Faculty Profiles - YOKOTA Kenji

MISC - YOKOTA Kenji

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Effects of nitrate-reducing bacteria from the gastric cancer patients in H. pylori co-infected mice

小松原万里奈, 山本由弥子, 内山淳平, 松下治, 後藤和義, 渡辺朱理, 横田憲治

日本細菌学雑誌(Web) 79 ( 2 ) 2024

The panel of antibiotic-resistant strains of Helicobacter pylori

林俊治, 大崎敬子, 竹内啓晃, 横田憲治, 横田伸一, 林原絵美子

日本細菌学雑誌(Web) 27回 ( 1 ) 180 - 180 2021.9

尿沈渣標本中に出現する顆粒状物質と尿路感染症細菌との関連について

佐藤妃映, 横田憲治, 渡辺朱理, 苔口進, 衛藤友美, 高阪翔士

日本環境感染学会総会プログラム・抄録集 33回 297 - 297 2018.2

環境汚染菌の消毒剤および除菌洗浄剤含浸ワイプによる拭き取り除去効果

横田憲治, 渡邉都貴子, 林俊治, 渡辺朱理, 苔口進, 平井義一, 松下治

日本防菌防黴学会誌 46 ( 1 ) 3 - 8 2018.1

Language：Japanese Publisher：日本防菌防黴学会

近年、環境汚染菌による院内感染が報告され、環境整備の重要性が認められつつある。今回、消毒剤および除菌剤の除染効果を比較検討するため、環境中の細菌の生存状態とATP測定の基礎的検討と各種消毒剤または除菌剤を含浸させたワイプによる拭き取り効果について検討した。乾燥による生菌数への影響に関する検討では、一定の濃度に調製した多剤耐性Acinetobacter baumanniiおよびBacillus cereusを乾燥状態で放置し、経時的に細菌数の指標としてATP値とコロニー数を計測した。シャーレの中で乾燥状態にしたB.cereusは1日目でATP値が有意に低下したが、A.baumanniiは有意な低下を認めるまでに7日間を要した。7日目のコロニー数を計測したところ、A.baumanniiおよびB.cereus共に生菌として検出された。拭き取りによる除菌効果は、ステンレス板とポリプロピレン板にA.baumanniiおよびB.cereusを塗布し、上記消毒剤または除菌剤含浸ワイプで拭き取り、その前後におけるATP量およびコロニー数を比較検討した。拭き取り効果は、材質による差は認められなかった。また、いずれの含浸ワイプによる拭き取りにおいても同様に有意な菌数の低下が認められ、いずれの細菌に対しても消毒剤または除菌剤は5log10CFU以上の減少を認めた。(著者抄録)

環境汚染菌の消毒剤および除菌洗浄剤含浸ワイプによる拭き取り除去効果

横田憲治, 渡邉都貴子, 林俊治, 渡辺朱理, 苔口進, 平井義一, 松下治

日本防菌防黴学会誌 46 ( 1 ) 3 - 8 2018.1

Language：Japanese Publisher：日本防菌防黴学会

近年、環境汚染菌による院内感染が報告され、環境整備の重要性が認められつつある。今回、消毒剤および除菌剤の除染効果を比較検討するため、環境中の細菌の生存状態とATP測定の基礎的検討と各種消毒剤または除菌剤を含浸させたワイプによる拭き取り効果について検討した。乾燥による生菌数への影響に関する検討では、一定の濃度に調製した多剤耐性Acinetobacter baumanniiおよびBacillus cereusを乾燥状態で放置し、経時的に細菌数の指標としてATP値とコロニー数を計測した。シャーレの中で乾燥状態にしたB.cereusは1日目でATP値が有意に低下したが、A.baumanniiは有意な低下を認めるまでに7日間を要した。7日目のコロニー数を計測したところ、A.baumanniiおよびB.cereus共に生菌として検出された。拭き取りによる除菌効果は、ステンレス板とポリプロピレン板にA.baumanniiおよびB.cereusを塗布し、上記消毒剤または除菌剤含浸ワイプで拭き取り、その前後におけるATP量およびコロニー数を比較検討した。拭き取り効果は、材質による差は認められなかった。また、いずれの含浸ワイプによる拭き取りにおいても同様に有意な菌数の低下が認められ、いずれの細菌に対しても消毒剤または除菌剤は5log10CFU以上の減少を認めた。(著者抄録)

歯科予防処置における飛散汚染状況調査 ATP測定法と細菌培養法からの検討

渡辺朱理, 苔口進, 横田憲治, 松山美和

日本歯科衛生学会雑誌 12 ( 1 ) 145 - 145 2017.8

H.pylori感染胃炎の内視鏡診断の進歩 H.pylori除菌後再感染は、内視鏡所見で診断できるか?

大林由佳, 武進, 榮浩行, 河野吉泰, 三浦公, 楠本智章, 横田憲治, 水野元夫, 岡田裕之

日本ヘリコバクター学会学術集会プログラム・抄録集 23回 109 - 109 2017.6

Beyondボノプラザン標準療法当院における3次除菌療法(PPI/P-CAB+AMPC+STFX)とペニシリンアレルギーに対する治療成績の検討

榮浩行, 横田憲治, 大林由佳, 河野吉泰, 三浦公, 岡田裕之

日本ヘリコバクター学会学術集会プログラム・抄録集 23回 90 - 90 2017.6

細菌性コラゲナーゼのマトリックス・アンカーの構造解析と骨新生誘導のための複合剤開発(Structural analysis of a matrix anchor in bacterial collagenase to develop an osteogenic therapeutic)

松下治, 内田健太郎, 関口裕之, 美間健彦, 後藤和義, 山本由弥子, 横田憲治, 高相晶士, Bauer Ryan, Sakon Joshua

日本細菌学雑誌 72 ( 1 ) 109 - 109 2017.2

Vibrio alginolyticusのコラゲナーゼ発現はHapRにより調節される(Expression of colA is regulated by HapR in Vibrio alginolyticus)

美間健彦, 西川裕太郎, 中田悠介, 波多野直哉, 後藤和義, 山本由弥子, 横田憲治, 松下治

日本細菌学雑誌 72 ( 1 ) 106 - 106 2017.2

腸肝在位Helicobacter感染症研究の最前線肝胆道系疾患とヘパティカス菌感染

横田憲治

日本細菌学雑誌 72 ( 1 ) 32 - 32 2017.2

エアロゾルサンプルからの非結核性抗酸菌の分離検出

平井一行, 横田憲治, 平井義一

日本環境感染学会総会プログラム・抄録集 32回 257 - 257 2017.2

Vibrio alginolyticusのコラゲナーゼ発現はHapRにより調節される(Expression of colA is regulated by HapR in Vibrio alginolyticus)

