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Anti-tumour necrosis factor agent and liver injury:literature review,recommendations for management

World Journal of Gastroenterology 2014年第46期20卷 17352-17359页

作者： Roberta Elisa Rossi Ioanna Parisi edward john despott Andrew Kenneth Burroughs James O'Beirne Dario Conte Mark Ian Hamilton Charles Daniel Murray Centre for Gastroenterology Royal Free HospitalLondon NW3 2QGUnited Kingdom Department of Pathophysiology and Organ Transplant Universita’ degli Studi di Milano20122 MilanoItaly Division of Gastroenterology and Endoscopy Fondazione IRCCS Ca' GrandaOspedale Maggiore Policlinico20122 MilanoItaly Sheila Sherlock Liver Centre Royal Free Hospital and Institute of Liver and Digestive HealthLondon NW3 2PFUnited Kingdom

Abnormalities in liver function tests,including transient and self-limiting hypertransaminasemia,cholestatic disease and hepatitis,can develop during treatment with anti-tumour-necrosis-factor(TNF)*** optimal management of liver injury related to antiTNF therapy is still a matter of *** some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than5 times the upper limit of normal,or the occurrence of jaundice,there are no standard guidelines for the management of anti-TNF-related liver *** searches were performed in Pub Med,using the following key words:inflammatory bowel disease(IBD);TNF inhibitors;hypertransaminasemia;drugrelated liver injury;*** to published data,elevation of transaminases in patients with IBD treated with anti-TNF is a common finding,but resolution appears to be the usual ***-TNF agents seem to be safe with a low risk of causing severe drugrelated liver *** to our centre experience,we found that hypertransaminasemia was a common,mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate *** algorithm for the management of liver impairment occurring during antiTNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of ***,hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.

关键词： Inflammatory bowel disease Tumour necrosis factor inhibitors Hypertransaminasemia Drug-related liver injury Infliximab

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Carbon Supply and the Regulation of Cell Wa Synthesis

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Molecular Plant 2018年第1期11卷 75-94页

作者： Jana Verbancic john edward Lunn Mark Stitt Staffan Persson Max Planck Institute of Molecular Plant Physiology Am Muhlenberg 1 14476 Potsdam-Golm Germany School of Biosciences University of Melbourne Parkville VIC 3010 Australia

All plant cells are surrounded by a cell wall that determines the directionality of cell growth and protects the cell against its environment. Plant cell walls are comprised primarily of polysaccharides and represent the largest sink for photosynthetically fixed carbon, both for individual plants and in the terrestrial biosphere as a whole. Cell wall synthesis is a highly sophisticated process, involving multiple enzymes and metabolic intermediates, intracellular trafficking of proteins and cell wall precursors, assembly of cell wall polymers into the extracellular matrix, remodeling of polymers and their interactions, and recycling of cell wall sugars. In this review we discuss how newly fixed carbon, in the form of UDP-glucose and other nucleotide sugars, contributes to the synthesis of cell wall polysaccharides, and how cell wall synthesis is influenced by the carbon status of the plant, with a focus on the model species Arabidopsis （Arabidopsis thaliana）.

关键词： carbon availability cell walls nucleotide sugars sucrose synthase

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Ineffective oesophageal motility:Manometric subsets exhibit different symptom profiles

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World Journal of Gastroenterology 2008年第23期14卷 3719-3724页

作者： Horst Gunter Haack Ross David Hansen Allison Malcolm john edward Kellow Department of Gastroenterology Gastrointestinal Investigation UnitRoyal North Shore HospitalUniversity of SydneyAustralia

AIM:To compare the demographic and clinical features of different manometric subsets of ineffective oesophageal motility(IOM;defined as ≥ 30% wet swallows with distal contractile amplitude < 30 mmHg) ,and to determine whether the prevalence of gastro-oesophageal reflux differs between IOM subsets. METHODS:Clinical characteristics of manometric subsets were determined in 100 IOM patients(73 female,median age 58 years) and compared to those of 100 age-and gender-matched patient controls with oesophageal symptoms,but normal manometry. Supine oesophageal manometry was performed with an eight-channel DentSleeve water-perfused catheter,and an ambulatory pH study assessed gastro-oesophageal reflux. RESULTS:Patients in the IOM subset featuring a majority of low-amplitude simultaneous contractions(LASC) experienced less heartburn(prevalence 26%) ,but more dysphagia(57%) than those in the IOM subset featuring low-amplitude propagated contractions(LAP;heartburn 70%,dysphagia 24%;both P ≤ 0.01) . LASC patients also experienced less heartburn and more dysphagia than patient controls(heartburn 68%,dysphagia 11%;both P < 0.001) . The prevalence of heartburn and dysphagia in IOM patients featuring a majority of non-transmitted sequences(NT) was 54%(P = 0.04 vs LASC) and 36%(P < 0.01 vs controls) ,respectively. No differences inage and gender distribution,chest pain prevalence,acid exposure time(AET) and symptom/reflux association existed between IOM subsets,or between subsets and controls. CONCLUSION:IOM patients with LASC exhibit a different symptom profile to those with LAP,but do not differ in gastro-oesophageal reflux prevalence. These findings raise the possibility of different pathophysiological mechanisms in IOM subsets,which warrants further investigation.

