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Homology Modeling of Human Alpha-Glucosidase Catalytic Domains and SAR Study of Salacinol Derivatives

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Open Journal of Medicinal Chemistry 2012年第3期2卷 50-60页

作者： shinya nakamura Kazunori Takahira Genzoh Tanabe Osamu Muraoka Isao Nakanishi Department of Pharmaceutical Sciences Kinki University Kinki Japan

Maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) belong to human intestinal alpha-glucosidase and their N-terminal side catalytic domains are called NtMGAM and NtSI, and their C-terminal side catalytic domains are called CtMGAM and CtSI. As an antidiabetic, alpha-glucosidase inhibitor is required to bind to all of these domains to inhibit disaccharides hydrolysis. Salacinol and kotalanol isolated from Salacia reticulata are novel seed compounds for al-pha-glucosidase inhibitor. Even though the complex structures of NtMGAM or NtSI have been determined experimen-tally, those of CtMGAM and CtSI have not been revealed. Thus, homology modeling for CtMGAM and CtSI has been performed to predict the binding mode of salacinol and its derivatives for each domain. The binding affinities for these compounds were also calculated to explain the experimental structure-activity relationships (SARs). After a docking study of the derivatives to each catalytic domain, the MM/PBSA method has been applied to predict the binding affinities. The predicted binding affinities were almost consistent with the experimental SARs. The comparison of the complex structures and binding affinities provided insights for designing novel compounds, which inhibit all catalytic domains.

关键词： Homology Modeling Docking Study MM/PBSA Alpha-Glucosidase Salacinol Kotalanol

Computational Study on the Comparative Differences in the Activity of Inhibitors of Human versus Rat Alpha-Glucosidase

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Open Journal of Medicinal Chemistry 2017年第2期7卷 19-28页

作者： shinya nakamura Kazuko Shimada Genzoh Tanabe Osamu Muraoka Isao Nakanishi Department of Pharmaceutical Sciences Kindai University Higashiosaka Japan

Differences between the inhibitory activities of specific compounds on analogous enzymes isolated from different animal species are one of the critical issues to evaluate when exploring structure-activity relationships. The activity of acarbose is about ten times stronger in rat than in human, and that of neosalacinol is similar in both species. Binding affinities of acarbose and neosalacinol to four catalytic domains of alpha-glucosidases in human and rat were compared to investigate the cause of activity differences among species. Species difference was brought about complicatedly by the balance of interaction with four domains, and the result was indicated that larger ligand would show larger species difference in activity.

关键词： Homology Modeling MM/PBSA Alpha-Glucosidase Salacinol Acarbose Species Difference

Proposals for the new maritime community in Japan

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Proposals for the new maritime community in Japan

Natural Postoperative Bone Metabolic Changes after Total Knee Arthroplasty Determined by Positron Emission Tomography Scans

Asia Navigation Conference 2005

作者： Yoshitaka Fukuo Kinzo Inoue Song Ninger shinya nakamura Japan Marine Science Inc Faculty of Maritime SciencesKobe UniversityFaculty of Maritime SciencesKobe UniverstiyJapan Marine Science 2-3-6MinamiShinagawaShinagawa-kuTokyoJapan 5-1-1FukaeminamimachiHigashinada-kuKobeJapan Japan Marine Science Inc Faculty of Maritime SciencesKobe UniversityFaculty of Maritime SciencesKobe UniverstiyJapan Marine Science 2-3-6MinamiShinagawaShinagawa-kuTokyoJapan 5-1-1FukaeminamimachiHigashinada-kuKobeJapan Japan Marine Science Inc Faculty of Maritime SciencesKobe UniversityFaculty of Maritime SciencesKobe UniverstiyJapan Marine Science 2-3-6MinamiShinagawaShinagawa-kuTokyoJapan 5-1-1FukaeminamimachiHigashinada-kuKobeJapan Japan Marine Science Inc Faculty of Maritime SciencesKobe UniversityFaculty of Maritime SciencesKobe UniverstiyJapan Marine Science 2-3-6MinamiShinagawaShinagawa-kuTokyoJapan 5-1-1FukaeminamimachiHigashinada-kuKobeJapan

