簡介：中文中文77007700字出處出處SATARUPAS,RAFALK,SATISHD,ETALROLEOFHEXOKINASE1INTHESURVIVALOFHIV1INFECTEDMACROPHAGESJCELLCYCLE,2015,JAN200EPUBAHEADOFPRINT7980989己糖激酶己糖激酶11在被HIV1HIV1感染的巨噬細胞的生存過程中的作用感染的巨噬細胞的生存過程中的作用SATARUPASEN，RAFALKAMINISKI，SATISHDESHMANE，DIANNELANGFORD，KAMELKHALILI，SHOHREHAMINI，ANDPRASUNKDATTA關鍵詞關鍵詞細胞凋亡，葡萄糖代謝，己糖激酶，HIV1，巨噬細胞，線粒體縮略語縮略語HK1，HEXOKINASE1（己糖激酶1）；VPR，VIRALPROTEINR（病毒蛋白R）；CTZ，CLOTRIMAZOLE（克霉唑）；G6P，GLUCOSE6PHOSPHATE（葡萄糖6磷酸）；G6PD，GLUCOSE6PHOSPHATEDEHYDROGENASE（葡萄糖6磷酸脫氫酶）；OMM，OUTERMITOCHONDRIALMEMBRANE（線粒體外膜）；VDAC，VOLTAGEDEPENDENTANIONCHANNEL（電壓依賴性陰離子通道）；COXIV，CYTOCHROMECOXIDASESUBUNITIV（細胞色素C氧化酶亞基IV），CART，COMBINATIONANTIRETROVIRALTHERAPY（抗逆轉(zhuǎn)錄病毒聯(lián)合療法）；MCSF，MACROPHAGECOLONYSTIMULATINGFACTOR（巨噬細胞菌落刺激因子）病毒已經(jīng)有多種方式來保護被感染的細胞免于凋亡。被HIV1感染的巨噬細胞壽命長，并且被當做是儲存HIV1的容器。細胞存活還是死亡的一個重要的決定性因素是葡萄糖代謝。我們推測，HIV1保護被感染的細胞免于凋亡，從某種程度上是通過調(diào)節(jié)宿主的糖酵解途徑更準確地說是調(diào)節(jié)己糖激酶1（一種將葡萄糖轉(zhuǎn)化為葡萄糖6磷酸的酶）來實現(xiàn)的。因此，我們分別分析了在HIV1接種的外周血單核細胞和長期接種HIV1的單核細胞系U1中己糖激酶1的調(diào)節(jié)。結果表明，HIV1誘導己糖激酶1的表達量顯著增強。令人驚奇的是，己糖激酶的酶活性在被感染的外周血單核細胞和PMA分化的U1細胞系中被顯著抑制。有趣的是，我們觀察了在PMA誘導的U1細胞和HIV1依附的蛋白病毒蛋白R轉(zhuǎn)換的巨噬細胞U937中與線粒體結合的己糖激酶1的增長水平。使用藥劑將U1細胞系線粒體中的己糖激酶1解離出來，此過程中克霉唑誘導線粒體膜去極化和細胞凋亡蛋白酶3和7介導細胞凋亡。從病毒蛋白R轉(zhuǎn)化的U937細胞線粒體中解離己糖激酶1同樣會增強細胞凋亡蛋白酶3和7的活性。這些觀察結果表明，己糖激酶1在HIV1感染的巨噬細胞中不參與代謝，而是結合到線粒體上從而維持其完整性。這些結果表明，靶向己糖激酶1與線粒體的相互作用從而持續(xù)誘導受到感染的巨噬細胞凋亡可能會被證明對凈化成為HIV儲存容器的巨噬細胞有好處。介紹介紹單核細胞和巨噬細胞在先天性免疫防御中起重要作用。但是在HIV1感染的情況下，巨噬細胞可以加快病毒從體表傳播到大腦等末梢器官。許多研究已經(jīng)證明，HIV1感染的單核細胞和巨噬細胞是相對耐凋亡的。因此，這些生存能力強的被感染細胞可以在大腦中作為HIV1持續(xù)存在的儲存容器，也可以促使病人中樞神經(jīng)系統(tǒng)的炎癥接受抗逆轉(zhuǎn)錄病毒聯(lián)合治療。了解被HIV1感染的巨噬細胞抵抗凋亡的機制對于這些病毒儲存容器的靶向治療是很重要的。被感染的巨噬細胞的對凋亡抗性可能是源于HIV1和宿主葡萄糖代謝之間的相互作用。事實上，早期研究表明，VPR基因可以調(diào)節(jié)巨噬細胞的糖酵解途徑。葡萄糖代謝的第一步是在己糖激酶的作用下葡萄糖轉(zhuǎn)化為葡萄糖6磷酸。在哺乳動物細胞中有4種同類型的己糖激酶HK1，HK2，HK3，HK4。在這些同型的己糖激酶中，HK1和HK2可以結合線粒體。線粒體結合的己糖激酶在維持線粒體外膜完整性上起了重要作用。研究表明，己糖激酶結合于電壓依賴性陰離子通道抑制了膜間蛋白收到凋亡信號刺激而釋放，并抑制了凋亡。當前時代，作為病毒容器的巨噬細胞，其生命力較頑強的持久性對于規(guī)劃用抗逆轉(zhuǎn)錄病毒聯(lián)合療法根除HIV1的策略而言是一個重要的挑戰(zhàn)。此外，闡明HIV1介導的葡萄糖代謝途徑阻截機制將會使我們對設計清除潛伏的HIV1病毒的治療策略有了更深刻的認識。在這項研究中，我們發(fā)現(xiàn)了HIV1誘導單核細胞和巨噬細胞中己糖激酶1的表達。但是，HIV1的表達抑制了己糖激酶的活性卻促使己糖激酶與線粒體結合以維持線粒體外膜的完整性。研究還發(fā)現(xiàn)，在巨噬細胞U937細胞中VPR基因的過度表達增強了線粒體與己糖激酶1的結合能力。