检索结果-南通市图书馆

Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

world Journal of Gastroenterology 2009年第6期15卷 705-712页

作者： Joan Oliva Jennifer Dedes samuel w french Fawzia Bardag-Gorce Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center TorranceCA 90502 United States

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 *** 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 *** 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 *** 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.

关键词：酒精肝损伤甜菜碱外部机理甲基转移酶抑制剂

Chaperones in hepatitis C virus infection

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

world Journal of Hepatology 2016年第1期8卷 9-35页

作者： Ronik Khachatoorian samuel w french Department of Pathology and Laboratory Medicine David Geffen School of Medicine at University of CaliforniaLos AngelesCA 90095United States Jonsson Comprehensive Cancer Center David Geffen School of Medicine at University of CaliforniaLos AngelesCA 90095United States UCLA AIDS Institute David Geffen School of Medicine at University of CaliforniaLos AngelesCA 90024United States

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.

关键词： Hepatitis C hepatitis C virus Chaperones Heat shock proteins viral life cycle

Mallory-Denk body pathogenesis revisited

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

world Journal of Hepatology 2010年第8期2卷 295-301页

作者： samuel w french Fawzia Bardag-Gorce Barbara A french Joan Oliva Department of Pathology Harbor-UCLA Medical Center

This editorial reviews the recent evidence showing that Mallory-Denk bodies(MDBs)form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome *** shift is the result of changes in gene expression induced in promoter activation,which is induced by the IFNγ and TNFa signaling *** activates TLR 2 and 4 *** TLR signaling pathway stimulates both the induction of a cytokine proinflammatory response and an up regulation of growth *** MDB-forming hepatocytes proliferate as a result of the increase in growth factor expression by the MDBforming cells,which selectively proliferate in response to drug *** of these mechanisms are induced by drug toxicity,and are prevented by feeding the methyl donors SAMe and betaine,supporting the epigenetic response of MDB formation.

关键词： Toll-like receptor Proinflammatory Methyl donors Epigenetic processes Drug toxicity 26s Proteasome Immunoproteasome

Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

world Journal of Gastroenterology 2016年第38期22卷 8497-8508页

作者： Natalia A Osna Dan Feng Murali Ganesan Priya F Maillacheruvu David J Orlicky samuel w french Dean J Tuma Kusum K Kharbanda Research Service Veterans Affairs Nebraska-Western Iowa Health Care System Department of Internal Medicine 982000 Nebraska Medical Center Department of Pathology University of Colorado Denver Department of Anatomic Pathology Harbor UCLA Medical Center Department of Biochemistry and Molecular Biology 985870 Nebraska Medical Center

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 *** 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 *** To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.

关键词： Methyl balance S-adenosylmethionine S-adenosylhomocysteine Guanidinoacetate Alcohol

Preneoplastic foci in mice fed diethyl 1, 4-dihydro, 1,4,6-trimethyl 3,5-pyridine decarboxylate are resistant toprotoporphyrin accumulation

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Hepatoma Research 2015年第1期1卷 50-51页

作者： samuel w.french Mwaheed Roomi Department of Pathology Harbor UCLA Medical CenterTorranceCA 90509USA Dr.Rath Research Institute Santa ClaraCA 95050USA

It has been shown that preneoplastic liver cell foci and hepatic nodules generated by thioacetamide(TAA)in drug-primed mice,which were first fed diethyl 1,4-dihydro,1,4,6-trimethyl 3,5-pyridine decarboxylate(DDC)or griseofulvin(GF)for 5 months were resistant to protoporphyrin accumulation.[1]DDC or GF are potent porphyrinogenic drugs and accumulate protoporphyrin in the mouse *** DDC or GF are withdrawn for 1 month,when treated with TAA,the nodules formed on the 5th or 7th day of treatment were devoid of protoporphyrin *** DDC or GF for 8 months induced liver tumors which were devoid of protoporphyrin *** contrast,the surrounding liver tissue contained numerous protoporphyrin *** could be attributed to the decreased activity of delta-aminolevulinate synthase,the first rate-limiting enzyme in protoporphyrin synthesis.

