Faculty Profiles - SONE, Hirohito

Papers - SONE, Hirohito

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Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles Reviewed

Yoshika Kurokawa, Hideko Sone, Tin-Tin Win-Shwe, Yang Zeng, Hiroyuki Kimura, Yosuke Koyama, Yusuke Yagi, Yasuto Matsui, Masashi Yamazaki, Seishiro Hirano

International Journal of Nanomedicine 12 3967 - 3975 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Dove Medical Press Ltd.

Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD), an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood–brain barrier (BBB) in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin–Landau– Verwey–Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media) confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis suggested that this was largely attributable to the reduced BBB permeability arising from the propensity of the particles to promptly aggregate upon mixing with body fluids.

DOI： 10.2147/IJN.S125808

Potential protective effect of lactation against incidence of type 2 diabetes mellitus in women with previous gestational diabetes mellitus: A systematic review and meta-analysis. Reviewed International journal

Tanase-Nakao K, Arata N, Kawasaki M, Yasuhi I, Sone H, Mori R, Ota E

Diabetes/metabolism research and reviews 33 ( 4 ) 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：John Wiley and Sons Ltd

Lactation may protect women with previous gestational diabetes mellitus (GDM) from developing type 2 diabetes mellitus, but the results of existing studies are inconsistent, ranging from null to beneficial. We aimed to conduct a systematic review to gather available evidence. Databases MEDLINE, CINAHL, PubMed, and EMBASE were searched on December 15, 2015, without restriction of language or publication year. A manual search was also conducted. We included observational studies (cross-sectional, case-control, and cohort study) with information on lactation and type 2 diabetes mellitus incidence among women with previous GDM. We excluded case studies without control data. Data synthesis was conducted by random-effect meta-analysis. Fourteen reports of 9 studies were included. Overall risk of bias using RoBANS ranged from low to unclear. Longer lactation for more than 4 to 12 weeks postpartum had risk reduction of type 2 diabetes mellitus compared with shorter lactation (OR 0.77, 95% CI 0.01-55.86; OR 0.56, 95% CI 0.35-0.89; OR 0.22, 95% CI 0.13-0.36; type 2 diabetes mellitus evaluation time < 2 y, 2-5 y, and >5 y, respectively). Exclusive lactation for more than 6 to 9 weeks postpartum also had lower risk of type 2 diabetes mellitus compared with exclusive formula (OR 0.42, 95% CI 0.22-0.81). The findings support the evidence that longer and exclusive lactation may be beneficial for type 2 diabetes mellitus prevention in women with previous GDM. However, the evidence relies only on observational studies. Therefore, further studies are required to address the true causal effect.

DOI： 10.1002/dmrr.2875

Comparison of clinicopathological characteristics between T-cell prolymphocytic leukemia and peripheral T-cell lymphoma, not otherwise specified. Reviewed International journal

Kawamoto K, Miyoshi H, Yanagida E, Yoshida N, Kiyasu J, Kozai Y, Morikita T, Kato T, Suzushima H, Tamura S, Muta T, Kato K, Eto T, Seki R, Nagafuji K, Sone H, Takizawa J, Seto M, Ohshima K

European journal of haematology 98 ( 5 ) 459 - 466 2017.5

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

OBJECTIVES: T-cell prolymphocytic leukemia (T-PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T-PLL and PTCL-NOS. METHODS: We analyzed 15 T-PLL and 91 PTCL-NOS patients and also compared clinical features between T-PLL and PTCL-NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared. RESULTS: T-PLL cells were smaller in size than those of PTCL-NOS with leukemic presentation (P=.0068); moreover, PTCL-NOS cells with leukemic presentation were smaller than those of PTCL-NOS without leukemic presentation (P=.0017). Immunophenotypic patterns in T-PLL and PTCL-NOS were similar. Five-year overall survival rates of T-PLL and all PTCL-NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T-PLL and PTCL-NOS with leukemic presentation had essentially equivalent characteristics. CONCLUSION: T-PLL and PTCL-NOS may share common biological and clinical characteristics in Japanese patients.

