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3. Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model

Author

Sasaki, Michihito, Sugi, Tatsuki, Iida, Shun, Hirata, Yuichiro, Kusakabe, Shinji, Konishi, Kei, Itakura, Yukari, Tabata, Koshiro, Kishimoto, Mai, Kobayashi, Hiroko, Ariizumi, Takuma, Intaruck, Kittiya, Nobori, Haruaki, Toba, Shinsuke, Sato, Akihiko, Matsuno, Keita, Yamagishi, Junya, Suzuki, Tadaki, Hall, William W., Orba, Yasuko, and Sawa, Hirofumi

Published
2024
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4. Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus: A randomized, crossover trial

Author

Murata, Takashi, Hosoda, Kiminori, Kunihiro Nishimura, Miyamoto, Yoshihiro, Sakane, Naoki, Satoh-Asahara, Noriko, Toyoda, Masao, Hirota, Yushi, Matsuhisa, Munehide, Kuroda, Akio, Kato, Ken, Kouyama, Ryuji, Miura, Junnosuke, Tone, Atsuhito, Kasahara, Masato, Kasama, Shu, Suzuki, Shota, Ito, Yukie, Watanabe, Tomokazu, Suganuma, Akiko, Shen, Zhuo, Kobayashi, Hiroko, Takagi, Satoshi, Hoshina, Sari, Shimura, Kanako, Tsuchida, Yukiko, Kimura, Moritsugu, Saito, Nobumichi, Shimada, Akira, Oikawa, Yoichi, Satomura, Atsushi, Haisa, Akifumi, Kawashima, Satoshi, Meguro, Shu, Itoh, Hiroshi, Saisho, Yoshifumi, Irie, Junichiro, Tanaka, Masami, Mitsuishi, Masanori, Nakajima, Yuya, Inaishi, Jun, Kinouchi, Kenichiro, Yamaguchi, Shintaro, Itoh, Arata, Sugiyama, Kazutoshi, Yagi, Kazuma, Tsuchiya, Tami, Kodani, Noriko, Shimizu, Ikki, Fukuda, Tetsuya, Kusunoki, Yoshiki, Katsuno, Tomoyuki, Matoba, Yuka, Hitaka, Yumi, Abe, Kentaro, Tanaka, Natsuko, Taniguchi, Ryoko, Nagao, Toshihiko, Hida, Kazuyuki, Iseda, Izumi, Takeda, Masaya, Matsushita, Yuichi, Tenta, Masafumi, Tanaka, Tsuyoshi, Kouyama, Kunichi, and Fukunaga, Michiru

Published
2023
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7. TAFRO syndrome complicated by porto-sinusoidal vascular liver disease with portal hypertension: a case report

Author

Hayashi, Manabu, Wada, Jun, Fujita, Masashi, Asano, Tomoyuki, Matsuoka, Naoki, Fujita, Yuya, Temmoku, Jumpei, Matsumoto, Haruki, Yashio-Furuya, Makiko, Sato, Shuzo, Kobayashi, Hiroko, Watanabe, Hiroshi, Ryoichiro, Kobashi, Waragai, Yuichi, Suzuki, Erina, Kiko, Yuichiro, Abe, Kazumichi, Takahashi, Atsushi, Masuda, Tomoyuki, Hashimoto, Yuko, Migita, Kiyoshi, and Ohira, Hiromasa

Published
2021
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15. Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Author

Miyata, Masayuki, Hirabayashi, Yasuhiko, Munakata, Yasuhiko, Urata, Yukitomo, Saito, Koichi, Okuno, Hiroshi, Yoshida, Masaaki, Kodera, Takao, Watanabe, Ryu, Miyamoto, Seiya, Ishii, Tomonori, Nakazawa, Shigeshi, Takemori, Hiromitsu, Ando, Takanobu, Kanno, Takashi, Komagamine, Masataka, Kato, Ichiro, Takahashi, Yuichi, Komatsuda, Atsushi, Endo, Kojiro, Murai, Chihiro, Takakubo, Yuya, Miura, Takao, Sato, Yukio, Ichikawa, Kazunobu, Konta, Tsuneo, Chiba, Noriyuki, Muryoi, Tai, Kobayashi, Hiroko, Fujii, Hiroshi, Sekiguchi, Yukio, Hatakeyama, Akira, Ogura, Ken, Sakuraba, Hirotake, Asano, Tomoyuki, Kanazawa, Hiroshi, Suzuki, Eiji, Takasaki, Satoshi, Asakura, Kenichi, Suzuki, Yoko, Takagi, Michiaki, Nakayama, Takahiro, Watanabe, Hiroshi, Miura, Keiki, and Mori, Yu

