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Development and treanment neurophysiological elucidation of the mechanism by bruxism-induced esophageal mucous membrane irritstion
No full text2011-2013年度科学研究費助成事業（基盤研究（C））研究成果報告書 課題番号：23593035 研究代表者：上村裕希（鹿児島大学・医歯（薬）学総合研究科・助教）食道への酸逆流と咬筋筋活動及び侵害受容器との関連については不明な点が多く、本研究では侵害受容器に着目し、ラット食道粘膜へ酸・ペプシン刺激を負荷し、咬筋筋活動と侵害受容器の発現亢進について検討した。Wister系雄性ラットに生理食塩水、酸ペプシン溶液を注入し、咬筋活動と食道の侵害受容器について調べた。咬筋筋活動、侵害受容器の発現が酸ペプシン溶液群で有意に多かった。本結果から、容器の活性化によって酸・ペプシンの食道への刺激が中枢へと伝達され、咬筋筋活動に関与する可能性が考えられ、食道への酸・ペプシン暴露によって咬筋筋活動が誘発され、それは食道における侵害受容器との関連が示唆された。Many questions about the context of the nociceptors and masseter muscle activity and acid reflux into the esophagus, we focus on the nociceptors In this study, we loaded with acid—pepsin stimulation to rat esophageal mucosa, infringement and masseter muscle activity We investigated the enhanced expression of receptors. Was injected saline, the acid pepsin solution in Wister male rats, were examined for nociceptors esophagus and masseter muscle activity. Masseter muscle activity, expression of nociceptors was significantly in acid pepsin solution group. From this result, esophageal irritation of acid—pepsin is transmitted to the central by the activation of the vessel, likely to be involved in masseter muscle activity can be considered, masseter muscle activity is induced by acid—pepsin exposure to road , it was suggested to be associated with nociceptors in the esophagus
pathological analysis of helper T cell abnormality induced obesity
No full text2011-2013年度科学研究費助成事業（基盤研究（C））研究成果報告書 課題番号：23592740 研究代表者：大西智和（鹿児島大学・医歯（薬）学総合研究科・准教授）DUSP16のドミナントネガティブをT細胞特異的に発現させたマウスであるMKP-M CSマウスを作成したところ、ヘルパーT細胞の機能に異常が認められた。さらに、このマウスは摂食過多による体重上昇が認められた。そこで、視床下部の神経ペプチドの発現を調べたところ、接触時に接触刺激性のNPYの減少が少ないことが判明した。次に、小腸が分泌し満腹シグナルであるコレシストキニン（CCK）の発現を検討したところ、摂食時における発現が少ないことが判明した。これらのことから、MKP-M CSマウスでは摂食時に、CCKが少なくなり、視床下部のNPYの発現が減少しないため多く摂食し体重増加が起こることが示唆された。We previously prepared MKP-M CS mice, which specifically express dominant negative DUSP16 in T cells. These mice had abnormality in helper T cell functions. We observed that MKP-M CS mice increased in food intake to obtain high body mass. Therefore, we analyzed expressions of various neuropeptides in their hypothalamus. We found that MKP-M CS mice decreased a reduction of expression of NPY, which stimulates feeding, during food feeding. Next, we detected expression of cholecystokinin (CCK), which is a satiety signal peptide, in small intestine. We found that T cell specific DUSP16 dominant negative decreased CCK expression in intestine of MKP-M CS mice during feeding. In summary, MKP-M mice increased inhibition CCK expression in small intestine and reduction of NPY in hypothalamus to increase in body mass and food intake during feeding
Functional analysis of an oncogene SnoN as atarget molecule to regulate progresion of osteoarthritis.
