研究者詳細 - 宮原　信明

Successful Extracorporeal Life Support for Life-threatening Hypercapnia with Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplantation 査読

Koichi Waseda, Yasushi Tanimoto, Shingo Ichiba, Nobuaki Miyahara, Toshi Murakami, Nobuaki Ochi, Michihisa Terado, Osamu Nagano, Yoshinobu Maeda, Arihiko Kanehiro, Yoshihito Ujike, Mitsune Tanimoto

ACTA MEDICA OKAYAMA 65 ( 6 ) 403 - 406 2011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：OKAYAMA UNIV MED SCHOOL

Bronchiolitis obliterans (BO) is a disease with a poor prognosis, and a key factor that limits long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). We here report a case of a 31-year woman with acute lymphatic leukemia, which was treated by chemotherapy and HSCT, and consequently developed BO 2 years after HSCT. A non-tuberculous mycobacterial infection occurred and showed gradual exacerbation. She started taking anti-mycobacterial drugs, but lost appetite, felt tired and finally lost consciousness one month after beginning medication. Arterial blood gas revealed marked hypercapnia. Using extracorporeal life support (ECLS), the carbon dioxide concentration was reduced and her consciousness recovered. To our knowledge, this is the first case in which ECLS was successfully used for hypercapnia in a patient with BO.

DOI： 10.18926/AMO/47266

Blocking the Leukotriene B4 Receptor 1 Inhibits Late-Phase Airway Responses in Established Disease 査読

Koichi Waseda, Nobuaki Miyahara, Arihiko Kanehiro, Genyo Ikeda, Hikari Koga, Yasuko Fuchimoto, Etsuko Kurimoto, Yasushi Tanimoto, Mikio Kataoka, Mitsune Tanimoto, Erwin W. Gelfand

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 45 ( 4 ) 851 - 857 2011年10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 THORACIC SOC

Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1 (BLT1) have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have been established, has not been defined. We investigated the effects of blocking BLT1 on early-and late-phase development of AHR and airway inflammation in previously sensitized and challenged mice. Female BALB/c mice were sensitized (Days 1 and 14) and challenged (primary, Days 28-30) with ovalbumin. On Day 72, mice were challenged (secondary) with a single OVA aerosol, and the early and late phases of AHR and inflammation were determined. Specific blockade of BLT1 was attained by oral administration of a BLT1 antagonist on Days 70 through 72. Administration of the antagonist inhibited the secondary ovalbumin challenge-induced alterations in airway responses during the late phase but not during the early phase, as demonstrated by decreases in AHR and in bronchoalveolar lavage neutrophilia and eosinophilia 6 and 48 hours after secondary challenge. The latter was associated with decreased levels of KC protein, macrophage inflammatory protein 2, and IL-17 in the airways. These data identify the importance of the LTB4-BLT1 pathway in the development of late-phase, allergen-induced airway responsiveness after secondary airway challenge in mice with established airway disease.

DOI： 10.1165/rcmb.2010-0455OC

Churg-Strauss Syndrome with Necrosis of Toe Tips 査読

Koichi Waseda, Yasushi Tanimoto, Kenjiro Hasegawa, Nobuaki Miyahara, Daisuke Nojima, Genyo Ikeda, Arihiko Kanehiro, Chiharu Okada, Yoshihiro Kimata, Mitsune Tanimoto

ACTA MEDICA OKAYAMA 65 ( 3 ) 215 - 218 2011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

Churg-Strauss syndrome (CSS) is a granulomatous necrotizing vasculitis of unknown etiology associated with bronchial asthma. Despite affecting small to medium-sized vessels, necrosis of the digits due to vasculitis is extremely rare. We report a case of CSS with necrosis of the toe tips. A 37-year-old woman with asthma, who had been diagnosed with CSS 2 years ago, was admitted to our hospital with an exacerbation of CSS. The patient had a high grade fever and complained of abdominal pain and numbness of the lower extremities. Blood examination revealed marked eosinophilia. The fever pattern, abdominal pain and blood eosinophilia showed improvement by combination treatment with prednisolone and cyclophosphamide. However, the color of her right toe tips changed, and necrosis finally resulted despite antithrombotic therapy. Arteriography showed narrowing of the dorsalis pedis artery and of the more peripheral arteries of her right leg. Stump plasty with negative pressure dressing therapy for the toe tips, but not amputation, was done to preserve the leg function. While numbness of the extremities remained, no recurrence of necrosis was seen. Clinicians need to be aware that rare complications of CSS, including necrosis of the digits, can occur.

