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2003 Fiscal Year Final Research Report Summary

Identification of therapeutic drug target genes by "genome-wide" expression profile analysis on animal models of human disease

Research Project

Project/Area Number 14370039
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKYOTO UNIVERSITY (2003)
National Research Institute for Child Health and Development (2002)

Principal Investigator

TSUJIMOTO Gozoh  KYOTO UNIVERSITY GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, KYOTO UNIVERSITY FACULTY OF PHARMACEUTICAL SCIENCES, PROFESSOR, 薬学研究科, 教授 (80172013)

Co-Investigator(Kenkyū-buntansha) SHIOJIMA Satoshi  DEPARTMENT OF MOLECULAR, CELL PHARMACOLOGY, NATIONAL CHILDREN'S MEDICAL RESEARCH CENTER, RESEARCHER, 薬剤治療研究部, 研究員
MIWA Yoshihisa  KYOTO UNIVERSITY GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, KYOTO UNIVERSITY FACULTY OF PHARMACEUTICAL SCIENCES, LECTURER, 薬学研究科, 講師 (20093320)
MATSUMOTO Osamu  KYOTO UNIVERSITY GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, KYOTO UNIVERSITY FACULTY OF PHARMACEUTICAL SCIENCES, ASSISTANT PROFESSOR, 薬学研究科, 助教授 (10231599)
KOSHIMIZU Takaaki  DEEPARTMENT OF MOLECULAR, CELL PHARMACOLOGY, NATIONAL CHILDREN'S MEDICAL RESEARCH CENTER, RESEARCHER, 薬剤治療研究部, 研究員
Project Period (FY) 2002 – 2003
KeywordsDNA-chip / disease-related gene / normalized cDNA library
Research Abstract

The advent of Genome Science had markedly changed the way how the life science research including.medical investigation is conducted; thus, "systematic" and "integrated" approach is required (so called "genome-wide" survey). Now, genome-wide transcriptome and proteomics scanning are becoming feasible. The stream of "Genome -Trariscriptome -Proteomics" is logical, and in each aspect approaches for functional genomics are now pursued at a high pace; however, still standardized approach is immature or lacking. Very recently, novel genome-based technology of cDNA microarray, DNA chips has been innovated and immediately applied for the medical researches. The cDNA microarray or DNA-chip technology allows expression monitoring of hundreds and thousands of genes simultaneously and provides a format for,identifying genes as well as changes in their activity. Microarrays can be constructed from specific cDNA clones of interest, a cDNA library, or a select number of open reading fragments from a genome sequencing database to allow a large-scale functional analysis of expressed sequences. Analyzing disease states and drug treatment with the new tools of genomics such as DNA microarray enables the identification of drug targets and should improve the odds of developing useful therapeutics, thereby it would provide a new approach to investigations in developmental biology. As a model system to verify the system, we examined the progression of GN in a rat model of anti-glomerular basement membrane serum-induced nephritis. cDNA microarray analysis identified disease-related, differentially expressed gene, which appear to be potentially important therapeutic targets.

  • Research Products

    (82 results)

All Other

All Publications (82 results)

