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Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis

Cellular & Molecular Immunology 2015年第4期12卷 493-503页

作者： Anna-karin E Palm Heike C Friedrich Anja Mezger Maya Salomonsson linda.k.myers Sandra kleinau Department of Cell and Molecular Biology Uppsala University Uppsala Sweden Department of Pediatrics University of Tennessee Health ScienceCenter Memphis TN USA

Polyreactive innate-type B cells account for many B cells expressing self-reactivity in the periphery. Improper regulation of these B cells may be an important factor that underlies autoimmune disease. Here we have explored the influence of self-reactive innate B cells in the development of collagen-induced arthritis （CIA）, a mouse model of rheumatoid arthritis. We show that splenic marginal zone （MZ）, but not B- 1 B cells exhibit spontaneous IgM reactivity to autologous collagen II in na＇=＇ve mice. Upon immunization with heterologous collagen II in complete Freund＇s adjuvant the collagen-reactive MZ B cells expanded rapidly, while the B-1 B cells showed a modest anti-collagen response. The MZ B cells were easily activated by toll-like receptor （TLR） 4 and 9-1igands in vitro, inducing proliferation and cytokine secretion, implying that dual engagement of the B-cell receptor and TLRs may promote the immune response to self-antigen. Furthermore, collagen-primed MZ B cells showed significant antigen-presenting capacity as reflected by cognate T-cell proliferation in vitroand induction of IgG anti-collagen antibodies in vivo. MZ B cells that were deficient in complement receptors I and 2 demonstrated increased proliferation and cytokine production, while Fcy receptor lib deficiency of the cells lead to increased cytokine production and antigen presentation. In conclusion, our data highlight self-reactive MZ B cells as initiators of the autoimmune response in CIA, where complement and Fc receptors are relevant in controlling the self-reactivity in the cells.

关键词： arthritis complement receptors Fc receptors marginal zone B cells, mice

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Association between admission haematocrit and mortality among men with acute ischaemic stroke

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Stroke & Vascular Neurology 2018年第3期3卷 160-168页

作者： Jason J Sico Laura J myers Brenda J Fenton John Concato linda S Williams Dawn M Bravata Neurology Service VA Connecticut Healthcare SystemWest HavenConnecticutUSA Department of Neurology Center for NeuroEpidemiological and Clinical Neurological ResearchYale University School of MedicineNew HavenConnecticutUSA Department of Internal Medicine Yale University School of MedicineNew HavenConnecticutUSA Clinical Epidemiology Research Center(CERC) VA Connecticut Healthcare SystemWest HavenConnecticutUSA Pain Research InformaticsMultimorbidities and Education(PRIME)Center of InnovationVA Connecticut Healthcare SystemWest HavenConnecticutUSA Communication and the HSR&D Stroke Quality Enhancement Research Initiative(QUERI) Richard L Roudebush VA Medical CenterIndianapolisIndianaUSA VA Health Services Research and Development(HSR&D) Center for Healthcare InformaticsRichard L Roudebush VA Medical CenterIndianapolisIndianaUSA Division of Chronic Disease Epidemiology Yale School of Public HealthWest HavenConnecticutUSA Medical Service VA Connecticut Healthcare SystemWest HavenConnecticutUSA Regenstrief Institute IndianapolisIndianaUSA Department of Neurology Indiana University School of MedicineIndianapolisIndianaUSA Department of Internal Medicine Indiana University School of MedicineIndianapolisIndianaUSA

