Updated on 2025/11/01

写真a

 
YOKOTA Kenji
 
Organization
Faculty of Health Sciences Professor
Position
Professor
Profile
昭和62年４月１日 研究生 札幌医科大学微生物学講座
平成４年７月１日 助手 岡山大学医学部細菌学講座
平成10年７月１日 同講師
平成11年７月16日 講師 岡山大学大学院医歯学総合研究科 （Ｄマル合教員）
平成17年4月1日 助教授 岡山大学医学部保健学科
平成20年4月1日 准教授 岡山大学大学院保健学研究科
平成28年4月1日 同教授
感染症学会評議員
ヘリコバクター学会代議員（耐性菌パネル委員）
External link

Degree

  • 医学博士 ( 1999.6   岡山大学 )

Research Areas

  • Life Science / Bacteriology

Education

  • Okayama University   医学部  

    - 1997.6

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    Notes： 医学博士

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Research History

  • Okayama University   Graduate School of Health Sciences   Professor

    2015.4

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  • Okayama University   Graduate School of Health Sciences   Associate Professor

    2005.4 - 2015.3

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  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   Lecturer

    1998.7 - 2005.3

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  • Okayama University   Medical School   Research Assistant

    1992.8 - 1998.6

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  • Sapporo Medical University   微生物学講座

    1987.4 - 1992.6

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Papers

  • Endoscopic and Histological Gastritis in University Students with Helicobacter pylori Infection.

    Shotaro Okanoue, Hiroyuki Sakae, Kenji Yokota, Takehiro Tanaka, Yuka Obayashi, Makoto Abe, Yoshiyasu Kono, Hiromitsu Kanzaki, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, Hiroyuki Yanai, Hiroyuki Okada

    Internal medicine (Tokyo, Japan)   63 ( 21 )   2875 - 2884   2024.11

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    Objective Although the characteristics of Helicobacter pylori infection have been extensively reported, there is a lack of consensus regarding its characteristics in young adults. The present study examined the endoscopic and histological characteristics of young adults who underwent eradication therapy for H. pylori infection. Methods We examined the H. pylori infection status of first-year students at Okayama University School of Medicine and Dentistry between 2014 and 2020. A total of 152 (6.8%) students who were positive for H. pylori antibody or pepsinogen tests were enrolled in the study. Among them, 107 students underwent endoscopy, and their biopsy samples were investigated. Seventy-five students were diagnosed with H. pylori infections. Results Of 75 H. pylori-positive patients, 57 (76.0%) had endoscopic atrophic gastritis, and 42 (56.0%) had histological atrophy. A few patients had severe atrophic gastritis. All 65 patients who underwent an eradication assessment were successfully treated. After successful eradication, 26 patients underwent endoscopic follow-up. The mean follow-up period was 32.9 months. A histological evaluation revealed that gastric antrum atrophy had subsided in 11 of 14 patients, and atrophy in the lesser curvature of the gastric body had subsided in 7 of 8 patients. Conclusion More than half of young adults with H. pylori infection had atrophic gastritis. We found mild atrophy in young adults, which subsided shortly after eradication treatment. This study provides a foundation for future studies to evaluate the validity of eradication therapy in preventing gastric cancer in patients.

    DOI： 10.2169/internalmedicine.1851-23

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  • 基礎研究1 ピロリ菌感染モデルにおける細胞性免疫の低下と硝酸塩還元菌の影響

    横田 憲治, 内山 淳平, 倉岡 紗樹子, 岡上 昇太郎, 河野 吉泰, 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   30回   70 - 70   2024.6

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  • 胃癌患者の胃内より分離した硝酸塩還元菌のピロリ菌共感染マウスへの影響

    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   79 ( 2 )   140 - 140   2024.6

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  • 胃炎-胃癌患者の胃粘膜より分離された硝酸塩還元菌の性状

    桑木 星里香, 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   79 ( 2 )   152 - 152   2024.6

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  • 消化管細菌叢と胃の疾患 胃癌患者の胃内より分離される硝酸塩還元菌ついて

    横田 憲治, 倉岡 紗樹子, 岡上 昇太郎, 河野 吉泰, 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   29回   95 - 95   2023.6

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  • Helicobacter pylori感染胃炎における硝酸塩還元菌の胃内生息状況に関する検討

    倉岡 紗樹子, 横田 憲治, 榮 浩行, 小嶋 日菜子, 岡上 昇太郎, 河野 吉泰, 岡田 裕之

    日本ヘリコバクター学会誌   24 ( 2 )   110 - 116   2023.1

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  • Effects of Helicobacter pylori and Nitrate-Reducing Bacteria Coculture on Cells. International journal

    Hinako Ojima, Sakiko Kuraoka, Shyoutarou Okanoue, Hiroyuki Okada, Kazuyoshi Gotoh, Osamu Matsushita, Akari Watanabe, Kenji Yokota

    Microorganisms   10 ( 12 )   2022.12

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    Helicobacter pylori infection is an important risk factor for developing gastric cancer. However, only a few H. pylori-infected people develop gastric cancer. Thus, other risk factors aside from H. pylori infection may be involved in gastric cancer development. This study aimed to investigate whether the nitrate-reducing bacteria isolated from patients with atrophic gastritis caused by H. pylori infection are risk factors for developing atrophic gastritis and gastric neoplasia. Nitrate-reducing bacteria were isolated from patients with atrophic gastritis caused by H. pylori infection. Among the isolated bacteria, Actinomyces oris, Actinomyces odontolyticus, Rothia dentocariosa, and Rothia mucilaginosa were used in the subsequent experiments. Cytokine inducibility was evaluated in monocytic cells, and mitogen-activated protein kinase (MAPK) activity and cell cycle were assessed in the gastric epithelial cells. The cytotoxicities and neutrophil-inducing abilities of the Actinomyces and Rothia species were enhanced when cocultured with H. pylori. Th1/Th2-related cytokines were also expressed, but their expression levels differed depending on the bacterial species. Moreover, H. pylori and Actinomyces activated MAPK (ERK and p38) and affected cell cycle progression. Some nitrate-reducing bacteria cocultured with H. pylori may promote inflammation and atrophy by inducing cytokine production. In addition, the MAPK activation and cell cycle progression caused by these bacteria can contribute to gastric cancer development.

    DOI： 10.3390/microorganisms10122495

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  • Helicobacter pylori感染胃炎における硝酸塩還元菌の胃内生息状況に関する検討

    倉岡 紗樹子, 横田 憲治, 榮 浩行, 小嶋 日菜子, 岡上 昇太郎, 河野 吉泰, 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   28回   106 - 106   2022.6

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  • 若年者におけるヘリコバクターピロリ除菌治療による腸内細菌叢の変化についての検討

    岡上 昇太郎, 後藤 和義, 倉岡 紗樹子, 稲生 祥子, 里見 拓也, 濱田 健太, 河野 吉泰, 神崎 洋光, 岩室 雅也, 川野 誠司, 河原 祥朗, 横田 憲治, 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   28回   103 - 103   2022.6

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  • ヘリコバクター感染の基礎研究の現況 Helicobacter pyloriと共培養される胃内硝酸塩還元菌の細胞に対する作用

    小嶋 日菜子, 倉岡 沙樹子, 岡上 昇太郎, 河野 吉泰, 岡田 裕之, 横田 憲治

    日本ヘリコバクター学会学術集会プログラム・抄録集   28回   85 - 85   2022.6

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  • Establishment of a reference panel of Helicobacter pylori strains for antimicrobial susceptibility testing. International journal

    Kenji Yokota, Takako Osaki, Shunji Hayashi, Shin-Ichi Yokota, Hiroaki Takeuchi, Emiko Rimbara, Hinako Ojima, Toyotaka Sato, Hideo Yonezawa, Keigo Shibayama, Kengo Tokunaga, Shigeru Kamiya, Kazunari Murakami, Mototsugu Kato, Toshiro Sugiyama

    Helicobacter   27 ( 3 )   e12874   2022.3

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    BACKGROUND: Eradication treatment for Helicobacter pylori gastritis is covered by national health insurance since 2013 in Japan. However, eradication failure due to the increase of antimicrobial resistance has become a serious problem. The present study aims to establish a reference panel of Japanese H. pylori strains for antimicrobial susceptibility testing. METHOD: A total of 28 strains were collected from 4 medical facilities in Japan. Antimicrobial susceptibility tests (ASTs) to clarithromycin (CLR), amoxicillin (AMX), and metronidazole (MNZ), were used to select standard reference strains. Complete genome sequences were also determined. RESULTS: Three H. pylori strains (JSHR3, JSHR6 and JSHR31) were selected as standard reference strains by the Japanese Society for Helicobacter Research (JSHR). The minimum inhibitory concentrations (MICs) of the antibiotics against these 3 strains by agar dilution method with Brucella-based horse-serum-containing agar medium were as follows: JSHR3 (CLR 16 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), JSHR6 (CLR 0.016 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), and JSHR31 (CLR 16 μg/ml, AMX 1 μg/ml and MNZ 64 μg/ml). CONCLUSIONS: A reference panel of H. pylori JSHR strains was established. The panel consisted of JSHR6, which was antibiotic-susceptible, JSHR3, which was CLR-resistant, and JSHR31, which was multi-resistant. This reference panel will be essential for standardized ASTs before the optimal drugs are selected for eradication treatment.

    DOI： 10.1111/hel.12874

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  • Use of ATP Bioluminescence Assay to Evaluate Oral Streptococci.

    Akari Watanabe, Naofumi Tamaki, Kenji Yokota, Susumu Kokeguchi, Hiro-O Ito, Miwa Matsuyama

    Biocontrol science   27 ( 4 )   229 - 233   2022

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    The statistical correlation between the number of oral streptococci and the results of ATP bioluminescence assay was examined and compared with the results from Streptococcus plate counts and an oral bacteria quantification system. Because a significant correlation was found between ATP (RLU) and the number of bacteria in the oral bacteria quantification system for all seven types of oral streptococci examined, ATP would reflect a conditions of oral hygiene. However, using this assay, it was observed it may be difficult to correctly evaluate bacteria that form aggregates. Furthermore, even a small number of bacteria (below 105 CFU/mL) , which cannot be measured by the oral bacteria quantification system, could be estimated by using ATP bioluminescence assay. It was suggested that this assay could be used for quantitative evaluation of the effect of oral cleaning.

    DOI： 10.4265/bio.27.229

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  • Helicobacter pylori感染胃炎における硝酸塩還元菌の胃内生息状況に関する検討

    倉岡 紗樹子, 横田 憲治, 榮 浩行, 岡上 昇太郎, 河野 吉泰, 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   27回   196 - 196   2021.9

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  • 大学新入生ピロリ検診の検討

    岡上 昇太郎, 岡田 裕之, 田中 健大, 横田 憲治, 倉岡 紗樹子

    日本ヘリコバクター学会学術集会プログラム・抄録集   27回   201 - 201   2021.9

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  • Elizabethkingia anophelis, an emerging pathogen, inhibits RAW 264.7 macrophage function. International journal

    I Putu Bayu Mayura, Kazuyoshi Gotoh, Hayato Nishimura, Erina Nakai, Takehiko Mima, Yumiko Yamamoto, Kenji Yokota, Osamu Matsushita

    Microbiology and immunology   65 ( 8 )   317 - 324   2021.8

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    Elizabethkingia anophelis is a pathogen that can cause a life-threatening infection in immunocompromised patients. The first case of E. anophelis infection was reported in 2013; subsequently, an increase in its incidence has been reported globally. Additionally, a mortality rate of more than 30% was observed in the US outbreak of 2015. To date, the pathogenic mechanisms underlying E. anophelis infection, such as toxin production, remain unclear. Since tissue macrophages act as the first line of defense against pathogens, in the present study the interactions between E. anophelis and a macrophage-like cell line RAW 264.7 were examined. Although E. anophelis showed no cytotoxicity toward RAW 264.7 macrophages, the infection inhibited LPS-induced morphological changes and activation of differentiation markers for the polarization of RAW 264.7 macrophages toward an M1-like phenotype. However, when the cell contact was restricted using Transwell inserts or bacterial culture supernatants were used instead of live bacteria, no such inhibition was observed. Moreover, it was shown that E. anophelis evaded phagocytosis. Overall, the results suggest that E. anophelis infection inhibits the differentiation of RAW 264.7 macrophages to a pro-inflammatory phenotype in a contact-dependent manner.

