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Expression of human FUS/TLS in yeast leads to protein aggregation and cytotoxicity,recapitulating key features of FUS proteinopathy

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Protein & Cell 2011年第2期2卷 141-149页

作者： kazuo Fushimi Charles Long Neha Jayaram Xiaoping Chen Liming Li Jane Y.Wu Department of Neurology Center for Genetic MedicineLurie Comprehensive Cancer CenterNorthwestern University Feinberg School of Medicine303 E.SuperiorChicagoIL 60611USA Department of Molecular Pharmacology and Biological Chemistry Northwestern University Feinberg School of Medicine303 E.SuperiorChicagoIL 60611USA

Mutations in the fused in sarcoma/translocated in liposarcoma(FUS/TLS)gene have been associated with amyotrophic lateral sclerosis(ALS).FUS-positive neuropathology is reported in a range of neurodegenerative diseases,including ALS and fronto-temporal lobar degeneration with ubiquitin-positive pathology(FTLDU).To examine protein aggregation and cytotoxicity,we expressed human FUS protein in *** of either wild type or ALS-associated R524S or P525L mutant FUS in yeast cells led to formation of aggregates and cytotoxicity,with the two ALS mutants showing increased ***,yeast cells expressing human FUS protein recapitulate key features of FUSpositive neurodegenerative ***,a significant fraction of FUS expressing yeast cells stained by propidium iodide were without detectable protein aggregates,suggesting that membrane impairment and cellular damage caused by FUS expression may occur before protein aggregates become microscopically detectable and that aggregate formation might protect cells from FUS-mediated *** N-terminus of FUS,containing the QGSY and G rich regions,is sufficient for the formation of aggregates but not *** C-terminal domain,which contains a cluster of mutations,did not show aggregation or *** to TDP-43 when expressed in yeast,FUS protein has the intrinsic property of forming aggregates in the absence of other human *** the other hand,the aggregates formed by FUS are thioflavin T-positive and resistant to 0.5%sarkosyl,unlike TDP-43 when expressed in yeast ***,TDP-43 and FUS display distinct domain requirements in aggregate formation and cytotoxicity.

关键词： FUS/TLS protein aggregation cytotoxicity

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Holographic augmented reality display with conical holographic optical element for wide viewing zone

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Light(Advanced Manufacturing) 2022年第1期3卷 166-174页

作者： Yusuke Sando kazuo Satoh Daisuke Barada Toyohiko Yatagai Osaka Research Institute of Industrial Science and Technology 2-7-1 AyuminoIzumiOsaka 594-1157Japan. Center for Optical Research&Education Utsunomiya University7-1-2 YotoUtsunomiyaTochigi 321-8585Japan. Graduate School of Engineering Utsunomiya University7-1-2 YotoUtsunomiyaTochigi 321-8585Japan

In this study, we propose a holographic augmented reality (AR) display with a wide viewing zone realized by using a special-designed reflective optical element. A conical holographic optical element (HOE) is used as such a reflective optical element. This conical HOE was implemented to reconstruct a diverging spherical wave with a wide spread angle. It has a sharp wavelength selectivity by recording it as a volume hologram, enabling augmented reality (AR) representation of real and virtual 3D objects. The quality of the generated spherical wave and the spectral reflectivity of the fabricated conical HOE were investigated. An optical superimposition between real and virtual 3D objects was demonstrated, thereby enhancing the validity of our proposed method. A horizontal viewing zone of 140° and a vertical viewing zone of 30° were experimentally confirmed. The fabrication procedure for the conical HOE is presented, and the calculation method of the computer-generated hologram (CGH) based on Fermat’s principle is explained in detail.

关键词： Holographic 3D display Holographic optical element Conical hologram Wide viewing zone

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Molecular targeting to treat gastric cancer

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World Journal of Gastroenterology 2014年第38期20卷 13741-13755页

作者： Keishiro Aoyagi Kikuo Kouhuji Junya Kizaki Taro Isobe Kousuke Hashimoto kazuo Shirouzu Department of Surgery Kurume University School of Medicine

Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.

