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Molecular mechanism of alcoholism : Ethanol and cell signaling

Research Project

Project/Area Number 08044264
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SUZUKI Osamu  Hamamatsu University School of medicine, 医学部, 教授 (70093044)

Co-Investigator(Kenkyū-buntansha) ADRIENNE Gor  カリフォルニア大学, 神経学教室, 教授
IVAN Diamond  カリフォルニア大学, 神経学教室, 教授
浅井 清文  名古屋市立大学, 分子医学研究所, 助手 (70212462)
石井 晃  浜松医科大学, 医学部, 助手 (30252175)
妹尾 洋  浜松医科大学, 医学部, 助教授 (50236113)
GORDON Adrie  カリフォルニア大学, 神経学教室, 教授
DIAMOND Ivan  カリフォルニア大学, 神経学教室, 教授
西川 正信  浜松医科大学, 医学部, 助手 (60262812)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1996: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywordsalcohol / neuronal culture cell / promotor / adenosine receptor / cAMP / protein kinase A / protein kinase C / intracellvlar distribution / cAMP
Research Abstract

Alcoholism induces serious functional and pathological abnormalities in many organs, particularly in the central nervous system. However, the molecular mechanisms accounting for these effects have not been identified, because ethanol can affect many different receptors and transpoters on the cell membrane. Recent studies suggest ethanol can modify intracellular signal transduction systems. We have proposed NG108-15, neuronal cultured cells as a model, and we have found that cAMP system is involved in the induction of heterologous desensitization, an example of ethanol tolerance at a cellular level. In the present project, we have established NG108-15 cells expressing transmitter receptors by stable transfection to identify receptors of which signal transduction system could be modified by chronic ethanol.
At first, we checked the effect of chronic ethanol on promotor activity. We chose CMV,RSV and SV40 promotors and assessed the changes of these activeties using receptor binding assays … More or CAT assay. In NG108 cells transiently expressing CAT,chronic ethanol activated the activities of all promotors. However, chronic ethanol treatment did not change the expression of A_1 or D_2 receptors or CAT in some stable transfectants. These finding suggest not only promotors, but also cis elements juxtaposing with inserted cDNA would affect the effect of ethanol on the gene expresion.
In our previous study, adenosine A_2 receptor is attributed to the generation of heterologous desensitization by accumulating extracellular adenosine after chronic ethanol treatment, but A_1 receptor seems not to be involved in the induction of these phenomenon.
Protein Kinases play important roles in the intracellular signal transduction system and the translocation of these kinases is accompanied with these activation. So we focused on the translocation of protein kinases, especially A kinase (PDA) and C kinase (PKC), induced by ethanol. In NG108 cells, ethanol translocated catalytic subunit of PKA from cytosol to nucleus, but RI,a regulatory subunit of PKA was not translocated. Also, ethanol translocated some isozymes of PKC in NG108 cells. We will perform further studies on those translocations by chronic ethanol. Less

Report

(2 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • Research Products

    (72 results)

All Other

All Publications (72 results)

