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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 | 在 7T 的多原子的磁性的回声光谱学的应用显示文摘 AIM: To discuss the advantages of ultra-high field (7T) for 1H and 13C magnetic resonance spectroscopy (MRS) studies of metabolism.made at both 3 and 7T using 1H MRS. Measurements of glycogen and lipids in muscle were measured using 13C and 1H MRS respectively. RESULTS: In the brain, increased signal-to-noise ratio (SNR) and dispersion allows spectral separation of the amino-acids glutamate, glutamine and γ-aminobutyric acid (GABA), without the need for sophisticated editing sequences. Improved quantification of these me-tabolites is demonstrated at 7T relative to 3T. SNR was 36% higher, and measurement repeatability (% coefficients of variation) was 4%, 10% and 10% at 7T, vs 8%, 29% and 21% at 3T for glutamate, glutamine and GABA respectively. Measurements at 7T were used to compare metabolite levels in the anterior cingulate cortex (ACC) and insula. Creatine and glutamate levels were found to be significantly higher in the insula compared to the ACC (P < 0.05). In muscle, the increased SNR and spectral resolution at 7T enables interleaved studies of glycogen (13C) and intra-myocellular lipid (IMCL) and extra-myocellular lipid (EMCL) (1H) following exercise and refeeding. Glycogen levels were sig-nificantly decreased following exercise (-28% at 50% VO2 max; -58% at 75% VO2 max). Interestingly, levels of glycogen in the hamstrings followed those in the quadriceps, despite reduce exercise loading. No changes in IMCL and EMCL were found in the study. CONCLUSION: The demonstrated improvements in brain and muscle MRS measurements at 7T will increase the potential for use in investigating human metabolism and changes due to pathologies. | Mary C Stephenson Frances Gunner Antonio Napolitano Paul L Greenhaff Ian A MacDonald Nadeem Saeed William Vennart Susan T Francis Peter G Morris | 2011 | World Journal of Radiology2011，3，4： | 2 |
| 3 | Chilling injury in peach and nectarine显示文摘 | Susan L Carlos H C | 2005 | Postharvest Biology and Technology2005，37，3： | 1 |
| 4 | Quantification of XPA gene expression levels in human and mouse cell lines by competitive RT-PCR显示文摘 | Susan K L James E C | 1997 | Mutaion Reasearch1997，387，1： | 1 |
| 5 | Genome sequence and analysis of the soil cellulolytic actinomyeete Thermobifidafusca YX 显示文摘 | Athanasios L Konstantinos M Natalia I lain A Miriam L Genevieve D Michele M Alia L Susan L Alex C Paul R David BW Nikos K | 2007 | J Bacteriol2007，189，6： | 1 |
| 6 | Persistent DDT metabolite, p,p'-DDE is a potent androgen receptor antagonist显示文摘 | William R K Christy R S Susan C L | 1995 | Nature1995，375，6532： | 1 |
| 7 | Centrosome amplification drives chromosomal instability in breast tumor development显示文摘 | Wilma L L Susan L B Vivian C N | 2002 | Proc Natl Acad Sci U S A2002，99，4： | 1 |
| 8 | The future of electrical and computer engineering education显示文摘 | Frederick C B Philip S D Susan L S | 2003 | IEEE Transactions on Education2003，46，4： | 1 |
| 9 | Training a neural-network based intrusion detector to recognize novel attacks显示文摘 | Susan C L David V H | 2001 | IEEE Transactions on systems man and cybernetics-part a:System and Humans2001，31，： | 1 |
| 10 | Detailed absorption,reflectance,and UV photoelectron spectroscopic and theoretical studies of the charge-transfer transitions of tetrachlorocuprate(2-) ion:correlation of the square-planar and the tetrahedral limits显示文摘 | Sylvie R D Kevin W Susan L C | 1983 | J Am Chem Soc1983，105，： | 1 |
| 11 | The Impact of psychiatric disorders on labor market outcomes 显示文摘 | Ettner Susan L Frank Richard G Ronald C Kessler | 1997 | Industrial and Labor Relations Review1997，，51： | 1 |
| 12 | A post-1990s sassessment of strategic hospital alliances and their marketplace orientations-time to refocus显示文摘 | Peter C O Susan D R Roice D L | 2002 | Health Care Management Review2002，27，2： | 1 |
| 13 | On- Line Trust: Concepts, Evolving Themes, A Model, Int显示文摘 | CORRITORE C L BEVERLY K SUSAN W | 2003 | Human-Commputer Studies2003，58，7： | 1 |
| 14 | Anomalous preservation of pure methane hydrate at I atm显示文摘 | Stem L A Susan C Stephen H K | 2001 | Physical Chemistry B2001，105，： | 1 |
| 15 | Nuclear factor-κB and cell death after experimental intraeerebral hemorrhage in rats 显示文摘 | Susan L Hickenbottom MD James C | 1999 | Stroke1999，30，： | 1 |
| 16 | Targeted Recombination within the Spike Gene of Murine Coro- navirus Mouse Hepatitis Virus-A59:Q159 Is a Deter- minant of Hepatotropism显示文摘 | Isabelle L G Susan T H MING M C | 1998 | J Virol1998，72，12： | 1 |
| 17 | Struc- ture-based design of potent and selective inhibitors of the metabolic kinase PFKFB3 显示文摘 | SCOTT B JOANAN L B SUSAN E C | 2015 | J Med Chem2015，58，8： | 1 |
| 18 | Training a Neural-network Based Intrusion Detector显示文摘 | Susan C L David V H | 2001 | IEEE Transaction son systems manandcybemetics-parta : System and Humans2001，31，4： | 1 |
| 19 | Persistent DDT metabolite P,P' -DDE is a potent, androgen receptor antagonist显示文摘 | William R Christy R S Susan C L | 1995 | Nature1995，375，15： | 1 |
| 20 | Multidrug resistance proteins : role of P-glycoprotein, MRP1, MRP2, and BCRP ( ABCG2 ) in tissue defense 显示文摘 | ELAINE M L ROGER G D SUSAN P C | 2005 | Toxicol Appl Pharmacol2005，204，3： | 1 |
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