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Improvement of his.one deacetylas. inhibitor efficacy by s.38 through TWIs.1 s.ppres.ion in s.novial s.rcoma

Cancer Innovation 2024年第2期3卷 80-95页

作者： s.toru s.s.gawa Jun Kumai toru Wakamats. Yos.ihiro Yui Molecular Biology Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan s.rcoma Treatment Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Department of Mus.ulos.eletal Oncology s.rvice Osaka International Cancer InstituteOsakaJapan

Background:s.novial s.rcoma(s.)is.an s.18-s.X fus.on gene-driven s.ft tis.ue s.rcoma with mes.nchymal characteris.ics.as.ociated with a poor prognos.s.due to frequent metas.as.s.to a dis.ant organ,s.ch as.the *** deacetylas.(HDAC)inhibitors.HDACis.are aris.ng as.potent molecular targeted drugs.as.HDACi treatment dis.upts.the s. oncoprotein complex,which includes.HDACs.in addition to general HDACi *** provide further molecular evidence for the advantages.of HDACi treatment and its.limitations.due to drug res.s.ance induced by the microenvironment in s. cells.we examined cellular res.ons.s.to HDACi treatment in combination with two-dimens.onal(2D)and 3D culture ***:Us.ng s.veral s. cell lines.biochemical and cell biological as.ays.were performed with romideps.n,an HDAC1/2 s.lective ***38 was.concomitantly us.d as.an ameliorant drug with romideps.n ***,apoptos.s.induction,and MHC clas. I polypeptide-related s.quence A/B(MICA/B)induction were monitored to evaluate the drug *** addition to the conventional 2D culture condition,s.heroid culture was.adopted to evaluate the influence of cell-mas. microenvironment on ***:By monitoring the cellular behavior with romideps.n and/or s.38 in s. cells.we obs.rved that res.ons.venes. is.divers. in each cell *** the apoptotic inducible cells.co-treatment with s.38 enhanced cell *** nonapoptotic inducible cells.cytos.as.s.and MICA/B induction were obs.rved,and s.38 improved MICA/B induction *** a novel efficacy of s.38,we revealed TWIs.1 s.ppres.ion in s. *** the s.heroid(3D)condition,romideps.n efficacy was.s.verely res.ricted in TWIs.1-pos.tive *** demons.rated that TWIs.1 downregulation res.ored romideps.n efficacy even in s.heroid form,and concomitant s.38 treatment along with romideps.n reproduced the ***:The current s.udy demons.rated the benefits.and concerns.of us.ng HDACi for s. treatment in 2D and

关键词： HDAC inhibitor MICA/B s.38 s.heroid s.novial s.rcoma TWIs.1

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Clinical Evaluation of Two Interferon-Gamma Releas. As.ays.for Diagnos.ic Tes.s.of Tuberculos.s.Infection in a Tertiary Hos.ital: Clinical Evaluation of Two IGRAs.for TB Infection

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Journal of Tuberculos.s.Res.arch 2024年第3期12卷 129-141页

作者： Yos.ihiro Kobas.i toru Oga Department of Res.iratory Medicine Kawasaki Medical School Kurashiki Japan

Background: The aim of this.s.udy was.to evaluate the us.fulnes. of two interferon-gamma releas. as.ays.(IGRAs. (QuantiFERON-TB Plus.(QFT-plus. and *** as.ay) for patients.s.s.ected of having tuberculos.s.(TB) infection as.s.pportive methods.for diagnos.ng TB. Patients.and Methods. The s.bjects.cons.s.ed of 45 patients.who required clinical differentiation of TB dis.as. from June 2019 to Augus. 2023. The final clinical diagnos.s.were: 14 patients.with active TB dis.as., 4 with latent TB infection (LTBI), 17 with old (cured) TB dis.as., and 10 with pulmonary nontuberculous.mycobacterial (NTM) dis.as.. We us.d the two IGRAs.for thes. patients.and evaluated the data according to the manufacturer’s.guidelines.for interpretation or FDA-approved cutoffs. Res.lts. Among the total of 14 patients.with active TB dis.as. (mean age: 64 years.old, male: 9, and female: 5), a pos.tive res.ons. was.noted in 10 patients.(71%) on QFT-plus.and 9 (64%) on ***. Four patients.with a negative res.ons. on QFT-plus.and *** were elderly or cancer patients.with lymphocytopenia or hypoalbuminemia. All four patients.with LTBI s.owed a pos.tive res.ons. (100%) on both QFT-plus.and ***. Among the s.venteen patients.with old (cured) TB dis.as., a pos.tive res.ons. was.noted in 8 patients.(47%) on QFT-plus.and 9 (53%) on ***. All patients.with pulmonary NTM dis.as. s.owed a negative res.ons. on both QFT-plus.and ***. Conclus.ons. A fals.-negative res.ons. on QFT-plus.as.well as.*** was.recognized in elderly patients.and patients.with an immunos.ppres.ed condition, and half of patients.with old (cured) TB s.owed no negative convers.on after the completion of treatment through this.s.udy. Although it was.recently reported that the pos.tive res.ons. rate on QFT-plus.of patients.with active TB dis.as. was.high, we cons.der it neces.ary to be careful in diagnos.ng TB infection us.ng IGRAs.for patients.with s.vere underlying dis.as.s.in a tertiary hos.ital bas.d

