The Type 1 Inositol 1,4,5-Trisphosphate Receptor Gene Is Altered in the opisthotonos Mouse
The opisthotonos (opt) mutation arose spontaneously in a C57BL/Ks-db2J colony and is the only known, naturally occurring allele of opt. This mutant mouse was first identified based on its ataxic and convulsive phenotype. Genetic and molecular data presented here demonstrate that the type 1 inositol...
Gespeichert in:
| Veröffentlicht in: | The Journal of neuroscience 1997-01, Vol.17 (2), p.635-645 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 645 |
|---|---|
| container_issue | 2 |
| container_start_page | 635 |
| container_title | The Journal of neuroscience |
| container_volume | 17 |
| creator | Street, Valerie A Bosma, Martha M Demas, Vasiliki P Regan, Melissa R Lin, Doras D Robinson, Linda C Agnew, William S Tempel, Bruce L |
| description | The opisthotonos (opt) mutation arose spontaneously in a C57BL/Ks-db2J colony and is the only known, naturally occurring allele of opt. This mutant mouse was first identified based on its ataxic and convulsive phenotype. Genetic and molecular data presented here demonstrate that the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) protein, which serves as an IP3-gated channel to release calcium from intracellular stores, is altered in the opt mutant. A genomic deletion in the IP3R1 gene removes two exons from the IP3R1 mRNA but does not interrupt the translational reading frame. The altered protein is predicted to have lost several modulatory sites and is present at markedly reduced levels in opt homozygotes. Nonetheless, a strong calcium release from intracellular stores can be elicited in cerebellar Purkinje neurons treated with the metabotropic glutamate receptor (mGluR) agonist quisqualate (QA). QA activates Group 1 mGluRs linked to GTP-binding proteins that stimulate phospholipase C and subsequent production of the intracellular messenger IP3, leading to calcium mobilization via the IP3R1 protein. The calcium response in opt homozygotes shows less attenuation to repeated QA application than in control littermates. These data suggest that the convulsions and ataxia observed in opt mice may be caused by the physiological dysregulation of a functional IP3R1 protein. |
| doi_str_mv | 10.1523/jneurosci.17-02-00635.1997 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6573232</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>16257596</sourcerecordid><originalsourceid>FETCH-LOGICAL-c430t-daa0b5ba886b8265c51f1e4d94cfdfeab6528a7dc74d4d0fafbdafbfc989aeb43</originalsourceid><addsrcrecordid>eNqFkdFqFDEUhoNY6rr6CEIQ9KqzJplkMvFCKEutK9VC3V55ETKZM52U2cmYZF36Nj6LT2baXYpeyeGcXPz_-cjhR-g1JQsqWPnudoRt8NG6BZUFYQUhVSkWVCn5BM2yQxWME_oUzQiTpKi45M_Q8xhvCSGSUHmMjmtVS1lXM_R93QNe302A6e9fq9FHl_yA6Qk_EcU6uDj1PrdJgK_AwpR8wOcwAl5FfDokCNBiN-KUIX5yMfU--QzBX_w2wgt01JkhwsvDO0fXH8_Wy0_FxeX5anl6UVheklS0xpBGNKauq6ZmlbCCdhR4q7jt2g5MUwlWG9layVveks50TZu7s6pWBhpeztGHPXfaNhtoLYwpmEFPwW1MuNPeOP2vMrpe3_ifuhKyZLnm6O0BEPyPLcSkNy5aGAYzQj5ES1UKlcd_jbRiQgpVZeP7vdHmnGKA7vE3lOj7DPXnr2fXV5fflitNpSZMP2So7zPMy6_-vudx9RBa1t_s9d7d9DsXQMeNGYbspnq322Ue0xlW_gGOJar_</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16257596</pqid></control><display><type>article</type><title>The Type 1 Inositol 1,4,5-Trisphosphate Receptor Gene Is Altered in the opisthotonos Mouse</title><source>MEDLINE</source><source>Free E-Journal (出版社公開部分のみ）</source><source>PubMed Central</source><creator>Street, Valerie A ; Bosma, Martha M ; Demas, Vasiliki P ; Regan, Melissa R ; Lin, Doras D ; Robinson, Linda C ; Agnew, William S ; Tempel, Bruce L</creator><creatorcontrib>Street, Valerie A ; Bosma, Martha M ; Demas, Vasiliki P ; Regan, Melissa R ; Lin, Doras D ; Robinson, Linda C ; Agnew, William S ; Tempel, Bruce L</creatorcontrib><description>The opisthotonos (opt) mutation arose spontaneously in a C57BL/Ks-db2J colony and is the only known, naturally occurring allele of opt. This mutant mouse was first identified based on its ataxic and convulsive phenotype. Genetic and molecular data presented here demonstrate that the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) protein, which serves as an IP3-gated channel to release calcium from intracellular stores, is altered in the opt mutant. A genomic deletion in the IP3R1 gene removes two exons from the IP3R1 mRNA but does not interrupt the translational reading frame. The altered protein is predicted to have lost several modulatory sites and is present at markedly reduced levels in opt homozygotes. Nonetheless, a strong calcium release from intracellular stores can be elicited in cerebellar Purkinje neurons treated with the metabotropic glutamate receptor (mGluR) agonist quisqualate (QA). QA activates Group 1 mGluRs linked to GTP-binding proteins that stimulate phospholipase C and subsequent production of the intracellular messenger IP3, leading to calcium mobilization via the IP3R1 protein. The calcium response in opt homozygotes shows less attenuation to repeated QA application than in control littermates. These data suggest that the convulsions and ataxia observed in opt mice may be caused by the physiological dysregulation of a functional IP3R1 protein.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/jneurosci.17-02-00635.1997</identifier><identifier>PMID: 8987786</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Amino Acid Sequence ; Animals ; Base Sequence ; Calcium - metabolism ; Calcium Channels - deficiency ; Calcium Channels - genetics ; Calcium Channels - physiology ; Cerebellar Ataxia - genetics ; Cerebellar Ataxia - pathology ; Cerebellar Ataxia - physiopathology ; Cerebellum - pathology ; DNA Mutational Analysis ; Epilepsy - genetics ; Epilepsy - pathology ; Epilepsy - physiopathology ; Exons - genetics ; Gene Expression Regulation ; Genes ; Genes, Recessive ; Genotype ; GTP-Binding Proteins - physiology ; Inositol 1,4,5-Trisphosphate Receptors ; Mice ; Mice, Neurologic Mutants - genetics ; Molecular Sequence Data ; Morphogenesis - genetics ; Nerve Tissue Proteins - deficiency ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - physiology ; Phosphatidylinositol Diacylglycerol-Lyase ; Purkinje Cells - drug effects ; Purkinje Cells - metabolism ; Purkinje Cells - pathology ; Quisqualic Acid - pharmacology ; Receptors, Cytoplasmic and Nuclear - deficiency ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - physiology ; Receptors, Metabotropic Glutamate - drug effects ; Receptors, Metabotropic Glutamate - physiology ; Second Messenger Systems - genetics ; Sequence Deletion ; Type C Phospholipases - physiology</subject><ispartof>The Journal of neuroscience, 1997-01, Vol.17 (2), p.635-645</ispartof><rights>Copyright © 1997 Society for Neuroscience 1997</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-daa0b5ba886b8265c51f1e4d94cfdfeab6528a7dc74d4d0fafbdafbfc989aeb43</citedby><cites>FETCH-LOGICAL-c430t-daa0b5ba886b8265c51f1e4d94cfdfeab6528a7dc74d4d0fafbdafbfc989aeb43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573232/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573232/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8987786$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Street, Valerie A</creatorcontrib><creatorcontrib>Bosma, Martha M</creatorcontrib><creatorcontrib>Demas, Vasiliki P</creatorcontrib><creatorcontrib>Regan, Melissa R</creatorcontrib><creatorcontrib>Lin, Doras D</creatorcontrib><creatorcontrib>Robinson, Linda