美間健彦, 西川裕太郎, 中田悠介, 波多野直哉, 後藤和義, 山本由弥子, 横田憲治, 松下治

日本細菌学雑誌 72 ( 1 ) 106 - 106 2017.2

病院内環境におけるメチシリン耐性ブドウ球菌調査

渡辺朱理, 横田憲治, 苔口進, 松山美和

日本歯科衛生学会雑誌 11 ( 1 ) 152 - 152 2016.8

合成コラーゲン様基剤とコラーゲン結合型線維芽細胞増殖因子を用いた複合剤による骨形成促進法の開発

濱本奈々, 内田健太郎, 関口裕之, 美間健彦, 後藤和義, 山本由弥子, 横田憲治, 高相晶士, 松下治

日本細菌学雑誌 71 ( 1 ) 126 - 126 2016.2

Vibrio alginolyticus I.029のコラゲナーゼ発現はHapRにより調節される

西川裕太郎, 美間健彦, 中田悠介, 後藤和義, 山本由弥子, 横田憲治, 松下治

日本細菌学雑誌 71 ( 1 ) 127 - 127 2016.2

口腔内におけるメトロニダゾール耐性歯周病細菌の調査

苔口進, 渡辺朱理, 横田憲治

日本環境感染学会誌 31 ( Suppl. ) 478 - 478 2016.2

歯ブラシへの付着・残存口腔内細菌調査

長瀬優里, 苔口進, 横田憲治, 松山美和, 渡辺朱理

四国公衆衛生学会雑誌 61 ( 1 ) 87 - 92 2016.2

Language：Japanese Publisher：四国公衆衛生学会

歯ブラシは使用の度に口腔内細菌が付着し、残存する。不潔な歯ブラシを使用することによって、齲蝕や口臭などの原因になることも報告されている。本研究は歯ブラシを清潔かつ衛生的に使用し、管理するという意識の向上に繋げることを目的とした。すなわち、1ヵ月間連続使用した歯ブラシに付着・残存する口腔内細菌数を調べて、同時に毛先の形態変化も確認した。さらに歯ブラシの使用条件や保管方法の違いによる歯ブラシに付着・残存した口腔内細菌数も比較した。1ヵ月間連続使用した歯ブラシには1.0×10^8CFUの口腔内細菌が付着・残存しており、毛先の広がりとともに歯ブラシへの付着・残存口腔内細菌の増加が認められた。また歯ブラシの使用条件による比較では、歯ブラシへの付着・残存していた口腔内細菌数にほとんど差はなく、保管方法ではケースに保管した場合に口腔内細菌が最も多く残存していた。今回の調査から1ヵ月間連続使用した歯ブラシの衛生状態は悪く、毛先の広がりや摩耗が口腔内細菌数の蓄積や残存の増加に影響していると考えられるため、定期的な交換が必要であろう。また湿潤状態が長く続く保管環境では、歯ブラシの付着・残存細菌数は増加していたので、歯ブラシの適切な保管方法が重要であると考える。(著者抄録)

DOI： 10.15053/2016.11.04

Examination of the Antimicrobial and Cleaning Effects of Commercially Available Soaps

YOSHIDA Yoko, WATANABE Tokiko, HAYASHI Shunji, HIRAI Yoshikazu, YOKOTA Kenji

40 ( 11 ) 685 - 691 2012.11

THERAPEUTIC POSSIBILITY FOR PATIENTS WITH BEHCET'S DISEASE BY THE PEPTIDES OF HEAT SHOCK PROTEIN-65/60 DERIVED FROM ORAL STREPTOCOCCI

Fumio Kaneko, Ari Togashi, Noritaka Oyama, Koichiro Nakamura, Emiko Isogai, Kenji Yokota, Keiji Oguma

CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 28 ( 4 ) S119 - S119 2010.7

ROLE OF ORAL STREPTOCOCCI IN THE PATHOGENESIS OF BEHCET'S DISEASE

Fumio Kaneko, Noritaka Oyama, Hirokatsu Yanagihori, Emiko Isogai, Kenji Yokota, Keiji Oguma

CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 26 ( 4 ) S16 - S16 2008.7

Eradication of Helicobacter pylori before the significant expansion of mucosal atrophy is most beneficial to prevent gastric cancer

Motowo Mizuno, Susumu Take, Yasuhiro Nagahara, Kuniharu Ishiki, Tomowo Yoshida, Kenji Yokota, Keiji Oguma

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 22 A63 - A63 2007.10

H. pylori-抗原刺激によるマンノースレセプターファミリーDEC205のマクロファージでの発現

藤本聖人, 横田憲治, 趙瑩, 綾田潔, 小熊惠二

日本細菌学雑誌 62 ( 1 ) 169 - 169 2007.2

ヘリコバクター・ピロリのフラボドキシン代謝におけるクラスC酸性ホスファターゼの関与

下村裕史, 林俊治, 横田憲治, 小熊恵二, 平井義一

日本細菌学雑誌 62 ( 1 ) 87 - 87 2007.2

Vibrio vulnificus 弱毒化株のマウス感染実験におけるワクチン効果

瀬川理恵, 井上美幸, 横田憲治, 小熊惠二, 山本耕一郎

日本細菌学雑誌 62 ( 1 ) 172 - 172 2007.2

署名Tagトランスポゾン挿入変異法による Vibrio vulnificus 弱毒化変異株の分離

細原浩平, 瀬川理恵, 光原沙織, 菅悠喜, 横田憲治, 小熊惠二, 山本耕一郎

日本細菌学雑誌 62 ( 1 ) 126 - 126 2007.2

ベーチェット病における炎症に関与している細菌抗原の解析

申蓮花, 横田憲治, 綾田潔, 阪口義彦, 平井一行, 長町栄子, 小熊惠二

日本細菌学雑誌 62 ( 1 ) 74 - 74 2007.2

胆汁検体よりの Helicobacter 属の存在確認と培養の試み

横田憲治, 綾田潔, 阪口義彦, 藤本聖人, 長町榮子, 小熊惠二

日本細菌学雑誌 62 ( 1 ) 179 - 179 2007.2

Behcet病発症における細菌抗原の意義 (第1土曜特集 Behcet病--病因の解明と難治性病態の克服に向けて) -- (病因・病態)

横田憲治, 小熊惠二

医学のあゆみ 215 ( 1 ) 19 - 22 2005.10

H. cinaedi, H. fenneliae, H. pullorum の性状と病原性

平井義一, 下村裕史, 林俊治, 横田憲治, 小熊恵二

臨床と微生物 = Clinical microbiology 32 ( 2 ) 175 - 180 2005.3

Helicobacter pylori heat-shock protein 60 induces production of the pro-inflammatory cytokine IL8 in monocytic cells

SN Lin, K Ayada, Y Zhao, K Yokota, R Takenaka, H Okada, R Kan, S Hayashi, M Mizuno, Y Hirai, Y Fujinami, K Oguma

JOURNAL OF MEDICAL MICROBIOLOGY 54 ( 3 ) 225 - 233 2005.3

Language：English Publisher：SOC GENERAL MICROBIOLOGY

Interleukin 8 (IL8) is usually produced in both epithelial and monocytic cells during bacterial infections, causing inflammation. Helicobacter pylori induces production of IL8 from gastric epithelial cells via its cag pathogenicity island (cag PAI) system, LPS and outer-membrane protein. In some bacteria, heat-shock protein 60 (HSP60) also elicits a strong pro-inflammatory response in cells of the innate immune system. Three recombinant H. pylori HSP60 (rHSP60) proteins of different sizes were produced and one of these was used to raise two monoclonal antibodies (2E7 and 7135). IL8 production was found to be induced in cultured monocytic cells treated with H. pylori cells or rHSP60 proteins, as measured by ELISA, and the amount of IL8 produced was dose-dependent. Pre-incubation of H. pylori cells or rHSP60 preparations with the antibody 2E7 significantly inhibited IL8 production from monocytic cells. These results indicated that HSP60 is closely associated with IL8 production in monocytic cells.

