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Koji Murakami

Section

Tohoku University Hospital

Job title

Assistant Professor

Degree

博士（医学）（東北大学）

researchmap

https://researchmap.jp/-_-123

J-GLOBAL ID

201801015842036459

Research Areas 1

Life sciences / Respiratory medicine /

Papers 54

Urine autotaxin levels reflect the disease activity of sarcoidosis Peer-reviewed

Koji Murakami, Tsutomu Tamada, Daisuke Saigusa, Eisaku Miyauchi, Masayuki Nara, Masakazu Ichinose, Makoto Kurano, Yutaka Yatomi, Hisatoshi Sugiura

Scientific Reports　12　(1)　2022/12
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/s41598-022-08388-6 　

eISSN： 2045-2322

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Abstract Since the clinical outcome of patients with sarcoidosis is still unpredictable, a good prognostic biomarker is necessary. Autotaxin (ATX) and phosphatidylserine-specific phospholipase A1 (PS-PLA1) function as main enzymes to produce lysophospholipids (LPLs), and these enzymes are attracting attention as useful biomarkers for several chronic inflammatory diseases. Here, we investigated the relationships between LPLs-producing enzymes and the disease activity of sarcoidosis. In total, 157 patients with sarcoidosis (active state, 51%) were consecutively enrolled. Using plasma or urine specimens, we measured the values of LPLs-producing enzymes. Urine ATX (U-ATX) levels were significantly lower in the active state compared to those in the inactive state, while the plasma ATX (P-ATX) and PS-PLA1 levels showed no significant difference between these two states. Concerning the comparison with existing clinical biomarkers for sarcoidosis, U-ATX showed a weak negative correlation to ACE, P-ATX a weak positive correlation to both ACE and sIL-2R, and PS-PLA1 a weak positive one to sIL-2R. Notably, only the U-ATX levels inversely fluctuated depending on the status of disease activity whether OCS had been used or not. These findings suggest that U-ATX is likely to be a novel and useful molecule for assessing the disease activity of sarcoidosis.
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force. International-journal Peer-reviewed

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, Yukinori Okada

Nature communications　13　(1)　4830-4830　2022/08/22

DOI： 10.1038/s41467-022-32276-2 　

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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.
DOCK2 is involved in the host genetics and biology of severe COVID-19. International-journal Peer-reviewed

Ho Namkoong, Ryuya Edahiro, Tomomi Takano, Hiroshi Nishihara, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Shuhei Azekawa, Yohei Mikami, Ho Lee, Takanori Hasegawa, Koji Okudela, Daisuke Okuzaki, Daisuke Motooka, Masahiro Kanai, Tatsuhiko Naito, Kenichi Yamamoto, Qingbo S Wang, Ryunosuke Saiki, Rino Ishihara, Yuta Matsubara, Junko Hamamoto, Hiroyuki Hayashi, Yukihiro Yoshimura, Natsuo Tachikawa, Emmy Yanagita, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Ryousuke Aoki, Ai Nakamura, Sonoko Harada, Hitoshi Sasano, 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, Takashi 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, Ken Suzuki, Yoko Naito, Yu-Chen Liu, Ayako Takuwa, Fuminori Sugihara, James B Wing, Shuhei Sakakibara, Nobuyuki Hizawa, Takayuki Shiroyama, Satoru Miyawaki, Yusuke Kawamura, Akiyoshi Nakayama, Hirotaka Matsuo, Yuichi Maeda, Takuro Nii, 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, Toshihiro Kishikawa, Shuhei Yamada, Shuhei Kawabata, Noriyuki Kijima, Masatoshi Takagaki, Noah Sasa, Yuya Ueno, Motoyuki Suzuki, Norihiko Takemoto, Hirotaka Eguchi, Takahito Fukusumi, Takao Imai, Munehisa Fukushima, Haruhiko Kishima, Hidenori Inohara, Kazunori Tomono, Kazuto Kato, Meiko Takahashi, Fumihiko Matsuda, 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, Kazuhiko Katayama, Masumi Ai, Yoshinori Fukui, 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, Yukinori Okada

Nature　609　(7928)　754-760　2022/08/08

DOI： 10.1038/s41586-022-05163-5 　

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Identifying the factors underlying severe COVID-19 in the host genetics is an emerging issue1-5. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls, which identified a variant on 5q35 (rs60200309-A) near DOCK2 associated with severe COVID-19 in younger (<65 ages) patients (nCase=440, odds ratio=2.01, P=1.2×10-8). This risk allele was prevalent in East Asians but rare in Europeans, showing a value of non-European GWAS. RNA-seq of 473 bulk peripheral blood identified decreasing effect of the risk allele on DOCK2 expression in younger patients. DOCK2 expression was suppressed in severe forms of COVID-19. Single cell RNA-seq analysis (n=61) identified cell type-specific downregulation of DOCK2 and COVID-19-specific decreasing effects of the risk allele on DOCK2 in non-classical monocytes. Immunohistochemistry of lung specimens from severe COVID-19 pneumonia showed suppressed DOCK2. Moreover, inhibition of DOCK2 function using CPYPP induced much more severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection characterized as weight loss, lung edema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 plays an important role in the host immune response to SARS-CoV-2 infection and development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
The Clinical Features of Patients with Sarcoidosis and Malignant Diseases in Japan. Peer-reviewed

Tsutomu Tamada, Masayuki Nara, Koji Murakami, Shunichi Gamo, Hidemi Aritake, Megumi Shimizu, Itsuro Kazama, Masakazu Ichinose, Hisatoshi Sugiura

Internal medicine (Tokyo, Japan)　60　(2)　209-216　2021

DOI： 10.2169/internalmedicine.5441-20 　

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Objective Recent studies suggest a significant association between sarcoidosis and malignancy, although the results have remained controversial. The aim of this study is to evaluate the clinical features of patients with sarcoidosis associated with malignant diseases in Japan. Patients We conducted a medical record review of all sarcoidosis patients in Tohoku University Hospital between January 1, 1981, and May 31, 2017. Methods The clinical records and pathology reports for each patient were screened, and the clinical characteristics of malignancies as well as sarcoidosis were reviewed. Results A total of 52 (18.8%) patients with malignancy were identified among 277 patients with sarcoidosis. Among those 52 patients, we identified 62 with malignant diseases. These patients were older and more likely to be women than the remaining 225 (81.2%) sarcoidosis patients without malignancy. The most prevalent malignant disease was breast cancer (14 cases, 22.6%), followed by stomach cancer (8 cases, 12.9%) and lung cancer (7 cases, 11.3%). Among the 14 patients with both sarcoidosis and breast cancer, 8 (57.1%) were diagnosed with breast cancer before sarcoidosis. All of these eight cases had undergone surgical resection of the cancer. Conclusion This study showed a higher incidence of patients with both sarcoidosis and malignancy in Japan than in some western countries. Breast cancer is the most prevalent malignant disease. The high frequency of sarcoidosis after surgical resection of breast cancer may suggest a causative association between malignancy and the development of sarcoidosis.
診断基準改訂前後のサルコイドーシスの臨床的特徴と予後予測因子としてのsIL-2R変化率の検討 Peer-reviewed

村上康司, 玉田勉, 奈良正之, 光石陽一郎, 村松聡士, 海老名雅仁, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　33　(1-2)　83-89　2013/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile. International-journal

Daisuke Narita, Eiji Hishinuma, Risa Ebina-Shibuya, Eisaku Miyauchi, Naomi Matsukawa, Ikuko N Motoike, Kengo Kinoshita, Seizo Koshiba, Yoko Tsukita, Hirotsugu Notsuda, Nozomu Kimura, Ryota Saito, Koji Murakami, Naoya Fujino, Tomohiro Ichikawa, Mitsuhiro Yamada, Tsutomu Tamada, Hisatoshi Sugiura

Lung cancer (Amsterdam, Netherlands)　200　108082-108082　2025/01/08

DOI： 10.1016/j.lungcan.2025.108082 　

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BACKGROUND: Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression. METHODS: Plasma samples from patients with recurrent or metastatic non-small cell lung carcinomas diagnosed at Tohoku University Hospital between 2019 and 2024 were used in this study. Metabolomic analysis was performed using the Biocrates Life Sciences MxP Quant 500 kit. Multivariate, principal component, and orthogonal partial least squares discriminant analyses were performed. RESULTS: The triglyceride and phosphatidylcholine concentrations were higher in the patients with early than in those with advanced lung adenocarcinomas. However, the cholesterol ester concentrations were higher for the patients with advanced lung cancer. The concentrations of hexosylceramide were higher in patients with early lung adenocarcinoma than in those with squamous cell carcinoma. Relative to epidermal growth factor receptor (EGFR)-mutation negative cases, the EGFR-mutation positive cases showed marked differences between the ceramide and triglyceride concentrations. For the best therapeutic effect of EGFR-TKI treatment, the hexosylceramide (HexCer) (d18:1/24:0), ceramide (Cer) (d18:2/22:0), and ceramide (Cer) (d18:2/24:0) concentrations were higher for the stable and progressive disease groups. The concentrations of phosphatidylcholine (PC) ae C42:2, sphingomyelin (SM) C24:1, and lysophosphatidylcholine (lysoPC) a C18:2 were higher in the partial response group treated with immune checkpoint inhibitors and chemotherapy. CONCLUSION: Metabolomic analysis may be useful for the diagnosis and treatment of lung cancer and may provide clues for new therapeutic strategies. PC ae C42:2, SM C24:1, and lysoPC a C18:2 can serve as predictive biomarkers for monitoring the therapeutic effects of the combination of immune checkpoint inhibitors and chemotherapy.
ステロイド治療中に自己免疫性肺胞蛋白症が続発した線維性過敏性肺炎の一例

杉山初美, 村上康司, 東出直樹, 玉田勉, 山本友梨, 鈴木眞奈美, 岩崎史, 相澤洋之, 沼倉忠久, 宮内栄作, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　43　(サプリメント号)　66-66　2023/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273

eISSN： 1884-6114
ステロイド治療中に自己免疫性肺胞蛋白症が続発した線維性過敏性肺炎の一例

杉山初美, 村上康司, 東出直樹, 玉田勉, 山本友梨, 鈴木眞奈美, 岩崎史, 相澤洋之, 沼倉忠久, 宮内栄作, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　43　(サプリメント号)　66-66　2023/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273

eISSN： 1884-6114
COVID-19 治療 COVID-19重症例に対するステロイド治療後の再燃リスク因子の検討

村上康司, 佐野寛仁, 東出直樹, 杉山初美, 徳田浩一, 金森肇, 玉田勉, 杉浦久敏

日本呼吸器学会誌　12　(増刊)　179-179　2023/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
専門的医療継続のためのCOVID-19診療体制変更の取り組み

杉山初美, 村上康司, 佐野寛仁, 東出直樹, 徳田浩一, 金森肇, 玉田勉, 杉浦久敏

日本呼吸器学会誌　12　(増刊)　346-346　2023/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
COVID-19 治療 COVID-19重症例に対するステロイド治療後の再燃リスク因子の検討

村上康司, 佐野寛仁, 東出直樹, 杉山初美, 徳田浩一, 金森肇, 玉田勉, 杉浦久敏

日本呼吸器学会誌　12　(増刊)　179-179　2023/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
専門的医療継続のためのCOVID-19診療体制変更の取り組み

杉山初美, 村上康司, 佐野寛仁, 東出直樹, 徳田浩一, 金森肇, 玉田勉, 杉浦久敏

日本呼吸器学会誌　12　(増刊)　346-346　2023/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
Antibody responses to second doses of COVID-19 vaccination in lung cancer patients undergoing treatment. International-journal

Daisuke Narita, Risa Ebina-Shibuya, Eisaku Miyauchi, Yoko Tsukita, Ryota Saito, Koji Murakami, Nozomu Kimura, Hisatoshi Sugiura

Respiratory investigation　61　(2)　247-253　2022/12/15

DOI： 10.1016/j.resinv.2022.11.005 　

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BACKGROUND: Several reports have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection tends to have more severe outcomes in cancer patients. Although vaccination reduces the risk of severe disease, data on antibody titers achieved by vaccination is scarce in cancer patients. METHODS: We collected 79 blood samples (69 lung cancer patients and 10 control individuals) and conducted an anti-SARS-CoV-2 antibody assay to compare the antibody titer achieved with current treatment. Sixty-eight patients (86%) received the BNT162 mRNA vaccine and 11 (14%) received the mRNA-1273 vaccine. They were categorized according to the current treatment: control individuals without cancer (cohort A), lung cancer patients who were treated with cytotoxic chemotherapy (cohort B), immunotherapy (cohort C), combination of cytotoxic chemotherapy and immunotherapy (cohort D), tyrosine kinase inhibitors (cohort E), and radiation therapy (cohort F). RESULTS: Among 69 lung cancer patients (cohort B-F), 57 (83%) had adenocarcinoma, and 66 (96%) had advanced-stage cancer. In the anti-SARS-CoV-2 antibody assay, the antibody titer was significantly lower in lung cancer patients than in control individuals (p = 0.01). The median antibody titers were 161 AU/ml in control individuals and 59.9 AU/ml in lung cancer patients. CONCLUSIONS: Antibody titers after the second vaccination were lower in cancer patients than those in healthy individuals. Our findings provide essential information for understanding the benefits and necessity of additional vaccination to prevent SARS-CoV-2 infection in lung cancer patients.
Characteristics of hospitalized patients with COVID-19 during the first to fifth waves of infection: a report from the Japan COVID-19 Task Force. International-journal

Ho Lee, Shotaro Chubachi, Ho Namkoong, Takanori Asakura, Hiromu Tanaka, Shiro Otake, Kensuke Nakagawara, Atsuho Morita, Takahiro Fukushima, Mayuko Watase, Tatsuya Kusumoto, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

BMC infectious diseases　22　(1)　935-935　2022/12/12

DOI： 10.1186/s12879-022-07927-w 　

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BACKGROUND: We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. METHODS: We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. RESULTS: Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9]) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p < 0.0001), and post-hospitalization complications, such as bacterial infections (21.3%, p < 0.0001), were also noticeable. In addition, there was an increase in the use of drugs such as remdesivir/baricitinib/tocilizumab/steroids during the latter COVID-19 waves. In the fifth COVID-19 wave, patients exhibited a greater number of presenting symptoms, and a higher percentage of patients required oxygen therapy at the time of admission. However, the percentage of patients requiring invasive mechanical ventilation was the highest in the first COVID-19 wave and the mortality rate was the highest in the third COVID-19 wave. CONCLUSIONS: We identified differences in clinical characteristics of hospitalized patients with COVID-19 in each COVID-19 wave up to the fifth COVID-19 wave in Japan. The fifth COVID-19 wave was associated with greater disease severity on admission, the third COVID-19 wave had the highest mortality rate, and the first COVID-19 wave had the highest percentage of patients requiring mechanical ventilation.
Impact of upper and lower respiratory symptoms on COVID-19 outcomes: a multicenter retrospective cohort study. International-journal