在HIV1感染的巨噬細胞中分離線粒體上的己糖激酶1和克霉唑會降低線粒體膜的電勢，以及誘導凋亡蛋白酶3和7介導的細胞凋亡。類似地，在病毒蛋白R另加一組二甲基亞砜作對照，10小時后測定胞質(zhì)和線粒體中的己糖激酶1蛋白水平。這項分析證明了己糖激酶1在胞質(zhì)中（圖3A3A、B）和線粒體中（圖3C3C、D）的含量比受到克霉唑劑量依賴性的調(diào)節(jié)。特別地，25ΜMOL/L克霉唑顯著地增加了胞質(zhì)中的己糖激酶水平（圖3A3A、B）并且伴隨著線粒體中己糖激酶水平下降（圖3C3C、D）。在接下來的實驗中，我們使用了25ΜMOL/L克霉唑。為了測定在線粒體中用25ΜMOL/L克霉唑改變己糖激酶的亞細胞定位帶來的影響，我們使用膜滲透性染料JC1測量了線粒體膜電位變化（ΔΨ）。在對照、PMA處理、PMA外加25ΜMOL/L克霉唑處理的U1細胞中極化細胞（紅色熒光）的百分比分別為7239±16、7398±28和3171±13，去極化細胞（綠色熒光）的百分比分別為2683±12、2128±35和6805±10（圖3E3E）。這些數(shù)據(jù)表明，25ΜMOL/L克霉唑改變了PMA處理的U1細胞的線粒體膜電位。線粒體膜電位的變化是細胞凋亡早期的一個顯著特點。因此我們測定了PMA處理的和PMA外加25ΜMOL/L克霉唑處理的U1細胞存活水平細胞事先用熒光激活細胞分選術和碘化丙啶（PI）染色處理過。克霉唑與PMA處理的凋亡率是單獨用PMA處理的3倍（圖4A4A）。半胱天冬酶家族成員細胞凋亡蛋白酶3和7在哺乳動物細胞凋亡中起著關鍵的作用。因此，我們使用凋亡蛋白酶血清球蛋白3/7鑒定法判斷克霉唑誘導U1細胞隨著己糖激酶1與線粒體分離而凋亡凋亡蛋白酶血清球蛋白3/7鑒定法利用激活發(fā)光的凋亡蛋白酶3/7作為測量凋亡蛋白酶活性的底物。結果表明，同對照組相比，克霉唑處理的細胞，其凋亡蛋白酶3/7活性增加了23倍（圖4B4B）。HIV1HIV1的病毒蛋白的病毒蛋白R基因在調(diào)節(jié)己糖激酶基因在調(diào)節(jié)己糖激酶11轉(zhuǎn)移中的作用轉(zhuǎn)移中的作用在觀察到HIV1感染的巨噬細胞的線粒體中己糖激酶1含量增加之后，我們提出如下問題是不是病毒蛋白VPR調(diào)節(jié)了己糖激酶1的亞細胞定位轉(zhuǎn)移。最近，使用穩(wěn)定同位素標記（SILAC）蛋白質(zhì)組學分析，我們證明了HIV1的病毒蛋白R誘導了巨噬細胞中己糖激酶1的表達。此外，研究表明，病毒蛋白R對于HIV1感染的巨噬細胞而言是必需的，因為在缺乏病毒蛋白R的巨噬細胞中病毒的復制效率降低。我們測定了VPR基因過度表達對于U937巨噬細胞中細胞質(zhì)和線粒體組分的己糖激酶1含量的影響。線粒體和細胞質(zhì)餾分的純度通過細胞色素C氧化酶亞基IV代表線粒體、微管蛋白代表細胞質(zhì)來確定。我們首先測定了U937細胞中VPR基因的表達量（轉(zhuǎn)換成ADVPR基因），然后定量測定這些細胞中己糖激酶的總活性。這些研究表明，VPR基因在轉(zhuǎn)入ADVPR基因的巨噬細胞中過度表達（圖5A5A）抑制了全部細胞的溶胞產(chǎn)物中己糖激酶的總活性（圖5B5B）。有趣的是，同單獨導入腺病毒的U937細胞相比，ADVPR顯著增加了線粒體組分中的己糖激酶含量（圖5C5C、D）并且顯著減少了細胞質(zhì)組分中的含量（圖5C5C、E）。這些發(fā)現(xiàn)證明，VPR確實調(diào)節(jié)了己糖激酶1從細胞質(zhì)到線粒體的轉(zhuǎn)移。為了顯示VPR介導己糖激酶1轉(zhuǎn)移至線粒體的重要性，我們使用克霉唑?qū)隫PR的U937細胞的線粒體和己糖激酶1分離，然后測定細胞凋亡蛋白酶3和7的活性。結果顯示同對照組（導入VPR的U937細胞）相比，使用25ΜMOL/L克霉唑處理后細胞凋亡蛋白酶3和7的活性增加了22倍（圖5F5F）?？偠灾@些發(fā)現(xiàn)闡明了VPR介導線粒體和己糖激酶1結合在維持線粒體完整上的重要性，因為在轉(zhuǎn)入VPR的細胞中用克霉唑?qū)⒕€粒體與己糖激酶1解離會誘導激活細胞凋亡蛋白酶3和7。討論討論同未被感染的單核細胞相比，持續(xù)受到感染的原單核細胞對于凋亡刺激并不敏感。HIV1感染的巨噬細胞比HIV1感染的其他細胞對凋亡有更強抗性，更有能力被當作病毒儲藏庫。此外，病毒從這些潛在儲藏庫中傳播可以促進病毒感染那些易受感染的靶細胞。HIV1感染的巨噬細胞抵抗凋亡的機制目前還不是很清楚。但是有推測認為巨噬細胞可能因為分化或者間接因為HIV感染又或者是因為表達了特殊的病毒蛋白如TAT和NEF激發(fā)了固有抵抗凋亡的方式。迄今為止的研究表明，細胞中的HIV1誘導巨噬細胞菌落刺激因子表達促進了抗凋亡蛋白如MCL1和BFL1的表達。研究還表明，活化HIV1感染的細胞的壓力誘導PI3K/AKT細胞存活途徑也會保護巨噬細胞免于凋亡。我們推測降低細胞凋亡蛋白酶3的活性可能是持續(xù)受到HIV1感染的細胞抵抗凋亡的一種機制。最近我們證明了HIV

