Published Papers - Masuzaki Hiroaki

γ-Oryzanol protects pancreatic β-cells against endoplasmic reticulum stress in male mice.

Kozuka C, Sunagawa S, Ueda R, Higa M, Tanaka H, Shimizu-Okabe C, Ishiuchi S, Takayama C, Matsushita M, Tsutsui M, Miyazaki J, Oyadomari S, Shimabukuro M, Masuzaki H

Endocrinology ( Endocrinology )  156 ( 4 ) 1242 - 50   2015.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Endoplasmic reticulum (ER) stress is profoundly involved in dysfunction of beta-cells under high-fat diet and hyperglycemia. Our recent study in mice showed that gamma-oryzanol, a unique component of brown rice, acts as a chemical chaperone in the hypothalamus and improves feeding behavior and diet-induced dysmetabolism. However, the entire mechanism whereby gamma-oryzanol improves glucose metabolism throughout the body still remains unclear. In this context, we tested whether gamma-oryzanol reduces ER stress and improves function and survival of pancreatic beta-cells using murine beta-cell line MIN6. In MIN6 cells with augmented ER stress by tunicamycin, gamma-oryzanol decreased exaggerated expression of ER stress-related genes and phosphorylation of eukaryotic initiation factor-2 alpha, resulting in restoration of glucose-stimulated insulin secretion and prevention of apoptosis. In islets from high-fat diet-fed diabetic mice, oral administration of gamma-oryzanol improved glucose-stimulated insulin secretion on following reduction of exaggerated ER stress and apoptosis. Furthermore, we examined the impact of gamma-oryzanol on low-dose streptozotocin-induced diabetic mice, where exaggerated ER stress and resultant apoptosis in beta-cells were observed. Also in this model, gamma-oryzanol attenuated mRNA level of genes involved in ER stress and apoptotic signaling in islets, leading to amelioration of glucose dysmetabolism. Taken together, our findings demonstrate that gamma-oryzanol directly ameliorates ER stress-induced beta-cell dysfunction and subsequent apoptosis, highlighting usefulness of gamma-oryzanol for the treatment of diabetes mellitus.

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Decreased expression of human heat shock protein 70 in the endometria and pathological lesions of women with adenomyosis and uterine myoma after GnRH agonist therapy.

Khan KN, Kitajima M, Hiraki K, Fujishita A, Nakashima M, Masuzaki H

European journal of obstetrics, gynecology, and reproductive biology   187   6 - 13   2015.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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ADIPOQ polymorphisms are associated with insulin resistance in Japanese women

A. Kitamoto, T. Kitamoto, R. So, T. Matsuo, Y. Nakata, H. Hyogo, H. Ochi, T. Nakamura, S. Kamohara, N. Miyatake, K. Kotani, R. Komatsu, N. Itoh, I. Mineo, J. Wada, Y. Ogawa, M. Yoneda, A. Nakajima, T. Funahashi, S. Miyazaki, K. Tokunaga, H. Masuzaki, T. Ueno, K. Chayama, K. Hamaguchi, K. Yamada, T. Hanafusa, S. Oikawa, T. Sakata, K. Tanaka, Y. Matsuzawa, K. Hotta

Endocrine J   62 ( 6 ) 513 - 521   2015.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Vaccination during the 2013-2014 influenza season in pregnant Japanese women.

Yamada T, Abe K, Baba Y, Inubashiri E, Kawabata K, Kubo T, Maegawa Y, Fuchi N, Nomizo M, Shimada M, Shiozaki A, Hamada H, Matsubara S, Akutagawa N, Kataoka S, Maeda M, Masuzaki H, Sagawa N, Nakai A, Saito S, Minakami H

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology   34 ( 3 ) 543 - 8   2015.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.

Noguchi K, Matsuzaki T, Sakanashi M, Hamadate N, Uchida T, Kina-Tanada M, Kubota H, Nakasone J, Sakanashi M, Ueda S, Masuzaki H, Ishiuchi S, Ohya Y, Tsutsui M

Journal of pharmacological sciences ( JAPANESE PHARMACOLOGICAL SOC )  127 ( 2 ) 217 - 22   2015.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in healthy subjects. A double-blind, placebo-controlled, crossover study was performed in 27 healthy volunteers. A cup of either caffeinated or decaffeinated coffee was drunk by the subjects, and reactive hyperemia of finger blood flow was assessed by laser Doppler flowmetry. In an interval of more than 2 days, the same experimental protocol was repeated with another coffee in a crossover manner. Caffeinated coffee intake slightly but significantly elevated blood pressure and decreased finger blood flow as compared with decaffeinated coffee intake. There was no significant difference in heart rate between caffeinated and decaffeinated coffee intake. Importantly, caffeinated coffee intake significantly enhanced post-occlusive reactive hyperemia of finger blood flow, an index of microvascular endothelial function, compared with decaffeinated coffee intake. These results provide the first evidence that caffeine contained in a cup of coffee enhances microvascular function in healthy individuals. (C) 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

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Authors' reply.

