研究者詳細 - 横田　憲治

論文 - 横田　憲治

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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年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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年6月

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年6月

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年6月

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年6月

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年1月

Effects of Helicobacter pylori and Nitrate-Reducing Bacteria Coculture on Cells. 国際誌

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

Microorganisms 10 ( 12 ) 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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年6月

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年6月

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年6月

Establishment of a reference panel of Helicobacter pylori strains for antimicrobial susceptibility testing. 国際誌

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年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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年9月

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年9月

Elizabethkingia anophelis, an emerging pathogen, inhibits RAW 264.7 macrophage function. 国際誌

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年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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年7月

掲載種別：研究論文（学術雑誌）

The infection caused by Helicobacter pylori is associated with several diseases, including gastric cancer. Several methods for the diagnosis of H. pylori infection exist, including endoscopy, the urea breath test, and the fecal antigen test, which is the serum antibody titer test that is often used since it is a simple and highly sensitive test. In this context, this study aims to find the association between different antibody reactivities and the organization of bacterial genomes. Next-generation sequences were performed to determine the genome sequences of four strains of antigens with different reactivity. The search was performed on the common genes, with the homology analysis conducted using a genome ring and dot plot analysis. The two antigens of the highly reactive strains showed a high gene homology, and Western blots for CagA and VacA also showed high expression levels of proteins. In the poorly responsive antigen strains, it was found that the inversion occurred around the vacA gene in the genome. The structure of bacterial genomes might contribute to the poor reactivity exhibited by the antibodies of patients. In the future, an accurate serodiagnosis could be performed by using a strain with few gene mutations of the antigen used for the antibody titer test of H. pylori.

DOI： 10.3390/toxins13070467

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年2月

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年2月

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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年

掲載種別：研究論文（学術雑誌）

Background: Helicobacter pylori infection poses a risk of the occurrence of gastrointestinal diseases, such as gastric cancer. Its incidence rate is significantly reduced by eradication, and thereby, eradication therapy is generally performed. Disulfiram is an oral prescription drug mainly used for the treatment of alcohol dependence. In recent years, reports have been made on its anticancer and antibacterial effects, and thus, it has recently become an interesting subject. This study aimed to examine the antibacterial activity of disulfiram, investigate the presence or absence of its antibacterial activity on H. pylori, and determine whether it could be a new bactericidal drug against drug-resistant H. pylori. Materials and Methods: Drug-sensitive strains of H. pylori and amoxicillin-resistant, clarithromycin-resistant, and metronidazole-resistant strains were used, and a growth inhibition test of H. pylori using disulfiram was performed. Furthermore, the expression of urease, vacuolating cytotoxin A (VacA), and CagA, the virulence proteins of H. pylori, was quantitatively analyzed using the Western blotting method. In addition, for H. pylori used in this study, the 16SrDNA sequence, a ribosomal gene involved in protein production, was analyzed to examine the presence or absence of gene mutation. Results: Disulfiram suppressed the growth of 7 out of 12 H. pylori strains at 1 µg/mL, and no correlation was observed between their susceptibility/resistance to current eradication antimicrobial drugs and disulfiram resistance. Disulfiram reduced the expression levels of urease, VacA, and CagA proteins. H. pylori, which showed resistance to disulfiram, tended to have fewer gene deletions/insertions in the 16S rDNA sequence; however, no specific mutation was detected. Conclusion: Disulfiram has a bactericidal effect on H. pylori at low concentrations, suggesting that it can be used as a supplement for current H. pylori eradication drugs.

DOI： 10.2147/IDR.S299177

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年12月

記述言語：日本語出版者・発行元：日本防菌防黴学会

健常人の尿沈渣標本中に,ステルンハイマー染色にて青色の顆粒状物質が出現することがある。この物質の成分や出現背景等に関して詳細は明らかとなっていないため,検討を行った。その結果,顆粒状物質は,健常な女性15名中8名(53%)に出現していた。SDS-PAGEによる電気泳動では,15名中11名(73%)に75KDaの単一のバンドを認め,質量分析にてTamm-Horsfall protein(THP)(Uromodulin)と同定された。THPは尿路細菌叢が存在した10名中9名(90%)で検出され,尿路に細菌や真菌が存在しなかった4名中3名(75%)では検出されなかった。また,顆粒状物質が出現していた8名中,THPと尿路細菌叢の両方を認めたのは4名(50%)であった。明らかな傾向を統計学的に証明できなかったが,顆粒状物質は,THPや尿路細菌叢と同時に検出される場合があることから,何らかの自然免疫学的な応答に関与している可能性が示された。今後,検体採取条件を再検討し,この関連性について検証する必要がある。(著者抄録)

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

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年3月

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

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年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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年2月

Increase in antibiotic resistant Helicobacter pylori in a University Hospital in Japan. 国際誌

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.2147/IDR.S196452

Association of host immunity with Helicobacter pylori infection in recurrent gastric cancer. 国際誌

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1186/s13027-019-0221-1

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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査読

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年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：(NPO)バイオテクノロジー標準化支援協会

入院患者や要介護者を対象に用いられている吸い飲み内残余飲料の微生物汚染状況について実験的な予備調査を実施した。吸い飲み内試料はミネラルウォーター、緑茶、経口補水液、果汁飲料を用いて、pHと糖度を測定した。ブラッシング後に吸い飲みで飲用した後、吸い飲み内に残余した各飲料を28℃で2時間および5時間保管した。保管後、残余飲料の微生物数(口腔内細菌数および真菌数)を計測した。さらに、緑茶を用いて食事中に飲用した後、吸い飲み内に残余した緑茶の微生物数を計測し、ブラッシング後に飲用した吸い飲み内の残余緑茶の微生物数と比較した。吸い飲み内の残余飲料すべてに、口腔内細菌(主にStreptococci)と口腔内真菌(主にCandida species)の混入が認められた(25 to 2,827 CFU/mL)。ミネラルウォーター、緑茶では、口腔微生物数が保管2時間後で最も多くなった。また、食事中に飲用した吸い飲み内の残余緑茶には口腔内微生物がより多く混入し、保管5時間後も微生物数の減少はみられなかった。口腔内の清掃・衛生管理状態は吸い飲みの微生物汚染状況に影響を与える。吸い飲みの十分な洗浄・消毒など、適切な衛生管理が重要である。(著者抄録)

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

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

Journal of Hospital Infection 99 ( 3 ) 303 - 305 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：W.B. Saunders Ltd

Aerosol and splatter produced during dental treatments (ultrasonic scaling and professional mechanical tooth cleaning) are potential sources of infection. Contamination patterns on the mask, goggles, chest and gowned right arm of operators, and on the goggles of patients before and after dental treatments were investigated using ATP bioluminescence analysis. Contamination on every surface tested increased significantly after dental treatment. Maximum contamination was found on the goggles of patients. Aerosol and splatter produced during dental treatments therefore have the potential to spread infection to operators and patients. ATP bioluminescence is a useful tool for monitoring surface contamination.

DOI： 10.1016/j.jhin.2018.03.002

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年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.18926/AMO/56068

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年5月

DEC205 mediates local and systemic immune responses to Helicobacter pylori infection in humans. 国際誌

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

Oncotarget 9 ( 22 ) 15828 - 15835 2018年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.18632/oncotarget.24574

Low incidence of esophageal adenocarcinoma after eradication of Helicobacter pylori in Japan. 査読国際誌

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年3月

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) 査読

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年2月

Elevated serum interferon γ-induced protein 10 kDa is associated with TAFRO syndrome. 査読

Sci Rep. 2017 Feb 13;7:42316. 7 42316 2017年2月

Monitoring of bacterial contamination of dental unit water lines using adenosine triphosphate bioluminescence. 査読国際誌

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

The Journal of hospital infection 94 ( 4 ) 393 - 396 2016年12月

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

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL

Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed. (C) 2015 Wiley Periodicals, Inc.

DOI： 10.1002/ajh.24242

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

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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Geranylgeranylacetone (GGA) is used to treat patients suffering from peptic ulcers and gastritis. We examined the effect of GGA on Helicobacter pylori, which is a causative factor of gastrointestinal diseases. Previously, we have reported that GGA binds specifically to the molecular chaperone HSP70. In this paper, we report that GGA bounds to H. pylori HSP70 (product of the DnaK gene) with 26-times higher affinity than to human HSP70, and induced large conformational changes as observed from surface plasmon resonance and circular dichroism. Binding of GGA suppressed the activity of the H. pylori chaperone. GGA also altered several characteristics of H. pylori cells. GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells. GGA also caused morphological alterations in H. pylori as reflected in fewer coccoid-like cells, suggesting that GGA converts H. pylori to an actively dividing, spiral state (vegetative form) from a non-growing, coccoid state. This morphological conversion by GGA resulted in accelerated growth of H. pylori. These results suggest a model in which GGA sensitizes H. pylori to antibiotic treatment by converting the cells to an actively growing state.