    DOI： 10.1111/1348-0421.12888

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  • Serodiagnosis and bacterial genome of helicobacter pylori infection

    Aina Ichihara, Hinako Ojima, Kazuyoshi Gotoh, Osamu Matsushita, Susumu Take, Hiroyuki Okada, Akari Watanabe, Kenji Yokota

    Toxins   13 ( 7 )   2021.7

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    DOI： 10.3390/toxins13070467

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  • カルバペネマーゼ産生腸内細菌科細菌に対するビアペネムの殺菌効果

    三好 諒, I Putu Bayu Mayura, 後藤 和義, 美間 健彦, 山本 由弥子, 横田 憲治, 松下 治, 萩谷 英大

    日本細菌学雑誌   76 ( 1 )   119 - 119   2021.2

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  • 敗血症性肺塞栓症患者から分離されたTsukamurella inchonensisの同定(Identification of Tsukamurella inchonensis isolated from septic pulmonary emboli(SPE) patient)

    I Putu Bayu Mayura, Gotoh Kazuyoshi, 美間 健彦, 山本 由弥子, 横田 憲治, 松下 治, 萩谷 英大

    日本細菌学雑誌   76 ( 1 )   89 - 89   2021.2

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  • Antibacterial effects of disulfiram in helicobacter pylori

    Tomomi Kobatake, Keiki Ogino, Hiroyuki Sakae, Kazuyoshi Gotoh, Akari Watanabe, Osamu Matsushita, Hiroyuki Okada, Kenji Yokota

    Infection and Drug Resistance   14   1757 - 1764   2021

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    DOI： 10.2147/IDR.S299177

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  • Environmental survey of Methicillin-Resistant Staphylococci in a Hospital in Japan.

    Akari Watanabe, Tokiko Watanabe, Susumu Kokeguchi, Yumiko Yamamoto, Osamu Matsushita, Kenji Yokota

    Biocontrol science   26 ( 3 )   137 - 145   2021

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    We examined the hospital-wide incidence of methicillin-resistant Staphylococcus contamination in a hospital environment to predict the risk of the nosocomial spread of infection. Samples were also taken different surfaces and medical equipment in a general hospital ward and a staff station. The isolates were identified bacterial strains and analyzed by PCR for detection of the mecA gene and staphylococcal cassette chromosome mec (SCCmec) types (I-V). Overall, out of 146 isolates that were screened, 15.7% of the samples in the hospital wards were contaminated with Staphylococcus aureus and 74.7% were isolated with coagulase-negative Staphylococci (CNS). The methicillin-resistant mecA gene was detected in all oxacillin-resistant S. aureus, and 89% of oxacillin-resistant CNS was identified as methicillin-resistant S. aureus (MRSA) and MRCNS respectively. All S. aureus and CNS from the hospital wards with MRSA patients were detected as MRSA and MRCNS. A widespread distribution of MRSA and MRCNS was detected in the Cuff. The majority of the MRSA and MRCNS isolates in this study were SCCmec type V, which are a community-acquired infection type. The increased incidence and prevalence of community-acquired MRSA and MRCNS, as well as hospital-acquired MRSA, should be recognized as serious healthcare problems.

    DOI： 10.4265/bio.26.137

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  • 尿沈渣標本中に出現する顆粒状物質と尿路細菌叢との関連について

    佐藤 妃映, 横田 憲治, 渡辺 朱理, 苔口 進, 衛藤 友美, 高阪 翔士

    日本防菌防黴学会誌   48 ( 12 )   623 - 628   2020.12

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  • Correction to: Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication. Reviewed

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Chiaki Kusumoto, Takayuki Imada, Fumihiro Hamada, Tomowo Yoshida, Kenji Yokota, Toshiharu Mitsuhashi, Hiroyuki Okada

    Journal of gastroenterology   55 ( 3 )   289 - 290   2020.3

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    In the original publication of the article, the figure 3 was published with errors. The corrected figure 3 should appear as in this correction.

    DOI： 10.1007/s00535-019-01654-x

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  • Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication. Reviewed

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Chiaki Kusumoto, Takayuki Imada, Fumihiro Hamada, Tomowo Yoshida, Kenji Yokota, Toshiharu Mitsuhashi, Hiroyuki Okada

    Journal of gastroenterology   55 ( 3 )   281 - 288   2020.3

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    BACKGROUND AND AIMS: Eradication of Helicobacter pylori reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of H. pylori. METHODS: We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of H. pylori infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade. RESULTS: During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53-26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk. CONCLUSIONS: The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of H. pylori irrespective of the severity of gastric atrophy.

    DOI： 10.1007/s00535-019-01639-w

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  • Hepatic Campylobacter jejuni infection in patients with Castleman-Kojima disease (idiopathic multicentric Castleman disease with thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome). International journal

    Chihiro Kageyama, Takuro Igawa, Yuka Gion, Noriko Iwaki, Tetsuya Tabata, Takehiro Tanaka, Eisei Kondo, Hajime Sakai, Koichi Tsuneyama, Kazuhiro Nomoto, Hiroko Noguchi, Tadashi Yoshino, Kenji Yokota, Yasuharu Sato

    Pathology international   69 ( 10 )   572 - 579   2019.10

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    Castleman-Kojima disease, also known as idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO), is a recently recognized systemic inflammatory disorder with a characteristic series of clinical symptoms, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Patients with iMCD-TAFRO often develop severe abdominal pain, elevated alkaline phosphatase levels, and systemic inflammation, but the etiological factors are unknown. To investigate the potential role of bacterial infection in the pathogenesis of iMCD-TAFRO, we performed polymerase chain reaction (PCR) for the bacterial 16S rRNA gene with DNA extracted from liver specimens of three patients with iMCD-TAFRO, four patients with amyotrophic lateral sclerosis, and seven patients with inflammatory conditions. Sequencing of the PCR product showed 99% DNA sequence identity with Campylobacter jejuni in all three patients with iMCD-TAFRO and in two patients with inflammatory conditions. Immunohistochemical and electron microscopy analyses could not identify C. jejuni in patients with iMCD-TAFRO. The findings indicated that C. jejuni infection is not the pathological cause of iMCD-TAFRO; however, this ubiquitous bacterium may play a role in uncontrolled systemic hypercytokinemia, possibly through the development of cross-reactive autoantibodies.

    DOI： 10.1111/pin.12856

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  • 地域在住高齢者におけるメチシリン耐性ブドウ球菌の保菌状況調査

    渡辺 朱理, 横田 憲治, 林 俊治, 苔口 進

    日本環境感染学会総会プログラム・抄録集   34回   [P - 005]   2019.2

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  • A survey of Lasioderma serricorne (Fabricius) in Japanese Dental Clinics.

    Akari Watanabe, Satoru Takaku, Kenji Yokota, Shunji Hayashi, Naofumi Tamaki, Susumu Kokeguchi

    Biocontrol science   24 ( 2 )   117 - 121   2019

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    This study was to survey the capturing rate in Japanese dental clinics of the Lasioderma serricorne (cigarette beetles) , and to evaluate the beetle's potential as a carrier for transmission of nosocomial pathogens. L. serricorne imagoes were captured in pheromone traps in 14 Japanese dental clinics in August and September 2012 and 2013, and their numbers recorded. Polymerase chain reaction (PCR) for the bacterial antibiotic-resistant genes mecA, vanA, vanB, blaIMP, and blaVIM was performed on the captured L. serricorne imagoes. Bacterial species in the captured specimens were identified by 16S rRNA PCR and sequencing analysis. The L. serricorne imagoes were captured from 10 dental clinics (71.4%) . We failed to detect the presence of nosocomial antibiotic-resistant pathogens in L. serricorne imagoes. The bacterial species detected most commonly in the imagoes was Wolbachia sp., an intracellular proteobacterium infecting certain insect species. Monitoring of insects including L. serricorne should be incorporated into regiment of the infection control.

    DOI： 10.4265/bio.24.117

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  • Increase in antibiotic resistant Helicobacter pylori in a University Hospital in Japan. International journal

    Chihiro Kageyama, Mayu Sato, Hiroyuki Sakae, Yuka Obayashi, Yoshiro Kawahara, Takehiko Mima, Osamu Matsushita, Kenji Yokota, Motowo Mizuno, Hiroyuki Okada

    Infection and drug resistance   12   597 - 602   2019

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    Background: Eradication effectively prevents Helicobacter pylori-associated diseases; however, H. pylori antibiotic resistance has increased throughout Japan and worldwide. This study aimed to assess rates of resistance to antibiotics; amoxicillin, clarithromycin and metronidazole in a University Hospital in Japan. Materials and methods: H. pylori (208 strains) were isolated from patients at the Okayama University Hospital in Japan. The minimum inhibitory concentrations (MIC) were determined using the mean values of the E-test to determine the antimicrobial susceptibilities of the strains. Sequencing and gene analysis were performed to analyze resistance genes to clarithromycin and amoxicillin. Results: Rates of amoxicillin, clarithromycin, and metronidazole resistance were 13%, 48%, and 49%, respectively. Genetic analysis indicated that the A2143G point mutation in 23S rDNA is closely associated with the MIC of clarithromycin. The MIC in amoxicillin-resistant strains increased with an increase in the number of PBP1A amino acids mutations. Conclusion: Genetic analysis for resistant strains is not clinically effective in cases of amoxicillin resistance. Numerous bacteria with already high antibiotic resistance rates have been isolated in large hospitals such as a University Hospital. For effective eradication therapy, MIC measurement should be considered via several methods.

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  • Association of host immunity with Helicobacter pylori infection in recurrent gastric cancer. International journal

    Mayu Sato, Kou Miura, Chihiro Kageyama, Hiroyuki Sakae, Yuka Obayashi, Yoshiro Kawahara, Osamu Matsushita, Kenji Yokota, Hiroyuki Okada

    Infectious agents and cancer   14   4 - 4   2019

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    Background: Helicobacter pylori infection is associated with the incidence of gastric cancer. Endoscopic resection has been developed as a proper technique to treat early stage of gastric cancer. However, some patients develop recurrent gastric cancer within 5 years after endoscopic treatment. The aim of the present study is to explore a biomarker for detecting people who has high risk of gastric cancer recurrence. Methods: We analyzed the Interleukin-10 (IL-10) single nucleotide polymorphism (SNP) and IgG subclass responses to the bacteria in patients with early gastric cancer and recurrent gastric cancer. Results: Patients with hetero-type in the 1082 SNP and CC genotype in the 592 SNP were at high risk of recurrence of gastric cancer. In patients with genotype carrying high risk of recurrence, IgG1 level tended to be higher than that in patients with other genotypes. Conclusions: Dominance of T helper 2 (Th2) immunity controlled by IL-10 cytokine may be associated with H. pylori-associated gastric cancer recurrence.

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  • 吸い飲み内残余飲料の微生物汚染状況に関する実験的予備調査 Reviewed

    渡辺朱理, 長岡仁美, 中江弘美, 吉岡昌美, 横田憲治, 松山美和, 苔口進

    医学と生物学   159 ( 4 )   i4_Oj01 - 6   2019

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  • Use of ATP bioluminescence to survey the spread of aerosol and splatter during dental treatments Reviewed

    A. Watanabe, N. Tamaki, K. Yokota, M. Matsuyama, S. Kokeguchi

    Journal of Hospital Infection   99 ( 3 )   303 - 305   2018.7

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    DOI： 10.1016/j.jhin.2018.03.002

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  • Vibrio alginolyticus VepA Induces Lysosomal Membrane Permeability and Cathepsin-Independent Cell Death.