DOI： 10.1099/jmm.0.45871-0

Mechanisms of inflammation induced by H. pylori-HSP60

Kenji Yokota, Kiyoshi Ayada, Son-NanLin, Keiji Oguma, Ryuta Takenaka

Nippon rinsho. Japanese journal of clinical medicine 63 75 - 79 2005

Helicobacter pylori heat-shock protein 60 induces inflammatory responses through the toll-like receptor-triggered pathway in cultured human gastric epithelial cells

R Takenaka, K Yokota, K Ayada, M Mizuno, Y Zhao, Y Fujinami, SN Lin, T Toyokawa, H Okada, Y Shiratori, K Oguma

MICROBIOLOGY-SGM 150 3913 - 3922 2004.12

Language：English Publisher：SOC GENERAL MICROBIOLOGY

Contact between Helicobacter pylori and gastric epithelial cells results in activation of NF-kappaB followed by secretion of interleukin (IL)-8. However, host-cell receptor(s) and their ligands involved in H. pylori-related IL-8 production have yet to be fully defined. In this study, the interaction between Toll-like receptors (TLRs), which are host receptors for pathogens involved in the innate immune response, and heat-shock protein (HSP) 60, an immune-potent antigen of H. pylori, was examined during H. pylori-induced IL-8 secretion in vitro. Recombinant H. pylori HSP60 (rHpHSP60) was prepared and added to cultured KATO III human gastric epithelial cells with or without pre-incubation with mouse monoclonal anti-TLR2 or anti-TLR4 antibodies. IL-8 mRNA expression and IL-8 protein release were analysed by Northern blotting and immunoassay. Involvement of NF-kappaB activation was analysed immunocytochemically by anti-NF-kappaB p65 antibody and ammonium pyrrolidinedithiocarbamate (PDTC), an inhibitor of NF-kappaB-mediated transcriptional activation. rHpHSP60 induced IL-8 mRNA expression and IL-8 secretion in a dose-dependent manner in KATO III cells. Anti-TLR2 antibody inhibited rHpHSP60-induced IL-8 secretion by 75%, and anti-TLR4 antibody inhibited it by 30%. rHpHSP60 induced nuclear translocation of NF-kappaB p65, which was inhibited by pretreatment with anti-TLR2 antibody. Treatment with PDTC significantly decreased the secretion of IL-8 induced by rHpHSP60. These findings suggest that H. pylori HSP60 activates NF-kappaB and induces IL-8 production through TLR-triggered pathways in gastric epithelial cells. Thus, it is possible that H. pylori HSP60 and TLR interaction in host cells contributes to the development of gastric inflammation caused by H. pylori infection.

DOI： 10.1099/mic.0.27527-0

Serum antibodies to Helicobacter pylori and its heat shock protein 60 correlate with the response of gastric mucosa-associated lymphoid tissue lymphoma to eradication of H. pylori

R Takenaka, H Okada, M Mizuno, C Makidono, SI Hori, A Fujiwara, T Yoshino, K Yokota, K Oguma, Y Shiratori

GASTROENTEROLOGY 126 ( 4 ) A181 - A181 2004.4

Characterization of elongated Helicobacter pylori isolated from a patient with gastric-mucosa-associated lymphoid-tissue lymphoma

T Toyokawa, K Yokota, M Mizuno, Y Fujinami, R Takenaka, H Okada, S Hayashi, Y Hirai, K Oguma, Y Shiratori

JOURNAL OF MEDICAL MICROBIOLOGY 53 ( 3 ) 207 - 212 2004.3

Language：English Publisher：SOC GENERAL MICROBIOLOGY

To date, two Helicobacter species, Helicobacter pylori and 'Helicobacter heilmanni' (formerly named 'Gastrospirillum hominis'), have been identified from the human stomach. In this study, we observed non-H. pylori-shaped bacteria in gastric tissue sections and successfully isolated them by cultivation. Elongated bacteria were isolated from a patient with gastric-mucosa-associated lymphoid-tissue lymphoma who had been diagnosed as H. pylori-negative by culture, rapid urease test and histopathology in another hospital. The bacteria were grown only on chocolate agar in a CO2 incubator, appeared more than 10 mum long in histological sections, formed small colonies and showed poor growth in a brain heart infusion broth; these characteristics apparently differed from common clinical isolates of H. pylori. However, the bacteria were identified as H. pyloriby PCR of the urease gene, 16S rDNA sequencing, protein profile and antigenicity examined by anti-H. pylori polyclonal antibody. These observations suggest that the H. pylori strain identified in this study may contribute to the development of gastroduodenal diseases in cases judged as H. pylori-negative by ordinary methods.

DOI： 10.1099/jmm.0.05281-0

ボツリヌスB型神経毒素に結合している無毒成分の免疫増強作用について

李在哲, 横田憲治, 崔錦花, 有満秀幸, 阪口義彦, 藤永由佳子, 金英姫, 松村拓大, 株本祐子, 小熊恵二

日本細菌学雑誌 59 ( 1 ) 282 - 282 2004.2

Immune response in Helicobacter pylori-induced low-grade gastric-mucosa-associated lymphoid tissue (MALT) lymphoma

R Yamasaki, K Yokota, H Okada, S Hayashi, M Mizuno, T Yoshino, Y Hirai, D Saitou, T Akagi, K Oguma

JOURNAL OF MEDICAL MICROBIOLOGY 53 ( 1 ) 21 - 29 2004.1

Language：English Publisher：SOC GENERAL MICROBIOLOGY

We have reported previously that heat-shock protein 60 kDa (hsp60) of Helicobacter pylori is an important antigen in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In order to investigate associations with host immune reactions and hsp60 antigen, CD40 ligand (CD40L) expression and cytokine production were analysed following stimulation with hsp60. To provide a clear antigen-driven immune response, peripheral blood mononuclear cells (PBMC) from patients with low-grade MALT lymphoma and gastritis and those from healthy volunteers were stimulated with recombinant H. pylori hsp60 and H. pylori cell lysate in the presence of cytokines (IL4 and granulocyte-macrophage colony-stimulating factor). mRNA expression was also analysed by a cDNA microarray containing 1100 genes. Expression of CD40L on PBMCs of patients with MALT lymphoma was increased by cytokines or by combination with stimulation with hsp60 antigens. The production of IL4 in PBMC cultures was increased in patients with MALT lymphoma; however, production of IFN-gamma was at low levels. DNA microarray analysis indicated increased levels of HLA-DR and integrin mRNAs. In cases of low-grade MALT lymphoma, adaptive immune responses against hsp60 may be enhanced by host factors, such as antigen presentation and T-cell activation, resulting in B-cell proliferation, which can be demonstrated during chronic H. pylori infection.

