2024-03-28T14:30:53Zhttp://ginmu.naramed-u.ac.jp/dspace-oai/request
oai:ginmu.naramed-u.ac.jp:10564/33582018-07-12T16:30:10Zhdl_10564_3445hdl_10564_3352Minimum Ten-Year Follow-UP of Computed Tomography Based, Custom Cementless Stem After Intertrochanteric Osteotomy for Dysplastic Hips.臼蓋形成不全の股関節に行った転子間骨切り術後症例に対するカスタムメイドセメントレスステムの術後10年以上の成績Masuda, YoshihideKawate, KenjiOhmura, TetsujiMunemoto, MitsuruUchihara, YoshinobuTanaka, Yasuhitoprimary total hip arthroplastyfemoral osteotomyCT based custom stemfixationstress shieldingBackground: During fixation of total hip arthroplasty (THA) after osteotomy, it is difficult to obtain a good cement mantle with a cemented stem and to obtain good fit along the medullary canal with a ready-made stem. We developed a CT-based custom stem, which was inserted after osteotomy in THA. Methods: We investigated 32 hips in 28 patients. The mean patient age at surgery was 62 and the mean follow-up period was 13 years. The previous osteotomy was intertrochanteric varus femoral osteotomy in 14 hips, intertrochanteric valgus femoral osteotomy in 17, and Schanz osteotomy in one. CT studies were obtained with a 5 mm slice intervals and 2 mm slice width. We produced stems made of Ti-6Al-4V. The stems did not have collars and the proximal third was coated with a 400-μ. m-thick porous coating covered with 20-μ m-hydroxyapatite (HA) coating. Results: The Harris Hip Score improved from a preoperative mean of 49.9 points to a postoperative mean of 82.7 points. One patient complained of postoperative thigh pain. Fractures occurred in two hips. Dislocation occurred in three patients. To date. no patient has reqired revision of the stem due to aseptic loosening. There was bone-ingrown fixation in all hips. Severe stress shielding was found in 14 hips (44%) Conclusion: Stable fixation was achieved with the proximal press-fit of the custom stem. Although stress shielding was observed in 14 hips, excellent results were obtained over a follow-up period of 10 years with this custom stem system for hips after intertrochanteric femoral osteotomy.博士(医学)・乙第1419号・平成30年6月27日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.67 No.4,5,6 p.65-72 (2016.12)13450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3358Journal of Nara Medical Association, 67(4,5,6): 65-72http://hdl.handle.net/10564/3358http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3358/4/01%e4%b9%991419%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3358/5/02%e4%b9%991419%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3358/1/03%e4%b9%991419%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association674,5,665722016-12-31engETD24601B14192018-06-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/34532019-06-19T04:18:55Zhdl_10564_3445Intravitreal injection of aflibercept, an anti-VEGF antagonist, down-regulates plasma von Willebrand factor in patients with age-related macular degeneration.抗VEGF薬アフリベルセプト硝子体注射は加齢黄斑変性患者の血漿中フォンビルブランド因子を減少させるYamashita, MarikoMatsumoto, MasanoriHayakawa, MasakiSakai, KazuyaFujimura, YoshihiroOgata, NahokoWe investigated the association between von Willebrand factor (VWF) and exudative age-related macular degeneration (AMD) in 114 Japanese patients. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitor is the most effective therapy for AMD. Therefore, we analyzed changes of VWF antigen (VWF:Ag) and VWF multimers (VWFMs) after intravitreal injection of aflibercept, an anti-VEGF antagonist. The relationship between polymorphisms in complement factor H (p.Y402H and p.I62V) and AMD was previously reported. In our patients, p.I62V, but not p.Y402H, was significantly associated with an increased risk of AMD. Pre-treatment plasma levels of VWF:Ag in patients with AMD were significantly higher than those in controls. Unusually large VWFMs (UL-VWFMs) were detected in the majority of AMD patients with concurrent vitreous or subretinal hemorrhage. After intravitreal injection of aflibercept, plasma levels of VWF:Ag and VEGF-A were significantly decreased. UL-VWFMs disappeared after aflibercept injection in three cases, but persisted even 1 month after injection in the other five cases. In conclusion, plasma VWF:Ag levels were significantly elevated in patients with AMD, and decreased after intravitreal aflibercept injection. VWF may play an important role in the pathophysiology of AMD, and aflibercept might improve AMD by reducing plasma levels of VWF in addition to VEGF-A.博士(医学)・甲第684号・平成30年6月27日© The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Springer NatureThesisThesis or DissertationScientific reports Vol.8 No.1 Article No.1491 (2018 Jan)20452322http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3453Scientific reports, 8(1): Article No.1491http://hdl.handle.net/10564/3453http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3453/1/01%e7%94%b2684%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3453/2/02%e7%94%b2684%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3453/3/03%e7%94%b2684%e6%9c%ac%e6%96%87.pdf20452322Scientific reports81Article No.14912018-01-24http://www.ncbi.nlm.nih.gov/pubmed/29367644http://dx.doi.org/10.1038/s41598-018-19473-0ETD24601A6842018-06-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/34542018-07-12T16:30:09Zhdl_10564_3445Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells.間欺的低酸素はヒト神経細胞においてGATA転写因子を介してPOMCとCARTのmRNAを増加させるShobatake, RyogoTakasawa, KenOta, HiroyoItaya-Hironaka, AsakoYamauchi, AkiyoSakuramoto-Tsuchida, SumiyoUchiyama, TomokoMakino, MaiSugie, KazumaTakasawa, ShinUeno, SatoshiSleep apnea syndromeIntermittent hypoxiaAppetitePOMC (proopiomelanocortin)CART (cocaine- and amphetamine-regulated transcript)GATASleep apnea syndrome (SAS) is characterized by intermittent hypoxia (IH) during sleep. SAS and obesity are strongly related to each other. Here, we investigated the effect of IH on the expression of major appetite regulatory genes in human neuronal cells. We exposed NB-1, SH-SY5Y, and SK-N-SH human neuronal cells to IH (64 cycles of 5 min hypoxia and 10 min normoxia), normoxia, or sustained hypoxia for 24 h and measured the mRNA levels of proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), galanin, galanin-like peptide, ghrelin, pyroglutamylated RFamide peptide, agouti-related peptide, neuropeptide Y, and melanocortin 4 receptor by real-time RT-PCR. IH significantly increased the mRNA levels of POMC and CART in all the neuronal cells. Deletion analysis revealed that the -705 to -686 promoter region of POMC and the -950 to -929 region of CART were essential for the IH-induced promoter activity. As possible GATA factor binding sequences were found in the two regions, we performed real-time RT-PCR to determine which GATA family members were expressed and found that GATA2 and GATA3 mRNAs were predominantly expressed. Therefore, we introduced siRNAs against GATA2 and GATA3 into NB-1 cells and found that GATA2 and GATA3 siRNAs abolished the IH-induced up-regulation of both POMC and CART mRNAs. These results indicate that IH stress up-regulates the mRNA levels of anorexigenic peptides, POMC and CART, in human neuronal cells via GATA2 and GATA3. IH can have an anorexigenic effect on SAS patients through the transcriptional activation of POMC and CART in the central nervous system.博士(医学)・甲第685号・平成30年6月27日© 2017 Elsevier Ltd. All rights reserved.ElsevierThesisThesis or DissertationThe international journal of biochemistry and cell biology Vol.95 p.100-107 (2018 Feb)13572725http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3454The international journal of biochemistry and cell biology, 95: 100-107http://hdl.handle.net/10564/3454http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3454/1/01%e7%94%b2685%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3454/2/02%e7%94%b2685%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3454/3/03%e7%94%b2685%e6%9c%ac%e6%96%87.pdf13572725AA11036038The international journal of biochemistry and cell biology951001072018-02enghttp://www.ncbi.nlm.nih.gov/pubmed/29275211http://dx.doi.org/10.1016/j.biocel.2017.12.012ETD24601A6852018-06-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/34552019-09-27T02:27:39Zhdl_10564_3445Biomechanical study of distal radioulnar joint ballottement test.遠位橈尺関節バロットメントテストの生体力学的研究Onishi, TadanobuOmokawa, ShoheiIida, AkioNakanishi, YasuakiKira, TsutomuMoritomo, HisaoRuxasagluwang, SompobKraisarin, JirchartShimizu, TakamasaTanaka, Yasuhitobiomechanicsdistal radioulnar jointballottement testhuman cadaverWe investigated the reliability and accuracy of the distal radioulnar joint (DRUJ) ballottement test using five fresh-frozen cadaver specimens in triangular fibrocartilage complex (TFCC)-intact, and TFCC-sectioned wrists. The humerus and proximal ulna were fixed. The ulna was allowed to translate in dorsopalmar directions without rotation, and the radius was allowed to move freely. Four sensors of a magnetic tracking system were attached to the radius and ulna, and the nails of each examiner's thumbs. Five examiners conducted the DRUJ ballottement test before and after TFCC sectioning. We used two techniques: With holding and without holding the carpal bones to the radius (holding and non-holding tests, respectively). We compared the magnitudes of bone-to-bone (absolute DRUJ) movement with that of the examiner's nail-to-nail (relative DRUJ) movement. The intrarater intraclass correlation coefficients (ICCs) were 0.92 (holding) and 0.94 (non-holding). The interrater ICCs were 0.84 (holding) and 0.75 (non-holding). Magnitudes of absolute and relative movements averaged 11.5 and 11.8 mm, respectively (p < 0.05). Before TFCC sectioning, the DRUJ movement during the holding and non-holding techniques averaged 9.8 and 10.8 mm, respectively (p < 0.05). The increase in DRUJ movement after TFCC sectioning was greater with the holding technique (average 2.3 mm) than with the non-holding technique (average 1.6 mm). The DRUJ ballottement test with magnetic markers is relatively accurate and reliable for detecting unstable joints. We recommend the holding technique for assessing DRUJ instability in clinical practice.博士(医学)・甲第686号・平成30年6月27日© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/jor.23355], which has been published in final form at [http://dx.doi.org/10.1002/jor.23355]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.WileyThesisThesis or DissertationJournal of orthopaedic research Vol.35 No.5 p.1123-1127 (2017 May)07360266http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3455Journal of orthopaedic research, 35(5): 1123-1127http://hdl.handle.net/10564/3455http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3455/1/01%e7%94%b2686%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3455/2/02%e7%94%b2686%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3455/3/03%e7%94%b2686%e6%9c%ac%e6%96%87.pdf07360266AA10625350Journal of orthopaedic research355112311272017-05enghttp://www.ncbi.nlm.nih.gov/pubmed/27356009http://dx.doi.org/10.1002/jor.23355ETD24601A6862018-06-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/34942018-12-12T16:30:09Zhdl_10564_3445Hidden Antioxidative Functions of Reduced Nicotinamide Adenine Dinucleotide Coexisting with Hemoglobin.