2022
MIF is a common genetic determinant of COVID-19 symptomatic infection and severity
Shin JJ, Fan W, Par-Young J, Piecychna M, Leng L, Israni-Winger K, Qing H, Gu J, Zhao H, Schulz WL, Unlu S, Kuster J, Young G, Liu J, Ko AI, Garcia A, Sauler M, Wisnewski AV, Young L, Orduña A, Wang A, Klementina O, Garcia AB, Hegyi P, Armstrong ME, Mitchell P, Ordiz DB, Garami A, Kang I, Bucala R. MIF is a common genetic determinant of COVID-19 symptomatic infection and severity. QJM 2022, 116: 205-212. PMID: 36222594, PMCID: PMC9620729, DOI: 10.1093/qjmed/hcac234.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLow-expression MIF alleleCOVID-19 infectionMIF allelesCATT7 alleleHealthy controlsCOVID-19Serum macrophage migration inhibitory factorSymptomatic SARS-CoV-2 infectionHigher serum MIF levelsHigh-expression MIF allelesRetrospective case-control studySARS-CoV-2 infectionFunctional polymorphismsAvailable clinical characteristicsMultinational retrospective studySerum MIF levelsUninfected healthy controlsSymptomatic COVID-19Tertiary medical centerHealthy control subjectsCase-control studyMigration inhibitory factorCoronavirus disease 2019Common functional polymorphisms
2020
Analysis of Lung Gene Expression Reveals a Role for Cl- channels in Diisocyanate Induced Airway Eosinophilia in a Mouse Model of Asthma Pathology
Wisnewski AV, Liu J, Redlich CA. Analysis of Lung Gene Expression Reveals a Role for Cl- channels in Diisocyanate Induced Airway Eosinophilia in a Mouse Model of Asthma Pathology. American Journal Of Respiratory Cell And Molecular Biology 2020, 0: 25-35. PMID: 32101465, PMCID: PMC7328250, DOI: 10.1165/rcmb.2019-0400oc.Peer-Reviewed Original ResearchConceptsRespiratory tract exposureAirway eosinophiliaMonocytes/macrophagesMouse modelGene expressionGene transcriptsBiological pathwaysAsthma pathologyUpregulated gene transcriptsIgE-independent mechanismsLung gene expressionLung tissue gene expressionCause of asthmaBALB/cTransgenic B cellsTissue gene expressionExpression changesDiisocyanate asthmaSensitized workersAsthma pathogenesisAirway fluidDeficient miceMRNA microarrayEosinophiliaB cellsMolecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates
Wisnewski AV, Liu J. Molecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates. Monoclonal Antibodies In Immunodiagnosis And Immunotherapy 2020, 39: 66-73. PMID: 32302507, PMCID: PMC7310211, DOI: 10.1089/mab.2020.0006.Peer-Reviewed Original ResearchConceptsBALB/c miceMonoclonal antibodiesOccupational asthmaC miceSerologic detectionDifferent carrier proteinsNew mAbsEpitope specificityUseful research reagentsDisease preventionImmune recognitionStable hybridomasWestern blotAlbumin adductsMouse skinMAbsSurveillance approachSurveillance effortsAntibodiesMolecular determinantsHybridomasAliphatic diComplementary determining regionsMolecular characterizationResearch reagents
2019
Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure?