簡介：1中文中文2740字出處出處WANGXJ,YUANSL,XIAOL,ETALTHEEXPRESSIONOFCSRCGENEINTHECARCINOGENESISPROCESSOFHUMANCARDIAADENOCARCINOMAJWORLDJOURNALOFGASTROENTEROLOGY,1999,56488491人賁門癌癌變進程中人賁門癌癌變進程中CSRC基因的表達基因的表達關鍵詞CSRC基因表達產(chǎn)物PP60CSRC；腫瘤轉(zhuǎn)移；摘要目的探討CSRC基因在人賁門癌（CA）癌變進程中的活性，表達和作用。方法對56例CA，34例正常，36例癌旁上皮和20例CA的轉(zhuǎn)移淋巴結用特異的單克隆抗體MAB327，免疫組化法檢測PP60CSRC和CSRC基因的表達。結果PP60CSRC的陽性率在正常上皮，增生上皮，CA和轉(zhuǎn)移淋巴結中分別為29410/34,94434/36,71440/56和60012/20。而且，各陽性率間有顯著的統(tǒng)計學差異P＜001。CA和增生上皮中的PP60CSRC的表達水平顯著高于正常上皮P＜001＝。PP60CSRC的陽性率在乳頭狀，管狀，低分化和粘膜腺癌中分別為7506/8,81818/22,50010/20和10006/6，管狀和粘膜腺癌中顯著高于乳頭狀和低分化腺癌（P005）。結論CSRC基因的活性和表達與人CA的發(fā)生和發(fā)展相關；PP60CSRC蛋白數(shù)量在發(fā)癌過程中增加；PP60CSRC的表達與淋巴結轉(zhuǎn)移相關。介紹目前遠端胃癌的發(fā)病率逐年下降，而賁門癌的發(fā)病率卻在穩(wěn)定增加。CA的生物學和流行病學特征于遠端胃癌明顯不同，且原因不明［13］。PP60CSRC是CSRC基因的產(chǎn)物，具有酪氨酸激酶活性。CSRC基因表達的增加在乳腺癌［4］，食管癌［5］，胃癌［6］和結腸癌［7］中都有報道。CSRC基因活性和表達可能與一些腫瘤的發(fā)生發(fā)展有關。我們先前的研究表明CSRC基因的活性和表達與食管鱗癌的分化和發(fā)展有關［8］。因此我們相信在賁門癌中也有相似的變化。材料和方法標本的收集和處理所有的56例CA標本均來自腫瘤中心的手術后CS患者。所有的標本均經(jīng)固定化程序，甲醛固定，石蠟包埋，至少兩套4ΜM6ΜM厚的石蠟切片。一個用HE染色，一個做免疫組化。試劑單克隆抗體MAB327小鼠IGG由日本大學分子病理系提供，抗生蛋白鏈菌素免疫組化試劑盒ZYMEDUSA從FUZHOUMAXIMBIOTECH公司購買。PP60CSRC蛋白的免疫組化分析PP60CSRC蛋白用LSAB方法的免疫組化分析。組織切片在梯度乙醇中脫蠟脫水后，用胰蛋白酶消化。用3H2O2阻滯內(nèi)源性過氧化物酶的活性，用正常血清處理后，切片在稀釋為1∶100的MAB327中孵育，4℃過夜。在室溫下，生物素化的第二抗體20分鐘，抗生蛋白鏈菌素30分鐘。再用含有0005H2O2的002的3,3四鹽酸二氨基聯(lián)苯胺染色。再用蘇木精復染。組織病理學檢查CA和有關的損傷的組織病理學診斷，以及CA的組織學類型均由2名有經(jīng)驗的病理醫(yī)生根據(jù)一定的標準做出［8］。PP60CSRC免疫組化染色的定性和定量分析PP60CSRC的免疫染色按照已知的標準分析［5］。CA中PP60CSRC陽性細胞的百分率按以下標準分級陰性,＜25,2550,＞50。PP60CSRC陽性細胞表性和細胞膜的染色強度與陰性對照陰性,弱,中度和強。結果組織病理學檢查在56例CA標本中，包括乳頭狀8/56，管狀22/56，低分化3多正常細胞中均可發(fā)現(xiàn)PP60CSRC的表達。在細胞增生，分化和轉(zhuǎn)化的調(diào)控中起重要的作用［4］。目前的研究顯示PP60CSRC蛋白數(shù)量和激酶活性的增加與一些人類腫瘤的發(fā)身發(fā)展相關，而且活性和表達增加是腫瘤發(fā)生的一個因素［48］。本研究中，PP60CSRC蛋白在CA，乳頭狀，管狀，低分化和粘液腺癌中的表達分別為71440/56,94434/36和29410/34，在CA和增生上皮中PP60CSRC的陽性率比在正常上皮中高（P001）。JANKOWISKIETAL分析了15例食管腺癌和15例BARRETT′S食管上皮中CSRC基因產(chǎn)物表達，陽性率為203/15，提示CSRC基因的表達于食管腺癌的發(fā)展相關。因此，本研究的結果顯示CSRC基因的活性和表達可能與CA的發(fā)生發(fā)展相關。但是，在增生上皮中PP60CSRC的高表達可能與老年大鼠的腺上皮細胞的增生相關［9］。在一些癌旁正常上皮PP60CSRC的低表達可能是由于在正常上皮中PP60CSRC的表達與癌的發(fā)生相關［58］。另一方面，也說明CSRC基因的活性和表達可能使CA發(fā)癌過程中的一個早期事件。