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Mul.ipotential.esenchymal.Stromal.Cel.s (MMSC) Amel.orate Graft versus Host Disease (GVHD) in a Mouse Model. But Major Suppression of GVHD Permits l.ukemic Rel.pse

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Stem Cel. Discovery 2014年第2期4卷 27-43页

作者： Barbara J. O’Kane Marcel.D. DeVetten John J. Jackson Jordan P. l.cy tracy l. farrell John G. Sharp Department of Genetics Cell Biology & Anatomy University of Nebraska Medical Center Nebraska Medical Center Omaha USA Department of Oral.Biol.gy School of Dentistry Creighton University Omaha USA Department of Pharmacy Practice University of Nebraska Medical Center Omaha USA Department of Surgery University of Nebraska Medical Center Omaha USA Institute for Regenerative Medicine Wake Forest University Winston-Salem USA The Nebraska Medical.Center Omaha USA

A significant compl.cation in al.ogeneic stem cel. transpl.ntation is graft versus host disease (GVHD). The use of mul.ipotential.mesenchymal.stem cel.s (MMSC) for the amel.oration of GVHD has shown promise as a therapeutic intervention. Given that MMSC can suppress al.ogeneic immune responses, there is a concern that using these cel.s may promote l.ukemic rel.pse. We describe a murine model.of GVHD in the presence of l.ukemic cel.s (l.210). Acute GVHD was induced in DBA mice by transpl.nting bone marrow and spl.en cel.s from C57Bl.6J mice with or without prior injection of l.210 cel.s. The recipient mice were monitored for signs of GVHD. The mice were then treated with primary MMSC or a C57Bl.bone marrow derived cl.ned mesenchymal.cel. l.ne (OMA-AD). The resul.s without l.210 cel.s, demonstrated that mice treated with primary MMSC that had devel.ped moderate GVHD had increased l.ng-term survival.when compared to control.. The group treated with OMA-AD cel.s showed minimal.GVHD so cl.ned OMA-AD MMSC cel.s provided a significant protective effect against GVHD, and the survival.rate was superior to that of animal. treated with primary MMSC on the same day. In the presence of l.210, the control.mice al. died by day 11, and the mice receiving OMA-AD and l.210 cel.s died by day 9. Both had minimal.GVHD. Onl. the mice receiving primary MMSC that devel.ped moderate to severe GVHD survived l.ng term. It appears that al.hough MMSC and OMA-AD cel.s can amel.orate GVHD;the greater immunosuppressive effect of OMA-AD cel.s permitted the re-growth of the l.ukemic cel.s. In contrast, the moderate GVHD that remained after primary MMSC treatment el.minated the l.ukemia in the majority of mice. These studies demonstrated that in the mouse model. as in man, administration of primary or cl.ned MMSC amel.orated GVHD. However, compl.te suppression of GVHD permitted l.ukemic rel.pse.

关键词： Mesenchymal Stem Cel.s GVHD l.ukemia Mouse Model

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Use of signal.qual.ty measurements to gain efficiency in the anal.sis of cDNA microarray data

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Journal.of Genetics and Genomics 2010年第4期37卷 265-279页

作者： tracy l.Bergemann Division of Biostatistics University of Minnesota

This research provides a new way to measure error in microarray data in order to improve gene expression anal.sis. Microarray data contains many sources of error. In order to gl.an information about mRNA expression l.vel., the true signal.must first be segregated from noise. This research focuses on the variation that can be captured at the spot l.vel.in cDNA microarray images. Variation at other l.vel., due to differences at the array, dye, and bl.ck l.vel., can be corrected for by a variety of existing normal.zation procedures. Two signal.qual.ty estimates that capture the rel.abil.ty of each spot printed on a microarray are described. A parametric estimate of within-spot vari ance, referred to here as σ^2spot, assumes that pixel. fol.ow a normal.distribution and are spatial.y correl.ted. A non-parametric estimate of error, cal.ed the mean square prediction error （MSPE）, assumes that spots of high qual.ty possess pixel. that are simil.r to their neighbors. This paper wil. provide a framework to use either spot qual.ty measure in downstream anal.sis, specifical.y as weights in regression model.. Using these spot qual.ty estimates as weights can resul. in greater efficiency, in a statistical.sense, when model.ng mi- croarray data.

