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Acta Pharmaceutica Sinica B 2012年第1期2卷 23-27页

作者： takashi fukuda Ryuji Uchida Hiroyo Inoue Satoshi Ohte Hiroyuki Yamazaki Daisuke Matsuda Takenobu Katagiri Hiroshi Tomoda Graduate School of Pharmaceutical Sciences Kitasato UniversityTokyoJapan Research Center for Genomic Medicine Saitama Medical UniversitySaitamaJapan

Fibrodysplasia ossificans progressiva(FOP)is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues.A constitutively activated mutation of a bone morphogenetic protein(BMP)receptor,ALK2,has been identified in patients with *** report here that four structurally related compounds,lucilactaene,hydroxylucilactaene,NG-391 and NG-393,produced by fungal strain Fusarium sp.B88,inhibit BMP signaling in *** phosphatase activity,a marker enzyme of osteoblastic differentiation,was decreased in C2C12 myoblasts stably expressing mutant ALK2 by treatment with those compounds with IC_(50) values of 5.7,6.8,6.9 and 6.1 mM,***,NG-391 and NG-393 inhibited BMP-specific luciferase reporter activity,which is directly regulated by transcription factor Smads,with IC50 values of 1.4 and 2.1 mM,*** findings suggest that these fungal metabolites may provide a new direction in the development of FOP therapeutics.

关键词： Lucilactaenes Fungal metabolites C2C12 myoblasts Fibrodysplasia ossificans progressiva

Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters

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Synthetic and Systems Biotechnology 2016年第3期1卷 158-168页

作者： Yaojun Tong Mei Liu Yu Zhang Xueting Liu Ren Huang Fuhang Song Huanqin Dai Biao Ren Nuo Sun Gang Pei Jiang Bian Xin-Ming Jia Guanghua Huang Xuyu Zhou Shaojie Li Buchang Zhang takashi fukuda Hiroshi Tomoda SatoshiOmura Richard DCannon Richard Calderone Lixin Zhang CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China The Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKgs.Lyngby2800Denmark Guangdong Laboratory Animals Monitoring Institute Guangzhou 510260China Institute of Health Sciences School of Life SciencesAnhui UniversityHefei 230601China State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Department of Immunology School of MedicineTongji UniversityShanghai 200092China Sir John Walsh Research Institute University of OtagoDunedin 9016New Zealand Department of Microbiology&Immunology Georgetown University Medical CenterWashingtonDC 20057US University of Chinese Academy of Sciences Beijing 100049China Research Center for Tropical Diseases Kitasato Institute for Life SciencesKitasato UniversityTokyo 108-8641Japan Graduate School of Pharmaceutical Sciences Kitasato UniversityTokyo 108-8641Japan

Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,particularly to immunocompromised *** high mortality of systematic fungal infections necessitates novel antifungal drugs and ***,with traditional drug discovery approaches,only echinocandins was approved by FDA as a new class of antifungals in the past two *** efflux is one of the major contributors to multi-drug resistance,the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug *** this study,we combined structure-based virtual screening and whole-cell based mechanism study,identified a natural product,beauvericin(BEA)as a drug efflux pump modulator,which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette(ABC)transporters;meantime,BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species(ROS).It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole(KTC)and could cure the murine model of disseminated *** evaluation of BEA,including acute toxicity test,Ames test,and hERG(human ether-a-go-go-related gene)test promised that BEA can be harnessed for treatment of candidiasis,especially the candidiasis caused by ABC overexpressed multi-drug resistant ***.

关键词： Candida albicans ABC transporter Beauvericin Virtual screening Multi-drug resistance Synergy

Effects of Earth's curvature and radial heterogeneity in dislocation studies:Case studies of the 2008 Wenchuan earthquake and the 2004 Sumatra earthquake

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Earthquake Science 2010年第4期23卷 301-308页

作者： Guangyu Fu Wenke Sun Yoichi fukuda Shanghua Gao takashi Hasegawa Institute of Earthquake Science China Earthquake Administration Beijing 100036 China Department of Geophysics Graduate School of Science Kyoto University Kyoto 606-8502 Japan Laboratory of Computational Geoclynamics Graduate University of Chinese Academy of Sciences Beijing 100049 China

