Clinicopathological analysis of H. heilmannii-related gastric malignant lymphoma

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Shinshu University
• Principal Investigator: OTA Hiroyoshi Shinshu University, School of Medicine, Professor (50273107)
• Co-Investigator(Kenkyū-buntansha): FUJITA Kiyotaka Shinshu University, School of Medicine, Associate Professor (90313866) ; SANO Kenji Shinshu University, Hospital, Assistant Professor (50205994) ; NAKAYAMA Jun Shinshu University, School of Medicine, Professor (10221459) ; KATSUYAMA Tsutomu Shinshu University, School of Medicine, Professor (90020809)
• Project Period (FY): 2005 – 2007
• Keywords: gastritis / gastric malignant lymphoma / Helicobacter heilmannii / pathophysiology

Research Abstract

1. We have established persistent Helicobacter heilmannii (H. heilmannii) infection in BALB/c mice. Mice were sacrificed at 8, 26 and 56 weeks after inoculation of homogenate of gastric mucosa of H. heilmannii -infected mouse, which had been established by inoculation with homogenate of gastric biopsy from the H. heilmannii -infected patient. Sections prepared from stomachs immediately fixed in 20% formalin were stained with hematoxylin and eosin and immunostaining with anti H. pylon antibody, and mouse CD45R/B220 or MECA-79. H. heilmannii infection induced in the Mongolian gerbil a chronic active gastritis, in which a slight mucosal infiltration of neutrophils on a background of predominant chronic inflammation with lymphoid follicles, Lymphoepithelial lesion (LEL) and high endothelial venule (HEV) became detectable 26 weeks after the inoculation and continued up to 56 weeks in fundic mucosa. H. heilmannii were colonized in clusters in deep in the gastric pits and pyloric glands, and did not attach to gastric epithelial cells.
The mice model is a useful model for the study of H. heilmannii infection.
2. 'H. heilmannii' has been classified into types I and 2. Despite the inability of its cultivation, phylogenetic analysis of the 16S rRNA and urease genes has disclosed the occurrence of the types of 'H. heilmannii'. Prior to the examination, mice were successfully infected with the 'H. heilmannii' strains derived from the 7 patients from different district in Japan. The genomic DNA was extracted from the infected mice, amplified by using the 16S rRNA and urease primers, and then sequenced. Phylogenetic analysis of the sequences of 16S rRNA and urease genes retrieved from BLAST revealed that 6 of the 7 strains studied were 'H. heilmannii' type 1, demonstrating 99% similarities of the sequences within the 6 strains tested.

