Fluorescent protein-based detection of unconjugated bilirubin in newborn serum
Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically...
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| Veröffentlicht in: | Scientific reports 2016-06, Vol.6 (1), p.28489-28489, Article 28489 |
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| creator | Iwatani, Sota Nakamura, Hajime Kurokawa, Daisuke Yamana, Keiji Nishida, Kosuke Fukushima, Sachiyo Koda, Tsubasa Nishimura, Noriyuki Nishio, Hisahide Iijima, Kazumoto Miyawaki, Atsushi Morioka, Ichiro |
| description | Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum. |
| doi_str_mv | 10.1038/srep28489 |
| format | Article |
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In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep28489</identifier><identifier>PMID: 27324682</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/308/3187 ; 692/53/2421 ; Animals ; Bilirubin - blood ; Biological Assay - methods ; Birth weight ; Eels ; Female ; Fish Proteins - chemistry ; Gestational age ; Hemoglobin ; Humanities and Social Sciences ; Humans ; Infant, Newborn ; Light therapy ; Lipids ; Luminescent Proteins - chemistry ; Male ; Methods ; multidisciplinary ; Oxidoreductases Acting on CH-CH Group Donors - chemistry ; Proteins ; Regression analysis ; Science</subject><ispartof>Scientific reports, 2016-06, Vol.6 (1), p.28489-28489, Article 28489</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jun 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c632t-b2f31c63ff24be9d37dc1a9ce71b109410dfe5e19977279b58d46a900103aeac3</citedby><cites>FETCH-LOGICAL-c632t-b2f31c63ff24be9d37dc1a9ce71b109410dfe5e19977279b58d46a900103aeac3</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/PMC4914990/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914990/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,41119,42188,51575,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27324682$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwatani, Sota</creatorcontrib><creatorcontrib>Nakamura, Hajime</creatorcontrib><creatorcontrib>Kurokawa, Daisuke</creatorcontrib><creatorcontrib>Yamana, Keiji</creatorcontrib><creatorcontrib>Nishida, Kosuke</creatorcontrib><creatorcontrib>Fukushima, Sachiyo</creatorcontrib><creatorcontrib>Koda, Tsubasa</creatorcontrib><creatorcontrib>Nishimura, Noriyuki</creatorcontrib><creatorcontrib>Nishio, Hisahide</creatorcontrib><creatorcontrib>Iijima, Kazumoto</creatorcontrib><creatorcontrib>Miyawaki, Atsushi</creatorcontrib><creatorcontrib>Morioka, Ichiro</creatorcontrib><title>Fluorescent protein-based detection of unconjugated bilirubin in newborn serum</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum.</description><subject>692/308/3187</subject><subject>692/53/2421</subject><subject>Animals</subject><subject>Bilirubin - blood</subject><subject>Biological Assay - methods</subject><subject>Birth weight</subject><subject>Eels</subject><subject>Female</subject><subject>Fish Proteins - chemistry</subject><subject>Gestational age</subject><subject>Hemoglobin</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Light therapy</subject><subject>Lipids</subject><subject>Luminescent Proteins - chemistry</subject><subject>Male</subject><subject>Methods</subject><subject>multidisciplinary</subject><subject>Oxidoreductases Acting on CH-CH Group Donors - chemistry</subject><subject>Proteins</subject><subject>Regression