Details of a Researcher - Masuzaki Hiroaki

Published Papers - Masuzaki Hiroaki

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Two Cases of Plasmablastic Myeloma Mimicking Plasmablastic Lymphoma With In-Depth Review of Literature.

Kitamura S, Morichika K, Nakachi S, Hanashiro T, Miyagi R, Nakajima T, Nishi Y, Tamaki K, Fukushima T, Masuzaki H

Cancer reports (Hoboken, N.J.) ( Cancer Reports ) 8 ( 2 ) e70094 2025.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Intramuscular abscess and multiple lymphadenitis due to Nocardia asiatica infection requiring differential diagnosis from smoldering adult T-cell leukemia/lymphoma

YAMASHIRO Mahito, NAKAJIMA Tomo, IREI Yuka, MIYAGI Riko, KITAMURA Sakiko, TAMAKI Keita, NISHI Yukiko, MORICHIKA Kazuho, NAKACHI Sawako, MAEHARA Hiroki, FUKUSHIMA Takuya, MASUZAKI Hiroaki

Rinsho Ketsueki ( The Japanese Society of Hematology ) 66 ( 2 ) 121 - 126 2025 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

A 72-year-old male engaged in horticulture developed a progressively enlarging painful mass in the left upper arm. The first biopsy revealed no malignancy or pathogenic bacteria. He completed an adequate course of antibiotics for infectious lymphadenitis, but showed no apparent improvement. Computed tomography demonstrated systemic lymphadenopathy, suggesting malignant lymphoma. Monoclonal integration of the HTLV-1 proviral genome in peripheral blood cells was confirmed by Southern blot analysis, but repeated lymph node biopsies identified no malignant cells. Based on these findings, a diagnosis of smoldering adult T-cell leukemia/lymphoma was made. After prolonged culture of the specimen, Nocardia sp. were detected and 16S rRNA sequencing confirmed infection by Nocardia asiatica. Combination therapy with sulfamethoxazole-trimethoprim and minocycline was started, and the systemic lymphadenopathy improved within 3 months. Although Nocardia asiatica infection manifesting as systemic lymphadenitis is extremely rare, it should be considered as a possibility in immunocompromised patients to ensure an accurate diagnosis.

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A Rare Case of Autoimmune-Mediated Lecithin:Cholesterol Acyltransferase Insufficiency Manifesting as the Acute Onset of Extremely Hypo-High-Density Lipoprotein-Cholesterolemia and Spontaneous Improvement: A Case Report with a Review of the Literature.

Tamaki A, Kuroda M, Yonaha K, Ishiki Y, Uehara M, Nakayama Y, Honma KI, Chinen R, Uema T, Okamoto S, Miyoshi J, Kirinashizawa M, Sato K, Aohara T, Yamamoto M, Maezawa Y, Yokote K, Masuzaki H

Journal of atherosclerosis and thrombosis ( 一般社団法人日本動脈硬化学会 ) advpub ( 0 ) 2024.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

A 59-year-old Japanese woman was referred for an extremely low level of circulating high-density lipoprotein cholesterol (HDL-C). The serum HDL-C level had long been within the normal range but suddenly decreased asymptomatically to 7 mg/dL. She had no typical symptoms associated with familial lecithin, cholesterol acyltransferase deficiency (FLD), including proteinuria, anemia, and corneal opacity. The circulating level of ApoA-1 was also markedly decreased at 48 mg/dL, and the proportion of esterified cholesterol to free cholesterol was irregularly low at 26%. Whole-genome sequencing revealed no apparent pathological mutations in the LCAT gene. Notably, anti-LCAT antibodies were detected in the serum at 146±1.7 ng/mL, resulting in her being diagnosed with acquired LCAT insufficiency (ALCATI) caused by anti-LCAT antibodies. Five years after her HDL-C levels spontaneously decreased, they increased without any identifiable cause. To our knowledge, only six cases of ALCATI caused by anti-LCAT antibodies have been reported to date. In contrast to the present case, previously reported cases of ALCATI manifested proteinuria that improved with steroid therapy. The unique clinical course in the present case highlights the heterogeneity of ALCATI, warranting further research to clarify the molecular pathophysiology of FLD and ALCATI.

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Machine learning-based reproducible prediction of type 2 diabetes subtypes.

Tanabe H, Sato M, Miyake A, Shimajiri Y, Ojima T, Narita A, Saito H, Tanaka K, Masuzaki H, Kazama JJ, Katagiri H, Tamiya G, Kawakami E, Shimabukuro M

Diabetologia ( Diabetologia ) 67 ( 11 ) 2446 - 2458 2024.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study.

Saito H, Tanabe H, Hirai H, Higa M, Tanaka K, Yamaguchi S, Maimaituxun G, Masuzaki H, Kazama JJ, Shimabukuro M

Journal of diabetes investigation ( Journal of Diabetes Investigation ) 15 ( 10 ) 1444 - 1456 2024.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Gut microbiota-based prediction for the transition from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) in a remote island cohort study.

Uema T, Tsukita M, Okamoto S, Uehara M, Honma KI, Nakayama Y, Tamaki A, Miyazato M, Ashikari A, Maeda S, Imamura M, Matsushita M, Nakamura K, Masuzaki H

Diabetes research and clinical practice ( Diabetes Research and Clinical Practice ) 213 111747 - 111747 2024.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

AIM: The present cohort study explored whether specific gut microbiota (GM) profile would predict the development of impaired glucose tolerance (IGT) in individuals with normal glucose tolerance (NGT). METHODS: A total of 114 study subjects with NGT in Kumejima island, Japan participated in the present study and underwent 75 g oral glucose tolerance tests at baseline and one year later. We compared the profile of GM at baseline between individuals who consistently maintained NGT (NRN, n = 108) and those who transitioned from NGT to IGT (NTI, n = 6). RESULTS: Within-individual bacterial richness and evenness as well as inter-individual bacterial composition showed no significant differences between NRN and NTI. Of note, however, partial least squares discriminant analyses revealed distinct compositions of GM between groups, with no overlap in their 95 % confidence interval ellipses. Multi-factor analyses at the genus level demonstrated that the proportions of CF231, Corynebacterium, Succinivibrio, and Geobacillus were significantly elevated in NTI compared to NRN (p < 0.005, FDR < 0.1, respectively) after adjusting for age, sex, HbA1c level, and BMI. CONCLUSIONS: Our data suggest that increased proportion of specific GM is linked to the future deterioration of glucose tolerance, thereby serving as a promising predictive marker for type 2 diabetes mellitus.

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Impact of the transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for the measurement of plasma aldosterone concentration (PAC) on the diagnosis of primary aldosteronism (PA) via retrospective analyses in Okinawa, Japan.

Honma KI, Nakayama Y, Tamaki A, Uehara M, Teruya T, Yabiku T, Ishiki Y, Yonaha K, Chinen R, Uema T, Okamoto S, Masuzaki H

Endocrine journal ( 一般社団法人日本内分泌学会 ) advpub ( 0 ) 895 - 906 2024.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

In Japan, the traditional method for measuring plasma aldosterone concentration (PAC) was radioimmunoassay (RIA), which had several challenges, including poor traceability of certified reference materials and reduced detection sensitivity at low concentrations. To overcome these issues, a chemiluminescent enzyme immunoassay (CLEIA) for PAC measurement was introduced in April 2021 and the Japan Endocrine Society published new guidelines for primary aldosteronism (PA). This study aimed to evaluate the impact of the transition from RIA to CLEIA for PAC measurement on PA diagnosis. Data from 190 patients admitted to the Second Department of Internal Medicine, University of the Ryukyus Hospital, between April 2012 and March 2021 were analyzed. Patients who were diagnosed with PA underwent adrenal venous sampling. The PAC measured by RIA (PAC(RIA)) was converted to the estimated PAC measured by CLEIA (ePAC(CLEIA)) using a conversion formula. The present study evaluated the discordance rates in diagnoses based on screening (SC), captopril challenge test (CCT), saline infusion test (SIT), and diagnosis of PA between results judged by PAC(RIA) according to the previous guidelines and those judged by ePAC(CLEIA) according to the new guidelines. The results revealed discordant diagnosis rates of 6.4% for SC and 10.1% for CCT, with no discordance for SIT. The discordant diagnosis rate for PA was 3.7%. Our study reveals the challenges in establishing appropriate diagnostic criteria for PA using PAC(CLEIA) and highlights the demand for further research on provisionally positive categories.

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Post-traumatic pituitary stalk transection syndrome (PSTS) expeditiously manifested after a fall from a height combined with acute traumatic spinal cord injury: a rare case report with review of literature.

Ishiki Y, Tamaki A, Honma KI, Yonaha K, Yabiku T, Teruya T, Uehara M, Nakayama Y, Chinen R, Uema T, Nakachi S, Okamoto S, Masuzaki H

Endocrine journal ( 一般社団法人日本内分泌学会 ) advpub ( 0 ) 817 - 824 2024.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitary hormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalk interruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to their similar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing to panhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor. She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably, menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism, hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights endocrinological landscape of transection of the pituitary stalk by acute trauma.

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Role of perirenal adiposity in renal dysfunction among CKD individuals with or without diabetes: a Japanese cross-sectional study.

Kono T, Maimaituxun G, Tanabe H, Higa M, Saito H, Tanaka K, Masuzaki H, Sata M, Kazama JJ, Shimabukuro M

BMJ open diabetes research & care ( BMJ Open Diabetes Research and Care ) 12 ( 2 ) 2024.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

INTRODUCTION: It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm3), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm3/m2). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m2 proteinuria onset, or both. RESULTS: Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm2, the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM. CONCLUSIONS: PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies.

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4. Conclusion

Masuzaki Hiroaki

Nihon Naika Gakkai Zasshi ( The Japanese Society of Internal Medicine ) 113 ( 3 ) 402 - 403 2024.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Impact of coronavirus disease 2019 on medical practice in endocrine and metabolic diseases in Japan: a nationwide surveillance study conducted by the Japan Endocrine Society.

Manaka K, Kato S, Sakamoto R, Yamakage H, Uema T, Kawai S, Shibata M, Hiratsuka I, Nakachi S, Onoue T, Tsuchiya T, Fukui M, Hashimoto K, Suzuki A, Makita N, Ogawa Y, Arima H, Satoh-Asahara N, Masuzaki H

Endocrine journal ( 一般社団法人日本内分泌学会 ) advpub ( 0 ) 499 - 514 2024.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.

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Sex differences in the association between epicardial adipose tissue volume and left atrial volume index.

Yamaguchi S, Maeda M, Oba K, Maimaituxun G, Arasaki O, Yagi S, Kusunose K, Soeki T, Yamada H, Fukuda D, Masuzaki H, Sata M, Shimabukuro M

BMC cardiovascular disorders ( BMC Cardiovascular Disorders ) 24 ( 1 ) 46 - 46 2024.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

BACKGROUND: Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated. METHODS: Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m2) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses. RESULTS: In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men. CONCLUSIONS: We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.

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Impact of treatment cessation on incidence and progression of retinopathy in Japanese patients with type 2 diabetes mellitus: a retrospective cohort study

Yukiko Shinzato, Yoshiro Nakayama, Shiki Okamoto, Jasmine F. Millman, Tsugumi Uema, Ken-ichiro Honma, Atsuko Tamaki, Moriyuki Uehara, Taiki Teruya, Takamitsu Yabiku, Yohei Ishiki, Ken Yonaha, Ko-ichiro Arakaki, Moritake Higa, Hideki Koizumi, Koshi Nakamura, Michio Shimabukuro, Hiroaki Masuzaki

Diabetology International ( Springer Science and Business Media LLC ) 15 ( 3 ) 535 - 543 2024 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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肺原発節外性NK/T細胞リンパ腫の一例

宮城理子, 仲地佐和子, 上間道仁, 横田雄太郎, 中島知, 北村紗希子, 玉城啓太, 森近一穂, 西由希子, 森島聡子, 福島卓也, 益崎裕章

日本血液学会学術集会 ( (一社)日本血液学会 ) 85回 1165 - 1165 2023.10

Type of publication: Research paper (other science council materials etc.)

遺伝子異常を伴わないPAI-1欠乏症が疑われた1例

森島聡子, 岩城孝行, 浦野哲盟, 宮城理子, 中島知, 北村紗希子, 花城多恵子, 西由希子, 玉城啓太, 森近一穂, 仲地佐和子, 益崎裕章

日本血液学会学術集会 ( (一社)日本血液学会 ) 85回 609 - 609 2023.10

Type of publication: Research paper (other science council materials etc.)

A Foreword to the Special Issue

Masuzaki Hiroaki

Journal of the Japan Diabetes Society ( THE JAPAN DIABETES SOCIETY ) 66 ( 6 ) 459 - 459 2023.06

Type of publication: Research paper (scientific journal)

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Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT): a multicenter, randomized, open-label, parallel-group study.

Kudo A, Machii N, Ono T, Saito H, Oshiro Y, Takahashi R, Oshiro K, Taneda Y, Higa M, Nakachi K, Yagi S, Masuzaki H, Sata M, Shimabukuro M

BMJ open diabetes research & care ( BMJ Open Diabetes Research and Care ) 11 ( 2 ) 2023.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

INTRODUCTION: This study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported oral therapy (BOT). RESEARCH DESIGN AND METHODS: Changes in mean daily blood glucose level before and after 48-72 hours of add-on or no add-on of dapagliflozin (primary end point) and diabetes-related biochemical variables and major safety variables during the 12 weeks (secondary end point) were evaluated in the multicenter, randomized, two-arm, open-label, parallel-group comparison study. RESULTS: Among 36 participants, 18 were included in the no add-on group and 18 were included in the dapagliflozin add-on group. Age, gender, and body mass index were comparable between the groups. There were no changes in continuous glucose monitoring metrics in the no add-on group. In the dapagliflozin add-on group, mean glucose (183-156 mg/dL, p=0.001), maximum glucose (300-253, p<0.01), and SD glucose (57-45, p<0.05) decreased. Time in range increased (p<0.05), while time above the range decreased in the dapagliflozin add-on group but not in the no add-on group. After 12-week treatment with dapagliflozin add-on, 8-hydroxy-2'-deoxyguanosine (8OHdG), as well as hemoglobin A1c (HbA1c), decreased. CONCLUSIONS: This study showed that the mean daily blood glucose and other daily glucose profiles were amended after 48-72 hours of dapagliflozin add-on in Japanese patients with type 2 diabetes who received BOT. The diabetes-related biochemical variables such as HbA1c and urinary 8OHdG were also obtained during the 12 weeks of dapagliflozin add-on without major adverse events. A preferable 24-hour glucose profile in 'time in ranges' and an improvement in reactive oxygen species by dapagliflozin warrant us to evaluate these benefits in larger clinical studies. TRIAL REGISTRATION NUMBER: UMIN000019457.

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A Comprehensive Study of the Immunophenotype and its Clinicopathological Significance in Adult T-cell Leukemia/Lymphoma.

