1. 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

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

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

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

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

6. The localization of H. pylori

7. TFSS

8. Urease For survival For survival Neutralize the stomach acid Neutralize the stomach acid NH 3 ： NH 3 ： Mucoprotein (mucin) decreases Mucoprotein (mucin) decreases Destroy the completeness of mucus ion Destroy the completeness of mucus ion NH 2 CONH 2 NH 3 ＋ H 2 CO 3 NH 2 CONH 2 NH 3 ＋ H 2 CO 3 Urease

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

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

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

14. TFSS IL-8IL-8

15. Process

16. Correa’s cascade

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

18. NH 2 CONH 2 NH 3 ＋ H 2 CO 3 NH 2 CONH 2 NH 3 ＋ H 2 CO 3 H 2 CO 3 → H 2 O ＋ CO 2 H 2 CO 3 → H 2 O ＋ CO 2 Urease

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

21. Summary 特優

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26. References-5 Pictures: Breath Tests. (2006). Retrieved from The Helicobacter foundation http://www.helico.com/diag_breath.html 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 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 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 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 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_factor s_ja.png/500px-H_pylori_virulence_factors_ja.png Retrieved from http://upload.wikimedia.org/wikipedia/commons/thumb/3/30/H_pylori_virulence_factor s_ja.png/500px-H_pylori_virulence_factors_ja.png Retrieved from http://upload.wikimedia.org/wikipedia/commons/archive/9/9a/20070124111126!H_pyl ori_virulence_factors_en.png Retrieved from http://upload.wikimedia.org/wikipedia/commons/archive/9/9a/20070124111126!H_pyl ori_virulence_factors_en.png