DOI： 10.18926/AMO/46635

Measurement of early-phase, late-phase, and nonspecific nasal responses in allergic rhinitis mouse by whole body plethysmography. 査読

Miyahara S, Miyahara N, Matsubara S

Nihon yakurigaku zasshi. Folia pharmacologica Japonica 137 ( 3 ) 141 - 145 2011年3月

The relationships between the peak inspiratory flow and the characteristics factors in the asthmatics with inhaled corticosteroid - A multicenter study in Chugoku Shikoku area 査読

Yasushi Obase, Arihiko Kanehiro, Yasushi Tanimoto, Nobuaki Miyahara, Mikio Oka, Ryosuke Eda, Tetsuya Kubota, Akihito Yokoyama, Kiryo Wakabayashi, Hiroyasu Takeyama, Chiharu Okada, Goro Kimura, Ryo Soda, Kiyoshi Takahashi, Mitsune Tanimoto

Japanese Journal of Allergology 60 ( 12 ) 1621 - 1629 2011年

記述言語：日本語掲載種別：研究論文（学術雑誌）

Background: Inhaled corticosteroid (ICS) will be effective if used properly. Inadequate intake may result in insufficiency, such as for elderly asthmatics, in particular, for use of dry powder inhalers. Methods: 312 asthmatics treated with ICS for at least 6 months in the 6 facilities belonging to the Chugoku Shikoku Adult Asthma Research Forum were subject to investigation of the peak inspiratory flow (PIF) measured using In-check® and related factors. Results: Nine (2.8%) patients were considered to have insufficient intake. By multivariate analysis, PIF (L/min) prediction formula was as follows: 79.0 + 0.19*peak expiratory flow (PEF: L/min) + 22.9*FVC (L) - 0.68*onset age (years) + 34.7*gender (male, 1
female, 0) + 16.1*V50/V25, [r∧2 = 0.677, p&lt
0.0001]. Using cluster analysis with Euclidean distance and Ward's method, the PIF without an adaptor was included in the same category as height and PEF, and the PIF with an adaptor was included in the same category as %FVC and %FEV 10. Conclusion: The cases with insufficient PIF are few but present. Adequate device selection and inhalation guidance may be important. The meaning of PIF differs depending on whether or not an adaptor is present. Further investigation of intake is considered necessary. ©2011 Japanese Society of Allergology.

Scopus

Plasticity of Invariant NKT Cell Regulation of Allergic Airway Disease Is Dependent on IFN-gamma Production 査読

Hiroyuki Matsuda, Katsuyuki Takeda, Toshiyuki Koya, Masakazu Okamoto, Yoshiki Shiraishi, Nobuaki Miyahara, Azzeddine Dakhama, Jennifer L. Matsuda, Laurent Gapin, Erwin W. Gelfand

JOURNAL OF IMMUNOLOGY 185 ( 1 ) 253 - 262 2010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 ASSOC IMMUNOLOGISTS

Invariant NKT cells (iNKT cells) play a pivotal role in the development of allergen-induced airway hyperresponsiveness (AHR) and inflammation. However, it is unclear what role they play in the initiation (sensitization) phase as opposed to the effector (challenge) phase. The role of iNKT cells during sensitization was examined by determining the response of mice to intratracheal transfer of OVA-pulsed or OVA-alpha-galactosylceramide (OVA/alpha GalCer)-pulsed bone marrow-derived dendritic cells (BMDCs) prior to allergen challenge. Wild-type (WT) recipients of OVA-BMDCs developed AHR, increased airway eosinophilia, and increased levels of Th2 cytokines in bronchoalveolar lavage fluid, whereas recipients of OVA/alpha GalCer BMDCs failed to do so. In contrast, transfer of these same OVA/alpha GalCer BMDCs into IFN-gamma-deficient (IFN-gamma(-/-)) mice enhanced the development of these lung allergic responses, which was reversed by exogenous IFN-gamma treatment following OVA-BMDC transfer. Further, J alpha 18deficient recipients, which lack iNKT cells, developed the full spectrum of lung allergic responses following reconstitution with highly purified WT liver or spleen iNKT cells and transfer of OVA-BMDCs, whereas reconstituted recipients of OVA/alpha GalCer BMDCs failed to do so. Transfer of iNKT cells from IFN-gamma(-/-) mice restored the development of these responses in J alpha 18-deficient recipients following OVA-BMDC transfer; the responses were enhanced following OVA/alpha GalCer BMDC transfer. iNKT cells from these IFN-gamma(-/-) mice produced higher levels of IL-13 in vitro compared with WT iNKT cells. These data identify IFN-gamma as playing a critical role in dictating the consequences of iNKT cell activation in the initiation phase of the development of AHR and airway inflammation. The Journal of Immunology, 2010, 185: 253-262.

