論文 - 益崎　裕章

Genetic profile of adult T-cell leukemia/lymphoma in Okinawa: Association with prognosis, ethnicity, and HTLV-1 strains.

Sakihama S, Morichika K, Saito R, Miyara M, Miyagi T, Hayashi M, Uchihara J, Tomoyose T, Ohshiro K, Nakayama S, Nakachi S, Morishima S, Sakai K, Nishio K, Masuzaki H, Fukushima T, Karube K

Cancer science ( Cancer Science )  112 ( 3 ) 1300 - 1309   2021年03月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

Genetic alterations in adult T-cell leukemia/lymphoma (ATLL), a T-cell malignancy associated with HTLV-1, and their clinical impacts, especially from the perspective of viral strains, are not fully elucidated. We employed targeted next-generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV-1 tax subgroup-A (HTLV-1-taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV-1-taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF-ĸB (eg, PRKCB, PLCG1, and CARD11) and T-cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome-associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV-1-taxB, HTLV-1-taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.

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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 ( 3 ) 259 - 259   2021年03月

掲載種別: 研究論文（その他学術会議資料等）

Extra-virgin olive oil and the gut-brain axis: influence on gut microbiota, mucosal immunity, and cardiometabolic and cognitive health.

Millman JF, Okamoto S, Teruya T, Uema T, Ikematsu S, Shimabukuro M, Masuzaki H

Nutrition reviews ( Oxford University Press (OUP) )  79 ( 12 ) 1362 - 1374   2021年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

<jats:title>Abstract</jats:title> <jats:p>Extra-virgin olive oil (EVOO), a popular functional food and major source of fat in the Mediterranean diet, possesses a variety of healthful components, including monounsaturated fatty acids and bioactive phenolic compounds that, individually and collectively, exert beneficial effects on cardiometabolic markers of health and act as neuroprotective agents through their anti-inflammatory and antioxidant activities. The gut microbiota and health of the intestinal environment are now considered important factors in the development of obesity, metabolic disease, and even certain neurodegenerative conditions via the gut-brain axis. Recently, data are emerging which demonstrate that the health-promoting benefits of EVOO may also extend to the gut microbiota. In this review, we aimed to examine findings from recent studies regarding the impact of EVOO on gut microbiota and intestinal health and explore how modulations in composition of gut microbiota, production of microbially produced products, and activity and functioning of the mucosal immune system may lead to favorable outcomes in cardiovascular, metabolic, and cognitive health.</jats:p>

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Retrospective exploratory analyses on gender differences in determinants for incidence and progression of diabetic retinopathy in Japanese patients with type 2 diabetes mellitus.

Nakayama Y, Yamaguchi S, Shinzato Y, Okamoto S, Millman JF, Yamashiro K, Takemoto N, Uema T, Arakaki K, Higa M, Koizumi H, Shimabukuro M, Masuzaki H

Endocrine journal ( 一般社団法人 日本内分泌学会 )  68 ( 6 ) 655 - 669   2021年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

<p>Gender differences in risks for macrovascular complications in type 2 diabetes mellitus (T2DM) have been well established. However, the impact of gender differences on diabetic retinopathy (DR) has not been fully elucidated. We therefore retrospectively explored gender-specific determinants for DR in patients with T2DM in a small sized Japanese cohort in Okinawa. There were 214 patients who were diagnosed as no DR (<i>n</i> = 142) and non-proliferative DR (<i>n</i> = 72) in 2009. During the follow-up of median 7 years, 41/142 of incidence, 26/72 of progression, and 67/214 of incidence and progression were observed, respectively. DR was assessed using the modified international clinical DR severity scales. The risks for incidence, progression as well as incidence and progression of DR were comparable between men and women, respectively. Cox proportional hazard models in multivariate analyses demonstrated that the only common determinant in both men and women for DR was the duration of T2DM. Regarding gender-specific determinants, lower level of serum albumin in men as well as higher HbA1c, lower level of estimated glomerular filtration rate, and lower level of serum uric acid in women were extracted, respectively. Although precise mechanisms for such gender-specific determinants of DR still remain unsolved, the present study would highlight a couple of factors associated with gender-specific determinants for DR in a limited numbers of Japanese cohort. Prospective observational studies on gender-specific determinants of DR in a large scale cohort are warranted to further clarify underlying mechanisms.</p>

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Novel STAR gene variant in a patient with classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency.

