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Noble Prize in Medicine 2005 Noble Prize in Medicine 2005 The discovery of the bacterium The discovery of the bacterium Helicobacter pylori Helicobacter pylori and its role and its role in gastritis and peptic ulcer in gastritis and peptic ulcer disease disease 指指指指 指指指 指指指指 指指指 指指指指 指指指 指指指指 指指指 指指指指指指指 指指指 指指指指指指指 指指指 指指指 指指指 指指指 指指指 指指指 指指指 指指指 指指指 指指指 指指指

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

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Page 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

Noble Prize in Medicine 2005Noble Prize in Medicine 2005

The discovery of the bacterium The discovery of the bacterium Helicobacter pyloriHelicobacter pylori and its role in and its role in gastritis and peptic ulcer diseasegastritis and peptic ulcer disease

指導老師:周淑娥指導老師:周淑娥指導助教:林博雅指導助教:林博雅

生物諾貝爾報告 第五組生物諾貝爾報告 第五組潘柏諺 劉正昇 賴暉元 謝馨儀 蘇家霈潘柏諺 劉正昇 賴暉元 謝馨儀 蘇家霈

Page 2: 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

Barry J. MarshallBarry J. Marshall

1975 (25) 1975 (25) Bachelor of Medicine, Bachelor of Bachelor of Medicine, Bachelor of Surgery Surgery

1981 (31)1981 (31) met Robin Warrenmet Robin Warren

1985 (35)1985 (35)experiment was publishedexperiment was published

2005 (55)2005 (55)awarded the Nobel Prize in Physiology or awarded the Nobel Prize in Physiology or MedicineMedicine

J. Robin WarrenJ. Robin Warren

1962 (25) 1962 (25) Adelaide UniversityAdelaide University

1979 (42)1979 (42)noticed bacteria growing on noticed bacteria growing on the surface of a gastric biopthe surface of a gastric biopsysy

1981 (44) 1981 (44) met Barry Marshallmet Barry Marshall

2005(68)2005(68)awarded the Nobel Prize in awarded the Nobel Prize in Physiology or MedicinePhysiology or Medicine

Page 3: 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

人體試驗人體試驗MarshallMarshall

1984.7. drink the solution with germs1984.7. drink the solution with germsAbdomen bloated → spit grume → headache → Abdomen bloated → spit grume → headache →

gastric inflammationgastric inflammationantibioticantibiotic

WarrenWarrenAbdomen ache → vomitAbdomen ache → vomitantibioticantibioticCause long-term chronic gastritisCause long-term chronic gastritis

Koch's postulatesKoch's postulates

Page 4: 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

H. pyloriH. pylori

Gram negative Gram negative Spiral bacillus Spiral bacillus 2~4 um2~4 umSecret ureaseSecret ureaseOral-to-oral infection Oral-to-oral infection

Page 5: 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

流行概況流行概況Age involvementAge involvement

H. pylori H. pylori %(Rate of being infected)%(Rate of being infected)

=(age × 1.1) =(age × 1.1) - - 9.79.7Racial differenceRacial difference

Associated with the economy developmentAssociated with the economy developmentDifferent sensitivitiesDifferent sensitivities

No sexual differenceNo sexual difference 「「 Occupational disease Occupational disease 」」

Page 6: 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

The localization of The localization of H. pyloriH. pylori

Page 7: 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

TFSS

Page 8: 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

UreaseUrease

For survivalFor survival

Neutralize the stomach acidNeutralize the stomach acidNHNH3 3 ::

Mucoprotein (mucin) decreasesMucoprotein (mucin) decreasesDestroy the completeness of mucus ionDestroy the completeness of mucus ion

NHNH22CONHCONH22         NHNH33  +  +  HH22COCO33

      

Urease

Page 9: 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

VacA VacA (Vacuolating cytotoxin A)(Vacuolating cytotoxin A)

––液泡毒素液泡毒素

DiscoverDiscover :: 19801980 diameterdiameter :: ~30nm~30nm Size Size :: ~87KD~87KD OligomerOligomer :: ~1000KD~1000KD

Page 10: 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

Functions of VacAFunctions of VacA

Vacuolation

Apoptosis

Inhibit Tcell activation

nutrition

IL-12

Tight junction

Page 11: 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

Variation of VacAVariation of VacA

特優

Page 12: 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

VacAVacA 基因的意外用途…基因的意外用途…

Page 13: 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

CagACagA(cytotoxin associated gene A)(cytotoxin associated gene A)

Translate to protein CagA ( Translate to protein CagA ( 細胞毒素細胞毒素攜帶抗原攜帶抗原 A )A )

cagA exists only in some cagA exists only in some H. pyloriH. pylori

People who are infected by People who are infected by H. pyloriH. pylori with cagA have more chances to catcwith cagA have more chances to catch gastric ulcer and cancer.h gastric ulcer and cancer.