Recently, effects of Earth＇s curvature and radial heterogeneity on coseismic deformations are often investi- gated based on the 2004 Sumatra earthquake. However, such effects are strongly related to earthquake types. As a low dip angle event, the 2004 Sumatra earthquake is not a good seismic case for such a topic since the effects for moderate dip angle events are much bigger. In this study, the half-space and spherical dislocation theories are used, respectively, to calculate co- seismic displacements caused by the 2008 Wenchuan earthquake and the 2004 Sumatra earthquake. Effects of Earth＇s curva- ture and stratification are investigated through the discrepancies of results calculated using the two dislocation theories. Re- sults show that the effects of Earth＇s curvature and stratification for the 2008 Wenchuan earthquake are much larger than those for the 2004 Sumatra earthquake. Ignoring the effects will cause errors up to 100%-200% in far field displacements for a moderate dip angle event like the 2008 Wenchuan earthquake. Such great effects are much bigger than those conclusions of previous studies. Besides, comparison with observations verifies that spherical dislocation theories yield better results than half-space ones in far fields.

关键词： coseismic displacement dislocation theory Earth model

Effects of Gaussian filter in processing GRACE data: Gravity rate of change at Lhasa,southern Tibet

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Science China Earth Sciences 2011年第9期54卷 1378-1385页

作者： SUN WenKe HASEGAWA takashi ZHANG XinLin fukuda Yoichi SHUM C. K. WANG Lei Key Laboratory of Computational Geodynamics Graduate University of Chinese Academy of Sciences Beijing 100049 China Department of Geophysics Kyoto University Japan Earthquake Research Institute The University of Tokyo Japan Division of Geodetic Science School of Earth Sciences The Ohio State University OH 43210-1398 USA

In this paper, the spatial gravity distribution over Tibetan Plateau and the gravity rate of change at Lhasa for different Gaussian filter radii are computed using GRACE data. Results show that the estimate of the gravity rate of change is spatialradius-dependent of the Ganssian filter. The GRACE-estimated gravity rate of change agrees well with the surface measured one. In other words, the GRACE-estimated gravity rate of change has a limited value as that obtained by surface measurement when the spatial filter radius reaches zero. Then numerical simulations are made for different spatial radii of the Gaussian filter to investigate its behaviors when applied to surface signals. Results show that the estimate of a physical signal is filter-radius dependent. If the computing area is equal to or less than the mass area, especially for a uniformly distributed mass, the estimate gives an almost correct result, no matter what filter radius is used. The estimate has large error because of the signal leakage caused by harmonic truncation if the computing area is much bigger than the mass distribution （or inverse for a small mass anomaly）. If a mass anomaly is too small, it is difficult to recover it from space observation unless the filter radius is extremely small. If the computing point （or area） is outside the mass distribution, the estimated result is almost zero, particularly for small filter radii. These properties of the Gaussian filter are helpful in applying GRACE data in different geophysical problems with different spatial position and geometrical size. We further discuss physical sources causing the scalar gravity change at Lhasa. Discussions indicate that the gravity rate of change at Lhasa is not caused by the present-day ice melting （PDIM）（or Little Ice Age, LIA） effect because no ice melting occurs in Lhasa city and nearby. The gravity rate of change is attributable mainly to tectonic deformation associated with the Indian Plate collision. Simultaneous surf

关键词： gravity change GRACE Gaussian filter Tibetan Plateau Lhasa

A Novel System for Xylem Cell Differentiation in Arabidopsis thaliana

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Molecular Plant 2015年第4期8卷 612-621页

作者： Yuki Kondo takashi Fujita Munetaka Sugiyama Hiroo fukuda Department of Biological Sciences Graduate School of Science The University of Tokyo 7-3-1 Hongo Bunkyo-ku tokyo 113-0033 Japan Botanical Gardens Graduate School of Science Tile University of Tokyo 3-7-1 Hakusan Bunkyo-ku Tokyo 112-0001 Japan

During vascular development, procambial and cambial cells give rise to xylem and phloem cells. Because the vascular tissue is deeply embedded, it has been difficult to analyze the processes of vascular development in detail. Here, we establish a novel in vitro experimental system in which vascular development is induced in Arabidopsis thaliana leaf-disk cultures using bikinin, an inhibitor of glycogen synthase kinase 3 proteins. Transcriptome analysis reveals that mesophyll cells in leaf disks synchronously turn into procambial cells and then differentiate into tracheary elements. Leaf-disk cultures from plants expressing the procambial cell markers TDRpro：GUS and TDRpro：YFP can be used for spatiotemporal visualization of procambial cell formation. Further analysis with the tdr mutant and TDIF （tracheary element differentiation inhibitory factor） indicates that the key signaling TDIF-TDR-GSK3s regulates xylem differentiation in leaf-disk cultures. This new culture system can be combined with analysis using the rich material resources for Arabidopsis including cell-marker lines and mutants, thus offering a powerful tool for analyzing xylem cell differentiation.

