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| 1 | Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors(Anti-TNFα)显示文摘AIM To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis(TB) infection in Crohn's disease(CD) patients treated with tumor necrosis factoralpha(TNFα) inhibitors.METHODS A meta-analysis of randomized, double-blind, placebocontrolled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction(EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds.RESULTS Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028(95%CI: 0.0011-0.055). The odds ratio was 4.85(95%CI: 1.02-22.99) with EBC and 5.85(95%CI: 1.13-30.38) without EBC.CONCLUSION The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition. | Brent L Cao Ahmad Qasem Robert C Sharp Latifa S Abdelli Saleh A Naser | 2018 | World Journal of Gastroenterology2018，24，25： | 4 |
| 2 | Role of PTPN2/22 polymorphisms in pathophysiology of Crohn's disease显示文摘AIM To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22(PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease(CD). METHODS All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms(SNPs) in PTPN2/22 using TaqMan^(?) genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis(MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin(PHA) mitogen or mycobacterial antigens by Brd U proliferation assays for T-cell activity. RESULTS Out of the nine SNPs examined, subjects with either heterozygous(TC)/minor(CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls(P-values < 0.05; OR = 3.03). Subjects with either heterozygous(GA)/minor(AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls(OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls(P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found(P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls(P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. T h e average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria. | Robert C Sharp Shazia A Beg Saleh A Naser | 2018 | World Journal of Gastroenterology2018，24，6： | 2 |
| 3 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 4 | Activities of several noveloxazolidinones against Mycobacterium tuberculosis in a murine model显示文摘 | Cynamon M H Klemens S P Sharpe C A | 1999 | Atimicrob AgentsChemother1999，43，： | 1 |
| 5 | The influence of the MAPK pathway on T cell lineage commitment显示文摘 | SHARP L L SCHWARZ D A BOTT C M | 1997 | Immunity1997，7，5： | 1 |
| 6 | siRNAs can function as miRNAs显示文摘 | Doench J G Petersen C P Sharp P A | | 0，，04： | 1 |
| 7 | FRVT 2006 and ICE 2006 large-scale ex- perimental results显示文摘 | Phillips P J Scruggs T O'Toole A Flynn P J Bowyer K W Sehott C Sharpe M | 2010 | IEEE Transactions on Pattern Analysis and Machine Intelligence2010，32，5： | 1 |
| 8 | Exercise beliefs and behaviors among older employees: A health promotion trial 显示文摘 | Sharpe P A Connel C M | 1992 | The Gerontologist1992，32，4： | 1 |
| 9 | Employment and location patterns of advanced services in non-urban Canada显示文摘 | WERNERHEIM C M SHARPE C A | 2005 | The Service Industries Journal2005，125，3： | 1 |
| 10 | Growth and'linkage of the East Tanka fault zone, Suez rift: Structural style and syn-rift stratigraphic response 显示文摘 | Jackson C A L Gawthorpe R L Sharp I A | 2002 | Journal of the Geological Society of London2002，159，： | 1 |
| 11 | Killing the messenger:short RNAs that silence gene expression显示文摘 | Dykxhoorn D M Novina C D Sharp P A | 2003 | Nat Rev Mol Cell Biol2003，4，6： | 1 |
| 12 | Oxidative desulphurisation of oils via hydrogen peroxide and heteropolyanion catalysis 显示文摘 | COLLINS E M LUCY A H SHARP C | 1997 | J Mol Catal A1997，117，13： | 1 |
| 13 | Broad-band optical parametric gain on a silicon photonie chip 显示文摘 | FOSTER M A TURNER A C SHARPING J E | 2006 | Nature2006，441，： | 1 |
| 14 | HAPl-huntingtin interac- tions do not contribute to the molecular pathology in Hnntingtin's disease transgenic mice 显示文摘 | Bertaux F Sharp A H Ross C A | 1998 | FEBS Lett1998，426，2： | 1 |
| 15 | Thyroxine - containing thyroglobulin peptide induces both lymphocytic and granulomatous forms of experimental autoimmune thyroiditis 显示文摘 | Braley - Mullen H Gordon C Sharp A | 1997 | J Autoimmune Dis1997，10，： | 1 |
| 16 | Isolation and characterization of human and mouse ZIRTL, a member of the IRT1 family of transporters, mapping within the epidermal differentiation complex 显示文摘 | Lioumi M Ferguson C A Sharpe P T | 1999 | Genomics1999，62，2： | 1 |
| 17 | B7 1PB7 eostimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low- density lipoprotein receptor- deficient mice显示文摘 | Buono C PangH Uchida Y Libby P Sharpe A Lichtman AH | 2004 | Circulation2004，109，16： | 1 |
| 18 | Diverse antibody recognition patterns of the multiple Sm-D antigen polypeptides显示文摘 | HOCH S O ELSENBERG R A SHARP G C | 1999 | Clini Immunol1999，92，2： | 1 |
| 19 | Spliced segments at the 5' terminus of adenovirus 2 late Mma显示文摘 | Berget S M Moore C Sharp P A | 1977 | PNAS1977，74，8： | 1 |
| 20 | Perioperative pain control显示文摘 | Dary T A Sharp C Lynch S | 2003 | Clin Pediatr Med Surg2003，20，2： | 1 |
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