DOI： 10.1111/ejh.12856

Japanese Kampo Medicines for Diabetes Mellitus

Hiroshi Suzuki, Hirohito Sone, Kenichi Watanabe

Japanese Kampo Medicines for the Treatment of Common Diseases: Focus on Inflammation 69 - 73 2017.3

Language：English Publishing type：Part of collection (book) Publisher：Elsevier

Diabetes mellitus is one of the most common disorders affecting a huge number of populations in both developed and developing countries. Despite the availability of various medicines for its treatment, the number of affected people is still increasing. The focus is now shifting to the use of natural medicines for the treatment of various chronic diseases. Because the Japanese Kampo medicine system has a long history and tradition, a discussion of the effects of a few of the available Kampo medicines would be interesting and helpful to both physicians and researchers.

DOI： 10.1016/B978-0-12-809398-6.00008-1

Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy. Reviewed International journal

Watanabe K, Sreedhar R, Thandavarayan RA, Karuppagounder V, Giridharan VV, Antony S, Harima M, Nakamura M, Suzuki K, Suzuki H, Sone H, Arumugam S

BioFactors (Oxford, England) 43 ( 2 ) 187 - 194 2017.3

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

Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017.

DOI： 10.1002/biof.1332

Carbohydrate intake during early pregnancy is inversely associated with abnormal glucose challenge test results in Japanese pregnant women. Reviewed International journal

Tajima R, Yachi Y, Tanaka Y, Kawasaki YA, Nishibata I, Hirose AS, Horikawa C, Kodama S, Iida K, Sone H

Diabetes/metabolism research and reviews 33 ( 6 ) 2017.3

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

BACKGROUND: In East Asian countries, which have a high prevalence of underweight individuals, there is little information about the association between dietary factors and abnormal glucose tolerance during pregnancy. We examined the association between carbohydrate intake and moderately abnormal glucose tolerance in Japanese pregnant women. METHODS: We conducted a prospective study on 325 Japanese pregnant women without a diagnosis of diabetes mellitus prior to pregnancy. Dietary carbohydrate intake (% of total energy intake) was assessed using a 3-day dietary record during weeks 8-15 of pregnancy. Glucose tolerance was assessed by the 50 g glucose challenge test (GCT) during weeks 24-28 of pregnancy. A positive GCT result was defined by a 1-hour plasma concentration ≥ 7.8 mmol/L. Odds ratios of a positive GCT were calculated for the top and middle tertile categories of carbohydrate intake using the bottom category as reference. RESULTS: Mean (standard deviation) body mass index at the first prenatal visit was 19.7 (1.9) kg/m2 , and 95 women were underweight. Seventy-four women had positive GCT results. Carbohydrate intake was negatively associated with a positive GCT result after adjusting for age, parity, body mass index at first prenatal visit, family history of diabetes mellitus, rate of gestational weight gain, energy intake, and dietary fiber intake (odds ratio for top category: 0.46 [95% CI, 0.23-0.93]). CONCLUSIONS: These findings suggest that high carbohydrate intake was negatively associated with moderately abnormal glucose tolerance in a population with a high prevalence of underweight individuals.

DOI： 10.1002/dmrr.2898

Dietary salt intake and diabetes complications in patients with diabetes: An overview. Reviewed

Chika Horikawa, Hirohito Sone

Journal of general and family medicine 18 ( 1 ) 16 - 20 2017.3

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Dietary salt restriction is an essential constituent of diabetes care in preventing or slowing the development of diabetes complications, and many diabetes management guidelines include recommendations for dietary salt intake. However, descriptions of guidelines for salt intake are sometimes confined to studies of participants without diabetes or small short-term studies of patients with diabetes. However, in response to such situations, recent longitudinal studies of patients with diabetes have reported an association between dietary salt intake and diabetes complications. Thus, this review summarizes important points in the current situation regarding guidelines on salt intake and the latest findings and future issues on dietary salt intake for diabetes care focusing on (i) the current status and issues regarding the leading guidelines for dietary salt intake for diabetes care in various regions worldwide, and (ii) findings on salt intake from recent longitudinal studies of patients with diabetes whose dietary salt intake was restricted.