DOI： 10.1099/jmm.0.05348-0

胃MALTリンパ腫に対するHelicobacter pylori(HP)除菌療法後の経過とsecond line治療としての放射線療法へのタイミング

岡田裕之, 水野元夫, 白鳥康史, 吉野正, 横田憲治

消化器科 38,1,53-58 2004

神経変性疾患髄液中の抗Helicobacter pylori heat shock protein 60抗体の検出

齊藤正樹, 千葉進, 青木雅俊, 松本博之, 杉山敏郎, 藤永由佳子, 横田憲治, 藤浪良仁, 小熊恵二

臨床神経学 43 ( 12 ) 1069 - 1069 2003.12

Heat shock protein 60 of Helicobacter pylori induces inflammatory responses through the toll-like receptor-triggered pathway in cultured human gastric epithelial cells

R Takenaka, K Yokota, M Mizuno, Y Fujinami, T Toyokawa, S Hiraoka, S Hori, C Makidono, S Take, H Okada, K Oguma, Y Shiratori

GASTROENTEROLOGY 124 ( 4 ) A590 - A590 2003.4

Mucosal immunisation with Clostridium botulinum type C16Stoxoid and its non-toxic component

N Mahmut, K Inoue, Y Fujinaga, H Arimitsu, Y Sakaguchi, L Hughes, R Hirst, T Murphy, T Tsuji, T Watanabe, T Ohyama, T Karasawa, S Nakamura, K Yokota, K Oguma

JOURNAL OF MEDICAL MICROBIOLOGY 51 ( 10 ) 813 - 820 2002.10

Language：English Publisher：SOC GENERAL MICROBIOLOGY

Clostridium botulinum types C and D produce a 16 S (500 kDa) toxin that is formed by conjugation of neurotoxin with a non-toxic component (nonTox). The amino acid sequences of type C and D nonTox components are almost identical. In a previous report it was proposed that nonTox is necessary for the effective absorption of the toxin from the small intestine. This suggested the hypothesis that mucosal immunity against nonTox in the small intestine might prevent the absorption of both C- and D-16 S toxins. The nonTox was purified from a mutant strain, (C)-N71, that does not produce neurotoxin. This nonTox or detoxified C-16 S toxin were mixed with adjuvant (a mutant form of heat-labile toxin of Escherichia coli), and inoculated into mice via the nasal or oral route, or both. The mice inoculated nasally four times with nonTox or toxoid produced high levels of antibodies (including IgA) against the immunogens, both in intestinal fluids and sera. When these nonTox-immunised mice were challenged orally with 2 and 20 oral minimum lethal doses (MLD) of C- or D-16 S toxins, the same results were obtained with both C and D; the mice survived after challenge with 2 MLD of either C or D but were killed by 20 MLD of either toxin although the time to death was significantly longer than in the control non-immunised mice. These results indicate that the local anti-nonTox antibodies reduce absorption of both C- and D-16 S toxins from the small intestine. The C-16 S toxoid-immunised mice showed similar behaviour with type D toxin challenge, probably due to the same mechanism, but were protected against 20 MLD of C-16 S toxin.

Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype

T Inaba, M Mizuno, K Kawai, K Yokota, K Oguma, M Miyoshi, S Take, H Okada, T Tsuji

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 17 ( 7 ) 748 - 753 2002.7

Language：English Publisher：BLACKWELL PUBLISHING ASIA

Background and aims: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism.
Method: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism.
Results: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%; P = 0.038).
Conclusion: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI. (C) 2002 Blackwell Publishing Asia Pty Ltd.

DOI： 10.1046/j.1440-1746.2002.02790.x

Reinfection rate following effective therapy against Helicobacter pylori infection in Japan

M Adachi, M Mizuno, K Yokota, M Miyoshi, Y Nagahara, T Maga, K Ishiki, T Inaba, H Okada, K Oguma, T Tsuji

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 17 ( 1 ) 27 - 31 2002.1

Language：English Publisher：BLACKWELL PUBLISHING ASIA

Background and Aim: In developed countries, reinfection of Helicobacter pylori (H. pylori) after eradication of the bacterium is unusual, while the reinfection rate in developing countries is variable. In this study, we determined the reinfection rate after successful H. pylori eradication in Japan, a country with a high prevalence of H. pylori infection.
Methods: After successful eradication, 377 patients were followed up by endoscopy and urea breath test annually. In reinfected patients, H. pylori strains isolated initially and after reinfection were compared by using random amplification of polymorphic DNA fingerprinting.
Results: H. pylori became positive in four of 337 patients (1.2%) 1 year after eradication and in two of 133 patients (1.5%) 2 years after eradication. One patient experienced an ulcer relapse 2 years after eradication therapy. Random amplification of polymorphic DNA fingerprinting of the isolated strains from four of the six patients showed two had identical strains (at 1 year) while the other two had different strains (one at 1 year and one at 2 years). When infection in the two patients reinfected with identical strains is considered a recrudescence, the true reinfection rate is < 0.8% per patient year.
Conclusions: The reinfection rate after eradication of H. pylori is low in Japan despite the country's high prevalence of H. pylori infection. (C) 2002 Blackwell Science Asia Pty Ltd.

DOI： 10.1046/j.1440-1746.2002.02666.x

臨床 H.pyloriのゲノムと病原性 (特集微生物ゲノム情報と医学--基礎と臨床)

林俊治, 平井義一, 横田憲治

現代医療 34 ( 5 ) 1091 - 1096 2002

Expression of heat shock protein 60 in normal and neoplastic human lymphoid tissues.

JIN Hua Shu, YOSHINO Tadashi, JIN Zaishun, OKA Takashi, KOBAYASHI Keita, YAMASAKI Rie, LIU Yi Xuan, YOKOTA Kenji, OGUMA Keiji, AKAGI Tadaatsu

J.Clin.Exp. Hematopathol 1, 25-32 ( 1 ) 25 - 32 2002

Language：English Publisher：The Japanese Society for Lymphoreticular Tissue Research

A molecular chaperonin in mammals, heat shock protein 60 (HSP60) is constitutively expressed in the mitochondria at a low level and is rapidly up-regulated under stress. However, the role of HSP60 in the lymphoid tissues has not been well clarified. In the present study, expression of HSP60 was examined by flow cytometry and immunohistochemistry in normal peripheral blood mononuclear cells, reactive lymphoid tissues, and malignant lymphomas. HSP60 was found to be present constitutively at low levels in a fraction of resting T cells and most monocytes. The blastic change upon mitogen stimulation induced HSP60 at much higher levels in more T, B and NK cells. In normal lymphoid tissues, HSP60 was expressed preferentially in the cytoplasm of large-sized lymphoid cells and macrophages in the germinal centers and the interfollicular area.<br>In non-Hodgkin lymphomas strong expression of HSP60 was detected in most cases of diffuse large B-cell lymphoma, follicular lymphoma, and grade 3 and NK/T cell lymphoma. No immunostaining was observed in low grade B-cell lymphomas, including follicular lymphoma, grade 1 and B-lymphoblastic lymphomas. HSP60 immunoreactivity was variable in T-cell lymphomas. Intense expression of HSP60 was observed in Reed-Sternberg cells in all cases of Hodgkin lymphoma.

