2024-03-29T07:35:11Zhttp://ginmu.naramed-u.ac.jp/dspace-oai/request
oai:ginmu.naramed-u.ac.jp:10564/10752017-08-21T01:23:16Zhdl_10564_2611hdl_10564_1491異型精子細胞における膜構造の電子顕微鏡的研究ELECTRON MICROSCOPE STUDY ON MEMBRANE STRUCTURE OF ATYPICAL SPERMATIDS手塚, 治異型精子細胞電子顕微鏡田螺タニシ手塚治虫The fine structure of the membrane of cell organelles appearing in the atypical spermatid of Cipangopaludina malleata Reeve has been studied in thin sections by an electron microscope.
The porous structure has been revealed in the wall of the flattened sacculus consisting the Golgi complex. The walls are calculated 35 A thick. The mitochondria consist of a small number of tubules and an osmiophilic matrix. The mitochondria represent a complex system of tubules projected from the inner layer of the limiting membrane, and the tubules consist of double dense mcmbrans involving a less dense interspace. The mitochondria aggregated along the developing tail filaments coalesce to form an elongated mass of relatively large size. The limiting membrane of the rough-surfaced endoplasmic reticulum appears apparcntly to be a single layer, which makes its appearance in the area where the tail filaments devlop. The smooth surfaced endoplasmic reticulum is bordcrcd by a double layercd membrane consisting two opaque layers with a less opaque interspace. The vesicles containing dense granules, which represent the smooth surfaced endoplasmic reticulum, migrate to the cell periphery. The smooth surfaced endoplasmic reticulum scems to function as an intraccllular conductor.博士(医学)・第88号・昭和36年2月7日奈良医学会ThesisDepartmental Bulletin Paperapplication/pdf奈良医学雑誌 Vol.11 No.5 p.719-73504695550http://ginmu.naramed-u.ac.jp/dspace/handle/10564/1075奈良医学雑誌, 11(5): 719-735http://hdl.handle.net/10564/1075http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/1075/4/01%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/1075/7/02%e6%9c%ac%e6%96%87.pdf04695550AN00180974奈良医学雑誌1157197351960-10jpnpublisher
oai:ginmu.naramed-u.ac.jp:10564/15842017-05-29T06:07:29Zhdl_10564_1585Outcomes of chest compression only CPR versus conventional CPR conducted by lay people in patients with out of hospital cardiopulmonary arrest witnessed by bystanders: nationwide population based observational studyOgawa, ToshioAkahane, ManabuKoike, SoichiTanabe, SeizanMizoguchi, TatsuhiroImamura, TomoakiOBJECTIVE: To compare the effectiveness of cardiopulmonary resuscitation (CPR) with chest compression only and conventional CPR on outcomes after cardiopulmonary arrest out of hospital.
DESIGN: Nationwide population based observational study.
SETTING: A nationwide emergency medical service system in Japan. Population All consecutive patients with out of hospital cardiopulmonary arrest, January 2005 to December 2007 in Japan, witnessed at the moment of collapse. Lay people attempted chest compression only CPR (n = 20,707) or conventional CPR (mouth to mouth ventilation and chest compression) (n = 19,328), and patients were transferred to hospital by ambulance.
MAIN OUTCOME MEASURES: Factors associated with better outcomes (assessed with χ(2), multiple logistic regression analysis, odds ratios and their 95% confidence intervals): one month survival and neurologically favourable one month survival rates defined as category one (good cerebral performance) or two (moderate cerebral disability) of the cerebral performance categories.
RESULTS: Conventional CPR was associated with better outcomes than chest compression only CPR, for both one month survival (adjusted odds ratio 1.17, 95% confidence interval 1.06 to 1.29) and neurologically favourable one month survival (1.17, 1.01 to 1.35). Neurologically favourable one month survival decreased with increasing age and with delays of up to 10 minutes in starting CPR for both conventional and chest compression only CPR. The benefit of conventional CPR over chest compression only CPR was significantly greater in younger people in non-cardiac cases (P = 0.025) and with a delay in start of CPR after the event was witnessed in non-cardiac cases (P = 0.015) and all cases combined (P = 0.037).
CONCLUSIONS: Conventional CPR is associated with better outcomes than chest compression only CPR for selected patients with out of hospital cardiopulmonary arrest, such as those with arrests of non-cardiac origin and younger people, and people in whom there was delay in the start of CPR.博士(医学)・乙第1266号・平成23年5月30日BMJ Publishing Group Ltd.ThesisThesis or Dissertationapplication/pdfBMJ 2010; 342:c710609598146http://ginmu.naramed-u.ac.jp/dspace/handle/10564/1584BMJ : British medical journal, 342: c7106http://hdl.handle.net/10564/1584http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/1584/1/bmj.c7106.full%5b1%5d.pdf09598146AA10789686BMJ : British medical journal342c71062011-01-27enghttp://dx.doi.org/10.1136/bmj.c7106http://www.ncbi.nlm.nih.gov/pubmed/21273279http://dx.doi.org/10.1136/bmj.c7106(c) 2011 BMJ Publishing Group Ltd.publisher
oai:ginmu.naramed-u.ac.jp:10564/16232017-06-11T23:20:26Zhdl_10564_1615hdl_10564_1640非定型抗酸菌(Mycobacterium avium-intracellulare complex)症患者における末梢血単核球サイトカイン産生能に関する研究STUDIES ON PRODUCTION OF CYTOKINES BY PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PATIENTS WITH MYCOBACTERIUM AVIUM-INTRACELLULARE COMPLEX INFECTION友田, 恒一atypical mycobacterial infectionMycobacterium avium-intracellulare complexinterferon gammatumor necrosis factor alphainterleukin-6Cytokine productions of peripheral blood lymphocytes (PBLs) and monocytes (PBMs) from patients with Mycobacterium avium-intracellulare complex (MAC) infection were assessed. PPD-S prepared from M. tuberculosis, PPD-B from M. intracellulare, and PPD-Y from M. kansasii, were used as stimulants. PBLs from patients with active MAC did not produce IFN-γ to a significant extent upon stimulation with any of three PPDs, while PBLs from patients with inactive MAC showed higher responses to each PPD with the maximal response to PPD-B antigens. On the other hand, PBLs from healthy controls produced IFN-γ with the maximal response to PPD-S. Spontaneous release of both TNFα and IL-6 by PBMs from patients at the active stage was higher than those by the cells of the inactive stage patients or healthy controls. When PBMs were stimulated with MAC-derived PPD (PPD-B), increased TNFα production was obtained for PBMs of the active stage and decreased IL-6 production was seen for the cells of both the active and inactive stages. Moreover, the in vitro increased production of TNFα upon stimulation with PPD-B seems to be related to persistent MAC infection, resulting in exhausted nutritional status. These results suggest that in vitro ability of both PBLs to produce IFN-γ and that of PBMs to produce TNFα and IL-6 are closely related to the clinical stage of MAC infection.博士(医学)・甲第318号・平成7年3月22日奈良医学会ArticleDepartmental Bulletin Paperapplication/pdf奈良医学雑誌 Vol.45 No.5 p.536-5440469555013450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/1623奈良医学雑誌, 45(5): 536-544http://hdl.handle.net/10564/1623http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/1623/1/536-544p%ef%bc%9a%e9%9d%9e%e5%ae%9a%e5%9e%8b%e6%8a%97%e9%85%b8%e8%8f%8c%28Mycobacterium_avium-intracellulare_complex%29%e7%97%87%e6%82%a3%e8%80%85%e3%81%ab%e3%81%8a%e3%81%91%e3%82%8b%e6%9c%ab%e6%a2%a2%e8%a1%80%e5%8d%98%e6%a0%b8%e7%90%83%e3%82%b5%e3%82%a4%e3%83%88%e3%82%ab%e3%82%a4%e3%83%b3%e7%94%a3%e7%94%9f%e8%83%bd%e3%81%ab%e9%96%a2%e3%81%99%e3%82%8b%e7%a0%94%e7%a9%b6.pdf4695550AN00180974奈良医学雑誌4555365441994-10-31jpnpublisher
oai:ginmu.naramed-u.ac.jp:10564/20832017-05-29T06:09:49Zhdl_10564_2082Development of a web-based survey for monitoring daily health and its application in an epidemiological surveySugiura, HiroakiOhkusa, YasushiAkahane, ManabuSano, TomomiOkabe, NobuhikoImamura, Tomoakiweb-based surveysyndromic surveillancelong-term operationBackground: Early detection of symptoms arising from exposure to pathogens, harmful substances, or environmental changes requires timely intervention. The administration of web-based questionnaires is a potential method for collecting information from a sample population.
Objective: To develop a web-based daily questionnaire for health (WDQH) for symptomatic surveillance.
Methods: We adopted two different survey methods to develop the WDQH: an internet panel survey, which included subjects already registered with an internet survey company, and the Tokyo Consumers’ Co-operative Union (TCCU) internet survey, in cooperation with the Japanese Consumers’ Co-operative Union, which recruited participants by website advertising. The internet panel survey participants were given a fee everyday for answers, and the survey was repeated twice with modified surveys and collection methods; Internet Panel Survey I was conducted every day, and Internet Panel Survey II was conducted every 3 days to reduce costs. We examined whether the survey remained valid by reporting health conditions on day 1 over a 3-day period, and whether the response rate would vary among groups with different incentives. In the TCCU survey, participants were given a fee only for initial registering, and health information was provided in return for survey completion. The WDQH included the demographic details of participants and prompted subjects to answer questions about the presence of various symptoms by e-mail. Health information collected by the WDQH was then used for the syndromic surveillance of infection.
Results: Response rates averaged 47.3% for Internet Panel Survey I, 42.7% for Internet Panel Survey II, and 40.1% for the TCCU survey. During a seasonal influenza epidemic, a rapid increase in the number of patients with fever was reported by the WDQH using the early aberration reporting system.
Conclusions: We developed a health observation method based on self-reporting by subjects via the internet. We validated the usefulness of the WDQH via its practical use in syndromic surveillance.博士(医学)・甲第581号・平成24年3月16日The definitive version is available at "http://www.jmir.org/2011/3/e66/"JMIR PublicationsThesisThesis or Dissertationapplication/mswordJournal of medical Internet research 2011 (Sep 23); 13(3):e6614388871http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2083Journal of medical Internet research, 13(3): e66http://hdl.handle.net/10564/2083http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2083/4/%e5%81%a5%e5%ba%b7%e6%94%bf%e7%ad%96%e5%8c%bb%e5%ad%a6%e8%ac%9b%e5%ba%a7_%e6%9d%89%e6%b5%a6%e5%bc%98%e6%98%8e.pdf14388871Journal of medical Internet research133e662011-09-23enghttp://www.ncbi.nlm.nih.gov/pubmed/21946004http://dx.doi.org/10.2196/jmir.1872author
oai:ginmu.naramed-u.ac.jp:10564/21032017-06-30T03:44:43Zhdl_10564_2082Olmesartan inhibits angiotensin II-induced migration of vascular smooth muscle cells through Src and MAP kinase pathwaysアンジオテンシンⅡによるSrc及びmitogen-activated protein kinaseを介した血管平滑筋細胞の遊走に対するオルメサルタンの阻害作用Kyotani, YojiZhao, JingTomita, SayukoNakayama, HitoshiIsosaki, MinoruUno, MasayukiYoshizumi, Masanoriangiotensin IIangiotensin receptor blockerARBolmesartancell migrationClinical studies have shown that Angiotensin receptor blockers (ARBs) reduce the risk of cardiovascular diseases in hypertensive patients. It is assumed that the reduction of the risk by ARBs may be attributed in part to the inhibition of AII-induced vascular smooth muscle cell (VSMC) migration associated with atherosclerosis. However, the effect of ARBs on AII-induced changes in intracellular signaling and resultant cell migration has not been well established. Here, we investigated the effect of olmesartan, an ARB, on AII-induced extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) activation and rat aortic smooth muscle cell (RASMC) migration. Olmesartan inhibited AII-induced ERK1/2 and JNK activation at lower concentrations (10 nM). On the other hand, PP2, an Src tyrosine kinase inhibitor, also inhibited AII-induced ERK1/2 and JNK activation, but its effect on ERK1/2 was less pronounced than that of olmesartan. Olmesartan, U0126 (an ERK1/2 inhibitor), SP600125 (a JNK inhibitor), and PP2 potently inhibited AII-induced RASMC migration. From these findings, it was inferred that angiotensin receptor blockade by olmesartan results in the inhibition of AII-induced activation of Src, ERK1/2, and JNK in RASMC. Olmesartan may be a potent inhibitor of AII-induced VSMC migration, which may be involved in the progression in atherosclerosis.博士(医学)・甲第584号・平成24年3月16日The definitive version is available at "http://dx.doi.org/10.1254/jphs.09332FP"公益社団法人日本薬理学会ThesisThesis or Dissertationapplication/pdfapplication/pdfJournal of Pharmacological Sciences Vol. 113 (2010) , No. 2 pp.161-16813478613http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2103Journal of Pharmacological Sciences, 113(2): 161-168http://hdl.handle.net/10564/2103http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2103/2/Figure.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2103/1/JPS113%ef%bc%882%ef%bc%89161-168.pdf13478613AA11806667Journal of Pharmacological Sciences11321611682010-05enghttp://www.ncbi.nlm.nih.gov/pubmed/20508392http://dx.doi.org/10.1254/jphs.09332FPauthor
oai:ginmu.naramed-u.ac.jp:10564/25872022-08-26T05:46:30Zhdl_10564_2586Lower prefrontal activity in adults with obsessive-compulsive disorder as measured by near-infrared spectroscopy近赤外線スペクトロスコピィで測定された成人強迫性障害における前頭前野の活動性の低下Okada, kojiOta, ToyosakuIida, JunzoKishimoto, NaokoKishimoto, Toshifumiobsessive-compulsive disordernear-infrared spectroscopyfunctional neuroimaging studyprefrontal hemodynamic responseStroop color-word taskRecent developments in near-infrared spectroscopy (NIRS) have enabled the non-invasive elucidation of the neurobiological underpinnings of psychiatric disorders. Functional neuroimaging studies in human patients have suggested that the frontal cortex and subcortical structures may play a role in the pathophysiology of obsessive-compulsive disorder (OCD). Here we used NIRS to investigate neurobiological function in 12 patients with OCD and 12 age- and sex-matched, healthy control subjects. The relative concentrations of oxyhemoglobin (oxy-Hb) were measured with prefrontal probes every 0.1 sec, during performance of a Stroop color-word task, using 24-channel NIRS. Oxy-Hb changes in the prefrontal cortex of the OCD group were significantly smaller than those in the control group, especially in the left lateral prefrontal cortex. These results suggest that patients with OCD have reduced prefrontal hemodynamic responses as measured by NIRS.博士(医学)・甲第599号・平成25年5月29日Copyright © 2012 Elsevier Inc. All rights reserved.Elsevier / PressThesisThesis or DissertationProgress in neuro-psychopharmacology & biological psychiatry Vol.43 p.7-13 (2013 Jun)02785846http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2587Progress in neuro-psychopharmacology & biological psychiatry, 43: 7-13http://hdl.handle.net/10564/2587http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2587/6/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2587/7/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2587/13/03%e6%9c%ac%e6%96%87.pdf02785846AA10532839Progress in neuro-psychopharmacology & biological psychiatry437132013-06-03enghttp://www.ncbi.nlm.nih.gov/pubmed/23220093http://dx.doi.org/10.1016/j.pnpbp.2012.11.013ETD24601A5992013-05-29博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/25882022-08-26T06:21:51Zhdl_10564_2586Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo.PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果Yasuda, SatoshiSho, MasayukiYamato, IchiroYoshiji, HitoshiWakatsuki, KoheiNishiwada, SatoshiYagita, HideoNakajima, YoshiyukiPD-1VEGFR2Immune checkpointAntiangiogenesisAntitumour immunityRecent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has a therapeutic potential against several human cancers. We hypothesized that anti-angiogeneic treatment might augment the efficacy of PD-1 blockade. To this end, we evaluated combining the blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2) in a murine cancer model using Colon-26 adenocarcinoma. Interestingly, simultaneous treatment with anti-PD-1 and anti-VEGFR2 monoclonal antibodies (mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR2 inhibited tumour neovascularization significantly, as demonstrated by the reduced number of microvessels, while PD-1 blockade had no impact on tumour angiogenesis. PD-1 blockade might promote T cell infiltration into tumours and significantly enhanced local immune activation, as shown by the up-regulation of several proinflammatory cytokine expressions. Importantly, VEGFR2 blockade did not interfere with T cell infiltration and immunological activation induced by PD-1 blockade. In conclusion, simultaneous blockade of PD-1 and VEGFR2 induced a synergistic in-vivo anti-tumour effect, possibly through different mechanisms that might not be mutually exclusive. This unique therapeutic strategy may hold significant promise for future clinical application.博士(医学)・甲第600号・平成25年5月29日© 2013 British Society for ImmunologyThis article has been accepted for publication in Clinical and experimental immunology Published by Oxford University Press.Oxford University PressThesisThesis or DissertationClinical and experimental immunology Vol.172 No.3 p.500-506 (2013 Jun)00099104http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2588Clinical and experimental immunology, 172(3): 500-506http://hdl.handle.net/10564/2588http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2588/6/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2588/7/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2588/8/03%e6%9c%ac%e6%96%87.pdf00099104AA00607716Clinical and experimental immunology17235005062013-06enghttp://www.ncbi.nlm.nih.gov/pubmed/23600839http://dx.doi.org/10.1111/cei.12069ETD24601A6002013-05-29博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/25892017-05-29T06:09:51Zhdl_10564_2586In vivo observation of age-related structural changes of dermal collagen in human facial skin using collagen-sensitive second harmonic generation microscope equipped with 1250-nm mode-locked Cr:Forsterite laser1250nm帯モード同期クロム・フォルステライトレーザーを光源とした第2高調波発生光顕微鏡によるヒト顔皮膚の老化性真皮コラーゲン構造変化のその場観察Yasui, TakeshiYonetsu, MakotoTanaka, RyosukeTanaka, YujiFukushima, Shu-ichiroYamashita, ToyonobuOgura, YukiHirao, TetsujiMurota, HiroyukiAraki, Tsutomunonlinear microscopysecond harmonic generationcollagendermatologyintrinsic agingphotoagingtissuedermisIn vivo visualization of human skin aging is demonstrated using a Cr:Forsterite (Cr:F) laser-based, collagen-sensitive second harmonic generation (SHG) microscope. The deep penetration into human skin, as well as the specific sensitivity to collagen molecules, achieved by this microscope enables us to clearly visualize age-related structural changes of collagen fiber in the reticular dermis. Here we investigated intrinsic aging and/or photoaging in the male facial skin. Young subjects show dense distributions of thin collagen fibers, whereas elderly subjects show coarse distributions of thick collagen fibers. Furthermore, a comparison of SHG images between young and elderly subjects with and without a recent life history of excessive sun exposure show that a combination of photoaging with intrinsic aging significantly accelerates skin aging. We also perform image analysis based on two-dimensional Fourier transformation of the SHG images and extracted an aging parameter for human skin. The in vivo collagen-sensitive SHG microscope will be a powerful tool in fields such as cosmeceutical sciences and anti-aging dermatology.博士(医学)・乙第1311号・平成25年5月29日SPIE--the International Society for Optical EngineeringThesisThesis or DissertationJournal of biomedical optics Vol.18 No.3 p.31108(1-10)10833668http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2589Journal of biomedical optics, 18(3): 31108-1-31108-10http://hdl.handle.net/10564/2589http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2589/4/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2589/3/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2589/1/03%e6%9c%ac%e6%96%87.pdf10833668AA11237889Journal of biomedical optics18331108-131108-102013-03http://www.ncbi.nlm.nih.gov/pubmed/23212157http://dx.doi.org/10.1117/1.JBO.18.3.031108ETD24601B13112013-05-29博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/25902017-05-29T06:09:49Zhdl_10564_2586Delayed maturation and differentiation of neurons in focal cortical dysplasia with the transmantle sign: analysis of layer-specific marker expression“Transmantle sign”を示す限局性皮質異形成における神経細胞の成熟と分化の未熟性:層特異的マーカー発現による解析Sakakibara, TakafumiSukigara, SayuriSaito, TakashiOtsuki, TaisukeTakahashi, AkioKaneko, YuuKaido, TakanobuSaito, YukoSato, NorikoKimura, YukioNakagawa, EijiSugai, KenjiSasaki, MasayukiGoto, Yu-ichiItoh, MasayukiEpilepsyFocal cortical dysplasiaLayer-specific markersNeural maturationTransmantle dysplasiaTransmantle signTransmantle dysplasia is a rare type of focal cortical dysplasia (FCD) characterized by expansion of the cortex from the deep white matter to the surface and in which there is a FCD IIA or IIB pathologic pattern. To characterize possible mechanisms underlying this regional disorder of radial migrating cells, we studied the expression patterns of neocortical layer-specific markers using immunohistochemistry in surgical specimens from 5 FCD IIA and 4 FCD IIB cases in children. All neuronal cells expressed the mature neuron marker MAP2/2B but not the microglia markers Iba-1 and CD68. Some layer-specific markers showed distinct expression patterns. TBR1-positive, SATB2-positive, and FOXP1-positive cells were diffusely distributed in the cortex and/or the white matter. TBR1-positive and FOXP1-positive cells were generally more numerous in FCD IIB than in FCD IIA and were mostly in the cortical molecular and upper layers. FOXP1-, FOXP2-, and CUTL1-positive cells also expressed the immature neuron marker, Nestin/PROX1, whereas TBR1-, CTIP2-, and SATB2-positive cells only expressed MAP2/2B. These data highlight differences between FCD IIB and FCD IIA with more cells having the immature marker in upper layer markers in the former. By analyzing layer-specific marker expression patterns, we identified apparent neuronal maturation differences between FCD IIA and FCD IIB in cases of transmantle dysplasia.博士(医学)・乙第1312号・平成25年5月29日Waverly PressThesisThesis or DissertationJournal of neuropathology and experimental neurology Vol.71 No.8 p.741-74900223069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2590Journal of neuropathology and experimental neurology, 71(8): 741-749http://hdl.handle.net/10564/2590http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2590/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2590/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2590/6/03%e6%9c%ac%e6%96%87.pdf00223069AA00703323Journal of neuropathology and experimental neurology7187417492012-08http://www.ncbi.nlm.nih.gov/pubmed/22805777http://dx.doi.org/10.1097/NEN.0b013e318262e41aETD24601B13122013-05-29博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/25912017-06-11T23:20:26Zhdl_10564_2586Phosphorylation status of Fas-associated death domain protein is associated with biochemical recurrence after radical prostatectomyFADDのリン酸化の状態と根治的前立腺全摘除術後の生化学的再発は関連するIkeda, TomohiroTanaka, NobumichiShimada, KeijiMatsumura, YoshiakiMiyake, MakitoAnai, SatoshiTomioka, AtsushiOkajima, EijiroHirayama, AkihideFujimoto, KiyohideKonishi, NoboruHirao, YoshihikoProstate cancerradical prostatectomyprognostic factorbiochemical recurrencep-FADDOBJECTIVE: To assess whether the phosphorylated Fas-associated death domain protein (FADD) at 194 serine (p-FADD) is valuable as a marker of biochemical recurrence in hormone-naive patients who had undergone radical prostatectomy.
MATERIALS AND METHODS: We used radical prostatectomy specimens from 106 patients. None of the patients had received neoadjuvant or adjuvant therapy. The percentage of positive p-FADD cells (nuclear staining) was immunohistochemically evaluated. The correlation between FADD phosphorylation and the clinicopathologic parameters was assessed. The correlation between the biochemical recurrence-free rate and the p-FADD expression level was analyzed using the Kaplan-Meier method.
RESULTS: Overall, 39 patients developed biochemical recurrence. We investigated the expression of p-FADD in 106 patients with prostate cancer using immunohistochemistry. We compared our findings with the clinicopathologic parameters, including the follow-up data. Patients with a greater positive p-FADD rate had a significantly lower biochemical recurrence rate than those with a lower positive p-FADD rate (P < .001). A significant inverse correlation was found between the positive p-FADD rate and the Gleason score.
CONCLUSION: A low expression of p-FADD could be a predictor of biochemical recurrence in hormone-naive patients who have undergone radical prostatectomy.博士(医学)・乙第1313号・平成25年5月29日Elsevier ScienceThesisThesis or DissertationUrology Vol.81 No.3 p.607-61000904295http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2591Urology, 81(3): 607-610http://hdl.handle.net/10564/2591http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2591/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2591/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2591/6/03%e6%9c%ac%e6%96%87.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2591/7/04Fig.1-3_and_table1.pdf00904295AA0087924XUrology8136076102013-03enghttp://www.ncbi.nlm.nih.gov/pubmed/23352370http://dx.doi.org/10.1016/j.urology.2012.11.032ETD24601B13132013-05-29博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/25922017-05-29T06:09:55Zhdl_10564_2586Evaluation of the neuroprotective effect of minocycline in a rabbit spinal cord ischemia modelウサギ脊髄虚血モデルにおけるミノサイクリンの神経保護作用の評価Watanabe, KeisukeKawaguchi, MasahikoKitagawa, KazuhikoInoue, SatokiKonishi, NoboruFuruya, HitoshiMinocyclineischemic spinal cord injuryreperfusionneuroprotective effectrabbitOBJECTIVE: To investigate whether postischemic administration of minocycline attenuates hind-limb motor dysfunction and gray and white matter injuries after spinal cord ischemia.
DESIGN: A prospective, randomized, laboratory investigation.
SETTING: Laboratory in university, single institution.
PARTICIPANTS: Male New Zealand White rabbits.
INTERVENTION: Spinal cord ischemia was induced by an occlusion of the infrarenal aorta for 15 minutes. The groups were administered minocycline 1 hour after reperfusion (M-1; n = 8), minocycline 3 hours after reperfusion (M-3; n = 8), saline 1 hour after reperfusion (control [C]; n = 8), or saline and no occlusion (sham; n = 4). Minocycline was administered intravenously at 10 mg/kg 6 times at 12-hour intervals until 60 hours after the initial administration.
MEASUREMENT AND MAIN RESULTS: Hind-limb motor function was assessed using the Tarlov score. For histologic assessments, gray and white matter injuries were evaluated 72 hours after reperfusion using the number of normal neurons and the percentage of areas of vacuolation, respectively. Motor function 72 hours after reperfusion was significantly better in group M-1 than in group C. The number of neurons in the anterior horn was significantly larger in group M-1 than in groups M-3 or C but did not differ significantly between groups M-3 and C. No significant difference was noted in the percentage of areas of vacuolation among the ischemia groups.
CONCLUSIONS: Minocycline administration beginning at 1 hour after reperfusion improved hind-limb motor dysfunction and attenuated gray matter injury in a rabbit spinal cord ischemia model.博士(医学)・乙第1314号・平成25年5月29日W.B. SaundersThesisThesis or DissertationJournal of cardiothoracic and vascular anesthesia Vol.26 No.6 p.1034-103810530770http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2592Journal of cardiothoracic and vascular anesthesia, 26(6): 1034-1038http://hdl.handle.net/10564/2592http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2592/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2592/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2592/6/03%e6%9c%ac%e6%96%87.pdf10530770AA10801216Journal of cardiothoracic and vascular anesthesia266103410382012-12enghttp://www.ncbi.nlm.nih.gov/pubmed/22763274http://dx.doi.org/10.1053/j.jvca.2012.05.003ETD24601B13142013-05-29博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26352022-08-26T06:49:00Zhdl_10564_2586Activated prothrombin complex concentrate (APCC)-mediated activation of factor (F)VIII in mixtures of FVIII and APCC enhances hemostatic effectiveness.Yada, KojiNogami, KeijiOgiwara, KenichiShima, Midoriactivation analysis;blood coagulation;factor IX, factor VII, factor X – prothrombin drug combinationfactor VIII – humanhemophilia AinhibitorsBACKGROUND AND OBJECTIVES: Activated prothrombin complex concentrates (APCCs), utilized in bypassing therapy for hemophiliacs with inhibitor, contain factors (Fs) VII, FII, FIX and FX, and their active forms. A recent report has demonstrated that mixtures of APCC and FVIII potentiated thrombin generation, in vitro, in plasma from patients with severe hemophilia A, but the mechanism(s) involved remains unknown.
RESULTS: APCC (0.05 U mL(-1) ) increased FVIII activity ~ 4-fold within 1 min in one-stage clotting assays, followed by a return to initial levels within 10 min. This reaction was dependent on the presence of tissue factor and phospholipid. Thrombin generation produced from APCC was ~ 3.5-fold greater in the presence of FVIII than that in its absence. SDS-PAGE analysis revealed that APCC sequentially proteolyzed the heavy chain of FVIII at Arg(372) and Arg(740) , followed by cleavage at Arg(336) . Proteolysis was prevented by FVIIa inhibitor, but not by hirudin, supporting the concept that APCC itself possessed the potential to activate FVIII in early coagulation phases, and that FVIIa in APCC contributed mainly to this reaction. APCC-mediated FVIII activation was unaffected by the addition of anti-FVIII inhibitor antibodies, irrespective of epitope specificity. Anti-C2 type 1 inhibitors, however, diminished the inactivation phase of the APCC reaction by inhibiting cleavage at Arg(336) .