ヘモグロビンと共存する還元型ニコチンアミドアデニンジヌクレオチドの隠れた抗酸化機能Yamada, MagoheiSakai, HiromiFerrous oxyhemoglobin (HbO2) in red blood cells (RBCs) invariably and slowly autoxidizes to form ferric methemoglobin (metHb). However, the level of metHb is always maintained below 0.5% by intracellular metHb reduction of enzymatic systems with coenzymes, such as reduced nicotinamide adenine dinucleotide (NADH), and by superoxide dismutase (SOD) and catalase (CAT), which eliminate reactive oxygen species. Unquestionably, NADH cannot reduce metHb without the corresponding enzymatic system. Our study, however, demonstrated that a high concentration of NADH (100-fold of normal level, equimolar to HbO2) retarded autoxidation of HbO2 in a highly purified Hb solution with no enzymatic system. Furthermore, an inhibitory effect of NADH on metHb formation was observed with additions of oxidants such as H2O2, NO, and NaNO2. Our mechanism assessment elucidated extremely high pseudo-CAT and pseudo-SOD activities of NADH with coexistence of HbO2, and reactivity of NADH with NO. We prepared a model of RBCs (Hb-vesicles, Hb-V) encapsulating purified HbO2 solution and NADH, but no enzymatic system within liposome. We confirmed the inhibitory effect of NADH on both autoxidation and oxidant-induced metHb formation. In addition, an intravenous administration of these Hb-Vs to rats caused significant retardation of metHb formation by approximately 50% compared to the case without NADH coencapsulation. Based on these results, we elucidated a new role of NADH, that is, antioxidative effect via interaction with Hb, in addition to its classical role as a coenzyme.博士(医学)・甲第687号・平成30年9月26日This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS chemical biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/ 10.1021/acschembio.7b00174American Chemical SocietyThesisThesis or DissertationACS chemical biology Vol.12 No.7 p.1820-1829 (2017 Jul)15548929http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3494ACS chemical biology, 12(7): 1820-1829http://hdl.handle.net/10564/3494http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3494/5/01%e7%94%b2687%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3494/6/02%e7%94%b2687%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3494/7/03%e7%94%b2687%e6%9c%ac%e6%96%87.pdf15548929AA1212269XACS chemical biology127182018292017-07-21enghttp://www.ncbi.nlm.nih.gov/pubmed/28485916http://dx.doi.org/ 10.1021/acschembio.7b00174ETD24601A6872018-09-26博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/34962018-12-12T16:30:11Zhdl_10564_3495hdl_10564_3445Is the linear-quadratic model appropriate for stereotactic irradiation of metastatic brain tumors?L-Qモデルは転移性脳腫瘍の定位放射線照射に適用可能か?Yoshimine, TadashiFujitani, NobumasaIkeguchi, ToshitakaIwami, HiroshiMatsuda, RyosukeTamamoto, TetsuroMorimoto, YokoHasegawa, MasatoshiLQ modelBEDstereotactic irradiationSRSSRTThe biologically effective dose (BED) based on the linear-quadratic (LQ) model has been commonly used to evaluate the dose-effect relationships among the different fractionation schedules, but whether the LQ model is appropriate for hypofractionated (HF) high-dose stereotactic irradiation (STI) is uncertain. The validity of the model at high doses per fraction has been critically examined. In this study, STI of metastatic brain tumors was evaluated to suggest the applicability of the LQ model to HF high-dose radiotherapy. No significant difference was found between stereotactic radiosurgery (SRS) and HF stereotactic radiotherapy (SRT) in the analyses of 151 tumors. Furthermore, no significant differences were found among SRS, HF-SRT, and non-HF SRT in 117 metastatic lung adenocarcinomas. The results of this study suggest that BED calculation is a reasonable approach for careful dose-effect evaluation based on the LQ model for HF high-dose radiotherapy for metastatic brain tumors, especially lung adenocarcinomas.博士(医学)・甲第688号・平成30年9月26日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.69 No.1,2,3 p.9-15 (2018.6)13450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3496Journal of Nara Medical Association, 69(1,2,3): 9-15http://hdl.handle.net/10564/3496http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3496/1/01%e7%94%b2688%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3496/2/02%e7%94%b2688%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3496/3/03%e7%94%b2688%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association691,2,39152018-06-30engETD24601A6882018-09-26博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/34972018-12-12T16:30:12Zhdl_10564_3445Computer-assisted cognitive remediation therapy increases hippocampal volume in patients with schizophrenia: a randomized controlled trial.コンピュータを用いた認知矯正療法は、統合失調症患者の海馬容積を増大する:ランダム化比較対照試験Morimoto, TsubasaMatsuda, YasuhiroMatsuoka, KiwamuYasuno, FumihikoIkebuchi, EmiKameda, HiroyukiTaoka, ToshiakiMiyasaka, ToshiteruKichikawa, KimihikoKishimoto, ToshifumiCognitive remediationRehabilitationStructural neuroimagingHippocampusSchizophreniaJcoresBACKGROUND:Cognitive remediation therapy (CRT) effectively reduces neurocognitive impairment in patients with schizophrenia, but few studies have used structural neuroimaging methods to assess its neuroanatomical effects. We investigated these effects, as well as the association between changes in cortical volume and neurocognitive performance. METHOD:Between August 2013 and September 2016, we performed a randomized controlled study comprising a CRT group (16 individuals) and a treatment-as-usual (TAU) group (15 individuals) of patients with schizophrenia. CRT participants engaged in twice-weekly computer-assisted CRT sessions and weekly group meetings for 12 weeks. T1-weighted magnetic resonance imaging was performed before and after the intervention period, and whole-brain voxel-based morphometric analysis was used to detect significant cortical gray matter volume changes. We also assessed the correlation between cortical volume changes and CRT-derived neurocognitive improvements. RESULTS:The CRT group exhibited significantly greater improvements than the TAU group in verbal fluency (P = 0.012) and global cognitive scores (P = 0.049). The CRT group also exhibited significantly greater increases in right hippocampal volume than the TAU group (P < 0.001). Changes in verbal fluency scores and right hippocampal volumes were positively correlated (r = 0.53, P = 0.001).
CONCLUSION:We found that CRT significantly increased right hippocampal volumes and that these enhancements were positively correlated with changes in verbal fluency scores. Our results indicate that CRT induces cognitive improvement through hippocampal plasticity. TRIAL REGISTRATION:Registration number:UMIN000026146 , 2017/02/15, retrospectively registered.博士(医学)・甲第689号・平成30年9月26日This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BioMed CentralThesisThesis or DissertationBMC psychiatry Vol.18 No.1 Article No.83 (2018 Mar)1471244Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/3497BMC psychiatry Vol. No. (2018 Mar), 18(1): Article No.83http://hdl.handle.net/10564/3497http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3497/1/01%e7%94%b2689%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3497/2/02%e7%94%b2689%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3497/3/03%e7%94%b2688%e6%9c%ac%e6%96%87.pdf1471244XAA12072671BMC psychiatry Vol. No. (2018 Mar)181Article No.832018-03-27enghttp://www.ncbi.nlm.nih.gov/pubmed/ 29587688http://dx.doi.org/10.1186/s12888-018-1667-1ETD24601A6892018-09-26博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/34982018-12-12T16:30:11Zhdl_10564_3445Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma.ME1発現はヒト口腔扁平上皮癌の進行と関連するNakashima, ChieYamamoto, KazuhikoFujiwara‐Tani, RinaLuo, YiMatsushima, SayakoFujii, KiyomuOhmori, HitoshiSasahira, TomonoriSasaki, TakamitsuKitadai, YasuhikoKirita, TadaakiKuniyasu, Hirokicancer invasionglutaminemalic enzymeprognosisstemnessMalic enzyme 1 (ME1) is a multifunctional protein involved in glycolysis, the citric acid cycle, NADPH production, glutamine metabolism, and lipogenesis. It is overexpressed in various cancers. We examined the expression of ME1 in 119 oral squamous cell carcinomas (OSCCs) using immunohistochemistry. Malic enzyme 1 expression was moderate to strong in 57 (48%) OSCCs and correlated with pT, pN, clinical stage, and histological grade. In 37 cases with prognostic evaluation, moderate to strong ME1 expression indicated a worse prognosis than did weak ME1 expression. Malic enzyme 1 knockdown or inactivation by lanthanide inhibited cell proliferation and motility and suppressed the epithelial-mesenchymal transition in HSC3 human OSCC cells. Knockdown of ME1 also shifted energy metabolism from aerobic glycolysis and lactate fermentation to mitochondrial oxidative phosphorylation, and the redox status from reductive to oxidative. In a mouse tumor model, lanthanide suppressed tumor growth and increased survival time. These findings reveal that ME1 is a valid target for molecular therapy in OSCC.博士(医学)・乙第1420号・平成30年9月26日This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and repro duction in any medium, provided the original work is properly cited and is not used for commercial purposes.©2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer AssociationThesisThesis or DissertationCancer science Vol.109 No.6 p.2036-2045 (2018 Jun)13479032http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3498Cancer science, 109(6): 2036-2045http://hdl.handle.net/10564/3498http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3498/1/01%e4%b9%991420%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3498/2/02%e4%b9%991420%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3498/3/03%e4%b9%991420%e6%9c%ac%e6%96%87.pdf13479032AA11808050Cancer science1096203620452018-06enghttp://www.ncbi.nlm.nih.gov/pubmed/29601126http://dx.doi.org/10.1111/cas.13594ETD24601B14202018-09-26博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35002020-12-23T01:06:06Zhdl_10564_3445Von Willebrand Factor Aggravates Hepatic Ischemia-Reperfusion Injury by Promoting Neutrophil Recruitment in Mice.Von Willebrand因子は、好中球の動員を促進してマウスの肝虚血再灌流障害を増悪させるUrisono, YasuyukiSakata, AsukaMatsui, HidetoKasuda, ShogoOno, ShiroYoshimoto, KiyomiNishio, KenjiSho, MasayukiAkiyama, MasashiMiyata, ToshiyukiOkuchi, KazuoNishimura, SatoshiSugimoto, Mitsuhikovon Willebrand factorADAMTS13hepatic ischaemiareperfusion injuryneutrophil recruitmentHepatic ischaemia-reperfusion (I/R) injury is a serious liver damage that critically influences the clinical outcome of liver surgery or transplantation. Since recent studies indicated the critical involvement of von Willebrand factor (VWF) in reperfusion injuries of brain and myocardium, we hypothesized that VWF-dependent thrombotic or inflammatory responses also play a role in hepatic I/R injury. Using a mouse model of hepatic I/R injury, we explored the functional relevance of the VWF-ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) axis in this pathologic condition. Time-course studies during hepatic I/R revealed significantly lower alanine aminotransferase (ALT) values, as well as greater hepatic blood flow, in VWF gene-deleted (KO) mice in comparison with wild-type (WT) mice. Histological analysis revealed a significantly lesser extent of neutrophil infiltration and hepatocellular necrosis in liver tissues of VWF-KO mice. Human recombinant ADAMTS13 significantly improved the impairment in ALT values and hepatic blood flow and decreased neutrophil infiltration within the liver tissue of WT mice. Real-time intravital imaging successfully visualized significantly reduced leukocyte-vessel wall interactions in I/R liver of VWF-KO mice. Taken together, our results indicate that VWF promotes neutrophil recruitment in ischaemic mouse liver, critically aggravating reperfusion injury, and suggest that functional regulation of VWF by ADAMTS13 represents a promising therapeutic option for hepatic I/R injury.