Kensuke Nakagawara, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ho Lee, Shuhei Azekawa, Shiro Otake, Takahiro Fukushima, Atsuho Morita, Mayuko Watase, Kaori Sakurai, Tatsuya Kusumoto, Takanori Asakura, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Ryuya Edahiro, Koji Murakami, Yasunori Sato, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Respiratory research　23　(1)　315-315　2022/11/15

DOI： 10.1186/s12931-022-02222-3 　

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BACKGROUND: Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients. METHODS: This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death. RESULTS: Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11-0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43-4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course. CONCLUSIONS: Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.
リゾリン脂質産生酵素によるサルコイドーシス疾患活動性の評価

村上康司, 玉田勉, 三枝大輔, 奈良正之, 宮内栄作, 蔵野信, 矢冨裕, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　42　(サプリメント号)　74-74　2022/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273

eISSN： 1884-6114
サルコイドーシスの自然寛解後に抗ARS抗体症候群を合併した一例

角藤翔, 村上康司, 玉田勉, 奈良正之, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　42　(1-2)　74-75　2022/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273

eISSN： 1884-6114
新型コロナウイルスワクチン接種後に発症したサルコイドーシスの一例

杉山初美, 沼倉忠久, 村上康司, 玉田勉, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　42　(サプリメント号)　66-66　2022/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273

eISSN： 1884-6114
リゾリン脂質産生酵素によるサルコイドーシス疾患活動性の評価

村上康司, 玉田勉, 三枝大輔, 奈良正之, 宮内栄作, 蔵野信, 矢冨裕, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　42　(サプリメント号)　74-74　2022/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273

eISSN： 1884-6114
Clinical clustering with prognostic implications in Japanese COVID-19 patients: report from Japan COVID-19 Task Force, a nation-wide consortium to investigate COVID-19 host genetics. International-journal

Shiro Otake, Shotaro Chubachi, Ho Namkoong, Kensuke Nakagawara, Hiromu Tanaka, Ho Lee, Atsuho Morita, Takahiro Fukushima, Mayuko Watase, Tatsuya Kusumoto, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

BMC infectious diseases　22　(1)　735-735　2022/09/14

DOI： 10.1186/s12879-022-07701-y 　

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BACKGROUND: The clinical course of coronavirus disease (COVID-19) is diverse, and the usefulness of phenotyping in predicting the severity or prognosis of the disease has been demonstrated overseas. This study aimed to investigate clinically meaningful phenotypes in Japanese COVID-19 patients using cluster analysis. METHODS: From April 2020 to May 2021, data from inpatients aged ≥ 18 years diagnosed with COVID-19 and who agreed to participate in the study were collected. A total of 1322 Japanese patients were included. Hierarchical cluster analysis was performed using variables reported to be associated with COVID-19 severity or prognosis, namely, age, sex, obesity, smoking history, hypertension, diabetes mellitus, malignancy, chronic obstructive pulmonary disease, hyperuricemia, cardiovascular disease, chronic liver disease, and chronic kidney disease. RESULTS: Participants were divided into four clusters: Cluster 1, young healthy (n = 266, 20.1%); Cluster 2, middle-aged (n = 245, 18.5%); Cluster 3, middle-aged obese (n = 435, 32.9%); and Cluster 4, elderly (n = 376, 28.4%). In Clusters 3 and 4, sore throat, dysosmia, and dysgeusia tended to be less frequent, while shortness of breath was more frequent. Serum lactate dehydrogenase, ferritin, KL-6, D-dimer, and C-reactive protein levels tended to be higher in Clusters 3 and 4. Although Cluster 3 had a similar age as Cluster 2, it tended to have poorer outcomes. Both Clusters 3 and 4 tended to exhibit higher rates of oxygen supplementation, intensive care unit admission, and mechanical ventilation, but the mortality rate tended to be lower in Cluster 3. CONCLUSIONS: We have successfully performed the first phenotyping of COVID-19 patients in Japan, which is clinically useful in predicting important outcomes, despite the simplicity of the cluster analysis method that does not use complex variables.
Clinical features of COVID-19 patients with rebound phenomenon after corticosteroid therapy

Koji Murakami, Hirohito Sano, Naoki Tode, Yoko Tsukita, Kei Sato, Daisuke Narita, Nozomu Kimura, Shuichiro Matsumoto, Yoshinao Ono, Chikashi Iwasaki, Hatsumi Sugiyama, Manami Suzuki, Sho Kakuto, Shuichi Konno, Hajime Kanamori, Hiroaki Baba, Kengo Oshima, Kentarou Takei, Koichi Tokuda, Tsutomu Tamada, Hisatoshi Sugiura

BMJ OPEN RESPIRATORY RESEARCH　9　(1)　2022/09

DOI： 10.1136/bmjresp-2022-001332 　

eISSN： 2052-4439
U-shaped association between abnormal serum uric acid levels and COVID-19 severity: reports from the Japan COVID-19 Task Force. International-journal Peer-reviewed

Takahiro Fukushima, Shotaro Chubachi, Ho Namkoong, Shiro Otake, Kensuke Nakagawara, Hiromu Tanaka, Ho Lee, Atsuho Morita, Mayuko Watase, Tatsuya Kusumoto, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases　122　747-754　2022/09

DOI： 10.1016/j.ijid.2022.07.014 　

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OBJECTIVES: This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population. METHODS: We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia. RESULTS: Patients with high serum uric acid levels were older and had higher body weight and body mass index than those without. In addition, the multiple logistic regression analysis revealed a significant association between high serum uric acid levels or a history of hyperuricemia and an increased risk of IMV (odds ratio [OR] = 1.77; P = 0.03/OR = 1.56; P = 0.04). Moreover, patients with low uric acid levels on admission were also associated significantly with the requirement of IMV (OR = 5.09; P <0.0001). CONCLUSION: Abnormal serum uric acid levels or a history of hyperuricemia were significantly associated with COVID-19 severity in the Japanese cohort.
A Novel Development of Sarcoidosis following COVID-19 Vaccination and a Literature Review. Peer-reviewed

Tadahisa Numakura, Koji Murakami, Tsutomu Tamada, Chiaki Yamaguchi, Chihiro Inoue, Shinya Ohkouchi, Naoki Tode, Hirohito Sano, Hiroyuki Aizawa, Kei Sato, Ayumi Mitsune, Hajime Kurosawa, Toru Nakazawa, Hisatoshi Sugiura

Internal medicine (Tokyo, Japan)　61　(20)　3101-3106　2022/08/10

DOI： 10.2169/internalmedicine.0104-22 　

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BNT162b2 (Pfizer/BioNTech) is a coronavirus disease 2019 (COVID-19) vaccine containing nucleoside-modified messenger RNA encoding the severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Recently, ocular complications of mRNA vaccines have been reported increasingly frequently. However, immunological adverse events due to mRNA vaccines in real-world settings are not fully known. We herein report the novel development of sarcoidosis manifested as uveitis, bilateral hilar lymphadenopathy, angiotensin-converting enzyme elevation, and epithelioid and giant cell granuloma formation in the lung soon after the first BNT162b2 injection and review the current literature, including three reported cases of sarcoid-like reaction following COVID-19 vaccination.
Effects of mild obesity on outcomes in Japanese patients with COVID-19: a nationwide consortium to investigate COVID-19 host genetics. International-journal Peer-reviewed

Ho Lee, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Shiro Otake, Kensuke Nakagawara, Atsuho Morita, Takahiro Fukushima, Mayuko Watase, Tatsuya Kusumoto, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Nutrition & diabetes　12　(1)　38-38　2022/08/09

DOI： 10.1038/s41387-022-00217-z 　

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BACKGROUND: Obesity is reported to be a risk factor for severe disease in patients with coronavirus disease 2019 (COVID-19). However, there are no specific reports on the risk of severe disease according to body mass index (BMI) in Japan. Thus, this study aimed to investigate the effect of obesity stratified by BMI on the severity of COVID-19 in the general Japanese population. METHODS: From February 2020 to May 2021, 1 837 patients aged ≥18 years were enrolled in the Japan COVID-19 Task Force. Patients with known BMI and disease severity were analyzed. Severity was defined as critical if the patient was treated in the intensive care unit, required invasive mechanical ventilation, or died. RESULTS: Class 1 obesity (25.0 ≤ BMI < 30.0 kg/m2), class 2 obesity (30.0 ≤ BMI < 35.0 kg/m2), and class 3 or 4 obesity (BMI ≥ 35 kg/m2) were present in 29%, 8%, and 3% of the cases, respectively. Multiple logistic regression analysis with known risk factors for critical illness indicated that class 2 obesity was an independent risk factor for oxygenation (adjusted odds ratio, 4.75) and critical cases (adjusted odds ratio, 1.81). Class 1 obesity and class 3 or 4 obesity were independent risk factors for oxygen administration (adjusted odds ratios 2.01 and 3.12, respectively), but not for critical cases. However, no differences in the mortality rates were observed between the BMI classes (P = 0.5104). CONCLUSION: Obesity is a risk factor for respiratory failure in Japanese patients with COVID-19, regardless of the degree of obesity. However, it may not cause severe COVID-19 in a dose-response relationship with BMI. COVID-19 patients with mild obesity may benefit from aggressive intensive care.
COVID-19 in a Hairy Cell Leukemia Patient: A Rare Case Report. Peer-reviewed

Hirohito Sano, Koji Murakami, Hisayuki Yokoyama, Chie Suzuki, Yudai Iwasaki, Eiichi Kodama, Hisatoshi Sugiura

The Tohoku journal of experimental medicine　258　(1)　63-68　2022/07/21

DOI： 10.1620/tjem.2022.J058 　

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The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.
COVID-19に対するステロイド治療後再燃例の検討

村上康司, 佐野寛仁, 東出直樹, 佐藤慶, 徳田浩一, 大島謙吾, 金森肇, 馬場啓聡, 武井健太郎, 玉田勉, 杉浦久敏

日本呼吸器学会誌　11　(増刊)　212-212　2022/04
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
The Immediate Onset of Isolated and Unilateral Abducens Nerve Palsy Associated with COVID-19 Infection: A Case Report and Literature Review. Peer-reviewed

Takafumi Kubota, Naoto Sugeno, Hirohito Sano, Koji Murakami, Kensuke Ikeda, Tatsuro Misu, Masashi Aoki

Internal medicine (Tokyo, Japan)　61　(11)　1761-1765　2022

DOI： 10.2169/internalmedicine.9308-22 　

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Cranial nerve palsy associated with coronavirus disease 2019 (COVID-19) is rare. We herein report the first Asian case of the immediate onset of isolated and unilateral abducens nerve palsy (ANP) accompanied with COVID-19 infection. A 25-year-old man developed diplopia one day after the COVID-19 symptom onset. Neurological examination revealed limitation of left eye abduction without ataxia and hyporeflexia. Negative anti-ganglioside antibody results and mild albuminocytological dissociation were noted. The patient was diagnosed with left ANP accompanied by COVID-19 infection. The ANP spontaneously recovered without treatment. ANP can develop during the early phase of COVID-19 infection and adversely affect patients' quality of life.
Mapping the human genetic architecture of COVID-19

