研究者詳細 - 益崎　裕章

論文 - 益崎　裕章

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A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL).

Tanaka Y, Tanaka R, Imaizumi N, Mizuguchi M, Takahashi Y, Hayashi M, Miyagi T, Uchihara J, Ohshiro K, Masuzaki H, Fukushima T

Frontiers in immunology ( Frontiers in Immunology ) 13 921606 2022年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection.

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公益社団法人日本麻酔科学会第68回学術集会講演特集号招待講演人生100年時代の健康脳を創る　脳科学・分子栄養学からの学び

益崎裕章, 岡本士毅

麻酔 ( 克誠堂出版(株) ) 70 ( 13 ) S138 - S148 2021年11月

掲載種別: 研究論文（学術雑誌）

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Spontaneous pulmonary emphysema in mice lacking all three nitric oxide synthase isoforms.

Kato K, Tsutsui M, Noguchi S, Iha Y, Naito K, Ogoshi T, Nishida C, Tahara M, Yamashita H, Wang KY, Toyohira Y, Yanagihara N, Masuzaki H, Shimokawa H, Tanimoto A, Yatera K

Scientific reports ( Scientific Reports ) 11 ( 1 ) 22088 - 22088 2021年11月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

The roles of endogenous nitric oxide (NO) derived from the entire NO synthases (NOSs) system have yet to be fully elucidated. We addressed this issue in mice in which all three NOS isoforms were deleted. Under basal conditions, the triple n/i/eNOSs-/- mice displayed significantly longer mean alveolar linear intercept length, increased alveolar destructive index, reduced lung elastic fiber content, lower lung field computed tomographic value, and greater end-expiratory lung volume as compared with wild-type (WT) mice. None of single NOS-/- or double NOSs-/- genotypes showed such features. These findings were observed in the triple n/i/eNOSs-/- mice as early as 4 weeks after birth. Cyclopaedic and quantitative comparisons of mRNA expression levels between the lungs of WT and triple n/i/eNOSs-/- mice by cap analysis of gene expression (CAGE) revealed that mRNA expression levels of three Wnt ligands and ten Wnt/β-catenin signaling components were significantly reduced in the lungs of triple n/i/eNOSs-/- mice. These results provide the first direct evidence that complete disruption of all three NOS genes results in spontaneous pulmonary emphysema in juvenile mice in vivo possibly through down-regulation of the Wnt/β-catenin signaling pathway, demonstrating a novel preventive role of the endogenous NO/NOS system in the occurrence of pulmonary emphysema.

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特集糖尿病性腎臓病(DKD) DKDの治療　AI・IoT活用による肥満症予防とDKD　沖縄県久米島デジタルヘルスプロジェクトの試み

益崎裕章, 上間次己, 仲村武裕, 山城清人, 岡本士毅

腎と透析 ( (株)東京医学社 ) 91 ( 4 ) 737 - 742 2021年10月

掲載種別: 研究論文（学術雑誌）

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Full-length HLA sequencing in adult T cell leukemia-lymphoma uncovers multiple gene alterations.

Tamaki K, Morishima S, Suzuki S, Shigenari A, Nomura I, Yokota Y, Morichika K, Nishi Y, Nakachi S, Okamoto S, Fukushima T, Shiina T, Masuzaki H

Leukemia ( Leukemia ) 35 ( 10 ) 2998 - 3001 2021年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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【糖尿病性腎臓病(DKD)】DKDの治療 AI・IoT活用による肥満症予防とDKD 沖縄県久米島デジタルヘルスプロジェクトの試み

益崎裕章, 上間次己, 仲村武裕, 山城清人, 岡本士毅

腎と透析 ( (株)東京医学社 ) 91 ( 4 ) 737 - 742 2021年10月

掲載種別: 研究論文（その他学術会議資料等）

Novel strategies for glycaemic control and preventing diabetic complications applying the clustering-based classification of adult-onset diabetes mellitus: A perspective.

