简介：<正>Manyvirusesestablishlife-longinfectionsintheirnaturalhostwithfewifanyclinicalmanifestations.Therelationshipbetweenvirusandhostisadynamicprocessinwhichthevirushasevolvedthemeanstocoexistbyreducingitsvisibility,whilethehostimmunesystemattemptstosuppressandeliminateinfectionwithoutdamagetoitself.Wearenowbeginningtounderstandthatvirusescanemployavarietyofstrategiestoevadehostimmuneresponses.TheseincludeescapefromTcellrecognition,resistanceto

简介：Majoradvanceshavebeenmadeoverthelastdecadeinourunderstandingofthemolecularbasisofseveralcardiacconditions.Hypertrophiccardiomyopathy(HCM)wasthefirstcardiacdisorderinwhichageneticbasiswasidentifiedandassuch,hasactedasaparadigmforthestudyofaninheritedcardiacdisorder.HCMcanresultinclinicalsymptomsrangingfromnosymptomstosevereheartfailureandprematuresuddendeath.HCMisthecommonestcauseofsuddendeathinthoseagedlessthan35years,includingcompetitiveathletes.Atleasttengeneshavenowbeenidentified,defectsinwhichcauseHCM.Allofthesegenesencodeproteinswhichcomprisethebasiccontractileunitoftheheart,i.e.thesarcomere.Whilemuchisnowknownaboutwhichgenescausediseaseandthevariousclinicalpresentations,verylittleisknownabouthowthesegenedefectscausedisease,andwhatfactorsmodifytheexpressionofthemutantgenes.StudiesinbothcellcultureandanimalmodelsofHCMarenowbeginningtoshedlightonthesignallingpathwaysinvolvedinHCM,andtheroleofbothenvironmentalandgeneticmodifyingfactors.Understandingthesemechanismswillultimatelyimproveourknowledgeofthebasicbiologyofheartmusclefunction,andwillthereforeprovidenewavenuesfortreatingcardiovasculardiseaseinman.

简介：Thetherapeuticeffectofherpessimplexvirusthymidinekinase/ganciclovir(HSV-tk/GCV)systemonhepatocellularcarcinomawasstudiedinthisexperiment.Thetk-containingretroviralrecombinantswereusedtoinfecthepatomacells(BEL-7402)andthecellsweretreatedwithganciclovir(0-100μg/ml).TheresultsshowedthatHSV-tkgenecouldbeefficientlytransferredinvitrointohepatomacellsandstablyexpressed.Thegrowthpotentialofthetk-containingcellswassignificantlyinhibitedbyGCV(P<0.01)ascomparedtothenon-tk-containingcells.TheantitumoreffectofHSV-tk/GCVsystemwasalsoproducedexvivointk-containingtumorofnudemiceascharacterizedbyamarkeddecreaseintumorgrowthafterGCVtreatmentcontrarytoaprogressiveenlargementofnon-tk-containingtumors.Althoughthehistologicalexaminationdemonstratedthattheefficiencyofthegenetransferwaslessthan30%,thekillingeffectofHSV-tk/GCVsystemonhepatocellularcarcinomawasstillsignificantlygenerated.ThegropermechanismofHSV-tkgenetherapyonhepatictumorreferredas“bystandereffect”intherapeuticapproachhasnotbeenfoundinthisstudyandrequiredtobeexploredfurther.

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