Tamaki T, Karube K, Sakihama S, Tsuruta Y, Awazawa R, Hayashi M, Nakada N, Matsumoto H, Yagi N, Ohshiro K, Nakazato I, Kitamura S, Nishi Y, Miyagi T, Yamaguchi S, Nakachi S, Morishima S, Masuzaki H, Takahashi K, Fukushima T, Wada N

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc ( Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc ) 36 ( 8 ) 100169 - 100169 2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell tumor caused by human T-lymphotropic virus type 1 (HTLV-1). The typical ATLL immunophenotypes are described in the 2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (positive: CD2, CD3, CD5, CD4, and CD25; negative: CD7, CD8, and cytotoxic markers; and partially positive: CD30, CCR4, and FOXP3). However, limited studies are available on the expression of these markers, and their mutual relationship remains unknown. Furthermore, the expression status of novel markers associated with T-cell lymphomas, including Th1 markers (T-bet and CXCR3), Th2 markers (GATA3 and CCR4), T follicular helper markers (BCL6, PD1, and ICOS), and T-cell receptor (TCR) markers, and their clinicopathologic significance is unclear. In this study, we performed >20 immunohistochemical stains in 117 ATLL cases to determine the comprehensive immunophenotypic profile of ATLL, which were compared on the basis of clinicopathologic factors, including morphologic variants (pleomorphic vs anaplastic), biopsy locations, treatments, Shimoyama classification-based clinical subtype, and overall survival. CD3+/CD4+/CD25+/CCR4+ was considered a typical immunophenotype of ATLL, but approximately 20% of cases did not conform to this pattern. Simultaneously, the following new findings were obtained: (1) most cases were negative for TCR-β and TCR-δ (104 cases, 88.9%), indicating the usefulness of negative conversion of TCR expression to provide differentiation from other T-cell tumors; (2) the positivity of CD30 and CD15 and the negativity of FOXP3 and CD3 were significantly associated with anaplastic morphology; and (3) atypical cases, such as T follicular helper marker-positive (12 cases, 10.3%) and cytotoxic molecule-positive cases (3 cases, 2.6%), were identified. No single markers could predict the overall survival among patients with acute/lymphoma subtypes of ATLL. The results of this study illustrate the diversity of ATLL phenotypes. In T-cell tumors occurring in HTLV-1 carriers, the possibility of ATLL should not be eliminated even when the tumor exhibits an atypical phenotype, and the confirmation of HTLV-1 in the tissue is recommended.

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Markers for obese and non-obese Type 2 diabetes identified using whole blood metabolomics.

Teruya T, Sunagawa S, Mori A, Masuzaki H, Yanagida M

Scientific reports ( Scientific Reports ) 13 ( 1 ) 2460 2023.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Fatal acquired coagulation factor V deficiency after hepatectomy for advanced hepatocellular carcinoma as a possible immune checkpoint inhibitor-related adverse event: a case report.

Arakaki S, Ono S, Kawamata F, Ishino S, Uesato Y, Nakajima T, Nishi Y, Morishima S, Arakaki S, Maeshiro T, Souri M, Ichinose A, Masuzaki H, Takatsuki M

Surgical case reports ( SpringerOpen ) 9 ( 1 ) 16 - 7 2023.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Background Atezolizumab plus bevacizumab therapy was recently introduced as the first line for unresectable advanced hepatocellular carcinoma (HCC), but immune-related adverse events (IrAEs) due to atezolizumab are a great concern. Here, we report the case of a patient who developed fatal acquired coagulation factor deficiency after hepatectomy for HCC, treated with atezolizumab and bevacizumab before surgery. Case presentation A 70-year-old man received right trisegmentectomy of the liver with hepaticojejunostomy for advanced HCC with bile duct invasion, after atezolizumab and bevacizumab therapy. The patient suffered the sudden onset of severe multiple coagulation factor deficiency (II, V, VII, VIII, IX, X, XI and XII) immediately following reoperation for anastomotic leakage of hepaticojejunostomy, 7 days after hepatectomy. The coagulation factor deficiency did not reverse even with intensive treatment, and the patient died of uncontrollable bleeding 32 days after hepatectomy. An IrAE due to atezolizumab was suspected because the patient had developed the possible IrAE of enthesitis of the right gastrocnemius muscle before surgery, and specific inhibitors against factor V and anti-factor V autoantibodies were detected, leading to an ultimate diagnosis of autoimmune FV/5 deficiency (AiF5D). Conclusion Severe acquired coagulopathy should be recognized as a possible life-threatening IrAE when using atezolizumab and bevacizumab for HCC.

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A nutritional assessment tool, GNRI, predicts sarcopenia and its components in type 2 diabetes mellitus: A Japanese cross-sectional study.

Shiroma K, Tanabe H, Takiguchi Y, Yamaguchi M, Sato M, Saito H, Tanaka K, Masuzaki H, Kazama JJ, Shimabukuro M

Frontiers in nutrition ( Frontiers in Nutrition ) 10 1087471 - 1087471 2023 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

BACKGROUND: There are few reports evaluating the relationship between undernutrition and the risk of sarcopenia in type 2 diabetes mellitus (T2DM) patients. OBJECTIVE: We investigated whether undernutritional status assessed by the geriatric nutritional risk index (GNRI) and controlling nutritional status (CONUT) were associated with the diagnosis of sarcopenia. METHODS: This was a cross-sectional study of Japanese individuals with T2DM. Univariate or multivariate logistic regression analysis was performed to assess the association of albumin, GNRI, and CONUT with the diagnosis of sarcopenia. The optimal cut-off values were determined by the receiver operating characteristic (ROC) curve to diagnose sarcopenia. RESULTS: In 479 individuals with T2DM, the median age was 71 years [IQR 62, 77], including 264 (55.1%) men. The median duration of diabetes was 17 [11, 23] years. The prevalence of sarcopenia was 41 (8.6%) in all, 21/264 (8.0%) in men, and 20/215 (9.3%) in women. AUCs were ordered from largest to smallest as follows: GNRI > albumin > CONUT. The cut-off values of GNRI were associated with a diagnosis of sarcopenia in multiple logistic regression analysis (odds ratio 9.91, 95% confidential interval 5.72-17.2), P < 0.001. The superiority of GNRI as compared to albumin and CONUT for detecting sarcopenia was also observed in the subclasses of men, women, body mass index (BMI) < 22, and BMI ≥ 22. CONCLUSIONS: Results showed that GNRI shows a superior diagnostic power in the diagnosis of sarcopenia. Additionally, its optimal cut-off points were useful overall or in the subclasses. Future large and prospective studies will be required to confirm the utility of the GNRI cut-off for undernutrition individuals at risk for sarcopenia.

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Analysis of spot urine biomarkers and association with body weight in Japanese elementary schoolchildren.

Takemoto N, Millman J, Uema T, Yamakawa F, Okamoto S, Mori M, Mori H, Nakamura K, Yamori Y, Masuzaki H

European journal of pediatrics ( European Journal of Pediatrics ) 181 ( 11 ) 3879 - 3888 2022.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Childhood obesity is rapidly increasing worldwide and is largely the consequence of adoption of unhealthy diets excessive in calories and salt (NaCl) as well as devoid in pivotal micronutrients such as potassium (K) and magnesium (Mg). Education-based programs aiming to encourage healthy food knowledge and behaviors are crucial at a young age, and for this purpose, convenient ways to assess daily dietary intake are warranted. We therefore attempted to evaluate the dietary intake of Okinawan schoolchildren in Japan by analyzing a series of biomarkers in morning spot urine samples and explore whether these biomarkers correlate with body weight and a series of metabolic parameters. We enrolled 98 third-grade elementary schoolchildren in Okinawa, Japan. Morning spot urine samples were collected and analyzed using high-performance liquid chromatography (HPLC) to assess dietary intake. We found that estimated daily NaCl intake was higher in obese/overweight children as compared to healthy-weight children (p = 0.0001). There was also a significant positive correlation between body mass index (BMI) and NaCl intake (Spearman) (ρ = 0.45, p < 0.0001) and a negative correlation between BMI and Mg/Cr (ρ = -0.27, p = 0.01). Furthermore, Na/K ratio was higher in samples collected on Monday (weekend) as compared to samples collected on Thursday or Friday (weekday) (p < 0.0001). CONCLUSION: Via the use of morning spot urine analyses, our results show that NaCl intake was associated with obesity, and Mg excretion negatively correlated with BMI in Japanese schoolchildren, highlighting the potential role of these micronutrients in maintaining a healthy body weight. WHAT IS KNOWN: •Overweight and obesity are largely due to excessive consumption of calories and positively correlated with salt (NaCl) intake. •Spot urine methods are convenient for assessing the nutritional needs and targeting prevention programs in children. WHAT IS NEW: •Utilizing morning spot urine analyses, estimated NaCl intake is positively correlated and Mg/Cr negatively correlated with BMI in Okinawan schoolchildren. •As estimated via morning spot urine samples, a greater proportion of children likely exceeds the recommended NaCl intake on the weekend as compared to weekday.

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Profile of gut microbiota and serum metabolites associated with metabolic syndrome in a remote island most afflicted by obesity in Japan.

Uema T, Millman JF, Okamoto S, Nakamura T, Yamashiro K, Uehara M, Honma KI, Miyazato M, Ashikari A, Saito S, Maeda S, Imamura M, Ishida H, Matsushita M, Nakamura K, Masuzaki H

Scientific reports ( Scientific Reports ) 12 ( 1 ) 17292 - 13 2022.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Abstract Numerous studies have revealed distinct differences in the profiles of gut microbiota between non-obese and obese individuals. To date, however, little is known if any disparities in the community of gut microbiota exist between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) subjects. We therefore aimed to comprehensively characterize the gut microbiota and circulating metabolites in serum from both MHO and MUO residing in the remote island, Kumejima, where the prevalence of obesity is one of the highest in Japan, and explored possible correlations between the gut microbiota profile and markers of metabolic syndrome. Results revealed that MUO showed significantly higher levels of genera such as g_Succinivibrio, g_Granulicatella, g_Brachyspira, g_Oribacterium and g_Atopobium in comparison to MHO. Moreover, abundance of g_Succinivibrio, g_Brachyspira and g_Atopobium were positively correlated with value of fasting insulin, HOMA-R, circulating triglycerides, diastolic blood pressure, BMI, body weight, waist circumference and HbA1c. In addition, MUO compared to MHO showed an imbalance of serum metabolites, with a significant elevation in 2-oxoisovaleric acid, pyruvic acid, 2-hydroxybutyric acid, and creatine. Our data highlight unmet needs in precision approaches for the treatment of obesity, targeting the gut microbiota profile and serum metabolites in a distinct population affected by obesity.

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Metabolism, clinical and experimental: seventy years young and growing.

Polyzos SA, Hill MA, Fuleihan GE, Gnudi L, Kim YB, Larson S, Masuzaki H, Matarese G, Sanoudou D, Tena-Sempere M, Mantzoros CS

Metabolism: clinical and experimental ( Metabolism: Clinical and Experimental ) 137 155333 - 155333 2022.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Amyloid beta clearance and microglia: Effects of glycative stress and melatonin

Yonei Yoshikazu, Taira Toshio, Otaka Shino, Sekiguchi Shizuko, Mamun-or-Rashid ANM, Yagi Masayuki, Masuzaki Hiroaki

Glycative Stress Research ( 一般社団法人糖化ストレス研究会 ) 9 ( 3 ) 135 - 145 2022.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

The physiological role of amyloid-β (Aβ) is unknown, while it plays an important role in the onset and progression of Alzheimer's disease (AD). Aβ polymerization leads to enhanced neurotoxicity, persistent degradation, and deposition in the brain, resulting in decreased Aβ clearance. Diabetes mellitus and poor sleep quality are representative risk factors for the development of AD. Methylglyoxal (MGO) and acrolein are increased in diabetic patients, a representative disease with high glycative stress, and melatonin secretion is decreased during poor sleep quality. In this study, we focused on the Aβ phagocytosis of microglia, which plays a role in Aβ clearance, and examined the effects of Aβ glycation and melatonin. Glycated Aβ was prepared by MGO or acrolein treatment. Fluorescently labeled TAMRA-Aβ and primary rat microglial cells (Cosmo Bio) were used in the experiments. Several new findings were obtained from this experiment. First, microglia phagocytose Aβ, while their phagocytic capacity for glycated Aβ was markedly reduced. Second, Aβ phagocytosis was enhanced by melatonin. Concurrently, spontaneous death of cultured microglia was greater when Aβ was not added than when Aβ was. These findings suggest that prevention of Aβ glycation by countermeasures against glycative stress and prevention of AD progression by lifestyle, i.e., improvement of sleep quality, are important, rather than elimination of Aβ as has been conventionally practiced.

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Clinically Amyopathic Dermatomyositis Manifested After the Allogeneic Hematopoietic Stem Cell Transplantation: Case Presentation and Literature Review.

Miyagi R, Nakachi S, Tamaki Y, Doi M, Nakajima T, Kitamura S, Tomori S, Hanashiro T, Tamaki K, Morichika K, Nishi Y, Morishima S, Fukushima T, Masuzaki H

Modern rheumatology case reports ( Modern Rheumatology Case Reports ) 7 ( 1 ) 102 - 107 2022.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

BACKGROUND: Clinically amyopathic dermatomyositis (CADM) lacks muscle symptoms, associating with rapidly progressive interstitial lung disease (RPILD). Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody has been identified as a disease-labeling autoantibody. We report two cases of CADM manifested after the allogeneic hematopoietic stem cell transplantation (allo-HSCT). CASE SERIES: Case 1: A 56-year-old man with acute leukemia received the allo-HSCT. Case 2: A 45-year-old female patient with lymphoma received the allo-HSCT. She received donor lymphocyte infusion (DLI) because of a post-transplant relapse. After allo-HSCT or DLI, Gottron papules emerged, and both patients were diagnosed as CADM based on dermatological findings coupled with the positivity of anti-MDA-5 antibody, accompanied by interstitial shadows consistent with ILD on chest CT. Case 2 was initially diagnosed as a kind of chronic graft versus host disease. Their symptoms were improved by the combination of immunosuppressive agents with a concomitant decrease in anti-MDA-5 antibody levels. For Case 2, Rituximab was subsequently started for relapse of lymphoma, resulting in a substantial decrease in level of anti-MDA-5 antibody and improvement in rash and ILD. CONCLUSION: Our cases raise a possibility that CADM emerges after the HSCT, highlighting the importance of early diagnosis to avoid fated progression into ILD.

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Detecting Sarcopenia Risk by Diabetes Clustering: A Japanese Prospective Cohort Study.

Tanabe H, Hirai H, Saito H, Tanaka K, Masuzaki H, Kazama JJ, Shimabukuro M

The Journal of clinical endocrinology and metabolism ( The Journal of clinical endocrinology and metabolism ) 107 ( 10 ) 2729 - 2736 2022.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Obesity and Voiding Parameters in a Community-Based Population of Okinawa, Japan: Kumejima Digital Health Project (KDHP).

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

Metabolites ( Metabolites ) 12 ( 5 ) 468 - 468 2022.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

(1) Background: Evidence has accumulated regarding the etiology of lower urinary tract symptoms associated with obesity and metabolic syndrome. Therefore, the present study aimed to identify which subjectively and objectively measured voiding parameters were associated with obesity in a community-based population. (2) Methods: Voiding parameters on a self-administered questionnaire and a digital self-health monitoring system for urine excretion (s-HMSU) were compared between participants with and without obesity, defined as a body mass index ≥ 25 kg/m2 (n = 30 and 29, respectively), from a community in Okinawa, Japan. Logistic regression analysis was employed to calculate the odds ratios of abnormalities in voiding parameters for the obese group, with the non-obese group serving as a reference. (3) Results: The obese group had odds ratios of 5.17 (95% confidence interval: 1.33-20.0) for shortened hours of undisturbed sleep (<302 min) by s-HMSU and 7.65 (1.88-31.1) for nighttime urinary frequency by a questionnaire after adjusting for age and sex. In addition, the obese group had an adjusted odds ratio of 2.27 (0.76-6.78) for decreased maximum bladder capacity (<212 mL) by s-HMSU. (4) Conclusion: the results of the present study suggest that nocturia and shortened hours of undisturbed sleep are signs of obesity.

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Fermented brown rice beverage distinctively modulates the gut microbiota in Okinawans with metabolic syndrome: A randomized controlled trial.

Akamine Y, Millman JF, Uema T, Okamoto S, Yonamine M, Uehara M, Kozuka C, Kaname T, Shimabukuro M, Kinjo K, Mitsuta M, Watanabe H, Masuzaki H

Nutrition research (New York, N.Y.) ( Nutrition Research ) 103 68 - 81 2022.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Accumulating evidence to date suggests that brown rice is superior to white rice in regard to its beneficial impact on a number of risk factors of the metabolic syndrome (MetS). However, little is known about the influence of fermented brown rice beverage on the gut microbiota in humans. We therefore hypothesized that its impact would beneficially alter the gut microbiota composition of patients with MetS. Using a 4-week randomized, single-arm study design, subjects (n = 40) were advised to consume a daily fermented brown rice beverage (BA) or fermented white rice beverage (WA) as a replacement of their main meal. Clinical and anthropometric measurements as well as fecal samples were collected at baseline and immediately after completion of the intervention. Gut microbiota was analyzed using 16S ribosomal RNA sequencing and capillary electrophoresis-time-of-flight mass spectrometry was used to measure plasma short-chain fatty acids. Interestingly, ingestion of BA in contrast to WA resulted in a unique elevation in the abundance of number of beneficial species belonging to the Clostridia class, associated with reduced inflammation, and increased short-chain fatty acid production: Lactobacillales bacterium DJF B280 (P = .005), Butyrate producing bacterium A2 207 (P = .012), and Firmicutes bacterium DJF VP44 (P = .038). This study demonstrates that consumption of BA is effective to beneficially modulate the gut microbiota compared with WA in patients with MetS.