Subjects
rheumatoid arthritis, tocilizumab, long-standing, methotrexate, discontinuation
Abstract

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

Published
2023

20. Different effects of crizotinib treatment in two non‐small cell lung cancer patients with SDC4::ROS1 fusion variants.

Author

Ohishi, Yuta, Nakanishi, Yoko, Hirotani, Yukari, Suzuki, Atsuko, Tanino, Tomoyuki, Nishimaki‐Watanabe, Haruna, Kobayashi, Hiroko, Nozaki, Fumi, Ohni, Sumie, Tang, Xiaoyan, Hayashi, Kentaro, Nakagawa, Yoshiko, Shimizu, Tetsuo, Tsujino, Ichiro, Takahashi, Noriaki, Gon, Yasuhiro, and Masuda, Shinobu

Subjects
LUNG cancer, PROTEINS, PROTEIN kinase inhibitors, IMMUNOHISTOCHEMISTRY, ONCOGENES, LUNG tumors, PIPERIDINE, TUMOR classification, CANCER patients, PROTEIN-tyrosine kinases, GLYCOPROTEINS, TRANSFERASES, DESCRIPTIVE statistics, REACTIVE oxygen species, TUMOR markers, CYTOLOGY, POLYMERASE chain reaction, THYROID gland
Abstract

The possibility of stratifying patients according to differences in ROS proto‐oncogene 1 (ROS1) fusion partners has been discussed. This study aimed to clarify the clinicopathological differences between two SDC4::ROS1 positive NSCLC cases who had different responses to crizotinib. Cytology and pathology samples from two NSCLC cases with SDC4::ROS1 who were diagnosed and treated with crizotinib at Nihon University Itabashi Hospital were obtained. Case 1 has been well‐controlled with crizotinib for over 5 years, but case 2 was worse and overall survival was 19 months. Sequencing analysis of ROS1 fusion genes was performed by reverse‐transcription‐PCR and Sanger's sequencing methods. In addition, thyroid transcription factor (TTF)‐1, ROS‐1, Ki67, and phosphorylated extracellular signal‐regulated kinase (pERK)1/2 expression were investigated using immunohistochemistry. Sequencing analysis showed SDC4 exon2::ROS1 exon 32 (exon33 deleted) in case 1, and coexistence of SDC4 exon2::ROS1 exon 34 and SDC4 exon2::ROS1 exon35 in case 2. The Ki67 index was not different, but ROS1 and pERK1/2 expression levels tended to be higher in the tumor cells of case 2 than in case 1. Therapeutic response to crizotinib and patients' prognosis in ROS1 rearranged NSCLC may be related to the activation of ROS1 signaling, depending on ROS1 and pERK1/2 overexpression status, even if the ROS1 fusion partner is the same. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Intestinal Behçet disease associated with myelodysplastic syndrome accompanying trisomy 8 successfully treated with abdominal surgery followed by hematopoietic stem cell transplantation: A case report

Author

Asano, Tomoyuki, Sato, Shuzo, Furuya, Makiko Yashiro, Takahashi, Hiroshi, Shichishima-Nakamura, Akiko, Ohkawara, Hiroshi, Fujiwara, Tatsuo, Gunji, Naohiko, Hashimoto, Choichiro, Momma, Tomoyuki, Saito, Motonobu, Nakano, Hiroshi, Watanabe, Guy, Temmoku, Jumpei, Fujita, Yuya, Matsuoka, Naoki, Kobayashi, Hiroko, Watanabe, Hiroshi, Mouri, Mariko, Mashiyama, Fumi, Sakuma, Hiroko, Ohira, Hiromasa, Mori, Masaaki, Ikezoe, Takayuki, and Migita, Kiyoshi