DOI： 10.1038/srep13738

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年8月

Signature-tagged mutagenesis of Vibrio vulnificus. 査読

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年7月

記述言語：英語

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.

DOI： 10.1292/jvms.14-0655

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

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

JOURNAL OF GASTROENTEROLOGY 50 ( 6 ) 638 - 644 2015年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER JAPAN KK

We previously reported that eradication of Helicobacter pylori in our cohort of patients with peptic ulcer disease reduced their risk of developing gastric cancer to approximately one-third after a mean follow-up period of 3.4 years (up to 8.6 years). We have now followed these patients for a longer period.
A total of 1,222 consecutive patients with peptic ulcer diseases who completed more than 1-year follow-up after receiving H. pylori eradication therapy were followed with annual endoscopic surveillance for a mean of 9.9 years (as long as 17.4 years).
H. pylori infection was judged cured in 1,030 patients (eradication-success group) but persisted in 192 (eradication-failure group) after initial eradication therapy. In the eradication-failure group, 114 patients received re-treatment at a mean of 4.4 years after the start of follow-up, and 105 of these were cured of infection. Gastric cancer developed in 21 of the 1,030 patients in the eradication-success group and in nine of the 192 in the failure group (p = 0.04). The risk of developing gastric cancer in the eradication-success group (0.21 %/year) was significantly lower than that in the failure group (0.45 %, p = 0.049). The longest interval between the initial H. pylori eradication and the occurrence of gastric cancer was 14.5 years in the eradication-success group and 13.7 years in the eradication-failure group.
A prophylactic effect for gastric cancer persists for more than 10 years after H. pylori eradication therapy, but we should be aware that cancer can develop even after that interval.

DOI： 10.1007/s00535-014-1004-5

[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]. 査読

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

Rinsho byori. The Japanese journal of clinical pathology 63 ( 2 ) 180 - 186 2015年2月

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年1月

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年1月

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 査読

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

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 140 17 - 25 2014年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Helicobacter pylori, a pathogen responsible for gastric and duodenal diseases, absorbs various steroid compounds into the cell membrane even though some are toxic to this bacterium. An earlier study by our group has demonstrated that progesterone is bactericidal to H. pylori. In this study, we newly synthesized a steroid compound, 17 alpha-hydroxyprogesterone linoleic acid ester (17hPL), to examine antibacterial activity against H. pylori. As expected, 17hPL acted as a bactericidal agent to H. pylori and had no effect on the survival of other common bacterial species. This steroidal substance interacted with phosphatidylethanolamine (PE) on the outer membrane of H. pylori to induce the release of PE from the bacterial cell membrane and to ultimately lyse the bacterial cells. One of the hormonal effects of progesterone is the inhibition of nitric oxide (NO) production from mouse macrophages activated by lipopolysaccharide (LPS). We therefore examined the inhibition effect of 17hPL on the NO production of RAW 264.7 cells, a murine macrophage-like cell line, stimulated with LPS and demonstrated that 17hPL is relatively weaker in its capability to inhibit NO production in LPS-activated cells than progesterone. These results suggest the possibility that 17hPL could be an oral medicine for selectively treating patients infected with H. pylori. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jsbmb.2013.10.023

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年1月

[New Helicobacters other than H. pylori]. 査読

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

Nihon rinsho. Japanese journal of clinical medicine 71 ( 8 ) 1374 - 1379 2013年8月

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

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年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Atrophy of the gastric mucosa is a precursor of intestinal-type gastric cancer, and Helicobacter pylori infection causes atrophic gastritis. The aim of this study was to determine whether the genetic diversity of H. pylori virulence genes is associated with the development and progression of gastric atrophy in humans. We isolated and cultured H. pylori strains from patients with gastric ulcer and duodenal ulcer accompanied by atrophic gastritis in background mucosa. H. pylori strains were stored at -80 degrees C prior to the experiments being carried out. We analyzed iceA, babA, vacA, cagA, and cagE genes by PCR. The cagA gene was analyzed through sequencing of the C-terminal region containing the EPIYA motif, which is related to tyrosine phosphorylation. Severe atrophy was observed in patients with gastric ulcer. The major phenotype of the vacA gene was slc/ml (93%). The cagA gene was detected in all strains. The cagE gene was not detected in 2 and 5 strains from the mild cases and severe cases, respectively. The major cagA EPIYA motif, which is amino acids repeat in the C terminus, was the A-B-D type (44 of 58 strains). The virulence genes were not statistically associated with the severity of atrophy in the background gastric mucosa in humans. Not only identification of bacterial virulence factors but also studies of the host response will be necessary to investigate the progression of gastric atrophy and subsequent cancer development in humans.

DOI： 10.18926/AMO/49667

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

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

JOURNAL OF BACTERIOLOGY 195 ( 2 ) 359 - 367 2013年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC MICROBIOLOGY

The glucosylation of free cholesterol (FC) by Helicobacter pylori cells has various biological significances for the survival of this bacterium. H. pylori cells with glucosylated FC are capable of evading host immune systems, such as phagocytosis by macrophages and activation of antigen-specific T cells, and surviving in the gastric mucosal tissues for long periods. An additional role of cholesterol glucosylation in the survival of H. pylori which is distinct from the role of escaping the host immune system, however, has yet to be identified. This study demonstrated that 7-dehydrocholesterol (7dFC), an FC precursor, is a toxic compound fatal to H. pylori cells, but the cell membrane of H. pylori is capable of absorbing this toxic sterol via glucosylation. In contrast to the case with 7dFC, no toxicity to H. pylori cells was detected from the glucosylated 7dFC. In addition, cgt gene mutant H. pylori cells that cannot glucosylate cholesterols had higher susceptibility to the toxic action of 7dFC than wild-type H. pylori cells. These results indicate that the cgt gene product of H. pylori serves to detoxify the sterol fatal to this bacterium and to permit this toxic sterol as a cell membrane lipid component. In summary, this study defined a novel role of cholesterol glucosylation in H. pylori.

DOI： 10.1128/JB.01495-12

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

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年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

We previously reported that the reinfection rate with Helicobacter pylori in Japan was low despite a high prevalence of infection. In the present study, we extended our previous work to more accurately determine the reinfection rate.
We enrolled 1625 patients (219 women and 1406 men, mean age 50.8 years) who had received H. pylori eradication therapy. After documentation of eradication, bacterial culture and urea breath test were carried out yearly. H. pylori strains were analyzed by using random amplification of polymorphic DNA fingerprinting.
A total of 1609 patients were followed for up to 12.5 years (mean 4.7 years); H. pylori became re-positive in 26 patients. In 13 of the 26 patients, H. pylori became positive at the first-year follow up. Stored H. pylori isolates were available for analysis from ten of the 13 patients; four of the isolates were genetically different from the initial strain, but the other six were identical to the initial strain. In the other 13 patients, H. pylori became positive at later follow up (mean 4.8 years; range 1.8-8.0 years). In all of the four of these patients whose isolates could be analyzed, the H. pylori strains were different from the initial strain. Assuming that reinfection occurred in the four patients positive for different strains of H. pylori at the first-year follow up and in the 13 positive at later follow up, the reinfection rate was 0.22% per year.
When probable recrudescence (H. pylori positivity with identical strains) was excluded, the reinfection rate of H. pylori in this Japanese population was very low, but we note that reinfection can occur over many years.

DOI： 10.1007/s00535-012-0536-9

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

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

ACTA MEDICA OKAYAMA 66 ( 3 ) 253 - 261 2012年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Cultured Clostridium botulinum strains produce progenitor toxins designated as 12S, 16S, and 19S toxins. The 12S toxin consists of a neurotoxin (NTX, 7S) and a non-toxic non-hemagglutinin (NTNH). The 16S and 19S toxins are formed by conjugation of the 12S toxin with hemagglutinin (HA), and the 19S toxin is a dimer of the 16S toxin. Type A cultures produce all 3 of these progenitor toxins, while type E produces only the 12S toxin. The 7S toxin is cleaved into heavy (H) and light (L) chains by a protease(s) in some strains, and the H chain has 2 domains, the N-terminus (Hn) and C-terminus (Hc). It has been reported that type A toxins bind to the intestinal cells or cultured cells via either HA or Hc. In this study, we investigated the binding of type A and E toxins to Caco-2 cells using Western blot analysis. Both the type E 7S and 12S toxins bound to the cells, with the 7S toxin binding more strongly, whereas, in the type A strain, only the 16S/19S toxins showed obvious binding. Pre-incubation of the type E 7S toxin with IgG against recombinant type E Hc significantly inhibited the 7S toxin binding, indicating that He might be a main binding domain of the type E toxin.

