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1Diagnosis of alcoholic liver disease显示文摘Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease(ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean cor-puscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential.Cara Torruellas Samuel W French Valentina Medici 2014World Journal of Gastroenterology2014,20,33:26
2Characterization and functions of beta defensins in the epididymis显示文摘附睾β - defensins 由重复基因复制和分叉演变编码对病原体提供直接保护并且也在它的主要功能支持男繁殖的道的蛋白质的一个家庭。男道 defensins 也从病原体攻击便于恢复。β - defensins 拥有古老的保存顺序和在多细胞的有机体普遍的结构的特征,在种幸存建议基本角色。首领 SPAG11,二祖先地独立的β - defensin 基因的功能的熔化,生产根据 tissue-specificand 被表示的或者拼接的抄本的一个大家庭种类特定的限制。SPAG11 的复杂性在哺乳动物的进化的不同分支变化。有主人蛋白质的人的 SPAG11D 的相互作用在多重发信号的小径显示参与。Susan H. Hall Suresh Yenugu Yashwanth Radhakrishnan Maria Christina W. Avellar Peter Petrusz Frank S. French 2007Asian Journal of Andrology2007,9,4:18
3Alcohol,nutrition and liver cancer:Role of Toll-like receptor signaling显示文摘This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (TLR) signaling as the mechanism of liver stem cell/progenitor transformation to HCC. Two exemplary models of this phenomenon are reviewed in detail. One model applies chronic ethanol/lipopolysaccharide feeding to the activated TLR4 signaling pathway. The other applies chronic feeding of a carcinogenic drug, in which TLR2 and 4 signaling pathways are activated. In the drug-induced model, two major methyl donors, S-adenosylmethionine and betaine, prevent the upregulation of the TLR signaling pathways and abrogate the stem cell/progenitor proliferation response when fed with the carcinogenic drug. This observation supports a nutritional approach to liver cancer prevention and treatment. The observation that upregulation of the TLR signaling pathways leads to liver tumor formation gives evidence to the popular concept that the chronic pro-inflammatory response is an important mechanism of liver oncogenesis. It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases.Samuel W French Joan Oliva Barbara A French Fawzia Bardag-Gorce 2010World Journal of Gastroenterology2010,16,11:11
4睾丸核蛋白表达和基因重排在上呼吸道睾丸核蛋白中线癌中的应用显示文摘目的探讨睾丸核蛋白(NUT)抗体表达及基因重排在上呼吸道NUT中线癌(NMC)中的应用,以及NMC的发病情况、临床病理学特点、诊断及其鉴别诊断。方法收集北京同仁医院病理科1990年至2010年诊断的上呼吸道小圆细胞型恶性肿瘤163例,包括低分化鳞状细胞癌(31例)及未分化癌(1例)、非角化型未分化鼻咽癌(60例)、小细胞神经内分泌癌(6例)及其他非上皮性小圆细胞型恶性肿瘤(65例)。分析其临床特征及病理学特点,行EB病毒编码的小RNA探针(EBER)原位杂交检测及NUT单克隆抗体的免疫组织化学En Vision法染色。NUT抗体阳性表达的病例以荧光原位杂交(FISH)法检测NUT基因重排、以免疫组织化学染色方法标记角蛋白(AE1/AE3、CK7、CK8)、p63及神经内分泌标志物(神经元特异性烯醇化酶、突触素、嗜铬粒素A、S-100蛋白、CD56)。结果(1)3例低分化鳞状细胞癌及1例未分化癌中发现NUT抗体呈强阳性核表达,约占该组病例的12.5%(4/32),占本组上皮性恶性肿瘤的4.1%(4/98),全部病例的2.5%(4/163);其年龄范围为42~59岁;其他各组病例NUT抗体均为阴性;(2)4例NUT抗体阳性表达的病例其瘤细胞均表达角蛋白及p63,而神经内分泌标志物及EBER检测均阴性;(3)4例NUT阳性表达的病例中2例FISH检测证实有NUT基因重排,此2例患者死亡,另2例未检测到NUT基因重排,患者存活(分别为40及12个月)。结论(1)NMC是发生于上呼吸道的少见小圆细胞型恶性肿瘤,既往被归于低分化鳞状细胞癌及未分化癌中,其NUT抗体阳性表达及NUT基因重排阳性;(2)NMC好发于中线器官,特别是鼻腔鼻窦,与EB病毒感染无关,临床病程及预后有所不同;(3)NUT免疫组织化学染色及FISH检测在其诊断及鉴别诊断中发挥主要作用。方微 Christopher A. French Michael J. Cameron 韩一丁 刘红刚 2012中华病理学杂志2012,41,8:8
5Acute liver injury induced by weight-loss herbal supplements显示文摘We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients dem onstrated f indings consistent with drug-induced acute liver injury. To our knowledge, we are the fi rst instit ute to report acute liver injury from both of these two typ es of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supp lements for the purpose of weight loss.Gary C Chen Vivek S Ramanathan David Law Pauline Funchain George C Chen Samuel French Boris Shlopov Viktor Eysselein David Chung Sonya Reicher Binh V Pham 2010World Journal of Hepatology2010,2,11:5
