Acta Medica Okayama2007Improving the Water Use Efficiency and Quality of Muscat of Alexandria Grapes by Partial Root-zone Drying and Regulated Deficit IrrigationENDiaa OsamaEl-AnsaryNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007気温上昇が水稲,ダイズの生育収量,乾物生産におよぼす影響ENIzumiOh-eNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007メロン果実の成熟関連形質とエチレンシグナル伝達系ENKiyomiNishiyamaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007エンドウ細胞壁における病原菌シグナル認識・応答機構の解析 −病原菌シグナルに応答するアポプラストCu/Zn-SODについて−ENTomonariKasaiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007高速酸化物イオン伝導体ランタンガレート系ペロブスカイト化合物の結晶構造と伝導特性に関する研究ENMasahiroKajitaniNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007油の流動帯電に関する基礎研究ENショウシンズゥンNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007ガスエンジンの燃焼排出物と性能特性に関する研究ENNobuhikoFukataniNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Experimental and Numerical Study on Flow Drag Reduction and Heat Transfer of Surfactant Solutions in Straight and Helical PipesENIbrahim Ahmed AlyWaelNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007液体サイクロンに伴う旋回流に関する研究ENMitsuhiroTaniwakiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007鉄鋼スラグ水和固化体の性能改善と設計手法に関する研究ENTakashiFujiiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007鉛直ジョイント部の離接をモデル化したアーチダムの堤体挙動解析に関する研究ENTatsuoNishiuchiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007河道内植生の管理と礫河原再生に関する研究ENSatoshiWatanabeNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Studies on the Assessment of Management Frameworks for Waste Electronic Home AppliancesENシェンビンリュウNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007大気−海洋間のCO2交換測定方法についての研究ENKeikoYoshikawaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007System Engineering Approach for Improvement in Healthcare Waste ManagementENMochammadChaerulNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007渦相関法による大気−海洋間の二酸化炭素輸送量の直接測定に関する研究ENFumiyoshiKondoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007三畳系成羽層群分布地域に発生する地すべりの地質素因 −小褶曲構造と“破砕炭質層”に規制される地すべり−ENHajimeTanakaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Stable carbon and hydrogen isotopic compositions of organic matter in carbonaceous meteorites and its implication to alteration processesENYasuhiroOhbaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Paleoenvironments of the late Middle to early Late Miocene Chiang Muan Formation in northern ThailandENAkiraFukuchiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Characterization of a novel reovirus isolated in a hypovirulent stain (9B21) of the chestnut blight fungus that is infectious as particlesENSupyaniNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Studies on the biological properties of Beet necrotic yellow vein virus RNA4ENMuhammad DahialRahimNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007植物のセリンラセマーゼの構造と機能に関する研究ENYoshiyukiFujitaniNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007殺虫剤亜致死薬量処理による卵サイズ小型化が、コナガ抵抗性発達と感受性回復過程に関与する機構ENXueDongChenNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007タガメと餌動物および捕食者間の種間相互作用に関する生態学的研究ENShinyaOhbaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Ecological study on expansion pattern and process of bamboo forests in urban fringes of JapanENFabiola BabySaroinsongNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007植物由来色素による血圧抑制作用に関する研究ENMakotoShindoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Studies on Biological and Chemical Conversion of Microbial Secondary MetabolitesENPanarratArunrattiyakornNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Physiological roles of interleukin-18 in the mouse uterus and pituitaryENKenjiKusumotoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Molecular aspects of hatching and heat stress response in decapod crustaceansENOlegGusevNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Tissue-specific interactions of Troponin I with other TN subunits and tropomyosins isoforms in Caenorhabditis elegansENAminMd. ZiaulNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Genomic distribution of and transcriptional control by a novel non-coding DNA in Caenorhabditis elegansENYasuoTakashimaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Creation of the human betacellulin mutein with low affinity for ErbB1ENTadahiroNagaokaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007機能性遺伝子の細胞内送達のための新規システムである遺伝子治療用センダイウイルスベクター改良のための基盤研究ENMarikoYoshizakiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Analysis of an antigen-stimulated B cell migration into germinal centers during a T-dependent immune responseENEmiKouyamaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Structure Analysis of Diol Dehydratase-Reactivating Factor and Characterization of Ethanolamine Ammonia Lyase-Reactivating FactorENNaokiHiedaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007新規バイオセンサのための酸化還元酵素の機能検出法および人工機能付与法の研究ENAkiraFujiiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007New Antimalarial Endoperoxides: Action and Resistance Analysis Against Plasmodium falciparum Malaria ParasitesENNagwa ShabanMohamed ALYNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007血管周囲神経を介したニコチンによる血管弛緩反応機序に関する神経薬理学的研究ENShinjiEguchiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007血清タンパク質との相互作用の解析に基づく微粒子性薬物キャリアーの肝移行動態制御に関する研究ENSusumuNagayamaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007胃粘膜付着性細粒剤に関する研究ENNaokiNagaharaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007難水溶性薬物 Ca++拮抗剤ニルバジピンの固体分散体を適用した新規持続性製剤の設計と評価ENNobuyukiTanakaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Vibrio vulnificus溶血毒素の分子生物学的研究ENMitsutoshiSenoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007霊長類CYP2C酵素の構造と機能に関する研究: CYP2C19を中心にしてENKeitaSaitoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Studies on the structural protein of the toxin-converting phage and the vaccine effect of different size of recombinant neurotoxin-proteins of Clostridium botulinum type C and DENHyun-JungHwangNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007緑膿菌の多剤排出ポンプMexHI-OpmDの解析ENHiroshiSekiyaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007水溶性金属ポルフィリン固定化担体のカテコールアミン類に対する酸化触媒機能に関する研究ENTsutomuTakatsukiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007分子内ビアリールカップリング反応を利用する天然有機分子の合成研究ENShigemitsuTakedaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007SYNTHESES AND PROPERTIES OF THE IRON OXIDES MATERIALSENMD. TAREQULISLAM BHUIYANNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007衣服の着用性能の客観評価に関する研究ENNobuyukiMichiakiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Studies on Novel Collection/Concentration Resins for Trace Elements Using Chitosan as Polymer Base and Their Analytical ApplicationsENAkhmadSabarudinNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007励起芳香族化合物と脂肪族アミン間の多様な励起錯体形成と発光スペクトルの溶媒効果ENToyaSuchinNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Elucidation of Chemiluminescence Reaction of Lophine PeroxidesENGonhoRuNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Studies on Cyanine Dye and Acridine Dye Dimer ModelsENTakeshiFukaiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007人間工学分野への応用のための長さ・時間の感覚・知覚特性の解明ENMisorokuSoraiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007柔軟機能要素の開発と柔軟索状ロボットへの応用ENSyuichiWakimotoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007金融工学技術の生産管理への応用ENTakashiIwamotoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007化学プラントにおけるLCAの実行支援モデル及び事故の関連分析に関する研究ENHaityunFunNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007単一工程における異なる組立時間及び部品価格に基づく製品の投入順序決定法ENZyazyunZanNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007トラクション性能に及ぼすクラウニングの影響ENBayasgalanSeesregdorjNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007転がり軸受用新材料の寿命特性に関する研究ENHiroshiOhsakiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007プラズマを利用した,窒化アルミニウム,炭化珪素,及び,窒化硼素膜作製手法の研究ENYujiMorikawaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007一次元および単分子磁性体の極低温電子物性ENKoichiKajiyoshiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007シリコン中の白金−水素複合欠陥における水素の運動に関する研究ENNamulaBaoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007The Role of the Government Incentive & Assistance in Encouraging Investment and Employment in the UKENCan TekinAbdulkadirNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007戦略的R&D投資とスピルオーバーENKatsunariOhhashiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007A Study of Risk Reporting on Japanese Company -Focus on the Practice in Annual Reports and Security Reports-ENMd. MohobbotAliNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007国際仲裁と国際私法ENHakuteiGenNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007わが国における治療決定過程の特質と手続的正義の研究 ―重症障害新生児の治療選択における医療的基準と当事者の支援―ENMiekoYamaguchiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007近世の善事褒賞と家族・女性 ―岡山藩を中心にして―ENAtsukoMegaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Effects of Scutellaria Baicalensis Georgi on Virulence Factors of Mutans StreptococciENShun-enDanNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007太陽電池を付与した棒状半導体酸化チタンの歯科臨床応用への可能性−Streptococcus mutansに対する光触媒効果−ENHarumiIshiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007鉄ニトリロ三酢酸によるラット脳における酸化ストレス反応に関する研究ENIchiroNakatsukaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007ビスフォスフォネートの局所投与による義歯床下組織の骨動態の変化に関する研究ENShunshiHanadaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007骨髄由来間質細胞の接着,増殖,遊走に対するCCN2/CTGFの効果−新たな骨再生療法の確立に向けて−ENMitsuakiOnoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007象牙質接着におけるレジンの親水性の影響ENYukinoriHayashiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007フッ素徐放性ワンステップ接着システムのう蝕象牙質への接着性ENKyoukaTyoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007EFFECTS OF SPHERICAL SIRICA FILLER ADDITION ON IMPROVING THE MECHANICAL CHARACTERISTICS OF REZIN-MODIFIED GLASS-IONOMER CEMENTENKenjiHatanakaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007CCN2/CTGFによるコラーゲン特異的分子シャペロンHSP47/関節リウマチ関連抗原RA-A47発現変動とその意義ENMayumiYaoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007口腔癌細胞におけるDNAメチル化による放射線耐性獲得機構に関する研究ENMikiKatsuranoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007骨破壊部における癌細胞のMMP-13の発現制御機構に関する研究ENSoichiroIbaragiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007骨破壊部において癌細胞自身の産生する副甲状腺ホルモン関連蛋白による血管内皮増殖因子の制御およびその作用に関する研究ENSachikoIsowaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007歯肉線維芽細胞上のヒト白血球抗原クラスII 分子を介したサイトカインの産生に関与する細胞内シグナル伝達分子に関する研究ENSayuriYoshizawaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007ラット創傷歯髄から単離したFIP-2 遺伝子の発現動態およびその炎症制御因子と細胞死に与える影響ENKyokoSenooNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Biological Analysis of a Candidate Stem Cell -KUSA/A1 cell- for Bone Tissue EngineeringENPaolaRodriguez AndreaThe basic principle of bone induction for tissue engineering is to use stem cells, growth factors and organic matrix. KUSA/A1 cell is an example of bone marrow stromal stem cell, capable of differentiating into osteoblasts, chondrocytes and myotubes under inducing conditions. It has been reported that mature KUSA/A1 osteoblasts cultured in osteogenic condition, were able to induce a few bone formation in collagen hybridized PLGP sponge in vivo. This may be due to their low proliferation potential thereby not being able to obtain sufficient number of cells to promote large tissue repair. Because of this, in order to use KUSA/A1 cells with high cell proliferation activity to induce large amount of new bone, we evaluated whether KUSA/A1 cells in non-induction condition will maintain their immature stage. The result demonstrated that KUSA/A1 cells cultured in α-MEM maintained their immature stage in vitro. We further examined the osteoblastic differentiation under the influence of the host microenvironment in intraperitoneal diffusion chamber. The results indicated that immature KUSA/A1 cells in vivo cell culture differentiated into osteoblasts and produced mineralized bone-like tissue. Finally, we evaluated the effect of honeycomb scaffold to produce abundant bone formation using KUSA/A1 cells implanted in subcutaneous tissues of SCID mice. 1x10^6KUSA/Al cells with honeycomb scaffold showed abundant new bone formation. While, 5x10^6KUSA/Al cells alone showed only few small islands of new bone formation. This study support that KUSA/A1 cell is a good candidate as stem cells for basic research in bone tissue engineering.