Phosphatidylethanolamine of Helicobacter pylori functions as a steroid-binding lipid in the assimilation of free cholesterol and 3β-hydroxl steroids into the bacterial cell membrane. 査読

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

Journal of bacteriology 194 ( 10 ) 2658 - 2667 2012年5月

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

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

J Med Micorobiol Diagnosis 2012年

Steroid hormones as bactericidal agents to Helicobacter pylori 査読

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

FEMS MICROBIOLOGY LETTERS 318 ( 1 ) 68 - 75 2011年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL

Helicobacter pylori is a unique bacterial species that assimilates various steroids as membrane lipid components. Our group has recently found, however, that certain steroids may impair the viability of H. pylori. In this study, we go on to reveal that estradiol, androstenedione, and progesterone (PS) all have the potential to inhibit the growth of H. pylori. Of these three steroid hormones, progesterone demonstrated the most effective anti-H. pylori action. 17 alpha-hydroxyprogesterone caproate (17 alpha PSCE), a synthetic progesterone derivative, had a much stronger anti-H. pylori action than progesterone, whereas 17 alpha-hydroxyprogesterone, a natural progesterone derivative, completely failed to inhibit the growth of the organism. Progesterone and 17 alpha PSCE were both found to kill H. pylori through their bacteriolytic action. Among five bacterial species investigated, H. pylori was the only species susceptible to the bactericidal action of progesterone and 17 alpha PSCE. The other four species, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epiderimidis, all resisted this action. Progesterone and free-cholesterol (FC) obstructed each other's effects against the H. pylori cell. Taken in sum, these results suggest that progesterone and FC may bind to the identical region on the H. pylori cell surface. We expect these findings to contribute to the development of a novel anti-H. pylori steroidal agent.

DOI： 10.1111/j.1574-6968.2011.02239.x

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

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年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

We previously reported that eradication of Helicobacter pylori reduced the risk of developing gastric cancer in patients with peptic ulcer diseases. In the present study, we further followed up our patient group to investigate the occurrence and clinical features of gastric cancers that developed after cure of the infection.
Prospective post-eradication evaluations were conducted on 1674 consecutive patients who had received successful H. pylori eradication therapy. The patients had undergone endoscopic examination before eradication therapy to evaluate peptic ulcers, background gastric mucosal atrophy, and H. pylori infection. After confirmation of cure of the infection, follow-up endoscopy was performed yearly.
The patients were followed for up to 14.1 years (a mean of 5.6 years). During the follow-up, gastric cancer developed in 28 of the 1674 patients as long as 13.7 years after the cure of H. pylori infection. The risk of developing gastric cancer was 0.30% per year. Histologically, 16 of the gastric cancers were the intestinal type and 12 were the diffuse type; the risk of each cancer type was 0.17 and 0.13% per year, respectively. There was no significant inflammatory cell infiltration in the background gastric mucosa at the time the cancers were recognized.
There is a risk of developing gastric cancer of both the intestinal and diffuse types even after the cure of H. pylori infection and extinction of gastric inflammation. It is important to inform patients about the risk of gastric cancer after eradication therapy and offer them surveillance endoscopy.

DOI： 10.1007/s00535-010-0347-9

Behçet's disease (Adamantiades-Behçet's disease). 査読

Kaneko F, Togashi A, Saito S, Sakuma H, Oyama N, Nakamura K, Yokota K, Oguma K

Clinical & developmental immunology 2011 681956 2011年

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

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年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

In an attempt to prepare egg yolk immunoglobulin (IgY) to treat and prevent cholera, hens were immunized by a mixture of heat- or formalin-killed Vibrio cholerae O1 and O139 organisms, or by the recombinant cholera toxin B subunit (CTB). The IgYs were partially purified from egg yolk and orally administered to suckling mice before or after challenge with live O1 or O139 cells. The anti-O1 and O139 IgYs and the mixture of either IgY with anti-CTB IgY significantly protected the occurrence of cholera caused by both O1 and O139 infection. Since large amounts of IgY can be prepared very easily and at low cost, this seems to be a useful procedure for preventing and treating cholera.

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年3月

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

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

FEMS MICROBIOLOGY LETTERS 301 ( 1 ) 84 - 94 2009年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Helicobacter pylori assimilates various steroids as membrane lipid components, but it can also survive in the absence of steroids. It thus remains to be clarified as to why the organism relies on steroid physiologically. In this study, we have found that phosphatidylcholine carrying a linoleic acid molecule or arachidonic acid molecule has the potential to kill steroid-free H. pylori. The bactericidal action of phosphatidylcholines against H. pylori was due to the lytic activity of the phosphatidylcholines themselves and not due to the lytic activity of the unsaturated fatty acids or lyso-phosphatidylcholine resulting from the hydrolysis of the phosphatidylcholines. In contrast to the steroid-free H. pylori, the organism that absorbed and glucosylated free cholesterol was unaffected by the bactericidal action of the phosphatidylcholines. Similarly, H. pylori that absorbed estrone without glucosylating it also resisted the bactericidal action of the phosphatidylcholines. The steroids absorbed by H. pylori existed in both the outer and inner membranes, while the glucosyl-steroids produced via the steroid absorption were localized in the outer membrane rather than in the inner membrane. These results indicate that H. pylori absorbs the steroids to reinforce the membrane lipid barrier and thereby expresses resistance to the bacteriolytic action of hydrophobic compounds such as phosphatidylcholine.

DOI： 10.1111/j.1574-6968.2009.01807.x

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

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

HELICOBACTER 14 ( 6 ) 545 - 551 2009年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL

Background: Since the discovery of Helicobacter pylori, various enterohepatic Helicobacter spices have been detected in the guts of humans and animals. Some enterohepatic Helicobacters have been associated with inflammatory bowel disease or liver disease in mice. However the association of these bacteria with human diseases remains unknown. Materials and
Methods: We collected 126 bile samples from patients with cholelithiasis, cholecystitis, gallbladder polyp, and other nonbiliary diseases. Samples were screened for the presence of enterohepatic Helicobacter spp. using Cultures, nested PCR, or in situ hybridization. We tested for antibodies to H. pylori and H. hepaticus by Western blot analysis.
Results: Attempts at cultivation were unsuccessful. However, H. hepaticus was detected in bile samples with nested PCR whereas H. bilis was not. Helicobacter hepaticus in the bile was confirmed by in situ hybridization, but H. hepaticus from bile samples was coccoid in appearance. We detected immunoglobulin G antibodies to H. hepaticus in bile samples by Western blotting. Helicobacter hepaticus was detected in 40 (32%) of total 126 samples as H. hepaticus positive if at least one of the three methods with nested PCR, in situ, or Western blotting. Patients with cholelithiasis (41%) and cholecystitis with gastric cancer (36%) had significantly higher (p = .029) prevalence of H. hepaticus infection than samples from patients with other diseases.
Conclusion: Helicobacter hepaticus may closely associate with diseases of the liver and biliary tract in humans.

DOI： 10.1111/j.1523-5378.2009.00729.x

Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis 査読

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年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SAGE PUBLICATIONS LTD

Helicobacter pylori (H. pylori) is a predominant pathogen that causes not only gastroduodenal diseases but also extra-alimentary tract diseases. In this study, we demonstrated that H. pylori infection promoted atherogenesis in heterozygous apoe(+/-) ldlr(+/-) mice. The male mice were fed with high fat diet from the age of 6 weeks. At the age of 16 weeks, development of atherosclerotic lesions was observed in the H. pylori-infected mice, and it seemed to be associated with an elevation of Th1-immune response against H. pylori origin-heat shock protein 60 (Hp-HSP60) and an increment of transendothelial migration of T cells. Subcutaneous immunisation with Hp-HSP60 or H. pylori eradication with antibiotics significantly reduced the progression of atherosclerosis, accompanied by a decline of Th1 differentiation and reduction of their chemotaxis beyond the endothelium. Thus, oral infection with H. pylori accelerates atherosclerosis in mice and the active immunisation with Hp-HSP60 or the eradication of H. pylori with antibiotics can moderate/prevent cellular immunity, resulting in a reduction of atherosclerosis. Lupus (2009) 18, 1154-1168.

