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| 1 | Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease progression in murine hepatitis virus type 3-induced fulminant hepatitis and in patients with severe viral hepatitis B显示文摘AIM: To evaluate the expression of fibrinogenlike protein 2 (fgl2) and its correlation with disease progression in both mice and patients with severe viral hepatitis.METHODS: Balb/cJ or A/J mice were infected intraperitoneally (ip) with 100 PFU of murine hepatitis virus type 3 (MHV-3), liver and serum were harvested at 24, 48, and 72 h post infection for further use. Liver tissues were obtained from 23 patients with severe acute chronic (AOC) hepatitis B and 13 patients with mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with cirrhosis and 4 liver donors served as normal controls. In addition, peripheral blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant activity representing functional prothrombinaseactivity in PBMC and white blood cells was also assayed. A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies. Alanine aminotransferase (ALT) and total bilirubin (TBil) in serum were measured to assess the severity of liver injury.RESULTS: Histological changes were found in liver sections 12-24 h post MHV-3 infection in Balb/cJ mice.In association with changes in liver histology, marked elevations in serum ALT and TBil were observed. Mouse fgl2 (mfgl2) protein was detected in the endothelium of intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3 infection. Liver tissues from the patients with severe AOC hepatitis B had classical pathological features of acute necroinflammation. Human fgl2 (hfgl2)was detected in 21 of 23 patients (91.30%)with severe AOC hepatitis B, while only 1 of 13 patients(7.69%) with mild chronic hepatitis B and cirrhosis had hfgl2 mRNA or protein expression. Twenty-eight of thirty patients (93.33%) with severe AOC hepatitis B and 1of 10 with mild chronic hepatitis B had detectable hfgl2expression in PBMC. No hfgl2 expression was found either in the liver tissue or in the PBMC from normal donors. There was a positive correlation between hfgl2expression and the severity of the liver disease as indicated by the levels of TBil. PCA significantly increased in PBMC in patients with severe AOC hepatitis B.CONCLUSION: The molecular and cellular results reported here in both mice and patients with severe viral hepatitis suggest that virus-induced hfgl2prothrombinase/fibroleukin expression and the coagulation activity associated with the encoded fgl2protein play a pivotal role in initiating severe hepatitis.The measurement of hfgl2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of AOC hepatitis B and a target for therapeutic intervention. | Chuan-Long Zhu Wei-Ming Yan Fan Zhu Yong-Fen Zhu Dong Xi De-Ying Tian Gary Levy Xiao-Ping Luo Qin Ning | 2005 | World Journal of Gastroenterology2005，11，44： | 26 |