DOI： 10.1002/jgf2.10

Patients with type 2 diabetes having higher glomerular filtration rate showed rapid renal function decline followed by impaired glomerular filtration rate: Japan Diabetes Complications Study. Reviewed International journal

Moriya T, Tanaka S, Sone H, Ishibashi S, Matsunaga S, Ohashi Y, Akanuma Y, Haneda M, Katayama S

Journal of diabetes and its complications 31 ( 2 ) 473 - 478 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

AIMS: The Japan Diabetes Complications Study (JDCS), a nation-wide, multicenter, prospective study of patients with type 2 diabetes, reported that hemoglobin A1c (HbA1c), systolic blood pressure, and smoking were risk factors for the onset of macroalbuminuria. This study explored the risk factors for glomerular filtration rate (GFR) decline in the JDCS patients. METHODS: We examined the 1407 JDCS patients (667 women, mean age 59years, 974 normoalbuminuria, 433 microalbuminuria) whose urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR) were determined at baseline with an 8-year follow-up. We divided all the patients into four groups according to baseline eGFR: G1 (120≤eGFR), G2 (90≤eGFR<120), G3 (60≤eGFR<90), G4 (eGFR<60). RESULTS: The eGFRs in groups G1 and G2 decreased at follow-up compared to those at the baseline. The risk of annual eGFR decline rate≥3ml/min/1.73m2 (rapid decliners) increased as the baseline eGFR increased. Advanced age, high HbA1c, and UACR, or diabetic retinopathy at baseline were risk factors for the rapid decliners. Especially the G1 group had a significant risk for the rapid decliners. The frequency of the patients with GFR<60ml/min/1.73m2 at the follow-up amounted to 31.1% in the rapid decliners, which was higher than 12% in the non-rapid decliners. CONCLUSIONS: In normo- and microalbuminuric patients with type 2 diabetes, extra careful attention should be paid to patients with eGFR ≥120ml/min/1.73m2 to detect cases with rapidly decreased GFR under the normal range.

DOI： 10.1016/j.jdiacomp.2016.06.020

Comparison of baseline characteristics and clinical course in Japanese patients with type 2 diabetes among whom different types of oral hypoglycemic agents were chosen by diabetes specialists as initial monotherapy (JDDM 42). Reviewed International journal

Fujihara K, Igarashi R, Matsunaga S, Matsubayashi Y, Yamada T, Yokoyama H, Tanaka S, Shimano H, Maegawa H, Yamazaki K, Kawai K, Sone H

Medicine 96 ( 7 ) e6122 2017.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Little is known about the relationships between patient factors and the antihyperglycemic agents that have been prescribed as initial therapy by diabetes specialists for patients with type 2 diabetes. Moreover, there has been little clarification of the subsequent usage patterns and related factors that influenced the continuation or discontinuation of the drug or the addition of another drug. To provide information on these issues, we evaluated the clinical characteristics of Japanese patients with type 2 diabetes for whom different types of oral hypoglycemic agents (i.e., either sulfonylureas, biguanides, or DPP-4 inhibitors (DPP-4Is)) were chosen as initial monotherapy by diabetes specialists and evaluated subsequent usage patterns.Prescription data on 3 different antidiabetic agents from December 2009 to March 2015 from diabetes specialists' patient registries were used to identify variables at baseline related to initial prescriptions; also, the addition of another hypoglycemic drug or discontinuation of the initial therapy was evaluated 1 year after the initial prescription. Analyzed were data on 2666 patients who received initial monotherapy with either a sulfonylurea (305 patients), biguanide (951 patients), or DPP-4I (1410 patients). Patients administered sulfonylureas were older, had a lower body mass index (BMI), longer duration of diabetes, and worse glycemic control than recipients of biguanides. Use of biguanides was related to younger age, short duration of diabetes, and obesity but was negatively associated with poor glycemic control. Older age but neither obesity nor poor glycemic control was associated with DPP-4Is. In all 3 groups a high HbA1c value was related to adding another hypoglycemic agent to the initial therapy. Moreover, adding another drug to a DPP-4I was related to a younger age and higher BMI.Patients' age, duration of diabetes, obesity, and glycemic control at baseline influenced the choice of hypoglycemic agents. Selection of a biguanide differs greatly from that of a sulfonylurea or DPP-4I with regard to age and obesity.