＜正＞This research and study was a joint effort made by members of the Faculty of Maritime Sciences, Kobe University （former Kobe University of Mercantile Marine） and Japan Marine Science Inc. The objective of the study was to make specific proposals for the structuring of a new maritime society from a national viewpoint. The study started with a questionnaire and interviews conducted with subjects from the maritime industry to get an idea of the current and near-futuristic pictures of marine technicians in our country. It revealed a growing need for human resources of management level with experience in sea service as officers/engineers. It also showed that the growth of such a job market is doomed to be restricted if the current system of life-time employment is maintained by shipping companies in our country. Then, research was conducted with its focus placed on European maritime communities. It uncovered initiatives undertaken in Europe to encourage seafarers to completely shift, earlier than before, to jobs ashore in order to cope with a shortage of marine technicians of management level. Following the results of the research, we have, as a conclusion of the study, proposed that: （1） Our country also promptly bring about a two-stage career system in which seafarers shift to shore-based work completely, after finishing sea service in the middle of their thirties;and （2） Initiatives be launched to structure some organizational and systematic arrangements in which each young marine technician can elect his own period of sea service as a career path because the current industrial landscape would be difficult to change if the two-stage career system is put in place under the life-time employment arrangement within the current framework in each group of shipping companies.

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Open Journal of Orthopedics 2018年第12期8卷 443-457页

作者： Masakazu Kanetaka Soichiro Kaneko Kei Wagatsuma Kenji Ishii Kimiteru Ito shinya nakamura Hiroshi Hamaji Yukimasa Yamato Yorito Anamizu Fumiaki Tokimura Tsuyoshi Miyazaki Department of Orthopaedic Surgery Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan Research Team for Neuroimaging Research Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan Department of Diagnostic Radiology Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan Department of Spine Surgery Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan

Artificial joint replacement surgery is the orthopedic procedure of choice to relieve pain, correct joint deformities, and help patients resume everyday activities. However, the detailed mechanisms regulating peri-implant bone remodeling at the bone-prosthesis interface remain elusive. To address this gap in knowledge, we evaluated the natural postoperative course of bone metabolism by using [18F] NaF positron emission tomography (PET)/computed tomography in 57 patients (104 joints) who underwent asymptomatic total knee arthroplasty (TKA). First, we measured total tracer uptake around TKA to determine the total bone metabolism (TBM) and used the ischial tuberosity as the reference tissue for normalization of PET images. Second, we calculated the TBM ratio (TBMR) by dividing the TBM by tracer uptake in the reference tissue. A moderate increase in TBMR was observed 4 - 5 days after implantation, and its intensity reached the maximum on the seventh postoperative day. The TBMR showed no differences until 12 weeks, after which it decreased slowly and returned to the basal levels. The new parameter TBMR and the unique pattern of postoperative metabolic changes in the bone around the prosthesis may help set accurate interpretation criteria to diagnose complications such as loosening or infections.

关键词： NaF PET Bone Metabolism Total Knee Arthroplasty Ischial Tuberosity

Heterogeneous tunable Ⅲ-Ⅴ-on-silicon-nitride mode-locked laser emitting wide optical spectra

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Photonics Research 2024年第3期12卷 I0021-I0027页

作者： MAXIMILIEN BILLET STIJN CUYVERS STIJN POELMAN ARTUR HERMANS SANDEEP SEEMA SASEENDRA TASUKU nakamura shinya OKAMOTO YASUHISA INADA KAZUYA HISADA TAKU HIRASAWA JOAN RAMIREZ DELPHINE NÉEL NICOLAS VAISSIÈRE JEAN DECOBERT PHILIPPE SOUSSAN XAVIER ROTTENBERG GUNTHER ROELKENS JONØ.KJELLMAN BART KUYKEN Photonics Research Group Department of Information TechnologyGhent University-imec9052 GhentBelgium imec 3001 LeuvenBelgium Technology Division Panasonic Holdings CorporationMoriguchi-CityOsakaJapan Ⅲ-Ⅴ Lab F91767 PalaiseauFrance

We demonstrate a Ⅲ-Ⅴ-on-silicon-nitride mode-locked laser through the heterogeneous integration of a semiconductor optical amplifier on a passive silicon-nitride cavity using the technique of micro-transfer printing. In the initial phase of our study, we focus on optimizing the lasing wavelength to be centered at 1550 nm. This optimization is achieved by conducting experiments with 27 mode-locked lasers, each incorporating optical amplifiers featuring distinct multiple-quantum-well photoluminescence values. Subsequently we present a comprehensive study investigating the behavior of the mode-locking regime when the electrical driving parameters are varied. Specifically, we explore the impact of the gain voltage and saturable absorber current on the locking stability of a tunable mode-locked laser. By manipulating these parameters, we demonstrate the precise control of the optical spectrum across a wide range of wavelengths spanning from 1530 to 1580 nm. Furthermore, we implement an optimization approach based on a Monte Carlo analysis aimed at enhancing the mode overlap within the gain region. This adjustment enables the achievement of a laser emitting a 23-nm-wide spectrum while maintaining a defined 10 dB bandwidth for a pulse repetition rate of 3 GHz.

