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簡介：RADIOLOGYORIGINALARTICLEVALUEOFAPPARENTDIFFUSIONCOEFFICIENTMEASUREMENTFORDISCRIMINATIONOFFOCALBENIGNANDMALIGNANTHEPATICMASSESOKILICKESMEZ,1SBAYRAMOGLU,2EINCI2ANDTCIMILLI21DEPARTMENTOFRADIOLOGY,SCHOOLOFMEDICINE,YEDITEPEUNIVERSITYAND2DEPARTMENTOFRADIOLOGY,ISTANBULBAKIRKOYDRSADIKONUKTRAININGANDRESEARCHHOSPITAL,ISTANBUL,TURKEYOKILICKESMEZMDSBAYRAMOGLUMDEINCIMDTCIMILLIMDCORRESPONDENCEDROZGURKILICKESMEZ,DEPARTMENTOFRADIOLOGY,SCHOOLOFMEDICINE,YEDITEPEUNIVERSITY,DEVLETYOLUANKARASTREET102/104,KOZYATAGI34752,ISTANBUL,TURKEYEMAILOKILICKESMEZYAHOOCOMCONFLICTSOFINTERESTNONESUBMITTED30JULY2008ACCEPTED31JULY2008DOI101111/J17549485200902036XSUMMARYTHEPURPOSEOFOURSTUDYWASTOINVESTIGATETHEVALUEOFDIFFUSIONWEIGHTEDMAGNETICRESONANCEIMAGINGDWMRITODISCRIMINATEBENIGNANDMALIGNANTFOCALLESIONSOFTHELIVERUSINGPARALLELIMAGINGTECHNIQUEATOTALOF77PATIENTSAND65HEALTHYCONTROLSWEREENROLLEDINTHESTUDYDWMRIWASPERFORMEDWITHBFACTORSOF0,500AND1000S/MM2,ANDTHEAPPARENTDIFFUSIONCOEFFICIENTSADCVALUESOFTHENORMALLIVERANDTHELESIONSWERECALCULATEDTHEMEANADCVALUEOFTHEFOCALLIVERLESIONSWEREASFOLLOWSSIMPLECYSTS316±018?1023MM2/S,HYDATIDCYSTS258±053?1023MM2/S,HEMANGIOMAS197±049?1023MM2/S,METASTASES114±041?1023MM2/SANDHEPATOCELLULARCARCINOMASHCC115±036?1023MM2/STHEMEANADCVALUESOFALLTHEDISEASEGROUPSWERESTATISTICALLYSIGNIFICANTWHENCOMPAREDWITHTHEMEANADCVALUEOFTHENORMALLIVER156±014?1023MM2/S,P001THEREWEREALSOSTATISTICALLYSIGNIFICANTDIFFERENCESAMONGTHEADCVALUESOFHEMANGIOMASANDHCCMETASTASESP001,ANDSIMPLEANDHYDATIDCYSTSP0008HOWEVER,THEREWASNOSTATISTICALLYSIGNIFICANTDIFFERENCEBETWEENHCCANDMETASTASESTHEPRESENTSTUDYSHOWEDTHATADCMEASUREMENTHASTHEPOTENTIALTODIFFERENTIATEBENIGNANDMALIGNANTFOCALHEPATICLESIONSWEPROPOSETOADDDWSEQUENCEINTHEMRPROTOCOLFORTHEDETECTIONANDQUANTITATIVEDISCRIMINATIONOFHEPATICPATHOLOGIESKEYWORDSABDOMENDIFFUSIONWEIGHTEDIMAGINGLIVERMAGNETICRESONANCEIMAGINGINTRODUCTIONMAGNETICRESONANCEIMAGINGISCONSIDEREDTHEMOSTACCURATEMODALITYTOIMAGETHELIVERFORDETECTIONANDCHARACTERIZATIONOFDIFFUSEANDFOCALLIVERDISEASESANDTODISCRIMINATEBENIGNFROMMALIGNANTTUMORS,REFLECTINGITSABILITYONTHEBASISOFVARIOUSDATAACQUIRED,SUCHAST1,T2,ANDEARLYANDLATEPOSTGADOLINIUMIMAGES1,2CHARACTERIZATIONOFFOCALLIVERLESIONSISVERYIMPORTANTBECAUSEPATIENTSWITHKNOWNPRIMARYMALIGNANTNEOPLASMSOFTENHAVEBENIGNFOCALLIVERLESIONS,WHICHMUSTBEDIFFERENTIATEDFROMMETASTASESTHELACKOFIONIZINGRADIATIONWITHMRIMAGINGANDTHESAFETYOFGADOLINIUMCHELATES,ASCOMPAREDWITHIODINATEDCONTRASTAGENTS,ARETWOIMPORTANTCONSIDERATIONSFORTHEPREFERENTIALUSEOFMRIMAGINGOVERCTSCANNINGINTHEINVESTIGATIONOFLIVERDISEASE3FURTHERMORE,DWIHASEMERGEDASANEWDIAGNOSTICTOOLWITHTHEABILITYTODETECTFOCALLESIONSANDTODISCRIMINATEMALIGNANTONESWITHOUTTHENEEDFORCONTRASTMATERIAL4–7WEAIMEDTOINVESTIGATEWHETHERDWIHASTHEABILITYTODETECTMALIGNANCYANDTODISCRIMINATEMETASTASESANDHEPATOCELLULARCARCINOMASMETHODSTHISWASARETROSPECTIVESTUDYCONDUCTEDATOURINSTITUTIONBETWEENJANUARY2006ANDMARCH2007ATOTALOF77PATIENTS42WOMEN,35MENMEANAGE,59YEARSAND65HEALTHYCONTROLS35WOMEN,30MENMEANAGE,35YEARSWITHCOMPLETELYNORMALLIVERMRIANDLABORATORYFINDINGSWEREENROLLEDINTHESTUDYTHERESEARCHPROTOCOLWASAPPROVEDBYTHEETHICSCOMMITTEEOFOURINSTITUTIONWRITTENCONSENTWASOBTAINEDFROMALLPATIENTSPRIORTOCOMMENCEMENTOFTHESTUDYMAGNETICRESONANCEIMAGINGWASPERFORMEDONA1,5TBODYSCANNERAVANTOSIEMENS,ERLANGEN,GERMANYJOURNALOFMEDICALIMAGINGANDRADIATIONONCOLOGY53200950–5550a2009THEAUTHORSJOURNALCOMPILATIONa2009THEROYALAUSTRALIANANDNEWZEALANDCOLLEGEOFRADIOLOGISTSCLOSESTTHREEMEASUREMENTSINTHEPATIENTGROUP,AFREEHANDROIWASDEFINEDFORTHELESIONSDETECTEDONTHET2WEIGHTEDEPIIMAGEB0,WHILEREFERRINGTOTHECONVENTIONALSEQUENCESFORVERIFICATIONOFTHELESIONBOUNDARIESTHEROIWASTHENCOPIEDTOTHECORRESPONDINGADCMAPSTATISTICALANALYSISALLSTATISTICALANALYSESWEREPERFORMEDUSINGSPSSSTATISTICALPACKAGEFORSOCIALSCIENCESFORWINDOWS100THEADCVALUESOFCASESAREREPORTEDASTHEMEAN±STANDARDDEVIATIONVARIANCEANALYSISANDPAIREDSAMPLESTESTWEREALSOCONDUCTEDFORCOMPARISONOFSEGMENTSOFABDOMINALORGANSAPVALUEOFLESSTHAN005WASCONSIDEREDTOINDICATEASTATISTICALLYSIGNIFICANTDIFFERENCERESULTSAPPARENTDIFFUSIONCOEFFICIENTVALUESOFALLTHEPATIENTSWHOUNDERWENTCONVENTIONALANDDIFFUSIONWEIGHTEDMREXAMINATIONSARELISTEDASBOXPLOTSINFIGURE1THEMEANADCVALUEOFTHELIVERLESIONSWEREASFOLLOWSTABLE1SIMPLECYSTS,20CASES316±018?1023MM2/SHYDATIDCYSTS,13CASES258±053?1023MM2/SHEMANGIOMAS,15CASES197±049?1023MM2/SMETASTASES,13CASES114±041?1023MM2/SANDHEPATOCELLULARCARCINOMASHCC13CASES115±036?1023MM2/STHEMEANADCVALUESOFALLOFTHEDISEASEGROUPSWERESTATISTICALLYSIGNIFICANTWHENCOMPAREDWITHMEANADCVALUEOFTHENORMALLIVERGROUP156±014?1023MM2/S,P001THEREWEREALSOSTATISTICALLYSIGNIFICANTDIFFERENCESAMONGTHEADCVALUESOFHEMANGIOMASANDHCCMETASTASESP001,ANDSIMPLEANDHYDATIDCYSTSP0008HOWEVER,THEREWASNOSTATISTICALLYSIGNIFICANTDIFFERENCEBETWEENHCCANDMETASTASESREPRESENTATIVECASESARESHOWNINFIGURES2–5DISCUSSIONDIFFUSIONISTHETERMUSEDTODESCRIBETHERANDOMBROWNIANMOTIONOFWATERMOLECULES8WITHAVERYSTRONGBIPOLARGRADIENTPULSEINSERTEDINTOEITHERASPINECHOPULSESEQUENCEIESTEJSKALTANNERTECHNIQUEORAGRADIENTECHOPULSESEQUENCE,MRIMAGINGCANBEMADESENSITIVETOTHEDIFFUSIONOFWATERMOLECULESINTHETISSUE6,9DIFFUSIONRESTRICTIONINCREASESINHIGHLYCELLULARTISSUESINCONTRAST,ITDECREASESINLOWCELLULARTISSUESWITHLARGEEXTRACELLULARSPACEORWITHBROKENDOWNCELLULARMEMBRANES7STUDIESHAVEBEENPUBLISHEDCONCERNINGTHEDIFFUSIONPROPERTIESOFFOCALHEPATICLESIONSMOSTOFTHESTUDIESREVEALEDTHATADCVALUESOFBENIGNLESIONSCYSTSANDHEMANGIOMASWERESIGNIFICANTLYHIGHERTHANTHOSEOFMALIGNANTLESIONSATTRIBUTEDTOHIGHCELLULARITYOFMALIGNANTMASSES10–12ASWITHTHEPREVIOUSSTUDIES,WEFOUNDTHATHEPATICCYSTSHADTHEHIGHESTADCBECAUSEOFTHEIRFLUIDCONTENT,WITHNONRESTRICTEDMOTIONOFWATERMOLECULES4,10TABLE1ADCVALUESOFTHEFOCALLIVERLESIONSLESIONSNMEANADCMM2/SNORMALLIVER65156±014?1023MM2/SSIMPLECYSTS20316±018?1023MM2/SHYDATIDCYSTS13258±053?1023MM2/SHEMANGIOMAS15197±049?1023MM2/SHEPATOCELLULARCARCINOMAS13115±036?1023MM2/SMETASTASES13114±041?1023MM2/SADC,APPARENTDIFFUSIONCOEFFICIENTSFIG2FORTYYEAROLDWOMANWITHHEMANGIOMAAAXIALFST2WIMAGEREVEALSAMARKEDHYPERINTENSELESIONBAXIALDIFFUSIONWEIGHTEDB1000S/MM2IMAGEREVEALSMODERATEHYPERINTENSITYCAPPARENTDIFFUSIONCOEFFICIENTSADCWERECALCULATEDTUMORONADCIMAGESHOWSMILDHYPERINTENSITYSLIGHTLYINCREASEDDIFFUSIONCOMPAREDWITHNORMALPARENCHYMAREGIONOFINTERESTWASPLACEDONMASSROI1,CADCOFLESIONWAS192?1023MM2/SOKILICKESMEZETAL52a2009THEAUTHORSJOURNALCOMPILATIONa2009THEROYALAUSTRALIANANDNEWZEALANDCOLLEGEOFRADIOLOGISTS

