116 results on '"Shin Ohta"'
Search Results
2. Comprehensive Gene Expression Signature Using RNA-Seq in Airways of Mouse Model of Severe Asthma with Fungal Sensitization
- Author
-
Hironori Sagara, Yoshitaka Uchida, Tomoki Uno, Shintaro Suzuki, Yoshito Miyata, Akihiko Tanaka, Kaho Akimoto, Shin Ohta, Hitoshi Ikeda, Tetsuya Homma, Mayumi Yamamoto, Kuniaki Hirai, Hideki Inoue, Yosuke Fukuda, Tomoko Kawahara, and Hiroki Sato
- Subjects
Receptor complex ,Immunology ,Inflammation ,Respiratory Mucosa ,Biology ,Mice ,Downregulation and upregulation ,Gene expression ,medicine ,Animals ,Immunology and Allergy ,RNA-Seq ,medicine.diagnostic_test ,Gene Expression Profiling ,Fungi ,Alternaria ,Computational Biology ,General Medicine ,Allergens ,Immunohistochemistry ,Mucus ,Asthma ,Eosinophils ,Disease Models, Animal ,Gene Ontology ,Bronchoalveolar lavage ,Gene Expression Regulation ,biology.protein ,Airway Remodeling ,Respiratory epithelium ,Female ,Immunization ,medicine.symptom ,Antibody ,Transcriptome ,Bronchoalveolar Lavage Fluid - Abstract
Introduction: Inhalation of fungal allergens induces airway epithelial damage following airway inflammation and excessive mucus secretion, which can lead to severe asthma with fungal sensitization (SAFS). Comprehensive gene expression analysis in Alternaria-exposed mouse airways, a model of SAFS, has not been conducted. Methods: BALB/c mice received intranasal administration of Alternaria extract or phosphate-buffered saline twice a week for 6 weeks. Lung sections and bronchoalveolar lavage fluid were obtained to assess airway inflammation. RNA-Seq in the central airway was performed, and gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted for pathway analyses. An in vitro experiment using human airway epithelial cell 16HBE14o- was performed to validate the RNA-Seq findings. Results: Eosinophilic airway inflammation with mucus overproduction and airway remodeling was observed in mice exposed to Alternaria. RNA-Seq analysis revealed 403 upregulated and 108 downregulated genes in airways of Alternaria-exposed mice. In GO analysis, the functions of immunoglobulin (Ig) receptor binding, Ig production, inflammatory response, and T-cell activation were upregulated, while those of keratinization and defense response to other organisms were downregulated. GSEA revealed positive enrichment in T-cell receptor complex, immunological synapse, antigen binding, mast cell activation, and Ig receptor binding, and negative enrichment in keratinization and cornification in Alternaria-exposed mice relative to control. Alternaria exposure to 16HBE14o- cells validated the downregulation of epithelial keratinization-related genes, including SPRR1A, SPRR1B, and KRT6B. Conclusion: RNA-Seq analysis showed that Alternaria exposure induced inflammatory response and impaired defense mechanisms in mice airway epithelium, which might be therapeutic targets for SAFS.
- Published
- 2021
3. Author response for 'Clinical significance of pre‐diabetes, undiagnosed diabetes, and diagnosed diabetes on clinical outcomes in COVID‐19: Integrative analysis from the Japan COVID‐19 Task Force'
- Author
-
null Takahiro Fukushima, null Shotaro Chubachi, null Ho Namkoong, null Takanori Asakura, null Hiromu Tanaka, null Ho Lee, null Shuhei Azekawa, null Yukinori Okada, null Ryuji Koike, null Akinori Kimura, null Seiya Imoto, null Satoru Miyano, null Seishi Ogawa, null Takanori Kanai, null Koichi Fukunaga, null Shiro Otake, null Kensuke Nakagawara, null Atsuho Morita, null Mayuko Watase, null Kaori Sakurai, null Takuya Kusumoto, null Katsunori Masaki, null Hiroki Kabata, null Hirofumi Kamata, null Makoto Ishii, null Naoki Hasegawa, null Kazuhisa Takahashi, null Norihiro Harada, null Toshio Naito, null Makoto Hiki, null Yasushi Matsushita, null Haruhi Takagi, null Ryousuke Aoki, null Ai Nakamura, null Sonoko Harada, null Hitoshi Sasano, null Shinnosuke Ikemura, null Satoshi Okamori, null Hideki Terai, null Junichi Sasaki, null Hiroshi Morisaki, null Yoshifumi Uwamino, null Kosaku Nanki, null Yohei Mikami, null Sho Uchida, null Shunsuke Uno, null Rino Ishihara, null Yuta Matsubara, null Tomoyasu Nishimura, null Takunori Ogawa, null Toshiro Sato, null Tetsuya Ueda, null Masanori Azuma, null Ryuichi Saito, null Toshikatsu Sado, null Yoshimune Miyazaki, null Ryuichi Sato, null Yuki Haruta, null Tadao Nagasaki, null Yoshinori Yasui, null Yoshinori Hasegawa, null Soichiro Ueda, null Ai Tada, null Masayoshi Miyawaki, null Masaomi Yamamoto, null Eriko Yoshida, null Reina Hayashi, null Tomoki Nagasaka, null Sawako Arai, null Yutaro Kaneko, null Kana Sasaki, null Takashi Ishiguro, null Taisuke Isono, null Shun Shibata, null Yuma Matsui, null Chiaki Hosoda, null Kenji Takano, null Takashi Nishida, null Yoichi Kobayashi, null Yotaro Takaku, null Noboru Takayanagi, null Etsuko Tagaya, null Masatoshi Kawana, null Ken Arimura, null Yasushi Nakamori, null Kazuhisa Yoshiya, null Fukuki Saito, null Tomoyuki Yoshihara, null Daiki Wada, null Hiromu Iwamura, null Syuji Kanayama, null Shuhei Maruyama, null Takanori Hasegawa, null Kunihiko Takahashi, null Tatsuhiko Anzai, null Satoshi Ito, null Akifumi Endo, null Yuji Uchimura, null Yasunari Miyazaki, null Takayuki Honda, null Tomoya Tateishi, null Shuji Tohda, null Naoya Ichimura, null Kazunari Sonobe, null Chihiro Tani Sassa, null Jun Nakajima, null Masumi Ai, null Takashi Yoshiyama, null Ken Ohta, null Hiroyuki Kokuto, null Hideo Ogata, null Yoshiaki Tanaka, null Kenichi Arakawa, null Masafumi Shimoda, null Takeshi Osawa, null Yasushi Nakano, null Yukiko Nakajima, null Ryusuke Anan, null Ryosuke Arai, null Yuko Kurihara, null Yuko Harada, null Kazumi Nishio, null Yoshikazu Mutoh, null Tomonori Sato, null Reoto Takei, null Satoshi Hagimoto, null Yoichiro Noguchi, null Yasuhiko Yamano, null Hajime Sasano, null Sho Ota, null Yusuke Suzuki, null Sohei Nakayama, null Keita Masuzawa, null Tomomi Takano, null Kazuhiko Katayama, null Koji Murakami, null Mitsuhiro Yamada, null Hisatoshi Sugiura, null Hirohito Sano, null Shuichiro Matsumoto, null Nozomu Kimura, null Yoshinao Ono, null Hiroaki Baba, null Rie Baba, null Daisuke Arai, null Takayuki Ogura, null Hidenori Takahashi, null Shigehiro Hagiwara, null Genta Nagao, null Shunichiro Konishi, null Ichiro Nakachi, null Hiroki Tateno, null Isano Hase, null Shuichi Yoshida, null Shoji Suzuki, null Miki Kawada, null Hirohisa Horinouchi, null Fumitake Saito, null Keiko Mitamura, null Masao Hagihara, null Junichi Ochi, null Tomoyuki Uchida, null Ryuya Edahiro, null Yuya Shirai, null Kyuto Sonehara, null Tatsuhiko Naito, null Kenichi Yamamoto, null Shinichi Namba, null Ken Suzuki, null Takayuki Shiroyama, null Yuichi Maeda, null Takuro Nii, null Yoshimi Noda, null Takayuki Niitsu, null Yuichi Adachi, null Takatoshi Enomoto, null Saori Amiya, null Reina Hara, null Toshihiro Kishikawa, null Shuhei Yamada, null Shuhei Kawabata, null Noriyuki Kijima, null Masatoshi Takagaki, null Noa Sasa, null Yuya Ueno, null Motoyuki Suzuki, null Norihiko Takemoto, null Hirotaka Eguchi, null Takahito Fukusumi, null Takao Imai, null Munehisa Fukushima, null Haruhiko Kishima, null Hidenori Inohara, null Kazunori Tomono, null Kazuto Kato, null Haruhiko Hirata, null Yoshito Takeda, null Atsushi Kumanogoh, null Naoki Miyazawa, null Yasuhiro Kimura, null Reiko Sado, null Hideyasu Sugimoto, null Akane Kamiya, null Naota Kuwahara, null Akiko Fujiwara, null Tomohiro Matsunaga, null Yoko Sato, null Takenori Okada, null Takashi Inoue, null Toshiyuki Hirano, null Keigo Kobayashi, null Hatsuyo Takaoka, null Koichi Nishi, null Masaru Nishitsuji, null Mayuko Tani, null Junya Suzuki, null Hiroki Nakatsumi, null Hidefumi Koh, null Tadashi Manabe, null Yohei Funatsu, null Fumimaro Ito, null Takahiro Fukui, null Keisuke Shinozuka, null Sumiko Kohashi, null Masatoshi Miyazaki, null Tomohisa Shoko, null Mitsuaki Kojima, null Tomohiro Adachi, null Motonao Ishikawa, null Kenichiro Takahashi, null Kazuyoshi Watanabe, null Yoshihiro Hirai, null Hidetoshi Kawashima, null Atsuya Narita, null Kazuki Niwa, null Yoshiyuki Sekikawa, null Hisako Sageshima, null Yoshihiko Nakamura, null Kota Hoshino, null Junichi Maruyama, null Hiroyasu Ishikura, null Tohru Takata, null Takashi Ogura, null Hideya Kitamura, null Eri Hagiwara, null Kota Murohashi, null Hiroko Okabayashi, null Takao Mochimaru, null Shigenari Nukaga, null Ryosuke Satomi Yoshitaka Oyamada, null Nobuaki Mori, null Tomoya Baba, null Yasutaka Fukui, null Mitsuru Odate, null Shuko Mashimo, null Yasushi Makino, null Kazuma Yagi, null Mizuha Hashiguchi, null Junko Kagyo, null Tetsuya Shiomi, null Kodai Kawamura, null Kazuya Ichikado, null Kenta Nishiyama, null Hiroyuki Muranaka, null Kazunori Nakamura, null Satoshi Fuke, null Hiroshi Saito, null Tomoya Tsuchida, null Shigeki Fujitani, null Mumon Takita, null Daiki Morikawa, null Toru Yoshida, null Takehiro Izumo, null Minoru Inomata, null Naoyuki Kuse, null Nobuyasu Awano, null Mari Tone, null Akihiro Ito, null Toshio Odani, null Masaru Amishima, null Takeshi Hattori, null Yasuo Shichinohe, null Takashi Kagaya, null Toshiyuki Kita, null Kazuhide Ohta, null Satoru Sakagami, null Kiyoshi Koshida, null Morio Nakamura, null Koutaro Yokote, null Taka‐Aki Nakada, null Ryuzo Abe, null Taku Oshima, null Tadanaga Shimada, null Kentaro Hayashi, null Tetsuo Shimizu, null Yutaka Kozu, null Hisato Hiranuma, null Yasuhiro Gon, null Namiki Izumi, null Kaoru Nagata, null Ken Ueda, null Reiko Taki, null Satoko Hanada, null Naozumi Hashimoto, null Keiko Wakahara, null Koji Sakamoto, null Norihito Omote, null Akira Ando, null Yu Kusaka, null Takehiko Ohba, null Susumu Isogai, null Aki Ogawa, null Takuya Inoue, null Nobuhiro Kodama, null Yasunari Kaneyama, null Shunsuke Maeda, null Takashige Kuraki, null Takemasa Matsumoto, null Masahiro Harada, null Takeshi Takahashi, null Hiroshi Ono, null Toshihiro Sakurai, null Takayuki Shibusawa, null Yusuke Kawamura, null Akiyoshi Nakayama, null Hirotaka Matsuo, null Yoshifumi Kimizuka, null Akihiko Kawana, null Tomoya Sano, null Chie Watanabe, null Ryohei Suematsu, null Makoto Masuda, null Aya Wakabayashi, null Hiroki Watanabe, null Suguru Ueda, null Masanori Nishikawa Ayumi Yoshifuji, null Kazuto Ito, null Saeko Takahashi, null Kota Ishioka, null Yusuke Chihara, null Mayumi Takeuchi, null Keisuke Onoi, null Jun Shinozuka, null Atsushi Sueyoshi, null Yoji Nagasaki, null Masaki Okamoto, null Sayoko