CONCLUSION: Small amounts of APCC, relative to the standard concentration used for clinical purposes, could activate FVIII directly, even in the presence of anti-FVIII antibodies. Combination therapy based on mixtures of APCC and FVIII could have significant beneficial implications for the treatment of hemophilia A patients with inhibitors.博士(医学)・甲第601号・平成25年7月22日© 2013 International Society on Thrombosis and Haemostasis.Blackwell Pub.ThesisThesis or DissertationJournal of thrombosis and haemostasis Vol.11 No.5 p.902-91015387933http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2635Journal of thrombosis and haemostasis, 11(5): 902-910http://hdl.handle.net/10564/2635http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2635/5/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2635/6/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2635/7/03%e6%9c%ac%e6%96%87.pdf15387933AA11811179Journal of thrombosis and haemostasis1159029102013-05-15enghttp://www.ncbi.nlm.nih.gov/pubmed/23517528http://dx.doi.org/10.1111/jth.12197none24601A6012013-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26362017-05-29T06:09:53Zhdl_10564_2586Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces.Doi, MasaakiSugimoto, MitsuhikoMatsui, HidetoMatsunari, YasunoriShima, MidoriHaemophiliavon Willebrand factorfactor VIIIflowFibrin generationCoagulation factor VIII (FVIII) plays an essential role in haemostasis. To date, physiologic activity of FVIII circulating in the bloodstream (S-FVIII) is evaluated by classic coagulation assays. However, the functional relevance of FVIII (-von Willebrand factor complex) immobilised on thrombogenic surfaces (I-FVIII) remains unclear. We used an in vitro perfusion chamber system to evaluate the function of I-FVIII in the process of mural thrombus formation under whole blood flow conditions. In perfusion of either control or synthetic haemophilic blood, the intra-thrombus fibrin generation on platelet surfaces significantly increased as a function of I-FVIII, independent of S-FVIII, under high shear rate conditions. This I-FVIII effect was unvarying regardless of anti-FVIII inhibitor levels in synthetic haemophilic blood. Thus, our results illustrate coagulation potentials of immobilised clotting factors, distinct from those in the bloodstream, under physiologic flow conditions and may give a clue for novel therapeutic approaches for haemophilic patients with anti-FVIII inhibitors.博士(医学)・甲第602号・平成25年7月22日The definitive version is available at " http://dx.doi.org/10.1160/TH13-02-0159 "SchattauerThesisThesis or DissertationThrombosis and haemostasis Vol.110 No.2 p.316-32203406245http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2636Thrombosis and haemostasis, 110(2): 316-322http://hdl.handle.net/10564/2636http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2636/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2636/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2636/4/03%e6%9c%ac%e6%96%87.pdf03406245AA00863137Thrombosis and haemostasis11023163222013-08enghttp://www.ncbi.nlm.nih.gov/pubmed/23636463http://dx.doi.org/10.1160/TH13-02-0159ETD24601A6022013-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26372017-05-29T06:09:52Zhdl_10564_2586Reduced prefrontal hemodynamic response in pediatric obsessive-compulsive disorder as measured by near-infrared spectroscopy.Ota, ToyosakuIida, JunzoSawada, MasayukiSuehiro, YukoYamamuro, KazuhikoMatsuura, HirokiTanaka, ShoheiKishimoto, NaokoNegoro, HidekiKishimoto, ToshifumiPediatric obsessive–compulsive disorderNear-infrared spectroscopyFunctional neuroimaging studyPrefrontal hemodynamic responseRecent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. Functional neuroimaging studies of patients with obsessive–compulsive disorder (OCD) have suggested that the frontal cortex and subcortical structures may play a role in the pathophysiology of the disorder. Twelve treatment-naïve children with OCD and 12 age- and sex-matched healthy control subjects participated in the present study after giving consent. The relative concentrations of oxyhemoglobin (oxy-Hb) were measured with prefrontal probes every 0.1 s during the Stroop color-word task, using 24-channel NIRS machines. During the Stroop color-word task, the oxy-Hb changes in the OCD group were significantly smaller than those in the control group in the prefrontal cortex, especially in the frontopolar cortex. The present study suggests that children with OCD have reduced prefrontal hemodynamic response as measured by NIRS.博士(医学)・乙第1315号・平成25年7月22日Springer USThesisThesis or DissertationChild psychiatry and human development Vol.44 No.2 p.265-2770009398Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2637Child psychiatry and human development, 44(2): 265-277http://hdl.handle.net/10564/2637http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2637/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2637/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2637/4/03%e6%9c%ac%e6%96%87.pdf0009398XAA0013246XChild psychiatry and human development4422652772013-04http://www.ncbi.nlm.nih.gov/pubmed/22833309http://dx.doi.org/10.1007/s10578-012-0323-0ETD24601B13152013-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26382017-05-29T06:09:54Zhdl_10564_2586Application of susceptibility weighted imaging (SWI) for evaluation of draining veins of arteriovenous malformation: utility of magnitude images.Miyasaka, ToshiteruTaoka, ToshiakiNakagawa, HiroyukiWada, TakeshiTakayama, KatsutoshiMyochin, KaoruSakamoto, MasahikoOchi, TomokoAkashi, ToshiakiKichikawa, KimihikoSusceptibility weighted imageMagnitude imageArteriovenous malformationMagnetic resonance imagingINTRODUCTION: The current study evaluated the signal characteristics of susceptibility weighted imaging (SWI) of arteriovenous malformation (AVM), especially for draining veins. For this purpose, we identified the draining veins of the AVM on angiography and evaluated the signal on magnitude image for SWI (SWI-mag) and minimum intensity projection image (SWI-minIP).
METHODS: Subjects were 14 cases with angiographically proven AVM. SWI-mag, SWI-minIP, and time-of-flight (TOF) magnetic resonance angiography were acquired. For the draining veins of the AVM identified on angiography, we analyzed signal intensity on the images listed above, and classified it into hyperintensity (hyper), mixed intensity (mixed), hypointensity (hypo), and no visualization.
RESULTS: On the analysis of 27 angiographically proven draining veins, 19 draining veins were classified as hyper, 3 as mixed, 0 as hypo, and 6 as no visualization on SWI-mag. On TOF images, 21 draining veins were classified as hyper, 2 as mixed, 0 as hypo, and 4 as no visualization, while 6 draining veins did not show hyperintensity on TOF, and SWI-mag visualized 3 of these 6 veins as hyper.
CONCLUSION: SWI-mag depicted most draining veins of AVM as hyperintensity. We speculate that this is mainly due to the higher concentration of oxygenated hemoglobin (oxy-Hb) and inflow effect of the draining vein. SWI-mag seems to be useful in the analysis and follow-up for AVM as the signal on the image may reflect physiological status.博士(医学)・乙第1316号・平成25年7月22日Springer-VerlagThesisThesis or DissertationNeuroradiology Vol.54 No.11 p.1221-122700283940http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2638Neuroradiology, 54(11): 1221-1227http://hdl.handle.net/10564/2638http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2638/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2638/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2638/5/03%e6%9c%ac%e6%96%87.pdf00283940AA00754889Neuroradiology5411122112272012-11-01enghttp://www.ncbi.nlm.nih.gov/pubmed/22592320http://dx.doi.org/10.1007/s00234-012-1029-5ETD24601B13162013-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26392017-05-29T06:09:51Zhdl_10564_2586The application of tetanic stimulation of the unilateral tibial nerve before transcranial stimulation can augment the amplitudes of myogenic motor-evoked potentials from the muscles in the bilateral upper and lower limbs.Hayashi, HironobuKawaguchi, MasahikoYamamoto, YuriInoue, SatokiKoizumi, MunehisaUeda, YuritoTakakura, YoshinoriFuruya, Hitoshimotor evoked potentialsmonitoringtetanic stimulationnervespinal cordBACKGROUND: Recently, we reported a new technique to augment motor-evoked potentials (MEPs) under general anesthesia, posttetanic MEP (p-MEP), in which tetanic stimulation of the peripheral nerve before transcranial stimulation enlarged amplitudes of MEPs from the muscle innervated by the nerve subjected to tetanic stimulation. In the present study, we tested whether tetanic stimulation of the left tibial nerve can also augment amplitudes of MEPs from the muscles which are not innervated by the nerve subjected to tetanic stimulation.
METHODS: Thirty patients undergoing spinal surgery under propofol-fentanyl anesthesia with partial neuromuscular blockade were examined. For conventional MEP (c-MEP) recording, transcranial stimulation with train-of-five pulses was delivered to C3-4, and the compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis, abductor hallucis (AH), tibialis anterior, and soleus muscles. For p-MEP recording, tetanic stimulation (50 Hz, 50 mA of stimulus intensity) with a duration of 5 s was applied to the left tibial nerve at the ankle 1 s before transcranial stimulation. Transcranial stimulation and recording of compound muscle action potentials were performed in the same manner as c-MEP recording. Amplitudes of c-MEP and p-MEP were compared using Wilcoxon's signed rank test.
RESULTS: Amplitudes of p-MEPs from the left AH muscle innervated by the left tibial nerve with tetanic stimulation were significantly larger compared with those of c-MEPs. Amplitudes of p-MEPs from the bilateral abductor pollicis brevis and soleus muscles and right AH and tibialis anterior muscles, which were not innervated by the left tibial nerve with tetanic stimulation, were also significantly larger compared with those of c-MEPs.
CONCLUSION: In patients under propofol and fentanyl anesthesia with partial neuromuscular blockade, the application of tetanic stimulation to the left tibial nerve augmented the amplitudes of MEPs from the muscles without tetanic nerve stimulation and those with stimulation.博士(医学)・乙第1317号・平成25年7月22日Lippincott, Williams & WilkinsThesisThesis or DissertationAnesthesia and analgesia vol.107 No.1 p.215-22000032999http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2639Anesthesia and analgesia, 107(1): 215-220http://hdl.handle.net/10564/2639http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2639/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2639/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2639/3/03%e6%9c%ac%e6%96%87.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2639/4/04Figure1-3.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2639/5/05Table1.pdf00032999AA00525156Anesthesia and analgesia10712152202008-07enghttp://www.ncbi.nlm.nih.gov/pubmed/18635490http://dx.doi.org/10.1213/ane.0b013e318177082eETD24601B13172013-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26402017-05-29T06:09:53Zhdl_10564_2586Ratio of von Willebrand factor propeptide to ADAMTS13 is associated with severity of sepsis.Fukushima, HidetadaNishio, KenjiAsai, HidekiWatanabe, TomooSeki, TadahikoMatsui, HidetoSugimoto, MitsuhikoMatsumoto, MasanoriFujimura, YoshihiroOkuchi, Kazuosepsisvon Willebrand factor propeptideADAMTS13multiple organ dysfunctionVon Willebrand factor (VWF)-cleaving protease (ADAMTS13) cleaves ultralarge VWF (ULVWF) secreted from endothelium and by which is regulating its physiologic function. An imbalance between ULVWF secretion and ADAMTS13 level occurs in sepsis and may cause multiple organ dysfunction. We evaluated the association between the VWF-propeptide (VWF-pp)/ADAMTS13 ratio and disease severity in patients with severe sepsis or septic shock. In 27 patients with severe sepsis or septic shock and platelet count less than 120,000/μL, we measured plasma VWF, VWF-pp, and ADAMTS13 levels on hospital days 1, 3, 5, and 7. The VWF-pp/ADAMTS13 ratio was increased greater than 12-fold in patients with severe sepsis or septic shock on day 1 and remained markedly high on days 3, 5, and 7 compared with normal control subjects. The VWF-pp/ADAMTS13 ratio significantly correlated with Acute Physiology and Chronic Health Evaluation II score on days 1 and 5; Sepsis-related Organ Failure Assessment score on days 1, 3, and 5; maximum Sepsis-related Organ Failure Assessment score and tumor necrosis factor α level on days 1, 3, 5, and 7; and creatinine level on days 1, 5, and 7. Patients with greater than stage 1 acute kidney injury had significantly higher VWF-pp/ADAMTS13 ratio than patients without acute kidney injury. In summary, the VWF-pp/ADAMTS13 ratio was associated with disease severity in patients with severe sepsis or septic shock and may help identify patients at risk for multiple organ dysfunction by detecting severe imbalance between ULVWF secretion and ADAMTS13 level.博士(医学)・乙第1318号・平成25年7月22日Lippincott, Williams & WilkinsThesisThesis or DissertationShock Vol.39 No.5 p.409-41410732322http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2640Shock, 39(5): 409-414http://hdl.handle.net/10564/2640http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2640/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2640/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2640/4/03%e6%9c%ac%e6%96%87.pdf10732322AA11017168Shock3954094142013-05enghttp://www.ncbi.nlm.nih.gov/pubmed/23481506http://dx.doi.org/10.1097/SHK.0b013e3182908ea7ETD24601B13182013-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26682017-05-29T06:09:58Zhdl_10564_2586Longitudinal white matter changes in Alzheimer's disease: a tractography-based analysis studyアルツハイマー型認知症における白質経時変化の検討 : トラクトグラフィーを用いた研究Kitamura, SoichiroKiuchi, KuniakiTaoka, ToshiakiHashimoto, KazumichiUeda, ShotaroYasuno, FumihilkoMorikawa, MasayukiKichikawa, KimihikoKishimoto, ToshifumiAlzheimer's diseaseDementiaDiffusion tensor imagingDisease progressionTract-based analysisAlzheimer's disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.博士(医学)・甲第603号・平成25年11月27日ElsevierThesisThesis or DissertationBrain research Vol.1515 p.12-1800068993http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2668Brain research, 1515: 12-18http://hdl.handle.net/10564/2668http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2668/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2668/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2668/3/03%e6%9c%ac%e6%96%87.pdf00068993AA0057324XBrain research151512182013-06-17enghttp://www.ncbi.nlm.nih.gov/pubmed/23583480http://dx.doi.org/10.1016/j.brainres.2013.03.052ETD24601A6032013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26692017-05-29T06:09:58Zhdl_10564_2586Increased ratio of FoxP3+ regulatory T cells/CD3+ T cells in skin lesions in drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms薬剤性過敏症症候群(DIHS)の皮疹部においてCD3陽性T細胞数に対するFoxP3陽性制御性T細胞数の割合は増加しているMorito, HironoriOgawa, KoheiFukumoto, TakayaKobayashi, NobuhikoMorii, TakeshiKasai, TakahikoNonomura, AkitakaKishimoto, ToshifumiAsada, Hideo博士(医学)・甲第604号・平成25年11月27日© 2014 British Association of Dermatologists / The definitive version is available at http://onlinelibrary.wiley.com/Blackwell ScientificThesisThesis or DissertationClinical and Experimental Dermatology Vol.39 No.3 p.284–29103076938http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2669Clinical and experimental dermatology, 39(3): 284-291http://hdl.handle.net/10564/2669http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2669/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2669/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2669/6/03%e6%9c%ac%e6%96%87.pdf03076938AA00607691Clinical and experimental dermatology3932842912014enghttp://dx.doi.org/10.1111/ced.12246ETD24601A6042013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26702017-05-29T06:09:56Zhdl_10564_2586Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma口腔扁平上皮癌におけるmelanoma inhibitory activity 2 (MIA2)の腫瘍促進性Kurihara, MiyakoKirita, TadaakiSasahira, TomonoriOhmori, HitoshiMatsushima, SayakoYamamoto, KazuhikoBosserhoff, Anja KatrinKuniyasu, HirokiapoptosisVEGFintegrinMAPKThe role of melanoma inhibitory activity 2 (MIA2) was examined in human oral squamous cell carcinoma (OSCC). MIA2 expression was observed in 62 (66.7%) of 93 OSCCs and was associated with tumor expansion and nodal metastasis. MIA2 expression was inversely correlated with intratumoral infiltration of lymphocytes. MIA2 expression was found in 3 human OSCC lines. Invasion and anti-apoptotic survival were reduced by MIA2 knockdown in HSC3 cells. The number of MOLT-3 lymphocytes infiltrating the HSC3 cell layer was increased by MIA2 knockdown or MIA2 depletion by MIA2 knockdown and absorption with the antibody. In HSC3 cells, MIA2 knockdown decreased the expressions of vascular endothelial growth factor (VEGF), VEGF-C, VEGF-D. The downregulation of VEGF-C and -D was caused by inhibition of p38 and extracellular signal-regulated kinase (ERK)1/2, respectively. MIA2 was coprecipitated with integrin α4 andα5 in HSC3 cells. Integrin α4 knockdown decreased p38 phosphorylation and increased apoptosis, whereas integrin α5 knockdown decreased c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis. Inhibition of JNK decreased apoptosis in the HSC3 cells. These findings suggest that the roles of MIA2 might be based on the variety of the integrins and the subtypes of mitogen-activated protein kinase.博士(医学)・甲第605号・平成25年11月27日Nature PublishingThesisThesis or DissertationBritish journal of cancer Vol.108 No.7 p.1460-146900070920http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2670British journal of cancer, 108(7): 1460-1469http://hdl.handle.net/10564/2670http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2670/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2670/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2670/3/03%e6%9c%ac%e6%96%87.pdf00070920AA00574355British journal of cancer1087146014692013-04-16enghttp://www.ncbi.nlm.nih.gov/pubmed/23511560http://dx.doi.org/http://www.ncbi.nlm.nih.gov/pubmed/ETD24601A6052013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26712022-08-02T05:34:15Zhdl_10564_2586Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model前立腺癌マウスモデルにおけるジクロフェナク局所投与によるCOX-2発現の阻害はTRAILの増幅を介して放射線感受性を増強させるInoue, TakeshiAnai, SatoshiOnishi, SayuriMiyake, MakitoTanaka, NobumichiHirayama, AkihideFujimoto, KiyohideHirao, YoshihikoProstate cancerRadiation therapyCOX-2TRAILApoptosisTopical therapyRadiosensitizerDiclofenacRadioresistanceBACKGROUND: COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation.
METHODS: LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy) with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT).
RESULTS: LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (p<0.05).
CONCLUSIONS: These in vitro and in vivo findings suggest that conventional COX inhibitor, diclofenac enhances the effect of RT on prostate cancer cells that express COX-2. Thus, diclofenac may have potential as radiosensitizer for treatment of prostate cancer.博士(医学)・甲第606号・平成25年11月27日© 2013 Inoue et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BioMed CentralThesisThesis or DissertationBMC urology Vol.13 Article No.1 (2013 Jan)14712490http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2671BMC urology, 13: Article No.1http://hdl.handle.net/10564/2671http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2671/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2671/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2671/3/03%e6%9c%ac%e6%96%87.pdf14712490AA12035460BMC urology13Article No.12013-01-05enghttp://www.ncbi.nlm.nih.gov/pubmed/23289871http://dx.doi.org/10.1186/1471-2490-13-1ETD24601A6062013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26722017-05-29T06:09:56Zhdl_10564_2586Osteogenesis of cryopreserved osteogenic matrix cell sheets冷凍保存骨芽細胞シートの骨形成能評価Shimizu, TakamasaAkahane, ManabuUeha, TomoyukiKido, AkiraOmokawa, ShoheiKobata, YasunoriMurata, KeiichiKawate, KenjiTanaka, YasuhitoBone marrow mesenchymal stem cellsCryopreservationCell sheetHydroxyapatiteOsteogenesisTissue engineered boneCryopreservation of tissue engineered bone (TEB), whilst maintaining its osteogenic ability, is imperative for large-scale clinical application. We previously reported a novel cell transplantation method, in which bone-marrow-derived mesenchymal stem cells (BMSCs) were cultured to confluence and differentiated down the osteogenic lineage to form osteogenic matrix cell sheets (OMCS). OMCS have high alkaline phosphatase (ALP) activity and osteocalcin (OC) contents and can be easily used for producing TEB. The aim of the present study was to investigate whether TEB produced by cryopreserved OMCS maintains sufficient osteogenic potential in vivo. OMCS were prepared and divided into three groups according to storage period of cryopreservation (fresh (no cryopreservation), 4 week and 12 week cryopreservation groups). OMCS were cryopreserved by storage in freezing medium (Cell Banker 1®) at -80 °C. Cryopreserved OMCSs were rapidly thawed at room temperature and wrapped around Hydroxyapatite (HA) scaffolds prior to implantation into subcutaneous sites in rats, to determine their in vivo bone-forming capability. The constructs were harvested 4 weeks after transplantation and examined histologically and biochemically. Histological analysis of the constructs showed extensive bone formation in the HA pores with high ALP activity and OC content detected in the cryopreservation groups. The present study clearly indicates that cryopreserved/thawed OMCS are still capable of producing mineralized matrix on scaffolds, resulting in bone formation. This cryopreservation technique could be applied for hard tissue reconstruction to ease the cell preparation method prior to time of use.博士(医学)・甲第607号・平成25年11月27日Rockville / ElsevierThesisThesis or DissertationCryobiology Vol.66 No.3 p.326-33200112240http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2672Cryobiology, 66(3): 326-332http://hdl.handle.net/10564/2672http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2672/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2672/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2672/3/03%e6%9c%ac%e6%96%87.pdf00112240AA00620601Cryobiology6633263322013-06enghttp://www.ncbi.nlm.nih.gov/pubmed/23562780http://dx.doi.org/10.1016/j.cryobiol.2013.03.011ETD24601A6072013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26732022-08-02T05:57:31Zhdl_10564_2586Osteogenic matrix cell sheet transplantation enhances early tendon graft to bone tunnel healing in rabbits.骨形成細胞シートを用いた家兎移植腱骨孔間の早期治癒促進Inagaki, YusukeUematsu, KotaAkahane, ManabuMorita, YusukeOgawa, MunehiroUeha, TomoyukiShimizu, TakamasaKura, TomohikoKawate, KenjiTanaka, YasuhitoThe objective of this study was to determine whether osteogenic matrix cell sheets (OMCS) could induce bone formation around grafted tendons, thereby enhancing early stage tendon to bone tunnel healing in skeletally mature male Japanese white rabbits. First, the osteogenic potential of rabbit OMCS was evaluated. Then, the OMCS were transplanted into the interface between the grafted tendon and the bone tunnel created at the tibia. Histological assessments and biomechanical tensile testing were performed after 3 weeks. The rabbit OMCS showed high alkaline phosphatase (ALP) activity, positive staining of ALP, and osteogenic potential when transplanted subcutaneously with beta tricalcium phosphate disks. Newly formed bony walls and positive collagen type I staining were seen around the grafted tendon with OMCS transplantation, whereas such bony walls were thinner or less frequent without OMCS transplantation. Micro-computed tomography images showed significantly higher bone volume in the OMCS transplantation group. The pullout strength was significantly higher with OMCS (0.74 ± 0.23 N/mm(2)) than without OMCS (0.58 ± 0.15 N/mm(2)). These results show that OMCS enhance early tendon to bone tunnel healing. This method can be applied to cases requiring early tendon to bone tunnel healing after ligament reconstruction surgery.博士(医学)・甲第608号・平成25年11月27日Copyright © 2013 Yusuke Inagaki et al. This is an open access article distributed under the Creative Commons Attribution License(https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Hindawi Pub. Co.ThesisThesis or DissertationBioMed research international Vol.2013 Article ID:84219223146141http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2673BioMed research international, 2013: Article ID:842192http://hdl.handle.net/10564/2673http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2673/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2673/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2673/3/03%e6%9c%ac%e6%96%87.pdf23146141BioMed research international2013Article ID:8421922013enghttp://www.ncbi.nlm.nih.gov/pubmed/24106718http://dx.doi.org/10.1155/2013/842192ETD24601A6082013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26742017-06-11T23:20:26Zhdl_10564_2586Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome原発性シェーグレン症候群患者における再生因子REG(regenerating gene)に対する自己免疫の関与Yoshimoto, KiyomiFujimoto, TakashiItaya-Hironaka, AsakoMiyaoka, TomokoSakuramoto-Tsuchida, SumiyoYamauchi, AkiyoTakeda, MaikoKasai, TakahikoNakagawara, Kan-ichiNonomura, AkitakaTakasawa, ShinREG family genesREG Iα proteinanti-REG Iα autoantibodiesSjögren’s syndromeductal epithelial cellsThe regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.博士(医学)・乙第1319号・平成25年11月27日The definitive version is available at " http://dx.doi.org/10.1111/cei.12142 "Blackwell Scientific Pub.ThesisThesis or DissertationClinical and experimental immunology Vol.174 No.1 p.1-900099104http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2674Clinical and experimental immunology, 174(1): 1-9http://hdl.handle.net/10564/2674http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2674/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2674/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2674/6/03%e6%9c%ac%e6%96%87.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2674/7/04Figure_1-4.pdf00099104AA00607716Clinical and experimental immunology1741192013-10enghttp://www.ncbi.nlm.nih.gov/pubmed/23701206http://dx.doi.org/10.1111/cei.12142ETD24601B13192013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26752017-05-29T06:09:57Zhdl_10564_2586Neuroprotective effect of ceftriaxone on the penumbra in a rat venous ischemia modelラット静脈虚血モデ、ルにおけるペナンブラ領域でのセフトリアキソンの神経保護効果Inui, ToshitakaAlessandr, BeatHeimann, AxelNishimura, FumihikoFrauenknecht, KatrinSommer, ClemensKempski, Oliverceftriaxonecortical spreading depressionglutamate transporter-1penumbravenous ischemiaOBJECTIVE: Glutamate transporter-1 (GLT-1) maintains low concentrations of extracellular glutamate by removing glutamate from the extracellular space. It is controversial, however, whether upregulation of GLT-1 is neuroprotective under all ischemic/hypoxic conditions. Recently, a neuroprotective effect of preconditioning with a β-lactam antibiotic ceftriaxone (CTX) that increases expression of GLT-1 has been reported in animal models of focal ischemia. On the other hand, it is said that CTX does not play a neuroprotective role in an in vitro study. Thus, we examined the effect of CTX on ischemic injury in a rat model of two-vein occlusion (2VO). This model mimics venous ischemia during, e.g. tumor surgery, a clinical situation that is best suitable for pretreatment with CTX.
METHODS: CTX (100mg/kg, 200mg/kg per day) or vehicle (0.9% NaCl) was intraperitoneally injected into Wistar rats for 5days before venous ischemia (n=57). Then, animals were prepared for occlusion of two adjacent cortical veins (2VO) by photothrombosis with rose bengal that was followed by KCl-induced cortical spreading depression (CSD). Infarct volume was evaluated with hematoxylin and eosin (H&E) staining 2days after venous occlusion. [(3)H]MK-801, [(3)H]AMPA and [(3)H]Muscimol ligand binding were examined autoradiographically in additional two groups without 2VO (n=5/group). Animals were injected either with NaCl (vehicle) or CTX 200mg/kg for 5days in order to evaluate whether NMDA, AMPA and GABAA ligand binding densities were affected.
RESULTS: CTX pretreatment reduced infarct volume compared to vehicle pretreatment (p<0.05). The effect of CTX pretreatment was attenuated by administration of the GLT-1 inhibitor, dihydrokainate (DHK) 30min before 2VO. CTX had no effect on the number of spontaneous spreading depressions after 2VO. Analysis of quantitative receptor autoradiography showed no statistically significant difference between rats after administration with CTX compared to control rats.
CONCLUSIONS: Pretreatment with CTX has neuroprotective potential without effect on NMDA, AMPA and GABAA receptor density and spontaneous spreading depression. This effect can be abolished by GLT-1 inhibition, indicating that upregulation of GLT-1 is an important mechanism for neuroprotective action in penumbra-like conditions, e.g. if neurosurgeons plan to occlude cerebral veins during tumor surgery.博士(医学)・乙第1320号・平成25年11月27日Elsevier ScienceThesisThesis or DissertationNeuroscience Vol.242 p.1-1003064522http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2675Neuroscience, 242: 1-10http://hdl.handle.net/10564/2675http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2675/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2675/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2675/3/03%e6%9c%ac%e6%96%87.pdf03064522AA0075489XNeuroscience2421102013-07-09enghttp://www.ncbi.nlm.nih.gov/pubmed/23523747http://dx.doi.org/10.1016/j.neuroscience.2013.03.018ETD24601B13202013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26762020-09-30T04:28:59Zhdl_10564_2586Post-ischemic administration of vascular endothelial growth factor inhibitor in a rat model of cerebral venous infarction.ラット脳静脈モデルにおける血管内皮増殖因子桔抗薬の虚血後投与Miyake, HitoshiNakagawa, IchiroTakeshima, YasuhiroNishimura, FumihikoPark, Young-SuNakamura, MitsutoshiNakase, Hiroyukicerebral venous infarctionvascular endothelial growth factorantagonistbrain edemaCerebral venous ischemia can result in severe brain edema. Inhibition of vascular endothelial growth factor (VEGF) activity by a neutralizing antibody can completely block the hypoxia-induced increase in vascular permeability. VEGF, which induces angiogenesis, also acts as a vascular permeability (VP) factor. We previously showed that inhibition of VEGF attenuates VP and reduces cerebral venous infarction (CVI) in the acute stage. The present study investigated the therapeutic time window during which inhibition of VEGF can reduce CVI in a rat two-vein occlusion (2-VO) model. A 2-VO model was created by photochemically occluding two adjacent cortical veins. Male Wistar rats (n = 42) were assigned to one of four groups: Group 1 was treated with a VEGF antagonist at 24 hours after 2-VO (n = 11); Group 2 was treated with phosphate-buffered solution (PBS) at 24 hours after 2-VO (n = 11); Group 3 was treated with a VEGF antagonist at 48 hours after 2-VO (n = 10); and Group 4 was treated with PBS at 48 hours after 2-VO (n = 10). The developing ischemic infarct was evaluated histologically at 7 days after 2-VO. CVI areas were significantly smaller in Group 1 than in Groups 2, 3, and 4 (p <0.05) but were similar when comparing Groups 3 and 4. Anti-VEGF therapy was effective in reducing CVI in rats if started within 24 hours after 2-VO.博士(医学)・乙第1321号・平成25年11月27日Copyright © 日本脳神経外科学会 | The Japan Neurosurgical Society / 学会誌名(Neurologia medico-chirurgica)とJ-STAGEからの出典である日本脳神経外科学会ThesisThesis or DissertationNeurologia medico-chirurgica Vol.53 No.3 p.135-14004708105http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2676Neurologia medico-chirurgica, 53(3): 135-140http://hdl.handle.net/10564/2676http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2676/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2676/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2676/6/03%e6%9c%ac%e6%96%87.pdf04708105AN00358613Neurologia medico-chirurgica5331351402013enghttp://www.ncbi.nlm.nih.gov/pubmed/23524495http://dx.doi.org/10.2176/nmc.53.135ETD24601B13212013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26772018-12-13T06:18:54Zhdl_10564_2586ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant: Implications for selection of plasma preparations for TTP treatmentクリオ上清中の高分子VWFマルチマー非結合型ADAMTS13の存在:血栓性血小板減少性紫斑病の治療に、より効果的な血漿分画製剤の選択Hori, YujiHayakawa, MasakiIsonishi, AyamiSoejima, KenjiMatsumoto, MasanoriFujimura, YoshihiroIEFVWF-ADAMTS13 complexVWFADAMTS13BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is characterized by deficient ADAMTS13 activity. Treatment involves plasma exchange (PE). Both fresh-frozen plasma (FFP) and cryosupernatant (CSP) are used, but it remains to be determined which is more effective.
