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Analysis of lamivudine resistance acquisition by hepatitis B virus.

Research Project

Project/Area Number 13557049
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

CHAYAMA Kazuaki  Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00211376)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥9,700,000 (Direct Cost: ¥9,700,000)
Keywordshepatitis B virus / HBs antigen / HBe antigen / HBV DNA / replication / core promoter / adefovir / lamivudine / YMDDvariant / HBV / real time PCR / whole genome / mutation / 薬剤耐性
Research Abstract

Hepatitis B virus infection is a serious health problem worldwide. As the hepatitis B virus infects only humans and chimpanzees, establishment of reliable culture system is necessary to study this important pathogen. We cloned a fu11 length genotype C clone of the hepatitis B virus from a patient with a very mild hepatitis. About one and half genome was cloned into a plasmid vector. The 1.4 length clone was transfected to a HepG2 cell line. The resultant cell line produced HBs antigen, HBe antigen and HBV DNA to a supernatant. The titer of HBV DNA was 10^6-10^7 copy/ml. The production of the HBV DNA was reduced by incubation of lamivudine and interferons. The clones should be useful to further develop anti-hepatitis B virus agents and study biological properties of the hepatitis B virus.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] W.Ohshi, H.Shirakawa, K.Chayamaほか5名: "Identification of Rare polymerase Variants of Hepatitis B Virus Using Two-Stage PCR with Peptide Nucleic Acid Clamping"Journal of Medical Virology. 72・4. 558-565 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Waka Ohishi, K.Chayama: "Rare Quasispecies in the YMDD motif of Hepatitis B Virus Detected by Polymerase Chain Reaction with Peptitde Nucleic Acid Clamping"Intervirology. 46・6. 355-361 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 大石和佳, 茶山一彰: "Lamivudine耐性ウイルスとその治療"臨床雑誌 内科. 93・3. 491-494 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 木村そのこ, 大石和佳, 茶山一彰ほか15名: "B型肝炎に対するラミブジン治療中にみられたHBe抗体価の低下"肝臓. 44・7. 369-370 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 大石和佳, 茶山一彰: "HBVの変異"臨床医. 29・5. 594-595 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chayama K: "Management of chronic hepatitis C and prevention of hepatocellular carcinoma."Journal of Gastroenterology. 37 Supplement13. 69-73 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Kameda, M.Kitamoto, Chayama.K.ほか5名: "Combination of transcatheter arterial chemoempolization using cisplatin-lipiodol suspension and percutaneous ethanol injection for treatment of advanced small hepatocellular carcinoma."Biochem J. 362,Pt1. 105-112 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Tazuma, T.Nishioka, Chayama K ほか13名: "Impaired gallbladder mucosal function in aged gallstone patients suppresses gallstone recurrence after successful extracorporeal shockwave lithotripsy."J Gastroenterol Hepatol.. 18,2. 157-161 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Tanaka, H.Kumada, K.Ikeda, Chayama K.ほか7名: "Natural histories of hepatitis C virus infection in men and woman simulated by the markov model."Journal of medical virology. 70,3. 378-386 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, M.Kitamoto, Chayama K.ほか7名: "Impact of aging on the development of hepatocellular carcinoma in patients with hepatitis C virus infection in japan."Scand J Gastroenterol. 38,8. 894-900 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Nakai, S.Tazuma, T.Nishioka, Chayama K.: "Inhibiton of cholesterol crystallization under bilirubin deconjugation: partial characterization of mechanisms whereby infected bile accelerates pigment stone formation."Biochim Biophys Acta. 1632,1-3. 48-54 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kameda, K.Haruma, Chayama K.ほか7名: "Significance of an exaggerated meal-stimulated gastrin response in pathogenesis of Helicobacter pylori-negative duodenalulcer."Dig Dis Sci. 48,4. 644-651 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Tsuboi, S.Tazuma, H.Ochi, Chayama K.: "Hydrophilic bile salts have a cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity."Hepatol Res. 25,1. 38-47 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, Chayama K.: "Rare quasispecies in the YMDD motif of hepatitis B virus detected by polymerases chain reaction with paptide nucleic acid clamping."Intervirology. 46,6. 355-361 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 茶山一彰: "B型・C型肝炎の病態と治療"犬山シンポジウム記録刊行会. 