簡介：MAGE,BAGE,ANDGAGEGENEEXPRESSIONINPATIENTSWITHESOPHAGEALSQUAMOUSCELLCARCINOMAANDADENOCARCINOMAOFTHEGASTRICCARDIAANNALISAZAMBON,PHD1SUSANNAMANDRUZZATO,PHD1ANNAPARENTI,MD2BEATRICEMACINO,PHD1PIERODALERBA,MD1ALBERTORUOL,MD3STEFANOMERIGLIANO,MD3GIOVANNIZANINOTTO,MD3PAOLAZANOVELLO,PHD11DEPARTMENTOFONCOLOGYANDSURGICALSCIENCES,ONCOLOGYSECTION,UNIVERSITYOFPADOVA,PADOVA,ITALY2DEPARTMENTOFONCOLOGYANDSURGICALSCIENCES,PATHOLOGYSECTION,UNIVERSITYOFPADOVA,PADOVA,ITALY3DEPARTMENTOFMEDICALANDSURGICALSCIENCES,CLINICACHIRURGICA4,UNIVERSITYOFPADOVA,PADOVA,ITALYPRESENTEDATTHE33RDCONGRESSOFTHEEUROPEANSOCIETYFORSURGICALRESEARCHESSR,PADOVA,ITALY,APRIL22–25,1998ANDATTHEINTERNATIONALSOCIETYFORTHEDISEASESOFTHEESOPHAGUSISDESEVENTHWORLDCONGRESS,MONTREAL,QUEBEC,CANADA,SEPTEMBER1–41998SUPPORTEDBYTHEASSOCIAZIONEITALIANAPERLARICERCASULCANCROAIRC,MILAN,ITALYANDTHEREGIONEVENETOGRANT657/02/96,RICERCASANITARIAFINALIZZATASMWASSUPPORTEDBYAPOSTDOCTORALFELLOWSHIPFROMICGEB,TRIESTE,ITALYANDBMWASSUPPORTEDBYAPERSONALGRANTFROMAIRCTHEAUTHORSAREGRATEFULTODRGLDESALVOANDMEPIFANIFORSTATISTICALANALYSISANDTOPSEGATOFORHELPINARTICLEPREPARATIONADDRESSFORREPRINTSALBERTORUOL,MD,CLINICACHIRURGICA4,UNIVERSITYOFPADOVA,VIAGIUSTINIANI,2,35128PADOVA,ITALYFAX?390498213152EMAILARUOLUX1UNIPDITRECEIVEDJUNE28,2000REVISIONRECEIVEDJANUARY10,2001ACCEPTEDJANUARY19,2001BACKGROUNDTHEMAGE,BAGE,ANDGAGEGENEFAMILIESCODEFORDISTINCT,TUMORSPECIFICANTIGENSTHATARERECOGNIZEDBYCYTOTOXICTLYMPHOCYTESINTHECONTEXTOFHLAMOLECULESTHEPURPOSEOFTHISSTUDYWASTOANALYZEMAGE,BAGE,ANDGAGEGENEEXPRESSIONINTHETWOMAJORHISTOLOGICTYPESOFESOPHAGEALCARCINOMA,SQUAMOUSCARCINOMAESCCANDADENOCARCINOMACAC,ANDTOCORRELATETHEIREXPRESSIONPATTERNSWITHTHEPRINCIPALPROGNOSTICPARAMETERSANDLONGTERMSURVIVALMETHODSGENEEXPRESSIONWASANALYZEDINSURGICALSAMPLESFROM24PATIENTSWITHESCCAND24PATIENTSWITHCACBYREVERSETRANSCRIPTASEPOLYMERASECHAINREACTIONAMPLIFICATIONRTPCRNONEOFTHEPATIENTSHADRECEIVEDPREOPERATIVECHEMOTHERAPYORRADIOTHERAPY,ANDALLWEREFOLLOWEDUNTILDEATHORFORAMINIMUMOF4YEARSRESULTSSIXTEENESCCSAMPLES67AND9CACSAMPLES375EXPRESSEDATLEASTONEOFTHEGENESUNDERSTUDYTHEEXPRESSIONOFEACHMAGEGENEINTHETWOHISTOLOGICTYPESWASNOTSIGNIFICANTLYDIFFERENT,WITHTHEEXCEPTIONOFMAGE4,WHICHWASEXPRESSEDMOREINESCCSAMPLESTHANINCACSAMPLESBAGEANDGAGEEXPRESSIONWASRATHERLOWAND,INEVERYCASE,WASASSOCIATEDWITHTHEEXPRESSIONOFATLEASTONEMAGEGENECONCLUSIONSINTHEGROUPASAWHOLE,ANDINBOTHESCCANDCACSUBGROUPS,NOSIGNIFICANTCORRELATIONEMERGEDBETWEENTHEEXPRESSIONOFANYGENEANDPROGNOSTICPARAMETERS,SUCHASPATHOLOGICTUMOR,LYMPHNODE,ORDISEASESTAGENEVERTHELESS,BAGEORGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAPOORPROGNOSIS,WHEREASTHEEXPRESSIONOFMAGEGENESINTHEABSENCEOFBAGEANDGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAGOODPROGNOSISCANCER2001911882–8?2001AMERICANCANCERSOCIETYKEYWORDSESOPHAGEALCARCINOMA,TUMORANTIGENS,MAGE,BAGE,GAGEINRECENTYEARS,NUMEROUSHUMANTUMORANTIGENSTHATARERECOGNIZEDBYAUTOLOGOUSCYTOTOXICTLYMPHOCYTESCTLSHAVEBEENIDENTIFIED1ANIMPORTANTCATEGORYOFTHESESOCALLEDTCELLDEFINEDTUMORANTIGENSCONSISTSOFNORMALGENEPRODUCTSTHATARENOTEXPRESSEDINMOSTBODYTISSUES,WITHTHEEXCEPTIONOFMALEGERMLINECELLSANDPLACENTA,ANDAREACTIVATEDINANUMBEROFDIFFERENTTUMORSANTIGENICPEPTIDESENCODEDBYTHEMAGE,BAGE,ANDGAGEGENEFAMILIESAREPROTOTYPESOFTHISCATEGORYOFSHAREDTUMORANTIGENS2–5ALTHOUGHTHEYINITIALLYWEREDESCRIBEDINMELANOMA,THESEGENESHAVEBEENFOUNDTOBEEXPRESSEDINASUBSTANTIALNUMBEROFSOLIDTUMORSINVARIOUSORGANS,SUCHASLUNG,BREAST,BLADDER,HEADANDNECK,ESOPHAGUS,ANDSTOMACH,ASWELLASINSEVERALTUMORCELLLINES2BECAUSEOFTHEIRSTRICTTUMORSPECIFICITY,THEYAREOFPARTICULARINTERESTFORCANCERIMMUNOTHERAPY1882?2001AMERICANCANCERSOCIETYDEOXYNUCLEOTIDESDNTPS,1?LOFA500?G/MLSOLUTIONOFOLIGODT12–18PRIMERS,20UNITSOFRNASEOUTGIBCOBRL,2?LOF01M1,4DITHIOTHREITOL,AND200UNITSOFMOLONEYMURINELEUKEMIAVIRUSREVERSETRANSCRIPTASEGIBCOBRLTHEREACTIONWASINCUBATEDAT42°CFOR60MINUTESANDTHENDILUTEDTO40?LWITHWATERTWOMICROLITERSOFTHECDNAMIXTUREWEREUSEDFOREACHPOLYMERASECHAINREACTIONPCRAMPLIFICATIONINA50?LREACTIONVOLUMECONTAINING1?LOFEACHPRIMER40?M,1?LEACHOF25MMDNTP,15MMMGCL2,AND2UNITSTAQDNAPOLYMERASEPROMEGA,MADISON,WIINBUFFERA,WHICHWASSUPPLIEDBYTHEMANUFACTURERTHEPRIMERSUSEDINTHISSTUDYTOENSURESPECIFICITYFOREACHGENEWEREDESCRIBEDPREVIOUSLY3,4,9THIRTYTWOAMPLIFICATIONCYCLESWERERUN1MINUTEAT94°CAND3MINUTESAT72°CFORMAGE1ANDMAGE31MINUTEAT94°C,2MINUTESAT68°C,AND2MINUTESAT72°CFORMAGE2ANDMAGE41MINUTEAT94°C,2MINUTESAT70°C,AND2MINUTESAT72°CFORMAGE61MINUTEAT94°C,2MINUTESAT62°C,AND2MINUTESAT73°CFORBAGEAND1MINUTEAT94°C,2MINUTESAT55°C,AND2MINUTESAT72°CFORALLOFTHEGAGEGENESCYCLINGWASCONCLUDEDWITHAFINALEXTENSIONSTEPOF15MINUTESAT72°CTOVERIFYRNAINTEGRITYINEACHSAMPLE,23CYCLESFOR1MINUTEAT94°C,2MINUTESAT68°C,AND2MINUTESAT72°CWERERUNWITHPRIMERSSPECIFICFOR?ACTINAFTERAMPLIFICATION,PCRPRODUCTSWEREANALYZEDBYAGAROSEGELELECTROPHORESISSTATISTICALANALYSISSTATISTICALANALYSESWEREPERFORMEDUSINGTHESASSTATISTICALPACKAGESAS,INC,CARY,NCDIFFERENCESBETWEENGROUPSWEREASSESSEDBYCHISQUAREANALYSIS,FISHEREXACTTEST,ORSTUDENTTTEST,ASINDICATEDALLPVALUES?005WERECONSIDEREDSIGNIFICANTSURVIVALWASMEASUREDFROMTHEDATEOFSURGERYTODEATHORLASTDATEOFFOLLOWUPSURVIVALRATESANDSTANDARDERRORSWERECALCULATEDBYTHEKAPLAN–MEIERMETHOD,INCLUDINGDEATHSFROMALLCAUSES,EXCEPTTHETWOHOSPITALDEATHSTHATWERERELATEDTOPOSTOPERATIVECOMPLICATIONSTHESTATISTICALSIGNIFICANCEOFDIFFERENCESINSURVIVALWASANALYZEDBYTHELOGRANKTEST,WITHP?005CONSIDEREDSIGNIFICANTTHEPROGNOSTICIMPORTANCEOFCLINICALVARIABLESWASEVALUATEDBYACOXPROPORTIONALHAZARDREGRESSIONUSINGMULTIVARIATEANALYSISRESULTSMAGE1,MAGE2,MAGE3,MAGE4,MAGE6,BAGE,ANDGAGEGENEEXPRESSIONWASEVALUATEDIN48SURGICALSPECIMENS,OFWHICH24SPECIMENSWEREESCC,AND24SPECIMENSWERECACTABLE1,ANDIN5SAMPLESOFNORMALESOPHAGEALTISSUEADJACENTTOTHETUMORSIXTYSEVENPERCENTOFTHEESCCTUMORSAND375OFTHECACTUMORSEXPRESSEDATLEASTONEOFTHESEGENESFIGURE1SHOWSTHEDIFFERENTPATTERNSOFMAGEBAGEGAGEGENEEXPRESSIONINEIGHTREPRESENTATIVECACSAMPLESTOGETHERWITHAPPROPRIATECONTROLSTABLE2SHOWSTHATTHEPATTERNOFMAGEGENEEXPRESSIONWASVERYSIMILARINBOTHESCCANDCACSAMPLES,EXCEPTFORMAGE4,WHICHWASEXPRESSEDSIGNIFICANTLYMOREINTHEESCCSAMPLES58VS25,RESPECTIVELYP?0019TWOESCCSAMPLES8,BUTNONEOFTHECACSAMPLES,EXPRESSEDBAGEP?0149GAGEGENEEXPRESSIONWASOBSERVEDINFOURESCCSAMPLES17ANDINTHREECACSAMPLES13P?0683NONEOFTHEGENESUNDERSTUDYWASEXPRESSEDINNORMALESOPHAGEALTISSUESAMPLESDATANOTSHOWNWEINVESTIGATEDTHEASSOCIATIONBETWEENMAGE,BAGE,ANDGAGEGENEEXPRESSION,ANDTHECLINICOPATHOLOGICPARAMETERSLISTEDINTABLE1INTHEGROUPOFPATIENTSASAWHOLEANDINBOTHESCCANDCACSUBGROUPS,NOSIGNIFICANTCORRELATIONEMERGEDBETWEENTHEEXPRESSIONOFANYOFTHESEGENES,ANDPATIENTGENDERANDAGE,HISTOLOGICTUMORTYPEANDGRADINGPT,PN,ANDPSTAGE,ANDTYPEOFRESECTION,WITHTHESINGLEEXCEPTIONOFTHEGAGEGENE,WHICHWASEXPRESSEDSIGNIFICANTLYMOREINTUMORSAMPLESOBTAINEDFROMPATIENTSWHOUNDERWENTR1–R2RESECTIONP?0027DATANOTSHOWNMAGE,BAGE,ANDGAGEGENEEXPRESSIONAPPEAREDTOBECLUSTEREDINASUBSETOFTHETUMORSEXAMINED,BECAUSEMOSTLESIONSEITHERDIDNOTEXPRESSANYGENE4823OF48PATIENTSORSIMULTANEOUSLYCOEXPRESSEDTHREEORMOREGENES3517OF48PATIENTSTABLE3BAGEANDGAGEGENESALWAYSWERECOEXPRESSEDWITHONEORMOREMEMBERSOFTHEMAGEFAMILYTHEOVERALL1YEAR,3YEAR,AND5YEARACTUARIALSURVIVALRATESOFPATIENTSSURVIVINGESOPHAGECTOMYN?46PATIENTSWERE85,41,AND24,RESPECTIVELYTHE1YEAR,3YEAR,AND5YEARACTUARIALSURVIVALRATESAFTERR0RESECTIONN?37PATIENTSWERE89,51,AND30,RESPECTIVELYTABLE4SUMMARIZESTHEUNIVARIATEANALYSISOFTHEPROGNOSTICVALUEOFSEVERALCLINICOPATHOLOGICPARAMETERSINTHEFIRSTSETOFSURVIVALANALYSES,THESAMPLESWEREDIVIDEDINTOTWOCOHORTSTHOSEEXPRESSINGONEORMOREOFTHEGENESSTUDIEDANDTHOSESHOWINGNOGENEEXPRESSIONINTHEENTIREGROUPOFPATIENTSANDINBOTHESCCANDCACSUBGROUPS,WHICHWEREEVALUATEDSEPARATELY,NOSIGNIFICANTASSOCIATIONWASFOUNDBETWEENTHEABOVETWOCOHORTSANDSURVIVALDATANOTSHOWNASIMILARANALYSISWASCARRIEDOUTFOREACHOFTHEMAGE,BAGE,ANDGAGEGENESSEPARATELYONLYBAGEORGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAPOORPROGNOSISTABLE4FINALLY,WEGROUPEDTHEPATIENTSACCORDINGTOTHE1884CANCERMAY15,2001/VOLUME91/NUMBER10