STUDY DESIGN AND METHODS: To analyze the interaction between von Willebrand factor (VWF) and ADAMTS13, we used large-pore isoelectric focusing (IEF) analysis followed by detection with anti-ADAMTS13 monoclonal antibody. FFP, CSP, cryoprecipitate (CP), and purified ADAMTS13 were analyzed for their effects on high shear stress-induced platelet aggregation (H-SIPA).
RESULTS: IEF analysis of normal plasma revealed three groups of ADAMTS13 bands with pI of 4.9 to 5.6, 5.8 to 6.7, and 7.0 or 7.5. Two band groups (pI 4.9-5.6 and 5.8-6.7) were found in plasma of a patient with Type 3 von Willebrand disease, in which VWF is absent, whereas no bands were found in plasma of a patient with congenital ADAMTS13 deficiency. Mixing these plasmas generated the bands at pI 7.0 or 7.5, representing the VWF-ADAMTS13 complex; these bands were absent in CSP. FFP and purified ADAMTS13 down regulated H-SIPA in a dose-dependent manner. However, CP did not inhibit H-SIPA in the initial phase, and the degree of inhibition at the endpoint was almost indistinguishable from those of the other two plasma products.
CONCLUSION: Both plasma products (FFP and CSP) are effective for PE in TTP patients. However, CSP may be more favorable, because it has lower levels of VWF and almost normal ADAMTS13 activity, but lower levels of ADAMTS13 in complex with larger VWF multimers.博士(医学)・乙第1322号・平成25年11月27日© 2013 American Association of Blood BanksCopyright © 1999-2018 John Wiley & Sons, Inc. All rights reservedThis is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/trf.12182], which has been published in final form at [http://dx.doi.org/10.1111/trf.12182]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Blackwell PublishingThesisThesis or DissertationTransfusion Vol.53 No.12 p.3192–320200411132http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2677Transfusion, 53(12): 3192-3202http://hdl.handle.net/10564/2677http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2677/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2677/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2677/6/03%e6%9c%ac%e6%96%87.pdf00411132AA00868753Transfusion5312319232022013-12enghttp://www.ncbi.nlm.nih.gov/pubmed/23560518http://dx.doi.org/10.1111/trf.12182ETD24601B13222013-11-27博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26882022-08-02T06:09:33Zhdl_10564_2586Health-related Quality of Life (HRQOL) Decreases Independently of Chronic Conditions and Geriatric Syndromes in Older Adults With Diabetes: The Fujiwara-kyo Study.糖尿病罹患高齢者の健康関連QOL は合併する慢性疾患や老年症候群と独立している 藤原京スタディNezu, SatokoOkamoto, NozomiMorikawa, MasayukiSaeki, KeigoObayashi, KenjiTomioka, KimikoKomatsu, MasayoIwamoto, JunkoKurumatani, Noriodiabetesolder adultsgeriatric syndromeschronic conditionsSF-36Background: Very few studies have investigated the association between diabetes and impaired health-related quality of life (HRQOL) in older adults, independent of chronic conditions and geriatric syndromes.
Methods: We conducted a self-administered questionnaire survey and structured interviews with 3946 people aged 65 years or older to obtain medical histories of diabetes, chronic conditions, and geriatric syndromes. Blood tests were performed to measure glycated hemoglobin (HbA1c) and plasma glucose levels. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), and multiple logistic regression analysis was used to calculate adjusted odds ratios and 95% CIs for low HRQOL.
Results: A total of 3521 participants had not received a physician diagnosis of diabetes. Of these, 2345 participants with an HbA1c less than 5.7% were defined as the referent group. As compared with the referent group, 1029 participants with an HbA1c of at least 5.7% but less than 6.5% showed no significant decrease in QOL on the SF-36 physical, mental, and role component summaries, after adjustment for chronic conditions, geriatric syndromes, and other potential confounders. However, 572 patients who had received a physician diagnosis of diabetes and/or had an HbA1c of 6.5% or higher had a significantly higher adjusted odds ratio (1.48; 95% CI, 1.18–1.84) for the low physical component summary. No significant differences in relation to glycemic control, treatment regimen, or diabetes duration were found in any of the 3 component summaries among the 425 participants who were undergoing diabetes treatment.
Conclusions: Older Japanese adults with diabetes had decreased physical QOL, independent of chronic conditions and geriatric syndromes.博士(医学)・甲第609号・平成26年3月17日Copyright © 2014 Satoko Nezu et al. This is an open access article distributed under the terms of Creative Commons Attribution License(https://creativecommons.org/licenses/by/3.0/), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.日本疫学会ThesisThesis or DissertationJournal of epidemiology Vol.24 No.4 p.259-266 (2014)09175040http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2688Journal of epidemiology, 24(4): JE20130084-266http://hdl.handle.net/10564/2688http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2688/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2688/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2688/11/03%e6%9c%ac%e6%96%87.pdf09175040AA10952696Journal of epidemiology244JE201300842592662014-05-10http://www.ncbi.nlm.nih.gov/pubmed/24814506http://dx.doi.org/10.2188/jea.JE20130131ETD24601A6092014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26892017-05-29T06:07:04Zhdl_10564_2586Neurocognitive functioning in patients with first-episode schizophrenia 1 year from onset in comparison with patients 5 years from onset.統合失調症初発エピソードの認知機能障害の経過と発症5 年経過群との比較Matsuda, YasuhiroSato, SayakaHatsuse, NorifumiWatanabe, YukakoKishimoto, ToshifumiIkebuchi, EmiSchizophreniafirst-episodeneurocognitive functioningprospective studysocial functioningOBJECTIVE: The course of neurocognitive deficits in schizophrenia has not yet been established. Therefore, we followed patients with first-episode schizophrenia to verify the course of these deficits.
METHODS:In Study 1, tests of neurocognitive functioning were administered to patients with first-episode schizophrenia (FE group) every 6 months. Of the 26 patients who completed the baseline assessment, 19 completed a 6-month follow-up, and 13 completed a 1-year follow-up. In Study 2, 19 patients in FE group at 6-months when the neuropsychological measures was less influenced by psychotic symptoms and other patients who experienced schizophrenia 5-years earlier (5-year group) were compared.
RESULTS:In Study 1, verbal memory, motor speed, and executive functions significantly improved at the 1-year follow-up. In Study 2, patients in 5-year group performed worse in verbal memory and executive functions than patients in FE at 6-month group, but marginally but significantly better in verbal fluency.
CONCLUSIONS:Verbal memory, executive functions, and verbal fluency were significantly different between 5-year group and FE at 6-month group, and may indicate progression of schizophrenia. Executive functions may reflect the state of psychosis. Working memory and processing speed which did not change significantly from onset are needed to verify the course in further research.博士(医学)・甲610号・平成26年3月17日Informa HealthcareThesisThesis or DissertationInternational journal of psychiatry in clinical practice Vol.18 No.1 p.63-6913651501http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2689International journal of psychiatry in clinical practice, 18(1): 63-69http://hdl.handle.net/10564/2689http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2689/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2689/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2689/6/03%e6%9c%ac%e6%96%87.pdf13651501AA11853816International journal of psychiatry in clinical practice18163692014-01enghttp://www.ncbi.nlm.nih.gov/pubmed/24047425http://dx.doi.org/10.3109/13651501.2013.845220ETD24601A6102014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26902017-05-29T06:07:03Zhdl_10564_2586A New Quantitative Multi-parameter Method Improves the Accuracy of Age Estimation from Oral Findings.口腔内所見を用いた新たな年齢推定法Kawashima, WataruHatake, KatsuhikoMorimura, YoshifumiKudo, RisaNakanishi, MariTamaki, ShigehiroKasuda, ShogoYuui, KatsuyaIshitani, AkikoAge estimationDental parametersForensic scienceMacroscopic examinationOral findingsIn forensic science, age estimation is an important step in identifying unidentified cadavers. As teeth are resistant to environmental degradation for long periods of time, they are often used to estimate age. Although there have been many reports of age estimation based on dental morphology, these methods tend to be subjective and cannot be used i n the case of edentulous jaws. In the present study, we developed a new method of age estimation from dental parameters (number of upper teeth [UT], lower teeth [LT], and prostheses [NP]; tooth attrition [TA]; and occlusal area [OA]) and the mandibular angle (MA) measured at proposed an equation for calculating the age. The results show that the mean error of this method is similar to that of previous methods, and even demonstrated improved accuracy in subjects aged >60 years. We also proposed an equation for age estimation from only the MA, and showed that we can perform age estimation even in edentulous cases using this equation. Because our method is superior in its simplicity, objectivity, and applicability when compared with previous methods, we believe our method wll prove useful for age estimation in a wide variety of cases.博士(医学)・甲611号・平成26年3月17日法医学談話会(東北大学大学院医学系研究科社会医学講座法医学分野内)ThesisThesis or Dissertation法医学の実際と研究 56号 p.211-21802890755http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2690法医学の実際と研究(56): 211-218http://hdl.handle.net/10564/2690http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2690/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2690/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2690/3/03%e6%9c%ac%e6%96%87.pdf02890755AN00223931法医学の実際と研究562112182013-11ETD24601A6112014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26912017-05-29T06:07:12Zhdl_10564_2586hdl_10564_2692Hypoxia-Induced Long-Term Potentiation in the Vestibular Nucleus.前庭神経核における低酸素性長期増強Okamoto, HideyukiYamanaka, ToshiakiHosoi, Hiroshivestibular nucleushypoxiaglutamateelectrophysiological techniquelong-term potentiationTransient ischemia due to a decrease in vertebrobasilar insufficiency (VBI) induces the hypoxia of vestibular nucleus (VN) and frequently cause vertigo. Furthermore, it is occasionally experienced that dizziness continues in the long term after strong rotatory vertigo in VBI. Since glutamate is thought to play an important role in the neurotransmission of VN, this study was undertaken to examine the effect of hypoxia on the VN neuron and the role of the glutamate in the hypoxia induced neuronal activities using electrophysiological and microiontophoretic technique. Cats anesthetized with α-chloralose were ventilated with a respirator. A silver recording microelectrode was inserted into the VN and the spontaneous firing of the neurons was continuously recorded on an ink-writing recorder through a spike counter. Micropipettes attached along the microelectrode were used for microiontophoretic application of 6,7-Dinitroquinoxaline-2,3-dione (DNQX), non-NMDA receptor antagonist and (+) 5-methyl-l0,l1-dihydro-5H-dibenzo(a,d) cyclohepten- 5,10-imine (MK801), NMDA receptor antagonist. The spontaneous firing in VN neurons increased transiently and then decreased, resulting in the disappearance in firings during 3 minutes inhalation of 5%O2. However, the firings appeared again and persistently increased after the cessation of 5%O2. Transient increase of the firing during hypoxia and persistent increase after the cessation of hypoxia were herein termed Hypoxic Depolarization (HD) and Post Hypoxic Potentiation (PHP), respectively. HD was significantly (P<0.01) suppressed by DNQX and MK801. Since HD was suppressed by glutamate receptor antagonist, HD was assumed to be caused by excessive glutamate released from presynaptic terminals in the VN neurons. HD correlated significantly with PHP (R=0.609, p<0.01). We indicate that enhancement of PHP was the change of glutamate receptor-mediated synaptic plasticity caused by HD in the VN neurons. In conclusion, it is suggested that HD and PHP shown in this electrophysiological study might imply possible mechanism underlying the onset of acute vertigo and persistent dizziness in VBI.博士(医学)・乙1332号・平成26年3月17日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.64 No.4 p.49-5613450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2691Journal of Nara Medical Association, 64(4): 49-56http://hdl.handle.net/10564/2691http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2691/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2691/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2691/3/03%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association64449562013-11-30engETD24601B13322014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26942017-05-29T06:07:03Zhdl_10564_2586hdl_10564_2692Auditory habituation is revented in the background sound of 4-kHz pure tone : A magnetoencephalography study.聴覚順応は、4kHz純音の背景音により阻止される : 脳磁図研究Koizumi, ToshizoNishimura, TadashiNakagawa, SeijiHosoi, Hiroshiauditory attention, , magnetoencephalographyauditory evoked magnetic fieldN1mAuditory evoked magnetic field (AEF) is gradually attenuated as the number of presentation of auditory stimuli increases. The attenuation of AEF is auditory habituation, and is prevented in the condition where a noise exists in the background. In this study, we investigated whether the background sound of pure tone prevent the auditory habituation to repeating stimuli. Subjects were 17 normal hearing individuals. Auditory stimuli were 1-kHz tone bursts set at 30 dB SL with durations of 100 ms and inter-stimulus intervals of 1.9-2.l s. The background sounds were silent, 4-kHz pure tone presented set at 5 and 20 dB SL which were presented with 1-kHz tone bursts. N1m component of AEF induced by auditory stimuli was measured using 122-channel neuromagnetometer. As a result, N1m amplitudes induced by repeating auditory stimuli were gradually attenuated in the condition of silent background due to the auditory habituation. Meanwhile, the attenuation of N1m amplitude was small in the conditions of background sounds of 4-kHz pure tones at 5 and 20 dB SL, compared to the conditions of silent background. Moreover, the time course of N1m amplitudes was not different between the condition of background sound at 5 and 20 dB SL. These results suggested that the background sound of pure tone, independent of its intensity, drove the subject to unconsciously pay attention to repeating auditory stimuli without disturbing signal-to-noise ratio of them, or the neural process of the background pure tone continuously activated the auditory pathway and resulted in the prevention of auditory habituation.博士(医学)・乙1333号・平成26年3月17日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.64 No.4 p.57-6413450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2694Journal of Nara Medical Association, 64(4): 57-64http://hdl.handle.net/10564/2694http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2694/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2694/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2694/3/03%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association64457642013-11-30engETD24601B13332014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26952017-05-29T06:07:11Zhdl_10564_2586hdl_10564_2692Abnormal distribution of aquaporin-5 and lymphoid infiltration in salivary glands of primary sjögren's syndrome.原発性シェーグレン症候群の唾液腺におけるリンパ球浸潤とアクアポリン5の分布異常についてKobayashi, TakehikoFujimoto, TakashiYane, KatsunariHosoi, Hiroshiaquaporin-5salivary glandSjögren's syndromexerostomiaObjectives: Patients with Sjögren's syndrome (SS) suffer from impaired saliva secretion due to an autoimmune destruction of salivary glands. Based upon its abnormal distribution in SS salivary glands, a potential role for the water channel protein aquaporin-5 (AQP5) is proposed in the pathogenesis of SS. Methods: The immunohistochemical distribution of AQP5 was compared in minor salivary gland (MSG) biopsies obtained from primary SS with a variety of lymphoid cells infiltration in MSG, and healthy volunteers. Results: Biopsies from normal subjects revealed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, biopsies from SS patients with both moderate and severe lymphoid infiltration revealed AQP5 expression diffusely at the cytoplasm of the acinus. Computer-assisted microscopy was performed to quantitatively evaluate AQP5 distribution in the acini. Biopsies of SS patients exhibited lower labeling indices (LI) at the apical membrane compared with biopsies from control subjects. The LI of the acini obtained from SS patients with both moderate and severe lymphoid infiltration showed no difference. Conclusions: Abnormal distribution of AQP5 in salivary gland acini could be responsible for a loss of saliva secretion, and this abnormal distribution is likely to develop during the stage of moderate lymphoid infiltration in salivary gland.博士(医学)・乙1334号・平成26年3月17日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.64 No.4 p.65-7213450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2695Journal of Nara Medical Association, 64(4): 65-72http://hdl.handle.net/10564/2695http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2695/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2695/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2695/3/03%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association64465722013-11-30engETD24601B13342014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26962017-05-29T06:07:03Zhdl_10564_2586hdl_10564_2692Left-right difference in high frequency sensitivity : application for unilateral cochlear disorder evaluation.高周波聴力の左右差 : 一側性の蝸牛障害の評価への応用Uratani, YukaNishimura, TadashiOhara, NariYamanaka, ToshiakiHosoi, Hiroshihigh frequency audiometryhigh frequency soundtinnitusHigh-frequency audiometry has the potential to detect hearing impairment at its early stage. However, several problems prevent the clinical application of high-frequency audiometry. In this study, the dispersion and left-right difference in the high-frequency sensitivity were investigated in normal hearing volunteers. In our results, the difference between the left and right ears varied only slightly among individuals or age groups, while dispersion of hearing threshold values became marked with an increase in frequency. The results suggest that the measurement of left-right difference in high-frequency sensitivity may be useful for the evaluation of unilateral impairment. To investigate this usefulness, the left-right differences were measured in the patients complaining of unilateral cochlear symptom with normal hearing. Considering the results of normal hearing, we determined that abnormal left-right difference in high-frequency sensitivity was over 20 dB. In 12 patients with unilateral tinnitus, 7 showed left-right differences, and 6 had tinnitus in the ear with increased thresholds. Our results suggested a relationship between tinnitus with normal hearing and hearing impairment in the high-frequency range.博士(医学)・乙1335号・平成26年3月17日奈良医学会奈良県立医科大学ThesisThesis or DissertationJournal of Nara Medical Association Vol.64 No.4 p.73-7813450069http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2696Journal of Nara Medical Association, 64(4): 73-78http://hdl.handle.net/10564/2696http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2696/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2696/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2696/3/03%e6%9c%ac%e6%96%87.pdf13450069AA11252383Journal of Nara Medical Association64473782013-11-30engETD24601B13352014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26972017-05-29T06:07:12Zhdl_10564_2586Direct renin inhibitor, aliskiren, attenuates the progression of non-alcoholic steatohepatitis in the rat model.直接的レニン阻害薬であるアリスキレンはラットモデルにおいて非アルコール性脂肪肝炎の進行を抑制するAihara, YosukeYoshiji, HitoshiNoguchi, RyuichiKaji, KosukeNamisaki, TadashiShirai, YusakuDouhara, AkitoshiMoriya, KeiKawaratani, HidetoFukui, Hiroshiangiotensin-IIhepatocarcinogenesisliver fibrosisnon-alcoholicsteatohepatitisreninAIM: Renin is a rate-limiting enzyme of the renin-angiotensin system (RAS), and
several reports have shown that renin plays an important role in several
pathological processes. Although RAS is known to play a pivotal role in the
progression of non-alcoholic steatohepatitis (NASH), the role of renin is still
obscure. The aim of the current study was to examine the effect of the clinically
used direct renin inhibitor (DRI), aliskiren, on the progression of NASH in a rat
model.
METHODS: The effects of DRI on the choline-deficient L-amino acid-defined (CDAA)
diet-induced rat NASH model was examined in conjunction with the activated
hepatic stellate cells (Ac-HSC) and neovascularization, both of which are known
to play important roles in liver fibrosis development and hepatocarcinogenesis,
respectively.
RESULTS: DRI exerted a marked inhibitory effect against liver fibrosis
development and glutathione-S-transferase placental form (GST-P) positive
preneoplastic lesions along with suppression of the Ac-HSC and neovascularization
in a dose-dependent manner. DRI also inhibited the hepatic expressions of
transforming growth factor-beta 1 (TGF-beta 1), angiotensin-II (AT-II) and
vascular endothelial growth factor (VEGF). These results indicated that renin
played a pivotal role in the liver fibrosis development and hepatocarcinogenesis
of NASH.
CONCLUSION: Because DRI is already widely used in the clinical practice with
safety, this drug may represent a potential new strategy against the progression
of NASH in the future.博士(医学)・甲612号・平成26年3月17日Wiley / The Japan Society of HepatologyThesisThesis or DissertationHepatology research Vol.43 No.11 p.1241-125013866346http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2697Hepatology research, 43(11): 1241-1250http://hdl.handle.net/10564/2697http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2697/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2697/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2697/6/03%e6%9c%ac%e6%96%87.pdf13866346AA11140867Hepatology research4311124112502013-11enghttp://www.ncbi.nlm.nih.gov/pubmed/23448275http://dx.doi.org/10.1111/hepr.12081ETD24601A6122014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26982017-05-29T06:07:13Zhdl_10564_2586ADAMTS13 activity may predict the cumulative survival of patients with liver cirrhosis in comparison with the Child-Turcotte-Pugh score and the Model for End-Stage Liver Disease score.血漿ADAMTSは肝硬変患者の予後をChild-PughスコアやMELDスコアと同様に生存率を予測できる可能性があるTakaya, HiroakiUemura, MasahitoFujimura, YoshihiroMatsumoto, MasanoriMatsuyama, TomomiKato, SeijiMorioka, ChieIshizashi, HiromichiHori, YujiFujimoto, MasaoTsujimoto, TatsuhiroKawaratani, HidetoToyohara, MasahisaKurumatani, NorioFukui, HiroshiADAMTS13 activityChild-Turcotte-Pugh scoreliver cirrhosisModel for End-Stage Liver Disease scoreprognosisAim: Decreased plasma ADAMTS13 activity (ADAMTS13:AC) results in accumulation of unusually large von Willebrand factor multimers and platelet thrombi formation. Our aim was to evaluate whether ADAMTS13:AC is a prognostic marker in patients with liver cirrhosis. Methods: Plasma ADAMTS13:AC and its related parameters were examined in 108 cirrhotic patients. Results: ADAMTS13:AC decreased as the severity of liver disease increased (means: controls 100%, Child A-cirrhotics 79%, Child B-cirrhotics 63%, and Child C-cirrhotics 31%). ADAMTS13:AC markedly decreased in the cirrhotics with hepatorenal syndrome, refractory ascites and hepatic encephalopathy. The cumulative survival time was the shortest (median: 4.5 months) in the cirrhotics with severe to moderate ADAMTS13:AC deficiency (<3-25%), followed by those with mild ADAMTS13:AC deficiency (25-50%), and was the longest in those with normal activity (>50%). In contrast, based on the Child-Turcotte-Pugh (CTP) score, Child C-cirrhotics had the worst survival, but the survival probabilities did not differ between Child A and B cirrhotics. Based on the Model for End-Stage Liver Disease (MELD) score, the survival was the worst for the cirrhotics in the fourth quartile, but it was not different among cirrhotics in the first three quartiles. Cox proportional-hazards regression analysis showed that ADAMTS13:AC and serum albumin were independent factors affecting the survival. Conclusions: ADAMTS13:AC concomitantly decreases as the functional liver capacity decreases. This activity may be a useful prognostic marker that is equal or superior to the CTP score and the MELD score to predict not only the short-term prognosis but also the long-term survival of the cirrhotic patients.博士(医学)・甲613号・平成26年3月17日Wiley / The Japan Society of HepatologyThesisThesis or DissertationHepatology research Vol.42 No.5 p.459-47213866346http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2698Hepatology research, 42(5): 459-472http://hdl.handle.net/10564/2698http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2698/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2698/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2698/3/03%e6%9c%ac%e6%96%87.pdf13866346AA11140867Hepatology research4254594722012-05enghttp://www.ncbi.nlm.nih.gov/pubmed/22292786http://dx.doi.org/10.1111/j.1872-034X.2011.00950.xETD24601A6132014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/26992017-05-29T06:07:12Zhdl_10564_2586Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease.慢性腎臓病では血中可溶型fms様チロシンキナーゼ-1産生の減少が動脈硬化症を悪化させるMatsui, MasaruTakeda, YukijiUemura, ShiroMatsumoto, TakakiSeno, AyakoOnoue, KenjiTsushima, HideoMorimoto, KatsuhikoSoeda, TsunenariOkayama, SatoshiSomekawa, SatoshiSamejima, Ken-ichiKawata, HiroyukiKawakami, RikaNakatani, KimihikoIwano, MasayukiSaito, Yoshihikoatherosclerosischronic kidney diseaseplacental growth factorsoluble fms-liketyrosine kinase-1Patients with chronic kidney disease (CKD) die of cardiovascular diseases for unknown reasons. Blood vessel formation in plaques and its relationship with plaque stability could be involved with signaling through the Flt-1 receptor and its ligands, vascular endothelial growth factor, and the closely related placental growth factor (PlGF). Flt-1 also exists as a circulating regulatory splice variant short-inhibitory form (sFlt-1) that serves as a decoy receptor, thereby inactivating PlGF. Heparin releases sFlt-1 by displacing the sFlt-1 heparin-binding site from heparin sulfate proteoglycans. Heparin could provide diagnostic inference or could also induce an antiangiogenic state. In the present study, postheparin sFlt-1 levels were lower in CKD patients than in control subjects. More importantly, sFlt-1 levels were inversely related to atherosclerosis in CKD patients, and this correlation was more robust after heparin injection, as verified by subsequent cardiovascular events. Knockout of apolipoprotein E (ApoE) and/or sFlt-1 showed that the absence of sFlt-1 worsened atherogenesis in ApoE-deficient mice. Thus, the relationship between atherosclerosis and PlGF signaling, as regulated by sFlt-1, underscores the underappreciated role of heparin in sFlt-1 release. These clinical and experimental data suggest that novel avenues into CKD-dependent atherosclerosis and its detection are warranted.博士(医学)・甲614号・平成26年3月17日Nature PublishingThesisThesis or DissertationKidney international Vol.85 No.2 p.393-40300852538http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2699Kidney international, 85(2): 393-403http://hdl.handle.net/10564/2699http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2699/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2699/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2699/6/03%e6%9c%ac%e6%96%87.pdf00852538AA00710996Kidney international8523934032014-02enghttp://www.ncbi.nlm.nih.gov/pubmed/24048373http://dx.doi.org/10.1038/ki.2013.339ETD24601A6142014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27002017-05-29T06:07:11Zhdl_10564_2586An elevated ratio of placental growth factor to soluble fms-like tyrosine kinase-1 predicts adverse outcomes in patients with stable coronary artery disease.胎盤増殖因子の可溶性Fms様チロシンキナーゼ-1に対する血中濃度比の上昇は安定冠動脈疾患患者における有害事象発症の予測因子であるMatsumoto, TakakiUemura, ShiroTakeda, YukijiMatsui, MasaruOkada, SadanoriNishida, TakuSoeda, TsunenariOkayama, SatoshiSomekawa, SatoshiIshigami, Ken-ichiOnoue, KenjiKawata, HiroyukiKawakami, RikaHorii, ManabuSaito, Yoshihikostable coronary artery diseaseprognosisbiomarkerplacental growth factorsoluble Flt-1OBJECTIVE:
To investigate the predictive values of placental growth factor (PlGF) and its endogenous antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1), for the long-term prognosis of patients with stable coronary artery disease (CAD). Both PlGF and sFlt-1 play important roles in the pathological mechanisms of atherosclerosis. We recently demonstrated that the plasma levels of these molecules are correlated with the severity of coronary atherosclerosis.
METHODS:
We enrolled 464 patients with stable CAD who consecutively underwent coronary angiography. Baseline blood samples were collected from the femoral artery immediately before coronary angiography (after the administration of 20 units of heparin), and the plasma levels of PlGF and sFlt-1 were measured. A Cox proportional hazard regression analysis was performed to evaluate the relationship between these parameters and the occurrence of all-cause death (ACD) and total cardiovascular events (TCVE) during a median follow-up of 3.3 years.
