2024
Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA‑1 in Pathologic Responses to Diisocyanate
Wisnewski A, Liu J. Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA‑1 in Pathologic Responses to Diisocyanate. Chemical Research In Toxicology 2024, 37: 476-485. PMID: 38494904, DOI: 10.1021/acs.chemrestox.3c00325.Peer-Reviewed Original ResearchLung gene expressionNonsensitized miceImmune-sensitizationType I interferon-stimulated genesI interferon-stimulated genesAllergen-induced asthmaChemical-induced asthmaMolecular pathwaysADAR-1Ovalbumin-induced asthmaRegulation of innateInterferon-stimulated genesGene transcriptionGene expressionPathological responseAdenosine Deaminase ActingMurine modelAsthma-likeNonsensitized hostsLevels up to 10-foldLung tissueInnate responseLungTissue damageMice
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 polymorphismsGlutathione reactivity with aliphatic polyisocyanates
Wisnewski AV, Liu J. Glutathione reactivity with aliphatic polyisocyanates. PLOS ONE 2022, 17: e0271471. PMID: 35839242, PMCID: PMC9286259, DOI: 10.1371/journal.pone.0271471.Peer-Reviewed Original ResearchConceptsHexamethylene diisocyanateAliphatic polyisocyanatesReaction productsMS/MSTandem MS/MSReversed-phase LC-MSPositive ion modeMajor reaction productsLiquid chromatography-coupled mass spectrometryCoupled-mass spectrometryPolymeric formulationsIon modeGlutathione reactivityFragmentation patternsGSH reactivityS linkageO groupLC-MSPolyisocyanatesIonsIsocyanate productsDiisocyanateImportant productsReactivityMSChanges Over Time in COVID-19 Incidence, Vaccinations, Serum Spike IgG, and Viral Neutralizing Potential Among Individuals From a North American Gaming Venue
Wisnewski AV, Cantley L, Luna J, Liu J, Smith RF, Hager K, Redlich CA. Changes Over Time in COVID-19 Incidence, Vaccinations, Serum Spike IgG, and Viral Neutralizing Potential Among Individuals From a North American Gaming Venue. Journal Of Occupational And Environmental Medicine 2022, 64: 788-796. PMID: 36054278, PMCID: PMC9426317, DOI: 10.1097/jom.0000000000002617.Peer-Reviewed Original ResearchConceptsOccupational risk factorsCOVID-19 historyRisk factorsAnti-spike IgG levelsIndividual humoral responsesSerum antiviral antibodiesCOVID-19 vaccinationEnzyme-linked immunosorbent assayCOVID-19 ratesCOVID-19 incidenceSpike IgGVaccine nonrespondersVaccination statusIgG levelsVaccine responsesVaccine typesAntiviral antibodiesHumoral responseCOVID-19 casesVaccine availabilityImmunosorbent assayVaccinationInfectionMonthsParticipantsDevelopment and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses
Wisnewski AV, Liu J, Lucas C, Klein J, Iwasaki A, Cantley L, Fazen L, Luna J, Slade M, Redlich CA. Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses. PLOS ONE 2022, 17: e0262657. PMID: 35041700, PMCID: PMC8765639, DOI: 10.1371/journal.pone.0262657.Peer-Reviewed Original ResearchConceptsPlaque reduction neutralization testCOVID-19 patientsVaccine responsesRecovered COVID-19 patientsSARS-CoV-2 immunityBooster vaccine dosesMRNA vaccine responsePost-vaccine seraCompetitive ELISAEnzyme 2 (ACE2) receptorReduction neutralization testType of vaccineSARS-CoV-2 spike protein receptorSpike protein receptorVaccine seraVaccine recipientsPost vaccinationVaccinated individualsVaccine dosesViral culturePrior historyViral neutralizationNeutralization testBooster shotsPost vaccineSevere asthma and death in a worker using methylene diphenyl diisocyanate MDI asthma death
Wisnewski AV, Cooney R, Hodgson M, Giese K, Liu J, Redlich CA. Severe asthma and death in a worker using methylene diphenyl diisocyanate MDI asthma death. American Journal Of Industrial Medicine 2022, 65: 166-172. PMID: 35028957, PMCID: PMC8846433, DOI: 10.1002/ajim.23323.Peer-Reviewed Case Reports and Technical NotesConceptsCause of deathMedical recordsDiisocyanate asthmaSevere asthmaSerum IgEParaffin-embedded lung tissue sectionsWorkers' medical recordsSmooth muscle hypertrophyTotal serum IgEHallmark of asthmaSevere asthma attacksBasement membrane thickeningLung tissue sectionsPost-mortem findingsEnzyme-linked immunosorbent assayPotential chemical exposuresInflamed airwaysMucus pluggingOccupational asthmaPulmonary embolismTotal IgEAsthma deathsAsthma attacksLung pathologyAutopsy findings
2021
Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines
Wisnewski AV, Redlich CA, Liu J, Kamath K, Abad QA, Smith RF, Fazen L, Santiago R, Luna J, Martinez B, Baum-Jones E, Waitz R, Haynes WA, Shon JC. Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines. PLOS ONE 2021, 16: e0252849. PMID: 34499652, PMCID: PMC8428655, DOI: 10.1371/journal.pone.0252849.Peer-Reviewed Original ResearchConceptsCOVID-19 mRNA vaccine recipientsLinear epitopesSARS-CoV-2 neutralizationCOVID-19 mRNA vaccinesVaccine-induced IgGMRNA vaccine recipientsSARS-CoV-2 spike proteinDominant linear epitopeElicit IgGVaccine recipientsVaccine effectivenessMRNA vaccinesVaccination samplesImmune escapeHuman coronavirusesHealthy adultsSARS-CoVVaccine epitopesCritical epitopesAdverse responsesReverse vaccinologySpike proteinNatural infectionS2 subunitIgGAssociations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel
Zell J, Wisnewski AV, Liu J, Klein J, Lucas C, Slade M, Iwasaki A, Redlich CA. Associations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel. PLOS ONE 2021, 16: e0251114. PMID: 34460832, PMCID: PMC8405017, DOI: 10.1371/journal.pone.0251114.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Live SARS-CoV-2Moderate SARS-CoV-2SARS-CoV-2 seroprevalenceWork-related risk factorsTransportation-related occupationsSerum IgG levelsAntigen-specific IgGIgG seropositivity rateBiomarkers of infectionSARS-CoV-2 spikeCOVID-19 exposureUS National Guard soldiersMilitary personnelIgG levelsSeropositivity rateHumoral responseSerum IgGViral exposureBlack raceRisk factorsOdds ratioStudy populationNational Guard soldiersDemographic data
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
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.
Wisnewski AV, Liu J, Nassar AF. LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate. EC Pharmacology And Toxicology 2019, 7: 205-219. PMID: 31143884, PMCID: PMC6536005.Peer-Reviewed Original ResearchDilysine-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
Polymerization of hexamethylene diisocyanate in solution and a 260.23 m/z [M+H]+ ion in exposed human cells
Wisnewski AV, Liu J, Redlich CA, Nassar AF. Polymerization of hexamethylene diisocyanate in solution and a 260.23 m/z [M+H]+ ion in exposed human cells. Analytical Biochemistry 2017, 543: 21-29. PMID: 29175138, PMCID: PMC5826792, DOI: 10.1016/j.ab.2017.11.017.Peer-Reviewed Original ResearchConceptsHexamethylene diisocyanateCollision-induced dissociation (CID) fragmentation patternsNucleophilic additionImportant industrial chemicalPrimary aminesFragmentation patternsO groupLC-MS/MSLC-MS/MS analysisLC-MSReaction productsIonsMS analysisFormula CIndustrial chemicalsDiisocyanatePolymerizationPolymersReaction targetWaterSolutionAminesDefinitive characterizationMoleculesDimersReaction 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
Corrigendum to “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” [Toxicol. In vitro (2016) 97–104]
Wisnewski AV, Liu J, Nassar AF. Corrigendum to “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” [Toxicol. In vitro (2016) 97–104]. Toxicology In Vitro 2016, 38: 193. PMID: 27784537, DOI: 10.1016/j.tiv.2016.10.008.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 Research
2015
In vitro cleavage of diisocyanate-glutathione conjugates by human gamma-glutamyl transpeptidase-1
Wisnewski AV, Liu J, Nassar AF. In vitro cleavage of diisocyanate-glutathione conjugates by human gamma-glutamyl transpeptidase-1. Xenobiotica 2015, 46: 726-732. PMID: 26678254, PMCID: PMC4848134, DOI: 10.3109/00498254.2015.1118576.Peer-Reviewed Original ResearchImmunochemical 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 regionsGlutathione 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
2014
Inception cohort study of workers exposed to toluene diisocyanate at a polyurethane foam factory: Initial one‐year follow‐up
Gui W, Wisnewski AV, Neamtiu I, Gurzau E, Sparer JA, Stowe MH, Liu J, Slade MD, Rusu OA, Redlich CA. Inception cohort study of workers exposed to toluene diisocyanate at a polyurethane foam factory: Initial one‐year follow‐up. American Journal Of Industrial Medicine 2014, 57: 1207-1215. PMID: 25266741, PMCID: PMC4198484, DOI: 10.1002/ajim.22385.Peer-Reviewed Original ResearchMeSH KeywordsAdultAir Pollutants, OccupationalAirway ObstructionAsthma, OccupationalFemaleFollow-Up StudiesForced Expiratory VolumeHumansImmunoglobulin EImmunoglobulin GLost to Follow-UpMaleMiddle AgedOccupational ExposurePolyurethanesPrevalenceProspective StudiesTime FactorsToluene 2,4-DiisocyanateVital CapacityYoung AdultConceptsAsthma symptomsIsocyanate asthmaInception cohort studyHealth effectsCurrent asthma symptomsTDI levelsFirst yearFurther longitudinal evaluationAirflow obstructionCohort studyInception cohortOccupational asthmaTDI exposureRespiratory healthSkin exposureLongitudinal evaluationAsthmaOne-yearPersonal samplingSymptomsRiskExposureFindingsFEV1Spirometry