DOI： 10.1097/md.0000000000006122

Is the Proportion of Carbohydrate Intake Associated with the Incidence of Diabetes Complications?-An Analysis of the Japan Diabetes Complications Study. Reviewed International journal

Horikawa C, Yoshimura Y, Kamada C, Tanaka S, Tanaka S, Matsunaga S, Hanyu O, Araki A, Ito H, Tanaka A, Ohashi Y, Akanuma Y, Sone H

Nutrients 9 ( 2 ) 2017.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

The appropriate proportions of macronutritional intake have been controversial in medical nutritional therapy for diabetes, and evidence of the effects of carbohydrate consumption on diabetes complications in prospective settings is sparse. We investigated the relationships between proportions of carbohydrate intake as the % of total energy and diabetes complications in a nationwide cohort of Japanese patients with type 2 diabetes aged 40-70 years with hemoglobin A1c ≥6.5%. The analysis was of 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to overt nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) after 8 years. Hazard ratios (HRs) for proportions of carbohydrate intake were estimated by Cox regression adjusted for confounders. High carbohydrate intake was significantly related to higher intakes of grain, fruits, and sweets/snacks and lower intakes of soybean and soy products, vegetables, seaweed, meat and processed meat, fish and processed fish, eggs, milk and dairy products, oil, and alcoholic beverages. During the eight-year follow-up, there were 81, 275, and 129 events of overt nephropathy, diabetic retinopathy, and CVD, respectively. After adjustment for confounders, HRs for complications in patients with carbohydrate intake in the second or third tertiles (51.0%-56.4% and ≥56.5%, respectively) compared with carbohydrate intake in the first tertile (<50.9%, referent) were analyzed. No significant associations were shown in the second and third tertiles relative to first tertile (overt nephropathy: 1.05 (95% Confidence Interval, 0.54-2.06) and 0.98 (0.40-2.44); diabetic retinopathy: 1.30 (0.90-1.88) and 1.30 (0.78-2.15); and CVD: 0.95 (0.55-1.63) and 1.37 (0.69-2.72)). By exploring potentially nonlinear relationships, trends for the incidence of diabetes complications according to proportions of carbohydrate intake were not clearly shown. Findings suggested that proportions of carbohydrate intake were not associated with the incidence of diabetes complications among type 2 diabetes patients in Japan.

DOI： 10.3390/nu9020113

Advanced glycation end products induce brain-derived neurotrophic factor release from human platelets through the Src-family kinase activation. Reviewed International journal

Furukawa K, Fuse I, Iwakura Y, Sotoyama H, Hanyu O, Nawa H, Sone H, Takei N

Cardiovascular diabetology 16 ( 1 ) 20 - 20 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts beneficial effects not only on diabetic neuropathies but also on cardiovascular injury. There is argument regarding the levels of serum BDNF in patients with diabetes mellitus (DM). Because BDNF in peripheral blood is rich in platelets, this may represent dysregulation of BDNF release from platelets. Here we focused on advanced glycation end products (AGEs), which are elevated in patients with DM and have adverse effects on cardiovascular functions. The aim of this study is to elucidate the role of AGEs in the regulation of BDNF release from human platelets. METHODS: Platelets collected from peripheral blood of healthy volunteers were incubated with various concentrations of AGE (glycated-BSA) at 37 °C for 5 min with or without BAPTA-AM, a cell permeable Ca2+ chelator, or PP2, a potent inhibitor of Src family kinases (SFKs). Released and cellular BDNF were measured by ELISA and calculated. Phosphorylation of Src and Syk, a downstream kinase of SFKs, in stimulated platelets was examined by Western blotting and immunoprecipitation. RESULTS: AGE induced BDNF release from human platelets in a dose-dependent manner, which was dependent on intracellular Ca2+ and SFKs. We found that AGE induced phosphorylation of Src and Syk. CONCLUSIONS: AGE induces BDNF release from human platelets through the activation of the Src-Syk-(possibly phospholipase C)-Ca2+ pathway. Considering the toxic action of AGEs and the protective roles of BDNF, it can be hypothesized that AGE-induced BDNF release is a biological defense system in the early phase of diabetes. Chronic elevation of AGEs may induce depletion or downregulation of BDNF in platelets during the progression of DM.

