Published Papers - Masuzaki Hiroaki

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)

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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)

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<p><b><i>Background:</i></b>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).</p><p><b><i>Methods and Results:</i></b>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 (EAT_RCA), left anterior descending artery (EAT_LAD), left circumflex artery (EAT_LCX), right ventricle (EAT_RV), left ventricle (EAT_LV), right atrium (EAT_RA), and left atrium (EAT_LA) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m², P=0.010), EAT_LCX(10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EAT_LV(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, EAT_LCXand EAT_LVwere markedly associated with decreased lateral e' and increased lateral E/e'. Multiple regression analysis indicated that EAT_LCXand EAT_LVwere strongly associated with LV diastolic function parameters.</p><p><b><i>Conclusions:</i></b>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.</p>

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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)

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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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Transplant-related complications are impediments to the success of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia patients in non-complete remission.

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)

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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)

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<p>　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。</p><p>　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。</p><p>　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。</p>

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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)

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<p>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. </p>

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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)

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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)

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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 ]

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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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