Higa M, Zaha A, Takushi A, Morishima N, Majikina T, Touma T, Shimabukuro M, Masuzaki H, Honda M, Hasegawa T

Human genome variation ( Human Genome Variation )  8 ( 1 ) 6   2021年02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と機械学習を用いた体重減少と糖尿病予防効果の検討

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

日本遠隔医療学会学術大会プログラム・抄録集 ( (一社)日本遠隔医療学会 )  24回   175 - 175   2021年02月

掲載種別: 研究論文（その他学術会議資料等）

Clinicopathological features of adult T-cell leukemia/lymphoma with HTLV-1-infected Hodgkin and Reed-Sternberg-like cells.

Karube K, Takatori M, Sakihama S, Tsuruta Y, Miyagi T, Morichika K, Kitamura S, Nakada N, Hayashi M, Tomori S, Nakazato I, Ohshiro K, Imaizumi N, Kikuti YY, Nakamura N, Morishima S, Masuzaki H, Fukushima T

Blood advances ( Blood Advances )  5 ( 1 ) 198 - 206   2021年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

Hodgkin and Reed-Sternberg (HRS) cells, a hallmark of classic Hodgkin lymphoma (CHL), are occasionally detected in non-Hodgkin lymphomas, including adult T-cell leukemia/lymphoma (ATLL), a lymphoid neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). HRS-like cells associated with ATLL have been described to be of B-cell lineage and infected with Epstein-Barr virus (EBV), not HTLV-1. We herein describe clinicopathological findings in 8 cases (4 males and 4 females; median age, 73 years [range, 55-81 years]) of ATLL with HTLV-1-infected HRS-like cells identified by ultrasensitive RNA in situ hybridization for HTLV-1 basic leucine zipper factor (HBZ-ISH), a specific viral transcript of HTLV-1. All patients showed nodal or mediastinal lesions, and 5 of the 8 patients were at an advanced disease stage. HRS-like cells were positive for CD30, CD15, MUM1, CD25, and HBZ-ISH and negative for B-cell markers, including PAX5, pan-T-cell antigens, and EBV in all cases. Five cases were positive for CD4, and 6 cases were positive for fascin. HBZ was identified in both HRS-like cells and surrounding lymphoid cells in 1 case with an aggressive clinical course and only HRS-like cells in 7 cases, most of whom showed a clinical response regardless of the chemotherapeutic regimen. Even though the definitive lineage typing of the HTLV-1-infected HRS cells is one of the limitations of this study in the absence of single-cell microdissection for polymerase chain reaction analysis, the combination of diffuse HBZ-ISH positivity and negativity for PAX5 and EBV deemed these cases distinct from CHL arising in HTLV-1 carriers.

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Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13.

Suzumori N, Sekizawa A, Takeda E, Samura O, Sasaki A, Akaishi R, Wada S, Hamanoue H, Hirahara F, Sawai H, Nakamura H, Yamada T, Miura K, Masuzaki H, Nakayama S, Kamei Y, Namba A, Murotsuki J, Yamaguchi M, Tairaku S, Maeda K, Kaji T, Okamoto Y, Endo M, Ogawa M, Kasai Y, Ichizuka K, Yamada N, Ida A, Miharu N, Kawaguchi S, Hasuo Y, Okazaki T, Ichikawa M, Izumi S, Kuno N, Yotsumoto J, Nishiyama M, Shirato N, Hirose T, Sago H

European journal of obstetrics, gynecology, and reproductive biology   256   75 - 81   2021年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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Risk factors for cerebral palsy in neonates due to placental abruption.

Ichizuka K, Toyokawa S, Ikenoue T, Satoh S, Hasegawa J, Ikeda T, Tamiya N, Nakai A, Fujimori K, Maeda T, Kanayama N, Masuzaki H, Iwashita M, Suzuki H, Takeda S

The journal of obstetrics and gynaecology research   47 ( 1 ) 159 - 166   2021年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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Regional Variations of Insulin Secretion and Insulin Sensitivity in Japanese Participants With Normal Glucose Tolerance.

Watanabe K, Higa M, Hasegawa Y, Kudo A, Allsopp RC, Willcox BJ, Willcox DC, Sata M, Masuzaki H, Shimabukuro M

Frontiers in nutrition ( Frontiers in Nutrition )  8   632422 - 632422   2021年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

Purpose: Regional differences in dietary patterns in Asian countries might affect the balance of insulin response and sensitivity. However, this notion is yet to be validated. To clarify the regional differences in the insulin response and sensitivity and their relationship to nutrients, we compared the insulin secretory response during an oral glucose tolerance test in Japanese participants. Methods: This observational retrospective cohort study analyzed the data from participants with normal glucose tolerance (NGT) from four distinct areas of Japan with regard to the food environment: Fukushima, Nagano, Tokushima, and Okinawa based on data available in the Japanese National Health Insurance database. Results: Although the glucose levels were comparable among the four regions, the insulin responses were significantly different among the regions. This difference was observed even within the same BMI category. The plot between the insulin sensitivity index (Matsuda index) and insulinAUC/glucoseAUC or the insulinogenic index showed hyperbolic relationships with variations in regions. The indices of insulin secretion correlated positively with fat intake and negatively with the intake of fish, carbohydrate calories, and dietary fiber. Conclusions: We found that significant regional differences in insulin response and insulin sensitivity in Japanese participants and that nutritional factors may be linked to these differences independently of body size/adiposity. Insulin response and insulin sensitivity can vary among adult individuals, even within the same race and the same country, and are likely affected by environmental/lifestyle factors as well as genetic traits.