簡介：中文中文3650字，字，2660單詞，單詞，14000英文字符英文字符出處出處TORRICELLIFCM,DES,SARKISSIANC,ETALHYDROPHILICGUIDEWIRESEVALUATIONANDCOMPARISONOFTHEIRPROPERTIESANDSAFETYJUROLOGY,2013,82511821186親水導絲親水導絲評估和比較其性能與安全性評估和比較其性能與安全性FABIOCESARMIRANDATORRICELLI，SHUBHADE，CARLSARKISSIAN，ANDMANOJMONGA目的目的比較10種市售親水導絲的物理和機械性能方法方法進行體外測試評估10種不同的直型親水導絲（5種普通導絲和5種硬導絲）GLIDEWIRE，NICORE，EZGLIDER，HIWIRE與ZIPWIRE。測量所有這10種導絲的頭端穿刺力，頭端彎曲力，桿彎曲力以及在運動中的摩擦力。采用高倍光學顯微鏡測量頭端輪廓。結果結果GLIDEWIRE穿刺我們的模型所需的力最大（P01）。EZGLIDER，ZIPWIRE和GLIDEWIRE頭端彎曲力最?。≒＜001）。GLIDEWIRE桿最硬（P＜001）。EZGLIDER和GLIDEWIRE在摩擦力測試中力最大。就硬導絲而言，GLIDEWIRES在穿刺測試中力最大（P≤05）。GLIDEWIRES和EZGLIDERS頭端彎曲力最小。ZIPWIRES和NICORES桿最硬（P≤01）GLIDEWIRES在摩擦測試中力最大（P≤001）。頭端輪廓測試顯示ZIPWIRE，HIWIRES以及EZGLIDERS頭端最圓。結論結論每一種導線都有其獨特的優(yōu)點和缺點。雖然GLIDEWIRE（硬導絲和普通導絲兩種）潤滑性較差，但是其刺穿的可能性最低。GLIDEWIRE和EZGLIDER頭端彎曲的力最小。在腔道泌尿外科手術過程中選擇正確的導絲可以幫助提高成功率，減少發(fā)病率。當通過狹窄的輸尿管段或嵌頓結石時，可以使用親水性柔韌導絲繞過阻塞，不會發(fā)生穿孔或創(chuàng)傷。目前存在大量的市售導絲，每個都有其獨特的屬性，這些屬性可以影響它們的性能和潛在的發(fā)病率。導絲的功能是在輸尿管撕裂的情況下提供連續(xù)性和作為器械能夠通過的引導。由于術中對導絲的需求在不同情況下是不一樣的，可以使用各種不同的組成材料、形狀、桿剛性、潤滑性，表面涂層、頭端設計和柔韌性的導絲?？紤]所有這些屬性是為臨床應用選擇合適的導絲的關鍵。在遇到嚴重曲折、障礙物或嘗試用普通導絲失敗等復雜的情況下，親水導絲通常會被用來幫助疏通通道。這些導絲通常有一個堅實的鎳鈦或金屬合金核心，以及持久的親水涂層，親水涂層顯著減少了其濕潤時的摩擦系數。圖1A穿刺實驗；B桿彎曲試驗；C頭端彎曲試；D摩擦實驗統計分析導絲被分為2組（普通VS硬），使用單向方差分析來確定各組中的各個測試的所有導絲之間的統計學差異。T檢驗用于各試驗中的導線之間的成對比較。使用MICROSOFTEXCEL分析工具庫（微軟，華盛頓州雷蒙德市）來分析所收集的數據。顯著性被定為P005。結果所有導絲的直徑為0889毫米，長150厘米，帶3厘米軟頭。單因素方差分析結果顯示，在所有測試每個組內導絲之間平均力測量有顯著的統計學差異（P0001表1）。普通硬導絲普通GLIDEWIRE刺穿我們的模型需要約的力量比其他導絲大約40（0363±0704N），其次是ZIPWIRE（0328±0085N，P340），EZGLIDER（0261±0071N，P06），HIWIRE（0259±0038N，P001），以及NICORE（0257±0048N，P01）。桿彎曲測試表明GLIDEWIRE最硬（0134±0005），明顯比其他導絲需要更大

簡介：PROCNATLACADSCIUSAVOL95,PP8801–8805,JULY1998MEDICALSCIENCESMYOCYTEPROLIFERATIONINENDSTAGECARDIACFAILUREINHUMANSMITOTICINDEX?CYTOKINESISJANKAJSTURA?,ANNAROSALERI,NICOLETTAFINATO?,CARLADILORETO?,CARLOABELTRAMI?,ANDPIEROANVERSADEPARTMENTOFMEDICINE,NEWYORKMEDICALCOLLEGE,VALHALLA,NY10595AND?DEPARTMENTOFPATHOLOGY,UNIVERSITYOFUDINE33100,UDINE,ITALYCOMMUNICATEDBYEUGENEBRAUNWALD,PARTNERSHEALTHCARESYSTEM,INC,BOSTON,MA,MAY18,1998RECEIVEDFORREVIEWJANUARY14,1998ABSTRACTINTRODUCEDSEVERALDECADESAGO,THEDOGMAPERSISTSTHATCARDIACMYOCYTESARETERMINALLYDIFFERENTIATEDCELLSANDTHATDIVISIONOFMUSCLECELLSISIMPOSSIBLEINTHEADULTHEARTMORERECENTLY,NUCLEARMITOTICDIVISIONSINMYOCYTESOCCASIONALLYWERESEEN,BUTTHOSEOBSERVATIONSWERECHALLENGEDONTHEASSUMPTIONTHATTHERATEOFCELLPROLIFERATIONWASINCONSEQUENTIALFORACTUALTISSUEREGENERATIONMOREOVER,MITOSESWERENEVERDETECTEDINNORMALMYOCARDIUMHOWEVER,THEANALYSISOFROUTINEHISTOLOGICPREPARATIONSCONSTITUTEDTHEBASISFORTHEBELIEFTHATMYOCYTESWEREUNABLETOREENTERTHECELLCYCLEANDDIVIDE,IGNORINGTHELIMITATIONSOFTHESETECHNIQUESWEREPORTHEREBYCONFOCALMICROSCOPYTHAT14MYOCYTESPERMILLIONWEREINMITOSISINCONTROLHUMANHEARTSANEARLY10FOLDINCREASEINTHISPARAMETERWASMEASUREDINENDSTAGEISCHEMICHEARTDISEASE152MYOCYTESPERMILLIONANDINIDIOPATHICDILATEDCARDIOMYOPATHY131MYOCYTESPERMILLIONBECAUSETHELEFTVENTRICLECONTAINS58?109MYOCYTES,THESEMITOTICINDICESIMPLYTHAT812?103,882?103,AND760?103MYOCYTESWEREINMITOSISINTHEENTIREVENTRICULARMYOCARDIUMOFCONTROLHEARTSANDHEARTSAFFECTEDBYISCHEMICANDIDIOPATHICDILATEDCARDIOMYOPATHY,RESPECTIVELYADDITIONALLY,MITOSISLASTSLESSTHAN1HR,SUGGESTINGTHATLARGENUMBERSOFMYOCYTESCANBEFORMEDINTHENONPATHOLOGICANDPATHOLOGICHEARTWITHTIMEEVIDENCEOFCYTOKINESISINMYOCYTESWASOBTAINED,PROVIDINGUNEQUIVOCALPROOFOFMYOCYTEPROLIFERATIONITISAGENERALCONTENTIONTHATCARDIACMYOCYTESAREUNABLETODIVIDEINTHEADULTHEART1,2HOWEVER,QUANTITATIVERESULTSSUGGESTTHATANINCREASEINMYOCYTENUMBEROCCURSWITHSEVEREMYOCARDIALHYPERTROPHY3,4,BUTBECAUSEMITOSESINMYOCYTESWERENOTIDENTIFIED,THISDEFICIENCYLEDTODISBELIEFOFTHESEMORPHOMETRICRESULTSTHEOCCASIONALDETECTIONOFNUCLEARMITOTICDIVISIONSINTHEPATHOLOGICHEART5,6,WASCONSIDEREDOFNOVALUEINTERMSOFACTUALREGENERATIONOFMYOCARDIALMASSADDITIONALLY,MITOSESWERENEVEROBSERVEDINCONTROLMYOCARDIUMSIMILARLY,DOCUMENTATIONOFCYTOKINESISINMYOCYTESWASLACKINGISCHEMICANDIDIOPATHICDILATEDCARDIOMYOPATHIESINHUMANSARECHARACTERIZEDSTRUCTURALLYBYSEVEREMYOCARDIALSCARRINGCONSISTINGOFMULTIPLESITESOFREPLACEMENTFIBROSISANDDIFFUSEINTERSTITIALFIBROSIS7–10MOREOVER,AREASOFSEGMENTALFIBROSISAREPRESENTINALLCASESOFISCHEMICMYOPATHIES7,9SEGMENTAL,REPLACEMENT,ANDINTERSTITIALFIBROSISARETHECONSEQUENCEOFMYOCYTENECROSISHOWEVER,ADISCREPANCYEXISTSBETWEENTHEEXTENSIVECOLLAGENACCUMULATIONANDTHEMODESTREDUCTIONINTHENUMBEROFVENTRICULARMYOCYTESINTHEPOSTINFARCTEDHUMANHEART9THEDEPOSITIONOF1MM3OFCOLLAGENREFLECTSTHELOSSOF50?103MUSCLECELLS11,ANDTHEMAGNITUDEOFFIBROSISINENDSTAGEISCHEMICCARDIOMYOPATHYWOULDIMPLYANEARLY90DECREASEINTHETOTALNUMBEROFLEFTVENTRICULARMYOCYTES9CONVERSELY,DECREASESOFLESSTHAN30HAVEBEENREPORTED9THISDISCREPANCYISEVENMOREAPPARENTINIDIOPATHICDILATEDCARDIOMYOPATHYINWHICHMYOCARDIALFIBROSISISASSOCIATEDWITHPRESERVATIONOFTHENUMBEROFMYOCYTESINTHEVENTRICLES10UNDERSTANDINGOFTHECELLULARBASISOFWALLRESTRUCTURINGINTHEDISEASEDHEARTISCOMPLICATEDFURTHERBYTHEDOCUMENTATIONTHATPROGRAMMEDMYOCYTECELLDEATHOCCURSWITHVENTRICULARDECOMPENSATION12,13APOPTOSISDOESNOTRESULTINTISSUEFIBROSISDYINGMYOCYTESAREREMOVEDFROMNEIGHBORINGCELLSINTHEABSENCEOFANINFLAMMATORYREACTION14THESEPHENOMENA,INDICATINGSEVEREONGOINGNECROTICANDAPOPTOTICMYOCYTEDEATH,POINTTOTHEPOSSIBILITYTHATMYOCYTESARENOTTERMINALLYDIFFERENTIATEDANDCELLPROLIFERATIONMAYBESTIMULATEDINTHEPATHOLOGICHEARTIMMUNOCYTOCHEMISTRYANDCONFOCALMICROSCOPYWEREUSEDHERETOMEASUREAMITOTICINDEXINMYOCYTESOFHEARTSOBTAINEDFROMPATIENTSUNDERGOINGCARDIACTRANSPLANTATIONASARESULTOFCHRONICISCHEMICHEARTDISEASEANDDILATEDCARDIOMYOPATHYHEARTSCOLLECTEDATAUTOPSYWEREUSEDASCONTROLSMATERIALSANDMETHODSCARDIACCHARACTERISTICSTWENTYSEVENPATIENTSUNDERGOINGCARDIACTRANSPLANTATION,12FORISCHEMICAND15FORIDIOPATHICDILATEDCARDIOMYOPATHY,WERESTUDIEDTHEFIRSTGROUPINCLUDED11MALESANDONEFEMALE,WITHANAVERAGEAGEOF52?9YEARS,ANDTHESECOND11MALESANDFOURFEMALES,WITHANAVERAGEAGEOF55?11YEARSNINECONTROLHEARTS,SEVENMALESANDTWOFEMALES,WITHANAVERAGEAGEOF48?15YEARS,WERECOLLECTEDATAUTOPSYWITHIN15HRAFTERDEATHDEATHOCCURREDFROMCAUSESOTHERTHANCARDIOVASCULARDISEASEMITOTICINDEXINTHE27EXPLANTEDANDNINECONTROLHEARTS,SPECIMENSCOMPRISINGTHEENTIRETHICKNESSOFTHEANTERIORANDPOSTERIORASPECTSOFTHELEFTVENTRICULARWALLWEREOBTAINEDHALFWAYBETWEENTHEAPEXANDTHEBASEOFTHEHEARTSAMPLESWEREFIXEDINFORMALINANDEMBEDDEDINPARAFFINSECTIONSWERESTAINEDWITHPROPIDIUMIODIDE20?G?MLAND?SARCOMERICACTINANTIBODYCLONE5C5,SIGMATOVISUALIZEDNAANDMYOFIBRILLARSTRUCTURESTHESESECTIONSWEREEXAMINEDBYCONFOCALMICROSCOPYMRC1000,BIORADWITHANOPTICALSECTIONTHICKNESSOF057?MTHEPERCENTAGEOFMYOCYTENUCLEIUNDERGOINGMITOSISWASOBTAINEDBYSAMPLINGANUMBEROFMYOCYTENUCLEI,VARYINGFROM12,000TO67,000VALUESINCONTROLHEARTSWERE75,000AND230,000THEEVALUATIONOFAMITOTICINDEXININTERSTITIALCELLSINCLUDEDSEVENCASESWITHISCHEMICCARDIOMYOPATHY,FIVEWITHDILATEDCARDIOMYOPATHY,ANDFOURCONTROLHEARTSINEACHPATHOLOGICANDNORMALHEART30,000AND100,000NUCLEIWERESAMPLED,RESPECTIVELYDATACOLLECTIONANDANALYSISRESULTSAREPRESENTEDASMEAN?SDSIGNIFICANCEBETWEENTWOMEASUREMENTSWASDETERMINEDBYTHESTUDENT’STTEST,ANDINMULTIPLECOMPARISONSWASEVALUATEDBYTHEBONFERRONIMETHOD15P?005WASCONSIDEREDSIGNIFICANTTHEPUBLICATIONCOSTSOFTHISARTICLEWEREDEFRAYEDINPARTBYPAGECHARGEPAYMENTTHISARTICLEMUSTTHEREFOREBEHEREBYMARKED‘‘ADVERTISEMENT’’INACCORDANCEWITH18USC§1734SOLELYTOINDICATETHISFACT?1998BYTHENATIONALACADEMYOFSCIENCES00278424?98?9588015200?0PNASISAVAILABLEONLINEATHTTP??WWWPNASORG?TOWHOMREPRINTREQUESTSSHOULDBEADDRESSEDATDEPARTMENTOFMEDICINE,VOSBURGHPAVILION,ROOM302,NEWYORKMEDICALCOLLEGE,VALHALLA,NY105958801RESULTSPATIENTSALLPATIENTSHADNEWYORKHEARTASSOCIATIONFUNCTIONALCLASSIIIORIVLEFTANDRIGHTVENTRICULARWEIGHTSWERE189?26AND62?18G,RESPECTIVELY,INCONTROLS,281?51AND110?33G,RESPECTIVELY,INISCHEMICCARDIOMYOPATHY,AND362?129AND96?36G,RESPECTIVELY,INDILATEDCARDIOMYOPATHYTHE49P?005AND92P?0001INCREASEINLEFTVENTRICULARWEIGHT,AND77P?001AND55P?005INCREASEINRIGHTVENTRICULARWEIGHTWITHISCHEMICANDDILATEDCARDIOMYOPATHY,RESPECTIVELY,WERESIGNIFICANTTISSUESAMPLINGOFTHELEFTVENTRICLEWASRESTRICTEDTOREGIONSINWHICHAREASOFSCARRINGWERENOTMACROSCOPICALLYVISIBLEHOWEVER,SMALLFOCIOFREPLACEMENTFIBROSISANDDIFFUSEINTERSTITIALFIBROSISWEREPRESENTINTHETISSUESECTIONSFROMPATHOLOGICHEARTSAREASOFREPARATIVEANDINTERSTITIALFIBROSISOCCASIONALLYWERESEENINTHELEFTVENTRICLEOFCONTROLHEARTSCONFOCALMICROSCOPYSECTIONSOFMYOCARDIUMWERELABELEDWITHPROPIDIUMIODIDEAND?SARCOMERICACTINANTIBODYTHISANTIBODYISSPECIFICFORIBANDSOFCARDIACANDSKELETALMUSCLECELLSANDDOESNOTREACTWITHOTHERACTINISOFORMS16CONFOCALMICROSCOPYALLOWEDANACCURATEIDENTIFICATIONOFMITOSISINMYOCYTESCHROMOSOMESWEREDEPICTEDBYTHEGREENCOLORASSIGNEDTOPROPIDIUMIODIDEFLUORESCENCE,ANDMYOFIBRILLARSTRUCTURESWERERECOGNIZEDBYTHEREDCOLORASSIGNEDTOTHEFLUORESCENCEOF?SARCOMERICACTINANTIBODYLABELINGFIG1A–CILLUSTRATESANUCLEUSINMITOSISANDTWODAUGHTERCELLSATTHECOMPLETIONOFCYTOKINESISINAPATIENTAFFECTEDBYDILATEDCARDIOMYOPATHYINTHISLATTEREXAMPLE,THEAGGREGATESOFCHROMOSOMESMIRROREACHOTHERINTHETWONEWLYGENERATEDMYOCYTESFIG1ESHOWSALATEPROPHASETHATISCHARACTERIZEDBYTHEPRESERVATIONOFNUCLEARSHAPEINTHEABSENCEOFNUCLEARMEMBRANETWOMOREMYOCYTENUCLEIEXHIBITINGMETAPHASECHROMOSOMESAREDEPICTEDINFIG1DANDFTHEINITIALSEPARATIONOFCHROMOSOMESINFIG1DMAYCORRESPONDTOLATEMETAPHASEORONSETOFANAPHASETHESETHREEMITOTICFIGURESWEREFOUNDINACASEOFISCHEMICCARDIOMYOPATHY,DILATEDCARDIOMYOPATHY,ANDACONTROLHEART,RESPECTIVELYAMITOTICIMAGEINANINTERSTITIALCELLANDTHREEADDITIONALMITOSESINMYOCYTESAREDEPICTEDINFIG1G–LUNDIFFERENTIATEDCYTOPLASMSURROUNDINGTHENUCLEUSUNDERGOINGDIVISIONFIG1IWASOBSERVEDIN52OFTHECASES74OF142ORGANELLESBREAKUPINTOSMALLFRAGMENTSTOALLOWMOREUNIFORMDISTRIBUTIONOFTHESECOMPONENTSINTHETWODAUGHTERCELLSTHEDISTINCTIONBETWEENMYOCYTEANDNONMYOCYTENUCLEIWASEXTREMELYSIMPLE,BECAUSEINTERSTITIALCELLSWERENOTSTAINEDBY?SARCOMERICACTINANTIBODYANDONLYTHENUCLEUSCOULDBEIDENTIFIEDBYPROPIDIUMIODIDESTAININGFIG1G,H,ANDJ–LTHISWASAPPARENTINNONDIVIDINGANDDIVIDINGINTERSTITIALCELLSFIG1GTHEREWASNOAPPARENTDIFFERENCEINTHELOCALIZATIONOFMITOSESINTHEANTERIORANDPOSTERIORASPECTSOFTHELEFTVENTRICLEINCONTROLANDPATHOLOGICHEARTSTHEAVERAGEAREAOFMYOCARDIUMEXAMINEDBYCONFOCALMICROSCOPYINEACHPATIENTWAS609?240MM2INCONTROLS,327?193MM2INISCHEMICCARDIOMYOPATHY,AND341?194MM2INDILATEDCARDIOMYOPATHYCORRESPONDINGNUMBERSOFMYOCYTENUCLEICOUNTEDWERE141,136?56,699,38,854?16,766,AND36,013?17,134VALUESFORMYOCYTEMITOTICFIGURESWERE18?06,51?35,AND43?20,RESPECTIVELYTHESEDATAALLOWEDTHECOMPUTATIONOFAMYOCYTEMITOTICINDEXINEACHGROUPFIG2INNORMALLEFTVENTRICLES,ANAVERAGEOF14MYOCYTESPERMILLIONCELLSWEREUNDERGOINGMITOSIS,BUTAMUCHHIGHERMITOTICINDEXWASMEASUREDINPATHOLOGICHEARTSINISCHEMICCARDIOMYOPATHY,152MYOCYTESPERMILLIONWEREDIVIDING,ANDINDILATEDCARDIOMYOPATHY,131MYOCYTESPERMILLIONWEREINMITOSISTHESMALLDIFFERENCEBETWEENTHETWOGROUPSOFPATIENTSWITHCARDIACFAILUREWASNOTSIGNIFICANT,YIELDINGANAVERAGEVALUEOF140PROLIFERATINGMYOCYTESPERMILLIONCELLSINCOMPARISONWITHHEALTHYMYOCARDIUM,CARDIACFAILUREWASCHARACTERIZEDBYA10FOLDINCREASEINTHENUMBEROFDIVIDINGMYOCYTESP?00001NOGENDERDIFFERENCEINTHISPARAMETERCOULDBEDETECTEDTHEMITOTICINDEXININTERSTITIALCELLSWAS18?13PERMILLIONCELLSINCONTROLSN?4AND106?42PERMILLIONCELLSINFAILINGHEARTSN?12SEVENISCHEMICANDFIVEIDIOPATHICMYOPATHIESWITHRESPECTTOMYOCYTES140?50N?27,THE24LOWERVALUEININTERSTITIALCELLSWASNOTSIGNIFICANTDISCUSSIONCARDIACHYPERTROPHYINTHEEARLY1920S,ANATOMICALSTUDIESEMPHASIZEDTHEDIFFICULTIESOFDETECTINGMITOTICFIGURESINMYOCYTESAND,ONTHISBASIS,INTRODUCEDTHECONCEPTTHATMUSCLECELLPROLIFERATIONISABSENTINTHEADULT,FULLYDIFFERENTIATED,MAMMALIANMYOCARDIUM1MOREOVER,EXPERIMENTALRESULTSOFACUTECARDIACHYPERTROPHYINRODENTSDEMONSTRATEDTHEINABILITYOFMYOCYTESTOREENTERTHECELLCYCLE,SYNTHESIZEDNA,ANDUNDERGOMITOTICDIVISION17–19THESEOBSERVATIONSWERERESPONSIBLEFORTHECREATIONOFTHEDOGMATHAT,SHORTLYAFTERBIRTH,VENTRICULARMYOCYTESWITHDRAWPERMANENTLYFROMTHECELLCYCLEANDAREDESTINEDTODIEWITHOUT

簡介：中文中文3500字出處出處CHOIWH,KWONSU,JWAYJ,ETALTHEPULMONARYEMBOLISMSEVERITYINDEXINPREDICTINGTHEPROGNOSISOFPATIENTSWITHPULMONARYEMBOLISMJKOREANJOURNALOFINTERNALMEDICINE,2009,242123127肺栓塞嚴重程度指數預測肺栓塞患者的預后分析肺栓塞嚴重程度指數預測肺栓塞患者的預后分析CHOIWH,KWONSU,JWAYJ,ETAL【摘要】背景/目的許多預后模型已經被建立來幫助醫(yī)生做出醫(yī)療決定以更好的治療肺栓塞患者。在這些模型中，肺栓塞嚴重程度指數（PESI）已被證明是一個成功的急性肺栓塞患者危險分層工具。然而，PESI，沒有被應用在韓國的肺栓塞患者。方法在這項研究中的患者由仁濟大學一山白醫(yī)院進行計算機斷層掃描，時間1999年12月至2007年3月。為病人進行危險分層使用的PESI。根據PESI計算死亡風險。結果在這項研究中，90例患者中，有10例為PESI，29例為PESIII類，22例Ⅲ類，8例IV級，10例V級。30天之后，在每個級別的死亡率分別為0，103，91，0和50％（P00016），而分別的醫(yī)院內死亡率為48，138，136，125，和50％（P值00065）?？傮w死亡率為95，276，318，500和60％（P00019）。死亡率與PESI分級顯著相關。結論PESI分級被發(fā)現與30天死亡率，醫(yī)院內死亡率和整體死亡率顯著相關。我們的數據表明的PESI可以被用來預測肺栓塞患者的預后和決定患者的治療?！娟P鍵詞】急性肺栓塞預后簡介肺動脈栓塞發(fā)生比較頻繁，在美國每年每10萬人有23例1，但是，由于其臨床特點是非特異的，因此診斷肺栓塞不是容易的。進而，如果沒有適當的治療，肺栓塞是致命的。因此，恰當的懷疑和適當的評估對于預后是很重要的。一旦預后被預測，通過適當的治療，死亡率可以降低。雖然已經取得了明確的肺栓塞的危險因素分類及治療方法，預后指標數據仍是相對少。然而，自2000年日內瓦評分發(fā)現2和2005年肺栓塞嚴重性指數（PESI）3被提出，這兩種模型已被引入。PESI評分被證明具有更高的預測精度4。表面上，韓國人可能會有較少肺栓塞的危險因素，如肥胖或深靜脈血栓形成，與西方人相比，并可能有較好的預后5,6。然而，在目前的較少有數據支持這一論斷。出于這個原因，我們分析了用的PESI3分析韓國肺栓塞患者的預后預測。方法病人選擇1999年12月至2007年3月，我們招收在仁濟大學的一山白醫(yī)院的195例確診為急性肺栓塞的住院病人或門診病人，根據韓國疾病指南（KCD）。在這些患者中，84診斷不充分（即沒有經計算機斷層掃描（CT）證實肺栓塞），21人生存或死亡沒能由醫(yī)療記錄錄或電話或保存病歷中獲得，將他們排除在外。在這項研究中，共對90名患者進行了評價。研究設計1999年12月，我們選擇經胸部CT檢查證實肺栓塞的患者，對他們的醫(yī)療記錄進行了分析。除了11項的被認為包括在PESI指數中的項目外，還記錄了年齡，性別，既往病史，合并癥，臨床癥狀3。根據AUJESKY等人3提出的方法，分數計算如下年齡每歲為1分，男性10分，心率110次/分鐘為20分，癌癥為30分，心臟衰竭10分，慢性肺疾病10分，收縮壓30次/分鐘為20分，體溫36℃為20分，精神狀態(tài)改變?yōu)?0討論肺栓塞患者的死亡率報告的各種各樣（從2％到95％）79。根據我們的數據，30天的死亡率為111％，而住院期間的死亡率為156％，總死亡率為300％。我們懷疑該報告的死亡率，因為每個病人有一些混雜因素，可能會影響他/她的預后，如不同的合并疾病和不同程度的肺栓塞。然而，很少有報告中均提到的因素，可以影響預后或肺栓塞的預測因素。要創(chuàng)建一個肺栓塞患者預后預測系統，日內瓦評分22000年開發(fā)，PESI評分3在2005年首次提出。自那時以來，PESI評分已被證明是一個較好的預后模型4。AUJESKY等3報道，PESI評分IV級的患者30天的死亡率為08271％，意味著PESI評分越高的患者死亡率有增加的傾向。PESI被應用于韓國，30天的死亡率，住院期間死亡率和總死亡率為060％。由于所有的結果都有顯著的意義，PESI預測韓國肺栓塞患者的預后是有意義的（30天死亡率P00016，住院死亡率P00065，整體死亡率P00019）。AUJESKY等人3斷言，PESI可以被用來確定低風險群體，并制定一個治療計劃。他們報告說，PESI評分I和II的患者30天的死亡率為16％和35％以下。治療過程中出血的危險肺動脈栓塞復發(fā)的頻率要低一些。他們還聲稱，在I級和II級的患者，低分子量肝素可以安全地使用，即使在門診病人，這些患者實際上是一個低風險組10。然而，當根據PESI計算韓國患者30天的死亡率，I級患者為0％，而II級患者為103％，組間有顯著差異。AUJESKY等報道3，PESI為II級的病人難以通過日間護理治療。住院期間死亡率（I級48％，Ⅱ級138％）（P0029）和總死亡率（I級95％，Ⅱ級276％）（P0115），但兩組之間的差異無統計學意義。這可能因為PESI評分I級患者21個，II級患者的數量為29人。因此，對于兩個PESIⅠ和Ⅱ級為低風險群體門診治療可能是危險的。IIIV級的患者表現出了類似的30天死亡率，住院期間的死亡率和總死亡率。等級越高沒有死亡率增加的傾向（P0424，0995和0281），當PESI評分IIIV被重新分組為中等風險組，分級越高，死亡率明顯增加（30天死亡率P00016→00003，住院死亡率P00065→00038，整體死亡率P00019→00034）。因此，如果的PESI分級被重新分為低危（I級），中危（IIIV級），高危（V級），可改善后預測指標的便利性，可行性和準確性。比較各組死亡率，在低，中，高危人群分別為0，82％和50％，而30天死亡率住院期間死亡率分別為48，131和50％。相比較而言，總死亡率為95，311，和60％（表2）。肺栓塞要確定合適的治療方案，最重要的考慮病人的血流動力學穩(wěn)定和超聲心動圖結果。在這項研究中，觀察右心室運動障礙三個75例患者采取了心電圖，值得注意的是，這些患者中1人是在PESIⅢ級和其他兩個人在IV級，表明所有實例發(fā)生在相對較高的PESI類。這表明，可以用來確定高危人群以及低風險人群治療方案。這項研究有任何追溯性研究，包括在病人的選擇和治療計劃不一致的內在限制。根據患者組（N90），對他們來說，死亡原因未分類的數量相對較少。然而，我們的研究結果的精度提高，只有那些情況下，肺栓塞，通過胸部CT確認都包括在內。此外，使用的電話使我們能夠進行相對長期隨訪，以確認在30天的死亡率，以及死亡率住院期間總死亡率。這項研究表明，PESI是一個有用的預測，不只是30天的死亡率，也包括住院期間死亡率及總死亡率。風險組分類使用PESI可以預測不僅是30天的死亡率，也包括住院期間死亡率及總死亡率，這表明它是一個相對準確的預后預測的指標。

