認知症予防のための食品・生薬・漢方薬

認知症患者数の急増と高齢者医療費増が深刻な社会問題となっている。国は健康21（二次）を制定し、生活習慣病の予防を中心に掲げ医療費削減を目指している。また、最近認知症の発症を抑える数値目標が立てられた。認知症はアルツハイマー型認知症がほぼ50％でレビー小体型認知症と血管性認知症が続く。治療薬として進行を遅らせる薬が数種市販されているが、抜本的な治療薬や予防薬は上市されていない。このため疫学調査等で認知症予防に有効と認められた食品や生薬、また漢方薬等に頼らざるを得ない現状である。疫学調査による認知症予防には魚、野菜、緑茶、ワイン等、また、社会的な活動が明らかとなっている。脳循環性認知症予防にはニンニク、イチョウ葉等を取り上げた。サフランについては筆者等の研究を中心に詳述した。アルツハイマー型認知症に対する加味温胆湯の有効性に触れ、配合生薬の中で遠志に活性があり、更にオンジサポニンが活性本体である事が明らかとなり、現在は遠志が「物忘れ」に対する一般医薬品として販売されるに至っている

Intelligent Agents: Authors, Makers, and Owners of Computer-Generated Works in Canadian Copyright Law

The central objective of this article is to propose a clarification of copyright law as applied to works created by intelligent agents. In Part I, the concepts of artificial intelligence and intelligent agents are introduced. Part II identifies the challenges that are presented to the tests of originality and authorship in the application of copyright to works generated by intelligent agents. It is argued that works created by intelligent agents may meet the tests of originality and authorship. It is also argued that the con- cepts of ‘‘author’’, ‘‘owner’’, and ‘‘maker’’ are distinct from one another in Canadian copyright law. Part III addresses copyright policy arguments. It is shown that intelligent agents may be authors of works but not owners of copy- right, and that there is no clear candidate who should be designated the maker of works created by intelligent agents. The role of the public domain is also considered, and it is concluded that the best solution is for no copy- right ownership to be vested in anyone. Database protec- tion legislation is examined in Part IV. The paper con- cludes with some suggestions that should be considered as part of the ongoing process of Canadian copyright law reform

サフランの薬理活性

サフランとその主活性成分であるクロシンの薬理作用を検討した。サフランエキスは、アルコールにより記憶学習を障害したマウスの記憶学習能を改善した。本活性本体はクロシンであり、クロセチンに結合するグルコースの数が少なくなるにつれて活性が低下した。PC-１２ 細胞を用いてクロシンのアポトーシス抑制効果を検討した。アポトーシス惹起条件下においてもクロシンを培地へ添加することによりアポトーシスが抑制されることが明らかとなった。クロシンのアポトーシス抑制効果について各アポトーシス誘導ステップを検討した結果、クロシンはスフインゴミエリネース活性を低下することによりセラミドレベルを低下させ、また、グルタチオンレベルを上昇させることにより細胞の安定化を促進し、PC-１２ 細胞のアポトーシスを抑制することが明らかとなった。We investigated the improvement effect of crocin for ethanol-induced impairment of learning behaviors of mice in passive avoidance tasks.　Further it became evident that crocin prevents the inhibitory effect of ethanol on long-term potentiation（LTP）in the dentate gyrus in vivo.　We confirmed that crocin inhibits tumor necrosis factor（TNF）-α-induced apoptosis of PC-１２ cells.　PC-１２ cells rapidly increased the cellular ceramide levels, followed by an increase in the phosphorylation of c-jun kinase（JNK）leading to apoptosis by serum/glucose deprivation in medium.　The production of ceramide was dependent on the activation of magnesium-dependent neutral sphingomyelinase（N-SMase）, but not on de novo synthesis.　The oxidative stress also decreased the cellular levels of glutathione（GSH）, which is the potent inhibitor of N-SMase.　Crocin treatment resulted in the prevention of N-SMase activation, ceramide production, and JNK phosphorylation.　Exploration of the crocin\u27s preventive mechanism for oxidative stress-induced cell death revealed that the activities of GSH reductase and γ-glutamylcysteinyl synthase（γ-GCS）in the γ-glutamyl cycle affected to the stable GSH supply that blocks the activation of N-SMase.　These results strongly support the importance of the proposed GSH-dependent inhibitory mechanism in oxidative stress-mediated cell death