DOI： 10.4049/jimmunol.0902301

Effects of combination therapy with montelukast and carbocysteine in allergen-induced airway hyperresponsiveness and airway inflammation 査読

Takeda K, Shiraishi Y, Matsubara S, Miyahara N, Matsuda H, Okamoto M, Joetham A, Gelfand E.W

British Journal of Pharmacology 160 ( 6 ) 1399 - 1407 2010年7月

Experimental Pulmonary Granuloma Mimicking Sarcoidosis Induced by Propionibacterium acnes in Mice 査読

Kouji Iio, Tomoe Ueno Iio, Yuhei Okui, Hirohisa Ichikawa, Yasushi Tanimoto, Nobuaki Miyahara, Arihiko Kanehiro, Mitsune Tanimoto, Yasunari Nakata, Mikio Kataoka

ACTA MEDICA OKAYAMA 64 ( 2 ) 75 - 83 2010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

Propionibacterium acnes has been implicated as an etiologic agent of sarcoidosis since the isolation of this bacterium from sarcoid lesions. We experimentally produced a murine pulmonary granuloma model using P. acnes with several features that simulate sarcoidosis. Mice were sensitized with heat-killed P. acnes and complete Freund's adjuvant and were subsequently challenged with heat-killed P. acnes at 2-week intervals. P. acnes-challenged mice developed epitheloid cell granulomas in the lungs. These mice showed a pulmonary immune response characterized by an increased number of T-lymphocytes, especially CD4+ cells, and the ratio of CD4+/CD8+ in bronchoalveolar lavage (BAL) fluid also increased. Furthermore, significant elevations in both angiotensin-converting enzyme (ACE) serum levels and antibody titers against P. acnes were observed. Mice sensitized with P. acnes without complete Freund's adjuvant were capable of forming pulmonary granulomas, which appeared to be caused by indigenous P. acnes. The genome of P. acnes was found in the lungs, BAL cells, hilar lymph nodes, liver, and spleen in non-sensitized mice, which were thought to be germ-free. These results suggest that the immune response against indigenous P. acnes may play an important role in the pathogenesis of granuloma formation in a murine model.

DOI： 10.18926/AMO/32852

Diffuse alveolar hemorrhage with chronic thyroiditis in an advanced-age adult 査読

Masanori Fujii, Nobuaki Miyahara, Yasushi Tanimoto, Nagio Takigawa, Masahiro Tabata, Arihiko Kanehiro, Katsuyuki Kiura, Mitsune Tanimoto

Respiratory Medicine CME 3 ( 2 ) 90 - 92 2010年

記述言語：英語掲載種別：研究論文（学術雑誌）

Idiopathic pulmonary hemosiderosis (IPH) is one of the rare causes of diffuse alveolar hemorrhage (DAH), and usually occurs in children. The mechanism underlying this disease development has not been defined. During the acute phase, death due to massive alveolar hemorrhage and subsequent severe respiratory failure with multiple organ failure often occurs. We report a case of IPH which occurred in an advanced-aged adult during following thyroidectomy for chronic thyroiditis. Following surgery this 83-year-old male developed acute onset dyspnea and pulmonary hemorrhage. In a search for underlying causes, no disorders were found and the only finding was the presence of anti-thyroid antibody. Systemic corticosteroid therapy was effective and he fully recovered. To our knowledge, this is the second documentation of IPH in association with chronic thyroiditis. © 2009 Elsevier Ltd.

DOI： 10.1016/j.rmedc.2009.04.006

Scopus

P8-8 血性の気管支肺胞洗浄液所見のために診断が遅れた肺胞蛋白症の1例(感染・びまん性肺疾患,ポスター8,第33回日本呼吸器内視鏡学会学術集会)

谷口暁彦, 谷本安, 能島大輔, 小崎佐恵子, 南大輔, 田中寿明, 高田三郎, 堀田勝幸, 宮原信明, 瀧川奈義夫, 金廣有彦, 田端雅弘, 木浦勝行, 片岡幹男, 谷本光音

気管支学 32 S200 2010年

OR5-2 超音波気管支鏡ガイド下針生検(EBUS-TBNA)有用症例の検討(EBUS-TBNA1,一般口演5,第33回日本呼吸器内視鏡学会学術集会)

南大輔, 瀧川奈義夫, 村上斗司, 谷口暁彦, 小崎佐恵子, 田中寿明, 高田三郎, 市原英基, 堀田勝幸, 宮原信明, 谷本安, 田端雅弘, 金廣有彦, 木浦勝行, 谷本光音

気管支学 32 S137 2010年

P3-2-5 ステロイド薬の減量中に再燃を繰り返す慢性好酸球性肺炎にシクロフォスファミドの併用が有効であった1例(P3-2好酸球性肺炎・過敏性肺炎,一般演題,第22回日本アレルギー学会春季臨床大会)