Wisnewski AV, Nassar AF, Liu J, Bello D. Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure? Chemical Research In Toxicology 2019, 32: 557-565. PMID: 30724074, PMCID: PMC6465083, DOI: 10.1021/acs.chemrestox.8b00262.Peer-Reviewed Original ResearchConceptsRespiratory tract exposureMDI exposureUrine biomarkersSkin exposureUrine of miceFuture translational investigationsWestern blot studiesUrinary biomarkersRespiratory tractExposure surveillanceTranslational investigationsDisease preventionMDI conjugatesMiceUrineBiomarkersCollision-induced dissociation (CID) fragmentation patternsExposureUnderstanding pathwaysMDIIndustrial hygieneAlbuminMS/MSTractPrevention
2017
Mass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4'-methylene diphenyl diisocyanate aerosol
Hettick JM, Law BF, Lin CC, Wisnewski AV, Siegel PD. Mass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4'-methylene diphenyl diisocyanate aerosol. Xenobiotica 2017, 48: 626-636. PMID: 28629263, PMCID: PMC5864557, DOI: 10.1080/00498254.2017.1344791.Peer-Reviewed Original ResearchConceptsLavage fluidOccupational allergic respiratory diseaseBALB/c mouse modelMurine bronchoalveolar lavage fluidDiisocyanate-induced asthmaBronchoalveolar lavage fluidAllergic respiratory diseasesBronchoalveolar lavage samplesDiphenyl diisocyanate aerosolsLabel-free quantitative proteomic strategyMDI conjugationWestern blot analysisHealth burdenLavage samplesRespiratory diseaseAerosol exposureMouse modelDisease pathogenesisRespiratory exposureCausative agentBlot analysisCytochrome P450Argininosuccinate synthaseQuantitative proteomic strategyCellular fractionsReaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy
Wisnewski AV, Kanyo J, Asher J, Goodrich JA, Barnett G, Patrylak L, Liu J, Redlich CA, Nassar AF. Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy. Xenobiotica 2017, 48: 488-497. PMID: 28489470, PMCID: PMC5863241, DOI: 10.1080/00498254.2017.1329569.Peer-Reviewed Original ResearchConceptsCollision-induced dissociation (CID) fragmentation patternsReaction productsLower airwaysChemical reactivityLow molecular weight fractionWeight fractionHigh molecular weight fractionAliphatic diisocyanateMolecular weight fractionFragmentation patternsHexamethylenediisocyanateLC-MSHDI vaporAirways of rabbitsBronchoalveolar lavage fluidRabbit bronchoalveolar lavage fluidMoleculesDiisocyanate vaporsMs. 4Albumin. 5Occupational asthmaReactivityBAL fluidAsthma pathogenesisLavage fluid
2016
UPLC–MS for metabolomics: a giant step forward in support of pharmaceutical research
Nassar AF, Wu T, Nassar SF, Wisnewski AV. UPLC–MS for metabolomics: a giant step forward in support of pharmaceutical research. Drug Discovery Today 2016, 22: 463-470. PMID: 27919805, PMCID: PMC5721520, DOI: 10.1016/j.drudis.2016.11.020.Peer-Reviewed Original ResearchIdentification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction
Wisnewski AV, Liu J, Nassar AF. Identification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction. Toxicology In Vitro 2016, 36: 97-104. PMID: 27453132, PMCID: PMC5010927, DOI: 10.1016/j.tiv.2016.07.011.Peer-Reviewed Original ResearchProgress in automation of mass cytometry barcoding for drug development
Nassar AF, Wisnewski AV, Raddassi K. Progress in automation of mass cytometry barcoding for drug development. Bioanalysis 2016, 8: 1429-1435. PMID: 27323800, DOI: 10.4155/bio-2016-0135.Peer-Reviewed Original ResearchBiotransformation and Rearrangement of Laromustine