  • [Publications] Sugawara T: "Differences in the subcellular localization of α 1-adrecoceptor subtypes can affect the subtype selectivity of drugs in a study with the fluorescent ligand BODIPY-FL prazosin."Life Sciences.. 70. 2113-2124 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugimoto Y: "β1-Selective agonist (-)-1-(3,4-Dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for β1-selective binding in resting and active states."J.Pharamacol.Exp.Ther.. 301. 51-58 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chalothorn D: "Differences in the cellular localization and agonist mediated internalization properties of the alpha1-adrenoceptor subtypes."Mol. Pharmacol.. 61. 1008-1016 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koshimizu T: "Recent progress in α_1-adrenoceptor pharmacology."Biol.Pharm.Bull.. 25. 401-408 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanoue A: "The α_<1D>-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction."J Clin.Invest.. 109. 765-775 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanoue A: "Two novel transcripts for human endothelin B receptor produced by RNA editing/alternativesplicing from a single gene."J.Biol.Chem.. 277. 33205-33212 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanoue A: "Role of the α1D-adrenergic receptor in the development of salt-induced hypertension"Hypertension. 40. 101-106 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamauchi J: "Role of Dbl's big sister in the anti-mitogenic pathway from alpha1B-"Biochem.Biophys.Res.Commum. 296. 85-92 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsuma S: "Global analysis of differentially expressed genes during progression of calcium oxalate nephrolithiasis."Biochem Biophys Res Commun.. 296. 544-551 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koshimizu TA: "Heteromultimerization modulates P2X receptor-functions through participating extracellular and C-terminal subdomains."J Biol Chem.. 277. 46891-46899 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamauchi J: "Endothelin suppresses cell migration via the JNK signaling pathway in a manner dependent upon Src kinase, Rac1, and Cdc42."FEBS Lett.. 527. 284-288 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura H: "Antagonistic effects of antimuscarinic drugs on α1-adrenoceptors."Naunyn Schmiedebergs Arch Pharmacol.. 366. 368-371 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashizume K: "Implantation and placental development in somatic cell clone recipient cows."Cloning and Stem Cells.. 4. 197-209 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Heishi M: "High-density oligonucleotide array analysis of mRNA transcripts in peripheral blood cells of severe atopic dermatitis patients."Int. Arch. Allergy Immunol.. 129. 57-66 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takei Y: "The MCM3 acetylase MCM3AP inhibits initiation, but not elongation, of DNA replication via interaction with MCM3."J.Biol.Chem.. 277. 43121-43125 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T: "Marked increase in CC chemokine gene expression in both human and mouse mast cell transcriptomes folllowing Fce receptor I cross-linking"Blood. 100. 3861-3868 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imai Y: "Cloning and characterization of the highly expressed ETEA gene from blood cells of atopic dermatitis patients."Biochem.Biophys.Res.Commun.. 297. 1282-1290 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura H.: "Key amino acids for differential coupling of α1-adrenergic receptor subtypes to Gs."Biochem.Biophys.Res.Commun.. 299. 142-147 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsumoto Y: "Identification of highly expressed genes in peripheral blood T cells from patients with atopic dermatitis."Int Arch Allergy Immunol.. 129. 327-340 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsuma S: "Signaling mechanisms in sphingosine 1-phosphate-promoted mesangial cell proliferation."Genes to Cells.. 7. 1217-1230 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Richardson J: "Agonist-specific coupling of a cloned human alpha(1A)-adrenoceptor to different second messenger pathways."Naunyn-Schmiedeberg's Arch.. 367. 333-341 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa K: "Analysis of gene expression in peripheral blood eosinophils from patients with atopic dermatitis and in vitro cytokine-stimulated blood eosinophils."Clin.Exp.Immunol.. 131. 436-445 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuhara Y: "Gene expression profiles in the regenerating rata liver after partial hepatectomy."J.Hepatology.. 38. 784-792 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanada M: "Granzyme A mediates glucocorticoid-induced apoptosis in leukemia cells."FASEB. Journal.. 17. 1712-1714 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hasida R: "Analysis of Gene Expression in Peripheral Blood Eosinophils from Patients with Atopic Dermatitis by Differential Display."Int. Arch. Allergy. Immunol.. 131. 26-33 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Endo F: "Animal models reveal pathophysiologies of tyrosinemias."J.Nutr.. 133. 2063-2067 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Harasawa I: "Responses To Noxious Stimuli in Mice Lacking α1d-Adrenergic Receptors."Neuro Report.. 14. 1857-1860 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagata N: "Analysis of highly expressed genes in monocytes from atopic dermatitis patients."Int. Arch. Allergy. Innunol.. 132. 