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1. Refractory Hemoptysis Caused by Severe Pulmonary Vein Stenosis after Multiple Catheter Ablations

Author

Motoyasu Iikura, Masayuki Hojo, Akinari Tsukada, Takashi Katsuno, Manabu Suzuki, Yusaku Kusaba, Shinyu Izumi, Sachi Matsubayashi, Haruhito Sugiyama, Yuichiro Takeda, and Shuichiro Matsumoto

Subjects
Male, Hemoptysis, medicine.medical_specialty, Cox maze procedure, Radiofrequency ablation, medicine.medical_treatment, Case Report, Catheter ablation, maze procedure, pulmonary vein stenosis, law.invention, law, medicine.artery, Atrial Fibrillation, Internal Medicine, medicine, Humans, Pulmonary vein stenosis, business.industry, Atrial fibrillation, General Medicine, Middle Aged, medicine.disease, Surgery, bronchial artery embolization, Stenosis, Stenosis, Pulmonary Vein, Pulmonary Veins, Catheter Ablation, Bronchial artery, business, Left Pulmonary Vein
Abstract

We herein report a 48-year-old man with a history of chronic atrial fibrillation (AF) and repeated hemoptysis after radiofrequency ablation. Contrast tomography showed soft tissue thickening of the left hilar region and left pulmonary vein stenosis. We performed bronchial artery embolization, but the hemoptysis did not disappear, and AF was not controlled. We performed left lung lobectomy and maze procedures since we considered surgical removal necessary as radical treatment. After the surgery, hemoptysis and atrial fibrillation did not recur. Refractory hemoptysis after catheter ablation is rare, but occasionally occurs in patients with severe pulmonary vein stenosis.

Published
2021
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2. Author response for 'Clinical significance of pre‐diabetes, undiagnosed diabetes, and diagnosed diabetes on clinical outcomes in COVID‐19: Integrative analysis from the Japan COVID‐19 Task Force'

