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Autoregulatory mechanisms of renal blood flow-Selective responses of afferent arteriole to renal perfusion pressure

Research Project

Project/Area Number 11470024
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKagawa Medical University

Principal Investigator

ABE Youichi  Kagawa Medical University, Department of Pharmacology, Professor, 医学部, 教授 (10047227)

Co-Investigator(Kenkyū-buntansha) NISHIYAMA Akira  Kagawa Medical University, Department of Pharmacology, Assistant, 医学部, 助手 (10325334)
KIMURA Shoji  Kagawa Medical University, Department of Pharmacology, Assistant Professor, 医学部, 助教授 (30253264)
福井 敏樹  香川医科大学, 医学部, 助手 (90294751)
安岐 康晴  香川医科大学, 医学部, 助手 (50231816)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsrenal autoregulation / tubuloglomenilar feedback / renal interstitium / adenosine / ATP / nitric oxide / microdialvsis / afferent arteriole / 腎微小透析 / 腎血流量 / サイクリックGMP / アデノシンA_1受容体拮抗薬 / 糸球体濾過量 / アデノシンA1受容体拮抗薬
Research Abstract

Renal blood flow (RBF) remains constant despite wide variations in the renal perfusion pressure (RPP), a phenomenon known as autoregulation. Two resistance vessels are located in the kidney, and afferent arteriole but not efferent arteriole exhibits autoregulation-mediated changes in vascular resistance in response to alterations in RPP. However, it remains to be elucidated why the afferent arteriole selectively responds to the changes in RPP. It is now well established that renal autoregulation is mediated by tubulo-glomerular feedback (TGF). TGF is a negative feedback system that stabilizes RBF, glomerular filtration rate (GFR), and the tubular flow rate. An increase in RPP increases the tubular flow late via an increase in GFR. The increased tubular flow rate causes an elevation of sodium chloride concentration at the macula densa. This is sensed by the macula densa and results in an increase in the afferent arteriolar resistance. The purpose of the present investigation to determin … More e what endogeneous substances transmit information from the macula densa as a sensor cell to the afferent arteriole as an effector. We have focused on an adenosine, nitric oxide (NO) and ATP as possible candidates for the transmitter.
We have measured the renal interstitial concentrations of adenosine, ATP or NOx (metabolites of NO) using microdialysis technique at following experimental conditions and analyzed the relations between interstitial concentrations of these substances and renal vascular resistance. 1) The intrarenal infusion of hypertonic saline resulted in a decrease of RBF following a transient increase of RBF and a significant increase of intersitial adenosine concentration. An adenosine 1 receptor antagonist completely blocked the reduction of RBF induced by the hypertonic saline, indicating a role of adenosine for TGF. 2) Changes in RPP within the autoregulatory pressure range did not affect the interstitial concentration of NOx, but the reduction of RPP below than the lower limit of autoregulatory pressure range limit significantly reduced interstitial NOx. Thus, there are no relations between changes in NOx concentration and renal vascular resistance. 3) In contrast to NOx, stepwise reduction of RPP significantly reduced the renal interstitial concentration of ATP arid changes in ATP levels were highly correlated with changes in renal vascular resistance. Further studies demonstrated that stimulation of TGF by increasing distal volume delivery elicited with acetazolamide also led to increases in renal interstitial concentrations of ATP. Thus, these data clearly indicate that ATP in the renal interstitial fluid contribute to the TGF-dependent changes in renal vascular resistance.
Based on these findings, we concluded that adenosine and ATP exert significant roles in TGF, and that NO may contribute to TGF via the modulation of the actions of various vasoactive substances including adenosine and ATP. Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (71 results)

All Other

All Publications (71 results)