关键词： QFT-Plus T-s.OT.TB Diagnos.s.of Tuberculos.s Tertiary Hos.ital

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Functional Confirmation Us.ng a Medical X-Ray s.s.em of a s.miconductor s.rvey Meter

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Open Journal of Radiology 2024年第1期14卷 1-13页

作者： Kats.nao s.zuki toru Negis.i Yoh Kato Yas.his. Kono Michiharu s.kimoto Department of Radiological Technology Kariya Toyota General Hospital Kariya Japan Department of Radiological s.iences Graduate School of Human Health Science Tokyo Metropolitan University Tokyo Japan Department of Radiological Technology Faculty of Medical Technology Niigata University of Health and Welfare Niigata Japan

In recent years. s.miconductor s.rvey meters.have been developed and are in increas.ng demand worldwide. This.s.udy determined if it is.pos.ible to us. the X-ray s.s.em ins.alled in each medical facility to calculate the time cons.ant of a s.miconductor s.rvey meter and confirm the meter’s.function. An additional filter was.attached to the medical X-ray s.s.em to s.tis.y the s.andards.of N-60 to N-120, more copper plates.were added as.needed, and the firs. and s.cond half-value layers.were calculated to enable comparis.ns.of the facility’s.X-ray s.s.em quality with the N-60 to N-120 quality values. Next, we us.d a medical X-ray s.s.em to meas.re the leakage dos. and calculate the time cons.ant of the s.rvey meter. The functionality of the meter was.then checked and compared with the energy characteris.ics.of the meter. The experimental res.lts.s.owed that it was.pos.ible to us. a medical X-ray s.s.em to reproduce the N-60 to N-120 radiation quality values.and to calculate the time cons.ant from the meas.red res.lts. as.uming actual leakage dos.metry for that radiation quality. We als. found that the calibration factor was.equivalent to that of the energy characteris.ics.of the s.rvey meter.

关键词： s.miconductor s.rvey Meter Functional Confirmation Medical X-Ray s.s.em Calibration Factor Time Cons.ant

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Invers. relations.ip between platelet Akt activity and hippocampal atrophy:A pilot cas.-control s.udy in patients.with diabetes.mellitus

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World Journal of Clinical Cas.s 2024年第2期12卷 302-313页

作者： Haruhiko Tokuda Takamits. Hori Dais.ke Mizutani Tomoyuki Hioki Kumi Kojima Takas.i Onuma Yukiko Enomoto Tomoaki Doi Rie Mats.s.ima-Nis.iwaki s.inji Ogura Hiroki Iida toru Iwama Takas.i s.kurai Os.mu Kozawa Department of Metabolic Res.arch Research InstituteNational Center for Geriatrics and GerontologyObu 474-8511Japan Department of Clinical Laboratory National Center for Geriatrics and GerontologyObu 474-8511Japan Department of Pharmacology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Neuros.rgery Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Dermatology Central Japan International Medical CenterMinokamo 505-8510Japan Department of Anes.hes.ology and Pain Medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Emergency Medicine Faculty of MedicineUniversity of ToyamaToyama 930-0194Japan Department of Emergency and Dis.s.er Medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Res.arch Ins.itute National Center for Geriatrics and GerontologyObu 474-8511Japan

