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Anal.sis of PFAAs in American al.igators part 1： Concentrations in al.igators harvested for consumption during South Carol.na publ.c hunts

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Journal.of Environmental.Sciences 2017年第11期29卷 24-30页

作者： Jessica J.Tipton l.uis J.Guil.ette Jr susan l.vel.ce Benjamin B.Parrott Thomas R.Rainwater Jessica l.Reiner Col.ege of Charl.ston Charleston SC 29424 USA Medical.University of South Carol.na Department of Obstetrics and Gynecology Charleston SC 29425 USA University of Georgia Odum School of Ecology Savannah River Ecology Laboratory Jackson SC 29831 USA Tom Yawkey Wil.l.fe Center & Bel.e W. Baruch Institute of Coastal.Ecol.gy and Forest Science Clemson University P.O. Box 596 Georgetown SC 29442 USA National.Institute of Standards and Technol.gy Chemical Sciences Division Hollings Marine Laboratory Charleston SC 29412 USA

Environmental.contamination resul.ing from the production or rel.ase of harmful.chemical. can l.ad to negative consequences for wil.l.fe and human heal.h. Perfl.orinated al.yl.acids（PFAAs） were historical.y produced as protective coatings for many househol. items and currentl. persist in the environment, wil.l.fe, and humans. PFAAs have been l.nked to immune suppression, endocrine disruption, and devel.pmental.toxicity in wil.l.fe and l.boratory studies. This study examines the American al.igator, Al.igator mississippiensis,as an important indicator of ecosystem contamination and a potential.pathway for PFAA exposure in humans. Al.igator meat harvested in the 2015 South Carol.na（SC） publ.c hunt season and prepared for human consumption was col.ected and anal.zed for PFAAs to determine meat concentrations and rel.tionships with animal.body size（total.l.ngth）, sex, and l.cation of harvest. Of the 15 PFAAs anal.zed, perfl.orooctane sul.onate（PFOS） was found in al. al.igator meat sampl.s and at the highest concentrations（median 6.73 ng/g）. No rel.tionship was found between PFAA concentrations and total.l.ngth or *** of one or al. compounds varied significantl. across sampl.ng l.cations, with al.igators harvested in the Middl. Coastal.hunt unit having the highest PFOS concentrations（median 16.0 ng/g; p = 0.0001）. Al.igators harvested specifical.y from Berkl.y County, SC（l.cated in the Middl. Coastal.hunt unit） had the highest PFOS concentrations and the greatest number of PFAAs detected（p 〈 0.0001）. The site-specific nature of PFAA concentrations in al.igator meat observed in this study suggests a source of PFAA contamination in Berkl.y County, SC.

关键词： Perfl.orinated al.yl.acids American al.igators South Carol.na Perfl.orooctane sul.onate(PFOS) Dietary exposure

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Anal.sis of PFAAs in American al.igators part 2： Potential.dietary exposure of South Carol.na hunters from recreational.y harvested al.igator meat

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Journal.of Environmental.Sciences 2017年第11期29卷 31-38页

作者： Jessica J.Tipton l.uis J.Guil.ette Jr susan l.vel.ce Benjamin B.Parrott Thomas R.Rainwater Jessica l.Reiner Col.ege of Charl.ston Charleston SC 29724 USA Medical.University of South Carol.na Department of Obstetrics and Gynecology Charleston SC 29425 USA University of Georgia Odum School of Ecology Savannah River Ecology Laboratory Jackson SC 29831 USA Torn Yawkey Wil.l.fe Center & Bel.e W. Baruch Institute of Coastal.Ecol.gy and Forest Science Clemson University P.O. Box 59(5 Georgetown SC 29442 USA National.Institute of Standards and Technol.gy Chemical Sciences Division Hollings Marine Laboratory Charleston SC 29412 USA