簡介：中文中文3400字出處出處KILICKESMEZO,BAYRAMOGLUS,INCIE,ETALVALUEOFAPPARENTDIFFUSIONCOEFFICIENTMEASUREMENTFORDISCRIMINATIONOFFOCALBENIGNANDMALIGNANTHEPATICMASSESJJOURNALOFMEDICALIMAGINGRADIATIONONCOLOGY,2009,5315055表觀擴散系數對肝臟良惡性腫塊的鑒別表觀擴散系數對肝臟良惡性腫塊的鑒別KILICKESMEZO,BAYRAMOGLUS,INCIE,ETAL摘要我們研究的目的是探討使用并行成像技術的磁共振彌散加權成像（DWI）區(qū)分肝臟良性和惡性局灶性病變的價值。77例患者和65例健康對照者被納入研究中。DWI選取B值0，500和1000S/毫米2，計算出病灶及正常肝臟表觀擴散系數（ADC）值。肝局灶性病變的ADC值如下單純性囊腫（316±01810?3毫米2／S），包蟲囊腫（258±05310?3毫米2／S），血管瘤（197±04910?3毫米2／S），轉移（114±04110?3毫米2／S）和肝細胞癌（HCC）（115±03610?3毫米2／S）。與正常肝平均ADC值（156±01410?3毫米2／S）相比，所有疾病組的ADC值差異均有統計學意義（P＜001）。血管瘤和肝癌轉移瘤間的ADC值也有統計上的顯著差異（P001），兩者與單純的包蟲囊腫間也有統計學差異（P＜0008。然而，HCC和轉移瘤之間有無統計學差異。目前的研究表明，ADC的測量對鑒別肝臟局灶性良、惡性病變有很大潛力。我們建議添加DWI序列在MR掃描中和肝臟病理定量鑒別檢測。前言磁共振成像是檢測肝臟彌漫性和局灶性病變及區(qū)分良惡性腫瘤的特性最準確的方法，其反映了其對各種數據采集的基礎能力，如T1，T2和注射造影劑釓后的早期和晚期增強圖像。肝臟局灶性病變的表征是非常重要的，患者知道原發(fā)惡性腫瘤長需與已知的常見良性肝臟局灶性病變及轉移灶相鑒別。在肝臟疾病的調查中，也由于磁共振成像缺少電離輻射，且釓螯合物與碘造影劑相比相對安全等以上兩個重要因素使MR成像優(yōu)先使用CT掃描。此外，DWI已經成為一個新的無對比材料的診斷工具來檢測和區(qū)分惡性局灶性病變。4我們的目的是研究DWI是否有檢測和區(qū)分惡性腫瘤的轉移和原發(fā)性肝細胞癌的能力。這是我們的機構2006年1月至2007年3月進行了一項回顧性研究。77例患者（42名女性，35名男性；平均年齡，59歲）和65名健康對照者（35名女性，30名男性；平均年齡，35歲）與完全正常的肝臟MRI及實驗室檢查患者的研究。研究方案是經我們機構的道德委員會批準。所有患者的書面同意書已在研究開始之前獲得。統計分析統計分析所有的統計分析采用SPSSWINDOWS100分析。病例的ADC值表示為平均值±標準偏差。方差分析和配對樣本的測試也被用于腹部器官段進行比較。一個P值小于005被認為是表示統計上有顯著差異。結果結果所有患者行常規(guī)及彌散加權MR檢查表觀擴散系數的值列為箱形圖。肝臟病變的平均ADC值為（表1）單純性囊腫，20例（316±01810?3毫米2／S）；包蟲囊腫，13例（258±05310?3毫米2／S）；血管瘤，15例（197±04910?3毫米2／S）；轉移，13例（114±04110?3毫米2／S）；與肝細胞癌（HCC）13例（115±03610?3毫米2／S）。與正常肝組平均ADC值相比，所有的疾病組的平均ADC值差異有統計學意義（156±01410?3毫米2／S），（P＜001）。肝臟血管瘤和肝癌轉移瘤的ADC值也有統計上的顯著差異，（P001），它們與單純的包蟲囊腫間也有統計學意義（P＜0008）。然而，HCC和轉移瘤之間差異無統計學意義。討論討論擴散加權成像是用來描述水分子的隨機（布朗）運動。插入一個自旋回波脈沖序列的一個非常強大的雙極性梯度脈沖或梯度回波脈沖序列，MRI可以對在組織中的水分子的擴散更敏感。在多細胞組織擴散限制增加；相反，它減少了在大細胞外空間或破壞細胞膜的低細胞組織。7很多關于肝臟局灶性病變的擴散特性的文章已經被發(fā)表。大多數研究表明，良性病變的ADC值（囊腫、血管瘤）明顯高于惡性病變高細胞的惡性腫塊。與先前的研究中，我們發(fā)現肝囊腫有最高的ADC值，無限制運動的水分子。有人發(fā)現基于擴散信號的不同，單純肝囊腫與其他病變有顯著的統計學差異。作者認為這種差異是由于粘性包蟲囊腫由頭節(jié)，小鉤，氯化鈉，葡萄糖，蛋白質，脂類和多糖的離子。同樣，我們也發(fā)現了單純肝囊腫與其他病變有顯著間有統計學差異。與以往的研究中相比，我們的研究表明，定性和定量指標容易區(qū)分血管瘤、囊腫及惡性腫塊。血管瘤相比囊腫有較低的ADC值，這可能與血管瘤成分是相關的。陳等人的報道稱，DWI可以鑒別膿腫與囊性腫瘤。在這項研究中所有膿腫腔顯示有較低的ADC值與腫瘤壞死部分不重疊。

簡介：中文中文4125字出處出處OKOCHIM,OHTAH,TANAKAT,ETALELECTROCHEMICALPROBEFORONCHIPTYPEFLOWIMMUNOASSAYIMMUNOGLOBULINGLABELEDWITHFERROCENECARBOALDEHYDEJBIOTECHNOLOGYKOJIMAETAL,2003LIMETAL,2002,2003SALEH和SOHN,2003SATOETAL,2002WANGETAL,1998,2002WANG和JIN,2003二茂鐵衍生物常被用來做免疫分析LIMETAL,2002,2003PADESTEETAL,2000WANGETAL,2002以及DNA雜化測定的（FIG1B）。在兩種方法中，未標記的二茂鐵是通過YM30超濾而除去的。超濾常進行1215次，直至二茂鐵的響應峰消失。與IGG結合的二茂鐵數目的確定結合的二茂鐵數目的確定羊抗人IGEIGG結合的二茂鐵平均數目通過原子吸收光譜儀（AA6600G型號，SHIMAZU,KYOTO,JAPAN）檢測鐵離子濃度而測定。FCCOOH的水溶液作為鐵離子的標準溶液。IGG的濃度可以通過BCA蛋白質分析方法檢測（SMITHETAL,1985）。蛋白質的濃度是通過三次測定而最終確定。FCCHO標記標記IGG的ELISA分析分析將抗原溶液（10MM人抗原IGE，100ΜL/WELL）置于96孔的聚苯乙烯高密度檢測板（CORNINGGLASS,CORNING,NY）中，室溫下培育1小時。此板用含005％TWEEN20的PBS溶液沖洗三次，然后將200ΜL含有01％BSA（W/V）的PBS溶液加入每個孔中，室溫下培育1小時以抑制活性位點的非特異性吸收。經過清洗步驟之后，加入10MM標記FCCHO的羊抗人IGEIGG100ΜL，反應1小時。然后再次清洗實驗板，加入100ΜL的ALP兔抗羊IGG在PBS中稀釋100倍二次抗體，反應1小時；每次親合反應后，實驗板用PBST洗三次。將ALP的底物魯米諾530，滴入每個孔中，然后用LUCY2ANTHOSLABTECINSTRUMENTS,SALZBURG,AUSTRIA檢測光的強度。

簡介：THEPULMONARYEMBOLISMSEVERITYINDEXINPREDICTINGTHEPROGNOSISOFPATIENTSWITHPULMONARYEMBOLISMWONHOCHOI1,SUNGUKKWON1,2,YOONJUNGJWA1,JUNGAKIM1,YUNHOCHOI1,JEHOCHANG1,HOONJUNG1,JOONHYUNGDOH1,2,JUNENAMGUNG1,2,SUNGYUNLEE1,2ANDWONROLEE1,2DEPARTMENTSOF1INTERNALMEDICINEAND2VISION21CARDIAC24123127KEYWORDSPULMONARYEMBOLISMPROGNOSISRECEIVEDAPRIL13,2008ACCEPTEDJULY28,2008CORRESPONDENCETOSUNGUKKWON,MDDEPARTMENTOFINTERNALMEDICINE,INJEUNIVERSITYILSANPAIKHOSPITAL,2240DAEHWADONG,ILSANGU,GOYANG411706,KOREATEL82319107830,FAX82319107219,EMAILMDKSUILSANPAIKACKRINTRODUCTIONPULMONARYEMBOLISMSOCCURRELATIVELYFREQUENTLY,WITH23CASESPER100,000ANNUALLYINTHEUNITEDSTATES1HOWEVER,SINCEITSCLINICALFEATURESARENONSPECIFIC,ADIAGNOSISOFPULMONARYEMBOLISMISNOTEASYTOMAKEFURTHERMORE,WITHOUTAPPROPRIATETREATMENT,APULMONARYEMBOLISMCANBEFATALTHEREFORE,SUSPECTINGSUCHACONDITIONANDEVALUATINGITAPPROPRIATELYISIMPORTANTINMAKINGAPROGNOSISONCEAPROGNOSISHASBEENMADE,THEMORTALITYRATECANBELOWEREDTHROUGHPROPERTREATMENTHOWEVER,WHILESIGNIFICANTEFFORTHASBEENMADETOCLARIFYTHERISKFACTORSANDTREATMENTOFPULMONARYEMBOLISM,RELATIVELYLITTLEDATAAREAVAILABLEREGARDINGAPROGNOSTICINDEXNEVERTHELESS,SINCETHEDEVELOPMENTOFTHEGENEVASCORE2IN2000ANDTHEPULMONARYEMBOLISMSEVERITYINDEXPESI3IN2005,TWOMODELSHAVEBEENINTRODUCEDASPROGNOSTICPREDICTIVEINDEXESOFTHESE,THEPESIHASBEENSHOWNTOHAVEHIGHERPREDICTIVEACCURACY4OSTENSIBLY,KOREANSMAYAPPEARTOHAVEFEWERRISKFACTORSFORPULMONARYEMBOLISM,SUCHASOBESITYORDEEPVEINTHROMBOSIS,COMPAREDTOPEOPLEINTHEWEST,ANDMAYTHUSBEEXPECTEDTOSUFFERFROMPULMONARYEMBOLISMS133HADDIABETES,AND16178HADEITHERBEENDIAGNOSEDWITHCANCERORWEREBEINGTREATEDFORCANCERNINEPATIENTS10WERECONFIRMEDASHAVINGEMPHYSEMATHROUGHCHESTCT,WHILETENPATIENTS111HADACEREBRALHEMORRHAGEANDCEREBRALINFARCTION,AND26289HADASURGICALHISTORYTABLE1PESICLASSIFICATICHWITHREGARDTOTHEDISTRIBUTIONOFTHEPATIENTSACCORDINGTOTHEIRPESIRISKCLASS,2123,3465POINTS,AVERAGE499POINTSPATIENTSWEREINCLASSI126PESIPOINTSTHUS,MOSTOFTHEPATIENTSWEREINCLASSIIWHILETHESMALLESTNUMBERWEREINCLASSIVFIG1MORTALITYRATEBASEONTHEPESITHEMORTALITYRATEAFTER30DAYS,MORTALITYRATEDURINGHOSPITALIZATION,ANDTOTALMORTALITYRATEWERECOMPAREDACCORDINGTOTHEPESIRISKCLASSESOFTHEPATIENTSAT30DAYS,THEMORTALITYRATEWAS111WHENTHISRESULTWASANALYZEDACCORDINGTOPESICLASS,ASIGNIFICANTTRENDTOWARDINCREASEDMORTALITYWITHAHIGHERCLASSWASDETECTEDP00016,WITH0INCLASSI,103INCLASSII,91INCLASSIII,0INCLASSIV,AND50INCLASSVINCONSIDERINGTHE0MORTALITYRATEDETECTEDFORCLASSIV,NOTETHATTHEAVERAGEHOSPITALSTAYFORTHISGROUPWAS10DAYSSHORTERTHANTHATFORTHEOTHERGROUPSTHUS,THEPOSSIBILITYOFUNDERESTIMATIONEXISTSINCOMPARISON,THEHOSPITALMORTALITYRATEWAS156WHENITWASANALYZEDACCORDINGTOPESICLASS,ASIGNIFICANTTRENDP00065WASOBSERVED,WITH48INCLASSI,138INCLASSII,136INCLASSIII,125INCLASSIV,AND50INCLASSVFIG2THETOTALMORTALITYRATEWAS30WHENITWASANALYZEDACCORDINGTOPESICLASS,ANINCREASINGTENDENCYTOWARDTHEHIGHERCLASSWASOBSERVED,WITH95INCLASSI,276INCLASSII,318INCLASSIII,50INCLASSIV,AND60INCLASSVP00019FIG3MORTALITYRATEOFTHEREDISTRIBUTEDPESIGROUPINGOFTHEPESICLASSESINTOLOWCLASSI,INTERMEDIATECLASSESIIIV,ANDHIGHRISKCLASSVGROUPSPRODUCEDA30DAYMORTALITYRATEOF0,82,AND50,RESPECTIVELYCOMPAREDTOTHERESULTSBEFORETHEREDISTRIBUTION,THETENDENCYWASQUITECLEARP00016→00003THEMORTALITYRATEDURINGHOSPITALIZATIONWAS48,131,AND50FORTHELOW,INTERMEDIATE,ANDHIGHRISKGROUPS,RESPECTIVELY,ANDTHETENDENCYWASMUCHCLEARERP00065→00038,ASWASTHE30DAYMORTALITYRATETHETOTALMORTALITYRATEWAS95,311,AND60FORTHELOW,INTERMEDIATE,ANDHIGHRISKGROUPS,RESPECTIVELY,CHOIWH,ETALUSEOFPESITOPREDICTPROGNOSISOFPULMONARYEMBOLISM125FIGURE1PATIENTSDISTRIBUTIONACCORDINGTOPESIRISKCLASS23N2132N2925N229N811N10CLASSICLASSIICLASSIIICLASSIVCLASSVFIGURE2HOSPITALMORTALITYACCORDINGTOPESIRISKCLASSIFICATIONPESI,PULMONARYEMBOLISMSEVERITYINDEXNS,NOTSIGNIFICANT5000000000000000CLASSICLASSIICLASSIIICLASSIVCLASSVHOSPITALMORTALITYP0026PNS4808013601250PFIGURE3OVERALLMORTALITYACCORDINGTOPESIRISKCLASSIFICATIONPESI,PULMONARYEMBOLISMSEVERITYINDEXNS,NOTSIGNIFICANT6000P00000000000000CLASSICLASSIICLASSIIICLASSIVCLASSVOVERALLMORTALITYP0038PNS950603180P00