DOI： 10.3960/jslrt.42.25

Immunoglobulin G1 antibody response to Helicobacter pylori heat shock protein 60 is closely associated with low-grade gastric mucosa-associated lymphoid tissue lymphoma

E Ishii, K Yokota, T Sugiyama, Y Fujinaga, K Ayada, Hokari, I, S Hayashi, Y Hirai, M Asaka, K Oguma

CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY 8 ( 6 ) 1056 - 1059 2001.11

Language：English Publisher：AMER SOC MICROBIOLOGY

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is related to Helicobacter pylori infection. Specifically, it has been pointed out that pathogenesis of MALT lymphoma involves the 60-kDa heat shock protein (hsp60). To investigate humoral immune responses to the H. pylori hsp60 in patients with gastroduodenal diseases and patients with MALT lymphoma, the hsp60 of H. pylori was expressed with a glutathione S-transferase fusion protein and was purified (recombinant hsp60). Sera were obtained from H. pylori-positive patients with gastroduodenal diseases (MALT lymphoma, n = 13; gastric ulcer, n = 20; duodenal ulcer, n = 20; gastritis, n = 20) and from H. pylori-negative healthy volunteers (n = 9). Sera from patients with MALT lymphoma were also obtained at two times: before and after eradication therapy. Antibodies to hsp60 and H. pylori were assessed by enzyme-linked immunosorbent assay. The levels of immunoglobulin G (IgG) antibodies to the hsp60 of H. pylori-positive patients with gastroduodenal diseases were significantly elevated compared to those in the controls. The levels of IgG1 antibodies to hsp60 were elevated and correlated with the levels of anti-H. pylori antibodies in patients with MALT lymphoma. Humoral immunity against hsp60 may be important and relevant to gastroduodenal diseases induced by H. pylori infection.

DOI： 10.1128/CDLI.8.6.1056-1059.2001

牛乳由来 globotriaosylceramide によるベロ毒素の細胞障害能の抑制

ターナ, 渡来仁, 児玉洋, 櫛泰典, 井上薫, 横田憲治, 小熊恵二

脂質生化学研究 43 203 - 206 2001.5

Inhibition of vero cell cytotoxic activity in Escherichia coli O157 : H7 lysates by globotriaosylceramide, Gb3, from bovine milk

S Watarai, Tana, K Inoue, Y Kushi, E Isogai, K Yokota, K Naka, K Oguma, H Kodama

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 65 ( 2 ) 414 - 419 2001.2

Language：English Publisher：TAYLOR & FRANCIS LTD

In order to clarify the presence and verotoxin (VT) inhibitory activity of globotriaosylceramide (Gb3) in bovine milk, we analyzed neutral glycosphingolipids (GSLs) from bovine milk and investigated the inhibitory effect of bovine milk Gb3 on the cytotoxicity of VT2. Five species of neutral GSLs, designated as N-1, N-2, N-3, N-4, and N-5, were separated on thin-layer chromatography (TLC). N-1, N-2, and N-3 showed the same mobility as glucosglceramide, lactosylceramide, and Gb3 on the TLC plate, respectively. N-4 and N-5 GSLs migrated below globoside on the TLC plate. N-3 GSL having the same TLC mobility as Gb3 from bovine milk was immunologically identified as Gb3 by monoclonal antibody against Gb3, anti-CD77 monoclonal antibody. Furthermore, the effect of bovine milk Gb3 on VT2-induced cytotoxicity mas investigated. We found that treatment of VT2 with bovine milk Gb3 can reduce the cytotoxic effect of VT2.

DOI： 10.1271/bbb.65.414

Relationship between susceptibility to hemolytic-uremic syndrome and levels of globotriaosylceramide in human sera

S Watarai, K Yokota, Tana, T Kishimoto, T Kanadani, K Taketa, K Oguma

JOURNAL OF CLINICAL MICROBIOLOGY 39 ( 2 ) 798 - 800 2001.2

Language：English Publisher：AMER SOC MICROBIOLOGY

The relationship between differential susceptibility to hemolytic-uremic syndrome (HUS) and levels of globotriaosylceramide (Gb3) in serum was studied in patients infected with verotoxin-producing Escherichia coli (VTEC). The serum Gb3 levels in patients with HUS were lower than these in diarrheal patients without subsequent HUS or in patients without clinical symptoms, indicating that individuals with a lower content of serum Gb3 show a higher incidence of HUS following VTEC infection.

DOI： 10.1128/JCM.39.2.798-800.2001

H. pylori感染と胃粘膜免疫応答.

横田憲治, 綾田潔, 石井栄子, 山崎理恵, 小林計太, 吉野正, 林俊治, 平井義一, 赤木忠厚, 小熊恵二

日本臨床 59,342-348 2001

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism

Masatsugu Miyoshi, Motowo Mizuno, Kuniharu Ishiki, Yasuhiro Nagahara, Toshirou Maga, Tomomi Torigoe, Junichirou Nasu, Hiroyuki Okada, Kenji Yokota, Keiji Oguma, Takao Tsuji

Journal of Gastroenterology and Hepatology (Australia) 16 ( 7 ) 723 - 728 2001

Language：English Publisher：Blackwell Publishing

Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. Methods: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [13C]-urea breath test at 1-2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. Results: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56-75) and 62.4% (95% CI, 52-71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression
smoking was the only significant independent factor for treatment failure. Conclusion: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy. © 2001 Blackwell Science Asia Pty Ltd.

DOI： 10.1046/j.1440-1746.2001.02526.x

Gastric mucosal immunity induced by H. pylori infection

K. Yokota, K. Ayada, E. Ishii, K. Oguma, R. Yamasaki, K. Kobayashi, T. Yoshino, T. Akagi, S. Hayashi, Y. Hirai

Nippon rinsho. Japanese journal of clinical medicine 59 ( 2 ) 342 - 348 2001

Language：Japanese Publishing type：Book review, literature introduction, etc.

H. pylori infection induces various humoral and cellular immunities in gastric mucosa. Some reports indicate predominant CD4+ cells infiltrate in H. pylori infected gastric mucosa, and these cells express the T helper 1 phenotype. Local humoral immunity is also induced. Gastric plasma cells produce anti-H. pylori antibodies, however, their protective immunity is not enough to eradicate bacteria in human. We found heat shock protein 60 kDa (hsp60) may be closely associated with pathogenesis in MALT lymphoma. IgG1 antibodies to hsp60 were significantly correlated with the antibodies to H. pylori whole cell in patients with MALT lymphoma. CD40-CD40L dependent B cell proliferation was induced by cytokine and/or hsp60 stimulations in those patients. Cytotoxicity of gastric epithelial cells which is associated with host immunity induced by H. pylori infection is still unclear. We found that lymphocytes from patients with peptic ulcer showed cytotoxicity to gastric cell line HGC-27 in vitro. Cytotoxicity was enhanced by cytokine stimulus to T-lymphocytes and by heat stress and/or patients' antibodies treatment of HGC-27 cells. The pathogenicity of H. pylori may involve not only bacterial virulence factor but also host immunity. Studies of mucosal local immunity will help explain the mechanisms of H. pylori induced gastrodoudenal diseases.