Author

null Takahiro Fukushima, null Shotaro Chubachi, null Ho Namkoong, null Takanori Asakura, null Hiromu Tanaka, null Ho Lee, null Shuhei Azekawa, null Yukinori Okada, null Ryuji Koike, null Akinori Kimura, null Seiya Imoto, null Satoru Miyano, null Seishi Ogawa, null Takanori Kanai, null Koichi Fukunaga, null Shiro Otake, null Kensuke Nakagawara, null Atsuho Morita, null Mayuko Watase, null Kaori Sakurai, null Takuya Kusumoto, null Katsunori Masaki, null Hiroki Kabata, null Hirofumi Kamata, null Makoto Ishii, null Naoki Hasegawa, null Kazuhisa Takahashi, null Norihiro Harada, null Toshio Naito, null Makoto Hiki, null Yasushi Matsushita, null Haruhi Takagi, null Ryousuke Aoki, null Ai Nakamura, null Sonoko Harada, null Hitoshi Sasano, null Shinnosuke Ikemura, null Satoshi Okamori, null Hideki Terai, null Junichi Sasaki, null Hiroshi Morisaki, null Yoshifumi Uwamino, null Kosaku Nanki, null Yohei Mikami, null Sho Uchida, null Shunsuke Uno, null Rino Ishihara, null Yuta Matsubara, null Tomoyasu Nishimura, null Takunori Ogawa, null Toshiro Sato, null Tetsuya Ueda, null Masanori Azuma, null Ryuichi Saito, null Toshikatsu Sado, null Yoshimune Miyazaki, null Ryuichi Sato, null Yuki Haruta, null Tadao Nagasaki, null Yoshinori Yasui, null Yoshinori Hasegawa, null Soichiro Ueda, null Ai Tada, null Masayoshi Miyawaki, null Masaomi Yamamoto, null Eriko Yoshida, null Reina Hayashi, null Tomoki Nagasaka, null Sawako Arai, null Yutaro Kaneko, null Kana Sasaki, null Takashi Ishiguro, null Taisuke Isono, null Shun Shibata, null Yuma Matsui, null Chiaki Hosoda, null Kenji Takano, null Takashi Nishida, null Yoichi Kobayashi, null Yotaro Takaku, null Noboru Takayanagi, null Etsuko Tagaya, null Masatoshi Kawana, null Ken Arimura, null Yasushi Nakamori, null Kazuhisa Yoshiya, null Fukuki Saito, null Tomoyuki Yoshihara, null Daiki Wada, null Hiromu Iwamura, null Syuji Kanayama, null Shuhei Maruyama, null Takanori Hasegawa, null Kunihiko Takahashi, null Tatsuhiko Anzai, null Satoshi Ito, null Akifumi Endo, null Yuji Uchimura, null Yasunari Miyazaki, null Takayuki Honda, null Tomoya Tateishi, null Shuji Tohda, null Naoya Ichimura, null Kazunari Sonobe, null Chihiro Tani Sassa, null Jun Nakajima, null Masumi Ai, null Takashi Yoshiyama, null Ken Ohta, null Hiroyuki Kokuto, null Hideo Ogata, null Yoshiaki Tanaka, null Kenichi Arakawa, null Masafumi Shimoda, null Takeshi Osawa, null Yasushi Nakano, null Yukiko Nakajima, null Ryusuke Anan, null Ryosuke Arai, null Yuko Kurihara, null Yuko Harada, null Kazumi Nishio, null Yoshikazu Mutoh, null Tomonori Sato, null Reoto Takei, null Satoshi Hagimoto, null Yoichiro Noguchi, null Yasuhiko Yamano, null Hajime Sasano, null Sho Ota, null Yusuke Suzuki, null Sohei Nakayama, null Keita Masuzawa, null Tomomi Takano, null Kazuhiko Katayama, null Koji Murakami, null Mitsuhiro Yamada, null Hisatoshi Sugiura, null Hirohito Sano, null Shuichiro Matsumoto, null Nozomu Kimura, null Yoshinao Ono, null Hiroaki Baba, null Rie Baba, null Daisuke Arai, null Takayuki Ogura, null Hidenori Takahashi, null Shigehiro Hagiwara, null Genta Nagao, null Shunichiro Konishi, null Ichiro Nakachi, null Hiroki Tateno, null Isano Hase, null Shuichi Yoshida, null Shoji Suzuki, null Miki Kawada, null Hirohisa Horinouchi, null Fumitake Saito, null Keiko Mitamura, null Masao Hagihara, null Junichi Ochi, null Tomoyuki Uchida, null Ryuya Edahiro, null Yuya Shirai, null Kyuto Sonehara, null Tatsuhiko Naito, null Kenichi Yamamoto, null Shinichi Namba, null Ken Suzuki, null Takayuki Shiroyama, null Yuichi Maeda, null Takuro Nii, null Yoshimi Noda, null Takayuki Niitsu, null Yuichi Adachi, null Takatoshi Enomoto, null Saori Amiya, null Reina Hara, null Toshihiro Kishikawa, null Shuhei Yamada, null Shuhei Kawabata, null Noriyuki Kijima, null Masatoshi Takagaki, null Noa Sasa, null Yuya Ueno, null Motoyuki Suzuki, null Norihiko Takemoto, null Hirotaka Eguchi, null Takahito Fukusumi, null Takao Imai, null Munehisa Fukushima, null Haruhiko Kishima, null Hidenori Inohara, null Kazunori Tomono, null Kazuto Kato, null Haruhiko Hirata, null Yoshito Takeda, null Atsushi Kumanogoh, null Naoki Miyazawa, null Yasuhiro Kimura, null Reiko Sado, null Hideyasu Sugimoto, null Akane Kamiya, null Naota Kuwahara, null Akiko Fujiwara, null Tomohiro Matsunaga, null Yoko Sato, null Takenori Okada, null Takashi Inoue, null Toshiyuki Hirano, null Keigo Kobayashi, null Hatsuyo Takaoka, null Koichi Nishi, null Masaru Nishitsuji, null Mayuko Tani, null Junya Suzuki, null Hiroki Nakatsumi, null Hidefumi Koh, null Tadashi Manabe, null Yohei Funatsu, null Fumimaro Ito, null Takahiro Fukui, null Keisuke Shinozuka, null Sumiko Kohashi, null Masatoshi Miyazaki, null Tomohisa Shoko, null Mitsuaki Kojima, null Tomohiro Adachi, null Motonao Ishikawa, null Kenichiro Takahashi, null Kazuyoshi Watanabe, null Yoshihiro Hirai, null Hidetoshi Kawashima, null Atsuya Narita, null Kazuki Niwa, null Yoshiyuki Sekikawa, null Hisako Sageshima, null Yoshihiko Nakamura, null Kota Hoshino, null Junichi Maruyama, null Hiroyasu Ishikura, null Tohru Takata, null Takashi Ogura, null Hideya Kitamura, null Eri Hagiwara, null Kota Murohashi, null Hiroko Okabayashi, null Takao Mochimaru, null Shigenari Nukaga, null Ryosuke Satomi Yoshitaka Oyamada, null Nobuaki Mori, null Tomoya Baba, null Yasutaka Fukui, null Mitsuru Odate, null Shuko Mashimo, null Yasushi Makino, null Kazuma Yagi, null Mizuha Hashiguchi, null Junko Kagyo, null Tetsuya Shiomi, null Kodai Kawamura, null Kazuya Ichikado, null Kenta Nishiyama, null Hiroyuki Muranaka, null Kazunori Nakamura, null Satoshi Fuke, null Hiroshi Saito, null Tomoya Tsuchida, null Shigeki Fujitani, null Mumon Takita, null Daiki Morikawa, null Toru Yoshida, null Takehiro Izumo, null Minoru Inomata, null Naoyuki Kuse, null Nobuyasu Awano, null Mari Tone, null Akihiro Ito, null Toshio Odani, null Masaru Amishima, null Takeshi Hattori, null Yasuo Shichinohe, null Takashi Kagaya, null Toshiyuki Kita, null Kazuhide Ohta, null Satoru Sakagami, null Kiyoshi Koshida, null Morio Nakamura, null Koutaro Yokote, null Taka‐Aki Nakada, null Ryuzo Abe, null Taku Oshima, null Tadanaga Shimada, null Kentaro Hayashi, null Tetsuo Shimizu, null Yutaka Kozu, null Hisato Hiranuma, null Yasuhiro Gon, null Namiki Izumi, null Kaoru Nagata, null Ken Ueda, null Reiko Taki, null Satoko Hanada, null Naozumi Hashimoto, null Keiko Wakahara, null Koji Sakamoto, null Norihito Omote, null Akira Ando, null Yu Kusaka, null Takehiko Ohba, null Susumu Isogai, null Aki Ogawa, null Takuya Inoue, null Nobuhiro Kodama, null Yasunari Kaneyama, null Shunsuke Maeda, null Takashige Kuraki, null Takemasa Matsumoto, null Masahiro Harada, null Takeshi Takahashi, null Hiroshi Ono, null Toshihiro Sakurai, null Takayuki Shibusawa, null Yusuke Kawamura, null Akiyoshi Nakayama, null Hirotaka Matsuo, null Yoshifumi Kimizuka, null Akihiko Kawana, null Tomoya Sano, null Chie Watanabe, null Ryohei Suematsu, null Makoto Masuda, null Aya Wakabayashi, null Hiroki Watanabe, null Suguru Ueda, null Masanori Nishikawa Ayumi Yoshifuji, null Kazuto Ito, null Saeko Takahashi, null Kota Ishioka, null Yusuke Chihara, null Mayumi Takeuchi, null Keisuke Onoi, null Jun Shinozuka, null Atsushi Sueyoshi, null Yoji Nagasaki, null Masaki Okamoto, null Sayoko Ishihara, null Masatoshi Shimo, null Yoshihisa Tokunaga, null Masafumi Watanabe, null Sumito Inoue, null Akira Igarashi, null Masamichi Sato, null Nobuyuki Hizawa, null Yoshiaki Inoue, null Shigeru Chiba, null Kunihiro Yamagata, null Yuji Hiramatsu, null Hirayasu Kai, null Satoru Fukuyama, null Yoshihiro Eriguchi, null Akiko Yonekawa, null Keiko Kano, null Koichiro Matsumoto, null Kensuke Kanaoka, null Shoichi Ihara, null Kiyoshi Komuta, null Koichiro Asano, null Tsuyoshi Oguma, null Yoko Ito, null Satoru Hashimoto, null Masaki Yamasaki, null Yu Kasamatsu, null Yuko Komase, null Naoya Hida, null Takahiro Tsuburai, null Baku Oyama, null Yuichiro Kitagawa, null Tetsuya Fukuta, null Takahito Miyake, null Shozo Yoshida, null Shinji Ogura, null Minoru Takada, null Hidenori Kanda, null Shinji Abe, null Yuta Kono, null Yuki Togashi, null Hiroyuki Takoi, null Ryota Kikuchi, null Shinichi Ogawa, null Tomouki Ogata, null Shoichiro Ishihara, null Arihiko Kanehiro, null Shinji Ozaki, null Yasuko Fuchimoto, null Sae Wada, null Nobukazu Fujimoto, null Kei Nishiyama, null Mariko Terashima, null Satoru Beppu, null Kosuke Yoshida, null Osamu Narumoto, null Hideaki Nagai, null Nobuharu Ooshima, null Mitsuru Motegi, null Akira Umeda, null Kazuya Miyagawa, null Hisato Shimada, null Mayu Endo, null Yoshiyuki Ohira, null Hironori Sagara, null Akihiko Tanaka, null Shin Ohta, null Tomoyuki Kimura, null Yoko Shibata, null Yoshinori Tanino, null Takefumi Nikaido, null Hiroyuki Minemura, null Yuki Sato, null Yuichiro Yamada, null Takuya Hashino, null Masato Shinoki, null Hajime Iwagoe, null Hiroshi Takahashi, null Kazuhiko Fujii, null Hiroto Kishi, null Tomoo Ishii, null Masayuki Kanai, null Tomonori Imamura, null Tatsuya Yamashita, null Masakiyo Yatomi, null Toshitaka Maeno, null Shinichi Hayashi, null Mai Takahashi, null Mizuki Kuramochi, null Isamu Kamimaki, null Yoshiteru Tominaga, null Mitsuyoshi Utsugi, null Akihiro Ono, null Toru Tanaka, null Takeru Kashiwada, null Kazue Fujita, null Yoshinobu Saito, null Masahiro Seike, null Masahiro Kanai, null Ryunosuke Saiki, null Takayoshi Hyugaji, null Eigo Shimizu, null Kotoe Katayama, null Satoru Miyawaki, null Meiko Takahashi, null Fumihiko Matsuda, null Yosuke Omae, null Yasuhito Nannya, null Takafumi Ueno, null Yuko Kitagawa, null Katsushi Tokunaga, and null The Japan COVID‐19 Task Force

Published
2022
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3. The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

Author

Qingbo S. Wang, Ryuya Edahiro, Ho Namkoong, Takanori Hasegawa, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Ho Lee, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Masahiro Kanai, Tatsuhiko Naito, Noah Sasa, Kenichi Yamamoto, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Masako Ichikawa, Ai Nakamura, Sonoko Harada, Yuuki Sandhu, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashri Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Takayuki Shiroyama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Kazunori Tomono, Kazuto Kato, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-o, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, and Yukinori Okada

Subjects
Multidisciplinary, Membrane Glycoproteins, Quantitative Trait Loci, General Physics and Astronomy, COVID-19, General Chemistry, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Japan, Viral infection, Humans, Lectins, C-Type, Gene expression, Receptors, Immunologic, Transcriptomics, Genome-Wide Association Study
Abstract

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., 「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.