博士(医学)・乙第1421号・平成30年9月26日Copyright © 2018 Schattauer© 2018. Thieme. All rights reserved.This is a non-final version of an article published in final form in "http://dx.doi.org/10.1055/s-0038-1636529"ThiemeThesisThesis or DissertationThrombosis and haemostasis Vol.118 No.4 p.700-708 (2018 Apr)03406245http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3500Thrombosis and haemostasis, 118(4): 700-708http://hdl.handle.net/10564/3500http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/1/01%e4%b9%991421%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/2/02%e4%b9%991421%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/6/03%e4%b9%991421%e6%9c%ac%e6%96%87.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/7/04%e4%b9%991421Figure01-05.pdf03406245AA00863137Thrombosis and haemostasis11847007082018-04enghttp://www.ncbi.nlm.nih.gov/pubmed/29618155http://dx.doi.org/10.1055/s-0038-1636529ETD24601B14212018-09-26博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35012019-01-07T16:30:09Zhdl_10564_3445Magnetic resonance imaging analysis of the extensor carpi ulnaris tendon and distal radioulnar joint in triangular fibrocartilage complex tears.三角線維軟骨複合体損傷における尺側手根伸筋腱と遠位橈尺関節のMRI画像分析Santo, ShigeruOmokawa, ShoheiIida, AkioShimizu, TakamasaHasegawa, HideoTanaka, YasuhitoBACKGROUND: We compared the incidence of extensor carpi ulnaris (ECU) tendon and distal radioulnar joint (DRUJ) abnormalities using magnetic resonance imaging (MRI) between patients with triangular fibrocartilage complex (TFCC) tears and subjects without ulnar wrist pain. Additionally, we aimed to identify potential predictors of these MRI lesions. METHODS: The TFCC group comprised 70 consecutive patients with TFCC tears. The control group comprised 70 age- and sex-matched subjects without ulnar wrist pain. We evaluated the presence or absence of fluid collection in the DRUJ and ECU peritendinous area and longitudinal ECU tendon splitting. Dimensions of the fluid collection area around the ECU tendon were measured to evaluate the severity. The incidences of these abnormal MRI findings were compared between the two groups. We analyzed the correlation between the presence of ECU tendon and DRUJ lesions and variables including age, magnitude of ulnar variance, and type of TFCC tear. RESULTS: Significant differences were found between the two groups in the incidence of fluid collection of the DRUJ and ECU peritendinous area, and longitudinal ECU tendon splitting. Among the 70 patients with TFCC tears, age and the magnitude of ulnar variance were significantly correlated with the severity of fluid collection around the ECU tendon. The magnitude of ulnar variance in patients with DRUJ fluid collection was significantly larger than that in patients without fluid collection. There was a significant correlation between the presence of disc tears and DRUJ fluid collection. CONCLUSION: We found a higher incidence of accompanying abnormal MRI findings of the ECU tendon and DRUJ in patients with TFCC tears than in the control group. The presence of disc tears, the magnitude of ulnar variance, and age may be risk factors for these MRI lesions associated with TFCC tears.博士(医学)・甲第690号・平成30年11月30日Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.ElsevierThesisThesis or DissertationJournal of orthopaedic science Vol.23 No.6 p.953-958 (2018 Nov)09492658http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3501Journal of orthopaedic science Vol. No. p.- (2018 Nov), 23(6): 953-958http://hdl.handle.net/10564/3501http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3501/1/01%e7%94%b2690%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3501/2/02%e7%94%b2690%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3501/3/03%e7%94%b2690%e6%9c%ac%e6%96%87.pdf09492658AA11052566Journal of orthopaedic science Vol. No. p.- (2018 Nov)2369539582018-11enghttps://www.ncbi.nlm.nih.gov/pubmed/29983214http://dx.doi.org/10.1016/j.jos.2018.05.009ETD24601A6902018-11-30博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35022019-01-08T16:30:09Zhdl_10564_3445Influence of Underlying Diseases and Age on the Association between Obesity and All-Cause Mortality in Post-Middle Age.肥満と全原因死亡率との関連に基礎疾患と年齢が及ぼす影響Yoshimoto, KazukiNoda, TatsuyaImamura, TomoakiUnderlying DiseasesObesityAll-Cause MortalityPost-Middle AgeBackground: Studies on the association between obesity and all-cause mortality have found that the degree of obesity is directly proportional to all-cause mortality. In contrast, there have been studies indicating that obese people with underlying diseases have a higher survival rate. We hypothesized that age and underlying diseases lead to such contrasting results. Therefore, we conducted a study to clarify the influence of post-middle age obesity and underlying diseases on all-cause mortality. Methods: This study used data from longitudinal studies in the United States, which conducted follow-up for 19 years on 33,708 participants in different age groups: ≥45, 45 - 64, and ≥65 years. Hazard ratio (HR) was determined using the Cox proportional hazards model to analyze a group consisting of all participants, a group of those with underlying diseases, and a group of those without underlying diseases, considering age, gender, education history, marital status, household income, smoking history, and BMI category as covariates. Results: In the group aged ≥65 without underlying diseases, HR was almost 1 in those with BMI 25 - <30, 30 - <35, and BMI > 35 kg/m2. Further, HR was higher in the 45 - 64 age group without underlying diseases if BMI was >35 kg/m2. However, HR was approximately 1 in the ≥65 age group. Conclusions: The study revealed that among individuals aged ≥65 years without underlying diseases, there was no association between obesity and all-cause mortality. Among individuals without underlying diseases, HR was higher in the 45 - 64 age group with BMI > 35 kg/m2 but was approximately 1 among those aged ≥65 years. Therefore, an interaction based on age was detected. These findings may lead to recommendations regarding the need to modify the advice and education provided to obese individuals in different age groups.博士(医学)・甲第691号・平成30年11月30日Copyright © 2018 by authors and Scientific Research Publishing Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).
http://creativecommons.org/licenses/by/4.0/Scientific Research Publishing Inc.ThesisThesis or DissertationHealth Vol.10 No.9 p.1171-1184 (2018 Sep)19494998http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3502Health, 10(9): 1171-1184http://hdl.handle.net/10564/3502http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3502/1/01%e7%94%b2691%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3502/2/02%e7%94%b2691%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3502/3/03%e7%94%b2691%e6%9c%ac%e6%96%87.pdf19494998Health109117111842018-09-11enghttp://dx.doi.org/10.4236/health.2018.109089ETD24601A6912018-11-30博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35032019-01-08T16:30:12Zhdl_10564_3445Molecular epidemiology and clinical features of extended-spectrum beta-lactamase- or carbapenemase-producing Escherichia coli bacteremia in Japan.日本における基質拡張型β -ラクタマーゼまたはカルバペネマーゼ産生大腸菌菌血症の分子疫学と臨床的特徴Komatsu, YukoKasahara, KeiInoue, TakashiLee, Sang-TaeTamamoto, TetsuroYano, HisakazuKirita, TadaakiMikasa, KeiichiOBJECTIVES: To identify risk factors and clinical outcomes in patients with bacteremia due to extended-spectrum beta-lactamase (ESBL) or carbapenemase-producing Escherichia coli, as well as to determine the prevalence and genetic background of such isolates. METHODS: Case control study was performed with patients with E. coli bacteremia between January 2008 and May 2013 (n = 115) at a tertiary university hospital in Japan. Cases had ESBL-producing E. coli (ESBL-EC) whereas controls had non-ESBL-producing E. coli (non-ESBL-EC) isolates. A retrospective chart review was performed to identify risk factors and clinical outcomes. Isolates were characterized by antimicrobial susceptibility testing, polymerase chain reaction analysis for beta-lactamase genes, and multi-locus sequence typing. RESULTS: Of 115 unique cases of E. coli bacteremia, 30 (26.1%) were due to ESBL-EC and three (2.6%) were due to carbapenemase-producing E. coli. All three carbapenemase-producing E. coli isolates were IMP-6 and concurrently produced ESBL (ESBL/IMP-6-EC). ESBL-EC isolates showed multidrug resistance. Of the ESBL-EC isolates, CTX-M-27 was the most prevalent (33.3%), followed by CTX-M-14 (30%). Multi-locus sequence typing revealed that 19 (63.3%) isolates were ST131. The multivariate analysis identified nursing home-associated infections and antibiotic administration in the preceding 30 days as risk factors for ESBL-EC bacteremia. The 14-day mortality non-ESBL-EC, ESBL-EC, and ESBL/IMP-6-EC was 4.7% (4/85), 20% (6/30), and 66.7% (2/3), respectively. CONCLUSIONS: CTX-M-27, CTX-M-14, and ST131 were the most prevalent ESBL-EC isolates from bacteremic patients in a Japanese hospital. Further studies with larger sample sizes are warranted to investigate the clinical significance of ESBL-EC and ESBL/IMP-6-EC.博士(医学)・甲第692号・平成30年11月30日Copyright: © 2018 Komatsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Public Library of ScienceArticleThesis or DissertationPloS one Vol.13 No.8 Article No.e0202276 (2018 Aug)19326203http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3503PloS one, 13(8): e0202276http://hdl.handle.net/10564/3503http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3503/1/01%e7%94%b2692%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3503/2/02%e7%94%b2692%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3503/3/03%e7%94%b2692%e6%9c%ac%e6%96%87.pdf19326203PloS one138e02022762018-08-29enghttp://www.ncbi.nlm.nih.gov/pubmed/30157275https://doi.org/10.1371/journal.pone.0202276ETD24601A6922018-11-30博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35042019-01-08T16:30:12Zhdl_10564_3445Benefits of Computed Tomography in Reducing Mortality in Emergency Medicine.救急医療におけるCT使用による各疾患の死亡率低減効果Imai, ShinyaAkahane, ManabuKonishi, YutoImamura, TomoakiComputed tomographyMortalityEmergency medicineTraffic accidentHospital managementPerforming accurate diagnosis using computed tomography (CT) in emergency medicine may reduce mortality rates in various diseases. In this observational, correlational and cross-sectional study, we conducted multiple regression analyses to investigate the relationship between CT utilization rates and mortality. In addition, we estimated the annual net profits from CT to show the profitability of introducing a CT system in each Japanese prefecture. We conducted a multiple regression analysis to investigate correlations between CT utilization rates and mortality from each disease adjusted for the population density, number of doctors, as well as transportation time to the medical institution. The results of multiple regression analysis showed that traffic accident mortality was related to CT utilization rate and population density. Extrinsic death such as mortality due to falling, drowning and asphyxia was related to CT utilization, indicating that CT in emergency medicine reduced mortality. Moreover, the annual net profit from multi-slice CT (MSCT) was estimated as positive. Our study clearly demonstrates that CT utilization rates relate to a reduction in mortality from accidents, indicating that screening patients with CT in the emergency room has a beneficial effect and reduces mortality. Therefore, CT equipment has a beneficial effect in both emergency medicine and hospital management.