CAP18(抗菌および抗エンドトキシン蛋白)の生体防御因子としての役割

平田陸正, 切替照雄, 横田憲治, 田村弘志, 田中重則, 小熊恵二, 佐藤成大

日本細菌学雑誌 55 ( 2 ) 347 2000.4

The Bacteriocidal Effect of the Electrolysed Functioning Water against Helicobacter pylori

NAKAO Miyuki, YOKOTA Kenji, OGUMA Keiji, TAKAI Kenichi

74 ( 2 ) 120 - 127 2000.2

H. pyloriの胃リンパ腫への関与

吉野正, 赤木忠厚, 横田憲治, 小熊恵二, 河原祥朗

癌の臨床 46:839-845 2000

Treatment of Helicobacter pylori infection

Hayashi, S, Hirai, Y, Isogai, H, Isogai, E, Yokota, K, Oguma, K

Res. Adv. Antimicrob. Chemother. 1 7 - 12 2000

Association of Helicobacter pylori with gastroduodenal diseases

Y Hirai, S Hayashi, H Shimomura, K Oguma, K Yokota

JAPANESE JOURNAL OF INFECTIOUS DISEASES 52 ( 5 ) 183 - 197 1999.10

Language：English Publishing type：Book review, literature introduction, etc. Publisher：NATL INST INFECTIOUS DISEASES

Helicobacter pylori was first cultured in vitro in 1982. This bacterium is a spiral gram negative rod which grows under microaerophilic conditions. The ecological niche is the mucosa of the human stomach which had been thought to be aseptic before the discovery of this bacterium. This organism causes a long-lasting infection throughout a person's life if there is no medical intervention. Numerous persons are infected with the organism around the world, and the rate of infection in Japan is nearly 50% of the population. However, the route of infection remains unclear because the organism has not been isolated from any environment other than several animals. H. pylori is now recognized as a causative agent of gastritis and peptic ulcers. Though gastritis, and especially chronic active gastritis, is observed at least histologically in all persons with H. pylori, peptic ulcers develop in only some infected persons. Specific factors in the host and/or the bacteria are needed for the development of peptic ulcer disease. Furthermore, H. pylori is considered to be related to the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, especially those of low grade. Also, H. pylori infection is a major determinant for initiating the sequence of events leading to gastric cancer. In some patients with low-grade gastric MALT lymphoma, the eradication of H. pylori led to a regression of lesion. Gastric cancer has been induced in Mongolian gerbils with long-term H. pylori infection. The combinations of drugs, which consist of an antisecretory agent (acid-supressing agent) and antimicrobial agents, are used for the eradication of the organism. Eradication therapy is recommended at least for patients with peptic ulcers.

Antibodies to human gastric epithelial cells and heat shock protein 60 in Helicobacter pylori positive mucosa associated lymphoid tissue lymphoma

Y Kawahara, K Yokota, M Mizuno, N Yunoki, T Uesu, H Okada, K Kobayashi, Y Hirai, K Oguma, T Tsuji

GUT 45 ( 1 ) 20 - 23 1999.7

Language：English Publisher：BRITISH MED JOURNAL PUBL GROUP

Background-Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions to Helicobacter pylori.
Aim-To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by PI pylori and human gastric epithelial cells. IC
Methods-Sera were obtained from H pylori positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; nonulcer dyspepsia, n = 20) and from H pylori, negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting.
Results-Antibody titres to HGC-27 cells were significantly elevated in H pylori positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and H pylori HspB was documented by immunoblotting experiments.
Conclusions-Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between H pylori HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma.

【感染症とその治療細菌感染症】ボツリヌス症

小熊惠二, 藤永由佳子, 井上薫, 横田憲治, 武士甲一

最新医学 54 ( 増刊 ) 652 - 664 1999.3

ボツリヌスprogenitor toxinのHAサブコンポーネントの小腸微絨毛及び赤血球への結合活性について

藤永由佳子, 井上薫, 横田憲治, 長町榮子, 小熊惠二

日本細菌学雑誌 54 ( 1 ) 117 - 117 1999.2

Helicobacter pyloriのHSP60の発現と生物活性の検討

横田憲治, 石井栄子, 綾田潔, 平井義一, 林俊治, 藤永由佳子, 小熊惠二

日本細菌学雑誌 54 ( 1 ) 212 - 212 1999.2

岡山県における腸管出血性大腸菌O157:H7の分子疫学的検討

船守有香, 横田憲治, 藤永由佳子, 井上薫, 小熊惠二

日本細菌学雑誌 54 ( 1 ) 203 - 203 1999.2

Gastric ulcers in SCID mice induced by Helicobacter pylori infection after transplanting lymphocytes from patients with gastric lymphoma

YOKOTA K

Gastroenterology 117 893 - 899 1999

Structure and function of Clostridium botulinum progenitor toxin

K Oguma, K Inoue, Y Fujinaga, K Yokota, T Watanabe, T Ohyama, K Takeshi, K Inoue

JOURNAL OF TOXICOLOGY-TOXIN REVIEWS 18 ( 1 ) 17 - 34 1999

Language：English Publisher：MARCEL DEKKER INC

Clostridium botulinum strains produce seven immunologically distinct neurotoxins (NTX), type A to G. The NTXs associate with nontoxic components in cultures, and become large complexes with three forms (128, 16S, and 19S) designated progenitor toxins. The 12S toxin consists of a NTX and a nontoxic component having no hemagglutinin (HA) activity (described here as non-toxic non-HA, NTNH), and the 168 and 19S toxins are formed by conjugation of the 12S toxin with HA. Based on the genetic- and protein chemical-analyses of the progenitor toxins it became clear that 1) the HA consists of four subcomponents namely HA1 (Mr. 33 similar to 35 kDa), HA2 (15 similar to 17 kDa), HA3a (19 similar to 23 kDa), and HA3b (52 similar to 53 kDa), 2) the genes coding for NTX (ntx), NTNH (ntnh), and HA (ha) occur as a cluster; ha lies just upstream of ntnh, and ntx lies just downstream of ntnh, 3) ha is in the opposite orientation from that of ntnh and ntx, 4) ha consists of three ORFs (ha1, ha2, and ha3), 5) the gene product (70 kDa) of ha3 is split into HA3a and HA3b after translation, 6) HA3a is cleaved at several different sites of its N-terminal region to form proteins with slightly different Mrs, 7) the 19S toxin is a dimer of 16S toxin crosslinked by HA1, 8) The NTNHs of type A to D 12S toxins have a cleavage(s) on their N-terminal regions. It also became clear that the HA prays an important role when the 16S land 19S) toxin is absorbed from the small intestine.

Classification of Clostridium butyricum based on sodium dodecyl sulfate polyacrylamide gel electrophoresis and pulsed-field gel electrophoresis

K Yokota, Y Fujinaga, K Inoue, S Shimazaki, G Seo, K Takeshi, E Nagamachi, K Oguma

ANAEROBE 4 ( 4 ) 177 - 181 1998.8

Language：English Publisher：ACADEMIC PRESS LTD

Eleven strains of Clostridium butyricum collected from different sources were analysed by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and pulsed-field gel electrophoresis (PFGE). The strains could be classified into four groups based on their banding profiles of the proteins extracted from the cells on SDS-PAGE. Group I consisted of seven strains, and these strains were further divided into five subgroups by PFGE. The strains belonging to groups II, III, and IV on SDS-PAGE were also classified into the same II to IV groups by PFGE. These data indicate that grouping of the strains of C. butyricum can be performed by employing both SDS-PAGE and PFGE. (C) 1998 Academic Press.