6 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, H.Shirakawa, K.Chayama et al.: "Identification of Rare polymerase Variants of Hepatitis B Vines Using Two-Stage PCR with Peptide Nucleic Acid Clamping"Journal of Medical Virology. 72(4). 558-565 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, K.Chayama: "Rare Quasispecies in the YMDD motif of Hepa Titis B Virus Detected by Polymerase Chain Reaction with Peptitde Nucleic Acid Clamping."Intervirology. 46(6). 355-361 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, K.Chayama: "A Lamivudine-tolerance virus and its medical Treatment"Naika. 93(3). 491-494 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Kimura, W.Ohishi, K.Chayama et al.: "The fall of the HBe antibody value seen during the lamivudine medical treatment to hepatitis B"Kanzou. 44(7). 369-370 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, K.Chayama: "Variation magazine name of HBV"Rinshoui. 29(5). 594-595 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chayama K.: "Management of chronic hepatitis C and prevention of hepatocellular carcinoma."Journal of Gastroenterology. 37,Supplememt13. 69-73 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Kameda, M.Kitamoto, K.Chayama et al.: "Combination of transcatheter arterial chemoempolization using cisplatin-lipiodol suspension and percutaneous ethanol injection for treatment of advanced small hepatocellular carcinoma."Biochem J. 362,pt1. 105-112 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Tazuma, T.Nishioka, Chavama K.et al.: "Impaired gallbladder mucosal function in aged gallstone patients suppresses gallstone recurrence after successful extracorporeal shockwave lithotripsy."J Gastroenterol Hepatol. 18(2). 157-161 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Tanaka, H.Kumada, K.Ikeda, Chayama K.et al.: "Natural histories of hepatitis C virus infection in men and Woman simulated by the markov, model."Journal of medical virology. 70(3). 378-386 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, M.Kitamoto, Chayama K.et al.: "Impact of aging on the development of hepatocell ular carcinoma in patients with hepatitis C viruis infection in Japan"Scand J Gastroenterol. 38(8). 894-900 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Nakai, S.Tazuma, T.Nishioka, Chayama K.: "Inhibiton of cholesterol crystallization under bilirubin deconjugation : partial characterization of mechanisms whereby infected bile accelerates pigment stone formation."Biochim Biophys Acta. 1632(1-3). 48-54 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kameda, K.Haruma, Chayama K.et al.: "Significance of an exaggerated meal-stimulated gastrin response in pathogenesis of Helicobacter pylori-negative duodenalulcer."Dig Dis Sci. 48(4). 644-651 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Tsuboi, S.Tazuma, H.Ochi, Chayama K.: "Hydrophilic bile salts have a cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity."Hepatol Res. 25(1). 38-47 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, Chayama K: "Rare quasispecies in the YMDD motif of hepatitis B virus detected by polymerases chain reaction with paptide nucleic acid clamping."Intervirology. 46(6). 355-361 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chayama K: "A sick state and medical treatment of hepatitis B and hepatitis C"Inuyama Symposium Record Publication meeting. 6 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] W.Ohishi, H.Shirakawa, K.Chayama ほか5名: "Identification of Rare polymerase Variants of Hepatitis B Virus Using Two-Stage PCR with Peptide Nucleic Acid Clamping"Journal of Medical Virology. 72・4. 558-565 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] W.Ohishi, K.Chayama: "Rare Quasispecies in the YMDD motif of Hepatitis B Virus Detected by Polymerase Chain Reaction with Peptitde Nucleic Acid Clamping"Intervirology. 46・4. 355-361 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 大石和佳, 茶山一彰: "Lamivudine耐性ウイバレスとその治療"臨床雑誌内科. 93・3. 491-494 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 木村そのこ, 大石和佳, 茶山一彰 ほか15名: "B型肝炎に対するラミブジン治療中にみられたHBe抗体価の低下"肝臓. 44・7. 369-370 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 大石和佳, 茶山一彰: "HBVの変異"臨床医. 29・5. 594-595 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chayama K.: "Management of chronic hepatitis C and prevention of hepatocellular carcinoma."Journal of Gastroenterology. 37Supplement13. 69-73 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Kamada, M.Kitamoto, Chayama K.ほか5名: "Combination of transcatheter arterial chemoembolizaiton using cisplatin-lipiodol suspension and percutaneous ethanol injection for treatment of advanced small hepatocellular carcinoma"Am J Surg. 184,3. 