Mari E. K. Niemi, Juha Karjalainen, Mark Daly, Andrea Ganna, Juha Mehtonen, Mattia Cordioli, Mari Kaunisto, Sara Pigazzini, Kati Donner, Katja Kivinen, Aarno Palotie, Mark J. Daly, Rachel G. Liao, Masahiro Kanai, Kumar Veerapen, Camelia Minica, Amy Trankiem, Mary K. Balaconis, Huy Nguyen, Matthew Solomonson, Laurent Francioli, Qingbo Wang, Robert C. Green, Sam Bryant, Hilary Finucane, Alicia R. Martin, Wei Zhou, Lindokuhle Nkambule, Konrad J. Karczewski, Elizabeth G. Atkinson, Kristin Tsuo, Nikolas Baya, Patrick Turley, Rahul Gupta, Raymond K. Walters, Duncan S. Palmer, Gopal Sarma, Nathan Cheng, Wenhan Lu, Claire Churchhouse, Jacqueline Goldstein, Daniel King, Cotton Seed, Benjamin M. Neale, F. Kyle Satterstrom, Gita A. Pathak, Frank R. Wendt, Renato Polimanti, Shea J. Andrews, Laura Sloofman, Stuart C. Sealfon, Israel Fernandez-Cadenas, Eva C. Schulte, Ulrike Protzer, Pasquale Striano, Domenico A. Coviello, Federico Zara, Vincenzo Salpietro, Michele Iacomino, Paolo Scudieri, Renata Bocciardi, Carlo Minetti, Maria Stella Vari, Francesca Madia, Eirini Marouli, Stavroula Kanoni, Loukas Moutsianas, Mohd Anisul Karim, Maya Ghoussaini, Jeremy Schwartzentruber, Ian Dunham, Jeanne Savage, Danielle Posthuma, Elleke Tissink, Emil Uffelmann, Guillaume Butler-Laporte, J. Brent Richards, Tomoko Nakanishi, David R. Morrison, Vincenzo Forgetta, Biswarup Ghosh, Laetitia Laurent, Danielle Henry, Tala Abdullah, Olumide Adeleye, Noor Mamlouk, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk, Branka Vulesevic, Meriem Bouab, Charlotte Guzman, Louis Petitjean, Chris Tselios, Xiaoqing Xue, Jonathan Afilalo, Darin Adra, Han-Na Kim, Yukinori Okada, Jinyoung Byun, Younghun Han, Mohammed Jashim Uddin, George Davey Smith, Cristen J. Willer, Joseph D. Buxbaum, Laura G. Sloofman, Brett L. Collins, Tess Levy, Slayton J. Underwood, Bari Britvan, Katherine Keller, Lara Tang, Michael Peruggia, Liam L. Hiester, Kristi Niblo, Alexandra Aksentijevich, Alexander Labkowsky, Avromie Karp, Menachem Zlatopolsky, Jatin Arora, Soumya Raychaudhuri, Josep Mercader, Caroline Cusick, Bogdan Pasaniuc, Hanna Julienne, Hugues Aschard, Huwenbo Shi, Loic Yengo, Karolina Chwialkowska, Margherita Francescatto, Lea Davis, V. Eric Kerchberger, Sulggi Lee, James Priest, Nirmal Vadgama, Yosuke Tanigawa, Alessandra Renieri, Vijay G. Sankaran, David van Heel, Adolfo de Salazar, David A. van Heel, Karen A. Hunt, Bhavi Trivedi, Patrick Deelen, Lude Franke, Annique Claringbould, Esteban Lopera, Robert Warmerdam, Irene van Blokland, Pauline Lanting, Vincent Mooser, Rui Li, Alexandre Belisle, Pierre Lepage, Jiannis Ragoussis, Daniel Auld, G. Mark Lathrop, Les Biesecker, J. Kenneth Baillie, Sara Clohisey, Max Head Fourman, James Furniss, Chris Haley, Andy Law, Jonathan Millar, Erola Pairo-Castineira, Nicholas Parkinson, Konrad Rawlik, Clark D. Russell, Barbara Shih, Albert Tenesa, Bo Wang, Marie Zechner, Andrew Law, Ross Hendry, Ruth Armstrong, Ceilia Boz, Adam Brown, Louise Cullum, Nicky Day, Esther Duncan, Paul Finernan, Ailsa Golightly, Dawn Law, Rachel Law, Sarah Law, Hanning Mal, Ellie Mcmaster, Jen Meikle, Wilna Oosthuyzen, Trevor Paterson, Andrew Stenhouse, Maaike Swets, Helen Szoor-McElhinney, Filip Taneski, Tony Wackett, Mairi Ward, Jane Weaver, Judy Coyle, Bernadette Gallagher, Rebecca Lidstone-Scott, Debbie Hamilton, Fiona Griffiths, Sean Keating, Timothy Walsh, Andrew D. Bretherick, Graeme Grimes, Caroline Hayward, Lucija Klaric, Alison M. Meynert, Chris P. Ponting, Anne Richmond, Veronique Vitart, James F. Wilson, Francesca Mari, Mirjam Lista, Valentina Perticaroli, Chiara Fallerini, Sergio Daga, Margherita Baldassarri, Francesca Fava, Elisa Frullanti, Floriana Valentino, Gabriella Doddato, Annarita Giliberti, Mirella Bruttini, Susanna Croci, Ilaria Meloni, Giada Beligni, Andrea Tommasi, Laura Di Sarno, Maria Palmieri, Miriam Lucia Carriero, Diana Alaverdian, Nicola Iuso, Gabriele Inchingolo, Rossella Tita, Sara Amitrano, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Montagnani, Mario Tumbarello, Simone Furini, Elisa Benetti, Kristina Zguro, Katia Capitani, Giacomo Zanelli, Francesco Bianchi, Anna Bernasconi, Stefano Ceri, Pietro Pinoli, Stefano Ceri Baillie, Arif Canakoglu, Brooke Wolford, Annika Faucon, Atanu Kumar Dutta, Sanjay Patel, Claudia Schurmann, Emi Harry, Ewan Birney, Jamal Nasir, Minttu Marttila, Nicole Dueker, Sophie Limou, Souad Rahmouni, Hamdi Mbarek, Dima Darwish, Said I. Ismail, Chadi Saad, Yaser Al-Sarraj, Radja Messai Badji, Wadha Al-Muftah, Asma Al Thani, Md Mesbah Uddin, Raquel Albertos, Ricard Ferrer, Jordi Perez-Tur, Ruolin Li, Carolina Medina-Gomez, Bahar Sedaghati-Khayat, Costanza Vallerga, Cindy Boer, Ingrid Kennis-Szilagyi, Vid Prijatelj, Lasse Folkersen, Ida Moltke, Nils Koelling, Chris A. Spencer, Alexander Teumer, Athanasios Kousathanas, Dorota Pasko, Mark J. Caulfield, Richard H. Scott, Susan Walker, Alex Stuckey, Christopher A. Odhams, Daniel Rhodes, Tom Fowler, Augusto Rendon, Georgia Chan, Prabhu Arumugam, Alicia Utrilla, Ricardo A. Verdugo, Ruth Zarate, David Gomez-Cabrero, Elena Carnero-Montoro, Marta E. Alarcon-Riquelme, Manuel Martinez-Bueno, Carmen L. Cadilla, Andres Moreno-Estrada, Adriana Garmendia, Leire Moya, Palwende Romuald Boua, Marie-Julie Fave, Audrey Lemacon, Isabelle Migeotte, Reka Varnai, Jozsef L. Szentpeteri, Csilla Sipeky, Francesca Colombo, Kathrin von Hohenstaufen, Pietro Lio, Hogune Im, Chulho Han, Han Song, Jiwoo Lim, Younhe Lee, Sugyeong Kim, Biljana Atanasovska, Hajar Fauzan Ahmad, Philip Jansen, Jouke Jan Hottenga, Meike Bartels, Eco J. C. de Geus, Michel G. Nivard, Sergey A. Kornilov, Ilangkumaran Sivanadhan, Sarala Perumal, Sahar Esmaeeli, Nathaniel M. Pearson, Adam Auton, Janie F. Shelton, Anjali J. Shastri, Teresa Filshtein-Sonmez, Daniella Coker, Antony Symons, Stella Aslibekyan, Jared O'Connell, Chelsea Ye, Catherine H. Weldon, Jorge Esparza-Gordillo, Minoli Perera, Guang Yang, Cristina Alarcon, Stefanie Herrmann, Paula Friedman, Kevin O'Leary, Sophia Mazurek, Matthew Tuck, Jeff Banagan, Zacharia Hamidi, Travis O'Brien, David Meltzer, Noora Raffat, Carmen de la Horra, Peter O'Donnell, Edith Nutescu, Diana Moreno, April Barbour, Rocio Gallego-Duran, Bart Ferwerda, Diederik van de Beek, Matthijs C. Brouwer, Martijn Beudel, Rutger Koning, Alexander P. J. Vlaar, Anne Geke Algera, Frank van Baarle, Lieuwe Bos, Michela Botta, Sanne de Bruin, Esther Bulle, Dave Dongelmans, Paul Elbers, Lucas Fleuren, Armand Girbes, Laura Hagens, Leo Heunks, Janneke Horn, Niels van Mourik, Frederique Paulus, Jorinde Raasveld, Marcus J. Schultz, Marry Smit, Charlotte Teunissen, Patrick Thoral, Heder de Vries, W. Joost Wiersinga, Michiel van Agtmael, Marije Bomers, Justin de Brabander, Godelieve de Bree, Osoul Chouchane, Suzanne Geerlings, Bram Goorhuis, Martin P. Grobusch, Vanessa Harris, Sabine M. Hermans, Joppe W. Hovius, Jeannine Nellen, Edgar Peters, Tom van der Poll, Jan M. Prins, Tom Reijnders, Michiel Schinkel, Alex Schuurman, Kim Sigaloff, Cornelis S. Stijnis, Anissa Tsonas, Marc van der Valk, Michele van Vugt, A. H. Koos Zwinderman, Diane Bax, Alex Cloherty, Theo Geijtenbeek, Florianne Hafkamp, Bennedikt Preckel, Harm Jan Bogaard, Peter Bonta, Esther J. Nossent, Marianna Bugiani, Bart Geerts, Markus Hollmann, Denise Veelo, Jorg Hamann, Robert Hemke, Menno D. de Jong, Willemke Stilma, Dorien Wouters, Rene P. Minnaar, Adrie Kromhout, Kees W. J. van Uffelen, Ruud A. Wolterman, Genevieve Roberts, Danny Park, Catherine A. Ball, Marie Coignet, Shannon McCurdy, Spencer Knight, Raghavendran Partha, Brooke Rhead, Miao Zhang, Nathan Berkowitz, Michael Gaddis, Keith Noto, Luong Ruiz, Milos Pavlovic, Eurie L. Hong, Kristin Rand, Ahna Girshick, Harendra Guturu, Asher Haug Baltzell, Michel Georges, Sofia Melo, Nicolas Jacques, Emmanuel Di Valentin, Francois Giroule, Alice Collignon, Coraline Radermecker, Marielle Lebrun, Helene Peree, Samuel Latour, Olivia Barada, Judit Sanchez, Margot Meunier, Emeline Mariavelle, Sandy Anania, Helene Gazon, Myriam Mni, Marie Wery, Yasmine Belhaj, Julien Guntz, Laurent Jadot, Sabine Claassen, Yves Beguin, Stephanie Gofflot, Kamilia El Kandoussi, Raphael Thonon, Youssef Bouysran, Adeline Busson, Xavier Peyrassol, Francoise Wilkin, Bruno Pichon, Guillaume Smits, Isabelle Vandernoot, Jean-Christophe Goffard, Michel Moutschen, Benoit Misset, Gilles Darcis, Julien Guiot, Samira Azarzar, Patricia Dellot, Axelle Bertrand, Gilles Parzibut, Mathilde Clarinval, Catherine Moermans, Olivier Malaise, Pascale Huynen, Alyssia Mesdagh, Claire Josse, Bouchra Boujemla, Danusia Juszczak, Marjorie Fadeur, Severine Camby, Christelle Meuris, Marie Thys, Jessica Jacques, Monique Henket, Philippe Leonard, Frederic Frippiat, Jean-Baptiste Giot, Anne-Sophie Sauvage, Christian Von Frenckell, Alicia Staderoli, Bernard Lambermont, Edouad Louis, Marc Afilalo, Maureen Oliveira, Bluma Brenner, Nathalie Brassard, Madeleine Durand, Michael Chasse, Daniel E. Kaufmann, Erwin Schurr, Lea K. Davis, Nancy J. Cox, Jennifer E. Below, Julia M. Sealock, Annika B. Faucon, Megan M. Shuey, Hannah G. Polikowsky, Lauren E. Petty, Douglas M. Shaw, Hung-Hsin Chen, Wanying Zhu, Kerstin U. Ludwig, Julia Schroeder, Selina Rolker, Markus M. Nothen, Julia Fazaal, Carlo Maj, Verena Keitel, Bjorn-Erik Ole Jensen, Torsten Feldt, Lisa Knopp, Ingo Kurth, Thomas Eggermann, Nikolaus Marx, Michael Dreher, Isabell Pink, Markus Cornberg, Thomas Illig, Sonja Volland, Clara Lehmann, Philipp Schommers, Max Augustin, Jan Rybniker, Philipp Koehler, Oliver A. Cornely, Janine Altmuller, Marc M. Berger, Thorsten Brenner, Anke Hinney, Oliver Witzke, Robert Bals, Christian Herr, Nicole Ludwig, Jorn Walter, Christian Fuchsberger, Cristian Pattaro, Alessandro De Grandi, Peter Pramstaller, David Emmert, Roberto Melotti, Luisa Foco, Deborah Mascalzoni, Martin Gogele, Francisco Domingues, Andrew Hicks, Christopher R. Gignoux, Stephen J. Wicks, Kristy Crooks, Kathleen C. Barnes, Michelle Daya, Jonathan Shortt, Nicholas Rafaels, Sameer Chavan, David B. Goldstein, Krzysztof Kiryluk, Soumitra Sengupta, Amritha Menon, Yat S. So, Wendy Chung, Muredach P. Reilly, Atlas Khan, Chen Wang, Ali G. Gharavi, Ning Shang, Sheila M. O'Byrne, Renu Nandakumar, Gundula Povysil, Nitin Bhardwaj, Iuliana Ionita-Laza, Eldad Hod, Danielle Pendrick, Soo-Kyung Park, Hyung-Lae Kim, Chang Kyung Kang, Wan Beom Park, Hyo-Jung Lee, Kyoung-Ho Song, Sin Young Ham, Jongtak Jung, Eu Suk Kim, Hong Bin Kim, Kyung Jae Yoon, Nam-Jong Paik, Woojin Seok, Heejun Yoon, Eun-Jeong Joo, Yoosoo Chang, Seungho Ryu, Jeong Su Park, Kyoung Un Park, David Ellinghaus, Frauke Degenhardt, Simonas Juzenas, Florian Tran, Philip Rosenstiel, Stefan Schreiber, Andre Franke, Eike Matthias Wacker, Florian Uellendahl-Werth, Hesham ElAbd, Lars Wienbrandt, Malte Christoph Ruhlemann, Mareike Wendorff, Anja Tanck, Christoph Gassner, Georg Hemmrich-Stanisak, Jan Kassens, Maria E. Figuera Basso, Martin Schulzky, Michael Wittig, Nicole Braun, Tanja Wesse, Wolfgang Albrecht, Xiaoli Yi, Almut Nebel, Anna Peschuck, Sandra May, Banasik Karina, Soren Brunak, Mario Caceres, Jon Lerga-Jaso, Tobias L. Lenz, Ana Teles, Clinton Azuure, Onur Ozer, Agustin Albillos, Beatriz Mateos, Francisco Mesonero, Luis Tellez, Miguel Rodriguez-Gandia, Luis Bujanda, Jesus M. Banales, Manuel Romero-Gomez, Maria Buti, Douglas Maya-Miles, Koldo Garcia-Etxebarria, Laura Izquierdo-Sanchez, Pedro M. Rodrigues, Francisco Rodriguez-Frias, Mar Riveiro-Barciela, Antonio Julia, Adriana Palom, Sara Marsal, Bettina Heidecker, Florian Kurth, Leif Erik Sander, Alena Mayer, Alice Braun, Carsten Skurk, Charlotte Thibeault, Elisa T. Helbig, Julia Kraft, Lena J. Lippert, Phillip Suwalski, Stephan Ripke, Wolfgang Poller, Xiaomin Wang, Zehra Karadeniz, Federico Garcia, Jose Hernandez Quero, Natalia Chueca, Trinidad Gonzalez Cejudo, Frank Hanses, Sibylle Wilfling, Heinz Zoller, Benedikt Schaefer, Jan C. Holter, Johannes R. Hov, Tom H. Karlsen, Trine Folseraas, Aleksander Rygh Holten, Anne Ma Dyrhol-Riise, Kristian Tonby, Andreas Lind, Fredrik Muller, Susanne Dudman, Marit M. Grimsrud, Javier Fernandez, Carlos Ferrando, Enric Reverter, Joan Ramon Badia, Maria Hernandez-Tejero, Pedro Castro, Rafael de Cid, Anna Carreras Nolla, Beatriz Cortes, Ivan Galvan-Femenia, Natalia Blay, Xavier Farre, Rosanna Asselta, Stefano Duga, Alberto Mantovani, Alessandro Protti, Alessio Aghemo, Ana Lleo, Antonio Voza, Elena Azzolini, Elvezia Maria Paraboschi, Ilaria My, Maurizio Cecconi, Paolo Tentorio, Salvatore Badalamenti, Sara Bombace, Claudio Cappadona, Valeria Rimoldi, Siegfried Goerg, Ute Hehr, Emma F. Perez, Ole Bernt Lenning, May Sissel Vadla, Ronny Myhre, Aaron Blandino Ortiz, Raul de Pablo, Adolfo Garrido Chercoles, Beatriz Nafria-Jimenez, Agustin Ruiz, Isabel Hernandez, Itziar de Rojas, Marta Marquie, Merce Boada, Daniele Prati, Guido Baselli, Luca Valenti, Alessandro Cherubini, Antonio Muscatello, Cinzia Hu, Cristiana Bianco, Daniela Galimberti, Elio Scarpini, Ferruccio Ceriotti, Giuseppe Lamorte, Leonardo Terranova, Mahnoosh Ostadreza, Alberto