Page 14: 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

TFSS

IL-8

IL-8IL-8

Page 15: 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

ProcessProcess

Page 16: 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

Correa’s cascadeCorrea’s cascade

Page 17: 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

DiagnosesDiagnoses

Invasive testingInvasive testing ::HistologicHistologicalal examination examination CultureCulture P.C.R.P.C.R.Rapid urease testRapid urease test

Non-invasive testingNon-invasive testing ::Serology testSerology testScatologicalScatological examinationexaminationC-13-urea breath testC-13-urea breath test

特優

Page 18: 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

NHNH22CONHCONH22         NHNH33  +  +  HH22COCO33

         HH22COCO33  →  →  HH22OO  +  +  COCO22

Urease

Page 19: 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
Page 20: 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

Cures for Cures for Peptic Ulcer and Peptic Ulcer and GastritisGastritis

Triple therapy Triple therapy ::Two remediesTwo remedies ::

Antibiotics + bismuth subsalicylateAntibiotics + bismuth subsalicylateAntibiotics + proton pump inhibitors Antibiotics + proton pump inhibitors

CCurabilityurability can be can be 80%~90% 80%~90%.. In Taiwan, curability is 83% in a week.In Taiwan, curability is 83% in a week.Secret worrySecret worry :: The result of failureThe result of failure

Page 21: 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

SummarySummary

特優

Page 22: 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

References-1References-1 張朝勝張朝勝 . Identification of a new segment involved in cagA 3' region variation of . Identification of a new segment involved in cagA 3' region variation of HelicoHelico

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1, No.11, No.1 陳慈棻陳慈棻 . . 幽門螺旋桿菌誘導胃上皮細胞行程胃炎之作用機制幽門螺旋桿菌誘導胃上皮細胞行程胃炎之作用機制 . (2004). . (2004). 王玫瑛王玫瑛 . Development of enzyme-linked immunosorbent assay (ELISA) kit for the diag. Development of enzyme-linked immunosorbent assay (ELISA) kit for the diag

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t. (2006). t. (2006). 王靜雯王靜雯 . VacA and CagA in Taiwanese strains. VacA and CagA in Taiwanese strains 陳在玲陳在玲 . Smoking and Male Gender Rather than CagA Protein Are Associated With In. Smoking and Male Gender Rather than CagA Protein Are Associated With In

creased Risk for Duodenal Ulcer in creased Risk for Duodenal Ulcer in HelicobacterHelicobacter PyloriPylori-Infected Patients in Taiwan-Infected Patients in Taiwan 莊旭翔莊旭翔 . . 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 . (2007). Retrieved

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任剛任剛 . . 幽門螺桿菌致病機制的最新進展幽門螺桿菌致病機制的最新進展 . (1999).. (1999). 《醫學綜述》 《醫學綜述》 19991999 年 第年 第 55 卷 第卷 第 44 期期 新發現幽門螺旋桿菌致胃癌的兩種蛋白質新發現幽門螺旋桿菌致胃癌的兩種蛋白質 . (2001). Science 2001 Dec 13. (2001). Science 2001 Dec 13 陳立宗陳立宗 . . 幽門螺旋桿菌與胃癌幽門螺旋桿菌與胃癌 . Retrieved from http://www.tccf.org.tw/information/HP_. Retrieved from http://www.tccf.org.tw/information/HP_

G.HTMG.HTM

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References-2References-2 賈博琦賈博琦 . . 幽門螺桿菌感染的治療幽門螺桿菌感染的治療 --2.1--2.1 概論概論 ---- 胃十二指腸潰瘍病時幽門螺桿菌感染的治胃十二指腸潰瘍病時幽門螺桿菌感染的治

療療 . (2007). Retrieved from http://med.qe.cn/HTML/123894.html. (2007). Retrieved from http://med.qe.cn/HTML/123894.html 潘明亮潘明亮 . . 消化性潰瘍的藥物治療消化性潰瘍的藥物治療 . Retrieved from http://www.sccpc.com.cn/guanyuwo. Retrieved from http://www.sccpc.com.cn/guanyuwo

men/qi-kan/2/xiao-hua-xky.htmmen/qi-kan/2/xiao-hua-xky.htm 許博翔許博翔 , , 洪貴香洪貴香 , , 吳惠雯吳惠雯 , , 吳俊忠吳俊忠 . 2005. 2005 年諾貝爾生理醫學獎──揪出幽門桿菌的啟年諾貝爾生理醫學獎──揪出幽門桿菌的啟