DOI： 10.1006/anae.1998.0163

Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells

S Hayashi, T Sugiyama, KI Amano, H Isogai, E Isogai, M Aihara, M Kikuchi, M Asaka, K Yokota, K Oguma, N Fujii, Y Hirai

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 42 ( 8 ) 1895 - 1899 1998.8

Language：English Publisher：AMER SOC MICROBIOLOGY

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to human gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H, pylori adhesion is thus a therapeutic target in the prevention of H, pylori infection. Experiments were performed to evaluate the effect of rebamipide, a novel antiulcer agent, on H. pylori adhesion to gastric epithelial cells. MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells. Ten H. pylori strains isolated from patients with chronic gastritis and gastric ulcer were used in the study. We evaluated the effect of rebamipide on H. pylori adhesion to MKN-28 and MKN-45 cells quantitatively using our previously established enzyme-linked immunosorbent assay. The adhesion of H. pylori to MKN-28 and MKN-45 cells was significantly inhibited by pretreatment of these cells with 100 mu g of rebamipide per mi. However, the adhesion was not affected by the pretreatment of H. pylori with rebamipide. On the other hand, the viabilities of H. pylori, MKN-28 cells, and MKN-45 cells were not affected by rebamipide, Our studies suggest that rebamipide inhibits the adhesion of H. pylori to gastric epithelial cells.

ボツリヌス毒素

小熊惠二, 井上薫, 藤永由佳子, 横田憲治, 武士甲一, 大山徹, 池田徹也, 渡部俊弘, 井上勝弘

Modern Media 44 ( 7 ) 9-18,213-222 - 222 1998.7

Helicobacter pyloriのワクチン療法 (特集 Helicobacter pyloriの基礎と臨床)

小熊恵二, 横田憲治, 平井義一

診断と治療 86 ( 1 ) 89 - 94 1998.1

The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin

Y Fujinaga, K Inoue, S Watanabe, K Yokota, Y Hirai, E Nagamachi, K Oguma

MICROBIOLOGY-UK 143 3841 - 3847 1997.12

Language：English Publisher：SOC GENERAL MICROBIOLOGY

Binding of the purified type C 7S (neurotoxin), 12S and 16S botulinum toxins to epithelial cells of ligated small intestine or colon of the guinea pig (in vivo test) and to pre-fixed gastrointestinal tissue sections (in vitro test) wasanalysed. The 165 toxin bound intensely to the microvilli of epithelial cells of the small intestine in both in vivo and in vitro tests, but did not bind to cells of the stomach or colon. The neurotoxin and 12S toxin did not bind to epithelial cells of the small intestine or to cells of the stomach or colon. Absorption of the toxins was assessed by determining the toxin titre in the sera of guinea pigs 6-8 h after the intra-intestinal administration of the toxins. When the 165 toxin [1 x 10(5) minimum lethal dose (MLD)] was injected, 200-660 MLD ml(-1) was detected in the sera, whereas when the 12S toxin (2 x 10(5) MLD) or 7S toxin (2 x 10(5) MLD) was injected, little toxin activity was detected in the sera. Therefore, the haemagglutinin of type C 16S toxin is apparently very important in the binding and absorption of botulinum toxin in the small intestine.

DOI： 10.1099/00221287-143-12-3841

Effect of ecabet sodium on Helicobacter pylori adhesion to gastric epithelial cells

HAYASHI Shunji, SUGIYAMA Toshiro, YACHI Akira, YOKOTA Kenji, HIRAI Yoshikazu, OGUMA Keiji, FUJII Nobuhiro

32 ( 5 ) 593 - 597 1997.10

ボツリヌス神経毒素-無毒成分複合体の構造と機能

井上薫, 藤永由佳子, 横田憲治

蛋白質核酸酵素 42 ( 13 ) 2049 - 2060 1997.10

Helicobacter pylori. Prospects on development of Helicobacter pylori vaccine.

OGUMA KEIJI, HIRAI YOSHIKAZU, YOKOTA KENJI

臨床検査 41 ( 2 ) 185 - 188 1997.2

Structure and function of Clostridium botulinum progenitor toxins

K. Inoue, Y. Fujinaga, K. Yokota, K. Oguma

Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 42 ( 13 ) 2049 - 2060 1997

Helicobacter pylori and gastroduodenal disease

K Yokota, Y Hirai, K Oguma

JAPANESE JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH 42 ( 3 ) 193 - 209 1996.6

Language：Japanese Publishing type：Book review, literature introduction, etc. Publisher：PHARMACEUTICAL SOC JAPAN

Helicobacter pylori is a gram negative spiral bacterium, which is colonized in human gastric mucosa. This organism was first reported in Australia, 1983. Now H. pylori has been recognized to cause chronic active gastritis, and is a major factor in the pathogenesis of duodenal ulcer and gastric ulcer. It was also reported that its infection is a risk factor for both MALT (mucosa associated lymphoid tissue) lymphoma and gastric adenocarcinoma.
H. pylori has many virulence factors. Urease is one of the most important colonization and virulence factors studied. Ammonia made by urease protects the organisms from gastric low pH, and is toxigenic to gastric epithelial cells. Vacuolating toxin and CagA proteins are thought to be pathogenic agents especially for causing gastric and duodenal ulcers. Neutrophil reactions against the bacteria, and the abnormal immunological reactions are also considered to cause the damage of gastric epithelial cells, although the detailed pathogenic mechanisms are still not clear.
In developing countries, infection by H. pylori is established in childhood, and the organisms can be identified in the mouth and feces, indicating its infection through water.
The infected organisms can be eradicated by administration with proton pump inhibitor and one or two antibiotics. This may provide an useful therapeutic means to the patients especially with recurrent ulceration and MALT lymphoma.

Quantitative detection of secretory immunoglobulin a to Helicobacter pylori in gastric juice: Antibody capture enzyme-linked immunosorbent assay

S Hayashi, T Sugiyama, K Hisano, T Awakawa, Kurokawa, I, A Yachi, H Isogai, E Isogai, K Yokota, Y Hirai, K Oguma, N Fujii

JOURNAL OF CLINICAL LABORATORY ANALYSIS 10 ( 2 ) 74 - 77 1996

Language：English Publisher：WILEY-LISS

Helicobacter pylori is a major etiologic agent in gastroduodenal disorders. In this study, immunoglobulin A (IgA) antibodies to H. pylori were estimated in serum and gastric juice specimens from patients with gastritis and peptic ulcers using antibody capture enzyme-linked immunosorbent assays (ACELISAs). The antibody titers of the ACELISAs are independent of the antibody concentration and reflect the ratio of H. pylori-specific IgA to total IgA. The ratio is stable, although the antibody concentration fluctuates in gastric juice. Using the ACELISAs it was possible to evaluate quantitatively not only serum IgA (SR-IgA) antibodies but also secretory IgA (SC-IgA) antibodies in gastric juice. There were significant differences between the patients and control group in the SR-IgA and SC-IgA ACELISAs. Furthermore, the ACELISAs made it possible to compare between SR-IgA antibodies in serum and SC-IgA antibodies in gastric juice. In all patients, the ratios of H. pylori-specific IgA were higher in gastric juice than in serum. These results suggest that H. pylori SC-IgA antibodies are mainly produced by the local immune response in the gastric mucosa. Our studies indicate that ACELISA is well suited for the analysis of local immune response in mucosa. (C) 1996 Wiley-Liss, Inc.