Zanella, Alessandra Bandera, Andrea Gori, Anna Ludovica Fracanzani, Antonio Pesenti, Cinzia Paccapelo, Filippo Martinelli-Boneschi, Flora Peyvandi, Francesco Blasi, Giacomo Grasselli, Giorgio Costantino, Luigi Santoro, Luigia Scudeller, Maria Carrabba, Marina Baldini, Monica Miozzo, Nicola Montano, Roberta Gualtierotti, Serena Pelusi, Silvano Bosari, Stefano Aliberti, Valter Monzani, Pietro Invernizzi, Alessio Gerussi, Chiara Milani, Alfredo Ramirez, Victor Andrade, Ana Barreira, Anders Benjamin Kildal, Andreas Gluck, Thomas Bahmer, Anna Latiano, Orazio Palmieri, Ariadna Rando-Segura, Luisa Roade, Aurora Solier, David Jimenez, Rosa Nieto, Carla Bellinghausen, Carmen Quereda, Enrique Navas, Christoph D. Spinner, Jochen Schneider, Christoph Lange, Jan Heyckendorf, Cristina Sancho, Maider Intxausti, Dag Arne Lihaug Hoff, Jan Egil Afset, Sammra Haider, David Pestana, David Toapanta, Eloisa Urrechaga, Pedro P. Espana, Emanuele Pontali, Lucia Garbarino, Michela Mazzocco, Eunate Arana, Natale Imaz Ayo, Felix Garcia Sanchez, Francesco Malvestiti, Gianni Pezzoli, Holger Neb, Mauro D'Amato, Josune Goikoetxea, Karl Erik Muller, Lars Heggelund, Karoline Gaede, Lauro Sumoy, Manolis Kogevinas, Judith Garcia-Aymerich, Gemma Castano-Vinyals, Carlota Dobano, Victor Moreno, Maria A. Gutierrez-Stampa, Maria J. G. T. Vehreschild, Yascha Khodamoradi, Massimo Castoldi, Tenghao Zheng, Michael J. Seilmaier, Nilda Martinez, Per Hoffmann, Stefanie Heilmann-Heimbach, Petra Bacher, Sandra Ciesek, Ulf Landmesser, Vegard Skogen, Enrique J. Calderon, Francisco J. Medrano, Juan Delgado, Ruben Morilla, Vicente Friaza, Daniel F. Gudbjartsson, Kari Stefansson, Patrick Sulem, Gardar Sveinbjornsson, Pall Melsted, Gudmundur Norddahl, Kristjan Helgi Swerford Moore, Unnur Thorsteinsdottir, Hilma Holm, David Bernardo, Javier Ampuero, Silvia Rojo Rello, Reedik Magi, Lili Milani, Andres Metspalu, Triin Laisk, Kristi Lall, Maarja Lepamets, Tonu Esko, Ene Reimann, Helene Alavere, Kristjan Metsalu, Mairo Puusepp, Paul Naaber, Edward Laane, Jaana Pesukova, Part Peterson, Kai Kisand, Jekaterina Tabri, Raili Allos, Kati Hensen, Joel Starkopf, Inge Ringmets, Anu Tamm, Anne Kallaste, Kati Kristiansson, Sami Koskelainen, Markus Perola, Carlo Rivolta, Mathieu Quinodoz, Dhryata Kamdar, Pierre-Yves Bochud, Stephanie Bibert, Noemie Boillat, Semira Gonseth Nussle, Werner Albrich, Noemie Suh, Dionysios Neofytos, Veronique Erard, Cathy Voide, P. Y. Bochud, C. Rivolta, S. Bibert, M. Quinodoz, D. Kamdar, D. Neofytos, Erard, V, C. Voide, R. Friolet, P. Vollenweider, J. L. Pagani, M. Oddo, F. Meyer zu Bentrup, A. Conen, O. Clerc, O. Marchetti, A. Guillet, C. Guyat-Jacques, S. Foucras, M. Rime, J. Chassot, M. Jaquet, R. Merlet Viollet, Y. Lannepoudenx, L. Portopena, F. Desgranges, P. Filippidis, B. Guery, D. Haefliger, E. E. Kampouri, O. Manuel, A. Munting, M. Papadimitriou-Olivgeris, J. Regina, L. Rochat-Stettler, Suttels, V, E. Tadini, J. Tschopp, M. Van Singer, B. Viala, N. Boillat-Blanco, T. Brahier, O. Hugli, J. Y. Meuwly, O. Pantet, Tomas Pumarola, S. Gonseth Nussle, M. Bochud, D'Acremont, V, S. Estoppey Younes, W. C. Albrich, N. Suh, A. Cerny, L. O'Mahony, M. Frischknecht, G-R Kleger, M. Filipovic, C. R. Kahlert, H. Wozniak, T. Rochat Negro, J. Pugin, K. Bouras, C. Knapp, T. Egger, A. Perret, P. Montillier, C. di Bartolomeo, B. Barda, Anna Carreras, Josep Maria Mercader, Marta Guindo-Martinez, David Torrents, Marco Gori, Nicola Picchiotti, Mario Umberto Mondelli, Raffaele Bruno, Serena Ludovisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Massimo Vaghi, Stefano Rusconi, Agostino Riva, Matteo Siano, Arianna Gabrieli, Massimiliano Fabbiani, Barbara Rossetti, Ilaria Rancan, Elena Bargagli, Laura Bergantini, Miriana D'Alessandro, Paolo Cameli, David Bennet, Federico Franchi, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Maria Antonietta Mazzei, Susanna Guerrini, Luca Cantarini, Edoardo Conticini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Maria Bandini, Maurizio Spagnesi, Paolo Piacentini, Elena Desanctis, Silvia Cappelli, Gian Piero Caldarelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Alessandro Pancrazi, Maria Lorubbio, Antonella D'Arminio Monforte, Esther Merlini, Federica Gaia Miraglia, Massimo Girardis, Stefano Busani, Sophie Venturelli, Andrea Antinori, Arianna Emiliozzi, Alessandra Vergori, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Francesca Gatti, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Merla, Giuseppe Fiorentino, Marco Castori, Massimo Carella, Filippo Aucella, Antonio Di Biagio, Matteo Bassetti, Luca Masucci, Alessandra Guarnaccia, Maurizio Sanguinetti, Serafina Valente, Oreste De Vivo, Marco Mandala, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Ferdinando Giannattasio, Tullio Trotta, Gabriella Coiro, Cristina Mussini, Giancarlo Bosio, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Sandro Mancarella, Lia Crotti, Gianfranco Parati, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Sabrina Ravaglia, Ravaglia Sabrina, Rosangela Artuso, Antonio Perrella, Davide Romani, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Simona Dei, Marco Tanfoni, Maurizio Sanarico, Francesco Raimondi, Filippo Biscarini, Alessandra Stella, Mattia Bergomi, Marco Vecchia, Stefania Mantovani, Isabella Zanella, Andrea Cossarizza, Saverio Giuseppe Parisi, Stefano Baratti, Gabriella Maria Squeo, Pamela Raggi, Carmen Marciano, Rita Perna, Elisabetta Menatti, Fabio Lena, Chiara Gabbi, Tiziana Bachetti, Claudia Suardi, Giordano Botta, Paolo Di Domenico, Richard C. Trembath, Qin Qin Huang, Hilary C. Martin, Dan Mason, John Wright, Sarah Finer, Shaheen Akhtar, Mohammad Anwar, Elena Arciero, Samina Ashraf, Gerome Breen, Raymond Chung, Charles J. Curtis, Maharun Chowdhury, Grainne Colligan, Panos Deloukas, Ceri Durham, Chris Griffiths, Matt Hurles, Shapna Hussain, Kamrul Islam, Ahsan Khan, Amara Khan, Cath Lavery, Sang Hyuck Lee, Robin Lerner, Daniel MacArthur, Bev MacLaughlin, Hilary Martin, Shefa Miah, Bill Newman, Nishat Safa, Farah Tahmasebi, Christopher J. Griffiths, Albert Smith, Andrew P. Boughton, Kevin W. Li, Jonathon LeFaive, Aubrey Annis, Sebastian Zollner, Jiongming Wang, Andrew Beck, Cinthia E. Jannes, Jose E. Krieger, Alexandre C. Pereira, Mariliza Velho, Emanuelle Marques, Isabella Ramos Lima, Mauricio Teruo Tada, Karina Valino, Mark McCarthy, Carrie Rosenberger, Diana Chang, Christian Hammer, Julie Hunkapiller, Anubha Mahajan, Sarah Pendergrass, Lara Sucheston-Campbell, Brian Yaspan, Jong Eun Lee, Hyun Soo Lee, Eunsoon Shin, Hye Yoon Jang, Sunmie Kim, Sungmin Kym, Yeon-Sook Kim, Hyeongseok Jeong, Ana Alegria, Ki Tae Kwon, Shin-Woo Kim, Jin Yong Kim, Young Rock Jang, Hyun Ah Kim, Ji Yeon Lee, Jeong Eun Lee, Shinwon Lee, Kang-Won Choe, Yu Min Kang, Sun Ha Jee, Keum Ji Jung, Victoria Parikh, Matthew Wheeler, Karen Dalton, Jeff Christle, John Gorzynski, Hannah de Jong, Shirley Sutton, Nathan Youlton, Ruchi Joshi, David Jimenez-Morales, Christopher Hughes, David Amar, Steve Hershman, Anna Kirillova, Kinya Seo, Yong Huang, Archana Raja, Jimmy Zhen, Euan Ashley, Carlos Bustamante, Manuel Rivas, Alex Ioannidis, Benjamin Pinksy, Massa Shoura, Nathan Hammond, Nathaniel Watson, ChunHong Huang, Malaya Sahoo, Hannah Wang, Phillip Febbo, Kyle Farh, Gary P. Schroth, Francis DeSouza, Christopher Deboever, Sandor Szalma, Simone Rubinacci, Olivier Delaneau, Peter J. McGuigan, Christopher Wasson, Stephanie Finn, Jackie Green, Erin Collins, Bernadette King, Luke Stephen Prockter Moore, Marcela Paola Vizcaychipi, Laura Gomes de Almeida Martins, Jaime Carungcong, Kathryn Hall, Isheunesu Mapfunde, Andy Campbell, Sara Smuts, Joseph Duffield, Oliver Smith, Lewis Mallon, Watkins Claire, Ailstair Nichol, Kathy Brickell, Michelle Smyth, Lorna Murphy, Geraldine Ward, Pamela Bremmer, Valerie Joan Page, Siobhain Carmody, Malcolm G. Semple, Tom Solomon, Lance C. W. Turtle, Hayley Hardwick, Kayode Adeniji, Daniel Agranoff, Chi Eziefula, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Louise Allen, Eva Beranova, Nikki Crisp, Joanne Deery, Tracy Hazelton, Alicia Knight, Carly Price, Sorrell Tilbey, Salah Turki, Sharon Turney, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Sam Douthwaite, Marlies Ostermann, Manu Shankar-Hari, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Ingeborg Welters, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, Darell Tupper-Carey, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Cariad Evans, Gary H. Mills, Norfaizan Ahmad, Joann Barker, Kris Bauchmuller, Sarah Bird, Kay Cawthron, Kate Harrington, Yvonne Jackson, Faith Kibutu, Becky Lenagh, Shamiso Masuko, Ajay Raithatha, Matthew Wiles, Jayne Willson, Helen Newell, Alison Lye, Lorenza Nwafor, Claire Jarman, Sarah Rowland-Jones, David Foote, Joby Cole, Roger Thompson, James Watson, Lisa Hesseldon, Irene Macharia, Luke Chetam, Jacqui Smith, Amber Ford, Samantha Anderson, Kathryn Birchall, Kay Housley, Sara Walker, Leanne Milner, Helena Hanratty, Helen Trower, Patrick Phillips, Simon Oxspring, Ben Donne, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Andrew Drummond, Andrew Ustianowski, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Christopher Fegan, Adam Finn, Duncan Fullerton, Elijah Matovu, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Elinoor Moore, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Andrew Workman, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Caroline Kerrison, Ian Kerslake, Oliver Koch, Rosie Baruah, Sheila Morris, Susie Ferguson, Amy Shepherd, Gouri Koduri, George Koshy, Tamas Leiner, Katherine Mortimore, Shondipon Laha, Steven Laird, Susan Larkin, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Emily MacNaughton, Ravish Mankregod, Huw Masson, Katherine McCullough, Ruth McEwen, Lawrence Wilson, Manjula Meda, Jane Minton, Karl Ward, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Nigel Capps, Sanal Jose, Patrick Morgan, Craig Morris, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Matthew K. O'Shea, Christoper A. Green, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hollie Bancroft, Mary Bellamy, Margaret Carmody, Jacqueline Daglish, Faye Moore, Joanne Rhodes, Mirriam Sangombe, Salma Kadiri, James Scriven, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, Anna Cavazza, Maeve Cockrell, Eleanor Corcoran, Maria Depante, Clare Finney, Ellen Jerome, Mark McPhail, Monalisa Nayak, Harriet Noble, Kevin O'Reilly, Evita Pappa, Rohit Saha, Sian Saha, John Smith, Abigail Knighton, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Victoria Bastion, Daphene Clarke, Beena David, Harriet Kent, Rachel Lorusso, Gamu Lubimbi, Sophie Murdoch, Melchizedek Penacerrada, Alastair Thomas, Jennifer Valentine, Ana Vochin, Retno Wulandari, Brice Djeugam, Richard Smith, Catherine Snelson, Tony Whitehouse, Nick Spittle, Nikki Staines, Shico Visuvanathan, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Ascanio Tridente, Mary Twagira, Nick Vallotton, Lisa Vincent-Smith, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wooton, Bryan Yates, Peter Young, Rupert Beale, Charles Hinds, Elvina Gountouna, David J. Porteous, David Harrison, Kathy Rowan, Gavin Band, Paul Klenerman, Julian Knight, Debby Bogaert, Xia Shen, Zhijian Yang, Ranran Zhai, Chenqing Zheng, Cynthia M. Bulik, Mikael Landen, Bengt Fundin, Yang Wu, Jian Yang, Lisa Norman, Riinu Pius, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Catherine A. Shaw, Annemarie B. Docherty, Ewen M. Harrison, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Chloe Donohue, Gary Leeming, Murray Wham, James Scott-Brown, Beatrice Alex, Benjamin Bach, Colin Begg, Antonia Ying Wai Ho, Peter W. Horby, Lowell Ling, David Maslove, Danny McAuley, Hugh Montgomery, Alistair Nichol, Peter J. M. Openshaw, Ryan S. Thwaites, Shona C. 