Objective Anaemia is associated with higher mortality among patients with non-stroke cardiovascular conditions;less is known regarding the relationship between anaemia and mortality among patients with acute ischaemic *** Medical records were abstracted for n=3965 veterans from 131 Veterans Health Administration facilities who were admitted with ischaemic stroke in fiscal year *** values within 24 hours of admission were classified as≤27%,28%-32%,33%-37%,38%-42%,43%-47% or≥48%.Multivariate logistic regression was used to examine the relationship between anaemia and in-hospital,30-day,6-month and 1-year mortality,adjusting for age,medical comorbidities,modified Acute Physiology and Chronic Health Evaluation-III and stroke *** factors were calculated to standardise comparisons between haematocrit tier and other *** Among n=3750 patients included in the analysis,the haematocrit values were≤27%in 2.1%(n=78),28%-32% in 6.2%(n=234),33%-37%in 17.9%(n=670),38%-42% in 36.4%(n=1366),43%-47% in 28.2%(n=1059)and≥48% in 9.1%(n=343).Patients with haematocrit≤27%,compared with patients in the 38%-42% range,were more likely to have died across all follow-up intervals,with statistically significant adjusted ORs(aORs)ranging from 2.5 to *** with polycythaemia(ie,haematocrit≥48%)were at increased risk of in-hospital mortality(aOR=2.9;95%CI 1.4 to 6.0),compared with patients with mid-range admission *** differences between patients receiving and not receiving blood transfusion limited our ability to perform a propensity *** factors in the 1-year mortality model were 0.46(severe anaemia),0.06(cancer)and 0.018(heart disease).Conclusions Anaemia is independently associated with an increased risk of death throughout the first year post stroke;high haematocrit is associated with early poststroke *** anaemia is associated with 1-year mortality to a greater degree than cancer or heart dise

关键词： mortality admitted transfusion

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Registered Dietitian Wellness Insurance Benefit Makes a Difference in Adult Weight Management: A Pre-Post Study

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Food and Nutrition Sciences 2011年第10期2卷 1043-1047页

作者： linda Snetselaar karen L. Smith Donna Hollinger Esther myers Gwen Murphy Laura Goettinger Qualls 不详

Registered Dietitian (RD) services as part of insurance wellness programs offer a promising potential venue for improving public health. This study was conducted to evaluate the effectiveness of RD nutrition counseling services provided as part of an insurance benefit on body weight and associated health parameters. Eligible members could enroll to receive 6 RDs visits a year for assistance with weight management. The study RDs were randomized into either Usual Care (UC) or Lifestyle Case Management (LCM) groups. Body weight, waist circumference, and systolic and diastolic blood pressure measurements of program enrollees were evaluated for between group as well as start and end program comparisons. There was a statistically significant difference in the number of RD follow-up visits between the two groups as LCM patients had more RD contact than UC patients. Weight and waist circumference changes from baseline to end of study show statistically significant changes with a trend for improvement in systolic blood pressure. Additionally, a clinically significant reduction in weight was achieved in a quarter of program enrollees. In conclusion this study shows that through a coordinated health promotion program RDs’ services are of value to an insured population.

关键词： RD Nutrition Counseling Insurance Benefit Weight Loss Blood Pressure

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Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection

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World Journal of Gastrointestinal Oncology 2014年第10期6卷 413-419页

作者： HMC Shantha kumara Elizabeth A myers Sonali AC Herath Joon Ho Jang linda Njoh Xiaohong Yan Daniel kirchoff Vesna Cekic Martin Luchtefeld Richard L Whelan Division of Colon and Rectal Surgery Department of Surgery Mount Sinai-Roosevelt Hospital Center New York NY 10019 United States Division of Colon and Rectal Surgery Fer-guson Clinic Grand Rapids MI 49546 United States Icahn School of Medicine at-Mount Sinai New York NY 10029 United States Surgical Oncology Department of Surgery College of Physicians and Surgeons Columbia University New York NY 10032 United States

AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer(CRC) and benign patients and postoperatively after CRC ***: A plasma bank was screened for minimally invasive colorectal cancer resection(MICR) for CRC and benign disease(BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples(postoperative day 7-27) were available. Monocyte chemotactic protein-1(MCP-1) levels(pg/mL) were determined via enzyme linked immuno-absorbent assay. RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level(283.1, CI: 256.0, 294.3) was higher than the BEN group level(227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1(446.3, CI: 418.0, 520.1), postoperative day 3(342.7, CI: 320.4, 377.4), postoperative day 7-13(326.5, CI: 299.4, 354.1), postoperative day 14-20(361.6, CI: 287.8, 407.9), and postoperative day 21-27(318.1, CI: 287.2, 371.6; P < 0.001 for all). CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients(vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.