analysis</subject><subject>Science</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkVtLAzEQhYMottQ--AdkwRcVVnPZW14EKVYF0Rd9DsnubE3ZJjXZKP57U1pL1RDIwHycOZOD0DHBlwSz6so7WNIqq_geGlKc5SlllO7v1AM09n6O48kpzwg_RANaMpoVFR2ip2kXrANfg-mTpbM9aJMq6aFJGuih7rU1iW2TYGpr5mEm-9hRutMuKG2SeA18KutM4sGFxRE6aGXnYbx5R-h1evsyuU8fn-8eJjePaV0w2qeKtozEsm1ppoA3rGxqInkNJVEER5O4aSEHwnlZ0pKrvGqyQnKM48YSZM1G6HqtuwxqAc3KvZOdWDq9kO5LWKnF747Rb2JmP0TGScY5jgJnGwFn3wP4Xix0_ISukwZs8IKUvOKcFZxE9PQPOrfBmbieIFW0xFhFikidr6naWR8zabdmCBaroMQ2qMie7Lrfkj-xROBiDfjYMjNwOyP_qX0DlqeeFQ</recordid><startdate>20160621</startdate><enddate>20160621</enddate><creator>Iwatani, Sota</creator><creator>Nakamura, Hajime</creator><creator>Kurokawa, Daisuke</creator><creator>Yamana, Keiji</creator><creator>Nishida, Kosuke</creator><creator>Fukushima, Sachiyo</creator><creator>Koda, Tsubasa</creator><creator>Nishimura, Noriyuki</creator><creator>Nishio, Hisahide</creator><creator>Iijima, Kazumoto</creator><creator>Miyawaki, Atsushi</creator><creator>Morioka, Ichiro</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160621</creationdate><title>Fluorescent protein-based detection of unconjugated bilirubin in newborn serum</title><author>Iwatani, Sota ; Nakamura, Hajime ; Kurokawa, Daisuke ; Yamana, Keiji ; Nishida, Kosuke ; Fukushima, Sachiyo ; Koda, Tsubasa ; Nishimura, Noriyuki ; Nishio, Hisahide ; Iijima, Kazumoto ; Miyawaki, Atsushi ; Morioka, Ichiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c632t-b2f31c63ff24be9d37dc1a9ce71b109410dfe5e19977279b58d46a900103aeac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>692/308/3187</topic><topic>692/53/2421</topic><topic>Animals</topic><topic>Bilirubin - blood</topic><topic>Biological Assay - methods</topic><topic>Birth weight</topic><topic>Eels</topic><topic>Female</topic><topic>Fish Proteins - chemistry</topic><topic>Gestational age</topic><topic>Hemoglobin</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Light therapy</topic><topic>Lipids</topic><topic>Luminescent Proteins - chemistry</topic><topic>Male</topic><topic>Methods</topic><topic>multidisciplinary</topic><topic>Oxidoreductases Acting on CH-CH Group Donors - chemistry</topic><topic>Proteins</topic><topic>Regression analysis</topic><topic>Science</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwatani, Sota</creatorcontrib><creatorcontrib>Nakamura, Hajime</creatorcontrib><creatorcontrib>Kurokawa, Daisuke</creatorcontrib><creatorcontrib>Yamana, Keiji</creatorcontrib><creatorcontrib>Nishida, Kosuke</creatorcontrib><creatorcontrib>Fukushima, Sachiyo</creatorcontrib><creatorcontrib>Koda, Tsubasa</creatorcontrib><creatorcontrib>Nishimura, Noriyuki</creatorcontrib><creatorcontrib>Nishio, Hisahide</creatorcontrib><creatorcontrib>Iijima, Kazumoto</creatorcontrib><creatorcontrib>Miyawaki, Atsushi</creatorcontrib><creatorcontrib>Morioka, Ichiro</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwatani, Sota</au><au>Nakamura, Hajime</au><au>Kurokawa, Daisuke</au><au>Yamana, Keiji</au><au>Nishida, Kosuke</au><au>Fukushima, Sachiyo</au><au>Koda, Tsubasa</au><au>Nishimura, Noriyuki</au><au>Nishio, Hisahide</au><au>Iijima, Kazumoto</au><au>Miyawaki, Atsushi</au><au>Morioka, Ichiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluorescent protein-based detection of unconjugated bilirubin in newborn serum</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-06-21</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>28489</spage><epage>28489</epage><pages>28489-28489</pages><artnum>28489</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27324682</pmid><doi>10.1038/srep28489</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 692/308/3187 692/53/2421 Animals Bilirubin - blood Biological Assay - methods Birth weight Eels Female Fish Proteins - chemistry Gestational age Hemoglobin Humanities and Social Sciences Humans Infant, Newborn Light therapy Lipids Luminescent Proteins - chemistry Male Methods multidisciplinary Oxidoreductases Acting on CH-CH Group Donors - chemistry Proteins Regression analysis Science |
| title | Fluorescent protein-based detection of unconjugated bilirubin in newborn serum |
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