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Elevation of the Plasma Levels of TNF Receptor 2 in Association with Those of CD25, OX40, and IL-10 and HTLV-1 Proviral Load in Acute Adult T-Cell Leukemia.

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

Viruses ( Viruses ) 14 ( 4 ) 751 - 751 2022.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Adult T-cell leukemia/lymphoma (ATL) cells express TNF receptor type-2 (TNFR2) on their surface and shed its soluble form (sTNFR2). We previously reported that sTNFR2 levels were highly elevated in the plasma of patients with acute ATL. To investigate whether its quantitation would be helpful for the diagnosis or prediction of the onset of acute ATL, we examined the plasma levels of sTNFR2 in a large number of specimens obtained from a cohort of ATL patients and asymptomatic human T-cell leukemia virus type 1 (HTLV-1) carriers (ACs) and compared them to those of other candidate ATL biomarkers (sCD25, sOX40, and IL-10) by enzyme-linked immunosorbent assays (ELISA) and HTLV-1 proviral loads. We observed that sTNFR2 levels were significantly elevated in acute ATL patients compared to ACs and patients with other types of ATL (chronic, smoldering, and lymphoma). Importantly, sTNFR2 levels were significantly correlated with those of sCD25, sOX40, and IL-10, as well as proviral loads. Thus, the present study confirmed that an increase in plasma sTNFR2 levels is a biomarker for the diagnosis of acute ATL. Examination of plasma sTNFR2 alone or in combination with other ATL biomarkers may be helpful for the diagnosis of acute ATL.

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The power of gut-brain interaction as a promising target for healthy longevity

Masuzaki Hiroaki, Uema Tsugumi, Okamoto Shiki

Glycative Stress Research ( 一般社団法人糖化ストレス研究会 ) 9 ( 1 ) 1 - 6 2022.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Hippocrates, the sage of medicine, famously said, "All disease begins in the gut," The gut-brain axis plays an extremely important role in a high-quality strategy for anti-aging throughout the roughly 100-year life span of humans. When the gut-brain axis is functioning properly, it is possible to maintain a healthy body, mind, and cognitive function, while dysfunction in the gut-brain axis can lead to increased risks of a variety of diseases and subsequent deterioration. From this point of view, we call the unlimited power of the gut-brain interaction "gut-brain axis power" and have focused our attention on the molecular medicine of diet and exercise to enhance gut-brain axis power. The degree of gut-brain power varies greatly from person to person, and the power of gut-brain axis is greatly affected by one's lifestyle, including diet, exercise habits, sleep quality, and stress management. Based on this notion, gut brain power is highlighted as a possible factor X to explain individual and constitutional differences in the development and worsening of complications as well as differences in response to diet, exercise, and drug therapy, all of which have occasionally been overlooked in preventive and clinical medicine. The ingested dietary contents are sensed by enteroendocrine cells (EECs) as nutrients, bile acids, or fermentation metabolites of gut microbiota, and are involved in the regulation of secretion of gut-derived peptide hormones, i.e. CCK, GLP-1, PYY, and ghrelin. These gastrointestinal hormones then act on the central nervous system (brain) to exert a considerable influence on the control of appetite and food preference. In addition to sensing by EEC, the various bioactive substances in the gastrointestinal tracts send information to the brain via blood and lymph flow or directly via spinal afferents, and determine all modes of behaviour, including eating habits and physical activity, whether consciously or unconsciously. The ultimate key to the "behaviour modification" that is being discussed in various aspects of society can be said to be gut brain axis power.

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Impact of anti-diabetic sodium-glucose cotransporter 2 inhibitors on tumor growth of intractable hematological malignancy in humans.

Nakachi S, Okamoto S, Tamaki K, Nomura I, Tomihama M, Nishi Y, Fukushima T, Tanaka Y, Morishima S, Imamura M, Maeda S, Tsutsui M, Matsushita M, Masuzaki H

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie ( Biomedicine and Pharmacotherapy ) 149 112864 - 112864 2022.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Specific Expression of KCC2 in the α Cells of Normal and Type 1 Diabetes Model Mouse Pancreatic Islets.

Shimizu-Okabe C, Okada S, Okamoto S, Masuzaki H, Takayama C

Acta histochemica et cytochemica ( 日本組織細胞化学会 ) 55 ( 1 ) 47 - 56 2022.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the mature brain; however, it acts excitatory during development. This difference in action depends on the intracellular chloride ion concentration, primarily regulated by potassium chloride co-transporter2 (KCC2). Sufficient KCC2 expression results in its inhibitory action. GABA is also abundant in pancreatic islets, where it acts differentially on the islet cells, and is involved in carbohydrate metabolism. However, the mechanisms underlying the differential action remain unknown. We performed immunohistochemistry for glutamic acid decarboxylase (GAD), a synthetic enzyme for GABA, and KCC2 in normal adult islets. GAD was co-localized with insulin in β cells, whereas KCC2 was expressed in glucagon-positive α cells. These results are in line with previous observations that GABA decreases glucagon release but increases insulin release, and suggest that GABA and insulin may work together in reducing blood glucose levels under hyperglycemia. Next, we examined the streptozotocin-induced type1 diabetes mellitus mouse model. GAD and insulin expression levels were markedly decreased. KCC2 was expressed in glucagon-positive cells, whereas insulin- and somatostatin-positive cells were KCC2-negative. These findings suggest that in diabetes model, reduced GABA release may cause disinhibition of glucagon release, resulting in increased blood sugar levels and the maintenance of hyperglycemic state.

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Correction to: Metabolic surgery in treatment of obese Japanese patients with type 2 diabetes: a joint consensus statement from the Japanese Society for Treatment of Obesity, the Japan Diabetes Society, and the Japan Society for the Study of Obesity.

Sasaki A, Yokote K, Naitoh T, Fujikura J, Hayashi K, Hirota Y, Inagaki N, Ishigaki Y, Kasama K, Kikkawa E, Koyama H, Masuzaki H, Miyatsuka T, Nozaki T, Ogawa W, Ohta M, Okazumi S, Shimabukuro M, Shimomura I, Nishizawa H, Saiki A, Seki Y, Shojima N, Tsujino M, Ugi S, Watada H, Yamauchi T, Yamaguchi T, Ueki K, Kadowaki T, Tatsuno I, Joint Committee in the Japanese Society for Treatment of Obesity, the Japan Diabetes Society, the Japan Society for the Study of Obesity.

Diabetology international ( Diabetology International ) 13 ( 1 ) 33 - 34 2022.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Metabolic surgery in treatment of obese Japanese patients with type 2 diabetes: a joint consensus statement from the Japanese Society for Treatment of Obesity, the Japan Diabetes Society, and the Japan Society for the Study of Obesity.

Diabetology international ( Diabetology International ) 13 ( 1 ) 1 - 30 2022.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Bariatric surgery has been shown to have a variety of metabolically beneficial effects for patients with type 2 diabetes (T2D), and is now also called metabolic surgery. At the 2nd Diabetes Surgery Summit held in 2015 in London, the indication for bariatric and metabolic surgery was included in the "algorithm for patients with type T2D". With this background, the Japanese Society for Treatment of Obesity (JSTO), the Japan Diabetes Society (JDS) and the Japan Society for the Study of Obesity (JASSO) have formed a joint committee to develop a consensus statement regarding bariatric and metabolic surgery for the treatment of Japanese patients with T2D. Eventually, the consensus statement was announced at the joint meeting of the 38th Annual Meeting of JSTO and the 41st Annual Meeting of JASSO convened in Toyama on March 21, 2021. In preparing the consensus statement, we used Japanese data as much as possible as scientific evidence to consider the indication criteria, and set two types of recommendation grades, "recommendation" and "consideration", for items for which recommendations are possible. We hope that this statement will be helpful in providing evidence-based high-quality care through bariatric and metabolic surgery for the treatment of obese Japanese patients with T2D. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00551-0.

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Diabetology international ( Diabetology International ) 13 ( 1 ) 31 - 32 2022.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Maternal Urinary Cotinine Concentrations During Pregnancy Predict Infant BMI Trajectory After Birth: Analysis of 89617 Mother-Infant Pairs in the Japan Environment and Children's Study.

Hirai H, Okamoto S, Masuzaki H, Murata T, Ogata Y, Sato A, Horiuchi S, Shinohara R, Shinoki K, Nishigori H, Fujimori K, Hosoya M, Yasumura S, Hashimoto K, Yamagata Z, Shimabukuro M, JECS Group.

Frontiers in endocrinology ( Frontiers in Endocrinology ) 13 850784 - 13 2022 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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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 2021.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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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 2021.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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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 2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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 2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 2021.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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.

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2) Trial Application of IoT and AI for Management of Lifestyle-related Disease

Masuzaki Hiroaki

Nihon Naika Gakkai Zasshi ( The Japanese Society of Internal Medicine ) 110 ( 3 ) 427 - 434 2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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CiNii Research

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 2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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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 2021.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

<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 2021.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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 (n = 142) and non-proliferative DR (n = 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.

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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 2021.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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 2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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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 2020.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 2020.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 2020.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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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 2020.09

Type of publication: Research paper (other science council materials etc.)

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 2020.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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 2020.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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Walking Speed is the Sole Determinant Criterion of Sarcopenia of Mild Cognitive Impairment in Japanese Elderly Patients with Type 2 Diabetes Mellitus.

Machii N, Kudo A, Saito H, Tanabe H, Iwasaki M, Hirai H, Masuzaki H, Shimabukuro M

Journal of clinical medicine ( Journal of Clinical Medicine ) 9 ( 7 ) 1 - 17 2020.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Diabetes mellitus is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of MCI patients with type 2 diabetes mellitus are linked to sarcopenia and/or its criteria remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes mellitus (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, body mass index (BMI), duration of diabetes mellitus, hypertension, dyslipidemia, smoking, drinking, estimated glomerular filtration rate (eGFR), HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This study showed that slow walking speed is a sole determinant criterion of sarcopenia of MCI in patients with type 2 diabetes mellitus. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

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Factors Associated with Risk of Diabetic Complications in Novel Cluster-Based Diabetes Subgroups: A Japanese Retrospective Cohort Study.

Tanabe H, Saito H, Kudo A, Machii N, Hirai H, Maimaituxun G, Tanaka K, Masuzaki H, Watanabe T, Asahi K, Kazama J, Shimabukuro M

Journal of clinical medicine 9 ( 7 ) 2020.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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ヒト生検検体を用いた腎臓周囲と皮下の脂肪組織におけるアディポネクチン発現量とその決定因子(Levels of Adiponectin Expression in Peri-Renal and Subcutaneous Adipose Tissue and Its Determinants in Human Biopsied Samples)

Maimaituxun Gulinu, 福田大受, 井崎博文, 平田陽一郎, 金山博臣, 益崎裕章, 佐田政隆, 島袋充生

日本臨床分子医学会学術総会プログラム・抄録集 ( 日本臨床分子医学会 ) 57回 75 - 75 2020.04 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

マウスにて、エクストラヴァージンオリーブオイルと亜麻仁オイルは粘膜と代謝の健全性を促進し、腸内細菌叢を調節する(Extra virgin olive and flaxseed oils modulate gut microbiota, enhancing mucosal and metabolic health in mice)

ミルマン・ジャスミン, 岡本士毅, 木村碧樹, 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

日本臨床分子医学会学術総会プログラム・抄録集 ( 日本臨床分子医学会 ) 57回 64 - 64 2020.04

Type of publication: Research paper (other science council materials etc.)

Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL.

Guerrero CLH, Yamashita Y, Miyara M, Imaizumi N, Kato M, Sakihama S, Hayashi M, Miyagi T, Karimata K, Uchihara J, Ohshiro K, Todoroki J, Nakachi S, Morishima S, Karube K, Tanaka Y, Masuzaki H, Fukushima T

Blood advances ( Blood Advances ) 4 ( 6 ) 1062 - 1071 2020.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)-associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch's t test P < .00001), high discrimination capacity (area under the curve >0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.

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Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing.

Yotsumoto J, Sekizawa A, Inoue S, Suzumori N, Samura O, Yamada T, Miura K, Masuzaki H, Sawai H, Murotsuki J, Hamanoue H, Kamei Y, Endo T, Fukushima A, Katagiri Y, Takeshita N, Ogawa M, Nishizawa H, Okamoto Y, Tairaku S, Kaji T, Maeda K, Matsubara K, Ogawa M, Osada H, Ohba T, Kawano Y, Sasaki A, Sago H, Japan NIPT Consortium

BMC pregnancy and childbirth 20 ( 1 ) 112 2020.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The Incidence of Dichorionic Diamniotic Twin Pregnancy After Single Blastocyst Embryo Transfer and Zygosity: 8 Years of Single-Center Experience.

Konno H, Murakoshi T, Miura K, Masuzaki H

Twin research and human genetics : the official journal of the International Society for Twin Studies 23 ( 1 ) 51 - 54 2020.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction.

Maimaituxun G, Yamada H, Fukuda D, Yagi S, Kusunose K, Hirata Y, Nishio S, Soeki T, Masuzaki H, Sata M, Shimabukuro M

Circulation journal : official journal of the Japanese Circulation Society ( 一般社団法人日本循環器学会 ) 84 ( 2 ) 203 - 216 2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Background:Although full-volume quantification of epicardial adipose tissue (EAT) is a predictor of LV diastolic dysfunction (LVDD), how localized EAT depots are linked to LVDD remains unclear. We evaluated the effect of local EAT depots on LV diastolic function parameters in patients with preserved LV ejection fraction (LVEF).Methods and Results:From 423 consecutive patients who underwent cardiac CT angiography, we recruited 252 with sinus rhythm and normal LVEF. The EAT volume index (EATV/body surface area) and the localized EAT thickness around the right coronary artery (EATRCA), left anterior descending artery (EATLAD), left circumflex artery (EATLCX), right ventricle (EATRV), left ventricle (EATLV), right atrium (EATRA), and left atrium (EATLA) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m2, P=0.010), EATLCX(10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EATLV(2.6±1.6 vs. 2.1±1.4 mm, P=0.024) were greater than in the non-LVDD group (n=181). In contrast, EATLCXand EATLVwere markedly associated with decreased lateral e' and increased lateral E/e'. Multiple regression analysis indicated that EATLCXand EATLVwere strongly associated with LV diastolic function parameters.Conclusions:Localized EAT depots are linked to altered mitral annular motion. Further study is warranted to clarify whether localized EAT depots are functionally linked to the clinical manifestations of LVDD.

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Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction

Gulinu Maimaituxun, Hirotsugu Yamada, Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Yukina Hirata, Susumu Nishio, Takeshi Soeki, Hiroaki Masuzaki, Masataka Sata, Michio Shimabukuro

Circulation Journal ( Japanese Circulation Society ) 84 ( 2 ) 203 - 216 2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A combination of dietary fat intake and nicotine exposure enhances CB1 endocannabinoid receptor expression in hypothalamic nuclei in male mice.