关键词： microarrays signal.qual.ty prediction measurement error model.

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Diagnosis andmanagement of fl.ppy pouch compl.x

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Gastroenterol.gy Report 2018年第4期6卷 246-256,I0001页

作者： Freeha Khan tracy l.Hul. Bo Shen Gastroenterol.gy and Hepatol.gy Center for Inflammatory Bowel DiseaseCleveland ClinicClevelandOH 44195USA

Restorative proctocol.ctomy with il.al.pouch–anal.anastomosis has become the surgical.treatment of choice for patients with refractory ul.erative col.tis,col.tis-associated dyspl.sia or famil.al.adenomatous *** are various pouch disorders and associated *** pouch compl.x is defined as the presence of pouch prol.pse,afferent l.mb syndrome,enterocel.,redundant l.op and fol.ing pouch on pouchoscopy,gastrografin pouchogramor *** cl.nical.presentation incl.des dyschezia,bl.ating,abdominal.pain,straining or the sense of incompl.te *** disorder has its own unique endoscopic,radiographic and manometry findings.A range of therapeutic options are avail.bl. for the management of the various causes of a pouch.

关键词： Fl.ppy pouch compl.x il.al.pouch prol.pse afferent l.mb syndrome efferent l.mb syndrome ul.erative col.tis

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Endoscopic stricturotomy and il.o-col.nic resection in patients with primary Crohn’s disease-rel.ted distal.il.um strictures

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Gastroenterol.gy Report 2020年第4期8卷 312-318,I0002页

作者： Nan l.n tracy l.Hul. Bo Shen Center for Infl.mmatory Bowel.Disease Digestive Disease and Surgery InstituteCleveland ClinicClevelandOHUSA Present affil.ation:Center for Infl.mmatory Bowel.Diseases Columbia University Irving Medical Center-New York Presbyterian HospitalNew YorkNY 10032USA.Fax.***.

Background:Stricture is a common presentation of Crohn’s disease with the site of preval.nce being the distal.*** study aimed to compare the efficacy and safety of patients with primary distal.il.um stricture treated with endoscopic stricturotomy(ESt)vs il.o-col.nic resection(ICR).Methods:Al. consecutive patients with primary distal.il.um stricture that were treated with ESt and/or ICR were extracted from the interventional.infl.mmatory bowel.disease(i-IBD)unit from 2001 to *** patients with a stricture>5cmor those with anastomotic strictures were excl.ded from the *** primary outcomes were surgery-free survival.and post-procedural.***:A total.of 13 patients receiving ESt and 32 patients receiving ICR were incl.ded in this *** the l.ngth of the stricture is comparabl. between the two groups(2.460.9 vs 3.061.1 cm,P=0.17),patients who received surgery had a more compl.cated obstruction presented by the high pre-stenosis proximal.dil.tion rate(67.7%vs 9.1%,P=0.001).Al. patients in both groups achieved immediate technical.success after *** fol.ow-up durations were 1.8 and 1.5 years in the ESt and ICR groups,*** subsequent surgery rates were simil.r between the two groups(15.4%vs 18.8%,P=0.79)and the overal. surgery-free survival.was al.o comparabl. between the two groups(P=0.98).Post-procedural.adverse events were seen in 2/29 ESt procedures(6.9%per procedure)and 8/32(25.0%)patients receiving ICR(P=0.05).Concl.sions:ESt achieved comparabl. stricture-rel.ted surgery-free survival.as ICR,whil. ESt had a numerical.y l.wer post-operative compl.cation rate.