6Chaperones in hepatitis C virus infection显示文摘The hepatitis C virus(HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases including cirrhosis and hepatocellular carcinoma. HCV is the most common indication for liver transplantation in patients with cirrhosis worldwide. HCV is an enveloped RNA virus classified in the genus Hepacivirus in the Flaviviridae family. The HCV viral life cycle in a cell can be divided into six phases:(1) binding and internalization;(2) cytoplasmic release and uncoating;(3) viral polyprotein translation and processing;(4) RNA genome replication;(5) encapsidation(packaging) and assembly; and(6) virus morphogenesis(maturation) and secretion. Many host factors are involved in the HCV life cycle. Chaperones are an important group of host cytoprotective molecules that coordinate numerous cellular processes including protein folding, multimeric protein assembly, protein trafficking, and protein degradation. All phases of the viral life cycle require chaperone activity and the interaction of viral proteins with chaperones. This review will present our current knowledge and understanding of the role of chaperones in the HCV life cycle. Analysis of chaperones in HCV infection will provide further insights into viral/host interactions and potential therapeutic targets for both HCV and other viruses.Ronik Khachatoorian Samuel W French 2016World Journal of Hepatology2016,8,1:5
7Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically显示文摘AIM:To examine the effects of ethanol-induced proteasome inhibition,and the effects of proteasome inhibition in the regulation of epigenetic mechanisms. METHODS:Rats were fed ethanol for 1 mo using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341(Bortezomib, Velcade?)by intraperitoneal injection.Microarray analysis and real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei. RESULTS:Chronic ethanol feeding caused a significant inhibition of the ubiquitin proteasome pathway in the nucleus,which led to changes in the turnover of transcriptional factors,histone-modifying enzymes, and,therefore,affected epigenetic mechanisms. Chronic ethanol feeding was related to an increase in histone acetylation,and it is hypothesized that the proteasome proteolytic activity regulated histone modifications by controlling the stability of histone modifying enzymes,and,therefore,regulated the chromatin structure,allowing easy access to chromatin by RNA polymerase,and,thus,proper gene expression.Proteasome inhibition by PS-341 increased histone acetylation similar to chronic ethanol feeding. In addition,proteasome inhibition caused dramatic changes in hepatic remethylation reactions as there was a significant decrease in the enzymes responsible for the regeneration of S-adenosylmethionine,and, in particular,a significant decrease in the betaine- homocysteine methyltransferase enzyme.This suggested that hypomethylation was associated with proteasome inhibition,as indicated by the decrease in histone methylation. CONCLUSION:The role of proteasome inhibition in regulating epigenetic mechanisms,and its link to liver injury in alcoholic liver disease,is thus a promising approach to study liver injury due to chronic ethanol consumption.Joan Oliva Jennifer Dedes Samuel W French Fawzia Bardag-Gorce 2009World Journal of Gastroenterology2009,15,6:4
8BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization显示文摘BCL2 最好作为多功能的 anti-apoptotic 蛋白质被知道。然而,很少在房间粘合剂和活动性事件对它的角色被知道。这里,我们证明 BCL2 可以在房间粘附的规定起一个作用,传播,并且活动性。BCL2 什么时候是在有教养的鼠科、人的房间线,传播的房间,粘附,和活动性的 overexpressed,被损害。与这些结果一致, Bcl2 的损失导致了在 Bcl2 空的老鼠观察的更高的活动性与野类型相比的胚胎的成纤维细胞(MEF ) 房间。房间粘附和活动性的 BCL2 规定的机制可以包含包含 BCL2,肌动朊,和 gelsolin 的建筑群的形成,它看起来机能上地减少 gelsolin 的切断的活动。我们观察到从 overexpressed BCL2 提高了的 MCF-7 和 NIH3T3 房间的 lysate 肌动朊聚合在在 vitro 试金没有房间。BCL2 和 F 肌动朊的共焦的 immunofluorescent 本地化在一致地传播期间证明 BCL2 的那增加的表情导致了增加的 F 肌动朊聚合。因此, BCL2 和 gelsolin 建筑群的形成(它可能包含另外的蛋白质) 看起来在房间粘附和移植的规定起一个关键作用。与癌症转移给房间活动性的确定的关联,这结果可以解释在一些肿瘤房间类型的 BCL2 的表示为什么为转移减少潜力并且与改进耐心的预后被联系。Hengning Ke Vandy I Parron Jeff Reece Jennifer Y Zhang Steven K Akiyama John E French 2010Cell Research2010,20,4:3
9Human papillomavirus does not have a causal role in colorectal carcinogenesis显示文摘AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA.The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples.The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios.HPV16-positive tumors were also evaluated for(1) E2,E4,E5,E6 and E7 viral gene ng quantification;(2) relative quantification compared to W12 cells; and(3) viral E2,E4,E5,E6 and E7 mR NA transcripts by real-time polymerase chain reaction.RESULTS: HPV infection was detected in 16.9% of all tumors examined,and HPV16 was the most frequent type detected(63.6% of positive tissues).Notably,the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers(χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns).HPV16 DNA was present exclusively in episomal form,and the HPV16 E2,E4,E5,E6 and E7 genes were detected in tracenanogram quantities.Furthermore,the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage.Although the extractions were validated by housekeeping gene expression,all the HPV16 positive tissues were transcriptionally inactive for the E2,E4,E5,E6 and E7 mR NAs.CONCLUSION: Based on our results,HPV is unlikely involved in colorectal carcinogenesis.Laura Lorenzon Francesca Mazzetta Emanuela Pilozzi Giordana Uggeri Maria Rosaria Torrisi Mario Ferri Vincenzo Ziparo Deborah French 2015World Journal of Gastroenterology2015,21,1:3
10Oncological Feasibility of Laparoscopic Distal Pancreatectomy for Adenocarcinoma: A Single-Institution Comparative Study显示文摘S. Rehman S. K. P. John R. Lochan B. C. Jaques D. M. Manas R. M. Charnley J. J. French S. A. White 2014World Journal of Surgery2014,,2:3
11Langerhans cell histiocytosis masquerading as acute appendicitis: Case report and review显示文摘Langerhans cell histiocytosis(LCH) is a rare syndrome characterized by unifocal,multifocal unisystem,or disseminated/multi-system disease that commonly involves the bone,skin,lymph nodes,pituitary,or sometimes lung(almost exclusively in smokers) causing a variety of symptoms from rashes and bone lesions to diabetes insipidus or pulmonary infiltrates.We present a previously unreported case of gastrointestinal LCH as well as a novel characteristic lesion affecting the colon of a young woman who presented with signs and symptoms mimicking acute on chronic appendicitis.Immunohistochemical analysis of appendectomy specimen and nodular specimens on colonoscopy demonstrated S-100,CD1a,and langerin reactivity.The patient underwent systemic chemotherapy with cytarabine and demonstrated excellent response to therapy.Mohammad M Karimzada Michele N Matthews Samuel W French Daniel De Ugarte Dennis Y Kim 2017World Journal of Gastrointestinal Endoscopy2017,9,3:3
12Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy显示文摘AIM:To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)to diagnose pancreatic malignancy. METHODS:Patients who underwent EUS-FNA were retrospectively identified.Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53,Ki-67,carcinoembryonic antigen(CEA) and CA19-9.Sensitivity,specificity,positive and negative predictive values(PPV and NPV),and positive and negative likelihood ratios(PLR and NLR)were calculated in order to evaluate the performance of each test to detect malignancy. RESULTS:Sixty-one specimens had complete sets of stains,yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis,respectively.Cytology alone had sensitivity and specificity of 41%and 100%to detect malignancy, respectively.In 46%of the specimens,routine cytology alone was deemed indeterminate.The addition of either p53 or Ki-67 increased the sensitivity to 51%and 53%,respectively,with perfect specificity,PPV and PLR (100%,100%and infinite).Both stains in combination increased the sensitivity to 57%.While additional staining with CEA and CA19-9 further increased the sensitivity to 86%,the specificity,PPV and PLR were significantly reduced(at minimum 42%,84%and 1,respectively).Markers in all combinations performed poorly as a negative test(NPV 26%to 47%,and NLR 0.27 and 0.70).CONCLUSION:Immunohistochemical staining for p53 and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.Alexander W Jahng Sonya Reicher David Chung Donna Varela Rahul Chhablani Anil Dev Binh Pham Jose Nieto Rose J Venegas Samuel W French Bruce E Stabile Viktor E Eysselein 2010World Journal of Gastrointestinal Endoscopy2010,2,11:3
13Impaired CTLA-4 responses in COPD are associated with systemic inflammation显示文摘Dino BA Tan Sonia Fernandez PatriciaPrice Martyn A French Philip J Thompson Yuben P Moodley 2014Cellular & Molecular Immunology2014,11,6:3
14中国长江下游茅山遗址新石器时代晚期水稻耕作的水资源管理及农业集约化显示文摘加强水稻耕作的水资源管理及相关土地的利用需要增加劳力投入来改变当地的景观。在发掘长江下游茅山遗址保存完好的新石器时代晚期稻田时,应用地质考古调查研究获得了晚全新世关键时期的水资源管理、农业集约化、环境变迁和社会发展之间变化关系的详细信息。庄奕杰(著/校) 丁品 Charles French 宿凯(译) 靳桂云(译) 2015东方考古2015,,1:3
15一种新型数字式加速度传感器原理与设计显示文摘建立了一种新型纯数字式加速度传感器的理论模型,通过检测吸合时间差检测加速度.该传感器不存在吸合电压的限制,避免了寄生电容的影响,其芯片面积远小于传统电容式加速度传感器;由于输出时间信号,可采用简单的纯数字接口电路检测.理论分析表明,质量块在两个检测电极之间的吸合时间差ΔT与加速度成正比关系,通过检测ΔT的变化即可检测加速度,其灵敏度、非线性与传统电容式加速度传感器相当.设计了一个悬臂梁-质量块结构的加速度传感器,芯片有效面积仅为0.03mm2,模拟结果显示,工作电压为8V,加速度为1gn时,吸合时间的变化ΔT为1.0554μs.采用TTL电路进行检测,其分辨率可以达到0.01gn,满量程±10gn工作时,非线性度为1.23%.庞洁 Lukasz Pakula Paddy French 杨恒 王跃林 2007传感技术学报2007,20,9:2
16Gastric adenocarcinoma in patients 40 years of age or younger显示文摘Charles P. Theuer Christian de Virgilio Greg Keese Samuel French Tracey Arnell Jorge Tolmos Stanley Klein William Powers Tony Oh Bruce E. Stabile 1996The American Journal of Surgery1996,,5:2
17Primary angioplasty and selection bias inpatients presention late (>12 h) after onset of chest pain and ST elevation myocardial infarction显示文摘ELAD Y FRENCH W J SHAVELLE D M 2002J Am Coll Cardiol2002,39,5:2
18Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury显示文摘AIM To investigate the hypothesis that exposure to guanidinoacetate(GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage.METHODS Adult male Wistar rats were fed the control or ethanolLieber De Carli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macroand micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol.CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.Natalia A Osna Dan Feng Murali Ganesan Priya F Maillacheruvu David J Orlicky Samuel W French Dean J Tuma Kusum K Kharbanda 2016World Journal of Gastroenterology2016,22,38:2
19Cerebral Microbleeds in the Elderly: A Pathological Analysis显示文摘Mark Fisher Samuel French Ping Ji Ronald C. Kim 2010Stroke2010,,12:2
20Common risk factors in the returns on stocks and bonds显示文摘Fama E French K 1993Journal of Financial Economics1993,339,1:2
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