Guo T, Tanaka T, Matsumoto M, Kaneko K, Unzai T, Ogino Y, Aotani D, Kusakabe T, Iwakura H, Miyazawa T, Sawamoto K, Minokoshi Y, Masuzaki H, Inagaki N, Nakao K

Neuroscience letters ( Neuroscience Letters ) 714 134550 - 134550 2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

BACKGROUND: Cannabinoid receptor 1 (CB1R) is a GPCR expressed widely in the brain as well as in peripheral metabolic organs. Although pharmacological blockade of CB1R has been effective for the treatment of obesity and tobacco addiction, precise distribution of CB1R within the brain and potential changes by obesity or nicotine exposure have not been thoroughly addressed. METHODS: To examine CB1R distribution within the central energy center, we performed immunostaining and qPCR analysis of micro-dissected hypothalamic nuclei from male C57BL/6 mice. To address the effect of nicotine on food intake and body weight, and on potential changes of CB1R levels in the hypothalamus, mice kept on a high fat diet (HFD) for four weeks were challenged with nicotine intraperitoneally. RESULTS: Validity of the micro-dissected samples was confirmed by the expression of established nucleus-enriched genes. The expression levels of CB1R in the arcuate and lateral nuclei of the hypothalamus were higher than paraventricular and ventral-dorsal medial nuclei. Nicotine administration led to a significant suppression of food intake and body weight either under standard or high fat diet. Neither HFD nor nicotine alone altered CB1R levels in any nucleus tested. By contrast, treatment of HFD-fed mice with nicotine led to a significant increase in CB1R levels in the arcuate, paraventricular and lateral nuclei. CONCLUSIONS: CB1R was widely distributed in multiple hypothalamic nuclei. The expression of CB1R was augmented only when mice were treated with HFD and nicotine in combination. These data suggest that the exposure to nicotine may provoke an enhanced endocannabinoid response in diet-induced obesity.

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Tomori S, Morishima S, Nishi Y, Nakachi S, Tamaki K, Morichika K, Tedokon I, Shimabukuro N, Hanashiro T, Kitamura S, Uchibori S, Miyagi R, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tomoyose T, Karube K, Fukushima T, Masuzaki H

Bone marrow transplantation ( Bone Marrow Transplantation ) 55 ( 1 ) 233 - 241 2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with adult T cell leukemia/lymphoma (ATL) are not satisfactory, particularly in patients in non-complete remission at transplantation (Pt-non-CR). We conducted a regional retrospective study in the ATL endemic area of Okinawa, Japan. Of 62 ATL patients, 21 received allo-HSCT in CR and 41 in non-CR. The 3-year overall survival (3yOS) rate and median survival time for the whole cohort was 25.6% and 7.7 months, respectively. The 3yOS of Pt-non-CR was significantly lower than that of patients in CR (Pt-CR) (16.8% vs. 43.6%, P = 0.005). Transplant-related mortality (TRM) was significantly higher in Pt-non-CR than in Pt-CR (46.3% vs. 15.7%, P = 0.025), while there was no significant difference in disease-associated mortality (DAM) between Pt-non-CR and Pt-CR. Multivariable analysis for Pt-non-CR revealed that poor performance status (poor-PS) and higher sIL-2R level (high sIL-2R) adversely affected OS. Poor-PS was associated with higher TRM, but not with higher DAM in Pt-non-CR. High sIL-2R did not affect TRM or DAM in Pt-non-CR. Overall, high TRM rates rather than DAM contribute to the poor outcomes of Pt-non-CR, suggesting that not only disease control but also management of transplant-related complications is required for allo-HSCT in ATL patients.

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Impaired early-phase suppression of glucagon secretion after glucose load is associated with insulin requirement during pregnancy in gestational diabetes.

Horie I, Haraguchi A, Ito A, Nozaki A, Natsuda S, Akazawa S, Mori Y, Ando T, Higashijima A, Hasegawa Y, Yoshida A, Miura K, Masuzaki H, Kawakami A, Abiru N

Journal of diabetes investigation 11 ( 1 ) 232 - 240 2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16(INK4a) Expression.

Kawashita S, Matsuda K, Kondo H, Kitajima Y, Hasegawa Y, Shimada T, Kitajima M, Miura K, Nakashima M, Masuzaki H

Cancer control : journal of the Moffitt Cancer Center 27 ( 1 ) 1073274819901170 2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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人生100年時代の健康長寿の展望と課題:～沖縄クライシスからのレッスン～

益崎裕章

理学療法学Supplement ( 公益社団法人日本理学療法士協会 ) 47 ( 0 ) G - 10-G-10 2020 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

世界に冠たる健康長寿を誇ってきた沖縄県は現在，2型糖尿病や肥満症が蔓延し，65歳までに死亡する割合（早逝率）や糖尿病患者の血液透析導入率は全国トップレベルにあります。2017年の47都道府県平均寿命ランキングでは沖縄県の男性が36位，女性が7位にまで後退しており，この驚くべき現実を私達，琉球大学第二内科で"沖縄クライシス"と命名し，この10年間，その実態解明と啓発に取り組んできました。日本で最後の国立大学医学部として琉球大学医学部が新設された1980年当時の80歳台，90歳台の沖縄県民患者の解剖所見によると，大動脈や冠状動脈の粥状動脈硬化や石灰化が殆ど認められず，血管年齢の若々しさに病理医たちが驚嘆した様子が記録されています。戦後の沖縄県民の脂肪エネルギー摂取比率は常に全国平均よりも5%以上上回っており，動脈硬化症の温床となる肥満症，糖尿病，脂質異常症の蔓延と平均寿命ランキングの降下が見事な好対照をなしています。　健康に良くないと理屈ではわかっていても食べ過ぎや運動不足から脱却できないのはなぜでしょう？私達は2型糖尿病や肥満症の発症基盤にある"脳機能の異常"に注目し，脳科学と分子栄養学を用いて食事・運動療法の実効性を高める行動変容の分子基盤の解明に取り組んでいます。動物性脂肪の過剰摂取は脳をハッキングし，自らが必要とするエネルギー量や栄養成分を判断できない脳に変えてしまいます。このメカニズムには食欲中枢である視床下部における小胞体ストレスの上昇や幸せや歓びを受け取る報酬系におけるゲノム修飾というイヴェントが深く関わっています（Diabetologia 2017, Diabetes 2012）。また，肥満や動物性脂肪の過剰摂取に伴う脂肪細胞ホルモン，レプチンの作用不全（レプチン抵抗性）は脳内報酬系のドパミン神経に発現するレプチン受容体シグナルを介して運動欲求を低下させ，体重が増えていくほど，運動する意欲が減退してしまい，ますます太りやすくなります。運動嫌いな患者さんの脳の中ではこのようなことが生じていると考えられます。　本講演では運動や食事と生活習慣病との関わりをめぐる最新の医学エビデンスを御紹介し，効果的な行動変容を実現するための理学療法の重要性に言及したいと思います。

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Chest Computed Tomography Abnormalities and Their Relationship to the Clinical Manifestation of Respiratory Syncytial Virus Infection in a Genetically Confirmed Outbreak.

Nabeya D, Kinjo T, Parrott GL, Nakachi S, Yamashiro T, Ikemiyagi N, Arakaki W, Masuzaki H, Fujita J

Internal medicine (Tokyo, Japan) ( 一般社団法人日本内科学会 ) 59 ( 2 ) 247 - 252 2020 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Studies reporting chest images of respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) in an outbreak setting and their relationship to the clinical manifestation are limited. During a genetically confirmed RSV outbreak, eight patients underwent both chest X-ray and computed tomography (CT). Among these, 5 cases had newly appearing abnormalities on CT, although chest X-ray was able to detect abnormalities in only 2 cases (40%). Although bronchial wall thickening was common, other findings and their distribution were variable, even in an outbreak setting. All patients with both a history of anticancer chemotherapy against hematological cancer and lower respiratory symptoms, such as wheezing, sputum, and hypoxemia, had abnormalities on CT, suggesting that these two factors might be important for predicting the existence of LRTI in RSV-infected patients.

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Safety and efficacy of nanoparticulated brown rice germ extract on reduction of body fat mass and improvement of fuel metabolism in both pre-obese and mild obese subjects without excess of visceral fat accumulation.

Masuzaki Hiroaki, Fukuda Kotaro, Ogata Mika, Kinjo Ayano, Matsuo Takeru, Nishihira Jun

Glycative Stress Research ( 一般社団法人糖化ストレス研究会 ) 7 ( 1 ) 1 - 12 2020 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Beneficial effects on obesity and dysmetabolism of a variety of functional ingredients contained in brown rice have attracted academic as well as clinical attention. On the other hand, it is noteworthy that the absorption efficiency of some of the functional ingredients derived from brown rice from the digestive tract is significantly low. Based on these backgrounds, we developed the “nanoparticulated brown rice germ extract” by encapsulating brown rice germ extract containing γ-oryzanol, one of the functional ingredients abundantly and specifically in brown rice (rice bran), in nanoparticles, and conducted safety and efficacy tests in humans. The present study was performed appropriately after the approval from the ethics committee of Hokkaido Information University. Japanese men and women whose BMI is 23 kg/m2 or more and less than 25 kg/m2, or 25 kg/m2 or more and less than 30 kg/m2, and whose visceral fat area is less than 100 cm2 when measured by bioelectric-impedance methods were recruited for the study. We conducted a placebo-controlled, randomized, double-blind, parallel-group comparative study targeting approximately 78 people who met the eligible criteria, and examined metabolic improvements when the “nanoparticulated brown rice germ extract” tablets were ingested once-a-day continuously for 12 weeks. Although a decreasing trend was observed in the abdominal visceral fat area, which is a primary endpoint, there were no significant differences among the ingestion groups of test food (low dose group: 5 mg, and medium-dose group: 10 mg). Among the secondary endpoints, plasma LDL-cholesterol (LDL-C) level showed a marginally significant decrease in the medium and low dose (5 mg) groups compared to the control group (placebo ingestion) after 8 weeks of ingestion (p = 0.078, p = 0.098). The plasma lipid ratio (LDL-C/HDL-C) showed a significant decrease in the low dose group compared to the control group after 4 and 8 weeks of ingestion (p = 0.016, p = 0.018). The plasma non-HDL-C level showed a marginally significant or significant decrease in the medium and low dose groups compared to the control group after 8 weeks of ingestion (p = 0.099, p = 0.031). Blood level of HbA1c also showed a significant decrease in the medium-dose group compared to the control group after 4, 8, and 12 weeks of ingestion (p = 0.029, p = 0.011, p = 0.011). Furthermore, plasma level of adiponectin, which has potent anti-atherosclerotic actions, showed a marked increase in the high, medium, and low dose groups (p = 0.012, p = 0.039, p = 0.017) after 4 weeks of ingestion compared to the control group, and also showed a marginally significant or significant increase after 8 and 12 weeks of ingestion. During the hospital visit, problematic changes were not observed in blood pressure, pulse rate, general blood tests, liver and kidney functions, and urinalysis, and adverse events suggesting a causal relationship with the test food were not observed. This clinical intervention study confirmed the safety of ingestion of the “nanoparticulated brown rice germ extract”, which was also proven to improve the atherogenic lipid profile, reduce HbA1c level, and increase plasma adiponectin concentration. Results obtained tempt us to expect that nanoparticulated brown rice germ extract is well eligible for practical use.

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Deleterious Effects of Epicardial Adipose Tissue Volume on Global Longitudinal Strain in Patients With Preserved Left Ventricular Ejection Fraction.

Maimaituxun G, Kusunose K, Yamada H, Fukuda D, Yagi S, Torii Y, Yamada N, Soeki T, Masuzaki H, Sata M, Shimabukuro M

Frontiers in cardiovascular medicine ( Frontiers in Cardiovascular Medicine ) 7 607825 - 607825 2020 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function. Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%. Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116-117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects. Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.

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AMH Concentrations in Peritoneal Fluids of Women With and Without Endometriosis.

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

Frontiers in surgery 7 600202 2020 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Huge uterine fibroid arising from primary uterine cervical diverticulum: a case report and review of the literatures.

Noguchi M, Kitajima M, Abe S, Murakami N, Kitajima Y, Miura K, Masuzaki H

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 39 ( 8 ) 1186 - 1187 2019.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Somatic Mutations and Loss of Heterozygosity of HLA Genes Are Frequently Occurred and Tightly Associated with Poor Prognosis in Adult T Cell Leukemia-Lymphoma

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

BLOOD ( AMER SOC HEMATOLOGY ) 134 2019.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A pilot assessment of xanthine oxidase activity in plasma from patients with hematological malignancies using a highly sensitive assay.

Hokama N, Shirakura T, Sunagawa S, Morishima S, Nakachi S, Nishi Y, Murayama Y, Matsui C, Hase N, Tamura M, Okamoto S, Shimabukuro M, Nakamura K, Masuzaki H

Hematological oncology ( Hematological Oncology ) 37 ( 4 ) 527 - 530 2019.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Extra virgin oliveおよび亜麻仁油は腸内細菌叢を調節しマウス粘膜および代謝の正常化を促す(Extra virgin olive and flaxseed oil modulate gut microbiota, enhancing mucosal & metabolic health in mice)

Frances Millman Jasmine, 岡本士毅, 山崎聡, 上間次己, 益崎裕章

肥満研究 ( (一社)日本肥満学会 ) 25 ( Suppl. ) 260 - 260 2019.10

Type of publication: Research paper (other science council materials etc.)

Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T-cell leukemia/lymphoma.

Morichika K, Karube K, Kayo H, Uchino S, Nishi Y, Nakachi S, Okamoto S, Morishima S, Ohshiro K, Nakazato I, Fukushima T, Masuzaki H

Cancer science ( Cancer Science ) 110 ( 9 ) 2982 - 2991 2019.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. Based on previous integrated molecular analyses suggesting the importance of the JAK-STAT pathway in ATLL, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Expression of pSTAT3 was observed in 43% (50/116) of ATLL cases, whereas pSTAT5 and pSTAT6 were largely undetected. Cases with the lymphoma type showed significantly less frequent pSTAT3 expression (8/45, 18%) than those with the other subtypes (41/66, 62%; P < .001). STAT3 mutations were detected in 36% (10/28) and 19% (12/64) of cases with the smoldering and aggressive types of ATLL, respectively. The correlation between STAT3 mutation and pSTAT3 expression was not significant (P = .07). Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression-free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data show that only the lymphoma type showed a low prevalence of tumor cells positive for pSTAT3 expression, and raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.

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Adipose tissue-derived mesenchymal stem cells ameliorate bone marrow aplasia related with graft-versus-host disease in experimental murine models.

Nishi Y, Murakami A, Murayama Y, Tsukahara N, Okamoto S, Nakachi S, Morichika K, Tamaki K, Noguchi H, Matsushita M, Karube KN, Fukushima T, Morishima S, Kishimoto H, Masuzaki H

Transplant immunology ( Transplant Immunology ) 55 101205 - 101205 2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Graft-versus-host disease (GVHD) constitutes the most frequent complications after the allogeneic hematopoietic stem cell transplantation for a variety of hematological malignancies. In the present study, we explored the prophylactic potential of adipose tissue-derived mesenchymal stem cells (AD-MSCs) in controlling GVHD in murine models with a special focus on bone marrow aplasia related with acute GVHD. The CB6F1 mice were induced GVHD by the injection intravenously of C57BL/6 (B6-Ly-5.1) splenocytes without conditioning irradiation or chemotherapy. AD-MSCs from C3H mice were injected intravenously via tail veins. GVHD was assessed using flowcytometry analysis of peripheral blood cells and histopathologic analysis of target organs. Histopathological analyses revealed that AD-MSCs markedly suppressed the infiltration of lymphocytes into liver as well as the aplasia in bone marrow. This study is the first to clarify the effectiveness of AD-MSCs against bone marrow aplasia in GVHD, supporting a rationale of AD-MSCs for ameliorating bone marrow suppression and infectivity after allo-HSCT in human clinics.

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A pilot assessment of xanthine oxidase activity in plasma from patients with hematological malignancies using a highly-sensitive assay

Hokama N, Shirakura T, Sunagawa S, Morishima S, Nakachi S, Nishi Y, Murayama Y, Matsui C, Hase N, Tamura M, Okamoto S, Shimabukuro M, Nakamura K, Masuzaki H

Hematological Oncology 37 ( 4 ) 527 - 530 2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Comprehensive immune complexome analysis detects disease-specific immune complex antigens in seminal plasma and follicular fluids derived from infertile men and women.