C</creatorcontrib><creatorcontrib>Agnew, William S</creatorcontrib><creatorcontrib>Tempel, Bruce L</creatorcontrib><title>The Type 1 Inositol 1,4,5-Trisphosphate Receptor Gene Is Altered in the opisthotonos Mouse</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>The opisthotonos (opt) mutation arose spontaneously in a C57BL/Ks-db2J colony and is the only known, naturally occurring allele of opt. This mutant mouse was first identified based on its ataxic and convulsive phenotype. Genetic and molecular data presented here demonstrate that the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) protein, which serves as an IP3-gated channel to release calcium from intracellular stores, is altered in the opt mutant. A genomic deletion in the IP3R1 gene removes two exons from the IP3R1 mRNA but does not interrupt the translational reading frame. The altered protein is predicted to have lost several modulatory sites and is present at markedly reduced levels in opt homozygotes. Nonetheless, a strong calcium release from intracellular stores can be elicited in cerebellar Purkinje neurons treated with the metabotropic glutamate receptor (mGluR) agonist quisqualate (QA). QA activates Group 1 mGluRs linked to GTP-binding proteins that stimulate phospholipase C and subsequent production of the intracellular messenger IP3, leading to calcium mobilization via the IP3R1 protein. The calcium response in opt homozygotes shows less attenuation to repeated QA application than in control littermates. These data suggest that the convulsions and ataxia observed in opt mice may be caused by the physiological dysregulation of a functional IP3R1 protein.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Calcium - metabolism</subject><subject>Calcium Channels - deficiency</subject><subject>Calcium Channels - genetics</subject><subject>Calcium Channels - physiology</subject><subject>Cerebellar Ataxia - genetics</subject><subject>Cerebellar Ataxia - pathology</subject><subject>Cerebellar Ataxia - physiopathology</subject><subject>Cerebellum - pathology</subject><subject>DNA Mutational Analysis</subject><subject>Epilepsy - genetics</subject><subject>Epilepsy - pathology</subject><subject>Epilepsy - physiopathology</subject><subject>Exons - genetics</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genes, Recessive</subject><subject>Genotype</subject><subject>GTP-Binding Proteins - physiology</subject><subject>Inositol 1,4,5-Trisphosphate Receptors</subject><subject>Mice</subject><subject>Mice, Neurologic Mutants - genetics</subject><subject>Molecular Sequence Data</subject><subject>Morphogenesis - genetics</subject><subject>Nerve Tissue Proteins - deficiency</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>Phosphatidylinositol Diacylglycerol-Lyase</subject><subject>Purkinje Cells - drug effects</subject><subject>Purkinje Cells - metabolism</subject><subject>Purkinje Cells - pathology</subject><subject>Quisqualic Acid - pharmacology</subject><subject>Receptors, Cytoplasmic and Nuclear - deficiency</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - physiology</subject><subject>Receptors, Metabotropic Glutamate - drug effects</subject><subject>Receptors, Metabotropic Glutamate - physiology</subject><subject>Second Messenger Systems - genetics</subject><subject>Sequence Deletion</subject><subject>Type C Phospholipases - physiology</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdFqFDEUhoNY6rr6CEIQ9KqzJplkMvFCKEutK9VC3V55ETKZM52U2cmYZF36Nj6LT2baXYpeyeGcXPz_-cjhR-g1JQsqWPnudoRt8NG6BZUFYQUhVSkWVCn5BM2yQxWME_oUzQiTpKi45M_Q8xhvCSGSUHmMjmtVS1lXM_R93QNe302A6e9fq9FHl_yA6Qk_EcU6uDj1PrdJgK_AwpR8wOcwAl5FfDokCNBiN-KUIX5yMfU--QzBX_w2wgt01JkhwsvDO0fXH8_Wy0_FxeX5anl6UVheklS0xpBGNKauq6ZmlbCCdhR4q7jt2g5MUwlWG9layVveks50TZu7s6pWBhpeztGHPXfaNhtoLYwpmEFPwW1MuNPeOP2vMrpe3_ifuhKyZLnm6O0BEPyPLcSkNy5aGAYzQj5ES1UKlcd_jbRiQgpVZeP7vdHmnGKA7vE3lOj7DPXnr2fXV5fflitNpSZMP2So7zPMy6_-vudx9RBa1t_s9d7d9DsXQMeNGYbspnq322Ue0xlW_gGOJar_</recordid><startdate>19970115</startdate><enddate>19970115</enddate><creator>Street, Valerie