2024/07/10 更新

写真a

ヒサナリ ミユキ
久成 三有紀
Hisanari Miyuki
所属
教育学域 准教授
職名
准教授
通称等の別名
横路 三有紀
外部リンク

学位

  • 博士(栄養学) ( 2012年9月   岡山県立大学 )

研究キーワード

  • 若い世代の食生活

  • フレイル

  • サルコペニア

  • 地域在住高齢者

  • 栄養教育

  • 非対称性ジメチルアルギニン

研究分野

  • 人文・社会 / 家政学、生活科学  / 食生活科学・食生活教育

  • ライフサイエンス / 栄養学、健康科学  / 食生活・栄養教育

所属学協会

 

論文

  • Association between social network and dietary variety among community-dwelling older adults. 査読 国際誌

    Miyuki Yokoro, Naoto Otaki, Tomomi Imamura, Norikazu Tanino, Keisuke Fukuo

    Public health nutrition   26 ( 11 )   2441 - 2449   2023年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Social networks are critical social health factors for older adults. This study examined the association between social networks and dietary variety among community-dwelling older adults. DESIGN: A cross-sectional study, using the dietary variety score (DVS) developed for older Japanese people to assess dietary variety and the Lubben Social Network Scale (LSNS-6) to assess social networks. SETTING: N City, H Prefecture, Japan. PARTICIPANTS: Community-dwelling older adults aged ≥ 65 years (n = 1,229). RESULTS: The LSNS-6 score in the low DVS group was lower than that in the middle and high DVS groups (12.2 ± 5.6 vs. 13.4 ± 5.4 and 14.4 ± 5.7, P<0.001). The population of social isolation (LSNS-6, < 12) in the low DVS group was higher than that in the middle and high DVS groups (43.5% vs. 35.8% and 31.0%, P = 0.005). Multivariate linear regression analysis showed that the LSNS-6 score was positively correlated with DVS (standardized coefficient, 0.092; P = 0.002). Social isolation was also significantly associated with a low DVS in the multivariate-adjusted logistic analysis model (OR, 1.30; 95% CI, 1.00-1.68; P = 0.048). Stratified analysis results revealed the LSNS-6 and DVS were significantly associated in participants with the following characteristics: younger age (< 75 years), women, and those living with someone. CONCLUSIONS: Social networks were associated with dietary variety; social isolation was related to poor dietary variety among community-dwelling older adults. An association between social networks and dietary variety was observed among young-old older adults, women, and those living with someone.

    DOI: 10.1017/S1368980023001325

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  • 食育による小学4、5、6年生児童の知識・態度・行動の変化と定着 —食育動画教材の一例を用いた実践の検討— 査読

    脇本 景子, 横路 三有紀, 石井 有美子

    日本食育学会誌   17 ( 4 )   191 - 198   2023年10月

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    記述言語:日本語   出版者・発行元:一般社団法人 日本食育学会  

    DOI: 10.14986/shokuiku.17.191

    CiNii Books

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    その他リンク: https://search.jamas.or.jp/link/ui/2024009686

  • Association between asymmetric dimethylarginine and sarcopenia in community-dwelling older women. 査読 国際誌

    Miyuki Yokoro, Naoto Otaki, Megumu Yano, Tomomi Imamura, Norikazu Tanino, Keisuke Fukuo

    Scientific reports   13 ( 1 )   5510 - 5510   2023年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelium nitric oxide synthesis and causes endothelial dysfunction that may be related to sarcopenia. However, the association between ADMA and sarcopenia has not been studied. We evaluated the correlations between plasma ADMA levels and sarcopenia in community-dwelling older women. In total, 144 community-dwelling older women participated in this study. Plasma ADMA levels were measured using a competitive enzyme-linked immunosorbent assay. Skeletal muscle mass, measured in terms of bioimpedance and grip strength, was used to assess sarcopenia. Plasma ADMA levels were significantly higher in participants with sarcopenia than in those without sarcopenia. Through receiver-operating characteristic curve analysis, the cutoff value of plasma ADMA level for sarcopenia was estimated at 0.57 μM. Sarcopenia was significantly more prevalent in participants with higher plasma ADMA levels than in those with lower plasma ADMA levels. According to logistic regression analysis, the crude odds ratio of higher plasma ADMA levels in participants with sarcopenia was 4.57 (95% confidence interval, 1.82-11.47; p = 0.001). Reductions in the skeletal muscle mass index over 2 years were significantly greater in participants with higher plasma ADMA levels. In conclusion, plasma ADMA levels were significantly associated with sarcopenia in community-dwelling older women.

    DOI: 10.1038/s41598-023-32046-0

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  • 漢字・食育融合教材の開発ー持続可能な学習機会の創出を目指して―(査読あり) 査読

    設樂馨, 吉井美奈子, 横路三有紀

    武庫川女子大学 学校教育センター紀要   8   43 - 56   2023年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Association between social participation and life satisfaction among community-dwelling older adults who live alone(タイトル和訳中) 査読

    Akita Michiko, Otaki Naoto, Yokoro Miyuki, Yano Megumu, Nishimura Yuuki, Hayashi Koichi, Tanino Norikazu, Fukuo Keisuke

    日本予防医学会雑誌   17 ( 1 )   1 - 8   2023年3月

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    記述言語:英語   出版者・発行元:(一社)日本予防医学会  

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  • Low Dietary Variety Is Associated with Incident Frailty in Older Adults during the Coronavirus Disease 2019 Pandemic: A Prospective Cohort Study in Japan. 査読 国際誌

    Miyuki Yokoro, Naoto Otaki, Megumu Yano, Tomomi Imamura, Norikazu Tanino, Keisuke Fukuo

    Nutrients   15 ( 5 )   1145   2023年2月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Stagnation of social activity due to the COVID-19 pandemic probably reduces motivation to maintain a healthy diet. It is important to report on the dietary changes observed in older adults during a period of restriction on outings and to clarify the relationship between dietary variety and frailty. This one-year follow-up study examined the association between frailty and dietary variety during the COVID-19 pandemic. METHODS: Baseline and follow-up surveys were conducted in August 2020 and August 2021, respectively. The follow-up survey was distributed by mail to 1635 community-dwelling older adults aged ≥65 years. Of the 1235 respondents, 1008 respondents who were non-frail at baseline are included in this study. Dietary variety was examined using a dietary variety score developed for older adults. Frailty was assessed using a five-item frailty screening tool. The outcome was frailty incidence. RESULTS: In our sample, 108 subjects developed frailty. A linear regression analysis revealed a significant association between dietary variety score and frailty score (β, -0.032; 95% CI, -0.064 to -0.001; p = 0.046). This association was also significant in Model 1, adjusted for sex and age, (β, -0.051; 95% CI, -0.083 to -0.019; p = 0.002) and in a multivariate analysis that added adjustments for living alone, smoking, alcohol use, BMI, and existing conditions to Model 1 (β, -0.045; 95% CI, -0.078 to -0.012; p = 0.015). CONCLUSIONS: A low dietary variety score was associated with an increased frailty score during the COVID-19 pandemic. The restricted daily routine caused by the COVID-19 pandemic will probably continue to have a long-term effect in terms of reduced dietary variety. Thus, vulnerable populations, such as older adults, might require dietary support.

    DOI: 10.3390/nu15051145

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  • Associations between Dietary Variety and Frailty in Community-Dwelling Older People Who Live Alone: Gender Differences 査読

    M. Yokoro, Naoto Otaki, M. Yano, M. Tani, N. Tanino, K. Fukuo

    Journal of Frailty and Aging   12 ( 1 )   30 - 36   2023年

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)  

    Objectives: This study aimed to investigate the influences of living arrangements on the association between dietary variety and frailty by gender in community-dwelling older people. Design: A cross-sectional study. Setting: Nishinomiya city, Hyogo prefecture, Japan. Participants: A total of 4,996 randomly selected community-dwelling older people aged 65 years and older and living in Nishinomiya City. Measurements: Survey questionnaires were distributed via mail. The frailty score was evaluated by the 5-item frailty screening index. Dietary variety was assessed using the dietary variety score developed for the general older Japanese population. Results: A total of 2,764 community-dwelling participants aged ≥ 65 years responded to the questionnaires. After excluding missing data, 1,780 participants were included in the study analysis. The frailty scores in older men living alone were significantly higher than those in older men living with someone (P < 0.001). The dietary variety scores in older men living alone were significantly lower than those in older men living with someone (P < 0.001). However, differences in the frailty and dietary variety scores between living alone and living with someone were not were observed in older women (P = 0.360 and P = 0.265, respectively). In the multivariable regression analysis, the associations between dietary variety score and frailty score in living alone (β= −0. 271, P = 0.011) were stronger than those in living with someone in the case of older men (β= −0.131, P = 0.045). Similar associations between dietary variety and frailty were presented in older women living alone than in those living with someone (β −0.114, P = 0.002; β −0.088, P = 0.012, respectively). Conclusions: Older men who live alone had higher frailty score and lower dietary variety. The associations between dietary variety and frailty were different according to living arrangements in both older men and older women.