植物バイオテクノロジーによる薬用植物の育種研究

薬用植物の均質化を遂行するためにトリカブトのクローン増殖を行い、それらクローン苗を栽培してアコニチン系アルカロイドの均質性を確認すると共に、季節変動により含量に大きな差が出ることを明らかにした。また、バイオトロンにより温度による変動を検討し、温度が高いほどアコニチン系アルカロイド含量が高いことを明らかにした。ニンジンの花芽をカルス化し、不定胚から幼植物を得る手法を確立した。本手法により得られた植物の遺伝子分析によりその均質性を確認した。　除草剤耐性遺伝子をパーテイクルガンにより直接カラスビシャク細胞へ導入し、トランスジェニック植物に除草剤耐性が付与されることを明らかにした。抗ソラソジン配糖体モノクローナル抗体の小型化抗体(scFV)遺伝子をホスト植物へ、アグロバクテリュウムを介して形質導入し、トランスジェニック植物を得て、scFVタンパク発現の確認とソラソジン配糖体含量を分析した。その結果scFV遺伝子を導入することによりコントロールに比べて約３倍の含量になった。本手法は新しい育種法として展開可能と考えられ、ミサイルタイプ分子育種と命名した。In order to control the quality of crude drugs Aconitum species was clonally micropropagated by tip tissue culture. The clonally propagated plants were cultivated to make clear their homogeneity and I found that wide differences of aconitine-type alkaloid occurred depending on seasonal variation. To confirm the relation between cultivation temperature and the concentration of aconitine-type alkaloid the clonally propagated Aconitum species were cultivated in biotron resulted that the higher temperature induced the higher concentration of aconitine-type alkaloids. The flower buds of Panax ginseng (ginseng) were cultured to produce callus which regenerated via somatic embryogenesis. The homogeneity of regenerated ginseng plants was confirmed by RAPD analysis using suitable primers. Anti-herbicide gene was induced directly into the Pinellia cells by a particle gun to give the transgenic plants which possess the anti-herbicide activities. A gene of single chain fragment-variable (scFV) antibody against solasodine glycosides was cloned and inserted into the host plant, Solanum khasianum using Agrobacterium plasmid. We confirmed the expression of scFV protein in the transgenic S. khasianum plants by the western blotting and MALDI-tof mass spectrum and the concentration of solasodine glycosides by ELISA used anti-solamargine monoclonal antibody (MAb). The concentration of solasodine glycosides increased approximately three times compared to that of original plant. From this result this methodology can be used as a new breeding technique and we named it missile type molecular breeding

大麻研究

マリファナはアサから生産され、世界各国地域により色々な名称で呼ばれる。マリファナは特異のカンナビノイドと称するアルキールフェノールを含有する。それらの中で最も強い幻覚活性を持つのが THC である。THCA 生合成酵素を新鮮なアサから精製・単離し、その性状を明らかにした。THCA 生合成酵素は CBGA から環を形成して THCA を生成する過程を触媒する。また、THCA 生合成酵素はいかなる補酵素も要求しないので内在性の FAD 等の補酵素を持つことが予想される。そこで THCA 生合成酵素をクローニングし、昆虫細胞系で大量発現し結晶化に成功した。X-線結晶解析により全構造を明らかにした。これにより FAD がヒスチジン、システインと結合しポケット付近に位置すること、チロシンが環形成に必須であることを明らかにした。THCA 生合成酵素はアサの腺毛で生合成されそこで大麻成分を生合成することが明らかとなった。Marihuana is produced from Cannabis sativa L.(Cannabinaceae) and called variously as haschisch, bengh, antabamik, muraba, and so on in the world. Marihuana contains typical alkyl phenolics named as cannabinoid. Among them tetrahydrocannabinol(THC)is the most strong hallucinativelly active cannabinoid. Biosynthetic enzymes of cannabinoids like tetrahydrocan-nabinolic acid synthase(THCAsynthase) has been purified and isolated from the fresh Cannabis plant and its characterization has become evident. THCAsynthase can catalyze the formation of cyclic ring of THCA from cannabigerolic acid(CBGA). Since THCAsynthase no need any co-factor like FAD, NADP NADP and FMN, it seems to be that THCAsynthase itself has co-factor in a molecule. THCAsynthase gene was cloned and super expressed using insect cell system resulting in crystallization. X-ray analysis of THCAsynthase has been succeeded to make evident its whole structure. It became evident that THCAsynthase posses FAD conjugated with histidine and systeine as a co-factor and tyrosine residue in a pocket functions as an acceptor of hydrogen from a hydrogen oxide in CBGA. Granular hair of Cannabis plant accumulated THCA because THCAsynthase was biosynthesized and expressed in only granular hair

