{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:16:22Z","timestamp":1790702182543,"version":"4.1.0"},"reference-count":12,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,7,5]]},"abstract":"<jats:p>\n                    We describe a population of sickle cell anemia red cells (SS RBCs) (\u22484%) and a smaller fraction of normal RBCs (&lt;0.03%) that fail to dehydrate when permeabilized to K\n                    <jats:sup>+<\/jats:sup>\n                    with either valinomycin or elevated internal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    . The nonshrinking, valinomycin-resistant (\n                    <jats:italic>val-res<\/jats:italic>\n                    ) fractions, first detected by flow cytometry of density-fractionated SS RBCs, constituted up to 60% of the lightest, reticulocyte-rich (R1) cell fraction, and progressively smaller portions of the slightly denser R2 cells and discocytes. R1\n                    <jats:italic>val-res<\/jats:italic>\n                    RBCs had a mean cell hemoglobin concentration of \u224821 g of Hb per dl, and many had an elongated shape like \u201cirreversibly sickled cells,\u201d suggesting a dense SS cell origin. Of three possible explanations for\n                    <jats:italic>val-res<\/jats:italic>\n                    cells, failure of valinomycin to K\n                    <jats:sup>+<\/jats:sup>\n                    -permeabilize the cells, low co-ion permeability, or reduced driving K\n                    <jats:sup>+<\/jats:sup>\n                    gradient, the latter proved responsible: Both SS and normal\n                    <jats:italic>val-res<\/jats:italic>\n                    RBCs were consistently high-Na\n                    <jats:sup>+<\/jats:sup>\n                    and low-K\n                    <jats:sup>+<\/jats:sup>\n                    , even when processed entirely in Na-free media. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    + A23187-induced K\n                    <jats:sup>+<\/jats:sup>\n                    -permeabilization of SS R1 fractions revealed a similar fraction of\n                    <jats:italic>cal-res<\/jats:italic>\n                    cells, whose\n                    <jats:sup>86<\/jats:sup>\n                    Rb uptake showed both high Na\/K pump and leak fluxes.\n                    <jats:italic>val-res<\/jats:italic>\n                    \/\n                    <jats:italic>cal-res<\/jats:italic>\n                    RBCs might represent either a distinct erythroid genealogy, or an \u201cend-stage\u201d of normal and SS RBCs. This paper focuses on the discovery, basic characterization, and exclusion of artifactual origin of this RBC fraction. Many future studies will be needed to clarify their mechanism of generation and full pathophysiological significance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.130198797","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"8045-8050","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":49,"title":["Identification and characterization of a newly recognized population of high-Na\n                    <sup>+<\/sup>\n                    , low-K\n                    <sup>+<\/sup>\n                    , low-density sickle and normal red cells"],"prefix":"10.1073","volume":"97","author":[{"given":"Robert M.","family":"Bookchin","sequence":"first","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; Bayer Diagnostics, Tarrytown, NY 10591; Lawrence Berkeley National Laboratory, Berkeley, CA 94720; MultiImaging Centre, School of Biological Sciences, University of Cambridge, Cambridge CB2 3DY, United Kingdom; and Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zipora","family":"Etzion","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; Bayer Diagnostics, Tarrytown, NY 10591; Lawrence Berkeley National Laboratory, Berkeley, CA 94720; MultiImaging Centre, School of Biological Sciences, University of Cambridge, Cambridge CB2 3DY, United Kingdom; and Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sorette","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; Bayer Diagnostics, Tarrytown, NY 10591; Lawrence Berkeley National Laboratory, Berkeley, CA 94720; MultiImaging Centre, School of Biological Sciences, University of Cambridge, Cambridge CB2 3DY, United Kingdom; and Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narla","family":"Mohandas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; Bayer Diagnostics, Tarrytown, NY 10591; Lawrence Berkeley National Laboratory, Berkeley, CA 94720; MultiImaging Centre, School of Biological Sciences, University of Cambridge, Cambridge CB2 3DY, United Kingdom; and Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy N.","family":"Skepper","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; Bayer Diagnostics, Tarrytown, NY 10591; Lawrence Berkeley National Laboratory, Berkeley, CA 94720; MultiImaging Centre, School of Biological Sciences, University of Cambridge, Cambridge CB2 3DY, United Kingdom; and Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virgilio L.","family":"Lew","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; Bayer Diagnostics, Tarrytown, NY 10591; Lawrence Berkeley National Laboratory, Berkeley, CA 94720; MultiImaging Centre, School of Biological Sciences, University of Cambridge, Cambridge CB2 3DY, United Kingdom; and Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,6,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021908"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021256"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.3.710.710"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.1.249.249"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.4.C1111"},{"key":"e_1_3_3_6_2","first-page":"328","volume":"88","author":"Beutler E","year":"1976","unstructured":"E Beutler, C West, K-G Blume J Lab Clin Med 88, 328\u2013333 (1976).","journal-title":"J Lab Clin Med"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990030606"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1364\/AO.24.001355"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V68.2.506.506"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108735"},{"key":"e_1_3_3_11_2","volume-title":"The Reticulocyte","author":"Rapoport S M","year":"1986","unstructured":"S M Rapoport The Reticulocyte (CRC Press, Boca Raton, FL, 1986)."},{"key":"e_1_3_3_12_2","first-page":"653","volume":"110","author":"Horiuchi K","year":"1987","unstructured":"K Horiuchi, T Asakura J Lab Clin Med 110, 653\u2013660 (1987).","journal-title":"J Lab Clin Med"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.130198797","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:23:04Z","timestamp":1649802184000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.130198797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,6,20]]},"references-count":12,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2000,7,5]]}},"alternative-id":["10.1073\/pnas.130198797"],"URL":"https:\/\/doi.org\/10.1073\/pnas.130198797","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,6,20]]},"assertion":[{"value":"2000-02-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}