RESULTS:
A total of 31 ACDs and 51 TCVEs occurred. Patients with higher PlGF/sFlt-1 ratios (>4.22×10(-2)) had a significantly higher risk of both ACD and TCVE than patients with lower ratios (<4.22×10(-2)) (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.43 to 7.72, p=0.005, and HR: 2.23, 95% CI: 1.23 to 4.03, p=0.008, respectively). A multivariate analysis showed the PlGF/sFlt-1 ratio to be an independent predictor for ACD, but not TCVE.博士(医学)・甲615号・平成26年3月17日発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.2169/internalmedicine.52.9073"Japanese Society of Internal MedicineThesisThesis or DissertationInternal medicine Vol.52 No.10 p.1019-102709182918http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2700Internal medicine, 52(10): 1019-1027http://hdl.handle.net/10564/2700http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2700/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2700/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf09182918AA10827774Internal medicine5210101910272013enghttp://www.ncbi.nlm.nih.gov/pubmed/23676585http://dx.doi.org/10.2169/internalmedicine.52.9073none24601A6152014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27012017-05-29T06:06:51Zhdl_10564_2586Comparison of effects of a selective 5-HT reuptake inhibitor versus a 5-HT4 receptor agonist on in vivo neurogenesis at the rectal anastomosis in rats.選択的セロトニン再取り込み阻害薬とセロトニン4受容体作動薬の直腸吻合部におけるインビボ神経再建に与える効果の比較Kawahara, IsaoKuniyasu, HirokiMatsuyoshi, HirokoGoto, KeiObata, KojiMisawa, HiromiFujii, HisaoTakaki, Miyakoselective serotonin reuptake inhibitorneural stem cellserotonin-4 receptorenteric nervous systemIt was recently reported that activation of enteric neural 5-HT(4) receptors (SR4) promotes reconstruction of enteric neural circuit injury in distal gut of guinea pigs and that this reconstruction involves neural stem cells. We aimed to explore a novel approach using a selective serotonin reuptake inhibitor (SSRI), which increases endogenous 5-HT, to repair enteric nerve fiber injury in the rat distal gut. Enteric nerve fiber injury was performed by rectal transection and subsequent end-to-end one-layer anastomosis. The SSRI fluvoxamine maleate (100 μmol/l) was applied locally at the anastomotic site to compare with the 5-HT(4) agonist mosapride citrate (100 μmol/l) (applied for patent) applied locally and orally. Unlike mosapride, fluvoxamine failed to promote the regeneration of the nerve fiber tract across the anastomosis. Furthermore, fluvoxamine did not generate anti-distal-less homeobox 2 (DLX2)- and anti-SR4-positive cells (neural stem cells) and/or anti-neurofilament (NF)-positive cells (neural cells) in newly formed granulation tissue at the anastomosis, whereas these cell types were observed in mosapride-treated preparations. In contrast to its effects in guinea pigs, mosapride generated 5-bromo-2'-deoxyuridine (BrdU)-positive neural cells in ganglia sites 3 mm oral and anal from the anastomosis 2 wk after nerve fiber injury. All actions of mosapride were observed after local and or oral applications. These findings indicate that local SSRI treatment does not induce in vivo nerve fiber tract growth across the anastomosis in the rat distal gut. Mosapride induces nerve fiber tract growth across the anastomosis, mediated through enteric neural stem cells possibly from neural crest-derived stem cells or mesenchymal stem cells in the bone marrow.博士(医学)・甲616号・平成26年3月17日発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.1152/ajpgi.00284.2011"American Physiological SocietyThesisThesis or DissertationAmerican journal of physiology. Gastrointestinal and liver physiology Vol.302 No.6 p.G588-59701931857http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2701American journal of physiology. Gastrointestinal and liver physiology, 302(6): G588-G597http://hdl.handle.net/10564/2701http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2701/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2701/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf01931857AA00066478American journal of physiology. Gastrointestinal and liver physiology3026G588G5972012-03-15enghttp://www.ncbi.nlm.nih.gov/pubmed/22194416http://dx.doi.org/10.1152/ajpgi.00284.2011none24601A6162014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27022017-05-29T06:07:27Zhdl_10564_2586A new calpain inhibitor protects left ventricular dysfunction induced by mild ischemia-reperfusion in in situ rat hearts.新しいカルパイン阻害剤はラット生体位心における緩和な虚血再灌流による左心室機能障害を保護するTakeshita, DaisukeTanaka, MidoriMitsuyama, ShinichiYoshikawa, YoshirouZhang, Guo-XingObata, KojiIto, HaruoTaniguchi, ShigekiTakaki, MiyakoMild ischemic-reperfusion injuryCardioprotectionα-FodrinSNJ-1945We have previously indicated that a new soluble calpain inhibitor, SNJ-1945 (SNJ), attenuates cardiac dysfunction after cardioplegia arrest-reperfusion by inhibiting the proteolysis of α-fodrin in in vitro study. Nevertheless, the in vivo study design is indispensable to explore realistic therapeutic approaches for clinical use. The aim of the present in situ study was to investigate whether SNJ attenuated left ventricular (LV) dysfunction (stunning) after mild ischemic-reperfusion (mI-R) in rat hearts. SNJ (60 μmol/l, 5 ml i.p.) was injected 30 min before gradual and partial coronary occlusion at proximal left anterior descending artery. To investigate LV function, we obtained curvilinear end-systolic pressure–volume relationship by increasing afterload 60 min after reperfusion. In the mI-R group, specific LV functional indices at midrange LV volume (mLVV), end-systolic pressure (ESPmLVV), and pressure–volume area (PVAmLVV: a total mechanical energy per beat, linearly related to oxygen consumption) significantly decreased, but SNJ reversed these decreases to time control level. Furthermore, SNJ prevented the α-fodrin degradation and attenuated degradation of Ca2+ handling proteins after mI-R. Our results indicate that improvements in LV function following mI-R injury are associated with inhibition of the proteolysis of α-fodrin in in situ rat hearts. In conclusion, SNJ should be a promising tool to protect the heart from the stunning.博士(医学)・甲617号・平成26年3月17日Springer Japan / Physiological Society of JapanThesisThesis or DissertationThe journal of physiological sciences Vol.63 No.2 p.113-12318806546http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2702The journal of physiological sciences, 63(2): 113-123http://hdl.handle.net/10564/2702http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2702/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2702/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2702/3/03%e6%9c%ac%e6%96%87.pdf18806546AA12129145The journal of physiological sciences6321131232013-03enghttp://www.ncbi.nlm.nih.gov/pubmed/23242912http://dx.doi.org/10.1007/s12576-012-0243-6ETD24601A6172014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27032017-05-29T06:08:29Zhdl_10564_2586NHE-1 blockade reversed changes in calcium transient in myocardial slices from isoproterenol-induced hypertrophied rat left ventricle.イソプロテレノール誘導肥大心においてNHE-1阻害薬は、ラット左心室の筋スライスのCa2+トランジェントを正常化するHattori, HiroshiTakeshita, DaisukeTakeuchi, AyakoKim, BongjuShibata, MunetakaMatsuoka, SatoshiObata, KojiMitsuyama, ShinichiZhang, Guo-XingTakaki, MiyakoCalcium transientCardiac hypertrophyExcitation–contraction couplingMyocardial sliceNa+/H+ exchanger-1We previously reported that left ventricular (LV) slices from isoproterenol (ISO)-induced hypertrophied rat hearts showed an increase of energy expenditure due to remodeling of Ca2+ handling in excitation–contraction coupling, i.e., suppressed SERCA2a activity and enhanced Na+/Ca2+exchanger-1 (NCX-1) activity. Na+/H+ exchanger-1 (NHE-1) inhibitor (NHEI) has been demonstrated to exert beneficial effects in the development of cardiac remodeling. We hypothesized that a novel NHE-1 selective inhibitor, BIIB723 prevents remodeling of Ca2+ handling in LV slices of ISO-induced hypertrophied rat hearts mediated by inhibiting NCX-1 activity. The significant shortening in duration of multi-cellular Ca2+ transient in ISO group was normalized in ISO + BIIB723 group. The significant increase in amplitude of multi-cellular Ca2+ waves (CaW) generated at high [Ca2+]o of LV slices in ISO group was also normalized in ISO + BIIB723 group. However, the enhanced NCX-1 activity was not antagonized by BIIB723. We recently reported that ISO-induced down-regulation of a Ca2+ handling protein, SERCA2a, was normalized by BIIB723. Therefore, it seems likely that BIIB723 normalized shortened multi-cellular Ca2+ transient duration and increased CaW amplitude in LV slices mediated via normalization of SERCA2a activity. Furthermore, the results presented here suggest the multi-cellular Ca2+ transient duration and CaW amplitude in LV slices might be better indices reflecting SERCA2a activity than SERCA2a protein expression level.博士(医学)・甲618号・平成26年3月17日Academic Press / ElsevierThesisThesis or DissertationBiochemical and biophysical research communications Vol.419 No.2 p.431-4350006291Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2703Biochemical and biophysical research communications, 419(2): 431-435http://hdl.handle.net/10564/2703http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2703/8/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2703/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2703/3/03%e6%9c%ac%e6%96%87.pdf0006291XAA00564395Biochemical and biophysical research communications41924314352012-03-09enghttp://www.ncbi.nlm.nih.gov/pubmed/22366089http://dx.doi.org/10.1016/j.bbrc.2012.02.041ETD24601A6182014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27042017-05-29T06:07:13Zhdl_10564_2586Left ventricular mechanical and energetic changes in long-term isoproterenol-induced hypertrophied hearts of SERCA2a transgenic rats.SERCA2a過剰発現ラットにおけるイソプロテレノール持続投与誘導肥大心の左室力学的エネルギー学的性質の変化Mitsuyama, ShinichiTakeshita, DaisukeObata, KojiZhang, Guo-XingTakaki, MiyakoHeart failureCa2 + handlingOxygen consumptionExcitation–contraction couplingOverexpression of cardiac sarcoplasmic reticulum Ca2 +-ATPase (SERCA2a) has been suggested as a strategic intervention for cardiac failure. However, its benefit in wild-type (WT) rats with normal SERCA2a levels seems to be small. To investigate whether it would be beneficial in a cardiac failure model with down-regulated SERCA2a levels, we made a cardiac hypertrophy model using isoproterenol infusion (1.2 mg kg− 1 day− 1 for 1 or 4 weeks; TG-ISO1w and TG-ISO4w, respectively) in SERCA2a transgenic (TG) rats and compared these rats with littermate WT rats that underwent the same treatments (WT-ISO1w and WT-ISO4w). We analyzed the left ventricular (LV) mechanoenergetics in the excised heart using our original cross-circulation system. The downward shift of curvilinear LV end-systolic pressure–volume relations (ESPVRs) observed in WT-ISO4w rats was abolished in TG-ISO4w rats. The slope and VO2 intercept of the VO2 (myocardial oxygen consumption per beat)–PVA (systolic pressure–volume area: total mechanical energy per beat) linear relation did not differ in any of the groups. The most important finding was a significantly smaller O2 cost of LV contractility in the TG-ISO4w group, which means that less O2 is needed to exert the same LV contractility, compared with the other groups. The increased ratio of SERCA2a/phospholamban returned to the level of the WT-control group only in the TG-ISO4w group. Longer-term up-regulation of mitochondrial transcription factor A for genes of mitochondrial enzymes producing ATP was observed in TG rats. In conclusion, longer-term overexpression of SERCA2a will be beneficial in the present cardiac failure model with down-regulated SERCA2a levels.博士(医学)・甲619号・平成26年3月17日Academic Press / ElsevierThesisThesis or DissertationJournal of molecular and cellular cardiology Vol.59 p.95-10600222828http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2704Journal of molecular and cellular cardiology, 59: 95-106http://hdl.handle.net/10564/2704http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2704/8/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2704/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2704/3/03%e6%9c%ac%e6%96%87.pdf00222828AA00702819Journal of molecular and cellular cardiology59951062013-06enghttp://www.ncbi.nlm.nih.gov/pubmed/23458361http://dx.doi.org/10.1016/j.yjmcc.2013.02.012ETD24601A6192014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27052017-05-29T06:07:19Zhdl_10564_2586Distribution of corticosteroid receptors in mature oligodendrocytes and oligodendrocyte progenitors of the adult mouse brain.成体マウス脳の成熟および未成熟オリゴデンドロサイトにおけるコルチコイステロイドレセプタ−の分布Matsusue, YumikoHorii-Hayashi, NorikoKirita, TadaakiNishi, MayumiGlucocorticoid receptorcofactorcorticosteroid (glucocorticoid)mineralocorticoid receptoroligodendrocyteoligodendrocyte progenitorThe expression of glucocorticoid receptors (GRs) was investigated immunohistochemically in two different lineages of oligodendrocytes, using carbonic anhydrase (CA) II and neuron glial antigen (NG) 2 as markers of mature oligodendrocytes and oligodendrocyte progenitors, respectively. We focused on the gray matter regions, including CA1, CA3 and the dentate gyrus of the hippocampus, the primary somatosensory cortex barrel field and the basolateral amygdala, and the white matter regions, including the corpus callosum, external capsule and fimbria of the hippocampus. More than 80% of CAII-immunoreactive (IR) cells and more than 95% of NG2-IR cells expressed GRs in various regions of the brain. In contrast, neither CAII-IR cells nor NG2-IR cells expressed mineralocorticoid receptors (MRs) in the same regions. The intensity of GR expression was drastically reduced in CA II-IR cells and NG2-IR cells in the same regions in adrenalectomized mice. Finally, steroid receptor co-activator (SRC)-1 and p300, both of which are cofactors for GR, were expressed in the gray and white matter regions in NG2-IR cells, but not in CAII-IR cells. These results suggest that the expression of GRs in oligodendrocytes and their progenitor cells mediates several functions in vivo, including differentiation and myelination, as a major target of glucocorticoids and their cofactors.博士(医学)・甲620号・平成26年3月17日Copyright © 2014 by The Histochemical SocietySAGE PublicationsThesisThesis or DissertationThe journal of histochemistry and cytochemistry Vol.62 No.3 p.211-22600221554http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2705The journal of histochemistry and cytochemistry, 62(3): 211-226http://hdl.handle.net/10564/2705http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2705/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2705/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2705/6/03%e6%9c%ac%e6%96%87.pdf00221554AA0069926XThe journal of histochemistry and cytochemistry6232112262014-03enghttp://www.ncbi.nlm.nih.gov/pubmed/24309510http://dx.doi.org/10.1369/0022155413517700ETD24601A6202014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27062017-05-29T06:07:22Zhdl_10564_2586Sound transmission by cartilage conduction in ear with fibrotic aural atresia.軟組織による外耳道閉鎖症例での軟骨伝導Morimoto, ChihiroNishimura, TadashiHosoi, HiroshiSaito, OsamuFukuda, FumiShimokura, RyotaYamanaka, Toshiakiacquired aural atresiaairborne soundbinaural hearingbone-anchored hearing aidbone conductionexternal auditory canalA hearing aid using cartilage conduction (CC) has been proposed as an alternative to bone conduction (BC) hearing aids. The transducer developed for this application is lightweight, requires a much smaller fixation force than a BC hearing aid, and is more convenient to use. CC can be of great benefit to patients with fibrotic aural atresia. Fibrotic tissue connected to the ossicles provides an additional pathway (termed fibrotic tissue pathway) for sound to reach the cochlea by means of CC. To address the function of fibrotic tissue pathway, BC and CC thresholds were measured in six ears with fibrotic aural atresia. The relationship between the CC thresholds and the results of computed tomography was investigated. In the ears with the presence of a fibrotic tissue pathway, the CC thresholds were lower than the BC thresholds at 0.5 and 1.0 kHz. At 2.0 kHz, no significant difference was observed between the BC and CC thresholds. The current findings suggest that sound in the low to middle frequency range is transmitted more efficiently by CC via a fibrotic tissue pathway than BC. The development of hearing devices using CC can contribute to rehabilitation, particularly in patients with fibrotic aural atresia.博士(医学)・甲621号・平成26年3月17日U.S. Department of Veterans AffairsThesisThesis or DissertationJournal of Rehabilitation Research and Development Vol.51 No.2 p.325-33207487711http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2706Journal of Rehabilitation Research and Development, 51(2): 325-332http://hdl.handle.net/10564/2706http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2706/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2706/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2706/6/03%e6%9c%ac%e6%96%87.pdf07487711AA10644333Journal of Rehabilitation Research and Development5123253322014enghttp://dx.doi.org/10.1682/JRRD.2013.05.0128ETD24601A6212014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27072017-05-29T06:07:23Zhdl_10564_2586Sentinel Lymph Node Detection in Patients with Oral Cancer by MR Lymphography using Superparamagnetic Iron Oxide.超常磁性体を用いたMRリンフォグラフィーによる口腔癌患者のセンチネルリンパ節同定Uemura, HirokazuOta, IchiroFujii, TakashiSuzuki, MotoyukiSakai, MioNakanishi, KatsuyukiTomita, YasuhikoNoguchi, AtsushiHosoi, HiroshiYoshino, KunitoshiHead and neck cancersentinel lymph nodesuperparamagnetic iron oxideMR lymphographyThe purpose of this study was to examine the feasibility of interstitial MR lymphography using Superparamagnetic Iron Oxide (SPIO) to detect sentinel lymph nodes (SLNs) in head and neck cancer. For two patients with cT2N0 squamous cell carcinoma of the tongue, the submucosal injection of SPIO as well as sentinel lymph node navigation surgery (SLNNS) was performed before undergoing surgical treatment. SPIO was used for MR lymphography and Tc-99m phytate for SPECT. We compared the images by both modalities. Berlin blue stain was also performed postoperatively if SLNs had the uptake of SPIO. The lymph nodes with MR signal attenuation and those with hot spots were probed to be anatomically identical. All the lymph nodes detected as a SLN by a gamma-probe contained the blue granules from SPIO. These data suggest that SPIO can be a novel tracer for performing SLNNS and SLN biopsy in oral cancer patients with cN0 neck.博士(医学)・甲622号・平成26年3月17日Bentham OpenThesisThesis or DissertationOpen Otorhinolaryngology Journal Vol.7 p.14-1818744281http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2707Open Otorhinolaryngology Journal, 7: 14-18http://hdl.handle.net/10564/2707http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2707/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2707/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2707/3/03%e6%9c%ac%e6%96%87.pdf18744281Open Otorhinolaryngology Journal714182013-01enghttp://dx.doi.org/10.2174/1874428120131206002ETD24601A6222014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27082017-05-29T06:07:13Zhdl_10564_2586Intranasal priming of newborn mice with microbial extracts increases opsonic factors and mature CD11c+ cells in the airway.新生児マウス鼻腔への微生物抽出液の投与は気道中のオプソニン量及び、成熟CD1c+ 細胞を増加させるKasahara, KazukiMatsumura, YokoUi, KoujiKasahara, KeiKomatsu, YukoMikasa, KeiichiKita, Eijicommensal floraregulation of acute inflammationsurfactantsNasal exposure to the mixture of microbial extracts (MME) after ablactation enhanced airway resistance of newborn mice to Streptococcus pneumoniae (J Physiol Lung Cell Mol Physiol 298: L67, 2010). The present study was addressed to elucidate effective factors responsible for the enhanced innate resistance in the airway of MME-exposed newborn mice. MME exposure significantly increased the amount of pulmonary surfactants (SP-A and SP-D) in the airway. Bronchoalveolar lavage fluid of the exposed mice exhibited greater levels of opsonic activity, thereby enhancing the phagocytic and intracellular killing activities of alveolar macrophages (MØ) against S. pneumoniae. The exposure itself did not increase a complement component C3 and mannan-binding lectin-A (MBL-A) in the airway, whereas intratracheal infection with S. pneumoniae increased the quantity of SP-A, SP-D, C3, and MBL-A in the exposed mice to a significant extent compared with control mice. The exposure enhanced the expression of the class A scavenger MØ receptor with collagenous structure on alveolar MØ and also increased the frequency of major histocompatibility complex II+ CD11c+ cells in the lung; the cells were able to produce IL-10 and transforming growth factor-β in vitro. These results suggest that microbial exposure early in life increases the amounts of SP-A and SP-D and the number of scavenger MØ and also promotes maturation of CD11c+ cells in the airway of newborn mice, which may be involved in airway resistance to S. pneumoniae.博士(医学)・乙1323号・平成26年3月17日発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.1152/ajplung.00031.2012"American Physiological SocietyThesisThesis or DissertationAmerican journal of physiology. Lung cellular and molecular physiology Vol.303 No.9 p.L834-84310400605http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2708American journal of physiology. Lung cellular and molecular physiology, 303(9): L834-L843http://hdl.handle.net/10564/2708http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2708/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2708/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf10400605AA10700616American journal of physiology. Lung cellular and molecular physiology3039L834L8432012-11-01enghttp://www.ncbi.nlm.nih.gov/pubmed/22923643http://dx.doi.org/10.1152/ajplung.00031.2012none24601B13232014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27092017-05-29T06:07:22Zhdl_10564_2586Enhanced expression of ATP-binding cassette transporter A1 in non-rafts decreases the sensitivity of vascular endothelial cells to Shiga toxin.非ラフト部分のATP結合カセット輸送体A1の発現増強は、血管内皮細胞の志賀毒素に対する感受性を減少させるHigashi, NobutakaMatsumura, YoukoMizuno, FumikoKasahara, KazukiSugiura, ShigekiMikasa, KeiichiKita, EijiShiga toxinABCA1Gb3Cholesterol effluxPhosphodiesterase inhibitorVascular endothelial cellsShiga toxin (Stx) binds to globotriaosyl ceramide (Gb3) receptors on the surface of vascular endothelial cells, which is followed by Gb3-dependent endocytosis, and initiates a cascade leading to cell damage. The Gb3 receptor is localized in lipid rafts, in which cholesterol is tightly packed primarily with sphingolipids in a liquid-ordered state. Recent studies have indicated that phosphodiesterase (PDE) type 4 inhibitors enhance the expression of ATP-binding cassette 1 (ABCA1) which promotes cholesterol efflux from non-rafts at the plasma membrane. Here we report that rolipram, a PDE4 inhibitor, reduced the sensitivity to Stx2 of human umbilical vascular endothelial cells in association with increased apolipoproteinA-I (apoA-I)-mediated cholesterol efflux, and shift of some Gb3 molecules from lipid rafts into non-rafts. Although rolipram treatment did not reduce Gb3 content at the plasma membrane and Stx binding to whole cells of HUVECs, it reduced Stx2 endocytosis. Knockdown of ABCA1 by transfection with siRNA ABCA1 in vascular endothelial cells abrogated the protective effect of rolipram on Stx2-exposed cells. Our present results suggest that the expression level of ABCA1 protein is one of critical determinants of Stx sensitivity levels in vascular endothelial cells.博士(医学)・乙1324号・平成26年3月17日Academic Press / ElsevierThesisThesis or DissertationMicrobial pathogenesis Vol.49 No.4 p.141-15208824010http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2709Microbial pathogenesis, 49(4): 141-152http://hdl.handle.net/10564/2709http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2709/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2709/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2709/3/03%e6%9c%ac%e6%96%87.pdf08824010AA10609161Microbial pathogenesis4941411522010-10enghttp://www.ncbi.nlm.nih.gov/pubmed/20553836http://dx.doi.org/10.1016/j.micpath.2010.05.005ETD24601B13242014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27102017-05-29T06:07:27Zhdl_10564_2586Individuals' half-lives for 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) in blood: correlation with clinical manifestations and laboratory results in subjects with Yusho.血中の2,3,4,7,8-五塩化ダイベンゾフラン(PeCDF)の個人の半減期:油症患者における臨床症状並びに検診結果との関係Matsumoto, ShinyaAkahane, ManabuKanagawa, YoshiyukiKajiwara, JumbokuTodaka, TakashiYasukawa, FumikoUchi, HiroshiFurue, MasutakaImamura, TomoakiDibenzofuranCedar pollen allergyYushoHalf-lifeRed blood cell2,3,4,7,8-PentachlorodibenzofuranBACKGROUND:
In 1968, many people developed dioxin poisoning (Yusho) in Japan. Ingestion of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF) was considered to be the cause of this poisoning. Although some patients had high concentrations of 2,3,4,7,8-PeCDF in their blood, individuals' half-lives of 2,3,4,7,8-PeCDF were long.
OBJECTIVES:
To evaluate the relationship between clinical and laboratory parameters and the individual half-life of 2,3,4,7,8-PeCDF in blood.
METHODS:
Clinical and laboratory data were collected during annual check-ups from 2001 to 2008. We enrolled 71 patients, who were measured more than 3 times, and who had 2,3,4,7,8-PeCDF concentrations in blood >50pgg(-1) lipid. The half-life of 2,3,4,7,8-PeCDF for each patient was estimated using linear regression. Moreover, relationships between clinical and laboratory parameters and individual half-life were investigated by linear regression.
RESULTS:
A shortened individual half-life for 2,3,4,7,8-PeCDF was significantly correlated with an increased red blood cell count, increased viscous secretions from the meibomian glands, existing black comedones, and severe cedar pollen allergy.
CONCLUSIONS:
Symptoms that accelerate excretion of lipids from the body, such as viscous secretions from the meibomian glands, may lead to a shorter half-life of 2,3,4,7,8-PeCDF. Red blood cells are related to the half-life of 2,3,4,7,8-PeCDF. However, further studies are required to investigate the excretory mechanism of 2,3,4,7,8-PeCDF.博士(医学)・乙1325号・平成26年3月17日Elsevier Science LtdThesisThesis or DissertationChemosphere Vol.92 No.7 p.772-77700456535http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2710Chemosphere, 92(7): 772-777http://hdl.handle.net/10564/2710http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2710/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2710/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2710/3/03%e6%9c%ac%e6%96%87.pdf00456535AA00603442Chemosphere9277727772013-08enghttp://www.ncbi.nlm.nih.gov/pubmed/23651555http://dx.doi.org/10.1016/j.chemosphere.2013.04.005ETD24601B13252014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27112021-02-09T06:56:56Zhdl_10564_2586Oral administration of a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity for pulmonary arterial hypertension.肺高血圧症に対するトロンボキサン合成阻害作用をもった新規長期作用型プロスタサイクリンアゴニストの経口投与Nakamura, AtsuhiroNagaya, NoritoshiObata, HiroakiSakai, KatsuyaSakai, YoshikiYoshikawa, MasanoriHamada, KaoruMatsumoto, KunioKimura, HiroshicAMPHepatocyte growth factorMonocrotalinePulmonary arterial hypertensionThromboxane synthaseBACKGROUND:
Continuous administration of prostacyclin has improved the survival of patients with pulmonary arterial hypertension (PAH). However, this treatment has some problems, including its short duration of activity and difficult delivery. Therefore, we developed ONO-1301, an orally active, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity.
METHODS AND RESULTS:
We investigated whether oral administration of ONO-1301 can both prevent and reverse monocrotaline (MCT)-induced PAH in rats. Rats were randomly assigned to receive repeated oral administration of ONO-1301 twice daily beginning either 1 or 8 days after subcutaneous injection of MCT. A control group received oral saline, and a sham group received a subcutaneous injection of saline instead of MCT. MCT-treated controls developed significant pulmonary hypertension. Treatment with ONO-1301 from day 1 or 8 significantly attenuated the increases in right ventricular systolic pressure and the increase in medial wall thickness of pulmonary arterioles. Kaplan-Meier survival curves demonstrated that the effect of ONO-1301 was equivalent to that of an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. A single oral dose of ONO-1301 increased plasma cAMP levels for up to 6h. Treatment with ONO-1301 significantly decreased urinary 11-dehydro-thromboxane B2 and increased the plasma hepatocyte growth factor concentration.
CONCLUSIONS:
Oral administration of ONO-1301 ameliorated PAH in rats, an effect that may occur through cAMP and hepatocyte growth factor.博士(医学)・乙1326号・平成26年3月17日日本循環器学会の許諾を得て登録(2014年6月6日付)ジャーナル公式サイト(日本循環器学会HP内):https://www.j-circ.or.jp/journal/公開サイト(J-STAGE):https://www.jstage.jst.go.jp/browse/circj/日本循環器学会 / Japanese Circulation SocietyThesisThesis or DissertationCirculation journal Vol.77 No.8 p.2127-213313469843http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2711Circulation journal, 77(8): 2127-2133http://hdl.handle.net/10564/2711http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2711/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2711/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2711/6/03%e6%9c%ac%e6%96%87.pdf13469843AA11591968Circulation journal778212721332013-08enghttp://www.ncbi.nlm.nih.gov/pubmed/23676973http://dx.doi.org/10.1253/circj.CJ-13-0107ETD24601B13262014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27122017-06-11T23:20:26Zhdl_10564_2586Autofluorescence imaging with a transparent hood for detection of colorectal neoplasms: a prospective, randomized trial.大腸腫瘍性病変の拾い上げ診断における透明フードを併用した自家蛍光内視鏡の有用性:前向き無作為化比較試験Takeuchi, YojiInoue, TakuyaHanaoka, NoboruHigashino, KojiIishi, HiroyasuChatani, RikaHanafusa, MasaoKizu, TakashiIshihara, RyuTatsuta, MasaharuShimokawa, ToshioUedo, NoriyaBACKGROUND:
Colonoscopy is one of the most reliable methods for detection of colorectal neoplasms, but conventional colonoscopy can miss some lesions.
OBJECTIVE:
To evaluate the efficacy of autofluorescence imaging (AFI) with a transparent hood (TH) for detection of colorectal neoplasms.
DESIGN:
A 2 × 2 factorial designed, prospective, randomized, controlled trial.
SETTING:
This study was conducted at the Osaka Medical Center for Cancer and Cardiovascular Diseases, a tertiary cancer center.
PATIENTS:
A total of 561 patients.
INTERVENTIONS:
Patients were allocated to 1 of 4 groups: (1) white light imaging (WLI) alone--colonoscopy using WLI without a TH; (2) WLI+TH--colonoscopy using WLI with a TH; (3) AFI alone--colonoscopy using AFI without a TH; and (4) AFI+TH--colonoscopy using AFI with a TH. Eight colonoscopists used each allocated method.