東洋と西洋の紫色素

古来より紫色素は洋の東西を問わず高貴な色として尊ばれてきた｡本稿では東洋とﾖｰﾛｯﾊﾟで主に流通しているﾑﾗｻｷ科植物を取り上げて基原植物や歴史的な背景を検証した｡特にﾑﾗｻｷは日本における自生分布が広く､8～10世紀には各地で栽培が行われ大量の紫根が朝廷へ上納されていた状況について述べた｡紫根に含有する紫色素である shikonin は日本で単離構造決定されたのでそれらに付いても言及した｡さらにﾑﾗｻｷ科植物の shikonin や光学異性体の alkannin 等の生合成経路についても述べた｡又､光学異性体に関わる基原植物に関しても調査を行った｡一方､ﾖｰﾛｯﾊﾟで用いられているｱﾙｶﾝﾅ根から新化合物3種を含む8種の alkannin 関連化合物を単離･構造決定を行い､それらについてﾋﾄ大腸がん細胞を用いて細胞抑制作用を確認し､それらの中で最も抑制効果の高かった化合物につき､ｶｽﾊﾟｰｾﾞ-9を介したｱﾎﾟﾄｰｼｽ誘導が起こることを明らかにし､ﾄﾞｯｷﾝｸﾞ試験によりｱﾎﾟﾄｰｼｽ惹起のﾒｶﾆｽﾞﾑを明らかにした｡The historical background of purple pigment in Asia and Europe has been reviewed in this article. It became evident that major species for the production of purple pigment in Japan was Lithospermum erythrorhizon Sieb. et Zucc. which had been cultivating widely during 8 to 10 centuries in Japan. The structure of major component in L. erythrorhizon, shikonin was elucidated in Japan in 1918, and its biosynthetic pathway was confirmed together with alkannin isolated from Alkanna tinctoria in Europe. The author succeeded to isolate and elucidate the structures of 8 components related to alkannin including 3 novel compounds from A. tinctoria roots, and determined their anti-cancer activities using human colon cancer cell lines, and confirmed the apoptosis mechanism by docking evidence

Effective Use of External Electric Field for Charging and Levitation of Particles Under UV Irradiation

Electrostatic forces can be used to control the motion of charged particles. In this article, particle charging and motion in an electric field under ultraviolet (UV) irradiation were investigated. When the particle layers deposited on an insulating substrate were irradiated with UV light in a downward electric field, photoelectrons were emitted, and positive charges moved to the bottom of the particle layers. Subsequently, by reversing the direction of the electric field, the positive charges in the bottom moved upward; thus, the particles in the top layer were positively charged and levitated by Coulomb forces. The flux of the levitated particles increased with an increase in the strength of the electric field (downward and upward). As the upward electric field strength increased, the number of agglomerated particles in the levitation increased; however, the particle charge decreased. As the thickness of the particle layers increased, the time delay for particle levitation increased; however, the flux of the levitated particles decreased. The ratio of agglomerated particles to the total levitated particles increased. These results can be explained by the mechanisms of charge transfer and particle levitation