    DOI: 10.14283/jfa.2021.49

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  • 小学校高学年の児童の生きる力と家庭及び学校における食行動・態度との関連 査読

    脇本 景子, 横路 三有紀, 大倉 健太郎, 岸田 恵津

    日本健康教育学会誌   30 ( 4 )   283 - 293   2022年11月

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    記述言語:日本語   出版者・発行元:日本健康教育学会  

    目的:小学校高学年の児童の生きる力と家庭及び学校における食行動・態度との関連を明らかにすることを目的とした.

    方法:2019年7月に兵庫県K市内小学校4,5,6年生児童971名を対象に,自記式質問票を用いた横断研究デザインによる宿題調査を行った.家庭における夕食中の様子や家族との関わり,学校給食に関わる食行動・態度,さらに夕食中の会話の内容,食事の手伝い内容をとりあげた.食行動・態度の項目に分布の差を確認したため,男女別に解析を行った.生きる力の得点を従属変数に,児童の食行動・態度を独立変数とした強制投入法による重回帰分析を行った.さらに同様の方法で,会話の内容,手伝い内容との関連を検討した.

    結果:児童の生きる力は,男女ともに夕食時の家族との会話と正の関連(男子:標準化回帰係数β=0.20 P=0.002)(女子:β=0.12 P=0.044)があり,さらにその会話の内容は,学校のこと(男子:β=0.25 P=0.003)(女子:β=0.17 P=0.031)等であった.また男子では食事の手伝い行動全般に正の関連が確認された.加えて生きる力は,男子では給食で嫌いな食材を残さないようにする,女子では野菜が好きといった食態度にも関連していた.

    結論:児童の生きる力と家庭及び学校における食行動・態度の一部には,男女で異なる関連がみられた.夕食時の家族との会話は男女ともに生きる力に関連する食行動であった.

    DOI: 10.11260/kenkokyoiku.30.283

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  • 日本の独居高齢者における生活満足度と主観的健康感との関連(The association between life satisfaction and self-rated health among Japanese elderly who live alone) 査読

    Nishimura Yuuki, Otaki Naoto, Yokoro Miyuki, Yano Megumu, Akita Michiko, Hayashi Koichi, Tanino Norikazu, Fukuo Keisuke

    日本予防医学会雑誌   16 ( 3 )   45 - 51   2022年8月

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    記述言語:英語   出版者・発行元:(一社)日本予防医学会  

    70歳以上の独居高齢者を対象に、生活満足度や主観的健康感に関する質問票調査を行った。質問への回答者2027名のうち1915名(男性388名、女性1527名、平均78.3±5.7歳)のデータを解析した。1614名(84.3%)は生活満足度が高いと回答し、301名(157%)は低いと回答した。生活満足度は性別、年齢、独居歴、主観的健康感、人生の楽しみ、社会参加、自宅で調理する頻度、生活環境(経済的自律)と関連していた。主観的健康感が低い者の生活満足の粗オッズ比は有意に高かった。多変量解析で主観的健康感が低い者の生活満足の調整オッズ比は有意に高かった。性別および年齢層により層別解析しても生活満足度と主観的健康感の間に同様の関連性がみられた。以上の結果から、独居高齢者では生活満足度が独立して主観的健康感と関連すると考えられた。

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  • Social contact impacts physical activity and sedentary behavior among older adults in Japan due to COVID-19. 査読 国際誌

    Naoto Otaki, Miyuki Yokoro, Megumu Yano, Tomomi Imamura, Michiko Akita, Norikazu Tanino, Keisuke Fukuo

    BMC geriatrics   22 ( 1 )   491 - 491   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The coronavirus disease 2019 (COVID-19) has adversely affected social contact and physical activity. This study investigated the correlation between physical activity, social contact, and sedentary time among adults aged 65 years and above during the COVID-19 pandemic. METHODS: This study was conducted in N City, H Prefecture, Japan. The authors randomly selected 4,996 adults, aged 65 years and above (mean age 74.1 ± 6.1 years), living in N City, and survey forms were distributed by mail in mid-August 2020. Altogether, 1,925 participants were included in this study. The survey comprised questions concerning the participants' sex, height, weight, age, smoking and drinking habits, living arrangements, social contact assessments, physical activity levels, and sedentary time. Moreover, linear regression analysis was utilized to investigate the associations between the variables. RESULTS: The reported median physical activity was 1272 metabolic equivalent of task-min/week (interquartile range 528-2628), and the reported median sedentary time was 360 min/week (interquartile range 240-600). COVID-19 "somewhat," "quite a lot," or "completely" hindered the frequency of in-person contact with friends among 75.5% of the respondents and hampered the frequency of virtual contact with friends among 38.8% of the respondents. Physical activity was associated significantly with in-person contact indicators: "interaction with friends" (B = -0.111; 95%CI: -0.187, -0.035; p = 0.004) and "social participation" (B = -0.163; 95%CI: -0.248, -0.079; p < 0.001). These associations remained significant for both multivariate analysis Models 1 (sex and age) and 2 (addition of body mass index [BMI], alcohol use, smoking, living alone, and the number of illnesses to Model 1). Additionally, sedentary time was significantly associated with the social contact variable of "interaction with friends" (B = 0.04; 95%CI: 0.016, 0.064; p = 0.001). This association remained significant in both multivariate analysis models. CONCLUSIONS: Significant associations were confirmed between reduced social contact, decreased physical activity, and more sedentary behavior among older adults due to COVID-19. Hence, continuous monitoring and support for social activities among susceptible older adults in extraordinary circumstances are essential.

    DOI: 10.1186/s12877-022-03188-z

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  • 小学校高学年の児童の生きる力と食生活に関わる親の態度・行動との関係 査読

    脇本 景子, 横路 三有紀, 大倉 健太郎, 岸田 恵津

    日本健康教育学会誌   30 ( 1 )   3 - 13   2022年2月

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    記述言語:日本語   出版者・発行元:日本健康教育学会  

    目的:本研究は,小学校高学年の児童の生きる力と食生活に関わる親の態度・行動との関係を明らかにすることを目的とした.

    方法:小学校4・5・6年生の児童とその親を対象に,児童の生きる力と食生活に関わる親の態度・行動に関する質問票調査を行った.生きる力(心理社会的能力,徳育的能力,身体的能力)の得点を従属変数に,食生活に関わる親の態度・行動を独立変数としてステップワイズ法による重回帰分析により関連を検討した.

    結果:生きる力の得点には,親の態度・行動として,子どもの運動不足に対する親の心配(β=−0.15 P=0.001),子どもの朝食欠食に対する親の認識(β=−0.10 P=0.018),食事時に食事の挨拶を教える(β=0.10 P=0.016)との関連が認められた.徳育的能力,身体的能力にも同様の関連がみられた.心理社会的能力の得点には,親の朝食欠食,朝食調理時間との関連も認められた.

    結論:児童の生きる力には,子どもの運動不足に対する親の心配,子どもの朝食欠食に対する親の認識が負の要因として関わり,食事時に挨拶を教えることが正の要因として関わっていた.食生活に関わる親の態度・行動の改善により,児童の生きる力の育成を促進できる可能性が示された.

    DOI: 10.11260/kenkokyoiku.30.3

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    その他リンク: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20K02598/

  • Relationship Between Social Activity and Frailty in Japanese Older Women During Restriction on Outings due to COVID-19. 査読 国際誌

    Michiko Akita, Naoto Otaki, Miyuki Yokoro, Megumu Yano, Norikazu Tanino, Keisuke Fukuo

    Canadian geriatrics journal : CGJ   24 ( 4 )   320 - 324   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: This study investigated the relationship between social activities and frailty during the restriction on outings due to COVID-19. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: This study was conducted in City Nishinomiya of Prefecture Hyogo, in Japan. A mail survey was carried out among women aged 65 years or older in May 2020. A population of 293 women aged 65 years or older living in the community was recruited for the study and 213 of them were analyzed. MEASUREMENTS: The survey included questions on sex, age, height, weight, and social activity. Social activity consisted of participation in social organizations and their frequency, as well as frequency of interaction with family and friends. The survey also asked if regular social activity had been impeded by COVID-19. RESULTS: A significant association was found between frailty and hindered interaction with friends (β: 0.176, p = .014). Multivariate linear regression analysis confirmed that this association was also significant in Model 1 (β: 0.158, p = .025), and Model 2 (β: 0.148, p = .034). CONCLUSIONS: No association between being hindered in social activity and frailty was found in older women living in the community during the restriction on outings due to COVID-19.