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選択的静脈サンプリング検査が有用だった甲状腺内副甲状腺腫の一例

玉城 敦子, 中山 良朗, 益崎 裕章, 久高 将太, 照屋 理子, 本間 健一郎, 屋比久 賢光, 照屋 太輝, 吉村 蘭, 上原 盛幸, 山城 清人

日本内分泌学会雑誌 ( 一般社団法人 日本内分泌学会 )  97 ( 0 ) 56 - 58   2021年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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Retrospective exploratory analyses on gender differences in determinants for incidence and progression of diabetic retinopathy in Japanese patients with type 2 diabetes mellitus

Nakayama Yoshiro, Yamaguchi Satoshi, Shinzato Yukiko, Okamoto Shiki, Millman Jasmine F., Yamashiro Kiyoto, Takemoto Nozomi, Uema Tsugumi, Arakaki Koichiro, Higa Moritake, Koizumi Hideki, Shimabukuro Michio, Masuzaki Hiroaki

ENDOCRINE JOURNAL   68 ( 6 ) 655 - 669   2021年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

特集 動脈硬化進行予防のための肥満・脂質異常診療戦略 動脈硬化の病態・早期診断法・リスク　動脈硬化のリスクとしての肥満症・メタボリックシンドロームの臨床的位置づけ

益崎 裕章, 山城 清人, 竹本 のぞみ

診断と治療 ( (株)診断と治療社 )  108 ( 10 ) 1293 - 1297   2020年10月

掲載種別: 研究論文（学術雑誌）

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Ovarian reserve after three-step laparoscopic surgery for endometriomas utilizing dienogest: A pilot study.

Kitajima M, Matsumoto K, Murakami N, Harada A, Kitajima Y, Masuzaki H, Miura K

Reproductive medicine and biology   19 ( 4 ) 425 - 431   2020年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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Weekend and off-hour effects on the incidence of cerebral palsy: contribution of consolidated perinatal care.

Toyokawa S, Hasegawa J, Ikenoue T, Asano Y, Jojima E, Satoh S, Ikeda T, Ichizuka K, Takeda S, Tamiya N, Nakai A, Fujimori K, Maeda T, Masuzaki H, Suzuki H, Ueda S

Environmental health and preventive medicine   25 ( 1 ) 52   2020年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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Metabolically and immunologically beneficial impact of extra virgin olive and flaxseed oils on composition of gut microbiota in mice.

Millman J, Okamoto S, Kimura A, Uema T, Higa M, Yonamine M, Namba T, Ogata E, Yamazaki S, Shimabukuro M, Tsutsui M, Matsushita M, Ikematsu S, Masuzaki H

European journal of nutrition ( European Journal of Nutrition )  59 ( 6 ) 2411 - 2425   2020年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

PURPOSE: Extra virgin olive oil (EVOO) and flaxseed oil (FO) contain a variety of constituents beneficial for chronic inflammation and cardio-metabolic derangement. However, little is known about the impact of EVOO and FO on dysbiosis of gut microbiota, intestinal immunity, and barrier. We, therefore, aimed to assess the impact of EVOO and FO on gut microbiota, mucosal immunity, barrier integrity, and metabolic health in mice. METHODS: C57BL/6 J mice were exposed to a low-fat (LF), lard (HF), high fat-extra virgin olive oil (HF-EVOO), or high fat-flaxseed oil (HF-FO) diet for 10 weeks. Gut microbiota assessment was undertaken using 16S rRNA sequencing. Levels of mRNA for genes involved in intestinal inflammation and barrier maintenance in the intestine and bacterial infiltration in the liver were measured by qPCR. RESULTS: HF-EVOO or HF-FO mice showed greater diversity in gut microbiota as well as a lower abundance of the Firmicutes phylum in comparison with HF mice (P < 0.05). The qPCR analyses revealed that mRNA level of FoxP3, a transcription factor, and IL-10, an inducer of regulatory T cells, was significantly elevated in the intestines of mice-fed HF-EVOO in comparison with mice-fed HF (P < 0.05). The mRNA level of the antimicrobial peptide, RegӀӀӀγ, was markedly elevated in the intestines of HF-EVOO and HF-FO compared with HF group (P < 0.05). CONCLUSIONS: Our data suggest that the consumption of EVOO or FO can beneficially impact gut microbiota, enhance gut immunity, and assist in the preservation of metabolic health in mice.