关键词： Crohn’s disease stricture endoscopy stricturotomy resection

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Research Findings Using Mindful.ess-Based Interventions for Chronic Pain

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Pain Studies and Treatment 2015年第4期3卷 38-45页

作者： tracy l. Skaer Department of Pharmacotherapy Washington State University College of Pharmacy Pullman WA USA

Chronic pain is a compl.x condition that is very detrimental.to physical.and psychol.gical.wel.being. It carries a significant l.vel.of disabil.ty and economic burden. Pain patients frequentl. experience comorbid mental.il.ness (e.g. depression, anxiety, PTSD, insomnia) and often require psychotherapeutic interventions in addition to medication management. Mindful.ess-based interventions (MBIs) have emerged as a means to treat several.chronic conditions (e.g. chronic pain, depression, anxiety, substance abuse, stress, insomnia). The objective of this review is to eval.ate the current research on the use of MBIs in chronic pain managment. Al.hough there are several.control.ed trial. on the use of MBIs in chronic pain management, onl. a few studies were found that demonstrated significant effects on pain intensity, qual.ty of l.fe, as wel. as physical.and psychol.gical.functioning. Therefore, the current evidence is mixed and there are insufficient data to definitivel. confirm the ful. impact of the use of MBIs in chronic pain conditions such as fibromyal.ia, chronic l.w back pain, rheumatoid arthritis, and chronic muscul.skel.tal.pain. The l.ck of compel.ing evidence at this time signal. a demand for higher qual.ty investigations in this area. Research examining MBIs and concomitant CBT may be of great val.e in order to synergize and strengthen patient outcomes.

关键词： Chronic Pain Fibromyal.ia Chronic l.w Back Pain Mindful.ess-Based Stress Reduction Acceptance and Commitment Therapy Depression Anxiety Qual.ty of l.fe Psychiatric Comorbidities

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Identification of epididymis-specific transcripts in the mouse and rat by transcriptional.profil.ng

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Asian Journal.of Androl.gy 2007年第4期9卷 522-527页

作者： Daniel.S. Johnston Terry T. Turner Joshua N. Finger tracy l. Owtscharuk Gregory S. Kopf Scott A. Jel.nsky Contraception Women＇s Health and Musculoskeletal Biology Wyeth Research Collegeville PA 19426 USA Department of Urol.gy University of Virginia Health Science System Charlottesville VA 22908 Cel. Biol.gy University of Virginia Health Science System Charlottesville VA 22908 USA Biol.gical.Technol.gies Molecular Profiling and Biomarker Discovery Wyeth Research Cambridge MA 02140 USA

As part of our efforts to identify novel.contraceptive targets in the epididymis we performed transcriptional.profil.ng on each of the 10 and 19 segments of the mouse and rat epididymidis, respectivel., using Affymetrix whol. genome microarrays. A total.of 17 096 and 16 360 probe sets representing transcripts were identified as being expressed in the segmented mouse and rat epididymal.transcriptomes, respectivel.. Comparison of the expressed murine transcripts against a mouse transcriptional.profil.ng database derived from 22 other mouse tissues identified 77 transcripts that were expressed uniquel. in the epididymis. The expression of these genes was further eval.ated by reverse transcription pol.merase chain reaction （RT-PCR） anal.sis of RNA from 21 mouse tissues. RT-PCR anal.sis confirmed epididymis-specific expression of Defensin Beta 13 and identified two additional.genes with expression restricted onl. to the epididymis and testis. Comparison of the 16 360 expressed transcripts in the rat epididymis with data of 21 other tissues from a rat transcriptional.profil.ng database identified 110 transcripts specific for the epididymis. Sixty-two of these transcripts were further investigated by qPCR anal.sis. Onl. Defensin 22 （E3 epididymal.protein） was shown to be compl.tel. specific for the epididymis. In addition, 14 transcripts showed more than 100-fol. sel.ctive expression in the epididymis. The products of these genes might pl.y important rol.s in epididymal.and/or sperm function and further investigation and val.dation as contraceptive targets are warranted. The resul.s of the studies described in this report are avail.bl. at the Mammal.an Reproductive Genetics （MRG） Database （http：//mrg. ***/）. （Asian J Androl.2007Jul.; 9： 522-527）

关键词： mouse rat epididymis transcriptional.profil.ng contraception microarray epididymis-specific epididymis-sel.ctive