A</creator><creator>Bosma, Martha M</creator><creator>Demas, Vasiliki P</creator><creator>Regan, Melissa R</creator><creator>Lin, Doras D</creator><creator>Robinson, Linda C</creator><creator>Agnew, William S</creator><creator>Tempel, Bruce L</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</general><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>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19970115</creationdate><title>The Type 1 Inositol 1,4,5-Trisphosphate Receptor Gene Is Altered in the opisthotonos Mouse</title><author>Street, Valerie A ; Bosma, Martha M ; Demas, Vasiliki P ; Regan, Melissa R ; Lin, Doras D ; Robinson, Linda C ; Agnew, William S ; Tempel, Bruce L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-daa0b5ba886b8265c51f1e4d94cfdfeab6528a7dc74d4d0fafbdafbfc989aeb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Calcium - metabolism</topic><topic>Calcium Channels - deficiency</topic><topic>Calcium Channels - genetics</topic><topic>Calcium Channels - physiology</topic><topic>Cerebellar Ataxia - genetics</topic><topic>Cerebellar Ataxia - pathology</topic><topic>Cerebellar Ataxia - physiopathology</topic><topic>Cerebellum - pathology</topic><topic>DNA Mutational Analysis</topic><topic>Epilepsy - genetics</topic><topic>Epilepsy - pathology</topic><topic>Epilepsy - physiopathology</topic><topic>Exons - genetics</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Genes, Recessive</topic><topic>Genotype</topic><topic>GTP-Binding Proteins - physiology</topic><topic>Inositol 1,4,5-Trisphosphate Receptors</topic><topic>Mice</topic><topic>Mice, Neurologic Mutants - genetics</topic><topic>Molecular Sequence Data</topic><topic>Morphogenesis - genetics</topic><topic>Nerve Tissue Proteins - deficiency</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>Phosphatidylinositol Diacylglycerol-Lyase</topic><topic>Purkinje Cells - drug effects</topic><topic>Purkinje Cells - metabolism</topic><topic>Purkinje Cells - pathology</topic><topic>Quisqualic Acid - pharmacology</topic><topic>Receptors, Cytoplasmic and Nuclear - deficiency</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - physiology</topic><topic>Receptors, Metabotropic Glutamate - drug effects</topic><topic>Receptors, Metabotropic Glutamate - physiology</topic><topic>Second Messenger Systems - genetics</topic><topic>Sequence Deletion</topic><topic>Type C Phospholipases - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Street, Valerie A</creatorcontrib><creatorcontrib>Bosma, Martha M</creatorcontrib><creatorcontrib>Demas, Vasiliki P</creatorcontrib><creatorcontrib>Regan, Melissa R</creatorcontrib><creatorcontrib>Lin, Doras D</creatorcontrib><creatorcontrib>Robinson, Linda C</creatorcontrib><creatorcontrib>Agnew, William S</creatorcontrib><creatorcontrib>Tempel, Bruce L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Street, Valerie A</au><au>Bosma, Martha M</au><au>Demas, Vasiliki P</au><au>Regan, Melissa R</au><au>Lin, Doras D</au><au>Robinson, Linda C</au><au>Agnew, William S</au><au>Tempel, Bruce L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Type 1 Inositol 1,4,5-Trisphosphate Receptor Gene Is Altered in the opisthotonos Mouse</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>1997-01-15</date><risdate>1997</risdate><volume>17</volume><issue>2</issue><spage>635</spage><epage>645</epage><pages>635-645</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>The