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Recurrent ectopic pancreatitis of the jejunum and mesentery over a 30-year period

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Hepatobiliary & Pancreatic Diseases International 2011年第2期10卷 218-220页

作者： John CT Wong charlotte Robinson Edward C Jones Alison Harris Charles Zwirewich Robert Wakefield Richard K Simons Eric m Yoshida Department of medicine Department of medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Department of Radiology Department of medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Department of Pathology and Laboratory medicine Department of medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Department of Surgery Department of medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Division of Gastroenterology Department of medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9

BACKGROUND:Ectopic pancreas is defined as pancreatic tissue found outside its usual anatomical position,with no ductal or vascular communication with the native pancreas. We describe a case of ectopic pancreas of the small bowel and mesentery causing recurrent episodes of pancreatitis, initially suspected on computed tomography(CT)and magnetic resonance cholangiopancreatography(mRCP),and confirmed on histological review of the resection. mETHODS:A 67-year-old woman presented with clinical symptoms and biochemical evidence of *** had similar episodes over the past 30 years with unrevealing investigations,and was concluded to have idiopathic pancreatitis. She underwent CT and mRCP,with findings suggestive of ectopic pancreas,a diagnosis confirmed on histology of the resection. RESULTS:mRCP identified a mass in the proximal small bowel mesentery isointense to the native pancreas,with a small duct draining into a proximal jejunal *** resected specimen consisted of normal parenchyma with lobulated acinar tissue with scattered islets of Langerhans,an occasional ductular structure,and admixed areas of adipose *** patient remained asymptomatic with normal biochemistry six months post-operatively. CONCLUSION:In an individual with abdominal pain,elevated serum amylase/lipase,but imaging findings of a normal native pancreas,ectopic pancreatitis should be considered,and can be evaluated by CT and mRCP.

关键词： ectopic pancreas gastrointestinal tract endoscopic ultrasound computed tomography magnetic resonance cholangiopancreatography

Atm deficient zebrafish model reveals conservation of the tumour suppressor function and a role in fertility

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Genes & Diseases 2023年第2期10卷 381-384页

作者： Jeroen Vierstraete charlotte Fieuws David Creytens Jo Van Dorpe Andy Willaert Anne Vral Kathleen Bm Claes Center for medical Genetics Department of Biomolecular MedicineGhent University Hospital and Ghent University9000 GhentBelgium Department of Human Structure and Repair Ghent University9000 GhentBelgium Cancer Research Institute Ghent (CRIG) Ghent University and Ghent University Hospital9000 GhentBelgium Department of Pathology Ghent University and Ghent University Hospital9000 GhentBelgium

Biallelic loss-of-function variants in ATm (Ataxia Telangiectasia mutated) cause Ataxia Telangiectasia (AT), a rare disorder associated with cerebellar degeneration and ataxia, cancer predisposition, infertility, growth retardation, etc. ATm is a phosphoinositide 3-kinase-related kinase (PIKK) with a role in DNA repair and maintenance of genome stability. Studying a multisystem genetic disease like AT requires animal models to ascertain its pathogenesis at the level of tissues, organs and the organism. Due to its small size, cheap maintenance, large progeny, rapid development and initial transparency, zebrafish (Danio rerio) is an increasingly popular vertebrate model organism, suitable for genetic modifications and large-scale in vivo therapeutic screens as embryos are chemically permeable to small compounds. Currently, no zebrafish model for AT exists.1 We generated atm knock-outs through CRIPSR-Cas9 mutagenesis. We show that atm conserved its function as a tumour suppressor gene and is involved in gametogenesis and fertility. Therefore, this mutant is of great value for further studies investigating the role of atm in reproduction and tumorigenesis.

关键词： ATm function transparency

The comparative efficacy of ezetimibe added to atorvastatin 10 mg versus uptitration to atorvastatin 40 mg in subgroups of patients aged 65 to 74 years or greater than or equal to 75 years

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Journal of Geriatric Cardiology 2011年第1期8卷 1-11页

作者： Ori Ben-Yehuda Nanette K. Wenger Christian Constance Franklin Zieve mary E. Hanson Jian-Xin Lin Arvind K. Shah charlotte Jones-Burton Andrew m. Tershakovec University of California San Diego 200 West Arbor Drive La Jolla CA 92103 USA Emory University School of medicine 49 Jess Hill Jr Dr SE Atlanta GA 30303 USA SHopital maisonneuve-Rosemont Recherche Clinique/Polyclinique 5415 Boulevard de l＇Assomption Suite 295 Montreal Quebec QC H1T2M4 Canada mcGuire VA medical Center 1201 Broad Rock Blvd （151） Richmond VA 23249 USA merck-Sharp ＆ Dohme One Merck Drive Whitehouse Station NJ 08889 USA

Background Coronary heart disease （CHD） risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients 〉 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 nag ＋ ezetimibe 10 mg （EZ/Atorva） vs. increasing the atorvastatin dose to 40 mg, methods Patients 〉 65 years with atherosclerotic vascular disease （LDL-C ≥1.81 mmol/L） or at high risk for coronary heart disease （LDL-C 〉 2.59 mmol/L） were randomized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 nag for 6 wk followed by atorvastatin 40 nag for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk. Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients 〉 75 years （n = 228）, generally consistent with patients 65-74 years （n = 812）. more patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients 〉 75 years at 12 wk. At 12 wk, more patients 〉 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients 〉 75 years, generally consistent with the findings in patients 65-74 years. Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and 〉 75 years of age.