    Agus Eka Darwinata, Kazuyoshi Gotoh, Takehiko Mima, Yumiko Yamamoto, Kenji Yokota, Osamu Matsushita

    Acta medica Okayama   72 ( 3 )   231 - 239   2018.6

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    The bacterium Vibrio alginolyticus, an opportunistic pathogen in humans, has a type III secretion system (T3SS) that is responsible for its cytotoxicity toward eukaryotic cells. The effector of T3SS that is responsible for the cytotoxicity had not been identified. Here we demonstrate that VepA, a homolog of the T3SS effector in V. parahaemolyticus, is required for cytotoxicity in V. alginolyticus. VepA induces lysosomal membrane permeabilization, and it allows the leakage of only small molecules into the cytosol. Our findings revealed that VepA induces cathepsin-independent cell death in mammalian cells. The ferrous ion, one of the small molecules in the lysosome contents, appears to be involved in the cell death caused by V. alginolyticus VepA.

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  • TAFRO症候群を伴う特発性多中心性キャッスルマン病患者の3症例における肝臓Campylobacter jejuni感染症(Hepatic Campylobacter jejuni infection present in three idiopathic multicentric Castleman disease patients with TAFRO syndrome)

    井川 卓朗, 影山 千紘, 横田 憲治, 吉野 正, 佐藤 康晴

    日本リンパ網内系学会会誌   58   122 - 122   2018.5

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  • DEC205 mediates local and systemic immune responses to Helicobacter pylori infection in humans. International journal

    Masahide Kita, Kenji Yokota, Chihiro Kageyama, Susumu Take, Kazuyoshi Goto, Yoshiro Kawahara, Osamu Matsushita, Hiroyuki Okada

    Oncotarget   9 ( 22 )   15828 - 15835   2018.3

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    Helicobacter pylori infections cause gastritis and affect systemic immune responses; however, no direct association between immune cells and stomach bacteria has yet been reported. The present study investigated DEC205-mediated phagocytosis of H. pylori and the role of DEC205-positive macrophages in the human gastric mucosa. DEC205 mediated phagocytosis of H. pylori was detected immunocytochemically in PMA-stimulated macrophages differentiated from NOMO1 cells. Expression of DEC205 mRNA in peripheral blood mononuclear cells (PBMCs) from H. pylori-infected patients was analyzed following stimulation with H. pylori cell lysate. We found that anti-DEC205 antibodies inhibited phagocytosis of H. pylori. The number of cells double-positive for DEC205 and CD14 in human gastric mucosa was higher in H. pylori-infected patients. DEC205-positive macrophages invaded the extracellular space between epithelial cells within gastric pits. In addition, DEC205 mRNA expression was upregulated in human PBMCs stimulated with H. pylori lysate. These findings suggest DEC205-expressing macrophages are important for recognition of H. pylori in human gastric mucosa, which affects systemic immunity.

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  • Low incidence of esophageal adenocarcinoma after eradication of Helicobacter pylori in Japan. Reviewed International journal

    Take S, Mizuno M, Ishiki K, Hamada F, Yoshida T, Yokota K, Okada H

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association   16 ( 12 )   1995 - 1996   2018.3

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  • 細菌性コラゲナーゼのPKDドメインの構造機能解析と骨新生誘導剤の開発(Structure analysis of bacterial collagenases to develop therapeutics to induce osteogenesis) Reviewed

    松下 治, 内田 健太郎, 美間 健彦, 後藤 和義, 山本 由弥子, 横田 憲治, Bauer Ryan, 高相 晶士, Sakon Joshua

    日本細菌学雑誌   73 ( 1 )   114 - 114   2018.2

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  • Elevated serum interferon gamma-induced protein 10 kDa is associated with TAFRO syndrome Reviewed

    Noriko Iwaki, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Masao Hagihara, Yuko Hashimoto, Kenji Yokota, Masataka Okamoto, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato

    SCIENTIFIC REPORTS   7   42316   2017.2

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  • Monitoring of bacterial contamination of dental unit water lines using adenosine triphosphate bioluminescence. Reviewed International journal

    Watanabe A, Tamaki N, Yokota K, Matsuyama M, Kokeguchi S

    The Journal of hospital infection   94 ( 4 )   393 - 396   2016.12

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    Bacterial contamination of dental unit waterlines (DUWLs) was evaluated using ATP bioluminescence analysis and a conventional culture method. Water samples (N=44) from DUWLs were investigated for heterotrophic bacteria by culture on R2A agar, which gave counts ranging from 1.4×103 to 2.7×105 cfu/mL. The ATP bioluminescence results for DUWL samples ranged from 6 to 1189 relative light units and could be obtained within 1min; these correlated well with the culture results (r=0.727-0.855). We conclude that the results of the ATP bioluminescence assay accurately reflect the results of conventional culture-based testing. This method is potentially useful for rapid and simple monitoring of DUWL bacterial contamination.

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  • Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease Reviewed

    Noriko Iwaki, David C. Fajgenbaum, Christopher S. Nabel, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Isao Yoshida, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Kosei Matsue, Mitsutoshi Kurosawa, Masao Hagihara, Akio Saito, Masataka Okamoto, Kenji Yokota, Shinichiro Hiraiwa, Naoya Nakamura, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato

    AMERICAN JOURNAL OF HEMATOLOGY   91 ( 2 )   220 - 226   2016.2

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  • Geranylgeranylacetone selectively binds to the HSP70 of Helicobacter pylori and alters its coccoid morphology Reviewed

    Ewa Grave, Shin-ichi Yokota, Soh Yamamoto, Arisa Tamura, Takako Ohtaki-Mizoguchi, Kenji Yokota, Keiji Oguma, Kazuhiko Fujiwara, Nobuaki Ogawa, Tomoya Okamoto, Michiro Otaka, Hideaki Itoh

    SCIENTIFIC REPORTS   5   13738   2015.9

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  • 口腔清掃と洗口との併用効果の検討 口腔内細菌数を指標にして

    渡辺 朱理, 横田 憲治, 松山 美和, 苔口 進

    日本歯科衛生学会雑誌   10 ( 1 )   120 - 120   2015.8

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  • Signature-tagged mutagenesis of Vibrio vulnificus. Reviewed

    Mai Yamamoto, Takashige Kashimoto, Ping Tong, Jianbo Xiao, Michiko Sugiyama, Miyuki Inoue, Rie Matsunaga, Kohei Hosohara, Kazue Nakata, Kenji Yokota, Keiji Oguma, Koichiro Yamamoto

    The Journal of veterinary medical science   77 ( 7 )   823 - 8   2015.7

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    Vibrio vulnificus is the causative agent of primary septicemia, wound infection and gastroenteritis in immunocompromised people. In this study, signature-tagged mutagenesis (STM) was applied to identify the virulence genes of V. vulnificus. Using STM, 6,480 mutants in total were constructed and divided into 81 sets (INPUT pools); each mutant in a set was assigned a different tag. Each INPUT pool was intraperitoneally injected into iron-overloaded mice, and in vivo surviving mutants were collected from blood samples from the heart (OUTPUT pools). From the genomic DNA of mixed INPUT or OUTPUT pools, digoxigenin-labeled DNA probes against the tagged region were prepared and used for dot hybridization. Thirty tentatively attenuated mutants, which were hybridized clearly with INPUT probes but barely with OUTPUT probes, were negatively selected. Lethal doses of 11 of the 30 mutants were reduced to more than 1/100; of these, the lethal doses of 2 were reduced to as low as 1/100,000. Transposon-inserted genes in the 11 attenuated mutants were those for IMP dehydrogenase, UDP-N-acetylglucosamine-2-epimerase, aspartokinase, phosphoribosylformylglycinamidine cyclo-ligase, malate Na (+) symporter and hypothetical protein. When mice were immunized with an attenuated mutant strain into which IMP dehydrogenase had been inserted with a transposon, they were protected against V. vulnificus infection. In this study, we demonstrated that the STM method can be used to search for the virulence genes of V. vulnificus.

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  • Seventeen-year effects of eradicating Helicobacter pylori on the prevention of gastric cancer in patients with peptic ulcer; a prospective cohort study Reviewed

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Fumihiro Hamada, Tomowo Yoshida, Kenji Yokota, Hiroyuki Okada, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY   50 ( 6 )   638 - 644   2015.6

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  • [A Study to Determine the Optimum Antigens for the Serodiagnosis of Helicobacter Pylori Infection in Japanese Patients and the Association with IgG Subclass and Gastric Cancer]. Reviewed

    Kita M, Take S, Okada H, Matsushita O, Yokota K

    Rinsho byori. The Japanese journal of clinical pathology   63 ( 2 )   180 - 186   2015.2

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  • 環境汚染菌の消毒剤含浸ワイプによる拭き取り効果の検討

    横田 憲治, 渡邉 都貴子, 林 俊治, 渡辺 朱理, 苔口 進, 平井 義一

    日本環境感染学会誌   30 ( Suppl. )   206 - 206   2015.1

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  • 細菌必須遺伝子を標的とする阻害リード化合物の口腔細菌に対する効果

    苔口 進, 狩山 玲子, 横田 憲治, 渡辺 朱理

    日本環境感染学会誌   30 ( Suppl. )   438 - 438   2015.1

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  • Antibacterial activity of a novel synthetic progesterone species carrying a linoleic acid molecule against Helicobacter pylori and the hormonal effect of its steroid on a murine macrophage-like cell line Reviewed

    Avarzed Amgalanbaatar, Hirofumi Shimomura, Kouichi Hosoda, Shunji Hayashi, Kenji Yokota, Yoshikazu Hirai

    JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY   140   17 - 25   2014.3

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    DOI： 10.1016/j.jsbmb.2013.10.023

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  • 病院内の環境細菌調査

    横田 憲治, 渡邉 都貴子, 苔口 進, 林 俊治, 平井 義一

    日本環境感染学会誌   29 ( Suppl. )   287 - 287   2014.1

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  • [New Helicobacters other than H. pylori]. Reviewed

    Yokota K, Kita M, Okada H, Matsushita O, Oguma K

    Nihon rinsho. Japanese journal of clinical medicine   71 ( 8 )   1374 - 1379   2013.8

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    Since discovery of Helicobacter pylori, more than 30 species non-H. pylori Helicobacter spp. (NHPH) have been reported. Those NHPH were now classified into gastric Helicobacter spp. and enterohepatic Helicobacter spp.(EHS). Gastric NHPH show tight spiral and long shape in the gastric mucosa, and we can distinguish from H. pylori by light microscope. Some gastric NHPH may be zoonosis and cause gastritis in human. H. hepaticus and H. cinaedi belongs in EHS were detected in human diseases. H. hepaticus may be associated with hepatobiliary diseases in humans. Surprisingly, it was reported that H. cinaedi infection was associated with atrial arrhythmias and atherosclerosis. Many NHPH will be recognized as human pathogen in the future.