  • [Publications] O.Suzuki.,et al: "Analytical Toxicology" Forensic Science International. 80・1,2. 137-146 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Kumazawa.,et al: "Reduction of pyrroloquinoline quinone by DT-diaphorase from clostridium kluyveri" Biochemical Archives. 12. 201-206 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Kumazawa.,et al: "Extraction of local anaesthetics from human blood by direct immersion-solid phase micro extraction (SPME)" Chromatographia. 43・1,2. 59-62 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Kumazawa.,et al: "Detection of ethanol in human body fiuids by headspace solid-phasemicro extraction (SPME) /capillary gas chromatography" Chromatographia. 43・7,8. 393-398 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Minakata.,et al: "Effect of dietary paraquat on a rat mutant unable to synthesize ascorbic acid" Arch.Toxicol.70. 256-258 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Seno.,et al: "Datection of some phenothiazines by headspace solid phase microextraction and gas chromatography" Jpn.J.Forensic Toxicol.14・1. 30-34 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Seno.,et al: "Determination of some carbamate pesticides in human body fluids by headspace solid phase micro extraction and gas chromatography" Jpn.J.Forensic Toxicol.14・3. 199-203 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Seno.,et al: "Detection of benzodiazepines in human urine by direct immersion solid phase micro extraction and gas chromatography" Jpn.J.Forensic Toxicol.15・1. 16-20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii.,et al: "Simple and sensitive detection of phencyclidine in body fluids by gas chromatography with surface ionization detection" Int.J.Legal Med.108・5. 244-247 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii.,et al: "Sensitive quantitation of clozapine in body fluids by gas chromatography with surface ionization detection" Jpn.J.Forensic Toxicol.14・3. 215-220 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii.,et al: "Simple clean-up methamphetamine and amphetamine in human urineby directimmersion solid phase micro extraction (DI-SPME)" Jpn.J.Forensic Toxicol.14・3. 228-232 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii.,et al: "Simple extraction of phencyclidine from human body fluids by headspace solid-phase microextraction (SPME)" Chromatographia. 43・5,6. 331-334 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii.,et al: "A simple and sensitive quantitation of N,N-dimethyltryptamine by gas chromatography with surface ionization detection" J.Anal.Toxicol.21・1. 36-40 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X-P.Lee.,et al: "Detection of organophosphate pesticides in human body fluids by headspace solid-phase microextraction (SPME) and capillary gas chromatography with nitrogen-phosphorus detection" Chromatographia. 42・3,4. 135-140 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Nishikawa.,et al: "The ARS-independent synthesis of DNA complementary to transfer strand in a recipient yeast during trans-Kingdomconjugation between Escherecia coli and Saccharomyces cerevisiae" Nucleic Acids Symposium Series. 35. 273-274 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Watanabe.,et al: "Simultaneous determination of cocaethylene and cocainein blood gas chromatography with surface ionization detection" Chromatographia. 44・1,2. 55-58 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] I.Isobe.,et al: "Astrocytic contributions to blood-brain barrier (BBB) formation by endothelialcells : A possible use of aortic endothelial cell for in vitro BBB model" Neurochem Int. 28・5. 759-763 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Fuse.,et al: "Heat shock-mediated cell cycle arrest is accompanied by induction of p21 CKI" Biochem.Biophys.Res.Commum. 225・3. 759-763 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Matsukawa.,et al: "Tissue distribution of human gliostatin/plateletderived endothelial cell growth factor (PD-ECGF) and its drug-induced expression" Biochemica et Biophysica Acta. 1371. 71-82 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Mizuno.,et al: "Glucocorticoid induced the expression of mRNA and the secretion of lipocortin 1 in rat astrocytoma cells" Brain Reserch. 746. 256-268 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ivan Diamond.,et al: "Cellular and molecular neuroscience of alcoholism" Physiological Reviews. 77・1. 1-20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Douglas P.Dohrman.,et al: "Ethanol causes translocation of cAMP-dependent protein kinase catalytic subunit to nucleus" Cell Biology. 93. 10217-10221 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Imogen R.Coe.,et al: "The role of protein kinase C in cellular tolerance to ethanol" J.Biol.Chem.271・46. 29468-29474 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Imogen R.Coe.,et al: "Activation of a cyclic AMP-Dependent protein kinase reverses tolerance of nucleoside transporter to ethanol" J.Pharmacol.Exp.Therap.276・2. 365-369 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] O.Suzuki., et al: "Analytical Toxicology" Forensic Science International. 