| 2 | 暴发型病毒性肝炎小鼠模型的研究及应用显示文摘有关病毒诱导暴发型肝炎发病机制的研究主要存在两个障碍,一是尚无合适的细胞系进行人类肝炎病毒的体外培养,二是与人类暴发型肝衰竭临床综合症十分接近的较大实验动物不易获得.尽管如此,建立的两种病毒诱导的小型啮齿类动物模型为深入了解病毒诱导的暴发型肝衰竭的分子机制提供了新的方法. | 宁琴 杨东亮 罗小平 郝连杰 Gary Levy | 2002 | 中华肝脏病杂志2002，10，3： | 17 |
| 3 | mfgl2凝血酶原酶/纤维介素基因转录调控元件肝细胞核因子的研究显示文摘目的 研究鉴定mfg12凝血酶原酶 /纤维介素基因转录激活所必需的调控元件或转录因子。方法 应用免疫印迹法检测Ba1b/c小鼠的巨噬细胞内是否表达肝细胞核因子 4(HNF4) ,共聚焦显微镜免疫荧光技术检测鼠肝炎病毒 (MHV)的核心 (N)蛋白质是否进入被感染细胞核。应用DNA电泳迁移差异检测、竞争实验和定点诱变技术鉴定mfgl2基因转录激活所必需的调控元件或转录因子。结果 免疫印迹法表明巨噬细胞可持续表达HNF4。共聚焦显微镜免疫荧光技术证实MHV的N蛋白质可进入被感染细胞核内。凝胶移位分析和竞争实验显示HNF4和巨细胞病毒早期蛋白基因 1 2 (IE1 2 )均可与特异寡核苷酸竞争结合mfgl2启动子上特定位点而不与非特异寡核苷酸发生竞争。HNF4特异性多克隆抗体竞争试验可见超迁移带。定点突变mfgl2启动子上HNF4所结合的顺式调控元件可降低野生型mfgl2启动子的转录活动达 75 %,联合突变IE1 2结合位点未见协同效应。单纯突变IE1 2结合位点后 ,野生型mfgl2启动子的转录活动仍可保留 75 %~ 80 %。结论 HNF4具有与mfgl2 /fibroleukin启动子结合的特性 ,为MHV 3N蛋白质诱导mfgl2 /fibroleukin基因表达的必备转录因子。 | 宁琴 罗小平 汪之沫 韩梅芳 严伟明 刘铭锋 Gary Levy | 2003 | 中华医学杂志2003，83，8： | 8 |
| 4 | Hepatic and portal vein thrombosis in cirrhosis: Possible role in development of parenchymal extinction and portal hypertension显示文摘 | Ian R. Wanless Florence Wong Lawrence M. Blendis Paul Greig E.Jenny Heathcote Gary Levy | 1995 | Hepatology1995，，5： | 4 |
| 5 | 暴发性肝衰竭的临床治疗研究新进展显示文摘 | 宁琴 雷延昌 罗小平 杨东亮 郝连杰 Gary Levy | 2001 | 肝脏2001，6，4： | 4 |
| 6 | Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis显示文摘AIM To determine the effect of overexpression of fibrinogenlike protein 2(FGL2) on regulatory T cell(Treg) and effector T(Teff) cell function on T cell-induced colitis in Rag1-/-mice.METHODS Treg and Teff cells from fgl2-/-, fgl2+/+, and fgl2 Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/-mice. RESULTS In vitro, fgl2 Tg Treg had enhanced immunosuppressive activity, and fgl2 Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice(fgl2+/+) into Rag1-/-mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2 Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/-Treg were only partially protective. In mice that received fgl2 Tg Treg, the ratio of Foxp3+ to CD3+ cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2 Tg mice did not produce colitis. CONCLUSION Here we show that fgl2 Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2 Tg Treg prevent colitis in contrast to fgl2+/+ Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease. | Agata Bartczak Jianhua Zhang Oyedele Adeyi Achiya Amir David Grant Reginald Gorczynski Nazia Selzner Andrzej Chruscinski Gary A Levy | 2017 | World Journal of Gastroenterology2017，23，15： | 2 |