簡介：SAGEHINDAWIACCESSTORESEARCHMOLECULARBIOLOGYINTERNATIONALVOLUME2011,ARTICLEID437301,7PAGESDOI104061/2011/437301REVIEWARTICLEMIR146AINIMMUNITYANDDISEASENICOLERUSCAANDSILVIAMONTICELLIINSTITUTEFORRESEARCHINBIOMEDICINE,VIAVINCENZOVELA6,6500BELLINZONA,SWITZERLANDCORRESPONDENCESHOULDBEADDRESSEDTOSILVIAMONTICELLI,SILVIAMONTICELLIIRBUNISICHRECEIVED17DECEMBER2010ACCEPTED17FEBRUARY2011ACADEMICEDITORALESSANDRODESIDERICOPYRIGHT?2011NRUSCAANDSMONTICELLITHISISANOPENACCESSARTICLEDISTRIBUTEDUNDERTHECREATIVECOMMONSATTRIBUTIONLICENSE,WHICHPERMITSUNRESTRICTEDUSE,DISTRIBUTION,ANDREPRODUCTIONINANYMEDIUM,PROVIDEDTHEORIGINALWORKISPROPERLYCITEDMICRORNASMIRNASAREREGULATORYMOLECULESABLETOINFLUENCEALLASPECTSOFTHEBIOLOGYOFACELLTHEYHAVEBEENASSOCIATEDWITHDISEASESSUCHASCANCER,VIRALINFECTIONS,ANDAUTOIMMUNEDISEASES,ANDINRECENTYEARS,THEYALSOEMERGEDASIMPORTANTREGULATORSOFIMMUNERESPONSESMIR146AINPARTICULARISRAPIDLYGAININGIMPORTANCEASAMODULATOROFDIFFERENTIATIONANDFUNCTIONOFCELLSOFTHEINNATEASWELLASADAPTIVEIMMUNITYGIVENITSIMPORTANCEINREGULATINGKEYCELLULARFUNCTIONS,ITISNOTSURPRISINGTHATMIR146AEXPRESSIONWASALSOFOUNDDYSREGULATEDINDIFFERENTTYPESOFTUMORSINTHISPAPER,WESUMMARIZERECENTPROGRESSINUNDERSTANDINGTHEROLEOFMIR146AININNATEANDADAPTIVEIMMUNERESPONSES,ASWELLASINDISEASE1INTRODUCTIONMICRORNASMIRNASREPRESENTAPERVASIVEFEATUREOFALLCELLS,ASTHEYREGULATELARGEFRACTIONSOFTHECELL’STRANSCRIPTOMESOFAR,672MOUSEMIRNASAND1048HUMANMIRNASHAVEBEENDESCRIBEDINTHEMIRBASEDATABASEHTTP//WWWMIRBASEORG/,RELEASESEPT2010WITHEACHMIRNAPOTENTIALLYREGULATINGTHEEXPRESSIONOFHUNDREDSOFTARGETGENES,HIGHLIGHTINGTHEEXTENTOFTHISFORMOFREGULATION1WHEREASSOMEMIRNASAREWIDELYEXPRESSED,OTHERSEXHIBITONLYLIMITEDDEVELOPMENTALSTAGE,TISSUE,ORCELLTYPESPECIFICPATTERNS2SIMILARTOANYOTHERMAMMALIANCELLTYPE,CELLSOFTHEIMMUNESYSTEMRELYONMIRNASTOREGULATELINEAGECOMMITMENT,PROLIFERATION,MIGRATION,ANDDIFFERENTIATIONINMOSTCASES,THESEACTIVITIESAREORCHESTRATEDBYBOTHUBIQUITOUSLYEXPRESSEDANDCELLTYPESPECIFICMIRNASPECIES3–7THEIMPORTANCEOFMIRNASINREGULATINGDIFFERENTIATIONANDFUNCTIONOFIMMUNECELLSISUNDERLINEDBYTHEPHENOTYPICALPERTURBATIONSTHATOCCURWHENMIRNAEXPRESSIONISALTEREDGIVENTHEEMERGINGROLESOFMIRNASINMODULATINGIMMUNERESPONSES,ITISLIKELYTHATANYDYSREGULATIONOFMIRNAEXPRESSIONMAYCONTRIBUTETOTHEPATHOGENESISOFAUTOIMMUNEDISEASES,CHRONICINFLAMMATION,ANDMALIGNANCIESINDEED,SEVERALHUMANDISEASESHAVENOWBEENASSOCIATEDWITHDYSREGULATEDMIRNAEXPRESSION,ANDMIRNASHAVEBEENSHOWNTOFUNCTIONBOTHASONCOGENESANDTUMORSUPPRESSORGENES8,9MIR146AHASBEENRECENTLYSHOWNTOBEANIMPORTANTMODULATOROFDIFFERENTIATIONANDFUNCTIONOFCELLSOFINNATEASWELLASADAPTIVEIMMUNITYHERE,WESUMMARIZERECENTPROGRESSINUNDERSTANDINGTHEROLEOFMIR146AINIMMUNERESPONSESANDINDISEASESEEALSOTABLE12WHATAREMICRORNASMIRNASARESMALL20–25NUCLEOTIDES,NONCODINGRNAMOLECULESINVOLVEDINPOSTTRANSCRIPTIONALGENEREGULATIONTHEYDERIVEFROMPRIMARYTRANSCRIPTSPRIMIRNATHATAREPROCESSEDINTOHAIRPINPRECURSORSPREMIRNASWITHINTHENUCLEUSOFTHECELLBYTHEMICROPROCESSORCOMPLEX,WHICHINCLUDESTHERNASEIIIENZYMEDROSHAPREMIRNASARETRANSLOCATEDINTOTHECYTOPLASMANDPROCESSEDBYDICERINTOTHEIRMATUREFORMFORARECENTREVIEWSEE25ANEXCEPTIONTOTHISRULEISREPRESENTEDBYTHELESSABUNDANT“MIRTRONS”,THATBYPASSDROSHAANDAREPROCESSEDONLYBYDICER26MATUREMIRNASLOADEDONTOTHERNAINDUCEDSILENCINGCOMPLEXRISCRECOGNIZESITESLOCATEDMOSTLYINTHE3?UNTRANSLATEDREGION3?UTROFTARGETMRNASTHROUGHCANONICALBASEPAIRINGBETWEENTHESEEDSEQUENCEOFTHEMIRNANUCLEOTIDES2–8ATITS5?ENDANDITSCOMPLEMENTARYSEQUENCEINTHETARGETMRNATHISLEADSTOABLOCKINTRANSLATIONWITHORWITHOUTDESTABILIZATIONANDDEGRADATIONOFTHETARGETEDMRNAMIRNASMODULATEAMOLECULARBIOLOGYINTERNATIONAL3TCELLSUBSETSINDEED,TCELLSLACKINGDICERSHOWEDINCREASEDDIFFERENTIATIONTOTHETH1SUBSETWITHACORRESPONDINGLYREDUCEDPOLARIZATIONTOTH229ADDINGTOTHECOMPLEXITYOFGENEREGULATORYNETWORKS,PROLIFERATINGTCELLSEXPRESSGENESWITHSHORTER3?UTRSTHANTHOSEEXPRESSEDINRESTINGTCELLS,MAKINGTHESEMRNASLESSSUSCEPTIBLETOREGULATIONBYMIRNASDUETOTHELOSSOFMIRNABINDINGSITES41FINALLY,INDIVIDUALMIRNASWEREALSOSHOWNTOPLAYIMPORTANTROLESINTCELLDIFFERENTIATIONANDFUNCTIONFOREXAMPLE,MIR181A,WHICHISUPREGULATEDDURINGTCELLDEVELOPMENT,WASSHOWNTOENHANCETCELLRECEPTORTCRSIGNALLINGSTRENGTHBYDIRECTLYTARGETINGANUMBEROFPROTEINPHOSPHATASES32,WHILEMICELACKINGMIR155SHOWEDANALTEREDTH1/TH2POLARIZATIONWITHABIASTOWARDSTH2,INDICATINGTHATMIR155PROMOTESDIFFERENTIATIONTOWARDSTH1CELLS35ASFORTHEROLEOFMIR146AINTCELLS,BYANALYZINGTHEEXPRESSIONOFMIRNASINHIGHLYPURIFIEDSUBSETSOFCELLSOFTHEIMMUNESYSTEM,WESHOWEDTHATMIR146AISONEOFTHEVERYFEWMIRNASDIFFERENTIALLYEXPRESSEDBETWEENTH1ANDTH2CELLSINTHEMOUSE,SUGGESTINGTHATITMIGHTBEINVOLVEDINFATEDETERMINATIONOFTHESECELLS5RECENTWORKPERFORMEDINMIR146ADEFICIENTMICESHOWEDANINCREASEINTHEPERCENTAGEOFINFΓPRODUCINGTCELLSUBSETINTHEABSENCEOFMIR146A10INHUMANTCELLS,MIR146AISEXPRESSEDATLOWLEVELSINNA¨IVETLYMPHOCYTESWHILEITISABUNDANTLYEXPRESSEDINMEMORYTCELLSANDITISINDUCEDUPONTCRSTIMULATION,CONSISTENTWITHITSEXPRESSIONBEINGDEPENDENTONNFΚBINDUCTION12,13INDEED,NFΚBANDCETSBINDINGSITESWERESHOWNTOBEREQUIREDFORTHEINDUCTIONOFMIR146ATRANSCRIPTIONINHUMANTCELLS,ANDSUCHINDUCTIONPOTENTIALLYMODULATEDCELLDEATHINTHESECELLSBYTARGETINGFADDANDBYIMPAIRINGBOTHAP1ACTIVITYANDIL2PRODUCTION13TREGCELLSCONSTITUTEASPECIALIZEDTCELLSUBSETABLETOMAINTAINIMMUNEHOMEOSTASISBYLIMITINGTHEINFLAMMATORYRESPONSES,ANDTHEIRSUPPRESSIVEFUNCTIONISINDISPENSABLEFORIMMUNEHOMEOSTASISANDSURVIVALOFHIGHERORGANISMSRECENTLY,LUANDCOLLEAGUESREPORTEDTHATMIR146AISAMONGTHEMIRNASPREVALENTLYEXPRESSEDINTREGCELLSANDSHOWEDTHATITISCRITICALFORTREGFUNCTIONSINDEED,DEFICIENCYOFMIR146ARESULTEDININCREASEDNUMBERSBUTIMPAIREDFUNCTIONOFTREGCELLSANDASACONSEQUENCE,BREAKDOWNOFIMMUNOLOGICALTOLERANCEWITHMASSIVELYMPHOCYTEACTIVATION,ANDTISSUEINFILTRATIONINSEVERALORGANS10THEIMMUNEMEDIATEDLESIONSINDUCEDBYTHELACKOFMIR146AINTREGSWEREDEPENDENTONINFΓANDSTAT14MIR146ININNATEIMMUNITYANDNONIMMUNESYSTEMSCELLSOFTHEINNATEIMMUNESYSTEM,SUCHASGRANULOCYTES,NATURALKILLERNKCELLS,MONOCYTES,ANDMACROPHAGES,PROVIDEANIMPORTANTFIRSTLINEOFDEFENSEFORTHEORGANISMAGAINSTINVADINGPATHOGENSMIRNASHAVEBEENIMPLICATEDINBOTHTHEDEVELOPMENTANDFUNCTIONSOFINNATEIMMUNECELLSFOREXAMPLE,THEMACROPHAGEINFLAMMATORYRESPONSETOINFECTIONINVOLVESTHEUPREGULATIONOFSEVERALMIRNAS,SUCHTLR4ADAPTERMOLECULESIKKCOMPLEXPPIRAK1TRAF6CYTOPLASMNUCLEUSPRIMIR146AMIR146ARISCCOMPLEXIΚBΑNFΚBNFΚBFIGURE1MIR146ANEGATIVELYREGULATESSIGNALTRANSDUCTIONPATHWAYSLEADINGTONFΚBACTIVATIONUPONACTIVATIONOFACELLSURFACERECEPTORSUCHASTLR4,AMOLECULARCASCADEINCLUDINGTRAF6ANDIRAK1LEADSTOIΚBΑPHOSPHORYLATIONANDDEGRADATIONANDTONFΚBACTIVATIONANDNUCLEARTRANSLOCATION12,42NFΚBACTIVATIONINDUCESTRANSCRIPTIONOFMANYGENES,INCLUDINGPRIMIR146AONCETRANSLOCATEDTOTHECYTOPLASMANDLOADEDONTOTHERISCCOMPLEX,MATUREMIR146ACONTRIBUTESTOATTENUATERECEPTORSIGNALINGTHROUGHTHEDOWNMODULATIONOFIRAK1ANDTRAF6ASMIR155,MIR146,MIR147,MIR21,ANDMIR912,43–46SEVERALSTUDIESLINKEDMIR146AEXPRESSIONTONFΚBSIGNALINGWITHINTHEINNATEIMMUNESYSTEMFIGURE1ANDWEREINITIATEDBYASTUDYSHOWINGTHATMIR146AISQUICKLYINDUCEDUPONACTIVATIONOFHUMANMONOCYTES12INTHISSTUDY,MIR146AWASFOUNDTOBEINDUCIBLEUPONSTIMULATIONWITHLPSINANFΚBDEPENDENTMANNER,ANDTOTARGETTHETNFRECEPTORASSOCIATEDFACTOR6TRAF6ANDIL1RECEPTORASSOCIATEDKINASE1IRAK1GENESTHESEGENESENCODETWOKEYADAPTERMOLECULESDOWNSTREAMOFCYTOKINEANDTOLLLIKERECEPTORSTLR,POINTINGTOWARDSAROLEFORMIR146AINCONTROLLINGSIGNALINGFROMTHESERECEPTORSTHROUGHANEGATIVEFEEDBACKREGULATORYLOOPINVOLVINGDOWNREGULATIONOFTRAF6ANDIRAK112ITWASALSOSUGGESTEDTHATMIR146ACONTRIBUTESTOTHEESTABLISHMENTOFENDOTOXINTOLERANCEINMONOCYTESANDTOTHEREGULATIONOFTNFΑPRODUCTION14INTHISCONTEXT,MIR146AWOULDTHEREFOREACTASATUNINGMECHANISMTOPREVENTANOVERSTIMULATEDINFLAMMATORYSTATEINHUMANLANGERHANSCELLSLCS,MIR146AWASFOUNDTOBECONSTITUTIVELYEXPRESSEDATHIGHLEVELS,ASCOMPAREDTOINTERSTITIALDENDRITICCELLSINTDCS15INTHESECELLS,HIGHMIR146AEXPRESSIONWASINDUCEDBYTHETRANSCRIPTIONFACTORPU1INRESPONSETOTGFΒ1,AKEY