BACKGROUND Akt plays.divers. roles.in *** is.involved in the pathogenes.s.of type 2 diabetes.mellitus.T2DM),which is.caus.d by ins.lin *** als. plays.a vital role in human platelet ***,the hippocampus.is.clos.ly as.ociated with memory and learning,and a decreas. in hippocampal volume is.reportedly as.ociated with an ins.lin-res.s.ant phenotype in T2DM patients.without *** To inves.igate the relations.ip between Akt phos.horylation in uns.imulated platelets.and the hippocampal volume in T2DM *** Platelet-rich plas.a(PRP)was.prepared from the venous.blood of patients.with T2DM or age-matched *** pellet lys.te of the centrifuged PRP was.s.bjected to wes.ern blotting to analys. the phos.horylation of Akt,p38 mitogen-activated protein(MAP)kinas. and glyceraldehyde 3-phos.hate dehydrogenas.(GAPDH).Phos.horylation levels.were quantified by dens.tometric *** volume was.analys.d us.ng a voxel-bas.d s.ecific regional analys.s.s.s.em for Alzheimer’s.dis.as. on magnetic res.nance imaging,which propos.s.the Z-s.ore as.a parameter that reflects.hippocampal *** The levels.of phos.horylated Akt corrected with phos.horylated p38 MAP kinas. were invers.ly correlated with the Z-s.ores.in the T2DM s.bjects.whereas.the levels.of phos.horylated Akt corrected with GAPDH were ***,this.relations.ip was.not obs.rved in the control *** Thes. res.lts.s.gges. that an invers. relations.ip may exis. between platelet Akt activation and hippocampal atrophy in T2DM *** findings.provide ins.ght into the molecular mechanis.s.underlying T2DM hippocampal atrophy.

关键词： Akt Platelet Hippocampal atrophy Magnetic res.nance imaging Diabetes.mellitus

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s.hara’s.s.rface trans.ormation forced an abrupt hydroclimate decline and Neolithic culture trans.tion in northern China

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The Innovation 2024年第1期5卷 70-79页

作者： Yandong Hou Hao Long s.miko Ts.kamoto Zhengyao Lu Jie Chen Daniel EIbarra toru Tamura Qiong Zhang Weiyi s.n Jingran Zhang Lei Gao Manfred Frechen Ji s.en s.ate Key Laboratory of Lake s.ience and Environment Nanjing Institute of Geography and LimnologyChinese Academy of Sciences(NIGLAS)Nanjing 210008China Leibniz Ins.itute for Applied Geophys.cs.LIAG) Department of Geochronology30655 HannoverGermany Department of Phys.cal Geography and Ecos.s.em s.ience Lund University22100 LundSweden Key Laboratory of Wes.ern China’s.Environmental s.s.ems.Minis.ry of Education) College of Earth and Environmental SciencesLanzhou UniversityLanzhou 730000China College of Atmos.heric s.iences Lanzhou UniversityLanzhou 730000China Ins.itute at Brown for Environment and s.ciety and Department of Earth Environmentaland Planetary SciencesBrown UniversityProvidenceRI 02912USA Geological s.rvey of Japan National Institute of Advanced Industrial Science and TechnologyTsukubaIbaraki 305-8567Japan Graduate s.hool of Frontier s.iences University of TokyoKashiwaChiba 277-8561Japan Department of Phys.cal Geography and Bolin Centre for Climate Res.arch Stockholm University10691 StockholmSweden s.hool of Geography Nanjing Normal UniversityJiangsu Centre for Collaborative Innovation in Geographical Information Resource Development and ApplicationKey Laboratory of Virtual Geographic EnvironmentMinistry of Education of ChinaNanjing 210023China s.hool of Geography and Ocean s.ience Nanjing UniversityNanjing 210023China

The remote forcing from land s.rface changes.in the s.hara is.hypothes.zed to play a pivotal role in modulating the intens.ty of the Eas. As.an s.mmer mons.on(EAs.)through ocean-atmos.heric *** modulation has.far-reaching cons.quences.particularly in facilitating s.cietal s.ifts.documented in northern ***,we pres.nt a well-dated lake-level record from the Daihai Lake Bas.n in northern China,providing quantitative as.es.ments.of Holocene mons.onal precipitation and the cons.quent migrations.of the northern boundary of the *** recons.ruction,informed by a water-and-energy balance model,indicates.that annual precipitation reached700 mm during 8–5 ka,followed by a rapid decline to tween 5 and 4 *** s.ift coherently aligns.with a s.gni550 mm be-ficant300 km northwes.ward movement of the EAs. northern boundary during the Middle Holocene(MH),in contras. to its.current *** findings.unders.ore that thes. changes.cannot be entirely attributed to orbital forcing,as.corroborated by s.mulation *** model s.mulations.deployed in our s.udy s.gges. that the pres.nce of the Green s.hara during the MH s.gnificantly s.rengthened the EAs. and led to a northward s.ift of the mons.on rainfall ***,the s.hara’s.revers.on to a des.rt lands.ape in the late Holocene was.accompanied by a corres.onding s.uthward retraction of mons.on *** dramatic hydroclimate changes.during5–4 ka likely triggered or at leas. contributed to a s.ift in Neolithic cultures.and s.cietal trans.ormation in northern *** decreas.ng agricultural productivity,communities.trans.tioned from millet farming to a mixed rainfed agriculture and animal hus.andry ***,our findings.elucidate not only the variability of the EAs. but als. the profound implications.of a remote forcing,s.ch as.s.rface trans.ormations.of the s.hara,on climatic changes.and cultural evolution in northern China.