    DOI: 10.5770/cgj.24.507

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  • Relationship Between Dietary Variety and Frailty in Older Japanese Women During the Period of Restriction on Outings Due to COVID-19. 査読 国際誌

    Naoto Otaki, Megumu Yano, Miyuki Yokoro, Norikazu Tanino, Keisuke Fukuo

    The journals of gerontology. Series B, Psychological sciences and social sciences   76 ( 7 )   e256-e262   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: To investigate the relationship between diet and frailty in community-dwelling older adults during the period of restriction on outings due to novel coronavirus disease 2019 (COVID-19). METHOD: A mail survey targeting adults aged 65 years or older, including questions on sex, age, height, weight, and social participation, was conducted in May 2020. The participants' dietary variety score and frailty score were then calculated. RESULTS: Overall, 322 women aged 65 years or older and who were living in the community were recruited for the study; 253 were finally analyzed. The mean age of the 253 participants was 80.0 ± 6.4 years. The dietary variety score and frailty scores were significantly correlated in the linear regression analysis (β: -0.224, p < .001). In the multivariate regression analysis, these factors remained significantly correlated in Model 1, which was adjusted for age (β: -0.229, p < .001), and Model 2, which was adjusted for age, body mass index, and other confounding factors (β: -0.208, p = .001). DISCUSSION: Diet was correlated with frailty in older adults living in the community during the period of restriction on outings due to COVID-19.

    DOI: 10.1093/geronb/gbaa218

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  • Lower dietary variety is associated with worse sleep quality in community-dwelling elderly Japanese women. 査読 国際誌

    Miyuki Yokoro, Naoto Otaki, Megumu Yano, Tomomi Imamura, Norikazu Tanino, Kayoko Maeda, Keisuke Fukuo

    Asia Pacific journal of clinical nutrition   30 ( 2 )   275 - 282   2021年6月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND OBJECTIVES: Sleep disturbance is a common health problem in the elderly population. We examined the association between dietary variety and subjective sleep quality in community-dwelling elderly Japanese women. METHODS AND STUDY DESIGN: This cross-sectional study recruited 160 community-dwelling elderly women aged ≥65 years. Subjective sleep quality and dietary variety were assessed by Pittsburgh Sleep Quality Index (PSQI) and dietary variety score (DVS), respectively. DVS was calculated from the eating frequency of 10 food groups. Sleep disturbance was defined as PSQI score of ≥6. RESULTS: The DVS in subjects with sleep disturbance was significantly lower than that of those without the disturbance (4.1±2.1 vs 5.3±2.1, p<0.01). In the multivariable regression model, the PSQI score was negatively correlated with the DVS score in age-adjusted model (standardized coefficient; -0.234, p<0.01). In the further adjusted model that included depression levels, the negative association between PSQI score and DVS score was retained (standardized coefficient; -0.211, p<0.05). Among 10 food groups comprising DVS, the eating frequency of soybean and soybean products was the determinant of sleep disturbance in the stepwise liner regression analysis. In the further model that contained DVS, DVS was the independent determinant of sleep disturbance, while the eating frequency of soybean and soybean products was excluded. CONCLUSIONS: A worse sleep quality was associated with lower DVS in elderly Japanese women. Diet comprising various food groups was better for sleep quality than consuming only a particular food in the elderly.

    DOI: 10.6133/apjcn.202106_30(2).0012

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  • Increased Prevalence of Breakfast Skipping in Female College Students in COVID-19. 査読 国際誌

    Miyuki Yokoro, Keiko Wakimoto, Naoto Otaki, Keisuke Fukuo

    Asia-Pacific journal of public health   33 ( 4 )   438 - 440   2021年5月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/1010539521998861

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  • Urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine levels in patients with type 2 diabetes. 査読 国際誌

    Miyuki Yokoro, Miki Minami, Sumire Okada, Megumu Yano, Naoto Otaki, Hiroki Ikeda, Keisuke Fukuo

    Hypertension research : official journal of the Japanese Society of Hypertension   41 ( 11 )   913 - 922   2018年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Obesity modifies the association between sodium and potassium intake and blood pressure. However, the impact of obesity on the relationship between the sodium-potassium balance and cardiovascular risk in type 2 diabetes (T2DM) patients remains unclear. We investigated the relationship between the 24-h urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine (ADMA) level, which is a cardiovascular risk factor, in Japanese T2D patients with or without obesity. This cross-sectional study included 243 patients with T2DM who were hospitalized for diabetes education. Urinary sodium-to-potassium ratios were calculated from 24-h urine collection. The subjects were divided into two groups according to their BMIs (<25 and ≥25). The serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios in non-obese patients, but not in obese patients. Multivariate linear regression analyses showed that the serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios after adjustment for other confounders in non-obese patients. This correlation was observed in non-obese patients with hypertension, but not in those without hypertension. Measurement of the pulse wave velocity and intima-media thickness revealed that elevation of the serum ADMA levels was significantly associated with an increase in the degree of atherosclerotic progression in subjects with T2DM. Additionally, an assessment of dietary intake showed that the consumption of dairy products as well as of green and yellow vegetables was negatively associated with urinary sodium-to-potassium ratios in patients with T2DM. In conclusion, elevation of serum ADMA may be positively associated with the urinary sodium-to-potassium ratio in Japanese non-obese patients with T2DM.

    DOI: 10.1038/s41440-018-0098-1

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  • Relationship between Economic Security and Self-Rated Health in Elderly Japanese Residents Living Alone 査読

    N. Otaki, N. Tanino, M. Yokoro, M. Yano, M. Akita, H. Uemura, M. Maeda, Keisuke Fukuo

    Journal of Nutrition, Health and Aging   22 ( 6 )   695 - 699   2018年6月

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    掲載種別:研究論文(学術雑誌)  

    Objectives: The purpose of this study was to assess the relationship between economic security and self-rated health for elderly Japanese residents living alone. Design: A secondary analysis of a cross-sectional study. Setting: N City, H. Prefecture, Japan. Participants: Survey questionnaires were distributed to 2,985 elderly residents living alone, aged ≥70 years, of which, 1,939 (65.0%) were returned and treated as valid responses. Measurements: The survey included questions about gender, age, number of years spent in N City, self-rated health, economic security, number of years spent living alone, reason for living alone, life satisfaction, cooking frequency, frequency of seeing a doctor, long-term care service usage, as well as whether they enjoyed their lives, participated in social organizations. Results: Of the respondents, 1,563 (80.6%) reported that they were economically secure, and 376 (19.4%) responded that they were insecure. The odds ratio predicting poor self-rated health for the economically insecure participants was significantly high (odds ratio: 3.19, 95%, Confidence Interval (CI): 2.53−4.02, and P < 0.001). Similarly, the adjusted odds ratio for poor self-rated health was significantly high for the economically insecure participants in multivariate analyses controlling for factors such as age, gender, cooking frequency, and social participation (adjusted odds ratio: 2.21, 95%, CI: 1.70−2.88, and P < 0.001). Furthermore, a similar trend was observed in stratified analyses based on gender and age groups. Conclusion: Economic security predicted self-rated health independently of confounders, including social participation and cooking frequency, among the elderly Japanese living alone in communities.

    DOI: 10.1007/s12603-017-0994-0

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  • 在宅高齢女性における血中ビタミンD濃度と臨床指標との関係 査読

    矢野 めぐむ, 谷野 永和, 長谷川 裕紀, 横路 三有紀, 福尾 惠介

    New Diet Therapy   34 ( 1 )   3 - 12   2018年6月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床栄養協会  

    重篤な疾患を有さない健康な高齢女性148名(平均78.0±6.0歳)を対象とした。平均血中25-OH-ビタミンD(25-OHD)濃度は23.4±5.4g/mlであった。血中25-OHD濃度によってビタミンD欠乏群(20ng/ml未満)29.1%、ビタミンD不足群(20以上30ng/ml未満)57.4%、ビタミンD正常群(30ng/ml以上)13.5%であった。血中25-OHD濃度を4分位に分け、最小値群は、最大値群に比べ有意に年齢が高く、四肢の骨格筋指数SMIや握力と骨量が低値傾向を示した。血中のカルシウムと亜鉛の濃度、ヘマトクリット値は、最小値群が最大値群に比べ有意に低値を示し、血清アルブミンは最小値群が最大値群に比べ低値傾向を示した。単相関では、血中25-OHD濃度と年齢との間に負の相関関係、握力、骨量との間に正の相関関係を認めた。単相関において、血中25-OHD濃度と血中のアルブミンとカルシウム、亜鉛の濃度、ヘマトクリット値において、それぞれ正の相関関係、血中シスタチンCとの間に負の相関関係を認めた。年齢とともに、血中亜鉛濃度が血中25-OHD濃度の独立した規定因子として抽出された。

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  • 1人暮らし高齢者における社会参加継続性と栄養状態との関連 査読

