研究者詳細 - 横田　憲治

論文 - 横田　憲治

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H. pylori decreases gastric mucin synthesis via inhibition of galactosyltransferase

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

Hepato-Gastroenterology 50 ( 53 ) 1739 - 1742 2003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.

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

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

Hepato-Gastroenterology 50 ( 53 ) 1700 - 1703 2003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.

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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

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

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

Digestive Endoscopy 15 ( 1 ) 55 - 59 2003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

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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

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Bacteriology of H. pylori

Keiji Oguma, Kenji Yokota, Yoshikazu Hirai, Shunji Hayashi

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

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

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

Japanese Journal of Infectious Diseases 53 ( 1 ) 32 - 33 2000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.

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

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

Acta Medica Okayama 53 ( 4 ) 193 - 200 1999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

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

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

Japanese Journal of Infectious Diseases 52 ( 1 ) 27 1999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

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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.

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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

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

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

Digestive Diseases and Sciences 43 ( 9 ) 1998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.

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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.

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

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

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

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

田中智, 山本美保, 飯田憲治, 松田三千雄, 林俊治, 横田憲治, 小熊恵二

アレルギー 45 ( 8 ) 900 - 900 1996年

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