Murakami N, Kitajima M, Ohyama K, Aibara N, Taniguchi K, Wei M, Kitajima Y, Miura K, Masuzaki H

Clinica chimica acta; international journal of clinical chemistry 495 545 - 551 2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T-cell leukemia/lymphoma: Possible role of STAT3 phosphorylation in clinical subtype, progression, and prognosis

Morichika K, Karube K, Kayo H, Uchino S, Nishi Y, Nakachi S, Okamoto S, Morishima S, Ohshiro K, Nakazato I, Fukushima T, Masuzaki H

Cancer Sci 110 ( 9 ) 2982 - 2991 2019.07 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Validation of a novel digital health monitoring system to measure the volume of voided urine.

Miyazato M, Yonemoto K, Ashikari A, Saito S, Yamashiro K, Uehara M, Masuzaki H, Ishida H, Matsushita M

Neurourology and urodynamics ( Neurourology and Urodynamics ) 38 ( 4 ) 1106 - 1110 2019.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

AIM: To validate a novel digital health monitoring system to measure the volume of voided urine. METHODS: Micturition volume was calculated using our novel digital self-health monitoring system of urine excretion (s-HMSU) in 18 participants (16 women and 2 men; average age, 40.8 years), without a history of voiding symptoms. Participants completed a self-reported questionnaire regarding their medical history and water intake during the period of observation, as well as the Core Lower Urinary Tract Symptom Score (CLSS) questionnaire. To assess the reliability of the voided volumes measured using the s-HMSU, the intraclass correlation coefficient (ICC) was calculated between the volume and the change in body weight before and after micturition. RESULTS: The CLSS questionnaire confirmed the absence of urinary system diseases in all participants. The medical history was also negative with the exception of hypertension in one participant. The ICC (1,1) between the measured volume of urine excretion using the s-HMSU and the change in body weight was 0.972 (95% confidence interval, 0.957-0.982). CONCLUSIONS: The s-HMSU system provides a reliable measure of voiding volume and is appropriate for home use. It has the potential to facilitate large-scale clinical research to examine the relationship between medical diseases and voiding dysfunction.

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Adipose tissue-derived mesenchymal stem cells ameliorate bone marrow aplasia related with graft-versus-host disease in experimental murine models

Nishi Y, Murakami A, Murayama Y, Tsukahara N, Okamoto S, Nakachi S, Morichika K, Tamaki K, Noguchi H, Matsushita M, Karube K, Fukushima T, Morishima S, Kishimoto H, Masuzaki H

Transplant Immunology 55 101205 2019.04 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Validation of a novel digital health monitoring system to measure the volume of voided urine

Miyazato M, Yonemoto K, Ashikari A, Saito S, Yamashiro K, Uehara M, Masuzaki H, Ishida H, Matsushita M

Neurourol Urodyn 38 ( 4 ) 1106 - 1110 2019.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Levels of Adiponectin Expression in Peri-Renal and Subcutaneous Adipose Tissue and Its Determinants in Human Biopsied Samples.

Maimaituxun G, Fukuda D, Izaki H, Hirata Y, Kanayama HO, Masuzaki H, Sata M, Shimabukuro M

Frontiers in endocrinology ( Frontiers in Endocrinology ) 10 897 - 897 2019.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Background: The interactions of adipose tissue with the kidney are hypothesized to affect kidney function. Also, excessive peri-renal fat may increase the risk of cardiometabolic risk. However, the role(s) of peri-renal fat adipocytokine has never been evaluated. Objectives: To elucidate levels of adiponectin expression in peri-renal and subcutaneous adipose tissue and its determinants in human biopsied samples. Methods: A pair of subcutaneous and perirenal fat tissue samples were collected from 80 patients (men: 54; women: 26) who underwent urological operations. Subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area and peri-renal adipose tissue (RAT) volume were quantified on abdominal computed tomography. Cytokine/adipocytokine expression was evaluated by real-time semi-quantitative polymerase chain reaction (qPCR). Probability was considered significant if P < 0.05. Results: Current study evaluated determinants of plasma adiponectin levels and expression levels of adiponectin in SAT and RAT in human samples. We found that: first, plasma adiponectin levels were correlated with VAT area but not with BMI, waist circumference, SAT area, and RAT volume; second, expression levels of adiponectin in SAT were correlated with BMI, waist circumference, and SAT area but not with VAT area and RAT volume; and third, expression levels of adiponectin in RAT were correlated with all adiposity indices including BMI, waist circumference, SAT area, VAT area, and RAT volume. Conclusion: This study evaluated levels of adiponectin expression in RAT and SAT and its determinants in patients who underwent urological operation. Levels of adiponectin mRNA in RAT were negatively correlated with remote fat mass in SAT and VAT and also with local fat mass in RAT, while level of adiponectin in SAT was not correlated with RAT volume. Further studies are warranted to evaluate roles of peri-renal fat mass accumulation and its pathophysiological machineries.

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Radiation-induced dermatitis after administration of mogamulizumab for adult T-cell leukaemia/lymphoma: a multi-institutional retrospective study.

Maemoto H, Ariga T, Kusada T, Heianna J, Manabe Y, Miyakawa A, Nakachi S, Morishima S, Iraha S, Ganaha F, Masuzaki H, Murayama S

Japanese journal of clinical oncology ( Japanese Journal of Clinical Oncology ) 49 ( 2 ) 153 - 159 2019.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Appropriate radiation dose for symptomatic relief and local control in patients with adult T cell leukemia/lymphoma.

Maemoto H, Ariga T, Nakachi S, Toita T, Hashimoto S, Heianna J, Shiina H, Kusada T, Makino W, Kakinohana Y, Miyagi T, Yamamoto Y, Morishima S, Masuzaki H, Murayama S

Journal of radiation research ( Journal of Radiation Research ) 60 ( 1 ) 98 - 108 2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Activity of xanthine oxidase in plasma correlates with indices of insulin resistance and liver dysfunction in patients with type 2 diabetes mellitus and metabolic syndrome: A pilot exploratory study.

Sunagawa S, Shirakura T, Hokama N, Kozuka C, Yonamine M, Namba T, Morishima S, Nakachi S, Nishi Y, Ikema T, Okamoto S, Matsui C, Hase N, Tamura M, Shimabukuro M, Masuzaki H

Journal of diabetes investigation ( Journal of Diabetes Investigation ) 10 ( 1 ) 94 - 103 2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Brown rice-specific γ-oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans.

Masuzaki H, Kozuka C, Okamoto S, Yonamine M, Tanaka H, Shimabukuro M

Journal of diabetes investigation ( Journal of Diabetes Investigation ) 10 ( 1 ) 18 - 25 2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Activity of xanthine oxidase in plasma correlates with indices of insulin resistance and liver dysfunction in patients with type 2 diabetes mellitus and metabolic syndrome: A pilot exploratory study

Sunagawa S, Shirakura T, Hokama N, Kozuka C, Yonamine M, Namba T, Morishima S, Nakachi S, Nishi Y, Ikema T, Okamoto S, Matsui C, Hase N, Tamura M, Shimabukuro M, Masuzaki H

J Diabetes Investig 10 ( 1 ) 94 - 103 2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Brown rice-specific -oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans

Masuzaki H (senior, corresponding author, Kozuka C, Okamoto S, Yonamine M, Tanaka H, Shimabukuro M

J Diabetes Investig 10 ( 1 ) 18 - 25 2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Appropriate radiation dose for symptomatic relief and local control in patients with adult T cell leukemia/lumphoma

Maemoto H, Ariga T, Nakachi S, Toita T, Hashimoto S, Heianna J, Shiina H, Kusada T, Makino W, Kakinohana Y, Miyagi T, Yamamoto Y, Morishima S, Masuzaki H, Murayama M

Journal of Radiation Research 60 ( 1 ) 98 - 108 2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

Suzumori N, Sekizawa A, Takeda E, Samura O, Sasaki A, Akaishi R, Wada S, Hamanoue H, Hirahara F, Kuriki H, Sawai H, Nakamura H, Yamada T, Miura K, Masuzaki H, Yamashita T, Kamei Y, Namba A, Murotsuki J, Tanemoto T, Fukushima A, Haino K, Tairaku S, Matsubara K, Maeda K, Kaji T, Ogawa M, Osada H, Nishizawa H, Okamoto Y, Kanagawa T, Kakigano A, Endo M, Kitagawa M, Ogawa M, Izumi S, Katagiri Y, Takeshita N, Kasai Y, Naruse K, Neki R, Masuyama H, Hyodo M, Kawano Y, Ohba T, Ichizuka K, Nagamatsu T, Watanabe A, Nishikawa N, Hamajima N, Shirato N, Yotsumoto J, Nishiyama M, Koide K, Hirose T, Sago H

Prenatal diagnosis 39 ( 2 ) 100 - 106 2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Usefulness of Epicardial Adipose Tissue Volume to Predict Recurrent Atrial Fibrillation After Radiofrequency Catheter Ablation.

Maeda M, Oba K, Yamaguchi S, Arasaki O, Sata M, Masuzaki H, Shimabukuro M

The American journal of cardiology ( American Journal of Cardiology ) 122 ( 10 ) 1694 - 1700 2018.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with post-ablation atrial fibrillation (AF), ranges of EATV predictive of post-ablation recurrence of AF remain unclear. In this study, we evaluated: (1) relationships between EATV and characteristics of AF, (2) impact of EATV on recurrent AF after radiofrequency ablation; , and (3) cut-off point for recurrent AF using a receiver operating characteristic curve. In 218 consecutive symptomatic patients undergoing who underwent ablation for AF (143 paroxysmal AF; 78 persistent AF), the EATV index (EATVI: EATV/body surface area, mL/m2) was measured using 320-row multidetector computed tomography. The high EATV group showed specific cardiometabolic derangements as well as left atrial dilatation and left ventricular dysfunction. Multivariate regression analysis showed that the EATVI was an independent predictor of recurrent AF after catheter ablation. High EATV (EATVI ≥ 85 mL/m2) or EATVI cutoff ≥116 mL/m2 can predict recurrent AF after catheter ablation, independent of other risk factors. In conclusion, EATVI was an independent predictor of recurrent AF after catheter ablation; a high EATV tertile or EATVI cutoff may be useful for prediction of recurrent AF after catheter ablation. Future studies should determine the utility of the EATVI in the clinical setting of AF ablation.

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Correction: Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

Miyake H, Yamada S, Fujii Y, Sawai H, Arimori N, Yamanouchi Y, Ozasa Y, Kanai M, Sago H, Sekizawa A, Takada F, Masuzaki H, Matsubara Y, Hirahara F, Kugu K

Journal of human genetics 63 ( 11 ) 1195 2018.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Minimal Shortening of Leukocyte Telomere Length Across Age Groups in a Cross-Sectional Study for Carriers of a Longevity-Associated FOXO3 Allele.

Davy PMC, Willcox DC, Shimabukuro M, Donlon TA, Torigoe T, Suzuki M, Higa M, Masuzaki H, Sata M, Chen R, Murkofsky RL, Morris BJ, Lim E, Allsopp RC, Willcox BJ

The journals of gerontology. Series A, Biological sciences and medical sciences ( Journals of Gerontology - Series A Biological Sciences and Medical Sciences ) 73 ( 11 ) 1448 - 1452 2018.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Minimal shortening of leukocyte telomere length across age groups in a cross-sectional study for carriers of a longevity-associated FOXO3 allele

Davy PMC, Willcox DC, Shimabukuro M, Donlon TA, Torigoe T, Suzuki M, Higa M, Masuzaki H, Sata M, Chen R, Murkofsky R, Morris BJ, Lim E, Allsopp RC, Willcox BJ

J Gerontol A Biol Sci Med Sci 73 ( 11 ) 1448 - 1452 2018.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Usefulness of epicardial adipose tissue volume to predict recurrent atrial fibrillation after radiofrequency catheter ablation

Maeda M, Oba K, Yamaguchi S, Arasaki O, Sata M, Masuzaki H, Shimabukuro M

Am J Cardiol 122 ( 10 ) 1694 - 1700 2018.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Embryonic development of GABAergic terminals in the mouse hypothalamic nuclei involved in feeding behavior

Kobayashi M, Shimizu-Okabe C, Kim J, Kobayashi S, Matsushita M, Masuzaki H, Takayama C

Neurosci Res 134 39 - 48 2018.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Embryonic development of GABAergic terminals in the mouse hypothalamic nuclei involved in feeding behavior.

Kobayashi M, Shimizu-Okabe C, Kim J, Kobayashi S, Matsushita M, Masuzaki H, Takayama C

Neuroscience research ( Neuroscience Research ) 134 39 - 48 2018.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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高悪性度成人T細胞白血病/リンパ腫の予後予測におけるFDG-PET/CTの有用性(Clinical usefulness of FDG-PET/CT for predicting prognosis of aggressive ATL)

仲地佐和子, 森島聡子, 岡田真広, 東江ゆりか, 内堀幸恵, 北村紗希子, 友利昌平, 花城多恵子, 島袋奈津紀, 玉城啓太, 手登根伊織, 森近一穂, 西由希子, 加留部謙之輔, 福島卓也, 益崎裕章

臨床血液 ( (一社)日本血液学会-東京事務局 ) 59 ( 9 ) 1597 - 1597 2018.09

Type of publication: Research paper (other science council materials etc.)

Protective Role of Myelocytic Nitric Oxide Synthases against Hypoxic Pulmonary Hypertension in Mice.

Ogoshi T, Tsutsui M, Kido T, Sakanashi M, Naito K, Oda K, Ishimoto H, Yamada S, Wang KY, Toyohira Y, Izumi H, Masuzaki H, Shimokawa H, Yanagihara N, Yatera K, Mukae H

American journal of respiratory and critical care medicine ( American Journal of Respiratory and Critical Care Medicine ) 198 ( 2 ) 232 - 244 2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Evaluation of two prognostic indices for adult T cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan

Tamaki K, Morishima S, Nomura S, Nishi Y, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Taira N, Tomoyose T, Takashi Miyagi T, Karimata K, Ohama M, Yamanoha A, Tamaki K, Hayashi M, Uchihara J, Ohshiro K, Asakura Y, Kuba-Miyara M, Karube K, Fukushima T, Masuzaki H

Cancer Sci 109 ( 7 ) 2286 - 2293 2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Protective Role of Myelocytic Nitric Oxide Synthases Against Hypoxic Pulmonary Hypertension in Mice

Ogoshi T, Tsutsui M, Kido T, Sakanashi M, Naito K, Oda K, Ishimoto H, Yamada S, Wang KY, Toyohira Y, Izumi H, Masuzaki H, Shimokawa H, Yanagihara N, Yatera K, Mukae H

Am J Respir Crit Care Med 198 ( 2 ) 232 - 244 2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Evaluation of two prognostic indices for adult T-cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.

Tamaki K, Morishima S, Nomura S, Nishi Y, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Taira N, Tomoyose T, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tamaki K, Hayashi M, Uchihara JN, Ohshiro K, Asakura Y, Kuba-Miyara M, Karube K, Fukushima T, Masuzaki H

Cancer science ( Cancer Science ) 109 ( 7 ) 2286 - 2293 2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The efficacy of adjunct tacrolimus treatment in pregnancy outcomes in patients with systemic lupus erythematosus.

Ichinose K, Sato S, Kitajima Y, Horai Y, Fujikawa K, Umeda M, Fukui S, Nishino A, Koga T, Kawashiri SY, Iwamoto N, Tamai M, Nakamura H, Origuchi T, Yasuhi I, Masuzaki H, Kawakami A

Lupus 27 ( 8 ) 1312 - 1320 2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.

Oba K, Maeda M, Maimaituxun G, Yamaguchi S, Arasaki O, Fukuda D, Yagi S, Hirata Y, Nishio S, Iwase T, Takao S, Kusunose K, Yamada H, Soeki T, Wakatsuki T, Harada M, Masuzaki H, Sata M, Shimabukuro M

Circulation journal : official journal of the Japanese Circulation Society ( 一般社団法人日本循環器学会 ) 82 ( 7 ) 1778 - 1787 2018.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Background:Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m2) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m2, P<0.01).Conclusions:The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

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Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy.