示示 . (2006).. (2006). 《科學發展》《科學發展》 20062006 年年 77 月,月, 403403 期,期, 40 ~ 4740 ~ 47 頁頁 . Retrieved from http://w. Retrieved from http://www.nsc.gov.tw/_NewFiles/popular_science.asp?add_year=2006&popsc_aid=79ww.nsc.gov.tw/_NewFiles/popular_science.asp?add_year=2006&popsc_aid=79

崔乃林崔乃林 , , 牛換香牛換香 , , 李天元李天元 . . 幽門螺桿菌與胃癌的流行病學關係及致癌機制幽門螺桿菌與胃癌的流行病學關係及致癌機制 . (2007). Ret. (2007). Retrieved from http://www.bioon.com/Article/hpv/309299.shtmlrieved from http://www.bioon.com/Article/hpv/309299.shtml

譚健民譚健民 . . 抓出元兇!如何檢測「胃幽門螺旋桿菌」感染的存在?抓出元兇!如何檢測「胃幽門螺旋桿菌」感染的存在? . (2005). Retrieved fro. (2005). Retrieved from http://hospital.kingnet.com.tw/essay/essay.html?pid=11577&category=m http://hospital.kingnet.com.tw/essay/essay.html?pid=11577&category= 醫藥疾病醫藥疾病 &t&type=ype=

幽門螺桿菌致病機制的最新進展幽門螺桿菌致病機制的最新進展 . (2007). Retrieved from . (2007). Retrieved from 健康人家 健康人家 http://lw.jkrj.cn/HThttp://lw.jkrj.cn/HTML/62906_2.shtmlML/62906_2.shtml

幽門螺旋桿菌幽門螺旋桿菌 (( 一一 ). (2006). Retrieved from ). (2006). Retrieved from 台灣醫療網 台灣醫療網 http://tw16.net/monographDahttp://tw16.net/monographData.asp?m1No=4&m2No=63&m3No=413&mMo=3045ta.asp?m1No=4&m2No=63&m3No=413&mMo=3045

淺談胃藥淺談胃藥 . Retrieved from . Retrieved from 台北榮民總醫院 台北榮民總醫院 http://homepage.vghtpe.gov.tw/~gi/book/bhttp://homepage.vghtpe.gov.tw/~gi/book/book3.htmook3.htm

胃幽門螺旋桿菌呼氣檢測胃幽門螺旋桿菌呼氣檢測 . (2005). Retrieved from http://www.ch.com.tw/index.asp?ch. (2005). Retrieved from http://www.ch.com.tw/index.asp?chapter=ACH000007apter=ACH000007

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References-3References-3 胃潰瘍的祕密胃潰瘍的祕密 . (2006). Retrieved from http://tw.myblog.yahoo.com/clarinase-1/article?. (2006). Retrieved from http://tw.myblog.yahoo.com/clarinase-1/article?

mid=116&prev=157&next=103&l=f&fid=7mid=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日科學家稱解開幽門螺桿菌引發胃癌的機制 . (2007). Retrieved from . (2007). Retrieved from 美迪醫療網美迪醫療網 http:/http:/

/www.labsky.com/data/07/04/news/0428111735478.htm/www.labsky.com/data/07/04/news/0428111735478.htm 科學人雜誌科學人雜誌 3737 期期 p.68~p.81p.68~p.81 One Step One Step H.pyloriH.pylori Rapid Test Strip (Serum). Retrieved from http://www.gmb.com.tw/ht Rapid Test Strip (Serum). Retrieved from http://www.gmb.com.tw/ht

ml/pdf/uman.pdfml/pdf/uman.pdf Denise M. Monack, Anne Mueller and Stanley Falkow. Persistent bacterial infections: Denise M. Monack, Anne Mueller and Stanley Falkow. Persistent bacterial infections:

the interface of the pathogen and the host immune system. (2004). Retrieved from Nathe interface of the pathogen and the host immune system. (2004). Retrieved from Nature reviews Volume 2, September 2004ture reviews Volume 2, September 2004

H.H. pyloripylori's CagA deregulates gastric cell protein to induce abnormal proliferation.(200'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=1).Retrieved from http://www.oncolink.upenn.edu/resources/article.cfm?c=3&s=8&ss=23&Year=2001&Month=12&id=785223&Year=2001&Month=12&id=7852

J. W. KONTUREK. Discovery by Haworskiof J. W. KONTUREK. Discovery by Haworskiof helicobacter pylorihelicobacter pylori and its pathogenetic r and its pathogenetic role in peptic ulcer, gastritis and gastric cancer. (2003). Retrieved from http://www.jpp.ole in peptic ulcer, gastritis and gastric cancer. (2003). Retrieved from http://www.jpp.krakow.pl/journal/archive/1203_s3/articles/03_article.htmlkrakow.pl/journal/archive/1203_s3/articles/03_article.html