关键词： Arabidopsis thaliana bikinin leaf-disk culture transcriptome tracheary element differentiation signaling

Preventing pancreatic fistula after distal pancreatectomy: An invagination method

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World Journal of Gastroenterology 2017年第8期23卷 1507-1512页

作者： Nagato Katsura Yasuhiro Kawai takashi Gomi Kenji Okumura Takahiko Hoashi Seijun fukuda Katsushi Takebayashi Kenji Shimizu Masugi Satoh Department of Surgery Misugikai Otokoyama Hospital Department of Surgery Misugikai Satoh HospitalYobuhigashimachi Hirakata

Following an increase in the use of the GIA stapler for treating a pancreatic stump, more techniques to prevent postoperative pancreatic juice leakage have been required. We describe one successful case using our new technique of invaginating the cut end of the pancreas into the stomach to prevent a pancrea-tic fistula(PF) from occurring. A 50-year-old woman with pancreatic cancer in the tail of the pancreas underwent distal pancreatectomy, causing a grade A PF. We resected the distal pancreas without additional reinforcement to invaginate the stump into the gastric posterior wall with single layer anastomosis using a 3-0 absorbable suture. The drain tubes were removed on the third postoperative day. Although a grade A PF was noted, the patient was discharged on foot on the eleventh postoperative day. Our technique may be a suitable method for patients with a pancreatic body and tail tumor.

关键词： Amylases Pancreatectomy Pancreatic fistula Pancreatic juice Neoplasms

Individual Income Status Correlates with Chronic Kidney Disease in Japan beyond Metabolic Risk Factors: Cross Sectional Study

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Health 2017年第11期9卷 1516-1528页

作者： Hoichi Amano Yoshiharu fukuda Chiho Kitashima takashi Yokoo Kazue Yamaoka Graduate School of Public Health Teikyo University Tokyo Japan Division of Nephrology and Hypertension Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan

Background: Chronic kidney disease (CKD) is a pre-condition for end-stage kidney disease (ESKD) undergoing hemodialysis, as well as a risk factor for cardiovascular disease. Therefore, it is vital that CKD prevention measures be established. In particular, socioeconomic status (SES), as represented by income, contributes to non-communicable diseases like CKD. The purpose of this study was to examine the independent association between CKD and individual SES in Japan, with consideration of other metabolic risks. Methods: In the present study, we analyzed the 2011 National Health and Nutrition Survey by the Ministry of Health, Labor, and Welfare. Specifically, we analyzed 3,557 people out of 8,762 whose serum creatinine was measured. Logistic regression analysis was used to calculate the odds ratio (OR) of CKD by income distinction, after adjustment for age and metabolic risks (obesity, diabetes mellitus, dyslipidemia, and hypertension), which were assessed at the medical examination. Results: CKD was found in 385 participants (10.8%) and was associated with greater age, obesity, higher levels of low-density lipoprotein cholesterol, triglyceride, and glycated hemoglobin, and lower levels of hemoglobin and high-density lipoprotein cholesterol. The adjusted model indicated a significant association between lower income and CKD: the OR of the low income group (<2 million yen) was 1.33 (95% confidence interval: 1.01 - 1.78) in comparison with the high income group. Conclusions: The results of the present study indicate a substantial relationship between individual lower income status and CKD in Japan, where healthcare is easy to access. To prevent ESKD and cardiovascular diseases, early detection of CKD and its metabolic risks is necessary, especially among the socioeconomically vulnerable population.

关键词： Chronic Kidney Disease End-Stage Kidney Disease Socioeconomic Status Income Population Approach

Carcinoma of the papilla of Vater following treatment of pancreaticobiliary maljunction

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World Journal of Gastroenterology 2009年第48期15卷 6126-6128页

作者： Masato Watanabe Yutaka Midorikawa Taketoshi Yamano Hiroyuki Mushiake Naoto fukuda takashi Kirita Kunio Mizuguchi Yasuyuki Sugiyama Department of Surgery Teikyo University School of Medicine University Hospital Department of Surgery Yokohama Shin-midoriGeneral Hospital Department of Pathology Teikyo UniversitySchool of Medicine University Hospital

Pancreaticobiliary maljunction(PBM)is frequently associated with biliary cancer due to reflux of pancreatic enzymes into the choledochus,and even after surgery to correct the PBM such patients still have a risk of residual bile duct ***,we report the case of a 59-year-old female with carcinoma of the papilla of Vater which developed 2.5 years after choledochoduodenostomy for *** the postoperative follow-up period,computed tomography obtained 2 years after the first operation demonstrated a tumor in the distal end of the choledochus,although she did not have jaundice and laboratory tests showed no abnormalities caused by the previous *** a result,carcinoma of the papilla of Vater was diagnosed at an early stage,followed by surgical *** early detection of periampullary cancer in patients undergoing surgery for PBM,careful long-term follow-up is needed.