Nishijima K, Takahashi J, Orisaka M, Kurokawa T, Tamamura C, Yoshida A, Masuzaki H, Sekiya T, Yoshida Y, Kotsuji F

BJOG : an international journal of obstetrics and gynaecology   122 ( 3 ) 448 - 9   2015.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Involvement of hepatocyte growth factor-induced epithelial-mesenchymal transition in human adenomyosis.

Khan KN, Kitajima M, Hiraki K, Fujishita A, Nakashima M, Masuzaki H

Biology of reproduction   92 ( 2 ) 35   2015.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The intractable intra-abdominal hemorrhage with unknown etiology in a patient with severe hemophilia A

K.Morichika, T.Hanashiro, N.Shimabukuro, K.Tamaki, I.Tedokon, Y.Nishi, S.Nakachi, T.Tomoyose, T.Fukushima, H. Masuzaki

Am J Emerg Med   33 ( 1 ) 129 - e1-3   2015.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

The intractable intra-abdominal hemorrhage with unknown etiology in a patient with severe hemophilia A.

Morichika K, Tomoyose T, Nishi Y, Nakachi S, Fukushima T, Masuzaki H

The American journal of emergency medicine ( American Journal of Emergency Medicine )  33 ( 1 ) 129.e1 - 3   2015.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Effect of labor on plasma concentrations and postpartum clearance of cell-free, pregnancy-associated, placenta-specific microRNAs.

Morisaki S, Miura K, Higashijima A, Abe S, Miura S, Hasegawa Y, Yoshida A, Kaneuchi M, Yoshiura K, Masuzaki H

Prenatal diagnosis   35 ( 1 ) 44 - 50   2015.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A Case with falsely elevated HbAlc concentration caused by unknown modified hemoglobin

Shimajiri Y.

Journal of the Japan Diabetes Society ( Journal of the Japan Diabetes Society )  58 ( 12 ) 915 - 922   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

ADIPOQ polymorphisms are associated with insulin resistance in Japanese women.

Kitamoto A, Kitamoto T, So R, Matsuo T, Nakata Y, Hyogo H, Ochi H, Nakamura T, Kamohara S, Miyatake N, Kotani K, Mineo I, Wada J, Ogawa Y, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Masuzaki H, Ueno T, Chayama K, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Sakata T, Tanaka K, Matsuzawa Y, Hotta K

Endocrine journal ( 一般社団法人 日本内分泌学会 )  62 ( 6 ) 513 - 21   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Visceral fat accumulation contributes to the development of insulin resistance, leading to metabolic syndrome. Adiponectin provides a link between visceral fat accumulation and insulin resistance. In addition to environmental factors, genetic factors play important roles in visceral fat accumulation and circulating adiponectin levels. Genome-wide association studies (GWASs) have identified genetic variations in the adiponectin, C1Q and collagen domain containing (<i>ADIPOQ</i>) gene that are associated with adiponectin levels. In this study, we investigated whether <i>ADIPOQ</i> single nucleotide polymorphisms (SNPs) were associated with visceral fat accumulation and insulin resistance. We measured the visceral fat area (VFA) by computed tomography (CT) and examined the presence of the insulin resistance-related phenotype (fasting plasma glucose, fasting insulin, and homeostasis model assessment-insulin resistance [HOMA-IR]) in a set of Japanese individuals (731 men and 864 women) who were genotyped for seven <i>ADIPOQ</i> SNPs reported by recent GWASs (namely, rs6810075, rs10937273, rs1648707, rs864265, rs182052, rs17366568, and rs6773957). SNPs associated with the phenotype (<i>P</i> < 0.05) were then evaluated by association analysis using a second set of the study participants (383 men and 510 women). None of the SNPs was associated with body mass index (BMI) or VFA in men or women. However, the adiponectin-decreasing alleles of rs10937273 and rs1648707 were significantly associated with HOMA-IR (<i>P</i> = 0.0030 and <i>P</i> = 0.00074, respectively) in women, independently of BMI. These SNPs were significantly associated with decreased adiponectin levels in women. Our results suggested that rs10937273 and rs1648707 may affect insulin sensitivity by regulating adiponectin production by adipose tissue in women.