博士(医学)・甲第693号・平成30年11月30日© 2018 Shinya Imai et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License(https://creativecommons.org/licenses/by-nc-nd/4.0/).De Gruyter OpenThesisThesis or DissertationOpen medicine Vol.13 p.394-401 (2018 Sep)23915463http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3504Open medicine Vol. p.(2018 Sep), 13: 394-401http://hdl.handle.net/10564/3504http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3504/1/01%e7%94%b2693%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3504/2/02%e7%94%b2693%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3504/3/03%e7%94%b2693%e6%9c%ac%e6%96%87.pdf23915463Open medicine Vol. p.(2018 Sep)133944012018-09-14enghttps://www.ncbi.nlm.nih.gov/pubmed/30234160http://dx.doi.org/10.1515/med-2018-0058ETD24601A6912018-11-30博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35052020-08-13T02:58:58Zhdl_10564_3445Reduced prefrontal hemodynamic response in adult attention-deficit hyperactivity disorder as measured by near-infrared spectroscopy.近赤外線スペクトロスコピィを用いた成人期注意欠如・多動症の前頭前野における血液動態反応の低下Ueda, ShotaroOta, ToyosakuIida, JunzoYamamoto, KazuhikoYoshino, HirokiKishimoto, NaokoKishimoto, Toshifumiadult attention-deficit hyperactivity disorderfunctional neuroimaging studynear-infrared spectroscopyprefrontal hemodynamic responseStroop Color-Word TaskAIM: Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. In pediatric attention-deficit hyperactivity disorder (ADHD), reduced prefrontal hemodynamic responses have been observed with NIRS repeatedly. However, there are few studies of adult ADHD by multi-channel NIRS. Therefore, in this study, we used multi-channel NIRS to examine the characteristics of prefrontal hemodynamic responses during the Stroop Color-Word Task (SCWT) in adult ADHD patients and in age- and sex-matched control subjects. METHODS: Twelve treatment-naïve adults with ADHD and 12 age- and sex-matched healthy control subjects participated in the present study after giving consent. We used 24-channel NIRS to measure the oxygenated hemoglobin (oxy-Hb) changes at the frontal lobes of participants during the SCWT. We compared the oxy-Hb changes between adults with ADHD and control subjects by t-tests with Bonferroni correction. RESULTS: During the SCWT, the oxy-Hb changes observed in the ADHD group were significantly smaller than those in the control group in channels 11, 16, 18, 21, 22, 23, and 24, corresponding to the prefrontal cortex. At channels 16, 21, 23, and 24 of the ADHD group, there were negative correlations between the symptomatic severity and the oxy-Hb changes. CONCLUSION: The present study suggests that adults with ADHD have reduced prefrontal hemodynamic response as measured by NIRS.博士(医学)・乙第1422号・平成30年11月30日© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and NeurologyThis is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12643], which has been published in final form at [https://doi.org/10.1111/pcn.12643]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Japanese Society of Psychiatry and Neurology / John Wiley & Sons, Inc.ThesisThesis or DissertationPsychiatry and clinical neurosciences Vol.72 No.6 p.380-390 (2018 Jun)13231316http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3505Psychiatry and clinical neurosciences, 72(6): 380-390http://hdl.handle.net/10564/3505http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3505/1/01%e4%b9%991422%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3505/2/02%e4%b9%991422%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3505/6/03%e4%b9%991422%e6%9c%ac%e6%96%87.pdf13231316AA11040669Psychiatry and clinical neurosciences7263803902018-06enghttps://www.ncbi.nlm.nih.gov/pubmed/29405508http://dx.doi.org/10.1111/pcn.12643ETD24601B14222018-11-30博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35062019-01-08T16:30:12Zhdl_10564_3445Epidermal growth factor receptor inhibitors selectively inhibit the expressions of human β-defensins induced by Staphylococcus epidermidis.EGFR阻害薬は表皮ブドウ球菌によるβディフェンシンの発現を選択的に抑制するPark, KioOmmori, RieImoto, KyokoAsada, HideoErlotinibGefitinibHuman β-defensinsBACKGROUND: Epidermal growth factor receptor inhibitors (EGFRIs) have developed as one of the potential treatment options for various kinds of cancers. Although a variety of dermatological adverse reactions such as follicular acneiform eruptions is commonly encountered, the mechanism of the reactions remains unclear. OBJECTIVES: We investigated the effects of EGFRIs on the expression of human β-defensins against staphylococci to study the pathomechanism of cutaneous adverse reactions caused by EGFRIs. METHODS: We investigated the expressions of human β-defensins 1, 2, and 3 (hBD1, 2, and 3) from staphylococci-stimulated normal human epidermal keratinocytes (NHEKs) cultured with or without the effects of two EGFRIs, gefitinib and erlotinib. We stimulated NHEKs with the supernatant of Staphylococcus aureus (S. aureus) and S. epidermidis and the live staphylococci. We measured hBDs in the culture supernatants of NHEKs by enzyme-linked immunosorbent assay (ELISA). RESULTS: EGFRIs did not suppress the expressions of hBD1 and 3 induced by S. aureus. In contrast, EGFRIs suppressed the expressions of hBD2 and 3 induced by S. epidermidis. CONCLUSION: EGFRIs may cause cutaneous adverse effects through selectively perturbing innate immune responses induced by commensal and pathogenic bacteria.博士(医学)・乙第1423号・平成30年11月30日Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.ElsevierThesisThesis or DissertationJournal of dermatological science Vol.75 No.2 p.94-99 (2014 Aug)09231811http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3506Journal of dermatological science, 75(2): 94-99http://hdl.handle.net/10564/3506http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3506/1/01%e4%b9%991423%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3506/2/02%e4%b9%991423%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3506/3/03%e4%b9%991423%e6%9c%ac%e6%96%87.pdf09231811AA1075636XJournal of dermatological science75294992014-08enghttp://www.ncbi.nlm.nih.gov/pubmed/24831548http://dx.doi.org/10.1016/j.jdermsci.2014.04.011ETD24601B14222018-11-30博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35072019-01-08T16:30:11Zhdl_10564_3445Mesenchymal stem cells up-regulate the invasive potential of prostate cancer cells via the eotaxin-3/CCR3 axis.ヒト間葉系幹細胞はエオタキシン3/CCR3経路を介して前立腺癌細胞の浸潤能を増加させるIshida, YukakoKido, AkiraAkahane, ManabuKishi, ShingoTsukamoto, ShinjiFujii, HiromasaHonoki, KanyaTanaka, YasuhitoMesenchymal stem cellsCancer microenvironmentEotaxin-3CCR3Homing chemokinesThis study aimed to clarify the role of mesenchymal stem cells (MSCs) as a component of the cancer microenvironment. We investigated the homing-related chemokine expression levels of MSCs treated with a prostate cancer cell line (PC-3) -conditioned medium. Among several homing chemokines, an antibody array revealed that expression of eotaxin-3 (but not eotxin-1 and -2) was highly enhanced in MSCs treated with PC-3-conditioned medium. A gene expression array showed significantly increased expression of CCR3, a receptor of eotaxin-3, in PC-3. In a matrigel invasion assay, interferon-gamma, a specific inhibitor of eotaxin-related homing, significantly reduced the transmigration of PC-3 cells, under co-cultured condition with MSCs, in a dose-dependent manner (P < 0.05). Consistent with these results, anti-CCR3 antibody successfully reduced PC-3 migration under the co-cultured condition. These findings suggest that MSCs to modulation of the invasive potential of prostate cancer cells via the eotaxin-3/CCR3 axis.博士(医学)・乙第1424号・平成30年11月30日© 2018 Elsevier GmbH. All rights reserved.ElsevierThesisThesis or DissertationPathology, research and practice Vol.214 No.9 p.1297-1302 (2018 Sep)03440338http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3507Pathology, research and practice, 214(9): 1297-1302http://hdl.handle.net/10564/3507http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3507/1/01%e4%b9%991424%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3507/2/02%e4%b9%991424%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3507/3/03%e4%b9%991424%e6%9c%ac%e6%96%87.pdf03440338AA00769966Pathology, research and practice2149129713022018-09enghttps://www.ncbi.nlm.nih.gov/pubmed/30029937http://dx.doi.org/10.1016/j.prp.2018.06.012ETD24601B14242018-11-30博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35422019-06-10T16:30:13Zhdl_10564_3445Dapagliflozin improves treatment satisfaction in overweight patients with type 2 diabetes mellitus: a patient reported outcome study (PRO study).ダパグリフロジン投与における肥満2型糖尿病患者の治療満足度への影響:a patient reported outcome study (PRO study).Nakajima, HirokiOkada, SadanoriMohri, TakakoKanda, EiichiroInaba, NaoyukiHirasawa, YokoSeino, HiroakiKuroda, HisamotoHiyoshi, ToruNiiya, TetsujiIshii, HitoshiType 2 diabetes mellitusOral hypoglycemic agentSodium glucose cotransporters 2 inhibitorsSGLT2 inhibitorsDapagliflozinTreatment satisfactionOral Hypoglycemic Agent-QuestionnaireBody weightPatient reported outcomeQuality of lifeBackground: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. Methods: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. Results: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 0.19, P = 0.011). Conclusions: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.博士(医学)・甲第694号・平成31年3月15日© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/
publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BioMed CentralThesisThesis or DissertationDiabetology and metabolic syndrome Vol.10 Article No.11 (2018 Mar)17585996http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3542Diabetology and metabolic syndrome, 10: Article No.11http://hdl.handle.net/10564/3542http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3542/1/01%e7%94%b2694%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3542/2/02%e7%94%b2694%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3542/3/03%e7%94%b2694%e6%9c%ac%e6%96%87.pdf17585996Diabetology and metabolic syndrome10Article No.112018-03-01enghttp://www.ncbi.nlm.nih.gov/pubmed/29507611http://dx.doi.org/10.1186/s13098-018-0313-xETD24601A6942019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35432019-06-11T00:10:24Zhdl_10564_3445Topical and systemic immunoreaction triggered by intravesical chemotherapy in an N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model.N-ブチル-N-(4-ヒドロキシブチル)ニトロソアミン誘発膀胱癌マウスモデルを用いた膀胱内化学療法による局所及び全身の免疫応答Hori, ShuntaMiyake, MakitoTatsumi, YoshihiroOnishi, SayuriMorizawa, YosukeNakai, YasushiTanaka, NobumichiFujimoto, KiyohideIntravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC.博士(医学)・甲第695号・平成31年3月15日Copyright: © 2017 Hori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Public Library of ScienceThesisThesis or DissertationPloS one Vol.12 No.4 Article No.e0175494 (2017 Apr)19326203http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3543PloS one, 12(4): Article No.e0175494http://hdl.handle.net/10564/3543http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3543/1/01%e7%94%b2695%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3543/2/02%e7%94%b2695%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3543/3/03%e7%94%b2695%e6%9c%ac%e6%96%87.pdf19326203PloS one124Article No.e01754942017-04-13enghttp://www.ncbi.nlm.nih.gov/pubmed/28406993http://dx.doi.org/10.1371/journal.pone.0175494ETD24601A6952019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35442019-06-11T00:09:22Zhdl_10564_3445Propofol induces nuclear localization of Nrf2 under conditions of oxidative stress in cardiac H9c2 cells.プロポフォールは、酸化的ストレス条件下で心筋細胞株H9c2におけるNrf2の発現及び核局在を誘導するShinjo, TakeakiTanaka, TatuhideOkuda, HiroakiKawaguchi, AkiraOh-Hashi, KentaroTerada, YukiIsonishi, AyakoMorita-Takemura, ShokoTatsumi, KoukoKawaguchi, MasahikoWanaka, AkioOxidative stress contributes to myocardial ischemia-reperfusion injury, which causes cardiomyocyte death and precipitate life-threatening heart failure. Propofol has been proposed to protect cells or tissues against oxidative stress. However, the mechanisms underlying its beneficial effects are not fully elucidated. In the present study, we employed an in vitro oxidative injury model, in which rat cardiac H9c2 cells were treated with H2O2, and investigated roles of propofol against oxidative stress. Propofol treatment reduced H2O2-induced apoptotic cell death. While H2O2 induced expression of the antioxidant enzyme HO-1, propofol further increased HO-1 mRNA and protein levels. Propofol also promoted nuclear localization of Nrf2 in the presence of H2O2. Knockdown of Nrf2 using siRNA suppressed propofol-inducible Nrf2 and expression of Nrf2-downstream antioxidant enzyme. Knockdown of Nrf2 suppressed the propofol-induced cytoprotection. In addition, Nrf2 overexpression induced nuclear localization of Nrf2 and HO-1 expression. These results suggest that propofol exerts antioxidative effects by inducing nuclear localization of Nrf2 and expression of its downstream enzyme in cardiac cells. Finally, we examined the effect of propofol on cardiomyocytes using myocardial ischemia-reperfusion injury models. The expression level of Nrf2 protein was increased at 15 min after reperfusion in the ischemia-reperfusion and propofol group compared with ischemia-reperfusion group in penumbra region. These results suggest that propofol protects cells or tissues from oxidative stress via Nrf2/HO-1 cascade.博士(医学)・甲第696号・平成31年3月15日Copyright: © 2018 Shinjo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Public Library of ScienceThesisThesis or DissertationPloS one Vol.13 No.4 Article No.e0196191 (2018 Apr)19326203http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3544PloS one, 13(4): Article No.e0196191http://hdl.handle.net/10564/3544http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3544/1/01%e7%94%b2696%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3544/2/02%e7%94%b2696%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3544/3/03%e7%94%b2696%e6%9c%ac%e6%96%87.pdf19326203PloS one134Article No.e01961912018-04-24enghttp://www.ncbi.nlm.nih.gov/pubmed/29689082http://dx.doi.org/10.1371/journal.pone.0196191ETD24601A6962019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35452020-08-13T03:02:01Zhdl_10564_3445Aquaporin-2 plays an important role in water transportation through the bladder wall in rats.ラット膀胱での水吸収におけるアクアポリン-2の役割Morizawa, YosukeTorimoto, KazumasaHori, ShuntaGotoh, DaisukeNakai, YasushiMiyake, MakitoHirayama, AkihideTanaka, NobumichiFujimoto, Kiyohideaquaporinbladderdesmopressinintravesical fluid volumewater transportionAIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT-PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA-treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 ± 0.00 vs 0.83 ± 0.08 mL, 157.80 ± 1.30 vs 146.8 ± 1.92 mEq/mL, P < 0.01, respectively in the control group), administration of desmopressin did not affect the extent of volume change. Aquaporin-2 expression was significantly higher in the 3-h distended bladders than in the empty bladder. Aquaporin-2 siRNA treatment suppressed aquaporin-2 expression and the change of intravesical fluid volume from 0 to 3 h (1.00 ± 0.00 and 0.99 ± 0.02 mL), which was related to the suppression of sodium concentration change in comparison with control siRNA treatment (149.6 ± 2.4 vs 143.6 ± 3.67 mEq/mL, P < 0.05). CONCLUSIONS: The rat urinary bladder absorbs water and salts under the full-filled condition. Aquaporin-2 plays an important role in the transport of water, accompanied by sodium concentration change. We demonstrated a part of the bladder absorption mechanism, which may lead to development of a new method for regulating bladder storage function.博士(医学)・甲第697号・平成31年3月15日© 2018 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/nau.23715], which has been published in final form at [http://dx.doi.org/10.1002/nau.23715]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.John Wiley and Sons, Inc.ThesisThesis or DissertationNeurourology and urodynamics Vol.37 No.8 p.2434-2440 (2018 Nov)07332467http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3545Neurourology and urodynamics, 37(8): 2434-2440http://hdl.handle.net/10564/3545http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3545/1/01%e7%94%b2697%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3545/2/02%e7%94%b2697%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3545/6/03%e7%94%b2697%e6%9c%ac%e6%96%87.pdf07332467AA10631557Neurourology and urodynamics378243424402018-11enghttp://www.ncbi.nlm.nih.gov/pubmed/29797427http://dx.doi.org/10.1002/nau.23715ETD24601A6972019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35462019-06-11T16:30:09Zhdl_10564_3445NGF and BDNF expression in mouse DRG after spared nerve injury.Spared nerve injury後のマウス後根神経節におけるNGFとBDNFの発現Terada, YukiMorita-Takemura, ShokoIsonishi, AyamiTanaka, TatsuhideOkuda, HiroshiTatsumi, KoukoShinjo, TakeakiKawaguchi, MasahikoWanaka, AkioBDNFDorsal root ganglionNGFNeuropathic painSpared nerve injuryNeuropathic pain is initiated by a primary lesion in the peripheral nervous system and spoils quality of life. Neurotrophins play important roles in the development and transmission of neuropathic pain. There are conflicting reports that the dorsal root ganglion (DRG) in an injured nerve contribute to neuropathic pain, whereas several studies have highlighted the important contribution of the DRG in a non-injured nerve. Clarifying the role of neurotrophins in neuropathic pain is problematic because we cannot distinguish injured and intact neurons in most peripheral nerve injury models. In the present study, to elicit neuropathic pain, we used the spared nerve injury (SNI) model, in which injured DRG neurons are distinguishable from intact ones, and mechanical allodynia develops in the intact sural nerve skin territory. We examined nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRGs of SNI model mice. NGF and BDNF levels increased in the injured L3 DRG, while NGF decreased in the intact L5 DRG. These data offer a new point of view on the role of these neurotrophins in neuropathic pain induced by peripheral nerve injury.博士(医学)・甲第698号・平成31年3月15日© 2018 Elsevier B.V. All rights reserved.ElsevierThesisThesis or DissertationNeuroscience letters Vol.686 p.67-73 (2018 Nov)03043940http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3546Neuroscience letters, 686: 67-73http://hdl.handle.net/10564/3546http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3546/1/01%e7%94%b2698%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3546/2/02%e7%94%b2698%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3546/3/03%e7%94%b2698%e6%9c%ac%e6%96%87.pdf03043940AA00754925Neuroscience letters68667732018-11-01enghttp://www.ncbi.nlm.nih.gov/pubmed/30189228http://dx.doi.org/10.1016/j.neulet.2018.08.051ETD24601A6982019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35472019-06-11T16:30:11Zhdl_10564_3445Up-regulation of Human Herpesvirus 6B-derived microRNAs in the Serum of Patients with Drug-induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms.DIHS/DRESS患者における血清中HHV6B microRNAの変化Miyashita, KazuyaMiyagawa, FumiNakamura, YukiOmmori, RieAzukizawa, HiroakiAsada, Hideo博士(医学)・甲第699号・平成31年3月15日Copyright © 2018. Acta Dermato-Venereologica. All rights reserved.This is an open access article under the CC BY-NC license(http://creativecommons.org/licenses/by-nc/4.0/).Society for the Publication of Acta Dermato-VenereologicaThesisThesis or DissertationActa dermato-venereologica Vol.98 No.6 p.612-613 (2018 Jun)00015555http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3547Acta dermato-venereologica, 98(6): 612-613http://hdl.handle.net/10564/3547http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3547/1/01%e7%94%b2699%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3547/2/02%e7%94%b2699%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3547/3/03%e7%94%b2699%e6%9c%ac%e6%96%87.pdf00015555AA00507245Acta dermato-venereologica9866126132018-06-08enghttp://www.ncbi.nlm.nih.gov/pubmed/29542806http://dx.doi.org/10.2340/00015555-2925ETD24601A6992019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35482020-08-13T04:12:37Zhdl_10564_3445Suspected periprosthetic joint infection after total knee arthroplasty under propofol versus sevoflurane anesthesia: a retrospective cohort study.人工膝関節置換術後の関節周囲感染が疑われる症例の発生頻度は、術中麻酔維持使用薬剤の選択と関連するか(プロポフォールによる全静脈麻酔と、セボフルランでの麻酔維持での比較):後ろ向きコホート研究Kishimoto, MiwaYamana, HayatoInoue, SatokiNoda, TatsuyaAkahane, ManabuInagaki, YusukeMatsui, HirokiYasunaga, HideoKawaguchi, MasahikoImamura, TomoakiPURPOSE: Periprosthetic joint infection is a serious complication of total knee arthroplasty. Though there are many factors that might increase its risk, the use of propofol for maintaining general anesthesia could theoretically increase the incidence of infection because of its lipid component that supports bacterial growth. Nevertheless, the relationship between anesthetic maintenance agents and the occurrence of periprosthetic joint infection remains uncertain. The purpose of this study was to compare the incidence of suspected early-onset periprosthetic joint infection between patients undergoing total knee arthroplasty under propofol vs sevoflurane anesthesia. METHODS: We conducted a retrospective cohort study of patients in the national inpatient Diagnosis Procedure Combination database in Japan who underwent total knee arthroplasty. Suspected periprosthetic joint infection was surrogately defined as the need for arthrocentesis or debridement within 30 days of surgery. Propensity score matching was performed between patients who received either propofol or sevoflurane for anesthetic maintenance to determine the proportion of those with infection. RESULTS: Eligible patients (n = 21,899) were categorized into either the propofol (n = 7,439) or sevoflurane (n = 14,460) groups. In the 5,140 propensity-matched patient pairs, there was no significant difference in the proportion of arthrocentesis or debridement [1.3% propofol vs 1.7% sevoflurane; respectively (relative risk, 0.76; 95% CI, 0.55 to 1.04; P = 0.10)] between the groups. The mean (SD) length of stay in the propofol group was significantly longer than in the sevoflurane group [32.5 (18.4) days vs 31.4 (14.4) days, respectively; mean difference, 1.1; 95% CI, 0.5 to 1.8; P < 0.001]. CONCLUSION: Propensity score analysis suggested no significant association between the choice of anesthetic maintenance agent and the occurrence of suspected early-onset periprosthetic joint infection in patients undergoing total knee arthroplasty.