盡管CSRC基因的活性和表達與一些人類腫瘤的發(fā)生相關。用生化方法測定PP60CSRC的激酶活性和蛋白數(shù)量的結果因方法而不同。大部分的研究報道，PP60CSRC的激酶活性在癌細胞株和胃癌，腸癌，肺癌和腎癌的組織中有增加。但是與腫瘤相比，正常組織中無PP60CSRC蛋白數(shù)量的不同。PP60CSRC的激酶活性的增加無法用CSRC基因編碼的蛋白表達的增加而解釋［6,10］。本研究中，PP60CSRC蛋白用特異的單克隆抗體MAB327檢測，在CA和增生上皮中PP60CSRC的高表達分別為357和778，在癌旁的一些正常上皮中有PP60CSRC的低表達，兩者表達的不同有顯著的統(tǒng)計學意義（P001）。本研究的結果提示PP60CSRC蛋白數(shù)量在CA中增加。關于CSRC基因表達產(chǎn)物，PP60CSRC和癌細胞分化之間的關系，有不同的意見［6,8,9,11］。FANNINGETAL［1］報道了在高分化膀胱癌中有CSRC基因的高水平表達，提出PP60CSRC蛋白和激酶活性與泌尿道和ⅠⅡ期膀胱癌上皮細胞的分化相關。TAKEKURAETAL［6］PP60CSRC激酶活性在高分化和低分化胃癌中未發(fā)現(xiàn)不同。本研究中，不同組織類型的CA中PP60CSRC陽性率也不同。在粘液腺癌中陽性率為1000,6/6，在管狀腺癌中為818,18/22，比乳頭狀750,6/8和低分化500,10/20要高，這種不同有顯著性差異（P005）。在粘液和管狀腺癌中高水平的表達分別為10006/6和63614/18，在乳頭和低分化腺癌中只有低表達，這種不同也有顯著的差異（P001）。這些結果提示，PP60CSRC表達水平與CA的分化和組織學類型相關，在粘液和管狀腺癌中的PP60CSRC高表達可能與它們的高分化和其他的生物學行為相關。帶有激酶活性增加的PP60CSRC表達與結腸癌轉(zhuǎn)移的關系也有報道［12,13］。但是用免疫組化染色檢測轉(zhuǎn)移淋巴結中PP60CSRC蛋白暫無報導。TALAMONTIETAL［12］發(fā)現(xiàn)PP60CSRC激酶活性在原發(fā)和多發(fā)癌中也有增加。TERMUHLENETAL［13］報道了在結腸癌干轉(zhuǎn)移中也有PP60CSRC激酶活性的增加。本研究中，檢測CA的轉(zhuǎn)移淋巴結中的PP60CSRC蛋白，陽性率為60012/20，PP60CSRC表達水平與相同的原發(fā)腺癌相同。本研究的結果顯示，PP60CSRC表達與CA的淋巴結轉(zhuǎn)移相關。

簡介：中文中文3150字出處出處YINGD,XUY,LINGD,ETALDOWNREGULATIONOFMIR141INGASTRICCANCERANDITSINVOLVEMENTINCELLGROWTHJJOURNALOFGASTROENTEROLOGY,2009,446556561MIR141MIR141在胃癌和它相關細胞生長中的下調(diào)在胃癌和它相關細胞生長中的下調(diào)摘要摘要目的人類小RNA141（MIR141）是MIR200家族的成員之一，已經(jīng)被報道和多種人類惡性腫瘤相關。然而，它與胃癌發(fā)生機理是否相關仍然未知。因此，我們檢測了MIR141在胃癌組織中的表達和MIR141的過表達對于癌細胞增殖的影響。方法MIR141的表達水平在35組胃癌組織和癌旁組織以及5中胃癌細胞系中用實時定量PCR分別檢測。轉(zhuǎn)染MIRNA前體的MGC803細胞的生長通過MTT分析方法被檢測到。結果與對照的癌旁組織相比MIR141在80的初期胃癌組織中明顯下調(diào)。在人類胃癌細胞系MGC803,HGC27,SGC7901和BGC823中，同樣發(fā)現(xiàn)MIR141的表達大量減少。MIR141和它前體的過表達能夠明顯的抑制胃癌細胞的增殖。結論這些結果都暗示了，MIR141可能通過抑制細胞的增殖與胃癌的發(fā)展密切相關。關鍵詞關鍵詞MIR141，胃癌，MGC803細胞，細胞增殖引言引言MICRORNASMIRNAS，是新近在動物和植物中發(fā)現(xiàn)的一類新的內(nèi)源性，非編碼的單鏈RNA。他們觸發(fā)翻譯的阻滯和/或MRNA的降解，大多數(shù)通過互補的結合靶MRNA的3’非翻譯區(qū)。研究表明MIRNAS能夠廣泛調(diào)節(jié)生物進程，如細胞增殖，分化，凋亡。越來越多的證據(jù)表明，通過調(diào)節(jié)MIRNAS的表達可能在人類癌癥的病理機制中起到多種多樣的作用。一些MIRNAS已經(jīng)被證實有致癌或抑癌活性。高通量技術已經(jīng)被用于檢測在良性腫瘤和惡性腫瘤樣本中MIRNAS的差異表達，同時，在人類多種腫瘤中一些MIRNAS失控也被發(fā)現(xiàn)，包括肺癌，乳腺癌，肝癌，食道癌和前列腺癌。在這些