    榊原 典子, 谷野 永和, 横路 三有紀, 奥野 公美子, 矢野 めぐむ, 福尾 惠介

    栄養科学研究   6   1 - 8   2018年3月

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    記述言語:日本語   出版者・発行元:[出版社不明]  

    1人暮らし高齢者において、栄養状態が高齢者の社会参加の継続性にどのような影響を与えるかは明らかでない。2008年度の西宮市主催の「ふれあい昼食会」に参加した1人暮らし高齢者で、文書による同意が得られ、5年間経過観察可能であった135名を対象とした。途中で昼食会に参加しなくなった高齢者を脱落群、継続参加した高齢者を非脱落群とした。脱落群は47.4%と高率に存在し、脱落群は非脱落群に比し年齢が高く、Mini Nutritional Assessment(MNA)評価における低栄養の割合が高値を示した。Log-rank検定から80歳以上群は80歳未満群に比し、低栄養群は栄養状態良好群に比し、それぞれ有意に参加継続期間が短いことが分かった。また、Cox比例ハザードモデルによる多変量解析から、参加継続性の関連因子として、年齢とMNAによる低栄養がそれぞれ抽出された。男女全体に対し、女性では年齢と握力が関連因子として抽出された。以上より、1人暮らし高齢者において、年齢とともに低栄養が社会参加の継続性に関連する重要な因子であることが示唆された。
    Objective: We examined whether nutritional status affects the continuity of social participation in Japanese elderly people who live alone.Methods: In retrospective observational study, physical measurements and mini nutritional assessment(MNA) were performed in 135 elderly participants to Fureai-luncheon party (2008-2012) who live alone.Results: Frequency of dropout group was 47.4% for 5 years and subjects in dropout group were older and with higher incidence of malnourished status by MNA as compared with those in non-dropout group. Both age and malnutrition were independently associated with a higher risk of dropout from social participation.Conclusion: This study showed that malnutrition and age are two independent risk factors for dropout from social participation in Japanese elderly people who live alone.

    DOI: 10.14993/00002177

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  • RAGE-aptamer attenuates deoxycorticosterone acetate/salt-induced renal injury in mice. 査読 国際誌

    Kensei Taguchi, Sho-Ichi Yamagishi, Miyuki Yokoro, Sakuya Ito, Goh Kodama, Yusuke Kaida, Yosuke Nakayama, Ryotaro Ando, Nana Yamada-Obara, Katsuhiko Asanuma, Takanori Matsui, Yuichiro Higashimoto, Craig R Brooks, Seiji Ueda, Seiya Okuda, Kei Fukami

    Scientific reports   8 ( 1 )   2686 - 2686   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice. RAGE, GTP-bound Rac-1 (Rac1), and MR were co-localized in the podocytes of DOCA mice. The deletion of RAGE gene significantly inhibited mesangial matrix expansion and tubulointerstitial fibrosis in DOCA mice, which was associated with the reduction of glomerular oxidative stress, MR, Rac1, and urinary albumin excretion (UAE) levels. RAGE-apt attenuated the increase in carboxymethyllysine (CML), RAGE, nitrotyrosine, Rac1, and MR levels in the kidneys and reduced UAE in DOCA mice. Aldosterone (Aldo) increased nitrotyrosine, CML, and RAGE gene expression in murine podocytes, whereas CML stimulated MR and Rac1 levels, which were blocked by RAGE-apt. The present study indicates the crosstalk between the AGE-RAGE axis and Aldo-MR system, suggesting that RAGE-apt may be a novel therapeutic tool for the treatment of MR-associated renal diseases.

    DOI: 10.1038/s41598-018-21176-5

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  • Asymmetric Dimethylarginine Contributes to the Impaired Response to Erythropoietin in CKD-Anemia. 査読 国際誌

    Miyuki Yokoro, Yosuke Nakayama, Sho-Ichi Yamagishi, Ryotaro Ando, Miki Sugiyama, Sakuya Ito, Junko Yano, Kensei Taguchi, Yusuke Kaida, Daisuke Saigusa, Masumi Kimoto, Takaaki Abe, Seiji Ueda, Kei Fukami

    Journal of the American Society of Nephrology : JASN   28 ( 9 )   2670 - 2680   2017年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Erythropoietin-resistant anemia is associated with adverse cardiovascular events in patients with ESRD, but the underlying mechanism remains unclear. Here, we evaluated the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In 54 patients with advanced CKD, erythrocyte but not plasma ADMA levels independently associated with low hemoglobin values, although levels of both types of ADMA were elevated compared with those in healthy volunteers. Furthermore, erythrocyte ADMA level associated with the erythropoietin resistance index in patients receiving a weekly injected dose of erythropoiesis-stimulating agents standardized for hemoglobin levels and body weight, whereas it correlated with the erythropoietin demand index (plasma erythropoietin units divided by the hemoglobin value) in patients not receiving erythropoiesis-stimulating agents. Compared with sham-operated controls, wild-type mice with 5/6 subtotal nephrectomy (Nx), a remnant kidney model with advanced CKD, had decreased hemoglobin, hematocrit, and mean corpuscular volume values but increased erythrocyte and plasma ADMA and plasma erythropoietin levels. In comparison, dimethylarginine dimethlaminohydrolase-1 transgenic (DDAH-1 Tg) mice, which efficiently metabolized ADMA, had significant improvements in all of the values except those for erythropoietin after 5/6 Nx. Additionally, wild-type Nx mice, but not DDAH-1 Tg Nx mice, had reduced splenic gene expression of erythropoietin receptor and erythroferrone, which regulates iron metabolism in response to erythropoietin. This study suggests that erythrocyte ADMA accumulation contributes to impaired response to erythropoietin in predialysis patients and advanced CKD mice via suppression of erythropoietin receptor expression.

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  • L-Carnitine Supplementation Improves Self-Rating Depression Scale Scores in Uremic Male Patients Undergoing Hemodialysis. 査読 国際誌

    Kyoko Tashiro, Yusuke Kaida, Sho-Ichi Yamagishi, Hideharu Tanaka, Miyuki Yokoro, Junko Yano, Kazuko Sakai, Yuka Kurokawa, Kensei Taguchi, Yosuke Nakayama, Takahiro Inokuchi, Kei Fukami

    Letters in drug design & discovery   14 ( 6 )   737 - 742   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Depression is highly prevalent in uremic patients undergoing hemodialysis (HD). We previously found that low free-carnitine levels are associated with depression severity in male patients undergoing HD. However, whether L-carnitine supplementation improves the depression state in male patients undergoing HD remains unclear. METHODS: Sixteen male patients undergoing HD were orally administered 900 mg L-carnitine daily or intravenously administered 1000 mg L-carnitine immediately after undergoing HD for 3 months. The depression state and various types of carnitine levels were evaluated using the self-rating depression scale (SDS) and tandem mass spectrometry, respectively, at baseline and 3 months after treatment. RESULTS: L-carnitine supplementation significantly increased serum levels of free and other acylcarnitine types, associated with improved SDS scores in male patients undergoing HD. Univariate analysis revealed that low baseline butyryl- and isovaleryl-/2-methylbutyryl-carnitine levels were significantly correlated with SDS scores after treatment. Multiple regression analysis revealed that butyryl-carnitine levels were a sole independent predictor of SDS scores after treatment (r2 = 0.533). CONCLUSION: L-carnitine supplementation for 3 months improved the depression state in uremic male patients undergoing HD. Thus, low butyryl-carnitine levels may predict the clinical response to L-carnitine supplementation in male patients undergoing HD and who have mild depression.

    DOI: 10.2174/1570180814666170216102632

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  • 地域在住女性高齢者における腎機能と内皮型一酸化窒素合成酵素遺伝子一塩基多型の関連 査読

    岡田 菫, 横路 三有紀, 矢野 めぐむ, 今村 友美, 大滝 直人, 谷野 永和, 福尾 惠介

    栄養科学研究   5   11 - 18   2017年3月

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    記述言語:日本語   出版者・発行元:[出版社不明]  

    高齢者では慢性腎臓病(CKD)患者は増加するが、内皮型一酸化窒素合成酵素(eNOS)遺伝子G894T多型と高齢者の腎機能との関連は明らかではない。本研究は、地域在住女性高齢者109名を対象に、G894T多型と腎機能との関連を検討した。eNOS遺伝子G894T多型(rs1799983)はTaqMan PCR法で解析した。Tアリル群はGG群に比し、eGFRが有意に低値であり、CKD患者割合が有意に高かった。さらに、Tアリル群においてのみ、eGFRとHDL-Cとの間に有意な正の相関、炎症指標TNF-αとの間に負の相関関係を認めた。Tアリル群において清涼飲料水を飲む習慣がある場合、HDL-Cは有意に低値を示したが、この関連はGG群では認められなかった。以上より、eNOS遺伝子G894T多型は、女性高齢者においてeGFRに関連すること、環境因子との相互作用によりeGFRに影響を与える可能性が示唆された。
    Prevalence of chronic kidney diseases (CKD) is high in elderly. Although nitric oxide (NO) is an important regulator of renal function, relation between G894T polymorphic variant of endothelial NO synthase (eNOS) gene and renal function in the elderly is unclear. We investigated the association between G894T and renal function in 109 of community-dwelling elderly Japanese women. G894T polymorphic variants (rs1799983) are assessed by the TaqMan PCR method. T allele (GT and TT)group showed lower estimated glomerular filtration rate (eGFR) and a higher incidence of CKD(eGFR<60 ml/min/1.73m2) compared to those in GG genotype group. eGFR was associated with HDL-C and inversely associationed with TNF-α only in the T allele group. Additionally HDL-C was positively correlated with sweetened soft drink consumption habit in the T allele group, but not in the GG group. In conclusion, G894T polymorphism might be associated with eGFR and might interact with environmental factors to influence eGFR in community-dwelling elderly Japanese women.