156-167 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibata K: "Alpha1-Adrenergic receptor subtypes differentially control cell cycle of transfected CHO cells through a cAMP-dependent mechanism involving p27Kipl."J.Biol.Chem.. 278. 672-678 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsuma S: "Transcriptional profiling of gene expression patterns during sphingosine 1-phosphate-induced mesangial cell proliferation."Biochem.Biophys.Res.Commun.. 300. 577-584 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishiwata H: "Characterization of Gene Expression Profiles in Early Bovine Pregnancy Using a Custom cDNA Microarray."Mol. Reprod. Dev.. 65. 9-18 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida N: "Determination of a novel haplotype of β 2-adrenergic receptor in the Japanese population by the combination of the electronic microchip assay using the NanoChip system with allele-specific PCR."Drug Metabolism and Pharmacokinetics.. 17. 532-539 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koshimizu TA: "Recent advances in alpha1-adrenoceptor pharmacology."Pharmacol.Ther.. 98. 235-244 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura T: "Temporal gene expression changes of adipogenesis in human mesenchymal stem cells."Biochem.Biophys.Res.Comnun.. 303. 306-312 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanoue A: "Insights into alpha1-adrenoceptor function in health and disease from transgenic animal studies."Trends in Endocrinology and Metabolism.. 14. 107-113 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chalothorn D: "Differential cardiovascular regulatory activities of the alpha1B-and alpha1D-adrenoceptor subtypes."J.Pharmacol.Exp.Ther.. 305. 1045-1053 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oshikawa S: "Vasopressin stimulates insulin release from islet cells through V1b receptors : A combined pharmacological/knockout approach"Mol.Pharmacol.. 65. 623-629 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanoue A: "The Vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions."J.Clin.Invest.. 113. 302-309 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Herath CB: "Pregnancy-associated changes in genome-wide gene expression profiles in the liver of cow throughout pregnancy."Biochem.Biophys.Res.Conmun.. 313. 666-680 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yaguma K: "Crystallization and preliminary X-ray diffraction studies of DNA decamer d (CCAGGCCTGG) complexed with cobalt (III)-pepleomycin."Acta Crystallogr.D.Biol.Crystallogr.. 60. 144-145 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 辻本豪三: "薬物動態研究ガイド-創薬から臨床へ-"エル・アイ・シー. 11 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 辻本豪三: "薬物療法学"南江堂. 3 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugawara T: "Differences in the subcellular localization of α1-adrecoeeptor subtypes can affect the subtype selectivity of drugs in a study with the fluorescent ligand BODIPY-FL prazosin."Life Sciences.. 70. 2113-2124 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugimoto Y: "β1-Selective agonist (-)-1-(3,4-Dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-R0363] differentially interacts with, key amino acids responsible for ail-selective binding in resting and Fictive-states."J.Pharamacol.Exp.Ther. 301. 51-58 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chalothorn D: "Differences in the cellular localization and agonist mediated internalizaion properties of the. alphal-adrenoceptor subtypes."Mol.Phannacol.. 61. 1008-1016 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koshimizu T: "Recent progress in α_1-adrenoceptor pharmacology"Biol.Phann.Bull.. 25. 401-408 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanoue A: "The α_<1D>-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction"J.Clin.Invest.. 109. 765-775 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanoue A: "Two novel transcripts for human endothelin B receptor produced bu RNA editing /alternative splicing from a single gene."J.Biol.Chem.. 277. 33205-33212 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanoue A: "Role of the α1D-adrenergic receptor in the development of salt-induced hypertension."Hypertension.. 40. 101-106 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamauchi J: "Role of Dbl's big sister in the anti-mitogenic pathway from alpha 1B-adrenergic receptor to c-Jun N-terminal kinase."Biochem.Biophys.Res.Commun.. 296. 85-92 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsuma S: "Global analysis of differentially expressed genes during progression of calcium oxalate nephrolithiasis."Biochem.Biophys.Res.Commun.. 296. 544-552 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koshimizu TA: "Heteromultimerization modulates P2X receptor-functions through participating extracellular and C-terminal subdomains."J.Biol.Chem.. 277. 46891-46899 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamauchi J: "Endothelin suppresses cell migration via the JNK signaling pathway in a manner dependent upon Src kinase, Rac1, and Cdc42."FEBS.Lett.. 527. 284-288 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura H: "Antagonistic effects of antimuscarinic drugs on α1-adrenoceptors. Naunyn-Schmiedeberg's Arch."Pharmacol. 366. 368-371 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashizume K: "Implantation and placental development in somatic cell clone recipient cows."Cloning and Stem Cells.. 4. 