DOI： 10.1186/s12933-017-0505-y

Unstable bodyweight and incident type 2 diabetes mellitus: A meta-analysis. Reviewed

Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H

Journal of diabetes investigation 8 ( 4 ) 501 - 509 2017.1

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

AIMS/INTRODUCTION: The present meta-analysis aimed to clarify the association of unstable bodyweight with the risk of type 2 diabetes mellitus, an association that has been controversial among longitudinal studies. MATERIALS AND METHODS: An electronic literature search using EMBASE and MEDLINE was followed up to 31 August 2016. The relative risks (RRs) of type 2 diabetes mellitus in individuals with unstable bodyweight were pooled using the inverse variance method. RESULTS: Eight studies were eligible for the meta-analysis. The median duration of measurements of weight change and follow-up years for ascertaining type 2 diabetes mellitus were 13.5 and 9.4 years, respectively. The pooled RR for the least vs most stable category was 1.33 (95% confidence interval 1.12-1.57). Between-study heterogeneity was statistically significant (P = 0.048). Whether type 2 diabetes mellitus was ascertained by blood testing explained 66.0% of the variance in the logarithm of RR (P = 0.02). In three studies in which blood testing was carried out, type 2 diabetes mellitus risk was not significant (RR 1.06, 95% confidence interval 0.91-1.25). Furthermore, publication bias that inflated type 2 diabetes mellitus risk was statistically detected by Egger's test (P = 0.09). CONCLUSIONS: Unstable bodyweight might be modestly associated with the elevated risk of type 2 diabetes mellitus; although serious biases, such as diagnostic suspicion bias and publication bias, made it difficult to assess this association.

DOI： 10.1111/jdi.12623

Prevalence of non-communicable diseases and number of comorbidities according to differences in household income levels in Japan: Analysis from National Health and Nutrition Survey. Reviewed

Horikawa C, Murayama N, Ota A, Tsuruta M, Matsunaga S, Fujihara K, Hanyu O, Sone H

Food and nutrition Sciences 7 ( 1 ) 19 - 30 2017.1

Successful umbilical cord blood hematopoietic stem cell transplantation in a patient with adult T-cell leukemia/lymphoma initially achieving complete remission with anti-CC chemokine receptor 4 antibody combined chemotherapy. Reviewed

Suwabe T, Shibasaki Y, Kaihatsu A, Katagiri T, Miyakoshi S, Fuse K, Kobayashi H, Ushiki T, Moriyama M, Takizawa J, Narita M, Sone H, Masuko M

[Rinsho ketsueki] The Japanese journal of clinical hematology 58 ( 1 ) 32 - 36 2017

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

A 62-year-old man with CHOP refractory adult T-cell leukemia/lymphoma (ATLL) received anti-CC chemokine receptor 4 antibody (mogamulizumab) combined with CHOP and achieved complete remission. At 71 days after the final administration of mogamulizumab, he received umbilical cord blood transplantation (CBT) using reduced intensity conditioning. Umbilical cord blood engraftment was confirmed on day16. Grade II acute graft-versus-host disease (GVHD) was diagnosed on day60 and was controlled by administration of methylprednisolone. There was no evidence of relapse at 9 months after CBT. Ratios of regulatory T cells in CD4 positive T cells were remarkably low during all of these periods. Since mogamulizumab reduces regulatory T cells, the frequency and severity of acute GVHD were reported to be increased in patients administered mogamulizumab before allogenic stem cell transplantation. Further experiences are needed for selecting optimal donor sources, the portability period and GVHD prophylaxis for patients using mogamulizumab before allogeneic stem cell transplantation.