    DOI: 10.14993/00002176

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  • Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring. 査読

    Nana Yamada-Obara, Sho-Ichi Yamagishi, Kensei Taguchi, Yusuke Kaida, Miyuki Yokoro, Yosuke Nakayama, Ryotaro Ando, Katsuhiko Asanuma, Takanori Matsui, Seiji Ueda, Seiya Okuda, Kei Fukami

    Clinical and experimental nephrology   20 ( 6 )   853 - 861   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Maternal exposure to overnutrition during fetal development contributes to metabolic and renal damage in offspring. Adiponectin plays a protective role against obesity-related renal injury. However, role of adiponectin in renal injury of offspring exposed to maternal overnutrition remains unknown. We addressed the issue. METHODS: Female Sprague-Dawley rats were fed either a standard (N) or a high-fat and high-fructose (HFF)-diet for 6 weeks before mating, and kept each diet during the gestation and lactation period. After 4 weeks postpartum, all the offspring were fed N diet, and followed by 12 weeks. Kidney weight, urinary albumin excretion, blood pressure, and blood chemistry, including adiponectin and malondialdehyde, a marker of oxidative stress, were evaluated in the offspring. RESULTS: Compared with N-offspring, serum adiponectin levels of 1-day- and 4-week-old HFF-offspring were significantly lower, the latter of which was inversely associated with malondialdehyde. Kidney weight was significantly decreased in 1-day-old HFF-offspring, whereas increased in 4-week-old HFF-offspring. Urinary albumin excretion levels of HFF-offspring at 8, 12, and 16-week old were significantly higher than those of N-offspring at the same age, whose levels at 16-week old were inversely correlated with plasma adiponectin. Compared with N-offspring, HFF-offspring at 16-week old exhibited glomerulosclerosis, hyperglycemia, and high mean blood pressure associated with reduced podocin and increased transforming growth factor-β1 expression in the kidneys. CONCLUSIONS: Our present study suggests that exposure to maternal HFF-diet during fetal and early postnatal development induces hypoadiponectinemia in offspring, which might cause renal injury and metabolic derangements later in life.

    DOI: 10.1007/s10157-016-1265-9

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  • Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage. 査読 国際誌

    Takehiro Suzuki, Hiroaki Yamaguchi, Motoi Kikusato, Osamu Hashizume, Satoru Nagatoishi, Akihiro Matsuo, Takeya Sato, Tai Kudo, Tetsuro Matsuhashi, Kazutaka Murayama, Yuki Ohba, Shun Watanabe, Shin-Ichiro Kanno, Daichi Minaki, Daisuke Saigusa, Hiroko Shinbo, Nobuyoshi Mori, Akinori Yuri, Miyuki Yokoro, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yoichi Takeuchi, Koichi Kikuchi, Takafumi Toyohara, Chitose Suzuki, Takaharu Ichimura, Jun-Ichi Anzai, Masahiro Kohzuki, Nariyasu Mano, Shigeo Kure, Teruyuki Yanagisawa, Yoshihisa Tomioka, Masaaki Toyomizu, Kohei Tsumoto, Kazuto Nakada, Joseph V Bonventre, Sadayoshi Ito, Hitoshi Osaka, Ken-Ichi Hayashi, Takaaki Abe

    Journal of the American Society of Nephrology : JASN   27 ( 7 )   1925 - 32   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid-resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin-induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I-IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.

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  • Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients. 査読 国際誌

    Kei Fukami, Sho-ichi Yamagishi, Kazuko Sakai, Yusuke Kaida, Miyuki Yokoro, Seiji Ueda, Yoshifumi Wada, Masayoshi Takeuchi, Makiko Shimizu, Hiroshi Yamazaki, Seiya Okuda

    Journal of cardiovascular pharmacology   65 ( 3 )   289 - 95   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue. METHODS: Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured. RESULTS: Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043). CONCLUSIONS: This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.

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  • Gly m Bd 28K前駆体をコードするcDNAのクローニングとタバコBY2浮遊培養細胞におけるその液胞輸送(Cloning of a cDNA Encoding the Gly m Bd 28K Precursor and Its Vacuole Transport in Tobacco BY2 Suspension-Cultured Cells) 査読

    Yumioka-Ito Hitomi, Misaki Ryo, Yokoro Miyuki, Suzuki Makiko, Yamashita Hiromi, Hiemori-Kondo Miki, Kimoto Masumi, Kato Ko, Fujiyama Kazuhito, Tsuji Hideaki

    Journal of Nutritional Science and Vitaminology   60 ( 2 )   129 - 139   2014年4月

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    記述言語:英語   出版者・発行元:(公社)日本栄養・食糧学会  

    Gly m Bd 28K (Gm28K), a soybean allergen, is formed as a preproprotein consisting of a predicted signal peptide, Gm28K, and the 23-kDa peptide (Gm23K). Gm28K and Gm23K are found in the protein-storage vacuoles (PSVs) of developing soybean seeds. However, the complete structure of Gm28K has not yet been identified and its processing and transport to the vacuoles has never been clarified. In the present study, we elucidated the 5'-nucleotide sequence of cDNA encoding the Gm28K precursor and identified a putative signal peptide (SP) with 24 N-terminal amino acid residues. We expressed peptides from the Gm28K precursor as fusion proteins with enhanced green fluorescent protein (EGFP) in tobacco BY2 suspension-cultured cells. BY2 cells transformed by an expression vector for SP-EGFP-Gm28-Gm23K (SP-EGFP-Gm28-Gm23K/BY2 cells) and SP-Gm28-Gm23K-EGFP/BY2 cells produced the EGFP fused-Gm28K precursor, and the EGFP-fluorescence in their vacuoles were recorded. In the experiments with SP-EGFP/BY2 and SP-EGFP-Gm28K/BY2 cells, large amounts of the EGFP segments were secreted into the medium. On the other hand, the fluorescence of EGFP in SP-EGFP-Gm23K/BY2 cells was shown to accumulate only in the endoplasmic reticulum without secretion into the medium. These findings show that the SP signals the precursor to enter the lumen of the endoplasmic reticulum and that both the Gm28K and Gm23K components may be involved in the transport from the endoplasmic reticulum (ER) lumen via the Golgi to the vacuoles in a proprotein form.

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J04559&link_issn=&doc_id=20140513430009&doc_link_id=1390282681301589632&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282681301589632&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

  • Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury. 査読 国際誌

    Yosuke Nakayama, Seiji Ueda, Sho-ichi Yamagishi, Nana Obara, Kensei Taguchi, Ryotaro Ando, Yusuke Kaida, Ryuji Iwatani, Kumiko Kaifu, Miyuki Yokoro, Maki Toyonaga, Takuo Kusumoto, Kei Fukami, Seiya Okuda

    Kidney international   85 ( 3 )   570 - 8   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ischemia/reperfusion injury is the leading cause of acute tubular necrosis. Nitric oxide has a protective role against ischemia/reperfusion injury; however, the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in ischemia/reperfusion injury remains unclear. ADMA is produced by protein arginine methyltransferase (PRMT) and is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Here we examined the kinetics of ADMA and PRMT and DDAH expression in the kidneys of ischemia/reperfusion-injured mice. After the injury, DDAH-1 levels were decreased and renal and plasma ADMA values were increased in association with renal dysfunction. Renal ADMA was correlated with 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. An antioxidant, N-acetylcysteine, or a proteasomal inhibitor, MG-132, restored these alterations. Infusion of subpressor dose of ADMA exacerbated renal dysfunction, capillary loss, and tubular necrosis in the kidneys of ischemia/reperfusion-injured wild mice, while damage was attenuated in DDAH transgenic mice. Thus, ischemia/reperfusion injury-induced oxidative stress may reduce DDAH expression and cause ADMA accumulation, which may contribute to capillary loss and tubular necrosis in the kidney.