80・1,2. 137-146 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Kumazawa., et al: "Reduction of pyrroloquinoline quinone by dt-diaphorase from clostridium kluyveri" Biochemical Archives. 12. 201-206 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Kumazawa., et al: "Extraction of local anaesthetics from human blood by direct immersion-solid phase micro extraction (SPME)" Chromatographia. 43・1,2. 59-62 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Kumazawa., et al: "Detection of ethanol in human body fluids by headspace solid-phase micro extraction (SPME)/capillary gas chromato graphy" Chromatographia. 43・7,8. 393-398 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Minakata., et al: "Effect of dietary paraquat on a rat mutant unable to synthesize ascorbic acid." Arch.Toxicol.70. 256-258 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Seno., et al: "Detection of some phenothiazines by headspace solid phase microextraction and gas chromatog-raphy" Jpn.J.Forensic Toxicol. 14・1. 30-34 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Seno., et al: "Determination of some carbamate pesticides in human body in human body fluids by headspace solid phase micro extraction and gas chromatography" Jpn.J.Forensic Toxico l. 14・3. 199-203 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Seno., et al: "Detection of benzodiazepines in human urine by direct immersion solid phase micro extraction and gas chromatography" Jpn.J.Forensic Toxicol. 15・1. 16-20 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii., et al: "Simple and sensitive detection of phencyclidine in body fluids by gas chromatography with surface ionization detection" Int.J.Legal Med.108・5. 244-247 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii., et al: "Sensitive zuantitation of clozapine in body fluids by gas chromatography with surface ionization detection" Jpn.J.Forensic Toxicol.14・3. 2215-220 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii., et al: "Simple clean-up methamphetamine and amphetamine in human urine by direct-immersion solid phase micro extraction (DI-SPME)" Jpn.J.Forensic Toxicol.14・3. 228-232 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii., et al: "Simple extraction of phencyclidine from human body fruids by headspace solid-phase microextraction (SPME)" Chromatogrsphia. 43・5,6. 331-334 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira.Ishii., et al: "A simple and sensitive quantitation of N,N-dimethyltryptamine by gas chromatography with surface ionization detection" J.Anal.Toxicol.21・1. 36-40 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.-P.Lee., et al: "Detection of organophosphate pesticides in human body fluids by headspace solid-phase microextraction (SPME) and capillary gas chromatography with nitrogen-phosphorus detection" Chromatographia. 42・3,4. 135-140 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Nishikawa., et al: "ARS-independent synthesis of DNA complementary to transfer strand in arecipient yeast during trans-kingdomconjugation between Escherichia coli and Saccharomyces cerevisiae" Nucleic Acids Symposium Series, The. 273-274 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Watanabe., et al: "Simultaneous determination of cocaethylene and cocaine in blood gas chromatography with surface ionization detection" Chromatographia. 44・1,2. 55-58 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] I.Isobe., et al: "Astrocytic contributions to blood-brain barrier (BBB) formation by endothelial cells : A possible use of aortic endothelial cell for in vitro BBB model" Neurochem Int. 28・5. 523-533 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Fuse., et al: "Heat shock-mediated cell cycle arrest is accompanied by induction of p21 CKI" Biochem.Biophys.Res.Commum. 225・3. 759-763 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Matsukawa., et al: "Tissue distribution of human gliostatin/plateletderived endothelial cell growth factor (PD-ECGF) and its drug-induced expression" Biochemica et Biophysica Acta. 1371. 71-82 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Mizuno., et al: "Glucocorticoid induced the expression of mRNA and the secretion of lipocortin 1 in rat astrocytoma cells" Brain Reserch. 746. 256-268 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ivan Diamond., et al: "Cellular and molecular neuroscience of alcoholis" Physiclogical Reviews. 77・1. 1-20 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Douglas P.Dohrman., et al: "Ethanol causes translocation of cAMP-dependent protein kinase catalytic subunit to nucleus" Cell Biology. 93. 10217-10221 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Imogen R.Coe., et al: "The role of protein kinase Cin cellular tolerance to ethanol" J.Biol.Chem.271,46. 29468-29274 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Imogen R.Coe., et al: "Activation of a cyclic AMP-Dependent protein kinase reverses tolerance of nucleoside transporter to ethanol" J.Pharmacol.Exp.Therap.276・2. 365-369 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] O.Suzuki.,et al: "Analytical Toxicology" Forensic Science International. 80・1,2. 