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  • The Genetic Diversity of Helicobacter pylori Virulence Genes Is Not Associated with Gastric Atrophy Progression Reviewed

    Masahide Kita, Kenji Yokota, Hiroyuki Okada, Susumu Take, Ryuta Takenaka, Yoshiro Kawahara, Keiji Oguma, Osamu Matsushita, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   67 ( 2 )   93 - 98   2013.4

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  • Detoxification of 7-Dehydrocholesterol Fatal to Helicobacter pylori Is a Novel Role of Cholesterol Glucosylation Reviewed

    Hirofumi Shimomura, Kouichi Hosoda, David J. Mcgee, Shunji Hayashi, Kenji Yokota, Yoshikazu Hirai

    JOURNAL OF BACTERIOLOGY   195 ( 2 )   359 - 367   2013.1

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    DOI： 10.1128/JB.01495-12

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  • Reinfection rate of Helicobacter pylori after eradication treatment: a long-term prospective study in Japan Reviewed

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Takayuki Imada, Tetsuji Okuno, Tomowo Yoshida, Kenji Yokota, Keiji Oguma, Masahide Kita, Hiroyuki Okada, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY   47 ( 6 )   641 - 646   2012.6

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  • Clostridium botulinum Type E Toxins Bind to Caco-2 Cells by a Different Mechanism from That of Type A Toxins Reviewed

    Kai Zhang, Yumiko Yamamoto, Tomonori Suzuki, Kenji Yokota, Shaobo Ma, Ni Nengah Dwi Fatmawati, Keiji Oguma

    ACTA MEDICA OKAYAMA   66 ( 3 )   253 - 261   2012.6

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  • Phosphatidylethanolamine of Helicobacter pylori Functions as a Steroid-Binding Lipid in the Assimilation of Free Cholesterol and 3 beta-Hydroxl Steroids into the Bacterial Cell Membrane Reviewed

    Hirofumi Shimomura, Kouichi Hosoda, Shunji Hayashi, Kenji Yokota, Yoshikazu Hirai

    JOURNAL OF BACTERIOLOGY   194 ( 10 )   2658 - 2667   2012.5

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  • Role of heat shock protein derived from Streptococcus sanguinis in Behcet’s disease Reviewed

    Kaneko F, Togashi A, Nomura E, Isogai E, Yokota K, Oguma K

    J Med Micorobiol Diagnosis   2012

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  • Steroid hormones as bactericidal agents to Helicobacter pylori Reviewed

    Kouichi Hosoda, Hirofumi Shimomura, Shunji Hayashi, Kenji Yokota, Yoshikazu Hirai

    FEMS MICROBIOLOGY LETTERS   318 ( 1 )   68 - 75   2011.5

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    DOI： 10.1111/j.1574-6968.2011.02239.x

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  • The long-term risk of gastric cancer after the successful eradication of Helicobacter pylori Reviewed

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Tomowo Yoshida, Nobuya Ohara, Kenji Yokota, Keiji Oguma, Hiroyuki Okada, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY   46 ( 3 )   318 - 324   2011.3

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    DOI： 10.1007/s00535-010-0347-9

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  • Behcet's Disease (Adamantiades-Behcet's Disease) Reviewed

    Fumio Kaneko, Ari Togashi, Sanae Saito, Hideo Sakuma, Noritaka Oyama, Koichiro Nakamura, Kenji Yokota, Keiji Oguma

    CLINICAL & DEVELOPMENTAL IMMUNOLOGY   2011   681956   2011

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  • Passive Oral Immunization by Egg Yolk Immunoglobulin (IgY) to Vibrio cholerae Effectively Prevents Cholera Reviewed

    Kazuyuki Hirai, Hideyuki Arimitsu, Koji Umeda, Kenji Yokota, Lianhua Shen, Kiyoshi Ayada, Yoshikatsu Kodama, Takao Tsuji, Yoshikazu Hirai, Keiji Oguma

    ACTA MEDICA OKAYAMA   64 ( 3 )   163 - 170   2010.6

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  • コレラ菌およびコレラ毒素Bサブユニットに対するニワトリ抗体(IgY)の有用性

    平井 一行, 衛藤 友美, 大野 佑子, 田村 臣哉, 山本 由弥子, 難波 ひかる, 阪口 義彦, 横田 憲治, 小熊 惠二

    日本薬学会年会要旨集   130年会 ( 3 )   84 - 84   2010.3

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  • Steroids mediate resistance to the bactericidal effect of phosphatidylcholines against Helicobacter pylori Reviewed

    Hirofumi Shimomura, Kouichi Hosoda, Shunji Hayashi, Kenji Yokota, Keiji Oguma, Yoshikazu Hirai

    FEMS MICROBIOLOGY LETTERS   301 ( 1 )   84 - 94   2009.12

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    DOI： 10.1111/j.1574-6968.2009.01807.x

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  • Detection of Helicobacter hepaticus in Human Bile Samples of Patients with Biliary Disease Reviewed

    Toshihide Hamada, Kenji Yokota, Kiyoshi Ayada, Kazuyuki Hirai, Tomoari Kamada, Ken Haruma, Kazuaki Chayama, Keiji Oguma

    HELICOBACTER   14 ( 6 )   545 - 551   2009.12

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    DOI： 10.1111/j.1523-5378.2009.00729.x

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  • Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis Reviewed

    K. Ayada, K. Yokota, K. Hirai, K. Fujimoto, K. Kobayashi, H. Ogawa, K. Hatanaka, S. Hirohata, T. Yoshino, Y. Shoenfeld, E. Matsuura, K. Oguma

    LUPUS   18 ( 13 )   1154 - 1168   2009.11

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  • Anabolic utilization of steroid hormones in Helicobacter pylori Reviewed

    Kouichi Hosoda, Hirofumi Shimomura, Shunji Hayashi, Kenji Yokota, Keiji Oguma, Yoshikazu Hirai

    FEMS MICROBIOLOGY LETTERS   297 ( 2 )   173 - 179   2009.8

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    DOI： 10.1111/j.1574-6968.2009.01685.x

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  • Chronic Infections and Atherosclerosis Reviewed

    Kiyoshi Ayada, Kenji Yokota, Kazuko Kobayashi, Yehuda Shoenfeld, Eiji Matsuura, Keiji Oguma

    CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY   37 ( 1 )   44 - 48   2009.8

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    DOI： 10.1007/s12016-008-8097-7

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  • Helicobacter pylori eradication may induce de novo, but transient and mild, reflux esophagitis: Prospective endoscopic evaluation Reviewed

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Yasuhiro Nagahara, Tomowo Yoshida, Kenji Yokota, Keij Oguma, Hiroyuki Okada, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   24 ( 1 )   107 - 113   2009.1

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    DOI： 10.1111/j.1440-1746.2008.05606.x

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  • Helicobacter pylori heat shock protein 60 antibodies are associated with gastric cancer Reviewed

    Aki Tanaka, Tomoari Kamada, Kenji Yokota, Akiko Shiotani, Jiro Hata, Keiji Oguma, Ken Haruma

    PATHOLOGY RESEARCH AND PRACTICE   205 ( 10 )   690 - 694   2009

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    DOI： 10.1016/j.prp.2009.04.008

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  • Immune Reactions Against Elongation Factor 2 Kinase: Specific Pathogenesis of Gastric Ulcer from Helicobacter pylori Infection Reviewed

    Kiyoshi Ayada, Kenji Yokota, Yoshiro Kawahara, Yumiko Yamamoto, Kazuyuki Hirai, Tomoki Inaba, Masahide Kita, Hiroyuki Okada, Kazuhide Yamamoto, Keiji Oguma

    CLINICAL & DEVELOPMENTAL IMMUNOLOGY   2009

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    DOI： 10.1155/2009/850623

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  • The role of streptococcal hypersensitivity in the pathogenesis of Behcet's Disease Reviewed

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

    EUROPEAN JOURNAL OF DERMATOLOGY   18 ( 5 )   489 - 498   2008.9

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  • Antibodies against heat shock protein 60 derived from Helicobacter pylori: Diagnostic implications in cardiovascular disease

    Tomoyuki Okada, Kiyoshi Ayada, Shinichi Usui, Kenji Yokota, Jinhua Cui, Yoshiro Kawahara, Tomoki Inaba, Satoshi Hirohata, Motowo Mizuno, Daisuke Yamamoto, Shozo Kusachi, Eiji Matsuura, Keiji Oguma

    Journal of Autoimmunity   29 ( 2-3 )   106 - 115   2007.9

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  • Conversion of flavodoxin from holoenzyme to apoprotein during growth phase changes in Helicobacter pylori Reviewed

    Hirofumi Shimomura, Shunji Hayashi, Kenji Yokota, Keiji Oguma, Yoshikazu Hirai

    JOURNAL OF BACTERIOLOGY   189 ( 13 )   4960 - 4963   2007.7

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  • Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 and mitogen-activated protein (MAP) kinase pathway in human monocytes Reviewed

    Ying Zhao, Kenji Yokota, Kiyoshi Ayada, Yumiko Yamamoto, Tomayuki Okada, Lianhua Shen, Keiji Oguma

    JOURNAL OF MEDICAL MICROBIOLOGY   56 ( 2 )   154 - 164   2007.2

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  • Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases Reviewed

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

    JOURNAL OF GASTROENTEROLOGY   42   21 - 27   2007.1

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  • A better cure rate with 800 mg than with 400 mg clarithromycin regimens in one-week triple therapy for Helicobacter pylori infection in cigarette-smoking peptic ulcer patients Reviewed

    Hidehiko Ishioka, Motowo Mizuno, Susumu Take, Kuniharu Ishiki, Yasuhiro Nagahara, Tomowo Yoshida, Hiroyuki Okada, Kenji Yokota, Keiji Oguma

    DIGESTION   75 ( 2-3 )   63 - 68   2007

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  • Chronic infections and atherosclerosis

    Kiyoshi Ayada, Kenji Yokota, Kazuko Kobayashi, Yehuda Shoenfeld, Eiji Matsuura, Keiji Oguma

    Annals of the New York Academy of Sciences   1108   594 - 602   2007

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    DOI： 10.1196/annals.1422.062

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  • Production of anti-neurotoxin antibody is enhanced by two subcomponents, HA1 and HA3b, of Clostridium botulinum type B 16S toxin–haemagglutinin Reviewed

    Jae-Chul Lee, Kenji Yokota, Hideyuki Arimitsu, Hyun-Jung Hwang, Yoshihiko Sakaguchi, Jinhua Cui, Kouichi Takeshi, Toshihiro Watanabe, Tohru Ohyama, Keiji Oguma

    Microbiology   151 ( 11 )   3739 - 3747   2005.11

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    <italic>Clostridium botulinum</italic> type B strain produces two forms of progenitor toxin, 16S and 12S. The 12S toxin is formed by association of a neurotoxin (NTX) and a non-toxic non-haemagglutinin (NTNH), and the 16S toxin is formed by conjugation of the 12S toxin with a haemagglutinin (HA). HA consists of four subcomponents designated HA1, HA2, HA3a and HA3b. When mice were immunized with formalin-detoxified NTX, 12S or 16S, a significantly greater amount of anti-NTX antibody (Ab) was produced in the mice injected with 16S than in NTX- or 12S-injected mice. Immunization with NTX mixed with HA1 and/or HA3b also increased the anti-NTX Ab production, whereas NTX mixed with HA2 did not, indicating that HA1 and HA3b have adjuvant activity. This was further confirmed by immunizing mice with human albumin (Alb) alone or Alb mixed with either HA1 or HA3b. When mouse-spleen cells were stimulated with NTX, 16S or different HA subcomponents, 16S, HA1, HA3b and the mixture of HA1 and HA3 significantly increased interleukin 6 (IL6) production compared with NTX alone. Transcription of IL6 mRNA was low after stimulation with NTX alone, but increased to 16S-stimulation levels when NTX was mixed with HA1 or HA3b. In flow cytometry using labelled Abs against CD3 and CD19, the percentage of CD19 cells was higher following stimulation with 16S or NTX mixed with HA1 or HA3b compared with stimulation with NTX. The percentage of CD3 cells remained unchanged. These results suggest strongly that HA1 and HA3b demonstrate adjuvant activity via increasing IL6 production.