  • [Publications] M.Rahman et al.: "Effects of angiotensin II on the renal interstitial concentrations of NO2/NO3 and cyclic GMP in anesthetized rats"Jpn.J.Pharmacol. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] R-X.Tian et al.: "DOI,5-HT2 receptor agonist, induces renal vasodilation via nitric oxide in anesthetized dogs"Europ.J.Pharmacol.. 437. 79-84 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Renal interstitial adenosine metabolism during ischemia in dogs"Am.J.Physiol.. 280. F231-F238 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Nishjyama et al.: "Blood flow-dependent changes renal interstitial guanosine 3', 5'-cyclic monophosphate in rabbits"Am.J.Physiol.. 282. F238-F244 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Nishiyama et al.: "Renal interstitial fluid concentrations of angiotensins I and II in anesthetized rats"Hypertension. 39. 129-134 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Systemic and regional hemodynamic responses to tempol in angiotensin II-infused hypertensive rats"Hypertension. 37. 77-83 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang Yue et al.: "Benidipine dilates both pre-and post-glomerular arteriole in the kidney"Hypertens.Res.. 24. 429-436 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matlubur Rahman et al.: "Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs"Europ.J.Pharmacol.. 428. 113-119 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Renal interstitial ATP responses to changes in arterial pressure during alterations in tubuloglomerular feedback activity"Hypertension. 37. 753-759 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M-S.Zhou et al.: "L-Argiaine improves endothelial function in renal artery of hypertensive Dahl rats"J.Hypertension. 19. 421-429 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Nishiyama et al.: "Role of nitric oxide in regional blood flow in angiotensin II-induced Hypertensive rats"Hypertens.Res.. 24. 421-428 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Nishiyama et al.: "Interactions of adenosine A1 and A2a receptors on renal microvascular reactivity"Am.J.Physiol.. 280. F406-F414 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Noma et al.: "Possible role of uncoupling protein in regulation of myocardial energy metabolism in aortic regurgitation model rats"FASEB. 15. 1206-1208 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Fukui et al.: "Expression on p22-phox and gp91-phox, Essential Components of NADPH Oxidase Increases after Myocardial Infarction"Biochemical and Biophysical Research Communications. 281. 1200-1206 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Nishiyama et al.: "Relation between renal interstitial ATP concentrations and autoregulation-mediated changes in renal vascular resistance"Circ.Res.. 86. 656-662 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Miyake et al.: "Transforming Growth Factor-β 1 Stimulates Contraction of Human Glioblastoma Cell-Mediated Collagen Lattice through Enhanced α 2 Integrin Expression"J.Neuropathol.Exp.Neurol. 59. 18-28 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Murakami et al.: "Effeects of Perindopril on Left Ventricular Remodling and Aortic Regurgitation in Rats Assessed by Echocardiography"Angiology. 51. 943-952 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Fukui et al.: "Dietary troglitazone decreases oxidative stress in early stage type II diabetic rats"Life Sci.. 66. 2043-2049 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Mizushige et al.: "Effccts of troglitazone on collagen accumunlation and distensibility of aortic wall in prestage of non-insulin-dependent diabetes mellitus of Otsuka Long-Evans Tokushima Fatty rats"J.Cardiovasc.Pharmacol.35. 150-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Fujisawa et al.: "Role of nitric oxide in regulation of renal sympathetic nerve activity during hemorrhage in conscious rats"Am.J.Physiol.. 277. H8-H14 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.NiShiyama et al.: "Effects of halothane on renal hemodynamics and interstitial nitric oxide in rabbits"Europ.J.Phamacol.. 367. 299-306 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Nishiyama et al.: "Adenosine A1 receptor antagonist KW-3901 prevents hypoxia-induced renal vasoconstriction"J.Pharmacol.Exp.Ther.. 291. 1299-1305 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Noma et al.: "Alteration in aortic wall stiffness and accumulation of collagen during the prdiabetic stage of type II diabetes mellitus in rats"Jpn.Circ.J.. 63. 988-993 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安部陽一: "新生理科学体系19"医学書院. 21 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Rahman et al.: "Effects of angiotensin II on the renal interstitial concentrations of N02/N03 and cyclic GMP in anesthetized rats"J. J. Pharmacol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] R-X. Tian et al.: "DOI, 5-HT2 receptor agonist, induces renal vasodilation via nitric oxide in anesthetized dogs"Europ. J. Pharmacol.. 437. 79-84 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Renal interstitial adenosine metabolism during ischemia in dogs"Am. J. Physiol.. 280. F231-F238 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Blood flow-dependent changes renal interstitial guanosine 3', 5'-cyclic mbnophosphate in rabbits"Am. J. Physiol.. 282. F238-F244 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Nishiyama et al.: "Renal interstitial fluid concentrations of angiotensins I and II in anesthetized rats"Hypertension. 39. 129-134 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Systemic and regional hemodynamic responses to tempol in angiotensin II - infused hypertensive rats"Hypertension. 37. 77-83 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang Yue et al.: "Benidipine dilates both pre-and post-glomerular arteriole in the kidney"Hypertens. Res.. 24. 429-436 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matlubur Rahman et al.: "Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs"Europ. J. Pharmacol.. 428. 113-119 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Renal interstitial ATP responses to changes in arterial pressure during alterations tubuloglomerular feedback activity"Hypertension. 37. 753-759 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M-S. Zhou et al.: "L-Arginine improves endothelial function in renal artery of hypertensive Dahl rats"J. Hypertension. 19. 421-429 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Nishiyama et al.: "Role of nitric oxide in regional blood flow in angiotensin II-induced Hypertensive rats"Hypertens. Res.. 24. 421-428 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Nishiyama et al.: "Interactions of adenosine A1 and A2a receptors on renal microvascular reactivity"Am. J. Physiol.. 