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Role of Heparanase in the Release of Heparan Sulphate Binding Growth Factors in Odontogenic TumorsENHanPhuu PwintImmunolocalization of heparan sulphate(HS) and heparanase was evaluated in benign and malignant odontogenic tumors in order to know whether these molecules have potential roles in odontogenic tumorigenesis. Archival formalin-fixed, paraffin-embedded tissues of 6 human tooth germs, 7 adenomatoid odontogenic tumors, 10 ameloblastic fibromas, 20 ameloblastomas and 4 ameloblastic carcinomas were subjected to immunohistochemical staining using antibodies to HS, heparanase and BMP-4. HS was ubiquitously localized in tooth germ but heparanase and BMP-4 were observed in limited areas only. In benign epithelial tumors such as ameloblastoma and adenomatoid odontogenic tumor, these molecules were localized in neoplastic epithelium but in ameloblastic fibroma, positive reactions were observed in both epithelial and mesenchymal cells. Stromal localization of HS and BMP-4 accompanied by intense immunoexpression of epithelial heparanase was observed in ameloblastic carcinoma,and this may represent the malignant progression of ameloblastoma to ameloblastic carcinoma. Stronger intensity and more diffuse localization of heparanase in odontogenic tumors compare to that of human tooth germ was the most significant finding. Taken together, the results inferred that heparanase may be responsible for the growth and progression of odontogenic tumors by modulating the availability and function of HS binding growth factors and the derangement in immunoexpression and localization of HS and heparanase molecules may have important roles in progression of malignant odontogenic tumors.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Fine deletion mapping of chromosome 2q21-37 shows three preferentially deleted regions in oral cancerENBeyhanCengizWe analysed the loss of heterozygosity (LOH) of long arm of chromosome 2 by using 16 polymorphic microsatellite markers in 39 matched oral normal and cancer tissues, and defined the deletional mapping of the region with putative tumor suppressor genes. LOH was detected at least one location in 33 of 39 (85%) tumor tissues. Frequent deletions were detected at the locations of microsatellite markers, D2S2304 (35%), D2S111 (40%), D2S155 (35%), D2S1327 (29%), D2S164 (29%), D2S125 (68%) and D2S140 (32%). Three preferentially deleted regions at 2q21-24, 2q33-35 and 2q37.3 were observed. Several candidate tumor suppressor genes in these regions such as LRP1B, CASP8, CASP10, BARD1, ILKAP, PPP1R7, and ING5, are located. Further molecular analysis of each gene should be performed to clarify their roles in oral carcinogenesis.No potential conflict of interest relevant to this article was reported.Acta Medica OkayamaA human β-cell line for transplantation therapy to control type 1 diabetesENMichikiNarushimaA human pancreatic beta-cell line that is functionally equivalent to primary beta-cells has not been available. We established a reversibly immortalized human beta-cell clone (NAKT-15) by transfection of primary human beta-cells with a retroviral vector containing simian virus 40 large T-antigen (SV40T) and human telomerase reverse transcriptase (hTERT) cDNAs flanked by paired loxP recombination targets, which allow deletion of SV40T and TERT by Cre recombinase. Reverted NAKT-15 cells expressed beta-cell transcription factors (Isl-1, Pax 6, Nkx 6.1, Pdx-1), prohormone convertases 1/3 and 2, and secretory granule proteins, and secreted insulin in response to glucose, similar to normal human islets. Transplantation of NAKT-15 cells into streptozotocin-induced diabetic severe combined immunodeficiency mice resulted in perfect control of blood glucose within 2 weeks; mice remained normoglycemic for longer than 30 weeks. The establishment of this cell line is one step toward a potential cure of diabetes by transplantation.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Bilateral native lung-sparing lobar transplantation in a canine modelENSeiichiroSugimotoOBJECTIVE: Bilateral living-donor lobar lung transplantation has become an accepted approach in response to the cadaveric lung donor shortage. Because only one lobe is implanted in each chest cavity, this procedure is usually confined to patients of small size. The purpose of this study was to develop a technique of bilateral native lung-sparing lobar transplantation that can be applied to large adult patients. METHODS: Bilateral native lung-sparing lobar transplantation was performed in 12 pairs of dogs. In donor animals the right middle, lower, and cardiac lobes were separated as a right graft, and the left lower lobe was separated as a left graft. In recipient animals these 2 grafts were implanted in the natural anatomic position with sparing native right upper, left upper, and middle lobes. In an acute study (n = 6), transplanted graft function was assessed for 3 hours after ligation of the pulmonary artery branches to the native spared lobes. In a chronic study (n = 6) the immunosuppressed recipients were observed for 3 weeks to assess the quality of bronchial healing and long-term pulmonary function. RESULTS: Morphologic adaptation of the 2 grafts was found to be excellent. All 6 animals in the acute study showed excellent pulmonary function. Five of 6 animals in the chronic study survived for 3 weeks, with excellent pulmonary function and satisfactory bronchial healing. CONCLUSION: Bilateral native lung-sparing lobar transplantation was technically possible and associated with excellent pulmonary function and good bronchial healing in a canine experimental model.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Effect of glutamate receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated ratsENYoichiKawasakiThe neurobiological mechanism underlying the negative motivational component of withdrawal from acute opiate dependence is far from understood. Our objectives were to determine whether the glutamatergic system is involved in the motivational component of morphine withdrawal in acutely dependent rats and such an involvement is associated with dopaminergic neurotransmission. We examined the effects of various kinds of glutamate receptor antagonists on conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before. Furthermore, the influence of pretreatment with the dopamine receptor antagonist haloperidol on those effects of glutamate receptor antagonists was also investigated. CPA was attenuated in a dose-dependent manner by all glutamate receptor antagonists examined including the NMDA receptor antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK-801) and phencyclidine hydrochloride (PCP), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), and metabotropic receptor antagonists (+/-)-2-amino-3-phosphonopropionic acid (AP-3) and (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG). The effects of MK-801, GYKI 52466 and MCPG were blocked by haloperidol.These results suggest that the glutamatergic system involving multiple classes of receptors plays a role in the motivational component of withdrawal from acute morphine dependence, and the function of the glutamatergic system would be closely associated with dopaminergic neurotransmission.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Maintenance of Neovascularization at the Implantation Site of an Artificial Device by bFGF and Endothelial Cell TransplantENAtsushiMikiDevelopment of a subcutaneously implantable bioartificial pancreas (BAP) with immunoisolatory function could have a great impact on the treatment of diabetes mellitus. We have developed an implantable BAP device with an ethylene vinyl alcohol (EVAL) membrane. In the present study, we used basic fibroblast growth factors (bFGF), which was incorporated in a carrier for sustained release, in order to induce neovascularization when the device was implanted subcutaneously. To maintain the vasculature thus formed, a cell infusion port was attached to the BAP device, through which the device was filled with human liver vascular endothelial cell line TMNK-1, and the vasculature could be adequately maintained. Mice were divided into the following three groups. In group 1, a bFGF-free BAP device was implanted subcutaneously. In group 2, a sustained-release bFGF-impregnated BAP device was implanted. In group 3, a sustained-release bFGF-impregnated BAP device was implanted, and 3 x 10(6) TMNK-1 cells were infused into the implanted device every week. Neovascularization induced in the subcutaneous tissue around the implanted BAP device was macroscopically examined and histologically evaluated. In addition, the tissue blood flow was measured using a laser blood flow meter. In mice in group 3, neovascularization was significantly induced and maintained until week 8 postimplantation. It was confirmed by scanning electron microscopy that infused TMNK-1 cells adhered to the inner polyethylene surface of the device. It was demonstrated that the use of bFGF and vascular endothelial TMNK-1 cells induced and maintained adequate vasculature and tissue blood flow surrounding the implantable bag-type BAP device. We believe that the present study will contribute to BAP development for the treatment of diabetes.