Faculty Profiles - SONE, Hirohito

Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at ER monitoring and regulating fatty acids

WT1ペプチドワクチン投与後のCML患者におけるWT1特異的CTLの持続性と多様性(Persistence and diversity of WT1-specific CTLs in a CML patient vaccinated WT1 peptide)

諏訪部達也, 柴崎康彦, 田村秀, 片桐隆幸, 布施香子, 牛木隆志, 曽根博仁, 成田美和子, 増子正義

日本血液学会学術集会 83回 PS - 1 2021.9

ドナーリンパ球のコンドロイチン硫酸合成低下はGVHDを軽減する(Genetic manipulation resulting in decreased donor chondroitin sulfate mitigates GVHD in mice)

田村秀, 牛木隆志, 諏訪部達也, 片桐隆幸, 石黒創, 布施香子, 柴崎康彦, 進藤岳郎, 五十嵐道弘, 曽根博仁, 増子正義

日本血液学会学術集会 83回 OS3 - 1 2021.9

AMLにおける造血幹細胞移植後1年未満の再発は高い死亡率と相関する(Post-transplant relapse of AML within one year is associated with a high mortality rate)

片桐隆幸, 本宮奈津子, 武田ルイ, 水戸部正樹, 米沢穂高, 諏訪部達也, 布施香子, 柴崎康彦, 瀧澤淳, 曽根博仁, 増子正義

日本血液学会学術集会 83回 PS - 10 2021.9

Hirohito Sone

BioRxiv 2021.8

Developing a health economic model for Asians with type 2 diabetes based on the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial. International journal

Shiro Tanaka, Jakob Langer, Tim Morton, Nicki Hoskins, Lars Wilkinson, Sachiko Tanaka-Mizuno, Ryo Kawasaki, Tatsumi Moriya, Chika Horikawa, Rei Aida, Atsushi Araki, Kazuya Fujihara, Hirohito Sone

BMJ open diabetes research & care 9 ( 1 ) 2021.8

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Cost-effectiveness analyses are becoming increasingly important in Japan following the introduction of a health technology assessment scheme. The study objective was to develop an economic model to evaluate the cost-effectiveness of two interventions for type 2 diabetes in a Japanese population. RESEARCH DESIGN AND METHODS: The Japan Diabetes Complications Study/Japanese Elderly Diabetes Intervention Trial risk engine (JJRE) Cost-Effectiveness Model (JJCEM) was developed, incorporating validated risk equations in Japanese patients with type 2 diabetes from the JJRE. Weibull regression models were developed for progression of the model outcomes, and a targeted literature review was performed to inform default values for utilities and costs. To illustrate outcomes, two simulated analyses were performed in younger (aged 40 years) and older (aged 80 years) Japanese populations, comparing a hypothetical treatment with placebo. RESULTS: The model considers a population based on user-defined values for 11 baseline characteristic parameters and simulates rates of diabetic complications over a defined time horizon. Costs, quality-adjusted life years, and an incremental cost-effectiveness ratio are estimated. The model provides disaggregated results for two competing interventions, allowing visualization of the key drivers of cost and utility. A scatterplot of simulations and cost-effectiveness acceptability curve are generated for each analysis. CONCLUSIONS: This is the first cost-effectiveness model for East Asian patients with type 2 diabetes, developed using Japan-specific risk equations. This population constitutes the largest share of the global population with diabetes, making this model highly relevant. The model can be used to evaluate the cost-effectiveness of anti-diabetic interventions in patients with type 2 diabetes in Japan and other East Asian populations.

DOI： 10.1136/bmjdrc-2021-002177

Intensive oral care can reduce bloodstream infection with coagulase-negative staphylococci after neutrophil engraftment in allogeneic hematopoietic stem-cell transplantation. International journal

Tatsuya Suwabe, Kyoko Fuse, Kouji Katsura, Marie Soga, Takayuki Katagiri, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30 ( 1 ) 475 - 485 2021.7