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血液悪性腫瘍の増殖抑制におけるSGLT2阻害剤のインパクトと作用機構

仲地 佐和子, 岡本 士毅, 野村 育美, 富浜 真美子, 玉城 啓太, 森近 一穂, 西 由希子, 福島 卓也, 森島 聡子, 益崎 裕章

日本抗加齢医学会総会プログラム・抄録集 ( (一社)日本抗加齢医学会 )  20回   214 - 214   2020年09月

掲載種別: 研究論文（その他学術会議資料等）

マウスにおいてエクストラヴァージンオリーブオイルとアマニ油は腸内細菌叢に影響を及ぼして粘膜免疫と代謝的健康を促進する(Extra virgin olive and flaxseed oils impact gut microbiota, enhancing mucosal immunity and metabolic health in mice)

ミルマン・ジャスミン, 岡本 士毅, 上間 次己, 比嘉 萌子, 難波 豊隆, 山崎 聡, 島袋 充生, 池松 真也, 益崎 裕章

日本抗加齢医学会総会プログラム・抄録集 ( (一社)日本抗加齢医学会 )  20回   223 - 223   2020年09月

掲載種別: 研究論文（その他学術会議資料等）

Establishment of a novel diagnostic test algorithm for human T-cell leukemia virus type 1 infection with line immunoassay replacement of western blotting: a collaborative study for performance evaluation of diagnostic assays in Japan.

Okuma K, Kuramitsu M, Niwa T, Taniguchi T, Masaki Y, Ueda G, Matsumoto C, Sobata R, Sagara Y, Nakamura H, Satake M, Miura K, Fuchi N, Masuzaki H, Okayama A, Umeki K, Yamano Y, Sato T, Iwanaga M, Uchimaru K, Nakashima M, Utsunomiya A, Kubota R, Ishitsuka K, Hasegawa H, Sasaki D, Koh KR, Taki M, Nosaka K, Ogata M, Naruse I, Kaneko N, Okajima S, Tezuka K, Ikebe E, Matsuoka S, Itabashi K, Saito S, Watanabe T, Hamaguchi I

Retrovirology   17 ( 1 ) 26   2020年08月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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A new diagnostic algorithm using biopsy specimens in adult T-cell leukemia/lymphoma: combination of RNA in situ hybridization and quantitative PCR for HTLV-1.

Takatori M, Sakihama S, Miyara M, Imaizumi N, Miyagi T, Ohshiro K, Nakazato I, Hayashi M, Todoroki J, Morishima S, Masuzaki H, Fukushima T, Karube K

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc ( Modern Pathology )  34 ( 1 ) 51 - 58   2020年08月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

Histopathological distinction between adult T-cell leukemia/lymphoma (ATLL) and other T-cell neoplasms is often challenging. The current gold standard for the accurate diagnosis of ATLL is the Southern blot hybridization (SBH) assay, which detects clonal integration of human T-cell leukemia virus type I (HTLV-1) provirus. However, SBH cannot be performed with small biopsy or formalin-fixed paraffin-embedded (FFPE) tissue samples because this assay requires a large amount of DNA without degradation. Here we developed a new diagnostic algorithm for the accurate diagnosis of ATLL using FFPE samples. This method combines two HTLV-1 detection assays, namely, ultrasensitive RNA in situ hybridization using RNAscope for HTLV-1 bZIP factor (HBZ-RNAscope), and quantitative PCR targeting the tax gene (tax-qPCR). We analyzed 119 FFPE tissue specimens (62 ATLL, and 57 non-ATLL, including 41 HTLV-1 carriers) and compared them with the SBH results using the corresponding fresh-frozen samples. As a result, tax-qPCR had a higher ATLL identification rate than HBZ-RNAscope (88% [52/59], and 63% [39/62], respectively). However, HBZ-RNAscope clearly visualized the localization of HTLV-1-infected tumor cells and its identification rate increased to 94% (17/18) when the analysis was limited to samples up to 2 years old, indicating its usefulness in the daily diagnosis. The diagnostic algorithm combining these two assays successfully evaluated 94% (112/119) of samples and distinguished ATLL from non-ATLL cases including HTLV-1 carriers with 100% sensitivity and specificity. This method is expected to replace SBH and increase the accuracy of the diagnosis of ATLL.

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