Ishihara, null Masatoshi Shimo, null Yoshihisa Tokunaga, null Masafumi Watanabe, null Sumito Inoue, null Akira Igarashi, null Masamichi Sato, null Nobuyuki Hizawa, null Yoshiaki Inoue, null Shigeru Chiba, null Kunihiro Yamagata, null Yuji Hiramatsu, null Hirayasu Kai, null Satoru Fukuyama, null Yoshihiro Eriguchi, null Akiko Yonekawa, null Keiko Kano, null Koichiro Matsumoto, null Kensuke Kanaoka, null Shoichi Ihara, null Kiyoshi Komuta, null Koichiro Asano, null Tsuyoshi Oguma, null Yoko Ito, null Satoru Hashimoto, null Masaki Yamasaki, null Yu Kasamatsu, null Yuko Komase, null Naoya Hida, null Takahiro Tsuburai, null Baku Oyama, null Yuichiro Kitagawa, null Tetsuya Fukuta, null Takahito Miyake, null Shozo Yoshida, null Shinji Ogura, null Minoru Takada, null Hidenori Kanda, null Shinji Abe, null Yuta Kono, null Yuki Togashi, null Hiroyuki Takoi, null Ryota Kikuchi, null Shinichi Ogawa, null Tomouki Ogata, null Shoichiro Ishihara, null Arihiko Kanehiro, null Shinji Ozaki, null Yasuko Fuchimoto, null Sae Wada, null Nobukazu Fujimoto, null Kei Nishiyama, null Mariko Terashima, null Satoru Beppu, null Kosuke Yoshida, null Osamu Narumoto, null Hideaki Nagai, null Nobuharu Ooshima, null Mitsuru Motegi, null Akira Umeda, null Kazuya Miyagawa, null Hisato Shimada, null Mayu Endo, null Yoshiyuki Ohira, null Hironori Sagara, null Akihiko Tanaka, null Shin Ohta, null Tomoyuki Kimura, null Yoko Shibata, null Yoshinori Tanino, null Takefumi Nikaido, null Hiroyuki Minemura, null Yuki Sato, null Yuichiro Yamada, null Takuya Hashino, null Masato Shinoki, null Hajime Iwagoe, null Hiroshi Takahashi, null Kazuhiko Fujii, null Hiroto Kishi, null Tomoo Ishii, null Masayuki Kanai, null Tomonori Imamura, null Tatsuya Yamashita, null Masakiyo Yatomi, null Toshitaka Maeno, null Shinichi Hayashi, null Mai Takahashi, null Mizuki Kuramochi, null Isamu Kamimaki, null Yoshiteru Tominaga, null Mitsuyoshi Utsugi, null Akihiro Ono, null Toru Tanaka, null Takeru Kashiwada, null Kazue Fujita, null Yoshinobu Saito, null Masahiro Seike, null Masahiro Kanai, null Ryunosuke Saiki, null Takayoshi Hyugaji, null Eigo Shimizu, null Kotoe Katayama, null Satoru Miyawaki, null Meiko Takahashi, null Fumihiko Matsuda, null Yosuke Omae, null Yasuhito Nannya, null Takafumi Ueno, null Yuko Kitagawa, null Katsushi Tokunaga, and null The Japan COVID‐19 Task Force
- Published
- 2022
4. Fetal Lung Cells Transfer Improves Emphysematous Change in a Mouse Model of Neutrophil Elastase-Induced Lung Emphysema
- Author
-
Shin Ohta, Akihiko Tanaka, Tomoko Okazaki, Hatsuko Mikuni, Tomoki Uno, Yoshitaka Uchida, Tomoyuki Kimura, Yosuke Fukuda, Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Hideki Inoue, Tetsuya Homma, Mayumi Yamamoto, Shintaro Suzuki, and Hironori Sagara
- Subjects
Microbiology (medical) ,General Medicine ,Molecular Biology ,Microbiology - Abstract
Recently, several studies for lung regeneration have been reported. However, regenerating the lung tissue by the transfer of any cells directly to the lung has been hardly successful. The aim of this study was to evaluate the effect of fetal lung cells (FLCs) in a mouse model of lung emphysema. C57BL/6 mice were stimulated with neutrophil elastase (NE) intra-tracheally (i.t.) to generate lung emphysema. To collect fetal lung cells, C57BL/6-Tg (CAG-EGFP) mice were bred for 14 days. Before delivery, the bred mice were euthanized, and fetal lungs were harvested from the fetal mice and the cells were collected. The FLCs were transferred i.t. 24 h after the NE instillation. Four weeks after the NE instillation, mice were euthanized, and the samples were collected. The mean linear intercept (MLI) was significantly prolonged in the NE instillation group compared to the control group. However, in the FLCs transfer group stimulated with NE, the MLI became shorter than the NE-stimulated group without an FLCs transfer. This result shows that an FLCs transfer inhibited the progression of lung emphysema. Additionally, motility of the mice was also improved by the FLCs transfer. These results indicate that transfer of the FLCs, which were presumed to be progenitor cells for lung tissue, may improve the emphysematous change.
- Published
- 2022
5. Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with chronic obstructive pulmonary disease
- Author
-
Yoshito Miyata, Shintaro Suzuki, Kaho Akimoto, Yuiko Goto, Tetsuya Homma, Hideki Inoue, Kuniaki Hirai, Akihiko Tanaka, Uchida Yoshitaka, Tomoki Uno, Shin Ohta, and Hironori Sagara
- Subjects
Male ,0301 basic medicine ,Sarcopenia ,medicine.medical_specialty ,Exacerbation ,Pulmonary disease ,030209 endocrinology & metabolism ,Critical Care and Intensive Care Medicine ,Severity of Illness Index ,Gastroenterology ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,In patient ,Prospective Studies ,Cystatin C ,Aged ,Aged, 80 and over ,Creatinine ,COPD ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Hand Strength ,biology ,Surrogate endpoint ,business.industry ,Reproducibility of Results ,medicine.disease ,chemistry ,biology.protein ,business ,Biomarkers - Abstract
Sarcopenia is common in patients with chronic obstructive pulmonary disease (COPD). Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with COPD. Thus, the purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and clinical factors.In this prospective observational study, we enrolled 234 male outpatients with COPD. We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers and prospectively investigated the relationship of Cr/CysC ratio with the annual exacerbation rate.Serum Cr/CysC was significantly correlated with handgrip strength (r = 0.53, P 0.01) and muscle mass (r = 0.44, P 0.01). The area under the curve for sarcopenia was significantly larger for serum Cr/CysC ratio than for other biomarkers (Cr/CysC: 0.87, CysC: 0.63, Cr: 0.61, albumin: 0.57). Multivariate analysis showed no significant difference in the frequency of acute exacerbations between patients in the low- and high-Cr/CysC group, defined by the cutoff value 0.71; however, the frequency of severe acute exacerbations was significantly higher in the low-Cr/CysC group.Serum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with COPD. Our study shows that patients with Cr/CysC below 0.71 have poor physical clinical factors and are at high risk of severe acute COPD exacerbations.
- Published
- 2021
6. Interleukin-34 induces pulmonary inflammation in a murine model of lipopolysaccharide-induced acute lung injury
- Author
-
Takaya Ebato, Shin Ohta, Munehiro Yamaguchi, Hatsuko Mikuni, Hitoshi Ikeda, Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Hideki Inoue, Tetsuya Homma, Mayumi Yamamoto, Shintaro Suzuki, Akihiko Tanaka, and Hironori Sagara
- Published
- 2021
7. Usefulness of Ninjin'yoeito for Chronic Obstructive Pulmonary Disease Patients with Frailty
- Author
-
Kaho Akimoto, Sojiro Kusumoto, Ayaka Kashima, Shin Ohta, Tomohiro Matsunaga, Hiromitsu Suganuma, Shintaro Suzuki, Kuniaki Hirai, Akihiko Tanaka, Takaya Ebato, Hiroki Sato, Shigenori Yamamoto, Yoshito Miyata, Hironori Sagara, Tetsuya Homma, and Hideki Inoue
- Subjects
Male ,medicine.medical_specialty ,Pulmonary disease ,Anxiety ,Severity of Illness Index ,Poor quality ,Pulmonary Disease, Chronic Obstructive ,Japan ,Internal medicine ,Risk of mortality ,Humans ,Medicine ,Prospective Studies ,Fatigue ,Aged ,COPD ,Frailty ,business.industry ,Middle Aged ,medicine.disease ,Intervention studies ,Treatment Outcome ,Mood ,Complementary and alternative medicine ,Quality of Life ,Female ,business ,Drugs, Chinese Herbal - Abstract
Objectives: Frail patients with chronic obstructive pulmonary disease (COPD) have a higher risk of mortality, mood disorder, and poor quality of life (QOL). There are few intervention studies in fr...
- Published
- 2020
8. The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma
- Author
-
Yoshio Watanabe, Hiromitsu Suganuma, Megumi Jinno, Akihiko Tanaka, Yoshito Miyata, Kuniaki Hirai, Haruna Sato, Ayaka Kashima, Hitomi Ida, Shin Ohta, Mayumi Yamamoto, Tomoyuki Kimura, Tetsuya Homma, Hironori Sagara, Shintaro Suzuki, and Tomoki Uno
- Subjects
Ovalbumin ,Bronchoconstriction ,medicine.medical_treatment ,Immunology ,Mice ,Transforming Growth Factor beta ,Administration, Inhalation ,medicine ,Animals ,Humans ,Immunology and Allergy ,Lung ,Methacholine Chloride ,Asthma ,Mice, Inbred BALB C ,Goblet cell ,Inhalation ,medicine.diagnostic_test ,business.industry ,Macrophages ,General Medicine ,Allergens ,respiratory system ,medicine.disease ,respiratory tract diseases ,Eosinophils ,Disease Models, Animal ,medicine.anatomical_structure ,Bronchoalveolar lavage ,Cytokine ,Female ,Methacholine ,medicine.symptom ,business ,medicine.drug - Abstract
Introduction: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. Objective: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. Methods: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. Results: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-β in the lung. This result indicates that the production of TGF-β is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. Conclusions: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.
- Published
- 2020
9. The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- Author
-
Qingbo S. Wang, Ryuya Edahiro, Ho Namkoong, Takanori Hasegawa, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Ho Lee, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Masahiro Kanai, Tatsuhiko Naito, Noah Sasa, Kenichi Yamamoto, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Masako Ichikawa, Ai Nakamura, Sonoko Harada, Yuuki Sandhu, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashri Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Takayuki Shiroyama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Kazunori Tomono, Kazuto Kato, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-o, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, and Yukinori Okada
- Subjects
Multidisciplinary ,Membrane Glycoproteins ,Quantitative Trait Loci ,General Physics and Astronomy ,COVID-19 ,General Chemistry ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Japan ,Viral infection ,Humans ,Lectins, C-Type ,Gene expression ,Receptors, Immunologic ,Transcriptomics ,Genome-Wide Association Study - Abstract
Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., 「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.