MAIN OUTCOME MEASUREMENT:
The difference in neoplasm detection rate (number of detected neoplasms per patient) between the WLI alone and AFI+TH groups.
RESULTS:
Neoplasm detection rate (95% confidence interval) in the AFI+TH group was significantly higher than in the WLI alone group (1.96 [1.50-2.43] vs 1.19 [0.93-1.44]; P = .023, Tukey-Kramer multiple comparison test). Relative detection ratios (95% confidence interval) for polypoid neoplasms based on Poisson regression model were significantly increased by mounting a TH (1.69 [1.34-2.12], P < .001), and relative detection ratios for flat neoplasms were significantly increased by AFI observation (1.83 [1.24-2.71], P = .002).
LIMITATIONS:
Open trial performed in single cancer referral center.
CONCLUSION:
AFI colonoscopy with a TH detected significantly more colorectal neoplasms than did conventional WLI colonoscopy without a TH.博士(医学)・乙1327号・平成26年3月17日American Society for Gastrointestinal Endoscopy / ElsevierThesisThesis or DissertationGastrointestinal endoscopy Vol.72 No.5 p.1006-101300165107http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2712Gastrointestinal endoscopy, 72(5): 1006-1013http://hdl.handle.net/10564/2712http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2712/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2712/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2712/6/03%e6%9c%ac%e6%96%87.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2712/7/Figure_1-3.pdf00165107AA00653961Gastrointestinal endoscopy725100610132010-10enghttp://www.ncbi.nlm.nih.gov/pubmed/21034901http://dx.doi.org/10.1016/j.gie.2010.06.055ETD24601B13272014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27132017-05-29T06:07:02Zhdl_10564_2586Distribution of primary osteoarthritis in the ulnar aspect of the wrist and the factors that are correlated with ulnar wrist osteoarthritis: a cross-sectional study.尺側手関節の変形性関節症の頻度とその発現に影響を及ぼす要因Katayama, TakeshiOno, HiroshiSuzuki, DaisukeAkahane, ManabuOmokawa, ShoheiTanaka, YasuhitoOsteoarthritisUlnar aspectWristRadiographyOBJECTIVE:
The purpose of this cross-sectional study was to identify the distribution of primary osteoarthritis (OA) in the ulnar aspect of the wrist, and analyze the factors correlated with OA at this site.
MATERIALS AND METHODS:
A total of 1,128 cases of skeletally mature Japanese patients were collected over a 3-year period. We analyzed the posteroanterior and lateral wrist radiographs of these patients for the presence of primary OA in the ulnar aspect of the wrist, including the distal radioulnar (DRUJ), radiolunate, ulnolunate, lunotriquetral, triquetrohamate, lunohamate, and lunocapitate joints. All joints were examined for the frequency of primary OA. Multivariate logistic regression was used to investigate the factors correlated with the presence of degenerative arthritis in the ulnar aspect of the wrist joint.
RESULTS:
Primary OA of the ulnar wrist was identified in 145 out of 1,128 cases (12.8 %). Degenerative changes were most frequently identified in the DRUJ (12.3 %), followed by the ulnolunate joint (8.1 %). Variations in radial inclination (RI), carpal height ratio (CHR), and ulnar variance (UV) correlated with OA of the ulnar aspect of the wrist, with variations in UV showing the highest correlation.
CONCLUSION:
Primary OA of the ulnar wrist was most frequent in the DRUJ and second most frequent in the ulnolunate joint. UV correlated most with OA in the ulnar aspect of the wrist.博士(医学)・乙1328号・平成26年3月17日The definitive version is available at " http://dx.doi.org/10.1007/s00256-013-1665-9 "Springer VerlagThesisThesis or DissertationSkeletal radiology Vol.42 No.9 p.1253-125803642348http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2713Skeletal radiology, 42(9): 1253-1258http://hdl.handle.net/10564/2713http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2713/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2713/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2713/6/03%e6%9c%ac%e6%96%87.pdf03642348AA00843195Skeletal radiology429125312582013-09enghttp://www.ncbi.nlm.nih.gov/pubmed/23775319http://dx.doi.org/10.1007/s00256-013-1665-9ETD24601B13282014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27142022-08-02T06:48:49Zhdl_10564_2586Possible peripheral mechanism for taste disorder in rats administered S-1.S-1投与ラットにおける味覚障害の想定される末梢メカニズムAoki, KumikoObata, KojiKurihara, MiyakoKuniyasu, HirokiKirita, TadaakiTakaki, MiyakoTaste disorderAnticancer drug administrationNeuropathyS-1BACKGROUND:
Taste disorders are frequently observed in cancer patients undergoing chemotherapy and are serious adverse events which impair the quality of life (QoL) of the cancer patient. Nevertheless, taste disorder mechanisms in cancer patients undergoing chemotherapy have not yet been fully elucidated. The aim of this study was to reveal taste disorder-related peripheral mechanisms using the two-bottle preference test (TBPT) and histological examination of tongues by hematoxylin-eosin staining and immunohistochemistry with protein-gene product 9.5.
METHODS:
In the TBPT, one bottle was filled with the 0.01 mM quinine hydrochloride (quinine), as a bitter compound, and the other was filled with water. Doses of 50 and 100 mg kg-1 day-1 S-1 (tegafur/gimeracil/oteracil potassium) are lethal to Wistar rats. Therefore, doses ranging from 2-20 mg kg-1 day-1 were administered to the rats for 3 weeks. The S-1 dose of 2 mg kg-1 day-1 corresponds to the clinical dose administered to cancer patients. The part of the tongue containing the circumvallate papillae was excised the following TBPT.
RESULTS:
The rate of increase in terms of the average preference rate for the quinine vs. all intake (quinine plus water) was significant from the initial S-1 period to the final one, compared with that in control rats, suggesting the possibility of a worsening sensation for the bitter taste. In S-1 rats, the area of taste nerve fibers were significantly decreased and the rate of degeneration of intra-tongue ganglionic nerve cells was significantly increased. These changes were significantly correlated with the rate of increase in average preference rate of the quinine.
CONCLUSION:
Neuropathy of the gustatory nerve at the periphery may be involved in taste disorders induced by an anticancer drug.博士(医学)・乙1329号・平成26年3月17日© Japan Society of Clinical Oncology 2013This is a post-peer-review, pre-copyedit version of an article published in International journal of clinical oncology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10147-013-0572-3.Springer-Verlag TokyoThesisThesis or DissertationInternational journal of clinical oncology Vol.19 No.3 p.549-556 (2014)13419625http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2714International journal of clinical oncology, Epub ahead of print(2013 Jun 4)http://hdl.handle.net/10564/2714http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2714/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2714/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2714/3/03%e6%9c%ac%e6%96%87.pdf13419625AA11086579International journal of clinical oncologyEpub ahead of print2013 Jun 42013-06-04enghttp://www.ncbi.nlm.nih.gov/pubmed/23733353http://dx.doi.org/10.1007/s10147-013-0572-3ETD24601B13292014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27152017-05-29T06:07:26Zhdl_10564_2586Structure of vitreous body and its relationship with liquefaction.硝子体の構造とその液化との関係Kodama, MakotoMatsuura, ToyoakiHara, YoshiakiVitreous BodyLiquefactionCrystallinThe aim of the study is to clarify the vitreous body structure and liquefaction phenomena. It was found that when melting a frozen rabbit vitreous body, the gel-sol transition phenomenon occurs and the gel structure is broken. This is almost like the liquefaction of the vitreous body in vivo. We try to clarify the liquefaction phenomenon by using this animal model. The native vitreous body has three dimensional meshwork structures. After liquefaction, it is changed into two parts, namely fiber aggregates and soluble amorphous aggregates. The surface of native vitreous body meshwork is mucopolysacharide, but that of fiber aggregates after liquefaction is changed into connective tissue, which means the conformational change of vitreous body in liquefaction. The soluble proteins after liquefaction were analyzed and identified as crystallin family. It is suggested that the liquefaction is induced by detachment of non-collagenous protein beads containing crystallins, resulting in the collapse of the three dimensional structure to release watery liquid trapped within. And the new gel-sol transition model of vitreous bod is proposed.博士(医学)・乙1330号・平成26年3月17日Scientific Research Pub.ThesisThesis or DissertationJournal of biomedical science and engineering Vol.6 No.7 p.739-74519376871http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2715Journal of biomedical science and engineering Vol. No. p., 6(7): 739-745http://hdl.handle.net/10564/2715http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2715/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2715/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2715/3/03%e6%9c%ac%e6%96%87.pdf19376871Journal of biomedical science and engineering Vol. No. p.677397452013-07enghttp://dx.doi.org/10.4236/jbise.2013.67091ETD24601B13302014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27162017-05-29T06:07:26Zhdl_10564_2586Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model.22q11欠失症候群モデルマウスの神経発達障害には、マイクロRNAが介在するCxcr4/Cxcl12シグナリングの欠損が寄与するToritsuka, MichihiroKimoto, SoheiMuraki, KazueLandek-Salgado, Melissa AYoshida, AtsuhiroYamamoto, NorioHoriuchi, YasueHiyama, HidekiTajinda, KatsunoriKeni, NiIllingworth, ElizabethIwamoto, TakashiKishimoto, ToshifumiSawa, AkiraTanigaki, Kenjihippocampusdentate gyrus22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions, some of which are classified as schizophrenia and bipolar disorder in the current diagnostic categorization. However, it remains elusive how the chromosomal microdeletion leads to the mental manifestation at the mechanistic level. Here we show that a 22q11DS mouse model with a deletion of 18 orthologous genes of human 22q11 (Df1/+ mice) has deficits in migration of cortical interneurons and hippocampal dentate precursor cells. Furthermore, Df1/+ mice show functional defects in Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1) signaling, which reportedly underlie interneuron migration. Notably, the defects in interneuron progenitors are rescued by ectopic expression of Dgcr8, one of the genes in 22q11 microdeletion. Furthermore, heterozygous knockout mice for Dgcr8 show similar neurodevelopmental abnormalities as Df1/+ mice. Thus, Dgcr8-mediated regulation of microRNA is likely to underlie Cxcr4/Cxcl12 signaling and associated neurodevelopmental defects. Finally, we observe that expression of CXCL12 is decreased in olfactory neurons from sporadic cases with schizophrenia compared with normal controls. Given the increased risk of 22q11DS in schizophrenia that frequently shows interneuron abnormalities, the overall study suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator in the pathophysiology of schizophrenia and related mental conditions.博士(医学)・乙1331号・平成26年3月17日National Academy of SciencesThesisThesis or DissertationProceedings of the National Academy of Sciences of the United States of America Vol.110 No.43 p.17552-1755700278424http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2716Proceedings of the National Academy of Sciences of the United States of America Vol. No. p., 110(43): 17552-17557http://hdl.handle.net/10564/2716http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2716/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2716/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2716/3/03%e6%9c%ac%e6%96%87.pdf00278424AA10808769Proceedings of the National Academy of Sciences of the United States of America Vol. No. p.1104317552175572013-10-22enghttp://www.ncbi.nlm.nih.gov/pubmed/24101523http://dx.doi.org/10.1073/pnas.1312661110ETD24601B13312014-03-17博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27182017-05-29T06:07:00Zhdl_10564_2717Persistent overexpression of SERCA2a affects bladder functions under physiological conditions, but not in bladder outlet obstruction-induced sub-acute pathological conditions.SERCA2aの持続的過剰発現は、生理的条件下では膀胱機能に影響を及ぼすが、膀胱出口部閉塞亜急性期の病的条件下では膀胱機能に影響しないYamada, AtsushiTorimoto, KazumasaObata, KojiHirayama, AkihideFujimoto, KiyohideTakaki, MiyakoRat bladderSERCA2 overexpressionCystometryOutlet obstructionHypertrophyA functional impairment of the bladder and heart in a decompensated state caused by a pressure overload is accompanied by a decrease in the sarcoplasmic reticulum Ca2+-ATPase (SERCA2). The beneficial effects of SERCA2 overexpression in preserving cardiac functions have been previously reported. The aim of the present study was to investigate the effects of overexpressed SERCA2 on bladder functions under physiological and pathological conditions using partial bladder outlet obstruction (BOO) in SERCA2a transgenic Wistar rats (TG). Bladder cystometry and western blot analysis were performed using the wild-type Wistar rats (WT), TG, and BOO models (WTBOO and TGBOO). Persistent overexpression of SERCA2 induces reduced bladder compliance without hypertrophy in TG. BOO induces reduced bladder compliance and hypertrophy in WT and TG in the sub-acute phase, but persistent overexpression of SERCA2a in TG does not aggravate the bladder compliance and hypertrophy. In conclusion, SERCA2a overexpression affects bladder functions under physiological conditions, but not in BOO-induced sub-acute pathological conditions.博士(医学)・甲第623号・平成26年5月28日Physiological Society of Japan / Springer JapanThesisThesis or DissertationThe journal of physiological science Vol.64 No.1 p.21-3018806546http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2718The journal of physiological science, 64(1): 21-30http://hdl.handle.net/10564/2718http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2718/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2718/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2718/6/03%e6%9c%ac%e6%96%87.pdf18806546AA12129145The journal of physiological science64121302014-01enghttp://www.ncbi.nlm.nih.gov/pubmed/24037709http://dx.doi.org/10.1007/s12576-013-0286-3ETD24601A6232014-05-28博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27202017-05-29T06:08:36Zhdl_10564_2717Endothelin B receptor expression correlates with tumour angiogenesis and prognosis in oesophageal squamous cell carcinoma.食道扁平上皮癌におきてエンドセリンB受容体の高発現は腫瘍の血管新生と予後に関与するTanaka, TetsuyaSho, MasayukiTakayama, TomoyoshiWakatsuki, KoheiMatsumoto, SoheiMigita, KazuhiroIto, MasahiroHamada, KaoruNakajima, Yoshiyukiendothelin B receptoroesophageal cancerangiogenesisBACKGROUND:The endothelin axis has been shown to have a pivotal role in several human malignancies. The aim of this study was to clarify the clinical importance of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma (OSCC).
METHODS:We evaluated ETBR expression in 107 patients with OSCC by immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8, and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically analysed.RESULTS:Sixty-one (57%) cases showed high expression of ETBR. Endothelin receptor type B expression was correlated with several clinicopathological factors including tumour differentiation, tumour depth, and lymph node metastasis. The overall and disease-specific survival rates were significantly lower in patients with high ETBR expression than patients with low expression. Furthermore, multivariate analysis revealed that ETBR status was an independent prognostic factor for patient survival. Mechanistic analysis indicated that MVD was significantly higher in tumour tissues with high ETBR expression compared with those with low expression, suggesting that angiogenesis may be a key mechanism in tumour progression and metastasis of OSCC mediated by ETBR expression. By contrast, there were no significant correlations between TILs and ETBR expression.CONCLUSION:
Endothelin receptor type B has a pivotal role in oesophageal cancer and may be therapeutic target for this intractable malignancy.博士(医学)・乙第1336号・平成26年5月28日Nature Publishing GroupThesisThesis or DissertationBritish journal of cancer Vol.110 No.4 p.1027-103300070920http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2720British journal of cancer, 110(4): 1027-1033http://hdl.handle.net/10564/2720http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2720/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2720/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2720/6/03%e6%9c%ac%e6%96%87.pdf00070920AA00574355British journal of cancer1104102710332014-02enghttp://www.ncbi.nlm.nih.gov/pubmed/24357795http://dx.doi.org/doi:10.1038/bjc.2013.784ETD24601B13362014-05-28博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27212017-05-29T06:08:36Zhdl_10564_2717Significant involvement of herpesvirus entry mediator in human esophageal squamous cell carcinoma.ヒト食道扁平上皮癌におけるherpesvirus entry mediator関与の重要性Migita, KazuhiroSho, MasayukiShimada, KeijiYasuda, SatoshiYamato, IchiroTakayama, TomoyoshiMatsumoto, SoheiWakatsuki, KoheiHotta, KiyohikoTanaka, TetsuyaIto, MasahiroKonishi, NoboruNakajima, Yoshiyukiesophageal squamous cell carcinomaherpesvirus entry mediator (HVEM)prognosisimmunotherapyBACKGROUND:Herpesvirus entry mediator (HVEM) is known to regulate immune response and to be expressed in several human malignancies. However, to the authors's knowledge, the precise role of HVEM in human cancer biology remains unknown. The objective of the current study was to clarify the clinical significance of HVEM in human esophageal squamous cell carcinoma as well as its in vivo functions.METHODS:HVEM expression was evaluated in 103 patients with esophageal squamous cell carcinoma to explore its clinical relevance and prognostic value. The functions of HVEM in tumors were analyzed in vitro and in vivo using the small interfering RNA (siRNA) silencing technique.
RESULTS:HVEM expression was found to be significantly correlated with depth of tumor invasion and lymph node metastasis. Furthermore, it was found to be inversely correlated with tumor-infiltrating CD4(+) , CD8(+) , and CD45RO(+) lymphocytes. It is important to note that HVEM status was identified as an independent prognostic marker. HVEM gene silencing significantly inhibited cancer cell proliferation in vitro and cancer growth in vivo. This antitumor effect was associated with reduced cell proliferation activity. The effect was also correlated with the induction of CD8(+) cells and upregulation of local immune response.CONCLUSIONS:HVEM plays a critical role in both tumor progression and the evasion of host antitumor immune responses, possibly through direct and indirect mechanisms. Therefore, HVEM may be a promising therapeutic target for human esophageal cancer.博士(医学)・乙第1337号・平成26年5月28日Copyright © 1999-2015 John Wiley & Sons, Inc. All Rights Reserved.© 2013 American Cancer SocietyAmerican Cancer Society / WileyThesisThesis or DissertationCancer Vol.120 No.6 p.808-8170008543Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2721Cancer, 120(6): 808-817http://hdl.handle.net/10564/2721http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2721/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2721/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2721/6/03%e6%9c%ac%e6%96%87.pdf0008543XAA11616887Cancer12068088172014-03-15enghttp://www.ncbi.nlm.nih.gov/pubmed/24249528http://dx.doi.org/10.1002/cncr.28491none24601B13372014-05-28博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27222020-09-30T04:30:09Zhdl_10564_2717Surgical management of minimally invasive anterior lumbar interbody fusion with stand-alone interbody cage for L4-5 degenerative disorders: clinical and radiographic findings.第4-5腰椎変性疾患に対する椎間cageのみでの低侵襲前方固定術(mini-ALIF)の臨床成績と放射線学的検討Hironaka, YasuoMorimoto, TetsuyaMotoyama, YasushiPark, Young-SuNakase, Hiroyukianterior lumbar interbody fusioncircumferential fusiondegenerative lumbar spinal disorderminimally invasive therapySurgical treatment for degenerative spinal disorders is controversial, although lumbar fusion is considered an acceptable option for disabling lower back pain. Patients underwent instrumented minimally invasive anterior lumbar interbody fusion (mini-ALIF) using a retroperitoneal approach except for requiring multilevel fusions, severe spinal canal stenosis, high-grade spondylolisthesis, and a adjacent segments disorders. We retrospectively reviewed the clinical records and radiographs of 142 patients who received mini-ALIF for L4-5 degenerative lumbar disorders between 1998 and 2010. We compared preoperative and postoperative clinical data and radiographic measurements, including the modified Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score for back and leg pain, disc height (DH), whole lumbar lordosis (WL), and vertebral wedge angle (WA). The mean follow-up period was 76 months. The solid fusion rate was 90.1% (128/142 patients). The average length of hospital stay was 6.9 days (range, 3-21 days). The mean blood loss was 63.7 ml (range, 10-456 ml). The mean operation time was 155.5 min (range, 96-280 min). The postoperative JOA and VAS scores for back and leg pain were improved compared with the preoperative scores. Radiological analysis showed significant postoperative improvements in DH, WL, and WA, and the functional and radiographical outcomes improved significantly after 2 years. The 2.8% complication rate included cases of wound infection, liquorrhea, vertebral body fractures, and a misplaced cage that required revision. Mini-ALIF was found to be associated with improved clinical results and radiographic findings for L4-5 disorders. A retroperitoneal approach might therefore be a valuable treatment option.博士(医学)・乙第1338号・平成26年5月28日Copyright © 日本脳神経外科学会 | The Japan Neurosurgical Society / 学会誌名(Neurologia medico-chirurgica)とJ-STAGEからの出典である日本脳神経外科学会ThesisThesis or DissertationNeurologia medico-chirurgica Vol.53 No.12 p.861-86904708105http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2722Neurologia medico-chirurgica, 53(12): 861-869http://hdl.handle.net/10564/2722http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2722/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2722/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2722/6/03%e6%9c%ac%e6%96%87.pdf04708105AN00358613Neurologia medico-chirurgica53128618692013enghttp://www.ncbi.nlm.nih.gov/pubmed/24140782http://dx.doi.org/10.2176/nmc.oa2012-0379ETD24601B13382014-05-28博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27232017-05-29T06:08:35Zhdl_10564_2717REG Iα gene expression is linked with the poor prognosis of lung adenocarcinoma and squamous cell carcinoma patients via discrete mechanisms.肺癌におけるREG Iα遺伝子の発現は、腺癌、肩平上皮癌で異なったメカニズムにより、予後不良を示唆する。Kimura, MichitakaNaito, HiroshiTojo, TakashiItaya-Hironaka, AsakoDohi, YoshikoYoshimura, MamikoNakagawara, Kan-IchiTakasawa, ShinTaniguchi, ShigekiREG family genesREG Iα genelung cancerprognostic factorgene expressionThe aim of the present study was to evaluate the effects of the REG Iα and REG Iβ genes on lung cancer cell lines, and thereafter, the expression of REG family genes (REG Iα, REG Iβ, REG III, HIP/PAP and REG IV) in lung cancer in relation to patient prognosis was evaluated. Lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) cell lines expressing REG Iα or REG Iβ (HLC-1 REG Iα/Iβ and EBC-1 REG Iα/Iβ) were established, and cell number, cell invasive activity, and anchorage-independent cell growth were compared with these variables in the control cells. The expression levels of REG family genes were evaluated by real-time RT-PCR in surgically resected lung cancers, and disease-specific survival (DSS) curves were generated. The HLC-1 REG Iα/Iβ cell line showed significant increases in cell number and anchorage-independent cell growth compared with the control cells. EBC-1 REG Iα/Iβ cells showed significant increases in cell invasive activity and anchorage-independent cell growth as compared with the control cells. Except for the REG Iβ gene, expression of other REG family genes was observed in the surgically resected samples; however, DSS was significantly worse only in stage I patients who were positive for REG Iα expression than in patients who were negative for REG Iα expression. The effects of REG Iα on AD and SCC cells were different in the in vitro study, and a correlation between REG Iα expression and patient prognosis was noted in the in vivo study. Therefore, overexpression of REG Iα is a risk factor for poor prognosis caused by discrete mechanisms in AD and SCC patients.博士(医学)・乙第1339号・平成26年5月28日本文のリンク:http://dx.doi.org/10.3892/or.2013.2739Copyright © Spandidos Publications 2014National Hellenic Research Foundation / SpandidosThesisThesis or DissertationOncology reports Vol.30 No.6 p.2625-26311021335Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2723Oncology reports, 30(6): 2625-2631http://hdl.handle.net/10564/2723http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2723/5/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2723/6/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2723/11/03%e6%9c%ac%e6%96%87.pdf1021335XAA11016405Oncology reports306262526312013-12enghttp://www.ncbi.nlm.nih.gov/pubmed/24065141http://dx.doi.org/10.3892/or.2013.2739ETD24601B13392014-05-28博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27432022-08-05T03:56:56Zhdl_10564_2717Reduced renal α-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism.慢性腎臓病症例での腎臓におけるα-Klotho発現の低下とその腎臓でのリン制御とビタミンD代謝に対する影響についての検討Sakan, HirokazuNakatani, KimihikoAsai, OsamuImura, AkihiroTanaka, TomohiroYoshimoto, ShuheiIwamoto, NoriyukiKurumatani, NorioIwano, MasayukiNabeshima, Yo-ichiKonishi, NoboruSaito, YoshihikoRenal α-Klotho (α-KL) plays a fundamental role as a co-receptor for fibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3). Disruption of FGF23-α-KL signaling is thought to be an early hallmark of chronic kidney disease (CKD) involving reduced renal α-KL expression and a reciprocal rise in serum FGF23. It remains unclear, however, whether the rise in FGF23 is related to the loss of renal α-KL. We evaluated α-KL expression in renal biopsy samples and measured levels of several parameters of mineral metabolism, as well as soluble α-KL (sKL), in serum and urinary samples from CKD patients (n = 236). We found that although renal α-KL levels were significantly reduced and serum FGF23 levels were significantly elevated in early and intermediate CKD, serum phosphate levels remained within the normal range. Multiple regression analysis showed that the increases in FGF23 were significantly associated with reduced renal function and elevated serum phosphate, but were not associated with loss of renal α-KL. Moreover, despite falling renal α-KL levels, the increase in FGF23 enhanced urinary fractional excretion of phosphate and reduced serum 1,25VitD3 levels in early and intermediate CKD, though not in advanced CKD. Serum sKL levels also fell significantly over the course of CKD, and renal α-KL was a significant independent determinant of sKL. These results demonstrate that FGF23 levels rise to compensate for renal failure-related phosphate retention in early and intermediate CKD. This enables FGF23-α-KL signaling and a neutral phosphate balance to be maintained despite the reduction in α-KL. In advanced CKD, however, renal α-KL declines further. This disrupts FGF23 signaling, and serum phosphate levels significantly increase, stimulating greater FGF23 secretion. Our results also suggest the serum sKL concentration may be a useful marker of renal α-KL expression levels.博士(医学)・乙第1340号・平成26年7月22日© 2014 Sakan Hirokazu 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 ScienceThesisThesis or DissertationPloS one Vol.9 No.1 Article No.e86301 (2014 Jan)19326203http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2743PloS one, 9(1): Article No.e86301http://hdl.handle.net/10564/2743http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2743/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2743/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2743/3/03%e6%9c%ac%e6%96%87.pdf19326203PloS one91Article No.e863012014-01-23enghttp://www.ncbi.nlm.nih.gov/pubmed/24466013http://dx.doi.org/10.1371/journal.pone.0086301ETD24601B13402014-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27442017-05-29T06:08:32Zhdl_10564_2717Distribution of bone mineral content is associated with body weight and exercise capacity in patients with chronic obstructive pulmonary disease.慢性閉塞性肺疾患患者における骨塩量の分布と体重および運動能との関連Yamamoto, YoshifumiYoshikawa, MasanoriTomoda, KoichiFujita, YukioYamauchi, MotooFukuoka, AtsuhikoTamaki, ShinjiKoyama, NorikoKimura, Hiroshibone mineral contentCOPDbody mass indexexercise capacityBackground: Although low bone mineral density is highly prevalent in patients with chronic obstructive pulmonary disease (COPD), the distribution of the reduced bone mass has not been fully elucidated. Objectives: To determine regional bone mass loss in patients with COPD and investigate whether the change in distribution may be associated with body weight loss and functional capacity. Methods: Body mass index (BMI) was assessed, and height squared indices were derived for the bone mineral content index (BMCI) of the arms, legs and trunk by dual-energy X-ray absorptiometry in 45 male patients with COPD and 12 age- and sex-matched control subjects. Pulmonary function tests were performed, and maximal oxygen uptake (V·O2max) was measured. Results: The BMCI was lower in the total bone, legs and trunk of patients with COPD than in control subjects, although the BMCI in the arms was similar between the groups. BMI correlated significantly with the BMCI in all 3 segments. Bone mineral content (BMC) in the trunk, expressed as a percentage of total BMC (BMC trunk/total BMC), correlated significantly with BMI. The BMCI in the trunk was closely related with V·O2max but not with airflow limitation. Conclusions: There was a regional difference in BMC reduction, but a predominant reduction of bone mass in the trunk was not associated with the severity of airflow limitation but rather with body weight loss and exercise intolerance. These data suggest that body weight loss and exercise intolerance are important risk factors for vertebral fracture in patients with COPD.博士(医学)・乙第1341号・平成26年7月22日The definitive version is available at " http://dx.doi.org/10.1159/000355095 "Karger AGThesisThesis or DissertationRespiration Vol.87 No.2 p.158-16400257931http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2744Respiration, 87(2): 158-164http://hdl.handle.net/10564/2744http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2744/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2744/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2744/3/03%e6%9c%ac%e6%96%87.pdf00257931AA00816840Respiration8721581642014-02enghttp://www.ncbi.nlm.nih.gov/pubmed/24334752http://dx.doi.org/10.1159/000355095ETD24601B13412014-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27452017-05-29T06:08:33Zhdl_10564_2717Regional differences in elements of human peroneus longus tendons.長腓骨筋腱の各領域における元素分析の検討Matsumoto, NorikazuKumai, TsukasaIsomoto, ShinjiShinohara, YasushiTanaka, YasuhitoAzuma, ChoMinami, TakeshiTohno, YoshiyukiPeroneus longus tendonWraparound tendonProteoglycansCalciumSulfurMany studies have been performed on the structure, molecular composition, and biochemical properties of tendons. However, comparatively little research has been conducted on the content of various trace elements within tendons. Six elements were analyzed in four regions of the peroneus longus tendon: the tensional part of the tendon immediately proximal to the lateral malleolus (region A), the compressive region of the tendon in contact with the lateral malleolus (region B), the compressive region of the tendon in contact with the deep surface of the cuboid (region C), and the tensional part of the tendon between the cuboid and first metatarsal, to which the tendon is attached (region D). Regions B and C are wraparound regions. The calcium content was higher in region C (2.10 ± 0.93 mg/g) than in both regions A (1.25 ± 0.51 mg/g) and D (1.43 ± 0.41 mg/g) (p < 0.05), indicating that it is likely related to regional differences in cartilage degeneration. The phosphorus content was also higher in region C, possibly because of low alkaline phosphatase activity in this region. The sulfur content was higher in the wraparound regions (region B: 0.98 ± 0.09 mg/g, region C: 1.24 ± 0.19 mg/g) than in both regions A (0.83 ± 0.11 mg/g) and D (0.83 ± 0.1 mg/g) (p < 0.01); sulfur content is thought to be influenced by tendon–bone compression. Finally, the magnesium content in the wraparound regions was also higher, which is probably related to a higher level of fibrocartilage. No significant relationships were found with regard to zinc or iron. Overall, the findings of the present study indicate that element contents are related to function and anatomical differences in tendons, and that they may even vary within the same tendon.