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Prolonged Survival of Mice with Acute Liver Failure with Transplantation of Monkey Hepatocytes Cultured with an Antiapoptotic Pentapeptide V5ENKimiakiTanakaBACKGROUND: Because hepatocyte transplantation has been considered to be an attractive method to treat acute liver failure (ALF), efficient recovery of hepatocytes and maintenance of differentiated hepatocyte functions is of extreme importance. We here report the usefulness of an antiapoptotic pentapeptide V5, composed of Val-Pro-Met-Leu-Lys, in the monkey hepatocyte cultures. METHODS: We evaluated albumin production, metabolizing abilities of ammonia, lidocaine, and diazepam of monkey hepatocytes cultured with V5. The protein expression of apoptosis-associated molecules was analyzed using power blot analysis. An unwoven cloth inoculated with V5-treated monkey hepatocytes was transplanted on the surface of the spleen of both SCID mice and Balb/c mice suffering from ALF induced by 90% hepatectomy. RESULTS: When 100 microM V5 was utilized, ammonia-, lidocaine- and diazepam- metabolizing capacities and albumin production ability were significantly increased in V5-treated monkey hepatocytes. Such hepatocytes showed decreased Annexin V binding and increased the expression of anti-apoptotic and/or cytoprotective molecules, including Ku70, NF-kappaB, IKAP, hILP/XIAP, IkappaB, and CAS. Transplantation of the cloth containing the monkey hepatocytes significantly improved blood levels of glucose and ammonia and encephalopathy score and prolonged the survival of the mice with ALF. CONCLUSIONS: The present work clearly demonstrates the usefulness of V5 for maintaining the functions of monkey hepatocytes in tissue culture.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007The effect of ciprofloxacin on CD14 and toll-like receptor-4 expression on human monocytesENGotaroKatsunoCD14/toll-like receptor (TLR)-4 complex on monocytes/macrophages can bind lipopolysaccharide (LPS) and transduce the signals intracellularly. An antibacterial drug, ciprofloxacin (CIP), has been reported to modulate the inflammatory and immune responses. In the present study, we examined the effects of CIP on the LPS-induced activation of monocytes isolated from human peripheral blood mononuclear cells (PBMC). CIP suppressed the expression of CD14, TLR-4, intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, and CD40 and the production of tumor necrosis factor (TNF)-alpha induced by LPS in monocytes. CIP induced the production of prostaglandin (PG)E2 and increased intracellular cyclic adenosine monophosphate (cAMP) levels. Cyclooxygenase (COX)-2 inhibitors, NS398 and indomethacin, reversed the effects of CIP on TNF-alpha production and reduced the levels of different surface antigens, whereas a protein kinase A (PKA) inhibitor, H89, did not. Therefore, CIP might regulate the TNF-alpha production induced by LPS by inhibiting the expression of LPS receptor complex, which seems to be mediated by COX-2 but not the cAMP/PKA pathway.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Health Impact Assessment of Particulate Matter in Tokyo, JapanENTakashiYorifujiAmong industrialized countries, Japan still maintains an old set of guidelines for particulate matter (PM); therefore, we assessed the public health impacts of PM exposure in various situations using data from the Tokyo metropolitan area. Subjects were 7.8 million people aged older than 30 years. Based on a linear relationship between exposure and health effects, we estimated attributable cases of mortality caused by PM. Even at the recent exposure level, the number of deaths will occur after both short- and long-term exposure. When the guideline for PM2.5 (particles < 2.5 microm in diameter) long-term exposure was set at 12 microg/m3, we could prevent 8% of all causes mortality or 6,700 deaths in the Tokyo metropolitan area per year. This assessment shows that guidelines for long-term exposure, especially for PM2.5, should be recommended in Japan.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Supervisors’ attitudes and skills for active listening with regard to job stress and psychological stress reactions among subordinate workersENSachikoMineyamaWe investigated whether supervisors' listening attitudes and skills were related to working conditions and psychological stress reactions among their subordinates. The subjects included 41 male supervisors and their immediate subordinates (n=203). The supervisors completed a short version of the Active Listening Attitude Scale (ALAS) consisting of two subscales: Listening Attitude and Listening Skill for Active Listening. The subordinates rated working conditions and their psychological stress reactions using selected scales of the Job Content Questionnaire and the Brief Job Stress Questionnaire. Those subordinates who worked under supervisors with a higher score of Listening Attitude and Listening Skill reported a more favorable psychological stress reaction than those who worked under supervisors with a lower score of Listening Attitude and Listening Skill. Those subordinates who worked under supervisors with a higher score of Listening Skill reported higher worksite support than those who worked under supervisors with a lower score of Listening Skill. Those subordinates who worked under supervisors with a higher score of Listening Attitude reported higher job control than those who worked under supervisors with a lower score of Listening Attitude. A supervisor's listening attitude and skill appeared to affect psychological stress reactions predominantly among male subordinates than among female subordinates. Psychological stress reactions were lower among younger subordinates who worked under supervisors with high listening skill, while no statistically difference was observed among older subordinates. These findings suggest that a supervisor's listening attitude and skill have an effect on working conditions and psychological stress reactions among subordinates and that the effects vary according to the subordinates' sex and age.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007The Immediate Effects of 10-minute Relaxation Training on Salivary Immunoglobulin A (s-IgA) and Mood State for Japanese Female Medical Co-workersENToshiyoTaniguchiThis study examined the effects of relaxation training on salivary IgA (s-IgA) and mood state in Japanese female medical workers. Participants were enrolled and assigned to relaxation or control groups. The relaxation group Japanese female medical workers (n = 38, mean age = 33.5 years, SD = 9.6) participated in a lecture on stress for 1 h and had 10 min of relaxation training. The control group (n = 41, mean age = 35.0 years, SD = 8.6) participated in only the lecture. S-IgA was measured, and a self-report mood questionnaire administered before the lecture and then again after the relaxation training for the relaxation group. The control group was measured before and after the lecture. The results showed that s-IgA levels significantly increased after relaxation training in the relaxation group compared with the control group (p = 0.03). A marginally significant intervention effect was observed for mood state (p = 0.06) ; indicating that the relaxation group was more likely to reduce any fatigue and confusion than was the control group. These findings suggest that short-time relaxation training is effective in relaxing mood and causes changes in immunological function.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Practicality of Veterans Specific Activity Questionnaire in Evaluation of Exercise Capacity of Community-Dwelling Japanese ElderlyENShinjiKojimaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Human milk SIgA binds to botulinum type B 16S toxin and limits toxin adherence on T84 cellsENTakuhiroMatsumuraBotulinum neurotoxin produced by Clostridium botulinum type B is in the form of a complex of 12S and 16S toxins. Food-borne botulism is caused by these complex toxins which are ingested orally and absorbed from the digestive tract. Here, we show that the human milk SIgA binds to the type B16S toxin. The binding of SIgA to 16S toxin and HA was inhibited by carbohydrates such as galactose, suggesting that the interaction of carbohydrate side chain of the SIgA with the HA of the 16S toxin is important for SIgA-16S complex formation. We also demonstrate that SIgA inhibits the attachment of 16S toxin to intestinal epithelial cells. These data suggest that the interaction of antigen nonspecific SIgA with 16S toxin has a large influence on the absorption of 16S toxin from the intestinal epithelium, and that SIgA may provide insight into developing a therapeutic agent for type B food-borne botulism.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a toll-like receptor (TLR) 2 and mitogen-activated protein (MAP) kinase pathway in human monocytesENYingZhaoPrevious reports have indicated that Helicobacter pylori heat-shock protein 60 (H. pylori-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by which H. pylori-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by which H. pylori-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. Intact H. pylori, heat-killed H. pylori and H. pylori recombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 h in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partially inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-kappaB (NF-kappaB)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-kappaB activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway in H. pylori-HSP60-induced IL-8 secretion.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007ボツリヌスB型16S毒素のヒト腸管上皮細胞への結合活性の解析ENYingjiJinNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Hepatitis C Virus Genotype Distribution in Myanmar: Predominance of Genotype 6 and Existence of New Genotype 6 SubtypeENLwinAye AyeAim: This study was performed to determine the prevalence and distribution of hepatitis C virus (HCV) genotypes in Myanmar. Methods: A total of 1333 peripheral blood samples were collected from four different border cities of Myanmar. The anti-HCV antibody-positive serum samples were identified. HCV was genotyped by reverse transcriptase polymerase chain reaction, direct DNA sequencing and phylogenetic analysis on the partial core genome. Results: The overall prevalence of HCV infection was 11.6% (154/1333). Regionally, it was 13.5% (47/349) in the north-eastern city, 12.8% (64/501) in the north-western city, 4.2% (16/380) in the southern city and 26.2% (27/103) in the western city. HCV was genotyped in 145/154 (94.2%) samples. Genotype 6 was the most prevalent genotype in this study (71/145, 49%), followed by genotype 3 (57/145, 39.3%), genotype 1 (16/145, 11%), and genotype 2 (1/145, 0.7%). Genotype 6 was mostly found in the northern cities and genotype 3 in the southern and western cities of Myanmar. Multiple HCV genotypes/subtypes were successfully characterized as 1a, 1b, 2a, 3a, 3b, 6m, 6n, and a new 6 subtype. Among them, subtype 6n was the most predominant subtype (38.6%), followed by subtype 3b (29.7%), 3a (9.6%), 6m (9%), 1b (6.9%), 1a (4.1%), new 6 subtype (1.4%) and 2a (0.7%). Subtype 6n was more widely distributed in the northern cities whereas subtype 3b was more common in the western city. The newly discovered genotype 6 subtype was from the northern cities. Conclusions: The results indicate there are regional differences of HCV genotype distribution in Myanmar. There is a distinct geographic variation from other South-East Asian countries in terms of the existence of the new genotype 6 subtype.