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指導老師：周淑娥 指導助教：林博雅 生物諾貝爾報告 第五組 潘柏諺 劉正昇 賴暉元 謝馨儀 蘇家霈

Noble Prize in Medicine 2005 The discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease. 指導老師：周淑娥 指導助教：林博雅 生物諾貝爾報告 第五組 潘柏諺 劉正昇 賴暉元 謝馨儀 蘇家霈. J. Robin Warren. Barry J. Marshall. 1975 (25) Bachelor of Medicine, Bachelor of Surgery 1981 (31)

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指導老師：周淑娥 指導助教：林博雅 生物諾貝爾報告 第五組 潘柏諺 劉正昇 賴暉元 謝馨儀 蘇家霈

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  1. Noble Prize in Medicine 2005The discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease 指導老師：周淑娥 指導助教：林博雅 生物諾貝爾報告 第五組 潘柏諺 劉正昇 賴暉元 謝馨儀 蘇家霈

  2. J. Robin Warren Barry J. Marshall • 1975 (25) Bachelor of Medicine, Bachelor of Surgery • 1981 (31) met Robin Warren • 1985 (35) experiment was published • 2005 (55) awarded the Nobel Prize in Physiology or Medicine • 1962 (25) Adelaide University • 1979 (42) noticed bacteria growing on the surface of a gastric biopsy • 1981 (44) met Barry Marshall • 2005(68) awarded the Nobel Prize in Physiology or Medicine

  3. 人體試驗 • Marshall • 1984.7. drink the solution with germs • Abdomen bloated → spit grume → headache → gastric inflammation • antibiotic • Warren • Abdomen ache → vomit • antibiotic • Cause long-term chronic gastritis • Koch's postulates

  4. H. pylori • Gram negative • Spiral bacillus • 2~4 um • Secret urease • Oral-to-oral infection

  5. 流行概況 • Age involvement • H. pylori %(Rate of being infected) =(age × 1.1) － 9.7 • Racial difference • Associated with the economy development • Different sensitivities • No sexual difference • 「Occupational disease 」

  6. The localization of H. pylori

  7. TFSS

  8. Urease • NH2CONH2NH3　＋　H2CO3 Urease • For survival • Neutralize the stomach acid • NH3 ： • Mucoprotein (mucin) decreases • Destroy the completeness of mucus ion

  9. VacA (Vacuolating cytotoxin A)–液泡毒素 • Discover：1980 • diameter：~30nm • Size ：~87KD • Oligomer：~1000KD

  10. Apoptosis Vacuolation Inhibit Tcell activation Functions of VacA nutrition Tight junction IL-12

  11. Variation of VacA 特優

  12. VacA基因的意外用途…

  13. CagA(cytotoxin associated gene A) • Translate to protein CagA ( 細胞毒素攜帶抗原A ) • cagA exists only in some H. pylori • People who are infected by H. pylori with cagA have more chances to catch gastric ulcer and cancer.

  14. IL-8 TFSS IL-8

  15. Process

  16. Correa’s cascade

  17. Diagnoses • Invasive testing： • Histological examination • Culture • P.C.R. • Rapid urease test • Non-invasive testing： • Serology test • Scatological examination • C-13-urea breath test 特優

  18. Urease • NH2CONH2NH3　＋　H2CO3 H2CO3　→　H2O　＋　CO2

  19. Cures for Peptic Ulcer and Gastritis • Triple therapy ： • Two remedies： • Antibiotics + bismuth subsalicylate • Antibiotics + proton pump inhibitors • Curability can be 80%~90%. • In Taiwan, curability is 83% in a week. • Secret worry：The result of failure

  20. Summary 特優

  21. References-1 • 張朝勝. Identification of a new segment involved in cagA 3' region variation of Helicobacter pylori. (2002). • 譚健民. 幽門螺旋桿菌導致胃黏膜傷害的免疫致病機轉. (2008). 台灣醫界 2008, Vol.51, No.1 • 陳慈棻. 幽門螺旋桿菌誘導胃上皮細胞行程胃炎之作用機制. (2004). • 王玫瑛. Development of enzyme-linked immunosorbent assay (ELISA) kit for the diagnosis of Helicobacter pylori infection. (2006). • 劉作財. The retrospective study of Helicobacter pylori infection and antibiotic resistant. (2006). • 王靜雯. VacA and CagA in Taiwanese strains • 陳在玲. Smoking and Male Gender Rather than CagA Protein Are Associated With Increased Risk for Duodenal Ulcer in HelicobacterPylori-Infected Patients in Taiwan • 莊旭翔. 幽門桿菌刺激胃上皮細胞株表現腫瘤壞死因子的機制探討. (2007). Retrieved from http://fedetd.mis.nsysu.edu.tw/FED-db/cgi-bin/FED-earch/view_etd?identifier=oai:etdncku.lib.ncku.edu.tw:etd-0806107-151120&index_word= • 任剛. 幽門螺桿菌致病機制的最新進展. (1999).《醫學綜述》 1999年 第5卷 第4期 • 新發現幽門螺旋桿菌致胃癌的兩種蛋白質. (2001). Science 2001 Dec 13 • 陳立宗. 幽門螺旋桿菌與胃癌. Retrieved from http://www.tccf.org.tw/information/HP_G.HTM

