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Hepatitis C virus NS5A inhibitors and drug resistance mutations

World Journal of Gastroenterology 2014年第11期20卷 2902-2912页

作者： Shingo Nakamoto Tatsuo kanda Shuang Wu Hiroshi Shirasawa Osamu Yokosuka Department of Molecular Virology Graduate School of MedicineChiba UniversityChiba 260-8677Japan Department of Gastroenterology and Nephrology Graduate School of MedicineChiba UniversityChiba 260-8677Japan

Some direct-acting antiviral agents for hepatitis C virus (HCV), such as telaprevir and boceprevir have been available since 2011. It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis. HCV NS5A inhibitors efficiently inhibited HCV replication in vitro. Human studies showed that dual, triple and quad regimens with HCV NS5A inhibitors, such as daclatasvir and ledipasvir, in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin, could efficiently inhibit HCV replication according to HCV genotypes. These combinations might be a powerful tool for “difficult-to-treat” HCV-infected patients. “First generation” HCV NS5A inhibitors such as daclatasvir, ledipasvir and ABT-267, which are now in phase III clinical trials, could result in resistance mutations. “Second generation” NS5A inhibitors such as GS-5816, ACH-3102, and MK-8742, have displayed improvements in the genetic barrier while maintaining potency. HCV NS5A inhibitors are safe at low concentrations, which make them attractive for use despite low genetic barriers, although, in fact, HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors, HCV NS5B inhibitors or peginterferon plus ribavirin. This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants.

关键词： ACH-3102 Direct-acting antiviral agents Daclatasvir Hepatitis C virus Ledipasvir

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Gastrojejunostomy followed by induction chemotherapy for incurable gastric cancer with outlet obstruction

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World Journal of Gastroenterology 2010年第34期16卷 4367-4370页

作者： Yasuhiro Okumura Manabu Ohashi Souya Nunobe Tomohiro Iwanaga Tatsuo kanda Yoshiaki Iwasaki Department of Surgery Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Department of Gastrointestinal Surgery Tokyo University Hospital Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences

A 72-year-old male gastric cancer patient with outlet obstruction underwent laparoscopic exploration. The examination disclosed intraperitoneal free cancer cells with no overt peritoneal, lymphatic, or hepatic metastasis. The patient underwent laparoscopy-assisted gastroje-junostomy (LAGJ) and started chemotherapy with S-1 plus cisplatin on postoperative day 13. Three course of the chemotherapy shrank the tumor markedly. Then, the patient underwent gastrectomy with a curative intent. Laparotomy revealed no intraperitoneal free cancer cells, and microscopically complete resection was achieved. The patient received S-1 chemotherapy as postoperative adjuvant treatment for 1 year, and is still alive with no evidence of peritoneal recurrence. LAGJ followed by S-1 plus cisplatin is one of the optional treatments that should be considered for patients with outlet obstruction as it may widen opportunities for potentially curative resection.

关键词： Gastric cancer Outlet obstruction CY1 Laparoscopy-assisted gastrojejunostomy S-1 plus cisplatin

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Increased plasma galectin-1 correlates with advanced glycation end products and interleukin-1β in patients with proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2019年第4期12卷 692-694页

作者： Keitaro Hase Atsuhiro kanda Kousuke Noda Susumu Ishida Laboratory of Ocular Cell Biology and Visual Science Department of Ophthalmology Faculty of Medicine and Graduate School of Medicine Hokkaido University

Dear Editor,Galectin-1, one of galactoside-binding lectin family proteins, has been shown to regulate cell growth, migration, and proliferation, where it binds many receptors depending on their glycosylation profile, ... 详细信息

关键词： Increased plasma galectin-1 correlates with advanced glycation end products and interleukin-1β in patients with proliferative diabetic retinopathy diabetic retinopathy

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New Trend of Database for the Internet Era ——Object database and its application

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Wuhan University Journal of Natural Sciences 2001年第Z1期6卷 110-120页

作者： Takashi kanda, Kazuo Mineno Fujitsu Limited Software Group,Yokohama 222\|0033,Japan Fujitsu Limited Software Group Yokohama 222-0033 Japan

In the Internet era, the relational database in general use cannot be applied to some problems which should be solved. In this thesis, we describe the necessary capabilities for database management systems and compare them with the limitation of RDB. And also we introduce object database and its efficiency, which will be the new trend of the database. We use “Jasmine2000” as a concrete example of object database in business use, and are going to verify its efficiency with its applied cases. At the end, we will point the way of database's future.

关键词： object database ODB Jasmine Jasmine2000 multimedia internet web XML digital archive

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Data-Driven Determinant-Based Greedy Under/Oversampling Vector Sensor Placement

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Computer Modeling in Engineering & Sciences 2021年第10期129卷 1-30页

作者： Yuji Saito Keigo Yamada Naoki kanda Kumi Nakai Takayuki Nagata Taku Nonomura Keisuke Asai Tohoku University SendaiMiyagi980-8579Japan

A vector-measurement-sensor-selection problem in the undersampled and oversampled cases is considered by extending the previous novel approaches:a greedy method based on D-optimality and a noise-robust greedy method in this *** of the vector-measurement-sensor selection of the greedy algorithms are proposed and applied to randomly generated systems and practical datasets of flowfields around the airfoil and global climates to reconstruct the full state given by the vector-sensor measurement.

关键词： Sparse sensor selection vector-sensor measurement

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Effect of lamivudinein in BeAg-positive chronic hepatitis B: Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level

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World Journal of Gastroenterology 2005年第22期11卷 3346-3350页

作者： Tomoko Kurihara Fumio Imazeki Osamu Yokosuka Kenichi Fukai Tatsuo kanda Shigenobu Kawai Hiromitsu Saisho Department of Medicine and Clinical Oncology Graduate School of Medicine Chiba University 1-8-1 Inohana Chuou Ward Chiba 260-8670Japan

AM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo. RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs2, P= NS; groups 1 vs 3, P= 0.002; groups 1 vs4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P - NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02; groups 1 vs 3, P= NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.