关键词： tunable amplifier mode

Goblet cell carcinoid of the appendix:Six case reports

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World Journal of Clinical Cases 2024年第22期12卷 5217-5224页

作者： Toshiaki Toshima Ryo Inada shinya Sakamoto Eri Takeda Takahiro Yoshioka Kento Kumon Naoki Mimura Nobuo Takata Motoyasu Tabuchi Kazuyuki Oishi Takuji Sato Kenta Sui Takehiro Okabayashi Kazuhide Ozaki Toshio nakamura Yuichi Shibuya Manabu Matsumoto Jun Iwata Department of Gastroenterological Surgery Kochi Health Sciences CenterKochi 781-8555Japan Department of Diagnostic Pathology Kochi Health Sciences CenterKochi 781-8555Japan

BACKGROUND Goblet cell carcinoid(GCC)of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma *** preoperative diagnosis is very difficult,with most patients complaining mainly of abdominal *** tomography shows swelling of the appendix,so diagnosis is usually made incidentally after appendectomy based on a preoperative diagnosis of *** if a patient undergoes preoperative colonoscopy,accurate endoscopic diagnosis is very difficult because GCC shows a submucosal growth pattern with invasion of the appendiceal *** SUMMARY Between 2017 and 2022,6 patients with GCC were treated in our *** presenting complaint for 5 of these 6 patients was abdominal *** 5 patients underwent appendectomy,including 4 for a preoperative diagnosis of appendicitis and the other for diagnosis and treatment of an appendiceal *** sixth patient presented with vomiting and underwent ileocecal resection for GCC diagnosed from preoperative *** 2 patients with GCC underwent colonoscopy,no neoplastic changes were *** of the six patients showed lymph node metastasis on pathological *** of the last followup(median:15 mo),all cases remained alive without *** As preoperative diagnosis of GCC is difficult,this possibility must be considered during surgical treatments for presumptive appendicitis.

关键词： Goblet cell carcinoid Appendix Preoperative diagnosis Endoscopic diagnosis Surgical treatment Case report

Characteristics of glucose change in diabetes mellitus generalized through continuous wavelet transform processing:A preliminary study

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World Journal of Diabetes 2023年第10期14卷 1562-1572页

作者： Yoichi nakamura shinya Furukawa Cardiovascular Medicine&Diabetology Specified Clinic of Soyokaze CardioVascular Medicine and Diabetes CareMatsuyama 790-0026EhimeJapan Health Services Center Ehime UniversityMatsuyama 790-8577EhimeJapan

BACKGROUND The continuous glucose monitoring(CGM)system has become a popular evaluation tool for glucose fluctuation,providing a detailed description of glucose change *** hypothesized that glucose fluctuations may contain specific information on differences in glucose change between type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM),despite similarities in change patterns,because of different *** Fourier transform,continuous wavelet transform(CWT)is able to simultaneously analyze the time and frequency domains of oscillating *** To investigate whether CWT can detect glucose fluctuations in *** The 60-d and 296-d glucose fluctuation data of patients with T1DM(n=5)and T2DM(n=25)were evaluated *** data obtained every 15 min for 356 d were *** were assessed by CWT with Morlet form(n=7)as the mother *** methodology was employed to search for limited frequency glucose fluctuation in the daily glucose *** frequency and enclosed area(0.02625 scalogram value)of 18 emerged signals were *** specificity for T1DM was evaluated through multiple regression analysis using items that demonstrated significant differences between them as explanatory *** The high frequency at midnight(median:75 Hz,cycle time:19 min)and middle frequency at noon(median:45.5 Hz,cycle time:32 min)were higher in T1DM vs T2DM(median:73 and 44 Hz;P=0.006 and 0.005,respectively).The area of the>100 Hz zone at midnight to forenoon was more frequent and larger in T1DM vs *** a day,the lower frequency zone(15-35 Hz)was more frequent and the area was larger in T2DM than in *** threedimensional scatter diagrams,which consist of the time of day,frequency,and area of each signal after CWT,revealed that high frequency signals belonging to T1DM at midnight had a loose distribution of wave cycles that were 17-24 *** analysis revealed that the high frequency signal at midnight could c

关键词： Continuous glucose monitoring Pathophysiology Fourier,Pseudo-frequency Contour map Scalogram matrix

Maintenance time of sedative effects after an intravenous infusion of diazepam: A guide for endoscopy using diazepam