Published
2021

4. Upregulation of leukocyte immunoglobulin-like receptor B4 on interstitial macrophages in COPD; their possible protective role against emphysema formation

Author

Tsutomu Tamada, Toshiyuki Takai, Ayumi Mitsune, Koji Itakura, Shota Endo, Tomohiro Ichikawa, Mitsuhiro Yamada, Shuichiro Matsumoto, Ayumi Suzuki, Hisatoshi Sugiura, Naoya Fujino, Tadahisa Numakura, Satoshi O. Suzuki, Yoshinori Okada, Yoshiya Mitsuhashi, Masakazu Ichinose, Tomonori Makiguchi, and Akira Koarai

Subjects
Pathology, medicine.medical_specialty, Pulmonary emphysema, Inflammation, Pathogenesis, Diseases of the respiratory system, Mice, Pulmonary Disease, Chronic Obstructive, Immune system, Macrophages, Alveolar, medicine, Animals, Humans, Respiratory function, Receptors, Immunologic, Cells, Cultured, Mice, Knockout, COPD, Lung, Membrane Glycoproteins, RC705-779, business.industry, Monocyte, Research, Elastase, medicine.disease, respiratory tract diseases, Up-Regulation, Mice, Inbred C57BL, medicine.anatomical_structure, Pulmonary macrophage, medicine.symptom, business, Matrix metalloproteinase 12
Abstract

Background Leukocyte immunoglobulin-like receptor B4 (LILRB4) is one of the inhibitory receptors in various types of immune cells including macrophages. Previous reports suggested that LILRB4 could be involved in a negative feedback system to prevent excessive inflammatory responses. However, its role has been unclear in chronic obstructive pulmonary disease (COPD), in which macrophages play a crucial role in the pathogenesis. In this study, we aimed to examine the changes of LILRB4 on macrophages both in the lung specimens of COPD patients and the lungs of a mouse emphysema model. We then tried to compare the differences in both inflammation and emphysematous changes of the model between wild-type and LILRB4-deficient mice in order to elucidate the role of LILRB4 in the pathogenesis of COPD. Methods We prepared single-cell suspensions of resected lung specimens of never-smokers (n = 21), non-COPD smokers (n = 16), and COPD patients (n = 14). The identification of LILRB4-expressing cells and the level of LILRB4 expression were evaluated by flow cytometry. We analyzed the relationships between the LILRB4 expression and clinical characteristics including respiratory function. In the experiments using an elastase-induced mouse model of emphysema, we also analyzed the LILRB4 expression on lung macrophages. We compared inflammatory cell accumulation and emphysematous changes induced by elastase instillation between wild-type and LILRB4-deficient mice. Results The levels of surface expression of LILRB4 are relatively high on monocyte linage cells including macrophages in the human lungs. The percentage of LILRB4+ cells in lung interstitial macrophages was increased in COPD patients compared to non-COPD smokers (p = 0.018) and correlated with the severity of emphysematous lesions detected by CT scan (rs = 0.559, p p = 0.008). LILRB4-deficient mice showed severer emphysematous lesions with increased MMP-12 expression in the model. Conclusions LILRB4 on interstitial macrophages was upregulated both in human COPD lungs and in a mouse model of emphysema. This upregulated LILRB4 may have a protective effect against emphysema formation, possibly through decreasing MMP-12 expression in the lungs.

Published
2021

5. Clinical features of COVID-19 patients with rebound phenomenon after corticosteroid therapy

Author

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, and Hisatoshi Sugiura

Subjects
Pulmonary and Respiratory Medicine
Abstract

RationalCorticosteroid therapy plays a key role in the treatment of COVID-19 patients with respiratory failure. However, a rebound phenomenon after steroid cessation rarely occurs. Here, we investigated the clinical features of patients with rebound after steroid therapy.MethodsIn total, 84 patients with COVID-19 treated with corticosteroids were enrolled and analysed retrospectively. A rebound was defined as when a patient’s respiratory status deteriorated after the cessation of corticosteroid therapy, without secondary bacterial infection.ResultsSubjects in the rebound group were more likely to having severe respiratory failure than those in the non-rebound group. While the duration of steroid therapy was longer in the rebound group (8 days vs 10 days, p=0.0009), the dosage of steroid and the timing of the start or termination of steroid therapy did not show any differences between the two groups (p=0.17 and 0.68, respectively). The values of soluble interleukin-2 receptor (sIL-2R) at the baseline and the values of C reactive protein (CRP) or lactate dehydrogenase (LDH) at the end of steroid therapy were significantly higher in the rebound group (937 vs 1336 U/mL; p=0.002, 0.63 vs 3.96 mg/dL; p=0.01 and 278 vs 451 IU/mL; p=0.01, respectively). No patient in the rebound group suffered from thromboses, and the causes of death were exacerbation of COVID-19, ventilator-associated pneumonia or sepsis. The prediction model using baseline features for the rebound phenomenon included four variables of age >68 years, required supplemental oxygen >5 L/min, lymphocyte counts 1146 U/mL. The discrimination ability of this model was 0.906 (0.755–0.968).ConclusionThese findings suggest that severe respiratory failure has a higher risk for the rebound phenomenon after the cessation of corticosteroids, and the values of sIL-2R, LDH and CRP are useful to assess the probability of developing rebound. A multivariate model was developed to predict rebound risk, which showed acceptable discrimination ability.

Published
2022
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6. Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