关键词： Lamivudine Chronic hepatitis B HBeAg HBV DNA ALT

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Opening a new route to multiport coherent XUV sources via intracavity high-order harmonic generation

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Light(Science & Applications) 2020年第1期9卷 398-406页

作者： Natsuki kanda Tomohiro Imahoko Koji Yoshida Akihiro Tanabashi AAmani Eilanlou Yasuo Nabekawa Tetsumi Sumiyoshi Makoto Kuwata-Gonokami Katsumi Midorikawa RIKEN Center for Advanced Photonics RIKENWakoSaitama 351-0198Japan Photon Science Center The University of TokyoTokyo 113-8656Japan Intstitute for Solid State Physics The University of TokyoKashiwaChiba 277-8581Japan Cyber Laser Inc. WakoSaitama 351-0104Japan Institute for Photon Science and Technology The University of TokyoTokyo 113-0033Japan Department of Physics The University of TokyoTokyo 113-0033Japan

High-order harmonic generation(HHG)is currently utilized for developing compact table-top radiation sources to provide highly coherent extreme ultraviolet(XUV)and soft X-ray pulses;however,the low repetition rate of fundamental lasers,which is typically in the multi-kHz range,restricts the area of application for such HHG-based radiation ***,we demonstrate a novel method for realizing a MHz-repetition-rate coherent XUV light source by utilizing intracavity HHG in a mode-locked oscillator with an Yb:YAG thin disk laser medium and a 100-m-long ring *** have successfully implemented HHG by introducing two different rare gases into two separate foci and picking up each HH *** to the two different HH beams generated from one cavity,this XUV light source will open a new route to performing a time-resolved measurement with an XUV-pump and XUV-probe scheme at a MHzrepetition rate with a femtosecond resolution.

关键词： intracavity coherent repetition

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云峰山温泉度假村

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城市环境设计 2024年第1期147卷 70-75页

作者：横尾实秋山弘明猿田晓生神田刚隈研吾建筑都市设计事务所

这座温泉度假村坐落在中国云南省腾冲市的山区中。项目用地西面有一座山，名叫云峰山，被誉为道教圣地。于是，我们把这些建筑物布置得像是顺着道教“精神”从山上下来的水流。我们还利用了附近采石场的不同种类的石头，把各种石头像马...

这座温泉度假村坐落在中国云南省腾冲市的山区中。项目用地西面有一座山，名叫云峰山，被誉为道教圣地。于是，我们把这些建筑物布置得像是顺着道教“精神”从山上下来的水流。我们还利用了附近采石场的不同种类的石头，把各种石头像马赛克一样拼在一起。通过使用当地的石头，我们试图在我们设计的建筑中表达“大地的力量”。

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Rescue of white egg 1 mutant by introduction of the wildtype Bombyx kynurenine 3-monooxygenase gene

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Insect Science 2007年第2期14卷 85-92页

作者： GUO-XING QUAN ISAO KOBAYASHI KATSURA KOJIMA KEIRO UCHINO TOSHIO kanda HIDEKI SEZUTSU TORU SHIMADA TOSHIKI TAMURA Transgenic Silkworm Research Center National Institute of Agrobiological Sciences Tsukuba Ibaraki 305-8634 Japan Biomimetic Laboratory National Institute of Agrobiological Sciences Tsukuba Ibaraki 305-8634 Japan Department of Agricultural and Environmental Biology Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan

In silkworms, the white egg 1 （w-1） mutant, which is characterized by white eyes and white eggs, is deficient in Bombyx kynurenine 3-monooxygenase （KMO） activity. To investigate whether the w-1 mutant phenotype is rescued by introducing the wild-type KMO gene, we constructed transgenic silkworms with the wild-type Bombyx KMO gene under the control of either the cytoplasmic actin gene promoter （A3KMO） or the native KMO gene promoter （KKMO）. We created two transgenic lines with A3KMO and one line with KKMO constructs. The eyes of adults in these lines were brown, and the eggs laid by the transgenic females were also brown. Reverse transcription-polymerase chain reaction（RT-PCR） analysis showed that the A3KMO silkworm lines expressed the transcript in the mid-gut, fat bodies, and Malpighian tubules. The KKMO line expressed the transcript only in the fat bodies and Malpighian tubules. The intensity of eye and egg color in the transgenic lines was proportional to the KMO expression level. Interestingly, transgenic larvae with the A3KMO construct had a light brown larval cuticle, but the KKMO line did not. These results indicate that the wild-type KMO gene can be used as a marker gene for visually screening transgenic silkworms.

关键词： Bombyx mori KMO marker gene transgenic w-1

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<i>L<sup>p</sup></i>Polyharmonic Dirichlet Problems in the Upper Half Plane

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Advances in Pure Mathematics 2015年第14期5卷 828-834页

作者： kanda Pan Department of Mathematics Jinan University Guangzhou China

In this article, a class of Dirichlet problem with Lp boundary data for poly-harmonic function in the upper half plane is mainly investigated. By introducing a sequence of kernel functions called higher order Poisson kernels and a hierarchy of integral operators called higher order Pompeiu operators, we obtain a main result on integral representation solution as well as the uniqueness of the polyharmonic Dirichlet problem under a certain estimate.

关键词： Dirichlet Problem Polyharmonic Function Higher Order Poisson Kernels Higher Order Pompeiu Operators Non-Tangential Maximal Function Uniqueness

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