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Bloodstream infection (BSI) is a major complication of allogeneic hematopoietic stem-cell transplantation (allo-SCT). There are several causes of BSI; in particular, severe oral mucositis (OM) can induce BSI due to coagulase-negative staphylococci (CoNS). The OM severity may be reduced with intensive oral care. Thus, we evaluated whether the type of oral care affects the BSI incidence eventually. METHOD: We performed retrospective analysis on 206 recipients who underwent allo-SCT from 2006 to 2017 at our institute. Intensive oral care by a dental specialist was performed for 111 recipients (intensive-care group) and self-oral care was performed by 95 recipients (self-care group). Incidence of BSI was assessed by type of the oral care, before neutrophil engraftment (pre-E-BSI) and after neutrophil engraftment (post-E-BSI) period until 180 days after allo-SCT. RESULT: A total of 112 BSI occurred in 90 of the 206 recipients and 120 bacteria were identified, with CoNS being the most prevalent. There was no significant difference in the incidence of pre-E-BSI between the self-care and intensive-care groups (30.8% and 30.6%, respectively; P = 0.508). Meanwhile, the incidence of post-E-BSI was significantly lower in the intensive-care group than in the self-care group (14.3% and 28.6%; P = 0.008). In addition, the intensive-care group had significantly lower incidence of post-E-BSI with CoNS than the self-care group (8.5% and 21.5%, respectively; P = 0.009). CONCLUSION: Intensive oral care through the period of allo-HCT can significantly reduce the post-E-BSI occurrence, especially due to CoNS.

DOI： 10.1007/s00520-021-06447-8

Central diabetes insipidus after syndrome of inappropriate antidiuretic hormone secretion with severe hyponatremia in a patient with Rathke's cleft cyst.

Yudai Hinata, Nobumasa Ohara, Takeshi Komatsu, Yuki Sakurai, Yuichiro Yoneoka, Yasuhiro Seki, Katsuhiko Akiyama, Hirohito Sone

Internal medicine (Tokyo, Japan) 61 ( 2 ) 197 - 203 2021.7

Language：English Publishing type：Research paper (scientific journal)

A 49-year-old man developed severe hyponatremia associated with transient headache and was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction and sodium supplementation corrected the hyponatremia. However, several days later, the patient exhibited hypernatremia with thirst and polyuria. A detailed examination indicated central diabetes insipidus (CDI) with an intrasellar cystic lesion indicative of Rathke's cleft cyst (RCC). A case of RCC exhibiting headache, hyponatremia, and subsequent hypernatremia has been reported. Our case shows that CDI may appear after SIADH in patients with RCC, especially in those with serum sodium levels that unexpectedly increase rapidly beyond the reference range.

DOI： 10.2169/internalmedicine.6608-20

Meta-analytic research of the dose-response relationship between salt intake and risk of heart failure. Reviewed International journal

Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Mariko Hatta, Yasunaga Takeda, Rena Nedachi, Kiminori Kato, Kenichi Watanabe, Hirohito Sone

Hypertension research : official journal of the Japanese Society of Hypertension 44 ( 7 ) 885 - 887 2021.7

Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation of the sodium-glucose cotransporter-2 inhibitor tofogliflozin. International journal

Yasuhiro Matsubayashi, Akihiro Yoshida, Hideki Suganami, Momoko Oe, Takaaki Sato, Yuta Yaguchi, Kazuya Fujihara, Takaho Yamada, Shiro Tanaka, Kohei Kaku, Hirohito Sone

Diabetes, obesity & metabolism 23 ( 7 ) 1660 - 1665 2021.7

Language：English Publishing type：Research paper (scientific journal)

Sodium-glucose cotransporter-2 inhibitors (SGLT2) are drugs that have been reported to have several effects through the regulation of plasma volume, for example, antihypertensive effects. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2 inhibitor tofogliflozin on estimated plasma volume (ePV), brain natriuretic peptide (BNP) and the relationship between changes in ePV, BNP and body weight (BW). Data from 157 participants with type 2 diabetes receiving tofogliflozin monotherapy in a phase 3 study were analysed. Changes in variables or correlations among them during a 52-week administration and a 2-week post-treatment period were investigated. Percent change in ePV was calculated using the Strauss formula. Significant decreases in BW, ePV and ln-transformed BNP (ln-BNP) were noted by week 52. %ΔBW was not significantly correlated with %ΔePV and Δln-BNP, while %ΔePV was significantly correlated with Δln-BNP. Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased. %ΔBW was significantly correlated with %ΔePV and Δln-BNP. Furthermore, ePV and BNP were significantly higher than baseline levels.