关键词： Age Dysphagia Heartburn Ineffective oesophageal motility Oesophageal manometry Simultaneous contractions

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Gastric sarcoidosis mimicking irritable bowel syndrome-Cause not association?

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World Journal of Gastroenterology 2006年第29期12卷 4754-4756页

作者： john Samuel Leeds Mark edward McAlindon Eleanor Lorenz Asha Kumari Dube David Surendran Sanders Gastroenterology and Liver unit Royal Hallamshire Hospital SheffieldS10 2JFUnited Kingdom Department of Nuclear Medicine Royal Hallamshire Hospital SheffieldS10 2JFUnited Kingdom Department of Histopathology Hallamshire Hospital SheffieldS10 2JFUnited Kingdom Gastroenterology and Liver unit Royal Hallamshirc Hospital SheffieldS10 2JFUnited Kingdom

Sarcoidosis is a systemic disease of unknown aetiology that may affect any organ in the body. The gastrointestinal tract however is only rarely affected outside the liver. Symptoms may be non-specific. Irritable bowel syndrome （IBS） is a common diagnosis. The recognition of IBS is aided by the use of the Rome Ⅱ criteria-in the absence of organic disease. We describe the first case of a patient with gastric sarcoidosis who presented with IBS symptoms but subsequently responded to immunosuppressive therapy.

关键词： Gastrointestinal Sarcoidosis Irritable bowelsyndrome

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Higher incidence of steroid-induced ocular hypertension in keratoconus

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Eye and Vision 2016年第1期3卷 29-36页

作者： Anastasios john Kanellopoulos Emerson M.Cruz Robert edward T.Ang George Asimellis Laservision.gr Clinical and Research Eye Institute 17 Tsocha StreetAthens Postal Code:11521Greece NYU Medical School New YorkNYUSA Asian Eye Institute MakatiPhilippines

Background:To compare intraocular pressure(IOP)changes following topical dexamethasone administration for 1 month in keratoconic versus normal ***:This is a retrospective,single-center,non-randomized case series evaluation of 350 *** groups were formed:normal/control Group A(n_(A)=73),eyes that underwent excimer laser photorefractive keratectomy;and keratoconic(KCN)Group B(n_(B)=277),eyes that were subjected to partial laser photorefractive keratectomy combined with collagen cross-linking(The Athens Protocol).All eyes received the same post-operative regimen of topical dexamethasone 0.1%for at least 1 *** applanation tonometry IOP readings and central corneal thickness(CCT)measurements were *** with induced ocular hypertension(OHT,defined as post-operative IOP higher than 21 mmHg),were identified and correlated to refractive procedure,gender,and corneal ***:At 4 weeks postoperatively,OHT was noted on 27.4%(20/73 eyes)in Group A,and 43.7%(121/277 eyes)in KCN Group B,(p<0.01).Six months post-operatively(following 5-months of discontinuing topical dexamethasone treatment and commencing treatment of IOP-lowering medications),OHT rate was 1.8%in Group A and 3.9%in the KCN Group ***:This study demonstrates a potentially significant pre-disposition of keratoconic eyes to the development of steroid-induced OHT.

关键词： Keratoconus Intraocular pressure Corticosteroid induced ocular hypertension IOP spike Corneal collagen cross-linking CXL The Athens protocol Topography-guided Photorefractive keratectomy Dexamethasone topical ophthalmic solution

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Assembly of IMPDH2-Based,CTPS-Based,and Mixed Rod/Ring Structures Is Dependent on Cell Type and Conditions of Induction

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Journal of Genetics and Genomics 2015年第6期42卷 287-299页

作者： Gerson Dierley Keppeke S.john Calise edward K.L.Chan Luis Eduardo C.Andrade Rheumatology Division Federal University of Sao Paulo Department of Oral Biology University of Florida Immunology Division Fleury Medicine and Health Laboratories

Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR *** La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR *** He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS *** and MPA treatments induced only IMPDH2-based *** were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 *** 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based *** results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.

关键词： Nucleotide synthesis Enzyme aggregation Enzyme inhibition IMPDH2 CTPS

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Mucosal imaging in colon polyps:New advances and what the future may hold

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World Journal of Gastroenterology 2022年第47期28卷 6632-6661页

作者： edward john Young Arvinf Rajandran Hamish Lachlan Philpott Dharshan Sathananthan Sophie Fenella Hoile Rajvinder Singh Department of Gastroenterology Lyell McEwin HospitalNorthern Adelaide Local Health NetworkElizabeth Vale 5031South AustraliaAustralia Faculty of Health and Medical Sciences University of AdelaideAdelaide 5000South AustraliaAustralia

An expanding range of advanced mucosal imaging technologies have been developed with the goal of improving the detection and characterization of lesions in the gastrointestinal *** technologies have targeted colorectal neoplasia given the potential for intervention prior to the development of invasive cancer in the setting of widespread surveillance *** in adenoma detection reduces miss rates and prevents interval cancer *** imaging technologies aim to enhance detection without significantly increasing procedural *** polyp characterisation guides resection techniques for larger polyps,as well as providing the platform for the“resect and discard”and“do not resect”strategies for small and diminutive *** review aims to collate and summarise the evidence regarding these technologies to guide colonoscopic practice in both interventional and non-interventional endoscopists.