关键词： Pancreaticobiliary maljunction Biliary cancer Carcinoma of the papilla of Vater

Late-onset non-islet cell tumor hypoglycemia: A case report

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World Journal of Clinical Cases 2021年第1期9卷 163-169页

作者： Shunichi Matsumoto Eijiro Yamada Yasuyo Nakajima Naoki Yamaguchi takashi Okamura Toshiki Yajima Satoshi Yoshino Kazuhiko Horiguchi Emi Ishida Masashi Yoshikawa Jun Nagaoka Sho Sekiguchi Mai Sue Shuichi Okada Izumi fukuda Ken Shirabe Masanobu Yamada Department of Medicine and Molecular Science Gunma University Graduate School of MedicineMaebashi 371-8511GunmaJapan Division of General Thoracic Surgery Integrative Center of General SurgeryGunma University HospitalMaebashi 371-8511GunmaJapan Department of Endocrinology Diabetes and MetabolismGraduate School of Medicine Nippon Medical SchoolTokyo 1138602Japan

BACKGROUND Hypoglycemia due to non-insulin-producing tumors is referred to as non-islet cell tumor hypoglycemia(NICTH).As NICTH is a rare lesion,the natural course of NICTH is not well *** report a case of NICTH that was observed 30 years before the onset of *** SUMMARY A 50-year-old man was diagnosed with an abnormal right chest shadow during a routine X-ray examination,but no further examination was undertaken because the lesion appeared *** years after the tumor discovery,the patient was admitted to the hospital with symptoms of severe hypoglycemia,which was diagnosed as NICTH based on a complete *** tumor was resected and found to be a solitary fibrous mass(15.6 cm×13.7 cm×10.4 cm);thereafter,the patient’s blood glucose levels normalized and he completely *** NICTH can have an acute onset,even if the tumor has been present and asymptomatic over a long time period.

关键词： Hypoglycemia Non-islet cell tumor hypoglycemia Blood glucose Solitary tumor Late onset Case report Insulin-like growth factor II

Application of appropriate use criteria for percutaneous coronary intervention in Japan

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World Journal of Cardiology 2016年第8期8卷 456-463页

作者： Taku Inohara Shun Kohsaka Ikuko Ueda takashi Yagi Yohei Numasawa Masahiro Suzuki Yuichiro Maekawa Keiichi fukuda Department of Cardiology Hiratsuka City Hos-pital Department of Cardiology Keio University School of Medicine Keio inter--hospital Cardiovascular Studies

The aim of this review was to summarize the concept of appropriate use criteria(AUC) regarding percutaneous coronary intervention(PCI) and document AUC use and impact on clinical practice in Japan, in comparison with its application in the United States. AUC were originally developed to subjectively evaluate the indications and performance of various diagnostic and therapeutic modalities, including revascularization techniques. Over the years, application of AUC has significantly impacted patient selection for PCI in the United States, particularly in non-acute settings. After the broad implementation of AUC in 2009, the rate of inappropriate PCI decreased by half by 2014. The effect was further accentuated by incorporation of financial incentives(e.g., restriction of reimbursement for inappropriate procedures). On the other hand, when the United States-derived AUC were applied to Japanese patients undergoing elective PCI from 2008 to 2013, about one-third were classified as inappropriate, largely due to the perception gap between American and Japanese experts. For example, PCI for low-risk non-left atrial ascending artery lesion was more likely to be classified as appropriate by Japanese standards, and anatomical imaging with coronary computed tomography angiography was used relatively frequently in Japan, but no scenario within the current AUC includes this modality. To extrapolate the current AUC to Japan or any other region outside of the United States, these local discrepancies must be taken into consideration, and scenarios should be revised to reflect contemporary practice. Understanding the concept of AUC as well as its perception gap between different counties will result in the broader implementation of AUC, and lead to the quality improvement of patients' care in the field of coronary intervention.

关键词： Appropriate use criteria Acute coronary syndrome Percutaneous coronary intervention Japan Stable ischemic heart disease