DOI： 10.1111/dom.14387

Author Correction: Meta-analytic research of the dose-response relationship between salt intake and risk of heart failure. International journal

Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Mariko Hatta, Yasunaga Takeda, Rena Nedachi, Kiminori Kato, Kenichi Watanabe, Hirohito Sone

Hypertension research : official journal of the Japanese Society of Hypertension 44 ( 7 ) 894 - 894 2021.7

粘液水腫性昏睡に急性膵炎を合併した一例

齋藤啓輔, 矢口雄大, 滝澤祥子, 西井郁生, 竹内亮, 山本正彦, 川田亮, 石黒創, 北澤勝, 松林泰弘, 鈴木浩史, 岩永みどり, 山田貴穂, 藤原和哉, 曽根博仁

日本内分泌学会雑誌 97 ( Suppl.Update ) 38 - 40 2021.7

Starvation-induced transcription factor CREBH negatively governs body growth by controlling GH signaling. International journal

Yoshimi Nakagawa, Kae Kumagai, Song-Iee Han, Yuhei Mizunoe, Masaya Araki, Seiya Mizuno, Hiroshi Ohno, Kazuya Matsuo, Yasunari Yamada, Jun-Dal Kim, Takafumi Miyamoto, Motohiro Sekiya, Morichika Konishi, Nobuyuki Itoh, Takashi Matsuzaka, Satoru Takahashi, Hirohito Sone, Hitoshi Shimano

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35 ( 6 ) e21663 2021.6

Language：English Publishing type：Research paper (scientific journal)

cAMP responsive element-binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock-in flox mice, and then generated liver-specific CREBH transgenic (CREBH L-Tg) mice in an active form. CREBH L-Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L-Tg mice, but plasma insulin-like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L-Tg mice could not correct GH resistance at all. CREBH L-Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.

DOI： 10.1096/fj.202002784RR

陰茎・陰嚢病変を合併した精巣原発DLBCL

水戸部正樹, 武田ルイ, 米沢穂高, 田村秀, 諏訪部達也, 片桐隆幸, 河本啓介, 布施香子, 柴崎康彦, 増子正義, 井上佳菜子, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

臨床血液 62 ( 6 ) 668 - 668 2021.6

同種造血幹細胞移植後の慢性GVHDとしての類上皮肉芽腫および多発筋炎

諏訪部達也, 布施香子, 水戸部正樹, 武田ルイ, 米沢穂高, 片桐隆幸, 河本啓介, 牛木隆志, 柴崎康彦, 瀧澤淳, 成田美和子, 曽根博仁, 大島孝一, 増子正義

臨床血液 62 ( 6 ) 675 - 675 2021.6

Associations of Systolic Blood Pressure and Diastolic Blood Pressure With the Incidence of Coronary Artery Disease or Cerebrovascular Disease According to Glucose Status. International journal

Mayuko Harada Yamada, Kazuya Fujihara, Satoru Kodama, Takaaki Sato, Taeko Osawa, Yuta Yaguchi, Masahiko Yamamoto, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Hiroyasu Seida, Wataru Ogawa, Hirohito Sone

Diabetes care 44 ( 9 ) 2124 - 2131 2021.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To determine associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with new-onset coronary artery disease (CAD) or cerebrovascular disease (CVD) according to glucose status. RESEARCH DESIGN AND METHODS: Examined was a nationwide claims database from 2008 to 2016 on 593,196 individuals. A Cox proportional hazards model identified risks of CAD and CVD events among five levels of SBP and DBP. RESULTS: During the study period 2,240 CAD and 3,207 CVD events occurred. Compared with SBP ≤119 mmHg, which was the lowest quintile of SBP, hazard ratios (95% CI) for CAD/CVD in the 4 higher quintiles (120-129, 130-139, 140-149, ≥150 mmHg) gradually increased from 2.10 (1.73-2.56)/1.46 (1.27-1.68) in quintile 2 to 3.21 (2.37-4.34)/4.76 (3.94-5.75) in quintile 5 for normoglycemia, from 1.39 (1.14-1.69)/1.70 (1.44-2.01) in quintile 2 to 2.52 (1.95-3.26)/4.12 (3.38-5.02) in quintile 5 for borderline glycemia, and from 1.50 (1.19-1.90)/1.72 (1.31-2.26) in quintile 2 to 2.52 (1.95-3.26)/3.54 (2.66-4.70) in quintile 5 for diabetes. A similar trend was observed for DBP across 4 quintiles (75-79, 80-84, 85-89, and ≥90 mmHg) compared with ≥74 mmHg, which was the lowest quintile. CONCLUSIONS: Results indicated that cardiovascular risks gradually increased with increases in SBP and DBP regardless of the presence of and degree of a glucose abnormality. Further interventional trials are required to apply findings from this cohort study to clinical practice.