- Published
- 2021
10. β2‐adrenoceptor agonist inhalation induced paroxysmal atrial fibrillation and tachycardia in a patient with severe bronchial asthma
- Author
-
Kenji Momo, Tadanori Sasaki, Hironori Sagara, Shigenori Yamamoto, Haruki Funakoshi, Tomoki Uno, Takaya Ebato, Shin Ohta, and Keinosuke Okazaki
- Subjects
Pharmacology ,Tachycardia ,medicine.medical_specialty ,Inhalation ,business.industry ,Paroxysmal atrial fibrillation ,Adrenoceptor agonist ,medicine.disease ,Internal medicine ,Cardiology ,medicine ,Pharmacology (medical) ,medicine.symptom ,business ,Asthma - Published
- 2021
11. Serum cystatin C and CRP are early predictive biomarkers for emergence of hypoxia in COVID-19
- Author
-
Yoshito Miyata, Hideki Inoue, Kuniaki Hirai, Fumihiro Ishikawa, Shin Ohta, Haruna Sato, Kaoru Mochizuki, Takaya Ebato, Hatsuko Mikuni, Tomoyuki Kimura, Yosuke Fukuda, Yasunari Kishino, Tetsuya Homma, Hideto Oyamada, Sojiro Kusumoto, Mayumi Yamamoto, Shintaro Suzuki, Yuko Udaka, Akihiko Tanaka, Keiko Ishino, Yuji Kiuchi, and Hironori Sagara
- Subjects
C-Reactive Protein ,Predictive Value of Tests ,Humans ,COVID-19 ,General Medicine ,Cystatin C ,Biomarkers ,Retrospective Studies - Abstract
In Japan, during the coronavirus disease 2019 (COVID-19) pandemic, patients with non-hypoxia are recommended to recuperate at home or in pre-hospital facilities. However, it was observed that unexpected hypoxia may occur and become severe subsequently in patients whose symptoms were initially expected to improve naturally. The aim of this study is to validate biomarkers that can predict at an early stage the emergence of hypoxia in COVID-19 patients without hypoxia.We retrospectively enrolled 193 patients with COVID-19, excluding patients with hypoxia and severe disease from the onset. Participants were classified into two groups according to the emergence of hypoxia during the clinical course, and the laboratory data were compared to identify biomarkers that could predict early the emergence of hypoxia.The areas under the curve for serum cystatin C (CysC) and C-reactive protein (CRP) levels for the emergence of hypoxia during the clinical course were higher than those for other biomarkers (CysC, 0.84 and CRP, 0.83). Multivariate analysis showed that high serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course.Elevated serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course in COVID-19 patients without hypoxia. These findings may help determine the need for hospitalization in initially non-hypoxic COVID-19 patients.
- Published
- 2021
12. Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan
- Author
-
Shuichi Yoshida, Yoshihiro Hirai, Hiroshi Takahashi, Yoshiyuki Sekikawa, Saeko Takahashi, Yoshitaka Oyamada, Shunsuke Uno, Koutaro Yokote, Kunihiko Takahashi, Shigenari Nukaga, Yoshinao Ono, Shoichiro Ishihara, Nozomu Kimura, Tomohiro Adachi, Shigeki Fujitani, Eri Hagiwara, Motoyuki Suzuki, Tomouki Ogata, Namiki Izumi, Shinji Abe, Etsuko Tagaya, Yoshinori Hasegawa, Yoshimune Miyazaki, Junichi Sasaki, Yoshinori Tanino, Seishi Ogawa, Yuki Togashi, Satoshi Fuke, Yoshiaki Inoue, Hideo Ogata, Masaomi Yamamoto, Hiroshi Saito, Jun Shinozuka, Sho Uchida, Masayoshi Miyawaki, Atsushi Kumanogoh, Koichiro Matsumoto, Yuko Kitagawa, Mayu Endo, Mitsuru Odate, Hiroki Tateno, Fumitake Saito, Mizuki Kuramochi, Shoji Suzuki, Koji Murakami, Kenichi Arakawa, Shozo Yoshida, Hitoshi Sasano, Keigo Kobayashi, Takuro Nii, Takashi Ishiguro, Ryuichi Saito, Yohei Mikami, Takashi Inoue, Haruhiko Kishima, Daisuke Arai, Takao Mochimaru, Minoru Takada, Yuya Ueno, Takehiro Izumo, Reina Hara, Nobuyuki Hizawa, Atsuho Morita, Takanori Hasegawa, Masahiro Seike, Hisako Sageshima, Takeshi Hattori, Shinichi Namba, Shuko Mashimo, Tomoya Tsuchida, Hiromu Tanaka, Naoki Miyazawa, Masatoshi Kawana, Shunichiro Konishi, Takatoshi Enomoto, Takuya Hashino, Hiroki Watanabe, Kentaro Hayashi, Sumito Inoue, Satoshi Hagimoto, Toru Yoshida, Akiko Fujiwara, Masaki Okamoto, Hiroki Kabata, Shuji Tohda, Baku Oyama, Norihiko Takemoto, Nobuyasu Awano, Makoto Hiki, Yasutaka Fukui, Takahiro Fukui, Keisuke Onoi, Yuichiro Yamada, Takayuki Shiroyama, Mayuko Tani, Hiroyuki Muranaka, Kazuhide Ohta, Yoshifumi Kimizuka, Hajime Iwagoe, Yasuko Fuchimo, Hiroki Nakatsumi, Hiroyuki Minemura, Hisatoshi Sugiura, Haruhi Takagi, Hiroyuki Kokuto, Yasuhiro Kimura, Masatoshi Takagaki, Yuki Sato, Masao Hagihara, Junko Kagyo, Yusuke Kawamura, Sayoko Ishihara, Akinori Kimura, Aki Ogawa, Hironori Sagara, Noa Sasa, Masahiro Kanai, Isano Hase, Takenori Okada, Akiyoshi Nakayama, Osamu Narumoto, Norihito Omote, Kazunori Tomono, Toshiro Sato, Hatsuyo Takaoka, Mayumi Takeuchi, Keiko Kan-o, Satoshi Okamori, Yukinori Okada, Yoshito Takeda, Kazuto Ito, Tatsuhiko Naito, Reina Hayashi, Toshikatsu Sado, Kazuya Ichikado, Yasushi Matsushita, Nobuaki Mori, Takashi Nishida, Toshitaka Maeno, Tomomi Takano, Soichiro Ueda, Tomoyasu Nishimura, Masaru Nishitsuji, Ryusuke Anan, Arihiko Kanehiro, Akira Umeda, Syuji Kanayama, Yosuke Omae, Tomoki Nagasaka, Koichi Nishi, Yoshiyuki Ohira, Fumimaro Ito, Toru Tanaka, Kenichiro Takahashi, Hidenori Kanda, Hidenori Inohara, Kaoru Nagata, Kei Nishiyama, Masafumi Watanabe, Katsunori Masaki, Ryuzo Abe, Hirofumi Kamata, Masahiro Harada, Chihiro Tani Sassa, Tomoya Sano, Shoichi Ihara, Tadashi Manabe, Takafumi Ueno, Takahito Fukusumi, Meiko Takahashi, Kyuto Sonehara, Kana Sasaki, Hiroyuki Takoi, Chie Watanabe, Takahiro Tsuburai, Tomonori Sato, Yoichi Kobayashi, Kazuhisa Takahashi, Yasushi Nakano, Kenichi Yamamoto, Takayoshi Hyugaji, Hirohito Sano, Ho Namkoong, Atsushi Sueyoshi, Naoya Ichimura, Yoshiteru Tominaga, Masaru Amishima, Ken Suzuki, Ken Ohta, Shigehiro Hagiwara, Masayuki Kanai, Kota Hoshino, Shuhei Kawabata, Mitsuhiro Yamada, Toshio Naito, Akihiro Ono, Yotaro Takaku, Yoko Sato, Satoru Miyano, Junichi Ochi, Yoshikazu Mutoh, Hiroaki Baba, Yoko Shibata, Tatsuya Yamashita, Yoko Ito, Hiromu Iwamura, Munehisa Fukushima, Saori Amiya, Takayuki Honda, Yuta Kono, Susumu Isogai, Ryuya Edahiro, Makoto Masuda, Hisato Shimada, Hideaki Nagai, Tomoya Baba, Fukuki Saito, Toshihiro Sakurai, Ryota Kikuchi, Yoichiro Noguchi, Tatsuhiko Anzai, Mizuha Hashiguchi, Masamichi Sato, Naoki Hasegawa, Yasunari Miyazaki, Tetsuya Ueda, Yasuhiko Yamano, Shinji Ozaki, Yoshinobu Saito, Takuya Inoue, Sohei Nakayama, Sawako Arai, Yu Kusaka, Miki Kawada, Yuko Kurihara, Daiki Wada, Isamu Kamimaki, Motonao Ishikawa, Sumiko Kohashi, Sae Wada, Kazuma Yagi, Rino Ishihara, Hiroko Okabayashi, Nobuhiro Kodama, Mai Takahashi, Kiyoshi Komuta, Yusuke Chihara, Yoshihiko Nakamura, Akifumi Endo, Shuichiro Matsumoto, Akira Igarashi, Shuhei Yamada, Akiko Yonekawa, Yukiko Nakajima, Sakamoto Koji, Kazue Fujita, Masakiyo Yatomi, Makoto Ishii, Ryuji Koike, Eigo Shimizu, Shigeru Chiba, Satoru Miyawaki, Shunsuke Maeda, Toshio Odani, Hideyasu Sugimoto, Masanori Nishikawa, Yoshinori Yasui, Akira Ando, Takayuki Shibusawa, Nobuharu Ooshima, Toshiyuki Kita, Satoru Fukuyama, Ai Tada, Mariko Terashima, Tadao Nagasaki, Rie Baba, Atsuya Narita, Takanori Ogawa, Tetsuo Shimizu, Ken Ueda, Yuki Haruta, Satoru Hashimoto, Ryohei Suematsu, Ho Lee, Ryosuke Satomi, Hirotaka Eguchi, Kota Ishioka, Ryousuke Aoki, Yusuke Suzuki, Takemasa Matsumoto, Kazunari Sonobe, Hisato Hiranuma, Hirayasu Kai, Kosuke Yoshida, Ayumi Yoshifuji, Takeru Kashiwada, Yuko Harada, Reoto Takei, Aya Wakabayashi, Tomohiro Matsunaga, Haruhiko Hirata, Hiroshi Morisaki, Yoshifumi Uwamino, Yoshihisa Tokunaga, Kazuki Niwa, Hidetoshi Kawashima, Hideki Terai, Kenji Takano, Mumon Takita, Yuko Komase, Masaki Yamasaki, Chiaki Hosoda, Takayuki Ogura, Shun Shibata, Mitsuru Motegi, Takeshi Takahashi, Takehiko Ohba, Shinichi Hayashi, Satoshi Ito, Yu Kasamatsu, Shinnosuke Ikemura, Tetsuya Fukuta, Koichiro Asano, Taka-aki Nakada, Kota Murohashi, Tomoyuki Uchida, Hirotaka Matsuo, Satoko Hanada, Kenta Nishiyama, Minoru Inomata, Nobukazu Fujimoto, Tomoya Tateishi, Mitsuaki Kojima, Kazuto Kato, Kazuhiko Katayama, Yuichi Maeda, Takashi Kagaya, Keiko Wakahara, Takashi Ogura, Yasuhiro Gon, Taku Oshima, Ken Arimura, Shuhei Maruyama, Mari Tone, Ryuichi Sato, Koichi Fukunaga, Hidefumi Koh, Yuichiro Kitagawa, Noboru Takayanagi, Masatoshi Miyazaki, Ichiro Nakachi, Akihiko Kawana, Toshiyuki Hirano, Yohei Funatsu, Yasushi Nakamori, Reiko Sado, Yasuo Shichinohe, Junya Suzuki, Yasunari Kaneyama, Takahito Miyake, Kunihiro Yamagata, Yasuhito Nannya, Shinichi Ogawa, Naoya Hida, Tsuyoshi Oguma, Kazunori Nakamura, Kosaku Nanki, Naozumi Hashimoto, Fumihiko Matsuda, Tomoyuki Kimura, Daiki Morikawa, Yuji Uchimura, Yoshiaki Tanaka, Kazuhisa Yoshiya, Takashige Kuraki, Yoshihiro Eriguchi, Tomohisa Shoko, Tadanaga Shimada, Yuji Hiramatsu, Akihiko Tanaka, Hideya Kitamura, Yutaka Kozu, Ryosuke Arai, Taisuke Isono, Yasushi Makino, Seiya Imoto, Yuichi Adachi, Yuma Matsui, Masato Shinoki, Kazumi Nishio, Keiko Mitamura, Tomonori Imamura, Masanori Azuma, Sonoko Harada, Hiroshi Ono, Kotoe Katayama, Masumi Ai, Keisuke Shinozuka, Reiko Taki, Junichi Maruyama, Takao Imai, Yutaro Kaneko, Kensuke Kanaoka, Sho Ota, Yoji Nagasaki, Toshihiro Kishikawa, Takayuki Niitsu, Hirohisa Horinouchi, Naoyuki Kuse, Tetsuya Shiomi, Jun Nakajima, Katsushi Tokunaga, Norihiro Harada, Keita Masuzawa, Noriyuki Kijima, Takeshi Osawa, Satoru Sakagami, Kazuhiko Fujii, Shotaro Chubachi, Tomoyuki Yoshihara, Yoshimi Noda, Hiroyasu Ishikura, Kiyoshi Koshida, Shin Ohta, Ai Nakamura, Naota Kuwahara, Shinji Ogura, Suguru Ueda, Akihiro Ito, Morio Nakamura, Tohru Takata, Yuya Shirai, Hidenori Takahashi, Eriko Yoshida, Satoru Beppu, Mitsuyoshi Utsugi, Masafumi Shimoda, Masatoshi Shimo, Tomoo Ishii, Takefumi Nikaido, Takanori Asakura, Kazuya Miyagawa, Takanori Kanai, Hiroto Kishi, Akane Kamiya, Genta Nagao, Kodai Kawamura, Ryunosuke Saiki, Takashi Yoshiyama, Hajime Sasano, Kazuyoshi Watanabe, and Yuta Matsubara
- Subjects
Genetics ,education.field_of_study ,Population ,Mendelian Randomization Analysis ,Genome-wide association study ,Odds ratio ,Biology ,medicine.disease ,Obesity ,Confidence interval ,Minor allele frequency ,Pandemic ,medicine ,education - Abstract
To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.