    DOI: 10.1038/ki.2013.398

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  • Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction. 査読 国際誌

    Kiyomi Koike, Seiji Ueda, Sho-ichi Yamagishi, Hideo Yasukawa, Yusuke Kaida, Miyuki Yokoro, Kei Fukami, Akihiko Yoshimura, Seiya Okuda

    Clinical immunology (Orlando, Fla.)   150 ( 1 )   78 - 87   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Inflammation is involved in renal fibrosis, a final common pathway for kidney diseases. To clarify how JAK/STAT/SOCS system was involved in renal fibrosis, UUO was induced in BALB/c or SOCS3(+/-) mice in the presence or absence of JAK inhibitor-incorporated nanoparticle (pyridine6-PGLA). UUO increased pSTAT3 and subsequently elevated SOCS3 levels in the obstructed kidneys. pSTAT3 levels were further increased in SOCS3(+/-) mice. UUO-induced renal fibrosis was markedly suppressed in SOCS3(+/-) mice, while it was aggravated by pre-treatment with pyridine6-PGLA. Although there were no differences in renal mRNA levels of TGF-β and collagens between wild and SOCS3(+/-) mice, MMP-2 activity was enhanced in SOCS3(+/-) UUO mice. Activated MMP-2 was completely suppressed by pyridine6-PGLA-pre-treatment. TNF-α one of JAK/STAT activators, increased pSTAT3 levels and subsequently induced MMP-2 activation in proximal tubular cells. These results suggest that JAK/STAT3 signaling may play a role in repair process of renal fibrosis in UUO partly via MMP-2 activation.

    DOI: 10.1016/j.clim.2013.11.003

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  • Role of asymmetric dimethylarginine in cardiorenal syndrome. 国際誌

    Seiji Ueda, Sho-Ichi Yamagishi, Miyuki Yokoro, Seiya Okuda

    Current pharmaceutical design   20 ( 14 )   2448 - 55   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cardiorenal syndrome (CRS) is a condition in which there is a complex interrelationship between cardiovascular disease (CVD) and chronic kidney disease (CKD). Impairment of one organ could accelerate pathological processes in the other, which in turn accelerates the progression of failure of both. Although clinical studies hint at a specific bidirectional interaction between cardiovascular system and kidney, insight into the pathogenesis of CRS remains unknown. One possible factor that could explain this link is endothelial dysfunction (ED). ED is not only involved in initiation and progression of atherosclerosis, but also contributes to progression of renal injury. Asymmetric dimethylarginine (ADMA) is an endogenous NO synthase inhibitor found in the plasma and cells. Plasma ADMA levels are increased in CKD patients and known to be an independent biomarker and predictor for future cardiovascular events as well as the progression of CKD. These findings indicate that accumulated ADMA-mediated ED may play important roles in CRS in CKD patients. In this review, we discuss the roles of ADMA in the development of ED, especially focusing on its roles in CRS.

    PubMed

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  • Involvement of advanced glycation end product-induced asymmetric dimethylarginine generation in endothelial dysfunction. 査読 国際誌

    Ryotaro Ando, Seiji Ueda, Sho-ichi Yamagishi, Hiroshi Miyazaki, Yusuke Kaida, Kumiko Kaifu, Miyuki Yokoro, Yosuke Nakayama, Nana Obara, Kei Fukami, Masayoshi Takeuchi, Seiya Okuda

    Diabetes & vascular disease research   10 ( 5 )   436 - 41   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, plays a role in endothelial dysfunction, an initial step of atherosclerosis. Advanced glycation end products (AGEs) also contribute to accelerated atherosclerosis. However, a pathophysiological crosstalk between ADMA and AGEs remains unclear. In this study, we investigated the relationship between ADMA and AGE level in patients with end-stage renal disease (ESRD) due to diabetic nephropathy. We also examined whether and how AGEs increased ADMA generation by cultured endothelial cells (ECs). Plasma ADMA levels were positively associated with serum AGE level and were inversely correlated with endothelial function determined by flow-mediated vasodilatation. AGEs dose dependently increased reactive oxygen species (ROS) generation in ECs, which was blocked by antisense DNA raised against receptor for AGEs (RAGE). Furthermore, AGEs decreased messenger RNA (mRNA) level of dimethylarginine dimethylaminohydrolase (DDAH)-II, an enzyme for ADMA degradation, reduced its total enzymatic activity and resultantly increased ADMA, all of which were completely blocked by an antioxidant, N-acetylcysteine. These results suggest that the AGE-RAGE-mediated ROS generation could be involved in endothelial dysfunction in diabetic ESRD patients partly by increasing the ADMA generation via suppression of DDAH activity in ECs.

    DOI: 10.1177/1479164113486662

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  • Antiatherogenic effect of guava leaf extracts inhibiting leucocyte-type 12-lipoxygenase activity 査読

    Yuki Kawakami, Tomoko Hosokawa, Tomoko Morinaka, Shioka Irino, Shiori Hirano, Hirokazu Kobayashi, Akiko Yoshioka, Toshiko Suzuki-Yamamoto, Miyuki Yokoro, Masumi Kimoto, Hideaki Tsuji, Hiromi Yamashita, Shinobu Doi, Chikao Yutani, Rina Kato, Hiroyuki Itabe, Teruyuki Kanada, Takahiko Hada, Yoshitaka Takahashi

    Food Chemistry   131 ( 4 )   1069 - 1075   2012年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.foodchem.2011.10.011

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  • Development of an enzyme-linked immunosorbent assay system for the determination of asymmetric dimethylarginine using a specific monoclonal antibody. 査読 国際誌

    Miyuki Yokoro, Makiko Suzuki, Machiko Yatani, Hiromi Yamashita, Yoshitaka Takahashi, Hideaki Tsuji, Masumi Kimoto

    Bioscience, biotechnology, and biochemistry   76 ( 2 )   400 - 3   2012年

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We produced a monoclonal antibody (mAb) against N(G),N(G)-dimethyl-L-arginine (asymmetric dimethylarginine: ADMA), an endogenous competitive inhibitor of nitric oxide synthase (NOS), and developed an enzyme-linked immunosorbent assay (ELISA). The competitive ELISA method using the mAb determined 5 nM-100 nM ADMA, and ADMA levels in human plasma and urine were found to be 0.78 µM and 51.3 µmol/g of creatinine respectively.

    PubMed

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  • Asymmetric dimethylarginine, an endogenous NOS inhibitor, is actively metabolized in rat erythrocytes. 査読 国際誌

    Miyuki Yokoro, Makiko Suzuki, Kaeko Murota, Chie Otsuka, Hiromi Yamashita, Yoshitaka Takahashi, Hideaki Tsuji, Masumi Kimoto

    Bioscience, biotechnology, and biochemistry   76 ( 7 )   1334 - 42   2012年

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    N(G), N(G)-Dimethyl-L-arginine (asymmetric dimethylarginine: ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOS). Plasma ADMA concentrations have been reported to increase in connection with diseases associated with an impaired endothelial L-arginine/NO pathway. In this study, we investigated the metabolism of ADMA in circulating blood cell populations to elucidate the regulatory mechanism of elevation of plasma ADMA, a novel risk factor for cardiovascular disease. We found by RT-PCR and Western blot analyses that protein arginine methyltransferase (PRMT)1 and dimethylarginine dimethylaminohydrolase (DDAH)-1, responsible for the biosynthesis and degradation of ADMA respectively, are expressed in erythrocytes (ECs), leukocytes, and platelets. We also identified a major ADMA-containing protein in ECs as catalase, confirmed by GST-pull down assay to bind to PRMT1 in vitro. This is the first report that the ADMA-metabolizing system, including the arginine methylation of proteins and the breakdown of free ADMA, occurs in circulating blood cell-populations, and that catalase in ECs might be a potential protein targeted by PRMT1.

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  • Gastrointestinal digestion and absorption of Pen j 1, a major allergen from Kuruma prawn, Penaeus japonicus. 査読 国際誌

    Ayumi Kunimoto, Miyuki Yokoro, Kaeko Murota, Rintaro Yamanishi, Toshiko Suzuki-Yamamoto, Makiko Suzuki, Chikao Yutani, Shinobu Doi, Miki Hiemori, Hiromi Yamashita, Yoshitaka Takahashi, Hideaki Tsuji, Masumi Kimoto

    Bioscience, biotechnology, and biochemistry   75 ( 7 )   1249 - 58   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tropomyosin had been identified as a major allergen in shrimp. The digestion and absorption of tropomyosin (Pen j 1) from kuruma prawn were investigated by ex vivo, in vitro, and in vivo techniques in order to elucidate the relationship between the allergenicity of the allergen and its gastrointestinal behavior. Pen j 1 transported the Caco-2 monolayer in a dose-dependent manner, and also enhanced the permeability of lucifer yellow, a marker of paracellular transportation, at high concentrations of the allergen. Studies with everted sacs revealed that Pen j 1 was rapidly degraded to small peptides (MW<3.5 kDa) and amino acids by intestinal proteases and absorbed from enterocytes. Furthermore, Pen j 1 orally administered to rats tended to remain in the stomach rather than in the small intestine, after which the allergen moved to the epithelial cells. These observations suggest that Pen j 1 may be absorbed via the gastric mucosa prior to its digestion in the intestines.