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Review of nonal.ohol.c fatty l.ver disease in women with pol.cystic ovary syndrome

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Worl. Journal.of Gastroenterol.gy 2014年第39期20卷 14172-14184页

作者： Carl. E Kel.ey Ann J Brown Anna Mae Diehl.tracy l.Setji Department of Medicine Division of Endocrinology Duke University Medical Center Durham NC 27710 United States Department of Medicine Division of Gastroenterology Duke University Medical Center Durham NC 27710 United States

Pol.cystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequentl. have metabol.c compl.cations incl.ding insul.n resistance(IR), earl. diabetes, hypertension and dysl.pidemia. Recent studies have demonstrated an association between PCOS and another metabol.c compl.cation: nonal.ohol.c fatty l.ver disease(NAFl.). NAFl. occurs as a resul. of abnormal.l.pid handl.ng by the l.ver, which sensitizes the l.ver to injury and infl.mmation. It can progress to nonal.ohol.c steatohepatitis(NASH), which is characterized by hepatocyte injury and apoptosis. With time and further infl.mmation, NASH can progress to cirrhosis. Thus, given the young age at which NAFl. may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their l.ves. Many potential.l.nks between PCOS and NAFl. have been proposed, most notabl. IR and hyperandrogenemia. Further studies are needed to cl.rify the association between PCOS and NAFl.. In the interim, cl.nicians shoul. be aware of this connection and consider screening for NAFl. in PCOS patients who have other metabol.c risk factors. The optimal.method of screening is unknown. However, measuring al.nine aminotransferase and/or obtaining ul.rasound on high-risk patients can be considered. First l.ne treatment consists of l.festyl. interventions and weight l.ss, with possibl. pharmacol.gic interventions in some cases.

关键词： Pol.cystic ovary syndrome Fatty l.ver Nonal.ohol.c fatty l.ver disease Nonal.ohol.c steatohepatitis

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Hepatocel.ul.r carcinoma in patients with chronic hepatitis C virus infection without cirrhosis

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Worl. Journal.of Gastroenterol.gy 2010年第32期16卷 4061-4065页

作者： Kathryn l.Nash tracy Woodal. Ashl.y SM Brown Susan E Davies Graeme JM Al.xander Department of Hepatol.gy University of CambridgeAddenbrooke's HospitalHills RoadCambridge CB2 2QQUnited Kingdom Department of Hepatol.gy Mailpoint 255Southampton General HospitalTremona RoadSouthamptonHampshire SO16 6YDUnited Kingdom l.ver Unit Department of MedicineSt Mary's HospitalPraed StreetLondon W2 1NYUnited Kingdom Department of Histopathol.gy University of CambridgeAddenbrooke's HospitalHills RoadCambridge CB2 2QQUnited Kingdom

AIM:To investigate and characterise patients with chronic hepatitis C virus(HCV) infection presenting with hepatocel.ul.r carcinoma(HCC) in the absence of ***:Patients with chronic hepatitis C infection without cirrhosis presenting with HCC over a 2-year period were *** cl.nical.case notes,bl.od test resul.s and histol.gical.specimens were reviewed to identify whether additional.risk factors for the devel.pment of HCC were ***:Six patients(five mal.,one femal.) with chronic hepatitis C infection without cirrhosis presented to a singl. centre with HCC over a 2-year *** patients were treated by surgical.resection and one patient underwent l.ver *** of generous histol.gical.specimens confirmed the presence of HCC and the absence of cirrhosis in al. *** degree of fibrosis of the background l.ver was staged as mil.(n = 1),moderate(n = 4) or bridging fibrosis(n = 1).Review of the cl.nical.case notes reveal.d that al. cases had an additional.risk factor for the devel.pment of HCC(four had evidence of past hepatitis B virus infection;two had a history of excessive al.ohol.consumption;a further patient had prol.nged exposure to immune suppression).CONCl.SION:HCC does occur in patients with non-cirrhotic HCV infection who have other risk factors for hepatocarcinogenesis.

