsVLBW infantsBacterial infectionsSingle nucleotide polymorphismsLow birth weight infantsTLR single nucleotide polymorphismsBirth weight infantsElevated WBC countGenetic variantsWeight infantsMulticenter studyTLR4 variantsWBC countFemale infantImmune responseInfantsInfection rateInfectionAlters susceptibilityBlood cellsRegression modelsConfoundersCohort
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 levelsA TIR domain receptor–associated protein (TIRAP) variant SNP (rs8177374) confers protection against premature birth
Karody V, Le M, Nelson S, Meskin K, Klemm S, Simpson P, Hines R, Sampath V. A TIR domain receptor–associated protein (TIRAP) variant SNP (rs8177374) confers protection against premature birth. Journal Of Perinatology 2012, 33: 341-346. PMID: 23047423, DOI: 10.1038/jp.2012.120.Peer-Reviewed Original ResearchConceptsToll-like receptorsPreterm infantsTerm infantsSingle nucleotide polymorphismsExact testProspective case-control studyTLR single nucleotide polymorphismsPregnancy-induced hypertensionRisk of PTBNuclear factor kappa B1Case-control studyFischer's exact testChi-square testIRAK1 variantsMultiplexed single-base extension assayPlacental abruptionPremature birthNeonatal bloodVariant single nucleotide polymorphismsInfantsCaucasian infantsWeeksModulate susceptibilityAfrican AmericansBirth
2011
A TLR5 (g.1174C > T) variant that encodes a stop codon (R392X) is associated with bronchopulmonary dysplasia
Sampath V, Garland J, Le M, Patel A, Konduri G, Cohen J, Simpson P, Hines R. A TLR5 (g.1174C > T) variant that encodes a stop codon (R392X) is associated with bronchopulmonary dysplasia. Pediatric Pulmonology 2011, 47: 460-468. PMID: 22058078, DOI: 10.1002/ppul.21568.Peer-Reviewed Original ResearchMeSH KeywordsBronchopulmonary DysplasiaCodon, TerminatorCohort StudiesFemaleGenetic Predisposition to DiseaseGenetic VariationHeterozygoteHumansIncidenceInfant, NewbornInfant, PrematureInfant, Very Low Birth WeightInterleukin-1 Receptor-Associated KinasesMalePilot ProjectsPolymorphism, Single NucleotideProspective StudiesSeverity of Illness IndexToll-Like Receptor 5ConceptsSevere BPDExact testLow birth weight infantsVariant allelesToll-like receptor (TLR) familyBronchopulmonary dysplasia susceptibilityBirth weight infantsPathway single nucleotide polymorphismsTLR pathway genesMulti-center studyFisher's exact testSusceptibility/severityBPD outcomesEpidemiological confoundersBronchopulmonary dysplasiaMultiplexed single-base extension assayPreterm infantsBPD pathogenesisPremature infantsPulmonary homeostasisLower incidencePathogen recognitionBlood samplesClinical informationCurrent evidencePrenatal 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 catabolismThe NFKB1 (g.-24519delATTG) Variant is Associated with Necrotizing Enterocolitis (NEC) in Premature Infants
Sampath V, Le M, Lane L, Patel A, Cohen J, Simpson P, Garland J, Hines R. The NFKB1 (g.-24519delATTG) Variant is Associated with Necrotizing Enterocolitis (NEC) in Premature Infants. Journal Of Surgical Research 2011, 169: e51-e57. PMID: 21529841, DOI: 10.1016/j.jss.2011.03.017.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCohort StudiesEnterocolitis, NecrotizingFemaleGenetic Predisposition to DiseaseHumansIncidenceInfant, NewbornInfant, PrematureInfant, Very Low Birth WeightMaleNF-kappa B p50 SubunitPilot ProjectsPolymorphism, Single NucleotideProspective StudiesRetrospective StudiesSignal TransductionToll-Like ReceptorsConceptsNecrotizing enterocolitisImmune responseBlood samplesSingle nucleotide polymorphismsExact testToll-like receptor pathway genesLow birth weight infantsNFKB1 variantsBirth weight infantsIntestinal immune responseTLR pathway genesFisher's exact testInnate immune responseEnterocolitis (NEC) pathogenesisNEC pathogenesisNEC susceptibilityVLBW infantsWeight infantsCohort studyPreterm infantsPremature infantsTIRAP geneClinical informationGene-environment interactionsInfants
2009
Human hepatic CYP2B6 developmental expression: The impact of age and genotype
Croom E, Stevens J, Hines R, Wallace A, Hodgson E. Human hepatic CYP2B6 developmental expression: The impact of age and genotype. Biochemical Pharmacology 2009, 78: 184-190. PMID: 19464434, DOI: 10.1016/j.bcp.2009.03.029.Peer-Reviewed Original ResearchConceptsYears of ageMedian ageCYP2B6 expressionCYP2B6 levelsProtein levelsSemi-quantitative Western blottingImpact of ageWeeks' gestationNeonatal periodCYP2B6 protein levelsDonor ageCYP3A7 activityPostnatal dayLiver bankAge groupsFetal samplesAdult levelsPediatric samplesWestern blottingCYP2B6 proteinToxicant metabolismAgeSignificant inductionPercentage of samplesPossible role
2008
Developmental Changes in Human Liver CYP2D6 Expression
Stevens J, Marsh S, Zaya M, Regina K, Divakaran K, Le M, Hines R. Developmental Changes in Human Liver CYP2D6 Expression. Drug Metabolism And Disposition 2008, 36: 1587-1593. PMID: 18474679, DOI: 10.1124/dmd.108.021873.Peer-Reviewed Original ResearchDifferential 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 modelModeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: A case study with toluene
Nong A, McCarver D, Hines R, Krishnan K. Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: A case study with toluene. Toxicology And Applied Pharmacology 2006, 214: 78-87. PMID: 16464483, DOI: 10.1016/j.taap.2005.12.001.Peer-Reviewed Original ResearchConceptsHepatic CYP2E1 contentCYP2E1 contentLiver volumeHepatic CYP2E1 protein levelsInternal doseHepatic CYP2E1 levelsInterindividual variability factorsPBPK modelVenous blood concentrationsBlood concentration profilesCYP2E1 protein levelsSubgroup of childrenNeonate groupPercentile valuesPpm tolueneBlood concentrationsCYP2E1 levelsHepatic metabolismBody weightLower AUCAge groupsHuman volunteersInterindividual variabilityPharmacokinetic modelIntrinsic clearance