博士(医学)・甲第700号・平成31年3月15日© Canadian Anesthesiologists' Society 2018This is a post-peer-review, pre-copyedit version of an article published in Canadian journal of anaesthesia. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12630-018-1139-6.Springer Nature Publishing AGThesisThesis or DissertationCanadian journal of anaesthesia Vol.65 No.8 p.893-900 (2018 Aug)0832610Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/3548Canadian journal of anaesthesia, 65(8): 893-900http://hdl.handle.net/10564/3548http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3548/1/01%e7%94%b2700%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3548/2/02%e7%94%b2700%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3548/6/03%e7%94%b2700%e6%9c%ac%e6%96%87.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3548/7/04%e7%94%b2700Figure.pdf0832610XAA1066866XCanadian journal of anaesthesia6588939002018-08enghttp://www.ncbi.nlm.nih.gov/pubmed/29687360http://dx.doi.org/10.1007/s12630-018-1139-6ETD24601A7002019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35492020-08-18T02:29:16Zhdl_10564_3445Alteration of β-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study.急性期たこつぼ症候群症例の心内膜心筋生検を用いた左室心筋細胞におけるβ-アドレナリン受容体シグナル動態の検討Nakano, TomoyaOnoue, KenjiNakada, YasukiNakagawa, HitoshiKumazawa, TakuyaUeda, TomoyaNishida, TakuSoeda, TsunenariOkayama, SatoshiWatanabe, MakotoKawata, HiroyukiKawakami, RikaHorii, ManabuOkura, HiroyukiUemura, ShiroHatakeyama, KintaSakaguchi, YasuhiroSaito, YoshihikoAccumulating evidence indicates alteration of the β-adrenoceptor (AR), such as desensitization and subtype switching of its coupling G protein, plays a role in the protection against catecholamine toxicity in heart failure. However, in human takotsubo syndrome (TTS), which is associated with a surge of circulating catecholamine in the acute phase, there is no histologic evidence of β-AR alteration. The purpose of this study was to investigate the involvement of alteration of β-AR signaling in the mechanism of TTS development. Left ventricular (LV) biopsied samples from 26 patients with TTS, 19 with normal LV function, and 26 with dilated cardiomyopathy (DCM) were studied. G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, which initiate the alteration of β-AR signaling, were more abundantly expressed in the myocardium in acute-phase TTS than in those of DCM and normal control as indicated by immunohistochemistry. The percentage of cardiomyocytes that showed positive membrane staining for GRK2 and β-arrestin2 was also significantly higher in acute-phase TTS. Sequential biopsies in the recovery-phase for two patients with TTS revealed that membrane expression of GRK2 and β-arrestin2 faded over time. This study provided the first histologic evidence of the involvement of alteration of β-ARs in the development of TTS.博士(医学)・甲第701号・平成31年3月15日© The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.© 2018 Springer Nature Publishing AGSpringer Nature Publishing AGThesisThesis or DissertationScientific reports Vol.8 No.1 Article No.12731 (2018 Aug)20452322http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3549Scientific reports, 8(1): Article No.12731http://hdl.handle.net/10564/3549http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3549/1/01%e7%94%b2701%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3549/2/02%e7%94%b2701%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3549/3/03%e7%94%b2701%e6%9c%ac%e6%96%87.pdf20452322Scientific reports81Article No.127312018-08-24enghttp://www.ncbi.nlm.nih.gov/pubmed/30143703http://dx.doi.org/10.1038/s41598-018-31034-zETD24601A7012019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35502022-07-29T06:49:20Zhdl_10564_3445Evaluating Cervical Sagittal Alignment in Cervical Myelopathy: Are Sitting Cervical Radiographs and Standing Whole-Spine Radiographs Equally Useful?頚椎症性脊髄症症例における頚椎アライメント評価 : 坐位頚椎レントゲンと立位全脊椎レントゲンは等しく有用か?Morimoto, YasuhikoShigematsu, HidekiIwata, EiichiroTanaka, MasatoOkuda, AkinoriMasuda, KeisukeYamamoto, YusukeTakeshima, ToshichikaNakagawa, YoshiyukiTanaka, Yasuhitocervical lateral radiographwhole-spine lateral radiographcervical alignmentcervical spondylotic myelopathysitting positionoccipito-cervical alignmentStudy Design: Retrospective review of medical charts and radiographic data. Objectives: We aimed to clarify the differences in cervical alignment findings between sitting cervical lateral radiographs and standing whole-spine lateral radiographs with clavicle positioning in cervical spondylotic myelopathy (CSM) patients. Methods: We retrospectively evaluated the radiographs of 50 consecutive patients who underwent cervical surgery for CSM in our hospital. Cervical sagittal alignment was evaluated based on the C0-2 angles and C2-7 Gore and Cobb angles. Head position was evaluated in terms of the center of gravity of the head to C7 (CGH-C7) angle and the McGregor angle (ie, the angle between the McGregor line and a horizontal line). The T1-slope was also evaluated. Results: The mean values of the CGH-C7 angle and T1-slope were significantly lower, while the mean value of the McGregor angle was significantly higher on whole-spine lateral radiographs with clavicle positioning than on sitting cervical lateral radiographs. The mean values of the C0-2 and C2-7 angles did not differ significantly between the 2 radiographic positioning approaches. Conclusions: Using whole-spine lateral radiographs with clavicle positioning may result in a significantly lower T1-slope and a posterior tilt of the head. In the absence of a compensatory change in cervical alignment, clavicle positioning may force patients to adopt an upward gazing position of the head. These compensatory mechanisms should be considered while evaluating cervical alignment on whole-spine lateral radiographs with clavicle positioning. Surgical planning should take into account the effect of posture on the radiographic appearance of cervical alignment.博士(医学)・甲第702号・平成31年3月15日© The Author(s) 2018. Creative Commons Non Commercial No Derivs CC BY-NC-ND: This article is distributed under the terms of the Creative Commons Attribution-Non
Commercial-NoDerivs 4.0 License (http://www.creativecommons.org/licenses/by-nc-nd/4.0/) which permits non-commercial use, reproduction and distribution of
the work as published without adaptation or alteration, without further permission provided the original work is attributed as specified on the SAGE and Open
Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).SAGE PublicationsThesisThesis or DissertationGlobal spine journal Vol.9 No.6 p.591-597 (2019 Sep)21925682http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3550Global spine journal, 9(6): 591-597http://hdl.handle.net/10564/3550http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3550/1/01%e7%94%b2702%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3550/2/02%e7%94%b2702%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3550/3/03%e7%94%b2702%e6%9c%ac%e6%96%87.pdf21925682AA12633225Global spine journal965915972018-11-15enghttps://doi.org/10.1177/2192568218811841ETD24601A7022019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35512020-08-13T04:13:32Zhdl_10564_3445Increased Urine Production Due to Leg Fluid Displacement Reduces Hours of Undisturbed Sleep.臥床早期の下肢水分移行はHUSを減少させるKiba, KeisukeHirayama, AkihideYoshikawa, MotokiyoYamamoto, YutakaTorimoto, KazumasaShimizu, NobutakaTanaka, NobumichiFujimoto, KiyohideUemura, Hirotsugubioelectric impedance analysisbody position changinghours of undisturbed sleepleg edemanocturiaOBJECTIVE: To investigate whether or not the leg fluid displacement observed when moving from the standing to recumbent position at bedtime reduces the hours of undisturbed sleep (HUS). METHODS: Men aged 50 years or older who were hospitalized for urological diseases were investigated. Body water evaluation was performed three times with a bioelectric impedance method: (i) 17:00, (ii) 30 min after (short-term), and (iii) waking up (long-term). A frequency volume chart was used to evaluate the status of nocturnal urine production, and the factors affecting HUS were investigated. RESULTS: A total of 50 patients (mean age: 68 years) were enrolled. Short-term changes in extracellular fluid (ECF in the legs showed a significant positive correlation with urine production per unit of time at the first nocturnal voiding (UFN/HUS) (r = 0.45, P = 0.01). In the comparison between patients who had <3 HUS vs. those who had ≥3 HUS, the <3 HUS group showed significantly greater short-term changes in leg fluid volume, night-time water intake (17:00-06:00), and UFN/HUS. Multivariate analysis to assess the risk factors for <3 HUS indicated UFN/HUS as a risk factor in the overall model, and short-term changes in leg ECF and night-time water intake as risk factors in the model that only considered factors before sleep. CONCLUSIONS: Nocturnal leg fluid displacement may increase urine production leading up to first voiding after going to bed, and consequently, induce early awakening after falling asleep.博士(医学)・甲第703号・平成31年3月15日© 2017 John Wiley & Sons Australia, LtdThis is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/luts.12176], which has been published in final form at [http://dx.doi.org/10.1111/luts.12176]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.John Wiley and Sons, Inc.ThesisThesis or DissertationLower urinary tract symptoms Vol.10 No.3 p.253-258 (2018 Sep)17575664http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3551Lower urinary tract symptoms, 10(3): 253-258http://hdl.handle.net/10564/3551http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3551/1/01%e7%94%b2703%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3551/2/02%e7%94%b2703%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3551/6/03%e7%94%b2703%e6%9c%ac%e6%96%87.pdf17575664AA12809467Lower urinary tract symptoms1032532582018-09enghttp://www.ncbi.nlm.nih.gov/pubmed/28675633http://dx.doi.org/10.1111/luts.12176ETD24601A7032019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35522019-06-18T16:30:12Zhdl_10564_3445Three-Dimensional Kinematic Analysis of the Distal Radioulnar Joint in the Axial-Loaded Extended Wrist Position.