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via PLCγ-activated STAT1ENDaisukeHaradaThe most frequent type of rhizomelic dwarfism, achondroplasia (ACH), is caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Mutations in FGFR3 result in skeletal dysplasias of variable severity, including mild phenotypic effects in hypochondroplasia (HCH), severe phenotypic effects in thanatophoric dysplasia types I (TDI) and II (TDII), and severe but survivable phenotypic effects in severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN). To explore the molecular mechanisms that result in the different phenotypes, we investigated the kinetics of mutated versions of FGFR3. First, we assayed the phosphorylation states of the mutated FGFR3s and found that the level of phosphorylation in TDI-FGFR3 was lower than in ACH-FGFR3, although the other mutants were phosphorylated according to phenotypic severity. Second, we analyzed the duration of the phosphorylation. TDI-FGFR3 was not highly phosphorylated under ligand-free conditions, but the peak phosphorylation levels of TDI-FGFR3 and ACH-FGFR3 were maintained for 30 min after stimulation with FGF-1. Moreover, ligand-dependent phosphorylation of TDI-FGFR3, but not ACH-FGFR3, lasted for more than 8 h after FGF-1 administration. The other mutant proteins showed sustained phosphorylation independent of ligand presence. Third, we investigated the intracellular localization of the mutant proteins. Immunofluorescence analysis showed accumulations of TDII-FGFR3, SADDAN-FGFR3, and a portion of TDI-FGFR3 in the endoplasmic reticulum (ER). Based on these data, we concluded that sustained phosphorylation of FGFR3 causes chondrodysplasia, and the phenotypic severity depends on the proportion of ER-localized mutant FGFR3. In FGFR3 signaling, the transcription factor, signal transducer and activator of transcription 1 (STAT1) inhibit proliferation and induce apoptosis of chondrocytes. Here we reveal that phospholipase C gamma (PLCgamma) mediates FGFR3-induced STAT1 activation. Both PLCgamma and STAT1 were activated by FGFR3 signaling, but a dominant-negative form of PLCgamma (DN-PLCgamma) remarkably reduced STAT1 phosphorylation. Apoptosis assays revealed that the constitutively active forms of FGFR3 (TDII-FGFR3) and STAT1 (STAT1-C) induce apoptosis of chondrogenic ATDC5 cells via caspase activity. DN-PLCgamma reduced the apoptosis of ATDC5 cells expressing TDII-FGFR3, but over-expression of both DN-PLCgamma and STAT1-C induced apoptosis. Therefore, we conclude that a PLCgamma-STAT1 pathway mediates apoptotic signaling by FGFR3.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Risk Factors and Indications for Colectomy in Ulcerative Colitis Patients are Different According to Patient’s Clinical BackgroundENMotoakiKuriyamaPURPOSE: Despite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy. METHODS: The clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively. RESULTS: Of 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37-3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31-6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15-3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29-11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08-6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001). CONCLUSIONS: In ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patient's clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumorsENYukoOkamotoOBJECTIVE: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors. MATERIALS AND METHODS: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography. RESULTS: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (kappa coefficient=0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p=0.063). CONCLUSION: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Subventricular Zone-Derived Neuroblasts Migrate and Differentiate into Mature Neurons in the Post-Stroke Adult StriatumENToruYamashitaRecent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Intrathecal Injection of Epidermal Growth Factor and Fibroblast Growth Factor 2 Promotes Proliferation of Neural Precursor Cells in the Spinal Cords of Mice With Mutant Human SOD1 GeneENYasuyukiOhtaWe investigated three steps of neural precursor cell activation--proliferation, migration, and differentiation--in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Inhibitory Effect of Polyunsaturated Fatty Acids on Apoptosis Induced by Etoposide, Okadaic Acid and AraC in Neuro2a CellsENYumeiWuNeuronal apoptosis is involved in neurodegenerative diseases such as Alzheimer's disease and Parkinson.s disease. An efficient means of preventing it remains to be found. Some n-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA, 22 : 6n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) have been reported to be protective against the neuronal apoptosis and neuronal degeneration seen after spinal cord injury (SCI) [1]. However, it is unclear which kinds of PUFAs have the most potent ability to inhibit neuronal apoptosis and whether the simultaneous treatment of PUFAs inhibits the apoptosis. In the present study, we compared the abilities of various n-3- and n-6- PUFAs to inhibit the apoptosis induced after the administration of different apoptotic inducers, etoposide, okadaic acid, and AraC, in mouse neuroblastoma cells (Neuro2a). Preincubation with DHA (22 : 6n-3), eicosapentaenoic acid (EPA, 20 : 5n-3), alpha-linolenic acid (alpha-LNA, 18 : 3n-3), linoleic acid (LA, 18 : 2n-6), arachidonic acid (AA, 20 : 4n-3), and gamma-linolenic acid (gamma-LNA, 18 : 3n-6) significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells. There were no significant differences of the anti-apoptotic eff ect among the PUFAs. These results suggest that PUFAs may not be effective for inhibiting neuronal cell death after acute and chronic neurodegenerative disorders. However, dietary supplementation with PUFAs may be beneficial as a potential means to delay the onset of the diseases and/or their rate of progression.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Increased heme catabolism in critically ill patients: correlation among exhaled carbon monoxide, arterial carboxyhemoglobin, and serum bilirubin IXα concentrationsENHiroshiMorimatsuIt has been reported that exhaled carbon monoxide (CO) concentrations and arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in critically ill patients. However, there was no study that examined correlation among amount of CO in exhaled air, CO-Hb concentrations in erythrocytes, and bilirubin IXalpha (BR) in serum, i.e., the three major indexes of heme catabolism, within the same subject. Here, we examined CO concentrations in exhaled air, CO-Hb concentrations in arterial blood, and BR levels in serum in 29 critically ill patients. Measurements of exhaled CO, arterial CO-Hb, and serum total BR have been done in the intensive care unit. As control, exhaled CO concentration was also measured in eight healthy volunteers. A median exhaled CO concentration was significantly higher in critically ill patients compared with control. There was significant correlation between CO and CO-Hb and CO and total BR level. We also found CO concentrations correlated with indirect BR but not direct BR. Multivariate linear regression analysis for amount of exhaled CO concentrations also showed significant correlation with CO-Hb and total BR, despite the fact that respiratory variables of study subjects were markedly heterogeneous. We found no correlation among exhaled CO, patients' severity, and degree of inflammation, but we found a strong trend of a higher exhaled CO concentration in survivors than in nonsurvivors. These findings suggest there is an increased heme breakdown in critically ill patients and that exhaled CO concentration, arterial CO-Hb, and serum total BR concentrations may be useful markers in critically ill conditions.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Static Ocular Counterroll: Video-based Analysis After Minimizing the False-Torsion FactorsENIchiroHamasakiPURPOSE: To determine the validity and usefulness of a newly developed measurement method of static ocular counterrolling (s-OCR) that eliminates false-torsion factors and to test the Jampel hypothesis that s-OCR does not exist. METHODS: A lightweight measurement device, consisting of a video camera, a coaxial light source, and a laser pointer projecting a fixation target on the wall, was fixed to a subject's head by means of a mouthpiece. In 11 healthy adults (mean age: 30 +/- 15 years), digital images of the right eye were captured while the subject kept his head tilted at a randomly selected angle ranging from 0 degrees to 50 degrees . By a frame-by-frame analysis of movements of the corneal light reflex and the iris patterns, OCR was evaluated. RESULTS: Torsional eye movement in the opposite direction to head tilt was found in all subjects. The amount of torsion continuously increased until the head-tilt angle reached 40 degrees. The average (+/- SD) amplitude of a fitted sine curve was 7.6 +/- 3.2 degrees (range: 4.3 degrees-10.3 degrees), and the individual amplitude was significantly larger than the test-retest repeatability of the measurement (+/-1.7 degrees). CONCLUSIONS: The measurement method used in this study provided good test-retest repeatability and ease of application. The characteristics of torsional eye movements that we observed after minimizing the false-torsion factors agree with previous reports supporting the existence of s-OCR.