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▼全件表示

書籍等出版物

  • 人間の許容限界事典

    山崎, 昌廣, 坂本, 和義, 関, 邦( 担当: 分担執筆 ,  範囲: 第X章 栄養「5.アルコール」pp. 725-730)

    朝倉書店  2015年7月  ( ISBN:9784254102734

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    総ページ数:xvi, 1014p   記述言語:日本語

    CiNii Books

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MISC

  • 維持血液透析患者の栄養調査で用いる推定式は食事摂取実量と一致するか 陰膳法による食事実態調査から

    小池 清美, 横路 三有紀, 永松 あゆ, 奥田 誠也, 深水 圭

    日本透析医会雑誌   31 ( 1 )   181 - 187   2016年4月

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    記述言語:日本語   出版者・発行元:(公社)日本透析医会  

    目的:維持血液透析患者において、推定塩分摂取量やnormalized protein catabolic rate(nPCR)と摂取実量の相関を検討した。方法と結果:維持血液透析患者において陰膳法を用いて食事調査を行い、カロリーアンサー(ジョイ・ワールド・パシィフィック社)を用い食品カロリー測定を行った。推定塩分摂取量と塩分摂取実量、nPCRと蛋白摂取実量の相関を検討した。患者数は19名、評価数は23であった。推定塩分摂取量は摂取実量と有意な相関を認めなかった(p=0.23)。そこで、ステップワイズ法により新規塩分摂取量推定式を算出した。蛋白については、nPCRと蛋白摂取実量は相関傾向を認め(p=0.089)、蛋白摂取実量(g/kg/d)=0.483+0.436×nPCRで表された。結語:慣習の推定塩分摂取量は塩分摂取実量と相関しなかった。陰膳法から算出した新規推定塩分摂取量(g/day)=-34.3546-0.0538×年齢+0.270×透析前Na+0.0783×透析前体重+1.312×透析間体重増加、で示された。nPCRと蛋白摂取実量は相関傾向を認めたが、蛋白摂取実量に比べ高値を示していた。蛋白摂取実量(g/kg/d)=0.483+0.436×nPCRで表された。いずれも、簡便であり日常診療で汎用しやすいと考える。(著者抄録)

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  • (特集 腎とバイオマーカー)

    上田 誠二, 横路 三有紀, 奥田 誠也

    腎臓内科・泌尿器科   1 ( 3 )   268 - 273   2015年3月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

    CiNii Article

    CiNii Books

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    その他リンク: https://search.jamas.or.jp/link/ui/2015206585

  • 酸化ストレスと腎臓病 (第5土曜特集 腎臓病のすべて) -- (腎臓病研究の進歩と未来の治療)

    中山 陽介, 横路 三有紀, 上田 誠二

    医学のあゆみ   249 ( 9 )   991 - 996   2014年5月

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    記述言語:日本語   出版者・発行元:医歯薬出版(株)  

    生体内で酸素を利用する過程において種々の活性酵素種(ROS)が産生される。しかし、防御機構を凌駕するROS産生が起こる場合は"酸化ストレス"となり、腎障害進展に大きく関与する。生体内においてこの酸化ストレスと関連し、臓器障害を惹起する物質として、非対称性ジメチルアルギニン(ADMA)と終末糖化産物(AGEs)がある。慢性腎臓病(CKD)や糖尿病ではADMAやAGEsが蓄積してROSを亢進する結果、腎障害が進展する。Keap1-Nrf2系はこういったさまざまなタイプのストレス対応システムであることから、腎障害に対してKeap1-Nrf2系を活性化する治療戦略が検討されている。今後、酸化ストレスをターゲットとした治療の有用性が確立されることが期待される。(著者抄録)

    CiNii Article

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    その他リンク: https://search.jamas.or.jp/link/ui/2014230002

  • 尿毒症物質と心疾患 (特集 心腎貧血連関)

    横路 三有紀, 上田 誠二, 中山 陽介

    74 ( 5 )   489 - 494   2013年11月

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  • State of the ART 血管内皮障害因子ADMAと高血圧

    横路 三有紀, 上田 誠二, 奥田 誠也

    臨床高血圧   19 ( 2 )   92 - 101   2013年7月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • グァバ葉抽出物に含まれる白血球型12-リポキシゲナーゼ阻害物質の探索

    川上 祐生, 森中 朋子, 細川 朋子, 小林 弘和, 吉岡 晶子, 山本 登志子, 横路 三有紀, 木本 眞順美, 辻 英明, 山下 広美, 土井 忍, 由谷 親夫, 加藤 里奈, 板部 洋之, 金田 輝之, 高橋 吉孝

    脂質生化学研究   52   209 - 211   2010年5月

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▼全件表示

産業財産権

  • NOおよびNO-pathway刺激によるエリスロポエチン受容体を標的とした腎性貧血に対する新規治療薬

    中山 陽介, 横路 三有紀, 深水 圭, 山岸 昌一

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    出願人:学校法人 久留米大学

    出願番号:特願2017-014132  出願日:2017年1月30日

    公開番号:特開2018-123068  公開日:2018年8月9日

    特許番号/登録番号:特許第6949350号  登録日:2021年9月27日 

    J-GLOBAL

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  • 腎性貧血のバイオマーカーとしての赤血球ADMAの使用

    横路 三有紀, 中山 陽介, 三枝 大輔, 上田 誠二, 木本 眞順美, 阿部 高明, 奥田 誠也

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    出願人:学校法人 久留米大学

    出願番号:特願2015-242083  出願日:2015年12月11日

    公開番号:特開2016-114606  公開日:2016年6月23日

    特許番号/登録番号:特許第6782405号  登録日:2020年10月22日 

    J-GLOBAL

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受賞

  • ダイバーシティ推進センター女性研究者賞

    2019年   武庫川女子大学   血管内皮機能に着目した新しいサルコぺニア予防に対する栄養教育戦略の創出

    横路三有紀

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  • 若手優秀発表賞および奨励賞

    2014年12月   Kidney Summit 2014   腎性貧血に対する非対称性ジメチルアルギニン(ADMA)代謝系の関与

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共同研究・競争的資金等の研究

  • 子育て世代における子どもの食への関わりにおける食リテラシーとワーク・ライフ・バランスの役割の解明

    2024年04月 - 2025年03月

    三菱UFJ信託銀行株式会社  公益信託家政学研究助成 

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    担当区分:研究代表者 

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  • 子ども食堂の交流拠点機能研究:漢字・食育融合教材の開発と実践による教育効果の評価

    研究課題/領域番号:21K02343  2021年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    設樂 馨, 吉井 美奈子, 横路 三有紀

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    子ども食堂は地縁による既存のつながり(自治会や寺の檀家、PTAなど)から誕生したり、子ども食堂の誕生によって地縁が復活したりすることがある。研究では、子ども食堂を交流拠点とし、小学生と大学生の食生活向上と漢字学習の機会となるよう、4年計画で次の3つに取り組む。2021年度は1年目である。なお、大学生は専門の異なる3学部の共同作業を通し、多職種交流の観点から、大学生間のピアエデュケーションによる知の循環、相乗的に持続する大学生間の教育も期待している。
    ①小学生と大学生の食育プログラム開発:小学生と大学生へのアンケート形式の食育調査を実施するも、小学生についてはコロナ禍の影響で想定外に少ない調査対象者数となった。継続して調査を蓄積し、食育プログラムの開発や改良の資料とする。
    ②食育を題材とする漢字教材開発:3学部の学生が交流・協同することで、それぞれの専門性を生かし(例えば、漢字ミュージアム見学やカードゲーム参加)、公式な学習に縛られないノンフォーマルな食育・漢字学習機会を検討し、食材を集めて調理し献立を考える、コミュニケーションゲームの要素を盛り込んだカードゲームを試作した。
    ③子ども食堂の交流拠点機能の検証:子ども食堂で3学部の大学生と子ども、子ども食堂に集う地域の人々によるクリスマス会を企画・実施、②のカードゲームや漢字缶バッジ作り、手作りクリスマスカード交換を楽しんだ。3学部の学生は、食物栄養学・教育学・日本語学を専攻する。大学生の感想には学部を限定せず、小学生の社会参加への気づきや、大学生自身がボランティアとして社会参加する意義が認められる。また、子ども食堂という場で学年を超えた絆があることに対する驚き、運営側が子どもに期待する姿勢についての共感も見られた。
    今後は交流機会の活性化と、交流拠点機能としての客観的証拠を課題としたい。

