title: Endoscopic finding of spontaneous hemorrhage correlates with tumor necrosis factor alpha expression in colonic mucosa of patients with ulcerative colitis.
abstract: BACKGROUND
  Ulcerative colitis (UC) is an intractable colonic disease, and it shows several endoscopic findings. Recently, it was reported that the expression level of mucosal tumor necrosis factor alpha (TNF-α) was useful for predicting patient response to infliximab. However, no data regarding the value of endoscopic findings to predict treatment efficacy or cytokine expression level exist.
  
  
  OBJECTIVE
  We investigated the expression of leukocyte adhesion-related molecules and cytokines in colonic mucosa and compared it to endoscopic findings.
  
  
  METHODS
  One hundred and fifty-nine patients were enrolled. Tissue samples were obtained by colonic biopsy from patients with UC. Colitis activity was determined by Matts' criteria. The degree of mRNA expression of TNF-α, interferon gamma (IFN-γ), interleukin (IL)-8, IL-17A, and mucosal vascular addressin adhesion molecule-1 (MAdCAM-1) in mucosal samples was determined by real-time quantitative polymerase chain reaction. These expression levels were compared with the degree of Matts' grade and individual endoscopic findings.
  
  
  RESULTS
  The expression of TNF-α, IFN-γ, IL-8, IL-17A, and MAdCAM-1 mRNA significantly increased as Matts' endoscopic grade elevated. Actively inflamed mucosa with spontaneous hemorrhage revealed a significantly increased expression level of TNF-α mRNA than that without spontaneous hemorrhage. No other individual endoscopic parameter was significantly correlated with the expression level of TNF-α mRNA.
  
  
  CONCLUSIONS
  Inflamed mucosa with spontaneous hemorrhage may suggest increased expression of TNF-α mRNA levels in colonic mucosa of UC patients, which could predict a lower response to infliximab treatment and more aggressive induction regime or change to other therapy should be taken into account.
authors: Department of Internal Medicine, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors: Hideaki
authors: H
authors: Hozumi
authors: Ryota
authors: R
authors: Hokari
authors: Chie
authors: C
authors: Kurihara
authors: Kazuyuki
authors: K
authors: Narimatsu
authors: Hirokazu
authors: H
authors: Sato
authors: Shingo
authors: S
authors: Sato
authors: Toshihide
authors: T
authors: Ueda
authors: Masaaki
authors: M
authors: Higashiyama
authors: Yoshikiyo
authors: Y
authors: Okada
authors: Chikako
authors: C
authors: Watanabe
authors: Shunsuke
authors: S
authors: Komoto
authors: Kengo
authors: K
authors: Tomita
authors: Atsushi
authors: A
authors: Kawaguchi
authors: Shigeaki
authors: S
authors: Nagao
authors: Soichiro
authors: S
authors: Miura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D003113:Colonoscopy; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
references: Gut. 1999 Dec;45(6):856-63
references: 10562584
references: Vasc Health Risk Manag. 2008;4(4):805-17
references: 19065997
references: Stroke. 2006 Jan;37(1):231-4
references: 16322490
references: Microcirculation. 2001 Oct;8(5):283-301
references: 11687942
references: Eur J Med Res. 2002 Apr 30;7(4):171-6
references: 12010652
references: Gastroenterology. 1995 Oct;109(4):1344-67
references: 7557106
references: Gastroenterology. 2006 Jun;130(7):2060-73
references: 16762629
references: Gastroenterology. 2002 Mar;122(3):734-44
references: 11875006
references: Q J Med. 1961 Oct;30:393-407
references: 14471445
references: N Engl J Med. 2011 Nov 3;365(18):1713-25
references: 22047562
references: Gut. 2007 Sep;56(9):1181-3
references: 17698862
references: Am J Surg Pathol. 2000 Aug;24(8):1115-24
references: 10935652
references: Gastroenterology. 2009 Apr;136(4):1182-97
references: 19249397
references: Aliment Pharmacol Ther. 1996;10 Suppl 2:1-9
references: 8899095
references: Gastroenterology. 1994 Feb;106(2):533-9
references: 8299918
references: Cytokine. 1990 May;2(3):170-4
references: 2104220
references: N Engl J Med. 2002 Aug 8;347(6):417-29
references: 12167685
references: Am J Physiol. 1998 Jul;275(1):E27-31
references: 9688870
references: J Gastroenterol. 1997 Aug;32(4):480-6
references: 9250894
references: Neurosurgery. 2005 Sep;57(3):558-64; discussion 558-64
references: 16145536
references: Gut. 2011 May;60(5):571-607
references: 21464096
references: Am J Pathol. 1997 Jul;151(1):97-110
references: 9212736
references: Cytokine. 2009 May;46(2):222-7
references: 19286392
references: Nature. 2011 Jun 15;474(7351):307-17
references: 21677747
references: Gastroenterology. 1998 Jul;115(1):182-205
references: 9649475