研究者詳細 - 横田　憲治

論文 - 横田　憲治

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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)

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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

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

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地域在住高齢者におけるメチシリン耐性ブドウ球菌の保菌状況調査

渡辺朱理, 横田憲治, 林俊治, 苔口進

日本環境感染学会総会プログラム・抄録集 34回 [P - 005] 2019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

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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

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

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

Biocontrol science 24 ( 2 ) 117 - 121 2019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

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吸い飲み内残余飲料の微生物汚染状況に関する実験的予備調査査読

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)

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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

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

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

Acta medica Okayama 72 ( 3 ) 231 - 239 2018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

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

井川卓朗, 影山千紘, 横田憲治, 吉野正, 佐藤康晴

日本リンパ網内系学会会誌 58 122 - 122 2018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

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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

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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

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口腔清掃と洗口との併用効果の検討口腔内細菌数を指標にして

渡辺朱理, 横田憲治, 松山美和, 苔口進

日本歯科衛生学会雑誌 10 ( 1 ) 120 - 120 2015年8月

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