Author

Shuichi Yoshida, Yoshihiro Hirai, Hiroshi Takahashi, Yoshiyuki Sekikawa, Saeko Takahashi, Yoshitaka Oyamada, Shunsuke Uno, Koutaro Yokote, Kunihiko Takahashi, Shigenari Nukaga, Yoshinao Ono, Shoichiro Ishihara, Nozomu Kimura, Tomohiro Adachi, Shigeki Fujitani, Eri Hagiwara, Motoyuki Suzuki, Tomouki Ogata, Namiki Izumi, Shinji Abe, Etsuko Tagaya, Yoshinori Hasegawa, Yoshimune Miyazaki, Junichi Sasaki, Yoshinori Tanino, Seishi Ogawa, Yuki Togashi, Satoshi Fuke, Yoshiaki Inoue, Hideo Ogata, Masaomi Yamamoto, Hiroshi Saito, Jun Shinozuka, Sho Uchida, Masayoshi Miyawaki, Atsushi Kumanogoh, Koichiro Matsumoto, Yuko Kitagawa, Mayu Endo, Mitsuru Odate, Hiroki Tateno, Fumitake Saito, Mizuki Kuramochi, Shoji Suzuki, Koji Murakami, Kenichi Arakawa, Shozo Yoshida, Hitoshi Sasano, Keigo Kobayashi, Takuro Nii, Takashi Ishiguro, Ryuichi Saito, Yohei Mikami, Takashi Inoue, Haruhiko Kishima, Daisuke Arai, Takao Mochimaru, Minoru Takada, Yuya Ueno, Takehiro Izumo, Reina Hara, Nobuyuki Hizawa, Atsuho Morita, Takanori Hasegawa, Masahiro Seike, Hisako Sageshima, Takeshi Hattori, Shinichi Namba, Shuko Mashimo, Tomoya Tsuchida, Hiromu Tanaka, Naoki Miyazawa, Masatoshi Kawana, Shunichiro Konishi, Takatoshi Enomoto, Takuya Hashino, Hiroki Watanabe, Kentaro Hayashi, Sumito Inoue, Satoshi Hagimoto, Toru Yoshida, Akiko Fujiwara, Masaki Okamoto, Hiroki Kabata, Shuji Tohda, Baku Oyama, Norihiko Takemoto, Nobuyasu Awano, Makoto Hiki, Yasutaka Fukui, Takahiro Fukui, Keisuke Onoi, Yuichiro Yamada, Takayuki Shiroyama, Mayuko Tani, Hiroyuki Muranaka, Kazuhide Ohta, Yoshifumi Kimizuka, Hajime Iwagoe, Yasuko Fuchimo, Hiroki Nakatsumi, Hiroyuki Minemura, Hisatoshi Sugiura, Haruhi Takagi, Hiroyuki Kokuto, Yasuhiro Kimura, Masatoshi Takagaki, Yuki Sato, Masao Hagihara, Junko Kagyo, Yusuke Kawamura, Sayoko Ishihara, Akinori Kimura, Aki Ogawa, Hironori Sagara, Noa Sasa, Masahiro Kanai, Isano Hase, Takenori Okada, Akiyoshi Nakayama, Osamu Narumoto, Norihito Omote, Kazunori Tomono, Toshiro Sato, Hatsuyo Takaoka, Mayumi Takeuchi, Keiko Kan-o, Satoshi Okamori, Yukinori Okada, Yoshito Takeda, Kazuto Ito, Tatsuhiko Naito, Reina Hayashi, Toshikatsu Sado, Kazuya Ichikado, Yasushi Matsushita, Nobuaki Mori, Takashi Nishida, Toshitaka Maeno, Tomomi Takano, Soichiro Ueda, Tomoyasu Nishimura, Masaru Nishitsuji, Ryusuke Anan, Arihiko Kanehiro, Akira Umeda, Syuji Kanayama, Yosuke Omae, Tomoki Nagasaka, Koichi Nishi, Yoshiyuki Ohira, Fumimaro Ito, Toru Tanaka, Kenichiro Takahashi, Hidenori Kanda, Hidenori Inohara, Kaoru Nagata, Kei Nishiyama, Masafumi Watanabe, Katsunori Masaki, Ryuzo Abe, Hirofumi Kamata, Masahiro Harada, Chihiro Tani Sassa, Tomoya Sano, Shoichi Ihara, Tadashi Manabe, Takafumi Ueno, Takahito Fukusumi, Meiko Takahashi, Kyuto Sonehara, Kana Sasaki, Hiroyuki Takoi, Chie Watanabe, Takahiro Tsuburai, Tomonori Sato, Yoichi Kobayashi, Kazuhisa Takahashi, Yasushi Nakano, Kenichi Yamamoto, Takayoshi Hyugaji, Hirohito Sano, Ho Namkoong, Atsushi Sueyoshi, Naoya Ichimura, Yoshiteru Tominaga, Masaru Amishima, Ken Suzuki, Ken Ohta, Shigehiro Hagiwara, Masayuki Kanai, Kota Hoshino, Shuhei Kawabata, Mitsuhiro Yamada, Toshio Naito, Akihiro Ono, Yotaro Takaku, Yoko Sato, Satoru Miyano, Junichi Ochi, Yoshikazu Mutoh, Hiroaki Baba, Yoko Shibata, Tatsuya Yamashita, Yoko Ito, Hiromu Iwamura, Munehisa Fukushima, Saori Amiya, Takayuki Honda, Yuta Kono, Susumu Isogai, Ryuya Edahiro, Makoto Masuda, Hisato Shimada, Hideaki Nagai, Tomoya Baba, Fukuki Saito, Toshihiro Sakurai, Ryota Kikuchi, Yoichiro Noguchi, Tatsuhiko Anzai, Mizuha Hashiguchi, Masamichi Sato, Naoki Hasegawa, Yasunari Miyazaki, Tetsuya Ueda, Yasuhiko Yamano, Shinji Ozaki, Yoshinobu Saito, Takuya Inoue, Sohei Nakayama, Sawako Arai, Yu Kusaka, Miki Kawada, Yuko Kurihara, Daiki Wada, Isamu Kamimaki, Motonao Ishikawa, Sumiko Kohashi, Sae Wada, Kazuma Yagi, Rino Ishihara, Hiroko Okabayashi, Nobuhiro Kodama, Mai Takahashi, Kiyoshi Komuta, Yusuke Chihara, Yoshihiko Nakamura, Akifumi Endo, Shuichiro Matsumoto, Akira Igarashi, Shuhei Yamada, Akiko Yonekawa, Yukiko Nakajima, Sakamoto Koji, Kazue Fujita, Masakiyo Yatomi, Makoto Ishii, Ryuji Koike, Eigo Shimizu, Shigeru Chiba, Satoru Miyawaki, Shunsuke Maeda, Toshio Odani, Hideyasu Sugimoto, Masanori Nishikawa, Yoshinori Yasui, Akira Ando, Takayuki Shibusawa, Nobuharu Ooshima, Toshiyuki Kita, Satoru Fukuyama, Ai Tada, Mariko Terashima, Tadao Nagasaki, Rie Baba, Atsuya Narita, Takanori Ogawa, Tetsuo Shimizu, Ken Ueda, Yuki Haruta, Satoru Hashimoto, Ryohei Suematsu, Ho Lee, Ryosuke Satomi, Hirotaka Eguchi, Kota Ishioka, Ryousuke Aoki, Yusuke Suzuki, Takemasa Matsumoto, Kazunari Sonobe, Hisato Hiranuma, Hirayasu Kai, Kosuke Yoshida, Ayumi Yoshifuji, Takeru Kashiwada, Yuko Harada, Reoto Takei, Aya Wakabayashi, Tomohiro Matsunaga, Haruhiko Hirata, Hiroshi Morisaki, Yoshifumi Uwamino, Yoshihisa Tokunaga, Kazuki Niwa, Hidetoshi Kawashima, Hideki Terai, Kenji Takano, Mumon Takita, Yuko Komase, Masaki Yamasaki, Chiaki Hosoda, Takayuki Ogura, Shun Shibata, Mitsuru Motegi, Takeshi Takahashi, Takehiko Ohba, Shinichi Hayashi, Satoshi Ito, Yu Kasamatsu, Shinnosuke Ikemura, Tetsuya Fukuta, Koichiro Asano, Taka-aki Nakada, Kota Murohashi, Tomoyuki Uchida, Hirotaka Matsuo, Satoko Hanada, Kenta Nishiyama, Minoru Inomata, Nobukazu Fujimoto, Tomoya Tateishi, Mitsuaki Kojima, Kazuto Kato, Kazuhiko Katayama, Yuichi Maeda, Takashi Kagaya, Keiko Wakahara, Takashi Ogura, Yasuhiro Gon, Taku Oshima, Ken Arimura, Shuhei Maruyama, Mari Tone, Ryuichi Sato, Koichi Fukunaga, Hidefumi Koh, Yuichiro Kitagawa, Noboru Takayanagi, Masatoshi Miyazaki, Ichiro Nakachi, Akihiko Kawana, Toshiyuki Hirano, Yohei Funatsu, Yasushi Nakamori, Reiko Sado, Yasuo Shichinohe, Junya Suzuki, Yasunari Kaneyama, Takahito Miyake, Kunihiro Yamagata, Yasuhito Nannya, Shinichi Ogawa, Naoya Hida, Tsuyoshi Oguma, Kazunori Nakamura, Kosaku Nanki, Naozumi Hashimoto, Fumihiko Matsuda, Tomoyuki Kimura, Daiki Morikawa, Yuji Uchimura, Yoshiaki Tanaka, Kazuhisa Yoshiya, Takashige Kuraki, Yoshihiro Eriguchi, Tomohisa Shoko, Tadanaga Shimada, Yuji Hiramatsu, Akihiko Tanaka, Hideya Kitamura, Yutaka Kozu, Ryosuke Arai, Taisuke Isono, Yasushi Makino, Seiya Imoto, Yuichi Adachi, Yuma Matsui, Masato Shinoki, Kazumi Nishio, Keiko Mitamura, Tomonori Imamura, Masanori Azuma, Sonoko Harada, Hiroshi Ono, Kotoe Katayama, Masumi Ai, Keisuke Shinozuka, Reiko Taki, Junichi Maruyama, Takao Imai, Yutaro Kaneko, Kensuke Kanaoka, Sho Ota, Yoji Nagasaki, Toshihiro Kishikawa, Takayuki Niitsu, Hirohisa Horinouchi, Naoyuki Kuse, Tetsuya Shiomi, Jun Nakajima, Katsushi Tokunaga, Norihiro Harada, Keita Masuzawa, Noriyuki Kijima, Takeshi Osawa, Satoru Sakagami, Kazuhiko Fujii, Shotaro Chubachi, Tomoyuki Yoshihara, Yoshimi Noda, Hiroyasu Ishikura, Kiyoshi Koshida, Shin Ohta, Ai Nakamura, Naota Kuwahara, Shinji Ogura, Suguru Ueda, Akihiro Ito, Morio Nakamura, Tohru Takata, Yuya Shirai, Hidenori Takahashi, Eriko Yoshida, Satoru Beppu, Mitsuyoshi Utsugi, Masafumi Shimoda, Masatoshi Shimo, Tomoo Ishii, Takefumi Nikaido, Takanori Asakura, Kazuya Miyagawa, Takanori Kanai, Hiroto Kishi, Akane Kamiya, Genta Nagao, Kodai Kawamura, Ryunosuke Saiki, Takashi Yoshiyama, Hajime Sasano, Kazuyoshi Watanabe, and Yuta Matsubara