Suzumori N, Sekizawa A, Ebara T, Samura O, Sasaki A, Akaishi R, Wada S, Hamanoue H, Hirahara F, Izumi H, Sawai H, Nakamura H, Yamada T, Miura K, Masuzaki H, Yamashita T, Okai T, Kamei Y, Namba A, Murotsuki J, Tanemoto T, Fukushima A, Haino K, Tairaku S, Matsubara K, Maeda K, Kaji T, Ogawa M, Osada H, Nishizawa H, Okamoto Y, Kanagawa T, Kakigano A, Kitagawa M, Ogawa M, Izumi S, Katagiri Y, Takeshita N, Kasai Y, Naruse K, Neki R, Masuyama H, Hyodo M, Kawano Y, Ohba T, Ichizuka K, Nagamatsu T, Watanabe A, Shirato N, Yotsumoto J, Nishiyama M, Hirose T, Sago H

European journal of obstetrics, gynecology, and reproductive biology 224 165 - 169 2018.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Two consecutive successful live birth in woman with 17α hydroxylase deficiency by frozen-thaw embryo transfer under hormone replacement endometrium preparation.

Kitajima M, Miura K, Inoue T, Murakami Y, Kitajima Y, Murakami N, Taniguchi K, Yoshiura KI, Masuzaki H

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 34 ( 5 ) 381 - 384 2018.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Reference values for circulating pregnancy-associated microRNAs in maternal plasma and their clinical usefulness in uncomplicated pregnancy and hypertensive disorder of pregnancy.

Murakami Y, Miura K, Sato S, Higashijima A, Hasegawa Y, Miura S, Yoshiura KI, Masuzaki H

The journal of obstetrics and gynaecology research 44 ( 5 ) 840 - 851 2018.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Natural Course of Human T-Cell Leukemia Virus Type 1 Proviral DNA Levels in Carriers During Pregnancy.

Fuchi N, Miura K, Tsukiyama T, Sasaki D, Ishihara K, Tsuruda K, Hasegawa H, Miura S, Yanagihara K, Masuzaki H

The Journal of infectious diseases 217 ( 9 ) 1383 - 1389 2018.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Relevant obstetric factors associated with fetal heart rate monitoring for cerebral palsy in pregnant women with hypertensive disorder of pregnancy.

Hasegawa J, Ikeda T, Toyokawa S, Jojima E, Satoh S, Ichizuka K, Tamiya N, Nakai A, Fujimori K, Maeda T, Masuzaki H, Takeda S, Suzuki H, Ueda S, Ikenoue T, Prevention Recurrence Committee, Japan Obstetric Compensation System for Cerebral Palsy

The journal of obstetrics and gynaecology research 44 ( 4 ) 647 - 654 2018.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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マウスにおいて亜麻仁油とエクストラヴァージンオリーブオイルの食餌摂取は消化管細菌叢を調節して肥満と代謝機能障害を予防する(Dietary flaxseed and extra virgin olive oils modulate gut microbiota, protecting against obesity and metabolic dysfunction in mice)

ミルマン・ジャスミン, 岡本士毅, 上間次己, 與那嶺正人, 難波豊隆, 益崎裕章

日本内分泌学会雑誌 ( (一社)日本内分泌学会 ) 94 ( 1 ) 316 - 316 2018.04

Type of publication: Research paper (other science council materials etc.)

亜麻仁油とextra virgin olive oilは腸内細菌叢、腸バリア、免疫機能に影響を及ぼし健全な代謝を維持する(Flaxseed and extra virgin olive oils impact gut microbiota, gut barrier and immune function, supporting metabolic health)

Millman Frances Jasmine, 岡本士毅, 上間次己, 與那嶺正人, 難波豊隆, 益崎裕章

糖尿病 ( (一社)日本糖尿病学会 ) 61 ( Suppl.1 ) S - 266 2018.04

Type of publication: Research paper (other science council materials etc.)

Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat.

Okamoto S, Sato T, Tateyama M, Kageyama H, Maejima Y, Nakata M, Hirako S, Matsuo T, Kyaw S, Shiuchi T, Toda C, Sedbazar U, Saito K, Asgar NF, Zhang B, Yokota S, Kobayashi K, Foufelle F, Ferré P, Nakazato M, Masuzaki H, Shioda S, Yada T, Kahn BB, Minokoshi Y

Cell reports ( Cell Reports ) 22 ( 3 ) 706 - 721 2018.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral region of the paraventricular hypothalamus (PVH) induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism. These neurons manifest activation of AMP-activated protein kinase (AMPK) during food deprivation, and this activation is necessary and sufficient for selection of an HCD over an HFD. Furthermore, this effect is mediated by carnitine palmitoyltransferase 1c (CPT1c). Thus, our results identify the specific neurons and intracellular signaling pathway responsible for regulation of the complex behavior of selection between an HCD and an HFD. VIDEO ABSTRACT.

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Association between ovarian endometrioma and ovarian reserve.

Kitajima M, Khan KN, Harada A, Taniguchi K, Inoue T, Kaneuchi M, Miura K, Masuzaki H

Frontiers in bioscience (Elite edition) 10 ( 1 ) 92 - 102 2018.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Corrigendum: Feasibility of placenta-derived mesenchymal stem cells as a tool for studying pregnancy-related disorders.

Fuchi N, Miura K, Doi H, Li TS, Masuzaki H

Scientific reports 7 46922 2017.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adrenal venous sampling in patients with primary aldosteronism: Which is the best evaluation method for laterality assessments?

Azama K, Okada M, Yogi A, Koga T, Iraha Y, Heianna J, Nakamura H, Masuzaki H, Murayama S

Open Journal of Radiology 7 ( 4 ) 219 - 227 2017.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice.

Kozuka C, Shimizu-Okabe C, Takayama C, Nakano K, Morinaga H, Kinjo A, Fukuda K, Kamei A, Yasuoka A, Kondo T, Abe K, Egashira K, Masuzaki H

Drug delivery ( Drug Delivery ) 24 ( 1 ) 558 - 568 2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Our previous works demonstrated that brown rice-specific bioactive substance, gamma-oryzanol acts as a chaperone, attenuates exaggerated endoplasmic reticulum (ER) stress in brain hypothalamus and pancreatic islets, thereby ameliorating metabolic derangement in high fat diet (HFD)induced obese diabetic mice. However, extremely low absorption efficiency from intestine of gamma-oryzanol is a tough obstacle for the clinical application. Therefore, in this study, to overcome extremely low bioavailability of gamma-oryzanol with super-high lipophilicity, we encapsulated gamma-oryzanol in polymer poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Nano-Orz), and evaluated its metabolically beneficial impact in genetically obese-diabetic ob/ob mice, the bestknown severest diabetic model in mice. To our surprise, Nano-Orz markedly ameliorated fuel metabolism with an unexpected magnitude (similar to 1000-fold lower dose) compared with regular gamma-oryzanol. Furthermore, such a conspicuous impact was achievable by its administration once every 2 weeks. Besides the excellent impact on dysfunction of hypothalamus and pancreatic islets, Nano-Orz markedly decreased ER stress and inflammation in liver and adipose tissue. Collectively, nanotechnology-based developments of functional foods oriented toward gamma-oryzanol shed light on the novel approach for the treatment of a variety of metabolic diseases in humans.

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Clinical usefulness of FDG-PET/CT for the evaluation of various types of adult T-cell leukemia.

Nakachi S, Okada M, Morishima S, Agarie Y, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tamaki K, Tedokon I, Morichika K, Nishi Y, Tomoyose T, Karube K, Fukushima T, Murayama S, Masuzaki H

Hematology (Amsterdam, Netherlands) ( TAYLOR & FRANCIS LTD ) 22 ( 9 ) 536 - 543 2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Purpose: The aim was to explore undefined useful indices for clinically grading adult T-cell leukemia (ATL) using [F-18] 2-fluoro-2-deoxyglucose (FDG) - positron emission tomography/computed tomography (PET/CT). Methods: A total of 28 patients with ATL (indolent, 9; aggressive, 19) were enrolled; all patients with aggressive ATL underwent FDG-PET/CT before chemotherapy. Patients with indolent ATL underwent FDG-PET/CT at the time of suspected disease progression and/or transformation; some received lymph node biopsy. The quantitative parameters maximum standardized uptake values (SUVmax), and mean and peak SUV, metabolic tumor volume (MTV), and volume-based total lesion glycolysis were calculated with the margin threshold as 25%, and 50% of the SUVmax for all lesions. Results: All parameters except for MTV-25% showed significant differences (P0.05) in differentiating the aggressive type from the indolent type of ATL. Areas under the curve for receiver-operating characteristic (ROC) analysis regarding the series of parameters investigated ranged from 0.75 to 0.92; this indicated relatively high accuracy in distinguishing the aggressive type from the indolent type. No malignant findings were detected in lymph node biopsies in indolent ATL patients with lymphadenopathy. Discussion: We performed evaluation of a line of parameters of FDG-PET, thereby demonstrating their significantly high accuracy for grading malignancy in ATL patients. In particular, low accumulation of FDG in indolent ATL patients with lymphadenopathy might predict that it is not a sign of disease transformation, but rather a reactive manifestation. Conclusion: FDG-PET/CT findings could be useful for clinically grading ATL.

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Increased expression of 11β-hydroxysteroid dehydrogenase type 1 in experimental periodontitis induced by lipopolysaccharide from Porphyromonas gingivalis

Fujita A, Nakata T, Umeda M, Masuzaki H, Sawai H

Open Journal of Stomatology 7 ( 10 ) 429 - 438 2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Human T-cell leukemia virus type I Tax genotype analysis in Okinawa, the southernmost and remotest islands of Japan: Different distributions compared with mainland Japan and the potential value for the prognosis of aggressive adult T-cell leukemia/lymphoma.

Sakihama S, Saito M, Kuba-Miyara M, Tomoyose T, Taira N, Miyagi T, Hayashi M, Kinjo S, Nakachi S, Tedokon I, Nishi Y, Tamaki K, Morichika K, Uchihara JN, Morishima S, Karube KN, Tanaka Y, Masuzaki H, Fukushima T

Leukemia research ( Leukemia Research ) 61 18 - 24 2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Morichika K, Uchihara JN, Morishima S, Karube KN, Tanaka Y, Masuzaki H, Fukushima T

Leuk Res 61 18 - 24 2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Fetiform teratoma was a parthenogenetic tumor arising from a mature ovum.

Miura K, Kurabayashi T, Satoh C, Sasaki K, Ishiguro T, Yoshiura KI, Masuzaki H

Journal of human genetics 62 ( 9 ) 803 - 808 2017.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Impact of brown rice-specific γ-oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice.

Kozuka C, Kaname T, Shimizu-Okabe C, Takayama C, Tsutsui M, Matsushita M, Abe K, Masuzaki H

Diabetologia ( Diabetologia ) 60 ( 8 ) 1502 - 1511 2017.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The clinical and phylogenetic investigation for a nosocomial outbreak of respiratory syncytial virus infection in an adult hemato-oncology unit.

Nabeya D, Kinjo T, Parrott GL, Uehara A, Motooka D, Nakamura S, Nahar S, Nakachi S, Nakamatsu M, Maeshiro S, Haranaga S, Tateyama M, Tomoyose T, Masuzaki H, Horii T, Fujita J

Journal of medical virology ( Journal of Medical Virology ) 89 ( 8 ) 1364 - 1372 2017.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The clinical and phylogenetic investigation for a nosocomial outbreak of respiratory syncytial virus infection in an adult hemato-oncology unit

Nabeya D, Kinjo T, Parrott GL, Uehara A, Motooka D, Nakamura S, Nahar S, Nakachi S, Nakamatsu M, Maeshiro S, Haranaga S, Tateyama M, Tomoyose T, Masuzaki H, Horii T, Fujita J

J Med Virol 89 ( 8 ) 1364 - 1372 2017.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Impact of Brown Rice-Specific -Oryzanol on Epigenetic Modulation of Dopamine D2 Receptor in Brain Striatum of High Fat Diet-Induced Obese Mice

Kozuka C, Kaname T, Shimizu-Okabe C, Takayama C, Tsutsui M, Matsushita M, Abe K, Masuzaki H

Diabetologia 60 ( 8 ) 1502 - 1511 2017.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Current status of non-invasive prenatal testing in Japan.

Samura O, Sekizawa A, Suzumori N, Sasaki A, Wada S, Hamanoue H, Hirahara F, Sawai H, Nakamura H, Yamada T, Miura K, Masuzaki H, Nakayama S, Okai T, Kamei Y, Namba A, Murotsuki J, Tanemoto T, Fukushima A, Haino K, Tairaku S, Matsubara K, Maeda K, Kaji T, Ogawa M, Osada H, Nishizawa H, Okamoto Y, Kanagawa T, Kakigano A, Kitagawa M, Ogawa M, Izumi S, Katagiri Y, Takeshita N, Kasai Y, Naruse K, Neki R, Masuyama H, Hyodo M, Kawano Y, Ohba T, Ichizuka K, Kido Y, Fukao T, Miharu N, Nagamatsu T, Watanabe A, Hamajima N, Hirose M, Sanui A, Shirato N, Yotsumoto J, Nishiyama M, Hirose T, Sago H

The journal of obstetrics and gynaecology research 43 ( 8 ) 1245 - 1255 2017.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.

Kina-Tanada M, Sakanashi M, Tanimoto A, Kaname T, Matsuzaki T, Noguchi K, Uchida T, Nakasone J, Kozuka C, Ishida M, Kubota H, Taira Y, Totsuka Y, Kina SI, Sunakawa H, Omura J, Satoh K, Shimokawa H, Yanagihara N, Maeda S, Ohya Y, Matsushita M, Masuzaki H, Arasaki A, Tsutsui M

Diabetologia ( SPRINGER ) 60 ( 6 ) 1138 - 1151 2017.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Nitric oxide (NO) is synthesised not only from l-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate. Green leafy vegetables are abundant in nitrate, but whether or not a deficiency in dietary nitrite/nitrate spontaneously causes disease remains to be clarified. In this study, we tested our hypothesis that long-term dietary nitrite/nitrate deficiency would induce the metabolic syndrome in mice. To this end, we prepared a low-nitrite/nitrate diet (LND) consisting of an amino acid-based low-nitrite/nitrate chow, in which the contents of l-arginine, fat, carbohydrates, protein and energy were identical with a regular chow, and potable ultrapure water. Nitrite and nitrate were undetectable in both the chow and the water. Three months of the LND did not affect food or water intake in wild-type C57BL/6J mice compared with a regular diet (RD). However, in comparison with the RD, 3 months of the LND significantly elicited visceral adiposity, dyslipidaemia and glucose intolerance. Eighteen months of the LND significantly provoked increased body weight, hypertension, insulin resistance and impaired endothelium-dependent relaxations to acetylcholine, while 22 months of the LND significantly led to death mainly due to cardiovascular disease, including acute myocardial infarction. These abnormalities were reversed by simultaneous treatment with sodium nitrate, and were significantly associated with endothelial NOS downregulation, adiponectin insufficiency and dysbiosis of the gut microbiota. These results provide the first evidence that long-term dietary nitrite/nitrate deficiency gives rise to the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice, indicating a novel pathogenetic role of the exogenous NO production system in the metabolic syndrome and its vascular complications.

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Carbon dioxide angiography and arterial embolization could successfully control postpartum uterine hemorrhage for the patient with hypersensitivity to iodine compound.

Kawashita S, Kaneuchi M, Nakayama D, Fuchi N, Murakami Y, Miura K, Masuzaki H

Radiology case reports 12 ( 2 ) 261 - 264 2017.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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FOXO3 GENOTYPE PROTECTS AGAINST TELOMERE SHORTENING WITH AGE

Davy, PMC; Morris, BJ; Willcox, DC; Shimabukaro, M; Donlon, TA; Suzuki, M; Higa, M; Masuzaki, H; Sata, M; Chen, R; He, Q; Murkofsky, R; Lim, E; Allsopp, RC; Willcox, BJ

HYPERTENSION 69 ( 6 ) E30 - E31 2017.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Feasibility of placenta-derived mesenchymal stem cells as a tool for studying pregnancy-related disorders.