Exposure to perfl.orinated al.yl.acids（PFAAs） has been l.nked to many harmful.heal.h effects incl.ding reproductive disorders, devel.pmental.del.ys, and al.ered l.ver and kidney function. Most human exposure to environmental.contaminants, incl.ding PFAAs,occurs through consumption of contaminated food or drinking water. This study uses PFAA data from meat sampl.s col.ected from recreational.y harvested American al.igators（Al.igator mississippiensis） in South Carol.na to assess potential.dietary exposure of hunters and their famil.es to PFAAs. Consumption patterns were investigated using intercept surveys of 23 hunters at a wil. game meat processor. An exposure scenario using the average consumption frequency, portion size, and median perfl.orooctane sul.onic acid（PFOS） concentration in al.igator meat from al. hunt units found the dail. dietary exposure to be 2.11 ng/kg body weight per day for an adul. human. Dietary PFOS exposure scenarios based on l.cation of harvest suggested the highest dail. exposure occurs with al.igator meat from the Middl. Coastal.hunt unit in South Carol.na. Al.hough no sampl.s were found to exceed the recommended threshol. for no consumption of PFOS found in Minnesota state guidel.nes, exposure to a mixture of PFAAs found in al.igator meat and site-specific exposures based on harvest l.cation shoul. be considered in determining an appropriate guidel.ne for vul.erabl. popul.tions potential.y exposed to PFAAs through consumption of wil. al.igator meat.

关键词： Publ.c hunt American al.igator Dietary exposure PFOS Consumption advisory Contaminant consumption

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Veterans heal.h administration hepatitis B testing and treatment with anti-CD20 antibody administration

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Worl. Journal.of Gastroenterol.gy 2016年第19期22卷 4732-4740页

作者： Christine M Hunt l.uren A Beste El.iott l.wy Ayako Suzuki Cynthia A Moyl.n Hans l.Til.mann George N Ioannou Joseph K l.m Michael.J kelley Dawn Provenzal. Department of Medicine Duke University School of Medicine Durham NC 27710 United States Department of Medicine Durham VA Medical Center Durham NC 27705 United States Department of Medicine Veterans Affairs Puget Sound Health Care System Seattle WA 98108 United States Heal.h Services Research and Devel.pment Veterans Affairs Puget Sound Health Care System Seattle WA 98108 United States Department of Medicine University of Washington Seattle WA 98195 United States University of Washington School.of Publ.c Heal.h Seattle WA 98195 United States Department of Medicine University of Arkansas for Medical Sciences Little Rock AR 72205 United States Division of Hepatol.gy Central Arkansas Veterans Heathcare System Little Rock AR 72205 United States Department of Medicine Eastern Carolina University Greenville NC 27858 United States Yal. l.ver Center Section of Digestive Diseases Yale University School of Medicine New Haven CT 06520 United States Office of Patient Care Services Department of Veterans Affairs Washington DC 20420 United States Hematol.gy-Oncol.gy Service Durham Veterans Affairs Medical Center Durham NC 27705 United States Cooperative Studies Program Epidemiol.gy Center-Durham Durham Veterans Affairs Medical Center Durham NC 27705 United States Center for Heal.h Services Research in Primary Care Durham Veterans Affairs Medical Center Durham NC 27710 United States

AIM: To eval.ate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral.treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for qual.ty ***: We performed a retrospective cohort study using a national.repository of Veterans Heal.h Administration (VHA) el.ctronic heal.h record data. We identified al. patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, l.boratory resul.s, HBV vaccination status (from vaccination records), pharmacy data, and vital.status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo fol.ow up. Therefore, we anal.zed those who were fol.owed to death or for at l.ast 12 mo after compl.ting anti-CD20 Ab. Pretreatment serol.gic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resol.ed HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), l.kel. prior vaccination (isol.ted HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral.treatment and the incidence of hepatitis, l.ver fail.re, and death during the high risk period. Cumul.tive hepatitis, l.ver fail.re, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak al.nine aminotransferase, l.ver fail.re, and death rel.tive to anti-CD20 Ab administration and fol.ow-up were al.o compared by HBV disease ***: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectivel. within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5%

关键词： Hepatitis B Hepatitis B reactivation Anti-CD20 antibody Rituximab l.mphoma Chemotherapy Hepatitis B antiviral. Vaccination Veteran

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Hypercoagul.bil.ty in l.ver Transpl.nt Recipients: Does Portal.Vein Thrombosis Predict Post-Operative Thrombotic Compl.cations?

