Establishment of new treatment for chronic pulmonary aspergillosis with modulating microbiota of gut
Project/Area Number |
16K09936
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Infectious disease medicine
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Research Institution | Nagasaki University |
Principal Investigator |
IZUMIKAWA Koichi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (20404212)
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Co-Investigator(Kenkyū-buntansha) |
田代 将人 長崎大学, 医歯薬学総合研究科(医学系), 助教 (20713457)
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Research Collaborator |
NAKANO Yuichiro
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | アスペルギルス / マイクロバイオーム |
Outline of Final Research Achievements |
The aim of this study is to reveal the relation between the pathogenesis of chronic pulmonary aspergillosis and microbiota of gut and/or respiratory system. Chronic aspergillus infection with anti-aspergillus antibody production mouse model was established in first two years. The microbiota of this mouse model was modified with cefoperazone/sulbactam (C/S) contained drinking water and explore the influences to anti-aspergillus antibody production in C/S treated mice. The microbiota of mice treated with C/S was dramatically changed into only kind of enterobacteriaceae family, though varieties of enterobacteriaceae bacteria were proved in C/S un-treated mice group. The production of anti-aspergillus antibody was reduced in C/S treated mice with aspergillus challenged compared to those of C/S un-treated mice group. This result indicated that microbiota of gut influences the immunological effect against Aspergillus infection.
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Academic Significance and Societal Importance of the Research Achievements |
慢性肺アスペルギルス症は、難治性で予後不良な真菌症であり、おもに結核の治療後に罹患する。先進国でも結核の中蔓延国である我が国においては、潜在的に多くの患者が存在している。抗真菌薬が奏功しない例も多く、抗真菌薬に依存しない治療法の開発がもとめられる。腸内細菌叢はヒトの免疫能に影響を及ぼすと言われているが、今回のマウスを用いた動物実験結果から、アスペルギルス症において腸内細菌叢が、アスペルギルスに対する感染防御能を変化させるために重要な役割をしている可能性があることが証明された。腸内細菌叢をコントロールし、アスペルギルス症に対する免疫能を賦活化させる新しい治療につながる可能性を示した。
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Report
(4 results)
Research Products
(74 results)
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[Journal Article] Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings2018
Author(s)
Denning DW, Page ID, Chakaya J, Jabeen K, Jude CM, Cornet M, Alastruey-Izquierdo A, Bongomin F, Bowyer P, Chakrabarti A, Gago S, Guto J, Hochhegger B, Hoenigl M, Irfan M, Irurhe N, Izumikawa K, et al.
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Journal Title
Emerging Infectious Diseases
Volume: 24
Issue: 8
Pages: 171312-171312
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] In vitro and In vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gatiii: an emerging fungal pathogen.2017
Author(s)
Nishikawa H, Fukuda Y, Mitsuyama J, Tashiro M, Tanaka A, Takazono T, Saijo T, Yamamoto K, Nakamura S, Imamura Y, Miyazaki T, Kakeya H, Yamamoto Y, Yanagihara K, Mukae H, Kohno S, Izumikawa K.
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Journal Title
Journal of Antimicrobial Chemotherapy
Volume: 72
Issue: 6
Pages: 1709-1713
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Performance evaluation of the Verigene®Clostridium difficile nucleic acid test, an automated multiplex molecular testing system for detection of C. difficile toxin.2017
Author(s)
Kosai K, Iwanaga Y, Akamatsu N, Okada Y, Kaku N, Uno N, Morinaga Y, Hasegawa H, Miyazaki T, Izumikawa K, Mukae H, Yanagihara K.
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Journal Title
J Infect Chemother
Volume: 23
Issue: 10
Pages: 674-677
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A case series of histoplasmosis patients with elevated serum soluble interleukin-2 receptor levels2017
Author(s)
Hirayama T, Takazono T, Iwata K, Senju H, Shimazaki T, Tashiro M, Saijo T, Tanaka T, Nakamura S, Imamura Y, Kojiro M, Miyazaki T, Tsukamoto M, Furumoto A, Morimoto K, Muraosa Y, Matsubara Y, Yanagihara K, Mukae H, Kamei K, Kohno S, Izumikawa K
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Journal Title
J Infect Chemother.