Fuchi N, Miura K, Doi H, Li TS, Masuzaki H

Scientific reports 7 46220 2017.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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An Atypical Case of Late-Onset Systemic Lupus Erythematosus with Systemic Lymphadenopathy and Severe Autoimmune Thrombocytopenia/Neutropenia Mimicking Malignant Lymphoma

Tamaki K, Morishima S, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Nishi Y, Tomoyose T, Karube K, Fukushima T, Masuzaki H

Int J Hematol 105 ( 4 ) 526 - 531 2017.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

An atypical case of late-onset systemic lupus erythematosus with systemic lymphadenopathy and severe autoimmune thrombocytopenia/neutropenia mimicking malignant lymphoma.

Tamaki K, Morishima S, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Nishi Y, Tomoyose T, Karube K, Fukushima T, Masuzaki H

International journal of hematology ( International Journal of Hematology ) 105 ( 4 ) 526 - 531 2017.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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[Programs for Continuing Medical Education 2016: A Session: 4. Obesity Disease and Metabolic Syndrome: Clinical Progress and Future Outlook].

Masuzaki H, Shimabukuro M

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 106 ( 3 ) 477 - 83 2017.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Brown Rice-Specific -Oryzanol-Based Novel Approach toward Lifestyle-Related Brain Dysfunction and Impaired Glucose Metabolism

Masuzaki H (senior, corresponding author, Kozuka C, Yonamine M, Shimabukuro M

Glycative Stress Research 4 ( 1 ) 58 - 66 2017.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Purification of Two Novel Sugar Acid-binding Lectins from Haplomitrium Mnioides (bryophyte, Plantae) and their Preliminary Characterization.

Masuzaki H, Hosono M, Nitta K

Applied biochemistry and biotechnology 181 ( 1 ) 65 - 82 2017.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Circulating Levels of Pregnancy-Associated, Placenta-Specific microRNAs in Pregnant Women With Placental Abruption.

Miura K, Higashijima A, Murakami Y, Fuchi N, Tsukamoto O, Abe S, Hasegawa Y, Miura S, Masuzaki H

Reproductive sciences (Thousand Oaks, Calif.) 24 ( 1 ) 148 - 155 2017.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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4．肥満症とメタボリックシンドローム：最近の知見と展望

益崎裕章, 島袋充生

日本内科学会雑誌 ( 一般社団法人日本内科学会 ) 106 ( 3 ) 477 - 483 2017 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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孤立性脊髄硬膜外顆粒球肉腫で発症した急性骨髄性白血病の1例

北村紗希子, 益崎裕章, 森島聡子, 玉城啓太, 仲地佐和子, 手登根伊織, 島袋奈津紀, 花城多恵子, 玉城智子, 福島卓也

日本内科学会雑誌 ( 一般社団法人日本内科学会 ) 106 ( 10 ) 2214 - 2221 2017 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

28歳，男性．7カ月持続する臀部痛と左下腿運動麻痺があり，MRI（magnetic resonance imaging）で脊柱管内に腫瘤性病変を認め，精査で孤立性顆粒球肉腫の診断に至ったが，治療開始直前に急性骨髄性白血病に移行した．寛解導入療法後に分子遺伝学的寛解に到達し，地固め療法後に既往の統合失調症が増悪し治療中断となったが，22カ月経過した現在も完全寛解を維持している．顆粒球肉腫は急性骨髄性白血病に準じた治療が必要とされ，正確な診断と早期の治療介入が重要である．

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Embryonic development of GABAergic terminals in the mouse hypothalamic nuclei involved in feeding behavior

Kobayashi M, Shimizu-Okabe C, Kim J, Kobayashi S, Matsushita M, Masuzaki H, Takayama C

Neurosci Res 17 30313 - 30319 2017 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Round ligament varicosities diagnosed as inguinal hernia during pregnancy: A case report and series from two regional hospitals in Japan.

Mine Y, Eguchi S, Enjouji A, Fukuda M, Yamaguchi J, Inoue Y, Fujita F, Tsukamoto O, Masuzaki H

International journal of surgery case reports 36 122 - 125 2017 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A survey on awareness of genetic counseling for non-invasive prenatal testing: the first year experience in Japan.

Yotsumoto J, Sekizawa A, Suzumori N, Yamada T, Samura O, Nishiyama M, Miura K, Sawai H, Murotsuki J, Kitagawa M, Kamei Y, Masuzaki H, Hirahara F, Endo T, Fukushima A, Namba A, Osada H, Kasai Y, Watanabe A, Katagiri Y, Takeshita N, Ogawa M, Okai T, Izumi S, Hamanoue H, Inuzuka M, Haino K, Hamajima N, Nishizawa H, Okamoto Y, Nakamura H, Kanegawa T, Yoshimatsu J, Tairaku S, Naruse K, Masuyama H, Hyodo M, Kaji T, Maeda K, Matsubara K, Ogawa M, Yoshizato T, Ohba T, Kawano Y, Sago H, Japan NIPT Consortium

Journal of human genetics 61 ( 12 ) 995 - 1001 2016.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Catecholamines facilitate fuel expenditure and protect against obesity via a novel network of the gut-brain axis in transcription factor Skn-1 -deficient mice

Yoshiro Ishimaru, Shota Ushiama, Masataka Narukawa, Misako Yoshioka, Chisayo Kozuka, Naoki Watanabe, Makoto Tsunoda, Naomi Osakabe, Tomiko Asakura, Hiroaki Masuzaki, Keiko Abe

CHEMICAL SENSES ( OXFORD UNIV PRESS ) 41 ( 9 ) E218 - E218 2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

The expression of 11β-hydroxysteroid dehydrogenase type 1 is increased in experimental periodontitis in rats.

Nakata T, Umeda M, Masuzaki H, Sawai H

BMC oral health ( BMC Oral Health ) 16 ( 1 ) 108 2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Characterization of patients with aggressive adult T-cell leukemia-lymphoma in Okinawa, Japan: a retrospective analysis of a large cohort

Nishi Y, Fukushima T, Nomura S, Tomoyose T, Nakachi S, Morichika K, Tedokon I, Tamaki K, Shimabukuro N, Taira N, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tamaki K, Hayashi M, Arakaki H, Uchihara JN, Ohshiro K, Asakura Y, Kuba-Miyara M, Karube K, Masuzaki H

Int J Hematol 104 ( 4 ) 468 - 475 2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Characterization of patients with aggressive adult T-cell leukemia-lymphoma in Okinawa, Japan: a retrospective analysis of a large cohort.

International journal of hematology ( International Journal of Hematology ) 104 ( 4 ) 468 - 75 2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The expression of 11β-hydroxysteroid dehydrogenase type 1 is increased in experimental periodontitis in rats

Nakata T, Umeda M, Masuzaki H, Sawai H

BMC Oral Health 16 ( 1 ) 108 2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

Miyake H, Yamada S, Fujii Y, Sawai H, Arimori N, Yamanouchi Y, Ozasa Y, Kanai M, Sago H, Sekizawa A, Takada F, Masuzaki H, Matsubara Y, Hirahara F, Kugu K

Journal of human genetics 61 ( 10 ) 879 - 884 2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Long-term effect of sitagliptin on endothelial function in type 2 diabetes: A sub-analysis of the PROLOGUE study

Maruhashi T.

Cardiovascular Diabetology ( Cardiovascular Diabetology ) 15 ( 1 ) 2016.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe.

Shimabukuro M, Okawa C, Yamada H, Yanagi S, Uematsu E, Sugasawa N, Kurobe H, Hirata Y, Kim-Kaneyama JR, Lei XF, Takao S, Tanaka Y, Fukuda D, Yagi S, Soeki T, Kitagawa T, Masuzaki H, Sato M, Sata M

The Journal of nutritional biochemistry ( ELSEVIER SCIENCE INC ) 35 66 - 73 2016.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD + Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD + E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8 weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4 beta-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4 beta-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 413-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function. (C) 2016 Elsevier Inc. All rights reserved.

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A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population.

Miura K, Mishima H, Yasunami M, Kaneuchi M, Kitajima M, Abe S, Higashijima A, Fuchi N, Miura S, Yoshiura K, Masuzaki H

Journal of human genetics 61 ( 9 ) 793 - 6 2016.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adipocyte size distribution and depot-specific modulation of pro- and anti-atherosclerotic adipocytokines and innate immune molecules in human adipose tissue

Shimabukuro, M; Sato, H; Izaki, H; Fukuda, D; Uematsu, E; Hirata, Y; Yagi, S; Soeki, T; Sakaue, H; Kanayama, H; Masuzaki, H; Sata, M

EUROPEAN HEART JOURNAL 37 183 - 183 2016.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats.

Shirakura T, Nomura J, Matsui C, Kobayashi T, Tamura M, Masuzaki H

Naunyn-Schmiedeberg's archives of pharmacology ( SPRINGER ) 389 ( 8 ) 831 - 8 2016.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial. To explore the possible involvement of XO-derived oxidative stress in the pathophysiology of vascular dysfunction, by use of a selective XO inhibitor, febuxostat, we investigated the impact of pharmacological inhibition of XO on hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats (SHRs). Sixteen-week-old SHR and normotensive Wistar-Kyoto (WKY) rats were treated with tap water (control) or water containing febuxostat (3 mg/kg/day) for 6 weeks. Systolic blood pressure (SBP) in febuxostat-treated SHR (220 +/- 3 mmHg) was significantly (P < 0.05) decreased compared with the control SHR (236 +/- 4 mmHg) while SBP in febuxostat-treated WKY was constant. Acetylcholine-induced endothelium-dependent relaxation in aortas from febuxostat-treated SHR was significantly (P < 0.05) improved compared with the control SHR, whereas relaxation in response to sodium nitroprusside was not changed. Vascular XO activity and tissue nitrotyrosine level, a representative indicator of local oxidative stress, were considerably elevated in the control SHR compared with the control WKY, and this increment was abolished by febuxostat. Our results suggest that exaggerated XO activity and resultant increase in oxidative stress in this experimental model contribute to the hypertension and endothelial dysfunction, thereby supporting a notion that pharmacological inhibition of XO is valuable not only for hyperuricemia but also for treating hypertension and related endothelial dysfunction in human clinics.

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Biological differences between functionalis and basalis endometria in women with and without adenomyosis.

Khan KN, Fujishita A, Kitajima M, Masuzaki H, Nakashima M, Kitawaki J

European journal of obstetrics, gynecology, and reproductive biology 203 49 - 55 2016.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Depot- and gender-specific expression of NLRP3 inflammasome and toll-like receptors in adipose tissue of cancer patients.

Shimabukuro M, Sato H, Izaki H, Fukuda D, Uematsu E, Hirata Y, Yagi S, Soeki T, Sakaue H, Kanayama HO, Masuzaki H, Sata M

BioFactors (Oxford, England) ( WILEY-BLACKWELL ) 42 ( 4 ) 397 - 406 2016.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Gender difference in obesity-associated cardiovascular complication could be derived from divergent chronic inflammation. We evaluated depot- and gender-specific regulation of the innate immune system in human adipose tissues. Pair samples were obtained from subcutaneous (SAT) and visceral adipose tissue (VAT) during elective surgery (Male: 35; Female: 27). Expressions of pro- and anti-inflammatory adipocytokines were evaluated by semi-quantitative qPCR. Adipose cell-size distribution was obtained from tissue samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. Levels of adiponectin were higher in SAT and VAT of female than those of male (P<0.001 and P=0.011, respectively). NLRP3, IL1-IL18, TLR2 were comparable in SAT and VAT between genders. However, TLR4 and TLR9 were increased in female SAT and VAT and HMGB1 in female VAT. Levels of adiponectin were not correlated with mean diameter of adipocyte (phi, m) in SAT and VAT of male, but negatively well correlated in those of female (r=-0.392 and r=-0.616). Such negative correlations were also observed between levels of TLR2, TLR4, and HMGB1 and phi in female. Levels of NLRP3 and IL1 were positively correlated with phi in male, but not in female. In conclusion, Innate signals were differentially expressed in male and female adipose tissues, suggesting that the depot- and gender-specific signals could be related to gender difference in chronic inflammation. (c) 2016 BioFactors, 42(4):397-406, 2016

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Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.

Suzumori N, Ebara T, Yamada T, Samura O, Yotsumoto J, Nishiyama M, Miura K, Sawai H, Murotsuki J, Kitagawa M, Kamei Y, Masuzaki H, Hirahara F, Saldivar JS, Dharajiya N, Sago H, Sekizawa A, Japan NIPT Consortium

Journal of human genetics 61 ( 7 ) 647 - 52 2016.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Three-dimensional saline-infusion sonohysterography is useful for the identification of endometrial polyp.

Inoue T, Kitajima M, Taniguchi K, Masuzaki H

The journal of obstetrics and gynaecology research 42 ( 7 ) 855 - 9 2016.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1-deficient Mice.

Ushiama S, Ishimaru Y, Narukawa M, Yoshioka M, Kozuka C, Watanabe N, Tsunoda M, Osakabe N, Asakura T, Masuzaki H, Abe K

EBioMedicine ( ELSEVIER SCIENCE BV ) 8 60 - 71 2016.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis. This system is referred to as the gut-brain axis. Here we show that both brush cells and type II taste cells are eliminated in the gastrointestinal tract of transcription factor Skn-1 knockout (KO) mice. Despite unaltered food intake, Skn-1 KO mice have reduced body weight with lower body fat due to increased energy expenditure. In this model, 24-h urinary excretion of catecholamines was significantly elevated, accompanied by increased fatty acid beta-oxidation and fuel dissipation in skeletal muscle and impaired insulin secretion driven by glucose. These results suggest the existence of brain-mediated energy homeostatic pathways originating from brush cells and type II taste cells in the gastrointestinal tract and ending in peripheral tissues, including the adrenal glands. The discovery of food-derived factors that regulate these cells may open new avenues the treatment of obesity and diabetes. Research Context: Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis along the gut-brain axis. We propose the concept that taste-receiving cells in the oral cavity and/or food-borne chemicals-receiving brush cells in the gut are involved in regulation of the body weight and adiposity via the brain. The discovery of food-derived factors that regulate these cells may open new avenues for the treatment of obesity and diabetes. (C) 2016 The Authors. Published by Elsevier B.V.

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Impact of individual metabolic risk components or its clustering on endothelial and smooth muscle cell function in men.

Shimabukuro M, Higa N, Masuzaki H, Sata M, Ueda S

Cardiovascular diabetology ( Cardiovascular Diabetology ) 15 ( 1 ) 77 2016.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Impact of indivisual metabolic risk components or its clustering on endothelial and smooth muscle cell function in men

M. Shimabukuro, N. Higa, H. Masuzaki, M. Sata, S. Ueda

Cardiovasc Diabetology 15 77 2016.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Recurrence of psoriasis vulgaris accompanied by the treatment with C-C chemokine receptor type 4 (CCR4) antibody (Mogamulizumab) therapies in a patient with adult T cell leukemia/ lymphoma: Insight into autoinflammatory syndrome

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

Intern Med 55 ( 10 ) 1345 - 1349 2016.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Influenza 2014-2015 among pregnant Japanese women: primiparous vs multiparous women.

Yamada T, Kawakami S, Yoshida Y, Kawamura H, Ohta S, Abe K, Hamada H, Dohi S, Ichizuka K, Takita H, Baba Y, Matsubara S, Mochizuki J, Unno N, Maegawa Y, Maeda M, Inubashiri E, Akutagawa N, Kubo T, Shirota T, Oda Y, Yamada T, Yamagishi E, Nakai A, Fuchi N, Masuzaki H, Urabe S, Kudo Y, Nomizo M, Sagawa N, Maeda T, Kamitomo M, Kawabata K, Kataoka S, Shiozaki A, Saito S, Sekizawa A, Minakami H

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 35 ( 4 ) 665 - 71 2016.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Survey of prenatal testing for genetic disorders in Japan: Recent report.