- Published
- 2021
13. Comparison of three frailty models and a sarcopenia model in elderly patients with chronic obstructive pulmonary disease
- Author
-
Kuniaki Hirai, Ryo Manabe, Haruna Sato, Sojiro Kusumoto, Akihiko Tanaka, Keisuke Kaneko, Shin Ohta, Hironori Sagara, Fumihiro Yamaguchi, Tetsuya Homma, Tomoki Uno, and Shintaro Suzuki
- Subjects
Male ,Sarcopenia ,medicine.medical_specialty ,Frail Elderly ,Psychological intervention ,Pulmonary disease ,Kihon checklist ,Risk Assessment ,Pulmonary Disease, Chronic Obstructive ,Japan ,Older patients ,Quality of life ,Risk Factors ,Internal medicine ,Outpatients ,Prevalence ,medicine ,Humans ,Geriatric Assessment ,Aged ,COPD ,Frailty ,business.industry ,Prognosis ,medicine.disease ,Checklist ,Cross-Sectional Studies ,Mood disorders ,Quality of Life ,Female ,business - Abstract
Aim Frailty and sarcopenia affect the prognosis and quality of life of patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain which model is the most suitable for evaluating vulnerability in patients with COPD. We evaluated the validity of three frailty models - the Kihon Checklist (KCL), the Japanese version of the Cardiovascular Health Study and the Study of Osteoporotic Fractures - and one sarcopenia model for older patients with COPD. Methods This cross-sectional study included 201 older (aged ≥65 years) outpatients with COPD. We used three frailty models and one sarcopenia model to identify their correlation with various indices that can evaluate the status of COPD and determine the most ideal model for evaluating vulnerability in patients with COPD. Results The highest prevalence of frailty (38%) and lowest prevalence of robustness (26%) were observed using the KCL. Although all models reflected the characteristics of COPD, the KCL yielded the strongest correlations with clinically important physical, psychological and prognostic indices. The KCL yielded statistically significant differences in almost all indices among the three intergroup comparisons (robust, pre-frailty and frailty). The KCL was superior in extracting mood disorders to the other models. Conclusion Although all investigated models were useful, the KCL was the most suitable for evaluating the frailty status and might enable interventions in patients with COPD. Geriatr Gerontol Int 2019; 19: 896-901.
- Published
- 2019
14. Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma
- Author
-
Yoshito Miyata, Kuniaki Hirai, Sojiro Kusumoto, Tsukasa Ohnishi, Shin Ohta, Fumihiro Yamaguchi, Naota Kuwahara, Yoshitaka Uchida, Mayumi Yamamoto, Ryo Manabe, Tomoki Uno, Hiroko Mizuma, Shintaro Suzuki, Tetsuya Homma, Akihiko Tanaka, Munehiro Yamaguchi, Megumi Jinno, and Hironori Sagara
- Subjects
Chlorella ,biology ,business.industry ,Murine model ,Immunology ,Airway hyperresponsiveness ,Medicine ,Inhibitory postsynaptic potential ,biology.organism_classification ,Airway ,business ,medicine.disease ,Asthma - Published
- 2019
15. Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products
- Author
-
Hatsuko Mikuni, Hironori Sagara, Kuniaki Hirai, Yosuke Fukuda, Naruhito Oda, Shintaro Suzuki, Yoshitaka Uchida, Tomoko Kawahara, Yoko Sato, Akihiko Tanaka, Hideki Inoue, Tsukasa Ohnishi, Akiko Fujiwara, Fumihiro Yamaguchi, Shin Ohta, Tetsuya Homma, Haruhisa Saito, and Tomoki Uno
- Subjects
medicine.medical_specialty ,Health (social science) ,Younger age ,medicine.medical_treatment ,Medicine (miscellaneous) ,Pulmonary disease ,Logistic regression ,Quit smoking ,smoking ,chronic obstructive pulmonary disease ,heated tobacco products ,Diseases of the respiratory system ,Internal medicine ,Medicine ,Effective treatment ,In patient ,RC254-282 ,COPD ,RC705-779 ,business.industry ,Public Health, Environmental and Occupational Health ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Smoking cessation ,business ,cigarettes ,Research Paper - Abstract
Introduction Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. Methods This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. Results Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p
- Published
- 2021
16. Investigating Patient and Family Satisfaction with the Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease
- Author
-
Hatsuko Mikuni, Haruhisa Saito, Yoshito Miyata, Akihiko Tanaka, Tomoko Kawahara, Tsukasa Ohnishi, Shin Ohta, Hironori Sagara, Keisuke Kaneko, Akiko Fujiwara, Yuiko Goto, Fumihiro Yamaguchi, Yoshitaka Uchida, Tomoki Uno, Tetsuya Homma, Kuniaki Hirai, Naruhito Oda, and Shintaro Suzuki
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pulmonary disease ,Family satisfaction ,Personal Satisfaction ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Quality of life (healthcare) ,Surveys and Questionnaires ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Intensive care medicine ,COPD ,business.industry ,Healthy life expectancy ,medicine.disease ,Respiratory status ,Cross-Sectional Studies ,Dyspnea ,030228 respiratory system ,Copd assessment test ,Quality of Life ,business - Abstract
The current chronic obstructive pulmonary disease (COPD) management aims to improve the patients' quality of life and healthy life expectancy; however, few studies have evaluated the level of satisfaction with the patients' current respiratory status in COPD patients and their families. This study aimed to examine the level of patient and family satisfaction with the patients' current respiratory status and to identify the clinical factors closely linked to dissatisfaction.This multicenter, cross-sectional study included 454 outpatients with COPD and 296 family members. Patients and families were allocated to the satisfied and dissatisfied groups based on their satisfaction with the patients' current respiratory status. Patients' health status, dyspnoea, appetite, respiratory function, and mood disorders were assessed.Among the participants of this study, 67% of patients and 60% of their families were dissatisfied with the patients' current respiratory status. The COPD assessment test (CAT) was the most sensitive marker of dissatisfaction compared to other clinical factors (p 0.01). The statistical cut-off value of CAT for predicting patient dissatisfaction was 11. CAT reflected patient dissatisfaction independent of age, sex, dyspnoea, appetite, mood disorders, body mass index, and respiratory function (odds ratio: CAT; 1.12 (1.07-1.19): p 0.01).Many patients and families are dissatisfied with the patients' respiratory status, and the patients' CAT score is useful to predict dissatisfaction. Our findings are consistent with the Global Initiative for Chronic Obstructive Lung Disease indicating that treatment should be enhanced in patients with a CAT score ≥10. Furthermore, treatment strategies targeting CAT may contribute to an improved patient satisfaction.
- Published
- 2021
17. β
- Author
-
Haruki, Funakoshi, Kenji, Momo, Keinosuke, Okazaki, Takaya, Ebato, Shigenori, Yamamoto, Tomoki, Uno, Shin, Ohta, Hironori, Sagara, and Tadanori, Sasaki
- Subjects
Tachycardia ,Administration, Inhalation ,Atrial Fibrillation ,Humans ,Receptors, Adrenergic, beta-2 ,Asthma - Published
- 2020
18. Increased levels of circulating cell-free DNA in COVID-19 patients with respiratory failure
- Author
-
Katsuki Wakayama, Kiichi Nakahira, Akihiko Tanaka, Yosuke Hukuda, Jing Zhao, Shin Ohta, Hironori Sagara, and Masanori Yoshizumi
- Subjects
Applied Mathematics ,General Mathematics - Published
- 2022
19. [NEXT-GENERATION ARIA CARE PATHWAYS IN ALLERGIC RHINITIS]
- Author
-
Yoshitaka, Okamoto, Ken, Ohta, Maho, Suzukawa, Shin, Ohta, Mitsuhiro, Okano, Daiju, Sakurai, and Hiroyuki, Tashimo
- Subjects
Rhinitis, Allergic, Perennial ,Humans ,Immunotherapy ,Rhinitis, Allergic - Published
- 2020
20. The Relationship Between the 'Adherence Starts with Knowledge-20' Questionnaire and Clinical Factors in Patients with COPD: A Multi-Center, Cross-Sectional Study
- Author
-
Hironori Sagara, Tomoko Kawahara, Akiko Fujiwara, Tomohiro Matsunaga, Fumihiro Yamaguchi, Shin Ohta, Hatsuko Mikuni, Tetsuya Homma, Hideki Inoue, Sojiro Kusumoto, Yoshito Miyata, Kaho Akimoto, Akihiko Tanaka, Keisuke Kaneko, Shintaro Suzuki, Kuniaki Hirai, and Tomoki Uno
- Subjects
Male ,medicine.medical_specialty ,Respimat ,Cross-sectional study ,Hospital Anxiety and Depression Scale ,Severity of Illness Index ,ASK-20 ,inhaler ,Pulmonary function testing ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Japan ,Internal medicine ,Surveys and Questionnaires ,medicine ,Humans ,COPD ,Respiratory function ,030212 general & internal medicine ,adherence ,Original Research ,business.industry ,Inhaler ,General Medicine ,medicine.disease ,Obstructive lung disease ,Cross-Sectional Studies ,030228 respiratory system ,business - Abstract
Purpose Inhaler therapy is the mainstay of chronic obstructive pulmonary disease (COPD) management. Poor adherence causes disease exacerbation and affects patient mortality. Although the Adherence Starts with Knowledge-20 (ASK-20) questionnaire is a reliable tool for assessing medication adherence, the relationship between the ASK-20 and clinical factors in patients with COPD remains unknown. We investigated the relationship between the ASK-20 and clinical factors, and assessed real-world inhaler therapy use. Patients and Methods A multicenter, cross-sectional study of outpatients with COPD undergoing inhaler treatment who completed the ASK-20 questionnaire was performed. We investigated COPD-related health status using the COPD Assessment Test (CAT), psychological status using the Hospital Anxiety and Depression Scale (HADS-anxiety and HADS-depression), respiratory function, patient satisfaction levels, and real-world inhaler therapy use. Results Of the total 319 patients, 87% were male with a median age of 74 years. Most patients had mild or moderate COPD, according to Global Initiative for Chronic Obstructive Lung Disease stage. The total ASK-20 scores correlated significantly with the CAT, HADS-anxiety, and HADS-depression scores (r = 0.27, 0.33, and 0.29, respectively, p < 0.01). Multivariable analysis showed that CAT and HADS-anxiety scores had an independent and significant impact on the ASK-20 scores [β, standardized regression coefficient: 0.18 (95% CI, 0.03–0.35; p = 0.02), and 0.29 (95% CI, 0.17–0.42; p < 0.01), respectively]; however, the ASK-20 scores were not correlated with age, sex, body mass index, cohabitation, modified Medical Research Council Dyspnea Scale score, pulmonary function, disease duration, number of COPD exacerbations per year, comorbidities, inhaler numbers, nor inhaler components. Conclusion The ASK-20 scores in patients with COPD were significantly associated with CAT and HADS scores. In Japan, Respimat was prescribed to younger patients and patients with lower CAT scores. The ASK-20, a simple evaluation method, is useful for identifying clinical factors affecting adherence in patients with COPD.
