Long Persistent bcr-abl Positive Transcript Detected by Polymerase Chain Reaction After Marrow Transplant for Chronic Myelogenous Leukemia Without Clinical Relapse: A Study of 64 Patients

We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transc...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Blood 1993-02, Vol.81 (4), p.1089-1093
Hauptverfasser: Miyamura, Koichi, Tahara, Tohru, Tanimoto, Mitsune, Morishita, Yoshihisa, Kawashima, Kouhei, Morishima, Yasuo, Saito, Hidehiko, Tsuzuki, Shinobu, Takeyama, Kunihiko, Kodera, Yoshihisa, Matsuyama, Kohji, Hirabayashi, Noriyuki, Yamada, Hironori, Naito, Kazuyuki, Imai, Kuniyuki, Sakamaki, Hisashi, Asai, Osamu, Mizutani, Shuki
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1093
container_issue 4
container_start_page 1089
container_title Blood
container_volume 81
creator Miyamura, Koichi
Tahara, Tohru
Tanimoto, Mitsune
Morishita, Yoshihisa
Kawashima, Kouhei
Morishima, Yasuo
Saito, Hidehiko
Tsuzuki, Shinobu
Takeyama, Kunihiko
Kodera, Yoshihisa
Matsuyama, Kohji
Hirabayashi, Noriyuki
Yamada, Hironori
Naito, Kazuyuki
Imai, Kuniyuki
Sakamaki, Hisashi
Asai, Osamu
Mizutani, Shuki
description We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had ≥1 negative PCR result ≤1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had ≥1 positive PCR result ≥1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the f-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P < .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.
doi_str_mv 10.1182/blood.V81.4.1089.1089
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_75564270</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497120851337</els_id><sourcerecordid>75564270</sourcerecordid><originalsourceid>FETCH-LOGICAL-c407t-da01f1fba7d0fa529e8160d916780588daff12a1eeed76e3f564e6c6febb8e5c3</originalsourceid><addsrcrecordid>eNqFUctuEzEUtRCopIVPqHRX7Ca1J_PwsEFReEqpiKDA0vLY163BGU9tT9F8Gz-Hm0Rs2VwvzuPe40PIJaNLxnh51Tvv9fI7Z8tqySjvDuMJWbC65AWlJX1KFpTSpqi6lj0n5zH-pJRVq7I-I2e8KtuuowvyZ-uHW9hhiDYmHBL0KhSyd7Dz0Sb7gHAT5BBVsGOCt5hQJdTQzxl38x6DjAibO2kH-IJSJesHWJuEAa5lCP73UT06mZ2ND5ka_GAVXM_o_C0OfoqwxekX7q2EHzbd-SnBxtnMkS5bOjlGfA1r-JomPYM30FSwk8nmU-ML8sxIF_Hl6b0g396_u9l8LLafP3zarLeFqmibCi0pM8z0stXUyLrskLOG6o41Lac151oaw0rJEFG3Da5M3VTYqMZg33Os1eqCvDr6jsHfTxiT2Nuo0OVUmAOIts6KsqWZWB-JKvgYAxoxBruXYRaMisfSxKE0kUsTlXjs6zCy7vK0YOr3qP-pTi1l_M0Rx5zywWIQUeUfUKhtyIUI7e1_NvwF_q2uWA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>75564270</pqid></control><display><type>article</type><title>Long Persistent bcr-abl Positive Transcript Detected by Polymerase Chain Reaction After Marrow Transplant for Chronic Myelogenous Leukemia Without Clinical Relapse: A Study of 64 Patients</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Miyamura, Koichi ; Tahara, Tohru ; Tanimoto, Mitsune ; Morishita, Yoshihisa ; Kawashima, Kouhei ; Morishima, Yasuo ; Saito, Hidehiko ; Tsuzuki, Shinobu ; Takeyama, Kunihiko ; Kodera, Yoshihisa ; Matsuyama, Kohji ; Hirabayashi, Noriyuki ; Yamada, Hironori ; Naito, Kazuyuki ; Imai, Kuniyuki ; Sakamaki, Hisashi ; Asai, Osamu ; Mizutani, Shuki</creator><creatorcontrib>Miyamura, Koichi ; Tahara, Tohru ; Tanimoto, Mitsune ; Morishita, Yoshihisa ; Kawashima, Kouhei ; Morishima, Yasuo ; Saito, Hidehiko ; Tsuzuki, Shinobu ; Takeyama, Kunihiko ; Kodera, Yoshihisa ; Matsuyama, Kohji ; Hirabayashi, Noriyuki ; Yamada, Hironori ; Naito, Kazuyuki ; Imai, Kuniyuki ; Sakamaki, Hisashi ; Asai, Osamu ; Mizutani, Shuki</creatorcontrib><description>We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had ≥1 negative PCR result ≤1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had ≥1 positive PCR result ≥1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the f-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P &lt; .