能島大輔, 谷本安, 栗本悦子, 早稲田公一, 池田元洋, 古賀光, 宮原信明, 金廣有彦, 片岡幹男, 谷本光音

アレルギー 59 ( 3 ) 413 - 413 2010年

27.超音波気管支鏡ガイド下針生検(EBUS-TBNA)により診断に至ったLambert-Eaton症候群合併肺小細胞癌の1例(第18回日本呼吸器内視鏡学会中国四国支部会)

谷口暁彦, 瀧川奈義夫, 木浦勝行, 村上斗司, 栗本悦子, 高田三郎, 小崎佐恵子, 南大輔, 田中寿明, 市原英基, 堀田勝幸, 田端雅弘, 宮原信明, 谷本安, 金廣有彦, 谷本光音

気管支学 32 ( 2 ) 201 - 202 2010年

29.超音波気管支鏡ガイド下針生検(EBUS-TBNA)で診断したEGFR遺伝子変異陽性の高齢者肺癌(第18回日本呼吸器内視鏡学会中国四国支部会)

南大輔, 堀田勝幸, 瀧川奈義夫, 村上斗司, 谷口暁彦, 小崎佐恵子, 田中寿明, 高田三郎, 市原英基, 宮原信明, 谷本安, 田端雅弘, 金廣有彦, 木浦勝行, 谷本光音

気管支学 32 ( 2 ) 202 - 202 2010年

MW8-6 アレルギー性気道反応における経口免疫寛容の効果(MW8 動物モデルを用いた喘息病態と治療法開発,ミニワークショップ,第60回日本アレルギー学会秋季学術大会)

宮原信明, 武田勝行, 宮原聡子, 早稲田公一, 栗本悦子, 池田元洋, 古賀光, 谷口暁彦, 能島大輔, 渕本康子, 谷本安, 金廣有彦, 片岡幹男, Erwin Gelfand, 谷本光音

アレルギー 59 ( 9 ) 1353 - 1353 2010年

MW15-5 ヒト好塩基球の抗原提示能に関する検討 : IL-3で活性化された好塩基球はHLA-DRを発現する(MW15 マスト細胞/好塩基球,ミニワークショップ,第60回日本アレルギー学会秋季学術大会)

能島大輔, 谷本安, 栗本悦子, 早稲田公一, 宮原信明, 金廣有彦, 岸本卓巳, 片岡幹男, 高橋清, 谷本光音

アレルギー 59 ( 9 ) 1363 - 1363 2010年

Differential Effects of Dendritic Cell Transfer on Airway Hyperresponsiveness and Inflammation 査読

Toshiyuki Koya, Hiroyuki Matsuda, Shigeki Matsubara, Nobuaki Miyahara, Azzeddine Dakhama, Katsuyuki Takeda, Erwin W. Gelfand

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 41 ( 3 ) 271 - 280 2009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：AMER THORACIC SOC

Dendritic cells (DCs) are considered to be the most efficient antigen-presenting cells. Intratracheal administration of allergen-pulsed bone marrow-derived dendritic cells (BMDCs) before allergen challenge induces airway hyperresponsiveness (AHR) and inflammation. Ovalbumin (OVA)-pulsed BMDCs from wild-type (WT) mice were transferred into naive WT, CD4(-/-), CD8(-/-), or IL-13(-/-) mice. Two days (short protocol) or 10 days (long protocol) after BMDC transfer, mice were challenged with 1% OVA for 3 days and assayed 2 days later. Transfer of OVA-primed BMDCs into BALB/c or C57BL/6 mice elicited AHR in both protocols. Airway eosinophilia, Th2 cytokines, or goblet cell metaplasia were increased in the long but not short protocol. Lung T cells from both protocols produced Th2 cytokines in response to OVA in vitro. Carboxyfluorescein diacetate succinimidylester-labeled BMDCs were observed in bronchoalveolar lavage (BAL) fluid and lung parenchyma at early time points, and were detected in draining lymph nodes 48 hours after transfer. CD8(-/-) mice developed AHR comparable to WT mice in the short protocol, but decreased levels of AHR, airway eosinophilia, Th2 cytokines in BAL fluid, and goblet cell metaplasia compared with WT mice in the long protocol. CD4(-/-) or IL-13(-/-) mice did not develop AHR or airway inflammation in either protocol. These data suggest that allergen-pulsed BMDCs initiate development of AHR that is dependent initially on CD4(+) T cells, and at later time periods on CD8+ T cells and IL-13. Thus, the timing of allergen challenge after transfer of allergen-pulsed BMDC affects the development of AHR and airway inflammation.

DOI： 10.1165/rcmb.2008-0256OC