197-209 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Heishi M: "High-density oligonucleotide array analysis of mRNA transcripts in peripheral blood cells of severe atopic dermatitis patients."Int.Arch.Allergy.Immunol.. 129. 57-66 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takei Y: "The MCM3 acetylase MCM3AP inhibits initiation, but not elongation of DNA replication via interaction with MCM3."J.Biol.Chem.. 277. 43121-43125 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T: "Marked increase in CC chemokine gene expression in both humbug and mouse mast cell transcriptomes folllowing Fce resecptor I cross-linking."Blood.. 100. 3861-3868 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai Y: "Cloning and characterization of the highly expressed ETEA gene from blood cells of atopic dermatitis patients."Biochem.Biophys.Res.Commun.. 297. 1282-1290 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura H: "Key amino acids for differential coupling of al-adrenergic receptor subtypes to Gs."Biochem.Biophys.Res.Commun.. 299. 142-147 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsumoto Y: "Identification of highly expressed genes in peripheral blood T cells from patients with atopic dermatitis."Int.Arch.Allergy.Immunol.. 129. 327-340 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsuma S: "Signaling mechanisms in sphingosine 1-phosphate-promoted mesangial cell proliferation."Genes to Cells.. 7. 1217-1230 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibata K: "Alpha 1-Adrenergic receptor subtypes differentially control cell cycle of transfected CHO cells through a cAMP-dependent mechanism involving p27Kip1."J.Biol.Chem.. 278. 672-678 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsuma S: "Transcriptional profiling of gene expression patterns during sphingosine 1-phosphate-induced mesangial cell, proliferation."Biochem.Biophys.Res.Commun.. 300. 577-584 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishiwata H: "Characterization of Gene Expression Profiles in Early Bovine Pregnancy Using a Custom cDNA Microarray."Mol.Reprod.Dev.. 65. 9-18 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida N: "Determination of fl novel haplotype of β 2-adrenergic receptor in the Japanese population by the combination of the electronic microchip assay using the NanoChip system with allele-specific PCR."Drug Metabolism and Pharmacokinetics.. 17. 532-539 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koshimizu TA: "Recent advances in alpha1-adrenoceptor pharmacology."Pharmacol.Ther.. 98. 235-244 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura T: "Temporal gene expression changes of adipogenesis in human mesenchymal stem cells."Biochem.Biophys.Res.Commun.. 303. 306-312 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanoue A: "Insights into alpha1-adrenoceptor-function in health and disease from transgenic animal studies."Trends in Endocrinology and Metabolism.. 14. 107-113 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chalothorn D: "Differential cardiovascular regulatory activities of the alpha1 B-and alpha1 D-adrenoceptor subtypes."J.Pharmacol.Exp.Ther.. 305. 1045-1053 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Richardson J: "Agonist-specific coupling of a cloned human alpha(1A)-adrenoceptor to different second messenger pathways."Naunyn-Schmiedeberg's Arch.Pharmacol.. 367. 333-341 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogawa K: "Analysis of gene expression in peripheral blood eosinophils from patients with atopic dermatitis and in vitro cytokine-stimulated blood eosinophils."Clin.Exp.Immunol.. 131. 436-445 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuhara Y: "Gene expression profiles in the regenerating rata liver after partial hepatectomy."J.Hepatology.. 38. 784-792 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada M: "Granzyme A mediates glucocorticoid-induced apoptosis in leukemia cells."FASEB.Journal.. 17. 1712-1714 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasida R: "Analysis of Gene Expression in Peripheral Blood Eosinophils from Patients with Atopic Dermatitis by Differential Display."Int.Arch.Allergy.Immunol.. 131. 26-33 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Endo F: "Animal models reveal pathophysiologies of tyrosinemias."J.Nutr.. 133. 2063-2067 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Harasawa I: "Responses To Noxious Stimuli in Mice Lacking a1d-Adrenergic Receptors."Neuro Report.. 14. 1857-1860 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagata N: "Analysis of highly expressed genes in monocytes from atopic dermatitis patients."Int.Arch.Allergy.Immunol.. 132. 156-167 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oshikawa S: "Vasopressin stimulates insulin release from islet cells through V1b receptors: A combined pharmacological/knockout approach."Mol.Pharmacol.. 65. 623-629 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanoue A: "The Vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions."J.Clin.Invest.. 113. 302-309 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Herath CB: "Pregnancy-associated changes in genome-wide gene expression profiles in the liver of cow throughout pregnancy."Biochem.Biophys.Res.Commun.. 313. 666-680 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yaguma K: "Crystallization acid preliminary X-ray diffraction studies of DNA decamer d (CCAGGCCTGG) complexed with cobalt (III)-pepleomycin."Acta Crystallogr.D.Biol.Crystallogr.. 60. 144-145 (2004)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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