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McParland, Sophie Packham, Zoe Alldis, Raine Astin-Chamberlain, Fatima Bibi, Jack Biddle, Sarah Blow, Matthew Bolton, Catherine Borra, Ruth Bowles, Maudrian Burton, Yasmin Choudhury, David Collier, Amber Cox, Amy Easthope, Patrizia Ebano, Stavros Fotiadis, Jana Gurasashvili, Rosslyn Halls, Pippa Hartridge, Delordson Kallon, Jamila Kassam, Ivone Lancoma-Malcolm, Maninderpal Matharu, Peter May, Oliver Mitchelmore, Tabitha Newman, Mital Patel, Jane Pheby, Irene Pinzuti, Zoe Prime, Oleksandra Prysyazhna, Julian Shiel, Melanie Taylor, Carey Tierney, Suzanne Wood, Anne Zak, Olivier Zongo, Miranda Forsey, Anne Nicholson, Joanne Riches, Mark Vertue, Lina Grauslyte, Musarat Hussain, Tatiana Pogreban, Lace Rosaroso, Erika Salciute, George Franke, Joanna Wong, Aparna George, Louise Akeroyd, Shereen Bano, Matt Bromley, Lucy Gurr, Tom Lawton, James Morgan, Kirsten Sellick, Deborah Warren, Brian Wilkinson, Janet McGowan, Camilla Ledgard, Amelia Stacey, Kate Pye, Ruth Bellwood, Michael Bentley, Ronda Loosley, Heather McGuinness, Helen Tench, Rebecca Wolf-Roberts, Sian Gibson, Amanda Lyle, Fiona McNeela, Jayachandran Radhakrishnan, Alistair Hughes, Asifa Ali, Megan Brady, Sam Dale, Annalisa Dance, Lisa Gledhill, Jill Greig, Kathryn Hanson, Kelly Holdroyd, Marie Home, Diane Kelly, Ross Kitson, Lear Matapure, Deborah Melia, Samantha Mellor, Tonicha Nortcliffe, Jez Pinnell, Matthew Robinson, Lisa Shaw, Ryan Shaw, Lesley Thomis, Alison Wilson, Tracy Wood, Lee-Ann Bayo, Ekta Merwaha, Tahira Ishaq, Sarah Hanley, David Antcliffe, Dorota Banach, Stephen Brett, Phoebe Coghlan, Ziortza Fernandez, Anthony Gordon, Roceld Rojo, Sonia Sousa Arias, Maie Templeton, Rajeev Jha, Vinodh Krishnamurthy, Lai Lim, Li Lim, Rehana Bi, Barney Scholefield, Lydia Ashton, Alison Williams, Claire Cheyne, Anne Saunderson, Sam Moultrie, M. Odam, Angela Allan, Felicity Anderson, Callum Kaye, Jade Liew, Jasmine Medhora, Teresa Scott, Erin Trumper, Adriana Botello, Petra Polgarova, Katerina Stroud, Eoghan Meaney, Megan Jones, Anthony Ng, Shruti Agrawal, Nazima Pathan, Deborah White, Esther Daubney, Kay Elston, Robert Parker, Amie Reddy, Ian Turner-Bone, Laura Wilding, Peter Harding, Reni Jacob, Cathy Jones, Craig Denmade, Maria Croft, Ian White, Denise Griffin, Nycola Muchenje, Mcdonald Mupudzi, Richard Partridge, Jo-Anna Conyngham, Rachel Thomas, Mary Wright, Maria Alvarez Corral, Joy Dawson, Sweyn Garrioch, Melanie Tolson, Jonathan Aldridge, Sarah Beavis, Katie Dale, Rachel Gascoyne, Joanne Hawes, Kelly Pritchard, Lesley Stevenson, Amanda Whileman, Anne Cowley, Judith Highgate, Rikki Crawley, Abigail Crew, Mishell Cunningham, Allison Daniels, Laura Harrison, Susan Hope, Ken Inweregbu, Sian Jones, Nicola Lancaster, Jamie Matthews, Alice Nicholson, Gemma Wray, Leonie Benham, Zena Bradshaw, Joanna Brown, Melanie Caswell, Sarah Melling, Stephen Preston, Nicola Slawson, Emma Stoddard, Scott Warden, Edward Combes, Teishel Joefield, Sonja Monnery, Valerie Beech, Sallyanne Trotman, Bridget Hopkins, Laura Thrasyvoulou, Heather Willis, Susan Anderson, Janine Birch, Emma Collins, Kate Hammerton, Ryan O'Leary, Eleanor Andrews, Caroline Abernathy, Louise Foster, Andrew Gratrix, Vicky Martinson, Priyai Parkinson, Elizabeth Stones, Llucia Carbral-Ortega, Ritoo Kapoor, David Loader, Karen Castle, Craig Brandwood, Lara Smith, Richard Clark, Katie Birchall, Laurel Kolakaluri, Deborah Baines, Anila Sukumaran, Megan Meredith, Lucy Morris, Lucy Ryan, Amy Clark, Julia Sampson, Cecilia Peters, Martin Dent, Margaret Langley, Saima Ashraf, Shuying Wei, Angela Andrew, Manish Chablani, Amy Kirkby, Kimberley Netherton, Michelle Bates, Jo Dasgin, Jaspret Gill, Annette Nilsson, Elena Apetri, Cathrine Basikolo, Bethan Blackledge, Laura Catlow, Bethan Charles, Reece Doonan, Jade Harris, Alice Harvey, Daniel Horner, Karen Knowles, Stephanie Lee, Diane Lomas, Chloe Lyons, Tracy Marsden, Danielle McLaughlan, Liam McMorrow, Jessica Pendlebury, Jane Perez, Maria Poulaka, Nicola Proudfoot, Melanie Slaughter, Kathryn Slevin, Vicky Thomas, Danielle Walker, Angiy Michael, Matthew Collis, Martyn Clark, Martina Coulding, Edward Jude, Jacqueline McCormick, Oliver Mercer, Darsh Potla, Hafiz Rehman, Heather Savill, Victoria Turner, Miriam Davey, David Golden, Rebecca Seaman, Jodie Hunt, Joy Dearden, Emma Dobson, Michelle Mulcahy, Sheila Munt, Grainne O'Connor, Jennifer Philbin, Chloe Rishton, Redmond Tully, Sarah Winnard, Lenka Cagova, Adama Fofano, Lucie Garner, Helen Holcombe, Sue Mepham, Alice Michael Mitchell, Lucy Mwaura, K. 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Hadebe, Abdul Kayani, Bridgett Masunda, Ashar Ahmed, Anna Morris, Srinivas Jakkula, Kate Long, Simon Whiteley, Elizabeth Wilby, Bethan Ogg, Jeremy Bewley, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Rebekah Johnson, Katie Sweet, Denise Webster, Georgia Efford, Sara Bennett, Emma Goodwin, Matthew Jackson, Alissa Kent, Clare Tibke, Wiesia Woodyatt, Ahmed Zaki, Amelia Daniel, Joanne Finn, Rajnish Saha, J. Allan, T. Geary, Gordon Houston, A. Meikle, P. O'Brien, Dina Bell, Rosalind Boyle, Katie Douglas, Lynn Glass, Emma Lee, Liz Lennon, Austin Rattray, Rob Charnock, Denise McFarland, Denise Cosgrove, Ben Attwood, Penny Parsons, Metod Oblak, Monica Popescu, Mini Thankachen, Abdelhakim Altabaibeh, Ana Alvaro, Kayleigh Gilbert, Louise Ma, Loreta Mostoles, Chetan Parmar, Kathryn Simpson, Champa Jetha, Lauren Booker, Anezka Pratley, Tracey Cosier, Gemma Millen, Natasha Schumacher, Heather Weston, James Rand, Wendy S. Barclay, Meera Chand, Graham S. Cooke, Shiranee Sriskandan, Jake Dunning, Maria Zambon, Ana da Silva Filipe, Massimo Palmarini, David L. Robertson, Janet T. Scott, Emma C. Thomson, Sarah E. McDonald, Tom Fletcher, Julian A. Hiscox, Samreen Ijaz, Saye Khoo, Wei Shen Lim, Alexander J. Mentzer, Laura Merson, Louise Sigfrid, Gail Carson, Mahdad Noursadeghi, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, Vanessa Sancho-Shimizu, Thushan de Silva, David Stuart, Richard S. Tedder, A. A. Roger Thompson, Rishi K. Gupta, Carlo Palmieri, Olivia Swann, Marc-Emmanuel Dumas, Julian L. Griffin, Zoltan Takats, Petros Andrikopoulos, Anthonia Osagie, Michael Olanipekun, Sonia Liggi, Kanta Chechi, Matthew R. Lewis, Goncalo dos Santos Correia, Caroline J. Sands, Panteleimon Takis, Lynn Maslen, William Greenhalf, Victoria Shaw, Sarah Cole, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Katie Bullock, Benjamin W. A. Catterall, Jordan J. Clark, Emily A. Clarke, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W. S. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Benjamin Brennan, Annette Lake, Daniella Lefteri, John McLauchlan, Aislynn Taggart, Audrey Coutts, Lorna Donnelly, Angie Fawkes, Tammy Gilchrist, Katarzyna Hafezi, Louise Macgillivray, Katherine Schon, Anita Furlong, Heather Biggs, Alexander Rakitko, Valery Ilinsky, Danat Yermakovich, Iaroslav Popov, Alexander Chernitsov, Elena Kovalenko, Anna Krasnenko, Nikolay Plotnikov, Ivan Stetsenko, Anna Kim, Elizabeth T. Cirulli, Kelly M. Schiabor Barrett, Alexandre Bolze, Simon White, Nicole L. Washington, James T. Lu, Stephen Riffle, Francisco Tanudjaja, Xueqing Wang, Jimmy M. Ramirez Iii, Nicole Leonetti, Efren Sandoval, Iva Neveux, Joseph J. Grzymski, Shaun Dabe, Juan Ignacio Esteban Minano, Manuel de la Mata Pazos, Luciano Cerrato, Luis A. Aguirre, Eduardo Lopez-Collazo, Roberto Lozano-Rodriguez, Jose Avendano-Ortiz, Veronica Terron Arcos, Karla Marina Montalban-Hernandez, Jaime Valentin Quiroga, Alejandro Pascual-Iglesias, Charbel Maroun-Eid, Alejandro Martin-Quiros, Ho Namkoong, Koichi Fukunaga, Makoto Ishii, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Hiromu Tanaka, Atsuho Morita, Ho Lee, Takanori Asakura, Ryuya Edahiro, Kyuto Sonehara, Yuya Shirai, Ken Suzuki, Atsushi Kumanogoh, Seiya Imoto, Kazuhiko Katayama, Yuko Kitagawa, Toshiro Sato, Naoki Hasegawa, Yoshito Takeda, Haruhiko Hirata, Takayuki Shiroyama, Yuichi Maeda, Takuro Nii, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Akinori Kimura, Masumi Ai, Katsushi Tokunaga, Yosuke Omae, Takanori Kanai, Kosaku Nanki, Yohei Mikami, Satoru Miyano, Kunihiko Takahashi, Tatsuhiko Anzai, Takanori Hasegawa, Satoshi Ito, Seishi Ogawa, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kazunori Tomono, Kazuto Kato, Fumihiko Matsuda, Meiko Takahashi, Nobuyuki Hizawa, Satoru Miyawaki, Ryuji Koike, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Sassa, Jun Nakajima, Yasuhito Nannya, Kazuhisa Takahashi, Norihiro Harada, Haruhi Takagi, Ai Nakamura, Makoto Hiki, Etsuko Tagaya, Ken Arimura, Masatoshi Kawana, Takashi Ishiguro, Noboru Takayanagi, Taisuke Isono, Yotaro Takaku, Kenji Takano, Ryusuke Anan, Yukiko Nakajima, Yasushi Nakano, Kazumi Nishio, Soichiro Ueda, Reina Hayashi, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Keiko Mitamura, Fumitake Saito, Tetsuya Ueda, Masanori Azuma, Tadao Nagasaki, Yoshinori Hasegawa, Masaki Okamoto, Yoshinori Yasui, Yoshikazu Mutoh, Takashi Yoshiyama, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Kazuyoshi Watanabe, Tadashi Manabe, Fumimaro Ito, Takahiro Fukui, Yohei Funatsu, Hidefumi Koh, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Fukuki Saito, Kazuhisa Yoshiya, Tomoyuki Yoshihara, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Koichi Nishi, Masaru Nishitsuji, Maiko Tani, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Takashi Ogura, Hideya Kitamura, Kota Murohashi, Ichiro Nakachi, Rie Baba, Daisuke Arai, Satoshi Fuke, Hiroshi Saito, Naota Kuwahara, Akiko Fujiwara, Takenori Okada, Tomoya Baba, Junya Noda, Shuko Mashimo, Kazuma Yagi, Tetsuya Shiomi, Mizuha Hashiguchi, Toshio Odani, Takao Mochimaru, Yoshitaka Oyamada, Nobuaki Mori, Namiki Izumi, Kaoru Nagata, Reiko Taki, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Kentaro Hayashi, Tetsuo Shimizu, Yasuhiro Gon, Shigeki Fujitani, Toru Yoshida, Tomoya Tsuchida, Takashi Kagaya, Toshiyuki Kita, Satoru Sakagami, Yoshifumi Kimizuka, Akihiko Kawana, Yoshihiko Nakamura, Hiroyasu Ishikura, Tohru Takata, Takahide Kikuchi, Daisuke Taniyama, Morio Nakamura, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Yoji Nagasaki, Sayoko Ishihara, Akihiro Ito, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Naozumi Hashimoto, Keiko Wakahara, Akira Ando, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Hisako Sageshima, Taka-Aki Nakada, Ryuzo Abe, Tadanaga Shimada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Masaki Yamasaki, Satoru Hashimoto, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Minoru Takada, Hidenori Kanda, Yuko Komase, Fumiaki Sano, Koichiro Asano, Tsuyoshi Oguma, Masahiro Harada, Takeshi Takahashi, Takayuki Shibusawa, Shinji Abe, Yuta Kono, Yuki Togashi, Takehiro Izumo, Minoru Inomata, Nobuyasu Awano, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Yuichiro Kitagawa, Shozo Yoshida, Shinji Ogura, Kei Nishiyama, Kousuke Yoshida, Satoru Beppu, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Yoshiaki Inoue, Kunihiro Yamagata, Shigeru Chiba, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Yoko Shibata, Yoshinori Tanino, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Tomonori Imamura, Akira Umeda, Hisato Shimada, Mayu Endo, Shinichi Hayashi, Mai Takahashi, Shigefumi Nakano, Masakiyo Yatomi, Toshitaka Maeno, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Marike Boezen, Judith M. Vonk, Anil P. S. Ori, Ma'en Obeidat, Ana I. Hernandez Cordero, Don D. Sin, Yohan Bosse, Philippe Joubert, Ke Hao, Robert P. Sebra, Daniel M. Jordan, Kyle Gettler, Kumardeep Chaudhary, Irene Salib, Marissa Zyndorf, Eric E. Schadt, Judy H. Cho, Yuval Itan, Ron Do, David Nickle, Wim Timens, Maarten van den Berge, Yen-Chen Anne Feng, James B. Meigs, Scott T. Weiss, Elizabeth W. Karlson, Ann E. Woolley, Jordan W. Smoller, Shawn N. Murphy, Steven Ascolillo, Ryan C. Thompson, Noam D. Beckmann, Girish N. Nadkarni, Paul Boutros, Alexander W. Charney, Clive Hoggart, Sam Choi, Paul O'Reilly, Laura M. Huckins, Michael Preuss, Ruth J. F. Loos, Gillian M. Belbin, Noura S. Abul-Husn, Eimear E. Kenny, Daniel H. Geschwind, Manuel A. R. Ferreira, Goncalo R. Abecasis, Michael N. Cantor, Jack A. Kosmicki, Julie E. Horowitz, Aris Baras, Ashish Yadav, Joseph B. Leader, Matthew C. Gass, Anne E. Justice, Geetha Chittoor, Navya Shilpa Josyula, Dave J. Carey, Tooraj Mirshahi, Anurag Verma, Marylyn D. Ritchie, Daniel Rader, Shefali S. Verma, Anastasia Lucas, Yuki Bradford, Binglan Li, Alfredo Brusco, Giovanni Battista Ferrero, Manish J. Butte, Marcello Scala, Antonella Riva, Jean-Francois Rahier, Elisa Giorgio, Diana Carli, Nahla Afifi, Janis Klovins, Vita Rovite, Raimonds Rescenko, Raitis Peculis, Monta Ustinova, Hugo Zeberg, Robert Frithiof, Michael Hultstrom, Miklos Lipcsey, Ruth Johnson, Nelson Freimer, Yi Ding, Alec Chiu, Timothy S. Chang, Daniel J. Wilson, Sarah G. Earle, Shang-Kuan Lin, Nicolas Arning, Jacob Armstrong, Justine K. Rudkin, Derrick W. Crook, David H. Wyllie, Anne Marie O'Connell, Shawneequa Callier, Nicole Soranzo, Jing Hua Zhao, John Danesh, Emanuele Di Angelantonio, Adam S. Butterworth, Yan Sun, Jennifer E. Huffman, Christopher J. O'Donnell, Gina Peloso, Kelly Cho, J. Michael Gaziano, Yuk-Lam Ho, Phil Tsao, Michael Mian, Federica Scaggiante, Xiao Chang, Joseph R. Glessner, Hakon Hakonarson, Antonella Vincenti, Claudio Ferri, Davide Grassi, Gloria Pessina, Massimo Di Pietro, Sauro Luchi, Chiara Barbieri, Donatella Acquilini, Elena Andreucci, Monica Poscente, Paola Petrocelli, Giusy Tiseo, Marco Falcone, Francesco Vladimiro Segala, Silvia Baroni, Alba-Estela Garcia-Fernandez, Albert Blanco-Grau, Andrea Caballero-Garralda, Cristina Cea, Juan M. Guerrero, Claudio Angelini, Hayato Kurihara, Michele Ciccarelli, Monica Bocciolone, Paoletta Preatoni, Paolo Omodei, Eduardo Muniz-Diaz, Elena Sandoval, Fatima Aziz, Jose Ferrusquia-Acosta, Leticia Moreira, Giulia Cardamone, Giuseppe Foti, Giuseppe Matullo, Serena Aneli, Jan Kristian Damas, Kari Risnes, Laura Rachele Bettini, Javier Martin, Marialbert Acosta-Herrera, Jeanette Erdmann, Jonas Bergan, Andrea Biondi, Mariella D'Angio, Erik Solligard, Lise Tuset Gustad, Marco Schaefer, Wolfgang Peter, Maria G. Valsecchi, Marina Cazzaniga, Paola Faverio, Paolo Bonfanti, Ximo Dopazo

