著者

Takehiro Suzuki Hiroaki Yamaguchi Motoi Kikusato Tetsuro Matsuhashi Akihiro Matsuo Takeya Sato Yuki Oba Shun Watanabe Daichi Minaki Daisuke Saigusa Hiroko Shimbo Nobuyoshi Mori Eikan Mishima Hisato Shima Yasutoshi Akiyama Yoichi Takeuchi Akinori Yuri Koichi Kikuchi Takafumi Toyohara Chitose Suzuki Masahiro Kohzuki Jun-ichi Anzai Nariyasu Mano Shigeo Kure Teruyuki Yanagisawa Yoshihisa Tomioka Masaaki Toyomizu Sadayoshi Ito Hitoshi Osaka Ken-ichiro Hayashi Takaaki Abe

出版者

東北ジャーナル刊行会

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.236, no.3, pp.225-232, 2015 (Released:2015-06-26)

参考文献数

27

被引用文献数

2 34

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Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are characterized by the dysfunction of the mitochondrial respiratory chain, caused by mutations in the genes encoded by either nuclear DNA or mitochondrial DNA. We have hypothesized that chemicals that increase the cellular ATP levels may ameliorate the mitochondrial dysfunction seen in mitochondrial diseases. To search for the potential drugs for mitochondrial diseases, we screened an in-house chemical library of indole-3-acetic-acid analogs by measuring the cellular ATP levels in Hep3B human hepatocellular carcinoma cells. We have thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as a potential drug for enhancing ATP production. MA-5 is a newly synthesized derivative of the plant hormone, indole-3-acetic acid. Importantly, MA-5 improved the survival of fibroblasts established from patients with mitochondrial diseases under the stress-induced condition, including Leigh syndrome, MELAS (myopathy encephalopathy lactic acidosis and stroke-like episodes), Leber’s hereditary optic neuropathy, and Kearns-Sayre syndrome. The improved survival was associated with the increased cellular ATP levels. Moreover, MA-5 increased the survival of mitochondrial disease fibroblasts even under the inhibition of the oxidative phosphorylation or the electron transport chain. These data suggest that MA-5 could be a therapeutic drug for mitochondrial diseases that exerts its effect in a manner different from anti-oxidant therapy.

著者

Hiroki Mizuno Naoki Sawa Akinari Sekine Noriko Inoue Yuki Oba Daisuke Ikuma Masayuki Yamanouchi Eiko Hasegawa Tatsuya Suwabe Hisanori Suzuki Junichi Hoshino Yoshifumi Ubara

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.9624-22, (Released:2022-05-31)

参考文献数

12

被引用文献数

1

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A 79-year-old man was admitted with a compression fracture of the first lumbar vertebra. His alkaline phosphatase (ALP) level was 35 IU/L, and his dual energy X-ray absorptiometry T score was -3.7 standard deviations, indicating osteoporosis. A genetic analysis showed a mutation of the alkaline phosphatase biomineralization-associated gene encoding tissue-nonspecific alkaline phosphatase. Hypophosphatasia-related osteoporosis was diagnosed. Alendronate, teriparatide, and minodronate were administered in that order. The ALP level increased during teriparatide use. A bone biopsy performed after three years of teriparatide treatment showed that cancellous bone was adynamic. In cortical bone, tetracycline double-labeling indicates enhanced bone formation. Teriparatide may thus be a viable treatment option even in patients with hypophosphatasia.

著者

Makoto Fukuda Naoki Sawa Daisuke Ikuma Yuki Oba Hiroki Mizuno Masayuki Yamanouchi Akinari Sekine Eiko Hasegawa Tatsuya Suwabe Junichi Hoshino Kei Kono Keiichi Kinowaki Kenichi Ohashi Hiromichi Tamaki Motoaki Miyazono Yoshifumi Ubara

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.62, no.1, pp.81-85, 2023-01-01 (Released:2023-01-01)

参考文献数

9

被引用文献数

2 3

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A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate.

著者

Atsuhiko Suenaga Naoki Sawa Daisuke Ikuma Yuki Oba Akinari Sekine Masayuki Yamanouchi Eiko Hasegawa Hiroki Mizuno Tatsuya Suwabe Kei Kono Yukako Shintani-Domoto Keiichi Kinowaki Kenichi Ohashi Yoshiyuki Suzuki Motoaki Miyazono Tamiko Takemura Yutaka Yamaguchi Yoshifumi Ubara

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.1121-22, (Released:2023-02-01)

参考文献数

8

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We performed 3 kidney biopsies in a 71-year-old man. At the first biopsy, we made the diagnosis of immunoglobulin G4 (IgG4)-related interstitial nephritis characterized by the simultaneous presence of IgG4-positive plasma cells and characteristic fibrosis with a bird's-eye pattern. At the second biopsy, rather than finding fibrosis as a post-inflammatory scar, we noted that steroid treatment had caused the simultaneous disappearance of IgG4-positive plasma cells and fibrosis and had restored the normal tubular structure. The third biopsy showed the recurrence of the disease with inflammatory cells accompanied by fibrosis. These findings suggest that IgG4-positive plasma cells and fibrosis occur simultaneously.

著者

Atsuhiko Suenaga Naoki Sawa Katsuyuki Miki Takayoshi Yokoyama Yasuo Ishii Hiroki Mizuno Daisuke Ikuma Yuki Oba Akinari Sekine Masayuki Yamanouchi Eiko Hasegawa Tatsuya Suwabe Kei Kono Keiichi Kinowaki Kenichi Ohashi Kazuho Honda Motoaki Miyazono Yuki Nakamura Yoshifumi Ubara

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.0813-22, (Released:2023-02-01)

参考文献数

16

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We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.