DOI： 10.2337/dc20-2252

Accuracy of Japanese claims data in identifying diabetes-related complications. Reviewed International journal

Kazuya Fujihara, Mayuko Yamada-Harada, Yasuhiro Matsubayashi, Masaru Kitazawa, Masahiko Yamamoto, Yuta Yaguchi, Hiroyasu Seida, Satoru Kodama, Kohei Akazawa, Hirohito Sone

Pharmacoepidemiology and drug safety 30 ( 5 ) 594 - 601 2021.5

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

PURPOSE: To evaluate the accuracy of various claims-based definitions of diabetes-related complications (coronary artery disease [CAD], heart failure, cerebrovascular disease and dialysis). METHODS: We evaluated data on 1379 inpatients who received care at the Niigata University Medical & Dental Hospital in September 2018. Manual electronic medical chart reviews were conducted for all patients with regard to diabetes-related complications and were used as the gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each claims-based definition associated with diabetes-related complications based on Diagnosis Procedure Combination (DPC), International Classification of Diseases, Tenth Revision (ICD-10) codes, procedure codes and medication codes were calculated. RESULTS: DPC-based definitions had higher sensitivity, specificity, and PPV than ICD-10 code definitions for CAD and cerebrovascular disease, with sensitivity of 0.963-1.000 and 0.905-0.952, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. Sensitivity, specificity, and PPV were high using procedure codes for CAD and dialysis, with sensitivity of 0.963 and 1.000, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. DPC and/or ICD-10 codes + medication were better for heart failure than the ICD-10 code definition, with sensitivity of 0.933, specificity of 1.000, and PPV of 1.000. The PPVs were lower than 60% for all diabetes-related complications using ICD-10 codes only. CONCLUSION: The DPC-based definitions for CAD and cerebrovascular disease, procedure codes for CAD and dialysis, and DPC or ICD-10 codes with medication codes for heart failure could accurately identify these diabetes-related complications from claims databases.

DOI： 10.1002/pds.5213

WT1-specific CD8 + cytotoxic T cells with the capacity for antigen-specific expansion accumulate in the bone marrow in MDS. Reviewed

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pds.5213

Tatsuya Suwabe, Yasuhiko Shibasaki, Hiroyuki Sato, Suguru Tamura, Takayuki Katagiri, Hiroki Nemoto, Takuya Kasami, Takashi Kozakai, Ayako Nanba, Toshiki Kitajima, Kyoko Fuse, Takashi Ushiki, Hirohito Sone, Miwako Narita, Masayoshi Masuko

International journal of hematology 113 ( 5 ) 723 - 734 2021.5

Language：English Publishing type：Research paper (scientific journal)

Wilms' tumor 1 (WT1) is a tumor-associated antigen and immunotherapy target in myelodysplastic syndrome (MDS). Further information is needed on the characteristics of WT1-specific CD8 + T cells to develop immunotherapeutic strategies for MDS. To clarify the frequency, distribution, and phenotype of WT1-specific CD8 + T cells, which occur innately in MDS patients, we analyzed paired peripheral blood (PB) and bone marrow (BM) samples from 39 patients with MDS or acute myeloid leukemia with myelodysplasia-related changes. The median frequency of WT1 tetramer-binding CD8 + T cells in the CD8 + T cell population was 0.11% in PB and 0.18% in BM. A further tetramer assay combined with mixed lymphocyte peptide culture (MLPC assay) was used to detect functional WT1-specific CD8 + T cells that could respond to the WT1 peptide. Functional WT1-specific CD8 + T cells were detected in BM in 61% of patients, which was significantly higher than in PB (23%, p = 0.001). The frequency of these cells estimated by the MLPC assay was tenfold higher in BM than in PB. The majority of WT1 tetramer-binding CD8 + T cells in BM had a unique phenotype with co-expression of CD39 and CXCR4. These findings will facilitate the development of novel immunotherapeutic strategies for MDS.

DOI： 10.1007/s12185-021-03083-0