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Giant Septic Lymphadenitis with Marked Gas Formation Caused by Bacteroides fragilis in a Patient with Adult T-cell Leukemia/lymphoma.

Tomoyose T, Nakachi S, Nishi Y, Morichika K, Tedokon I, Tamaki K, Shimabukuro N, Hanashiro T, Samura H, Fukushima T, Masuzaki H

Internal medicine (Tokyo, Japan) ( 一般社団法人 日本内科学会 )  54 ( 22 ) 2919 - 22   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adult T-cell leukemia/lymphoma (ATL) sometimes causes opportunistic infections. A 53-year-old woman with systemic lymphadenopathies was diagnosed with ATL by inguinal lymph node biopsies and underwent oral chemotherapy. Two months later, high grade fever, lower abdominal pain and lymphadenopathy recurred. Computed tomography revealed the presence of lymphadenopathy with marked gas formation in the pelvic lesion. Blood cultures were suggestive of septic lymphadenitis by <i>Bacteroides fragilis</i> (<i>BF</i>). This represents the first demonstration of giant lymphadenitis with gas formation caused by <i>BF</i> in a patient with ATL. Notably, septic lymphadenitis is pivotal in the differential diagnosis of systemic lymphadenopathy in ATL.<br>

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著明な両側眼瞼腫脹を生じた皮下脂肪織炎様 T 細胞リンパ腫の 1 例

林 健太郎, 益崎 裕章, 上里 博, 宮城 拓也, 園崎 哲, 山口 さやか, 山本 雄一, 高橋 健造, 西 由希子, 仲地 佐和子, 友寄 毅昭

西日本皮膚科 ( 日本皮膚科学会西部支部 )  77 ( 5 ) 487 - 491   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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患者は 24 歳，女性。発熱と体幹，四肢に多発する紅斑や関節痛があり，病初期には自己免疫疾患との鑑別に苦慮していた。経過中に著明な両眼瞼腫脹を生じ，皮膚筋炎や原発性皮膚リンパ腫を疑った。ゴットロン徴候や爪囲紅斑，筋関連酵素の上昇はなく，再検した病理組織で，脂肪細胞を取り囲んで浸潤する異型細胞を認め，いわゆる rimming 像を呈していた。免疫染色で異型細胞は CD3，CD8，T cell restricted intercellular antigen (TIA-1) が 陽 性であり，CD4，CD30，CD56，EBV-encoded small RNA (EBER)は陰性であった。また異型細胞は T 細胞受容体 <i>αβ</i> 鎖が陽性で，<i>γδ</i> 鎖は陰性だった。以上の結果から，皮下脂肪織炎様 T 細胞リンパ腫(subcutaneous panniculitis-like T-cell lymphoma ; SPTCL)と診断した。自験例は血球貪食症候群も合併していたため，治療は多剤併用化学療法を開始した。その結果，病変は消失し，治療終了後2年間再発はない。眼瞼腫脹を生じた SPTCL の報告は少なく，眼瞼腫脹はSPTCL では稀な皮膚症状と思われる。一方，眼窩悪性リンパ腫の半数が眼瞼腫脹を初発症状とし，自験例のように眼瞼腫脹を契機に診断された眼窩悪性リンパ腫の報告もあるため，眼瞼腫脹の鑑別に悪性リンパ腫も念頭におくべきであると考えた。

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原因不明の修飾ヘモグロビンのためにHbA1cが偽高値を示した1例

島尻 佳典, 與那嶺 正人, 友寄 毅昭, 益崎 裕章, 三家 登喜夫, 原野 恵子, 和田 芳直, 古賀 正史

糖尿病 ( 一般社団法人 日本糖尿病学会 )  58 ( 12 ) 915 - 922   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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修飾ヘモグロビン（Hb）のためにHbA1cが偽高値を示した症例を経験したので報告する．症例は72歳男性．糖尿病精査を希望にて当院を受診．OGTTにて境界型，グリコアルブミンは16.4 %であったが，HbA1c（HPLC法）は8.1 %と高値を示し，そのクロマトグラムで異常ピークを認めた．一方，免疫法，酵素法で測定したHbA1cは各々2.8 %，4.0 %といずれも低値であった．高分離HPLC（KO500）法にて不安定HbA1c近傍およびHbAとHbA1cの間に2つの異常ピークを認めたが，グロビン遺伝子（<i>α</i>鎖および<i>β</i>鎖）に変異を認めなかった．高分離HPLCで認めた2つの異常ピークを質量分析にて解析した結果，両分画はともに<i>β</i>グロビンに88 Daの分子修飾を認めた．修飾分子の詳細は不明であるが，分子量から既知の修飾Hbは該当せず，新規の修飾Hbであった．HbA1cが偽高値を示す新たな原因の可能性がある．