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Axial Length Measurement Using Partial Coherence Interferometry in Myopic Children: Repeatability of the Measurement and Comparison with Refractive ComponentsENShuheiKimuraPURPOSE: To evaluate the test-retest repeatability of axial length (AL) measurements made with the IOLMaster in children with a wide range of myopic refractive errors, and to clarify the relationship between the AL and other refractive components. METHODS: The subjects were 95 children (mean age +/- SD, 10.8 +/- 1.3 years; range, 7-13 years; mean refractive error; -4.37 +/- 1.43 D; range, -1.50 to -8.19 D) who participated in a myopia-control trial. The AL of the right eye was measured three times using an IOLMaster, and the mean value was regarded as the representative measurement. After 5 min, the measurement was performed again, and the repeatability was evaluated by analyzing the distribution of differences between the two measurements. The relationships between the AL and age, cycloplegic autorefraction (RE), and corneal radius of curvature (CR) were also examined. RESULTS: The repeatability of the IOLMaster measurements was +/-0.05 mm (corresponding to a refractive error of +/-0.12 D) and was not affected by age or RE. AL was negatively correlated with RE (RE = -0.68 x AL + 12.74, r = -0.37) and positively correlated with CR (CR = 0.21 x AL + 2.53, r = 0.69). The highest correlation was found between the ratio of AL to CR and RE (AL/CR = -0.04 x RE + 3.08, r = -0.76). No association was observed between age and AL, nor between CR and RE. CONCLUSIONS: The IOLMaster provides high repeatability in AL measurement in myopic children. The associations between AL and each refractive component found in this study were consistent with those in previous studies that used the ultrasound A-mode method, except for slightly higher AL/CR ratios in our study.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007日本人Brugada症候群患者における心筋ナトリウムチャネル遺伝子(SCN5A)の変異と多型ENDaijiMiuraNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007The Effects of Caregiving Resources on the Incidence of Depression over One Year in Family Caregivers of Disabled ElderlyENYukiYajimaThe purpose of the study was to investigate the over-time effects of physical, psychological and social resources on the incidence of depression in family caregivers of the disabled elderly. Data were collected twice at a one-year interval from 1,141 primary caregivers of a disabled older person in an urban area of Japan using a self-reported questionnaire survey. The questionnaire included physical health as an indicator of physical resources, caregiving satisfaction and intention to care as indicators of psychological resources, and instrumental and emotional support network and formal home care service utilization as indicators of social resources. The mental health outcome measure was the General Health Questionnaire 12-item version (GHQ-12). Complete data on 235 non-depressed female caregivers were separated into 3 groups according to the relationship type (wife, daughter and daughter-in-law) and analyzed separately. Multivariate logistic regression models controlling for duration of caregiving, care-recipient's gender, ADL dependency and behavioral problems demonstrated that significant predictors of depression were caregiving satisfaction and intention to care in wives, caregiving satisfaction in daughters, and physical health and emotional support network in daughters-in-law. Noteworthy, intention to care increased the risk of depression in wives, while decreasing the risk of depression in daughters-in-law. The findings indicate that the effects of caregivers' resources on mental health may differ by relationship type.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Resolution of Pulmonary Multiplanar Reconstruction Images from 0.5-mm Theoretical Isotropic Data: A Fundamental Study Using an Inflated and Fixed Lung SpecimenENDaisukeMakiThe aim of the present study was to define the resolution of multiplanar reconstruction (MPR) of the lung from "theoretical isotropic data." Using inflated and fixed lung specimens of the pig placed in the chest wall phantom, 0.5-mm isotropic data were obtained with 2 different helical pitches: 1:7 (high-quality mode) or 1:13, (high-speed mode), and 2 different tube currents: 250 mAs (high-tube-current mode) or 100 mAs (low-tube-current mode), with or without overlapping reconstruction. MPRs were created from these axial data. The diameter of the smallest visible pulmonary artery and bronchi of these CT images were measured on the corresponding slices of the specimen. The high-speed and low-tube-current mode significantly degraded the image quality due to increased noise. The smallest visible pulmonary artery and bronchus resolved on MPRs from axial-spiral data with 0.5-mm collimation were approximately 100 micrometer and 1,000 micrometer in diameter, respectively. In conclusion, helical pitch and tube current influence the resolution of MPR of the lung.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blastsENKozoMasudaLoss or down-regulation of human leukocyte antigen (HLA) class I expression has been demonstrated in a variety of solid tumors. To date, such altered HLA expression has not been studied extensively in freshly isolated leukemic blasts. If it occurs, leukemic cells could escape T-cell surveillance as a consequence. Genotypes of nine leukemic cell lines were determined using a polymerase chain reaction for HLA classes I and II. Cells were also examined for HLA beta2-microglobulin, and allele-specific HLA protein expression using flow cytometry. Next, 44 samples of freshly isolated leukemic blasts from 43 patients with malignant hematological diseases were examined for allele-specific HLA expression using flow cytometry. Microsatellite analysis was performed to determine heterozygosity in the HLA region on chromosome 6. Genotype analysis for HLA class I together with microsatellite analysis demonstrated loss of HLA haplotype in HL-60 cells. No loss of HLA haplotype was observed in 44 samples of freshly isolated leukemic blasts. As reported previously, flow cytometric analysis rarely demonstrated loss or down-regulation of HLA expression at initial diagnosis (3/39; 7.7%); however, this was evident in two of five cases in relapse (40.0%), which contrasts with previous reports. In one patient with acute leukemia, HLA-A2 cell surface expression was present at initial diagnosis, lost at relapse, and completely restored after 48 h of culture in the presence of interferon-gamma. These results suggest loss of allele-specific HLA expression may be involved in the pathogenesis of relapse in patients with leukemia. The findings should be valuable in designing new strategies for clinical immunotherapy.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Donor-derived Thymic-dependent T cells Cause Chronic Graft-versus-Host DiseaseENYukimiSakodaChronic graft-versus-host disease (GVHD) is the most common cause of poor long-term outcomes after allogeneic bone marrow transplantation (BMT), but the pathophysiology of chronic GVHD still remains poorly understood. We tested the hypothesis that the impaired thymic negative selection of the recipients will permit the emergence of pathogenic T cells that cause chronic GVHD. Lethally irradiated C3H/HeN (H-2k) recipients were reconstituted with T-cell-depleted bone marrow cells from major histocompatibility complex [MHC] class II-deficient (H2-Ab1-/-) B6 (H-2b) mice. These mice developed diseases that showed all of the clinical and histopathological features of human chronic GVHD. Thymectomy prevented chronic GVHD, thus confirming the causal association of the thymus. CD4+ T cells isolated from chronic GVHD mice were primarily donor reactive, and adoptive transfer of CD4+ T cells generated in these mice caused chronic GVHD in C3H/HeN mice in the presence of B6-derived antigen-presenting cells. Our results demonstrate for the first time that T cells that escape from negative thymic selection could cause chronic GVHD after allogeneic BMT. These results also suggest that self-reactivity of donor T cells plays a role in this chronic GVHD, and improvement in the thymic function may have a potential to decrease chronic GVHD.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Clinical characteristics of synchronous colorectal cancer are different according to tumour locationENHirotoshiFukatsuAIMS: The purpose of this study was to investigate the clinical characteristics of synchronous cancer patients, with particular attention given to variations in tumour location. METHODS: A retrospective evaluation of 249 synchronous cancer cases out of 3061 consecutive colorectal cancer patients. RESULTS: Multivariate analysis of risk factors for synchronous cancer according to tumour location revealed that male gender was a significant risk for synchronous lesions in the left colon only (odds ratio=2.05, 95% confidence interval 1.34-3.13). Meanwhile, aging was a risk factor for synchronous cancer in the right colon only (odds ratio=1.05, 95% confidence interval 1.02-1.08), and in both sides of the colon (odds ratio=1.03, 95% confidence interval 1.01-1.05), but not in the left colon only (odds ratio=0.98, 95% confidence interval 0.97-1.00). In addition, patients with synchronous lesions in the right colon only tended to have adenomas in the right colon, while those with synchronous lesions in the left colon only tended to have adenomas in the left colon (each P value <0.05). CONCLUSION: The risk factors and status of concurrent adenomas of synchronous cancer cases varied according to tumour location, suggesting that the colonic site susceptible to neoplasia varies according to patient characteristics.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Quality of life for patients with schizophrenia in a Japanese psychiatric hospitalENAkiKugoProviding a good quality of life (QOL) has recently been recognized as a central purpose of health care in psychiatry. In this study, we performed a detailed evaluation of the subjective QOL of schizophrenic inpatients and examined the relationship of QOL to various patient characteristics. This study was conducted on schizophrenic inpatients and nursing staff members in a Japanese private psychiatric hospital. As a result, only depression showed a weak, but significant, relationship with subjective QOL. Other characteristics showed no meaningful correlation to subjective QOL. Comparison between the schizophrenic group and the nursing staff group revealed that schizophrenic inpatients showed a lower QOL in the domains of physical health and social relationships. Schizophrenia itself and/or accompanying disabilities might induce lower subjective QOL. It is difficult to determine what the important factors are, except for depression, for subjective QOL of schizophrenic inpatients. However, depression should receive more attention for the QOL in the physical health and psychological health domains.