簡介：中文中文5200字出處出處KAJSTURAJ,LERIA,FINATON,ETALMYOCYTEPROLIFERATIONINENDSTAGECARDIACFAILUREINHUMANSJPROCEEDINGSOFTHENATIONALACADEMYOFSCIENCES,1998,951588018805心臟衰竭末期的心肌細胞再生心臟衰竭末期的心肌細胞再生KAJSTURAJ,LERIA,FINATON,DILORETOC,BELTRAMICA,ANVERSAP前言前言在幾十年前，人們一直堅信心肌細胞是一種終極分化細胞，在成人心臟中心肌細胞分裂是不可能的。然而最近，偶爾有在心肌細胞中發(fā)現細胞核有絲分裂的報道，但是這種發(fā)現被一種假設所質疑如果心肌細胞存在有絲分裂，但現實中的卻沒有心肌組織再生。此外，心肌細胞有絲分裂的現象從來沒有在正常心肌細胞中被發(fā)現。然而，通過分析常規(guī)的組織組成的基礎需求，忽略設備的限制，確信心肌細胞沒有能力進入細胞周期及細胞分裂。在這里我們的研究通過顯微鏡發(fā)現在每100萬個心肌細胞中有14個在進行有絲分裂。在在缺血性心臟疾病及先天性擴張型心肌病中這個數字將是正常心臟的10倍（在缺血性心臟病中每100萬個心肌細胞中有152個，在先天性擴張性心肌病中每100萬個心肌細胞中有131個）。由于左心室大約有58109個心肌細胞，這些有絲分裂指數暗示在正常心肌，缺血性心肌病及先天性心肌病的整個左心室中將分別有812103,882103,76103個心肌細胞在進行有絲分裂。與此同時，有絲分裂時間通常少于一小時，提示在非病理及病理心臟中隨時間發(fā)展將有大量的心肌細胞生成。我們已經發(fā)現了細胞質分裂的證據，這清楚地證明了心肌細胞有絲分裂的存在。心肌細胞在成人心臟中是否能夠分裂一直是人們爭論的話題。然而大量證據提示在心肌嚴重肥厚時存在心肌細胞數目大量增長，但是心肌細胞是否進行有絲分裂卻沒有被證實，這個證據的缺乏質疑了體視學結論的可信性。偶有發(fā)現在有病理性心臟疾病的心臟中存在細胞核的有絲分裂，但是這個發(fā)現對證實心肌細胞的大量再生沒有任何價值。另外，心肌細胞的有絲分裂從沒有在正常心臟的心肌細胞中發(fā)現。于此同時，心肌細胞細胞質的有絲分裂證據也是不足的。人類缺血性心臟疾病及先天性擴張性心臟疾病的結構特征是由多處心肌纖維化及彌漫性的間質纖維化構成的心肌瘢痕。此外，在心肌缺血所有樣本中都有發(fā)現纖維片段。心肌細胞的壞死導致了纖維片段、纖維替代及間質纖維化的現象。然而，大量膠原的積累與梗死后人左心室心肌細胞的大量減少出現明顯的差異。每減少1MM3的膠原反映了大約50103心肌細胞的丟失，在缺血性心肌病末期，大量纖維化暗示了大約有90的心肌細胞減少。相反的，曾經報道實際心肌細胞的減少小于30。這種差異在先天性擴張性心肌病中更加明顯。在有先天性擴張性心肌病患者的心室肌中心肌纖維化，但是心肌細胞的數目卻沒有減少。在細胞基礎層面上研究疾病心臟的的心肌重塑機制是非常復雜的，遠遠超出心室的失代償導致的心肌細胞程序化死亡這樣的解釋。細胞凋亡不會導致組織纖維化；死亡的細胞被周圍細胞清除因此不會有炎癥反應的發(fā)生。在嚴重的心肌細胞死亡及凋亡中，這些現象指出心肌細胞可能不是終極分化細胞，細胞的再生可能由病理性刺激誘導。我們用免疫細胞化學及共焦顯微鏡來計算由于慢性缺血性心臟病機擴張性心肌病而需進行心臟移植的患者的心臟心肌細胞的有絲分裂指數。用來做解剖的心臟都是受法律保護的。性心肌病組327±193MM2，在擴張性心肌病組341±194MM2相應的細胞核的數目分別為14136±56699,38854±16766，36013±17134細胞分裂指數分別為18±06,51±35,43±20用這些數據可以估算在各個組中心肌細胞的有絲分裂指數。在正常的左心室中平均每100萬個心肌細胞有14個心肌細胞在進行有絲分裂，但在病理心臟左心室中這個指數要高得多。在缺血性心肌病中平均每100萬個心肌細胞中有152個在進行有絲分裂，在擴張性心肌病中每100萬中有131個心肌細胞在進行有絲分裂。在有心臟衰竭的這兩組患者中這種指數很小的差別沒有意義，平均一下每100萬個心肌細胞中有140個心肌細胞在進行著有絲分裂。與健康心肌相比，有絲分裂細胞數目在有心臟衰竭的患者總是正常健康人的10倍。實驗中沒有性別差異。在正常組有絲分裂指數為18±13/100萬細胞中，在衰竭的心臟中有106±42/100萬心肌細胞中。（N127個缺血性心肌病，5個先天性心肌?。Ｅc心肌細胞相比，間質細胞有絲分裂指數下降24是沒有意義的。討論討論心肌肥厚心肌肥厚在20世紀20年代初，在許多解剖研究中都強調，在心肌細胞中檢測核分裂有許多困難，并在此基礎上，介紹了細胞的增殖在成人、完全分化的生物及哺乳動物的心肌中是不存在的的概念（1）。此外，實驗結果證明，急性心肌肥厚的嚙齒類動物心肌細胞沒有再一次進入細胞周期、合成DNA并進行有絲分裂的能力。這些發(fā)現都證明了一個學說，在出生后不久，心室肌細胞就永久的不再進入細胞周期并注定不再復制最終細胞死亡。在20世紀50年代中期這種論點被LINZBACH在形態(tài)學研究中的成果所質疑。形態(tài)學研究表明在心衰患者的心肌中有發(fā)現心肌細胞增生。最近的數據結果支持LINZBACH的假說，并確認在人類心臟失代償期，心室肌細胞的數量幾乎增加了一倍（4，20，21）。定量分析未能成功記載心肌細胞的有絲分裂，更偏向于應用體視學定律分析心肌細胞數量上的變化。缺乏有絲分裂使得對心肌細胞分化機制的解釋更加復雜，其中包括心肌細胞的縱向分裂而細胞核卻不分裂。這種現象將導致在每個細胞中細胞核含量的減少。然而在人類心臟中單核細胞與雙核細胞的比例是不變的。如果細胞沒有完成最終分裂，在細胞處于G0期時，給予細胞一定刺激，細胞將再次進入細胞周期完成細胞核及細胞質的分裂。只有這種增長方式才會出現心肌細胞數量的增長與心肌細胞的再生。早期的發(fā)現及近期的數據都堅持了這種增值方式的可能性，因為在心力衰竭的心臟心機中已經被證實存在細胞核與細胞質的分裂。心肌細胞增殖心肌細胞增殖根據學說中提到，心室肌細胞是一種沒有再生能力的細胞，細胞壽命完全與個體或生物的壽命相對應。在人類試驗研究中證實，在人類出生幾個月后心肌細胞數量就已達到成人水平，他們一直以每分鐘70次的頻率收縮，直到細胞死亡。由于有一部分人口壽命能達到100歲或是更長，一個不可避免的結論由此產生心肌細胞在功能與形態(tài)上可能是不朽的。這種假說與細胞衰老、細胞程序化死亡及隨著哺乳動物心臟的衰老，細胞翻新速度減慢的邏輯產生矛盾。然而后者的可能性更大，在沒有疾病的正常心臟發(fā)現，從17歲到89歲，心肌細胞每年將減少64106個，這暗示了細胞是隨診年齡增長死亡的。除此之外，盡管缺少生理負荷需求，心肌細胞也可以再進入細胞周期，合成DNA。那些對與心臟細胞衰老及心肌細胞不斷更新的研究表明，在正常情況下，每100萬個心肌細胞中有14個細胞能進行有絲分裂。在衰竭的心肌中，心肌細胞這種再生與代替死亡細胞的能力明顯增強，每100

簡介：42–47|CANCERSCI|JANUARY2005|VOL96|NO1?JAPANESECANCERASSOCIATIONDOI101111/J13497006200500007XBLACKWELLPUBLISHING,LTDEPHA2/EFNA1EXPRESSIONINHUMANGASTRICCANCERRITSUKONAKAMURA,1HIDEKIKATAOKA,2,3NAOMISATO,4MASAOKANAMORI,5MEGUMIIHARA,1HISAKIIGARASHI,1SANJARRAVSHANOV,1YOUJIEWANG,6ZHONGYOULI,7TAKAHIROSHIMAMURA,8TOSHIHIKOKOBAYASHI,8HIROYUKIKONNO,9KAZUYASHINMURA,1MASAMITSUTANAKA10ANDHARUHIKOSUGIMURA1,111FIRSTDEPARTMENTOFPATHOLOGY,2FIRSTDEPARTMENTOFMEDICINE,HAMAMATSUUNIVERSITYSCHOOLOFMEDICINE,1201HANDAYAMA,HAMAMATSU4331923DEPARTMENTOFGASTROENTEROLOGY,HAMAMATSUMEDICALCENTER,328TOMITSUKA,HAMAMATSU43285804DEPARTMENTOFNURSING5DEPARTMENTOFLIFELONGSPORT,BIWAKOSEIKEISPORTCOLLEGE,1204SHIGACHOU,SHIGAGUN,SHIGA52005036SCHOOLOFPUBLICHEALTH,TONGIMEDICALCOLLEGE,13HONGKONGROAD,WUHAN430030,CHINA7DEPARTMENTOFCANCERGENETICS,ROSWELLPARKCANCERINSTITUTE,ELMANDCARLTONSTRBUFFALO,NY14263,USA8FIRSTDEPARTMENTOFSURGERY,AND9SECONDDEPARTMENTOFSURGERY,HAMAMATSUUNIVERSITYSCHOOLOFMEDICINE,1201HANDAYAMA,HAMAMATSU4313192AND10GROWTHFACTORDIVISION,NATIONALCANCERCENTER,511TSUKIJI,CYUOKU,TOKYO1040045RECEIVEDSEPTEMBER17,2004/REVISEDNOVEMBER15,2004/ACCEPTEDNOVEMBER16,2004/ONLINEPUBLICATIONJANUARY19,2005THEERYTHROPOIETINPRODUCINGHEPATOCELLULAREPHA2RECEPTOR,TYROSINEKINASE,ISOVEREXPRESSEDANDPHOSPHORYLATEDINSEVERALTYPESOFHUMANTUMORSANDHASBEENASSOCIATEDWITHMALIGNANTTRANSFORMATIONARECENTREPORT,HOWEVER,INDICATEDTHATSTIMULATIONOFTHEEPHA2RECEPTORLIGAND,EPHRINA1EFNA1,INHIBITSTHEGROWTHOFEPHA2EXPRESSINGBREASTCANCERTHEAUTHORSEXAMINEDTHEEXPRESSIONOFEPHA2ANDEFNA1USINGSEMIQUANTITATIVEREVERSETRANSCRIPTIONPOLYMERASECHAINREACTIONRTPCRINFOURGASTRICCANCERCELLLINESAND49PRIMARYGASTRICCANCERSAMPLES,ASWELLASINNORMALGASTRICTISSUEEPHA2WASMOREHIGHLYEXPRESSEDINTUMORTISSUETHANINNORMALTISSUEIN27CASES55EFNA1WASOVEREXPRESSEDINTUMORTISSUEIN28CASES57NOSIGNIFICANTCORRELATIONWASDETECTEDBETWEENTHEEXPRESSIONLEVELSANDHISTOLOGICFEATURESSUCHASTUMORSIZE,AGE,VESSELINVASION,ORLYMPHNODEINVOLVEMENTHOWEVER,EPHA2OVEREXPRESSIONWASMOREPROMINENTINMACROSCOPICTYPE3AND4TUMORSTHANINTYPE1OR2ADVANCEDGASTRICCANCERTHEAUTHORSOBSERVEDEPHA2EXPRESSIONINTHREEOFTHEFOURGASTRICCANCERCELLLINESAGS,KATO3,ANDMKN74THATWEREEXAMINEDINONECELLLINE,TMK1,EPHA2EXPRESSIONWASBARELYDETECTABLEUSINGNORTHERNBLOTTING,RTPCR,ANDWESTERNBLOTTINGINCONTRAST,EFNA1WASDETECTEDINALLCELLLINESINTHEGASTRICCANCERCELLLINESTHATENDOGENOUSLYEXPRESSEDEPHA2,STIMULATIONWITHEPHRINA1FCLEDTODECREASEDEPHA2PROTEINEXPRESSIONANDINCREASEDEPHA2PHOSPHORYLATIONFINALLY,THEGROWTHOFEPHA2EXPRESSINGCELLSWASINHIBITEDBYREPETITIVESTIMULATIONWITHSOLUBLEEPHRINA1FCTAKENTOGETHER,THESEFINDINGSSUGGESTTHATEPHA2ANDEFNA1EXPRESSIONMAYINFLUENCETHEBEHAVIOROFHUMANGASTRICCANCERCANCERSCI20059642–47THEERYTHROPOIETINPRODUCINGHEPATOCELLULAREPHRECEPTORSREPRESENTTHELARGESTKNOWNFAMILYOFRECEPTORTYROSINEKINASESANDAREACTIVATEDBYINTERACTIONWITHTHECELLSURFACELIGANDS,EPHRINSEFNTHEREISEVIDENCETOSUGGESTTHATSOMEMEMBERSOFTHEEPHFAMILYANDTHEIREFNLIGANDSAREINVOLVEDINANGIOGENESISANDONCOGENESISTHROUGHCELLADHESION,MORPHOGENESIS,CAPILLARYSPROUTING,ANDCHEMOATTRACTION1?5EPHRECEPTORSHAVEBEENCLASSIFIEDINTOTWOSUBFAMILIES,EPHAANDEPHBEPHARECEPTORSBINDMAINLYTOGLYCOSYLPHOSPHATIDYLINOSITOLANCHOREDEFNALIGANDS,ANDEPHBRECEPTORSBINDTOTRANSMEMBRANEEFNBLIGANDSTHEEXPRESSIONOFEPHFAMILYTRANSCRIPTSHASBEENDOCUMENTEDINSOMEMELANOMASANDCARCINOMAS6,7OVEREXPRESSIONOFEPHA2ISBELIEVEDTOBESUFFICIENTTOCONFERMALIGNANT/TUMORIGENICPOTENTIALONNONTRANSFORMEDMAMMARYEPITHELIALCELLS8ESOPHAGEALSQUAMOUSCELLCARCINOMASTHATOVEREXPRESSEFNA2HAVEAPOORERPROGNOSISTHANTHOSETHATDONOT9GASTRICCANCERREMAINSADISEASEWITHAVERYPOORPROGNOSIS,ANDTHEROLEOFKINASESINGASTRICCANCERCELLSHASBEENAFOCUSOFRESEARCHOGAWAETALIDENTIFIEDEFNA1ANDEPHA2EXPRESSIONINAVERYFEWCASESOFGASTRICCANCERIN2000,BUTTHEROLEOFTHESEMOLECULESHASREMAINEDUNCLEAR,10DESPITEANEXTENSIVESURVEYOFTYROSINEKINASESINGASTRICCANCER11THEREFORE,THEAUTHORSEXAMINEDTHEEXPRESSIONOFEPHA2ANDEFNA1INGASTRICCANCERSPECIMENSANDGASTRICCANCERCELLLINESUSINGSEMIQUANTITATIVEREVERSETRANSCRIPTIONPOLYMERASECHAINREACTIONRTPCR,NORTHERNBLOTTING,ANDWESTERNBLOTTINGTHISISTHEFIRSTDOCUMENTEDREPORTOFEFNA1ANDEPHA2EXPRESSIONINASERIESOFGASTRICCANCERCASESFURTHERMORE,THEAUTHORSEXAMINEDTHEEFFECTSOFEFNA1STIMULATIONONCANCERCELLLINESTHATENDOGENOUSLYEXPRESSEPHA2MATERIALSANDMETHODSTISSUESFORRTPCR,HUMANGASTRICCANCERSPECIMENSANDCORRESPONDINGNONTUMORTISSUESWEREOBTAINEDFROM49SURGICALRESECTIONSCARRIEDOUTATHAMAMATSUUNIVERSITYSCHOOLOFMEDICINETHECLINICOPATHOLOGICCHARACTERISTICSOFTHESEPATIENTSARESHOWNINTABLE1,ANDARECLASSIFIEDACCORDINGTOTHEJAPANESECLASSIFICATIONSYSTEMJCS12HISTOLOGICALLY,THESESPECIMENSCONSISTEDOF22CASESOFWELLDIFFERENTIATEDADENOCARCINOMATUBULARANDPAPILLARYTYPESAND24CASESOFPOORLYDIFFERENTIATEDADENOCARCINOMA,INCLUDINGTHEMUCINOUSTYPE,ANDTHREEOTHERTYPESTWOADENOSQUAMOUSANDONENEUROENDOCRINETHESAMPLESCONSISTEDOFSIXEARLYGASTRICCANCERSTHETUMORISINTHESUBMUCOSALANDMUCOSALLAYERSINTHEGASTRICWALLAND43ADVANCEDGASTRICCANCERSTHETUMORINVADESTHROUGHTHEPROPERMUSCLELAYEROFTHEGASTRICWALLACCORDINGTOTHEPATHOLOGICTNMCLASSIFICATION,THEREWERE18CASESATSTAGESIANDII,AND31CASESATSTAGESIIIA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簡介：中文中文3200字出處出處ICHIKAWAT,ERTURKSM,MOTOSUGIU,ETALHIGHBVALUEDIFFUSIONWEIGHTEDMRIINCOLORECTALCANCERJAMERICANJOURNALOFROENTGENOLOGY,2006,1871181184高B值彌散加權值彌散加權MRIMRI在結直腸癌中的應用在結直腸癌中的應用ICHIKAWAT,ERTURKSM,MOTOSUGIU,ETAL摘要摘要目的目的這篇文章的目的是評估高B值擴散加權成像（DWMRI）檢測大腸腺癌的實用性。結論結論高B值DWMRI在檢測大腸腺癌方面具有很高的靈敏度和特異性檢測。關鍵詞癌癥；結腸；彌散加權成像；磁共振前言彌散加權MRI（DWMRI），在評估的惡性腫瘤變得越來越重要。人們普遍接受DW核磁共振成像是在使生物組織的非侵入性的特性基礎上，反映它們的水擴散性征，它能提供組織生物物理性質方面的信息，如細胞的組織和密度，顯微組織及微循環(huán)。DW核磁共振成像已被廣泛用于在影像學，但其腹部內的應用卻受到大的生理運動的阻礙，如呼吸，腸蠕動，血流量，及比擴散更大的振幅等。高原直泰等提出了DWMRI的技術可能提供改進的信號噪聲比（信噪比）的圖像，這些圖像的對比度，在黑色和白色圖像對比度特性密切類似PET逆轉。我們猜測，由于不同的健康和腫瘤組織的細胞結構的不同，高B值DWMRI圖像，可以直接用于腫瘤的檢測。我們決定研究大腸腺癌，因為結腸MRI有一定的挑戰(zhàn)，包括非實體性質的器官，胃腸蠕動，和運動腔內的內容物的干擾等。因此，我們在這個初步研究的目的是評估的有用的高B值DWMRI檢測大腸腺癌。材料及方法材料及方法患者患者2004年8月至2005年2月，為期6個月期間內，在我們的機構和兩個相關的醫(yī)院中共收集了33例患者（平均年齡59歲，范圍3369歲，15名女性，18名男性），并納入本研究。其中33例均經結腸內窺鏡證實大腸癌，病灶從20毫米到70毫米不等（平均33毫米）被發(fā)現在，病變位于直腸（14例），乙狀結腸（8例），橫結腸（N2），升結腸（8例），盲腸（1例）。另外選取同一時期15名結腸鏡檢為陰性的患者作為對照。所有大腸癌患者手術切除并證實診斷。所有患者和陰性對照組的病例在檢查前均行增強CT及MR。本研究施行前已經我們的機構審查委員會批準且所有患者簽署知情同意書。MRIMRI序列及參數序列及參數研究為何高B值DWMR圖像上只有結腸腺癌，表現出強烈的信號強度，而健康的結腸則不是高信號的原因是一個具有挑戰(zhàn)性的問題，值得進一步研究。然而，理論解釋可能構造通過DW核磁共振成像良好的一般的假設。這是眾所周知的，擴散即隨機的平移分子運動，也被稱為布朗運動。DWMRI是唯一的成像方法，該方法可以評估在體內的擴散過程。在細胞外和細胞內的組件的組織的水分子的擴散速度是不同的。細胞內成分的擴散速度相對較慢，這是因為存在細胞膜。因此，表觀擴散系數（ADC），這是定量表達的組織中的擴散特性，與胞外和胞內組分的比例。他們往往會減少與增加組織細胞性或細胞密度。相反，細胞密度可能是腫瘤惡化的指標LYNG以等報道腫瘤細胞高轉移能力增加。此外，在除了細胞膜，細胞內的細胞骨架，細胞器，基質型纖維和可溶性大分子在腫瘤的擴散也限制。因此，擴散的曲線迅速衰減或大型ADC值可能是典型的外大空間和小細胞性健康組織或良性的病理過程，而曲線衰減慢或小的ADC值可能表示惡性腫瘤或細胞過多。因此，DWMRI應該可以敏感的鑒別病理組織特性。事實上，一些報道已經指出各種惡性病變ADC值下降。然而，以前相關DWMR的研究并沒有直接視覺評估和報告這種技術的腹部病癥的診斷性能。雖然在本研究中所使用的技術主要基于DW核磁共振成像，事實上，DW核磁共振成像并沒有被經常使用在臨床設置用于檢測大腸癌，但作為一個潛在的工具，用于治療監(jiān)測手段曾被提出過，建議使用的應用程序是非定性得，但定量基于ADC測量。我們在這項研究中使用的高B值DWMRI技術與多個激勵和使用收購法無屏氣，提高信噪比。因為屏氣掃描時間的限制，不允許獲得足夠的SNR和多個激發(fā)，就不可以用來獲得作為多平面重建源圖像的彌散加權的薄層圖像。相反，運動偽影的增加是可能存在的理論缺點，然而，在實踐中，被平均的運動偽影期間多次激發(fā)的應用使DW核磁共振成像和重建圖像變得不顯眼的運動探測梯度。因此，圖像有更好的信噪比都達到了絕對變得無法計算，因為信號平均ADC值交換。我們的初步結果證明，高B值DWMRI對于檢測大腸癌的診斷表現為高靈敏度，30/33（91％）和特異性（100％，15/15），這種技術的其他優(yōu)點是，它是完全非侵襲性的，并不需要暴露于電離輻射或注入造影材料，并且不會引起病人的不適。此外，因為它是來自行之有效的DWMRI技術，高B值DWMRI并不需要運營商提供先進的技術技能或高成本的基礎設施投資，如回旋加速器PET等。高B值DWMRI的另一個優(yōu)點是，它是一個可以很容易地添加到MR檢查序列，因為它只需要一個很短的掃描時間。在本研究中，我們沒有評估淋巴結轉移，我們的目的是評估高B值DWMRI檢測大腸腺癌的診斷能力。然而，在一些患者中，淋巴結在圖像上可以顯示?；谖覀兒喍痰挠跋駥W病理的相關性，大部分轉移淋巴結表現為高信號強度，所以可以被很好的檢測，但在一些患者健康的淋巴結也同樣顯示出很高的信號強度。關于特異性檢測淋巴結轉移，這種觀察可能是一個具有挑戰(zhàn)性的問題，有待進一步研究。我們的研究有一定的局限性。首先，研究人口相對較少，我們的研究結果需要在更大范圍的臨床研究證實。其次，研究包括陰性的病例，但不包括其他良性疾病，如發(fā)炎性腸道疾病或良性腫瘤。因此，應考慮在本研究中報道的靈敏度是相對的而不是絕對的?？傊?，根據我們的初步研究結果，高B值DWMRI可能是一個檢測大腸癌有用的工具，它顯示了較高的敏感性和特異性。然而，因為以上所描述的局限性，仍需要進一步的大樣本研究來支持我們的調查結果。

簡介：中文中文4900字出處出處RUSCAN,MONTICELLISMIR146AINIMMUNITYANDDISEASEJMOLECULARBIOLOGYINTERNATIONAL,2011,17免疫和疾病中的免疫和疾病中的MIR146MIRNA分子是一類在細胞中可以影響各種生物功能的分子。已經證實他們與癌癥、病毒感染和免疫性疾病相關，近些年，還發(fā)現它們成為免疫反應的重要調節(jié)者。尤其是MIR146A迅速成為一種重要的分化調節(jié)者，同樣在先天免疫和獲得性免疫中有很重要的作用。鑒于它在調節(jié)細胞功能方面的重要作用，MIRNA146A在各種腫瘤中被發(fā)現表達失調也不足為奇。這篇文章，我們主要總結了近些年對MIR146A在先天免疫和獲得性免疫反應及疾病中的作用的進展。1介紹介紹MIRNA代表了所有的細胞的普遍特征，因為它們調節(jié)了細胞轉錄過程中的大部分。至今，672個鼠的MIRNA分子和1048個人的MIRNA已經在MIRBASE數據庫中被描述（HTTP//WWWMIRBASEORG/,RELEASESEPT2010其中每個MIRNA潛在地調節(jié)了成百上千的目標基因，這顯著地擴展了調節(jié)模式。然而一些MIRNA表達廣泛，其他的僅僅抑制有限發(fā)展的階段、組織或者細胞特異的類型。類似于一些哺乳細胞的類型，細胞免疫系統依賴MIRNA來調節(jié)譜系的定型、增殖、遷移和分化。在大部分的情況下，這些活動都是十分和諧，在廣泛的表達和細胞特定的MIRNA類型方面。當MIRNA的表達被改變時MIRNA在調節(jié)分化和免疫細胞功能方面的重要性就通過表型干擾表現得尤為突出。MIRNA在修飾免疫反應的重要作用，可能任何MIRNA表達的失調都會導致自身免疫性疾病、慢性炎癥和惡性腫瘤的發(fā)生。事實上，已經證明人類的一些疾病和MIRNA的表達失調有關，MIRNA的功能可以充當癌基因和抑癌基因。MIR146A最近已經報道成為在先天和獲得性免疫中重要的細胞分化和功能的調節(jié)者。在此，我們總結了近來關于MIR146A在免疫反應和疾病中作用的理解（見表1）。2什么是什么是MIRNA（此部分未翻譯，和之前的文章基本重復）（此部分未翻譯，和之前的文章基本重復）MIRNA是一種非編碼小RNA分子（長度2025核苷酸），參與轉錄后基因的調控。它們最初為初級MIRNAPREMIRNA，這會在細胞核內通過微處理復合體形成前體發(fā)夾結構（PREMIRNA），這種復合體發(fā)函RNASEIII酶DROSHA。3MIRNA146A在獲得性免疫反應中在獲得性免疫反應中雖然獲得性免疫應答反應失調會導致自身免疫性疾病和慢性炎癥疾病，但是能有效地消滅病原體的感染。獲得性免疫反應的發(fā)展和進步對于侵入的病原體會形成一系列精密的反應步驟，包括免疫細胞的活化增殖和隨后遷移到炎癥部位。最初的跡象表明MIRNA參與調節(jié)免疫細胞的分化，這已經被陳和他的同事們用MIR181在造血干細胞中特異性的表達證明。在造血干細胞中的易位表達導致了部分B細胞系在體外誘導分化和大鼠的模型中的增加。接下來的開創(chuàng)性的研究，證明MIRNA是控制免疫細胞分化和功能重要的組成部分。當與抗原結合后，原始CD4T細胞升高了T細胞亞群（TH1，TH2，TH17，TREGS，濾泡輔助性T細胞）根據它們各自在宿主防御中的功能。最初的表達鑒定了MIRNA的表達譜在不同的T細胞亞群和部分分化階段。T細胞特異性切酶顯示在T細胞的發(fā)展中需要MIRNA通路，同時T細胞亞群的分化也需要。事實上，缺乏DICER酶的T細胞表現出向TH1亞群的分化增加，同時向TH2減少。根據復雜的基因調控網絡，增殖的T細胞比靜止的T細胞表達更短的3‘UTR，使得這些MRNA更不易被MIRNA調控由于缺失MIRNA結合位點。最終，個別的MIRNA對T細胞分化和功能有重要的作用。例如，MIR181A，面對病毒的入侵時免疫細胞使用各個層次的負向調節(jié)以防免疫應答不受控制，這種調節(jié)機制也可以被病毒使用為了逃離免疫監(jiān)視。發(fā)現MIR146A在調節(jié)皰疹性口腔炎病毒（VSV）的感染時有作用。在巨噬細胞中，VSV的感染上調了MIR146A的表達，導致負向調節(jié)VSV觸發(fā)的I型IFN通過下調TRAF6，IRAK1和IRAK2，因此促進了VSV在巨噬細胞中的復制。作者提出了一種模式，VSV的感染首先被RIGI（視黃酸誘導基因蛋白I）感受到，這反過來抑制I型IFN的產生來對抗VSV的感染。同時，VSV的感染上調了MIR146A的表達，通過破壞RIGI信號抑制了先天免疫應答。EBV（人類皰疹病毒4）感染過超過90的全世界的人口。EV病毒感染會導致惡性腫瘤，包括BURKITT’S和霍奇金淋巴瘤。LMP1潛伏膜蛋白是EV病毒編碼的主要的癌基因產物，它可以活化轉錄因子如NFKB和AP1，由此來控制宿主細胞、調節(jié)細胞分化、遷移和凋亡的過程。通過它的這種活化轉錄因子的能力，LMP1也能誘導細胞中MIRNA的表達，其中最顯著的是MIR146A，因此在感染EB病毒后對細胞的永生化和腫瘤發(fā)生有幫助。6MIR146和癌癥和癌癥癌癥是一系列復雜過程的結果，是一些基因各種順序改變的積累，包括編碼MIRNA。既然MIRNA參與保持基因平衡的任務，那么它也可以決定細胞的命運，它們的失調潛在地會減弱這種平衡，因此可能導致癌癥的發(fā)生、發(fā)展。事實上，MIRNA表達譜中已經發(fā)現在一些癌癥中MIRNA的表達被顯著地改變了。關于MIR146A可能參與癌癥發(fā)展的初步證據來自MIR146A在PTC（甲狀腺乳頭狀癌）樣本中被上調的研究與未受影響的甲狀腺組織相比。有趣的是，一組5個MIRNA，包括MIR221，MIR222，MIR146對區(qū)分PTC和正常甲狀腺組織是足夠的了。在免疫設置中進行同樣的觀察，MIR146A/B在代謝旺盛的人類乳腺癌細胞株MDAMB231中的過表達顯著下調了IRAK1和TRAF6的表達，負調節(jié)了NFKB的活性。在功能上，這導致與控制組的細胞相比這些細胞的侵襲和轉移的能力明顯受損。這些發(fā)現說明MIR146在乳腺癌細胞中不僅是NFKB的負向調節(jié)者，而且說明調節(jié)MIR146的水平或許可以潛在地抑制乳腺癌的轉移。用相同的路線，在眾多的MIRNA中發(fā)現與正常宮頸組織相比MIR146A在宮頸癌組織中上調。當引入細胞株時，發(fā)現MIR146A促進了細胞增殖。雖然這種增加增殖的分子機制已經被研究，但是這些發(fā)現說明MIR146A可能與宮頸癌的發(fā)生有關。另一種癌癥激素難治性前列腺癌（HRPC），MIR146A的水平減少了，與雄激素敏感性的非癌癥上皮細胞相比。在這方面，MIR146A扮演腫瘤抑制的角色，減少了它的靶點ROCK1的水平，ROCK1是參與HRPC轉化的一個關鍵激酶。因此，強化MIR146A的表達可以減少ROCK1蛋白的水平、細胞分化、侵襲和向人單層骨髓上皮細胞的轉移。同樣，MIR146A在胰腺癌細胞中水平較低與正常人胰腺細胞相比。MIR146A的表達通過下調EGFR（表皮生長因子受體）和IRAK1抑制了胰腺癌細胞的侵襲能力。最后，最近的一項研究說明用DZ（二氮嗪）治療骨髓源性的間充質肝細胞（MSCS）顯著地增加了MIR146A的表達，促進了細胞的存活。此外，通過反義抑制劑MIR146A水平的下調消除了DZ誘導的細胞保護作用。這說明MIR146A在MSC（骨髓基質細胞）存活中有重要作用。7基因多態(tài)性和轉錄后的修飾基因多態(tài)性和轉錄后的修飾基因多態(tài)性影響MIRNA的表達、成熟或者MRNA的識別可能對增加腫瘤的風險成為重要的決定因素。事實上，最近KIT癌基因3‘UTR遺傳變異被描述，這導致了MIR221種子區(qū)的不匹配，伴隨增加黑色素瘤的風險。至于MIR146A，單核苷酸多態(tài)性在前MIR146A的傳遞鏈上被發(fā)現。罕見的C等位基因降低了和前體MIR146A合成的過程，降低了PREMIR146A和成熟MIR146A的水平，解鎖了它的靶基因，包括TRAF6和IRAK1。一項與PTC患者有關的研究，GC雜合狀態(tài)會增加獲得性PTC的風險，但是兩個純合子狀態(tài)

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