手関節伸展荷重時の遠位橈尺関節の3次元動態解析Hojo, JunyaOmokawa, ShoheiIida, AkioOno, HiroshiMoritomo, HisaoTanaka, YasuhitoDistal radioulnar jointextended wristligamentsloaded wrist3-dimensional kinematic analysisPURPOSE: To assess the wrist joints of healthy volunteers in extended and loaded states versus the unloaded state by using computed tomography (CT) to analyze the in vivo 3-dimensional movements in the distal radioulnar joint (DRUJ). METHODS: The dominant arms of 9 volunteers with healthy wrists were studied. We mounted a compression device onto the elbows in an inverted position. A 0-kg and 7-kg load each was applied during low-dose radiation CT imaging and a bone model was produced. We marked the insertion sites for the 4 radioulnar ligaments stabilizing the DRUJ: palmar superficial radioulnar ligament (PS-RUL), dorsal superficial radioulnar ligament (DS-RUL), dorsal deep radioulnar ligament (DD-RUL), and palmar deep radioulnar ligament (PD-RUL). Using Marai's method, each ligament was virtualized and the length of each simulated ligament was measured. We also computed the 3-dimensional displacement and corresponding rotation of the distal ulna where it comes into contact with the radius in the sigmoid notch. RESULTS: The lengths of palmar ligaments (PS-RUL and PD-RUL) increased significantly under loaded conditions, and although not significant, the length of dorsal ligaments (DS-RUL and DD-RUL) tended to increase. When the wrist was loaded, the ulna rotated toward the open palmar side. CONCLUSIONS: The length of simulated radioulnar ligaments increased when the wrist joint was loaded in an extended position. This kinematic movement of DRUJ separation under a loading condition is different from physiological active movement. CLINICAL RELEVANCE: The 3-dimensional kinematic analysis revealed that palmar radioulnar ligaments were stretched during axial loading, suggesting that a tear of the palmer ligament can result from a fall on an outstretched hand.博士(医学)・甲第704号・平成31年3月15日© 2019 by the American Society for Surgery of the Hand. All rights reserved.ElsevierThesisThesis or DissertationThe Journal of hand surgery Vol.44 No.4 p.336.e1-336.e6 (2019 Apr)03635023http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3552The Journal of hand surgery, 44(4): 336.e1-336.e6http://hdl.handle.net/10564/3552http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3552/1/01%e7%94%b2704%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3552/2/02%e7%94%b2704%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3552/3/03%e7%94%b2704%e6%9c%ac%e6%96%87.pdf03635023AA10522529The Journal of hand surgery444336.e1336.e62019-04enghttp://www.ncbi.nlm.nih.gov/pubmed/30119953http://dx.doi.org/10.1016/j.jhsa.2018.06.019ETD24601A7042019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35532020-10-14T02:05:03Zhdl_10564_3747hdl_10564_3445Feasibility and Efficacy of Individualized Radiation Therapy for Primary Central Nervous System Lymphoma: Radiation Treatment Planning According to Treatment Response by Radiographic Assessment.中枢神経系原発悪性リンパ腫の放射線治療個別化の妥当性と有用性:画像評価を用いた治療効果に基づく放射線治療計画Morimoto, YokoInoue, KazuyaMatsuda, RyosukeMiyasaka, ToshiteruWakai, NobuhideYamaki, KaoriMiura, SachikoAsakawa, IsaoTamamoto, TetsuroHasegawa, MasatoshiPrimary central nervous system lymphomaRadiation therapyTreatment response evaluationWhole brain radiation doseBoost irradiationBackground: To assess the feasibility and efficacy of individualized treatment selection in radiation therapy (RT) for primary central nervous system lymphoma (PCNSL) according to treatment response by radiographic assessment. Methods: The details of recurrence and change in performance status (PS) were assessed in 31 patients with histologically confirmed PCNSL treated between 2000 and 2016. During the treatment period, radiographic assessment was conducted, and RT planning (RTP) was determined individually by treatment response. Results: At a median follow-up of 28.2 months, 9 patients were alive and 7 of whom were relapse-free. Two-year overall survival (OS) and progression-free survival (PFS) rates were 69.3% and 52.7%, with median survival times (MSTs) of 36.5 months and 24.4 months, respectively. Two-year local recurrence rate was 40.5% and the median time to local recurrence from treatment initiation was 27.9 months. All patients were scheduled to receive whole-brain RT (WBRT) and subsequent partial-brain RT(PBRT), with a median total dose to the tumor bed of 46 Gy and median WBRT dose of 30 Gy. Eight patients received reduced-dose WBRT (rd-WBRT) (<30 GY), and 13 patients who could not achive a complete response (CR) during the RT period received additional boost radiation after WBRT and PBRT, with a median dose of 6 Gy. Over 70% of local recurrence occurred within areas in which only WBRT was conducted (median dose of 30.3 Gy). Two-year occurrence rate of neurotoxicity over grade 2 was 49.5%. PS at 24 months after RT was maintained in 12 patIents. Conclusions: lndividual RTP using radiographic assessment led to reasonable survival and disease control rates with mild treatment-related toxicity. For patients not receiving chemotherapy or lacking a CR after chemotherapy and WBRT, WBRT followed by PBRT and additional boost radiation for poor RT responders might be effective. However, even for patients with CR after chemotherapy, a WBRT dose of 30 Gy or higher might be necessary for local control.博士(医学)・甲第705号・平成31年3月15日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.70 No.1,2,3 p.1-19 (2019.06)13450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3553Journal of Nara Medical Association, 70 (in press)(1,2,3 (in press))http://hdl.handle.net/10564/3553http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3553/1/01%e7%94%b2705%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3553/2/02%e7%94%b2705%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3553/9/03%e7%94%b2705%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association70 (in press)1,2,3 (in press)2019-06-19engETD24601A7052019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35542019-06-19T16:30:12Zhdl_10564_3445Abrogated Caveolin-1 expression via histone modification enzyme Setdb2 regulates brain edema in a mouse model of influenza-associated encephalopathy.ヒストン修飾酵素Setdb2を介したCaveolin-1はインフルエンザ脳症マウスモデルにおける脳浮腫を制御するImakita, NatsukoKitabatake, MasahiroOuji-Sageshima, NorikoHara, AtsushiMorita-Takemura, ShokoKasahara, KeiMatsukawa, AkihiroWanaka, AkioMikasa, KeiichiIto, ToshihiroInfluenza-associated encephalopathy (IAE) is a serious complication that can follow influenza virus infection. Once a cytokine storm is induced during influenza virus infection, tight junction protein disruption occurs, which consequently leads to blood-brain barrier (BBB) breakdown. However, the details of IAE pathogenesis are not well understood. Here, we established a murine IAE model by administration of lipopolysaccharide following influenza virus infection. Brains from IAE model mice had significantly higher expression of type I interferons and inflammatory cytokines. In addition, the expression of Caveolin-1, one of the key proteins that correlate with protection of the BBB, was significantly lower in brains from the IAE group compared with the control group. We also found that, among 84 different histone modification enzymes, only SET domain bifurcated 2 (Setdb2), one of the histone methyltransferases that methylates the lysine 9 of histone H3, showed significantly higher expression in the IAE group compared with the control group. Furthermore, chromatin immunoprecipitation revealed that methylation of histone H3 lysine 9 was correlated with repression of the Caveolin-1 promoter region. These studies identify Caveolin-1 as a key regulator of BBB permeability in IAE and reveal that it acts through histone modification induced by Setdb2.博士(医学)・甲第706号・平成31年3月15日© The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.© 2018 Springer Nature Publishing AGSpringer Nature Publishing AGThesisThesis or DissertationScientific reports Vol.9 No.1 Article No.284 (2019 Jan)20452322http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3554Scientific reports, 9(1): Article No.284http://hdl.handle.net/10564/3554http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3554/1/01%e7%94%b2706%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3554/2/02%e7%94%b2706%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3554/3/03%e7%94%b2706%e6%9c%ac%e6%96%87.pdf20452322Scientific reports91Article No.2842019-01-22enghttp://www.ncbi.nlm.nih.gov/pubmed/30670717http://dx.doi.org/10.1038/s41598-018-36489-8ETD24601A7062019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35552019-06-19T16:30:14Zhdl_10564_3445Sulforaphane Inhibits Liver Cancer Cell Growth and Angiogenesis.スルフォラファンの肝癌発育抑制効果および血管新生抑制効果に関する基礎的検討Sato, ShinyaMoriya, KeiFurukawa, MasanoriSaikawa, SoichiroNamisaki, TadashiKitade, MitsuteruKawaratani, HidetoKaji, KosukeTakaya, HiroakiShimozato, NaotakaSawada, YasuhikoSeki, KenichiroKitagawa, KouAkahane, TakemiMitoro, AkiraOkura, YasushiYoshiji, HitoshiYamao, JunichiSulforaphaneNrf2Liver cancerAngiogenesisSulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.博士(医学)・甲第707号・平成31年3月15日© The Author(s) 2018 Under License of Creative Commons Attribution 3.0 License https://creativecommons.org/licenses/by/3.0/iMedPub LTDThesisThesis or DissertationArchives in cancer research Vol.6 No.4 Article No.23 (2018 Dec)22546081http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3555Archives in cancer research, 6(4): Article No.23http://hdl.handle.net/10564/3555http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3555/1/01%e7%94%b2707%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3555/2/02%e7%94%b2707%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3555/3/03%e7%94%b2707%e6%9c%ac%e6%96%87.pdf22546081Archives in cancer research64Article No.232018-12enghttp://dx.doi.org/10.21767/2254-6081.100189ETD24601A7072019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35562020-07-27T00:16:27Zhdl_10564_3445hdl_10564_3564凍死の診断における血中尿素窒素およびクレアチニン測定の有用性UTILITY OF BLOOD UREA NITROGEN AND CREATININE MEASUREMENT FOR DIAGNOSIS OF FATAL HYPOTHERMIA.今井, 裕子粕田, 承吾工藤, 利彩勇井, 克也森本, 真未羽竹, 勝彦BUNcreatininefatal hypothermiapostmortem biochemistrymyoglobinuriaDiagnosis of fatal hypothermia using biochemical markers from blood obtained post mortem has not been fully studied. The objective of this study was to investigate biochemical markers useful for diagnosis of fatal hypothermia. We investigated 573 cases that were autopsied within 72 hours of death in our laboratory between January 2015 and February 2018. Right cardiac blood, left cardiac blood and the femoral vein were used as blood sampling sites. Levels of troponin T, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), and CK-MB in the blood, and blood and urinary myoglobin (Mb) were measured. Mb staining of kidney specimens was also performed. Although BUN and Cr levels did not differ from their respective clinical reference values, very high levels of the other markers compared with their respective reference values were observed. BUN and Cr values did not differ among the right cardiac, left cardiac, and femoral vein blood. The BUN value of right cardiac blood in patients who died due to fatal hypothermia was significantly higher than that in patients who died due to burns, heart disease, suffocation, hemorrhagic shock, drowning, and trauma; however, the Cr value for fatal hypothermia was not different from that for other causes of death. Also, the BUN/Cr ratio was significantly higher for fatal hypothermia than for other causes of death. The positive rates of Mb staining in the kidney were as follows: fatal hypothermia, 75%; drowning, 56.7%; drug addiction, 53.3%; trauma, 51.4%; burning death, 47.4%; heart disease, 34.8%; and suffocation, 23.1%. In addition, the amount of urine in the urinary bladder was higher in cases of fatal hypothermia than that in cases of other causes of death. These results suggest that a high BUN value and high BUN/Cr ratio are useful for diagnosis of fatal hypothermia; the increase in BUN value may not be due to acute renal failure caused by rhabdomyolysis but may be due to a decrease in renal blood flow caused by extrarenal factors such as dehydration or circulatory failure.