280. F406-F414 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Noma et al.: "Possible role of uncoupling protein in regulation of myocardial energy metabolism in aortic regurgitation model rats"FESEB Journal. 15. 1206-1208 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Fukui et al.: "Expression on p22-phox and pg91-phox, Essential components of NADPH Oxidase Increases after Myocardial Infarction"Biochemical and Biophysical Research Communications. 281. 1200-1206 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Nishiyama et al.: "Relation between renal interstitial ATP concentrations and autoregulation-mediated changes in renal vascular resistance"Circ. Res.. 86. 656-662 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Miyake et al.: "Transforming Growth Factor-β 1 Stimulates Contraction of Human Glioblastoma Cell-Mediated Collagen Lattice through Enhanced α 2 Integrin Expression"Journal of Neuropatholbgy and Experimental Neurology. 59. 18-28 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Murakami et al.: "Effects of Perindopril on Left Ventricular Remodling and Aortic Regurgitation in Rats Assessed by Echocardiography"Angiology. 51. 943-952 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Fukui et al.: "Dietary troglitazone decreases oxidative stress in early stage type II diabetic rats"Life Sci.. 66. 2043-2049 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Mizushige et al.: "Effects of troglitazone on collagen accumulation and distensibility of aortic wall in prestage of non-insulin-dependent diabetes mellitus of Otsuka Long-Evans Tokushima Fatty rats"J. Cardiovasc. Pharmacol.. 35. 150-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Fujisawa et al.: "Role of nitric oxide in regulation of renal sympathetic nerve activity during hemorrhage in conscious rats"Am. J. Physiol.. 277. H8-H14 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Nishiyama et al.: "Effects of halothane on renal hemodynamics and interstitial nitric oxide in rabbits"Europ. J. Pharmacol.. 367. 299-306 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Nishiyama et al.: "Adenosine A1 receptor antagonist KW-3901 prevents hypoxia-induced renal vasoconstriction"J. Pharmacol. Exp. Ther.. 291. 1299-1305 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Noma et al.: "Alteration in aortic wall stiffness and accumulation of collagen during the prediabetic stage of type II diabetes mellitus in rats"Jpn. Circ. J.. 63. 988-993 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Shin et al.: "Inhibition of topoisomerase II α subunit de novo synthesisby specific antisense oligonucleotides suppresses human glioma T98G cell growth"Neurol. medico-chirurgica. 39. 199-205 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Nishiyama et al.: "Renal interstitial concentration of adenosine during endotoxin shock"Eur. J. Pharmacol.. 385. 209-216 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Nishiyama et al.: "Blood flow-dependent changes renal interstitial guanosine 3', 5'-cyclic monophosphate in rabbits"Am. J. Physiol.. 282. F238-F244 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akira Nishiyama et al.: "Renal interstitial adenosine metabolism during ischemia in dogs"Am. J. Physiol.. 280. F231-F238 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akira Nishiyama et al.: "Systemic and regional hemodynamic responses to tempol in angiotensin II infused hypertensive rats"Hypertension. 37. 77-83 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wang Yue et al.: "Benidipine dilates both pre-and post-glomerular arteriole in the kidney"Hypertens. Res.. 24. 429-436 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matlubur Rahman et al.: "Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs"Europ. J. Pharmacol.. 428. 113-119 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akira Nishiyama et al.: "Renal interstitial ATP responses to changes in arterial pressure during alterations in tubuloglomerular feedback ack activity"Hypertension. 37. 753-759 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安部陽一: "新生理科学体系19"医学書院. 21 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akira Nishiyama et al.: "Renal interstitial adenosine metabolism during ischemia in dogs."Am.J.Physiol.. 280,2. F231-F238 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akira Nishiyama et al.: "Systemic and regional hemodynamic responses to tempol in angiotensin II-infused hypertensive rats."Hypertension. 37,1. 77-83 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshiki Fukui et al.: "Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases in infarcted sites of the left ventricle after myocardial infarction."BBRC. in press. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahisa Noma et al.: "Possible role of uncoupling protein in regulation of myocardial energy metabolism in aortic regurgitation model rats."FASEB J.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshiki Fukui et al.: "Dietary troglitazone decreases oxidative stress in early stage type II diabetic rats."Life Sci.. 66,21. 2043-2049 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Keisuke Miyake et al.: "Transforming growth factor-betal stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha2 integrin expression."J.Neur.Exp.Neurol.. 59,1. 18-28 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 安部陽一: "新生理科学体系19"医学書院. 21 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 安部陽一: "β遮断薬のすべて第5集"先端医学社. 6 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaki Shin et al.: "Inhibition of Topoisomerase II α Subunit De Novo Synthesis by Specific Antisense Oligonucleotides Suppresses Human Glioma T98G Cell Growth."Neurologia medico-chirurgica. 39,3. 199-205 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Nishiyama et al.: "Effects of halothane on renal hemodynamics and interstitial nitric oxide in rabbits."Eur.J.Pharmacol.. 367. 299-306 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshihide Fujisawa et al.: "Role of nitric oxide in regulation of renal sympathetic nerve activity during hemorrhage in conscious rats."Am.J.Physiol.. 277. H8-H14 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahisa Noma et al.: "Alteration in Aortic Wall Stiffness and Accumulation of Collagen During the Prediabetic Stage of Type II Diabetes Mellitus in Rats."Jap.Cir.J.. 63,12. 988-993 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Nishiyama et al.: "Renal interstitial concentration of adenosine during endotoxin shock."Eur.J.Pharmacol.. 385. 209-216 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Nishiyama: "Adenosine A_1 Receptor Antagonist KW-3902 Prevents Hypoxia-Induced Renal Vasoconstriction^1."J.Pharmacol.Exp.Ther.. 291,3. 988-993 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 安部陽一: "循環系治療薬の作用メカニズム"南江堂. 18 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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