National Digestive Diseases Information Clearinghouse. National Digestive Diseases Information Clearinghouse. H. pyloriH. pylori and Peptic Ulcer. (2 and Peptic Ulcer. (2004). Retrieved from http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/004). Retrieved from http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/

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References-4References-4

Richard M. Peek, Jr. and Martin J. Blaser. Richard M. Peek, Jr. and Martin J. Blaser. Helicobacter PyloriHelicobacter Pylori and gastrointestinal trac and gastrointestinal tract adenocarcinomas. (2002).Retrieved from Nature reviews Volume 2, January 2002t adenocarcinomas. (2002).Retrieved from Nature reviews Volume 2, January 2002

Richard M. Peek, Jr. Intoxicated cells and stomach ulcers. (2003).Retrieved from NatRichard M. Peek, Jr. Intoxicated cells and stomach ulcers. (2003).Retrieved from Nature Volume 33ure Volume 33

Steven F. Moss, MD. Premalignant Lesions: Steven F. Moss, MD. Premalignant Lesions: H. pyloriH. pylori and Gastric Cancer. (2001). Ret and Gastric Cancer. (2001). Retrieved from http://www.webtie.org/SOTS/Meetings/Gastrointestinal/March62001/lecturrieved from http://www.webtie.org/SOTS/Meetings/Gastrointestinal/March62001/lectures/MOSS/transcripts/transcripts.htm es/MOSS/transcripts/transcripts.htm

S.K. Mustapha, FWACP, etc. Endoscopic Findings And The Frequency Of S.K. Mustapha, FWACP, etc. Endoscopic Findings And The Frequency Of HelicobactHelicobacter Pylorier Pylori Among Dyspeptic Patients In North-Eastern Nigeria. (2008). Retrieved from Among Dyspeptic Patients In North-Eastern Nigeria. (2008). Retrieved from http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijge/vol6n1/pylori.xmlhttp://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijge/vol6n1/pylori.xml

Terry Kwok1, Dana Zabler1, Sylwia Urman, Manfred Rohde, Roland Hartig, Silja WesTerry Kwok1, Dana Zabler1, Sylwia Urman, Manfred Rohde, Roland Hartig, Silja Wessler, Rolf Misselwitz, Ju¨rgen Berger, Norbert Sewald, Wolfgang Ko¨nig1 & Steffen Basler, Rolf Misselwitz, Ju¨rgen Berger, Norbert Sewald, Wolfgang Ko¨nig1 & Steffen Backert. ckert. HelicobacterHelicobacter exploits integrin for type IV secretion and kinase activation. (2007). exploits integrin for type IV secretion and kinase activation. (2007). Retrieved from Nature 06187 Vol449 Retrieved from Nature 06187 Vol449

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References-5References-5

Pictures:Pictures: Breath Tests. (2006). Retrieved from The Breath Tests. (2006). Retrieved from The HelicobacterHelicobacter foundation http://www.helico.c foundation http://www.helico.c

om/diag_breath.htmlom/diag_breath.html C13 test. Retrieved from http://www.infai.com/images/infaikit.gifC13 test. Retrieved from http://www.infai.com/images/infaikit.gif H. pyloriH. pylori. Retrieved from http://www.nsc.gov.tw/files/popsc/2006_79/9507-07-02.JPG. 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_Konturek et al. (1998). Retrieved from http://www.jpp.krakow.pl/journal/archive/1203_

s3/gfx/rys04_9.gifs3/gfx/rys04_9.gif Rapid urease test. Retrieved from http://www.mednet.cn/CN/images/UpFileSmall/200Rapid urease test. Retrieved from http://www.mednet.cn/CN/images/UpFileSmall/200

6_7_6_15_31_44_2768.jpg6_7_6_15_31_44_2768.jpg Retrieved from http://upload.wikimedia.org/wikipedia/commons/thumb/3/30/H_pylori_Retrieved from http://upload.wikimedia.org/wikipedia/commons/thumb/3/30/H_pylori_

virulence_factors_ja.png/500px-H_pylori_virulence_factors_ja.pngvirulence_factors_ja.png/500px-H_pylori_virulence_factors_ja.png Retrieved from http://upload.wikimedia.org/wikipedia/commons/archive/9/9a/2007012Retrieved from http://upload.wikimedia.org/wikipedia/commons/archive/9/9a/2007012

4111126!H_pylori_virulence_factors_en.png4111126!H_pylori_virulence_factors_en.png