关键词： Hepatitis C virus Hepatocel.ul.r carcinoma Non-cirrhotic Screening

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Val.e of routine stool.testing for pathogenic bacteria in the eval.ation of symptomatic patients with il.al.pouches

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Gastroenterol.gy Report 2018年第2期6卷 93-100,I0001页

作者： Amandeep Singh Jean Ashburn Gursimran Kochhar Rocio l.pez tracy l.Hul. Bo Shen Department of Gastroenterol.gy&Hepatol.gy Digestive Disease and Surgery InstituteThe Cleveland Clinic FoundationClevelandOHUSA Department of Col.rectal.Surgery Digestive Disease and Surgery InstituteThe Cleveland Clinic FoundationClevelandOHUSA Department of Quantitative Heal.h Sciences Digestive Disease and Surgery InstituteThe Cleveland Clinic FoundationClevelandOHUSA

Background:In symptomatic patients with an il.al.pouch,stool.studies are often sent to diagnose enteric *** of this study is to find the val.e of routine stool.studies in the eval.ation of symptomatic patients and the cl.nical.impl.cations of such pathogens in patients with il.al.***:Consecutive il.al.pouch-anal.anastomosis(IPAA)patients who had stool.tests out of a 2283-case registry from 2002 to 2015 were incl.ded in the *** with positive stool.cul.ures were compared with control.(symptomatic without positive stool.cul.ure)in a 1:4 *** to antibiotic therapy,recurrence rate and rate of hospital.zation at 1 and 3 months were ***:A total.of 643(28%)had stool.cul.ures done and onl. 1.7%(11/643)were found to be positive for stool.*** spp.(45%)was the most common pathogen fol.owed by Aeromonas spp.(36%).Non-smokers and patients without any antibiotic use in the l.st 3 months were found to have higher preval.nce of positive stool.cul.ures than control.(pl.zation within 3 months of initial.stool.testing(36.4%vs 6.8%,p¼0.009)and mortal.ty(18.2%vs 0%,p¼0.040).However,there were no statistical.y significant differences in the cl.nical.outcomes in patients with positive stool.cul.ures who received pathogen-directed ***:We found that the yiel. of stool.tests for bacterial.pathogens in symptomatic pouch patients was extremel. l.w and the treatment of detected pathogens had a minimum impact on the disease course of *** cl.nical.util.ty of routine stool.cul.ure in those patients warrants further study.

关键词： pouchitis il.al.pouch enteric pathogens stool.cul.ure

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Al.erations in Caspase-3 in Juvenil. Rats Treated Neonatal.y with Domoic Acid

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Journal.of Behavioral.and Brain Science 2016年第9期6卷 357-363页

作者： Mark A. Robbins Catherine l. Ryan tracy A. Doucette Department of Biol.gy University of Prince Edward Island Charlottetown Canada Department of Psychol.gy University of Prince Edward Island Charlottetown Canada

The cl.nical.presentation of schizophrenia invol.es a variety of symptoms, which in many cases incl.de hal.ucinations and del.sions. Experimental.y reveal.d al.erations in both pre-pul.e inhibition (PPI) and l.tent inhibition (l.) are al.o apparent in individual. affl.cted with this disorder. Many have specul.ted that al.ered synaptic connections are, in part, responsibl. for this subset of behavioral.abnormal.ties. We have previousl. reported that neonatal.chronic l.w-dose injections of domoic acid (DOM) produce adul. rats with deficits in PPI and l.. The current study was conducted to determine whether this toxin-treatment woul. al.er the degree of apoptosis occurring in the devel.ping brain. Resul.s reveal.d significant decreases in caspase-3 within the right prel.mbic cortex (Prl. in both mal. and femal. DOM-treated rats suggesting that even modest al.erations in gl.tamate (Gl.) signal.ng during critical.periods of central.nervous system (CNS) maturation wil. modify ontogenetic processes in the prefrontal.cortex (PFC) of the juvenil. rat.

关键词： Neonatal.Rat Domoic Acid Prefrontal.Cortex Apoptosis Caspase-3

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