DOI： 10.1177/0961203309106600

Anabolic utilization of steroid hormones in Helicobacter pylori 査読

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

FEMS MICROBIOLOGY LETTERS 297 ( 2 ) 173 - 179 2009年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC

In this study, we have demonstrated that Helicobacter pylori absorbs a steroid prehormone (pregnenolone) and two androgens (dehydroepiandrosterone and epiandrosterone), glucosylates these steroids, and utilizes glucosyl-steroid hormone compounds as the membrane lipid components. The only common structure among the steroid prehormone and the two androgens is a 3 beta-OH in the steroid framework. Our results indicate that the 3 beta-OH in the steroid hormones is a crucial conformation required for steroid glucosylation by H. pylori. In addition, we found that H. pylori absorbs and holds estrogens possessing 3-OH (estrone and estradiol) into the membrane. The effective absorption of estrogen into the membrane appeared to be controlled by the number of hydroxyl groups modifying the steroid framework. In contrast, H. pylori induced neither membrane absorption nor glucosylation of the other steroid hormones possessing 3=O (progesterone, androstenedione and testosterone) or 3 alpha-OH (androsterone). These results indicate that H. pylori selectively absorbs 3 beta-OH and 3-OH steroid hormones, and utilizes only 3 beta-OH steroid hormones as the materials for glucosylation.

DOI： 10.1111/j.1574-6968.2009.01685.x

Chronic Infections and Atherosclerosis 査読

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

CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY 37 ( 1 ) 44 - 48 2009年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：HUMANA PRESS INC

The immune response against heat shock protein 60 (HSP60) derived from pathogens causing chronic infections is thought to be an important pro-atherogenic mechanism because high serum levels of antibodies against HSP60 have been associated with atherosclerotic diseases, such as coronary artery diseases, or cerebro-vascular events. Furthermore, the presence of HSP60-specific T lymphocytes in circulation may increase the risk of atherosclerosis. Our recent in vitro and in vivo studies have also shown an association of Helicobacter pylori-HSP60 (Hp-HSP60) specific Th1 immune responses elicited by H. pylori infection with the progression of atherosclerosis in a hyperlipidemic mouse model. These Th1 dominant immune responses may cross-react with endogenous HSP60 expressed on stressed cells of the vascular endothelium, likely due to molecular mimicry. However, the exact mechanisms by which endothelial cells display their HSP60 molecule or present HSP60 antigenic epitopes on the surface are still unclear.

DOI： 10.1007/s12016-008-8097-7

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

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年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC

Backgrounds and Aim: The effect on reflux esophagitis of eradicating Helicobacter pylori is variable and not fully defined. We previously reported that in patients who have reflux esophagitis associated with duodenal ulcer, a significant improvement in the preexisting reflux esophagitis occurred after H. pylori was eradicated. In the present study, we asked whether H. pylori eradication leads to de novo development of reflux esophagitis in peptic ulcer patients.
Methods: Prospective post-eradication evaluations were conducted in 1195 H. pylori-positive patients with peptic ulcer diseases who were confirmed not to have reflux esophagitis by endoscopic examination before eradication therapy. After eradication therapy, endoscopy and a urea breath test were performed yearly.
Results: A total of 1187 patients were followed for up to 10.0 years (a mean of 3.6 years). Reflux esophagitis developed in 279 of 1000 patients cured of infection and in 26 of 187 patients who had persistent infection (P < 0.0001, Fisher's exact test). The esophagitis was mild (Los Angeles grade A) in most patients, transient in approximately one-half, and rarely necessitated long-term medication for the condition. Cure of infection, alcohol consumption, younger age, and high body mass index were identified as significant factors for the risk of developing non-transient reflux esophagitis.
Conclusions: Cure of H. pylori infection may increase the risk of developing reflux esophagitis in patients with peptic ulcer, but the esophagitis is mostly mild and transient, and long-term medication is rarely required. Thus, H. pylori eradication therapy need not be withheld for fear of provoking reflux esophagitis.

DOI： 10.1111/j.1440-1746.2008.05606.x

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

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER GMBH, URBAN & FISCHER VERLAG

Helicobacter pylori infection causes atrophic gastritis, peptic ulcer, and gastric cancer. The host immune response plays an important role in the pathogenesis of H. pylori-related diseases. Heat shock proteins are antigens involved in various diseases This study evaluated seropositivity for antibodies to H. pylori heat shock protein 60 in patients with gastric cancer.
Serum samples were obtained from 57 patients with gastric cancer (25 patients with diffuse-type gastric cancer and 32 with intestinal-type gastric cancer), 45 H. pylori-positive patients, and 49 H. pylori-negative patients without gastric cancer. Antibodies to heat shock protein 60 and H. pylori were assessed by enzyme-linked immunosorbent assay.
The positivity rate for antibodies to hsp60 was significantly higher in H pylori-positive patients than in H. pylori-negative patients (73.3% vs. 24.5%. p<0.001). In addition, the positivity rate for antibodies to hsp60 was higher in patients with gastric cancer than in H. pylori-positive patients without gastric cancer (87.7% vs. 73.3%, p = 0.06), and the positivity rate for antibodies to hsp60 was significantly higher in patients with diffuse-type gastric cancer than in M pylori-positive patients Without gastric cancer (96% vs. 73 3%, p<0.05).
H. pylori hsp60 might be associated with gastric carcinogenesis, especially in the case of diffuse cancer. (C) 2009 Elsevier GmbH. All rights reserved.

DOI： 10.1016/j.prp.2009.04.008

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

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

CLINICAL & DEVELOPMENTAL IMMUNOLOGY 2009年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：HINDAWI PUBLISHING CORPORATION

Helicobacter pylori (H. pylori) infection is a definite causative factor for gastric ulcers (GUs). In the present study we detected a specific antigen of gastric epithelial cells (HGC-27) using cell ELISA, which was recognized by the sera of GU patients (n = 20) but not in patients with chronic gastritis (CG; n = 20) or in healthy volunteers (HC; n = 10). This antigen was over-expressed by a stressful (heat-stressed) environment, and was identified as elongation factor 2 kinase (EF-2K) by western blotting. The GU patients' lymphocytes stimulated by H. pylori specifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes) from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1) and cytotoxic T lymphocyte (CTL) as opposed to those from CG patients. The target cells (HGC-27) expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU. Copyright (C) 2009 Kiyoshi Ayada et al.

DOI： 10.1155/2009/850623

The role of streptococcal hypersensitivity in the pathogenesis of Behçet's Disease. 査読

Kaneko F, Oyama N, Yanagihori H, Isogai E, Yokota K, Oguma K

European journal of dermatology : EJD 18 ( 5 ) 489 - 498 2008年9月

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年9月

掲載種別：研究論文（学術雑誌）

Immune responses against heat shock protein 60 (HSP60) of pathogen-origin are thought to be defensive events which, due to molecular mimicry, misdirect to a human counterpart. Therefore, atherosclerosis may be serologically predicted by anti-HSP60 antibodies (Abs). In the present study, we analyzed the clinical prevalence of the serum IgG Abs against Helicobacter pylori (Hp)-derived HSP60 (Hp-HSP60) or its peptide fragments in patients with cardiovascular disease (CVD; n = 250), as compared to those in age- and gender-matched non-CVD patients (n = 293). Anti-Hp cell lysate Abs frequently appeared in Hp-infected patients who were not associated with CVD. In contrast, Abs against the particular amino acid sequence Hp-HSP60II3 (II3 region, Glu141-Leu160, in Hp-HSP60) predominantly appeared in CVD patients, as well as IgG anti-human HSP60 (Hu-HSP60w). Furthermore, neither titer of anti-Hp-HSP60II3 nor anti-Hu-HSP60w Abs was correlated with the levels of high sensitivity C-reactive protein (hsCRP). This data strongly suggested that IgG anti-Hp-HSP60II3 Abs cross-reacted with Hu-HSP60w were independent diagnostic markers relevant to CVD. Further, the 20 amino acid residues (Glu141-Leu160) might be predominant CVD-associated epitopes that induce anti-Hu-HSP60 auto-Abs, whose location was predicted in the tertiary structure of Hu-HSP60. © 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jaut.2007.05.004

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

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

JOURNAL OF BACTERIOLOGY 189 ( 13 ) 4960 - 4963 2007年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC MICROBIOLOGY

The catabolic pathway for flavodoxin has yet to be clarified for any bacterial species. In this study, we found that the flavin mononucleotide in the flavodoxin of Helicobacter pylori is degraded to riboflavin via the phosphomonoesterase activity of class C acid phosphatase. The result is a conversion of holoflavodoxin to apoflavodoxin.