Tanabe H, Masuzaki H, Shimabukuro M

Diabetes research and clinical practice ( Diabetes Research and Clinical Practice ) 180 109067 - 109067 2021年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Diabetes mellitus results from an interplay between insulin resistance and β-cell dysfunction. Since their relative contributions to its pathogenesis are difficult to quantify, therapeutic strategies for glycaemic control are determined primarily based on two limited metrics: plasma glucose and haemoglobin A1c. Recent attempts have been made to subclassify diabetes mellitus to better predict its associated pathology and plan appropriate therapeutic strategies. These classifications are based on data-driven cluster analysis using autoimmunity, age, obesity (metabolically unhealthy and healthy phenotypes), insulin secretory capacity and resistance, and ethnicity. This review addresses potential therapeutic strategies for the cluster-based classifications of adult-onset diabetes mellitus to achieve better glycaemic control and prevent or at least delay the concomitant complications.

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【高齢者肥満症と循環器疾患】運動と食事に関する分子医学

益崎裕章, 上間次己, 岡本士毅

循環器内科 ( (有)科学評論社 ) 90 ( 3 ) 270 - 276 2021年09月

掲載種別: 研究論文（その他学術会議資料等）

加齢に伴う摂食低下のメカニズム

益崎裕章, 根本雄飛, 照屋太輝, 島袋康貴, 上間次己, 仲地佐和子, 島袋充生, 岡本士毅

老年内科 ( (有)科学評論社 ) 4 ( 3 ) 276 - 281 2021年09月

掲載種別: 研究論文（その他学術会議資料等）

日本人の肥満2型糖尿病患者に対する減量・代謝改善手術に関するコンセンサスステートメント

佐々木章, 内藤剛, 横手幸太郎, 稲垣暢也, 益崎裕章, 綿田裕孝, 小川渉, 下村伊一郎, 山内敏正, 石垣泰, 笠間和典, 野崎剛弘, 島袋充生, 藤倉純二, 宮塚健, 庄嶋伸浩, 西澤均, 廣田勇士, 卯木智, 太田正之, 岡住慎一, 吉川絵梨, 小山英則, 齋木厚人, 関洋介, 辻野元祥, 林果林, 山口崇, 龍野一郎, 植木浩二郎, 門脇孝, 日本肥満症治療学会, 日本糖尿病学会, 日本肥満学会, 日本人の肥満2型糖尿病患者に対する減量・代謝改善手術の適応基準に関する3学会合同委員会

肥満研究 ( (一社)日本肥満学会 ) 27 ( 2 ) 1 - 74 2021年08月 [ 査読有り ]

掲載種別: 研究論文（その他学術会議資料等）

日本人の肥満2型糖尿病患者に対する減量・代謝改善手術に関するコンセンサスステートメント

肥満研究 ( (一社)日本肥満学会 ) 27 ( 2 ) 1 - 74 2021年08月 [ 査読有り ]

掲載種別: 研究論文（その他学術会議資料等）

書評 -石井均　編-誰も教えてくれなかった糖尿病患者の感染症診療-感染症合併例はココに気をつけて!

益崎裕章

medicina ( 株式会社医学書院 ) 58 ( 8 ) 1185 - 1185 2021年07月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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High FIB4 index is an independent risk factor of diabetic kidney disease in type 2 diabetes.

Saito H, Tanabe H, Kudo A, Machii N, Higa M, Yamaguchi S, Maimaituxun G, Abe K, Takahashi A, Tanaka K, Asahi K, Masuzaki H, Ohira H, Kazama JJ, Shimabukuro M

