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| 1 | Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy显示文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC 'responders'(n = 12) and 'non-responders'(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy. | Angela C Baird Dominic Mallon Graham Radford-Smith Julien Boyer Thierry Piche Susan L Prescott Ian C Lawrance Meri K Tulic | 2016 | World Journal of Gastroenterology2016，22，41： | 10 |
| 2 | Dynamic modeling of pressure reducing valves显示文摘 | Prescott S L Ulanicki B | 2003 | Journal of Hydraulic Engineering2003，129，10： | 1 |
| 3 | Probiotic supplementation for the first 6 months of Iife fails to reduce the risk of atopic dermatitis and in- creases the risk of allergen sensitization in highrisk children:a randomized controlled显示文摘 | TAYLOR A L DUNSTAN J A PRESCOTT S L | 2007 | J Allergy Clin Immunol2007，119，： | 1 |
| 4 | Body size, recrea- tional physical activity, and B-cell non-Hodgkin lymphoma risk among women in the California teachers study显示文摘 | Yani L Prescott J Sullivan-Halley J | 2009 | Am J Epide- miol2009，17，： | 1 |
| 5 | Prenatal fatty acid status and immune development : The path ways and the evidence显示文摘 | Prescott S L Dunstao J A | 2007 | Lipids2007，42，： | 1 |
| 6 | Anode phenomena in metal-vapor arcs at high currents显示文摘 | Rich J A Prescott L E Cobine J D | 1971 | J Appl Phys1971，42，： | 1 |
| 7 | Xenon purity analysis for exo-200 via mass spectrometry 显示文摘 | Dobi A Hall C Slutsky S Yen Y R Aharmin B Auger M Barbeau P S Benitez-Medina C Breidenbach M Cleveland B Conley R Cook J Cook S Counts I Craddock W Daniels T Davis C G Davis J Devoe R Dixit M Dolinski M J Donato K Fairbank Jr W Farine J Fierlinger P Franco D Giroux G Gornea R Graham K Gratta G Green C Hagemann C Hall K Hallman D Hargrove C Herrin S Hughes M Hodgson J Juget F Karelin A Kaufman L J Kuchenkov A Kumar K Leonard D S Lutter G Mackay D Maclellan R Marino M Mong B Montero Diez M Morgan P MUller A R Neilson R Odian A Oullivan K Piepke A Pocar A Prescott C Y Pushkin K Rivas A Rollin E Rowson P C Sabourov A Sinclair D Skarpaas K Stekhanov V Strickland V Swift M Twelker K Vuilleumier J L Vuilleumier J M Weber M Wichoski U Wodin J Wright J D Yang L | 2012 | Nuclear Instruments and Methods in Physics Research Section A: Accelerators Spectrometers Detectors and Associated Equipment2012，675，： | 1 |
| 8 | Causal relationship be- tween stressful life events and the onset of major depression显示文摘 | Kendler K S Karkowski L M Prescott C A | 1999 | Am J Psychiatry1999，156，6： | 1 |
| 9 | Preparation and characterization of the lower equilibrated phenylsilsesquioxanes 显示文摘 | Brown J F Vogt L H Prescott P I | 1964 | J Am Chem Soc1964，86，6： | 1 |
| 10 | Single- dose live-attenuated vesicular stomatitis virus-based vaccine protects African green monkeys from Nipah virus disease显示文摘 | Prescott J DeBuysscher B L Feldmann F | 2015 | Vaccine2015，33，： | 1 |
| 11 | Causal relationship between stressful life events and onset of major depression 显示文摘 | Kendler KS Karkowshi L M Prescott CA | 1999 | Am J Psychiatry1999，156，8： | 1 |
| 12 | Critical preservation injury in rat fatty liver is to hepatocytes, not sinusoidal lining cells 显示文摘 | Taneja C Prescott L Koneru B | 1998 | Transplantation1998，65，2： | 1 |
| 13 | Interrelations between relapses,drugregimens and compliance with treatment in tuberculosis显示文摘 | Ormerod L P Prescott R J | 1991 | Respir Med1991，85，3： | 1 |
| 14 | Nitrogen turnover in forest floors of coastal douglas-fir at sites differing in soil nitrogen capital显示文摘 | Prescott C E Chappell N H Vesterdal L | 2000 | Ecology2000，81，： | 1 |
| 15 | Protein kinase Cζ:A novel protective neonatal T-cell marker that can be upregulated by allergy prevention strategies显示文摘 | Susan L Prescott James Irvine | | 0，，1： | 1 |
| 16 | Barriers to Technology Adoption and Development 显示文摘 | PARENTE L PRESCOTT C | 1994 | Journal of Public Economics1994，120，2： | 1 |
| 17 | Causal relation-ship between stressful life events and onset of major depression 显示文摘 | KENDLER KS KARKOWSHI L M PRESCOTT CA | 1999 | Am J Psychiatry1999，156，8： | 1 |
| 18 | Nitrogen turnover in forest floors of coastal Douglas-fir at sites differing in soil nitrogen capital 显示文摘 | PRESCOTT C E CHAPPELL H N VESTERDAL L | 2000 | Ecology2000，81，7： | 1 |
| 19 | Monopoly Rights:A Barrier to Riches显示文摘 | PARENTE S L PRESCOTT E C | 1999 | American Economic Review 891999，，： | 1 |
| 20 | Diuresis or urinary alkalinisation for salicylate poisoning?显示文摘 | Prescott L F BalaliMood M Critchley J A | 1982 | Br Med J1982，285，6352： | 1 |
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