关键词： Colorectal cancer Monocyte chemotactic protein-1 Minimally invasive colorectal resection angio-genesis

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審計品質的持續性與會計師聲譽的資訊性——會計師個人層級的分析

審計品質的持續性與會計師聲譽的資訊性——會計師個人層級的分析

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2014第六届海峡两岸会计学术研讨会

作者：戚務君 Ling Lei Lisic linda A.myers Mikhail Pevzner 政治大學 George Mason University University of Arkansas University of Baltimore

本文以會計師個人層級為分析對象,檢視審計品質（以財務報表誤述衡量）的持續性以及會計師聲譽（以財務報表重述事件衡量）的資訊性(以是否影響會計師的市占率來衡量。實證結果支持,當分析焦點為個人會計師層及時,審計品質有持續性且聲... 详细信息

本文以會計師個人層級為分析對象,檢視審計品質（以財務報表誤述衡量）的持續性以及會計師聲譽（以財務報表重述事件衡量）的資訊性(以是否影響會計師的市占率來衡量。實證結果支持,當分析焦點為個人會計師層及時,審計品質有持續性且聲譽的確具資訊性。

关键词：審計品質合夥會計師誤述財務報表重述

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大自然的残酷与温柔

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空中英语教室（高级版．彭蒙惠英语） 2023年第3期 14-16,41,42页

作者： linda Robertson 不详

看看一对夫妻及其宠物们是如何在暴风雨中觅得避难所,以及圣送戈动物园是如何庆祝新生命降临的一名兽医和她的宠物们在停车场熬过飓风伊恩的凶暴之眼当飓风伊恩横扫佛罗里达州的迈尔斯堡,带来呼啸的狂风和泛滥的洪水淹没克卢萨哈奇河岸... 详细信息

看看一对夫妻及其宠物们是如何在暴风雨中觅得避难所,以及圣送戈动物园是如何庆祝新生命降临的一名兽医和她的宠物们在停车场熬过飓风伊恩的凶暴之眼当飓风伊恩横扫佛罗里达州的迈尔斯堡,带来呼啸的狂风和泛滥的洪水淹没克卢萨哈奇河岸时,兽医莎伦·鲍威尔和先生退避到他们为自己和宠物们能找到的最安全的地方——市中心的一座停车场。

关键词：宠物洪水淹没迈尔斯停车场一对夫妻鲍威尔避难所佛罗里达州

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Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 374-382页

作者： Yasser Fouad Melissa Palmer Minjun Chen Arie Regev Rajarshi Banerjee Rob myers Robert Riccio Richard Torstenson Ramy Younes Puneet SArora Henrik Landgren Morten A.karsdal Martin Blake David A.Shapiro Hans-Juergen Gruss Muhammad Y.Sheikh Dina Attia Steven Bollipo Alastair D.Smith Bradley Freilich Robert G.Gish Detlef Schuppan Department of Gastroenterology Hepatologyand Endemic MedicineFaculty of MedicineMinia UniversityMiniaEgypt Gan-nex/Ascletis Pharma Co Ltd BeijingChina Liver Consulting LLC New YorkNYUSA Division of Bioinformatics and Biostatis-tics National Center for Toxicological ResearchUS Food and Drug AdministrationJeffersonARUSA Eli Lilly and Company IndianapolisINUSA Perspectum Diagnostics Ltd OxfordUK Gilead Sciences Inc Foster CityCAUSA Syneos Health LLC MorrisvilleNCUSA Allergan Marlow International BuckinghamshireUKAstraZenecaCambridgeUK Boehringer Ingel-heim International GmbHIngelheimGermany Genentech IncSouth San FranciscoCAUSA AbbVie MarlowBuck-inghamshireUK Nordic Bioscience A/S HerlevDenmark Resonance Health BurswoodWAAustralia Intercept Phar-maceuticals Inc San DiegoCAUSA Fresno Clinical Research Center FresnoCAUSA Gastroenterology and Hepatology Department Beni-Suef UniversityBeni SuefEgypt Department of Gastroenterology and Endoscopy John Hunter HospitalNewcastleNSWAustralia School of Medicine and Public Health University of NewcastleNewcastleNSWAustralia kan-sas City Research Institute Kansas CityMOUSA Division of Gastroenterology and Hepatology Loma Linda UniversityLoma LindaCAUSA Institute of Translational Immunology and Research Center for Immune Therapy University Medical CenterMainzGermany Division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