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Subclinical Carotid Atherosclerosis Burden in the Japanese: Comparison between Okinawa and Nagano Residents

Michio Shimabukuro, Yoshimasa Hasegawa, Moritake Higa, Rie Amano, Hirotsugu Yamada, Shunsaku Mizushima, Hiroaki Masuzaki, Masataka Sata

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS ( JAPAN ATHEROSCLEROSIS SOC )  22 ( 8 ) 854 - 868   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Aim: The prevalence of overweight and a change in atherosclerotic lipid profiles may be linked to region-specific differences in atherosclerotic diseases. We evaluated whether the lipid phenotype could be linked to region-and sex-specific differences in the degree of atherosclerosis. Methods: Non-diabetic subjects included Okinawa (n=1674) and Nagano (n=1392) residents aged 30-75 years who underwent carotid ultrasonography for the measurement of maximum intima-media thickness (max IMT). Results: Average max IMT was higher in Okinawa men and women, and the increase in max IMT with age was enhanced in men. Multiple regression analysis showed that in addition to age and systolic blood pressure, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol were IMT determinants only in men for both Okinawa and Nagano. Meanwhile, HDL-cholesterol was a determinant for Okinawa men and women, but not for Nagano men and women. Conclusions: This is the first report to show region-and sex-specific differences in the determinants for max IMT in a Japanese population. The evaluation of the relationship between lipid profile patterns and region-and sex-specific differences in carotid atherosclerosis burden may be required.

Risk stratification of coronary artery disease in asymptomatic diabetic subjects using multidetector computed tomography.

Shimabukuro M, Saito T, Higa T, Nakamura K, Masuzaki H, Sata M, Fukuoka diabetologists group.

Circulation journal : official journal of the Japanese Circulation Society ( 一般社団法人 日本循環器学会 )  79 ( 11 ) 2422 - 9   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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<b><i>Background:</i></b>Patients with type 2 diabetes mellitus (T2DM) show a greater risk for coronary artery disease (CAD), but the risk stratification in asymptomatic CAD patients has not been established. This study investigated the prevalence and severity for asymptomatic CAD and predictors in T2DM patients.<b><i>Methods and Results:</i></b>In a multiclinic group, diabetic patients (320 men, 186 women) without known symptoms suggestive of CAD were recruited for multidetector computed tomography (MDCT). Patients were categorized according to severity of coronary atherosclerosis: Grade 1 (normal findings), Grade 2 (mild atherosclerosis without significant stenosis), Grade 3 (moderate stenosis/atherosclerosis, 50–74% stenosis), Grade 4 (moderate stenosis/atherosclerosis, 75–89% stenosis), Grade 5 (severe stenosis/atherosclerosis, ≥90% stenosis). The trend for severity grade of CAD was slightly higher in men than women (P=0.054). For critical lesions (combined Grades 3–5), the prevalence was almost equal (men 44% vs. women 37%; P=0.113). Multivariate models showed that in men, HbA_1c≥7.4%, dyslipidemia, duration of diabetes, retinopathy, and other type of cardiovascular diseases were predictors of critical lesions and in women, duration of diabetes and retinopathy were predictors.<b><i>Conclusions:</i></b>The prevalence and severity of asymptomatic CAD are comparably high in men and women with T2DM. Risk stratification by using MDCT might be useful to predict asymptomatic coronary lesions requiring coronary revascularization. (<i>Circ J</i> 2015; <b>79:</b> 2422–2429)

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Dietary supplementation with sodium nitrite can exert neuroprotective effects on global cerebral ischemia/reperfusion in mice

Kozuka C, Sunagawa S, Ueda R, Higa M, Tanaka H, Shimizu-Okabe C, Ishiuchi S, Takayama C, Matsushita M, Tsutsui M, Miyazaki JI, Oyadomari S, Shimabukuro M, Masuzaki H

J Anesth   29   609 - 617   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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