NATURE　600　(7889)　472-+　2021/12

DOI： 10.1038/s41586-021-03767-x 　

ISSN： 0028-0836

eISSN： 1476-4687
Clinical Characteristics of Patients with Coronavirus Disease (COVID-19): Preliminary Baseline Report of Japan COVID-19 Task Force, a Nationwide Consortium to Investigate Host Genetics of COVID-19. International-journal

Hiromu Tanaka, Ho Lee, Atsuho Morita, Ho Namkoong, Shotaro Chubachi, Hiroki Kabata, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases　113　74-81　2021/12

DOI： 10.1016/j.ijid.2021.09.070 　

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BACKGROUND AND DESIGN: The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. RESULTS: The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45-71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. CONCLUSIONS: Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.
Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane. International-journal Peer-reviewed

Hidemi Aritake, Tsutomu Tamada, Koji Murakami, Shunichi Gamo, Masayuki Nara, Itsuro Kazama, Masakazu Ichinose, Hisatoshi Sugiura

Pflugers Archiv : European journal of physiology　473　(6)　883-896　2021/06

DOI： 10.1007/s00424-021-02560-z 　

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An acquired dysregulation of airway secretion is likely involved in the pathophysiology of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Nowadays, it is widely known that several kinds of long-acting bronchodilators reduce the frequency of COPD exacerbations. However, limited data are available concerning the complementary additive effects on airflow obstruction. Using an optical method and a selective pH indicator, we succeeded in evaluating the gland secretion rate and the pH in swine tracheal membrane. A physiologically relevant concentration of acetylcholine (ACh) 100 nM induced a gradual increase in the amount of gland secretion. Lipopolysaccharides (LPS) accelerated the ACh-induced secretory responses up to around threefold and lowered the pH level significantly. Long-acting β2-agonists (LABAs) including indacaterol (IND), formoterol, and salmeterol restored the LPS-induced changes in both the hypersecretion and acidification. The subsequent addition of the long-acting muscarine antagonist, glycopyrronium, further increased the pH values. Two different inhibitors for cystic fibrosis transmembrane conductance regulator (CFTR), NPPB and CFTRinh172, abolished the IND-mediated pH normalization in the presence of both ACh and ACh + LPS. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, IND did not restore the LPS-induced decrease in CFTR expression on Calu-3 cells. These findings suggest that the activation of cAMP-dependent HCO3- secretion through CFTR would be partly involved in the IND-mediated pH normalization in gland secretion and may be suitable for the maintenance of airway defense against exacerbating factors including LPS.
Correction to: PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite. International-journal Peer-reviewed

Tsutomu Saito, Tomohiro Ichikawa, Tadahisa Numakura, Mitsuhiro Yamada, Akira Koarai, Naoya Fujino, Koji Murakami, Shun Yamanaka, Yusaku Sasaki, Yorihiko Kyogoku, Koji Itakura, Hirohito Sano, Katsuya Takita, Rie Tanaka, Tsutomu Tamada, Masakazu Ichinose, Hisatoshi Sugiura

Respiratory research　22　(1)　78-78　2021/03/08

DOI： 10.1186/s12931-021-01672-5 　

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BACKGROUND: The airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. METHODS: BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated. RESULTS: The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin. CONCLUSIONS: The current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.
Negative heart signを呈した肺サルコイドーシスの1例 Peer-reviewed

鈴木歩, 藤野直也, 平野泰三, 村上康司, 玉田勉, 杉浦久敏

日本呼吸器学会誌　10　(1)　78-82　2021/01
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
Mycobacterium Abscessus Infection Limited to the Main Bronchus. Peer-reviewed

Hirohito Sano, Koji Murakami, Tsutomu Tamada, Masakazu Ichinose

Internal medicine (Tokyo, Japan)　59　(19)　2431-2432　2020/10/01

DOI： 10.2169/internalmedicine.4883-20 　
声帯機能不全を合併した若年気管支喘息患者の1例 Peer-reviewed

佐野寛仁, 佐藤輝幸, 村上康司, 東條裕, 渋谷里紗, 光根歩, 山中駿, 玉田勉, 杉浦久敏, 一ノ瀬正和

アレルギー　69　(5)　353-357　2020/07
Publisher: (一社)日本アレルギー学会
ISSN： 0021-4884

eISSN： 1347-7935
Comment on: Aortarctia: a rare manifestation of relapsing polychondrits. International-journal Peer-reviewed

Tsuyoshi Shirai, Koji Murakami, Hiroshi Fujii, Tomonori Ishii, Hideo Harigae

Rheumatology (Oxford, England)　59　(7)　1784-1785　2020/07/01

DOI： 10.1093/rheumatology/keaa019 　
気管・気管支内に多発する転移結節を認めた小細胞肺癌の1例 Peer-reviewed

鈴木歩, 宮内栄作, 成田大輔, 相澤洋之, 東條裕, 小林誠, 村上康司, 山田充啓, 杉浦久敏, 一ノ瀬正和

気管支学　42　(3)　269-273　2020/05
Publisher: (NPO)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
[A CASE OF BRONCHIAL ASTHMA IN A YOUNGER PATIENT WITH VOCAL CORD DYSFUNCTION]. Peer-reviewed

Hirohito Sano, Teruyuki Satou, Koji Murakami, Yutaka Tojo, Risa Shibuya, Ayumi Mitsune, Shun Yamanaka, Tsutomu Tamada, Hisatoshi Sugiura, Masakazu Ichinose

Arerugi = [Allergy]　69　(5)　353-357　2020

DOI： 10.15036/arerugi.69.353 　

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We present a case of a 17-year-old woman with a history of bronchial asthma since two years of age. She had daily asthma attacks from the age of fourteen, and the addition of oral corticosteroids and omalizumab to regular inhaled corticosteroid inhalation failed to relieve symptoms. She was referred to our hospital for detailed examination. On admission, physical examination was normal, but she had complained of dyspnea at the round. Monophonic wheezes and stridor were heard over the anterior neck, while no rales were audible over any part of the chest. Laryngoscopy revealed paradoxical movement of the vocal cords, and a diagnosis of vocal cord dysfunction (VCD) was made. The apparent severe asthma symptoms were considered to reflect VCD, and the treatment for bronchial asthma was stepped down without any recurrence of asthma attacks. Although the etiology of the VCD was unknown, VCD is more common in young women, so stress and personality factors are thought to be involved. It has been noted that childhood asthma often improves between childhood and adolescence, but refractory cases have been noted. In intractable bronchial asthma cases, it is necessary to consider the complications of other diseases, such as VCD, and to perform appropriate management.
TLR7 agonist attenuates acetylcholine-induced, Ca²⁺ -dependent ionic currents in swine tracheal submucosal gland cells. International-journal Peer-reviewed

Gamo S, Tamada T, Murakami K, Muramatsu S, Aritake H, Nara M, Kazama I, Okazaki T, Sugiura H, Ichinose M

Experimental physiology　103　(11)　1543-1559　2018/11

DOI： 10.1113/EP087221 　

ISSN： 0958-0670

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NEW FINDINGS: What is the central question of this study? Does Toll-like receptor 7 (TLR7) have any direct effects on Ca2+ -dependent physiological function of tracheal submucosal gland cells? What is the main finding and its importance? TLR7 is co-localized with SERCA2 in tracheal submucosal gland cells and causes a rapid attenuation of acetylcholine (ACh)-induced, Ca2+ -dependent ionic currents through the activation of SERCA2-dependent Ca2+ clearance. TLR7 is abundantly expressed in the airways of both swine and healthy human subjects, but is significantly downregulated in chronic obstructive pulmonary disease (COPD) airways. These findings suggest that a dysfunction of TLR7 in COPD removes the brake on ACh-induced serous secretion during viral infections, resulting in prolonged airway hypersecretion, and that it is one of the triggers of COPD exacerbations. ABSTRACT: Airway surface fluids are mainly secreted from submucosal glands (SMGs) and play important roles in the defence of airways via the activation of mucociliary transport. Toll-like receptor 7 (TLR7) recognizes and eliminates single stranded RNA (ssRNA) viruses through the induction of innate immunity. However, there is no obvious connection between TLR7 and mucus secretion, aside from TLR7 recognizing ssRNA viruses, which are often associated with airway hypersecretion in chronic obstructive pulmonary disease (COPD). Here, we investigated whether TLR7 has any direct effects on the Ca2+ -dependent physiological function of tracheal SMG cells. Patch-clamp analyses revealed that TLR7 ligand inhibited the acetylcholine (ACh)-induced ionic currents in isolated tracheal SMG cells. Intracellular calcium assays and pharmacological analyses revealed that TLR7 attenuated the transient rises in the intracellular calcium concentration evoked by ACh by activating sarco/endoplasmic reticulum Ca2+ -ATPase 2 (SERCA2). Immunofluorescence staining and immunohistochemical staining revealed that TLR7 was co-localized with SERCA2. These findings suggest that the activation of TLR7 during viral infections contributes to the rapid attenuation of ACh-induced ionic currents through an increase in SERCA2-dependent Ca2+ clearance in healthy airway SMG cells. Our study also revealed that TLR7 expression was significantly downregulated in COPD airways. Based on these findings, we speculate that a dysfunction of TLR7 may not only have an adverse effect on the elimination of these viruses but also remove the brake on ACh-induced serous secretion, resulting in prolonged hypersecretion and acting as one of the triggers of COPD exacerbations.
家族性サルコイドーシスとの鑑別に難渋したTINU症候群の1例 Peer-reviewed

有竹秀美, 村上康司, 玉田勉, 蒲生俊一, 村松聡士, 奈良正之, 大友孝昭, 吉田真彰, 谷内真司, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　38　(1-2)　88-92　2018/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
Legionella gormanii感染が疑われた尿中抗原陰性喀痰PCR陽性のレジオネラ症の1例 Peer-reviewed

佐野寛仁, 山田充啓, 村上康司, 平野泰三, 玉田勉, 杉浦久敏, 舘田一博, 一ノ瀬正和

日本内科学会雑誌　106　(12)　2620-2624　2017/12
Publisher: (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
好酸球性肺炎の像を呈した肺接合菌症の1例 Peer-reviewed

平野泰三, 山田充啓, 村上康司, 佐藤慶, 玉井ときわ, 高橋秀徳, 岡崎達馬, 玉田勉, 杉浦久敏, 一ノ瀬正和

日本内科学会雑誌　106　(5)　1006-1011　2017/05
Publisher: (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
Invasive pulmonary mucormycosis: rare presentation with pulmonary eosinophilia Peer-reviewed

Taizou Hirano, Mitsuhiro Yamada, Kei Sato, Koji Murakami, Tokiwa Tamai, Yoshiya Mitsuhashi, Tsutomu Tamada, Hisatoshi Sugiura, Naomi Sato, Ryoko Saito, Junya Tominaga, Akira Watanabe, Masakazu Ichinose

