Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States 英文参考文献.docVIP

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Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States 英文参考文献.doc

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Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States 英文参考文献

MultiorganDetectionandCharacterizationofProtease- ResistantPrionProteininaCaseofVariantCJD ExaminedintheUnitedStates SilvioNotari1.,FranciscoJ.Moleres1.,StephenB.Hunter2,ErmiasD.Belay3,LawrenceB.Schonberger3, IgnazioCali1,PieroParchi4,Wun-JuShieh3,PaulBrown5,SherifZaki3,Wen-QuanZou1 ,Pierluigi Gambetti1* 1Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America, 2Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia, United States of America, 3National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Center for Disease Control and Prevention,Atlanta,Georgia,UnitedStatesofAmerica,4DipartimentodiScienzeNeurologiche,Universita’diBologna,Italy,5CEA/DSV/iMETI/SEPIA,France Abstract Background: VariantCreutzfeldt–Jakob disease(vCJD) isaprion diseasethought tobeacquiredby theconsumption of prion-contaminatedbeefproducts.Todate,over200caseshavebeenidentifiedaroundtheworld,butmainlyintheUnited Kingdom. Three cases have been identified in the United States; however, these subjects were likely exposed to prion infectionelsewhere.Herewereportonthefirstofthesesubjects. Methodology/Principal Findings: Neuropathological and genetic examinations were carried out using standard procedures. We assessed the presence and characteristics of protease-resistant prion protein (PrPres) in brain and 23 other organs and tissues using immunoblots performed directly on total homogenate or following sodium phosphotungstateprecipitationtoincreasePrPresdetectability.Thebrainshowedalackoftypicalspongiformdegeneration andhadlargeplaques,likelystemmingfromtheextensiveneuronallosscausedbythelongduration(32months)ofthe disease.ThePrPresfoundinthebrainhadthetypicalcharacteristicsofthePrPrespresentinvCJD.Inadditiontothebrain andotherorgansknowntobeprionpositiveinvCJD,suchasthelymphoreticularsystem,pituitaryandadrenalglands,and gastrointestinaltract,PrPreswasalsodetectedforthefirsttimeintheduramater,liver,pa