Subjects
Genetics, education.field_of_study, Population, Mendelian Randomization Analysis, Genome-wide association study, Odds ratio, Biology, medicine.disease, Obesity, Confidence interval, Minor allele frequency, Pandemic, medicine, education
Abstract

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Published
2021
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7. Clinical usefulness of End-Tidal CO2 measured by a novel portable capnograph in patients with respiratory disease

Author

Yuichiro Takeda, Manabu Suzuki, Shuichiro Matsumoto, Hiroshi Takumida, Haruhito Sugiyama, Yuriko Horikawa, Keita Sakamoto, Takashi Katsuno, Yoshie Tsujimoto, Masao Hashimoto, Shinyu Izumi, Motoyasu Iikura, Tamaki Kakuwa, Shota Fujimoto, Hiromu Watanabe, Hirokazu Arai, Go Naka, Yuriko Ueki, Masayuki Hojo, Satoru Ishii, Yusaku Kusaba, Junko Terada, and Jin Takasaki

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Respiratory disease, Cardiology, Medicine, In patient, business, medicine.disease, End tidal co2
Published
2020
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8. Successful Recovery from COVID-19-associated Acute Respiratory Failure with Polymyxin B-immobilized Fiber Column-direct Hemoperfusion

Author

Manabu Suzuki, Masayuki Hojo, Keita Sakamoto, Norio Ohmagari, Tadaki Suzuki, Harutaka Katano, Takashi Katsuno, Shinyu Izumi, Daisuke Katagiri, Yusaku Kusaba, Jin Takasaki, Haruhito Sugiyama, Shuichiro Matsumoto, and Masao Hashimoto

Subjects
Male, medicine.drug_class, medicine.medical_treatment, Polymyxin, Pneumonia, Viral, Case Report, 030204 cardiovascular system & hematology, polymyxin B-immobilized fiber column-direct hemoperfusion, Ground-glass opacity, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Internal Medicine, medicine, Humans, Respiratory system, Pandemics, Polymyxin B, Mechanical ventilation, Aged, 80 and over, Lung, acute respiratory failure, business.industry, SARS-CoV-2, COVID-19, Lopinavir, General Medicine, Hemoperfusion, Respiration, Artificial, Anti-Bacterial Agents, medicine.anatomical_structure, Respiratory failure, Anesthesia, 030211 gastroenterology & hepatology, medicine.symptom, business, Coronavirus Infections, Respiratory Insufficiency, Tomography, X-Ray Computed, medicine.drug
Abstract

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.

Published
2020

9. Cost-effectiveness of bronchial thermoplasty for severe asthmatic patients in Japan

Author

Motoyasu Iikura, Masao Hashimoto, Haruhito Sugiyama, Tamaki Kakuwa, Keita Sakamoto, Takashi Katsuno, Shinyu Izumi, Sachi Matsubayashi, Masayuki Hojo, Naoko Nagano, Yuichiro Takeda, Yusaku Kusaba, Shuichiro Matsumoto, Satoru Ishii, Yoshie Tsujimoto, Manabu Suzuki, and Go Naka

Subjects
medicine.medical_specialty, Bronchial thermoplasty, Cost effectiveness, business.industry, Medical record, Brief Report, medicine.disease, respiratory tract diseases, Outpatient visits, Emergency medicine, medicine, Asthmatic patient, business, Medical costs, Medical expenses, Asthma
Abstract

Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe bronchial asthma. Some studies have shown the clinical efficacy of this intervention, but its cost-effectiveness is unclear. The aim of this study was to evaluate the cost-effectiveness of BT. We collected data from the medical records of 16 Japanese patients who were treated with BT between February 2015 and April 2017, and compared asthma-related medical expenses between the year preceding and the year following BT. Four patients were Global Initiative for Asthma (GINA) treatment step 4, and 12 were step 5. In 8 patients who had a successful response to BT, the annual asthma-related medical expenses decreased because of a reduction in hospitalization and emergency outpatient visits due to asthma attacks, and termination of the use of biologics. Most patients in the non-responder group had increased asthma-related medical costs postoperatively. The main reason for the increase in medical costs was the add-on treatment of biologics. BT was cost-effective in the responder group. If its effects continue for more than 10 years, BT will be a cost-effective treatment. Medical costs will be reduced if those who respond to BT can be identified prior to commencement of treatment.

Published
2020

10. Systemic Psoriasiform Dermatitis Appeared after the Administration of Pembrolizumab

Author

Haruhito Sugiyama, Yuichiro Takeda, Shuichiro Matsumoto, and Manabu Suzuki

Subjects
PD-L1, medicine.medical_specialty, biology, business.industry, Immune checkpoint inhibitors, General Medicine, Pembrolizumab, Dermatology, immune checkpoint inhibitors, Pictures in Clinical Medicine, psoriasis-like rashes, Internal Medicine, biology.protein, psoriasiform dermatitis, Medicine, immune-related adverse event (irAE), business, Psoriasiform Dermatitis
Published
2020
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11. Idiopathic Pulmonary Fibrosis based on disease behavior: Workshop summary of a Japanese multicenter study

Author

Tomoo Kishaba, Akira Yamagata, Naoki Hamada, Takeshi Johkoh, Goshi Matama, Reiko Egashira, Yukihiro Nakamura, Yuki Matsui, Takahiko Kasai, Tomohisa Baba, Nobuhiko Nagata, Yoshinori Kawabata, Chikatoshi Sugimoto, Toru Arai, Naoko Takeuchi, Shuichiro Matsumoto, Yasuhiro Kondoh, Kensuke Kataoka, Shigeki Shimizu, Keisuke Tomii, Keita Sakamoto, Fumikazu Sakai, Ayaka Tanaka, Tamiko Takemura, Hiromi Tomioka, Shinyu Izumi, Kazuhito Hatanaka, Masanori Kitaichi, Ryobu Mori, Venerino Poletti, Yoshikazu Inoue, Hiromitsu Sumikawa, Tomonori Tanaka, Kazunobu Tachibana, and Masanori Akira