DOI： 10.11406/rinketsu.58.32

[Myelodysplastic syndrome with refractory hemorrhage due to reduced platelet aggregation activity]. Reviewed

Tanaka T, Kozakai T, Kitajima T, Fuse K, Kobayashi H, Ushiki T, Shibazaki Y, Moriyama M, Takizawa J, Sone H, Fuse I, Masuko M

[Rinsho ketsueki] The Japanese journal of clinical hematology 58 ( 12 ) 2402 - 2405 2017

Language：Japanese Publisher：The Japanese Society of Hematology

<p>A 75-year-old woman suffered a cat bite 10 months after myelodysplastic syndrome (MDS) diagnosis. She visited our hospital because the internal bleeding of the wound did not improve. Although the wound was treated, the bleeding did not stop. She was hospitalized for emergency medical treatment because the bleeding volume exceeded 200 m<i>l</i>. Although her platelet count was normal, the platelet function test showed a decrease in collagen and arachidonic acid aggregation. After platelet transfusion, her bleeding stopped. Patients with MDS may potentially have platelet dysfunction. In the case of bleeding without thrombocytopenia, a platelet function test should be performed and treatment intervention, such as platelet transfusion, should be considered.</p>

DOI： 10.11406/rinketsu.58.2402

Other Link： http://search.jamas.or.jp/link/ui/2018121562

Peripheral T-cell lymphoma, not otherwise specified: a retrospective single-center analysis. Reviewed

Takaharu Suzuki, Keisuke Kawamoto, Suguru Tamura, Shun Uemura, Akane Kaihatsu, Hiroki Nemoto, Hironori Kobayashi, Takashi Ushiki, Kyoko Fuse, Yasuhiko Shibazaki, Masato Moriyama, Masayoshi Masuko, Miwako Narita, Hirohito Sone, Sadao Aoki, Naoya Nakamura, Koichi Oshima, Jun Takizawa

[Rinsho ketsueki] The Japanese journal of clinical hematology 58 ( 8 ) 905 - 911 2017

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

We retrospectively analyzed clinical and pathological features, treatments, and prognoses in 28 patients with newly diagnosed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in Niigata University Medical and Dental Hospital. Of them, 16 were males and 12 were females, and their median age was 62.5 (range, 26-88) years. The International Prognostic Index was high-intermediate/high in 68% of patients. Twelve patients were treated with CHOP/THP-COP and nine with third-generation chemotherapy regimens. At a median follow-up period of 30 (range: 1-164) months, the 2-year overall survival and progression-free survival rates were 61% and 44%, respectively. Further investigation of novel agents for treating PTCL-NOS is warranted.

DOI： 10.11406/rinketsu.58.905

The SIL index is a simple and objective prognostic indicator in diffuse large B-cell lymphoma.

Tomita N, Suzuki T, Miyashita K, Yamamoto W, Motohashi K, Tachibana T, Takasaki H, Kawasaki R, Hagihara M, Hashimoto C, Takemura S, Koharazawa H, Yamazaki E, Taguchi J, Fujimaki K, Fujita H, Sakai R, Fujisawa S, Motomura S, Takizawa J

2016.12

Development and evaluation of the Japanese version of the Audit of Diabetes-Dependent Quality of Life for patients with diabetes. Reviewed

Ayumi Sugawara Hirose, Kazuya Fujihara, Flaminia Miyamasu, Shigeru Iwakabe, Misa Shimpo, Yoriko Heianza, Chika Horikawa, Yoko Yachi, Hirohito Sone