Volume: 23
Issue: 9
Pages: 642-647
DOI
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Peer Reviewed / Open Access
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[Journal Article] Executive summary of Japanese domestic guidelines for management of deep-seated mycosis 2014.2016
Author(s)
Kohno S, Tamura K, Niki Y, Izumikawa K, Oka S, Ogawa K, Kadota J, Kamei K, Kanda Y, Kiuchi T, Shibuya K, Takakura S, Takata T, Takesue Y, Teruya K, Tokimatsu I, Fukuda T, Maesaki S, Makimura K, Mikamo H, Mitsutake K, Miyazaki Y, Mori M, Yasuoka A, Yano K, Yamanaka N, Yoshida M
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Journal Title
NAID
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[Journal Article] Effect of long-term treatment with corticosteroids on skeletal muscle strength, functional exercise capacity and health status in patients with interstitial lung disease2016
Author(s)
Hanada M, Sakamoto N, Ishimatsu Y, Kakugawa T, Obase Y, Kozu R, Senjyu H, Izumikawa K, Mukae H, Kohno S
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Journal Title
Respirology
Volume: 21
Issue: 6
Pages: 1088-1093
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Successful Treatment of <i>Aspergillus</i> Empyema Using Open Window Thoracostomy Salvage Treatment and the Local Administration of an Antifungal Agent2016
Author(s)
Ashizawa N, Nakamura S, Ide S, Tashiro M, Takazono T, Imamura Y, Miyazaki T, Izumikawa K, Yamamoto Y, Yanagihara K, Miyazaki Y, Kohno S
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Journal Title
Internal Medicine
Volume: 55
Issue: 15
Pages: 2093-2099
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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[Journal Article] Premedication with clarithromycin is effective against secondary bacterial pneumonia during influenza virus infection in a pulmonary emphysema mouse model.2016
Author(s)
Harada T, Ishimatsu Y, Hara A, Morita T, Nakashima S, Kakugawa T, Sakamoto N, Kosai Y, Izumikawa K, Yanagihara K, Mukae H, Kohno S
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Journal Title
J Pharmacol Exp Ther
Volume: 358
Issue: 3
Pages: 457-463
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pharmacokinetic parameters of gefitinib predict efficacy and toxicity in patients with advanced non-small cell lung cancer harboring EGFR mutations2016
Author(s)
Mizoguchi K, Nakamura Y, Sano K, Sato S, Ikegami Y, Motoshima K, Takemoto S, Ogawara D, Senju H, Sugasaki N, Ikeda T, Yamaguchi H, Nakatomi K, Fukuda M, Izumikawa K, Mukae H
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Journal Title
Cancer Chemother Pharmacol
Volume: 72
Issue: 2
Pages: 377-382
DOI
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Peer Reviewed / Open Access
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[Journal Article] A mortality prediction rule for non-elderly patients with community-acquired pneumonia.2016
Author(s)
Tashiro M, Fushimi K, Takazono T, Kurihara S, Miyazaki T, Tsukamoto M, Yanagihara K, Mukae H, Tashiro T, Kohno S, Izumikawa K.
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Journal Title
BMC Pulm Med
Volume: 16
Issue: 1
Pages: 39-39
DOI
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[Journal Article] The world first two cases of severe fever with thrombocytopenia. syndrome: An epidemiological study in Nagasaki, Japan2016
Author(s)
Kurihara S, Satoh A, Yu F, Hayasaka D, Shimojima M, Tashiro M, Saijo T, Takazono T, Imamura Y, Miyazaki T, Tsukamoto M, Yanagihara K, Mukae H, Saijo M, Morita K, Kohno S, Izumikawa K
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Journal Title
J Infect Chemother
Volume: 22
Issue: 7
Pages: 461-465
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Toll-like Receptor 4 Agonistic Antibody Promotes Host Defense against Chronic Pseudomonas aeruginosa Lung Infection in Mice.2016
Author(s)
4)Nakamura S, Iwanaga N, Seki M, Fukudome K, Oshima K, Miyazaki T, Izumikawa K, Yanagihara K, Miyazaki Y, Mukae H, Kohno S.