No full text2011-2013年度科学研究費助成事業（基盤研究（C））研究成果報告書 課題番号：23592221 研究代表者：前田真吾（鹿児島大学・医歯（薬）学総合研究科・准教授）変形性関節症（OA）は、患者の活動性を奪い、生命をも脅かしうるロコモティヴ・シンドロームの主因である。その抑制機構としてTGF-βシグナルに注目し、その下流で誘導されるSnoNについて治療標的分子としての可能性について検討した。関節軟骨細胞は分化進行を止めているが、OAでは異常に分化成熟が起こる。SnoNは正常関節軟骨には発現せず、軟骨細胞が肥大成熟すると発現し、OA軟骨で誘導されていた。SnoNが軟骨細胞分化を進めるBMPシグナルを抑制する事で、結果として軟骨細胞成熟を抑制する事が分かった。SnoNの機能を強めるとTGF-β添加と同じ結果になったので、OA予防・治療の標的と成りうる。Osteoarthritis (OA) suppresses activity of patients, which conditions often lead patients to death. Loss of TGF-beta signaling in mice promotes hypertrophic maturation of chondrocytes in articular cartilage, the phenotype of OA. Among the downstream molecules of TGF-beta signaling, we focused on SnoN to examine its roles in chondrocyte maturation and pathogenesis of OA. SnoN was not expressed in human normal articular cartilage or immature chondrocytes of mice, while it was detected in human OA cartilage as well as in matured mouse chondrocytes. During BMP-induced chondrogenesis in vitro, SnoN suppressed BMP signaling to inhibit the chondrocyte maturation. Gain-of-function of SnoN mimicked the effects of TGF-beta application, therefore, SnoN was suggested to be a novel molecular target in treatment or prevention of OA
Characterization and targeting Folate receptor-beta expressed tumor associated macrophages in glioblastoma
No full text2011-2013年度科学研究費助成事業（基盤研究（C））研究成果報告書 課題番号：23592134 研究代表者：永井拓（鹿児島大学・医歯（薬）学総合研究科・講師）マクロファージは局在する組織で多様化する特徴を持つ。腫瘍組織では増殖や転移、腫瘍免疫回避に働くと考えられている。これまでに葉酸受容体β（FRβ）は、悪性度の高い脳腫瘍に局在するマクロファージで高発現する事を報告してきた。本研究では、抗がん免疫（ワクチン等）が生じ難い動物モデル（F98細胞移植ラットモデル）に抗FRβ抗体トキシンを投与し、FRβマクロファージ除去によるワクチン増強効果を検討した。その結果、抗体トキシンによる免疫原性はワクチン効果の減弱化に関与する可能性が示唆された。この問題を解決するために新たに抗体トキシンを設計・作製し、動物モデルで有効性（免疫原性）の検討を行った。Folate receptor-beta (FRb) is over expressed in tissue-activated macrophages in autoimmune diseases and some tumors (e.g. glioblastoma). We previously determined that FRb-macrophages in glioma may play a role to promote tumor growth. The present study evaluated the efficacy of targeting of FRb-macrophages by anti-FRb immunotoxin for treating immunotherapy of weakly immunogenic F98 glioma rat models. Fischer rats received an intracerebral implantation of F98 cells. After 3 days, subcutaneous administration of vaccination (freeze/thaw treated F98) were performed in presence/absence of immunotoxin (intraperitoneal administration). However, no significant differences in survival times were observed. When combined liveing cell F98 and immunotoxin administration enhanced survival times, but significance was not observed. We investigated the presence of anti-immunotoxin antibodies. We further developed newly immunotoxin which showed low immunogenicity and used for long-term administration
C-type natriuretic peptide modulates permeability of the blood; brain barrier
No full text2011-2013年度科学研究費助成事業（基盤研究（C））研究成果報告書 課題番号：23592100 研究代表者：永山哲也（鹿児島大学・医歯（薬）学総合研究科・客員研究員）C型ナトリウム利尿ペプチド（CNP）は、脳に豊富に存在することが報告されているが、血液脳関門（BBB）に対する機能は明らかではない。本研究では、CNPによるBBB透過性亢進作用とそのメカニズムを解明した。BBBのバリア機能は、CNPの濃度依存的に減少した。CNPの作用は、cGMPのアナログである8-Br-cGMPで再現され、PKGの阻害剤であるRp-8-CPT-cGMPで阻害された。さらに、マウスにCNPを静注すると、血中フルオロセインの脳実質移行性が増加した。以上の結果より、CNPはBBBの透過性を亢進することが可能で、この結果は脳に対するドラッグデリバリーシステムの構築に寄与できる。C-type natriuretic peptide (CNP) is abundant in brain, but its effect on blood-brain barrier (BBB) permeability has not been clarified yet. Here, we examined this effect. Transendothelial electrical resistance (TEER) of in vitro BBB model, was significantly dose dependently decreased by CNP. CNP treatment reduced both the messenger RNA and protein expressions of zonula occludens-1 (Z0-1). The effects on TEER, mRNA, and protein expressions of ZO-1 were mimicked by cyclic GMP (cGMP) analog 8-bromo-cGMP and reversed by protein kinase G (PKG) inhibitor Rp-8-CPT-cGMPS, thus implying the role of PKG and cGMP signaling in BBB function. In vivo study of mouse brain by fluorimetric analysis with intravenous administration of sodium fluorescein also showed a significant increase in BBB permeability by CNP. These findings suggest that CNP modulates the BBB permeability by altering ZO-1
Interaction of cognitive function and glucose metabolism: angiotenisn IV and IRAP system as a new therapeutic target