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V81.4.1089.1089</identifier><identifier>PMID: 8427990</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Bone Marrow Transplantation ; Child ; Female ; Fusion Proteins, bcr-abl - genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - surgery ; Leukocyte Count ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Polymerase Chain Reaction ; RNA, Messenger - analysis</subject><ispartof>Blood, 1993-02, Vol.81 (4), p.1089-1093</ispartof><rights>1993 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-da01f1fba7d0fa529e8160d916780588daff12a1eeed76e3f564e6c6febb8e5c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8427990$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyamura, Koichi</creatorcontrib><creatorcontrib>Tahara, Tohru</creatorcontrib><creatorcontrib>Tanimoto, Mitsune</creatorcontrib><creatorcontrib>Morishita, Yoshihisa</creatorcontrib><creatorcontrib>Kawashima, Kouhei</creatorcontrib><creatorcontrib>Morishima, Yasuo</creatorcontrib><creatorcontrib>Saito, Hidehiko</creatorcontrib><creatorcontrib>Tsuzuki, Shinobu</creatorcontrib><creatorcontrib>Takeyama, Kunihiko</creatorcontrib><creatorcontrib>Kodera, Yoshihisa</creatorcontrib><creatorcontrib>Matsuyama, Kohji</creatorcontrib><creatorcontrib>Hirabayashi, Noriyuki</creatorcontrib><creatorcontrib>Yamada, Hironori</creatorcontrib><creatorcontrib>Naito, Kazuyuki</creatorcontrib><creatorcontrib>Imai, Kuniyuki</creatorcontrib><creatorcontrib>Sakamaki, Hisashi</creatorcontrib><creatorcontrib>Asai, Osamu</creatorcontrib><creatorcontrib>Mizutani, Shuki</creatorcontrib><title>Long Persistent bcr-abl Positive Transcript Detected by Polymerase Chain Reaction After Marrow Transplant for Chronic Myelogenous Leukemia Without Clinical Relapse: A Study of 64 Patients</title><title>Blood</title><addtitle>Blood</addtitle><description>We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had ≥1 negative PCR result ≤1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had ≥1 positive PCR result ≥1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the f-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P &lt; .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Bone Marrow Transplantation</subject><subject>Child</subject><subject>Female</subject><subject>Fusion Proteins, bcr-abl - genetics</subject><subject>Humans</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - surgery</subject><subject>Leukocyte Count</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local</subject><subject>Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctuEzEUtRCopIVPqHRX7Ca1J_PwsEFReEqpiKDA0vLY163BGU9tT9F8Gz-Hm0Rs2VwvzuPe40PIJaNLxnh51Tvv9fI7Z8tqySjvDuMJWbC65AWlJX1KFpTSpqi6lj0n5zH-pJRVq7I-I2e8KtuuowvyZ-uHW9hhiDYmHBL0KhSyd7Dz0Sb7gHAT5BBVsGOCt5hQJdTQzxl38x6DjAibO2kH-IJSJesHWJuEAa5lCP73UT06mZ2ND5ka_GAVXM_o_C0OfoqwxekX7q2EHzbd-SnBxtnMkS5bOjlGfA1r-JomPYM30FSwk8nmU-ML8sxIF_Hl6b0g396_u9l8LLafP3zarLeFqmibCi0pM8z0stXUyLrskLOG6o41Lac151oaw0rJEFG3Da5M3VTYqMZg33Os1eqCvDr6jsHfTxiT2Nuo0OVUmAOIts6KsqWZWB-JKvgYAxoxBruXYRaMisfSxKE0kUsTlXjs6zCy7vK0YOr3qP-pTi1l_M0Rx5zywWIQUeUfUKhtyIUI7e1_NvwF_q2uWA</recordid><startdate>19930215</startdate><enddate>19930215</enddate><creator>Miyamura, Koichi</creator><creator>Tahara, Tohru</creator><creator>Tanimoto, Mitsune</creator><creator>Morishita, Yoshihisa</creator><creator>Kawashima, Kouhei</creator><creator>Morishima, Yasuo</creator><creator>Saito, Hidehiko</creator><creator>Tsuzuki, Shinobu</creator><creator>Takeyama, Kunihiko</creator><creator>Kodera, Yoshihisa</creator><creator>Matsuyama, Kohji</creator><creator>Hirabayashi, Noriyuki</creator><creator>Yamada, Hironori</creator><creator>Naito, Kazuyuki</creator><creator>Imai, Kuniyuki</creator><creator>Sakamaki, Hisashi</creator><creator>Asai, Osamu</creator><creator>Mizutani, Shuki</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>19930215</creationdate><title>Long Persistent bcr-abl Positive Transcript Detected by Polymerase Chain Reaction After Marrow Transplant for Chronic Myelogenous Leukemia Without Clinical Relapse: A Study of 64 Patients</title><author>Miyamura, Koichi ; Tahara, Tohru ; Tanimoto, Mitsune ; Morishita, Yoshihisa ; Kawashima, Kouhei ; Morishima, Yasuo ; Saito, Hidehiko ; Tsuzuki, Shinobu ; Takeyama, Kunihiko ; Kodera, Yoshihisa ; Matsuyama, Kohji ; Hirabayashi, Noriyuki ; Yamada, Hironori ; Naito, Kazuyuki ; Imai, Kuniyuki ; Sakamaki, Hisashi ; Asai, Osamu ; Mizutani, Shuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-da01f1fba7d0fa529e8160d916780588daff12a1eeed76e3f564e6c6febb8e5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Bone Marrow Transplantation</topic><topic>Child</topic><topic>Female</topic><topic>Fusion Proteins, bcr-abl - genetics</topic><topic>Humans</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - surgery</topic><topic>Leukocyte Count</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local</topic><topic>Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyamura, Koichi</creatorcontrib><creatorcontrib>Tahara, Tohru</creatorcontrib><creatorcontrib>Tanimoto, Mitsune</creatorcontrib><creatorcontrib>Morishita, Yoshihisa</creatorcontrib><creatorcontrib>Kawashima, Kouhei</creatorcontrib><creatorcontrib>Morishima, Yasuo</creatorcontrib><creatorcontrib>Saito, Hidehiko</creatorcontrib><creatorcontrib>Tsuzuki, Shinobu</creatorcontrib><creatorcontrib>Takeyama, Kunihiko</creatorcontrib><creatorcontrib>Kodera, Yoshihisa</creatorcontrib><creatorcontrib>Matsuyama, Kohji</creatorcontrib><creatorcontrib>Hirabayashi, Noriyuki</creatorcontrib><creatorcontrib>Yamada, Hironori</creatorcontrib><creatorcontrib>Naito, Kazuyuki</creatorcontrib><creatorcontrib>Imai, Kuniyuki</creatorcontrib><creatorcontrib>Sakamaki, Hisashi</creatorcontrib><creatorcontrib>Asai, Osamu</creatorcontrib><creatorcontrib>Mizutani, Shuki</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyamura, Koichi</au><au>Tahara, Tohru</au><au>Tanimoto, Mitsune</au><au>Morishita, Yoshihisa</au><au>Kawashima, Kouhei</au><au>Morishima, Yasuo</au><au>Saito, Hidehiko</au><au>Tsuzuki, Shinobu</au><au>Takeyama, Kunihiko</au><au>Kodera, Yoshihisa</au><au>Matsuyama, Kohji</au><au>Hirabayashi, Noriyuki</au><au>Yamada, Hironori</au><au>Naito, Kazuyuki</au><au>Imai, Kuniyuki</au><au>Sakamaki, Hisashi</au><au>Asai, Osamu</au><au>Mizutani, Shuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long Persistent bcr-abl Positive Transcript Detected by Polymerase Chain Reaction After Marrow Transplant for Chronic Myelogenous Leukemia Without Clinical Relapse: A Study of 64 Patients</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>1993-02-15</date><risdate>1993</risdate><volume>81</volume><issue>4</issue><spage>1089</spage><epage>1093</epage><pages>1089-1093</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had ≥1 negative PCR result ≤1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had ≥1 positive PCR result ≥1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the f-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P &lt; .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>8427990</pmid><doi>10.1182/blood.V81.4.1089.1089</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0006-4971
ispartof Blood, 1993-02, Vol.81 (4), p.1089-1093
issn 0006-4971
1528-0020
language eng
recordid cdi_proquest_miscellaneous_75564270
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Adolescent
Adult
Bone Marrow Transplantation
Child
Female
Fusion Proteins, bcr-abl - genetics
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - surgery
Leukocyte Count
Male
Middle Aged
Neoplasm Recurrence, Local
Polymerase Chain Reaction
RNA, Messenger - analysis
title Long Persistent bcr-abl Positive Transcript Detected by Polymerase Chain Reaction After Marrow Transplant for Chronic Myelogenous Leukemia Without Clinical Relapse: A Study of 64 Patients
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T22%3A53%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Long%20Persistent%20bcr-abl%20Positive%20Transcript%20Detected%20by%20Polymerase%20Chain%20Reaction%20After%20Marrow%20Transplant%20for%20Chronic%20Myelogenous%20Leukemia%20Without%20Clinical%20Relapse:%20A%20Study%20of%2064%20Patients&rft.jtitle=Blood&rft.au=Miyamura,%20Koichi&rft.date=1993-02-15&rft.volume=81&rft.issue=4&rft.spage=1089&rft.epage=1093&rft.pages=1089-1093&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood.V81.4.1089.1089&rft_dat=%3Cproquest_cross%3E75564270%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=75564270&rft_id=info:pmid/8427990&rft_els_id=S0006497120851337&rfr_iscdi=true