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Altered Response to Formalin by L5 Spinal Nerve Ligation in Rats: A Behavioral and Molecular StudyENRyujiKakuBACKGROUND: The status of neuropathic pain alters the responsiveness to formalin injection in rats. However, the mechanism by which this alteration occurs is unknown. METHODS: We used immunocytochemistry to examine the expression of brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP) in the spinal cord of rats with L5 spinal nerve ligation (SNL)-induced neuropathy, and investigated the expression of c-Fos in the spinal cord after injection of formalin in the hindpaw of rats with SNL. RESULTS: Four weeks after SNL, the withdrawal threshold was significantly lower in the SNL group than in the sham-operated (sham) group (n = 12 per group, P < 0.05). In the SNL group, expression of BDNF in the L4 (P < 0.05) and L5 (P < 0.01) superficial dorsal horn was significantly decreased compared to that in the sham group. CGRP protein in the L5 but not in the L4, dorsal horn was significantly decreased compared to that in the sham group (P < 0.01). After formalin injection, spontaneous pain responses in the SNL group were significantly decreased compared to those in the sham group (P < 0.05). Immunolabeling for c-Fos was significantly decreased in the L4 and L5 dorsal horn in the SNL group (P < 0.01). CONCLUSION: Our examination of c-Fos distribution indicates that decreased neuronal activity in the spinal cord in response to inflammatory pain may be important for altering the perception of acute pain. Decreased BDNF expression in response to SNL-induced neuropathy may be involved in this alteration.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on Propionibacterium acnes and lipopolysaccharide-induced hepatitis in miceENAkiraYokoyamaWe examined whether treatment with amodiaquine, a potent inhibitor of histamine N-methyltransferase protects mice from Propionibacterium acnes (P. acnes)-primed and lipopolysaccharide (LPS)-induced hepatitis. The subcutaneous injection of amodiaquine (2 and 5 mg/kg) significantly increased the histamine levels in the liver in comparison to saline treated mice. Pretreatment with amodiaquine also improved the survival rate of the hepatitis mice, and this improvement was partially associated with the decrease in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Amodiaquine partially suppressed increases of tumor necrosis factor (TNF)-alpha in the serum and TNF-alpha mRNA expression in the liver, whereas the expression of interleukin (IL)-18, interferon (IFN)-gamma and IL-12 in the liver was not changed by amodiaquine treatment. In conclusion, the present findings suggested that the elevation of endogenous histamine by amodiaquine may thus play a protective role through the regulation of TNF-alpha production in endotoxin-induced hepatic injury mice.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Deviated VH4 immunoglobulin gene usage is found among thyroid mucosa-associated lymphoid tissue lymphomas, similar to the usage at other sites, but is not found in thyroid diffuse large B-cell lymphomasENYumikoSatoIt remains unclear whether or not diffuse large B-cell lymphomas of extranodal sites arise from mucosa-associated lymphoid tissue (MALT) lymphomas. We studied the clinicopathological features of MALT lymphoma and diffuse large B-cell lymphoma in the thyroid gland, with special reference to VH usage of immunoglobulin gene rearrangement, to clarify the relationships between these two types of lymphomas. In addition, t(11; 18) (q21; q21) translocation was examined by multiplex reverse transcription-polymerase chain reaction. We examined 58 patients with primary thyroid lymphoma: 31 (male seven and female 24) with MALT lymphoma and 27 (male three and female 24) with diffuse large B-cell lymphoma. Interestingly, the sequence of VH genes revealed that the two subtypes differed significantly in their use of the VH4 family (P < 0.05). Of the seven MALT lymphomas, three used the VH4 family and the other four used the VH3 family, whereas eight out of nine diffuse large B-cell lymphoma used the VH3 family, one used the VH1 family, and none used the VH4 family. It was also interesting that, in one diffuse large B-cell lymphoma patient with MALT lymphoma, the diffuse large B-cell lymphoma component used the VH3 family and the MALT lymphoma component used the VH4 family. These data imply that, in a subset of cases, these two subtypes do not share a common origin and that at least some diffuse large B-cell lymphomas have a de novo origin. No t(11; 18) (q21; q21) was detected in thyroid lymphomas, which are different from MALT lymphoma of the stomach, lungs, large intestine and ocular adnexa. This strongly indicated that the presence of t(11; 18) (q21; q21) in MALT lymphoma is organ-specific.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007The Impact of Epidermal Growth Factor Receptor Gene Status on Gefitinib-Treated Japanese Patients with Non-Small-Cell Lung CancerENShujiIchiharaWe investigated the relationships between genetic factors and clinical outcome in Japanese non-small-cell lung cancer (NSCLC) patients treated with gefitinib. Ninety-eight NSCLC patients who had been treated with gefitinib, were screened for mutations in epidermal growth factor receptor (EGFR) exons 18-21, KRAS exon2, and polymorphisms including the CA simple sequence repeat in intron1 (CA-SSR1) and single nucleotide polymorphisms in the promoter region (-216G/T and -191C/A), using a PCR-based assay and direct sequencing. The EGFR copy number status was also evaluated using a fluorescence in situ hybridization assay. EGFR and KRAS mutations were found in 38 (38.8%) and 8 (8.2%) of the 98 patients, respectively. A high EGFR copy number status was identified in 31 (41.3%) of the 75 assessable patients. Drug-sensitive EGFR mutations limited to exon19 deletions and L858R were independent predictive factors of a stronger sensitivity to gefitinib (p = 0.0002), the overall survival (OS) (p = 0.0036), and prolonged progression-free survival (PFS) (p < 0.0001). The EGFR copy number status was not related to a sensitivity to gefitinib and prolonged OS and PFS. Regarding polymorphisms, patients with a short CA-SSR1 showed a prolonged OS as compared with those with a long length in patients with a drug-sensitive EGFR mutation, although this difference was not significant (p = 0.13). Thus, drug-sensitive EGFR mutations predict a favorable clinical outcome and a high EGFR copy number may not be related to clinical benefits in gefitinib-treated Japanese patients with NSCLC. Our findings also suggest that the CA-SSR1 length may influence the clinical outcome in patients with a drug-sensitive EGFR mutation.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007A novel, noninvasive diagnostic probe for hydroa vacciniforme and related disorders Detection of latency-associated Epstein-Barr virus transcripts in the crustsENTakenobuYamamotoOBJECTIVE: To establish a new diagnostic method for Epstein-Barr virus (EBV)-associated cutaneous disorders. DESIGN: Skin biopsy is usually required to confirm the latent EBV infections in cutaneous lesions of EBV-associated NK/T-cell lymphoproliferative disorders, including hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). We have devised a novel, noninvasive method to detect EBV-encoded small RNA (EBER), BamHI A rightward transcripts (BARTs) in the skin crusts and scales of such patients. PATIENTS: Six patients with EBV-associated cutaneous lesions were enrolled in the present study, including three patients with HV, one with HV-like eruptions and chronic active EBV infection, and two with EBV-associated cutaneous lymphoma. MAIN OUTCOME MEASURES: RNA was extracted from the crusts obtained from the cutaneous lesions by forceps, converted to cDNA, and processed for polymerase chain reaction (PCR) amplification with a specific set of primers. The PCR products were assayed by a DNA sequencer. RESULTS: Intact RNAs were successfully extracted from the crusts as well as control materials. EBER1 and BARTs RNAs were detected in all 7 crusts, and in 6 of 7 crusts of EBV-associated cutaneous diseases, respectively. One of 23 crusts from non EBV-associated diseases was positive for EBER1 RNA. The sensitivity and specificity of our assay for latent EBV infection were 100% and 95.8% for EBER1 RNA, and 85.7% and 100% for BARTs mRNA, respectively. The correct DNA sequence for EBER1 and BARTs was confirmed in the PCR products by a direct sequencing method. CONCLUSIONS: Our procedure may be of use as a biomarker for EBV-associated cutaneous lesions, including HV, HMB, and NK/T-cell lymphomas.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007A prospective study of clinical symptoms and skin test reactions in medical students exposed to formaldehyde gasENSachikoTakahashiPrevious investigators have reported the occurrence of both allergic and non-allergic systemic complications due to exposure to formaldehyde gas. However, little is known about the pathogenic link between formaldehyde-induced clinical symptoms and patch test results, or about the long-term effects of formaldehyde exposure. In the present study, a questionnaire was administered to 143 medical students, and 60 of them were tested by patch test for formaldehyde at the beginning and end of a human anatomy laboratory course. Another group of 76 students who had finished the course 2-4 years previously were administered another questionnaire, and the patch test was carried out on 58 of them. The frequencies of skin irritation, eye soreness, lacrimation, eye fatigue, rhinorrhea, throat irritation, general fatigue and mood swings increased after repeated exposure. Two (3.3%) of 60 students became positive to 1% formaldehyde at the end of the anatomy course (one male with allergic hand dermatitis due to direct contact with formaldehyde, and one female with an atopic background with unbearable physical symptoms) while the remaining 58 showed a negative reaction throughout the study period. The vast majority of students complained of various non-allergic, physical symptoms, and recovered from such symptoms without subsequent complications. No progression to multiple chemical sensitivity was found. Students with an episode of atopic dermatitis and allergic rhinitis were susceptible to formaldehyde exposure, and developed mucocutaneous symptoms, probably due to the impaired barrier function and remodeling of the skin and mucosa.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T cell responsesENYujiSugataHistamine not only mediates immediate allergic reactions, it also regulates cellular immune responses. H4R is the most recently identified histamine receptor (HR). In the present study, we examined the in vitro effect of histamine and H4R agonists on the responses of human T cells to purified protein derivative from Mycobacterium tuberculosis (PPD) and to Cry j1, the major allergen of Cryptomeria japonica pollen. Dimaprit, clobenpropit and clozapine, which are H4R agonists, dose-dependently blocked both PPD-induced interferon-gamma and Cry j1-induced interleukin-5 production by both peripheral blood mononuclear cells (PBMCs) and antigen-specific T-cell lines. However, the addition of thioperamide, an H3R/H4R antagonist, as well as a mixture of d-chlropheniramine, famotidine and thioperamide, did not reverse the inhibition. Pretreatment of PBMCs with SQ22536 and 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Rp-isomer, had varying abilities to reverse the inhibitory effects of H4R agonists, except for clobenpropit. Moreover, the addition of H4R agonists induced annexin-V expression on PBMCs, especially in CD19(+) and CD4(+) cells. cDNA microarray analysis revealed that, among 16,600 genes tested, increased expression following treatment with clozapine was seen in 0 x 8% of the genes, whereas decreased expression was seen in 3 x 0% of the genes. These results suggest that H4R agonists inhibit antigen-specific human T-cell responses, although H4R does not appear to be important for this effect. In addition, the present study indicated that there may be orphan receptors or HR subtypes which can bind dimaprit, clobenpropit and clozapine, and that can exert an inhibitory effect on antigen-specific cellular responses via a cAMP/cAMP-dependent protein kinase-dependent, apoptotic pathway.