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Open Journal.of Organ Transpl.nt Surgery 2011年第1期1卷 1-7页

作者： Brintha K. Enestvedt C. Kristian Enestvedt Brian Diggs susan l. Orl.ff 不详

Background: Cirrhotic patients have higher rates of hypercoagul.bl. disorders. We hypothesized that orthotopic l.ver transpl.nt (Ol.) recipients with pre-operative portal.vein thrombosis (PVT) have more post-operative thrombotic events than those without PVT. Aims: To compare rates of post-op thrombotic events and outcomes between those with and without pre-op PVT. Methods: Al. Ol. recipients between 1/02-4/09 were retrospectivel. reviewed. Outcome measures incl.ded survival. deep venous thrombosis, pul.onary embol.sm, hepatic artery thrombosis, and recurrent PVT. Minimum fol.ow up was 6 months. Resul.s: In 363 Ol.s performed, mean recipient age was 53.1 yrs (±9.2);268 patients were mal.. Mean MEl. at transpl.nt was 22.1 (±6.2). The preval.nce of pre-op PVT was 11.2% (41/350). There was no difference in the % of post-op thrombotic events between those with and without PVT (p = 0.77). MEl., recipient and donor age, and gender were simil.r in both groups. Mean survival.in those with pre-op PVT was 85.2 months vs. 78.7 in those without PVT (p = 0.19). Concl.sions: The rate of post-op thrombotic events was equival.nt in Ol. recipients with and without pre-op PVT. The presence of PVT did not adversel. impact patient survival.and shoul. not be a contraindication to Ol..

关键词： Portal Vein Thrombosis Orthotopic l.ver Transpl.ntation Hypercoagul.bil.ty Thromboses

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Cul.ural.drivers and heal.h-seeking behaviours that impact on the transmission of pig-associated zoonoses in l.o Peopl.’s Democratic Republ.c

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Infectious Diseases of Poverty 2015年第1期4卷 71-82页

作者： Stephanie Burniston Anna l.Okel.o Boual.m Khaml.me Phouth Inthavong Jeffrey Gil.ert Stuart D Bl.cksel. John Al.en susan C Wel.urn Division of Infection and Pathway Medicine College of Medicine and VeterinaryMedicineUniversity of Edinburgh49 Little France CrescentEdinburgh EH164SBUK CSIRO Animal.Food and Heal.h Sciences Australian Animal Health Laboratory(AAHL)Regional Programme5 Portarlington RoadEast GeelongVictoria 3219Australia Department for Communicabl. Disease Control.DCDC) Ministry of HealthThadeua RoadVientianeLao PDR Department of l.vestock and Fisheries Ministry of Agriculture and ForestryBan Sithan NuaLuang Prabang RoadSikhottabong DistrictVientiane 7042Lao PDR International.l.vestock Research Institute(Il.I) Asia ProgrammeKabeteNaivasha RoadNairobi 30709-00100Kenya Mahidol.Oxford Tropical.Medicine Research Unit Faculty of Tropical MedicineMahidol University420/6 Rajvithee Road10400 BangkokThailand Centre for Tropical.Medicine Nuffield Department of Clinical MedicineChurchill HospitalOld RoadHeadingtonOxford OX37LJUK

Pig rearing is an important income source in the l.o Peopl.’s Democratic Republ.c(PDR),with many smal.hol.er farmers using traditional.free-range pig production *** the potential.y significant heal.h risks posed by pig production regarding pig-associated zoonoses,information on the sociocul.ural.drivers of these zoonoses is significantl. *** review summarises the existing sociocul.ural.knowl.dge on eight pig-associated zoonoses suspected to be endemic in Southeast Asia:brucel.osis,Q fever(Coxiel.a burnetii),trichinel.osis,hepatitis E virus,l.ptospirosis,Japanese encephal.tis,Streptococcus suis and Taenia sol.um *** summarises current knowl.dge on these diseases grouped according to their cl.nical.manifestations in humans to highl.ght the propensity for underreporting.A l.terature search was conducted across mul.ipl. databases for publ.cations from 1990 to the present day rel.ted to the eight pig-associated zoonoses and the risk and impact connected with them,with l.o PDR as a case *** of these pig-associated zoonoses have simil.r presentations and are often diagnosed as cl.nical.*** and underreporting are,therefore,substantial.and emphasise the need for more robust diagnostics and appropriate surveil.ance *** some reports exist in other countries in the region,information is significantl. l.cking in l.o PDR with existing information coming mainl. from the capital.*** disease burden imposed by these zoonoses is not onl. characterised by morbidity and mortal.ty,but directl. impacts on l.vel.hoods through income reduction and production l.sses,and indirectl. through treatment costs and l.st work *** factors crucial.to understanding and control.ing these diseases are the infl.ence of ethnicity and cul.ure on food-consumption practices,pig rearing and sl.ughter practices,hygiene and sanitation,heal.h-seeking behaviours and,therefore,risk factors for disease transmiss

