1 / 65

Kenneth K. Wu 伍焜玉

研究生涯與社會關懷之經歷. Kenneth K. Wu 伍焜玉 Distinguished Investigator and President, National Health Research Institutes (NHRI), Taiwan Member, Academia Sinica, Taiwan. 中學時代. 大學時代. 醫學系（醫科）. 前二年 醫預科 （動植物學、物理、化學、有機化學、英文、歷史（近代史）） 3-4年 基礎醫學 （解剖、組織、生化、生理、毒理、病理、公共衛生、微生物、免疫） 5-6年 臨床醫學 （內科學、外科學等）

erik
Télécharger la présentation

Kenneth K. Wu 伍焜玉

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 研究生涯與社會關懷之經歷 • Kenneth K. Wu 伍焜玉 • Distinguished Investigator and President, National Health Research Institutes (NHRI), Taiwan • Member, Academia Sinica, Taiwan

  2. 中學時代

  3. 大學時代

  4. 醫學系（醫科） • 前二年 醫預科（動植物學、物理、化學、有機化學、英文、歷史（近代史）） • 3-4年 基礎醫學（解剖、組織、生化、生理、毒理、病理、公共衛生、微生物、免疫） • 5-6年 臨床醫學（內科學、外科學等） • 7年 實習

  5. 開業 醫學系 專業醫師訓練 研究、教學 公共衛生 政策

  6. 赴美國入研究所：微生物及免疫

  7. New Haven 在美國New Haven生活

  8. 進入臨床專科醫師訓練 • 內科學 • 內科血液腫瘤科

  9. 在美國愛荷華市生活 Iowa City

  10. 選擇血栓及血小版研究 血栓 動脈血栓 靜脈血栓 心血管疾病腦中風 肺血管阻塞

  11. Formation of an advanced, complicated lesion of atherosclerosis N Engl J Med. 1999;340:115-126

  12. 動脈血栓 靜脈血栓 血栓之成分 凝結蛋白質 血小板 紅血球 血小板 凝結蛋白質 血管壁硬化破裂 白血球

  13. 血小板之活性在動脈血栓扮演什麼角色？

  14. 個別血小板 刺激後 凝結並釋放出Active materials 血栓成分 血管壁傷害 （發炎） 血管病變

  15. 血小板（150,000-450,000 / ml） 數量減少 數量增多 功能減低 出血 血栓 出血

  16. 血小板功能增加時是否增加血栓？

  17. Lancet. 1974;2:924-926. A new method for the quantitative detection of platelet aggregates in patients with arterial insufficiency. Wu, K.K., Hoak, J.C.

  18. Thromb Haemost. 1976;35:702-711. Spontaneous platelet aggregation in arterial insufficiency: mechanisms and implications. Wu, K.K., Hoak, J.C.

  19. Ann Intern Med. 1978;88:7-11. Platelet hyperaggregability and thrombosis in patients with thrombocythemia. Wu, K.K.

  20. Aspirin (阿斯匹靈)

  21. Salix alba L.

  22. Willow bark extract • Hippocratea and other Greek physicians mentioned it. • Chinese used it over 2000 years ago. • 18th century: -- Japanese used it to treat emperor’s tension headache -- Rev. Edmund Stone used it to trat patients with fever and pain.

  23. Edmund Stone Philosophical Transactions. 1763;53:195-200. (Chipping Norton, London, Oxfordshire)

  24. Johann Buchner (Germany), 1828 Salicin isolation • Raffaele Piria (France), 1836 Conversion of salicin to salicylic acid (SA) • Felix Hoffmann (Germany), 1899 Derivatization of SA to aspirin

  25. Early aspirin product

  26. Aspirin (阿斯匹靈)減少血小板功能

  27. 服用Aspirin 引起出血

  28. Aspirin 引起出血是因為它能抑止血小板功能

  29. Aspirin 能抑止血小板功能，是否能用來治療血栓疾病？

  30. Ann Intern Med. 1978;88:7-11. Platelet hyperaggregability and thrombosis in patients with thrombocythemia. Wu, K.K.

  31. 適量Aspirin (65 mg-325 mg) 能減少血栓形成，預防病人血栓疾病

  32. Aspirin 抑止前列腺素 (Prostaglandin)之產生

  33. Discovery and purification of cyclooxygenases (COX) 1933-1934 – Discovery of prostaglandins (Goldblatt, von Euler). 1960s – Isolation and structural analysis of PGs (Berström, Samuelsson). 1970s – COX was purified from ram seminal vesicles (Bill Lands). 1980s – COX cDNA was cloned (Bill Smith). This COX is now known as COX-1. 1990 – COX-1 X-ray crystal structure (Garavito)

  34. Cloning of COX-2 • Phorbol ester-induced genes in NIH 3T3 (Hershman’s group) • Src-induced genes in chick embryo cells (Simmon’s group) • (~60% sequence homology with COX-1)

  35. Nature Structural & Molecular Biology. 2000;7:448.

  36. Phospholipids (PC) Phospholipase A2 Arachidonic acid + LysoPC COX-2 or COX-1 PGG2 + PGH2 PGI synthase TXA synthase PGI2 TXA2 6-keto-PGF1α TXB2

  37. Arachidonic acid (AA) Aspirin COX-1活性 PGH2 TXA synthase TXA2 血小管凝結 血管病變

  38. AA Aspirin COX-2基因表達 PGH2 PGE2 etc. 發炎、癌症

  39. Proc. Natl. Acad. Sci. USA. 1991;88:2384-2387. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells Wu KK, Sanduja R, Tsai AL, Frehanoglu B, Loose-Mitchell DS.

  40. Aspirin and sodium salicylic inhibit COX-2, IL-4 and IL-6 expressions with equal potency at the transcriptional level. • They inhibit gene transcription by blocking binding of C/EBPb and c-Rel (NF-kB) transcription activators

  41. Aspirin and salicylate IL-1b PMA C/EBPb COX-2 promoter COX-2 PGE2

  42. C/EBPβ mutants PKA ERK T235 S288 1 345 N C T266 S325 RSK CaMKIV Mutants: T235A (ERK) T266A (RSK) S288A (PKA) S325A (CaMKIV)

  43. Transactivator Streptavidin Biotin Agarose DNA probe Western analysis

  44. FLAG Vector WT T235A T266A S288A S325A

More Related