BMC PULMONARY MEDICINE　17　(1)　76　2017/04

DOI： 10.1186/s12890-017-0419-1 　

ISSN： 1471-2466
[Case Report; A case of acute sarcoidosis with fever and polyarthralgia]. Peer-reviewed

Onodera K, Tamada T, Muramatsu S, Murakami K, Nara M, Komatsu R, Kobayashi M, Yamada M, Sugiura H, Ichinose M

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine　105　(3)　540-544　2016/03

ISSN： 0021-5384
Simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy Peer-reviewed

Tadahisa Numakura, Tsutomu Tamada, Masayuki Nara, Soshi Muramatsu, Koji Murakami, Toshiaki Kikuchi, Makoto Kobayashi, Miho Muroi, Tatsuma Okazaki, Sho Takagi, Yoshinobu Eishi, Masakazu Ichinose

BMC PULMONARY MEDICINE　16　30　2016/02

DOI： 10.1186/s12890-016-0193-5 　

ISSN： 1471-2466
当科外来通院中に心臓病変が顕在化した心サルコイドーシス症例の臨床的検討 Peer-reviewed

蒲生俊一, 玉田勉, 村松聡士, 村上康司, 奈良正之, 杉村宏一郎, 杉浦久敏, 一ノ瀬正和

日本サルコイドーシス／肉芽腫性疾患学会雑誌　35　(1)　50-4-50-4　2015
Publisher: 日本サルコイドーシス/肉芽腫性疾患学会
DOI： 10.7878/jjsogd.35.Suppl1_50-4 　

ISSN： 1883-1273

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【背景】サルコイドーシス(サ症)の心病変は予後規定因子の一つで、非循環器内科医も早期発見に努める事が重要である。【目的】心病変を疑う端緒となった検査所見や診断確定法、治療や予後の検討。【方法】2000 年から 2014 年に当科外来初診、サ症と診断された 218 例中、サ症診断後心病変が判明した 14 例を A 群、サ症診断前に心病変があった 12 例を B 群、心病変の無い 192 例を C 群とし臨床的特徴を検討した。【結果】平均年齢は A、B、C 群で其々50.1、52.4、48.3 歳、女性の割合は 79%、58%、63%。無症候性は A 群の 12 例(85.7%)で、心エコー異常 4 例(中隔基部菲薄化 3 例、壁運動異常 1 例)、心電図異常 7 例(PVC Lown II以上 3 例、多源性 PVC 1 例、CRBBB 2 例、QT 延⻑ 1 例)、全身 PET 1 例。前年度も軽微な異常を認めたのは、PVC 3 例、 iCRBBB2 例であった。治療は全身ステロイド導入 22 例(A 群: B 群で 13 例:9 例)、PMI7 例(4 例:3 例)、ICD2 例(0 例:2 例)、CRTD2 例(1 例:1 例)、抗不整脈薬 2 例(0 例:2 例)。心サ症の死亡例は A 群 0 例、B 群 1 例(8.3%)。【考察】サ症を管理する非循環器内科医による定期的心臓スクリーニング検査の重要性が改めて認識されると共に、心サ症の予後改善に寄与している可能性が考えられた。
Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands Peer-reviewed

Soshi Muramatsu, Tsutomu Tamada, Masayuki Nara, Koji Murakami, Toshiaki Kikuchi, Masahiko Kanehira, Yoshio Maruyama, Masahito Ebina, Toshihiro Nukiwa, Masakazu Ichinose

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY　305　(11)　L819-L830　2013/12

DOI： 10.1152/ajplung.00053.2013 　

ISSN： 1040-0605

eISSN： 1522-1504
Miliary brain metastases in 2 cases with advanced non-small cell lung cancer harboring EGFR mutation during gefitinib treatment Peer-reviewed

Sayaka Mochizuki, Naoki Nishimura, Akira Inoue, Koji Murakami, Toshihiro Nukiwa, Naohiko Chohnabayashi

Respiratory Investigation　50　(3)　117-121　2012/09

DOI： 10.1016/j.resinv.2012.06.002 　

ISSN： 2212-5345
東日本大震災後に臨床所見に著しい変化を認めたサルコイドーシス5症例の臨床的検討 Peer-reviewed

村松聡士, 玉田勉, 奈良正之, 村上康司, 海老名雅仁, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　32　(1)　161-169　2012/09
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
Escherichia coli Pneumonia in Combination with Fungal Sinusitis and Meningitis in a Tsunami Survivor after the Great East Japan Earthquake Peer-reviewed

Ryotaro Igusa, Sodai Narumi, Koji Murakami, Yuko Kitawaki, Toru Tamii, Masahiro Kato, Mineshige Sato, Masahiro Tsuboi, Kozo Ota

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　227　(3)　179-184　2012/07

DOI： 10.1620/tjem.227.179 　

ISSN： 0040-8727

eISSN： 1349-3329
Toll-Like Receptor 4 Potentiates Ca2+-Dependent Secretion of Electrolytes from Swine Tracheal Glands Peer-reviewed

Koji Murakami, Tsutomu Tamada, Masayuki Nara, Soshi Muramatsu, Toshiaki Kikuchi, Masahiko Kanehira, Yoshio Maruyama, Masahito Ebina, Toshihiro Nukiwa

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY　45　(5)　1101-1110　2011/11

DOI： 10.1165/rcmb.2011-0020OC 　

ISSN： 1044-1549
RAPID IMPROVEMENT OF OSSEOUS SARCOIDOSIS AFTER THE TREATMENT OF PULMONARY ASPERGILLOSIS BY ITRACONAZOLE Peer-reviewed

K. Murakami, T. Tamada, K. Abe, M. Nara, S. Hisata, Y. Mitsuishi, S. Muramatsu, K. Gomi, M. Ebina, T. Nukiwa

SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES　28　(1)　75-78　2011/07

ISSN： 1124-0490
Acute eosinophilic pneumonia associated with the inhalation of phosgene gas under the presence of cigarette smoking Peer-reviewed

Tsutomu Tamada, Masayuki Nara, Koji Murakami, Soshi Muramatsu, Masahito Ebina, Toshihiro Nukiwa

Respiratory Medicine CME　4　(2)　96-98　2011

DOI： 10.1016/j.rmedc.2010.05.004 　

ISSN： 1755-0017
治療を要した骨サルコイドーシス4例の臨床的検討 Peer-reviewed

阿部恭子, 玉田勉, 奈良正之, 久田修, 光石陽一郎, 村上康司, 村松聡士, 五味和紀, 小倉健, 海老名雅仁, 貫和敏博

日本サルコイドーシス/肉芽腫性疾患学会雑誌　30　(1)　51-58　2010/09
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
MASSIVE PLEURAL EFFUSION AND BRONCHOPLEURAL FISTULA IN WEGENER'S GRANULOMATOSIS Peer-reviewed

S. Koyama, K. Murakami, T. Sakakibara, S. Muramatsu, M. Watanabe, M. Miki, M. Ebina, T. Nukiwa

SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES　27　(1)　76-79　2010/07

ISSN： 1124-0490

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Misc. 58

Clinical features of patients with severe COVID-19 relapsed after the cessation of corticosteroid therapy

村上康司, 佐野寛仁, 東出直樹, 杉山初美, 徳田浩一, 徳田浩一, 金森肇, 玉田勉, 杉浦久敏

日本呼吸器学会誌(Web)　12　2023

ISSN： 2186-5884
The change of medical system treating COVID-19 to continue specialized medical care

杉山初美, 村上康司, 佐野寛仁, 東出直樹, 徳田浩一, 金森肇, 玉田勉, 杉浦久敏

日本呼吸器学会誌(Web)　12　2023

ISSN： 2186-5884
Clinical features of patients with COVID-19 relapsed following cessation of corticosteroid therapy

村上康司, 佐野寛仁, 東出直樹, 佐藤慶, 徳田浩一, 大島謙悟, 金森肇, 馬場啓聡, 武井健太郎, 玉田勉, 杉浦久敏

日本呼吸器学会誌(Web)　11　2022

ISSN： 2186-5884
サルコイドーシスの自然寛解後に抗ARS抗体症候群を合併した一例

角藤翔, 村上康司, 玉田勉, 奈良正之, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　41　(サプリメント号)　67-67　2021/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
両側胸水と大量の腹水を認め診断に難渋した結核性胸腹膜炎の一例

松本周一郎, 宍倉裕, 伊藤辰徳, 佐藤輝幸, 村上康司, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　41　(1-2)　102-103　2021/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
サルコイドーシスの疾患活動性評価におけるリゾリン脂質産生酵素の有用性

村上康司, 玉田勉, 三枝大輔, 奈良正之, 宮内栄作, 矢冨裕, 杉浦久敏

日本呼吸器学会誌　10　(増刊)　265-265　2021/04
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
悪性リンパ腫に対するオビヌツズマブ併用療法により肺サルコイドーシスが増悪した1例

村上康司, 玉田勉, 奈良正之, 福原規子, 榊原智博, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　40　(サプリメント号)　52-52　2020/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
サルコイドーシスの血漿および尿中におけるリゾリン脂質産生酵素の解析

村上康司, 玉田勉, 三枝大輔, 奈良正之, 宮内栄作, 有竹秀美, 蒲生俊一, 矢冨裕, 一ノ瀬正和

日本呼吸器学会誌　9　(増刊)　205-205　2020/08
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
新鮮ブタ気道分泌液pHに対する長時間作用性β2刺激薬(LABA)の影響

有竹秀美, 玉田勉, 村上康司, 蒲生俊一, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　9　(増刊)　272-272　2020/08
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
胸腔鏡下肺切除術で診断された印環細胞癌様の形態を呈した肺腺癌の1例

宮内栄作, 成田大輔, 相澤洋之, 村上康司, 小林誠, 突田容子, 東出直樹, 齋藤良太, 佐藤輝幸, 杉浦久敏, 一ノ瀬正和, 齊藤涼子, 松田安史, 岡田克典

肺癌　59　(5)　511-511　2019/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
ヒトCOPD気道におけるToll様受容体(TLR)7の発現低下と気道分泌に与える影響の検討

蒲生俊一, 玉田勉, 村上康司, 有竹秀美, 村松聡士, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　8　(増刊)　191-191　2019/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
長時間作用型気管支拡張薬が新鮮気道分泌液の特性に与える影響の検討

有竹秀美, 玉田勉, 村上康司, 蒲生俊一, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　8　(増刊)　222-222　2019/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
ヒトCOPD気道におけるToll様受容体(TLR)7の発現低下と気道分泌に与える影響の検討

蒲生俊一, 玉田勉, 村上康司, 有竹秀美, 村松聡士, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　8　(増刊)　191-191　2019/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
長時間作用型気管支拡張薬が新鮮気道分泌液の特性に与える影響の検討

有竹秀美, 玉田勉, 村上康司, 蒲生俊一, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　8　(増刊)　222-222　2019/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
胸腔鏡下肺切除術で診断された印環細胞癌様の形態を呈した肺腺癌の1例

宮内栄作, 成田大輔, 相澤洋之, 村上康司, 小林誠, 突田容子, 東出直樹, 齋藤良太, 佐藤輝幸, 杉浦久敏, 一ノ瀬正和, 齊藤涼子, 松田安史, 岡田克典

肺癌(Web)　59　(5)　2019

ISSN： 1348-9992
食道静脈瘤破裂を来した肝病変合併サルコイドーシスの一例

有竹秀美, 玉田勉, 奈良正之, 村上康司, 蒲生俊一, 杉浦久敏, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　38　(サプリメント号)　78-78　2018/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
興味深い病態が示唆されたミオパチー型筋サルコイドーシスの2例

村上康司, 玉田勉, 奈良正之, 蒲生俊一, 有竹秀美, 三須建郎, 杉浦久敏, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　38　(サプリメント号)　79-79　2018/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
TLR7刺激によるSarco/Endoplasmic Reticulum Calcium ATPase(SERCA)作用亢進についての検討

蒲生俊一, 玉田勉, 村上康司, 有竹秀美, 村松聡士, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　7　(増刊)　193-193　2018/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
COPDに対する気管支拡張薬が気道被覆液の質的特性に及ぼす影響の検討

有竹秀美, 玉田勉, 村上康司, 蒲生俊一, 村松聡士, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　7　(増刊)　331-331　2018/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
TLR7リガンドによる気道分泌抑制作用の細胞内機序について

蒲生俊一, 玉田勉, 村松聡士, 村上康司, 奈良正之, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　6　(増刊)　300-300　2017/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
メタボロミクス解析を用いたサルコイドーシスの活動性予測バイオマーカーの検索

蒲生俊一, 玉田勉, 村上康司, 三枝大輔, 元池育子, 有竹秀美, 奈良正之, 村松聡士, 村松聡士, 杉浦久敏, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　37　2017

ISSN： 1883-1273
Upregulation Of Ca2+-Atpase By Tlr7 Decreases Electrolyte Secretion From Airway Submucosal Gland Cells

S. Gamo, T. Tamada, S. Muramatsu, K. Murakami, M. Nara, H. Sugiura, M. Ichinose

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　195　2017

ISSN： 1073-449X

eISSN： 1535-4970
CPC 日常臨床から学ぶこの症例の新しい意義は? 好酸球性肺炎の像を呈し全身播種に至った肺接合菌症の1例

山田充啓, 平野泰三, 佐藤慶, 高橋秀徳, 村上康司, 玉井ときわ, 玉田勉, 杉浦久敏, 佐藤直実, 齋藤涼子, 一ノ瀬正和

THE LUNG-perspectives　24　(4)　338-345　2016/11
Publisher: (株)メディカルレビュー社
ISSN： 0919-5742
尺骨動脈閉塞症を合併した肺腺癌の1例

山中駿, 宮内栄作, 平野泰三, 佐藤慶, 高橋秀徳, 村上康司, 玉井ときわ, 山田充啓, 岡崎達馬, 玉田勉, 杉浦久敏, 一ノ瀬正和, 井上彰

肺癌　56　(5)　404-404　2016/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
気管支鏡検査で菌検出が可能であった好酸球増多を伴う肺接合菌症の1例

突田容子, 平野泰三, 佐藤慶, 高橋秀徳, 村上康司, 玉井ときわ, 山田充啓, 玉田勉, 杉浦久敏, 一ノ瀬正和

肺癌　56　(5)　405-405　2016/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
メタボロミクス解析を用いたサルコイドーシス新規バイオマーカーの検索

村松聡士, 三枝大輔, 玉田勉, 奈良正之, 宮内栄作, 蒲生俊一, 村上康司, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　5　(増刊)　197-197　2016/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
TLR7の気道粘膜下腺細胞での発現と分泌機能への影響

蒲生俊一, 玉田勉, 村松聡士, 奈良正之, 村上康司, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　5　(増刊)　229-229　2016/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
発熱、多関節痛を伴った急性サルコイドーシスの1例