Subjects
Idiopathic pulmonary fibrosis, medicine.medical_specialty, Multicenter study, business.industry, Internal medicine, medicine, Disease, medicine.disease, business
Published
2019
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12. A CASE OF REPEATED HEMOPTYSIS AFTER CATHETER ABLATION

Author

Takashi Katsuno, Shinyu Izumi, Motoyasu Iikura, Shuichiro Matsumoto, Manabu Suzuki, Yusaku Kusaba, Sachi Matsubayashi, Keigo Sekihara, Haruhito Sugiyama, and Akinari Tsukada

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, medicine.medical_treatment, medicine, Catheter ablation, Radiology, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, business
Published
2019
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13. Hypothermic preservation effect on mammalian cells of type III antifreeze proteins from notched-fin eelpout

Author

Yoshiyuki Nishimiya, Satoru Todo, Michiaki Matsushita, Sakae Tsuda, Shuichiro Matsumoto, Ai Miura, Yasuo Komatsu, and Yu Hirano

Subjects
Cryopreservation, Fish Proteins, Gene isoform, biology, Antifreeze Proteins, Type III, General Medicine, biology.organism_classification, Recombinant Proteins, General Biochemistry, Genetics and Molecular Biology, Perciformes, Eelpout, law.invention, Biochemistry, law, Antifreeze protein, Recombinant DNA, Animals, Humans, Protein Isoforms, Viability assay, Zoarces elongatus, General Agricultural and Biological Sciences, Cells, Cultured, Intracellular
Abstract

Antifreeze proteins (AFPs) can bind to the surface of ice crystals and have also been suggested to protect cells from hypothermic damage. The present study reports that type III AFPs from notched-fin eelpout, Zoarces elongatus Kner, can protect cells during hypothermic storage. This fish naturally expresses at least 13 isoforms of type III AFP (denoted NfeAFPs), the primary sequences of which were categorized into SP- and QAE-Sephadex binding groups (SP- and QAE-isoforms). We compared the preservation ability between the extracted isoform mixtures (NfeAFPs) and a recombinant single SP-isoform (RcNfeAFP6). Experiments were performed using cultivated mammalian cells (HepG2) exposed to 4 degrees C for 24-72 h. The preserved cells were evaluated by measuring LDH released, intracellular ATP, and WST-8 reduction. It appeared that the protective effect of the 2 samples increases dose-dependently at concentrations between 2 and 10 mg/ml. Under highest soluble amount of the protein (approximately 10 mg/ml), cell viability significantly improved compared with the ordinary preservation fluid (P

Published
2008
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14. Microencapsule technique protects hepatocytes from cryoinjury

Author

Kousuke Yamada, Shuichiro Matsumoto, Satoru Todo, Tomokazu Kusano, Nobukazu Nishino, Keitatsu Kou, Noriyuki Murai, Takashi Niiya, Hirohisa Kato, Keitaro Mitamura, Mitsuo Kusano, Michiaki Matsusita, Tomotake Koizumi, Ken Hayashi, Daisuke Yasuda, Seiji Shioda, Yoshinori Shimizu, Yoshihiko Izumida, Yuta Enami, Takeshi Aoki, Masanori Odaira, Zhenghao Jin, and Yoshinori Furukawa

Subjects
Hepatology, Ethylenediaminetetraacetic acid, Biology, Cryopreservation, Cell biology, chemistry.chemical_compound, Hepatocyte nuclear factors, Infectious Diseases, medicine.anatomical_structure, Hepatocyte transplantation, chemistry, Biochemistry, Hepatocyte, medicine, Extracellular, Collagenase, Intracellular, medicine.drug
Abstract

AIM Hepatocyte transplantation is a potential alternative to whole organ liver transplantation. To realize this procedure, a hepatocyte bank system capable of supplying large numbers of hepatocytes must be established. We previously reported an easy method for cryopreserving hepatocytes using a microencapsulation technique. Here, we investigated how cryoinjury to microencapsulated hepatocytes could be avoided during cryopreservation. METHODS Hepatocytes from Sprague-Dawley rats were harvested in situ using a two-step ethylenediaminetetraacetic acid (EDTA)/collagenase digestion protocol. The cells were microencapsulated using alginate-poly L-lysine. The microencapsulated hepatocytes were put into vials and immediately immersed in liquid nitrogen. The growth of ice crystals in the vials containing the microencapsulated hepatocytes was observed using cryomicroscopy. The microencapsulated hepatocytes were sectioned for ultrastructural examination to investigate their intracellular conditions. Finally, total RNA was isolated from the cryopreserved microencapsulated hepatocytes and analyzed for hepatocyte nuclear factor (HNF) using reverse transcriptase polymerase chain reaction (RT-PCR) analysis. RESULTS Cryomicroscopy showed that the alginate microencapsulation technique protected the hepatocytes from physical damage caused by the growth of extracellular ice crystals. Ultrastructural examination revealed that the intracellular environment of the microencapsulated hepatocytes was maintained. The RT-PCR analysis additionally suggested that the alginate gel also maintained the HNF level. CONCLUSION Our microencapsulation technique protects hepatocytes from cryoinjury. This novel technique could be utilized by hepatocyte banks.

Published
2008
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15. IL-1 and IL-6 induce hepatocyte plasminogen activator inhibitor-1 expression through independent signaling pathways converging on C/EBPδ

Author

Satoru Todo, Michiaki Matsushita, Burton E. Sobel, Satoshi Fujii, Hiroyuki Tsutsui, Shuichiro Matsumoto, Jie Dong, and Shogo Imagawa

Subjects
CCAAT-Enhancer-Binding Protein-delta, Cell Extracts, Physiology, Interleukin-1beta, Down-Regulation, Response Elements, Mice, chemistry.chemical_compound, Downregulation and upregulation, Plasminogen Activator Inhibitor 1, medicine, Animals, Humans, RNA, Messenger, RNA, Small Interfering, Promoter Regions, Genetic, Interleukin 6, Cells, Cultured, Cell Nucleus, biology, Ccaat-enhancer-binding proteins, Interleukin-6, Binding protein, Chromosome Mapping, Cell Biology, medicine.anatomical_structure, chemistry, Hepatocyte, Plasminogen activator inhibitor-1, Hepatocytes, Cancer research, biology.protein, Signal transduction, Plasminogen activator, Signal Transduction
Abstract

To elucidate signaling pathways activated by IL-1 and IL-6 that contribute to increased expression of plasminogen activator inhibitor-1 (PAI-1), we studied human hepatoma (HepG2) cells and primary mouse hepatocytes. HepG2 cell PAI-1 mRNA increased in response to IL-1beta, IL-6, and IL-1beta plus IL-6 as shown by real-time PCR. Activity of the transiently transfected PAI-1 promoter (-829 to +36 bp) increased as well. Systematic promoter deletion assays showed that the region from -239 to -210 bp containing a putative CCAAT-enhancer binding protein (C/EBP) binding site was critical. Point mutations in this region abolished the IL-1beta and IL-6 responses. Antibody interference electrophoretic mobility shift assays showed that C/EBPdelta (but not C/EBPalpha or C/EBPbeta) binding and protein were increased by IL-1beta, IL-6, and IL-1beta plus IL-6 in HepG2 cells. IL-1beta and IL-6 increased expression of both PAI-1 mRNA and C/EBPdelta mRNA in mouse primary hepatocytes as well. Downregulation of C/EBPdelta induced with small interfering RNA (siRNA) decreased secretion of PAI-1. As judged from results obtained with inhibitors, signal transduction in all three of the mitogen-activated protein kinase pathways was involved in IL-1-inducible PAI-1 expression. By contrast, JAK signaling was responsible for the IL-6-induced inducible expression. Thus IL-1 and IL-6 exert directionally similar effects on PAI-1 expression, but the induction involves distinct signaling pathways with a final common mediator, C/EBPdelta.

