Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system
The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that dur...
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description | The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from
l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell–axon relationship causing axonal damage and regulating endoneurial cell life and death. |
doi_str_mv | 10.1016/j.expneurol.2004.01.026 |
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l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell–axon relationship causing axonal damage and regulating endoneurial cell life and death.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2004.01.026</identifier><identifier>PMID: 15144861</identifier><identifier>CODEN: EXNEAC</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; Axonal degeneration ; Biological and medical sciences ; Blotting, Northern ; Cell Membrane Permeability - physiology ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Demyelinating Diseases - enzymology ; Demyelinating Diseases - immunology ; Demyelinating Diseases - pathology ; Demyelination ; Disease Models, Animal ; Disease Progression ; Enzyme Induction - physiology ; Immunohistochemistry ; Injuries of the nervous system and the skull. Diseases due to physical agents ; iNOS ; Medical sciences ; Necrosis ; Nerve Fibers - enzymology ; Nerve Fibers - pathology ; Neuritis, Autoimmune, Experimental - enzymology ; Neuritis, Autoimmune, Experimental - immunology ; Neuritis, Autoimmune, Experimental - pathology ; Neurology ; Nitric Oxide Synthase - genetics ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type II ; Peripheral nerve ; Peripheral Nervous System - enzymology ; Peripheral Nervous System - pathology ; Rats ; Rats, Inbred Lew ; Sciatic Nerve - enzymology ; Sciatic Nerve - pathology ; Traumas. Diseases due to physical agents ; Wallerian Degeneration - enzymology ; Wallerian Degeneration - pathology</subject><ispartof>Experimental neurology, 2004-06, Vol.187 (2), p.350-358</ispartof><rights>2004 Elsevier Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-47404989a10e34e8da6b59acb496febdf4d96eb4e4a29cef8a3af54e446b8513</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.expneurol.2004.01.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15767570$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15144861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Conti, Giancarlo</creatorcontrib><creatorcontrib>Rostami, Abdolmohammed</creatorcontrib><creatorcontrib>Scarpini, Elio</creatorcontrib><creatorcontrib>Baron, PierLuigi</creatorcontrib><creatorcontrib>Galimberti, Daniela</creatorcontrib><creatorcontrib>Bresolin, Nereo</creatorcontrib><creatorcontrib>Contri, Miranda</creatorcontrib><creatorcontrib>Palumbo, Carla</creatorcontrib><creatorcontrib>De Pol, Anto</creatorcontrib><title>Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from
l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell–axon relationship causing axonal damage and regulating endoneurial cell life and death.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Axonal degeneration</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Cell Membrane Permeability - physiology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Demyelinating Diseases - enzymology</subject><subject>Demyelinating Diseases - immunology</subject><subject>Demyelinating Diseases - pathology</subject><subject>Demyelination</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Enzyme Induction - physiology</subject><subject>Immunohistochemistry</subject><subject>Injuries of the nervous system and the skull. Diseases due to physical agents</subject><subject>iNOS</subject><subject>Medical sciences</subject><subject>Necrosis</subject><subject>Nerve Fibers - enzymology</subject><subject>Nerve Fibers - pathology</subject><subject>Neuritis, Autoimmune, Experimental - enzymology</subject><subject>Neuritis, Autoimmune, Experimental - immunology</subject><subject>Neuritis, Autoimmune, Experimental - pathology</subject><subject>Neurology</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Peripheral nerve</subject><subject>Peripheral Nervous System - enzymology</subject><subject>Peripheral Nervous System - pathology</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Sciatic Nerve - enzymology</subject><subject>Sciatic Nerve - pathology</subject><subject>Traumas. Diseases due to physical agents</subject><subject>Wallerian Degeneration - enzymology</subject><subject>Wallerian Degeneration - pathology</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS1ERYfCK4A3VLBIuE4cJ15WFT-VqnZBJZaWY98wHjlOsJOq8wR9bVzNCLpjdXV1vvujcwh5z6BkwMTnXYkPc8A1Tr6sAHgJrIRKvCAbBhKKitfwkmwAGC9414lT8jqlHQBIXrWvyClrGOedYBvyeBXsalzvkQa3RGfo9OAs0rQPy1YnpB_dze2PT9QF6sZxDViMaJ1e0FKL4x69C3pxU6A6WPpTe4_R6ZC1XxgwHqRpoMsWae7onOV5mwVPs3w_rSlfSguOb8jJoH3Ct8d6Ru6-frm7_F5c3367ury4Lkwt26XgLQcuO6kZYM2xs1r0jdSm51IM2NuBWymw58h1JQ0Ona710OSWi75rWH1Gzg9r5zj9XjEtanTJoPc6YH5GtUxWFYg6g-0BNHFKKeKg5uhGHfeKgXqKQO3U3wjUUwQKmMoR5Ml3xxNrn736N3f0PAMfjoBORvsh6mBcesa1om1ayNzFgcPsx73DqJJxGEz2P6JZlJ3cf5_5AwFwrNc</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Conti, Giancarlo</creator><creator>Rostami, Abdolmohammed</creator><creator>Scarpini, Elio</creator><creator>Baron, PierLuigi</creator><creator>Galimberti, Daniela</creator><creator>Bresolin, Nereo</creator><creator>Contri, Miranda</creator><creator>Palumbo, Carla</creator><creator>De Pol, Anto</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040601</creationdate><title>Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system</title><author>Conti, Giancarlo ; Rostami, Abdolmohammed ; Scarpini, Elio ; Baron, PierLuigi ; Galimberti, Daniela ; Bresolin, Nereo ; Contri, Miranda ; Palumbo, Carla ; De Pol, Anto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-47404989a10e34e8da6b59acb496febdf4d96eb4e4a29cef8a3af54e446b8513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Axonal degeneration</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Cell Membrane Permeability - physiology</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Demyelinating Diseases - enzymology</topic><topic>Demyelinating Diseases - immunology</topic><topic>Demyelinating Diseases - pathology</topic><topic>Demyelination</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Enzyme Induction - physiology</topic><topic>Immunohistochemistry</topic><topic>Injuries of the nervous system and the skull. Diseases due to physical agents</topic><topic>iNOS</topic><topic>Medical sciences</topic><topic>Necrosis</topic><topic>Nerve Fibers - enzymology</topic><topic>Nerve Fibers - pathology</topic><topic>Neuritis, Autoimmune, Experimental - enzymology</topic><topic>Neuritis, Autoimmune, Experimental - immunology</topic><topic>Neuritis, Autoimmune, Experimental - pathology</topic><topic>Neurology</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Peripheral nerve</topic><topic>Peripheral Nervous System - enzymology</topic><topic>Peripheral Nervous System - pathology</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Sciatic Nerve - enzymology</topic><topic>Sciatic Nerve - pathology</topic><topic>Traumas. Diseases due to physical agents</topic><topic>Wallerian Degeneration - enzymology</topic><topic>Wallerian Degeneration - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Conti, Giancarlo</creatorcontrib><creatorcontrib>Rostami, Abdolmohammed</creatorcontrib><creatorcontrib>Scarpini, Elio</creatorcontrib><creatorcontrib>Baron, PierLuigi</creatorcontrib><creatorcontrib>Galimberti, Daniela</creatorcontrib><creatorcontrib>Bresolin, Nereo</creatorcontrib><creatorcontrib>Contri, Miranda</creatorcontrib><creatorcontrib>Palumbo, Carla</creatorcontrib><creatorcontrib>De Pol, Anto</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Conti, Giancarlo</au><au>Rostami, Abdolmohammed</au><au>Scarpini, Elio</au><au>Baron, PierLuigi</au><au>Galimberti, Daniela</au><au>Bresolin, Nereo</au><au>Contri, Miranda</au><au>Palumbo, Carla</au><au>De Pol, Anto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>187</volume><issue>2</issue><spage>350</spage><epage>358</epage><pages>350-358</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from
l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell–axon relationship causing axonal damage and regulating endoneurial cell life and death.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>15144861</pmid><doi>10.1016/j.expneurol.2004.01.026</doi><tpages>9</tpages></addata></record> |
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subjects | Animals Apoptosis Axonal degeneration Biological and medical sciences Blotting, Northern Cell Membrane Permeability - physiology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Demyelinating Diseases - enzymology Demyelinating Diseases - immunology Demyelinating Diseases - pathology Demyelination Disease Models, Animal Disease Progression Enzyme Induction - physiology Immunohistochemistry Injuries of the nervous system and the skull. Diseases due to physical agents iNOS Medical sciences Necrosis Nerve Fibers - enzymology Nerve Fibers - pathology Neuritis, Autoimmune, Experimental - enzymology Neuritis, Autoimmune, Experimental - immunology Neuritis, Autoimmune, Experimental - pathology Neurology Nitric Oxide Synthase - genetics Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Peripheral nerve Peripheral Nervous System - enzymology Peripheral Nervous System - pathology Rats Rats, Inbred Lew Sciatic Nerve - enzymology Sciatic Nerve - pathology Traumas. Diseases due to physical agents Wallerian Degeneration - enzymology Wallerian Degeneration - pathology |
title | Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system |
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