关键词： Colonoscopy Colorectal cancer Mucosal imaging Chromoendoscopy Polyp surveillance Polyp characterization

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Six psychotropics for pre-symptomatic ＆ early Alzheimer＇s (MCI), Parkinson＇s, and Huntington＇s disease modification

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Neural Regeneration Research 2016年第11期11卷 1712-1726页

作者： edward C. Lauterbach Psychiatry and Neurology Mercer University School of Medicine Macon GA USA

The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases （NDDs）, including Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, and Huntington＇s disease （HD）, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment （MCI） phase of AD： salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD： human epidemiological data indicate that lithium reduc- es AD risk. Animal model studies （AMS） reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD： valproate AMS findings show promise. Pre-symptomatic PD： lithium and valproate AMS findings are encouraging. Early HD： uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD： lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication （valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD） are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.

关键词： drug repositioning neuroprotective agents psychotropic drugs neurodegenerative diseases mildcognitive impairment humans animals animal models

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Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation

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Bone Research 2022年第4期10卷 826-837页

作者： Yugo Morita Motoo Saito Javier Rangel-Moreno Anthony M.Franchini john R.Owen john C.Martinez john L.Daiss Karen L.de Mesy Bentley Stephen L.Kates edward M.Schwarz Gowrishankar Muthukrishnan Center for Musculoskeletal Research University of Rochester Medical CenterRochesterNYUSA Division of Allergy Immunology and RheumatologyDepartment of MedicineUniversity of Rochester Medical CenterRochesterNYUSA Department of Environmental Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Orthopedic Surgery Virginia Commonwealth UniversityRichmondVAUSA Department of Orthopedics University of Rochester Medical CenterRochesterNYUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA

Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial,and its role in patients with *** osteomyelitis is *** address this knowledge gap,we completed a clinical study and observed elevated serum IL-27 levels(20-fold higher,P<0.05)in patients compared with healthy ***,IL-27 serum levels were 60-fold higher in patients immediately following septic death than in uninfected patients(P<0.05),suggesting a pathogenic role of *** test this hypothesis,we evaluated *** osteomyelitis in WT and IL-27Rα^(−/−)mice with and without exogenous IL27 induction by intramuscular injection of rAAV-IL-27p28 or rAAV-GFP,*** found that IL-27 was induced at the surgical site within 1 day of *** infection of bone and was expressed by M0,M1 and M2 macrophages and osteoblasts but not by ***,exogenous IL-27p28(~2 ng·mL^(−1) in serum)delivery ameliorated soft tissue abscesses and periimplant bone loss during infection,accompanied by enhanced local IL-27 expression,significant accumulation of RORγt^(+)neutrophils at the infection site,a decrease in RANK^(+) cells,and compromised osteoclast *** effects were not observed in IL-27Rα^(−/−)mice compared with WT mice,suggesting that IL-27 is dispensable for immunity but mediates redundant immune and bone cell functions during *** vitro studies and bulk RNA-seq of infected tibiae showed that IL-27 increased nos1,nos2,il17α,il17f,and rorc expression but did not directly stimulate ***,these results identify a novel phenomenon of IL-27 expression by osteoblasts immediately following *** infection of bone and suggest a protective role of systemic IL-27 in osteomyelitis.

关键词： abscess protective immunity

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Production TTR modeling and dynamic buckling analysis

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Engineering Sciences 2013年第4期11卷 61-66页

作者： Hugh Liu john Wei edward Huang DMAR Engineering Inc. FloaTEC LLC Technip USA

In a typical tension leg platform (TLP) design,the top tension factor (TTF),measuring the top tension of a top tensioned riser (TTR) relative to its submerged weight in water,is one of the most important design parameters that has to be specified properly. While a very small TTF may lead to excessive vortex induced vibration (VIV),clashing issues and possible compression close to seafloor,an unnecessarily high TTF may translate into excessive riser cost and vessel payload,and even has impacts on the TLP sizing and design in general. In the process of a production TTR design,it is found that its outer casing can be subjected to compression in a worst-case scenario with some extreme metocean and hardware conditions. The present paper shows how finite element analysis (FEA) models using beam elements and two different software packages (Flexcom and ABAQUS) are constructed to simulate the TTR properly,and especially the pipe-in-pipe effects. An ABAQUS model with hybrid elements (beam elements globally + shell elements locally) can be used to investigate how the outer casing behaves under compression. It is shown for the specified TTR design,even with its outer casing being under some local compression in the worst-case scenario,dynamic buckling would not occur;therefore the TTR design is adequate.

关键词： TLP TTR FEA pipe-in-pipe buckling analysis

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