DOI： 10.1128/JB.00272-07

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 査読

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

JOURNAL OF MEDICAL MICROBIOLOGY 56 ( 2 ) 154 - 164 2007年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SOC GENERAL MICROBIOLOGY

Previous reports have indicated that Helicobacter pylori heat-shock protein 60 (H. pylori-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by which H. pylori-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by which H. pylori-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. Intact H. pylori, heat-killed H. pylori and H. pylori recombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 In in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partialiy inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-kappa B (NF-kappa B)-mediated transcriptional activation, since U01 26, SB203580 and the anti-TLR2 antibody decreased NF-kappa B activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway in H. pylori-HSP60-induced IL-8 secretion.

DOI： 10.1099/jmm.0.46882-0

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 査読

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

JOURNAL OF GASTROENTEROLOGY 42 21 - 27 2007年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Background. We previously reported that eradication of Helicobacter pylori could reduce the risk of developing gastric cancer in patients with peptic ulcer diseases. In the present study, we further followed up out-patient groups to identify factors associated with the development of gastric cancer. Methods. Prospective posteradication evaluations were conducted in 1342 consecutive patients (1191 men and 151 women; mean age, 50 years) with peptic ulcer disease who had received H. pylori eradication therapy. The patients had undergone endoscopic examination before eradication therapy to evaluate peptic ulcers, background gastric mucosa, and H. pylori infection. After confirmation of eradication, follow-up endoscopy was performed yearly. Results. A total of 1131 patients were followed for up to 9.5 years (mean, 3.9 years). Gastric cancer developed in 9 of 953 patients cured of infection and in 4 of 178 who had persistent infection (P = 0.04). The risk of developing gastric cancer after receiving H. pylori eradication therapy was increased according to the grade of baseline gastric mucosal atrophy (P = 0.01). In patients with peptic ulcer diseases, persistent infection of H. pylori (hazard ratio, 3.9; P = 0.03), the grade of baseline gastric mucosal atrophy (3.3, P = 0.01) and age (2.0, P = 0.04) were identified as significant risk factors for developing gastric cancer. Conclusions. The grade of gastric atrophy was closely related to the development of gastric cancer after receiving H. pylori eradication therapy. Thus, eradication of H. pylori before the significant expansion of atrophy is most beneficial to prevent gastric cancer.

DOI： 10.1007/s00535-006-1924-9

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 査読

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：KARGER

Background/Aims: In Helicobacter pylori eradication therapy, using a proton pump inhibitor plus amoxicillin and clarithromycin (PPI/AC regimen), the impact of the clarithromycin dose and smoking on efficacy is conflicting. Here, we compared the efficacy of 400 and 800 mg of clarithromycin in the regimen in relation to smoking in patients with peptic ulcer disease. Methods: We studied 601H. pylori-positive patients with peptic ulcer disease who had received amoxicillin 750 mg and clarithromycin 200 or 400 mg together with lansoprazole 30 mg b. i. d. Results: 305 patients were treated with a regimen containing 400 mg of clarithromycin (C400 group), and 296 patients with a regimen containing 800 mg (C800 group). Overall cure rates between the two groups were not significantly different, but the cure rate in the C800 group was significantly better than that in the C400 group among patients infected with clarithromycin- sensitive strains (p = 0.03). This difference could be attributed to differences among smokers versus non-smokers: the cure rate among smokers in the C800 group (91.0%) was better than that in the C400 group (80.0%, p = 0.003). Conclusions: 800 mg of clarithromycin is recommended in the PPI/AC regimen for patients who smoke and are infected with clarithromycinsensitive H. pylori.

DOI： 10.1159/000102301

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年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）出版者・発行元：Blackwell Publishing Inc.

Immunoinflammatory processes due to chronic infection are thought to be one of the definitive atherogenetic processes. Especially, anti-heat shock protein antibodies have been related to the prevalence of disease such as coronary artery disease or cerebral infarction, etc., resulted from atherosclerosis. Furthermore, the presence of HSP60-specific T lymphocytes in circulation may increase the risk of atherosclerosis. We have recently demonstrated the evidences that Helicobacter pylori infection induced atherosclerosis in apoe+/-ldlr+/- mice and that Hp-anti-heat-shock protein specific Th1-dominant immune responses had a major involvement in the progression of atherosclerosis. These cellular immune responses caused autoimmunity against endogenous HSP60 (expressed on the stressed cells of vascular endothelium), due to the molecular mimicry. Therefore, an appropriate treatment with antibiotics or with anti-HSP60 antibodies, which regulates the Th1 induction, could sufficiently reduce the progression of atherosclerosis. © 2007 New York Academy of Sciences.

DOI： 10.1196/annals.1422.062

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

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年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Microbiology Society

<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.

DOI： 10.1099/mic.0.28421-0

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

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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background &amp
Aims: Immune responses to Helicobacter pylori are important in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In this retrospective case study, we investigated whether certain alleles and haplotypes of major histocompatibility complex genes are associated with gastric MALT lymphoma and the efficacy of H pylori eradication therapy on the lymphoma. Methods: Blood samples were obtained from 18 patients with H pylori-positive gastric MALT lymphoma (5 men and 13 women
age range, 51-80 years), 30 patients with H pylori-positive non-ulcer dyspepsia (17 men and 13 women
age range, 37-77 years), and 30 patients with H pylori-negative non-ulcer dyspepsia (12 men and 18 women
age range, 37-77 years). HLA-DQA1 and DQB1 allele typing was performed by use of a polymerase chain reaction sequence-specific oligonucleotide procedure. All patients with MALT lymphoma were treated with H pylori eradication therapy and followed up by repeated endoscopy and biopsy. Results: We found a significant increase in alleles HLA-DQA1*0103 and HLA-DQB1*0601, and a haplotype DQA1*0103-DQB1*0601, in MALT lymphoma patients when compared with non-ulcer dyspepsia patients who were either H pylori-positive or not and with a healthy control population. After H pylori eradication, the lymphomas regressed completely in all 10 patients who possessed the DQA1*0103-DQB1*0601 haplotype but in only 4 of the 8 without this haplotype (P = .023). Conclusions: DQA1*0103-DQB1*0601 haplotype-positive gastric MALT lymphoma is likely to respond to therapy by eradication of H pylori. © 2005 by the American Gastroenterological Association.

DOI： 10.1016/S1542-3565(05)00185-0

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

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年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Infection with Helicobacter pylori is a risk factor for the development of gastric cancer. However, it is not known whether eradication therapy can prevent the development of gastric cancer in persons in whom the cancer is not yet established. In the present study, we investigated whether the eradication of H. pylori in patients with peptic ulcer disease reduces the likelihood of their developing gastric cancer. METHODS: Prospective posteradication evaluations were conducted in 1,342 consecutive patients (1,191 men and 151 women
mean age: 50 yr) with peptic ulcer diseases who had received H. pylori eradication therapy. After confirmation of eradication, endoscopy and a urea breath test were performed yearly. RESULTS: A total of 1,120 patients completed more than 1-yr follow-up and were followed for up to 8.6 yr (a mean of 3.4 yr). Gastric cancer developed in 8 of 944 patients cured of infection and 4 of 176 who had persistent infection (p = 0.04
log-rank test). All the gastric cancer developed in patients with gastric ulcer, but none in patients with duodenal ulcer (p = 0.005
Fisher's exact test). In patients with gastric ulcer, persistent infection was identified as a significant factor for the risk of developing gastric cancer (hazard ratio: 3.35
95% confidence interval: 1.00-11.22
p = 0.04
Cox's proportional-hazards model). CONCLUSION: H. pylori eradication may reduce their risk of developing gastric cancer in patients with gastric ulcer. Large-scale studies in additional populations of this important international public-health issue are warranted. © 2005 by Am. Coll. of Gastroenterology Published by Blackwell Publishing.