Research Products

• [Journal Article] Quantitative determination of gland mucous cells-type mucin using a monoclonal antibody, HIK1083: its pathophysiological changes in human gastric juice. (2007)
  • Author(s): Kubota S, Yamauchi K, Kumagai T, Sugano M, Kawasaki K, Tozuka M, Akamatsu T, Matsuzawa K, Sugiyama A, Kurihara M, Katsuyama T, Ota H.
  • Journal Title: Clin Chim Acta 377 Pages: 61-67
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Quantitative analysis of the effect of Helicobacter pylori on the expressions of SOX2, CDX2, MUC2, MUC5AC, MUC6, TFF1, TFF2, and TFF3 mRNAs in human gastric carcinoma cells. (2007)
  • Author(s): Matsuda K, Yamauchi K, Matsumoto T, Sano K, Yamaoka Y, Ota H.
  • Journal Title: Scand J Gastroenterol 43 Pages: 25-33
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] In vivo bactericidal activities of Japanese rice-fluid against H. pylori in a Mongolian gerbil model. (2007)
  • Author(s): Ishizone S, Maruta F, Suzuki K, Miyagawa S, Takeuchi M, Kanaya K, Oana K, Hayama M, Kawakami Y, Ota H.
  • Journal Title: Int J Med Sci 4 Pages: 203-208
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Quantitative determination of gland mucous cells-type mucin using a monoclonal antibody, HIK1083 : its pathophysiological changes in human gastric juice (2007)
  • Author(s): Kubota, S., Yamauchi, K., Kumagai, T., Sugano, M., Kawasaki, K., Tozuka, M., Akamatsu, T., Matsuzawa, IC., Sugiyama, A., Kurihara, M., Katsuyama, T., Ota, H
  • Journal Title: Clin Chim Acta 377 Pages: 61-67
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Quantitative analysis of the effect of Helicobacter pylori on the expressions of SOX2, CDX2, MUC2, MUC5AC, MUC6, TFF1, TFF2, and TFF3 mRNAs in human gastric carcinoma cells (2007)
  • Author(s): Matsuda, K., Yamauchi, K., Matsumoto, T., Sano, K., Yamaoka, Y., Ota H
  • Journal Title: Scand J Gastroenterol 43 Pages: 25-33
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vivo bactericidal activities of Japanese rice-fluid against H. pylori in a Mongolian gerbil model (2007)
  • Author(s): Ishizone, S., Maruta, F., Suzuki, K., Miyagawa, S., Takeuchi, M., Kanaya, K., Oana, K., Hayama, M., Kawakami, Y., Ota, H
  • Journal Title: Int J Med Sci 4 Pages: 203-208
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Comparison of localized gastric mucosa-associated lymphoid tissue(MALT)lymphoma with and without Helicobacter pylori infection. (2006)
  • Author(s): Akamatsu T, Mochizuki T, Okiyama Y, Matsumoto A, Miyabayashi H, Ota H.
  • Journal Title: Helicobacter 11 Pages: 86-95
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Ultrastructure of Helicobacter pylori in human gastric mucosa and H. pylori-infected human gastric mucosa using transmission electron microscopy and the high-pressure freezing-freeze substitution technique. (2006)
  • Author(s): Liu Y, Hidaka E, Kaneko Y, Akamatsu T, Ota H.
  • Journal Title: J Gastroenterol 41 Pages: 569-574
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] In vitro bactericidal activities of Japanese rice-fluid against Helicobacter pylori strains. (2006)
  • Author(s): Kawakami Y, Oana K, Hayama M, Ota H, Takeuchi M, Miyashita K, Matsuzawa T, Kanaya K.
  • Journal Title: Int J Med Sci 3 Pages: 112-116
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] High salt diets dose-dependently promote gastric chemical carcinogenesis in Helicobacter pylori-infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells. (2006)
  • Author(s): Kato S, Tsukamoto T, Mizoshita T, Tanaka H, Kumagai T, Ota H, Katsuyama T, Asaka M, Tatematsu M.
  • Journal Title: Int J Cancer 119 Pages: 1558-1566
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa. (2006)
  • Author(s): Ota H, Hayama M, Momose M, El-Zimaity HM, Matsuda K, Sano K, Maruta F, Okumura N, Katsuyama T.
  • Journal Title: Histochem Cell Biol 126 Pages: 617-625
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Trefoil factor 2 in gland mucous cell mucin in the mucous gel covering normal or damaged gastric mucosa using the Mongolian gerbil model. (2006)
  • Author(s): Suzuki K, Hayama M, Nakamura M, Yamauchi K, Maruta F, Miyagawa S, Ota H.
  • Journal Title: Scand J Gastroenterol 41 Pages: 1390-1397
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Helicobacter heilmannii感染と胃粘膜病変 (2006)
  • Author(s): 左田浩良, 松澤賢治, 沖山葉子, 細田和貴, 川久保雅友, 日高惠子, 川上由行, 勝山努
  • Journal Title: Helicobacter research 10 Pages: 57-62
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Helicobacter pylori感染証-基礎と臨床 (2006)