- Published
- 2020
21. Steroid-Sparing Effect of Mepolizumab in Asthmatic Patients with Chronic Eosinophilic Pneumonia
- Author
-
Hironori Sagara, Shin Ohta, Megumi Jinno, Haruna Sato, Akihiko Tanaka, Hideki Inoue, Tetsuya Homma, and Yoshito Miyata
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Steroid sparing ,medicine ,Asthmatic patient ,Chronic eosinophilic pneumonia ,business ,Gastroenterology ,Mepolizumab ,medicine.drug - Published
- 2020
22. The Repeated Bronchodilation by Salbutamol Inhalation Induced the Development of M2 Macrophages in Murine Model of Asthma
- Author
-
Shin Ohta, Hitomi Ida, Kuniaki Hirai, Yusuke Watanabe, Hironori Sagara, Yoshito Miyata, Shintaro Suzuki, Yoshitaka Uchida, Tomoki Uno, Tomoyuki Kimura, Akihiko Tanaka, Sojiro Kusumoto, Yasunari Kishino, Tetsuya Homma, Mayumi Yamamoto, Hideki Inoue, Megumi Jinno, and Haruo Sato
- Subjects
Inhalation ,Murine model ,business.industry ,Bronchodilation ,medicine ,Salbutamol ,Pharmacology ,medicine.disease ,business ,Asthma ,medicine.drug - Published
- 2020
23. Eosinophilic Airway Inflammation and Activation of ERBB2 in Alternaria-Induced Asthma Mice Model
- Author
-
Shintaro Suzuki, Shin Ohta, Hironori Sagara, Akihiko Tanaka, Hideki Inoue, Kaho Akimoto, and M. Matsuda
- Subjects
biology ,business.industry ,Eosinophilic ,Immunology ,medicine ,Airway inflammation ,Alternaria ,biology.organism_classification ,medicine.disease ,business ,Asthma - Published
- 2020
24. Investigation of Df Induced Asthma Model in Each Age of Mice
- Author
-
Yoshito Miyata, Akihiko Tanaka, Tomoyuki Kimura, Yoshitaka Uchida, Yusuke Watanabe, Hironori Sagara, Tetsuya Homma, Megumi Jinno, Sojiro Kusumoto, Yasunari Kishino, Mayumi Yamamoto, Hideki Inoue, Hitomi Ida, Kuniaki Hirai, Shin Ohta, Haruo Sato, Shintaro Suzuki, and Tomoki Uno
- Subjects
business.industry ,Immunology ,Medicine ,Asthma model ,business - Published
- 2020
25. Oral meal intake as a prognostic predictor of community-acquired pneumonia: A retrospective cohort study
- Author
-
Shin Ohta, Hironori Sagara, Hiromitsu Suganuma, Sojiro Kusumoto, Kaho Akimoto, Hiroki Sato, Tomoko Kawahara, Shintaro Suzuki, Hatsuko Mikuni, Keisuke Kaneko, Akihiko Tanaka, Kuniaki Hirai, and Tetsuya Homma
- Subjects
0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,030106 microbiology ,Serum albumin ,03 medical and health sciences ,0302 clinical medicine ,Community-acquired pneumonia ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Meals ,Retrospective Studies ,Meal ,biology ,business.industry ,Mortality rate ,Area under the curve ,Retrospective cohort study ,Pneumonia ,medicine.disease ,Prognosis ,Confidence interval ,Community-Acquired Infections ,Hospitalization ,Infectious Diseases ,biology.protein ,business - Abstract
The association between oral intake volume and prognosis has not been studied in hospitalized patients with community-acquired pneumonia (CAP).We retrospectively examined 503 hospitalized CAP patients to evaluate whether early-phase meal intake (EMI) (within the first 24 h after hospitalization) and maximum meal intake (MMI) (on the day during hospitalization) are useful prognostic predictors.Of the 503 patients, 40 (8.0%) died within 30 days. Area under the curve (AUC) for prognosis was comparable between EMI, A-DROP, and serum albumin [EMI: 0.80, 95% confidence interval (CI) 0.75-0.84; A-DROP: 0.77, 95% CI 0.71-0.83; Serum albumin: 0.72, 95% CI 0.64-0.79]. Mortality rate was1% in patients with EMI ≥ 50%. Univariate analysis showed that patients with EMI50% showed poor prognosis [odds ratio 53.4, 95% CI 7.2-392.2]. Multivariate analysis showed that EMI was an independent prognostic predictor [odds ratio 23.6, 95% CI 3.11-179.7]. AUC of MMI for prognosis was 0.94 (95% CI 0.91-0.96); mortality rate was1% for patients who ingested ≥50% of meals on any day during hospitalization. We defined ingesting ≥50% of meals on any day during hospitalization as oral intake stability. Multivariate analyses revealed an association between oral intake stability and prognosis. Odds ratio of oral intake stability for prognosis was higher than that of conventional evaluations (vital sign and CRP level stability). Fewer days were required to reach oral intake stability than to reach vital sign and CRP level stability.Oral intake is a simple, non-invasive, cost-free, and powerful prognostic predictor for patients with CAP.
- Published
- 2019
26. Tokyo Anti-Fibrosis in the Lung Research Project
- Author
-
Maho Suzukawa, Shin Ohta, and Ken Ohta
- Subjects
Anti fibrosis ,Pathology ,medicine.medical_specialty ,Lung ,medicine.anatomical_structure ,business.industry ,medicine ,business - Published
- 2019
27. Prevalence and clinical features of asthma-COPD overlap in patients with COPD not using inhaled corticosteroids
- Author
-
Hatsuko Mikuni, Naruhito Oda, Shintaro Suzuki, Tomoko Kawahara, Tomoki Uno, Yoshito Miyata, Shin Ohta, Fumihiro Yamaguchi, Hironori Sagara, Akihiko Tanaka, Tetsuya Homma, Kuniaki Hirai, Hideki Inoue, and Yoshitaka Uchida
- Subjects
Male ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,MEDLINE ,Inhaled corticosteroids ,Comorbidity ,Pulmonary Disease, Chronic Obstructive ,Japan ,Adrenal Cortex Hormones ,Forced Expiratory Volume ,Internal medicine ,Administration, Inhalation ,Prevalence ,medicine ,Humans ,Immunology and Allergy ,In patient ,Asthma copd overlap ,Aged ,COPD ,business.industry ,General Medicine ,medicine.disease ,Asthma ,Cross-Sectional Studies ,Disease Progression ,Female ,lcsh:RC581-607 ,business - Published
- 2021
28. Antibody therapy for the management of severe asthma with eosinophilic inflammation
- Author
-
Maho Suzukawa, Hiroyuki Nagase, Shin Ohta, and Ken Ohta
- Subjects
Adult ,0301 basic medicine ,Thymic stromal lymphopoietin ,medicine.medical_treatment ,Immunology ,Omalizumab ,Antibodies, Monoclonal, Humanized ,Immunoglobulin E ,03 medical and health sciences ,0302 clinical medicine ,Eosinophilic ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Child ,Asthma ,Inflammation ,biology ,business.industry ,General Medicine ,Immunotherapy ,Eosinophil ,medicine.disease ,Eosinophils ,030104 developmental biology ,medicine.anatomical_structure ,Disease Progression ,biology.protein ,Cytokines ,business ,Mepolizumab ,medicine.drug - Abstract
One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as ‘refractory asthma’. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions. Humanized anti-human IgE antibody (anti-IgE; omalizumab) was the first biological preparation approved for treating asthma. Based on clinical evidence, treatment with anti-IgE (anti-IgE therapy) has been accepted as a new therapeutic approach for severe allergic asthma in adults since 2009 and in children since 2012 and has been shown to have ~60% efficacy. More recently, a humanized anti-IL-5 antibody (anti-IL-5; mepolizumab) was launched in June 2016 and has attracted great interest due to its potential effects. Several clinical studies are also ongoing to evaluate the biological preparations targeting IL-5 receptor α (IL-5Rα), IL-4 receptor α (IL-4Rα), which is shared by IL-4 and IL-13, thymic stromal lymphopoietin (TSLP) and IL-33. The new strategy with biologics targeting eosinophilic airway inflammation might open a new array for us to overcome severe refractory asthma in the future.
- Published
- 2017
29. Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma
- Author
-
Shin Ohta, Mayumi Muramoto, Shintaro Suzuki, Takuya Yokoe, Kuniaki Hirai, Yoshio Watanabe, Tetsuya Homma, Yoshito Miyata, Munehiro Yamaguchi, Megumi Jinno, Akihiko Tanaka, and Hironori Sagara
- Subjects
03 medical and health sciences ,Mice ,0302 clinical medicine ,Metaplasia ,medicine ,Respiratory Hypersensitivity ,Animals ,Hypoxia ,Asthma ,Inflammation ,Goblet cell ,Mice, Inbred BALB C ,Sleep Apnea, Obstructive ,biology ,business.industry ,Interleukin ,Intermittent hypoxia ,respiratory system ,Eosinophil ,medicine.disease ,respiratory tract diseases ,Obstructive sleep apnea ,Ovalbumin ,Disease Models, Animal ,medicine.anatomical_structure ,030228 respiratory system ,Otorhinolaryngology ,Immunology ,biology.protein ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity. We investigated whether intermittent hypoxia (IH), which is a physiological feature of OSAS, modifies allergic airway inflammation in a murine model of asthma. Balb/c mice were sensitized by ovalbumin (OVA) intraperitoneally twice (days 1 and 14) and challenged with intranasal OVA three times (days 21, 22, and 23). The mice were exposed to IH either from days 1 to 24 (long exposure) or only from days 21 to 24 (short exposure). The impact of IH exposure to allergic airway inflammation was investigated using these mice models by histologic, morphometric, and molecular techniques. Additionally, the airway responsiveness to acetylcholine was also assessed. OVA-sensitized and OVA-challenged mice exposed to room air (RA) showed increased total cell and eosinophil numbers in the BALF. The levels of interleukin (IL)-5 and IL-13 in the BALF also increased and goblet cell metaplasia was induced. In contrast, both long and short exposure to IH inhibited the increased total cell and eosinophil numbers. The levels of IL-5 and IL-13 in the BALF also decreased on exposure to IH. Moreover, the goblet cell hyperplasia and airway hyperresponsiveness were significantly reduced in mice exposed to IH compared to those exposed to RA. These results suggest that IH may not deteriorate the asthmatic condition in a murine model of asthma.