DOI： 10.1111/j.1572-0241.2005.41384.x

Neutrophil and lymphocyte responses to oral Streptococcus in Adamantiades-Behçet's disease. 査読

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

FEMS immunology and medical microbiology 43 ( 2 ) 125 - 131 2005年2月

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

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

FEMS Microbiology Letters 237 ( 2 ) 407 - 413 2004年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

In this analysis of membrane lipid compositions in Helicobacter pylori, the membrane lipid profiles drastically changed during coccoid formation: cholesteryl-6-O-tetradecanoyl-α-D-glucopyranoside levels increased, cholesteryl-α-D-glucopyranoside and phosphatidyl ethanolamine decreased, and a coordinated increase in cardiolipin and decrease in phosphatidyl glycerol were observed. Cholesteryl-6-O-phosphatidyl-α-D-glucopyranoside was hardly detected in the spiral forms in the logarithmic phase, but subsequently increased throughout the coccoid conversion. These results suggest that environmental stresses induce the expression of certain regulatory systems for lipid metabolism in H. pylori, and that the resulting alterations in lipid composition play an important role in inducing the coccoid conversion. © 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.femsle.2004.07.004

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

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年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Background & Aims: There has been significant controversy over the relationship between Helicobacter pylori infection and reflux esophagitis. We investigated the effects of eradicating H. pylori on the reflux esophagitis found in patients with peptic ulcers. Methods: Prospective posteradication evaluations were conducted yearly in 162 H. pylori-positive patients who had reflux esophagitis together with peptic ulcer disease (4 women and 158 men, mean age = 49.1 yr). The Los Angeles classification of the patients' esophagitis was: grade A, 90; grade B, 63; and grade C, 9. The follow-up evaluations began 1 to 2 months after completion of the eradication treatment (mean time of follow-up = 22 mo), and consisted of endoscopy and an interview focusing on heartburn. Results: Six patients were withdrawn from the study because of adverse drug reactions or a failure to regularly keep their appointments. After eradication therapy, we observed endoscopically that reflux esophagitis had improved in 87 (55.8%) of the 156 patients. The improvement rate was significantly higher in patients cured of infection (60.8%) than in those with persistent H. pylori infection (38.9%) (P = 0.04). Body mass index (odds ratio = 0.86, 95% confidence interval [CI] = 0.76-0.97), cure of infection (3.68, 95% CI = 1.56-8.69), the absence of a hiatal hernia (3.90, 95% CI = 1.83-8.28), and an ulcer located in the duodenum (2.75, 95% CI = 1.33-5.70) were identified as significant independent factors for the improvement of reflux esophagitis. Conclusions: In patients with reflux esophagitis associated with duodenal ulcer, a significant improvement in pre-existing reflux esophagitis was noted after H. pylori eradication.

DOI： 10.1053/S1542-3565(04)00165-X

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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background/Aims: Alterations of gastric mucin have been postulated as important pathogenic properties of Helicobacter pylori. In this study, we investigated gastric mucin synthesis in H. pylori-infected gastric mucosa by measuring UDP-galactosyltransferase activity, a key enzyme for the synthesis of mucin, and the amount of intracellular mucin in the gastric mucosa. Methodology: Gastric biopsy specimens were obtained from thirty-seven patients (20 H. pylori-positive and 17 H. pylori-negative). UDP-galactosyl-transferase activity of the biopsy specimens was measured by an assay system we had developed, using a peanut agglutinin lectin. The amount of intracellular mucin in the gastric epithelial cells was analyzed by measuring the cells' periodic acid-Schiff-alcian blue staining-positive substances. Results: UDP-galactosyltransferase activities in the antral mucosa, but not in the body mucosa, of H. pylori-positive patients were significantly lower than those of H. pylori-negative patients (p&lt
0.05). The amount of intracellular mucin in antral epithelial cells of H. pylori-positive patients was significantly lower than that of H. pylori-negative patients (p&lt
0.01). Conclusions: These findings suggest that H. pylori infection decreases gastric mucin synthesis via inhibition of UDP-galactosyltransferase. This effect may impair the gastric mucosal barrier and contribute to the mucosal injury induced by H. pylori infection.

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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background/Aims: At the assessment of eradication therapy of Helicobacter pylori, the results of 13C-urea breath test and other methods such as bacterial culture are occasionally inconsistent. In this study, we examined the outcomes of inconsistent results. Methodology: Four hundred and four patients with peptic ulcer who were H. pylori-positive and who had completed eradication therapy were studied. Bacterial culture, rapid urease tests and 13C-urea breath test were performed between one and three months after the end of the therapy. The cut-off value for the 13C-urea breath test used originally in this study was 2.5 per mil. We investigated the outcome of inconsistent results by following up the patients every 6 to 12 months. Results: At the initial assessment of eradication therapy, we observed inconsistent results with bacterial culture and 13C-urea breath test in 43 of 404 patients. Most of them (40 of 43) were culture-negative but urea breath test-positive, and the majority became negative for both tests. Based on the follow-up results, the optimum value for 13C-urea breath test at the assessment of eradication therapy was found to be 3.5 per mil. Conclusions: We found that outcomes of inconsistent results were variable, indicating the importance of the follow-up of patients after eradication therapy of H. pylori.

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

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年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier Inc.

OBJECTIVES: Genetic polymorphism of interleukin (IL)-1β is associated with differences in gastric acid suppression in response to Helicobacter pylori (H. pylori) infection. Thus, the polymorphism might affect H. pylori eradication therapy, as antibiotics used in treatment regimens may be acid sensitive. In this study, we examined the impact of IL-1β genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype and antibiotic resistance. METHODS: A total 249 patients with peptic ulcer disease were randomized to receive one of the following regimens: amoxicillin and clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19 and IL-1β-511 genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The intention-to-treat-based overall cure rate was 74.3% (95% CI = 68-79%). In the normal acid secretion IL-1β genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95% CI = 56-99%) was significantly higher than among subjects in the CYP2C19 homozygous (60.0%, 95% CI = 38-78%) and heterozygous (63.6%, 95% CI = 46-78%), i.e., extensive metabolizer, groups (p &lt
0.05). In the low acid secretion IL-1β genotype group, there was no difference in the cure rate among the CYP2C19 genotype groups. Multiple logistic regression analysis identified susceptibility to clarithromycin (p &lt
0.0001) and CYP2C19 genotype status (p = 0.03) as significant independent factors for treatment failure. CONCLUSION: IL-1β genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori infection. © 2003 Am. Coll. of Gastroenterology.

DOI： 10.1016/S0002-9270(03)00713-5

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

Mucosa-associated lymphoid tissue (MALT) lymphomata observed simultaneously in the stomach and colon are rare. We report concurrent gastric and colonic low-grade MALT lymphomata that originated from the same clone in a 58-year-old Japanese man without Helicobacter pylori infection. Endoscopy showed multiple erosive lesions in the gastric body and antrum, and a single flat elevation with an irregular margin in the sigmoid colon. Histopathological findings of both lesions suggested low-grade MALT lymphoma. Lymphoepithelial lesions were evident in the gastric lesions, but not in the colonic lesion. Southern blot analysis of lymphoma cells revealed the same immunoglobulin heavy-chain rearrangement pattern. The chromosomal translocation t(11
18)(q21
q21) was also observed. After six courses of cyclophosphamide, doxorubicin, vincristine and predonisolone, the gastric lesions disappeared endoscopically, while the colonic lesion persisted. A sigmoidectomy was consequently performed. The chromosomal translocation may be related to the pathogenesis of the present MALT lymphoma case without H. pylori infection. It is interesting that the gastric and colonic lesions differed in response to treatment and in their endoscopic and histologic features, despite having the same origin.

DOI： 10.1046/j.1443-1661.2003.00108.x

Characterisation of monoclonal antibodies against haemagglutinin associated with Clostridium botulinum type C neurotoxin 査読国際誌

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年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Microbiology Society

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.

DOI： 10.1099/0022-1317-51-4-286

Bacteriology of H. pylori

Keiji Oguma, Kenji Yokota, Yoshikazu Hirai, Shunji Hayashi

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

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

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年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC MICROBIOLOGY

Infection with Helicobacter pylori induces humoral immune responses against various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant antigens in various diseases including H. pylori infection. In the present study, we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected peptic ulcers during a bacterial eradication study. The patients were treated with a proton pump inhibitor and antimicrobial agents to eradicate the organism. Their sera were obtained at pretreatment and at 1 month and 6 months after the eradication therapy. The titers of immunoglobulin G antibodies to the H. pylori hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori hsp60 antibodies in sera collected 1 month after treatment had declined significantly, even when changes in the titers of antibodies to whole-cell and urease antigens were not apparent. These results suggest that measurement of antibodies to H. pylori hsp60 in serum is useful far the early monitoring of the effectiveness of eradication therapy.