关键词： synthesis. porphyrin pyridine

Diminishing Use of Liver Biopsy among Liver Transplant Recipients for Hepatitis C

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Clinical and Translational Hepatology 2017年第3期5卷 197-202页

作者： Elizabeth Aby Melissa A.Jimenez Jonathan F.Grotts Vatche Agopian samuel w.french Ronald w.Busuttil Sammy Saab Departments of Medicine at the University of California at Los Angeles Los Angeles California USA Departments of Surgery at the University of California at Los Angeles Los Angeles California USA Departments of Pathology at the University of California at Los Angeles Los Angeles California USA Departments of Medicine at the University of California at Los Angeles Los Angeles California USA Departments of Surgery at the University of California at Los Angeles Los Angeles California USA

Background and Aims:Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and *** biopsies are commonly used to identify recurrent HCV and determine the need for antiviral *** introduction of directacting antiviral agents (DAAs) has changed the management of recurrent HCV *** study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of ***:A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for *** analysis included 475 adult liver transplants for hepatitis C performed at the University of California,Los Angeles from January 1,2006 to October 1,*** were divided into two eras,pre-and post-introduction of DAAs on December 1,***:In the era before the introduction of DAAs,the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs.26.9%,p wing liver transplantation and the management of recurrent *** that DAAs are well tolerated and have high efficacy,liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation.

关键词： Hepatitis C Liver transplantation Biopsy

Diagnosis of alcoholic liver disease

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

world Journal of Gastroenterology 2014年第33期20卷 11684-11699页

作者： Cara Torruellas samuel w french Valentina Medici Division of Gastroenterology and Hepatology Department of Internal Medicine University of California Davis Sacramento CA 95817 United States Department of Pathology UCLA/Harbor Medical Center Torrance CA 90502 United States

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.

关键词： Alcoholic liver disease Diagnosis Alcohol screenin

Langerhans cell histiocytosis masquerading as acute appendicitis: Case report and review

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

world Journal of Gastrointestinal Endoscopy 2017年第3期9卷 139-144页

作者： Mohammad M Karimzada Michele N Matthews samuel w french Daniel De Ugarte Dennis Y Kim Department of Surgery Harbor-UCLA Medical Center Department of Pathology Harbor-UCLA Medical Center

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 *** 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 *** analysis of appendectomy specimen and nodular specimens on colonoscopy demonstrated S-100,CD1a,and langerin *** patient underwent systemic chemotherapy with cytarabine and demonstrated excellent response to therapy.

关键词： Langerhans cell histiocytosis Adult histiocytosis Appendicitis Gastrointestinal histiocytosis Right lower quadrant pain

High frequency of severe liver dysfunction in critically ill Dengue patients in the french west Indies

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Intensive Medicine 2024年第3期4卷 403-404页

作者： Laurent Camous samuel Markowicz Cecile Loraux Julien Jabot Jean David Pommier Réanimation Médicale et Chirurgicale CHU de GuadeloupeChemin ChauvelLes Abymes97139 GuadeloupeFrance Service de Maladies infectieuses et tropicales CHU de GuadeloupeChemin ChauvelLes Abymes97139 GuadeloupeFrance Service de Microbiologie CHU de GuadeloupeChemin ChauvelLes Abymes97139 GuadeloupeFrance Médecine Intensive et Réanimation Centre hospitalier universitaire de la Réunion 97460 Saint-PaulFrance Institut Pasteur de la Guadeloupe Morne Jolivière97183 AbymesFrance

Dear Editor,Dengue is a worldwide zoonosis,transmitted by mosquitoes and highly prevalent in tropical and subtropical *** recent years,its incidence has increased with a massive healthcare burden worldwide[1]and recent climatic changes have expanded the geographic range of the insect vector with described outbreaks in Europe.[2]Most patients present pauci-symptomatic infections,but some patients could present severe manifestations with high reported mortality[[3],[4],[5]]and no specific *** bleeding,hemodynamic failure and various organ damage(cardiac,renal,neurological,and hepatic)are described in severe dengue(SD)patients.[5]In the future,intensivists worldwide will be increasingly treating SD and the spectrum of severe organ impairment should be well known.

关键词： patients mortality expanded