Nassar AE, Wisnewski AV, King I. Biotransformation and Rearrangement of Laromustine. Drug Metabolism And Disposition 2016, 44: 1349-1363. PMID: 27278961, DOI: 10.1124/dmd.116.069823.Peer-Reviewed Original ResearchConceptsNuclear magnetic resonance spectroscopyCollision-induced dissociationFourier transform ion cyclotron resonance mass spectrometerIon cyclotron resonance mass spectrometerAccurate mass measurementsMass spectrometry studiesHydrogen-deuterium exchangeMagnetic resonance spectroscopyMass spectral rearrangementsExact massSpectrometry studiesEnzyme catalysisReactive intermediatesMass spectrometerDecomposition productsResonance spectroscopyConjugation reactionsElemental compositionPossibility of rearrangementMass measurementsSpectral rearrangementsDissociationRadioactive componentsLoss of nitrogenMetabolite products
2015
Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ
Wisnewski AV, Liu J. Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ. Journal Of Immunological Methods 2015, 429: 60-65. PMID: 26690039, PMCID: PMC4753098, DOI: 10.1016/j.jim.2015.12.008.Peer-Reviewed Original ResearchConceptsKeyhole limpet hemocyaninFreund's adjuvantDiisocyanate-induced asthmaComplete Freund's adjuvantIncomplete Freund's adjuvantLung tissue sectionsFormalin-fixed paraffinOccupational asthmaLower airwaysBooster injectionOccupational allergensAirway cellsAlveolar macrophagesLimpet hemocyaninAdjuvantHealth effectsTissue distributionTissue samplesTissue sectionsAsthmaDot blot analysisFurther studiesImmunochemical studiesBlot analysisEpithelial regionsImpact of recent innovations in the use of mass cytometry in support of drug development
Nassar AF, Ogura H, Wisnewski AV. Impact of recent innovations in the use of mass cytometry in support of drug development. Drug Discovery Today 2015, 20: 1169-1175. PMID: 26092491, PMCID: PMC4668584, DOI: 10.1016/j.drudis.2015.06.001.Peer-Reviewed Original ResearchConceptsSingle-cell technologiesSingle-cell levelDrug developmentSingle cellsDiseased statesCell levelMechanism of actionMass cytometryCellsDrug profilingIndividual biological cellsCyTOFImportant roleSignal overlapCytometryIndividual samplesBiological cellsProfilingSignificant advancesCell technologyMetabolic disposition of the anti-cancer agent [14C]laromustine in male rats
Nassar AF, Wisnewski A, King I. Metabolic disposition of the anti-cancer agent [14C]laromustine in male rats. Xenobiotica 2015, 45: 711-721. PMID: 25798740, PMCID: PMC4681490, DOI: 10.3109/00498254.2015.1016475.Peer-Reviewed Original ResearchConceptsQuantitative whole-body autoradiographyBolus doseDrug-derived radioactivityPeak plasma concentrationWhole-body autoradiographyGroup 1 animalsUrinary bladder contentsLong-Evans ratsExcretion of drugsSmall intestine contentsRecovery of radioactivityNovel sulfonylhydrazineAnti-cancer agentsSpinal cordMale ratsPlasma concentrationsIntravenous administrationRenal cortexBladder contentsTotal bodyMetabolic dispositionOrgan exposureSmall intestineRatsMedical guidelinesGlutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation
Wisnewski AV, Liu J, Colangelo CM. Glutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation. Chemical Research In Toxicology 2015, 28: 729-737. PMID: 25635619, PMCID: PMC4667722, DOI: 10.1021/tx5005002.Peer-Reviewed Original ResearchConceptsEosinophilic inflammatory responseAlternative macrophage activationInflammatory responseChemical allergensMacrophage activationAirway eosinophil numbersEosinophilic airway inflammationInnate immune responseGreater inflammatory responseAirway levelsMDI conjugationAirway inflammationOccupational asthmaIL-12MDI exposureAsthma pathogenesisEosinophil numbersNaïve miceAirway fluidRespiratory tractImmune responseMucus productionSkin exposureMDI conjugatesVivo evidence
2013
Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate
Wisnewski AV, Liu J. Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate. Molecular Immunology 2013, 54: 233-237. PMID: 23295252, PMCID: PMC3563841, DOI: 10.1016/j.molimm.2012.11.017.Peer-Reviewed Original ResearchConceptsEpitope specificityAutologous serum proteinsLow molecular weight chemicalsOccupational asthmaOccupational allergensMolecular determinantsDisease pathogenesisSecreting clonesCDR3 regionWestern blotGene usageMonoclonal antibodiesMajor causeWeight chemicalsIgG1 mAbGermline gene usageHuman albuminImmune specificityMAbsSerum proteinsELISADiagnostic reagentsUseful diagnostic reagentHybridomasSomatic hypermutation
2006
Suburban Leptospirosis: Atypical Lymphocytosis and γ-δ T Cell Response
Barry M, Wisnewski AV, Matthias MA, Inouye SK, Vinetz JM. Suburban Leptospirosis: Atypical Lymphocytosis and γ-δ T Cell Response. Clinical Infectious Diseases 2006, 43: 1304-1307. PMID: 17051497, DOI: 10.1086/508537.Peer-Reviewed Original ResearchConceptsAtypical lymphocytosisGamma delta T cellsT cell responsesCases of leptospirosisRate of infectionPeripheral bloodT cellsGlobal epidemiologyCell responsesCanine leptospirosisLeptospirosisZoonotic diseaseLymphocytosisSuburban settingsEpidemiologyReservoir hostsDiseasePathogenesisInfectionIncidenceSettingDiagnosisBlood
2003
Differential roles for CD4 and CD8 T cells after diisocyanate sensitization: Genetic control of TH2-induced lung inflammation
Herrick CA, Das J, Xu L, Wisnewski AV, Redlich CA, Bottomly K. Differential roles for CD4 and CD8 T cells after diisocyanate sensitization: Genetic control of TH2-induced lung inflammation. Journal Of Allergy And Clinical Immunology 2003, 111: 1087-1094. PMID: 12743574, DOI: 10.1067/mai.2003.1413.Peer-Reviewed Original ResearchConceptsContact hypersensitivityT cellsAirway eosinophiliaAirway inflammationBALB/c miceDiisocyanate-induced asthmaCD8 T cellsLung inflammatory responseMajor effector cellsIL-13 productionMeans of inhalationNovel mouse modelEpicutaneous exposureAtopic asthmaLung inflammationMucus hypersecretionOccupational asthmaEpicutaneous sensitizationEffector cellsCytokine productionC miceIL-5Serum antibodiesInflammatory responseC57BL/10 mice
2002
Mouse Models of Diisocyanate Asthma
Redlich CA, Wisnewski AV, Gordon T. Mouse Models of Diisocyanate Asthma. American Journal Of Respiratory Cell And Molecular Biology 2002, 27: 385-390. PMID: 12356570, DOI: 10.1165/rcmb.f249.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsA novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge
Herrick CA, Xu L, Wisnewski AV, Das J, Redlich CA, Bottomly K. A novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge. Journal Of Allergy And Clinical Immunology 2002, 109: 873-878. PMID: 11994714, DOI: 10.1067/mai.2002.123533.Peer-Reviewed Original ResearchConceptsDiisocyanate-induced asthmaNovel mouse modelLung inflammationMouse modelAirway eosinophiliaAntigen challengeHuman asthmaAntigen-induced lung inflammationBALB/c miceAllergic-type inflammationLung inflammatory cellsCytokine-deficient miceVigorous inflammatory responsePrevious mouse modelsAtopic asthmaMucus hypersecretionOccupational asthmaContact hypersensitivityInflammatory cellsC miceInflammatory responseType cytokinesIFN-gammaAsthmaHuman diseases
2001
Development of immunoassays for biomonitoring of hexamethylene diisocyanate exposure.
Lemus R, Lukinskeine L, Bier ME, Wisnewski AV, Redlich CA, Karol MH. Development of immunoassays for biomonitoring of hexamethylene diisocyanate exposure. Environmental Health Perspectives 2001, 109: 1103-1108. PMID: 11712993, PMCID: PMC1240469, DOI: 10.1289/ehp.011091103.Peer-Reviewed Original ResearchConceptsHexamethylene diisocyanateHuman serum albuminLaser desorption timeMatrix-assisted laser desorption timeFlight mass spectrometryWorkplace air monitoringMass spectrometryDesorption timeDiisocyanateAdductsDevelopment of immunoassaysHSA antigenSerum albuminMicrotiter platesReactionAir monitoringHexamethylene diisocyanate exposurePpbAbsence of reactionSensitive bioassayNumerous samplesSpectrometryDiphenylPolyurethaneCoatings