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年2月

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

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CENTER ACADEMIC PUBL JAPAN

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H, pylori to gastric epithelial cells is the initial step of N, pylori infection. Inhibition of H, pylori adhesion is thus a therapeutic target in the prevention of H, pylori infection. me have reported that rebamipide and ecabet sodium, mucoprotective antiulcer agents, independently inhibit H. pylori adhesion. However, the antiadhesion activity of each antiulcer agent was incomplete. Experiments were performed to evaluate the combined effect of rebamipide and ecabet sodium on H, pylori adhesion to gastric epithelial cells, MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells, Twelve clinical isolates of H, pylori were used in this study. We evaluated the effects of rebamipide and ecabet sodium, individually and in combination, on H. pylori adhesion to target cells quantitatively using our previously established enzyme-linked immunosorbent assay. Rebamipide and ecabet sodium each partially inhibited H. pylori adhesion. In contrast, adhesion was almost completely inhibited by pretreating target cells and N, pylori with the combination of rebamipide and ecabet sodium, Our studies suggest that the synergistic antiadhesion activity of rebamipide and ecabet sodium is greater than that of each antiulcer agent alone.

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年8月

記述言語：英語出版者・発行元：Okayama University Medical School

<p>Three outbreaks and many isolated cases of enterohemorrhagic Escherichia coli O157:H7 occurred in 1996 and 1997 in Okayama Prefecture, Japan. In an attempt to investigate the route of these infections, the strains isolated from the 3 outbreaks (total 33 strains) and 15 isolated cases (total 15 strains) were investigated using random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE). In addition, 10 strains from an outbreak in Tojo Cho, Hiroshima Prefecture (June 1996), 2 strains from the particular types of meat in Kochi Prefecture, and 42 strains isolated from bovine feces in a farm in Okayama Prefecture were also investigated in the same manner. PFGE was much more useful than RAPD for molecular typing of the clinical isolates, in that it allowed us to classify them into 10 PFGE groups. We noted that the strains differed according to the time and place of the outbreaks (or isolated cases). This indicates that O157:H7 infections in Okayama Prefecture were caused by different strains (although some cases were aggravated by the same strains as were found in other areas). The isolates from bovine feces were classified into 5 groups by PFGE profiles, but none of them were identical to those of the clinical isolates.</p>

DOI： 10.18926/AMO/31612

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年2月

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Society for General Microbiology

The 16S toxin and one subcomponent of haemagglutinin (HA), designated HA1, were purified from a type D culture of Clostridium botulinum by a newly established procedure, and their HA activities as well as that of purified type C 16S toxin were characterized. SDS-PAGE analysis indicated that the free HA1 forms a polymer with a molecular mass of approximately 200 kDa. Type C and D 16S toxins agglutinated human erythrocytes in the same manner. Their HA titres were dramatically reduced by employing erythrocytes that had been previously treated with neuraminidase, papain or proteinase K, and were inhibited by the addition of N-acetylneuraminic acid to the reaction mixtures. In a direct-binding test to glycolipids such as SPG (NeuAcα2-Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-Cer) and GM3 (NeuAcα2-3Galβ1-4Glcβ1-Cer), and glycoproteins such as glycophorin A and/or B prepared from the erythrocytes, both toxins bound to sialylglycolipids and sialoglycoproteins, but bound to neither neutral glycolipids nor asialoglycoproteins. On the basis of these results, it was concluded that type C and D 16S toxins bind to erythrocytes through N-acetylneuraminic acid. HA1 showed no haemagglutination activity, although it did bind to sialylglycolipids. We therefore speculate that binding to glycoproteins rather than to glycolipids may be important in causing haemagglutination by type C and D 16S toxins.

DOI： 10.1099/00221287-145-9-2533

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

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

ACTA MEDICA OKAYAMA 52 ( 1 ) 41 - 48 1998年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Helicobacter pylori (H. pylori) infection in the stomach is etiologically closely associated with chronic active gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. In this study, we examined the antibody responses and cytokine profiles of three strains of mice (BALB/c, C3H/He, and C57BL/6) infected with H. pylori. Following this, correlations between host-immune reactions and intensity of inflammation were analyzed. H. pylori (ATCC43504) was intragastrically administered once a week to the mice from 4 weeks of age, and they were sacrificed at the ages of 4 and 7 months. In these mice, we examined the histology of the stomach, antibody titers against H. pylori, and serum levels of cytokines (IL-4, IL-10, TNF-alpha, IL-2 and Interferon-gamma). In BALB/c mice, inflammation of the stomach was minimal. Inflammation was observed in 63.6% of C57BL/6 mice and 33.3% of C3H/He mice. In C57BL/6 and C3H/He mice, all the cytokines tended to increase, In contrast, BALB/c mice were inactive in cytokine production except for IL-2, Two C3H/He mice developed severe inflammation with lymph follicles; one showed a response largely typical of Th-1, and the other showed a response largely typical of Th-2. Although a definite correlation was not shown between Th-1/Th-2 response evaluated by cytokine production and intensity of inflammation, it appears that in H. pylori-induced inflammation both cell-mediated (Th-1) and humoral (Th-2) immunity play a role in pathogenesis.

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

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年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMJ Publishing Group

Aims - To investigate the localisation of Helicobacter pylori antigens and the expression of human heat shock proteins (HSP) in stomachs affected by MALT lymphoma. Methods - Surgically resected stomachs from 24 patients with MALT lymphoma were immunostained with anti-H pylori rabbit antibodies (ORP-1 and ORP-2) and anti-human HSP60 mouse monoclonal antibodies (mAb) (LK-1 and LK-2). Results - Follicular dendritic cells of germinal centres in the stomachs affected by MALT lymphoma were immunostained with anti-H pylori polyclonal antibodies and with anti-human HSP60 mAb, as were the epithelial cells. None of the lymph node samples reacted. Conclusions - Human HSP60, which cross reacts with anti-H pylori polyclonal antibodies, is often expressed on follicular dendritic cells in gastric MALT lymphoma tissues and may be aetiologically relevant to lymphomagenesis of MALT lymphoma.

DOI： 10.1136/jcp.51.5.396

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年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. H. pylori adhesion to human gastric mucosa is the initial step of H. pylori colonization. Inhibition of H. pylori adhesion is thus a therapeutic target in preventing H. pylori infection. We have previously established a method using the enzyme-linked immunosorbent assay to analyze quantitatively H. pylori adhesion to gastric epithelial cells. This method is suitable for screening antiadhesion agents. Some mucoprotective agents are proved to have antiadhesion effects in vitro, and they may modify H. pylori adhesion. This evidence gives us a useful clue to analyze the molecular mechanism of H. pylori adhesion to mucosa. Furthermore, in clinical trials, these mucoprotective agents enhanced the eradication rate when administered with antibiotics. In conclusion, the antiadhesion agents may have potential as therapeutic regimens against H. pylori infection.

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

K Yokota, K Oguma

MICROBIOLOGY AND IMMUNOLOGY 41 ( 12 ) 925 - 931 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CENTER ACADEMIC PUBL JAPAN

The production of IgA protease in twelve strains of Streptococcus sanguis isolated from patients with Behcet's disease (BD) was examined, Protease activity was detected in 10 out of 12 strains, The protease was purified from one representative strain, S. sanguis 113-20, by employing Rotofor and DEAE-Sephacel chromatography, The molecular mass of the purified protease was approximately 100 kDa, and it cleaved the proline-threonine site of the IgA, Both IgG and IgA titers against the cells (113-20) and the purified IgA protease in the sera of BD patients and healthy controls, 36 each, were assayed, The IgG titers against the cells and protease were not significant in the BD patients or controls, but the IgA titers against the cells and protease in the BD patients were significantly higher than those of the controls, These data indicate that the BD patients are infected with IgA protease-producing S. sanguis strains, which cause an increase of IgA titer against these organisms and IgA protease antigen. Since the organisms can proliferate in BD patients for a long period of time (years), it seems that IgA antibodies cannot effectively eliminate the organisms.

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blackwell Publishing

A rapid and simple method to quantitatively analyse Helicobacter pylori adhesion to human gastric epithelial cells was developed by using an enzyme- linked immunosorbent assay. This method made it possible to quantitatively evaluate the adhesion activities of many different H. pylori strains at a time. Our studies indicate that this method is well suited for the quantitative analysis of H. pylori adhesion to gastric epithelial cells.

