URMC Research Network - George Segel

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George Segel

Title	Professor Emeritus
Institution	School of Medicine and Dentistry
Department	Pediatrics
Address	University of Rochester Medical Center School of Medicine and Dentistry 601 Elmwood Ave, Box 704 Rochester NY 14642

Other Positions


Title	Professor (Part-Time)
Institution	School of Medicine and Dentistry
Department	Medicine
Division	Medicine - Hematology/Oncology

Awards And Honors

1975	-	1980	Recipient, Research Career Development Award U.S.P.H.S. #CA00019
1981	-	1982	Buswell Distinguished Service Fellowship for Senior Faculty Support, University of Rochester
1981	-	1982	Faculty Service Award, Department of Pediatrics, University of Rochester
1982	-	1992	Certificate of Appreciation - American Red Cross Board of Directors
1988	-	1992	Appointed to the Board of Directors for New York State, Genetics Task Force
1988			Clara Barton Honor Award for Meritorious Volunteer Leadership, American Red Cross
2005	-	2006	Outstanding Hospital Teaching Award from the University of Rochester Fourth Year Class
2007	-	2008	Outstanding Hospital Teaching Award from the University of Rochester Third year class
2011			Teaching Award - Morning Report MVP Award \| Award from the Pediatric and Med/Ped Residents

Overview

Dr. Segel's research interests are:
1) Chronic leukemia
2) Control of cell maturation
3) Early gene activation in chronic leukemia B lymphocytes induced toward a plasma cell phenotype

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of lymphocytes that are arrested at an intermediate stage of B lymphocyte development. CLL B lymphocytes transform (mature) to a plasmacytic phenotype when treated in vitro with phorbol esters. We have used array hybridization technology to describe gene expression patterns for untreated and tetradecanoyl phorbol acetate (TPA)-treated CLL B-cells at 5, 10, and 20 minutes following initial TPA exposure. Three genes, Early Growth Response Factor 1 (EGR-1), dual specificity phosphatase 2, and CD69 (Early T-cell Activation Antigen), showed a 2.0-fold or greater increase in mRNA transcription at four or more of six time points in two studies. Upregulation of expression of these genes was confirmed by real-time polymerase chain reaction (RT-PCR) in the TPA-treated cells of four CLL patients.

A progressive increase in gene expression was observed during the 20 minute time course for all three genes. In addition, protein expression of EGR-1 and CD69 was increased as measured by immunofluorescence cell analysis. Several genes (PKC, n-myc, jun D, BCL-2) previously reported as overexpressed in CLL lymphocytes were overexpressed in these studies also, but were not altered by TPA treatment. Genes for proteins whose upregulation requires hours of TPA exposure (the 4F2hc component of the L-system amino acid transporter, prohibition, and hsp60) were assessed, and their later expression contrasted with the early expression of EGR-1, dual specificity phosphatase 2, and CD69. EGR-1 encodes a zinc-finger transcription factor that is induced by pokeweed mitogen and TPA and promotes B lymphocyte maturation.

The dual specificity phosphatase 2 encodes an enzyme that reverses mitogen activated protein (MAP) kinase cell activation by dephosphorylation. The CD69 protein is induced by TPA in thymocytes and is a type II transmembrane signaling molecule in hematopoietic cells. These findings suggest that the products of these three genes may be central to early steps in the TPA-induced evolution of CLL B-cells to a plasmacytic phenotype.

Selected Publications

Aslam R, Hu Y, Gebremeskel S, Segel GB, Speck ER, Guo L, Kim M, Ni H, Freedman J, Semple JW. Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia. Blood. 2012 Sep 6; 120(10):2127-32.

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Brandao LR, Segel GB. Question from the clinician: risk of thrombophilia. Pediatr Rev. 2012 Jul; 33(7):321-2.

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Bredlau AL, Semple JW, Segel GB. Management of immune thrombocytopenic purpura in children: potential role of novel agents. Paediatr Drugs. 2011 Aug 1; 13(4):213-23.

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Segel GB, Simon W, Lichtman MA. Should we still be focused on red cell hemoglobin F as the principal explanation for the salutary effect of hydroxyurea in sickle cell disease? Pediatr Blood Cancer. 2011 Jul 15; 57(1):8-9.

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Segel GB, Halterman MW, Lichtman MA. The paradox of the neutrophil's role in tissue injury. J Leukoc Biol. 2011 Mar; 89(3):359-72.

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Segel GB, Feig SA. Controversies in the diagnosis and management of childhood acute immune thrombocytopenic purpura. Pediatr Blood Cancer. 2009 Sep; 53(3):318-24.

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Segel GB, Halterman JS. Neutropenia in pediatric practice. Pediatr Rev. 2008 Jan; 29(1):12-23; quiz 24.

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Simon W, Segel GB, Lichtman MA. Early allogeneic stem cell transplantation for chronic myelogenous leukemia in the imatinib era: a preliminary assessment. Blood Cells Mol Dis. 2006 Sep-Oct; 37(2):116-24; discussion 125-7.

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Lichtman MA, Segel GB. Uncommon phenotypes of acute myelogenous leukemia: basophilic, mast cell, eosinophilic, and myeloid dendritic cell subtypes: a review. Blood Cells Mol Dis. 2005 Nov-Dec; 35(3):370-83.

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Kabir MA, Kaminska J, Segel GB, Bethlendy G, Lin P, Della Seta F, Blegen C, Swiderek KM, Zoladek T, Arndt KT, Sherman F. Physiological effects of unassembled chaperonin Cct subunits in the yeast Saccharomyces cerevisiae. Yeast. 2005 Feb; 22(3):219-39.