Published
2019
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26. S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters

Author

1000070609403, Sasaki, Michihito, Tabata, Koshiro, Kishimoto, Mai, Itakura, Yukari, Kobayashi, Hiroko, Ariizumi, Takuma, Uemura, Kentaro, Toba, Shinsuke, Kusakabe, Shinji, Maruyama, Yuki, 1000050785996, Iida, Shun, 1000060333358, Nakajima, Noriko, 1000030527180, Suzuki, Tadaki, Yoshida, Shinpei, Nobori, Haruaki, Sanaki, Takao, Kato, Teruhisa, Shishido, Takao, Hall, William W., 1000060507169, Orba, Yasuko, Sato, Akihiko, 1000030292006, Sawa, Hirofumi, 1000070609403, Sasaki, Michihito, Tabata, Koshiro, Kishimoto, Mai, Itakura, Yukari, Kobayashi, Hiroko, Ariizumi, Takuma, Uemura, Kentaro, Toba, Shinsuke, Kusakabe, Shinji, Maruyama, Yuki, 1000050785996, Iida, Shun, 1000060333358, Nakajima, Noriko, 1000030527180, Suzuki, Tadaki, Yoshida, Shinpei, Nobori, Haruaki, Sanaki, Takao, Kato, Teruhisa, Shishido, Takao, Hall, William W., 1000060507169, Orba, Yasuko, Sato, Akihiko, 1000030292006, and Sawa, Hirofumi

Abstract

In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2 infection in vitro, few have proven to be effective in vivo. Here, we show that oral administration of S-217622 (ensitrelvir), an inhibitor of SARS-CoV-2 main protease (Mpro; also known as 3C-like protease), decreases viral load and ameliorates disease severity in SARS-CoV-2-infected hamsters. S-217622 inhibited viral proliferation at low nanomolar to submicromolar concentrations in cells. Oral administration of S-217622 demonstrated favorable pharmacokinetic properties and accelerated recovery from acute SARS-CoV-2 infection in hamster recipients. Moreover, S-217622 exerted antiviral activity against SARS-CoV-2 variants of concern, including the highly pathogenic Delta variant and the recently emerged Omicron BA.5 and BA.2.75 variants. Overall, our study provides evidence that S-217622, an antiviral agent that is under evaluation in a phase 3 clinical trial (clinical trial registration no. jRCT2031210350), has remarkable antiviral potency and efficacy against SARS-CoV-2 and is a prospective oral therapeutic option for COVID-19.

Published
2023

27. S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters

Author

Sasaki, Michihito, Tabata, Koshiro, Kishimoto, Mai, Itakura, Yukari, Kobayashi, Hiroko, Ariizumi, Takuma, Uemura, Kentaro, Toba, Shinsuke, Kusakabe, Shinji, Maruyama, Yuki, Iida, Shun, Nakajima, Noriko, Suzuki, Tadaki, Yoshida, Shinpei, Nobori, Haruaki, Sanaki, Takao, Kato, Teruhisa, Shishido, Takao, Hall, William W., Orba, Yasuko, Sato, Akihiko, Sawa, Hirofumi, Sasaki, Michihito, Tabata, Koshiro, Kishimoto, Mai, Itakura, Yukari, Kobayashi, Hiroko, Ariizumi, Takuma, Uemura, Kentaro, Toba, Shinsuke, Kusakabe, Shinji, Maruyama, Yuki, Iida, Shun, Nakajima, Noriko, Suzuki, Tadaki, Yoshida, Shinpei, Nobori, Haruaki, Sanaki, Takao, Kato, Teruhisa, Shishido, Takao, Hall, William W., Orba, Yasuko, Sato, Akihiko, and Sawa, Hirofumi