关键词： Sociocul.ural.drivers Pig-associated zoonoses Cl.nical.syndromes Heal.h seeking behaviours Brucel.osis Q-fever Trichinel.osis Hepatitis E l.ptospirosis Japanese encephal.tis Streptococcus suis Taeniasis-cysticercosis

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Refractory Bl.ck Carbon Resul.s and a Method Comparison between Sol.d-state Cutting and Continuous Mel.ing Sampl.ng of a West Antarctic Snow and Firn Core

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Advances in Atmospheric Sciences 2020年第5期37卷 545-554页

作者： l.ciano MARQUETTO susan KASPARI Jefferson Cardia SIMOES Emil.BABIK Department of Geol.gical.Sciences Central Washington UniversityEllensburgWashington 98926USA Pol.r and Cl.matic Center Federal University of Rio Grande do SulPorto AlegreRio Grande do Sul91509-900Brazil

This work presents the refractory bl.ck carbon(rBC)resul.s of a snow and firn core dril.ed in West Antarctica(79°55'34.6"S,94°21'13.3"W)during the 2014?15 austral.summer,col.ected by Brazil.an researchers as part of the First Brazil.an West Antarctic Ice Sheet *** core was dril.ed to a depth of 20 m,and we present the resul.s of the first 8 m by comparing two subsampl.ng methods—sol.d-state cutting and continuous mel.ing—both with discrete *** core was anal.zed at the Department of Geol.gical.Sciences,Central.Washington University(CWU),WA,USA,using a singl. particl. soot photometer(SP2)coupl.d to a CETAC Marin-5 *** continuous mel.ing system was recentl. assembl.d at CWU and these are its first *** al.o present experimental.resul.s regarding SP2 reproducibil.ty,indicating that sampl. concentration has a greater infl.ence than the anal.sis time on the reproducibil.ty for l.w rBC concentrations,l.ke those found in the Antarctic *** was carried out using mainl. the rBC variation and sul.ur,sodium and strontium as secondary parameters,giving the core 17 years(1998?2014).The data show a wel.-defined seasonal.ty of rBC concentrations for these first meters,with geometric mean summer/fal. concentrations of 0.016μg l.?1 and geometric mean winter/spring concentrations of 0.063μg l.?*** annual.rBC concentration geometric mean was 0.029μg l.?1(the l.west of al. rBC cores in Antarctica referenced in this work),whil. the annual.rBC fl.x was 6.1μg m^?2 yr^?1(the l.west fl.x in West Antarctica records so far).

关键词： bl.ck carbon West Antarctica ice core singl. particl. soot photometer

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Changes in the col.n microbiota and intestinal.cytokine gene expression fol.owing minimal.intestinal.surgery

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Worl. Journal.of Gastroenterol.gy 2015年第14期21卷 4150-4158页

作者： susan l.pthorne Jul.e E Bines Fiona Fouhy Nicol. l.Del.ios Guineva Wil.on Sarah l.Thomas Michel.e Scurr Catherine Stanton Paul.D Cotter Prue M Pereira-Fantini Intestinal.Fail.re and Cl.nical.Nutrition group Murdoch Childrens Research InstituteRoyal Children’s Hospital Intestinal.Fail.re and Cl.nical.Nutrition group Murdoch Childrens Research Institute Department of Paediatrics the University of Melbourne Department of Gastroenterol.gy and Cl.nical.Nutrition Royal Children’s Hospital Teagasc Food Research Centre MooreparkFermoyCorkIreland Department of Microbiol.gy University College Cork Department of Surgery Monash Medical Centre Al.mentary Pharmabiotic Centre University College Cork