小野寺克洋, 玉田勉, 村松聡士, 村上康司, 奈良正之, 小松理世, 小林誠, 山田充啓, 杉浦久敏, 一ノ瀬正和

日本内科学会雑誌　105　(3)　540-546　2016/03
Publisher: (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
Toll Like Receptor 7 Regulates The Electrolytes Secretion From Airway Submucosal Gland

S. Gamo, S. Muramatsu, K. Murakami, T. Tamada, M. Nara, H. Sugiura, M. Ichinose

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　193　2016

ISSN： 1073-449X

eISSN： 1535-4970
診断基準改定前後の当科におけるサルコイドーシスと悪性腫瘍の合併例の検討

村松聡士, 玉田勉, 奈良正之, 村上康司, 蒲生俊一, 菊地利明, 一ノ瀬正和

日本呼吸器学会誌　4　(増刊)　224-224　2015/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
気道分泌調整因子としてのTLRリガンドの細胞内カルシウム濃度への影響

蒲生俊一, 玉田勉, 村松聡士, 村上康司, 奈良正之, 菊地利明, 一ノ瀬正和

日本呼吸器学会誌　4　(増刊)　332-332　2015/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
中枢性尿崩症を合併したサルコイドーシス3例の臨床的検討

村松聡士, 玉田勉, 奈良正之, 村上康司, 蒲生俊一, 中島一郎, 杉浦久敏, 一ノ瀬正和

日本サルコイドーシス／肉芽腫性疾患学会雑誌　35　(1)　68-4-68-4　2015
Publisher: 日本サルコイドーシス/肉芽腫性疾患学会
DOI： 10.7878/jjsogd.35.Suppl1_68-4 　

ISSN： 1883-1273

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サルコイドーシス(サ症)症例において、下垂体にサ症病変を伴い中枢性尿崩症(CDI)を来す症例は約 1〜2%と稀である。一方、 CDI 症例においてサ症が原因であるのは 0.5%程度とさらに稀であるとされる。現時点では視床下部-下垂体系の肉芽腫形成を組織学的に検索するのは困難であり、画像所見によって診断される場合が多い。当科サ症外来通院症例において、CDI を伴った 3 例について全身ステロイドに対する効果を中心に臨床的特徴をまとめた。男性 2 例(29 歳、45 歳)、女性 1 例(58 歳)で、3 例とも他臓器および CDI を評価病変として全身ステロイドによる加療が行われていた。3 例ともサ症の他臓器病変は改善していたのに対し、CDI は 1 例が改善、1 例は増悪、もう 1 例はほぼ不変であった。サ症に CDI が合併していても必ずしもサ症が原因であるとは限らず、また仮にサ症が原因であっても非可逆的な変化を伴っている場合には全身ステロイドの効果が期待できないものと考えられた。CDI を伴うサ症の病態および管理方法について文献的検討を加えて考察する。
Effects Of Tlr Ligands On The Intracellular Calcium Signaling In Tracheal Submucosal Gland Acinar Cells

S. Muramatsu, T. Tamada, M. Nara, S. Gamow, K. Murakami, T. Kikuchi, M. Ichinose

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　191　2015

ISSN： 1073-449X

eISSN： 1535-4970
サルコイドーシスと悪性腫瘍の合併例についての臨床的検討

村松聡士, 玉田勉, 奈良正之, 村上康司, 蒲生俊一, 星川康, 菊地利明, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　34　(サプリメント号)　66-66　2014/10
Publisher: 日本サルコイドーシス
DOI： 10.7878/jjsogd.34.66-3 　

ISSN： 1883-1273
TLRと気道分泌

玉田勉, 奈良正之, 村上康司, 村松聡士, 一ノ瀬正和

呼吸　33　(10)　971-981　2014/10
Publisher: (一社)呼吸研究
ISSN： 0286-9314
壊疽性膿皮症と骨髄異形成症候群に合併した続発性肺胞蛋白症の一例

小荒井晃, 大河内眞也, 玉田勉, 光石陽一郎, 村上康司, 小林誠, 渋谷里紗, 菊地利明, 一ノ瀬正和

気管支学　36　(Suppl.)　S244-S244　2014/03
Publisher: (NPO)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
気道粘膜下腺

村松聡士, 玉田勉, 奈良正之, 村上康司, 菊地利明, 一ノ瀬正和

日本呼吸器学会誌　3　(増刊)　263-263　2014/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
サルコイドーシスの予後予測因子としての血清sIL-2R測定の意義

村上康司, 玉田勉, 奈良正之, 光石陽一郎, 村松聡士, 菊地利明, 海老名雅仁, 一ノ瀬正和

呼吸　32　(5)　478-479　2013/05
Publisher: (一社)呼吸研究
ISSN： 0286-9314
Flagellin/TLR 5シグナルの気道分泌に対する影響

村松聡士, 玉田勉, 奈良正之, 村上康司, 菊地利明, 兼平雅彦, 海老名雅仁, 一ノ瀬正和

日本呼吸器学会誌　2　(増刊)　235-235　2013/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
気道粘膜下腺細胞からのCl-及びHCO3-分泌調節におけるIndacaterolの関与

村上康司, 玉田勉, 奈良正之, 村松聡士, 菊地利明, 海老名雅仁, 一ノ瀬正和

日本呼吸器学会誌　2　(増刊)　236-236　2013/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
A Switching Effect Of Indacaterol On Anion Secretions From Cl- To Hco3-In Airway Submucosal Gland Cells

K. Murakami, T. Tamada, M. Nara, S. Muramatsu, T. Kikuchi, M. Ebina, M. Ichinose

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　187　2013

ISSN： 1073-449X

eISSN： 1535-4970
当科における新規診断サルコイドーシス症例の臨床的特徴の経年的変化について

村上康司, 玉田勉, 奈良正之, 光石陽一郎, 村松聡士, 海老名雅仁, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　32　(サプリメント号)　40-40　2012/09
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
複数回の気胸に伴うブラ切除術により両肺の組織学的検討が可能であった非喫煙サルコイドーシスの1例

村松聡士, 玉田勉, 奈良正之, 村上康司, 久田修, 福原達朗, 阿部恭子, 綿貫善太, 海老名雅仁, 一ノ瀬正和

日本サルコイドーシス/肉芽腫性疾患学会雑誌　32　(サプリメント号)　48-48　2012/09
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
Toll様受容体5シグナル気道粘膜の水-電解質分泌を増強する

村松聡士, 玉田勉, 奈良正之, 村上康司, 千葉茂樹, 菊地利明, 海老名雅仁, 貫和敏博

日本呼吸器学会誌　1　(増刊)　216-216　2012/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
気道粘膜下腺細胞におけるToll様受容体4シグナリングによる分泌調節機序の検討

村上康司, 玉田勉, 奈良正之, 村松聡士, 菊地利明, 兼平雅彦, 海老名雅仁

日本呼吸器学会誌　1　(増刊)　216-216　2012/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
イトラコナゾール投与後に症状の著しい改善を認めた骨サルコイドーシスの1例

村上康司, 玉田勉, 阿部恭子, 奈良正之, 久田修, 光石陽一郎, 村松聡士, 海老名雅仁, 貫和敏博

日本サルコイドーシス/肉芽腫性疾患学会雑誌　31　(サプリメント号)　45-45　2011/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
東日本大震災の影響で臨床症状が増悪または改善したサルコイドーシス症例の検討

村松聡士, 玉田勉, 奈良正之, 村上康司, 海老名雅仁, 貫和敏博

日本サルコイドーシス/肉芽腫性疾患学会雑誌　31　(サプリメント号)　45-45　2011/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
気道粘膜下腺細胞からの電解質分泌に対するPDE阻害効果の影響

村松聡士, 玉田勉, 奈良正之, 村上康司, 海老名雅仁, 貫和敏博

日本呼吸器学会雑誌　49　(増刊)　293-293　2011/03
Publisher: (一社)日本呼吸器学会
ISSN： 1343-3490
気道粘膜下腺細胞におけるToll様受容体4シグナリングによる分泌調節機序の検討

村上康司, 玉田勉, 奈良正之, 村松聡士, 菊地利明, 兼平雅彦, 海老名雅仁, 貫和敏博

日本呼吸器学会雑誌　49　(増刊)　293-293　2011/03
Publisher: (一社)日本呼吸器学会
ISSN： 1343-3490
Toll-Like Receptor 4 Signaling As A Potentiator In The Airway Submucosal Gland Secretion

K. Murakami, T. Tamada, M. Nara, S. Muramatsu, T. Kikuchi, M. Kanehira, M. Ebina, T. Nukiwa

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　183　2011

ISSN： 1073-449X

eISSN： 1535-4970
The Effects Of Clinically Used Phosphodiesterase Inhibitors On Ca2+-Dependent Electrolytes Secretion From Airway Submucosal Gland

S. Muramatsu, T. Tamada, M. Nara, K. Murakami, M. Ebina, T. Nukiwa

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　183　2011

ISSN： 1073-449X

eISSN： 1535-4970
エンドキサンパルス療法によって気管支胸腔瘻が改善したWegener肉芽腫症の一例

村上康司, 榊原智博, 小山正平, 井上彰, 玉田勉, 村松聡士, 渡辺みか, 清水川稔, 三木誠, 岡山博, 海老名雅仁, 貫和敏博

日本サルコイドーシス/肉芽腫性疾患学会雑誌　30　(サプリメント号)　45-45　2010/09
Publisher: 日本サルコイドーシス
ISSN： 1883-1273
Toll-like receptor signaling as a potentiator in the airway submucosal gland secretion

K. Murakami, T. Tamda, M. Nara, T. Kikuchi, M. Ebina, T. Nukiwa

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　181　2010

ISSN： 1073-449X
気道粘膜下腺細胞におけるToll様受容体シグナリングによる分泌調節機序の検討

村上康司, 玉田勉, 奈良正之, 菊地利明, 海老名雅仁, 貫和敏博

日本呼吸器学会雑誌　48　(増刊)　171-171　2010
3.Gefitinib治療中に微細粒状影を呈する脳転移を認めた1例(第47回日本肺癌学会東北支部会,東北支部,支部活動)

村上康司, 井上彰, 榊原智博, 貫和敏博

肺癌　48　(6)　792-792　2008/10/20
Publisher: 日本肺癌学会
ISSN： 0386-9628
Streptococcus oralisが原因と考えられた劇症型連鎖球菌感染症の1例

中村敦, 高橋俊明, 久米正晃, 斎藤良太, 村松聡士, 佐藤広規, 庄田三希子, 中嶋壮太, 村上康司, 相澤健太郎, 佐藤貴子, 宮内栄作, 遠藤秀晃, 深堀耕平, 武田智, 伏見悦子, 関口展代, 西村勇人, 荻原忠, 田畑雅央, 木村啓二, 林雅人

秋田県農村医学会雑誌　53　(1)　70-70　2007/07
Publisher: (一財)秋田県農村医学会
ISSN： 0002-368X
肺癌と鑑別を要したサルコイドーシスの1例

中村敦, 木村啓二, 田畑雅央, 斎藤良太, 村松聡士, 佐藤広規, 庄田三希子, 中嶋壮太, 村上康司, 相澤健太郎, 佐藤貴子, 宮内栄作, 遠藤秀晃, 深堀耕平, 武田智, 高橋俊明, 伏見悦子, 関口展代, 西村勇人, 久米正晃, 荻原忠, 林雅人

秋田県農村医学会雑誌　53　(1)　75-75　2007/07
Publisher: (一財)秋田県農村医学会
ISSN： 0002-368X
検診にて発見された気管支動脈肺動脈瘻(気管支動脈蔓状血管腫)の一例

田畑雅央, 木村啓二, 関口展代, 高橋俊明, 伏見悦子, 武田智, 深堀耕平, 遠藤秀晃, 荻原忠, 久米正晃, 西村勇人, 相澤健太郎, 宮内栄作, 佐藤貴子, 村上康司, 中村敦, 照山和秀, 岩間孝英, 大久保俊治, 林雅人

秋田県農村医学会雑誌　52　(2)　47-47　2007/02
Publisher: (一財)秋田県農村医学会
ISSN： 0002-368X

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Research Projects 2

気道粘膜防御能の脆弱性改善によるCOPD増悪抑制のための新規治療法開発

玉田勉, 村上康司

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北大学

2021/04/01 - 2024/03/31

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社会の高齢化とともにCOPDによる入院や死亡者数は年々増加している。COPD増悪頻回例は喀痰の多い症例に多く、症状悪化、呼吸機能低下、死亡率上昇を来す。COPD増悪病態は、細菌・ウイルス感染および好酸球などが関与し、それぞれ長時間作用性気管支拡張薬および吸入ステロイドのより一定の増悪抑制効果が認められているものの、COPD増悪を未だ完全に制御できてはいない。COPDでは気道粘膜防御能が脆弱であり、現時点でその脆弱性を改善する根本的治療法が存在しないことが要因である。本研究の主題は、気道感染に伴うCOPD増悪予防に対する包括的治療戦略として、①気道粘膜防御能の脆弱性に影響する質的変化の特定、②新鮮気道分泌液の特性最適化による脆弱性の改善、③全てのCOPD増悪予防を可能とする新規治療法の開発である。申請者はこれまでに、病原微生物由来抗原がToll様受容体(TLR)を介して気道分泌に異常な量的変化を引き起こしCOPD増悪に関与し得ることを報告している。気道粘膜防御能の維持には気道分泌腺からのHCO3-分泌によるpH調節や抗菌活性保持などの質的特性の最適化が重要である。本研究ではこの質的異常と気道粘膜防御能脆弱性との関連を明らかにし、細菌やウイルスに対する易感染性を改善する治療薬開発への基礎を提供する。感染に伴うCOPD増悪やICS投与中の気道感染を制御することで、全てのCOPD増悪予防を目的とした安全で有効な新規治療法の確立と早期臨床応用を目指す。
Exploring the fragility of mucosal defense systems caused by an acquired dysregulation of airway secretion

Tamada Tsutomu

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2018/04/01 - 2021/03/31

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An acquired dysregulation of airway secretion is likely involved in the pathophysiology of COPD. However, limited data are available concerning the complementary additive effects of bronchodilators on airway secretion. ACh 100 nM induced a gradual increase in the amount of gland secretion in swine tracheal membrane. LPS accelerated the ACh-induced secretory responses up to around 3-fold and significantly lowered the pH level. LABAs restored the LPS-induced changes in both the hypersecretion and acidification. Two different inhibitors for CFTR abolished the LABA-mediated pH normalization. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, LABA did not restore the LPS-induced decrease in CFTR expression. These findings suggest that the activation of cAMP-dependent HCO3- secretion through CFTR would be partly involved in the LABA-mediated pH normalization in gland secretion.