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

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年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Society for Microbiology

The lipid and fatty acid profiles of eight Helicobacter spp. (H. nemestrinae, H. acinonyx, H. canis, Helicobacter sp. strain CLO-3, 'H. rappini' [Flexispira rappini], H. pametensis, Helicobacter sp. strain Bird- B, and Helicobacter sp. strain Bird-C) and the fatty acid profiles of five additional species (H. pylori, H. felis, H. muridarum, H. mustelae, and H. fennelliae) were analyzed and compared. A heterologous fatty acid profile was observed among the Helicobacter spp., and on that basis the species could be divided into two groups. Group A had 19-carbon cyclopropane fatty acid (19:0cyc) and tetradecanoic acid (14:0) as the major fatty acids, and group B characteristically lacked the 19:0cyc and had hexadecanoic acid (16:0) and octadecenoic (18:1) acids as the major fatty acids. The species of group A are primarily gastric colonizers, and those of group B are primarily intestinal colonizers. Seven of the eight species studied showed the unusual and characteristic presence of cholesteryl glucosides (CGs), and most of these seven showed a very large amount (9.7 to 27.4% of the weight of total extractable lipid). The types of CGs and their distribution in different species were as follows: cholesteryl-6-O-acyl-α-D-glucopyranoside (cholesteryl-6-O-tetradecanoyl-α-D-glucopyranoside in H. nemestrinae and mainly cholesteryl-6-O-dodecanoyl-α-D-glucopyranoside in 'H. rappini'), cholesteryl-α-D-glucopyranoside (H. nemestrinae, H. acinonyx, H. canis, Helicobacter sp. strain CLO-3, and 'H. rappini'), and cholesteryl-6-O- phosphatidyl-α-D-glucopyranoside (H. nemestrinae, H. acinonyx, H. canis, and Helicobacter sp. strain CLO-3). Besides this, we could also detect cholesteryl acyl glucoside in H. acinonyx, cholesteryl glucoside in Helicobacter sp. strains Bird-B and -C, and cholesteryl phosphatidyl glucoside in 'H. rappini' and Helicobacter sp. strain Bird-C. A selective accumulation of free cholesterol was observed in the neutral lipid fractions. On the basis of the detection of CGs in 11 of the 13 species studied so far, the presence of CGs appears to be a characteristic feature of the genus Helicobacter. In view of this and also because of a simple and rapid detection method described herein, the CGs can be used as a valuable chemotaxonomic marker.

DOI： 10.1128/jb.178.7.2065-2070.1996

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

M HAQUE, Y HIRAI, K YOKOTA, K OGUMA

ACTA MEDICA OKAYAMA 49 ( 4 ) 205 - 211 1995年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Many of Helicobacter species have been found to have novel cholesteryl glucosides (CGs). To study the biosynthetic mechanism of CGs, the lipid profiles of H. pylori and H. mustelae grown in serum-supplemented and cholesterol-restricted serum-free media were investigated. In contrast to the serum-supplemented state, helicobacters had less CGs in the serum-free state; a trace amount of CGs and no CG was detected in H. pylori and H. mustelae, respectively. The proportion of total and individual phospholipid also showed significant alteration. Unknown lipids which did not contain phosphate and sugar were detected in the serum-free state, but not in the serum-supplemented state. The CGs were found to be distributed mainly in the membrane fractions, and one of the unknown lipids was found exclusively in the cytosol fraction. Based on these data,it is apparent that the CGs of helicobacters are synthesized by de novo uptake of cholesterol from the media. The unknown lipids detected in the serum-free state may be storage lipids, appearing in response to depletion of nutrients, especially cholesterol, or other factors in the media.

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年

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年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Society for Microbiology

A chloroform-methanol-extracted lipid of Helicobacter pylori was studied. Three kinds of glycolipids, accounting for about 25% (wt/wt) of the total lipid, were detected and identified to be cholesteryl glucosides. The structures of two of them were determined to be cholesteryl-α-D- glucopyranoside and cholesteryl-6-O-tetradecanoyl-α-D-glucopyranoside, and the plausible structure of the third one was identified as cholesteryl-6-O- phosphatidyl-α-D-glucopyranoside. Cholesteryl glucosides are very rare in animals and bacteria. Furthermore, those in H. pylori had an α-glycosidic linkage, which is rather unusual for natural glycosides, and a phosphate- linked cholesteryl glycoside like the cholesteryl-6-O-phosphatidyl-α-D- glucopyranoside has not been reported previously. As the cholesterol glucosides were detected in strains obtained from diverse geographical locations, the presence of cholesteryl glucosides in H. pylori is a very unique and a characteristic feature of the species. These findings add a new facet to the physiology and biochemistry, especially the cholesterol and glucose metabolism, of H. pylori. Furthermore, the cholesteryl glucosides of H. pylori showed hemolytic activities.

DOI： 10.1128/jb.177.18.5327-5333.1995

HELICOBACTER-PYLORI INDUCES INFLAMMATION IN MOUSE URINARY-BLADDER AND PELVIS 査読

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

MICROBIOLOGY AND IMMUNOLOGY 38 ( 5 ) 331 - 336 1994年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CENTER ACADEMIC PUBL JAPAN

Helicobacter pylori was transurethrally inoculated into the mouse urinary tract. The organism established infection and induced inflammation in the urinary bladder and pelvis. During the infection, urinary pH was elevated, probably due to the production of NH3 by bacterial urease. H. pylori was recovered from the urinary bladder, kidney and urine of the infected mice. Histopathologically, severe neutrophil infiltration was observed in the mucosal layer of both organs. H. pylori was detected on the surface of the epithelial cells. These results indicate that low pH and bacterial flora were not essential factors in establishing the mucosal infection with H. pylori. This experimental system is useful to investigate the pathogenicity of H. pylori in mucosal organs.

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

MICROBIOLOGY and IMMUNOLOGY 38 ( 5 ) 403 - 405 1994年

記述言語：英語出版者・発行元：Center For Academic Publications Japan

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

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年

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年

記述言語：日本語掲載種別：研究論文（学術雑誌）

In H. pylori, we examined the composition of total lipids. In thin-layer chromatography, three kinds of glycolipids were detected, which were named as G-1, G-2 and G-3. G-3 contained phosphates in addition to sugars. Total lipids consisted of 6.0% neutral lipids (weight %), 20.6% glycolipids (G-1, G-2) and 73.4% phospholipids (including G-3). Total glycolipids were approximately 25% of total lipids. After methanolysis, cholesterol was detected in the hexane extractable fraction and glucose was detected by GLC in the methanol fraction after trimethylsilylation, in all glycolipids. Therefore, these glycolipids are cholesteryl glycosides. Cholesteryl glycosides are found very rarely in bacteria, and have been detected only in a few species of mycoplasmas and spirochetes.

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年

記述言語：日本語掲載種別：研究論文（学術雑誌）

Helicobacter pylori is an emerging candidate agent for the genesis of chronic gastritis and peptic ulcer. There have been many challenges to establish an experimental infection with H. pylori in animals. In recent, several studies reported for animal infection with this organism. One of them was the study using urinary system. The study indicated the ability of H. pylori to induce inflammation without significant low pH condition. Experimental infection in Mongolian gerbils showed that H. pylori could colonize on the surface of the gastric mucosa in animals without human. The study of nude mice by Karita et al. showed several valuable facts concerning the relation between bacterial pathogenicity and potential of bacterial colonization in stomach. The study in which remaining of bacteria was extended showed that colonization of H. pylori was affected by bacterial flora in the stomach.

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年

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

MICROBIOLOGY and IMMUNOLOGY 36 ( 8 ) 815 - 822 1992年

記述言語：英語出版者・発行元：Center For Academic Publications Japan

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

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

Helicobacter pylori was orally inoculated into Mongolian gerbils. The organisms were able to colonize in the gastro-mucosal layer of the gerbils, especially in those gerbils which had mucosal lesions caused by indomethacin treatment. The pathological changes developed by H. pylori infection were restricted to the stomachs, and only slightly inflammatory cells were observed. © 1991, Center For Academic Publications Japan. All rights reserved.

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

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

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年

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

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年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

Zymosan-induced chemiluminescence was investigated in whole blood and in neutrophils: in both, the peak count was frequently elevated in Behçet's disease, and was significantly higher than in healthy controls
similarly the peak time was shorter. There were more uncommon serotypes of Streptococcus sanguis in the oral flora of patients with Behçet's disease. Common serotypes were present in the flora of healthy controls, but not in patients with the disease. The percentage of Strep. sanguis in the oral flora was significantly correlated with the level of chemiluminescence response. Thus infection with uncommon serotypes of Strep. sanguis may play a role in the aetiology of Behçet's disease. © 1990.

DOI： 10.1016/0003-9969(90)90113-O

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