Scientific reports 11 ( 1 ) 11753 - 11753 2021年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) may be linked to development of chronic kidney diseases (CKD). The FIB4 index, a noninvasive liver fibrosis score, has been reported to predict CKD in non-diabetic patients, but there are no reports yet in diabetic cases. Therefore, we evaluated the prognostic impact of FIB4 index on the risk of developing diabetic kidney disease (DKD) in Japanese patients with type 2 diabetes in a retrospective cohort study. We assessed patients with type 2 diabetes with an eGFR ≥ 60 mL/min/1.73 m2 and without dipstick positive proteinuria (≥ 1 +) at their first visit to our department. Participants were divided into two groups based on the FIB4 index at their first visit: FIB4 index > 1.3 and FIB4 index ≤ 1.3. The primary endpoint was defined as a decrease in eGFR < 60 mL/min/1.73 m2 or the onset of proteinuria during the course of treatment. The average age of all 584 type 2 diabetic participants (360 [61.6%] men) was 55 ± 11 years. There were 187 patients in the FIB4 index group > 1.3 (32.0%) and the median observation period was 6.0 (3.8-11.0) years. Kaplan-Meier survival analysis indicated that the risks of developing DKD, eGFR < 60 and proteinuria were all higher in FIB4 index > 1.3 patients than in FIB4 ≤ 1.3 patients. In the Cox regression analysis, an FIB4 index > 1.3 was a significant predictor for onset of DKD (HR 1.54, 95% CI 1.15-2.08) and proteinuria (HR 1.55, 95% CI 1.08-2.23), but not for an eGFR < 60 (HR 1.14, 95% CI 0.79-1.99). To the best of our knowledge, this is the first study to demonstrate that an FIB4 index > 1.3 has a prognostic impact on the development of CKD and proteinuria in type 2 diabetic patients. This warrants further investigation of the prognostic impact of the development of DKD or proteinuria.

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The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma.

Morichika K, Karube K, Sakihama S, Watanabe R, Kawaki M, Nishi Y, Nakachi S, Okamoto S, Takahara T, Satou A, Shimada S, Shimada K, Tsuzuki T, Fukushima T, Morishima S, Masuzaki H

The American journal of surgical pathology ( American Journal of Surgical Pathology ) 45 ( 6 ) 832 - 840 2021年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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沖縄県久米島デジタルヘルスプロジェクト IoTとAIによる体重減少・HbA1c改善効果

仲村武裕, 山城清人, 上原盛幸, 上間次己, 宮里実, 中村幸志, 松下正之, 石田肇, 益崎裕章

糖尿病 ( (一社)日本糖尿病学会 ) 64 ( Suppl.1 ) I - 4 2021年05月

掲載種別: 研究論文（その他学術会議資料等）

Effect of a mobile digital intervention to enhance physical activity in individuals with metabolic disorders on voiding patterns measured by 24-h voided volume monitoring system: Kumejima Digital Health Project (KDHP).

Miyazato M, Ashikari A, Nakamura K, Nakamura T, Yamashiro K, Uema T, Uehara M, Masuzaki H, Saito S, Maeda S, Ishida H, Matsushita M

International urology and nephrology ( International Urology and Nephrology ) 53 ( 8 ) 1497 - 1505 2021年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

PURPOSE: To evaluate the effect of a mobile digital intervention on voiding patterns, we performed 24-h voided volume monitoring in individuals with metabolic disorders. METHODS: Participants with metabolic disorders were grouped into either the intervention group (n = 17), who had access to a smartphone app (CARADA), or the non-intervention group (n = 11), who did not. Urine monitoring was conducted for 24 h using a novel digital self-health monitoring system for urine excretion (s-HMSU). Body weight, abdominal circumference, blood pressure, and biomarkers were measured. RESULTS: Physical findings and blood test results at baseline and 6 months indicated no significant between-group differences. Night-time frequency did not change between baseline and 6 months in the intervention group but significantly worsened at 6 months in the non-intervention group, as compared to baseline (1.0 ± 0.7 vs. 1.5 ± 0.5, p < 0.05). The change in night-time frequency over 6 months did not differ between the intervention and non-intervention groups. Furthermore, the change in hours of undisturbed sleep over 6 months did not differ between the two groups. However, compared with baseline, nocturnal polyuria index tended to worsen at 6 months in the non-intervention group. CONCLUSION: Our study results suggest that mobile digital intervention might be useful for behavioral therapy to improve night-time frequency and urine production and that s-HMSU might be beneficial for confirming the prevention of progress in individuals with metabolic disorders, which can aid in modifying lifestyle.