284-290 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Sakamoto, S.Tazma, Chayama K: "Less hydrophobic phosphatidylcholine species simptlity piliary vesicle morhology, but induce bile metastability with a broad spectrum of crystal forms"Biochem J. 362,Pt1. 105-112 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Tazuma, T.Nishioka, Chayama K.ほか13名: "Impaired gallbladder mucosal function in aged gallstone patients suppresses gallstione recurrence after successful extracorporeal shockwave lithotripsy"J Gastroenterol Hepatol. 18,2. 157-161 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J.Tanaka, H.Kumada, K.Ikeda, Chayama K.ほか7名: "Natural histories of hepatitis C virus infection in men and women simulated by the markov model"Journal of medical virology. 70,3. 378-386 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] W.Ohishi, M.Kitamoto, Chayama K.ほか7名: "Impact of aging on the development of hepatocellular carcinoma in patients with hepatitis C virus infection in japan"Scand J Gatroenterol. 38,8. 894-900 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Nakai, S.Tazuma, T.Nishioka, Chayama K.: "Inhibition of cholesterol crystallization uder pilirubin deconjugation : partial characterization of mechanisms whereby infected bile accelerates pigment stone formation"Biochem Biophys Acta. 1632,1-3. 48-54 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Kamada, K.Haruma, Chayama K.ほか7名: "Significance of an exaggerated meal-stimulated gastrin response in pathogenesis of Helicobacter pylori-negative duodenal ulcer"Dig Dis Sci. 48,4. 644-651 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Tsuboi, S.Tazuma, H.Ochi, Chayama K.: "Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity"Hepatol Res. 25,1. 38-47 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] W.Ohishi, Chayama K.: "Rare quasispecies in the YMDD motif of hepatitis B virus detected b y polymerases chain reaction with paptide nucleic acid clamping"Intervirology. 46,6. 355-361 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 茶山一彰: "B型・C型肝炎の病態と治療"犬山シンポジウム記録刊行会. 6 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 大石和佳: "B型慢性肝炎に対するラミブジン投与時のYMDD変異株出現例と比出現例でのreal time PCRによるウイルス動態の検討"肝臓. 43巻・4号. 214 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大石和佳: "ラミブジンはどのような人に始め、どのようにやめるか"medicina. 39巻・10号. 1725-1727 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大石和佳: "B型慢性肝炎におけるラミブジンの投与法と中止法"消化器科. 36巻・2号. 205-210 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akihito Tsubota: "Lamivudine therapy for spontaneously occurring severe acute exacerbation in chronic hepatitis B virus infection : a preliminary study"Am J Gastroenterol. 96巻・2号. 557-562 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 茶山一彰: "ラミブジンによるB型慢性肝炎の治療"VIRUS INFECTION. 13巻・4号. 80-81 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 茶山一彰: "B型・C型肝炎治療の新たな展開"犬山シンポジウム記録刊行会. 38-44 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Arase, K.Ikeda, K.Chayama et al.: "Efficacy of IFN therapy based on duration period of negative HCV-RNA during IFN administration"Hepatol Res. 19・1. 22-30 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi M, Suzuki Y, Suzuki F, K.Chayama et al.: "Lamivudine therapy for spontaneously occurring severe acute exacerbation in chronic hepatitis B virus infection : a preliminary study"Am J Gastroenterol. 96・2. 557-562 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Someya T, Suzuki Y, Arase Y, K.Chayama et al.: "Interferon therapy for flare-up of hepatitis B virus infection after emergence of lamivudine-induced YMDD motif mutant"J Gastroenterol. 36・2. 133-136 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Akuta, K.Chayama, F.Suzuki et al.: "Risk Factors of Hepatitis C Virus-Related Liver cirrhosis in young adults : Positive family history of liver disease and transporter associated with antigen processing 2(TAP2) ^*0201 Allele"J Med Virol. 64. 109-116 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Chayama, Suzuki F, Tsubota A et al.: "Evaluation of quantitative measurements of hepatitis C virus RNA to predict sustained response to interferon by genotype"J Virol Methods. 95・1-2. 33-45 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda K, Saitoh S, Kobayashi M, Chayama K et al.: "Long-term interferon therapy for 1 year or longer reduces the hepatocellular carcinogenesis rate in patients with liver cirrhosis caused by hepatitis C virus : a pilot study"J Gastroenterol Hepatol. 16. 406-415 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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