簡介：中文中文2500字出處出處ZAMBONA,MANDRUZZATOS,PARENTIA,ETALMAGE,BAGE,ANDGAGE,GENEEXPRESSIONINPATIENTSWITHESOPHAGEALSQUAMOUSCELLCARCINOMAANDADENOCARCINOMAOFTHEGASTRICCARDIAJCANCER,2001,911018828食管癌和賁門癌患者中食管癌和賁門癌患者中MAGE,MAGE,BAGEBAGE和GAGEGAGE基因的表達基因的表達關鍵詞關鍵詞食管癌；腫瘤抗原；MAGE,BAGE，GAGE摘要摘要方法從24例食管癌ESCC和24例賁門癌CAC患者中得到的手術標本用RTPCR檢測基因表達。這些患者均未經(jīng)化療和放療，生存時間都在4年以上。結果由16例ESCC67和9例CAC375樣本中有至少一種基因的表達。兩個組織類型中的MAGE基因表達無顯著性差異，但MAGE4基因在ESCC中的表達要多于CAC。BAGE和GAGE在每個樣本中表達得都相當少，與至少一個MAGE基因表達相關。結論從整體上以及從ESCC和CAC上來說，這些基因的表達與預后因素，如腫瘤程度，淋巴結或病期之間均無顯著的聯(lián)系。但是，BAGE和GAGE的表達與較差的預后顯著相關，而MAGE基因表達與較好的預后顯著相關。正文正文近些年，許多的人腫瘤抗原用自體的細胞毒淋巴細胞CTLS被確定。1即所謂的T細胞確定腫瘤抗原其中一個重要的類別包括正常的基因產(chǎn)物，其在大多數(shù)人體組織中并不表達，除了男性胚系細胞和胎盤，且在許多不同的腫瘤中起作用由MAGE,BAGE，GAGE基因家族編碼的抗原多肽也是這種腫瘤抗原的一部分。25雖然其最初是在黑色素瘤中被發(fā)現(xiàn)，但是也在許多實體瘤中也有表達，如肺，乳腺，膀胱，頭頸，食管和胃等2。因為它們對腫瘤有較強的特異性，所以對腫瘤的免疫治療有很大的幫助。食管癌主要有兩個組織類型鱗狀細胞癌ESCC和腺癌CAC?，F(xiàn)在對無轉(zhuǎn)移的食管癌患者的治療方法主要是單純手術切除或結合放療化療。但是，術后的整體預后不好，5年生存率為2035。67高轉(zhuǎn)移復發(fā)提示，在病程早期已有了少量細胞的擴散。因此，積極的免疫治療可能是其他方法之外的有效幫助。已有報道ESCC中有MAGE1,MAGE2,MAGE3和MAGE4的高表達。8還未見到關于CAC患者中腫瘤抗原表達的研究。我們研究了MAGE1,MAGE2,MAGE3和MAGE4，MAGE6，BAGE，GAGE基因在ESCC和CAC患者中的表達，基因表達和公認的預后因素的關系，如腫瘤的病理分期PT，淋巴結分期PN，病程PSTAGE和長期生存率。材料和方法材料和方法患者和材料的收集24例食管鱗癌和24例遠端食管或賁門癌患者的腫瘤標本從意大利PADOVA大學病理庫中獲得。所有的患者在手術切除前均未經(jīng)放化療。這些患者的臨床病理數(shù)據(jù)見表1腫瘤的分級和分期根據(jù)國際抗癌聯(lián)盟UICC第四版TNM分類。經(jīng)R0切除后的患者均為手術后輔助治療，包括化療和放療。而經(jīng)不完全腫瘤切除術的四個患者接受了術后輔助治療。所有的患者均接受隨訪，兩個患者死于術后并發(fā)癥，故排除在生存分析之外。所有的手術標本均經(jīng)規(guī)范的組織學分析，切除后立即經(jīng)液氮冷凍，在放入80度保存直到進行RNA分析。有五個患者還取了正常的食管粘膜作為對照。表124例食管鱗癌和遠端食管或賁門癌患者的臨床病理數(shù)據(jù)食管鱗癌N24賁門癌N24合計N48因的表達。圖1顯示了8例CAC樣本中MAGEBAGEGAGE基因的表達。表2顯示了MAGE基因在ESCC和CAC中的表達非常相似，除了MAGE4在ESCC中的表達顯著增多58比25,P0019。有兩個ESCC8,，而無CAC表達BAGEP0149。四個ESCC17和三個CAC13有GAGE表達（P0683）。在正常組織中無任何基因的表達。表2MAGE1,MAGE2,MAGE3和MAGE4，MAGE6，BAGE，GAGE基因表達的比例組織類型MAGE1MAGE2MAGE3MAGE4MAGE6BAGEGAGEESCC13384258A21817CAC17333825A17013合計1535404219415我們探討了MAGEBAGEGAGE基因的表達之間的聯(lián)系。從整體上以及從ESCC和CAC上來說，這些基因的表達與預后因素，如腫瘤程度，淋巴結或病期之間均無顯著的聯(lián)系。MAGEBAGEGAGE基因的表達呈現(xiàn)出集簇表達，可能是由于大部分損傷無其他基因的表達4848患者中有23或者有3個或多個基因的共表達3548患者中有17TABLE3。表3每個患者MAGE1,MAGE2,MAGE3和MAGE4，MAGE6，BAGE，GAGE基因表達的數(shù)量每個患者基因表達的編號食管癌N24賁門癌N24合計N48081523141523033325444850116213食管切除術后患者N46的1年，3年，5年精確生存率為85,41,AND24。R0切除術后患者N37的1年，3年，5年精確生存率為89,51,AND30。在第一組生存分析中，樣本被分為兩個隊列由基因表達和無基因表達。在所有的ESCC和CAC患者組中，發(fā)現(xiàn)兩個隊列與生存無顯著的差異。進而分析MAGEBAGEGAGE基因，只有