  22. References-2 • 賈博琦. 幽門螺桿菌感染的治療--2.1概論--胃十二指腸潰瘍病時幽門螺桿菌感染的治療. (2007). Retrieved from http://med.qe.cn/HTML/123894.html • 潘明亮. 消化性潰瘍的藥物治療. Retrieved from http://www.sccpc.com.cn/guanyuwomen/qi-kan/2/xiao-hua-xky.htm • 許博翔, 洪貴香, 吳惠雯, 吳俊忠. 2005年諾貝爾生理醫學獎──揪出幽門桿菌的啟示. (2006).《科學發展》2006年7月，403期，40 ~ 47頁. Retrieved from http://www.nsc.gov.tw/_NewFiles/popular_science.asp?add_year=2006&popsc_aid=79 • 崔乃林, 牛換香, 李天元. 幽門螺桿菌與胃癌的流行病學關係及致癌機制. (2007). Retrieved from http://www.bioon.com/Article/hpv/309299.shtml • 譚健民. 抓出元兇！如何檢測「胃幽門螺旋桿菌」感染的存在？. (2005). Retrieved from http://hospital.kingnet.com.tw/essay/essay.html?pid=11577&category=醫藥疾病&type= • 幽門螺桿菌致病機制的最新進展. (2007). Retrieved from 健康人家 http://lw.jkrj.cn/HTML/62906_2.shtml • 幽門螺旋桿菌(一). (2006). Retrieved from 台灣醫療網 http://tw16.net/monographData.asp?m1No=4&m2No=63&m3No=413&mMo=3045 • 淺談胃藥. Retrieved from 台北榮民總醫院 http://homepage.vghtpe.gov.tw/~gi/book/book3.htm • 胃幽門螺旋桿菌呼氣檢測. (2005). Retrieved from http://www.ch.com.tw/index.asp?chapter=ACH000007

  23. References-3 • 胃潰瘍的祕密. (2006). Retrieved from http://tw.myblog.yahoo.com/clarinase-1/article?mid=116&prev=157&next=103&l=f&fid=7 • 日科學家稱解開幽門螺桿菌引發胃癌的機制. (2007). Retrieved from 美迪醫療網http://www.labsky.com/data/07/04/news/0428111735478.htm • 科學人雜誌37期p.68~p.81 • One Step H.pylori Rapid Test Strip (Serum). Retrieved from http://www.gmb.com.tw/html/pdf/uman.pdf • Denise M. Monack, Anne Mueller and Stanley Falkow. Persistent bacterial infections: the interface of the pathogen and the host immune system. (2004). Retrieved from Nature reviews Volume 2, September 2004 • H.pylori's CagA deregulates gastric cell protein to induce abnormal proliferation.(2001).Retrieved from http://www.oncolink.upenn.edu/resources/article.cfm?c=3&s=8&ss=23&Year=2001&Month=12&id=7852 • J. W. KONTUREK. Discovery by Haworskiof helicobacter pylori and its pathogenetic role in peptic ulcer, gastritis and gastric cancer. (2003). Retrieved from http://www.jpp.krakow.pl/journal/archive/1203_s3/articles/03_article.html • National Digestive Diseases Information Clearinghouse. H. pylori and Peptic Ulcer. (2004). Retrieved from http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/

  24. References-4 • Richard M. Peek, Jr. and Martin J. Blaser. Helicobacter Pylori and gastrointestinal tract adenocarcinomas. (2002).Retrieved from Nature reviews Volume 2, January 2002 • Richard M. Peek, Jr. Intoxicated cells and stomach ulcers. (2003).Retrieved from Nature Volume 33 • Steven F. Moss, MD. Premalignant Lesions: H. pylori and Gastric Cancer. (2001). Retrieved from http://www.webtie.org/SOTS/Meetings/Gastrointestinal/March62001/lectures/MOSS/transcripts/transcripts.htm • S.K. Mustapha, FWACP, etc. Endoscopic Findings And The Frequency Of Helicobacter Pylori Among Dyspeptic Patients In North-Eastern Nigeria. (2008). Retrieved from http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijge/vol6n1/pylori.xml • Terry Kwok1, Dana Zabler1, Sylwia Urman, Manfred Rohde, Roland Hartig, Silja Wessler, Rolf Misselwitz, Ju¨rgen Berger, Norbert Sewald, Wolfgang Ko¨nig1 & Steffen Backert. Helicobacter exploits integrin for type IV secretion and kinase activation. (2007). Retrieved from Nature 06187 Vol449

  25. References-5 Pictures: • Breath Tests. (2006). Retrieved from The Helicobacter foundation http://www.helico.com/diag_breath.html • C13 test. Retrieved from http://www.infai.com/images/infaikit.gif • H. pylori. Retrieved from http://www.nsc.gov.tw/files/popsc/2006_79/9507-07-02.JPG • Konturek et al. (1998). Retrieved from http://www.jpp.krakow.pl/journal/archive/1203_s3/gfx/rys04_9.gif • Rapid urease test. Retrieved from http://www.mednet.cn/CN/images/UpFileSmall/2006_7_6_15_31_44_2768.jpg • Retrieved from http://upload.wikimedia.org/wikipedia/commons/thumb/3/30/H_pylori_virulence_factors_ja.png/500px-H_pylori_virulence_factors_ja.png • Retrieved from http://upload.wikimedia.org/wikipedia/commons/archive/9/9a/20070124111126!H_pylori_virulence_factors_en.png

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