关键词： cholesterol absorption inhibitor LDL-C hypercholesterolemia statin

Coordinated AR and microRNA regulation in prostate cancer

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Asian Journal of Urology 2020年第3期7卷 233-250页

作者： Ieva Eringyte Joanna N.Zamarbide Losada Sue m.Powell charlotte L.Bevan Claire E.Fletcher Imperial Centre for Translational and Experimental medicine Department of Surgery and CancerImperial College LondonHammersmith HospitalLondonUnited Kingdom

The androgen receptor(AR)remains a key driver of prostate cancer(PCa)progression,even in the advanced castrate-resistant stage,where testicular androgens are *** is therefore of critical importance to understand the molecular mechanisms governing its activity and regulation during prostate ***(miRs)are small w22 nt noncoding RNAs that regulate target gene,often through association with 30 untranslated regions(30UTRs)of *** display dysregulation during cancer progression,can function as oncogenes or tumour suppressors,and are increasingly recognised as targets or regulators of hormonal ***,understanding factors which modulate miRs synthesis is *** is increasing evidence for complex and dynamic bi-directional cross-talk between the multi-step miR biogenesis cascade and the AR signalling axis in *** review summarises the wealth of mechanisms by which miRs are regulated by AR,and conversely,how miRs impact AR’s transcriptional activity,including that of AR splice *** addition,we assess the implications of the convergence of these pathways on the clinical employment of miRs as PCa biomarkers and therapeutic targets.

关键词： microRNA Androgen receptor Androgen Prostate cancer Hormone Non-coding RNA

N-acetylcysteine and glycyrrhizin combination:Benefit outcome in a murine model of acetaminophen-induced liver failure

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World Journal of Hepatology 2020年第9期12卷 596-618页

作者： charlotte minsart Sandrine Rorive Arnaud Lemmers Eric Quertinmont Thierry Gustot Laboratory of Experimental Gastroenterology Erasme HospitalUniversitéLibre de BruxellesBrussels 1070Belgium Department of Pathology Erasme HospitalUniversitéLibre de BruxellesBrussels 1070Belgium DIAPATH-Center for microscopy and molecular Imaging UniversitéLibre de BruxellesGosselies 6041Belgium Department of Gastroenterology Hepato Pancreatology and Digestive OncologyErasme HospitalUniversitéLibre de BruxellesBrussels 1070Belgium Inserm Unité1149 Centre de Recherche sur l’inflammationParis 75006France UmR S_1149 UniversitéParis DiderotParis 75006France

BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed *** progress has been made in understanding the mechanism of hepatocellular injury,but N-acetylcysteine remains the only effective treatment despite its short therapeutic ***,other hepatoprotective drugs are needed for the delayed treatment of acetaminopheninduced *** interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1(HmGB1)protein,a member of the family of damage-associated molecular pattern,known to play an important pathological role in various *** To investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver *** Eight-week-old C57BL/6J wild-type female mice were used for all our *** fasted for 15 h were treated with acetaminophen(500 mg/kg)or vehicle(phosphate-buffered saline)by intraperitoneal injection and separated into the following groups:Glycyrrhizin(200 mg/kg);N-acetylcysteine(150 mg/kg);and N-acetylcysteine/*** all groups,mice were sacrificed 12 h following acetaminophen *** assessment of hepatotoxicity was performed by measuring plasma levels of alanine aminotransferase,aspartate aminotransferase and lactate *** was also evaluated by histological examination of hematoxylin and eosin-stained tissues *** rates were compared between various groups using Kaplan-meier *** Consistent with data published in the literature,we confirmed that intraperitoneal administration of acetaminophen(500 mg/kg)in mice induced severe liver injury as evidenced by increases in alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase but also by liver necrosis *** administration was shown to reduce the release of HmGB1 and significantly decreased the severity of liver injury.