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Novel Protein Transduction Method by Using 11R-An Effective New Drug Delivery System for the Treatment of Cerebrovascular Diseases-ENTomoyukiOgawaBACKGROUND AND PURPOSE: A motif of 11 consecutive arginines (11R) is reported to be one of the most effective protein transduction domains for introducing proteins into the cell membrane. We therefore examined the transduction efficiency of 11R in cerebral arteries. METHODS: Basilar arteries (BAs) obtained from rats were incubated with either 11R-enhanced green fluorescent protein (11R-EGFP) or EGFP without 11R. After incubation, expression of 11R-EGFP or EGFP in BA serial sections was observed by fluorescence microscope. In an additional in vivo experiment, 11R-EGFP or EGFP was injected into the cisterna magna with or without subarachnoid hemorrhage. The 11R-EGFP or EGFP was injected just after the autologous blood injection, and then the expression of 11R-EGFP or EGFP in BA sections was also observed by fluorescence microscope. RESULTS: The 11R-EGFP signal was much stronger than that of EGFP in all layers of the rat BA, in both in vivo and ex vivo experiments. Moreover, the 11R-EGFP was transduced into the BA immediately (2 hours after the injection). Interestingly, 11R-fused fluorescent protein was transduced especially into the tunica media of the BA. CONCLUSIONS: The 11R-fused fluorescent protein effectively penetrates into all layers of the rat BA, especially into the tunica media. This is the first study to our knowledge to demonstrate the successful transduction of a protein transduction domain fused protein into the cerebral arteries.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Limited Contribution of Cells of Intact Extrahepatic Tissue Origin to Hepatocyte Regeneration in Transplanted Rat LiverENKojiTomiyamaBACKGROUND: It is now well established that various adult somatic tissues harbor multipotent stem cells that can differentiate into a broad variety of cell types of all three germ layer origins. It remains controversial, however, whether they are a reservoir of cells utilized for emergent tissue repair or simply a vestige of evolution and, if the former is the case, to what extent they can potentially contribute to reconstitution of a specific organ. To get an insight in such a direction, we examined the extent of contribution of naive intact cells of extrahepatic origin to hepatocyte reconstitution in the transplanted liver with or without injury in the rat. METHODS: Liver from wild-type donor rats was transplanted to green fluorescent protein (GFP)-transgenic rats, and GFP-positive hepatocytes were examined with or without liver injury. RESULTS: The proportion of GFP-positive hepatocytes in the transplanted noninjured liver linearly increased by 0.0048% per week, that is, approximately 5 x 10(3) hepatocytes of extrahepatic origin were generated per day. Liver injury induced by treatment with 2-acetylaminofluorene and CCl4 or the additional application of hepatocyte growth factor did not further increase the percentage of GFP-positive hepatocytes. CONCLUSION: The present results indicate that cells derived from nonmanipulated extrahepatic tissues appreciably contribute, though limitedly, to hepatocyte reconstitution in the liver of the rat.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Pirfenidone Modulates Airway Responsiveness, Inflammation, and Remodeling after Repeated ChallengeENAtsushiHiranoWe investigated the therapeutic potential of a newly developed antifibrotic agent, pirfenidone, to regulate airway remodeling and the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenge. Administration of pirfenidone after sensitization but during the period of ovalbumin challenge significantly prevented the development of airway hyperresponsiveness and prevented eosinophil and lymphocyte accumulation in the airways. IL-4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid and ovalbumin-specific serum IgE antibody levels were also significantly reduced. Treatment with pirfenidone significantly reduced transforming growth factor-beta1 and platelet-derived growth factor levels in bronchoalveolar lavage fluid. Pirfenidone reduced the expression of transforming growth factor-beta1, the development of goblet cell hyperplasia and subepithelial collagenization, and the increases in contractile elements in the lung. These data indicate that pirfenidone may play an important role in the treatment of asthma and has the potential reduce or prevent airway remodeling.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Characterization of the short isoform of Helios overexpressed in patients with T-cell malignanciesENTakayukiTabayashiIn an earlier report, we demonstrated overexpression of a short isoform of Helios, Hel-5, which lacks three of four N-terminal zinc fingers, in patients with adult T-cell leukemia/lymphoma. Here, we characterized Hel-5 using immunoprecipitation, and gel shift and luciferase promoter assays, and found that Hel-5 lacks the repressor function observed with a full-length isoform of Helios. Moreover, Hel-5 associates with the full-length isoforms of the Ikaros gene family, Ikaros, Aiolos and Helios, and inhibits their DNA binding activity when present in excess, leading to dominant-negative effects on the full-length isoforms of the Ikaros gene family. Our results suggest a critical role for Helios in the mechanism of leukemogenesis.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Nucleotide change of codon 38 in the X gene of hepatitis B virus genotype C is associated with an increased risk of hepatocellular carcinomaENRyosukeMuroyamaBACKGROUND/AIMS: The hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, the HBV X gene, which encodes the pleiotropic transactivator HBx, has also been associated with the development of HCC. In this study, we investigated whether nucleotide changes in the X gene of genotype C are associated with the development of HCC. METHODS/RESULTS: We sequenced the X gene in age- and sex-matched 39 HBV-infected patients with HCC and 36 HBV-infected patients without HCC. A novel nucleotide change that resulted in a proline to serine substitution at codon 38 in HBx (codon-38 change) was preferentially found in patients with HCC. Then, sera were collected from a new group of age- and sex-matched 52 patients with HCC and 51 patients without HCC. In this cohort also, the codon-38 change was associated with HCC. Multiple logistic regression analysis showed the prevalence of the codon-38 change was significantly associated with HCC in all patients (P=0.001, odds ratio: 4.89). CONCLUSION: The codon-38 change in genotype C is an independent risk factor for the development of HCC and may serve as a useful molecular marker for predicting the clinical outcomes in patients infected with HBV.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Optimal Time for Post-mortem Heparinization in Canine Lung Transplantation with Non-heart-beating DonorsENMikioOkazakiBACKGROUND: We previously reported that post-mortem heparinization by closed-chest cardiac massage is beneficial in lung transplantation from non-heart-beating donors by preventing formation of microthrombi. In this study, we evaluated the optimal time for post-mortem heparinization in canine lung transplantation from non-heart-beating donors. METHODS: Left lung transplantation was performed in 25 weight-matched pairs of mongrel dogs. Donors were killed with an intravenous injection of potassium chloride and left at room temperature for 2 hours. The cadaver donors were assigned randomly to one of five study groups. In Group H0, heparin sodium (1,000 U/kg) was given intravenously before cardiac arrest. In Groups H10, H30, H45 and H60, heparin sodium (1,000 U/kg) was given intravenously 10, 30, 45 and 60 minutes after cardiac arrest, respectively, followed by closed-chest cardiac massage for 2 minutes. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran glucose solution and preserved for 60 minutes. After left lung allotransplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 3 hours. Uni- and multivariate repeat analyses were utilized for statistical assessment.
RESULTS: After transplantation, gas exchange was significantly worse in Groups H45 and H60 than in Groups H0, H10 and H30. Thrombin/anti-thrombin III complex concentration during warm ischemia was significantly higher in Groups H30, H45 and H60 than in Groups H0 and H10.
CONCLUSIONS: The optimal time for post-mortem heparinization in lung transplantation from non-heart-beating donors is approximately 30 minutes after cardiac arrest.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007果実の成熟に対するMADS-box様転写因子の役割に関する研究ENMikiYamaneNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007栽培メロンにおける核及び細胞質ゲノムの多様性とマクワ・シロウリの起源に関する分子遺伝学的研究ENKatsunoriTanakaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007ソロ珪酸塩型層状結晶の構造歪に関する構造化学的研究ENYasuoOchiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007中国地方東部地域,矢の峯超苦鉄質岩体の接触変成作用−特にFe-Ni-S系鉱物と含アルカリ鉱物について−ENYoshinoriInoueNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007実用レベルで利用できるブタ胚の長期保存技術の確立ENYukihiroFujinoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007糖転移酵素による機能性物質の生産に関する研究ENKatsuhideOkadaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007ラットCYP2D1及びCYP2D2による位置選択的基質酸化反応におけるアミノ酸残基の役割ENKimioKiryuNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007低分子化合物が関わるタンパク質のX線解析法による解明−ニトリルヒドラターゼおよびビタミンDレセプターの三次元構造解析−ENShinjiHoraiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007移動面模様の視覚追跡と記憶による移動体の誘導制御ENIsakuNagaiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007高速ベクトル量子化とその応用に関する研究ENShuichiMakiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Primes in quadratic and cubic polynomialsENKen-ichiShimizuNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007一歯科医院におけるコーヌステレスコープ義歯と部分床義歯の予後調査の比較ENKoichiShimamuraNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007一歯科医院における根管治療の予後調査ENKozoTsujiNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007The Design of Non-occlusal Intraoral Appliances on Hard Palate and Their Effect on Masseter Muscle Activity during SleepENKoichiHasegawaThis study aimed to reveal whether masseter muscle activity during sleep is affected by the difference in design of non-occlusal intraoral appliances on hard palate. Eight healthy Japanese participants were selected and wore each of the four types of appliances (horse shoe, thin, thick and medium thick) during sleep for one week with a one week interval without appliance during sleep. A masseter muscle electromyograph (EMG) was recorded during sleep. The EMG activities were analyzed by calculating the number of bursts per hour, episodes per hour, and bursts per episode. The EMG parameters with the thick type appliance were significantly lower than the baseline condition without appliance. In this study, it is suggested that a thick type appliance has an active effect on suppression of masseter muscle activity.