博士(医学)・甲第708号・平成31年3月15日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.69 No.4,5,6 p.67-75 (2018.12)13450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3556Journal of Nara Medical Association Vol. No. p.- (2018.12), 69(4,5,6): 67-75http://hdl.handle.net/10564/3556http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3556/1/01%e7%94%b2708%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3556/2/02%e7%94%b2708%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3556/8/03%e7%94%b2708%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association Vol. No. p.- (2018.12)694,5,667752018-12-31jpnETD24601A7082019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35572019-06-20T16:30:08Zhdl_10564_3445Childhood cancer incidence and survival in Japan and England: A population-based study (1993-2010).がん登録データを用いた、小児がんの罹患率・死亡率の日英比較(1993-2010年)Nakata, KayoIto, YukiMagadi, WinnieBonaventure, AudreyStiller, Charles A.Katanoda, KotaMatsuda, TomohiroMiyashiro, IsaoPritchard-Jones, KathyRachet, Bernardcancer registry datachildhood cancerchildhood cancer incidence and survivalepidemiologypopulation-based studyThe present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5192 children with cancer (age 0-14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993-2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5-year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in 2005-2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1-14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib).博士(医学)・乙第1425号・平成31年3月15日© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.This is an open access article under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.John Wiley & Sons, Inc.ThesisThesis or DissertationCancer science Vol.109 No.2 p.422-434 (2018 Feb)13479032http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3557Cancer science, 109(2): 422-434http://hdl.handle.net/10564/3557http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3557/1/01%e4%b9%991425%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3557/2/02%e4%b9%991425%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3557/3/03%e4%b9%991425%e6%9c%ac%e6%96%87.pdf13479032AA11808050Cancer science10924224342018-02enghttp://www.ncbi.nlm.nih.gov/pubmed/29178401http://dx.doi.org/10.1111/cas.13457ETD24601B14252019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35582020-08-13T04:15:54Zhdl_10564_3445Plaque modification of severely calcified coronary lesions by scoring balloon angioplasty using Lacrosse non-slip element: insights from an optical coherence tomography evaluation.冠動脈高度石灰化病変に対するスコアリングバルーンラクロスNon-Slip Elementを用いた冠動脈形成術-光干渉断層法による有用性の評価Sugawara, YuUeda, TomoyaSoeda, TsunenariWatanabe, MakotoOkura, HiroyukiSaito, YoshihikoPercutaneous coronary interventionScoring balloon angioplastyCoronary calcified lesionOptical coherence tomographyPercutaneous coronary intervention (PCI) for heavily calcified lesions is challenging because these lesions are resistant to balloon dilatation and stenting. Lacrosse non-slip element (NSE) may have the potential to dilate heavily calcified lesions. We aimed to investigate predictors of successful lesion modification using Lacrosse NSE angioplasty via optical coherence tomography (OCT)-guided PCI. We investigated 32 patients with severe target lesion calcification treated with OCT-guided PCI. Successful lesion modification was defined as the complete fracture of calcification after Lacrosse NSE angioplasty. Before PCI, 172 segments with calcification were identified. After pre-dilatation using Lacrosse NSE, successful lesion modification was achieved in 117 segments (68.0%). Calcification was significantly thinner in successfully disrupted segments than in non-disrupted segments (p < 0.001). Calcification angle tended to be larger in disrupted than in non-disrupted segments (p = 0.08). Convex types were less frequently observed in disrupted than in non-disrupted segments (p < 0.001). At minimal lumen area sites, 26 segments (81.3%) were successfully modified. Similar to the overall results, the disrupted group had significantly thinner calcification than the non-disrupted group (p < 0.001). The angle of the calcified plaque was similar between the 2 groups (p = 0.39). Convex-type calcifications were less frequently observed in the disrupted group than in the non-disrupted group (p = 0.05). Receiver-operating characteristic curve analysis showed that calcification thickness < 565 μm was the best predictor of completely disrupted calcification. The thickness and shape of calcifications were predictors of successful lesion modification after Lacrosse NSE angioplasty.博士(医学)・乙第1426号・平成31年3月15日© Japanese Association of Cardiovascular Intervention and Therapeutics 2018This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular intervention and therapeutics. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12928-018-0553-6.Springer Nature Publishing AGThesisThesis or DissertationCardiovascular intervention and therapeutics Vol.34 No.3 p.242-248 (2019 Jul)18684300http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3558Cardiovascular intervention and therapeutics, 34(3): 242-248http://hdl.handle.net/10564/3558http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3558/1/01%e4%b9%991426%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3558/2/02%e4%b9%991426%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3558/6/03%e4%b9%991426%e6%9c%ac%e6%96%87.pdf18684300AA12510961Cardiovascular intervention and therapeutics3432422482019-07enghttp://www.ncbi.nlm.nih.gov/pubmed/30341585http://dx.doi.org/10.1007/s12928-018-0553-6ETD24601B14262019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35592020-08-13T16:30:07Zhdl_10564_3445Emicizumab, the bispecific antibody to factors IX/IXa and X/Xa, potentiates coagulation function in factor XI-deficient plasma in vitro.第IX(a)因子および第X因子に対する二重特異性抗体であるエミシズマブはin vitroで第XI因子欠乏血漿における凝固機能を増強するMinami, HiroakiNogami, KeijiYada, KojiOgiwara, KenichiFurukawa, ShokoSoeda, TetsuhiroKitazawa, TakehisaShima, Midoriclot waveform analysisemicizumabfactor XI deficiencyplasmathrombin generation assayEssentials Emicizumab mimics factor (F)VIIIa cofactor function, augments the intrinsic tenase activity. We assessed the emicizumab-driven hemostatic function in FXI-deficient plasmas. Emicizumab improved the coagulation potentials in severe FXI-deficient plasma. Emicizumab may provide a possibility for clinical application in patients with FXI deficiency. SUMMARY: Background Patients with factor (F)XI deficiency commonly present with markedly prolonged activated partial thromboplastin times (APTT), although bleeding phenotypes are heterogeneous. Emicizumab, a bispecific monoclonal antibody to FIX/FIXa and FX/FXa, mimics FVIIIa cofactor function on phospholipid (PL) surfaces. Antibody reactions were designed, therefore, to augment mechanisms during the propagation phase of blood coagulation. Aim To assess emicizumab-driven hemostatic function in FXI-deficient plasmas. Methods and Results Standard ellagic acid (Elg)/PL-based APTTs of different FXI-deficient plasmas (n = 13; FXI activity, < 1 IU dl-1 ) were markedly shortened dose dependently by the presence of emicizumab. To further analyze the effects of emicizumab, clot waveform analysis (CWA) in FXI-deficient plasmas with emicizumab, triggered by tissue factor (TF)/Elg demonstrated improvements in both clot times, reflecting the initiation phase, and coagulation velocity, which represents the propagation phase. Emicizumab also enhanced the TF/Elg-triggered thrombin generation in FXI-deficient plasmas dose-dependently although the degree of enhancement varied in individual cases. Thrombin generation with either FVII-deficient plasma or FIX-deficient plasma treated with anti-FXI antibody showed little or no increase by the co-presence of emicizumab, suggesting that the accelerated thrombin generation in FXI-deficient plasmas by emicizumab should depend on the FIXa-involved coagulation propagation initially triggered by FVIIa/TF. The ex vivo addition of emicizumab to whole blood from three patients with severe FXI deficiency demonstrated modest, dose-dependent improvements in Ca2+ -triggered thromboelastograms (NATEM mode). Conclusion Emicizumab appeared to improve coagulation function in severe FXI-deficient plasma, and might provide possibilities for clinical application in patients with FXI deficiency.博士(医学)・乙第1427号・平成31年3月15日© 2018 International Society on Thrombosis and HaemostasisThis is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/jth.14334], which has been published in final form at [http://dx.doi.org/10.1111/jth.14334]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.John Wiley and Sons, Inc.ThesisThesis or DissertationJournal of thrombosis and haemostasis Vol.17 No.1 p.126-137 (2019 Jan)15387933http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3559Journal of thrombosis and haemostasis, 17(1): 126-137http://hdl.handle.net/10564/3559http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3559/1/01%e4%b9%991427%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3559/2/02%e4%b9%991427%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3559/6/03%e4%b9%991427%e6%9c%ac%e6%96%87.pdf15387933AA11811179Journal of thrombosis and haemostasis1711261372019-01enghttp://www.ncbi.nlm.nih.gov/pubmed/30444568http://dx.doi.org/10.1111/jth.14334ETD24601B14272019-03-15博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/35602019-07-18T08:01:39Zhdl_10564_3445hdl_10564_3564A Sensitive and Time-Saving Method for the Diagnosis of Drowning by Multiplex PCR.Multiplex PCRを用いた簡便で感度の高い溺死診断法の開発Nakanishi, MariNakayama, AkifumiKasuda, ShogoKudo, RisaYuui, KatsuyaIshitani, AkikoHatake, KatsuhikoDiagnosis of drowningMultiplex PCRAquatic bacteriaRespiratory tract bacteriaFor diagnosing death due to drowning, the method of acid digestion of diatoms is widely used to detect plankton in the organs of the corpse. However, the method is limited by its being complex, hazardous, time-consuming, and insufficiently sensitive. We therefore, developed a novel simple method to diagnose death due to drowning, and determined the location of drowning by detecting genes of representative bacteria in the environment. To procure all the information in one step, the multiplex PCR method was designed. For the diagnosis of drowning, the genes of upper respiratory indigenous bacteria, Streptococcus salivarius and Streptococcus sanguinis were used as indicators. For detection of the location of drowning, Aeromonas hydrophila and Microcystis aeruginosa were used as indicators of freshwater, and Vibrio harveyi as an indicator of seawater. A set of primers was designed for multiplex PCR. to amplify all the bacterial genes simultaneously. Using this method, 47 cases of drowning were examined, and the causes and locations of death were diagnosed.博士(医学)・乙第1428号・平成31年3月15日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.69 No.4,5,6 p.77-85 (2018.12)13450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3560Journal of Nara Medical Association, 69(4,5,6): 77-85http://hdl.handle.net/10564/3560http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3560/1/01%e4%b9%991428%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3560/2/02%e4%b9%991428%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3560/8/03%e4%b9%991428%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association694,5,677852018-12-31engETD24601B14282019-03-15博士(医学)奈良県立医科大学