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(shù)。圖1A穿刺實驗；B桿彎曲試驗；C頭端彎曲試；D摩擦實驗統(tǒng)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(tǒng)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(shù)據(jù)。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(nèi)導絲之間平均力測量有顯著的統(tǒng)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(shù)預測肺栓塞患者的預后分析肺栓塞嚴重程度指數(shù)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(jīng)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(shù)（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(jù)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(nèi)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(xiàn)與30天死亡率，醫(yī)院內(nèi)死亡率和整體死亡率顯著相關。我們的數(shù)據(jù)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?shù)闹委煟嗡ㄈ侵旅?。因此，恰當?shù)膽岩珊瓦m當?shù)脑u估對于預后是很重要的。一旦預后被預測，通過適當?shù)闹委?，死亡率可以降低。雖然已經(jīng)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(shù)據(jù)仍是相對少。然而，自2000年日內(nèi)瓦評分發(fā)現(xiàn)2和2005年肺栓塞嚴重性指數(shù)（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(shù)據(jù)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(jù)韓國疾病指南（KCD）。在這些患者中，84診斷不充分（即沒有經(jīng)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(jīng)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(shù)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(jù)AUJESKY等人3提出的方法，分數(shù)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(jù)我們的數(shù)據(jù)，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(tǒng)，日內(nèi)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(jù)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(tǒng)計學意義。這可能因為PESI評分I級患者21個，II級患者的數(shù)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(xiàn)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(nèi)在限制。根據(jù)患者組（N90），對他們來說，死亡原因未分類的數(shù)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(nèi)。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(shù)對肝臟良惡性腫塊的鑒別表觀擴散系數(shù)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(shù)（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(zhuǎn)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(tǒng)計學意義（P＜001）。