Diabetology international 7 ( 4 ) 384 - 390 2016.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Objectives: Our objective was to undertake linguistic validation and cultural adaptation of the Japanese version of the Audit of Diabetes-Dependent Quality of Life (JP-ADDQoL) and to evaluate its psychometric properties when completed by Japanese patients with diabetes. Methods: We followed the standard linguistic validation procedure and subsequently evaluated the reliability (internal consistency) and construct validity (exploratory and confirmatory factor analyses) of the translated version by surveying 239 Japanese patients with diabetes. Results: We translated 19 items for the JP-ADDQoL. The internal consistency was excellent (Cronbach's alpha = 0.933). In the exploratory factor analysis, four factors were extracted, and most of the items in all four factors had high loadings. Forced one-factor analysis revealed all factor loadings other than those for sex life to be >0.40 (sex life: 0.398). Confirmatory factor analysis indicated an acceptable fit for the JP-ADDQoL. Conclusions: The JP-ADDQoL showed adequate reliability and acceptable validity. Examining not only the impact of diabetes on a specific domain of life but also its importance for each patient leads to more accurate and individualized measurement of the patient's QoL.

DOI： 10.1007/s13340-016-0260-4

CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα. Reviewed International journal

Nakagawa Y, Satoh A, Tezuka H, Han SI, Takei K, Iwasaki H, Yatoh S, Yahagi N, Suzuki H, Iwasaki Y, Sone H, Matsuzaka T, Yamada N, Shimano H

Scientific reports 6 39182 - 39182 2016.12

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

CREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3-/- mice exhibited reduction of expression of genes for fatty oxidation and ketogenesis comparable to Ppara-/- mice. Most of the genes were further suppressed in double knockout mice indicating independent contribution of hepatic CREB3L3. During fasting, dependency of ketogenesis on CREB3L3 is lesser extents than Ppara-/- mice suggesting importance of adipose PPARα for supply of FFA and hyperlipidemia in Creb3l3-/- mice. In conclusion CREB3L3 plays a crucial role in hepatic adaptation to energy starvation via two pathways: direct related gene regulation and an auto-loop activation of PPARα. Furthermore, as KD-fed Creb3l3-/- mice exhibited severe fatty liver, activating inflammation, CREB3L3 could be a therapeutic target for NAFLD.

DOI： 10.1038/srep39182

Clinicopathological, Cytogenetic, and Prognostic Analysis of 131 Myeloid Sarcoma Patients. Reviewed International journal

Kawamoto K, Miyoshi H, Yoshida N, Takizawa J, Sone H, Ohshima K

The American journal of surgical pathology 40 ( 11 ) 1473 - 1483 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Myeloid sarcoma (MS) is an extramedullary tumor of immature myeloid cells. We analyzed 131 patients with MS, including: (1) de novo MS; (2) MS with concomitant acute myeloid leukemia (AML); (3) MS following myelodysplastic syndrome, myeloproliferative neoplasm, or chronic myelogenous leukemia; and (4) MS as a recurrence of AML. The most common development site was the lymph node. Testicular lesions were statistically more frequent in MS as a recurrence of AML than in other types of MS (P=0.0183). MS tended to lack myeloid markers (myeloperoxidase was present in 63.2%, CD68 in 51.3%, CD13 in 48.7%, and CD33 in 48.7% of patients) and express T-cell markers such as CD3 (20.7%) and CD5 (34.2%). All T-cell marker-positive MS cases were negative for the αβ and γδ T-cell receptors on immunohistochemistry. Underlying myelodysplastic syndrome or myeloproliferative neoplasm was a poor prognostic factor (vs. de novo MS: P=0.0383; vs. MS with concomitant AML: P=0.0143). However, there was no statistical difference in prognosis between de novo MS and MS with concomitant AML (P=0.288). There were no significant differences in prognosis between the prognoses of T-cell marker-positive and T-cell marker-negative MS cases. In addition, CXCR4 expression was a poor prognostic factor in MS (P=0.0229). This study involves the largest MS cohort to date and expands the clinical and pathologic knowledge of the disease.

DOI： 10.1097/pas.0000000000000727

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