No full text2011-2013年度科学研究費助成事業（基盤研究（C））研究成果報告書 課題番号：23590877 研究代表者：大石充（鹿児島大学・医歯（薬）学総合研究科・教授）レニン‐アンジオテンシン系のサブ・コンポーネントAng IVが海馬に発現するIRAPと呼ばれるGLUT4の細胞膜への移動に関係する酵素を受容体とすることが留学中の研究室より報告された。Ang (1-7) が独立してMEF1およびGLUT4産生亢進を介して耐糖能異常抑制することを我々は証明した。さらに我々は、アミロイドβ1-40脳室内投与認知障害モデルを作成して、Ang IVがIRAPを介して記憶に関連する可能性を検討したが、認知機能障害が非常に不安定で、詳細な検討に用いることが難しいと判断した。現在、APP遺伝子改変マウスとIRAPノックアウトマウスの掛け合わせを行う実験の準備中である。The Australian laboratory which I investigated before cloned the insulin-regulated aminopeptidase (IRAP) as a receptor for angiotensin IV, sub-component of renin-angiotensin system. It is a member of the family of zinc- dependent membrane aminopeptidases, which is mainly located in hippocampus and plays an important role for translocation to membrane of GLUT4. We reported another sub-component, angiotensin (1-7) improved glucose intolerance via increased MEF1 and GLUT4 production. We planned angiotensin IV and IRAP as a new therapeutic target for cognitive impairment using amyloid beta 1-40 intra-ventricular infusion model with IRAP knockout mice donated from the Australian laboratory. The cognitive function of this model is too unstable to evaluate angiotensin IV and IRAP function for cognitive impairment, we are now planning to make double knockout mice with IRAP and APP
Food Security in Small Islands: Case Studies in the Federated States of Micronesia
No full textIn the 1950s, people in the Federated States of Micronesia (FSM) still ate a “traditional” diet based on starchy staple crops and marine resources, but this began to be replaced by imported food such as rice, flour, sugar, fatty foods, and other processed foods after the United States Department of Agriculture started its supplementary feeding program in the 1960s. This phenomenon accelerated after a Compact of Free Association was signed between the FSM and the United States in 1986. Since then, the FSM has faced serious public health problems due to this new diet and other lifestyle changes. On small islands and atolls, imported foods and medicines may not arrive for more than a month if a typhoon or an oil crisis occurs. In this study, a detailed study of household food consumption is shown to represent the present situation of food security on Piis-Paneu Island (Chuuk Atoll, Chuuk State) and Pingelap Island (Pohnpei State)
Citrus Genetic Resources Grown on the Ryukyu Islands, Japan
No full textThe Ryukyu Islands are located southwest part of Japan. Various local citrus are grown in this subtropical region. Since there are large geographical and climatic differences between the Ryukyu Islands and the main islands (Honshu, Kyushu, and Shikoku) of Japan, there are unique local citrus genetic resources on the Ryukyu Islands. Shiikuwasha (Citrus depressa) is an indigenous mandarin species in this region. This species is clearly distinguished from the mandarin grown in China and India based on the results of isozyme and DNA analyses. DNA analysis also revealed that wide diversity exists in Shiikuwasha. Although Kunenbo (C. nobilis) and Daidai (C. aurantium) have been grown in most the islands, they were introduced from China and/or Southeast Asia. Indigeneous Shiikuwasha and introduced species probably played a part in the origin of many local citrus on the Ryukyu Islands. Various unique species in this region such as Kabuchii (C. keraji), Oto (C. oto), and Rokugatsu-mikan (C. rokugatsu) have been widely cultivated. Fruit of some local citrus contains high levels of polymethoxyflavonoids, one of the most important health-promoting components of citrus
Mosquito Borne Diseases in Ambon Municipality
No full textMosquitoes are very dominant vectors of common diseases in tropical region including Ambon Municipality, Indonesia. Three genera of mosquitoes namely Anopheles, Aedes, and Culex transmitted malaria, dengue fever, and lymphatic filariasis, respectively. Breeding sites of Anopheles and Culex are usually outdoors in dirty water such as drainage, gutters, and swamps, while that of Aedes is indoors in
clean water such as flower vase, tubs, and opened water drum. Annual Parasite Incidence (API), which is number of cases per a thousand populations, is used to determine malaria cases in Ambon Municipality. The highest API of 6.54 was in Nusaniwe District in 2012, while that of 5.92 was in Teluk Ambon-Baguala District in 2013. Number of cases of dengue fever increased in the last three years. Since 2011, there are 8 cases of lymphatic filariasis in Ambon Municipality. Methods that are commonly used to control the vectors are source reduction as well as larval and adult controls. Surveillance was generally done by observing only the presence or absence of larvae in their breeding sites. Intensive surveillance in terms of collection and identification of the vectors as well as development of effective control methods are needed
霧島地区の温泉資源を活用するエネルギー，環境，ヘルスケアを統合した開発プロジェクトの可能性について
Get PDF霧島地区の温泉資源を活用した、町おこしのための様々な開発プロジェクトの可能性について検討した。バイナリーサイクル発電を利用したエコハウス、エコタウンの実現が可能であることが示された。熱電素子を用いた温泉廃熱のエネルギーハーベスティングによるLED 照明が可能であることが実験的に示された。またヘルスケアへの温泉利用の観点から、温泉入浴のストレス抑制効果の評価のための方法として、筋電計による心拍・脈波計測、無線型脳波計の利用による脳波計測について検討した。携帯情報端末を利用した研究者間での情報共有の手法について検討した