137-146 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Kumazawa.,et al: "Reduction of pyrroloquinoline quinone by dt-diaphorase from clostridium kluyveri" Biochemical Archives. 12. 201-206 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Kumazawa.,et al: "Extraction of local anaesthetics from human blood by direct immersion-solid phase micro extraction(SPME)" Chromatographia. 43・1,2. 59-62 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Kumazawa.,et al: "Detection of ethanol in human body fluids by headspace solid-phase micro extraction(SPME)/capillary gas chromatography" Chromatographia. 43・7,8. 393-398 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.MInakata.,et al: "Arch Toxicol" Effect of dietary paraquat on a rat mutant unable to synthesize. 70. 256-258 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Seno.,et al: "Detection of some phenothiazines by headspace solid phase microextraction and gas chromatography" Jpn.J.Forensic Toxicol. 14・1. 30-34 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Seno.,et al: "Determination of some carbamate pesticides in human body fluids by headspacesolid phase microextraction and gas chromatography" Jpn.J.Forensic Toxicol. 14・3. 199-203 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Seno.,et al: "Detection of benzodiazepines in human urine by direct immersion solid phase micro extraction and gas chromatography" Jpn.J.Forensic Toxicol. 15・1. 16-20 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akira.Ishii.,et al: "Siple and sensitive detection of phencyclidine in body fruids by gas chromatography with surface ionization detection" Int J Legal Med. 108・5. 244-247 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akira.Ishii.,et al: "Sensitive quantitation of clozapine in body fruids by gas chromatography with surface ionization detection" Jpn.J.Forensic Toxicol. 14・3. 215-220 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akira.Ishii.,et al: "Simple clean-up methamphetamine and amphetamine in human urine by direct-immersion solid phase micro extraction(DI-SPME)" Jpn.J.Forensic Toxicol. 14・3. 228-232 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akira.Ishii.,et al: "Simple extraction of phencyclidine from human body fruids by headspace solid-phase microextraction(SPME)" Chromatographia. 43・5,6. 331-334 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akira.Ishii.,et al: "A simple and sensitive quantitation of N,N-Dimethyltryptamine by gas chromatography with surfase ionization detection" Journal of Analytical Toxicology. 21・1. 36-40 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] X.-P.Lee.,et al: "Detection of organophosphate pesticides in human body fruids by headspace solid-phasemicroextraction(SPME) and capillary gas chromatography with nitrogen-phosphorus detection" Chromatographia. 42・3,4. 135-140 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Nishikawa.,et al: "The ARS-independent synthesis of DNA complementary to transfer strand in arecipient yeast during transkingdomconjugation between Escherichia coli and Saccharomyces cerevisiae" Nucleic Acids Symposium Series. 35. 273-274 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Watanabe.,et al: "Simultaneous determination of cocaethylene and cocaine in blood gas chromatography with surface ionization detection" Chromatographia. 44・1,2. 55-58 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] I.Isobe.,et al: "Astrocytic contributions to blood-brain barrier(BBB) formation by endothelial cells:A possible use of aortic endothelial cell for in vitro BBB model" Neurochem Int. 28・5. 523-533 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Fuse.,et al: "Heat shock-meditated cell cycle arrest is accompanied by induction of p21 CKI" Biochem. Biophys. Res. Commum. 225・3. 759-763 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Matsukawa.,et al: "Tissue distribution of human gliostatin/platelet-derived endothelial cell growth factor(PD-ECGF) and its drug-induced expression" Biochemica et Biophysica Acta. 1371. 71-82 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Mizno.,et al: "Glucocorticoid induced the expression of mRNA and the secretion of lipocortin 1 in rat astrocytoma cells" Brain Reserch. 746. 256-268 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ivan Diamond.,et aal: "Cellular and molecular neuroscience of alcoholism" Physiological Reviews. 77・1. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Douglas P. Dohrman.,et al: "Ethanol causes translocation of cAMP-dependent protein kinase catalytic subunit to nucleus" Cell Biology. 93. 10217-10221 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Imogen R. Coe.,et al: "The role of protein kinase C in cellular tolerance to ethanol" The Journal of Biological Chemistry. 271・46. 29468-29274 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Imogen R. Coe.,et al: "Activation of a cyclic AMP-Dependent protein kinase reverses tolerance of nucleoside transporter to ethanol^1" The Journal of Pharmacology and Experimental Therapeutics. 276・2. 365-369 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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