博士(医学)・乙第1342号・平成26年7月22日The original publication is available at www.springerlink.comThe definitive version is available at " http://dx.doi.org/10.1007/s12011-013-9735-3 "Humana Press / Springer USThesisThesis or DissertationBiological trace element research Vol.154 No.2 p.185-18901634984http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2745Biological trace element research, 154(2): 185-189http://hdl.handle.net/10564/2745http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2745/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2745/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2745/3/03%e6%9c%ac%e6%96%87.pdf01634984AA00110004Biological trace element research15421851892013-08enghttp://www.ncbi.nlm.nih.gov/pubmed/23812651http://dx.doi.org/10.1007/s12011-013-9735-3ETD24601B13422014-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27462022-08-05T07:45:16Zhdl_10564_2717Regional tissue oxygen saturation measured by near-infrared spectroscopy to assess the depth of burn injuries.近赤外線分光法を用いた局所酸素飽和度による熱傷深度測定の検討Seki, TadahikoFujioka, MasayukiFukushima, HidetadaMatsumori, HiroakiMaegawa, NaokiNorimoto, KazunobuOkuchi, KazuoNIRSrSO2laser Doppler imagingburn depthThe burn severity depends on the wound depth and area affected. Hitherto burn depth has been judged mainly by visual observation, although concerns have been raised about its validity. The regional tissue blood flow (rTBF) measured by laser Doppler imaging (LDI) in damaged tissue correlates with the depth. However, very few reports are available on the significance of the regional tissue oxygen saturation (rSO2) as an indicator of burn depth. We investigated whether rSO2 by Near-infrared spectroscopy (NIRS) in burn injuries correlates with rTBF by LDI, which would facilitate quantification of the severity of the tissue damage. Methods: We measured rTBF and rSO2 in 50 lesions from 14 patients of burn injury within 24 hours after injury. The correlation between rTBF and rSO2 was evaluated by Spearman rank correlation analysis. Results: The rSO2 (%; range, 52-82) by NIRS and the rTBF (perfusion unit; range, 61-704) by LDI in burn lesions were positively correlated (r=0.755, p<0.001). This statistically positive correlation still remained significant (r=0.678, p<0.001) after the rSO2 values were standardized. Conclusion: This study suggests that NIRS determination of rSO2 in burn injuries shows promise as a reliable and quick method to estimate the depth of burn lesion.博士(医学)・乙第1343号・平成26年7月22日© 2014 Seki Tadahiko et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License(https://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.e-Century Pub. Corp.ThesisThesis or DissertationInternational journal of burns and trauma Vol.4 No.1 p.40-4421602026http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2746International journal of burns and trauma, 4(1): 40-44http://hdl.handle.net/10564/2746http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2746/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2746/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2746/3/03%e6%9c%ac%e6%96%87.pdf21602026International journal of burns and trauma4140442014-02enghttp://www.ncbi.nlm.nih.gov/pubmed/24624313ETD24601B13432014-07-22博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27472022-08-05T07:29:13Zhdl_10564_2717Association of Adolescent Smoking with Maternal Smoking.思春期の喫煙と母親の喫煙の関係Morikawa, HidekoAkahane, ManabuYamada, MasahiroImamura, TomoakiAdolescenceSmokingMotherFatherObjective: To determine the effect of family smoking habits on adolescent smoking experience for information for anti-smoking strategies. Subjects and Methods: We analyzed data from 4776 junior high school students and 5047 high school students responding to the “Survey on Prevention of Life-Style Related Diseases of Children” conducted in Nara Prefecture of Japan in 2004. The chi-square test determined the odds ratios (ORs) for smoking experience rates of the two groups of students according to the smoking habits of their fathers, mothers, older brothers, and older sisters. Logistic regression analysis was also performed for smoking experience according to school year, sex, and family smoking habit. Results: The OR for smoking in junior high school students with a father as the only smoking family member against all other cases was 0.60, and the OR with a mother as the only smoking family member was 2.50. The OR with a smoking father against cases with no smoking family members was 1.23, and the OR with a smoking mother against cases with no smoking family members was 3.50. The OR for smoking in high school students with a father as the only smoking family member against all other cases was 0.76, and the OR with a mother as the only smoking family member was 2.66. The OR with a smoking father against cases with no smoking family members was 1.59, and the OR with a smoking mother against cases with no smoking family member was 3.26. All these ORs showed significance. Conclusion: Maternal smoking was associated with a particularly high risk of smoking experience in junior high and high school students. Prevention of maternal smoking should be given high priority to reduce smoking rates in adolescents.博士(医学)・甲第624号・平成26年12月3日© 2014 Morikawa Hideko et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Scientific Research PublishingThesisThesis or DissertationOpen Journal of Preventive Medicine Vol.4 No.5 p.347-35321622477http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2747Open Journal of Preventive Medicine, 4(5): 347-353http://hdl.handle.net/10564/2747http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2747/6/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2747/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2747/3/03%e6%9c%ac%e6%96%87.pdf21622477Open Journal of Preventive Medicine453473532014-05enghttp://dx.doi.org/10.4236/ojpm.2014.45042ETD24601A6242014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27482022-08-05T03:56:01Zhdl_10564_2717Azelnidipine inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch.アゼルニジピンは周期性伸展負荷による培養ラット大動脈平滑筋細胞死を抑制するZhao, JingOzawa, KentaroKyotani, YojiNagayama, KosukeIto, SatoyasuKomatsubara, Akira T.Tsuji, YuichiYoshizumi, MasanoriAcute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. Clarifying the detailed mechanism for aortic dissection is of great significance for establishing effective pharmacotherapy for this high mortality disease. In the present study, we evaluated the influence of biomechanical stretch, which mimics an acute rise in blood pressure using an experimental apparatus of stretching loads in vitro, on rat aortic smooth muscle cell (RASMC) death. Then, we examined the effects of azelnidipine and mitogen-activated protein kinase inhibitors on mechanical stretch-induced RASMC death. The major findings of the present study are as follows: (1) cyclic mechanical stretch on RASMC caused cell death in a time-dependent manner up to 4 h; (2) cyclic mechanical stretch on RASMC induced c-Jun N-terminal kinase (JNK) and p38 activation with peaks at 10 min; (3) azelnidipine inhibited RASMC death in a concentration-dependent manner as well as inhibited JNK and p38 activation by mechanical stretch; and (4) SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor) protected against stretch-induced RASMC death; (5) Antioxidants, diphenylene iodonium and tempol failed to inhibit stretch-induced RASMC death. On the basis of the above findings, we propose a possible mechanism where an acute rise in blood pressure increases biomechanical stress on the arterial walls, which induces RASMC death, and thus, may lead to aortic dissection. Azelnidipine may be used as a pharmacotherapeutic agent for prevention of aortic dissection independent of its blood pressure lowering effect.博士(医学)・乙第1344号・平成26年12月3日© 2014 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, 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.9 No.7 Article No.e102813 (2014 Jul)19326203http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2748PLoS ONE, 9(7): Article No.e102813http://hdl.handle.net/10564/2748http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2748/7/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2748/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2748/5/03%e6%9c%ac%e6%96%87.pdf19326203PLoS ONE97Article No.e1028132014-07-17enghttp://www.ncbi.nlm.nih.gov/pubmed/25032824http://dx.doi.org/10.1371/journal.pone.0102813ETD24601B13442014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27492017-05-29T06:08:31Zhdl_10564_2717Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1β transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1.卵巣明細胞腺癌における転写因子HNF-1βはDNA損傷チェックポイント機構の一つであるCHK1タンパクを制御し、抗癌剤耐性を獲得するShigetomi, HiroshiSudo, TamotsuShimada, KeijiUekuri, ChiharuTsuji, YorikoKanayama, SeijiNaruse, KatsuhikoYamada, YoshihikoKonishi, NoboruKobayashi, HiroshiTranscription factorsDNA damage responseCell cycleCheckpoint controlChemoresistanceObjective
Appropriate cell cycle checkpoints are essential for the maintenance of normal cells and chemosensitivity of cancer cells. Clear cell adenocarcinoma (CCA) of the ovary is highly resistant to chemotherapy. Hepatocyte nuclear factor-1β (HNF-1β) is known to be overexpressed in CCA, but its role and clinical significance is unclear. We investigated the role of HNF-1β in regulation of the cell cycle in CCA.
Methods
To clarify the effects of HNF-1β on cell cycle checkpoints, we compared the cell cycle distribution and the expression of key proteins involved in CCA cells in which HNF-1β had been stably knocked down and in vector-control cell lines after treatment with bleomycin. HNF-1β (+) cells were arrested in G2 phase because of DNA damage.
Results
HNF-1β (−) cells died because of a checkpoint mechanism. G2 arrest of HNF-1β (+) cells resulted from sustained CHK1 activation, a protein that plays a major role in the checkpoint mechanism. HNF-1β (+) cells were treated with a CHK1 inhibitor after bleomycin treatment. Flow cytometric analysis of the cell cycle demonstrated that DNA damage–induced G2-arrested cells were released from the checkpoint and killed by a CHK1 inhibitor.
Conclusions
The chemoresistance of CCA may be due to aberrant retention of the G2 checkpoint through overexpression of HNF-1β. This is the first study demonstrating cell cycle regulation and chemosensitization by a CHK1 inhibitor in CCA.博士(医学)・乙第1345号・平成26年12月3日© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.Lippincott Williams & WilkinsThesisThesis or DissertationInternational journal of gynecological cancer Vol.24 No.5 p.838-8431048891Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2749International journal of gynecological cancer, 24(5): 838-843http://hdl.handle.net/10564/2749http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2749/5/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2749/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2749/7/03%e6%9c%ac%e6%96%87.pdf1048891XAA10778114International journal of gynecological cancer2458388432014-06enghttp://www.ncbi.nlm.nih.gov/pubmed/24804869http://dx.doi.org/10.1097/IGC.0000000000000136ETD24601B13452014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27502017-05-29T06:08:32Zhdl_10564_2717Primary cerebral and cerebellar astrocytes display differential sensitivity to extracellular sodium with significant effects on apoptosis.大脳由来と小脳由来の初代培養アストロサイトは、アポトーシスに関連する細胞外ナトリウム感受性が異なるTakeda, TomohikoMakinodan, ManabuFukami, Shin-ichiToritsuka, MichihiroIkawa, DaisukeYamashita, YasunoriKishimoto, Toshifumiastrocytesodium ionapoptosishyponatraemiacentral pontine myelinolysisschizophreniaCentral pontine myelinolysis is one of the idiopathic or iatrogenic brain dysfunction, and the most common cause is excessively rapid correction of chronic hyponatraemia. While myelin disruption is the main pathology, as the diagnostic name indicates, a previous study has reported that astrocyte death precedes the destruction of the myelin sheath after the rapid correction of chronic low Na+ levels, and interestingly, certain brain regions (cerebral cortex, hippocampus, etc.) are specifically damaged but not cerebellum. Here, using primary astrocyte cultures derived from rat cerebral cortex and cerebellum, we examined how extracellular Na+ alterations affect astrocyte death and whether the response is different between the two populations of astrocytes. Twice the amount of extracellular [Na+] and voltage-gated Na+ channel opening induced substantial apoptosis in both populations of astrocytes, while, in contrast, one half [Na+] prevented apoptosis in cerebellar astrocytes, in which the Na+–Ca2+ exchanger, NCX2, was highly expressed but not in cerebral astrocytes. Strikingly, the rapid correction of chronic one half [Na+] exposure significantly increased apoptosis in cerebellar astrocytes but not in cerebral astrocytes. These results indicate that extracellular [Na+] affects astrocyte apoptosis, and the response to alterations in [Na+] is dependent on the brain region from which the astrocyte is derived.博士(医学)・乙第1346号・平成26年12月3日Copyright © 2014 John Wiley & Sons, Ltd.Wiley-BlackwellThesisThesis or DissertationCell biochemistry and function Vol.32 No.4 p.395-40002636484http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2750Cell biochemistry and function, 32(4): 395-400http://hdl.handle.net/10564/2750http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2750/4/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2750/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2750/7/03%e6%9c%ac%e6%96%87.pdf02636484AA1064014XCell biochemistry and function3243954002014-06enghttp://www.ncbi.nlm.nih.gov/pubmed/24888443http://dx.doi.org/10.1002/cbf.3030ETD24601B13462014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27512022-08-05T07:47:25Zhdl_10564_2717Profiling Psychiatric Inpatient Suicide Attempts in Japan.日本における精神科入院患者の自殺企図の特徴Ikeshita, KatsumiShimoda, ShigeroNorimoto, KazunobuArita, KeisukeShimamoto, TakuyaMurata, KiyoshiMakinodan, ManabuKishimoto, ToshifumiInpatientsuicidePsychiatryJapanSuicide is an adverse event that can occur even when patient are hospitalized in psychiatric facilities. This study delineates the demographic characteristics of suicide attempts in mental hospitals and psychiatric wards of general hospitals in Japan, a country where the suicide rate is remarkably high. Analyses of incident reports on serious suicide attempts in psychiatric inpatients were performed using prefectural incident records between April 1, 2001, and December31, 2012. Suicide reports were included for 35 incidents that occurred over 11years, and demonstrated that 83% of patients (n=29) committed suicide and 17% (n=6) survived their attempt with serious aftereffects, such as cognitive impairment or persistent vegetative state. The male/female ratio of inpatient suicide was 1.5:1. The mean age of the attempters was 50.5 years (SD = 18.2). The most common psychiatric diagnoses for those with suicide incident reports were schizophrenia spectrum disorders (51.4%) and affective disorders (40%). Hanging (60%) was the most common method of suicide attempt, followed by jumping in front of moving objects (14.3%) and jumping from height (11.4%). Fifty-four percent of suicides (n=19) occurred within hospital sites and the remainder (46%; n=16) occurred outside hospital sites (e.g., on medical leave or elopement) while they were still inpatients.博士(医学)・乙第1347号・平成26年12月3日© 2014 Ikeshita Katsumi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.OMICS GroupThesisThesis or DissertationInternational Journal of Emergency Mental Health and Human Resilience Vol.16 No.1 p.40-4315224821http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2751International Journal of Emergency Mental Health and Human Resilience, 16(1): 40-43http://hdl.handle.net/10564/2751http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2751/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2751/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2751/3/03%e6%9c%ac%e6%96%87.pdf15224821AA11572500International Journal of Emergency Mental Health and Human Resilience16140432014enghttp://www.ncbi.nlm.nih.gov/pubmed/25345233http://dx.doi.org/10.4172/1522-4821.1000107ETD24601B13472014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27522017-05-29T06:08:31Zhdl_10564_2717Guidance on water intake effectively improves urinary frequency in patients with nocturia.飲水指導は夜間頻尿患者の頻尿症状を有効に改善するTani, MitsuruHirayama, AkihideTorimoto, KazumasaMatsushita, ChieYamada, AtsushiFujimoto, Kiyohide24-h urine production/bodyweightlifestyle therapynocturianocturnal polyuriawater intake guidanceOBJECTIVES:
To evaluate how guidance on water-intake impacts the degree of nocturia.
METHODS:
A total of 67 male patients were enrolled in the present study. Patients were asked to adjust their water and food intakes so that their 24-h urine production/bodyweight would be equal or lower than 30 mL/kg. One month after the treatment, the therapeutic gain from and adverse effects of fluid restriction were examined by comparing the pretreatment and post-treatment value of various parameters.
RESULTS:
Overall, 65 eligible patients were evaluated. In 44 patients (67%), the frequency of nocturia was improved to one or more times. The change in frequency of nocturia showed a positive correlation with the change in nocturnal urine volume. The change in nocturnal urine volume showed a positive correlation with the changes in 24-h urine production/bodyweight, 24-h drinking volume and daytime drinking volume. The changes in 24-h urine production/bodyweight and daytime drinking volume were independent factors influencing therapeutic effect. None of the participants reported any adverse event.
CONCLUSIONS:
In patients with a 24-h urine production/bodyweight equal or higher than 30 mL/kg, guidance on water intake might be considered effective and safe as a lifestyle therapy. Water restriction should be carried out not only in the evening, but also during daytime.博士(医学)・乙第1348号・平成26年12月3日© 2014 The Japanese Urological AssociationWiley-Blackwell / Japanese Urological AssociationThesisThesis or DissertationInternational journal of urology Vol.21 No.6 p.595-60009198172http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2752International journal of urology, 21(6): 595-600http://hdl.handle.net/10564/2752http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2752/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2752/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2752/6/03%e6%9c%ac%e6%96%87.pdf09198172AA11042471International journal of urology2165956002014-06enghttp://www.ncbi.nlm.nih.gov/pubmed/24405404http://dx.doi.org/10.1111/iju.12387ETD24601B13482014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27532017-05-29T06:08:36Zhdl_10564_2717The impact of obstructive sleep apnea syndrome on nocturnal urine production in older men with nocturia.高齢夜間頻尿患者における夜間尿産生に対する閉塞性睡眠時無呼吸症候群の影響Hoshiyama, FumiakiHirayama, AkihideTanaka, MasahiroTaniguchi, MitsutakaOhi, MotoharuMomose, HitoshiNakamura, TakahitoOgawa, ShuheiTorimoto, KazumasaTanaka, NobumichiFujimoto, KiyohideOBJECTIVE:
To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria.
MATERIALS AND METHODS:
One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed.
RESULTS:
We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P < .0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups.
CONCLUSION:
Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.博士(医学)・乙第1349号・平成26年12月3日Copyright © 2014 Elsevier Inc. All rights reserved.Elsevier ScienceThesisThesis or DissertationUrology Vol.84 No.4 p.892-89600904295http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2753Urology, 84(4): 892-896http://hdl.handle.net/10564/2753http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2753/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2753/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2753/6/03%e6%9c%ac%e6%96%87.pdf00904295AA0087924XUrology8448928962014-10enghttp://www.ncbi.nlm.nih.gov/pubmed/25096335http://dx.doi.org/10.1016/j.urology.2014.02.073ETD24601B13492014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27542022-08-16T07:18:01Zhdl_10564_2717Quantitative lung perfused blood volume imaging on dual-energy CT: capability for quantitative assessment of disease severity in patients with acute pulmonary thromboembolism.Dual-Energy CTを用いた肺血液量画像の定量的評価:急性肺血栓塞栓症患者に対する定量的重症度評価Miura, SachikoOhno, YoshiharuKimura, HiroshiKichikawa, KimihikoCTLungdual-energy CTperfusionpulmonary thromboembolismBACKGROUND:Regional iodine distribution assessment on dual-energy computed tomography (DECT) has been suggested as useful for management of acute pulmonary thromboembolism (APTE) patients. However, no reported studies have made a direct comparison between quantitatively assessed DECT and right-to-left ventricular (RV/LV) ratio on CT for differentiation of right heart dysfunction (RHD) from non-right heart dysfunction (NRHD) in APTE patients.
PURPOSE:To determine the capability of DECT for differentiation of RHD from NRHD in APTE patients.
MATERIAL AND METHODS:Thirteen APTE patients underwent DECT and echocardiography at onset of APTE. Patients were divided into RHD (n = 7) and NRHD (n = 6) groups based on echocardiography. A normalized lung perfused blood volume map was generated, and two kinds of overall perfusion (OP) index were determined, one placed over each lung field (OP index A) and as the average from six regions of interest (ROIs) placed over each lung field (OP index B). The heterogeneity index was also determined as the standard deviation for the six ROIs. RV/LV ratio evaluations were also performed. To assess differences between the two groups, each index was statistically compared with the Mann-Whitney U test. The receiver-operating curve-based positive test was then performed to determine the feasible threshold value for dividing patients into the two groups. Finally, differentiation capabilities of the indexes were compared using McNemar's test.
RESULTS:Significant differences between the two groups were found for both OP indexes and RV/LV ratio (P < 0.05). For each of the feasible threshold values, accuracy of each OP index with and without RV/LV ratio was better than that of the RV/LV ratio.
CONCLUSION:Quantitative DECT has good potential for differentiation of APTE patients with and without right heart dysfunction.博士(医学)・乙第1350号・平成26年12月3日© The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.To access the final edited and published work see http://dx.doi.org/10.1177/0284185114524953.Sage / Foundation Acta RadiologicaThesisThesis or DissertationActa radiologica Vol.56 No.3 p.284-293 (2015 Mar)02841851http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2754Acta radiologica, 56(3): 284-293http://hdl.handle.net/10564/2754http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2754/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2754/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2754/3/03%e6%9c%ac%e6%96%87.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2754/4/04Fig.1-6.pdf02841851AA10668717Acta radiologica5632842932014-02-24enghttp://www.ncbi.nlm.nih.gov/pubmed/24567523http://dx.doi.org/10.1177/0284185114524953ETD24601B13502014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27552017-05-29T06:08:31Zhdl_10564_2717Retained placental tissue: role of MRI findings in diagnosis and clinical assessment.遺残胎盤組織:診断と臨床的取り扱いにおけるMRI所見の役割Takahama, JunkoKitano, SatoruMarugami, NagaakiUehara, TomokoTakahashi, AkiTakewa, MegumiItoh, TakahiroKichikawa, KimihikoRetained placental tissueMRIPostpartum hemorrhagePlacental polypUterine arterial embolizationOBJECTIVE:To assess the role of MRI in diagnosis and predicting clinical outcome in women with retained placental tissue.
PATIENTS AND METHODS:Eleven patients with pathologically proven RPT were retrospectively studied. All underwent MRI. The following MRI parameters of RPT were studied: size, signal intensity on T1- and T2-weighted images, enhancement pattern on dynamic study, extent of attachment to the uterine myometrium, and myometrial thickness at the attachment site. Clinical reports were reviewed and MRI findings were compared with respect to outcome.
RESULTS:RPT diameter varied from 30 to 102 mm. On T2-weighted images, 10 cases showed high intensity, while on T1-weighted images, seven cases showed high intensity. Nine cases were hypervascular. The myometrium was thinner at the attachment side than at the opposite side. All five cases in which RPT was delivered spontaneously showed an attachment area of less than a semicircle, hence broad attachment appears to impede detachment and necessitate additional therapy. After uterine arterial embolization, two patients showed complete infarction of RPT on enhanced MRI.
CONCLUSION:MRI is useful for diagnosis and follow-up of RPT. The evaluation of extent of RPT attachment to the myometrium and vascularity on MRI can help the clinical assessment.博士(医学)・乙第1351号・平成26年12月3日© Springer Verlag. The definitive version is available at " http://dx.doi.org/10.1007/s00261-010-9604-x "Springer InternationalThesisThesis or DissertationAbdominal imaging Vol.36 No.1 p.110-11409428925http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2755Abdominal imaging, 36(1): 110-114http://hdl.handle.net/10564/2755http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2755/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2755/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2755/3/03%e6%9c%ac%e6%96%87.pdf09428925AA10881951Abdominal imaging3611101142011-02enghttp://www.ncbi.nlm.nih.gov/pubmed/20174922http://dx.doi.org/10.1007/s00261-010-9604-xETD24601B13512014-12-03博士(医学)奈良県立医科大学
oai:ginmu.naramed-u.ac.jp:10564/27572017-05-29T06:08:33Zhdl_10564_2756Internet survey of the influence of environmental factors on human health: environmental epidemiologic investigation using the web-based daily questionnaire for health.環境因子が健康に与える影響について インターネット調査;WDQH(Web-based Daily Questionnaire for Health)を利用した環境疫学調査Sano, TomomiAkahane, ManabuSugiura, HiroakiOhkusa, YasushiOkabe, NobuhikoImamura, Tomoakiweb-based surveyenvironmental factorminimum temperaturegeneral populationWith increasing Internet coverage, the use of a web-based survey for epidemiological study is a possibility. We performed an investigation in Japan in winter 2008 using the web-based daily questionnaire for health (WDQH). The WDQH is a web-based questionnaire survey formulated to obtain information about the daily physical condition of the general public on a real-time basis, in order to study correlations between changes in physical health and changes in environmental factors. Respondents were asked whether they felt ill and had specific symptoms including fever. We analysed the environmental factors along with the health conditions obtained from the WDQH. Four factors were found to influence health: minimum temperature, hours of sunlight, median humidity and weekday or holiday. The WDQH allowed a daily health survey in the general population in real time via the Internet.博士(医学)・甲第593号・平成24年11月27日© 2013 Taylor & Francis GroupTaylor and FrancisThesisThesis or DissertationInternational journal of environmental health research Vol.23 No.3 p.247-25709603123http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2757International journal of environmental health research, 23(3): 247-257http://hdl.handle.net/10564/2757http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2757/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2757/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf09603123AA10856375International journal of environmental health research2332472572013enghttp://www.ncbi.nlm.nih.gov/pubmed/22946467http://dx.doi.org/10.1080/09603123.2012.717916none
oai:ginmu.naramed-u.ac.jp:10564/27582017-05-29T06:08:34Zhdl_10564_2756Diffuse vascular injury: convergent-type hemorrhage in the supratentorial white matter on susceptibility-weighted image in cases of severe traumatic brain damage.びまん性血管損傷 磁化率強調画像を用いた重症頭部外傷での収束性出血Iwamura, AsamiTaoka, ToshiakiFukusumi, AkioSakamoto, MasahikoMiyasaka, ToshiteruOchi, TomokoAkashi, ToshiakiOkuchi, KazuoKichikawa, KimihikoSusceptibility-weighted imageApparent diffusion coefficientDiffuse axonal injuryDiffuse vascular injuryGlasgow Coma ScaleINTRODUCTION:Susceptibility-weighted image (SWI) is one of the most sensitive methods for detect microbleeding and useful for evaluation of traumatic brain damage. The purpose of this study is to delineate the characteristics and importance of supratentorial deep white matter hemorrhages detected by SWI in cases of traumatic brain damage.
METHODS:Twenty-one consecutive cases with severe traumatic head injury were included in the current study. MRI examinations were made within 1 month after injury. We evaluated the degree and distribution of the supratentorial hemorrhages on SWI retrospectively. We classified the degree of bleeding into four grades: "small hemorrhage," "single bead-like hemorrhage," "convergent-type hemorrhage," and "massive hemorrhage." We then correlated the degree and distribution of the hemorrhage to clinical outcomes. We also evaluated the apparent diffusion coefficient (ADC) image of lobes with "convergent-type hemorrhage."
RESULTS:Existence of "massive hemorrhage" correlated with a poor outcome, that is, worse than "severely disabled" on the Glasgow Outcome Scale. The number of lobes affected by "convergent-type hemorrhage" also correlated with poor outcome. There were 45 lobes with "convergent-type hemorrhage" and 27 of them showed increased diffusivity on ADC images.
CONCLUSION:Supratentorial massive hemorrhages and supratentorial convergent-type multiple hemorrhages were associated with poor prognosis after traumatic brain injury. The increased diffusivity in lobes with convergent-type hemorrhages may indicate that congestion of the proximal medullary vein may play some role for these hemorrhages.博士(医学)・甲第594号・平成25年3月15日© Springer International Publishing AG,2012Springer-VerlagThesisThesis or DissertationNeuroradiology Vol.54 No.4 p.335-34300283940http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2758Neuroradiology, 54(4): 335-343http://hdl.handle.net/10564/2758http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2758/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2758/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf00283940AA00754889Neuroradiology5443353432012-04enghttp://www.ncbi.nlm.nih.gov/pubmed/21611726http://dx.doi.org/10.1007/s00234-011-0892-9none
oai:ginmu.naramed-u.ac.jp:10564/27592017-05-29T06:08:35Zhdl_10564_2756Brain structural changes and neuropsychological impairments in male polydipsic schizophrenia.多飲水統合失調症男性患者における脳構造変化と神経心理学的障害Nagashima, TomohisaInoue, MakotoKitamura, SoichiroKiuchi, KuniakiKosaka, JunOkada, KojiKishimoto, NaokoTaoka, ToshiakiKichikawa, KimihikoKishimoto, ToshifumiSchizophreniaPolydipsiaVolumetryMRINeuropsychological impairmentBrief assessment of cognition in schizophreniaBACKGROUND:Polydipsia frequently occurs in schizophrenia patients. The excessive water loading in polydipsia occasionally induces a hyponatremic state and leads to water intoxication. Whether polydipsia in schizophrenic patients correlates with neuropsychological impairments or structural brain changes is not clear and remains controversial.
METHODS:Eight polydipsic schizophrenia patients, eight nonpolydipsic schizophrenia patients, and eight healthy controls were recruited. All subjects underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural abnormalities were analyzed using a voxel-based morphometry (VBM) approach, and patients' neuropsychological function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J).