关键词： Acetaminophen Acute liver injury Glycyrrhizin N-acetylcysteine Nacetylcysteine/glycyrrhizin combination murine model High mobility group box 1

Likelihood of hospitalization for a chronic respiratory condition following pediatric infection with enterovirus and rhinovirus strains

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Infectious medicine 2022年第4期1卷 245-252页

作者： charlotte Switzer Chris PVerschoor Kenneth Gavina Dominik mertz Kathy Luinstra Jeffrey mPernica marek Smieja Dept.of Health methods Evaluation and ImpactMcMaster UniversityHamiltonON CANADA Dept.of medicine McMaster UniversityHamiltonON CANADA Dept.of Pediatrics McMaster UniversityHamiltonON CANADA Dept.of Pathology and molecular medicine McMaster UniversityHamiltonON CANADA Research Institute of St Joseph’s Healthcare Hamilton HamiltonON CANADA Health Sciences North Research Institute SudburyON CANADA

Background:Rhino-enteroviruses,particularly enterovirus strain D68(EV-D68),have been associated with severe respiratory distress in *** goal of this study was to compare the long-term outcomes of children with EV-D68 infection to that of children with other enterovirus/***:Nasopharyngeal swabs from 174 children presenting with respiratory distress were tested by PCR for respiratory *** primary outcome was diagnosis of a chronic respiratory condition within the followup *** to intensive care,and length of stay were *** ratios were determined using multinomial logistic ***:During 5 years of follow-up,the crude odds of diagnosis with a chronic respiratory condition were significantly more likely in EV-D68 cases(OR:1.95,95%CI:1.02,3.82),but failed to remain significant after adjusting for a past history of *** admission for a primary concern of asthma,length of stay both in hospital and intensive care were significantly longer in EV-D68 cases(OR:2.10[95%CI:1.56,2.82,pment for a history of asthma,EV-D68 cases had significantly longer length of stay in hospital,admitted for 1.94 days for each day that controls were admitted(95%CI:1.40,2.68).In admissions to intensive care,EV-D68 cases spent 2.74 days for each day of admission in controls(95%CI:1.62,4.97,pmes of patients infected with EV-D68 in *** study finds that EV-D68 cases were significantly more likely be hospitalized for longer than other enterovirus/rhinovirus controls in subsequent admissions for respiratory *** for intensive care was significantly longer in EV-D68 *** next steps will be validation in a larger sample size.

关键词： Enterovirus-D68 Pediatric infectious disease Respiratory infection Asthma

SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

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Journal of molecular Cell Biology 2020年第12期12卷 916-932页

作者： Ganna Petruk manoj Puthia Jitka Petrlova Firdaus Samsudin Ann-charlotte Stromdahl Samuel Cerps Lena Uller Sven Kjellstrom Peter J.Bond Artur Schmidtchen Division of Dermatology and Venereology Department of Clinical SciencesLund UniversitySE-22184 LundSweden Bioinformatics Institute(BI) Agency for ScienceTechnology and Research(A*STAR)Singapore 138671Singapore Unit of Respiratory Immunopharmacology Department of Experimental MedicineLund UniversitySE-22184 LundSweden Division of mass Spectrometry Department of Clinical SciencesLund UniversitySE-22184 LundSweden Department of Biological Sciences National University of SingaporeSingapore 117543Singapore Copenhagen Wound Healing Center Bispebjerg HospitalDepartment of Biomedical SciencesUniversity of CopenhagenDK 2400 CopenhagenDenmark Dermatology Skane University HospitalSE-22185 LundSweden

There is a link between high lipopolysaccharide(LPS)levels in the blood and the metabolic syndrome,and metabolic syndrome predisposes patients to severe ***,we define an interaction between SARS-CoV-2 spike(S)protein and LPS,leading to aggravated inflammation in vitro and in *** gel electrophoresis demonstrated that SARS-CoV-2 S protein binds to *** thermophoresis yielded a of〜47 nm for the *** modeling and all-atom molecular dynamics simulations further substantiated the experimental results,identifying a main LPS-binding site in SARS-CoV-2 S protein.S protein,when combined with low levels of LPS,boosted nuclear factor-kappa B(NF-k B)activation in monocytic THP-1 cells and cytokine responses in human blood and peripheral blood mononuclear cells,*** in vitro inflammatory response was further validated by employing NF-kB reporter mice and in vivo *** light scattering,transmission electron microscopy,and LPS-FITC analyses demonstrated that S protein modulated the aggregation state of LPS,providing a molecular explanation for the observed boosting *** together,our results provide an interesting molecular link between excessive inflammation during infection with SARS-CoV-2 and comorbidities involving increased levels of bacterial endotoxins.