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Downregulation of topoisomerase IIβ in myeloid leukemia cell lines leads to activation of apoptosis following all-trans retinoic acid-induced differentiation/growth arrestENKen-ichiChikamoriAmong the topoisomerase (topo) II isozymes (alpha and beta), topo IIbeta has been suggested to regulate differentiation. In this study, we examined the role of topo IIbeta in all-trans retinoic acid (ATRA)-induced differentiation of myeloid leukemia cell lines. Inhibition of topo IIbeta activity or downregulation of protein expression enhanced ATRA-induced differentiation/growth arrest and apoptosis. ATRA-induced apoptosis in topo IIbeta-deficient cells involved activation of the caspase cascade and was rescued by ectopic expression of topo IIbeta. Gene expression profiling led to the identification of peroxiredoxin 2 (PRDX2) as a candidate gene that was downregulated in topo IIbeta-deficient cells. Reduced expression of PRDX2 validated at the mRNA and protein level, in topo IIbeta-deficient cells correlated with increased accumulation of reactive oxygen species (ROS) following ATRA-induced differentiation. Overexpression of PRDX2 in topo IIbeta-deficient cells led to reduced accumulation of ROS and partially reversed ATRA-induced apoptosis. These results support a role for topo IIbeta in survival of ATRA-differentiated myeloid leukemia cells. Reduced expression of topo IIbeta induces apoptosis in part by impairing the anti-oxidant capacity of the cell owing to downregulation of PRDX2. Thus, suppression of topo IIbeta and/or PRDX2 levels in myeloid leukemia cells provides a novel approach for improving ATRA-based differentiation therapy.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infectionENShinyaUeharaChanges in the indigenous vaginal microflora with uropathogenic bacteria can predispose women to frequently recurring bacterial cystitis. Lactobacilli used as probiotics have played an important role in preventing the colonization of pathogenic bacteria in the vagina. A prospective clinical pilot study was performed to confirm the safety and effectiveness of Lactobacillus vaginal suppositories against the recurrence of bacterial urinary tract infection (UTI). The patients enrolled in the study were instructed to administer vaginal suppositories containing the strain Lactobacillus crispatus GAI 98322. A significant reduction in the number of recurrences was noted, without any adverse complication (P=0.0007). The administration of vaginal suppositories containing L. crispatus GAI 98332 seemed to be a safe and promising treatment for the prevention of recurrent UTI.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancerENJun-ichiSoThe importance of epidermal growth factor receptor (EGFR) gene mutation has been recognized in nonsmall cell lung cancer (NSCLC), requiring the standardization of mutation screening system including the kind of samples. Here, we examined the EGFR mutation status in 61 pleural fluid samples from NSCLC cases using direct sequencing, nonenriched PCR, mutant-enriched PCR and peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay. The mutant-enriched PCR assay detected 16 mutant cases. Among them, the nonenriched PCR assay failed to detect 3 mutant cases. Regarding the discrepancy between mutant-enriched PCR and PNA-LNA PCR clamp assays, 3 cases of exon19-deletions were detected only by mutant-enriched PCR assay and no difference at the L858R mutation. There was no difference in results between direct sequencing and nonenriched PCR assay. We also correlated the EGFR mutation with clinical outcome of gefitinib-treated 29 cases. EGFR mutations were present in 10 cases, revealing 7 partial response and 3 no change (NC). In EGFR wild-type cases, 10 revealed NC and 9 progressive disease. The responders were significantly more frequent among the EGFR mutant cases than among the wild-type (p < 0.0001). Overall survival (p = 0.0092) and progression-free survival (p = 0.018) were significantly longer among the EGFR mutant cases than among the wild-type. In summary, we evaluated the utility of EGFR mutation screening in pleural fluid using 4 assays that showed some discrepancies arising from the designs of the assays. As clinical importance, the EGFR mutation status in pleural fluid can be a biomarker for the favorable outcome of gefitinib-treated NSCLC cases.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Suppression Effects of Human Recombinant Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) on Tumor Proliferation Using in Vivo Treatment Model of Well-differentiated Colon Cancer Cell Line, HT29ENYuOhtaniTo investigate the suppressive effect of human recombinant TIMP-1 (rh-TIMP-1) on tumor proliferation using an in vivo xenograft system, HT29 was suspended in 0.1 ml phosphate buffered saline (PBS) and then subcutaneously injected in the back of female mice (BALB/C nu/nu). The mice were divided into 2 groups an and the tumor diameter was measured after rh-TIMP-1 (2 mg/kg) (rh-TIMP-1 group) or PBS (control group) was administered injections according to the following schedules. Schedule 1 : Beginning 2 weeks after the subcutaneous injection of HT29, an intraperitoneal injection of rh-TIMP-1 or PBS were performed twice a day (every 12 h) for 14 consecutive days. Schedule 2 : Beginning 1 week after the subcutaneous injection of HT29, an intraperitoneal injection was performed twice a day for 14 consecutive days. Schedule 3 : Intraperitoneal injections were started simultaneously with the subcutaneous injection of HT29, and then performed twice a day for 21 consecutive days. The mice were sacrificed and the tumors extirpated for immunohistochemical investigation. In addition, gelatin zymography and a cell proliferation assay were performed. With Schedule 1, the changes in the tumor diameter in the rh-TIMP-1 group followed the same course as those in the control group, and no suppressive effect on tumor proliferation was observed. However, with Schedule 3, a remarkable suppressive effect was observed throughout the treatment period. In immunostaining, more cases negative for MMP-9 were observed in the rh-TIMP-1 group than in the control group. Cases negative for CD34 were significantly more observed in the rh-TIMP-1 group than in the control group with Schedule 3. All of the results were obtained through the suppressive effect of rh-TIMP-1 on angiogenesis.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Change of Clinical Characteristics of Ulcerative Colitis in Japan; Analysis of 844 Hospital Based Patients from 1981 to 2000ENTsuyoshiFujimotoAlthough the number of ulcerative colitis patients has increased rapidly in Japan, few reports have been published regarding their clinical aspects. We investigated the clinical characteristics and chronological change of ulcerative colitis in Japanese patients. METHODS: Patients diagnosed with ulcerative colitis during the period from 1981 to 2000 were registered and their clinical profiles were analyzed. The chronological changes in clinical aspects, such as onset age, sex distribution, severity, extent of disease, clinical course, and corticosteroid use, were also determined. RESULTS: A total of 844 patients were registered, composed of 431 men and 413 women, with a median onset age of 34 years. The proportion of mild colitis and proctitis was significantly larger in patients with an onset at over 60 years of age, relative to those with an onset at less than 30 years (P<0.016). The proportion of ulcerative colitis patients with old age onset (P=0.09), male sex (P<0.01), mild colitis (P<0.01), proctitis (P<0.01), one-attack-only type (P<0.01), and not-treated-with-corticosteroid (P<0.01) demonstrated a chronological increase from 1981 to 2000. CONCLUSIONS: The distinctive clinical features and chronological change were seen in Japanese ulcerative colitis patients in recent years. Our data can help understand clinical aspects of ulcerative colitis patients in Asia, where the incidence of ulcerative colitis is still increasing.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Coronary pressure measurement to determine treatment strategy for equivocal left main coronary artery lesionsENShunjiSuemaruIt is often hard to select a treatment strategy for equivocal left main coronary artery (LMCA) disease. We investigated the usefulness of coronary pressure (CP) measurement for determining the treatment strategy in intermediate LMCA disease. We measured CP in 15 consecutive patients with equivocal LMCA disease (age 67.6 +/- 7.5 years, 14 males). Myocardial fractional flow reserve (FFRmyo) was obtained as the ratio of CP distal to the lesion/aortic pressure under maximal coronary dilation. Patients with FFRmyo > or = 0.75 and <0.75 received medical therapy and coronary artery bypass grafting (CABG), respectively, and were followed up for 32.5 +/- 9.7 (20-47) months. Eight patients received medical therapy and 7 patients underwent CABG in accordance with the FFRmyo criteria noted above. FFRmyo of the LMCA was 0.91 +/- 0.01 and 0.61 +/- 0.03 in patients who received medical and surgical therapy, respectively. Neither reference vessel diameter, minimal lumen diameter, nor percent diameter stenosis was significantly different between patients who received medical and surgical therapy. During the follow-up period, no patients with medical therapy showed symptoms due to the LMCA lesion. Similarly, 5 of 7 patients with CABG showed improvement of symptoms and the remaining 2 patients were hospitalized with congestive heart failure. No cardiac death was recorded in the patients with medical or surgical therapy. In conclusion, the present results clearly demonstrated that CP is clinically useful for determining the treatment strategy for equivocal LMCA lesions but coronary angiography is not.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007深部前梨状葉皮質の間欠的電気刺激によるてんかん発作重積モデルENFumihikoKoyamaNo potential conflict of interest relevant to this article was reported.