RESULTS:No significant differences were found between the two patient groups with respect to the clinical characteristics. Compared with healthy controls, polydipsic patients showed widespread brain volume reduction and neuropsychological impairment. Furthermore, the left insula was significantly reduced in polydipsic patients compared with nonpolydipsic patients. These nonpolydipsic patients performed intermediate to the other two groups in the neuropsychological function test.
CONCLUSIONS:It is possible that polydipsia or the secondary hyponatremia might induce left insula volume reduction. Furthermore, this structural brain change may indirectly induce more severe neuropsychological impairments in polydipsic patients. Thus, we suggest that insula abnormalities might contribute to the pathophysiology of polydipsic patients.博士(医学)・甲第595号・平成25年3月15日© 2012 BioMed Central LtdBioMed CentralThesisThesis or DissertationBMC Psychiatry Vol.12 p.2101471244Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2759BMC Psychiatry, 12: 210-210http://hdl.handle.net/10564/2759http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2759/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2759/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf1471244XAA12072671BMC Psychiatry122102102012-11enghttp://www.ncbi.nlm.nih.gov/pubmed/23181904http://dx.doi.org/10.1186/1471-244X-12-210none
oai:ginmu.naramed-u.ac.jp:10564/27602017-05-29T06:08:35Zhdl_10564_2756Efficacy of FDG-PET for defining gross tumor volume of head and neck cancer.頭頸部癌の肉眼的腫療体積の境界限定におけるFDG-PET の有用性Kajitani, ChikaeAsakawa, IsaoUto, FumiakiKatayama, EmikoInoue, KazuyaTamamoto, TetsuroShirone, NorihisaOkamoto, HideyukiKirita, TadaakiHasegawa, MasatoshiFDG-PETgross tumor volumetarget delineationhead and neck cancerWe analyzed the data for 53 patients with histologically proven primary squamous cell carcinoma of the head and neck treated with radiotherapy between February 2006 and August 2009. All patients underwent contrast-enhanced (CE)-CT and 18F-fluorodeoxyglucose (FDG)-PET before radiation therapy planning (RTP) to define the gross tumor volume (GTV). The PET-based GTV (PET-GTV) for RTP was defined using both CE-CT images and FDG-PET images. The CE-CT tumor volume corresponding to a FDG-PET image was regarded as the PET-GTV. The CE-CT-based GTV (CT-GTV) for RTP was defined using CE-CT images alone. Additionally, CT-GTV delineation and PET-GTV delineation were performed by four radiation oncologists independently in 19 cases. All four oncologists did both methods. Of these, PET-GTV delineation was successfully performed in all 19 cases, but CT-GTV delineation was not performed in 4 cases. In the other 15 cases, the mean CT-GTV was larger than the PET-GTV in 10 cases, and the standard deviation of the CT-GTV was larger than that of the PET-GTV in 10 cases. Sensitivity of PET-GTV for identifying the primary tumor was 96%, but that of CT-GTV was 81% (P < 0.01). In patients with oropharyngeal cancer and tongue cancer, the sensitivity of CT-GTV was 63% and 71%, respectively. When both the primary lesions and the lymph nodes were evaluated for RTP, PET-GTV differed from CT-GTV in 19 cases (36%). These results suggested that FDG-PET is effective for defining GTV in RTP for squamous cell carcinoma of the head and neck, and PET-GTV evaluated by both CE-CT and FDG-PET images is preferable to CT-GTV by CE-CT alone.博士(医学)・甲第596号・平成25年3月15日Copyright © 2013 Japan Radiation Research Society and Japanese Society for Radiation OncologyOxford University Press / Japan Radiation Research SocietyThesisThesis or DissertationJournal of radiation research Vol.54 No.4 p.671-67804493060http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2760Journal of radiation research, 54(4): 671-678http://hdl.handle.net/10564/2760http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2760/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2760/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf04493060AA00705792Journal of radiation research5446716782013-07enghttp://www.ncbi.nlm.nih.gov/pubmed/23287772http://dx.doi.org/10.1093/jrr/rrs131none
oai:ginmu.naramed-u.ac.jp:10564/27612017-05-29T06:08:27Zhdl_10564_2756Identification of thymus and activation-regulated chemokine (TARC/CCL17) as a potential marker for early indication of disease and prediction of disease activity in drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS).血清TARC/CCL17値は薬剤性過敏症症候群(DIHS) の早期診断および病勢の指標となりうる。Ogawa, KoheiMorito, HironoriHasegawa, AyakoDaikoku, NatsukoMiyagawa, FumiOkazaki, AikoFukumoto, TakayaKobayashi, NobuhikoKasai, TakahikoWatanabe, HideakiSueki, HirohikoIijima, MasafumiTohyama, MikikoHashimoto, KojiAsada, HideoDIHSDRESSTARCDendritic cellsTh2BACKGROUND:Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes.
OBJECTIVE:We investigated the pathogenic role of TARC in patients with DIHS.
METHODS:Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab.
RESULTS:Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS.
CONCLUSION:Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS.博士(医学)・甲第597号・平成25年3月15日Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.Elsevier ScienceThesisThesis or DissertationJournal of dermatological science Vol.69 No.1 p.38-4309231811http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2761Journal of dermatological science, 69(1): 38-43http://hdl.handle.net/10564/2761http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2761/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2761/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf09231811AA1075636XJournal of dermatological science69138432013-01enghttp://www.ncbi.nlm.nih.gov/pubmed/23141052http://dx.doi.org/10.1016/j.jdermsci.2012.10.002none
oai:ginmu.naramed-u.ac.jp:10564/27622017-05-29T06:08:26Zhdl_10564_2756Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation.p53 変異型ヒト口腔がん細胞における高LET 放射線によるp53 非依存Akt 生存シグナルの抑制Nakagawa, YosukeTakahashi, AkihisaKajihara, AtsuhisaYamakawa, NobuhiroImai, YuichiroOta, IchiroOkamoto, NoritomoMori, EiichiroNoda, TaichiFurusawa, YoshiyaKirita, TadaakiOhnishi, TakeoHigh LETAktCaspaseApoptosisCell cycleAlthough mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G(2)/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp53 bearing cancer cells.博士(医学)・甲第598号・平成25年3月15日Copyright © 2012 Elsevier Inc. All rights reservedElsevier / Academic PressThesisThesis or DissertationBiochemical and biophysical research communications Vol.423 No.4 p.654-6600006291Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2762Biochemical and biophysical research communications, 423(4): 654-660http://hdl.handle.net/10564/2762http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2762/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2762/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf0006291XAA00564395Biochemical and biophysical research communications42346546602012-07-13enghttp://www.ncbi.nlm.nih.gov/pubmed/22695120http://dx.doi.org/10.1016/j.bbrc.2012.06.004none
oai:ginmu.naramed-u.ac.jp:10564/27632017-05-29T06:08:29Zhdl_10564_2756就労女性の妊娠判明後の退職行動規定要因に関する疫学研究Epidemiological Study of Factors Associated with Quitting a Job among Pregnant Working Women.大原, 賢了佐伯, 圭吾鴻池, 義純岡本, 希冨岡, 公子西岡, 久之車谷, 典男Maternity protectionNon-regular employeePregnant workerQuitting a job就労女性の妊娠判明後の退職行動規定要因に関する疫学研究:大原賢了ほか.奈良県立医科大学地域健康医学講座―目的:女性の社会進出が進む中,就労女性の妊娠判明後の退職割合が,日本は他の先進国より未だ高いことを踏まえ,退職割合減少のため介入すべき要因を明らかにする.対象と方法:2004年11月から12月に,奈良県内の7産科医療機関を健診や出産目的で受診入院した全妊産婦にアンケート調査を実施し,この内,妊娠判明時に就労中であった603人を研究対象とした.退職をイベントの発生,調査時に就労中の者を打ち切り例(censored case)として,妊娠経過に伴う退職割合の推移をKaplan-Meier法により求めた.また,対象者の年齢や就労先の従業員規模や雇用形態のほか,職場の母性保護制度の有無などの職場要因,本人や夫の就業継続に関する考え方などの個人要因と,退職との関係について,Coxの比例ハザードモデルを用いて検討を行った.結果:出産までの退職割合は63.1%であり,第1子妊娠に限ると69.8%であった.妊娠経過の健康診査などを受けるための時間保障の制度がある(HR=0.59, 95%CI(0.41–0.83)),育児休業制度がある(0.37(0.22–0.63)),産休・育休からの復職後の支援体制が比較的整っている職場である(0.60(0.42–0.87)),結婚や子供の誕生があると勤めにくい雰囲気のある職場でない(0.59(0.43–0.81)),子どもができても,ずっと仕事を続けるのがよいと本人(0.63(0.43–0.93))または夫(0.50(0.30–0.86))が思っているが,妊娠判明後の退職行動に有意につながりにくい独立した要因であった.一方,非正規雇用者(1.93(1.46–2.56))であること,低年齢(1.74(1.10–2.75))であることが退職につながりやすい要因であった.結論:妊娠判明後も就労を継続させる条件づくりとしては,従来からの母性保護制度に加え,職場環境の工夫や,本人と夫の就労意思形成の働きかけが重要である.また,非正規雇用者全てが対象となっていない育児休業制度の全面適用が望まれる.博士(医学)・乙第1291号・平成24年5月28日Copyright © 2012 公益社団法人 日本産業衛生学会日本産業衛生学会ThesisThesis or Dissertation産業衛生学雑誌 54巻2号 p.61-7013410725http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2763産業衛生学雑誌, 54(2): 61-70http://hdl.handle.net/10564/2763http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2763/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2763/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf13410725AN10467364産業衛生学雑誌54261702012-03jpnhttp://www.ncbi.nlm.nih.gov/pubmed/22277289http://dx.doi.org/10.1539/sangyoeisei.B11017none
oai:ginmu.naramed-u.ac.jp:10564/27642017-05-29T06:08:28Zhdl_10564_2756Work-related aggression and violence committed by patients and its psychological influence on doctors.医師が患者から受ける暴力被害とその心理的影響Saeki, KeigoOkamoto, NozomiTomioka, KimikoObayashi, KenjiNishioka, HisayukiOhara, KenryoKurumatani, NorioAggression and violenceDoctorsIncidence ratePeriod prevalencePost-traumatic stress disorderRisk factorsObjectives: To determine the incidence rate of work-related aggression and violence (WRAV) against doctors and investigate risk factors and psychological influences of WRAV doctors. Methods: We sent a self-administered questionnaire on WRAV committed by patients and their associates to 1,148 doctors in Nara Prefecture, Japan. We calculated the incidence rate of WRAV using the number of incidents encountered during the previous 12 mo and the doctor's average weekly working hours. Risk factors for the incidence WRAV were analyzed by Poisson regression, and the influence of WRAV on the symptoms of post-traumatic stress disorder (PTSD) was evaluated by multiple logistic regression analysis. Results: A total of 758 (66.0%) doctors returned the questionnaire. The incidence rate of WRAV was 0.20 [95% CI: 0.17-0.24]×10-3 per practice hour. Adjusted incidence rate ratios of WRAV were significantly increased among doctors 1) with a shorter career (11.0; 95% CI: 5.0-24.2), 2) working in a region with the lowest average taxable income (1.6; 1.1-2.4), and 3) whose specialties were dermatology (3.8; 2.3-6.3), psychiatry (2.7; 1.3-5.6) and ophthalmology (1.9; 1.2-3.2). Of 289 subjects who had encountered WRAV at least once during their career, 26 doctors (8.2%) had symptoms suggestive of PTSD due to the most severe incident. Conclusions: Doctors encountered WRAV at an incidence rate of 0.20×10-3 per practice hour, and some of them might develop PTSD. Countermeasures are required to maintain sound health and safe workplaces for doctors.博士(医学)・乙第1292号・平成24年5月28日Copyright © 2011 by the Japan Society for Occupational Health日本産業衛生学会ThesisThesis or DissertationJournal of occupational health Vol.53 No.5 p.356-36413419145http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2764Journal of occupational health, 53(5): 356-364http://hdl.handle.net/10564/2764http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2764/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2764/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf13419145AA11090645Journal of occupational health5353563642011enghttp://www.ncbi.nlm.nih.gov/pubmed/21828959http://dx.doi.org/10.1539/joh.11-0108-OAnone
oai:ginmu.naramed-u.ac.jp:10564/27652017-05-29T06:08:29Zhdl_10564_2756Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion.早期糖尿病性腎症での腎臓におけるα-Klotho 発現の低下とその尿中カルシウム排世に対する役割についての検討Asai, OsamuNakatani, KimihikoTanaka, TomohiroSakan, HirokazuImura, AkihiroYoshimoto, ShuheiSamejima, Ken-ichiYamaguchi, YukinariMatsui, MasaruAkai, YasuhiroKonishi, NoboruIwano, MasayukiNabeshima, YoichiSaito, Yoshihikodiabetic nephropathyhypercalciuriahypoxiaHypercalciuria is one of the early manifestations of diabetic nephropathy. We explored here the role of α-Klotho, a protein expressed predominantly in distal convoluted tubules that has a role in calcium reabsorption. We studied 31 patients with early diabetic nephropathy and compared them with 31 patients with IgA nephropathy and 7 with minimal change disease. Renal α-Klotho expression was significantly lower and urinary calcium excretion (UCa/UCr) significantly higher in diabetic nephropathy than in IgA nephropathy or minimal change disease. Multiple regression analyses indicated that α-Klotho mRNA was inversely correlated with calcium excretion. We next measured these parameters in a mouse model of streptozotocin (STZ)-induced diabetic nephropathy, characterized by glomerular hyperfiltration, as seen in early diabetic nephropathy. We also confirmed a reduction of renal α-Klotho mRNA down to almost 50% and enhanced calcium excretion in mice with STZ-induced diabetic nephropathy in comparison with nondiabetic mice. Hypercalciuria was exacerbated in heterozygous α-Klotho knockout mice in comparison with wild-type mice, each with STZ-induced diabetic nephropathy. Thus, α-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of α-Klotho may affect urinary calcium excretion in early diabetic nephropathy.博士(医学)・乙第1293号・平成24年5月28日© 2012 International Society of NephrologyNature Publishing GroupThesisThesis or DissertationKidney international Vol.81 No.6 p.539-54700852538http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2765Kidney international, 81(6): 539-547http://hdl.handle.net/10564/2765http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2765/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2765/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf00852538AA00710996Kidney international8165395472012-03enghttp://www.ncbi.nlm.nih.gov/pubmed/22217880http://dx.doi.org/10.1038/ki.2011.423none
oai:ginmu.naramed-u.ac.jp:10564/27662017-05-29T06:08:35Zhdl_10564_2756Reduced larger von Willebrand factor multimers at dawn in OSA plasmas reflect severity of apnoeic episodes.閉塞型睡眠時無呼吸症候群患者における早朝の高分子量フォンウィルブランド因子減少は無呼吸の重症度を反映するKoyama, NorikoMatsumoto, MasanoriTamaki, ShinjiYoshikawa, MasanoriFujimura, YoshihiroKimura, HiroshiADAMTS13obstructive sleep apnoeavon Willebrand factorPlasma von Willebrand factor (VWF), produced in and released from vascular endothelial cells by various stimuli including hypoxia, induces platelet aggregation under high shear stress and plays dual pivotal roles in haemostasis and thrombosis within arterioles, which are regulated by the size of vWF multimers (VWFMs). Patients with obstructive sleep apnoea (OSA) have increased risk of thrombotic cardiovascular events, but the pathogenesis is unclear. We examined the relationship between VWF and OSA by measuring VWF antigen (VWF:Ag), VWFMs, VWF collagen binding activity (VWF:CB) and a disintegrin-like, metalloproteinase, and thrombospiondin type 1 motifs 13. A total of 58 OSA patients were enrolled. Blood samples were collected before sleep, after sleep, and after one night of nasal continuous positive airway pressure therapy. Based on VWFM analysis, OSA patients were classified into three groups; consistently normal VWFMs (group 1, n=29), increased high molecular weight (HMW)-VWFMs at 06:00 h (group 2, n=18), and decreased or absent HMW-VWFMs at 06:00 h (group 3, n=11). Patients in group 3 had significantly worse apnoea/hypopnoea index; VWF:CB followed a similar pattern. We observed a significant decrease in platelet count between 21:00 h and 06:00 h in OSA patients, potentially associated with reduced larger VWFMs together with decreased VWF:Ag levels. Severe OSA may contribute to an arterial pro-thrombotic state.博士(医学)・乙第1294号・平成24年5月28日Copyright © 2012 by the European Respiratory SocietyEuropean Respiratory SocietyThesisThesis or DissertationThe European respiratory journal Vol.40 No.3 p.657-66409031936http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2766The European respiratory journal, 40(3): 657-664http://hdl.handle.net/10564/2766http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2766/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2766/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf09031936AA10688995The European respiratory journal4036576642012-09enghttp://www.ncbi.nlm.nih.gov/pubmed/22362856http://dx.doi.org/10.1183/09031936.00186210none
oai:ginmu.naramed-u.ac.jp:10564/27672017-05-29T06:08:27Zhdl_10564_2756Predictors of distal radioulnar joint instability in distal radius fractures.不安定型橈骨遠位端骨折に合併する橈尺靭帯損傷の予測因子Fujitani, RyotaroOmokawa, ShoheiAkahane, ManabuIida, AkioOno, HiroshiTanaka, YasuhitoRadioulnarligamentdistal radiusfracturePURPOSE:A tear of the triangular fibrocartilage complex (TFCC) is the most frequent soft tissue injury associated with fractures of the distal radius, and repair of the deep ligamentous portion of the TFCC is considered when the tear contributes to instability of the distal radioulnar joint (DRUJ). The purpose of this prospective cohort study was to identify predictors of DRUJ instability accompanying unstable distal radius fractures.
METHODS:Between 2002 and 2007, we prospectively treated 163 consecutive patients with unstable distal radius fractures with the volar locking plating system. Complete radioulnar ligament tears representing DRUJ instability were present in 11 of 163 distal radius fractures. We tested univariate associations between DRUJ instability and potential predictors and conducted multivariate analysis to establish independent predictors of instability. We applied receiver operating characteristics curves within the significant risk factors to determine threshold values.
RESULTS:In univariate analyses, only the radial and sagittal translation ratios of the fracture site were significant predictors of DRUJ instability. Multivariate logistic regression analysis confirmed that the radial translation ratio, which corresponds to a normalized DRUJ gap, was a significant risk factor. According to the receiver operating characteristics curve for the radial translation ratio, the area under the curve was 0.89. A cutoff value of 15% for the radial translation ratio showed the highest diagnostic accuracy rate.
CONCLUSIONS:A radiographic finding of a normalized DRUJ gap on posteroanterior views was the most important predictor to identify DRUJ instability accompanying unstable distal radius fractures. The relative risk of instability increases by 50% when the ratio of DRUJ widening increases by 1%.博士(医学)・乙第1295号・平成24年5月28日Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reservedAmerican Society for Surgery of the Hand / ElsevierThesisThesis or DissertationThe Journal of hand surgery Vol.36 No.12 p.1919-192503635023http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2767The Journal of hand surgery, 36(12): 1919-1925http://hdl.handle.net/10564/2767http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2767/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2767/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf03635023AA10522529The Journal of hand surgery3612191919252011-11enghttp://www.ncbi.nlm.nih.gov/pubmed/22036131http://dx.doi.org/10.1016/j.jhsa.2011.09.004none
oai:ginmu.naramed-u.ac.jp:10564/27682017-05-29T06:08:30Zhdl_10564_2756Low concentrations of alendronate increase the local invasive potential of osteoblastic sarcoma cell lines via connexin 43 activation.低濃度アレンドロネートはコネキシン43 活性を介して造骨系肉腫細胞株の局所浸潤能を増加させるYoshitani, KazuhiroKido, AkiraHonoki, KanyaAkahane, ManabuFujii, HiromasaTanaka, YasuhitoLow-concentrationAlendronateOsteoblastic sarcomaConnexin 43OleamideBisphosphonates (BPs) are agents used for treating disorders of excessive bone resorption. In addition, due to their cell-killing activity, BPs were potent candidates for adjuvant cancer therapy. On the other hand, low-concentrations of BPs have been reported to increase cellular viability in several types of tumor cells. Therefore, we focused on the effect of BPs on cellular aggressiveness of malignant bone tumors at low concentrations. MTS assay was performed using osteosarcoma cell lines MG63 and HOS, fibrosarcoma cell line HT1080, and prostate cancer cell line PC3. All the cell lines showed toxicity at high concentrations. On the other hand, at lower concentrations, the cellular viabilities of HOS and MG63 were rather higher than those of untreated controls. Since this tendency was most evident, HOS was used for further assays, including cellular motility, bone resorption activity, and cathepsin K activity. The low-concentration of alendronate enhanced cellular viability and motility, which correlated with the expression of connexin 43 at the mRNA and protein levels. Interestingly, oleamide, a potent connexin 43 inhibitor, had an inhibitory effect on the enhanced proliferation. Our data suggest that alendronate may enhance the proliferation of osteoblastic cell line through connexin 43 activation.博士(医学)・乙第1296号・平成24年5月28日Copyright © 2011 Elsevier GmbH. All rights reserved.ElsevierThesisThesis or DissertationPathology, research and practice Vol.207 No.7 p.417-42203440338http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2768Pathology, research and practice, 207(7): 417-422http://hdl.handle.net/10564/2768http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2768/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2768/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf03440338AA00769966Pathology, research and practice20774174222011-07-15enghttp://www.ncbi.nlm.nih.gov/pubmed/21665377http://dx.doi.org/10.1016/j.prp.2011.04.007none
oai:ginmu.naramed-u.ac.jp:10564/27692017-05-29T06:08:35Zhdl_10564_2756The factor VIIIa C2 domain (residues 2228-2240) interacts with the factor IXa Gla domain in the factor Xase complex.活性化第VIII 因子のC2 ドメイン(残基2228-2240) はFactor Xase 複合体における活性化第IX 因子のGla ドメインと相互作用するSoeda, TetsuhiroNogami, KeijiNishiya, KatsumiTakeyama, MasahiroOgiwara, KenichiSakata, YoichiYoshioka, AkiraShima, MidoriFactor VIIIa functions as a cofactor for factor IXa in the phospholipid surface-dependent activation of factor X. Both the C2 domain of factor VIIIa and the Gla domain of factor IXa are involved in phospholipid binding and are required for the activation of factor X. In this study, we have examined the close relationship between these domains in the factor Xase complex. Enzyme-linked immunosorbent assay-based and surface plasmon resonance-based assays in the absence of phospholipid showed that Glu-Gly-Arg active site-modified factor IXa bound to immobilized recombinant C2 domain (rC2) dose-dependently (Kd = 108 nm). This binding ability was optimal under physiological conditions. A monoclonal antibody against the Gla domain of factor IXa inhibited binding by approximately 95%, and Gla domainless factor IXa failed to bind to rC2. The addition of monoclonal antibody or rC2 with factor VIIIa inhibited factor IXa-catalyzed factor X activation in the absence of phospholipid. Inhibition was not evident, however, in similar experiments in the absence of factor VIIIa, indicating that the C2 domain interacted with the Gla domain of factor IXa. A fragment designated C2-(2182-2259), derived from V8 protease-cleaved rC2, bound to Glu-Gly-Arg active site-modified factor IXa. Competitive assays, using overlapping synthetic peptides encompassing residues 2182-2259, demonstrated that peptide 2228-2240 significantly inhibited both this binding and factor Xa generation, independently of phospholipid. Our results indicated that residues 2228-2240 in the factor VIIIa C2 domain constitutes an interactive site for the Gla domain of factor IXa. The findings provide the first evidence for an essential role for this interaction in factor Xase assembly.博士(医学)・乙第1297号・平成24年5月28日Copyright © 2009 American Society for Biochemistry and Molecular BiologyAmerican Society for Biochemistry and Molecular BiologyThesisThesis or DissertationThe Journal of biological chemistry Vol.284 No.6 p.3379-338800219258http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2769The Journal of biological chemistry, 284(6): 3379-3388http://hdl.handle.net/10564/2769http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2769/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2769/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf00219258AA00251083The Journal of biological chemistry2846337933882009-02-06enghttp://www.ncbi.nlm.nih.gov/pubmed/19047063http://dx.doi.org/10.1074/jbc.M804955200none
oai:ginmu.naramed-u.ac.jp:10564/27702017-05-29T06:08:35Zhdl_10564_2756A putative inhibitory mechanism in the tenase complex responsible for loss of coagulation function in acquired haemophilia A patients with anti-C2 autoantibodies.後天性血友病A (抗C2 自己抗体)の凝固機能低下におけるFX 複合体阻害様式の解明Matsumoto, TomokoNogami, KeijiOgiwara, KenichiShima, Midorithrombin generationtenase complexAcquired haemophilia Aanti-C2 autoantibodyFXa generationAcquired haemophilia A (AHA) is caused by the development of factor (F)VIII autoantibodies, demonstrating type 1 or type 2 inhibitory behaviour, and results in more serious haemorrhagic symptoms than in congenital severe HA. The reason(s) for this remains unknown, however. The global coagulation assays, thrombin generation tests and clot waveform analysis, demonstrated that coagulation parameters in patients with AHA-type 2 inhibitor were more significantly depressed than those in patients with moderate HA with similar FVIII activities. Thrombin and intrinsic FXa generation tests were significantly depressed in AHA-type 1 and AHA-type 2 compared to severe HA, and more defective in AHA-type 1 than in AHA-type 2. To investigate these inhibitory mechanism(s), anti-FVIII autoantibodies were purified from AHA plasmas. AHA-type 1 autoantibodies, containing an anti-C2 ESH4-epitope, blocked FVIII(a)-phospholipid binding, whilst AHA-type 2, containing an anti-C2 ESH8-epitope, inhibited thrombin-catalysed FVIII activation. The coagulation function in a reconstituted AHA-model containing exogenous ESH4 or ESH8 was more abnormal than in severe HA. The addition of anti-FIX antibody to FVIII-deficient plasma resulted in lower coagulation function than its absence. These results support the concept that global coagulation might be more suppressed in AHA than in severe HA due to the inhibition of FIXa-dependent FX activation by steric hindrance in the presence of FVIII-anti-C2 autoantibodies. Additionally, AHA-type 1 inhibitors prevented FVIIIa-phospholipid binding, essential for the tenase complex, whilst AHA-type 2 antibodies decreased FXa generation by inhibiting thrombin-catalysed FVIII activation. These two distinct mechanisms might, in part, contribute to and exacerbate the serious haemorrhagic symptoms in AHA.博士(医学)・乙第1298号・平成24年5月28日© Schattauer Publishers, Stuttgart, 2012SchattauerThesisThesis or DissertationThrombosis and haemostasis Vol.107 No.2 p.288-30103406245http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2770Thrombosis and haemostasis, 107(2): 288-301http://hdl.handle.net/10564/2770http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2770/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2770/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf03406245AA00863137Thrombosis and haemostasis10722883012012-02enghttp://www.ncbi.nlm.nih.gov/pubmed/22234708http://dx.doi.org/10.1160/TH11-05-0331none
oai:ginmu.naramed-u.ac.jp:10564/27712021-05-25T01:52:01Zhdl_10564_2756A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma.腹膜および胸膜悪性中皮腫におけるEGFR発現の比較Enomoto, YasunoriKasai, TakahikoTakeda, MaikoTakano, MasatoMorita, KouheiKadota, EijiIizuka, NorishigeMaruyama, HiroshiHaratake, JojiKojima, YuIkeda, NaoyaNonomura, Akitakaepidermal growth factor receptorFISHgene copy number gainimmunohistochemistrymalignant mesotheliomaAn evaluation of epidermal growth factor receptor (EGFR) phenotypic expression in malignant pleural and peritoneal mesothelioma was undertaken, using immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Thirty-eight malignant mesothelioma (MM) specimens were subjected to IHC staining and FISH to evaluate the expression of EGFR protein and gene status. Overall positive IHC reaction was detected in 20/38 (53%) cases, in 11/22 (50%) pleural MM, and in 9/16 (56%) peritoneal MM. Our study confirmed that EGFR membranous expression is a common feature in MM, but not in benign mesothelial lesion. Thirty-seven cases did not show a gene copy number gain. Only one case showed a copy number gain. The protein overexpression of EGFR was not related to a gene copy number gain.博士(医学)・乙第1299号・平成24年5月28日© 2012 The Authors. Pathology International© 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.Blackwell Scientific Pub. for the Japanese Society of PathologyThesisThesis or DissertationPathology international Vol.62 No.4 p.226-23113205463http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2771Pathology international, 62(4): 226-231http://hdl.handle.net/10564/2771http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2771/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2771/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf13205463AA10984364Pathology international6242262312012-04enghttp://www.ncbi.nlm.nih.gov/pubmed/22449226http://dx.doi.org/10.1111/j.1440-1827.2011.02778.xnone