opisthotonos (opt) mutation arose spontaneously in a C57BL/Ks-db2J colony and is the only known, naturally occurring allele of opt. This mutant mouse was first identified based on its ataxic and convulsive phenotype. Genetic and molecular data presented here demonstrate that the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) protein, which serves as an IP3-gated channel to release calcium from intracellular stores, is altered in the opt mutant. A genomic deletion in the IP3R1 gene removes two exons from the IP3R1 mRNA but does not interrupt the translational reading frame. The altered protein is predicted to have lost several modulatory sites and is present at markedly reduced levels in opt homozygotes. Nonetheless, a strong calcium release from intracellular stores can be elicited in cerebellar Purkinje neurons treated with the metabotropic glutamate receptor (mGluR) agonist quisqualate (QA). QA activates Group 1 mGluRs linked to GTP-binding proteins that stimulate phospholipase C and subsequent production of the intracellular messenger IP3, leading to calcium mobilization via the IP3R1 protein. The calcium response in opt homozygotes shows less attenuation to repeated QA application than in control littermates. These data suggest that the convulsions and ataxia observed in opt mice may be caused by the physiological dysregulation of a functional IP3R1 protein.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>8987786</pmid><doi>10.1523/jneurosci.17-02-00635.1997</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0270-6474 |
| ispartof | The Journal of neuroscience, 1997-01, Vol.17 (2), p.635-645 |
| issn | 0270-6474 1529-2401 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6573232 |
| source | MEDLINE; Free E-Journal (出版社公開部分のみ）; PubMed Central |
| subjects | Amino Acid Sequence Animals Base Sequence Calcium - metabolism Calcium Channels - deficiency Calcium Channels - genetics Calcium Channels - physiology Cerebellar Ataxia - genetics Cerebellar Ataxia - pathology Cerebellar Ataxia - physiopathology Cerebellum - pathology DNA Mutational Analysis Epilepsy - genetics Epilepsy - pathology Epilepsy - physiopathology Exons - genetics Gene Expression Regulation Genes Genes, Recessive Genotype GTP-Binding Proteins - physiology Inositol 1,4,5-Trisphosphate Receptors Mice Mice, Neurologic Mutants - genetics Molecular Sequence Data Morphogenesis - genetics Nerve Tissue Proteins - deficiency Nerve Tissue Proteins - genetics Nerve Tissue Proteins - physiology Phosphatidylinositol Diacylglycerol-Lyase Purkinje Cells - drug effects Purkinje Cells - metabolism Purkinje Cells - pathology Quisqualic Acid - pharmacology Receptors, Cytoplasmic and Nuclear - deficiency Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - physiology Receptors, Metabotropic Glutamate - drug effects Receptors, Metabotropic Glutamate - physiology Second Messenger Systems - genetics Sequence Deletion Type C Phospholipases - physiology |
| title | The Type 1 Inositol 1,4,5-Trisphosphate Receptor Gene Is Altered in the opisthotonos Mouse |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T09%3A45%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Type%201%C2%A0Inositol%201,4,5-Trisphosphate%20Receptor%20Gene%20Is%20Altered%20in%20the%20opisthotonos%20Mouse&rft.jtitle=The%20Journal%20of%20neuroscience&rft.au=Street,%20Valerie%20A&rft.date=1997-01-15&rft.volume=17&rft.issue=2&rft.spage=635&rft.epage=645&rft.pages=635-645&rft.issn=0270-6474&rft.eissn=1529-2401&rft_id=info:doi/10.1523/jneurosci.17-02-00635.1997&rft_dat=%3Cproquest_pubme%3E16257596%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=16257596&rft_id=info:pmid/8987786&rfr_iscdi=true |