  • Author(s): 太田浩良, 羽山正義, 金子靖典, 松本竹久, 川上由行, 熊谷俊子, 久保田聖子, 勝山努
  • Journal Title: 臨床化学 35 Pages: 37-47
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ultrastructure of Helicobacter pylori in human gastric mucosa and H. pylon-infected human gastric mucosa using transmission electron microscopy and the high-pressure freezing-freeze substitution technique (2006)
  • Author(s): Liu, Y., Hidaka, E., Kaneko, Y., Akamatsu, T., Ota, H
  • Journal Title: J Gastroenterol 41 Pages: 569-574
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa (2006)
  • Author(s): Ota, H., Hayama, M., Momose, M., El-Zimaity, HM., Matsuda, K., Sano, K., Maruta, F., Okumura, N., Katsuyama, T
  • Journal Title: Histochem Cell Biol 126 Pages: 617-625
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Phylogenetic analysis of Helicobacter heilmannii isolates from different Japanese patients based on DNA sequences of 16S rRNA and urease genes (2006)
  • Author(s): Matsumoto, T., Kawkubo, M., Ota, H., Shiohara, M., Kumagai, T., Yamauchi, K., Katsuyama, T., Kawakami, Y
  • Journal Title: Helicobacter 11
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vitro bactericidal activities of Japanese rice-fluid against Helicobacter pylori strains (2006)
  • Author(s): Kawakami, Y., Oana, K., Hayama, M., Ota, H., Takeuchi, M., Miyashita, K., Matsuzawa, T., Kanaya, K
  • Journal Title: Int J Med Sci 3 Pages: 112-116
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Trefoil factor 2 in gland mucous cell mucin in the mucous gel covering normal or damaged gastric mucosa using the Mongolian gerbil model (2006)
  • Author(s): Suzuki, K., Hayama, M., Nakamura, M., Yamauchi, K., Maruta, F., Miyagawa, S., Ota, H
  • Journal Title: Scand J Gastroenterol 41 Pages: 1390-1397
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] H. pyloriの最近5年間における耐性獲得推移H. pylori除菌と消化性潰瘍・関連疾患-基礎・臨床研究のアップデート- (2005)
  • Author(s): 川上由行, 沖村幸枝, 小穴こず枝, 太田浩良, 勝山努
  • Journal Title: 日本臨床63(増刊号11) 63 Pages: 203-208
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 胃ムチンとの関係からみたHelicobacter pylori感染症-組織化学的および免疫組織化学的検討- (2005)
  • Author(s): 太田浩良, 小林幸弘, 羽山正義
  • Journal Title: Helicobacter research 9 Pages: 470-475
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] H.heilmannii infection and gastric mucosal lesions (in Japansese) (2005)
  • Author(s): Ota, H., Matsuzawa, K., Okiyama, Y., Hosoda, Y., Kawakubo, Hidaka, K., Kawakami,. Y, Katsuyama, T
  • Journal Title: Helicobacter research 9 Pages: 470-475
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] H. heilmannii長期感染マウスモデルによるH. heilmannii感染胃粘膜病変の解析 (2008)
  • Author(s): 鈴木彰、川久保雅友、小林基弘、太田浩良
  • Organizer: 第5回Helicobacter heilmannii研究会
  • Place of Presentation: 松本
  • Year and Date: 2008-02-09
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Heicobacter heilmannii-related gastric mucosal lesions induced in Mouse infection model (2008)
  • Author(s): Suzuki, A., Kawakubo, M., Kobayashi, M., Ota, H
  • Organizer: Vth Helicobacter heilmannii conference
  • Place of Presentation: Matsumoto
  • Year and Date: 2008-02-09
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Phylogenetic analysis of 'Helicobacter heilmannii' -like organisms from different Japanese patients based on DNA sequences of 16S rRNA and Urease genes (2007)
  • Author(s): Matsumoto T, Kawakubo M, Ota H, Shiohara M, Kumagai T, Yamauchi K, Katsuyama T, Kawakami Y
  • Organizer: International Symposium on Helicobacter heilmannii
  • Place of Presentation: 東京
  • Year and Date: 2007-04-25
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Phylogenetic analysis of 'Helicobacter heilmannii'-like organisms from different Japanese patients based on DNA seauences of 16S rRNA and Urease genes (2007)
  • Author(s): Matsumoto, T., Kawakubo, M., Ota, H., Shiohara, M., Kumagai, T., Yamauchi, K., Katsuyama, T., Kawakami, Y
  • Organizer: International Symposium on Helicobacter heilmannii
  • Place of Presentation: Tokyo
  • Year and Date: 2007-04-25
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Phylogenetic analysis of Helicobacter heilmannii isolates from different Japanese patients based on DNA sequences of 16s rRNA and urease genes (2006)
  • Author(s): Matsumoto T, Kawakubo M, Ota H, Shiohara M, Kumagai T, Yamauchi K, Katsuyama T, Kawakami Y
  • Organizer: XIXth International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation
  • Place of Presentation: Wroclaw, Poland
  • Year and Date: 2006-09-07
  • Description: 「研究成果報告書概要(和文)」より