Metabolic(dysfunction)-associated fatty liver disease(MAFLD)affects a third of the population and is a leading cause of liver-related *** no effective treatments exist,novel approaches to drug development are ***,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and *** international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLD)to MAFLD,includ-ing a proposal for how the disease should be *** allies with the many stakeholders in MAFLD care―including patients,patients’advocates,clinicians,researchers,nurse and allied health groups,regional societies,and others―we are aware of the negative consequences of the NAFLD term and *** share the sense of urgency for change and will act in new ways to achieve our *** there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLD initiative provides a firm foundation to build *** provides a roadmap for moving for-ward toward more efficient care and affordable,sustainable drug and device innovation in MAFLD *** hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health *** this viewpoint,we have revisited this initiative through the perspectives of drug development and regulatory science.

关键词： NAFLD MAFLD NASH Fatty liver disease Liver Fibrosis

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Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

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World Journal of Gastroenterology 2016年第12期22卷 3418-3431页

作者： Ira Jacobson Stefan Zeuzem Robert Flisiak Brygida knysz Stefan Lueth Dorota Zarebska-Michaluk Ewa Janczewska Peter Ferenci Moises Diago Anna linda Zignego Rifaat Safadi Yaacov Baruch Dzhamal Abdurakhmanov Stephen Shafran Dominique Thabut Rafael Bruck Adrian Gadano Alexander James Thompson Justin kopit Fiona Mc Phee Tracy Michener Eric A Hughes Philip D Yin Stephanie Noviello Weill Cornell Medical College New YorkNY 10029United States Icahn School of Medicine at Mount Sinai New YorkNY 10029United States JW Goethe University Hospital 60323 FrankfurtGermany Uniwersytet Medyczny w Bialymstoku 15-089 BialystokPoland EMC and Medical University 50-220 WroclawPoland Universitatsklinikum Hamburg-Eppendorf 20246 HamburgGermany Wojewodzki Szpital Zespolony w kielcach 25-736 KielcePoland ID Clinic 41-400 MyslowicePoland Medizinische Universitat Wien 1090 ViennaAustria Clinica Quiron 46010 ValenciaSpain Universita degli Studi di Firenze 50121 FlorenceItaly Holy Family Hospital Nazareth 6004Israel Rambam Medical Center Haifa 31096Israel 1st Moscow State Medical University N.A.I.M.Sechenov 119991 MoscowRussia University of Alberta Hospital EdmontonAlberta T6G 2B7Canada Groupe Hospitalier Pitie-Salpetriere 75013 ParisFrance Tel Aviv Sourasky Medical Center and Tel Aviv University Tel Aviv 64239Israel Hospital Italiano de Buenos Aires Buenos Aires C1181ACHArgentina St.Vincents Hospital and the University of Melbourne Melbourne 3065Australia Fiona McPhee Bristol-Myers Squibb Research and DevelopmentWallingfordCT 06492United States Bristol-myers Squibb Research and Development PrincetonNJ 08450United States

AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin(peg IFN/RBV), in treatment-naive hepatitis C virus(HCV) genotype(GT) 1-infected ***: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned(2:1) to daclatasvir vs telaprevir, stratified by IL28 B rs12979860 host genotype(CC vs non-CC), cirrhosis status(compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype(GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus peg IFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus peg IFN/RBV; those without an extended rapid virologic response(e RVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of peg IFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus peg IFN/RBV followed by 12(with e RVR) or 36(no e RVR) wk of peg IFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12(SVR12) in GT1b-infected patients. key secondary objectives were to demonstrate that the rates of anemia(hemoglobin k 12, were lower with daclatasvir + peg IFN/RBV than with telaprevir + peg IFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5 A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/m L, to investigate any link between NS5 A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups(6.0% and 8.2% in the GT1 b and GT1 a groups, respectively) than in the telaprevi

关键词： Direct-acting antiviral Chronic hepatitis C Daclatasvir Genotype 1b NS5A inhibitor Liver disease

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