DOI： 10.1002/(SICI)1098-2825(1996)10:2<74::AID-JCLA3>3.0.CO;2-L

Characterization of Streptococcus sanguis Isolated from Patients with Behcet's Disease

YOKOTA Kenji, HAYASHI Shynji, ARAKI Yoshio, ISOGAI Emiko, KOTAKE Satoshi, YOSHIKAWA Kouji, FUJII Nobuhiro, HIRAI Yoshikazu, OGUMA Keiji

Microbiol Immunol 39 ( 9 ) 729 - 732 1995.9

スナネズミおよびマウスを用いる感染実験モデル． Helicobacter pylori と胃粘膜障害

磯貝浩, 磯貝恵美子, 横田憲治, 小熊恵二

日本臨床 51 ( 12 ) 3183 - 3143 1993

Development and Evaluation of Capture Enzyme-Linked Immunosorbent Assays for Detection of Immunoglobulin G and M Antibodies to Group A Streptococcal Antigens

Hayashi Shunji, Yokota Kenji, Takizawa Yoshihiko, Tomizawa Isao, Nejime Tetsuya, Oguma Keiji

Japanese Journal of Microbiology 37 ( 4 ) 271 - 279 1993

Language：English Publisher：Center For Academic Publications Japan

Capture enzyme-linked immunosorbent assays (ELISAs) were developed to detect immunoglobulin G and M antibodies to group A streptococcal (GAS) antigens, streptolysin O, streptokinase, and group A carbohydrate. The sensitivities and the specificities of the IgM capture ELISAs to each GAS antigen were high enough to distinguish the patients with GAS infections (diagnosed as GAS pharyngitis or scarlet fever) from the control groups (healthy people and patients with pharyngitis from whom GAS could not be isolated). On the other hand, the specificities of the IgG capture ELISAs were not very effective in diagnosis of GAS infections. When the capture ELISA and an indirect ELISA detecting IgM antibodies to group A carbohydrate were compared, false-positive reactions due to rheumatoid factor occurred in the indirect ELISA, but did not occur in the capture ELISA. These results indicate that the capture ELISA works better than the indirect ELISA in detecting the IgM antibody, and that the IgM capture ELISA to GAS antigen provides a rapid and highly reliable serodiagnosis for GAS infections employing only a single serum.

Demonstration of antigen-specific immune response against Streptococcus sanguis

Norihisa Ishii, Emiko Isogai, Yuko Yamakawa, Hiroshi Nakajima, Shigeaki Ohno, Hiroshi Isogai, Shunji Hayashi, Kenji Yokota, Keiji Oguma

Journal of Dermatological Science 5 ( 3 ) 182 - 189 1993

Language：English

The genetic control of Streptococcus sanguis antigen response was studied. Mice sensitized with inactivated S. sanguis organisms antigen-injected at the base of the tail developed footpad swelling. Those with an I-Ak,q,r region of H-2 showed a strong footpad response, whereas those with an I-Ab,d,s region showed a weak response to S. sanguis cell wall antigen. Footpad response was mediated by CD4+, 8- T cells by using in vitro monoclonal antibody treatment. Similar evidence of genetic control was obtained with an in vitro T cell proliferation assay. However, quantitation of antibodies against S. sanguis showed that antibody production was not controlled by H-2. These results indicated that both in vivo footpad swelling and in vitro T cell proliferation responses were functions of helper (CD3+, 4+, 8-) T cells and controlled by the I-A region of H-2. © 1993.

DOI： 10.1016/0923-1811(93)90765-H

A NOVEL ENZYME-IMMUNOASSAY FOR SERODIAGNOSIS OF HELICOBACTER-PYLORI INFECTION

T SUGIYAMA, K IMAI, H YOSHIDA, Y TAKAYAMA, T YABANA, K YOKOTA, K OGUMA, A YACHI

GASTROENTEROLOGY 101 ( 1 ) 77 - 83 1991.7

PLATELET-AGGREGATION INDUCED BY UNCOMMON SEROTYPES OF STREPTOCOCCUS-SANGUIS ISOLATED FROM PATIENTS WITH BEHCETS-DISEASE

E ISOGAI, H ISOGAI, K YOKOTA, S HAYASHI, N FUJII, K OGUMA, K YOSHIKAWA, Y SASAMOTO, S KOTAKE, S OHNO

ARCHIVES OF ORAL BIOLOGY 36 ( 6 ) 425 - 429 1991

Language：English Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Uncommon serotypes were tested for their ability to induce aggregation in platelet-rich plasma. Both uncommon and common serotypes induced platelet aggregation in rabbit platelet-rich plasma, but serotonin release was higher with the uncommon serotypes. Aggregation at ATP release varied between uncommon and common serotypes. With human platelet-rich plasma, only uncommon serotypes showed aggregation. Differences in serotype selectivity and the rate of aggregation were noted among platelet donors. About half of the patients with Behcet's disease and 30% of health controls showed platelet aggregation. Plasma from non-responder patients with Behcet's disease inhibited aggregation of healthy responder platelets within 20 min. Thus selective binding of uncommon serotypes of Strep. sanguis to plateletes might cause the vasculitis in Behcet's disease.

Adhesive properties of streptococcus sanguis isolated from patients with behçet's disease

E. Isogap, H. Isogai, N. Fujii, K. Yokota, M. Yamaguchi, K. Oguma, K. Yoshikawa, Y. Sasamoto, S. Ohnot

Microbial Ecology in Health and Disease 3 ( 6 ) 321 - 328 1990

Language：English Publisher：Informa Healthcare

Various strains of Streptococcus sanguis adhered to the buccal epithelial cells from both healthy controls and patients with Behçet's disease (BD). Almost all of them strongly adhered to the epithelial cells from patients with BD, whereas smaller numbers of the bacteria were observed on the cells from healthy controls. This phenomenon was especially clear when uncommon serotypes (clinical isolates) were used. Two or more peaks were observed in the distribution of the epithelial cells from patients with BD in the adherence test. In contrast, a single peak was observed in the distribution of the epithelial cells from healthy controls. Cytological differences of the epithelial cells between both groups were not observed in the microscopic image analysis. All the strains of S.sanguis showed agglutination of rabbit erythrocytes, but not agglutination of sheep, horse, swine and duck erythrocytes. Line cell adherence of S.sanguis uncommon serotypes was greater than that of common ones. All strains of S.sanguis showed a reactivity with aggregated human β2-microglobulin, but not with the monomer. The different level of reactivity to aggregated β2-microglobulin was recognised between uncommon and common serotypes. The reaction between aggregated β2-microglobulin and S.sanguis is one of human-bacterium interaction which should be considered in studies of BD. ©1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

DOI： 10.3109/08910609009140254

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