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| 1 | Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease显示文摘The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflamma-tion and fi brosis, and play a role in the development and/or progression of ALD. | Courtney S Schaffert Michael J Duryee Carlos D Hunter Bartlett C Hamilton 3rd Amy L DeVeney Mary M Huerter Lynell W Klassen Geoffrey M Thiele | 2009 | World Journal of Gastroenterology2009，15，10： | 20 |
| 2 | Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation显示文摘AIM: To investigate over-expression of Osteopontin(OPN) pathway expression and mechanisms of action in human alcoholic liver disease(ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, αvβ3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell(HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcoholinduced effects on hepatic stellate cell functions and liver fibrogenesis. | Devanshi Seth Alastair Duly Paul C Kuo Geoffrey W McCaughan Paul S Haber | 2014 | World Journal of Gastroenterology2014，20，36： | 5 |
| 3 | Whey and whey proteins: From 'gutterto-gold'显示文摘 | GEOFFREY W SMITHER S | 2008 | International Dairy Journal2008，18，： | 1 |
| 4 | Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial显示文摘 | Stephen M Davis Geoffrey A Donnan Mark W Parsons Christopher Levi Kenneth S Butcher Andre Peeters P Alan Barber Christopher Bladin Deidre A De Silva Graham Byrnes Jonathan B Chalk John N Fink Thomas E Kimber David Schultz Peter J Hand Judith Frayne Graeme | 2008 | Lancet Neurology2008，，4： | 1 |
| 5 | Bioactivity of β-Lactoglobulin and α-alctalbumin-Technological Implications for Processing显示文摘 | DERECK E W C GEOFFREY S PETER R | 2006 | Intemational Dairy Journal2006，，： | 1 |
| 6 | Electroactive conducting polymers for corrosion control Part 2:Ferrous metals显示文摘 | Geoffrey M S Anton J D Gordon G W | 2002 | Journal of Solid State Electrochemistry2002，6，： | 1 |
| 7 | Clustering mandibular organ-inhibiting hormone and moult-inhibiting hormone genes in the crab, Cancer pagurgs, and implications for regulation of expression 显示文摘 | Lu W Q Geoffrey W W Webster S G | 2000 | Gene2000，253，： | 1 |
| 8 | Effects of pentoxifylline of cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy显示文摘 | KAREN S ANGELA W GEOFFREY C | 2002 | Am J Cardiol2002，90，： | 1 |
| 9 | Effect organic-matter type and lhermal maturity on methane adsorption in shale-gas systems 显示文摘 | Zhang T W Geoffrey S E | 2012 | Organic Geochemistry2012，47，6： | 1 |
| 10 | Compara- tive study of silylation methods to improve the stability of silicate MCM-41 in aqueous solutions显示文摘 | Jenny M K Michelle L G Geoffrey W S | 2003 | Chem Mater2003，15，3： | 1 |
| 11 | Microscopic enteritis:Bucharest consensus显示文摘Microscopic enteritis(ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms,nutrient and micronutrient deficiency.It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy.This work recognises a need to characterize disorders with microscopic and submicroscopic features,currently regarded as functional or non-specific entities,to obtain further understanding of their clinical relevance.The consensus working party reviewed statements about the aetiology,diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment.Following the 5th International Course in Digestive Pathology in Bucharest in November 2012,an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME.A five-step agreement scale(from strong agreement to strong disagreement) was used to score 21 statements,independently.There was strong agreement on all statements about ME histology(95%-100%).Statements concerning diagnosis achieved 85% to 100% agreement.A statement on the management of ME elicited agreement from the lowest rate(60%) up to 100%.The remaining two categories showed general agreement between experts on clinical presentation(75%-95%) and pathogenesis(80%-90%) of ME.There was strong agreement on the histological definition of ME.Weaker agreement on management indicates a need for further investigations,better definitions and clinical trials to produce quality guidelines for management.This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy. | Kamran Rostami David Aldulaimi Geoffrey Holmes Matt W Johnson Marie Robert Amitabh Srivastava Jean-Francois Fléjou David S Sanders Umberto Volta Mohammad H Derakhshan James J Going Gabriel Becheanu Carlo Catassi Mihai Danciu Luke Materacki Kamran Ghafarzadegan Sauid Ishaq Mohammad Rostami-Nejad A Salvador Pe?a Gabrio Bassotti Michael N Marsh Vincenzo Villanacci | 2015 | World Journal of Gastroenterology2015，21，9： | 1 |
| 12 | The role of perceived risk in the quality-value relationship: A study in a retail environment 显示文摘 | Sweeney J C Geoffrey S N Lester J W | 1999 | Journal of Retailing1999，75，1： | 1 |
| 13 | Effect of Hydrocarbon Type on Thermochemical Sulfate Reduction 显示文摘 | Zhang T W Geoffrey S E Kang-Shi W | 2007 | Org Geochem2007，38，： | 1 |
| 14 | Comparison of polyaniline primers prepared with different dopants for corrosion protection of steel显示文摘 | Anton J D Geoffrey M S Gordon G W | 2003 | Progress in Organic Coatings2003，48，： | 1 |
| 15 | Bioactivity of β - lactoglobulin and cr-lactalbumin: teacnological implications for processing显示文摘 | DERECKE E W C GEOFFREY S PETER R | 2006 | International Dairy Journal2006，16，11： | 1 |
| 16 | Non-interest Income and Total Income Stability 显示文摘 | Rosie S Christos S Geoffrey W | 2003 | Bank of England Quarterly Bulle- tin2003，43，9： | 1 |
| 17 | Non aqueous synthesis of mesostructured tin dioxide 显示文摘 | Robert W J S Neil C Geoffrey A O | 2003 | Journal of Materials Chemistry2003，13，4： | 1 |
| 18 | Recognition and management of complex sleep-disordered breathing 显示文摘 | Geoffrey S Gilmarlin Robert W Daly Robert J Thomas | 2005 | Current Opinion in Puhnonary Medicine2005，11，： | 1 |
| 19 | The multi-targeted kinase inhibitor SU5416 inhibits small cell lung cancer growth and angiogenesis,in part by blocking Kit-mediated VEGF expression显示文摘 | Julie LG Sakuntala W Geoffrey S | | 0，，46： | 1 |
| 20 | Effect of organic mat-ter type and thermal maturity on methane adsorption in shale gassystem显示文摘 | Zhang T W Geoffrey S E Stephen C R | 2012 | Organic Geochemistry2012，47，： | 1 |
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