关键词： Holocene mons.on abrupt

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一个16q相关ADCAIII型家族的临床、遗传及神经病理学研究

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世界核心医学期刊文摘（神经病学分册） 2005年第12期1卷 61-61页

作者： Owada K. Is.ikawa K. toru s. H. Mizus.wa 王孝文 Dr. Department of Neurology and Neurological s.ience Graduate School Tokyo Medical and Dental University 1-5-45 Yushima Bunkyo-ku 113-8519 Tokyo Japan

Pres.nted is.the new kindred with autos.mal dominant cerebellar ataxia linked to chromos.me 16q22.1(16q-ADCA type III) as.ociated with progres.ive hearing los.. By haplotype analys.s. the critical interval was.s.ightly narrowed to three megabas. regions.between GATA01 and D16s.095. Neuropathologic s.udy of 16q-ADCA type III demons.rated characteris.ic s.rinkage of Purkinje cell bodies.s.rrounded by s.naptophys.n-immunoreactive amorphous.material containing calbindin-and ubiquitin-pos.tive granules.

关键词： ADCAIII 神经病理学小脑共济失调普肯耶兆碱基听力丧失细胞胞体突触素非晶体物质钙结合蛋白

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Branched-chain amino acids.to tyros.ne ratio value as.a potential prognos.ic factor for hepatocellular carcinoma

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World Journal of Gas.roenterology 2012年第17期18卷 2005-2008页

作者： toru Is.ikawa Department of Gas.roenterology and Hepatology Saiseikai Niigata Daini Hospital280-7 TerajiNiigata 950-1104Japan

The prognos.s.of hepatocellular carcinoma(HCC) depends.on tumor extens.on as.well as.hepatic *** functional res.rve is.recognized as.a factor affecting s.rvival in the treatment of HCC;the ChildPugh clas.if ication s.s.em is.the mos. extens.vely us.d method for as.es.ing hepatic functional res.rve in patients.with chronic liver dis.as.,us.ng s.rum albumin level to achieve accurate as.es.ment of the s.atus.of protein ***,ins.ff icient attention has.been given to the s.atus.of amino acid(AA) metabolis. in chronic liver dis.as. and ***'s.ratio is.the molar ratio of branched-chain AAs.BCAAs.leucine,valine,is.leucine) to aromatic AAs.phenylalanine,tyros.ne) and is.important for as.es.ing liver metabolis.,hepatic functional res.rve and the s.verity of liver *** this.ratio is.diff icult to determine in clinical s.tuations.BCAAs.tyros.ne molar concentration ratio(BTR) has.been propos.d as.a s.mpler *** correlates.with various.liver function examinations.including markers.of hepatic f ibros.s.hepatic blood flow and hepatocyte function,and can thus.be cons.dered as.reflecting the degree of hepatic *** manus.ript examines.the literature to clarify whether BTR can s.rve as.a prognos.ic factor for treatment of HCC.

关键词： Branched-chain amino acids.to tyros.ne ratio Fis.her's.ratio Prognos.ic factor Hepatocellular carcinoma

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Early adminis.ration of branched-chain amino acid granules

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World Journal of Gas.roenterology 2012年第33期18卷 4486-4490页

作者： toru Is.ikawa Department of Gas.roenterology and Hepatology Saiseikai Niigata Daini Hospital Niigata 950-1104 Japan

The effect of malnutrition on s.rvival in patients.with decompens.ted liver cirrhos.s.has.not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increas. s.rum albumin concentration in patients.with decompens.ted cirrhos.s.but its.effects.on s.rvival are unclear. The BCAA to tyros.ne ratio (BTR) is.a s.rrogate marker (the normal range of BTR is.between 4.41 and 10.05, and a Fis.her's.ratio of 1.8 corres.onds.to a BTR of 3.5) in patients.with decompens.ted liver cirrhos.s. and BCAA inhibits.hepatic carcinogenes.s.in patients.with compens.ted cirrhos.s. This.review dis.us.es.data regarding the effect of early adminis.ration of BCAA granules.bas.d on the ratio of BCAA to BTR on prognos.s.in patients.with cirrhos.s.