oai:ginmu.naramed-u.ac.jp:10564/27722017-05-29T06:08:24Zhdl_10564_2756Prognostic importance of tumour-infiltrating memory T cells in oesophageal squamous cell carcinoma.食道扁平上皮癌における腫瘍浸潤メモリーT細胞の予後因子としての重要性についてEnomoto, KojiSho, MasayukiWakatsuki, KoheiTakayama, TomoyoshiMatsumoto, SoheiNakamura, ShinjiAkahori, TakahiroTanaka, TetsuyaMigita, KazuhiroIto, MasahiroNakajima, YoshiyukiCD45ROmemory cellsoesophagusprognosissurgeryMemory T cells survive for many months and years and are critically important for host defence in humans. In tumour immunity, they have been also suggested to play a significant role in tumour progression and metastasis. However, the role of memory T cells in actual human cancer remains largely unknown. In this study, the clinical importance of tumour-infiltrating CD45RO(+) memory T cells was investigated in human oesophageal squamous cell carcinoma (OSCC). CD45RO(+) T cells were evaluated by immunohistochemistry in primary OSCC tumours from 105 patients. Patients were classified into two groups as CD45RO(+hi) or CD45RO(+lo) based on the number of cells stained positively for CD45RO. No significant difference was observed between CD45RO status and several clinicopathological prognostic factors. However, the postoperative overall and disease-free survival for CD45RO(+hi) patients was significantly better than for CD45RO(+lo) patients. Furthermore, there were significant correlations of CD45RO status in the primary tumour with postoperative lymph node and pulmonary recurrence, suggesting that memory T cells may control postoperative metastatic recurrence. Most importantly, CD45RO(+) memory T cell status has a significant prognostic value for OSCC independently of conventional tumour-node-metastasis (TNM) classification. Our study may provide a rationale for developing a novel immunotherapy in intentional induction of memory T cells for the treatment of oesophageal cancer.博士(医学)・乙第1300号・平成24年7月26日© 2012 The Authors;Clinical and Experimental Immunology© 2012 British Society for ImmunologyBlackwell Scientific Publications / British Society for ImmunologyThesisThesis or DissertationClinical and experimental immunology Vol.168 No.2 p.186-19100099104http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2772Clinical and experimental immunology, 168(2): 186-191http://hdl.handle.net/10564/2772http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2772/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2772/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf00099104AA00607716Clinical and experimental immunology16821861912012-05enghttp://www.ncbi.nlm.nih.gov/pubmed/22471279http://dx.doi.org/10.1111/j.1365-2249.2012.04565.xnone
oai:ginmu.naramed-u.ac.jp:10564/27802017-05-29T06:08:34Zhdl_10564_2756Significance of hyperglobulinemia in severe chronic liver diseases--with special reference to the correlation between serum globulin/IgG level and ICG clearance.重症慢性肝疾患における高γク口ブリン血症の意義 : とくに血清グ口プリン/IgG とICG除去能との相聞に関連してTanaka, ShinobuOkamoto, YasuyukiYamazaki, MasaharuMitani, NoriakiNakajima, YoshiyukiFukui, HiroshiHyperglobuiinemiaICGlg6Liver cirrhosisGlycosylationBACKGROUND/AIMS:Although hyperglobulinemia is frequently detected in severe chronic liver diseases (CLD) such as liver cirrhosis (LC), the mechanism for this is still uncertain. Hyperglobulinemia may represent a functional aspect of the liver.METHODOLOGY:
The correlation between serum globulin (GLB) level and each of various liver function tests including the indocyanine green (ICG) retention rate at 15 min (ICGR15) was studied using 146 patients with liver dysfunction. The correlations among GLB, IgG and ICGR15 were also studied in other 32 patients with LC, in whom the glycosylation pattern of IgG was determined by enzyme-linked immunosorbent assay to detect terminal galactose (Gal) and neuraminic acid (NA) using biotinylated lectins.RESULTS:GLB level was predominantly correlated with ICGR15 (r = 0.449) among various liver function tests in 146 patients with liver dysfunction. In the 32 patients with LC, strong positive correlations between GLB and IgG (r = 0.875), between GLB and ICGR15 (r = 0.435), and between IgG and ICGR15 (r = 0.557) were evident. The glycosylation pattern of IgG showed that the proportions of both Gal and NA were inversely correlated with serum IgG levels (r = -0.516 and -0.390, respectively) in these patients. Significant decreases of the proportions were found in patients with IgG elevation (> 20 g/L, n = 13).CONCLUSIONS:The correlation between GLB and ICGR15 suggested that hyperglobulinemia is related to a common dysfunction estimated by ICG clearance, which represents mainly the liver's blood flow and removal capacity. The removal of immunoglobulins by the liver may be impaired in patients with severe liver dysfunction because the liver is a major catabolic site for immunoglobulins. The glycation pattern suggested that the proportions of asialo IgG and agalactosyl IgG were increased in the LC patients with IgG elevation possibly by deficient receptor-mediated removal in the liver. Although further investigations will be needed, hyperglobulinemia could be predictive for a certain impaired hepatic function estimated by ICG clearance in severe CLD such as LC.博士(医学)・乙第1301号・平成24年7月26日Hepato Gastroenterology © 2007H.G.E. Update Medical PublishingThesisThesis or DissertationHepato-gastroenterology Vol.54 No.80 p.2301-230501726390http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2780Hepato-gastroenterology, 54(80): 2301-2305http://hdl.handle.net/10564/2780http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2780/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2780/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf01726390AA00213244Hepato-gastroenterology5480230123052007-12enghttp://www.ncbi.nlm.nih.gov/pubmed/18265652none
oai:ginmu.naramed-u.ac.jp:10564/27812017-05-29T06:08:34Zhdl_10564_2756Determination of advanced glycation end-products on IgG in liver cirrhosis.肝硬変におけるIgGの終末糖化産物量測定Tanaka, ShinobuYamazaki, MasaharuOkamoto, YasuyukiHyperglobulinemiaHepatic removal functionHalf-lifeNεε-(carboxymethyl) lysine (CML)BACKGROUND/AIMS:Our previous report showed that IgG levels are strongly correlated with the indocyanine green (ICG) retention rate in patients with liver cirrhosis (LC). This correlation suggests that hyperglobulinemia in LC could be explained by impairment of hepatic removal function. To estimate IgG turnover in LC, in the present paper was determined the advanced glycation end-products (AGE) on IgG as a marker of half-life.METHODOLOGY:Serum samples were obtained from patients with LC, rheumatoid arthritis (RA), and Sjögren syndrome (SjS), and from age-matched control patients. IgG was purified from serum by the protein G-based affinity method, concentrated by filtration, and used for assay of Nepsilon-(carboxymethyl) lysine (CML), a predominant AGE, by ELISA.RESULTS:CML on IgG was significantly lower in patients with LC than in control patients, whereas there was no significant difference in total serum CML levels among patients with LC, RA, and SjS, and control patients. CML levels on IgG were negatively correlated with serum IgG levels in patients with LC, RA, and Sjögren syndrome SjS.CONCLUSIONS:Based on these findings, it is suggested that IgG turnover is not likely to be prolonged but rather may be shortened in LC It may be concluded that, hyperglobulinemia is primarily caused by enhanced synthesis followed by up-regulation of catabolism of immunoglobulins.博士(医学)・乙第1301号・平成24年7月26日Hepato Gastroenterology © 2009H.G.E. Update Medical PublishingThesisThesis or DissertationHepato-gastroenterology Vol.56 No.96 p.1735-173701726390http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2781Hepato-gastroenterology, 56(96): 1735-1737http://hdl.handle.net/10564/2781http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2781/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2781/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf01726390AA00213244Hepato-gastroenterology5696173517372009-12enghttp://www.ncbi.nlm.nih.gov/pubmed/20214227none
oai:ginmu.naramed-u.ac.jp:10564/27822020-09-30T04:26:39Zhdl_10564_2756Carnitine-induced senescence in glioblastoma cells.神経膠芽腫細胞におけるカルニチンによるセネッセンスの誘導Yamada, ShuichiMatsuda, RyosukeNishimura, FumihikoNakagawa, IchiroMotoyama, YasushiPark, Young-SuNakamura, MitsutoshiNakase, HiroyukiOuji, YukiteruYoshikawa, MasahidecarnitineglioblastomasenescenceCarnitine is essential for lipid metabolism in cells and is known to possess antioxidant properties. Previous reports have suggested that antioxidants are able to induce senescence in glioblastoma cells, consequently, in the present study, we investigated the effect of carnitine on glioblastoma cells. Under conditions of hyponutrition (undernutrition), the proliferation of glioblastoma cells was attenuated and the level of intracellular carnitine was increased. Glioblastoma cell proliferation was also attenuated in cultures that were supplemented with exogenous carnitine, where the induction of senescence was detected by senescence-associated β-gal (SA-β-gal) staining. However, there was no evidence of the induction of apoptosis. These effects were not detected when cells were cultured with carnitine plus an inhibitor of p38 mitogen-activated protein kinase (MAPK). It, therefore, appears that carnitine has antioxidant actions in normal cells but induces senescence, which may be regarded as an opposite phenomenon, in glioblastoma cells. Senescence has been reported in cells exposed to temozolomide, which is a standard drug used for the treatment of glioblastoma. Carnitine could, therefore, represent an attractive alternative therapy for glioblastoma.博士(医学)・乙第1302号・平成24年11月27日Copyright © Spandidos Publications 2012Spandidos PublicationsThesisThesis or DissertationExperimental and therapeutic medicine Vol.4 No.1 p.21-2517920981http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2782Experimental and therapeutic medicine, 4(1): 21-25http://hdl.handle.net/10564/2782http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2782/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2782/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf17920981AA12610820Experimental and therapeutic medicine4121252012-07enghttp://www.ncbi.nlm.nih.gov/pubmed/23060917http://dx.doi.org/10.3892/etm.2012.556none
oai:ginmu.naramed-u.ac.jp:10564/27832017-05-29T06:08:34Zhdl_10564_2756Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach.再生骨組み込みコバルトクロム製インプラントと骨との早期固着性についての基礎的研究Ogawa, MunehiroTohma, YasuakiOhgushi, HajimeTakakura, YoshinoriTanaka, Yasuhitocobalt chromium alloyimplant-bone interfacemarrow mesenchymal cellosteogenesistissue engineeringTo establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation.博士(医学)・乙第1303号・平成24年11月27日© 2012 MDPI AGMDPI : Multidisciplinary Digital Publishing InstituteThesisThesis or DissertationInternational journal of molecular sciences Vo.13 No.5 p.5528-554114220067http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2783International journal of molecular sciences Vo. No. p., 13(5): 5528-5541http://hdl.handle.net/10564/2783http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2783/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2783/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf14220067AA12038549International journal of molecular sciences Vo. No. p.135552855412012-05enghttp://www.ncbi.nlm.nih.gov/pubmed/22754313http://dx.doi.org/10.3390/ijms13055528none
oai:ginmu.naramed-u.ac.jp:10564/27842017-05-29T06:08:34Zhdl_10564_2756Validity and reliability of the Japanese Orthopaedic Association score for osteoarthritic knees.変形性膝関節症患者に対するJOA スコアの妥当性と信頼性の検討Okuda, MasayoshiOmokawa, ShoheiOkahashi, KohjiroAkahane, ManabuTanaka, YasuhitoBACKGROUND:A variety of outcome measures are available to evaluate physical impairment and disability in patients with knee osteoarthritis, and most physician-rated measures are not validated. The objective of this study was to assess the validity and reliability of an observer-based knee scoring system of the Japanese Orthopaedic Association (the JOA) commonly used in Japanese clinical practice, and to determine demographic variables affecting the score. METHODS:A consecutive series of 85 patients with primary knee osteoarthritis completed the JOA (four domains pain on walking, pain on ascending or descending stairs, range of motion, and joint effusion), two validated patient-rated measures including the generic instrument of the Medical Outcomes Study 36-Item Short-Form (the SF-36) Health Survey, and the disease-specific scale of the Japanese Knee Osteoarthritis Measure (the JKOM), and a performance based timed-up-and-go test (TUG). Concurrent validity was determined by examining correlations of the JOA with the SF-36 and the JKOM. Construct validity was verified by correlating each domain of the JOA with objective measurements of TUG using Spearman's rank correlation coefficient. Intra- and interobserver reliability and internal consistency of the JOA were evaluated with another cohort of 32 patients who had a knee disorder at baseline and again at a mean of 18 days later. RESULTS:The JOA was significantly correlated with validated patient-rated outcome measures (the JKOM, the SF-36), indicating concurrent validity of the JOA. Domains of the JOA had significant correlations with the TUG, showing adequate construct validity. Intra- and interobserver reliability for the JOA showed a moderate to almost perfect agreement, and internal consistency of Cronbach's α indicated that the JOA score was a highly reliable instrument to assess knee osteoarthritis. As a demographic variable, age was highly correlated with the JOA. CONCLUSIONS:The JOA, generally used as an observer-derived knee scoring system, is a valid and reliable tool for evaluating functional status in patients with knee osteoarthritis.博士(医学)・乙第1304号・平成24年11月27日© Springer International Publishing AG,2012© The Japanese Orthopaedic Association 2012Springer Japan / Japanese Orthopaedic AssociationThesisThesis or DissertationJournal of orthopaedic science Vol.17 No.6 p.750-75609492658http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2784Journal of orthopaedic science, 17(6): 750-756http://hdl.handle.net/10564/2784http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2784/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2784/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf09492658AA11052566Journal of orthopaedic science1767507562012-11enghttp://www.ncbi.nlm.nih.gov/pubmed/22868702http://dx.doi.org/10.1007/s00776-012-0274-0none
oai:ginmu.naramed-u.ac.jp:10564/27852017-05-29T06:08:33Zhdl_10564_2756Branching pattern of lenticulostriate arteries observed by MR angiography at 3.0 T.3.OT MRA で観察される外側線条体動脈の分枝形態Akashi, ToshiakiTaoka, ToshiakiOchi, TomokoMiyasaka, ToshiteruWada, TakeshiSakamoto, MasahikoTakewa, MegumiKichikawa, KimihikoMRA3.0 TLenticulostriate arteryInfarctionLacunarPURPOSE:We hypothesized that the pattern of branching of the lenticulostriate arteries (LSAs) is involved in the variation of the distribution of the infarction within the LSA region. Our purpose was to evaluate the visibility of LSAs in 3D time-of-flight (TOF) MR angiography (MRA) with a 3.0 T scanner and to investigate the branching patterns of LSAs.MATERIALS AND METHODS:We performed 3D TOF MRA at 3.0 T for 100 healthy subjects. We assessed the number of LSAs and the number of branches arising from each LSA by evaluating MRA source images.RESULTS:In 200 hemispheres, 330 LSAs were visualized (mean = 1.65/hemisphere). In 3.5% of all hemispheres, no LSA was depicted; one LSA was depicted in 39%, two in 46.5%, and three in 11%. The maximum number of depicted LSA branches was five in 2% of all subjects, four in 7%, three in 26%, and two in 49% (mean = 2.3/subject). A large LSA trunk with three or more branches was found in 35% of subjects.CONCLUSION:
Visualization of LSAs was possible in 96.5% of subjects by use of 3.0 T MRA. LSA branching patterns were variable, and a large LSA trunk with three or more branches was common.博士(医学)・乙第1305号・平成24年11月27日© Springer International Publishing AG,2012Copyright © 2012 Japan Radiological SocietySpringer Japan / Japan Radiological SocietyThesisThesis or DissertationJapanese journal of radiology Vol.30 No.4 p.331-33518671071http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2785Japanese journal of radiology Vol. No. p., 30(4): 331-335http://hdl.handle.net/10564/2785http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2785/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2785/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf18671071AA12375935Japanese journal of radiology Vol. No. p.3043313352012-05enghttp://www.ncbi.nlm.nih.gov/pubmed/22350636http://dx.doi.org/10.1007/s11604-012-0058-7none
oai:ginmu.naramed-u.ac.jp:10564/27862017-05-29T06:08:33Zhdl_10564_2756Influence of mouth guards on autonomic nervous system activities: A quantitative study of pupillary flash responses.マウスガードの自律神経活動への影響 : 瞳孔フラッシュ応答による定量的評価Ishida, Jun-ichiWada, YoshiroImai, YuichiroHirata, YutakaYamashita, MasayukiKirita, TadaakiMouth guardsAutonomic nervous systemPupillary flash responsesUnpleasant sensationsSports injuriesBackground:Recently, it has been reported that mouth guards (MGs), which reduce the incidence and severity of traumatic oral injuries in contact sports, may actually affect sports performance. We have observed that a majority of subjects showed improved dynamic visual acuity during head rotation when using a MG, but subjects who were unwilling to use a MG showed the opposite effect. Thus, we hypothesized that unpleasant sensations due to MGs may decrease sports performance.Methods:In this study, we measured autonomic nervous system activity to evaluate unpleasant sensations objectively and quantitatively by measuring the pupillary flash response (PFR) and heart rate variability (HRV), before, during, and after wearing 3- and 5-mm-thick custom-made MGs in 10 healthy subjects.Results:It was found that the 5-mm MG had a higher incidence of unpleasant sensations (50% of subjects) than did the 3-mm MG (10%). PFR (not HRV) analysis showed that both sympathetic and parasympathetic nervous system activities increased in subjects with unpleasant sensations.Conclusions:We suggest that the unpleasant sensation induced this unusual autonomic nervous system response, which could not be detected by traditional methods such as HRV analysis. By using PFR analysis, it is possible to make MGs without unpleasant sensations for better sports performance.博士(医学)・乙第1306号・平成24年11月27日Copyright © 2012 Japanese Stomatological Society. Published by Elsevier Japan KKJapanese Stomatological Society / ElsevierThesisThesis or DissertationOral Science International Vol.9 No.2 p.38-4213488643http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2786Oral Science International, 9(2): 38-42http://hdl.handle.net/10564/2786http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2786/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2786/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf13488643AA1196972XOral Science International9238422012-11enghttp://dx.doi.org/10.1016/S1348-8643(12)00026-2none
oai:ginmu.naramed-u.ac.jp:10564/27872017-05-29T06:08:34Zhdl_10564_2756Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet.終末糖化産物(AGE) は高リノール酸および高グルコース摂取下のアゾキシメタン投与F344 ラットの大腸粘膜においてAGE 受容体(RAGE) を発現誘導するShimomoto, TakasumiLuo, YiOhmori, HitoshiChihara, YoshitomoFujii, KiyomuSasahira, TomonoriDenda, AyumiKuniyasu, HirokiColon carcinogenesisLinoleic acidSugarAGEBACKGROUND:Advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) are closely associated with colorectal cancer progression. The association between RAGE and AGE in colon carcinogenesis needs to be clarified.METHODS:Levels of RAGE and AGE were examined in azoxymethane (AOM)-injected Fischer 344 rats fed a control diet (Group C), a 15 % linoleic acid (LA) diet (Group L), a control diet with 10 % glucose drink (Group G), and a 15 % LA diet with 10 % glucose drink (Group L + G). Group L + G showed the most pronounced increase of body weight, blood sugar, and serum insulin.RESULTS:The rats in Group L + G showed the most pronounced multiplicity of aberrant crypt foci (ACF) and carcinomas with increased mucosal RAGE and AGE. IEC6 rat intestinal epithelial cells treated with AGE showed increased RAGE expression, which was inhibited by treatment with metformin or losartan. In the AOM-injected rat colon cancer model, the levels of RAGE and AGE, and the multiplicity of ACF and carcinomas, in Group L + G rats were suppressed by treatment with metformin or losartan.CONCLUSIONS:These results suggest that AGE-RAGE induced by high-LA and high-glucose diets substantially enhances colon cancer development; thus, suppression of AGE-RAGE could be a potential target for colon cancer chemoprevention.博士(医学)・乙第1307号・平成25年3月15日© Springer International Publishing AG,2012© Japanese Society of Gastroenterology 2012Springer / Japanese Society of GastroenterologyThesisThesis or DissertationJournal of gastroenterology Vol.47 No.10 p.1073-108309441174http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2787Journal of gastroenterology, 47(10): 1073-1083http://hdl.handle.net/10564/2787http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2787/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2787/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf09441174AA10988015Journal of gastroenterology4710107310832012-10enghttp://www.ncbi.nlm.nih.gov/pubmed/22467055http://dx.doi.org/10.1007/s00535-012-0572-5none
oai:ginmu.naramed-u.ac.jp:10564/27882017-05-29T06:08:33Zhdl_10564_2756Positive effect of daylight exposure on nocturnal urinary melatonin excretion in the elderly: a cross-sectional analysis of the HEIJO-KYO study.高齢者における日中光曝露が夜間尿中メラトニン分泌への与える影響 : 平城京スタディ横断解析Obayashi, KenjiSaeki, KeigoIwamoto, JunkoOkamoto, NozomiTomioka, KimikoNezu, SatokoIkada, YoshitoKurumatani, NorioCONTEXT:Melatonin is involved in a variety of diseases, including cancer, insomnia, depression, dementia, hypertension, and diabetes; its secretion is influenced by environmental light. Although daylight exposure increases nocturnal melatonin secretion in a controlled laboratory setting, whether it increases nocturnal melatonin secretion in an uncontrolled daily life setting remains unclear.OBJECTIVE:We aimed to determine the association between daylight exposure in an uncontrolled daily life setting and urinary 6-sulfatoxymelatonin excretion.DESIGN AND PARTICIPANTS:A cross-sectional study was conducted in 192 elderly individuals (mean age, 69.9 yr).MEASURES:We measured ambulatory daylight exposure using a wrist light meter in two 48-h sessions; furthermore, we measured overnight urinary 6-sulfatoxymelatonin excretion, an index of melatonin secretion, on the second night of each session.RESULTS:The median duration of daylight exposure of at least 1000 lux was 72 min (interquartile range, 37-124). Univariate linear regression analysis showed marginal to significant associations between log-transformed urinary 6-sulfatoxymelatonin excretion and age, current smoking status, benzodiazepine use, day length, log-transformed duration of daylight exposure of at least 1000 lux, and daytime physical activity. In a multivariate model, log-transformed duration of daylight exposure of at least 1000 lux was significantly associated with log-transformed urinary 6-sulfatoxymelatonin excretion (regression coefficient, 0.101; 95% confidence interval, 0.003-0.199; P = 0.043). Furthermore, an increase in the duration of daylight exposure of at least 1000 lux from 37 to 124 min (25th to 75th percentiles) was associated with a 13.0% increase in urinary 6-sulfatoxymelatonin excretion (6.8 to 7.7 μg).CONCLUSIONS:Daylight exposure in an uncontrolled daily life setting is positively associated with urinary 6-sulfatoxymelatonin excretion in the elderly.博士(医学)・乙第1308号・平成25年3月15日Copyright © 2012 by The Endocrine SocietyEndocrine SocietyThesisThesis or DissertationThe Journal of clinical endocrinology and metabolism Vol.97 No.11 p.4166-41730021972Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2788The Journal of clinical endocrinology and metabolism, 97(11): 4166-4173http://hdl.handle.net/10564/2788http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2788/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2788/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf0021972XAA00695484The Journal of clinical endocrinology and metabolism9711416641732012-11enghttp://www.ncbi.nlm.nih.gov/pubmed/22948764http://dx.doi.org/10.1210/jc.2012-2561none
oai:ginmu.naramed-u.ac.jp:10564/27892017-05-29T06:08:36Zhdl_10564_2756The dichotomy in the histogenesis of endometriosis-associated ovarian cancer: clear cell-type versus endometrioid-type adenocarcinoma.子宮内膜症と関連する卵巣癌 : 明細胞腺癌と類内膜腺癌の発癌機序における相違点Kajihara, HirotakaYamada, YoshihikoShigetomi, HiroshiHigashiura, YumiKobayashi, HiroshiEndometriosisOvarian cancerEndometrioidClear cellImmunohistochemistryThe histogenesis of endometriosis and endometriosis-associated ovarian cancer is one of the most mysterious aspects of pathology. To better understand the histogenesis of endometriosis and endometriosis-associated ovarian cancer, we analyzed the possibility of a link of endometrium, ovarian surface epithelium, and a cortical inclusion cyst to ovarian endometriosis and endometriosis-associated ovarian cancer by immunohistochemistry using the epithelial membrane antigen (an epithelial marker), calretinin (a mesothelial marker), and hepatocyte nuclear factor (HNF)-1β (a clear cell carcinoma-specific transcription factor). During ovarian surface epithelium invagination, cortical inclusion cyst epithelial cells may, in some cases, undergo mesothelial–epithelial transition and subsequently differentiate into endometriosis. This case of endometriosis that has undergone Müllerian metaplasia arises from the HNF-1β-negative cells. The remaining endometriosis may develop from the late secretory and menstrual endometria, with HNF-1β-positive staining, by retrograde menstruation. Endometrioid adenocarcinoma and clear cell carcinoma arise from the HNF-1β-negative and HNF-1β-positive epithelial cells of endometriosis, respectively. It has been proposed that clear cell and endometrioid-type adenocarcinomas arise from distinct types of endometriosis with different cells of origin.博士(医学)・乙第1309号・平成25年3月15日©2012 International Society of Gynecological PathologistsLippincott Williams & Wilkins / International Society of Gynecological PathologistsThesisThesis or DissertationInternational journal of gynecological pathology Vol.31 No.4 p.304-31202771691http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2789International journal of gynecological pathology, 31(4): 304-312http://hdl.handle.net/10564/2789http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2789/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2789/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf02771691AA1063069XInternational journal of gynecological pathology3143043122012-06enghttp://www.ncbi.nlm.nih.gov/pubmed/22653342http://dx.doi.org/10.1097/PGP.0b013e318243a97bnone
oai:ginmu.naramed-u.ac.jp:10564/27902017-05-29T06:08:35Zhdl_10564_2756ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia-reperfusion injury.ADAMTS13 遺伝子欠損は脳虚血再灌流傷害における血漿high mobility group box1 の上昇を促進し神経炎症を悪化させる。Fujioka, MasayukiNakano, TakafumiHayakawa, KazuhideIrie, KeiichiAkitake, YoshiharuSakamoto, YuyaMishima, KenichiMuroi, CarlYonekawa, YasuhiroBanno, FumiakiKokame, KoichiMiyata, ToshiyukiNishio, KenjiOkuchi, KazuoIwasaki, KatsunoriFujiwara, MichihiroSiesjö, Bo K.Brain ischemia–reperfusionHigh-mobility group box1ADAMTS13InflammationVon Willebrand factorThrombotic thrombocytopenic purpuraHighly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia–reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia–reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24 h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24 h after MCAO (p < 0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia–reperfusion (p < 0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia–reperfusion injury by regulating VWF-dependent inflammation as well as microvascular plugging.博士(医学)・乙第1310号・平成25年3月15日© Springer International Publishing AG,2012Springer / Società italiana di neurologiaThesisThesis or DissertationNeurological sciences Vol.33 No.5 p.1107-111515901874http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2790Neurological sciences, 33(5): 1107-1115http://hdl.handle.net/10564/2790http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2790/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2790/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf15901874AA11469873Neurological sciences335110711152012-10enghttp://www.ncbi.nlm.nih.gov/pubmed/22212812http://dx.doi.org/10.1007/s10072-011-0913-9none
oai:ginmu.naramed-u.ac.jp:10564/29372017-05-29T06:09:03Zhdl_10564_2717Expression of REG Ⅲ and prognosis in head and neck cancer頭頸部癌におけるREG Ⅲ の発現と予後Masui, TakashiOta, IchiroItaya-Hironaka, AsakoTakeda, MaikoKasai, TakahikoYamauchi, AkiyoSakuramoto-Tsuchida, SumiyoMikami, ShinjiYane, KatsunariTakasawa, ShinHosoi, HiroshiREG Ⅲhead and neck cancerchemoradiosensitivityIdentification of a reliable biomarker for predicting prognosis in head and neck cancers is highly desirable and has long been sought. There have been several reports that members of the regenerating gene (REG) family are highly expressed in chronic inflammation and in tumors of the digestive organs. In addition, it has been described in several reports that REG expression is associated with the progression of digestive cancers. In the present study, we evaluated the effect of REG expression on the prognosis of hypopharyngeal cancer. We investigated 37 cases with hypopharyngeal squamous cell carcinoma, determined REG mRNA expression, which is easily detected in formalin-fixed paraffin-embedded tissues using the real-time reverse transcriptase-polymerase chain reaction method, and evaluated the survival rate using the Kaplan-Meier method. According to these results, REG Ⅲ mRNA expression was significantly associated with prolonged survival. Therefore, we constructed hypopharyngeal cancer cell lines transfected with REG Ⅲ and assessed the cell proliferation and chemosensitivity and/or radiosensitivity in vitro. Cells transfected with REG Ⅲ exhibited significantly lower cell proliferation and higher chemosensitivity and/or radiosensitivity compared with the control cells. These data suggest that REG Ⅲ may be a reliable biomarker of prognosis in hypopharyngeal cancer. This is the first report concerning the association of REG Ⅲ expression and the prognosis of head and neck squamous cell carcinoma including hypopharyngeal cancer.博士(医学)・甲第625号・平成27年3月16日本文のリンク:http://dx.doi.org/10.3892/or.2013.2521Copyright © Spandidos Publications 2014National Hellenic Research Foundation / SpandidosThesisThesis or DissertationOncology reports Vol.30 No.2 p.573-5781021335Xhttp://ginmu.naramed-u.ac.jp/dspace/handle/10564/2937Oncology reports, 30(2): 573-578http://hdl.handle.net/10564/2937http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2937/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2937/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdfhttp://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2937/3/03%e6%9c%ac%e6%96%87.pdf1021335XAA11016405Oncology reports3025735782013-08enghttp://www.ncbi.nlm.nih.gov/pubmed/23743605http://dx.doi.org/10.3892/or.2013.2521ETD24601A6252015-03-16博士(医学)奈良県立医科大学
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