Published
2007
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16. Effects of synthetic antifreeze glycoprotein analogue on islet cell survival and function during cryopreservation

Author

Shuhei Koshida, Shusaku Tsukiyama, Satoru Todo, Yoshinori Furukawa, Shin-Ichiro Nishimura, Tsunehiko Morita, Shuichiro Matsumoto, Yuki Tachibana, Hirofumi Kamachi, and Michiaki Matsusita

Subjects
Male, Erythrocytes, Cell Survival, medicine.medical_treatment, Biology, General Biochemistry, Genetics and Molecular Biology, Cryopreservation, Andrology, Islets of Langerhans, chemistry.chemical_compound, Antifreeze Proteins, Freezing, medicine, Animals, Rats, Wistar, geography, geography.geographical_feature_category, Dimethyl sulfoxide, Insulin, Cryoelectron Microscopy, Galactose, General Medicine, Islet, In vitro, Rats, Enzyme Activation, Transplantation, Biochemistry, chemistry, Antifreeze, Collagenase, General Agricultural and Biological Sciences, medicine.drug
Abstract

The antifreeze glycoprotein (AFGP), found in the blood of polar fish, is known to prevent ice crystal growth and to depress the freezing temperature, which may in turn protect tissues from freezing injury. The chemical synthesis of AFGP is an attractive alternative to its difficult isolation from natural sources, and this would permit quality control and mass production. In spite of recent success in islet transplantation for the treatment of type 1 diabetes mellitus, existing methods for the long-term preservation of islets are considered to be suboptimal and inadequate, which indicates the need for the development of improved methods. Rat islets were isolated from male Wistar rats, using intraductal collagenase distention, mechanical dissociation, and Ficoll-Conray gradient purification. Islets were cultured overnight and then cryopreserved in RPMI1640 in the presence of dimethyl sulfoxide (Me2SO) and 10% FCS with various concentrations of syAFGP, followed by slow cooling (0.3 degrees C/min) and rapid thawing (200 degrees C/min) as described by Rajotte. The freezing process was observed by cryomicroscopy. Islet recovery post-cryopreservation was 85.0 +/- 6.2% with syAFGP and 63.3 +/- 14.2% without syAFGP, both compared with the pre-cryopreservation counts (P < 0.05). The in vitro islet function measured by insulin release was equivalent to a static stimulation index of 3.86+/-0.43 for the islets that were frozen-and-thawed with syAFGP, compared to 2.98 +/- 0.22 without syAFGP (P < 0.05). At a concentration of around 500 microg/ml syAFGP, a strong attenuation of ice crystal growth and formation was observed by cryomicroscopy and these ice crystals did not cause cryoinjury. In conclusion, the attenuation of ice crystallization by syAFGP improves islet survival and function following cryopreservation and thawing.

Published
2006
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17. Transduction of Exogenous Constitutively Activated Stat3 into Dispersed Islets Induces Proliferation of Rat Pancreatic β-cells

Author

Michitaka Ozaki, Satoru Kobayashi, Satoru Todo, Shusaku Tsukiyama, Tsunehiko Morita, Hitosi Tamura, Michiaki Matsushita, Shuichiro Matsumoto, and Hirohumi Kamachi

Subjects
Male, STAT3 Transcription Factor, medicine.medical_specialty, Genetic Vectors, Fluorescent Antibody Technique, Cell Separation, Biology, Adenoviridae, Transduction (genetics), Transduction, Genetic, Insulin-Secreting Cells, Internal medicine, Pancreatic beta Cells, medicine, Animals, Rats, Wistar, Growth Substances, STAT3, Gene, Cells, Cultured, Cell Proliferation, Regulator gene, geography, geography.geographical_feature_category, Epidermal Growth Factor, Hepatocyte Growth Factor, Gene Transfer Techniques, General Engineering, Drug Synergism, Cell cycle, Islet, Rats, Cell biology, Glucose, Endocrinology, biology.protein, In vitro proliferation
Abstract

In vitro proliferation of functional islet mass/beta-cells by transduction of cell cycle regulatory genes has not been well documented due to the lack of either an effective method for gene transduction to islets or effective genes for beta-cell proliferation. Signal transducers and activators of transcription- 3 (Stat3) are among the most important molecules for cell proliferation and for cell antiapoptosis. In this study, adenovirus-mediated gene transduction was performed on dispersed islet cells, and reaggregated islet mass functions, such as capabilities for reaggregation, proliferation, and glucose- stimulated insulin secretion (GSIS), were evaluated. The constitutively activated form of Stat3 (Stat3-C) was effectively transduced to most of the islet cells, even at a low density of adenovirus vector. There was no difference in the spontaneous reaggregation capability between Stat3-C transduced and control islet cells. BrdU incorporation in Stat3-C-transduced islet cells was significantly higher (2.8-fold) than that in the control cells, and it was significantly elevated (4-fold) by the addition of HGF in culture media. GSIS in Stat3-C-transduced islet cells was preserved to the level in controls by 5 days in culture. The results indicated that gene transduction into islet cells could be enhanced by first dispersing the cells. Stat3-C induced cell proliferation of beta-cells without loss of insulin secretion activity at the glucose challenge, and HGF enhanced the beta-cell proliferative activity of Stat3-C.

Published
2006
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18. Effect of Intrasplenic Transplantation of Immortalized Human Hepatocytes in the Treatment of Acetaminophen-Induced Acute Liver Failure SCID Mice

Author

Satoru Todo, Tohru Kiyono, Michiaki Matsushita, Yosuke Tsuruga, Tohru Takahashi, N. Kasai, and Shuichiro Matsumoto

Subjects
Male, Pathology, medicine.medical_specialty, Cell Transplantation, medicine.medical_treatment, Transplantation, Heterologous, Intraperitoneal injection, Population, Spleen, Mice, SCID, Andrology, Mice, medicine, Animals, Humans, education, Acetaminophen, Transplantation, Severe combined immunodeficiency, education.field_of_study, business.industry, Graft Survival, Albumin, medicine.disease, Survival Analysis, Treatment Outcome, medicine.anatomical_structure, Hepatocyte, Acute Disease, Hepatocytes, Surgery, business, Liver Failure, medicine.drug
Abstract

Objective. We have established immortalized human hepatocytes by transduction of HPV16 E6/E7 and hTERT (HHE6E7T-1). The cells retained the characteristics of differentiated hepatocytes, but the functional characteristics such as albumin secretion, ureogenesis, and glyconeogenesis decreased gradually as the passages progressed beyond 200 population doublings (PDs). In this report, we transplanted minimally differentiated HHE6E7T-1 cells into the spleens of acute liver failure severe combined immunodeficiency (SCID) mice to examine the potential of the cells to redifferentiate in vivo. Materials and Methods. Acute liver failure was induced in SCID mice by intraperitoneal injection of 400 mg/kg acetaminophen. Two hours later, HHE6E7T-1 cells at 200 PDs were transplanted: group 1 (n = 10) 50 μL phosphate-buffered saline (PBS); group 2 (n = 9), lysate of 1 X 10 6 HHE6E7T-1 cells at 200 PDs resuspended in 50 μL PBS; and group 3 (n = 8), 1 X 10 6 HHE6E7T-1 cells. Survival rates at 7 days after transplantation were compared. Blood glucose levels, plasma ammonia levels, and spleen histology were examined at 24 hours after transplantation. Results. Survivals in each group were: 30% for group 1, 33% for group 2, and 100% for group 3. The survival of group 3 was significantly higher than groups 1 or 2 (P