血管瘤和肝癌轉(zhuǎn)移瘤間的ADC值也有統(tǒng)計上的顯著差異（P001），兩者與單純的包蟲囊腫間也有統(tǒng)計學差異（P＜0008。然而，HCC和轉(zhuǎn)移瘤之間有無統(tǒng)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(shù)據(jù)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(zhuǎn)移灶相鑒別。在肝臟疾病的調(diào)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(jīng)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(zhuǎn)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(jīng)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(tǒng)計分析統(tǒng)計分析所有的統(tǒng)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(tǒng)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(shù)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(zhuǎn)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(tǒng)計學意義（156±01410?3毫米2／S），（P＜001）。肝臟血管瘤和肝癌轉(zhuǎn)移瘤的ADC值也有統(tǒng)計上的顯著差異，（P001），它們與單純的包蟲囊腫間也有統(tǒng)計學意義（P＜0008）。然而，HCC和轉(zhuǎn)移瘤之間差異無統(tǒng)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(jīng)被發(fā)表。大多數(shù)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(xiàn)肝囊腫有最高的ADC值，無限制運動的水分子。有人發(fā)現(xiàn)基于擴散信號的不同，單純肝囊腫與其他病變有顯著的統(tǒng)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(zhì)，脂類和多糖的離子。同樣，我們也發(fā)現(xiàn)了單純肝囊腫與其他病變有顯著間有統(tǒng)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(shù)目的確定結合的二茂鐵數(shù)目的確定羊抗人IGEIGG結合的二茂鐵平均數(shù)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(zhì)分析方法檢測（SMITHETAL,1985）。蛋白質(zhì)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(jīng)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(xiàn)細胞核有絲分裂的報道，但是這種發(fā)現(xiàn)被一種假設所質(zhì)疑如果心肌細胞存在有絲分裂，但現(xiàn)實中的卻沒有心肌組織再生。此外，心肌細胞有絲分裂的現(xiàn)象從來沒有在正常心肌細胞中被發(fā)現(xiàn)。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(xiàn)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(shù)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(shù)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(jīng)發(fā)現(xiàn)了細胞質(zhì)分裂的證據(jù)，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(jù)提示在心肌嚴重肥厚時存在心肌細胞數(shù)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(jù)的缺乏質(zhì)疑了體視學結論的可信性。