{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:04:22Z","timestamp":1782889462237,"version":"3.54.5"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T00:00:00Z","timestamp":1414540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:p>\n                    In phenylketonuria, elevated plasma phenylalanine concentrations may disturb blood-to-brain large neutral amino acid (LNAA) transport and cerebral protein synthesis (CPS). We investigated the associations between these processes, using data obtained by positron emission tomography with l-[1-\n                    <jats:sup>11<\/jats:sup>\n                    C]-tyrosine (\n                    <jats:sup>11<\/jats:sup>\n                    C-Tyr) as a tracer. Blood-to-brain transport of non-Phe LNAAs was modeled by the rate constant for\n                    <jats:sup>11<\/jats:sup>\n                    C-Tyr transport from arterial plasma to brain tissue (K\n                    <jats:sub>1<\/jats:sub>\n                    ), while CPS was modeled by the rate constant for\n                    <jats:sup>11<\/jats:sup>\n                    C-Tyr incorporation into cerebral protein (k\n                    <jats:sub>3<\/jats:sub>\n                    ). Brain phenylalanine concentrations were measured by magnetic resonance spectroscopy in three volumes of interest (VOIs): supraventricular brain tissue (VOI 1), ventricular brain tissue (VOI 2), and fluid-containing ventricular voxels (VOI 3). The associations between k\n                    <jats:sub>3<\/jats:sub>\n                    and each predictor variable were analyzed by multiple linear regression. The rate constant k\n                    <jats:sub>3<\/jats:sub>\n                    was inversely associated with brain phenylalanine concentrations in VOIs 2 and 3 (adjusted R\n                    <jats:sup>2<\/jats:sup>\n                    =0.826, F=19.936, P=0.021). Since brain phenylalanine concentrations in these VOIs highly correlated with each other, the specific associations of each predictor with k\n                    <jats:sub>3<\/jats:sub>\n                    could not be determined. The associations between k\n                    <jats:sub>3<\/jats:sub>\n                    and plasma phenylalanine concentration, K\n                    <jats:sub>1<\/jats:sub>\n                    , and brain phenylalanine concentrations in VOI 1 were nonsignificant. In conclusion, our study shows an inverse association between k\n                    <jats:sub>3<\/jats:sub>\n                    and increased brain phenylalanine concentrations.\n                  <\/jats:p>","DOI":"10.1038\/jcbfm.2014.183","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T04:59:34Z","timestamp":1414558774000},"page":"200-205","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["Phenylketonuria: Brain Phenylalanine Concentrations Relate Inversely to Cerebral Protein Synthesis"],"prefix":"10.1177","volume":"35","author":[{"given":"Martijn J","family":"de Groot","sequence":"first","affiliation":[{"name":"Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Department of Digestive and Metabolic Diseases, Center for Liver, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E","family":"Sijens","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk-Jan","family":"Reijngoud","sequence":"additional","affiliation":[{"name":"Department of Digestive and Metabolic Diseases, Center for Liver, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Paans","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francjan J","family":"van Spronsen","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Department of Digestive and Metabolic Diseases, Center for Liver, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,10,29]]},"reference":[{"key":"bibr1-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60961-0"},{"key":"bibr2-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-0946-2"},{"key":"bibr3-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.10.016"},{"key":"bibr4-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014370"},{"key":"bibr5-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.09.002"},{"key":"bibr6-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-28117-7"},{"key":"bibr7-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.01.009"},{"key":"bibr8-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1016\/S1090-3798(03)00039-4"},{"key":"bibr9-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014257"},{"key":"bibr10-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.12.019"},{"key":"bibr11-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-133"},{"key":"bibr12-jcbfm.2014.183","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1985.87"},{"key":"bibr13-jcbfm.2014.183","first-page":"411","volume":"36","author":"Willemsen 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