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Journal Title
Infect Immun.
Volume: 84
Issue: 7
Pages: 1986-1993
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata.2016
Author(s)
Nishikawa H, Miyazaki T, Nakayama H, Minematsu A, Yamauchi S, Yamashita K, Takazono T, Shimamura S, Nakamura S, Izumikawa K, Yanagihara K, Kohno S, Mukae H.
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Journal Title
FEMS Yeast Res.
Volume: 16
Issue: 5
Pages: fow054-fow054
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Pulmonary Nocardiosis Caused by <i>Nocardia concava</i> with a Literature Review2016
Author(s)
Hirayama T, Takazono T, Horai Y, Tashiro M, Saijo T, Kosai K, Morinaga Y, Kurihara S, Nakamura S, Imamura Y, Miyazaki T, Tsukamoto M, Izumikawa K, Yanagihara K, Kawakami A, Kohno S
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Journal Title
Internal Medicine
Volume: 55
Issue: 9
Pages: 1213-1217
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
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[Journal Article] Relapsed pulmonary cryptococcosis during tumor necrosis factor α inhibitor treatment2016
Author(s)
Takazono T, Sawai T, Tashiro M, Saijo T, Yamamoto K, Imamura Y, Miyazaki T, Suyama N, Izumikawa K, Kakeya H, Yanagihara K, Mukae H, Kohno S
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Journal Title
Intern Med
Volume: 55
Pages: 2877-2880
NAID
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[Journal Article] Recurrent Streptococcus agalactiae toxic shock syndrome triggered by a tumor necrosis factor-α inhibitor2016
Author(s)
Yoshida M, Takazono T, Tashiro M, Saijo T, Morinaga Y, Yamamoto K, Nakamura S, Imamura Y, Miyazaki T, Sawai T, Nishino T, Izumikawa K, Yanagihara K, Mukae H, Kohno S
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Journal Title
Intern Med
Volume: 55
Pages: 3211-3214
NAID
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Peer Reviewed / Open Access
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[Journal Article] The risk factors for developing of chronic pulmonary aspergillosis in nontuberculous mycobacteria patients and clinical characteristics and outcomes in chronic pulmonary aspergillosis patients coinfected with nontuberculous mycobacteria.2016
Author(s)
Takeda K, Imamura Y, Takazono T, Yoshida M, Ide S, Hirano K, Tashiro M, Saijo T, Kosai K, Morinaga Y, Nakamura S, Kurihara S, Tsukamoto M, Miyazaki T, Tashiro T, Kohno S, Yanagihara K, Izumikawa K.
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Journal Title
Med Mycol.
Volume: 54
Issue: 2
Pages: 120-127
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[Journal Article] 帯状疱疹ウイルスによる急性咽頭炎に対して術前治療を行った後に生体肝移植を施行し良好な経過を得た1例2016
Author(s)
山口 峻, 曽山 明彦, 日高 匡章, 夏田 孔史, 釘山 統太, 原 貴信, 今村 一歩, 岡田 怜美, 大野 慎一郎, 北里 周, 藤田 文彦, 田代 将人, 黒木 保, 泉川公一, 江口 晋
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Journal Title
移植
Volume: 51
Pages: 218-221
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[Journal Article] 当院における血液培養検査推進キャンペーンとその効果2016
Author(s)
塚本千絵, 小佐井康介, 志岐直美, 寺坂陽子, 今村政信, 賀来敬仁, 田代将人, 塚本美鈴, 栗原慎太郎, 泉川公一, 迎 寛, 栁原克紀
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Journal Title
環境感染誌
Volume: 31
Pages: 241-246
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[Book] 今日の処方2017
Author(s)
田代将人、泉川公一
Total Pages
1220
Publisher
南江堂
ISBN
9784524268115
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