偶有發(fā)現(xiàn)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(xiàn)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(xiàn)。于此同時，心肌細胞細胞質(zhì)的有絲分裂證據(jù)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(zhì)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(xiàn)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(zhì)纖維化的現(xiàn)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(xiàn)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(jīng)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(shù)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(xiàn)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(shù)。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(shù)目分別為14136±56699,38854±16766，36013±17134細胞分裂指數(shù)分別為18±06,51±35,43±20用這些數(shù)據(jù)可以估算在各個組中心肌細胞的有絲分裂指數(shù)。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(shù)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(shù)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(shù)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(shù)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?。?。與心肌細胞相比，間質(zhì)細胞有絲分裂指數(shù)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(diào)，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(xiàn)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(zhì)疑。形態(tài)學研究表明在心衰患者的心肌中有發(fā)現(xiàn)心肌細胞增生。最近的數(shù)據(jù)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(shù)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(shù)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(xiàn)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(zhì)的分裂。只有這種增長方式才會出現(xiàn)心肌細胞數(shù)量的增長與心肌細胞的再生。早期的發(fā)現(xiàn)及近期的數(shù)據(jù)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(jīng)被證實存在細胞核與細胞質(zhì)的分裂。心肌細胞增殖心肌細胞增殖根據(jù)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(shù)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(chǎn)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(chǎn)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(xiàn)，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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