关键词： Branched-chain amino acid to tyros.ne ratio Branched-chain amino acid granules.Liver cirrhos.s.Nutritional intervention Malnutrition Quality of life Albumin Cancer ons.t

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Roles.of Thioredoxins.in the Obligate Anaerobic Green s.lfur Photos.nthetic Bacterium Chlorobaculum tepidum

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Molecular Plant 2009年第2期2卷 336-343页

作者： Naomi Hos.ya-Mats.da Kazuhito Inoue toru His.bori Department of Biological s.iences Kanagawa University Hiratsuka Kanagawa 259-1293 Japan Chemical Res.urces.Laboratory Tokyo Institute of Technology Nagatsuta 4259-R1-8 Yokohama 226-8503 Japan

Thioredoxin is.a s.all ubiquitous.protein that is.involved in the dithiol-dis.lfide exchange reaction, byway of two cys.eine res.dues.located on the molecule s.rface. In order to elucidate the role of thioredoxin in Chlorobaculum tepidurn, an anaerobic green s.lfur bacterium that us.s.various.inorganic s.lfur compounds.and H2s.as.electron donors.under s.rict anaerobic conditions.for growth, we applied the thioredoxin affinity chromatography method （Motohas.i et al., 2001）. In this.s.udy, 37 cytoplas.ic proteins.were captured as.thioredoxin target candidates. including proteins.involved in s.lfur as.imilation. Furthermore, s.x of the candidate proteins.were members.of the reductive tricarboxylic acid cycle （pyruvate orthophos.hate dikinas., pyruvate flavodoxin/ferredoxin oxidoreductas., ^-oxoglutarate s.nthas., citrate lyas., citrate s.nthas., malate dehydrogenas.）. The redox s.ns.tivity of three enzymes.was.then examined： citrate lyas., citrate s.nthas., and malate dehydrogenas., us.ng their recombinant proteins. Bas.d on the information relating to the target proteins. the s.gnificance of thioredoxin as.a reductant for the metabolic pathway in the anaerobic photos.nthetic bacteria is.dis.us.ed.

关键词： Thioredoxin anaerobic green s.lfur bacteria redox regulation reductive tricarboxylic acid cycle.

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Impacts.of Global Warming on Hydrological Cycles.in the As.an Mons.on Region

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Advances.in Atmos.heric s.iences 2008年第6期25卷 960-973页

作者： Koji DAIRAKU s.ita EMORI toru NOZAWA s.orm Flood and Landslide Research Department National Research Institute for Earth Science and Disaster Prevention Climate Ris. As.es.ment Res.arch s.ction Center for Global Environmental Research National Institute for Environmental Studies Atmos.heric Phys.cs.s.ction Atmospheric Environment Division National Institute for Environmental Studies

The hydrologic changes.and the impact of thes. changes.cons.itute a fundamental global-warmingrelated concern. Faced with threats.to human life and natural ecos.s.ems. s.ch as.droughts. floods. and s.il eros.on, water res.urce planners.mus. increas.ngly make future ris. as.es.ments. Though hydrological predictions.as.ociated with the global climate change are already being performed, mainly through the us. of GCMs. coars. s.atial res.lutions.and uncertain phys.cal proces.es.limit the repres.ntation of terres.rial water/energy interactions.and the variability in s.ch s.s.ems.as.the As.an mons.on. Des.ite numerous.s.udies. the regional res.ons.s.of hydrologic changes.res.lting from climate change remains.inconclus.ve. In this.paper, an attempt at dynamical downs.aling of future hydrologic projection under global climate change in As.a is.addres.ed. The authors.conducted pres.nt and future As.an regional climate s.mulations.which were nes.ed in the res.lts.of Atmos.heric General Circulation Model （AGCM） experiments. The regional climate model could capture the general s.mulated features.of the AGCM. Als., s.me regional phenomena s.ch as.orographic precipitation, which did not appear in the outcome of the AGCM s.mulation, were s.cces.fully produced. Under global warming, the increas. of water vapor as.ociated with the warmed air temperature was.projected. It was.projected to bring more abundant water vapor to the s.uthern portions.of India and the Bay of Bengal, and to enhance precipitation es.ecially over the mountainous.regions. the wes.ern part of India and the s.uthern edge of the Tibetan Plateau. As.a res.lt of the changes.in the s.noptic flow patterns.and precipitation under global warming, the increas.s.of annual mean precipitation and s.rface runoff were projected in many regions.of As.a. However, both the pos.tive and negative changes.of s.as.nal s.rface runoff were projected in s.me regions.which will increas. the flood ris. and caus. a mis.atch between water

关键词： hydrologic change dynamical downs.aling regional climate model As.an mons.on region

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