| 7 | A multicenter United States—Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B显示文摘 | Robert P. Perrillo Teresa Wright Jorge Rakela Gary Levy Eugene Schiff Robert Gish Paul Martin Jules Dienstag Paul Adams Rolland Dickson Gaya Anschuetz Steve Bell Lynn Condreay Nathaniel Brown | 2001 | Hepatology2001，，2： | 2 |
| 8 | Making sense of regulatory T cell suppressive function显示文摘 | Itay Shalev Moritz Schmelzle Simon C. Robson Gary Levy | 2011 | Seminars in Immunology2011，，4： | 2 |
| 9 | fgl2凝血酶原酶多肽抗体的制备和应用显示文摘目的 利用人工合成多肽制备针对人源、鼠源fgl2凝血酶原酶 (hfgl2、mfgl2 )的特异性多克隆抗体 ,以期用于与fgl2表达异常密切相关的疾病的研究和诊治。方法 根据mfgl2、hfgl2基因编码的氨基酸序列合成多肽 3(Pep3)和多肽 4 (Pep4 ) ,并用化学方法与匙孔血蓝蛋白 (KLH)连接 ,纯品Pep3 KLH和Pep4 KLH免疫动物 ,所制备的抗血清用ELISA、Westernblot和前凝血质活性 (PCA)实验鉴定 ,并采用免疫组化法应用于乙型肝炎患者肝组织中hfgl2的检测。结果 ELISA检测表明 ,所制备的抗血清可分别与Pep3和Pep4发生特异性免疫反应 ;Westernblot结果显示 ,抗血清可识别MHV 3感染BALB cJ小鼠腹腔巨噬细胞特异性条带 ,相对分子质量 (Mr)为 6 5× 10 3;PCA实验提示 ,抗血清具有中和mfgl2分子酶活性的作用。对病毒性乙型肝炎患者肝组织免疫组织化学染色发现hfgl2仅在重型乙型肝炎患者高表达 ,而在慢性乙型肝炎和肝硬化患者的肝组织中无表达。结论 所制备的fgl2的多肽抗体 (多克隆抗体 )可识别mfgl2和hfgl2分子 ,具有与抗原特异性结合、中和其酶活性的特征 ,为深入研究这一新发现的分子提供了有力的科学手段。 | 韩梅芳 宁琴 严伟明 习东 Laisum Fung Gary Levy 罗小平 | 2004 | 中华微生物学和免疫学杂志2004，24，8： | 2 |
| 10 | 鼠肝炎病毒3型N蛋白Ⅰ区激活mfg12凝血酶原酶基因显示文摘目的:研究鉴定激活mfgl2凝血酶原酶基因之冠状病毒3型或A59型鼠肝炎病毒(MHV-3,MHV-A59)核心(N)蛋白的功能区域. 方法:应用定点突变技术、与mfg12启动子共转染实验明确mfgl2凝血酶原酶基因之MHV-3或MHV-A59 N蛋白的功能区域.N蛋白内含I基因突变病毒株A1b 110和其野生株A1b 111体外感染Balb/cJ小鼠巨噬细胞、I基因表达载体与mfgl2启动子共转染实验阐明I蛋白在mfgl2基因激活中的作用. 结果:N蛋白包含由两个可变问隔区(A,B)隔开的三个结构区(Ⅰ,Ⅱ,Ⅲ),MHV-A59N蛋白I区可增强mfgl2转录活性,当其基因序列突变为非嗜肝性MHV-JHM或MHV- 21区序列时,则丧失激活mfgl2启动子转录活性的功能.I 基因突变病毒株Alb 110和其野生株Alb 111体外感染Balb/cJ小鼠巨噬细胞后对mfgl2的激活无显著差异,共转染实验阐明I蛋白并非mfgl2基因激活中的必备因素,该组mfgl2启动子转录活性与对照组无显著差异,而N蛋白可激活mfgl2启动子,使其转录活性提高62倍. 结论:鼠肝炎病毒N蛋白I区为激活mfgl2凝血酶原酶基因的病毒蛋白功能区域. | 宁琴 严伟明 汪之沫 习东 刘铭锋 Gary Levy 罗小平 | 2004 | 世界华人消化杂志2004，12，3： | 2 |
| 11 | Changes in Arterial Stiffness and Wave Reflection With Advancing Age in Healthy Men and Women: The Framingham Heart Study显示文摘 | Gary F. Mitchell Helen Parise Emelia J. Benjamin Martin G. Larson Michelle J. Keyes Joseph A. Vita Ramachandran S. Vasan Daniel Levy | 2004 | Hypertension: Journal of the American Heart Association2004，，6： | 2 |
| 12 | Genomic Characterization, Localization, and Functional Expression of FGL2, the Human Gene Encoding Fibroleukin: A Novel Human Procoagulant显示文摘 | Sivashankary Yuwaraj JinWen Ding Mingfeng Liu Philip A. Marsden Gary A. Levy | 2001 | Genomics2001，，3： | 1 |
