著者

Akihiko Nakamura Kei-ichi Okazaki Tadaomi Furuta Minoru Sakurai Jun Ando Ryota Iino

出版者

The Biophysical Society of Japan

雑誌

Biophysics and Physicobiology (ISSN:21894779)

巻号頁・発行日

vol.17, pp.51-58, 2020 (Released:2020-07-10)

参考文献数

26

被引用文献数

4 5

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Motor proteins are essential units of life and are well-designed nanomachines working under thermal fluctuations. These proteins control moving direction by consuming chemical energy or by dissipating electrochemical potentials. Chitinase A from bacterium Serratia marcescens (SmChiA) processively moves along crystalline chitin by hydrolysis of a single polymer chain to soluble chitobiose. Recently, we directly observed the stepping motions of SmChiA labeled with a gold nanoparticle by dark-field scattering imaging to investigate the moving mechanism. Time constants analysis revealed that SmChiA moves back and forth along the chain freely, because forward and backward states have a similar free energy level. The similar probabilities of forward-step events (83.5%=69.3%+14.2%) from distributions of step sizes and chain-hydrolysis (86.3%=(1/2.9)/(1/2.9+1/18.3)×100) calculated from the ratios of time constants of hydrolysis and the backward step indicated that SmChiA moves forward as a result of shortening of the chain by a chitobiose unit, which stabilizes the backward state. Furthermore, X-ray crystal structures of sliding intermediate and molecular dynamics simulations showed that SmChiA slides forward and backward under thermal fluctuation without large conformational changes of the protein. Our results demonstrate that SmChiA is a burnt-bridge Brownian ratchet motor.

著者

Ryo Kodera Kenichi Shikata Akihiko Nakamura Satoru Okazaki Ryo Nagase Tatsuaki Nakatou Shigeru Haisa Kazuyuki Hida Katsuhiro Miyashita Hirofumi Makino

出版者

一般社団法人 日本内科学会

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.56, no.6, pp.605-613, 2017-03-15 (Released:2017-03-17)

参考文献数

26

被引用文献数

9

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Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors are the most frequently prescribed oral hypoglycemic agents in Japan. Although a relationship between the efficacy of DPP-4 inhibitors and the body mass index (BMI) has been reported, this relationship is controversial. We investigated whether the BMI value affects the glucose-lowering efficacy of sitagliptin in obese Japanese patients with type 2 diabetes. Methods One hundred sixty-two outpatients with inadequate glycemic control were divided into four groups based on their baseline BMI values. They were then treated with sitagliptin (a DPP-4 inhibitor) for 3 months and followed-up for 12 months. Results Sitagliptin significantly reduced the hemoglobin A1c level (HbA1c: -0.71±0.55%) after 3 months, and continued to reduce the HbA1c level until 12 months. There was no significant difference in the efficacy of sitagliptin among the four BMI groups. A multiple linear regression analysis indicated that the factors contributing to the change in the HbA1c level were the baseline level of HbA1c and the homeostasis model assessment of β-cell function (HOMA-β). In terms of the relationship between the baseline BMI value and the efficacy of sitagliptin treatment, the number of patients who responded to sitagliptin treatment after 3 months was lowest in the group of patients with the highest BMI values. A multiple logistic regression analysis revealed that the baseline HOMA-β function and HbA1c level and a baseline BMI value of ≥30 kg/m2 significantly contributed to the response to sitagliptin treatment. Conclusion The results indicated that sitagliptin treatment was effective in controlling glucose metabolism disorder in obese Japanese patients with type 2 diabetes. However, the efficacy of sitagliptin treatment might be attenuated in severely obese patients, such as those with a BMI value of ≥30 kg/m2.

著者

Akihiko Nakamura Kei-ichi Okazaki Tadaomi Furuta Minoru Sakurai Jun Ando Ryota Iino

出版者

The Biophysical Society of Japan

雑誌

Biophysics and Physicobiology (ISSN:21894779)

巻号頁・発行日

pp.BSJ-2020004, (Released:2020-06-09)

被引用文献数

5

著者

Akihiko Nakamura Tadao Asai Kazuhiro Yoshida Kohtaro Baba Kimihiro Nakae

出版者

The Oto-Rhino-Laryngological Society of Japan, Inc.

雑誌

Nippon Jibiinkoka Gakkai Kaiho (ISSN:00306622)

巻号頁・発行日

vol.105, no.3, pp.215-224, 2002-03-20 (Released:2010-10-22)

参考文献数

40

被引用文献数

12 10

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アレルギー性鼻炎に関する全国疫学調査を行った. 全国の耳鼻咽喉科医師9471名およびその家族を対象とし, 1998年6月にアレルギー性鼻炎に関する質問用紙を郵送し, 同年9月末日までに回収した. 回収率は42.8%で, 17301名が対象になった. 年齢構成を日本人人口ものと比較すると調査対象者は20歳代がやや多く, 60歳以上特に男性に多い以外ほとんど差異はみられなかった.スギ花粉症の有症率は, 人口分布調整を行ったところ17.3%であった. 全体に日本海側, 瀬戸内地方に比べ太平洋側, 中部地方に高く, 高緯度あるいは低緯度地域で有症率は低かった. 年齢層別有症率をみると, 10歳代で急激に増加し60歳代になると低下した. スギ花粉飛散が多い地域で有症率が高く, 住環境に関しては郊外, 住宅地, 都会の順で高かった.スギ以外の花粉症についても同様に検討した. 年齢層別有症率および住環境と有症率との関係は, スギ花粉症とほぼ同様の結果で, 人口分布調整後の有症率は11.7%であった.通年性アレルギー性鼻炎の人口分布調整後の有症率は19.8%で, スギ花粉症に比べやや高率であった. 年齢層別有症率は, 5~9歳で急激な上昇がみられ, スギ花粉より若年者での発症が多く, 60歳以降での有症率の低下はみられなかった. スギ花粉症と異なり, 地域や住環境による有症率の差異はみられなかった.今回の調査は全国に住居する耳鼻咽喉科医師およびその家族を対象としており, スギ花粉症はもとより通年性アレルギー性鼻炎の地域による有症率の差異を知ることができた. また回収率も他のアンケート調査より優れており, 回答内容の信用度も高いため, 日本全国のスギを主としたアレルギー性鼻炎に関する疫学的調査として有用なものと思われた.