著者

Misa Miura Ryo Yoshizawa Shigeru Oowada Aki Hirayama Osamu Ito Masahiro Kohzuki Teruhiko Maeba

出版者

The Japanese Association of Rehabilitation Medicine

雑誌

Progress in Rehabilitation Medicine (ISSN:24321354)

巻号頁・発行日

vol.2, pp.20170008, 2017 (Released:2017-06-15)

参考文献数

14

被引用文献数

2 2

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Objective: Hemodialysis (HD) patients have lower fitness levels than healthy subjects because of various structural, metabolic, and functional abnormalities secondary to uremic changes in skeletal muscles. Aerobic and resistance exercises are beneficial in improving not only physical function, including maximal oxygen uptake and muscle strength, but also anthropometrics, nutritional status, and hematologic indices. The use of electric ergometers that place light loads on patients has been implemented at many dialysis facilities in Japan. However, reports comparing the effects on body function of electric and variable-load ergometers are few. This study aimed to compare electric ergometers and variable-load ergometers in terms of exercise outcomes in HD patients. Methods: A total of 15 ambulatory HD patients were randomly divided into two groups: the variable-load ergometer group (n=8) and the electric ergometer group (n=7). HD patients exercised at a level based on their physical function three times a week for 12 weeks. Results: After the 12-week intervention period, only the variable-load ergometer group experienced significant increases in lower extremity muscle strength and exercise tolerance. Conclusion: This study confirmed that conventional aerobic training and electric bike exercise during HD were efficacious and safe without causing sudden hypotension or any other side effects. However, exercise using a variable-load ergometer may be more effective than exercise using an electric bike in improving the physical function of HD patients. Exercise using a variable-load ergometer elicited specific whole-body and local effects.

著者

Ryo Yoshizawa Nobuhisa Umeki Akihiro Yamamoto Masayuki Murata Yasushi Sako

出版者

The Biophysical Society of Japan

雑誌

Biophysics and Physicobiology (ISSN:21894779)

巻号頁・発行日

vol.18, pp.1-12, 2021 (Released:2021-02-05)

参考文献数

47

被引用文献数

7

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RTK-RAS-MAPK systems are major signaling pathways for cell fate decisions. Among the several RTK species, it is known that the transient activation of ERK (MAPK) stimulates cell proliferation, whereas its sustained activation induces cell differentiation. In both instances however, RAS activation is transient, suggesting that the strict temporal regulation of its activity is critical in normal cells. RAS on the cytoplasmic side of the plasma membrane is activated by SOS through the recruitment of GRB2/SOS complex to the RTKs that are phosphorylated after stimulation with growth factors. The adaptor protein GRB2 recognizes phospho-RTKs both directly and indirectly via another adaptor protein, SHC. We here studied the regulation of GRB2 recruitment under the SHC pathway using single-molecule imaging and fluorescence correlation spectroscopy in living cells. We stimulated MCF7 cells with a differentiation factor, heregulin, and observed the translocation, complex formation, and phosphorylation of cell signaling molecules including GRB2 and SHC. Our results suggest a biphasic regulation of the GRB2/SOS-RAS pathway by SHC: At the early stage (<10 min) of stimulation, SHC increased the amplitude of RAS activity by increasing the association sites for the GRB2/SOS complex on the plasma membrane. At the later stage however, SHC suppressed RAS activation and sequestered GRB2 molecules from the membrane through the complex formation in the cytoplasm. The latter mechanism functions additively to other mechanisms of negative feedback regulation of RAS from MEK and/or ERK to complete the transient activation dynamics of RAS.