- Published
- 2019
30. Introduction for Various Activities for Improvement of Heating Efficiency and Dealing of Adverse Events in Hyperthermia
- Author
-
Hikaru Kakishita, Takayuki Ohguri, Shin Ohta, Yuko Higuchi, Katsuya Yahara, Hajime Imada, Ryo Kawasaki, Hiroyuki Narisada, Tomoaki Morioka, Yoshinori Tomoda, and Akiko Kitamura
- Subjects
Hyperthermia ,business.industry ,Anesthesia ,medicine ,medicine.disease ,business ,Adverse effect ,Heating efficiency - Published
- 2016
31. Late Breaking Abstract - Clinical utility of basophil activating test (BAT) in subjects with drug-induced lung disease
- Author
-
Shintaro Suzuki, Shin Ohta, Tsukasa Ohnishi, Kyoko Fujiwara, Yoshito Miyata, Tetsuya Homma, Akihiko Tanaka, Hironori Sagara, and Yasunari Kishino
- Subjects
Drug ,medicine.anatomical_structure ,business.industry ,Lung disease ,media_common.quotation_subject ,Immunology ,medicine ,Basophil ,business ,media_common - Published
- 2018
32. Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease
- Author
-
Ryo Manabe, Sojiro Kusumoto, Hirofumi Yamaguchi, Hitomi Ida, Yoshito Miyata, Megumi Jinno, Takuya Yokoe, Tomoko Kawahara, Yosuke Fukuda, Kuniaki Hirai, Shintaro Suzuki, Yoshio Watanabe, Tetsuya Homma, Haruna Sato, Akiko Fujiwara, Yoshitaka Uchida, Tomoyuki Kimura, Mayumi Yamamoto, Hatsuko Mikuni, Tsukasa Ohnishi, Munehiro Yamaguchi, Tomoki Uno, Yasunori Murata, Akihiko Tanaka, Hironori Sagara, Yasunari Kishino, Shin Ohta, and Naota Kuwahara
- Subjects
Male ,medicine.medical_specialty ,Exacerbation ,Immunology ,Garenoxacin ,Moraxella catarrhalis ,03 medical and health sciences ,chemistry.chemical_compound ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Internal medicine ,medicine ,Immunology and Allergy ,Blood test ,Humans ,030223 otorhinolaryngology ,Adverse effect ,Asthma ,Aged ,COPD ,medicine.diagnostic_test ,biology ,Bacteria ,business.industry ,General Medicine ,Bacterial Infections ,Middle Aged ,biology.organism_classification ,medicine.disease ,respiratory tract diseases ,Anti-Bacterial Agents ,Clinical trial ,030228 respiratory system ,chemistry ,Acute Disease ,Female ,business ,Fluoroquinolones - Abstract
Background: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. Objective: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. Method: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). Results: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. Conclusion: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.
- Published
- 2018
33. Influence of Omalizumab on Allergen-Specific IgE in Patients with Adult Asthma
- Author
-
Hiroko, Mizuma, Akihiko, Tanaka, Yoshitaka, Uchida, Akiko, Fujiwara, Ryo, Manabe, Hitomi, Furukawa, Naota, Kuwahara, Yosuke, Fukuda, Tomoyuki, Kimura, Megumi, Jinno, Shin, Ohta, Mayumi, Yamamoto, Satoshi, Matsukura, Satoshi, Matsukara, Mitsuru, Adachi, and Hironori, Sagara
- Subjects
Adult ,Male ,medicine.drug_class ,Immunology ,Anti immunoglobulin e ,chemical and pharmacologic phenomena ,Omalizumab ,Immunoglobulin E ,Monoclonal antibody ,medicine ,Humans ,Immunology and Allergy ,In patient ,Anti-Asthmatic Agents ,Seroconversion ,Allergen specific IgE ,Aged ,Asthma ,biology ,business.industry ,hemic and immune systems ,General Medicine ,Allergens ,Middle Aged ,medicine.disease ,biology.protein ,Female ,business ,medicine.drug - Abstract
Background: Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, inhibits the binding of circulating IgE to mast cells and basophils, resulting in fewer episodes of airway inflammation, asthma symptoms and exacerbations in patients with severe allergic asthma. Treatment of patients with asthma using omalizumab increases serum total IgE (tIgE) levels. However, little is known about the influence of omalizumab on allergen-specific IgE (sIgE). Methods: tIgE and sIgE in 47 adult patients with severe asthma were measured with a fluorescent enzyme immunoassay (ImmunoCAP-FEIA) before and after omalizumab treatment. Results: Treatment with omalizumab increased tIgE and sIgE levels. The increases in sIgE by class category after omalizumab treatment were positively correlated with baseline sIgE positivity before treatment. The mean changes in sIgE levels after omalizumab treatment were also correlated with baseline sIgE levels before treatment. The mean changes in tIgE levels were positively correlated with the mean changes in IgE levels against Dermatophagoides pteronyssinus, crude house dust, Japanese cedar and moth. Omalizumab markedly influenced the negative-to-positive seroconversion rate for IgE against Japanese cedar (30.8%), Candida (29.0%) and moth (28.0%). Finally, all patients with negative-to-positive seroconversion for Japanese cedar-specific IgE had cedar pollinosis before beginning omalizumab treatment. Conclusions: The changes in sIgE levels after omalizumab treatment may be dependent on the baseline sIgE levels. Our data may indicate the presence of undetectable but functional sIgE.
- Published
- 2015
34. Outcomes of Institutional Manual for Troubles with 8 MHz Heating Device
- Author
-
Yoshinori Tomoda, Yuko Higuchi, Katsuya Yahara, Akiko Kitamura, Hajime Imada, Hikaru Kakishita, Shin Ohta, Ryo Kawasaki, Takayuki Ohguri, Hiroyuki Narisada, and Tomoaki Morioka
- Published
- 2015
35. Predicting future risk of exacerbations in Japanese patients with adult asthma: A prospective 1-year follow up study
- Author
-
Shintaro Suzuki, Yoshito Miyata, Mayumi Yamamoto, Shin Ohta, Tomoki Uno, Takuya Yokoe, Hironori Sagara, Tetsuya Homma, Kuniaki Hirai, Munehiro Yamaguchi, Megumi Jinno, Haruna Sato, and Akihiko Tanaka
- Subjects
lcsh:Immunologic diseases. Allergy ,Adult ,Male ,Vital capacity ,Pediatrics ,medicine.medical_specialty ,Exacerbation ,Comorbidity ,Nitric Oxide ,Logistic regression ,Risk Assessment ,Severity of Illness Index ,Pulmonary function testing ,Future risk ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,Risk Factors ,Asthma control ,medicine ,Humans ,Immunology and Allergy ,FeNO ,Prospective Studies ,030212 general & internal medicine ,Aged ,Asthma ,Aged, 80 and over ,COPD ,business.industry ,Pulmonary function test ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,respiratory tract diseases ,Respiratory Function Tests ,030228 respiratory system ,Disease Progression ,Female ,lcsh:RC581-607 ,business ,Body mass index ,Biomarkers ,Follow-Up Studies - Abstract
Background: To avoid future risk is a definitive goal of long-term asthma management. Exacerbations are considered to be the most relevant future risk in real life asthma management. Few comparative studies have evaluated the risk factors associated with exacerbations in Japanese patients with asthma. Methods: We performed the prospective 1-year follow up study in Japanese patients with adult asthma. A total of 189 patients with asthma were enrolled and followed up for 1 year. Finally, 181 patients completed the study protocol. Results: Of 181 patients, 43 patients (23.8%) had exacerbations during the follow-up period. Among the 45 patients who had exacerbations during the preceding year, 32 patients (71.1%) had exacerbations. Prevalence of patients with previous exacerbations and those with previous admissions were significantly higher in patients with exacerbations than those with no exacerbation. Logistic regression analysis also identified a significant association between exacerbations during the follow-up period and exacerbations during the preceding year, admissions during the preceding 3 years, ACT score below 20, low %FVC (
- Published
- 2017
- Full Text
- View/download PDF
36. Cardiac and respiratory effects of deep regional hyperthermia using an 8 MHz radiofrequency-capacitive device on patients with cancer
- Author
-
Hajime Imada, Chiduko Takakura, Shin Ohta, Kanae Fujita, Takayuki Ohguri, Akiko Chishaki, Mami Miyazono, Nobuko Hashiguchi, Hiroyuki Sawatari, Hideki Hirata, Rieko Izukura, Hiromi Kuroda, Tomoko Ohkusa, Chie Magota, and Keiko Yamasaki
- Subjects
Hyperthermia ,Cancer Research ,medicine.medical_specialty ,Respiratory rate ,Physiology ,business.industry ,Diastole ,Cancer ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Physiology (medical) ,Anesthesia ,Internal medicine ,medicine ,Adjuvant therapy ,Cardiology ,Respiratory system ,business ,Lead (electronics) ,030217 neurology & neurosurgery ,Oxygen saturation (medicine) - Abstract
Purpose: Hyperthermia (HT), an adjuvant therapy for variable cancers, may cause physiological changes in the patients, which may lead to cardiovascular problems. Among various HT treatments, the physiological effects of deep regional HT are still unclear. We examined the physiological alterations throughout deep regional HT to improve the HT safety.Materials and methods: Thirty-one patients (age: 61 ± 12 years) with cancer received HT in the thoracic or upper abdominal regions using an 8-MHz radiofrequency-capacitive-device for 50 min. Rectal temperature (Trec), systolic and diastolic blood pressures (SBP and DBP), pulse rate (PR), respiratory rate (RR), percutaneous oxygen saturation (SpO2) and sweating volume were evaluated throughout HT.Results: At 50 min after starting HT, Trec, PR and RR were significantly increased compared with the baseline values (Trec: 38.2 ± 1.4 vs. 36.3 ± 0.8 °C, p
- Published
- 2017
37. The effect of muscarinic M3 receptor blockage in development of M2 macrophages in allergic inflammation
- Author
-
Shin Ohta, Naota Kuwahara, Munehiro Yamaguchi, Yosuke Fukuda, Tsukasa Ohnishi, Megumi Jinno, Akihiko Tanaka, Tomoyuki Kimura, Hironori Sagara, Tomoki Uno, Ryo Manabe, Yoshitaka Uchida, Yoshito Miyata, Shintaro Suzuki, Sojiro Kusumoto, Yoshio Watanabe, Kukniaki Hirai, Fumihiro Yamaguchi, Hitomi Ida, and Tetsuya Homma
- Subjects
business.industry ,Immunology ,Muscarinic acetylcholine receptor ,Immunology and Allergy ,Medicine ,Muscarinic acetylcholine receptor M3 ,business ,Allergic inflammation - Published
- 2019
38. A Toxicity Risk Index, An Index for Warning Idiosyncratic Drug Toxicity
- Author
-
Kazuo Samizo, Miyoshi Morimoto, Takashi Mizuma, and Shin Ohta
- Subjects
Drug ,Drug-Related Side Effects and Adverse Reactions ,business.industry ,Drug candidate ,media_common.quotation_subject ,Pharmaceutical Science ,Covalent binding ,Pharmacology ,Pharmaceutical Preparations ,Drug development ,Pharmacokinetics ,Risk Factors ,Risk index ,Drug Discovery ,Toxicity ,Humans ,Medicine ,business ,Drug toxicity ,Algorithms ,Protein Binding ,media_common - Abstract
Drug toxicity impedes drug development and its clinical use. In the present study, a toxicity risk index (TRI), which is an index for warning idiosyncratic drug toxicity (IDT), was proposed. The TRI of drugs was defined as a function of dose, pharmacokinetic parameters, and toxicokinetic data from covalent binding experiment. Twenty drugs, which were classified into three categories by a report (Nakayama S, Atsumi R, Takakusa H, Kobayashi Y, Kurihara A, Nagai Y, Nakai D, Okazaki O. 2009. Drug Metab Dispos 37:1970–1977), were studied with TRI. The three categories were BBW (drugs with a block box warning for IDT), WNG (drugs without a black box warning but with a warning for IDT), and SAFE (drugs without any warning). The TRIs of drugs classified as SAFE were distinctly different from those classified as BBW. The TRI of the SAFE drugs were lower than 0.456 (nmol/mg protein). In contrast, the TRI of the BBW drugs were higher than 1.10 (nmol/mg protein). These results warned us that a drug candidate, where the TRI is higher than 1.0 nmol/mg protein, should be categorized as a BBW drug. Further study with more data of TRI will give a cutoff value with a statistical meaning. Thus, TRI may be useful for decision making in drug development and its clinical use.