Nobuzane T, Yamada T, Miura K, Sawai H, Masuzaki H, Kudo Y

The journal of obstetrics and gynaecology research 42 ( 4 ) 375 - 9 2016.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Molecular detection of intrauterine microbial colonization in women with endometriosis.

Khan KN, Fujishita A, Masumoto H, Muto H, Kitajima M, Masuzaki H, Kitawaki J

European journal of obstetrics, gynecology, and reproductive biology 199 69 - 75 2016.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adult T-cell leukemia-lymphoma in a pregnant woman diagnosed as a human T-cell lymphotropic virus type 1 carrier.

Fuchi N, Miura K, Imaizumi Y, Hasegawa H, Yanagihara K, Miyazaki Y, Masuzaki H

The journal of obstetrics and gynaecology research 42 ( 3 ) 336 - 40 2016.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Novel molecular mechanisms of brown rice-derived bioactive substance on anti-obesity and anti-diabetic properties

Kozuka, C; Masuzaki, H

JOURNAL OF PHARMACOLOGICAL SCIENCES 130 ( 3 ) S69 - S69 2016.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Potency of umbilical cord blood- and Wharton's jelly-derived mesenchymal stem cells for scarless wound healing.

Doi H, Kitajima Y, Luo L, Yan C, Tateishi S, Ono Y, Urata Y, Goto S, Mori R, Masuzaki H, Shimokawa I, Hirano A, Li TS

Scientific reports 6 18844 2016.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The Increased Ratio of 11β-Hydroxysteroid Dehydrogenase Type 1 versus Type 2 in Chronic Periodontitis Irrespective of Obesity

T. Nakata, A. Fujita, M. Umeda, H. Yoshida, K. Inami, H. Masuzaki, H. Sawai

SpringerPlus 5 40 2016.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Association of maternal pre-pregnancy weight, weight gain during pregnancy, and smoking with small-for-gestational-age infants in Japan.

Akahoshi E, Arima K, Miura K, Nishimura T, Abe Y, Yamamoto N, Oishi K, Masuzaki H, Aoyagi K

Early human development 92 33 - 6 2016.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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CDH13 Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome Traits Independently of Visceral Fat Mass.

Kitamoto A, Kitamoto T, Nakamura T, Matsuo T, Nakata Y, Hyogo H, Ochi H, 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

Journal of atherosclerosis and thrombosis ( 一般社団法人日本動脈硬化学会 ) 23 ( 3 ) 309 - 19 2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Aim: Visceral fat accumulation contributes to the development of metabolic syndrome. As visceral fat accumulation increases, adiponectin levels decrease; therefore, adiponectin provides a link between visceral fat accumulation and metabolic disorders. Genome-wide association studies (GWASs) have identified genetic variations in the cadherin 13 (CDH13) gene that are associated with adiponectin levels. Methods: We investigated whether single nucleotide polymorphisms (SNPs) in CDH13 was associated with adiponectin levels and metabolic syndrome traits independent of the visceral fat area (VFA), as measured using computed tomography (CT) in 945 Japanese individuals. Results: We found that three CDH13 SNPs reported by recent GWASs (i.e., rs3865188, rs4783244, and rs12051272) were significantly associated with higher adiponectin levels (P＜1×10 －14 ), even after adjustment for VFA. However, these adiponectin-inducing alleles of CDH13 SNPs were significantly associated with traits consistent with deteriorating metabolic symptoms, such as higher fasting insulin, homeostasis model assessment–insulin resistance (HOMA-IR) scores, and triglycerides and lower high-density lipoprotein (HDL)-cholesterol levels, similar to increasing VFA and decreasing adiponectin levels. Conclusion: These results suggested that CDH13 SNPs cause an adiponectin-resistant status to compensate for increasing adiponectin levels and could result in the deterioration of metabolic syndrome traits.

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CDH13 Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome Traits Independently of Visceral Fat Mass

Aya Kitamoto, Takuya Kitamoto, Takahiro Nakamura, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ikuo Mineo, Jun Wada, Yuji Ogawa, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kikuko Hotta

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS ( JAPAN ATHEROSCLEROSIS SOC ) 23 ( 3 ) 309 - 319 2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Aim: Visceral fat accumulation contributes to the development of metabolic syndrome. As visceral fat accumulation increases, adiponectin levels decrease; therefore, adiponectin provides a link between visceral fat accumulation and metabolic disorders. Genome-wide association studies (GWASs) have identified genetic variations in the cadherin 13 (CDH13) gene that are associated with adiponectin levels. Methods: We investigated whether single nucleotide polymorphisms (SNPs) in CDH13 was associated with adiponectin levels and metabolic syndrome traits independent of the visceral fat area (VFA), as measured using computed tomography (CT) in 945 Japanese individuals. Results: We found that three CDH13 SNPs reported by recent GWASs (i.e., rs3865188, rs4783244, and rs12051272) were significantly associated with higher adiponectin levels (P < 1 x 10(-14)), even after adjustment for VFA. However, these adiponectin-inducing alleles of CDH13 SNPs were significantly associated with traits consistent with deteriorating metabolic symptoms, such as higher fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) scores, and triglycerides and lower highdensity lipoprotein (HDL)-cholesterol levels, similar to increasing VFA and decreasing adiponectin levels. Conclusion: These results suggested that CDH13 SNPs cause an adiponectin-resistant status to compensate for increasing adiponectin levels and could result in the deterioration of metabolic syndrome traits.

Recurrence of Psoriasis Vulgaris Accompanied by Treatment with C-C Chemokine Receptor Type 4 (CCR4) Antibody (Mogamulizumab) Therapies in a Patient with Adult T cell Leukemia/ Lymphoma: Insight into Autoinflammatory Diseases.

Morichika K, Tomoyose T, Hanashiro T, Shimabukuro N, Tamaki K, Tedokon I, Nishi Y, Nakachi S, Karube KN, Fukushima T, Katoh T, Ohshima K, Masuzaki H

Internal medicine (Tokyo, Japan) ( 一般社団法人日本内科学会 ) 55 ( 10 ) 1345 - 9 2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Adult T cell leukemia / lymphoma (ATL) is one of the most aggressive hematological malignancies caused by human T-lymphotropic virus type-I (HTLV-1). Mogamulizumab is a new defucosylated humanized monoclonal antibody agent which targets C-C chemokine receptor type 4 (CCR4) expressed occasionally on the surface of ATL cells. However, adverse events such as drug eruptions have also been highlighted, at least in part, via the dysfunction of regulatory T cells (Tregs). We herein report a pronounced recurrence of systemic psoriasis vulgaris accompanied by the treatment of mogamulizumab in a patient with ATL. Pathological examinations may suggest a mechanistic link between the recurrence of autoinflammatory diseases and anti-CCR4 antibody therapies.

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Thromboembolism Supervened on Eosinophilia Induced by Mycoplasma Pneumonia.

Morichika K, Nakachi S, Tomoyose T, Masuzaki H

Internal medicine (Tokyo, Japan) ( 一般社団法人日本内科学会 ) 55 ( 18 ) 2741 - 2 2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The increased ratio of 11β-hydroxysteroid dehydrogenase type 1 versus 11β-hydroxysteroid dehydrogenase type 2 in chronic periodontitis irrespective of obesity.

Nakata T, Fujita A, Umeda M, Yoshida H, Inami K, Masuzaki H, Sawai H

SpringerPlus ( SpringerPlus ) 5 ( 1 ) 40 - 7 2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Screening of Coronary Artery Disease in Diabetic Patients: Who and How? - Reply.

Shimabukuro M, Saito T, Masuzaki H, Sata M

Circulation journal : official journal of the Japanese Circulation Society ( 一般社団法人日本循環器学会 ) 80 ( 2 ) 544 - 544 2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Background: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.Methods and Results: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, HbA1c≥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.Conclusions: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. (Circ J 2015; 79: 2422–2429)

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Relevant Obstetric Factors for Cerebral Palsy: From the Nationwide Obstetric Compensation System in Japan.

Hasegawa J, Toyokawa S, Ikenoue T, Asano Y, Satoh S, Ikeda T, Ichizuka K, Tamiya N, Nakai A, Fujimori K, Maeda T, Masuzaki H, Suzuki H, Ueda S, Prevention Recurrence Committee, Japan Obstetric Compensation System for Cerebral Palsy

PloS one 11 ( 1 ) e0148122 2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Authors' reply re: Transverse uterine fundal incision for placenta praevia with accreta, involving the entire anterior uterine wall: a case series.

Nishijima K, Orisaka M, Takahashi J, Yamamoto M, Nakago S, Yoshida A, Masuzaki H, Kotsuji F, Yoshida Y

BJOG : an international journal of obstetrics and gynaecology 122 ( 13 ) 1844 - 5 2015.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Increased Levels of Cell-Free miR-517a and Decreased Levels of Cell-Free miR-518b in Maternal Plasma Samples From Placenta Previa Pregnancies at 32 Weeks of Gestation.

Hasegawa Y, Miura K, Higashijima A, Abe S, Miura S, Yoshiura K, Masuzaki H

Reproductive sciences (Thousand Oaks, Calif.) 22 ( 12 ) 1569 - 76 2015.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Fatal pneumonia and viremia due to human parainfluenza virus type 1 in a patient with adult T-cell leukemia-lymphoma treated with mogamulizumab.

Tamaki K, Kinjo T, Aoyama H, Tomoyose T, Nakachi S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Nishi Y, Taira N, Fujita J, Yoshimi N, Fukushima T, Masuzaki H

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy ( Journal of Infection and Chemotherapy ) 21 ( 11 ) 820 - 3 2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Fatal pneumonia and viremia due to human parainfluenza virus type 1 in a patient with adult T-cell leukemia-lymphoma treated with mogamulizumab

K. Tamaki, T. T. Kinjo, H. Aoyama, Tomoyose, S. Nakachi, T. Hanashiro, N. Shimabukuro, I. Todokon, K. Morichika, Y. Nishi, N. Taira, J. Fujita, N. Yoshimi, T.Fukushima, H. Masuzaki

J Infect Chemother 21 ( 11 ) 820 - 823 2015.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Circulating chromosome 19 miRNA cluster microRNAs in pregnant women with severe pre-eclampsia.

Miura K, Higashijima A, Murakami Y, Tsukamoto O, Hasegawa Y, Abe S, Fuchi N, Miura S, Kaneuchi M, Masuzaki H

The journal of obstetrics and gynaecology research 41 ( 10 ) 1526 - 32 2015.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A novel insulinotropic mechanism of whole grain-derived γ-oryzanol via the suppression of local dopamine D2 receptor signalling in mouse islet.

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

British journal of pharmacology ( British Journal of Pharmacology ) 172 ( 18 ) 4519 - 4534 2015.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Background and Purpose gamma-Oryzanol, derived from unrefined rice, attenuated the preference for dietary fat in mice, by decreasing hypothalamic endoplasmic reticulum stress. However, no peripheral mechanisms, whereby -oryzanol could ameliorate glucose dyshomeostasis were explored. Dopamine D-2 receptor signalling locally attenuates insulin secretion in pancreatic islets, presumably via decreased levels of intracellular cAMP. We therefore hypothesized that -oryzanol would improve high-fat diet (HFD)-induced dysfunction of islets through the suppression of local D-2 receptor signalling. Experimental Approach Glucose metabolism and regulation of molecules involved in D-2 receptor signalling in pancreatic islets were investigated in male C57BL/6J mice, fed HFD and treated with gamma-oryzanol . In isolated murine islets and the beta cell line, MIN6 , the effects of gamma-oryzanol on glucose-stimulated insulin secretion (GSIS) was analysed using siRNA for D-2 receptors and a variety of compounds which alter D-2 receptor signalling. Key Results In islets, -oryzanol enhanced GSIS via the activation of the cAMP/PKA pathway. Expression of molecules involved in D-2 receptor signalling was increased in islets from HFD-fed mice, which were reciprocally decreased by -oryzanol. Experiments with siRNA for D-2 receptors and D-2 receptor ligands in vitro suggest that gamma-oryzanol suppressed D-2 receptor signalling and augmented GSIS. Conclusions and Implications gamma-Oryzanol exhibited unique anti-diabetic properties. The unexpected effects of gamma-oryzanol on D-2 receptor signalling in islets may provide a novel; natural food-based, approach to anti-diabetic therapy.

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Risk stratification of coronary artery disease in asymptomatic diabetic subjects using multi-detector computed tomography

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

Circ J 79 2422 - 2429 2015.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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

Shimabukuro M, Hasegawa Y, Higa M, Amano R, Yamada H, Mizushima S, Masuzaki H, Sata M

Journal of atherosclerosis and thrombosis ( 一般社団法人日本動脈硬化学会 ) 22 ( 8 ) 854 - 68 2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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.

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Estrogen deficiency heterogeneously affects tissue specific stem cells in mice.

Kitajima Y, Doi H, Ono Y, Urata Y, Goto S, Kitajima M, Miura K, Li TS, Masuzaki H

Scientific reports 5 12861 2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Successful treatment of toxoplasmic encephalitis diagnosed early by polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: Two case reports and review of the literature

Miyagi T.

Transplant Infectious Disease ( Transplant Infectious Disease ) 17 ( 4 ) 593 - 598 2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Successful treatment of toxoplasmic encephalitis quickly diagnosed by polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: two cases reports and review of the literature

T. Miyagi, H. Itonaga, F. Aosai, J. Taguchi, K. Norose, K. Mochiduki, H. Fujii, A. Furumoto, M. Ohama, K. Karimata, A. Yamanoha, H.Taniguchi, S. Sato, N. Taira, Y. Moriuchi, T. Fukushima, H. Masuzaki, Y. Miyazaki

Transpl Infect Dis 17 ( 4 ) 593 - 598 2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Experience with recombinant activated factor VII for severe post-partum hemorrhage in Japan, investigated by Perinatology Committee, Japan Society of Obstetrics and Gynecology.

Murakami M, Kobayashi T, Kubo T, Hata T, Takeda S, Masuzaki H

The journal of obstetrics and gynaecology research 41 ( 8 ) 1161 - 8 2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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National survey of fibrinogen concentrate usage for post-partum hemorrhage in Japan: investigated by the Perinatology Committee, Japan Society of Obstetrics and Gynecology.

Makino S, Takeda S, Kobayashi T, Murakami M, Kubo T, Hata T, Masuzaki H

The journal of obstetrics and gynaecology research 41 ( 8 ) 1155 - 60 2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis.

Khan KN, Kitajima M, Inoue T, Fujishita A, Nakashima M, Masuzaki H

Reproductive sciences (Thousand Oaks, Calif.) 22 ( 5 ) 585 - 94 2015.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Pregnancy-associated microRNAs in plasma as potential molecular markers of ectopic pregnancy.

Miura K, Higashijima A, Mishima H, Miura S, Kitajima M, Kaneuchi M, Yoshiura K, Masuzaki H

Fertility and sterility 103 ( 5 ) 1202 - 8.e1 2015.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Circulating levels of maternal plasma cell-free miR-21 are associated with maternal body mass index and neonatal birth weight.

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

Prenatal diagnosis 35 ( 5 ) 509 - 11 2015.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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[Discussion Meeting on Care and Treatment of Obesity Syndrome: Latest Approach through Nutrition, Diets, Exercise, Lifestyle Modification and Psychological Aspects].

Masuzaki H, Yabe D, Onishi Y, Matsuzawa Y, Matsuda Y

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine ( 一般社団法人日本内科学会 ) 104 ( 4 ) 748 - 62 2015.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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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)

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)

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)

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 (ADIPOQ) gene that are associated with adiponectin levels. In this study, we investigated whether ADIPOQ 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 ADIPOQ SNPs reported by recent GWASs (namely, rs6810075, rs10937273, rs1648707, rs864265, rs182052, rs17366568, and rs6773957). SNPs associated with the phenotype (P < 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 (P = 0.0030 and P = 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)

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 Bacteroides fragilis (BF). This represents the first demonstration of giant lymphadenitis with gas formation caused by BF in a patient with ATL. Notably, septic lymphadenitis is pivotal in the differential diagnosis of systemic lymphadenopathy in ATL.

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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)

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 αβ 鎖が陽性で，γδ 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)

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（α鎖およびβ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β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)

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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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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