| 13 | Acute Heart Failure Syndromes: Emergency Department Presentation, Treatment, and Disposition: Current Approaches and Future Aims: A Scientific Statement From the American Heart Association显示文摘 | Neal L. Weintraub Sean P. Collins Peter S. Pang Phillip D. Levy Allen S. Anderson Cynthia Arslanian-Engoren W. Brian Gibler James K. McCord Mark B. Parshall Gary S. Francis Mihai Gheorghiade | 2010 | Circulation2010，，： | 1 |
| 14 | Disclosing Medical Errors to Patients: Attitudes and Practices of Physicians and Trainees显示文摘 | Lauris C. Kaldjian Elizabeth W. Jones Barry J. Wu Valerie L. Forman-Hoffman Benjamin H. Levi Gary E. Rosenthal | 2007 | Journal of General Internal Medicine2007，，7： | 1 |
| 15 | Biomarkers in uterine leiomyoma显示文摘 | Gary Levy Micah J. Hill Torie C. Plowden William H. Catherino Alicia Y. Armstrong | 2013 | Fertility and Sterility2013，，： | 1 |
| 16 | 美国临床生化科学院检验医学实践指南:心血管疾病和卒中一级预防中新的生物标志物 第3章 炎症生物标志物和心血管疾病危险显示文摘对炎症生物标志物的建议
炎症参与许多疾病过程,近10年来,炎症参与CVD的病理生理过程这一理论受到广泛赞同。目前发现多种炎症标志物,表3中24种炎症标志物已被许多观察研究数据所证实。根据炎症标志物的临床应用实际,如是否可有标准化的商品化检测试剂及观察数据是否充分等进行归类。CRP、Fib和WBC被挑选作进一步评估。 | Mary Cushman Christie M.Ballantyne Daniel Levy Nader Rifai Gerald R.Cooper Gary L.Myers 梁红艳 王腾姣 姜晓峰 郑芳 鄢盛恺 | 2013 | 临床检验杂志2013，31，5： | 1 |
| 17 | Live Donor Liver Transplantation in High MELD Score Recipients显示文摘 | Markus Selzner Arash Kashfi Mark S. Cattral Nazia Selzner Ian D. McGilvray Paul D. Greig Gary A. Levy Eberhard L. Renner David R. Grant | 2010 | Annals of Surgery2010，，1： | 1 |
| 18 | Do instant messaging interruptions help or hinder knowledge workers' task performance显示文摘 | Mansi Gary Levy Yair | | 0，，06： | 1 |
| 19 | 猪FGL2基因cDNA末端序列检测及结构分析显示文摘检测猪FGL2基因cDNA末端序列并对该基因结构初步分析。α 32PdCTP放射性同位素标记cDNA探针筛选猪基因组DNA文库;cDNA末端快速扩增(rapidamplificationofcDNAend,RACE)。以猪正常小肠及心脏组织提取新鲜总RNA,反转录后作为模板,设计基因特异性引物,采用Advantage2聚合酶混合物进行PCR扩增;依据猪与人FGL2基因3′端已知同源序列设计PCR上游引物,以人FGL2基因3′末端序列设计下游引物,以猪基因组DNA为模板采用Advantage2聚合酶混合物进行PCR反应;PCR载体重组质粒DNA亚克隆扩增。同位素探针未能筛选到特异阳性克隆,RACE反应检测到特异性转录起始位置及第一个转录终止位置,但仍未检测到第二个转录终止位置。猪基因组DNA行PCR扩增成功检测到猪FGL2基因3′末端未知序列及第二个转录终止位置。 | 刘浩 Anand Ghanekar Matthew Chan Ming Feng Liu 刘永锋 Gary Levy | 2003 | 遗传2003，25，1： | 1 |
| 20 | Direct Evidence of Endothelial Oxidative Stress With Aging in Humans: Relation to Impaired Endothelium-Dependent Dilation and Upregulation of Nuclear Factor-κB显示文摘 | Anthony J. Donato Iratxe Eskurza Annemarie E. Silver Adam S. Levy Gary L. Pierce Phillip E. Gates Douglas R. Seals | 2007 | Circulation Research2007，，11： | 1 |
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