关键词： Gastric cancer Molecular targeting therapy Human epidermal growth factor receptor 2 protein Vascular endothelial growth factors/Vascular endothelial growth factor receptor pathway Epidermal growth factors pathway

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Clinical study using novel endoscopic system for measuring size of gastrointestinal lesion

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World Journal of Gastroenterology 2014年第14期20卷 4050-4058页

作者： Kiyoshi Oka Takeshi Seki Tomohiro Akatsu Takao Wakabayashi kazuo Inui Junji Yoshino OK Fiber Technology Co. Ltd. Graduate School of engineering and Resource Science Akita University A-tech Co. Ltd. Department of Internal Medicine Banbuntane Hotokukai HospitalFujita Health University

AIM: To verify the performance of a lesion size measurement system through a clinical study.

关键词： Lesion size Non-contact measurement Endoscope Grid scale Low level laser

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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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Readout Properties of Polychromatic Reconstruction for Nondestructive Holographic Data Storage

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红外与激光工程 2016年第9期45卷 36-42页

作者： Ryushi Fujimura Tsutomu Shimura kazuo Kuroda Department of Optical Engineering Utsunomiya University Center for Optical Research and Education Utsunomiya University Institute of Industrial Science The University of Tokyo

Polychromatic reconstruction(PCR) is a novel nondestructive readout method that utilizes a spectrally broad light source for the probe beam. The stored image can be completely reconstructed even though the probe wavelength is very different from the recording one. The large spectral width of the polychromatic probe beam also causes adverse effect on the storage density. But this can be overcomed if an additional optical component is inserted in the imaging system. Therefore, PCR has a great potential to achieve nondestructive readout and large storage density simultaneously. In addition, PCR enables us to design a simple memory system because its readout tolerance is quite large as compared to the conventional monochromatic readout. Unique and attractive features of the polychromatic reconstruction method was theoretically and experimentally demonstrated.

关键词：激光雷达成像仿真空间目标在轨

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Effect of NaCI and Helicobacter pylori vacuolating cytotoxin on cytokine expression and viability

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World Journal of Gastroenterology 2006年第14期12卷 2174-2180页

作者： Juan Sun kazuo Aoki Jin-Xu Zheng Bing-Zhong Su Xiao-Hui Ouyang Junichi Misumi Department of Public Health and Hygiene(Ⅱ) Faculty of Medicine Oita University Oita 879-5593 Japan Department of Pulmonary Medicine Affiliated Hospital School of Medicine Jiang Su University Zhenjiang 212001China First Affiliated Hospital of Inner Mongolia Medical College Hohhot 010000 Inner Mongolia China

AIM; To determine whether Helicobacter pylori （H pylon） vacuolating cytotoxin （VacA） regulates release of proinflammatory cytokines （IL-1β, IL-8, TNF-α, and IL-6） or alters gastric epithelial cell viability and to determine whether NaCl affects these VacA-induced changes. METHODS： Vacuolating activity was determined by measuring the uptake of neutral red into vacuoles of VacA-treated human gastric epithelial （AGS） cells. AGS cell viability was assessed by direct cell counting. Specific enzyme-linked immunosorbent assays （ELISA） and reverse transcdptase-polymerase chain reaction（RT-PCR） were performed to examine the effects of H pylori VacA and NaCl on cell pro-inflammatory cytokine production in AGS cells. Immunohistochemical staining of gastric tissue from Mongolian gerbils was used to confirm VacAinduced pro-inflammatory cytokine production and the effects of NaCl on this VacA-induced response. RESULTS： Addition of VacA alone reduced AGS cell viability （P〈 0.05）, and this reduction was enhanced by high doses of NaCl （P〈0.05）. VacA alone induced expression of TNF-α, IL-8 and IL-1β, while NaCl alone induced expression of TNF-α and IL-1β. Changes in mRNA levels in the presence of both VacA and NaCl were more complicated. For the case of TNF-α, expression was dosedependent on NaCl. IL-6 mRNA was not detected. However, low levels of IL-6 were detected by EUSA. Positive immunohistochemical staining of IL-1, IL-6, and TNF-α was found in gastric tissue of H pylori-infected gerbils fed with either a normal diet or a high salt diet. However, the staining of these three cytoldnes was sb＇onger in H pylori-infected animals fed with a 5g/kg NaCl diet. CONCLUSION： VacA decreases the viability of AGS cells, and this effect can be enhanced by NaCl. NaCl also affects the production of pro-inflammatory cytokines in- duced by VacA, suggesting that NaCl plays an important role in Hpylori-induced gastric epithelial cell cytotoxicity.