关键词： COVID-19 SARS-CoV-2 spike protein lipopolysaccharide inflammation aggregation metabolic syndrome

Theplant cytosolic m^(6)A RNA methylome stabilizes photosynthesis in the cold

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Plant Communications 2023年第6期4卷 70-84页

作者： Alexandre magno Vicente Nikolay manavski Paul Torben Rohn Lisa-marie Schmid Antoni Garcia-molina Dario Leister charlotte Seydel Leo Bellin Torsten möhlmann Gregor Ammann Stefanie Kaiser Jörg meurer Plant molecular Biology Faculty of BiologyLudwig-Maximilians-University MunichGroßhaderner Street 2-482152 Planegg-MartinsriedGermany Plant Development Faculty of BiologyLudwig-Maximilians-University MunichGroßhaderner Street 2-482152 Planegg-MartinsriedGermany Plant Physiology Faculty of BiologyUniversity of KaiserslauternErwin-Schröodinger-Street767663 KaiserslauternGermany Pharmaceutical Chemistry Goethe University FrankfurtMax-von-Laue-Str.960438 Frankfurt am MainGermany Present address:Loewe Biochemica GmbH Möuhlweg 2a82054 SauerlachGermany Present address:Center for Research in Agricultural Genomics 08193

The sessile lifestyle of plants requires an immediate response to environmental stressors that affect photosynthesis,growth,and crop ***,we showed that three abiotic perturbations—heat,cold,and high light—triggered considerable changes in the expression signatures of 42 epitranscriptomic factors(writers,erasers,and readers)with putative chloroplast-associated functions that formed clusters of commonly expressed genes in *** expression changes under all conditions were reversible upon deacclimation,identifying epitranscriptomic players as modulators in acclimation *** dysfunctions,particularly those induced by the oxidative stress-inducing norflurazon in a largely GENOmE UNCOUPLED-independent manner,triggered retrograde signals to remodel chloroplastassociated epitranscriptomic expression patterns.N6-methyladenosine(m^(6)A)is known as the most prevalent RNA modification and impacts numerous developmental and physiological functions in living *** cold treatment,expression of components of the primary nuclear m^(6)A methyltransferase complex was upregulated,accompanied by a significant increase in cellular m^(6)A mRNA *** the cold,the presence of FIP37,a core component of the writer complex,played an important role in positive regulation of thylakoid structure,photosynthetic functions,and accumulation of photosystemⅠ,the Cytb6f complex,cyclic electron transport proteins,and Curvature Thylakoid1 but not that of photosystemⅡcomponents and the chloroplast ATP *** of FIP37 affected abundance,polysomal loading,and translation of cytosolic transcripts related to photosynthesis in the cold,suggesting m^(6)Adependent translational regulation of chloroplast *** summary,we identified multifaceted roles of the cellular m^(6)A RNA methylome in coping with cold;these were predominantly associated with chloroplasts and served to stabilize photosynthesis.

关键词： m^(6)A RNA methylation cold acclimation stress response Arabidopsis thaliana photosynthesis chloroplast

Transitioning patients with inflammatory bowel disease from hospital-based to rapid home-based infliximab: A stepwise, safety and patient-orientated process towards sustainability

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World Journal of Gastroenterology 2020年第36期26卷 5437-5449页

作者： Anuj Bohra Qurat-Al-Ain Rizvi charlotte Yuen Yu Keung Abhinav Vasudevan Daniel R van Langenberg Department of Gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Eastern Health Clinical School Monash UniversityBox Hill 3128VictoriaAustralia

BACKGROUND Infliximab and other intravenous biologic infusions are increasingly used for chronic disorders like inflammatory bowel disease(IBD).Rapid infliximab and home-based infusions are attractive solutions to address resource and capacity issues for infusion centres,yet infliximab infusion reactions reportedly occur in up to 25%of patients with IBD,even at the manufacturers’recommended infusion duration of 2 *** To evaluate the safety,cost and patient satisfaction of transitioning from hospitalbased,standard 2 h to rapid home-based,30-min infliximab *** All patients receiving rapid infliximab infusions for IBD between 2014 to 2017(39 mo)were compared with those who received standard two-hour IFX infusions between 2005-2013(96 mo)at a single IBD ***(per-infusion and perindividual)including adverse drug reactions(ADR),duration(based on needledeparture time)and other clinical data were extracted from electronic medical *** logistical regression analysis assessed factors potentially associated with increased risk of ADRs to rapid *** primary outcome was the safety[as per relative risk(RR)of (ADR)of(1)rapid 30 m infusions(both hospital-and home-based)vs standard 2 h infliximab ***,relative cost per infusion and patient satisfaction and productivity were evaluated in rapid infusion recipients who transitioned to home-based *** Of 129 patients who received 1461 rapid IFX infusions(2014-2017)were compared with 169 patients who received 2214 standard IFX infusions(2005-2013).Within the rapid cohort,55(42.6%)were males,median age 42 years(range 18,86),114(84%)had Crohn’s disease(CD)with a median disease duration 5 years(0,36).median needle to departure time was higher in the standard than the rapid protocol group,108(70,253)vs 50(33,90)min,(Pmedian infusion duration or costs between rapi

关键词： Inflammatory bowel disease Infliximab Safety Cost Therapy Drug reaction