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  • HLA-DQA1*0103-DQB1*0601 haplotype and Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma Reviewed

    Yoshiro Kawahara, Motowo Mizuno, Tadashi Yoshino, Kenji Yokota, Keiji Oguma, Hiroyuki Okada, Shigeatsu Fujiki, Yasushi Shiratori

    Clinical Gastroenterology and Hepatology   3 ( 9 )   865 - 868   2005.9

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  • The effect of eradicating Helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease Reviewed

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Yasuhiro Nagahara, Tomowo Yoshida, Kenji Yokota, Keiji Oguma, Hiroyuki Okada, Yasushi Shiratori

    American Journal of Gastroenterology   100 ( 5 )   1037 - 1042   2005.5

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  • Neutrophil and lymphocyte responses to oral Streptococcus in Adamantiades-Behcet's disease Reviewed

    T Kurauchi, K Yokota, T Matsuo, Y Fujinami, E Isogai, H Isogai, H Ohtsuki, K Oguma

    FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY   43 ( 2 )   125 - 131   2005.2

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  • Alteration in the composition of cholesteryl glucosides and other lipids in Helicobacter pylori undergoing morphological change from spiral to coccoid form Reviewed

    Hirofumi Shimomura, Shunji Hayashi, Kenji Yokota, Keiji Oguma, Yoshikazu Hirai

    FEMS Microbiology Letters   237 ( 2 )   407 - 413   2004.8

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    DOI： 10.1016/j.femsle.2004.07.004

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  • Helicobacter pylori Eradication Improves Pre-Existing Reflux Esophagitis in Patients With Duodenal Ulcer Disease Reviewed

    Kuniharu Ishiki, Motowo Mizuno, Susumu Take, Yasuhiro Nagahara, Tomowo Yoshida, Kazuhide Yamamoto, Hiroyuki Okada, Kenji Yokota, Keiji Oguma, Yasushi Shiratori

    CLINICAL GASTROENTEROLOGY AND HEPATOLOGY   2 ( 6 )   474 - 479   2004.6

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    DOI： 10.1053/S1542-3565(04)00165-X

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  • H. pylori decreases gastric mucin synthesis via inhibition of galactosyltransferase

    Shouichi Tanaka, Motowo Mizuno, Toshirou Maga, Fumiya Yoshinaga, Jun Tomoda, Junichirou Nasu, Hiroyuki Okada, Kenji Yokota, Keiji Oguma, Yasushi Shiratori, Takao Tsuji

    Hepato-Gastroenterology   50 ( 53 )   1739 - 1742   2003.9

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  • Outcome of patients with inconsistent results from 13C-urea breath test and bacterial culture at the time of assessment of Helicobacter pylori eradication therapy in Japan

    Yasuhiro Nagahara, Motowo Mizuno, Toshirou Maga, Kuniharu Ishiki, Tetsuji Okuno, Tomowo Yoshida, Kenji Yokota, Keiji Oguma, Hiroyuki Okada, Takao Tsuji

    Hepato-Gastroenterology   50 ( 53 )   1700 - 1703   2003.9

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  • Antimicrobial activity of synthetic human CAP18 peptides to Streptococcus sanguis isolated from patients with Behcet's disease Reviewed

    E Isogai, M Hirata, H Isogai, K Matuo, K Kimura, K Yokota, K Oguma, M Tojo, F Kaneko, S Kotake, S Ohno

    ADAMANTIADES-BEHCET'S DISEASE   528   195 - 200   2003

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  • Interleukin-1β Genetic Polymorphism Influences the Effect of Cytochrome P 2C19 Genotype on the Cure Rate of 1-Week Triple Therapy for Helicobacter pylori Infection

    Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Yasuhiro Nagahara, Tomowo Yoshida, Tomoki Inaba, Kazuhide Yamamoto, Hiroyuki Okada, Kenji Yokota, Keiji Oguma, Yasushi Shiratori

    American Journal of Gastroenterology   98 ( 11 )   2403 - 2408   2003

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    DOI： 10.1016/S0002-9270(03)00713-5

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  • Concurrent gastric and colonic low-grade mucosa-associated lymphoid tissue lymphomata in a patient without Helicobacter pylori infection

    Hiroyuki Okada, Motowo Mizuno, Tadashi Yoshino, Kenji Yokota, Hiroaki Okazaki, Nobuaki Okano, Junichirou Nasu, Tomohiko Mannami, Keiji Oguma, Tadaatsu Akagi, Takao Tsuji, Yasushi Shiratori

    Digestive Endoscopy   15 ( 1 )   55 - 59   2003

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    DOI： 10.1046/j.1443-1661.2003.00108.x

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  • Characterisation of monoclonal antibodies against haemagglutinin associated with Clostridium botulinum type C neurotoxin Reviewed International journal

    NAZIRA MAHMUT, KAORU INOUE, YUKAKO FUJINAGA, LYNN HUGHES, HIDEYUKI ARIMITSU, YOSHIHIKO SAKAGUCHI, AIJI OHTSUKA, TAKURO MURAKAMI, KENJI YOKOTA, KEIJI OGUMA

    Journal of Medical Microbiology   51 ( 4 )   286 - 294   2002.4

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    Of 11 monoclonal antibodies (MAbs) prepared against the non-toxic component of type C Clostridium botulinum 16S toxin to clarify the function of the non-toxic component, seven recognised HA1, three recognised HA3b and one recognised HA2. Results of epitope mapping indicated that three of the seven anti-HA1 MAbs recognised the region between amino acid residues 121 and 140 and four recognised the three-dimensional structure of HA1. Three anti-HA3b MAbs recognised different regions between (approximately) amino acids 405-430, 180-270 and 275-297. The ability of these MAbs to interfere with binding of 16S toxin or non-toxic component, HA1 or HA3b to erythrocytes and to intestine tissue sections of guinea-pig was observed. MAbs against HA3b and HA2 did not inhibit 16S toxin binding to either erythrocytes or epithelial cells, whereas some MAbs against HA1 did inhibit binding. The seven anti-HA1 MAbs can be classified into four groups based on their binding inhibition activities. The anti-HA1 MAbs that inhibited the binding of 16S toxin to the epithelial cells also neutralised or reduced the oral toxicity in mice, indicating that HA may play an important role in the absorption of the 16S toxin from the small intestine.

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  • Bacteriology of H. pylori

    Keiji Oguma, Kenji Yokota, Yoshikazu Hirai, Shunji Hayashi

    Nippon rinsho. Japanese journal of clinical medicine   60   74 - 83   2002

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  • Antibody to heat shock protein can be used for early serological monitoring of Helicobacter pylori eradication treatment Reviewed

    N Yunoki, K Yokota, M Mizuno, Y Kawahara, M Adachi, H Okada, S Hayashi, Y Hirai, K Oguma, T Tsuji

    CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY   7 ( 4 )   574 - 577   2000.7

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  • Characterization of hemagglutinin activity of clostridium botulinum type A, C and D HA positive progenitor toxins and type D HA1

    Kaoru Inoue, Yukako Fujinaga, Kenji Yokota, Toshihiro Watanabe, Kouichi Takeshi, Tohru Ohyama, Katsuhiro Inoue, Keiji Oguma

    Japanese Journal of Infectious Diseases   53 ( 1 )   32 - 33   2000.2

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  • Combined effect of rebamipide and ecabet sodium on Helicobacter pylori adhesion to gastric epithelial cells Reviewed

    S Hayashi, T Sugiyama, K Yokota, H Isogai, E Isogai, H Shimomura, K Oguma, N Asaka, Y Hirai

    MICROBIOLOGY AND IMMUNOLOGY   44 ( 7 )   557 - 562   2000

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  • Molecular typing of enterohemorrhagic Escherichia coli O157:H7 isolated in Okayama Prefecture using pulsed field gel electrophoresis and random amplification of polymorphic DNA.

    Funamori Yuka, Fujinaga Yukako, Yokota Kenji, Inoue Kaoru, Hirai Yoshikazu, Oguma Keiji, Kira Shohei, Taketa Kazuhisa

    Acta Medica Okayama   53 ( 4 )   193 - 200   1999.8

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    DOI： 10.18926/AMO/31612

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  • Expression and characterization of the hemagglutinin-subcomponents of Clostridium botulinum type C progenitor toxin

    Yukako Fujinaga, Kaoru Inoue, Kenji Yokota, Kouichi Takeshi, Tohru Ohyama, Toshihiro Watanabe, Katsuhiro Inoue, Keiji Oguma

    Japanese Journal of Infectious Diseases   52 ( 1 )   27   1999.2

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  • Characterization of haemagglutinin activity of Clostridium botulinum type C and D 16S toxins, and one subcomponent of haemagglutinin (HA1)

    Kaoru Inoue, Yukako Fujinaga, Koichi Honke, Kenji Yokota, Tetsuya Ikeda, Tohru Ohyama, Kouichi Takeshi, Toshihiro Watanabe, Katsuhiro Inoue, Keiji Oguma

    Microbiology   145 ( 9 )   2533 - 2542   1999

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    DOI： 10.1099/00221287-145-9-2533

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  • Antibody and cytokine responses in Helicobacter-pylori-infected various mouse strains Reviewed

    A Dey, K Yokota, K Kosavashi, K Oguma, Y Hirai, T Akagi

    ACTA MEDICA OKAYAMA   52 ( 1 )   41 - 48   1998.2

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  • Analysis of immunoglobulin A antibodies to Helicobacter pylori in serum and gastric juice in relation to mucosal inflammation Reviewed

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

    Clin. Diag. Labo. Immunol.   5 ( 5 )   617 - 621   1998

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  • Detection of Helicobacter pylori associated antigen and heat shock protein 60 on follicular dendritic cells in the germinal centres of low grade B cell lymphoma of gastric mucosa associated lymphoid tissue (MALT)

    Keita Kobayashi, Kenji Yokota, Tadashi Yoshino, Yoshiro Kawahara, Ashoka Dey, Yoshikazu Hirai, Keiji Oguma, Tadaatsu Akagi

    Journal of Clinical Pathology   51 ( 5 )   396 - 398   1998

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    DOI： 10.1136/jcp.51.5.396

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  • Modification of Helicobacter pylori adhesion to human gastric epithelial cells by antiadhesion agents

    S. Hayashi, T. Sugiyama, M. Asaka, K. Yokota, K. Oguma, Y. Hirai

    Digestive Diseases and Sciences   43 ( 9 )   1998

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  • IgA protease produced by Streptococcus sanguis and antibody production against IgA protease in patients with Behcet's disease Reviewed

    K Yokota, K Oguma

    MICROBIOLOGY AND IMMUNOLOGY   41 ( 12 )   925 - 931   1997

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  • Brief communication: A rapid and simple method to quantify Helicobacter pylori adhesion to human gastric MKN-28 cells

    Shunji Hayashi, Toshiro Sugiyama, Akira Yachi, Kenji Yokota, Yoshikazu Hirai, Keiji Oguma, Nobuhiro Fujii

    Journal of Gastroenterology and Hepatology (Australia)   12 ( 5 )   373 - 375   1997

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    DOI： 10.1111/j.1440-1746.1997.tb00445.x

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  • 80 尋常性乾癬患者におけるCandida albicans血中抗体価の特徴と時間的推移について

    田中 智, 山本 美保, 飯田 憲治, 松田 三千雄, 林 俊治, 横田 憲治, 小熊 恵二

    アレルギー   45 ( 8 )   900 - 900   1996

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  • Lipid profile of Helicobacter spp.: Presence of cholesteryl glucoside as a characteristic feature

    Mahmudul Haque, Yoshikazu Hirai, Kenji Yokota, Noriko Mori, Israt Jahan, Hideyuki Ito, Hisako Hotta, Ikuya Yano, Yasuhiro Kanemasa, Keiji Oguma

    Journal of Bacteriology   178 ( 7 )   2065 - 2070   1996

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    DOI： 10.1128/jb.178.7.2065-2070.1996

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  • LIPID PROFILES OF HELICOBACTER-PYLORI AND HELICOBACTER-MUSTELAE GROWN IN SERUM-SUPPLEMENTED AND SERUM-FREE MEDIA Reviewed

    M HAQUE, Y HIRAI, K YOKOTA, K OGUMA

    ACTA MEDICA OKAYAMA   49 ( 4 )   205 - 211   1995.8

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  • 240 尋常性乾癬におけるCandida albicans血中抗体価の検討

    田中 智, 飯田 憲治, 松田 三千雄, 林 俊治, 続 佳代, 横田 憲治, 小熊 恵二

    アレルギー   44 ( 3 )   414 - 414   1995

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  • 231 アトピー性皮膚炎におけるCandida albicans血中抗体価の検討

    飯田 憲治, 田中 智, 林 俊治, 続 佳代, 松田 三千雄, 横田 憲治, 小熊 恵二

    アレルギー   44 ( 3 )   412 - 412   1995

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  • Unique cholesteryl glucosides in Helicobacter pylori: Composition and structural analysis

    Y. Hirai, M. Haque, T. Yoshida, K. Yokota, T. Yasuda, K. Oguma

    Journal of Bacteriology   177 ( 18 )   5327 - 5333   1995

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    DOI： 10.1128/jb.177.18.5327-5333.1995

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  • HELICOBACTER-PYLORI INDUCES INFLAMMATION IN MOUSE URINARY-BLADDER AND PELVIS Reviewed

    H ISOGAI, E ISOGAI, K KIMURA, N FUJII, K YOKOTA, K OGUMA

    MICROBIOLOGY AND IMMUNOLOGY   38 ( 5 )   331 - 336   1994

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  • Heat Shock Protein Produced by Helicobacter pylori

    Yokota Kenji, Hirai Yoshikazu, Haque Mahmudul, Hayashi Shyunji, Isogai Hiroshi, Sugiyama Toshiro, Nagamachi Eiko, Tsukada Yutaka, Fujii Nobuhiro, Oguma Keiji

    Japanese Journal of Microbiology   38 ( 5 )   403 - 405   1994

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    The cells of Helicobacter pylori were suspended in the medium containing 35S-methionine. After a heat shock of the cells at 42C for 5, 10, and 30min, the production of proteins was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Out of many proteins produced by the cells, only 66kDa protein production was dramatically increased by heat treatment. The N-terminal amino acid sequence of 66kDa protein was quite similar to that of 62kDa and 54kDa proteins previously suggested as heat shock protein (HSP) of H. pylori based on the reaction with polyclonal and monoclonal antibodies against HSP 60 family proteins produced by other bacteria. Therefore, it was concluded that H. pylori produces the 66kDa protein as its major heat shock protein which belongs to HSP 60 family.