Abstract

In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2 infection in vitro, few have proven to be effective in vivo. Here, we show that oral administration of S-217622 (ensitrelvir), an inhibitor of SARS-CoV-2 main protease (Mpro; also known as 3C-like protease), decreases viral load and ameliorates disease severity in SARS-CoV-2-infected hamsters. S-217622 inhibited viral proliferation at low nanomolar to submicromolar concentrations in cells. Oral administration of S-217622 demonstrated favorable pharmacokinetic properties and accelerated recovery from acute SARS-CoV-2 infection in hamster recipients. Moreover, S-217622 exerted antiviral activity against SARS-CoV-2 variants of concern, including the highly pathogenic Delta variant and the recently emerged Omicron BA.5 and BA.2.75 variants. Overall, our study provides evidence that S-217622, an antiviral agent that is under evaluation in a phase 3 clinical trial (clinical trial registration no. jRCT2031210350), has remarkable antiviral potency and efficacy against SARS-CoV-2 and is a prospective oral therapeutic option for COVID-19.

Published
2023

28. Light-sheet microscopy reveals dorsoventral asymmetric membrane dynamics of Amoeba proteus during pressure-driven locomotion

Author

Taniguchi, Atsushi, 1000080639021, Nishigami, Yukinori, Kajiura-Kobayashi, Hiroko, Takao, Daisuke, Tamaoki, Daisuke, Nakagaki, Toshiyuki, Nonaka, Shigenori, Sonobe, Seiji, Taniguchi, Atsushi, 1000080639021, Nishigami, Yukinori, Kajiura-Kobayashi, Hiroko, Takao, Daisuke, Tamaoki, Daisuke, Nakagaki, Toshiyuki, Nonaka, Shigenori, and Sonobe, Seiji

Abstract

Amoebae are found all around the world and play an essential role in the carbon cycle in the environment. Therefore, the behavior of amoebae is a crucial factor when considering the global environment. Amoebae change their distribution through amoeboid locomotion, which are classified into several modes. In the pressure-driven mode, intracellular hydrostatic pressure generated by the contraction of cellular cortex actomyosin causes the pseudopod to extend. During amoeboid locomotion, the cellular surface exhibits dynamic deformation. Therefore, to understand the mechanism of amoeboid locomotion, it is important to characterize cellular membrane dynamics. Here, to clarify membrane dynamics during pressure-driven amoeboid locomotion, we developed a polkadot membrane staining method and performed light-sheet microscopy in Amoeba proteus, which exhibits typical pressure-driven amoeboid locomotion. It was observed that the whole cell membrane moved in the direction of movement, and the dorsal cell membrane in the posterior part of the cell moved more slowly than the other membrane. In addition, membrane complexity varied depending on the focused characteristic size of the membrane structure, and in general, the dorsal side was more complex than the ventral side. In summary, the membrane dynamics of Amoeba proteus during pressure-driven locomotion are asymmetric between the dorsal and ventral sides.

Published
2023

29. Galectin-9 in autoimmune hepatitis: Correlation between serum levels of galectin-9 and M2BPGi in patients with autoimmune hepatitis

Author

Matsuoka, Naoki, Kozuru, Hideko, Koga, Tomohiro, Abiru, Seigo, Yamasaki, Kazumi, Komori, Atsumasa, Fujita, Yuya, Tenmoku, Junpei, Asano, Tomoyuki, Sato, Shuzo, Suzuki, Eiji, Furuya, Makiko, Kobayashi, Hiroko, Watanabe, Hiroshi, Naganuma, Atsushi, Yoshizawa, Kaname, Shimada, Masaaki, Ario, Keisuke, Yamashita, Haruhiro, Kohno, Hiroshi, Kaneyoshi, Toshihiko, Nakamura, Minoru, Furukawa, Hiroshi, Takahashi, Atsushi, Kawakami, Atsushi, Ohira, Hiromasa, Yatsuhashi, Hiroshi, and Migita, Kiyoshi

Published
2019
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32. S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters

Author

Sasaki, Michihito, primary, Tabata, Koshiro, additional, Kishimoto, Mai, additional, Itakura, Yukari, additional, Kobayashi, Hiroko, additional, Ariizumi, Takuma, additional, Uemura, Kentaro, additional, Toba, Shinsuke, additional, Kusakabe, Shinji, additional, Maruyama, Yuki, additional, Iida, Shun, additional, Nakajima, Noriko, additional, Suzuki, Tadaki, additional, Yoshida, Shinpei, additional, Nobori, Haruaki, additional, Sanaki, Takao, additional, Kato, Teruhisa, additional, Shishido, Takao, additional, Hall, William W., additional, Orba, Yasuko, additional, Sato, Akihiko, additional, and Sawa, Hirofumi, additional

Published
2023
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34. Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis

Author

Migita, Kiyoshi, Horai, Yoshiro, Kozuru, Hideko, Koga, Tomohiro, Abiru, Seigo, Yamasaki, Kazumi, Komori, Atsumasa, Fujita, Yuya, Asano, Tomoyuki, Sato, Shuzo, Suzuki, Eiji, Matsuoka, Naoki, Kobayashi, Hiroko, Watanabe, Hiroshi, Naganuma, Atsushi, Naeshiro, Noriaki, Yoshizawa, Kaname, Ohta, Hajime, Sakai, Hironori, Shimada, Masaaki, Nishimura, Hideo, Tomizawa, Minoru, Ario, Keisuke, Yamashita, Haruhiro, Kamitsukasa, Hiroshi, Kohno, Hiroshi, Nakamura, Minoru, Furukawa, Hiroshi, Takahashi, Atsushi, Kawakami, Atsushi, Ohira, Hiromasa, and Yastuhashi, Hiroshi

Published
2018
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47. Understanding mental health trends during COVID-19 pandemic in the United States using network analysis.

Author

Kobayashi, Hiroko, Saenz-Escarcega, Raul, Fulk, Alexander, and Agusto, Folashade B.

Subjects
*COVID-19 pandemic, *MENTAL health, *SARS-CoV-2 Delta variant, *MENTAL health policy, *COMMUNITIES
Abstract

The emergence of COVID-19 in the United States resulted in a series of federal and state-level lock-downs and COVID-19 related health mandates to manage the spread of the virus. These policies may negatively impact the mental health state of the population. This study focused on the trends in mental health indicators following the COVID-19 pandemic amongst four United States geographical regions, and political party preferences. Indicators of interest included feeling anxious, feeling depressed, and worried about finances. Survey data from the Delphi Group at Carnegie Mellon University were analyzed using clustering algorithms and dynamic connectome obtained from sliding window analysis. Connectome refers to the description of connectivity on a network. United States maps were generated to observe spatial trends and identify communities with similar mental health and COVID-19 trends. Between March 3rd, 2021, and January 10th, 2022, states in the southern geographic region showed similar trends for reported values of feeling anxious and worried about finances. There were no identifiable communities resembling geographical regions or political party preference for the feeling depressed indicator. We observed a high degree of correlation among southern states as well as within Republican states, where the highest correlation values from the dynamic connectome for feeling anxious and feeling depressed variables seemingly overlapped with an increase in COVID-19 related cases, deaths, hospitalizations, and rapid spread of the COVID-19 Delta variant. [ABSTRACT FROM AUTHOR]

Published
2023
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50. Nationwide prospective and retrospective surveys for hepatitis B virus reactivation during immunosuppressive therapies

Author

Mochida, Satoshi, Nakao, Masamitsu, Nakayama, Nobuaki, Uchida, Yoshihito, Nagoshi, Sumiko, Ido, Akio, Mimura, Toshihide, Harigai, Masayoshi, Kaneko, Hiroshi, Kobayashi, Hiroko, Tsuchida, Tetsuya, Suzuki, Hiromichi, Ura, Nobuyuki, Nakamura, Yuichi, Bessho, Masami, Dan, Kazuo, Kusumoto, Shigeru, Sasaki, Yasutsuna, Fujii, Hirofumi, Suzuki, Fumitaka, Ikeda, Kenji, Yamamoto, Kazuhiko, Takikawa, Hajime, Tsubouchi, Hirohito, and Mizokami, Masashi

Published
2016
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