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World Journal of Gastroenterology 2008年第33期14卷 5197-5203页

作者： Mitsushige Sugimoto Takahisa Furuta Akiko nakamura Naohito Shirai Mutsuhiro Ikuma Shingen Misaka shinya Uchida Hiroshi Watanabe Kyoichi Ohashi Takashi Ishizaki Akira Hishida First Department of Medicine Hamamatsu University School of Medicine1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan Center for Clinical Research Hamamatsu University School of Medicine1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan Department of Gastroenterology Enshu General Hospital1-1-1 Tyuou Naka-ku Hamamatsu 430-0929 Japan Department of Pharmacoki-netics and Pharmacodynamics School of Pharmaceutics Sciences University of Shizuoka52-1 Yada Suruga-ku Shizuoka 422-8526 Japan Department of Clinical Pharmacology and Therapeutics Hamamatsu University School of Medicine1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan Department of Clinical Pharmacology and Therapeutics Oita University1-1 Idaigaoka Hazama Yufu 879-5593 Japan

AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP ) 2C19 genotypes after an infusion regimen of diazepam commonly used forgastrointestinal endoscopy in Japan. METHODS: Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical ? icker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg). RESULTS: The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P < 0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests. CONCLUSION: With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within 1 h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved.

关键词： Diazepam Sedation cytochrome P450(CYP) 2C19 Endoscopy Complication Critical flicker fusion test Eye movement analysis Postural sway test Visual analog scale

Carcinoembryonic antigen-producing adrenal adenoma resected using combined lateral and anterior transperitoneal laparoscopic surgery

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World Journal of Gastroenterology 2007年第45期13卷 6094-6097页

作者： Tomohide Hori Kentaro Taniguchi Masashi Kurata Kenji nakamura Kenji Kato Yoshifumi Ogura Makoto Iwasaki shinya Okamoto Koichiro Yamakado Shintaro Yagi Taku Iida Takuma Kato Kanako Saito Linan Wang Yoshifumi Kawarada Shinji Uemoto Department of Hepatobiliary Pancreatic Surgery Mie University Graduate School of Medicine 2-174 Edobashi Tsu City Mie Prefecture 514-8507 Japan Department of Surgery Matsusaka City Hospital 1550 Tono-machi Matsusaka City Mie Prefecture 515-8544 Japan Department of Anesthesiology Matsusaka City Hospital 1550 Tono-machi Matsusaka City Mie Prefecture 515-8544 Japan Department of Surgery Iwasaki Hospital 333 Isshinden-cho Tsu City Mie Prefecture 514-0114 Japan Department of Cardiology Mie University Graduate School of Medicine 2-174 Edobashi Tsu City Mie Prefecture 514-8507 Japan Department of Radiology Mie University Graduate School of Medicine 2-174 Edobashi Tsu City Mie Prefecture 514-8507 Japan Department of Hepatobiliary Pancreatic and Transplant Surgery Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Department of Cellular and Molecular Immunology Mie University Graduate School of Medicine 2-174 Edobashi Tsu City Mie Prefecture 514-8507 Japan Department of Medical Oncology and Immunology Mie University Graduate School of Medicine 2-174 Edobashi Tsu City Mie Prefecture 514-8507 Japan

A 74-year-old woman presented with symptoms consistent with hyperadrenocorticism and hyperca- techolaminism. She had a cushingoid appearance and her cortisol level was elevated. Her serum dopamine and noradrenalin levels were also elevated. Computed tomography detected a left adrenal mass measuring 3.5 cm x 3.0 cm in diameter. Metaiodobenzylguanidine scintigraphy was negative. Unexpectedly, the serum Serum carcinoembryonic antigen （CEA） level waselevated. Fluorodeoxyglucose positron emission tomography showed increased uptake in the adrenal tumor only, with a maximum standardized uptake value of 2.8. Selective venography and blood sampling revealed that the concentrations of cortisol, catecholamines and CEA were significantly elevated in the vein draining the tumor. A diagnosis of CEA-producing benign adenoma was made. After preoperative management, we performed a combined lateral and anterior transpedtoneal laparoscopic adrenectomy. Her vital signs remained stable during surgery. Histopathological examination revealed a benign adenoma. Her cortisol, catecholamine and CEA levels normalized immediately after surgery. We present, to the best of our knowledge, the first case of CEA-producing adrenal adenoma, along with a review of the relevant literature, and discuss our laparoscopic surgery techniques.

关键词： Carcinoembryonic antigen Laparoscopy Adenoma Adrenal gland Cushing syndrome