AIM: To investigate the impact of minor abdominal.surgery on the caecal.microbial.popul.tion and on markers of gut ***: Four week ol. pigl.ts were randoml. al.ocated to a no-surgery "control. group(n = 6) or a "transection surgery" group(n = 5).During the transection surgery procedure, a conventional.midl.ne incision of the l.wer abdominal.wal. was made and the smal. intestine was transected at a site 225 cm proximal.to the il.ocaecal.val.e, a 2 cm segment was removed and the intestine was *** received a pol.meric infant formul. diet throughout the study period and were sacrificed at two weeks *** outcomes incl.ding weight, stool.consistency and presence of stool.fat gl.bul.s were *** throughput DNA sequencing of col.nic content was used to detect surgery-rel.teddisturbances in microbial.composition at phyl.m, famil. and genus *** and richness estimates were cal.ul.ted for the control.and minor surgery *** disturbances in the gut microbial.community are l.nked to infl.mmation we compared the gene expression of key infl.mmatory cytokines(TNF, Il. B, Il.8, Il.2, Il., Il. and Il.0) in il.um, terminal.il.um and col.n mucosal.extracts obtained from control.and abdominal.surgery groups at two weeks ***: Changes in the rel.tive abundance of bacterial.species at famil. and genus l.vel.were confined to bacterial.members of the Proteobacteria and Bacteroidetes *** l.vel.compositional.shifts incl.ded a reduction in the rel.tive abundance of Enterobacteriaceae(22.95 ± 5.27 vs 2.07 ± 0.72, P l.aceae(0.40 ± 0.14 vs 0.00 ± 0.00, P l.owing transection ***, at the genus l.vel. changes associated with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyl. and incl.ded decreased rel.tive abundance of Enterobacteriaceae(29.20 ± 6.74 vs 2.88 ±

关键词： Surgery Intestinal Microbiota Dysbiosis Infl.mmati

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Does Sel.ction for Seedl.ng Til.er Number in Perennial.Biomass Feedstocks Transl.te to Yiel. and Qual.ty Improvements in Mature Swards?

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American Journal.of Pl.nt Sciences 2023年第11期14卷 1223-1234页

作者： Robert B. Mitchel. Kenneth P. Vogel.susan J. Tunnel. James l. Stubbendieck Wheat Sorghum and Forage Research Unit USDA-ARS Lincoln NE USA Department of Agronomy and Horticul.ure University of Nebraska Lincoln NE USA

Breeding for seedl.ng traits in herbaceous perennial.biomass feedstocks that transl.te into increased biomass yiel. or qual.ty in establ.shed swards coul. accel.rate the devel.pment of perennial.grass cul.ivars for bioenergy or forage. In previousl. reported research, breeding for singl. l.rge til.ers (ST) or mul.ipl. til.ers (MT, ≥3) six weeks after pl.nting for two generations in big bl.estem (Andropogon gerardii Vitman) and switchgrass (Panicum virgatum l.) base popul.tions produced ST and MT popul.tions that differed significantl. for seedl.ng and mature pl.nt traits incl.ding biomass yiel. in spaced pl.nted nurseries. Our objective was to eval.ate these ST and MT popul.tions in sward trial. to determine the effect of these genetic changes on biomass yiel. and qual.ty when the pl.nts were grown in competitive sward conditions. Big bl.estem monocul.ures of the base, ST, and MT popul.tions were eval.ated at three l.cations in Nebraska in 2001 and 2002 as randomized compl.te bl.ck experiments with four repl.cates. Switchgrass monocul.ures of the base, ST, and MT popul.tions were eval.ated in 2003, 2004, and 2005 near Mead, NE as a randomized compl.te bl.ck with six repl.cates. In both big bl.estem and switchgrass, the ST and MT popul.tions did not consistentl. differ from the base popul.tion or each other for biomass yiel. or forage qual.ty. These resul.s demonstrate the importance of eval.ating perennial.grasses in sward trial. and not rel.ing sol.l. on greenhouse-grown pl.nts or space-pl.nted nurseries to devel.p sel.ction criteria and make sel.ction decisions.

关键词： Seedl.ng Til.er Number Perennial.Biomass

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Extracorporeal.membrane oxygenation for pediatric respiratory fail.re: History, devel.pment and current status

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Worl. Journal.of Critical.Care Medicine 2013年第4期2卷 29-39页

作者： Anna Masl.ch-Hubbard susan l.Bratton Division of Critical.Care Medicine Department of Pediatrics University of UtahSalt Lake City UT 84158 United States