关键词： Helicobacter pylori Vacuolating cytotoxin Cytokine Gerbil AGS cell

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Can We Use Consumer-Wearable Activity Tracker Fitbit in Parkinson Disease?

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Advances in Parkinson's Disease 2021年第2期10卷 15-23页

作者： kazuo Abe Department of Neurology Hyogo College of Medicine Hospital Nishinomiya Japan Headquarter Medical Welfare Corporation Kyowakai Kawanishi Japan Center of Neurology Gratia Hospital Minoo Japan

Consumer-wearable activity trackers have been used for monitoring health-related metrics to estimate steps, distance, physical activity, energy expenditure, and sleep. The purpose of this mini review was to summarize the evidence for validity of the most popular wrist-worn activity tracker (Fitbit) to estimate those health-related metrics in Parkinson disease. We researched full-length English studies in PubMed, Science Direct, Google Scholar, and Scopus, through September, 2021. In total, 27 studies and a textbook description were included in the review. To adapt consumer-wearable activity trackers for evaluating health-related metrics in Parkinson’s disease (PD) patients, there may be some points to be elucidated and conquered. First, measurement accuracy and precision are required. Second, inter-device reliability for measuring steps, distance, and energy expenditure must be considered. Third, wearability: there are some types of device such as wrist-worn, ankle-worn, belt-fixed, and so on. Overall, Fitbit has advantage for these points. This mini review indicates that Fitbit has enough measurement accuracy and precision to estimate health-related metrics of PD patients including amount of step, physical activity energy expenditure, and quality of sleep.

关键词： Parkinson Disease Consumer-Wearable Activity Trackers Fitbit Physical Activity Sleep

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Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy

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World Journal of Gastroenterology 2011年第14期17卷 1858-1865页

作者： Mitsushige Sugimoto Masafumi Nishino Chise Kodaira Mihoko Yamade Takahiro Uotani Mutsuhiro Ikuma kazuo Umemura Takahisa Furuta Center for Clinical Research Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan First Department of Medicine Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan Department of Pharmacology Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan

AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dosages and frequency of administration of RPZ,median intragastric pH significantly increased,and FSSG scores significantly decreased. With RPZ 10 mg qid,potent acid inhibition was attained throughout 24 h. However,five subjects were refractory to RPZ 10 mg qid,although the median intragastric pH in these subjects (6.6,range:6.2-7.1) was similar to that in the remaining five responsive subjects (6.5,range:5.3-7.3). With baseline RPZ 10 mg od,FSSG scores in responsive patients improved by > 30%,whereas there was no significant decrease in the resistant group. CONCLUSION:NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.

关键词： Non-erosive reflux disease Rabeprazole CYP2C19

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Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia

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World Journal of Gastroenterology 2009年第42期15卷 5307-5315页

作者： Kohei Tatsumi kazuo Ohashi Sanae Taminishi Soichi Takagi Rie Utoh Akira Yoshioka Midori Shima Teruo Okano Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University8-1 Kawada-choShinjuku-kuTokyo 162-8666Japan Department of Pediatrics Nara Medical Univrsity840 Shijo-choKashiharaNara 634-8522Japan

AIM： To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia （DH）-mediated liver regeneration. METHODS： Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bisr2-（3,5-dichloropyridyloxy）] benzene （TCPOBOP）, a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 （D0： prior to injection）, 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢβ , plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF）. The corresponding plasma levels of coagulation factors （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and VWF） were also analyzed and compared with their mRNA levels. RESULTS： Gavage administration of TCPOBOP （3 mg/kg body weight） resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the DO （control） ratios. At the peak of liver regeneration （D1 and D2）, the gene expression levels for most of the coagulationrelated factors （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ,Ⅺ, Ⅻ, ⅩⅢβ, plasminogen, antithrombin, protein C, ADAMTS13, VWF） were found to be downregulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors （prothrombin, factors Ⅷ, Ⅸ, Ⅺ, and Ⅻ） demonstrated a significant decrease （P 〈 0.05） during the regeneration phase compared with DO. Among these 5 factors, factor Ⅸ and factor Ⅺ showed the most dramatic decline in their activities by about 50% at D2 compared to

关键词： Coagulation factor 1,4-bis[2-(3,5-dichlo- ropyridyloxy)] benzene Direct hyperplasia Liver regeneration

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