- Published
- 2013
39. Group V Secretory Phospholipase A2 Is Involved in Macrophage Activation and Is Sufficient for Macrophage Effector Functions in Allergic Pulmonary Inflammation
- Author
-
Wei Xing, Shin Ohta, Mitsuru Imamura, Joshua A. Boyce, and Barbara Balestrieri
- Subjects
Adoptive cell transfer ,Chemokine ,T-Lymphocytes ,T cell ,Immunology ,Fluorescent Antibody Technique ,Inflammation ,Biology ,Lymphocyte Activation ,Article ,Group V Phospholipases A2 ,Mice ,Hypersensitivity ,medicine ,Animals ,Humans ,Immunology and Allergy ,Macrophage ,CCL17 ,Mice, Knockout ,Effector ,Macrophages ,Pneumonia ,Macrophage Activation ,Immunohistochemistry ,Mice, Inbred C57BL ,medicine.anatomical_structure ,biology.protein ,medicine.symptom ,CCL22 - Abstract
We reported that Pla2g5-null mice lacking group V secretory phospholipase A2 (gV-sPLA2) showed reduced eosinophilic pulmonary inflammation and Th2 cytokine generation when challenged with an extract from house dust mite Dermatophagoides farinae, compared with wild-type (WT) controls. Adoptive transfer studies suggested that gV-sPLA2 in dendritic cells was necessary for sensitization of Pla2g5-null mice, but was not sufficient to induce the effector phase of pulmonary inflammation. In this study, we demonstrate that gV-sPLA2 is inducibly expressed in mouse and human macrophages (Mϕ) activated by IL-4 and is required for the acquisition of Mϕ effector functions that facilitate the effector phase of pulmonary inflammation. We demonstrate that gV-sPLA2 expression in Mϕ is sufficient for the development of pulmonary inflammation, even when inflammation is induced by intrapulmonary administration of IL-4. The concentrations of CCL22/CCL17 and effector T cell recruitment are severely impaired in Pla2g5-null mice. Intratracheal transfers of enriched CD68+ cells isolated from the lungs of D. farinae–challenged WT donor mice induce eosinophilia, chemokine production, and recruitment of T cells into the lungs of Pla2g5-null recipients previously sensitized by WT D. farinae–loaded dendritic cells. Our studies identified a unique function of gV-sPLA2 in activation of Mϕ and in their capacity to recruit T cells to amplify the effector phase of pulmonary inflammation.
- Published
- 2013
40. Inhibitory effect of protopanaxatriol ginseng metabolite M4 on the production of corticosteroids in ACTH-stimulated bovine adrenal fasciculata cells
- Author
-
Shin Ohta, Eiichi Tachikawa, Yoshikazu Miyate, Katsuo Takahashi, Eri Hasegawa, Susumu Yamato, and Saori Nakagawa
- Subjects
endocrine system ,medicine.medical_specialty ,Sapogenins ,Hydrocortisone ,medicine.drug_class ,Metabolite ,Panax ,Pharmacology ,complex mixtures ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Ginseng ,Adrenocorticotropic Hormone ,Adrenal Cortex Hormones ,Corticosterone ,Internal medicine ,Cyclic AMP ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Cells, Cultured ,Protopanaxatriol ,Forskolin ,General Medicine ,Gastrointestinal Tract ,Cholesterol ,Endocrinology ,chemistry ,Ginsenoside ,Pregnenolone ,Corticosteroid ,Cattle ,Zona Fasciculata ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Aims We investigated the pharmacological effects of saponins isolated from ginseng root and their metabolites, which occur by hydrolysis of the sugar moieties connecting the aglycone of saponins in the digestive tract, on the production of corticosteroids in bovine adrenal fasciculata cells in vitro. Main methods The levels of corticosteroids produced from adrenal corticotropic hormone (ACTH)-stimulated bovine adrenal fasciculata cells were determined under the presence or absence of ginseng saponins (ginsenosides) and their metabolites using fluorometry, gas-chromatography–mass spectrometry, and sweeping-micellar electrokinetic capillary chromatography. Key findings An end metabolite of the protopanaxatriol saponins in ginseng, 20(s)-protopanaxatriol (M4), strongly reduced ACTH-stimulated cortisol production. M4 significantly inhibited the production of cortisol induced by different stimuli, alamethicin, dibutyryl cyclic AMP, forskolin, and 22(R)-hydroxycholesterol, a membrane-permeable cholesterol. However, it did not affect the production of cortisol by either pregnenolone, a precursor of cortisol synthesis, or cyclic AMP. Furthermore, M4 significantly inhibited the production of pregnenolone, progesterone, deoxycorticosterone, cortisol, and corticosterone in a dose-dependent manner. Significance Results strongly suggest that protopanaxatriol saponins in ginseng are prodrugs metabolized in the digestive tract so that the end metabolite, M4, produces inhibitory activity of corticosteroid production in the adrenal fasciculata cells in vivo. The results also suggest that M4 inhibits the conversion from cholesterol to pregnenolone because the production of pregnenolone was reduced.
- Published
- 2013
41. Simple column-switching HPLC method for determining levels of the antifungal agent micafungin in human plasma and application to patient samples
- Author
-
Shin Ohta, Susumu Yamato, Sadahiko Shimoeda, Naoko Kuwabara, Hikaru Kobayashi, and Saori Nakagawa
- Subjects
Pharmacology ,Antifungal ,Chromatography ,Echinocandin ,Calibration curve ,medicine.drug_class ,Clinical Biochemistry ,Micafungin ,General Medicine ,bacterial infections and mycoses ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,Matrix (chemical analysis) ,chemistry.chemical_compound ,chemistry ,Human plasma ,Drug Discovery ,medicine ,Molecular Biology ,Ammonium acetate ,medicine.drug - Abstract
Micafungin is an echinocandin antifungal agent that is important for treating candidiasis in emergency and intensive care medicine; however, current methods for measuring micafungin plasma levels are lengthy and complicated. We report a simple quantitative method using column-switching high-performance liquid chromatography (HPLC) for determining micafungin in human plasma samples. Human plasma was directly injected into a column-switching HPLC system with a MAYI-ODS pre-column to remove the plasma matrix. The calibration curve for micafungin showed good linearity in the range 0.1-10 µg/mL in human plasma. The mean relative standard deviation value of the intra-day and inter-day precision was less than 7.3%. More than 450 successive, accurate measurements were made before the system had to be washed with ammonium acetate solution. The therapeutic micafungin level in patients' plasma was successfully measured using this method. Because the pretreatment is simple and reproducible, our method can be used for routine therapeutic monitoring.
- Published
- 2012
42. Airway resistance correlates with the frequency of exacerbation in patient with COPD
- Author
-
Mayumi Yamamoto, Shintaro Suzuki, Shin Ohta, Takuya Yokoe, Akihiko Tanaka, Tsukasa Ohnishi, Hironori Sagara, Hitomi Furukawa, Tetsuya Honma, Yasunari Kishino, Yasunori Murata, and Sojiro Kusumoto
- Subjects
COPD ,medicine.medical_specialty ,Exacerbation ,business.industry ,Reactance ,medicine.disease ,respiratory tract diseases ,Airway resistance ,Internal medicine ,medicine ,Oscillometry ,Cardiology ,Physical therapy ,Outpatient clinic ,In patient ,business ,Gold stage - Abstract
Background: Many studies have reported that increasing rate of airflow limitation is correlated with frequency of exacerbation. Whereas the relationship between peripheral airway resistance and frequency of exacerbation in COPD has not yet been investigated. Aim: The aim of this study was to evaluate the airway resistance and reactance measured by forced oscillometry, and to correlate these with frequency of exacerbation in COPD patients. Methods: 310 patients with COPD (GOLD stage I to IV) who attended our outpatient clinic from September 2014 through January 2015 were selected. 110 patients fulfilled our criteria. We divided the patients into two groups. The 1st group was exacerbator group and the 2nd group was non-exacerbator group. The frequency of exacerbations, airway resistance and reactance were evaluated retrospectively on the basis of our database. Results: There were significant differences in expiratory and inspiratory resistance between the exacerbator group and non-exacerbator group. Differences in both expiratory and inspiratory were found at 20 Hz (R20), reactance at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area (ALX). Difference in only inspiratory resistance was found in differences between R5 and R20 (R5-R20). Conclusion: Airway resistance and reactance shown by X5, Fres and ALX may be useful to predict the risk of exacerbation in COPD patients.
- Published
- 2016
43. A case of anti-nuclear matrix protein 2 antibody positive myopathy associated with lung cancer
- Author
-
Fumiharu Kimura, Yasuhito Hamaguchi, Shin Ohta, Soichiro Ikeda, Kiichi Unoda, and Hideto Nakajima
- Subjects
0301 basic medicine ,myalgia ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,03 medical and health sciences ,Pneumonectomy ,0302 clinical medicine ,medicine ,Humans ,Myopathy ,Lung cancer ,Myositis ,Juvenile dermatomyositis ,Autoantibodies ,030203 arthritis & rheumatology ,Adenosine Triphosphatases ,business.industry ,Large cell ,Interstitial lung disease ,Chemoradiotherapy, Adjuvant ,medicine.disease ,Combined Modality Therapy ,Magnetic Resonance Imaging ,DNA-Binding Proteins ,030104 developmental biology ,Treatment Outcome ,Carcinoma, Large Cell ,Neurology (clinical) ,medicine.symptom ,business ,Tomography, X-Ray Computed - Abstract
Myositis-specific autoantibodies (MSAs) are associated with myositis. Anti-nuclear matrix protein 2 (NXP-2) antibody was recently identified as a major MSA and was observed mostly in juvenile dermatomyositis. We report the case of a 44-year-old man who presented with myopathy with anti-NXP-2 antibody and large cell carcinoma of the lung. He was hospitalized because of myalgia and edema of limbs. Neurological examination revealed mild proximal-dominant weakness in all four extremities, and laboratory studies showed elevated creatine kinase level (6,432 IU/l). Needle electromyography showed myogenic patterns. MRI of the lower limbs demonstrated inflammatory lesions in the thighs. Biopsied specimen from the left quadriceps femoris muscle showed mild mononuclear inflammatory infiltrate surrounding muscle fibres but no fiber necrosis. He was diagnosed with myopathy based on neurological examinations and clinical symptoms. His chest X-ray and CT showed tumor shadow on the right upper lung field, but CT didn't indicate the findings of interstitial lung disease. This was surgically removed, and a histological diagnosis of non-small cell lung cancer was suspected. He was also treated with definitive chemoradiotherapy before and after operation. His symptoms of myopathy promptly remitted with the preoperative chemotherapy. His serum analysis was positive for the anti-NXP-2. Further investigation and experience of MSAs are necessary to evaluate the therapeutic strategy against cancer-associated myopathy/myositis.