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  • Apop-1を標的とした脂肪肝や肝癌の発症機構とミトコンドリア機能との関係の解明

    研究課題/領域番号:21H03369  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    福尾 惠介, 安田 修, 西川 浩樹, 榎本 平之, 大谷 直子, 横路 三有紀

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    配分額:17160000円 ( 直接経費:13200000円 、 間接経費:3960000円 )

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  • 血管内皮機能に着目した新しいサルコペニア予防に対する栄養教育戦略の創出

    研究課題/領域番号:20K19730  2020年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    横路 三有紀

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本年度は過去の身体測定データを用いて、非対称性ジメチルアルギニン(ADMA)とサルコペニアの関連を解析した。その結果、サルコペニア群は、非サルコペニア群に比し有意に血漿ADMA濃度が高値を示した(P=0.038)。ロジスティック回帰分析の結果、サルコペニアに対する血漿ADMA高値の粗オッズ比は4.57(95%CI 1.82-11.47)であった。年齢、BMI、喫煙、飲酒歴、高血圧薬、脂質異常症薬、低栄養、腎機能で調整したオッズ比は4.45(95%CI 1.13-14.96)であった。さらに高ADMA群は低ADMA群よりも、2年後のSMIの減少量が有意に大きいことが示された(P=0.032)。以上より、高齢者においてADMAはサルコペニアと関連することが示唆され、血漿ADMA高値はサルコペニアを増悪させる可能性が示された。
    次に、食品多様性スコアを求める食品群別摂取頻度と血漿ADMA濃度の関連を検討した。その結果、肉類の摂取頻度が多い人ほど血漿ADMA濃度が低い関連が認められた。さらに検証が必要であるが、食生活への介入によって血管内皮機能が維持できる可能性が示唆された。
    また、サルコペニア・フレイルと食生活の関連の解析を進めるために、地域で実施した横断調査のデータ(n=2,746)を用いて、フレイルと食品多様性の関連を解析した。その結果、高齢者の食品多様性には独居・同居の差に性差が影響することが明らかとなった。すなわち、独居の高齢男性は同居の高齢男性に比し、有意に食品多様性スコアが低値を示したが(P<0.001)、独居の高齢女性と同居の高齢女性には食品多様性スコアの差は認められなかった。一方、男女ともにフレイルと食品多様性スコアの関連が同居に比し、独居の方が強い関連性が認められた。この結果から、独居高齢者にフォーカスした食生活教育の必要性が示唆された。

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  • ADMAを標的とした腎性貧血治療薬の探索

    2018年07月 - 2020年03月

    国立研究開発法人日本医療研究開発機構  革新的医療品創出のための実用化支援の創薬ブースター 

    中山陽介, 横路三有紀

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    担当区分:研究分担者 

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  • 新たな非対称性ジメチルアルギニン分解活性測定法の開発と機能性食品成分探索への展開

    研究課題/領域番号:17K18275  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    横路 三有紀

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    非対称性ジメチルアルギニン(ADMA)の過剰な増加は血管内皮障害の一因となる。本研究は、体内ADMA濃度を低下させる効果を有する機能性食品成分の探索に向けて、ADMA分解活性を評価するスクリーニング系を確立を目指すものである。まず、ADMA分解酵素の活性を評価するバイオセンサーの作成を試みた。研究期間内に完遂できなかったため、今後も作成を継続する。別のアプローチとして我々が独自に樹立したADMA-ELISA系を簡便化し、スクリーニング系として実用性を高め、培養細胞を用いたADMA低減効果の評価を行った。今後、本法を用いてADMA低減効果を有する機能食品成分の探索を進めていく。

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  • 新規ミトコンドリア蛋白質Apopと加齢による腎機能障害に関する基礎的・疫学的研究

    研究課題/領域番号:16K01844  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    福尾 惠介, 安田 修, 横路 三有紀

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    本研究はミトコンドリア機能に関わるApoptogenic protein-1(Apop-1)が加齢による老化関連ストレスや腎機能低下に与える影響を明らかにすることを目的とした。老化の原因となる慢性炎症を惹起させるため、Apop-1欠損マウス(Apop-1KO)に高脂肪食を6か月間与えた結果、予想に反して腎機能に有意な変化は認められなかった一方、野生型マウスと比較して肝臓への脂肪蓄積が顕著に低下した。この機序として、Apop-1KOではエネルギー代謝関連遺伝子PGC1αの肝臓における発現を制御し、エネルギー過剰産生を抑制することにより、脂肪肝を防いだ可能性が示唆された。

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  • NO-ADMA系の破綻によるエリスロポエチン抵抗性貧血発症機序の解明と治療戦略

    2016年04月 - 2017年03月

    武庫川女子大学  科学研究費補助金学内奨励金 

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    担当区分:研究代表者 

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  • 常温ガラス化保存技術開発のための基礎的研究

    研究課題/領域番号:26640140  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    吉田 徹, 櫻井 実, 阪上 綾, 矢野 めぐむ, 横路 三有紀, 福尾 惠介

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    本研究は、アルテミアなどの極限環境生物で保存されている特徴的なクリプトビオシスに注目し、生物資源保存のための新規保存技術の開発を目指して行われた。まず試験管レベルのゲルモデル系によるシミュレーションを行って、常温ガラス化のための適正条件を検索した。具体的には、アガロースゲルにトレハロース等の各種糖類を添加したゲルの水分含量と糖類別のガラス化傾向の対応関係を明らかにした。さらに、うずら卵ゲルに対して、トレハロースと乾燥耐性をもったLEAペプチドを添加したところ、LEAペプチド濃度に応じたガラス化促進作用が得られた。

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  • 慢性腎不全患者における腎性貧血に対する赤血球ADMA代謝系の影響の解明

    研究課題/領域番号:25931003  2013年04月 - 2014年03月

    日本学術振興会  科学研究費助成事業 奨励研究  奨励研究

    横路 三有紀

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    配分額:600000円 ( 直接経費:600000円 )

    本研究では、心腎貧血症候群発症機序に赤血球非対称性ジメチルアルギニン(ADMA)代謝系が関わっているという仮説のもと、慢性腎臓病患者における赤血球中ADMA濃度および赤血球ADMA代謝動態を精査し、腎不全の進行や心血管疾患の合併リスクとの関係性を明らかにすることを目的とした。本年度は、保存期慢性腎不全(CKD)患者の血液を採取し、①腎性貧血に伴う赤血球減少がADMAの蓄積に与える影響、②CKD患者における赤血球のADMA取り込み代謝能の異常の有無の精査、赤血球中ADMAが全身のADMA蓄積の新たなバイオマーカーとなり得るか、③エリスロポエチン(EPO)投与が如何にこの系に作用するかの三点について検討することを計画した。結果、鉄剤非投与群においてCKD患者の赤血球ADMA濃度と赤血球数には有意な負の相関がみられ、赤血球ADMA濃度と腎性貧血の関係性があることが明らかとなった。さらに、赤血球ADMA濃度は血清鉄とも逆相関を示したことから、CKD患者において鉄代謝の不均衡を介して腎性貧血を増悪させる因子として知られるヘプシジンの血中濃度との関連性を検討したところ、赤血球ADMA濃度と血中ヘプシジン濃度には有意な正相関がみられた。したがって、赤血球ADMA濃度は鉄代謝と関連して腎性貧血の一因となり、EPO抵抗性を惹起している可能性も示唆された。また高赤血球ADMA群は、血中NT-proBNPが有意に高く、心腎貧血症候群を媒介する一因である可能性を示す結果が得られた。CKD患者赤血球のADMA取り込み能は、検討中であり、③のEPO投与の影響についても患者のエントリーに時間を要したため現在検討を進めながらエントリーを増やしている。得られた結果は、腎性貧血に対して赤血球ADMA低下という新たな治療標的を提示した。今後のさらなる検討によりEPO抵抗性を惹起しにくいより効果的な腎性貧血治療を可能にする創薬に繋がると考える。

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  • 心血管疾患のリスクファクター、ADMAの代謝機構の解明と病態生理的役割

    研究課題/領域番号:20590582  2008年 - 2010年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    木本 真順美, 脇野 修, 山西 倫太郎, 山下 広美, 横路 三有紀

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    心血管疾患のリスクファクターである非対称性ジメチルアルギニン(ADMA)の血中レベルを調節する機構を解明するために,血球細胞における本アミノ酸の代謝系について精査した.赤血球において,ADMAの代謝系が活発に働いていること,ならびに産生と分解に関わる酵素としてPRMT1およびDDAH1の存在を立証し,それらの部分精製品の酵素学的性質を明らかにした.また,ADMAを含むタンパク質としてカタラーゼを同定し,PRMT1 のターゲットタンパク質であることを立証した.このように,赤血球におけるADMAの全体像を明らかにしたのは本研究が初めてである.

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