    DOI： 10.1111/j.1348-0421.1994.tb01799.x

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  • 356 アトピー性皮膚炎におけるCandida albicans血中抗体価の検討

    飯田 憲治, 田中 智, 横田 憲治, 小熊 恵二, 松田 三千雄

    アレルギー   42 ( 9 )   1398 - 1398   1993

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  • Experimental animal models in Mongolian gerbils and mice

    H. Isogai, E. Isogai, K. Yokota, K. Oguma

    Nippon rinsho. Japanese journal of clinical medicine   51 ( 12 )   3138 - 3143   1993

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  • Lipid composition of Helicobacter pylori

    Y. Hirai, M. Haque, K. Yokota, K. Oguma

    Nippon rinsho. Japanese journal of clinical medicine   51 ( 12 )   3094 - 3101   1993

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  • P 140 Characterization and functional properties of Streptococcus sanguis isolated from patient with Behçet's disease

    E. Isogai, K. Yokota, N. Fujii, S. Hayashi, K. Kimura, H. Isogai, N. Ishii, Y. Yamakawa, H. Nakajima, S. Ohno, S. Kotake, K. Oguma

    La Revue de medecine interne   14 ( 1 )   123   1993

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    DOI： 10.1016/s0248-8663(05)82442-7

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  • Antibody Response to Oral Streptococci in Behçet's Disease

    YOKOTA Kenji, HAYASHI Syunji, FUJII Nobuhiro, YOSHIKAWA Kouji, KOTAKE Satoshi, ISOGAI Emiko, OHNO Shigeaki, ARAKI Yoshio, OGUMA Keiji

    Japanese Journal of Microbiology   36 ( 8 )   815 - 822   1992

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    The serum antibody titers against oral streptococci were studied by enzyme-linked immunosorbent assay (ELISA) both in patients with Behçet's disease (BD) and control groups. The patients with BD showed significantly higher antibody titers to S. sanguis strains 113-20, 114-23, and 118-1 which were isolated from patients with BD, in comparison with control groups. Also, the reactions of high-titered sera to the crude cell wall and soluble (or membrane) fractions of the 113-20 strain were observed by western blot test. The sera of the patients with BD demonstrated strong bands of approximately 36kDa, 82kDa, and 87kDa in the crude cell wall fractions, and many bands of 80kDa to 150kDa in the membrane fractions, indicating that these proteins are the ones leading the high antibody titers to this bacterium in the sera of patients with BD.

    DOI： 10.1111/j.1348-0421.1992.tb02083.x

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  • Colonization of Helicobacter pylori in the Gastric Mucosa of Mongolian Gerbils

    Kenji Yokota, Keiji Oguma, Shunji Hayashi, Yoshikazu Takayama, Kouzou Imai, Tsuyoshi Yabana, Akira Yachi, Hiroshi Isogai, Emiko Isogai, Youichi Kurebayashi

    Microbiology and Immunology   35 ( 6 )   475 - 480   1991

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    DOI： 10.1111/j.1348-0421.1991.tb01577.x

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  • 胃壁中のCampylobacter pyloriの同定法の検討と血中抗菌抗体の測定 Reviewed

    横田憲治, 小熊恵二, 吉田博清, 高山義一, 杉山敏郎, 矢花 剛, 谷内 昭, 榑林陽一, 磯貝 浩, 磯貝恵美子

    感染症学会誌   64   597 - 603   1990

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    DOI： 10.11150/kansenshogakuzasshi1970.64.597

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  • Close association of Streptococcus sanguis uncommon serotypes with Behcet's disease Reviewed

    Isogai, E, Ohno, S, Takeshi, K, Yoshikawa, K, Tsurumizu, T, Isogai, H, Yokota, K, Kotake, S, Sasamoto, Y, Hashimoto, T, Shimizu, H, Fujii, N, Yamaguchi, M, Oguma, K

    Bifidobact. Microflora   9   27 - 41   1990

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    DOI： 10.12938/bifidus1982.9.1_27

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  • Chemiluminescence of neutrophils from patients with Behçet's disease and its correlation with an increased proportion of uncommon serotypes of Streptococcus sanguis in the oral flora

    E. Isogai, S. Ohno, S. Kotake, H. Isogai, T. Tsurumizu, N. Fujii, K. Yokota, B. Syuto, M. Yamaguchi, H. Matsuda, K. Oguma

    Archives of Oral Biology   35 ( 1 )   43 - 48   1990

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    DOI： 10.1016/0003-9969(90)90113-O

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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

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  • Characteristics of nitrate-reducing bacteria from patients with gastritis and gastric cancer

    桑木星里香, 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

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  • Helicobacter pylori株の長期凍結保存(Long-term cryopreservation of Helicobacter pylori strains)

    Hayashi Shunji, Uchiyama Jumpei, Yokota Kenji, Shimomura Hirofumi

    日本ヘリコバクター学会学術集会プログラム・抄録集   28回   185 - 185   2022.6

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  • 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

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  • 薬剤感受性試験用Helicobacter pylori耐性菌株の基準パネル作成

    竹内 啓晃, 横田 憲治, 横田 伸一, 林 俊治, 大崎 敬子, 林原 絵美子

    医療検査と自動化   46 ( 4 )   481 - 481   2021.8

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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    DOI： 10.15053/2016.11.04

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  • 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

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  • THERAPEUTIC POSSIBILITY FOR PATIENTS WITH BEHCET&apos;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

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  • ROLE OF ORAL STREPTOCOCCI IN THE PATHOGENESIS OF BEHCET&apos;S DISEASE

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

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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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    DOI： 10.1111/j.1083-4389.2004.00225.x

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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    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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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    DOI： 10.1046/j.1440-1746.2001.02526.x

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  • 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

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  • 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

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    J-GLOBAL

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 【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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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

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    Other Link： http://search.jamas.or.jp/link/ui/1998108533

  • 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

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  • 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

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  • 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

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    Other Link： http://search.jamas.or.jp/link/ui/1998021783

  • 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

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  • 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

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  • Helicobacter pylori and gastroduodenal disease

    K Yokota, Y Hirai, K Oguma

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

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  • 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

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  • 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

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  • 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

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  • 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

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    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.

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  • 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

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  • 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

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  • 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

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  • 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

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    Language：English   Publisher：Informa Healthcare  

    DOI： 10.3109/08910609009140254

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Research Projects

  • 新興病原体エリザベスキンギア菌によるマクロファージ成熟抑制現象の解明

    Grant number：22K07069  2022.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    後藤 和義, 横田 憲治, 中山 真彰

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

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  • オゾン水の歯科医療環境感染予防対策実用化に向けた研究

    Grant number：22K10290  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    渡辺 朱理, 横田 憲治, 玉木 直文, 松山 美和

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

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  • プロトンポンプ阻害剤服用時に歯周病原細菌が腸内細菌叢へ及ぼす影響

    Grant number：21K09893  2021.04 - 2024.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    平井 公人, 横田 憲治, 高柴 正悟

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    本研究の目的は胃酸分泌抑制剤であるプロトンポンプ阻害薬(PPI)の服用により胃酸の殺菌作用が低下した状態で，歯周病原細菌であるPorphyromonas. gingivalisもしくはその代謝産物が腸内細菌叢へ与える影響を調査することである。健康なマウスでは経口投与された細菌はほとんどが胃酸で殺菌されるが，PPI投与により胃酸の殺菌作用が低下した状態ではP.gingivalisは胃を生菌として通過し遠位腸管まで到達できるかどうかを検討した。
    まずはPPIであるランソプラゾールのマウスへの経口投与が胃酸のpHをどの程度上昇させるかを検討するためにPPI投与後24時間後に安楽死させ切除した胃の内容物のpHを計測した。PPI投与群でも非投与群でもpHは2-3程度と差がなかった。これはマウスの餌の摂取制限ができないために胃内容物が多かったことが原因と考えられるため，今後はPPIの薬効の確認には血中ガストリン濃度の測定などで評価する必要がある。
    歯周病感染モデルではマウスに1週間PPIの経口投与を行った後にP.gingivalisを2日間経口投与し，24時間後に盲腸の糞便を回収した。回収した糞便から約10mg採取し変法GAMブイヨン寒天培地上で嫌気培養し得られた菌体から採取したDNAと，盲腸糞便から直接採取したDNAを用いてP.gingivalisを特異的に認識するプライマーを用いてのDNA量をリアルタイムPCR法を用いて評価したとこと，PPIの有無に関わらず盲腸内で生菌としては確認されなかったが，盲腸内からはP.gingivalis遺伝子を確認することができた。また大腸組織の病理学的評価においてはPPI投与群で非投与群に比べてP.gingivalis経口投与によると思われる腸管粘膜の炎症性細胞浸潤や腸管上皮の傷害などの炎症所見が重症化する傾向にあった。

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  • ピロリ菌感染に伴う硝酸塩還元菌の胃内動向と疾患との関連

    Grant number：21K07366  2021.04 - 2024.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    横田 憲治, 岡田 裕之, 渡辺 朱理

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    胃癌（intestinal type）は日本人に多いがんであり、その原因はHelicobacter pylori（ピロリ菌）の高い感染率に由来している。ピロリ菌感染は、その他にも胃炎や胃粘膜委縮を起こし、消化性潰瘍、MALTリンパ腫の原因になる。胃癌以外の疾患は除菌により治癒するものがあるが、胃癌は除菌のみでは治癒できない。高齢者は感染率が高く、除菌している人も多いが、除菌後でも胃癌を発症する人はいる。この除菌後の胃癌発症は、長期のピロリ菌感染による胃粘膜萎縮が治らないためと考えられる。また萎縮胃粘膜においては、胃の酸度が低下し、胃内が中性化することによって、他の常在菌の繁殖が起こってくる。これら常在菌の中には発癌物質を産生する硝酸塩還元菌が存在し、胃癌発症の要因となる可能性がある。これら硝酸塩還元菌の胃内分布と炎症や発癌における役割を研究する。ピロリ菌による胃粘膜萎縮が発癌物質であるN-ニトロソ化合物を産生する硝酸塩還元菌の胃粘膜での増加と関係している可能性があり、ピロリ菌感染による発がん機構の新しい原因が証明できる可能性がある。ピロリ菌感染の影響による硝酸塩還元菌の胃への定着と増加が証明されれば新しい概念を提唱できる可能性がある。１）ピロリ菌培養の時に同時に培養される常在菌を分離培養し、硝酸塩還元能を調べる。２）硝酸塩還元菌のDNAを抽出し16SｒDNAの配列から菌種を同定する。３）硝酸塩還元菌の炎症反応との関係を、単球系培養細胞を使い検討する。４）細胞性免疫を抑制した、マウスモデルに投与し、発癌するか調べる。