- Published
- 2016
44. [The Safety and efficacy of airway-hyperresponsiveness test for asthma using by SK-1211 (Methacholine Chloride)]
- Author
-
Hironori, Sagara, Akihiko, Tanaka, Shin, Ohta, Emi, Jinno, Naoki, Uchida, Takehiko, Sambe, Noriko, Hida, Yutaka, Suehiro, Satoru, Doi, Makoto, Kameda, Yukinori, Yoshida, Junji, Fukuoka, and Yuko, Kinoshita
- Subjects
Adult ,Male ,Young Adult ,Adolescent ,Humans ,Female ,Child ,Asthma ,Bronchial Provocation Tests ,Methacholine Chloride ,Bronchodilator Agents - Abstract
In abroad, Methacholine Chloride (Provocholine®) is used to meet the indications of the diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma. We examined efficacy, safety and pharmacokinetics of Methacholine Chloride (name of study drug: SK-1211) in order to get approved for the airway hyperresponsiveness test in Japan.Fifteen adult healthy volunteers, fifteen adult patients with asthma and ten pediatric patients with asthma were enrolled in this study. The airway hyperresponsiveness test with SK-1211 was conducted in accordance with Japanese Society of Allergology Standard Method.When the threshold value of PC20 was 8 mg/mL, the sensitivity of adult patients with asthma was 66.7% (10/15 subjects) and the specificity of adult healthy volunteers was 86.7% (13/15 subjects). The sensitivity of pediatric patients with asthma was 70.0% (7/10 subjects). Not all subjects experienced some adverse reactions during inhalation of SK-1211, all of which were mild in severity and resolved soon with inhalation of a bronchodilator. There were no serious adverse reactions reported.The airway hyperresponsiveness test with SK-1211 was no specific concern with safety and useful in the diagnosis of bronchial airway hyperresponsiveness.
- Published
- 2016
45. Evaluation of the association between sensitization to common inhalant fungi and poor asthma control
- Author
-
Akiko Fujiwara, Shin Ohta, Hironori Sagara, Yoshio Watanabe, Mayumi Yamamoto, Shintaro Suzuki, Akihiko Tanaka, Takuya Yokoe, Tetsuya Homma, Munehiro Yamaguchi, and Yoshitaka Uchida
- Subjects
0301 basic medicine ,Male ,Immunoglobulin E ,Severity of Illness Index ,Airborne allergen ,0302 clinical medicine ,immune system diseases ,Antibody Specificity ,Risk Factors ,Odds Ratio ,Immunology and Allergy ,Sensitization ,biology ,Middle Aged ,Respiratory Function Tests ,medicine.anatomical_structure ,Treatment Outcome ,Exhalation ,Penicillium ,Female ,Cladosporium ,Pulmonary and Respiratory Medicine ,Adult ,Immunology ,Nitric Oxide ,03 medical and health sciences ,Young Adult ,medicine ,Animals ,Humans ,Risk factor ,Asthma ,Aged ,business.industry ,Fungi ,Allergens ,medicine.disease ,biology.organism_classification ,respiratory tract diseases ,030104 developmental biology ,Cross-Sectional Studies ,030228 respiratory system ,Mycoses ,Exhaled nitric oxide ,biology.protein ,Immunization ,business - Abstract
Background Fungi are well-known airborne allergens that are predisposing environmental factors to asthma. Few comparative studies have evaluated sensitization to common inhalant fungi in relation to poor asthma control in patients with asthma. Objective To evaluate the association between sensitization to individual fungi and asthma control and elucidate the characteristics of patients with poorly controlled asthma sensitized to fungi. Methods This cross-sectional study was performed at Showa University Hospital between September 2014 and December 2014. The specific IgE levels for several major aeroallergens, including house dust mites, Japanese cedar, various types of pollen, furry animals, or insects, were measured with a fluorescent enzyme immunoassay in 160 patients with adult asthma. Results Fungal sensitization was predominant in men with asthma, and it was associated with poor asthma control. Sensitization to house dust mites, Japanese cedar, pollen, furry animals, or insects was not associated with poor asthma control. Logistic regression analyses revealed that patients sensitized to Aspergillus and Penicillium had a significantly increased risk of poor asthma control. More Penicillium IgE–positive patients were men and pet owners compared with Penicillium IgE–negative patients; in addition, Penicillium IgE–positive patients had higher total IgE levels. The Asthma Control Test level was significantly higher in Penicillium IgE–positive patients than in Penicillium IgE–negative patients. However, there were no differences in fractional exhaled nitric oxide, forced vital capacity, and forced expiratory volume in 1 second. Finally, sensitization to Aspergillus , Cladosporium , and Trichophyton were positively correlated with sensitization to Penicillium . Conclusion Sensitization to fungi is predominant in men, and it is associated with poor asthma control. In particular, sensitization to Penicillium and Aspergillus is a risk factor for asthma severity. These results have potential relevance in asthma management.
- Published
- 2016
46. The Purinergic G Protein-Coupled Receptor 6 Inhibits Effector T Cell Activation in Allergic Pulmonary Inflammation
- Author
-
Giorgio Giannattasio, Barbara Balestrieri, Shin Ohta, Joshua A. Boyce, Joshua R. Boyce, and Wei Xing
- Subjects
medicine.medical_treatment ,T cell ,Immunology ,Purinergic receptor ,Biology ,Molecular biology ,Cytokine ,medicine.anatomical_structure ,FLOX ,medicine ,Immunology and Allergy ,Antigen-presenting cell ,Receptor ,CD8 ,G protein-coupled receptor - Abstract
We show that the P2Y6 receptor, a purinergic G protein-coupled receptor with a high affinity for the nucleotide uridine diphosphate, is an important endogenous inhibitor of T cell function in allergic pulmonary inflammation. Mice conditionally deficient in P2Y6 receptors [p2ry6 (flox/flox);cre/+ mice] exhibited severe airway and tissue pathology relative to P2Y6-sufficient [p2ry6 (flox/flox)] littermates (+/+ mice) when treated intranasally with an extract of the dust mite Dermatophagoides farinae (Df). P2Y6 receptors were inducibly expressed by lung, lymph node, and splenic CD4+ and CD8+ T cells of Df-treated +/+ mice. Df-restimulated P2Y6-deficient lymph node cells produced higher levels of Th1 and Th2 cytokines, and polyclonally stimulated P2Y6-deficient CD4+ T cells proliferated faster than comparably stimulated P2Y6-sufficient cells. The absence of P2Y6 receptors on CD4+ cells, but not APCs, was sufficient to amplify cytokine generation. Thus, P2Y6 receptors protect the lung against exuberant allergen-induced pulmonary inflammation by inhibiting the activation of effector T cells.
- Published
- 2011
47. High-performance liquid chromatography determination of ketone bodies in human plasma by precolumn derivatization with p-nitrobenzene diazonium fluoroborate
- Author
-
Katsushi Inamura, Takashi Miida, Susumu Yamato, Shin Ohta, Kumiko Shinohara, Satoshi Hirayama, Saori Nakagawa, Ai Kubota, and Gen Watanabe
- Subjects
Chromatography ,Phenylpropionates ,Calibration curve ,Elution ,Biophysics ,Diazonium Compounds ,Ketone Bodies ,Cell Biology ,Standard solution ,Biochemistry ,High-performance liquid chromatography ,chemistry.chemical_compound ,chemistry ,Reagent ,Calibration ,Ketone bodies ,Humans ,Diazo ,Methanol ,Molecular Biology ,Chromatography, High Pressure Liquid - Abstract
We developed and validated a sensitive and convenient high-performance liquid chromatography (HPLC) method for the specific determination of ketone bodies (acetoacetate and D-3-hydroxybutyrate) in human plasma. p-Nitrobenzene diazonium fluoroborate (diazo reagent) was used as a precolumn derivatization agent, and 3-(2-hydroxyphenyl) propionic acid was used as an internal standard. After the reaction, excess diazo reagent and plasma proteins were removed by passing through a solid-phase cartridge (C(18)). The derivatives retained on the cartridge were eluted with methanol, introduced into the HPLC system, and then detected with UV at 380 nm. A calibration curve for acetoacetate standard solution with a 20-microl injection volume showed good linearity in the range of 1 to 400 microM with a 0.9997 correlation coefficient. For the determination of D-3-hydroxybutyrate, it was converted to acetoacetate before reaction with the diazo reagent by an enzymatic coupling method using D-3-hydroxybutyrate dehydrogenase and lactate dehydrogenase. A calibration curve for D-3-hydroxybutyrate standard solution also showed good linearity in the range of 1.5 to 2000 microM with a 0.9988 correlation coefficient. Analytical recoveries of acetoacetate and D-3-hydroxybutyrate in human plasma were satisfactory. The method was successfully applied to samples from diabetic patients, and results were consistent with those obtained using the thio-NAD enzymatic cycling method used in clinical laboratories.
- Published
- 2009
48. Risk Factors for Frequent Asthma Exacerbation in Japanese Patients with Refractory Asthma
- Author
-
Yoshio Watanabe, Mayumi Yamamoto, Kenji Minoguchi, Naruhito Oda, Toshiyuki Tazaki, Takashi Hirose, Yoshitaka Yamamoto, Akihiko Tanaka, Takuya Yokoe, Mitsuru Adachi, and Shin Ohta
- Subjects
medicine.medical_specialty ,Aspirin ,Asthma exacerbations ,Exacerbation ,business.industry ,Internal medicine ,medicine ,Refractory asthma ,medicine.disease ,business ,Asthma ,medicine.drug - Published
- 2009
49. Inhibitory Effects of the Mucoactive Agent, Fudosteine, on Leukocyte Elastase-induced Lung Inflammation and Goblet Cell Metaplasia in the Mouse
- Author
-
Mayumi Yamamoto, Naruhito Oda, Takuya Yokoe, Akihiko Tanaka, Yoshitaka Yamamoto, Toshio Nakadate, Toshiyuki Tazaki, Yoshio Watanabe, Shin Ohta, and Mitsuru Adachi
- Subjects
Goblet cell ,Chemokine ,Lung ,biology ,business.industry ,medicine.medical_treatment ,Elastase ,Inflammation ,Inhibitory postsynaptic potential ,medicine.anatomical_structure ,Cytokine ,Metaplasia ,Immunology ,medicine ,biology.protein ,medicine.symptom ,business - Published
- 2009
50. Clinical Significance of Measuring Serum Concentrations of Voriconazole in the Hematological Field
- Author
-
Susumu Yamato, Kenji Kawano, Hikaru Kobayashi, Sadahiko Shimoeda, Shin Ohta, Mutsuko Sasaki, Kazuyoshi Nakazawa, and Saori Nakagawa
- Subjects
Voriconazole ,medicine.medical_specialty ,Pathology ,Bilirubin ,business.industry ,Renal function ,Serum concentration ,Gastroenterology ,chemistry.chemical_compound ,chemistry ,Oral administration ,Internal medicine ,medicine ,Clinical significance ,Analysis of variance ,Liver dysfunction ,business ,medicine.drug - Abstract
To promote the proper use of voriconazole (VRCZ),we monitored VRCZ blood concentrations,and investigated the clinical significance of doing this.On comparing C/D (blood VRCZ concentration/VRCZ dose) values for different VRCZ administration methods we found that there was no significant difference between the intravenous drip and oral administration methods (t-test : P=0.607)in this respect.There was also no correlation between the dose of VRCZ per unit body weight and its blood concentration (variance analysis : R2=0.012,P=0.449).Though total bilirubin (T-Bil) levels were correlated with C/D values (variance analysis : R2=0.104,P=0.020),serum creatinine clearance (CCr) and C/D values (variance analysis : R2=0.062,P=0.078)were not correlated.Furthermore,C/D values in males were significantly higher than those in females (t-test : P=0.001).Approximately 25% of the patients had a blood concentration trough value exceeding 4.5μg/mL,which indicates an enhanced risk of liver dysfunction,and this suggests that the measurement of blood VRCZ concentrations is clinically important for preventing side effects.
- Published
- 2008
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.