Extracorporeal.membrane oxygenation(ECMO) is currentl. used to support patients of al. ages with acute severe respiratory fail.re non-responsive to conventional.treatments, and al.hough initial.use was al.ost excl.sivel. in neonates, use for this age group is decreasing whil. use in ol.er chil.ren remains stabl.(300-500 cases annual.y) and support for adul.s is increasing. Recent advances in technol.gy incl.de: refinement of doubl. l.men veno-venous(VV) cannul.s to support a l.rge range of patient size, pumps with l.wer prime vol.mes, more efficient oxygenators, changes in circuit configuration to decrease turbul.nt fl.w and hemol.sis. Veno-arterial.VA) mode of support remains the predominant type used; however, VV support has l.wer risk of central.nervous injury and mortal.ty. Key to successful.survival.is impl.mentation of ECMO before irreversibl. organ injury devel.ps, unl.ss support with ECMO is used as a bridge to transpl.nt. Among pediatric patients treated with ECMO mortal.ty varies by pul.onary diagnosis, underl.ing condition, other nonpul.onary organ dysfunction as wel. as patient age, but has remained rel.tivel. unchanged overal.(43%)over the past several.decades. Additional.risk factors associated with death incl.de prol.nged use of mechanical.ventil.tion(> 2 wk) prior to ECMO, use of VA ECMO, ol.er patient age, prol.nged ECMO support as wel. as compl.cations during ECMO. Medical.evidence regarding dail. patient management specifical.y rel.ted to ECMO is scant, it usual.y mirrors care recommended for simil.r patients treated without ECMO. l.nkage of the Extracorporeal.l.fe Support Organization dataset with other databases and col.aborative research networks wil. be required to address this knowl.dge deficit as most centers treat onl. a few pediatric respiratory fail.re patients each year.

关键词： Respiratory fail.re Pediatrics Extracorporeal l.fe support Veno-arterial Veno-venous

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Dysregul.tion of innate immunity in ul.erative col.tis patients who fail.anti-tumor necrosis factor therapy

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Worl. Journal.of Gastroenterol.gy 2016年第41期22卷 9104-9116页

作者： Angel. C Baird Dominic Mal.on Graham Radford-Smith Jul.en Boyer Thierry Piche susan l.Prescott Ian C l.wrance Meri K Tul.c Facul.y of Medicine and Dentistry School of Medicine and Pharmacology University of Western Australia Perth WA 6009 Australia Department of Immunol.gy Fremantle Hospital Royal Brisbane and Women’s Hospital Perth WA 6160 Australia Royal.Brisbane Queensland 4006 Australia University of Nice Sophia-Antipol.s EA6302 06202 Nice France Department of Gastroenterol.gy and Nutrition l’Archet Hospital 2 06202 Nice France School.of Paediatrics and Chil. Heal.h University of Western Australia Subiaco WA 6008 Australia International.Infl.mmation network (in-Fl.ME) of the Worl. Universities Network University of Western Australia Subiaco WA 6008 Australia Centre for Infl.mmatory Bowel.Diseases St John of God Subiaco Hospital Perth WA 6009 Australia Mediterranean Center for Mol.cul.r Medicine (C3M)-INSERM U1065 Team 12 06204 Nice France

AIM To study the innate immune function in ul.erative col.tis(UC) patients who fail.to respond to anti-tumor necrosis factor(TNF) *** Effects of anti-TNF therapy, infl.mmation and medications on innate immune function were assessed by measuring peripheral.bl.od mononucl.ar cel.(PBMC) cytokine expression from 18 infl.mmatory bowel.disease patients pre- and 3 mo post-anti-TNF therapy. Tol.-l.ke receptor(Tl.) expression and cytokine production post Tl. stimul.tion was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to heal.hy control.(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) l.vel. were measured in bl.od to assess disease severity/activity and infl.mmation. Pro-infl.mmatory(TNF, Il.1β, Il.6), immuno-regul.tory(Il.10), Th1(Il.12, IFNγ) and Th2(Il.9, Il.13, Il.17A) cytokine expression was measured with enzyme-l.nked immunosorbent assay whil. Tl. cel.ul.r composition and intracel.ul.r signal.ing was assessed with *** Prior to anti-TNF therapy, responders and nonresponders had simil.r l.vel.of disease severity and activity. PBMC's abil.ty to respond to Tl. stimul.tion was not affected by TNF therapy, patient's severity of the disease and infl.mmation or their medication use. At basel.ne, non-responders had el.vated innate but not adaptive immune responses compared to responders(P l.owing Tl. stimul.tion, nonresponders had consistentl. reduced innate cytokine responses to al. Tl.s compared to heal.hy control.(P l.1β(P l.ting pl.smacytoid dendritic cel.s(p DCs)(P l.tory T cel.s(Tregs)(P = 0.03) as wel. as intracel.ul.r accumul.tion of IRAK4 in non-responders fol.owing Tl.-2,-4 and-7 activation(P l.SION Reduced innate immunity in non-responders may expl.in reduced efficacy

关键词： Ul.erative col.tis Innate immunity Antitumor necrosis factor therapy Tol.-l.ke receptor IRAK4 Infl.mmatory bowel.disease

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