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  • ピロリ菌除菌療法における腸内エコシステム破綻のメカニズムと制御

    Grant number：19K08395  2019.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岡田 裕之, 後藤 和義, 横田 憲治, 松下 治, 田中 健大, 岡上 昇太郎

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    大学新入生において標準的なピロリ菌除菌レジメンの下で下痢・軟便を主とした副作用を起こす患者の腸内細菌叢に共通するファクターを見出すことを目的とする。さらにはメタゲノムデータと常在細菌叢の抗菌薬感受性を融合させることで、なぜ特定の菌叢を持つ(または持たない)ことでDysbiosisが起こるのか、そ のメカニズムを説明する。さらに内視鏡的胃炎、組織学的胃炎評価も行い、最終的に腸内細菌叢解析データと融合する。2019年度から岡山大学医学部・歯学部新入生(医学科・保健学科・歯学部)に対してピロリ菌検診を例年通り実施し、H.pylori-IgG抗体陽性例を本研究の対象とする。 2019年度は新入生314人中17人が抗体陽性であった。また，2020年度は新入生320人中12人が抗体陽性であった。抗体陽性者のうち内視鏡検査を受けた14人に内視鏡的胃炎、組織学的胃炎の評価および菌株培養を行った。組織学的陽性例は現感染と診断した。組織学的胃炎、菌株培養陰性例に対しては、さらに尿素呼気試験も行い、それら3検査とも陰性の場合は抗体検査が偽陽性と判断し、未感染と診断した。その結果、現感染11名、未感染3名であった。現感染者には除菌治療を行い、除菌前、除菌1週後、2ケ月後の糞便採取を行うとともに、 除菌前後2週間の排便回数も含めた消化管症状についてアンケートを実施した。未感染者に対して も1回糞便採取とアンケートを実施した。 得られた糞便の核酸を抽出し、16SrRMA遺伝子のシークエンスにより糞便細菌菌叢解析を行った。α多様性分析では腸内細菌叢の多様性は、治療により一時的に減少するが、除菌2か月後には治療前のレベルにおおむね回復した。また、除菌直後はクレブシエラ属細菌の有意な増加を認めたが、除菌2か月後には治療前のレベルに減少した。

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  • Survay on carcinogenic risks by oral bacteria and their measures

    Grant number：19K10087  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kokeguchi Susumu

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    Helicobacter pylori is a well-known bacterial carcinogen in gastric cancer. The possible association between intestinal bacterial flora and colorectal cancer has been also most studied. The several oral bacteria species such as Fusobacterium nucleatum etc. have been frequently isolated from various cancer regions. However, the relationship between oral bacteria and cancer development remains inadequate. The aim of this study is to reveal direct or indirect carcinogenic potential in oral bacteria. The extracts of F. nucteatum was not mutagenic in the Ames test. Several Nitrate-reducing oral bacteria, including Actinomyces and Streptococcus were isolated from the Gastroscopy samples in the gastric precancerous state, which produce the main carcinogenic N-nitroso compounds. These bacteria showed the potential production of inflammatory mediators such as IL-8 and TNF-α with THP cells in the relation to mutagenesis. The genome analyses of oral bacteria to find oncoprotein CagA are ongoing.

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  • Detection of nontuberculous mycobacteria (NTM) from shower aerosols and automatic endoscope washers

    Grant number：18K10016  2018.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hirai Kazuyuki

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    The purpose of this study was the investigation of nontuberuculous mycobacteria (NTM) in shower water, shower aerosols and automatic endoscope washer.
    By replacing the shower head with a sterile-grade water filter, the number of NTM colony-forming units in the shower water and aerosols samples was below the detection levels.
    We conducted the survey on the NTM contamination of six automatic endoscope washers before and after use before maintenance and before use after maintenance. NTM was detected only three times of 54 surveys on the day before maintenance.

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  • Diagnosis of gastric cancer due to Helicobacter pylori infection and analysis of mechanism

    Grant number：18K07447  2018.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Yokota Kenji

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    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    1) Th1 / 2 immunity and gastric cancer: An infected mouse model was created, and blood sampling was performed to monitor the antibody titer subclass. After confirming infection in all mice, cytokines were administered to each mouse to induce an immune response between Th1 and Th2. From the measurement results of the IgG1 / IgG2 subclass, and 20U administration is effective in inducing immunity for cytokine administration. In addition, it was found that cell-mediated immunity was suppressed and humoral immunity was predominant in the IL-10-administered group than in the IFN-γ-administered group.
    2) Cistatin A: We investigated whether Cystatin A was affected by the antigens used for stimulation during culture and various cytokines. PMA or GM-CSF / IL-4 stimulation reduced the expression of Cystatin A. The expression of Cystatin A was considered to be related to the activation of immune functions such as cytokine stimulation.

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  • Establishment of new infection control for home dental care environment as indicator of oral pathogenic bacteria

    Grant number：17K12008  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    WATANABE Akari

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    The opportunities of home dental care for elderly in need of nursing care and immunocompromised patients have been increasing. The improvement and establishment of the infection control for home dental care under differing environment with dental clinic are present urgent issues. The purpose of this study was to investigate the pollution status of the environments during home dental care and the habitat of oral pathogenic bacteria in the elderly in need of nursing care at home. This study revealed the spread of the community-acquired methicillin-resistant staphylococci in their oral cavities. It is necessary to pay attention to their future trends. The ATP measurement values used for the survey of environmental cleanliness showed the positive correlation with the number of bacteria in oral cavity, which could be led to the oral hygiene state evaluation.

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  • Construction of standard environmental infection prevention system in Home Dental Care

    Grant number：26463163  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    WATANABE Akari

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    Grant amount：\4940000 （ Direct expense: \3800000 、 Indirect expense：\1140000 ）

    Home Dental Care, also called Domiciliary Oral Healthcare, is a special dental service that elderly requiring long-term care or immunocompromised patients receive in their home. So, the most urgent problem is maintenance and improvement of infection control for Home Dental Care environment. The aim of this study was to investigate the cleanness and microbial contamination in Home Dental Care environment which has not been reported. It was revealed the surrounding environment during Home Dental Care treatments were exposed by aerosol and droplets scattering from patients’ saliva including oral bacteria and adequate oral hygiene management would lead to environmental infection prevention. The ATP-bioluminescence method and the survey for the pathogenic pest were possibly easy and quick methods to evaluate visually the cleanness and contamination in Home Dental Care environment. They were also useful and effective for the environmental hygiene monitoring and management.

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  • Study on the elucidation and prevention for cardiovascular disorder by HACEK group oral bacteria

    Grant number：23390428  2011.04 - 2014.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KOKEGUCHI Susumu, MAEDA Hiroshi, MURAKAMI Jun, KARIYAMA Reiko, YOKOTA Kenji, NISHIMURA Fusanori

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    Grant amount：\19370000 （ Direct expense: \14900000 、 Indirect expense：\4470000 ）

    Several microbiologic and epidemiologic studies have suggested an association between oral bacteria and systemic health such as diabetes, respiratory diseases and cardiovascular diseases. The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) among oral bacteria are noted as the pathogens of infective endocarditis. The aim of this study is to determine the possible pathogenic factors of Aggregatibacter actinomycetemcomitans and oral methanogenic Archaea on infective endocarditis, and to analyze clinical and microbiological characteristics of the patients with infective endocarditis. Cell surface enolase and RNA chaperone protein, Hfq in A. actinomycetemcomitans and group II chaperonin of oral methanogenic Archaea were further characterized. The antimicrobial activity of inhibitor for methionine aminopeptidase and vitamin K analogues were also examined as a candidate of new therapeutic agents.

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  • Role of macrophage in Helicobacter pylori infection

    Grant number：20590445  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YOKOTA Kenji, AYADA Kiyoshi, OGUMA Kenji

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    Expression of DEC205, which is antigen uptake receptor on macrophage, was increased in H.pylori infected patients with early gastric cancer. However mRNA of DEC205 was also increased in the patient without gastric cancer. Expression of Th1 cytokines was detected in lymphocyte stimulated with HSP60 from patients with gastric cancer. HSP60 stimulation and its response in T helper CD4 may be available for diagnosis or prediction of gastric cancer caused by H.pylori infection. On the other hand, HSP60 antibody may be associated with cardiovascular disease (CVD) induced by H.pylori infection.

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  • Establishment of new procedure for botulism including bioterrorism, and application of botulinum toxin to the treatment

    Grant number：19390126  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    OGUMA Keiji, YOKOTA Kenji, AYADA Kiyoshi, SAKAGUCHI Yoshihiko, YAMAMOTO Yumiko, ARIMITSU Hideyuki

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    Grant amount：\19110000 （ Direct expense: \14700000 、 Indirect expense：\4410000 ）

    ボツリヌス菌や毒素、抗毒素抗体の検出方法と毒素の治療への応用を検討した。菌の検出法としては、A~F型毒素遺伝子を増幅できるPCRを開発した。毒素の検出法としてはイムノクロマト法を開発したが、現在、改良中である。抗体の検出法としては、毒素の一部を結合させたカラムを用いて抗体を濃縮して検出する方法を開発した。治療への応用としては、三叉神経痛と前立腺肥大症に適用できることをとラットを用いて実証した。

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  • Roles of Monocytes/Macrophage for Acquired Immunity in Helicobacter pylori Infection

    Grant number：18590425  2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YOKOTA Kenji, AYADA Kiyoshi, OGUMA Keiji

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    Grant amount：\4010000 （ Direct expense: \3500000 、 Indirect expense：\510000 ）

    We have been studying functions of macrophage in Hefrcobacter pylori inffection. Because we think that acquired immunity may play important roles in the diseases caused by H. pylori infection. To investigate immunity of H.pylori infection, we have shown the H.pylori- HSP60 (heat shock protein 60 kDa) activates macrophage and it is useful antigen.
    We have shown some results supporting by this Grant.
    1) HSP60 stimulated and activated a macrophage though TLR2 and TLR4. IL8 was produced from the macrophage depending on MAPK and NE-〓B activation.
    2) Arteriosclerosis in Apo-E KO mouse was progressed by H. pylori infection. The pathology was associated with immunity to HSP60 and T helper 1.
    3) Patients with arteriosclerosis possessed antibody to peptides from H. pylori-HSP60. The peptides might be available for diagnosis of arteriosclerosis.
    4) DNA chip study indicated that DEC205 is an important receptor for macrophage activation in patients with gastritis caused by H pylori infection. We are now studying function of DEC205 on macrophage using NOMO-1 cell differenciated by PMA.

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  • Establishment of new procedures for botulism including bio-terrorism and for the treatment of patients with dystonia.

    Grant number：17390127  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    OGUMA Keiji, YOKOTA Kenji, AYADA Kiyoshi, KOUICHI Takeshi, ARIMITSU Hideyuki

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    Grant amount：\14600000 （ Direct expense: \14600000 ）

    1. Development of vaccine and immuno-strip for detecting toxin
    In order to prepare the safe and effective type C and D vaccines for animal botulism, the heavy chains (100 kDa) and their C-terminal (Hc, 50 kDa) and N-terminal (Hn, 50 kDa) half fragments were prepared as GST fusion proteins. Production level of Hc and Hn was quite higher than that of H. H and He showed good vaccine effects but that of Hn was quite low. GST fused-or GST-eliminated He preparation showed similar vaccine effect. Therfore, it was concluded that He with or without GST can be used as commercially effective vaccine. Immuno-strip method was prepared using polyclonal antisera against A, B, E, and F neurotoxins. They could detect approximately 1 ng of each toxin.
    2. Development of neurotoxin preparations for treating dystonia
    We found that HAI and HA3b, which are the subcomponents of HA, have adjuvant activity. Therefore, we tried to treat the patients with the neurotoxins rather than the progenitor toxins. We found that Type A and B neurotoxins can easily be purified by using a lactose gel column, and that they can be stocked in a deep freezer without reducing the toxin activity by mixing with 0.05% albumin (for type B) or 0.05% albumin plus 1% terehalose (for type A). When this preparation was used for the treatment of 18 patients with urinary incontinence caused by refractory idiopathic and neurogenic detrusor overactivity, 16 patients showed excellent improvement; it started within 1 week after injection in most cases and lasted 3 to 12 months.