Published
2008
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19. Donor pretreatment with DHMEQ improves islet transplantation

Author

Yosuke Tsuruga, Tohru Takahashi, Kazuo Umezawa, Hirofumi Kamachi, Michitaka Ozaki, Hiroyuki Furukawa, Shuichiro Matsumoto, Masaaki Watanabe, Hironori Kasai, Michiaki Matsushita, and Satoru Todo

Subjects
Male, endocrine system, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Islets of Langerhans Transplantation, Transplants, Caspase 3, Apoptosis, Biology, chemistry.chemical_compound, Islets of Langerhans, Mice, Internal medicine, Insulin Secretion, medicine, In Situ Nick-End Labeling, Animals, Insulin, bcl-2-Associated X Protein, Caspase 7, geography, geography.geographical_feature_category, Cyclohexanones, NF-kappa B, NF-κB, Glucose Tolerance Test, Islet, Tissue Donors, Transplantation, Mice, Inbred C57BL, Transplantation, Isogeneic, Endocrinology, Cytokine, Glucose, chemistry, Liver, Benzamides, Cancer research, Cytokines, Surgery, Pancreatic islet transplantation
Abstract

Background Currently, pancreatic islet transplantation to achieve normoglycemia in insulin-dependent diabetes mellitus (IDDM) requires two or more donors. This may be due to the inability to transplant functionally preserved and viable islets after isolation. Islets have already been subjected to various harmful stresses during the isolation process leading to apoptosis. One of the intracellular signaling pathways, the transcription factor nuclear factor-κB (NF-κB)-related pathway, is relevant to the mechanism of β-cell apoptosis in isolated islets. We attempted to prevent islet apoptosis during isolation by a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). Materials and Methods DHMEQ was injected intraperitoneally into donor mice 2 h prior to isolation. NF-κB activation, the functioning of isolated islets, apoptosis after isolation, and cytokine- and apoptosis-related genes were analyzed. After 160 equivalents of islets were transplanted into diabetic mice, graft survival and function were evaluated. Results Intra-islet NF-κB was activated immediately after isolation, and DHMEQ inhibited NF-κB activation without deterioration of islet function. DHMEQ significantly prevented apoptosis by inhibiting caspase 3/7 activities and down-regulated Bax, a pro-apoptotic gene. Donor pretreatment with DHMEQ significantly improved engraftment in syngeneic islet transplantation in mice, thus preserving insulin contents in the graft liver, as assessed by functional and histologic analyses. Conclusions DHMEQ is a promising agent in islet transplantation because it protects islets from apoptosis during isolation stress. Donor pretreatment with DHMEQ can significantly affect the success of islet engraftment.

Published
2009

20. Establishment of immortalized human hepatocytes by introduction of HPV16 E6/E7 and hTERT as cell sources for liver cell-based therapy

Author

Yosuke, Tsuruga, Tohru, Kiyono, Michiaki, Matsushita, Tohru, Takahashi, Hironori, Kasai, Shuichiro, Matsumoto, and Satoru, Todo

Subjects
Human papillomavirus 16, Papillomavirus E7 Proteins, Mice, SCID, Oncogene Proteins, Viral, Liver Failure, Acute, Cell Transformation, Viral, Repressor Proteins, Mice, Liver, Karyotyping, Hepatocytes, Animals, Humans, Tumor Suppressor Protein p53, Telomerase, Cells, Cultured, Spleen, Acetaminophen
Abstract

For future cell-based therapies for liver diseases, the shortage of cell sources must be resolved. Immortalized human hepatocytes are expected to be among the new sources. In addition to telomerase activation by the introduction of human telomerase reverse transcriptase (hTERT), inactivation of the p16/RB pathway and/ or p53 by E6/E7 of human papillomavirus type 16 (HPV16) has been shown to be useful for efficient immortalization of several human cell types. Here we report the immortalization of human hepatocytes by the introduction of HPV16 E6/E7 and hTERT. Human adult hepatocytes were lentivirally transduced with HPV16 E6/E7 and hTERT. Two human immortalized hepatocyte cell lines were established and were named HHE6E7T-1 and HHE6E7T-2. Those cells proliferated in culture beyond 200 population doublings (PDs). Albumin synthesis and expression of liver-enriched genes were confirmed, but gradually decreased as passages progressed. Karyotype analysis showed that HHE6E7T-1 cells remained near diploid but that HHE6E7T-2 cells showed severe aneuploidy at 150 PDs. Subcutaneous injection of these cells into severe combined immunodeficiency (SCID) mice did not induce tumor development. Intrasplenic transplantation of dedifferentiated HHE6E7T-1 cells over 200 PDs significantly improved the survival of acetaminophen-induced acute liver failure SCID mice. In conclusion, we successfully established immortalized human hepatocytes that retain the characteristics of differentiated hepatocytes. We also showed the reduction of hepatocyte-specific functions in long-term culture. However, the results of intrasplenic transplantation to SCID mice with acetaminophen-induced acute liver failure showed the possibility of HHE6E7T-1 serving as a cell source for hepatocyte transplantation.

Published
2009

21. Noble gene transduction into pancreatic beta-cells by singularizing islet cells with low doses of recombinant adenoviral vector

Author

Satoru Todo, Yosuke Tsuruga, Tohru Takahashi, Tsunehiko Morita, Hirofumi Kamachi, Shusaku Tsukiyama, Hironori Kasai, Michiaki Matsushita, and Shuichiro Matsumoto

Subjects
Male, endocrine system, medicine.medical_specialty, Time Factors, endocrine system diseases, Cell, Genetic Vectors, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, Cell Separation, Biology, Gene delivery, Viral vector, Adenoviridae, Biomaterials, Transduction (genetics), Islets of Langerhans, Multiplicity of infection, Transduction, Genetic, Internal medicine, Insulin-Secreting Cells, Dispase, medicine, Animals, Insulin, Rats, Wistar, Cell Shape, Cells, Cultured, Cell Aggregation, geography, geography.geographical_feature_category, General Medicine, Islet, beta-Galactosidase, Molecular biology, Rats, medicine.anatomical_structure, Endocrinology, Glucose, Collagenase, medicine.drug
Abstract

Adenovirus-mediated gene transduction into the intact islets has thus far been limited to the surface cells of islets. We evaluated the efficiency of gene delivery by singularization of islets, followed by self-reorganization into islet-like masses. Adenovirus-mediated gene transduction was performed on dispersed islet cells, obtained by two-step digestion of collagenase and ethylene glycol tetraacetic acid/dispase. Good self-reorganization of islet cells in culture was observed until 120 h in islet cells of a control group, a group with a multiplicity of infection (MOI) of 1, and a group with an MOI of 5, with their sizes of 66.7 +/-14.17, 64.0 +/- 15.14, and 60.8 +/- 23.71 microm, respectively. No significant difference in spontaneous reaggregation capability among the islet cell masses was noticed. However, fragmentation of the reaggregated islet mass was observed in the groups with an MOI of 10 and 50 at 72 and 48 h, respectively. The gene transduction rates at an MOI of 0.5, 1, and 5 into islet cells were 56.1 +/- 1.43, 97.6 +/- 0.92, and 100 +/- 0.00%, respectively. The insulin stimulation indices of the reaggregated islet mass at an MOI of 0.5 and 1 were preserved to the level of a nontransduced islet mass; those at an MOI greater than 5 were significantly low. Efficient adenovirus-mediated gene transduction into islet/beta-cells was achieved by adding a process of dispersion of islets into single cells prior to gene transduction without losing the characteristic ability of islet cells to form a functional islet mass in culture.

Published
2008

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