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  • Analysis of tertial structure and function of non-toxic components associating with Clostridium botulinum neurotoxins.

    Grant number：14370093  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    OGUMA Keiji, NISHIKAWA Jun, FUJINAGA Yukako, YOKOTA Kenji, INOUE Kaoru

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    Grant amount：\13400000 （ Direct expense: \13400000 ）

    Clostridium botulinum type A to D hemagglutinin positive progenitor toxins (PTX) consist of three distinct components : neurotoxin (NTX), hemagglutinin (HA), and non-toxic non-HA (NTNH). The HA consists of four subcomponents designated HA1 (〜33kDa), 2 (〜17kDa), 3a (〜22kDa), and 3b (〜53kDa).
    We have established an easy procedure for purifying type B HA-positive PTX and NTX by employing an affinity gel column-linked lactose. By employing the purified type A to D toxins and their each HA subcomponents prepared as GST-fusion proteins, we have shown that HA, especially HA1 and HA3b, works as an adhesin in the attachment of HA-positive PTXs to the-microvilli of the upper small intestine as well as erythrocytes. Type A (and B) toxin bound to the galactose mainly via HA1, whereas type C (and D) bound to the sialic acid mainly via HA3b. By analyses of primary and tertiary structure of HA1 and HA3b, It became clear that HA1 has two β-trefoil domains like as lectin B-chain of the ricin, whereas HA3b has carbohydrate recognition domain (CRD) of sialo-adhesin family (or Siglec family). In the binding and internalization tests with C HA-positive toxin and human colon carcinoma HT-29 cells, the toxin bound to glycoproteins with high molecular mass, and internalized within 4 min, but not if the cells were pretreated with neuraminidase, indicating that sialic acid of glycoprotein is the receptor for type C toxin and the toxin can internalize quickly into the cells. It was also found that both HA1 and HA3b have adjuvant activity.

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  • 熱ショック蛋白質HSP60の胃MALTリンパ腫発生への関与

    Grant number：13877026  2001 - 2002

    日本学術振興会  科学研究費助成事業  萌芽研究

    赤木 忠厚, 横田 憲治

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    Grant amount：\2000000 （ Direct expense: \2000000 ）

    1.HSP60に対するヒト免疫系の反応性、とくにMALTリンパ腫患者リンパ球の反応性
    MALTリンパ腫患者では、HSP60に対する自己抗体ができることを報告しているが,この機序を解明するために、MALTリンパ腫患者リンパ球をGM-CSFとIL-4存在下にHSP60で刺激し,リンパ球の反応性を調べた。抗原刺激により,MALTリンパ腫患者のリンパ球はIL-4を産生するが、健常者や胃炎患者のリンパ球はIFN-γを多く産生した。またB細胞の抗原刺激に際してco-stimulatory signalとして働くCD4T細胞のCD40リガンド(CD40L)の発現が、MALTリンパ腫患者では増強した。H.pylori菌全体を使った抗原刺激では,胃炎患者とMALTリンパ腫患者でCD40Lの発現に差は認められなかった。これらの結果より、MALTリンパ腫患者ではHSP60に対するTh-2の液性免疫反応が強く誘導され、B細胞の増殖が起こることが判明した。
    2.HSP-60の末梢血並びにリンパ組織単核細胞における発現
    HSP60は末梢血中ではTリンパ球の一部と単球の大部分に発現し、マイトゲンで刺激すると,T.B.NK細胞における発現率と発現量が著しく増強した。反応性リンパ組織では、芽中心及び濾胞間のマクロファージとリンパ芽球の胞体内に発現していた。
    3.感染動物実験による宿主因子の解析
    マウスの系統によって、H.pylori感染後に発症する胃炎の程度が異なることが知られている。あらかじめ感染させたマウスに大腸菌のリコンビナント易熱性毒素をアジュバントとして、rHSP60を鼻腔より免疫した。Th-1優位なC57BL/6でもTh-2優位なBALB/Cマウスでも、HSP60を用いた局所免疫により、感染早期から胃炎が高率に発症することを認めた。またT細胞を活性化しやすいアミノ酸配列を含んだ領域を部分発現させたHSP60を免疫すると,胃炎の発症が強く誘導された。

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  • Roles of HSP60 in Helicobacter pylori infection

    Grant number：12670256  2000 - 2002

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YOKOTA Kenji, OGUMA Keiji

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    Grant amount：\2200000 （ Direct expense: \2200000 ）

    We have previously reported that heat shock protein 60kDa (HSP60) is an important antigen in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma. To investigate association with host immunity and HSP60, DC40 ligand (CD40L) and cytokine production in peripheral blood mononuclear cells (PBMCs) from the patients were analyzed following stimulation with HSP60. PBMCs obtained from patients with gastritis and MALT lymphoma, and those from healthy volunteer were stimulated with recombinant-HSP60 or H. pylori cell fysate in the presence of cytokines (IL-4) and GM-CSF). The mRNA expression was also analyzed by a cDNA microarray containing 1100 genes. The expression of CD40L on the CD4 positive cells was increased in the PBMCs from patients with MALT lymphoma stimulated by cytokines and/or HSP60 antigens. The production of IL-4 in PBMCs cultures was increased in patients with MALT lymphoma ; however, the production of IFN-_γ was at low levels. A cDNA microarray analysis indicated increased mRNA levels of HLA-DR and integrin. 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 H. pylori infection.
    To study immunological roles of HSP60 in H. pylori infection, we immunized HSP60 to H. pylori infected mice. Whole HSP60 and two partial regions of helicobacterial hsp60 were expressed as GST-fusion proteins. Three recombinant proteins were designated rHSPw, rHSP2, and rHSP4-5. rHSPw was expressed as whole hsp60 (MeT_1-Met_<545>). rHSP2 (Glu_<101>-Ser_<200>) contained a domainT cell epitope cluster (Lys_<159>-Tnr_<178>). The rHSP4-5 contained a domain existing in both T cell epilope cluster (Asp_<396>-Gly_<4l2>) and its upstream of region (Ser_<356>-Asp_<392>) in common between H. pylori and human hsp60. Recombinant heat-labile enterotoxin (rLT) of E. coli was also employed as adjuvant for nasal immunization. Three different mouse groups (BALB/c, C3H/He, C57BL/6) were injected 10^8 CRJ of live H. pylori (SS -1) at two times a week and kept in a clean isolator for 2 weeks. Those mice were immunized H. pylori lysate or rHSPs (10μg/mouse) with rLT (10μg/mouse) by injecting into nasal mucosa four times in 1 month. Mice were sacrificed at 1 momtn after last immunization, and then histopathology and antibodies were investigated. Mucosal immunization by H. pylori lysate and rHSPs induced severe gastritis in BALB/c and C57BL/6 mice. Inflammation grades in those two groups immunized by rHSP4-5 were highest in aft groups. Mucosal immunization by hsp60 accelerated production of IgG and IgA.
    These -results indicated that HSP60 was closely associated with H. pylori induced gastric inflammation.

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  • In vivoおよびIn vitroの細胞障害実験によるH.pylori病態研究

    Grant number：09770181  1997 - 1998

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    横田 憲治

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    Grant amount：\1900000 （ Direct expense: \1900000 ）

    (1) 動物実験による宿主反応の検討
    胃十二指腸疾患の原因であるHelicobacter pylori感染の宿主反応について調べるため、各種感染にたいする免疫反応の異なるマウス(BALB/c,C57BL/6,C3H/He)に感染させ、経時的にその病理、抗体価、サイトカインを測定した。感染により誘導された胃炎は、C57BL/6最も頻度が高く、C3H/He,BALB/cの順であった。しかし、リンパ濾胞を伴う激しい炎症はC3H/Heの一部に認められた。抗体価は、全てのマウスで経時的に上昇していた。最も炎症の激しい炎症の認められた2匹のC3H/Heのサイトカインを調べたところ。一方はTh-2優位であり、もう一方はTh-1優位の傾向を認めた。これらの結果より、H.pyloriによる炎症の誘導および病原性には、宿主側の要因が深く関わっていると考えられた。
    (2) In vitro細胞傷害(熱ショック蛋白を介した細胞傷害の検討)
    胃のMALTリンパ腫は、H.pyloriの感染により発生したリンパ増殖性の疾患である。この患者は、HSP60が腫瘍性リンパ濾胞芽中心の細胞(抗原提示細胞)に発現している事、さらに血清中にHSP60に対する抗体が存在することを認めた。そこでH.pyloriのHSP60をクローニングし蛋白を発現させた。
    MALTリンパ腫のリンパ球を重症免疫不全マウス(SCIDマウス)に移植し菌を投与すると、潰瘍性病変が出現した。潰瘍の発生したマウスには、自己抗体とH.pylori反応性のT細胞が存在していた事から、抗体依存性細胞傷害の可能性が示唆された。

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  • Physiological aspects of cholesteryl glucosides in Helicobacter pylori

    Grant number：09670281  1997 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HIRAI Yosikazu, YOKOTA Kenji

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    Grant amount：\2700000 （ Direct expense: \2700000 ）

    We have detected three types of cholesteryl glucosides (CGs) in H.pylofl (HP) cultured in a serum-supplemented medium. The structures of the CGs were cholesteryl glucoside (CGL), acylated CGL (CAG), and phosphatidyl CGL (CPG).
    Firstly, we investigated bacterial growth in a serum-supplemented medium with shaking under microaerophlic conditIon using with a chamber (Concept plus, Ruskinn tech., UK). Under this condition, subculture and culture of HP can be done without exposing usual air.
    We investigated the lipid, especially CGs, compositions of HP in each bacterial growth phase under the condition mentioned above. In CGs, CGL and CAG were detected at all growth phases. However, little of CPG was detected at exponential phase. CPG was detected In spiral form bacteria of stationary phase, and its content dramatically increased at declining phase (phase of coccoid formation), whereas the content of phosphatidyl ethanolarnine, main phosphoilpid of HP, was dramatically decreased at declining phase. The metabolism of phosphate was appeared to be dramaticaliy changed after stationary phase in HP.
    We investigated the uptakes of sterols and those related compounds, and the synthesis of glucosides from those in a serum-free medium under the same condition mentIoned above. HP accumulated free cholesterol, ergosterol, stigmasterol, beta-sitosterol, and synthesize glucosides from those. However, HP did not accumulate cholesterol ester. Therefore, the structure of 3 beta-ol could be important for the accumulation of sterol. HP accumulated vitamin D3, cholecalciferol, but did not synthesize glucoside from it. For the synthesis of glucosides after the accumulation, the base structure of sterol would be important. Furthermore, vitamin D3 inhibited the growth of HP, and its MIC against HP In a serum-free medium was 12.5 mug/ml. The hydrophobic substances which are accumulated but not synthesized to glucosides such as vitamin D3 may inhibited the growth in HP.

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  • Prevention of cattle-botulism in Australia

    Grant number：06044152  1994

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for international Scientific Research

    OGUMA Keiji, YOKOTA Kenji, INOUE Kaoru, HIRST Robert, HOLDEN Janet

    　 More details

    Grant amount：\2200000 （ Direct expense: \2200000 ）

    The type C and D botulinum strains were isolated from the ground of a cattle farm (a pasture) in Australia. The type C toxin was purified from one type C culture, and its antigenicity was analyzed by monoclonal antibodies. Based on the results of antigenicity and toxin-neutralization tests, it was concluded that the C-terminal of the toxin can be used as effective vaccine.
    The peptide (15 amino acid residues) which is conserved in the light chain components of any different types of botulinum toxins was synthesized, and the monoclonal antibodies against it were prepared in rats. Though two monoclonal antibodies reacting with any types of toxins were obtained, they did not neutralize the toxigenicity, indicating that this peptide can not be used as vaccine, but the monoclonal antibodies thus obtained can be used for diagnosis of botulism caused by any types of toxins.

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