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Segel GB, Lichtman MA. Familial (inherited) leukemia, lymphoma, and myeloma: an overview. Blood Cells Mol Dis. 2004 Jan-Feb; 32(1):246-61.

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Segel GB, Woodlock TJ, Xu J, Li L, Felgar RE, Ryan DH, Lichtman MA, Wang N. Early gene activation in chronic leukemic B lymphocytes induced toward a plasma cell phenotype. Blood Cells Mol Dis. 2003 May-Jun; 30(3):277-87.

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Segel GB, Hirsh MG, Feig SA. Managing anemia in a pediatric office practice: Part 2. Pediatr Rev. 2002 Apr; 23(4):111-22.

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Segel GB, Hirsh MG, Feig SA. Managing anemia in pediatric office practice: Part 1. Pediatr Rev. 2002 Mar; 23(3):75-84.

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Woodlock TJ, Bethlendy G, Segel GB. Prohibitin expression is increased in phorbol ester-treated chronic leukemic B-lymphocytes. Blood Cells Mol Dis. 2001 Jan-Feb; 27(1):27-34.

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Segel GB, Francis CA. Anticoagulant proteins in childhood venous and arterial thrombosis: a review. Blood Cells Mol Dis. 2000 Oct; 26(5):540-60.

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Schwartz GJ, Kittelberger AM, Segel GB. Cloning of rabbit Cct6 and the distribution of the Cct complex in mammalian tissues. Exp Nephrol. 2000 May-Jun; 8(3):152-60.

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Palis J, Segel GB. Developmental biology of erythropoiesis. Blood Rev. 1998 Jun; 12(2):106-14.

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Lin P, Cardillo TS, Richard LM, Segel GB, Sherman F. Analysis of mutationally altered forms of the Cct6 subunit of the chaperonin from Saccharomyces cerevisiae. Genetics. 1997 Dec; 147(4):1609-33.

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Smith BD, Segel GB. Abnormal erythrocyte endothelial adherence in hereditary stomatocytosis. Blood. 1997 May 1; 89(9):3451-6.

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Woodlock TJ, Chen X, Young DA, Bethlendy G, Lichtman MA, Segel GB. Association of HSP60-like proteins with the L-system amino acid transporter. Arch Biochem Biophys. 1997 Feb 1; 338(1):50-6.

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Li WZ, Lin P, Frydman J, Boal TR, Cardillo TS, Richard LM, Toth D, Lichtman MA, Hartl FU, Sherman F, et al. Tcp20, a subunit of the eukaryotic TRiC chaperonin from humans and yeast. J Biol Chem. 1994 Jul 15; 269(28):18616-22.

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Woodlock TJ, Young DA, Boal TR, Lichtman MA, Segel GB. Phorbol ester-induced membrane proteins in chronic leukemic B-lymphocytes. Candidate proteins for the L-system amino acid transporter. J Biol Chem. 1993 Jul 25; 268(21):16020-7.

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Segel GB, Boal TR, Cardillo TS, Murant FG, Lichtman MA, Sherman F. Isolation of a gene encoding a chaperonin-like protein by complementation of yeast amino acid transport mutants with human cDNA. Proc Natl Acad Sci U S A. 1992 Jul 1; 89(13):6060-4.

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Liang SL, Woodlock TJ, Whitin JC, Lichtman MA, Segel GB. Signal transduction in N-formyl-methionyl-leucyl-phenylalanine and concanavalin A stimulated human neutrophils: superoxide production without a rise in intracellular free calcium. J Cell Physiol. 1990 Nov; 145(2):295-302.

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Woodlock TJ, Brown R, Mani M, Pompeo L, Hoffman H, Segel GB, Silber R. Decreased L system amino acid transport and decreased gamma-glutamyl transpeptidase are independent processes in human chronic lymphocytic leukemia B-lymphocytes. J Cell Physiol. 1990 Nov; 145(2):217-21.

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Costa-Casnellie MR, Cragoe EJ, Segel GB, Lichtman MA. Activation of the Na+/H+ exchanger by phorbol ester and osmotic shock is dependent on the degree of neutrophilic maturation. J Cell Physiol. 1989 Nov; 141(2):294-300.

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Segel GB, Woodlock TJ, Murant FG, Lichtman MA. Photoinhibition of 2-amino-2-carboxybicyclo[2,2,1]heptane transport by O-diazoacetyl-L-serine. An initial step in identifying the L-system amino acid transporter. J Biol Chem. 1989 Oct 5; 264(28):16399-402.

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Woodlock TJ, Segel GB, Lichtman MA. Diacylglycerol and calcium induce rapid enhancement of A-system amino acid transport by independent mechanisms in human T-lymphocytes. J Cell Physiol. 1989 Oct; 141(1):33-9.

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Simon W, Segel GB, Lichtman MA. Upper and lower time limits in the decision to recommend marrow transplantation for patients with chronic myelogenous leukaemia. Br J Haematol. 1988 Sep; 70(1):31-6.

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Segel GB. Anemia. Pediatr Rev. 1988 Sep; 10(3):77-88.

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Costa-Casnellie MR, Segel GB, Lichtman MA. The Na+/H+ exchanger in immature and mature granulocytic HL-60 cells. Property changes induced by intracellular acidification and cell maturation. J Biol Chem. 1988 Aug 25; 263(24):11851-5.

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Segel GB, Woodlock TJ, Lichtman MA. Trans-stimulation of L-system amino acid transport in normal and chronic leukemic human lymphocytes: phorbol ester restores function in CLL. J Cell Physiol. 1988 Mar; 134(3):503-8.

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Woodlock TJ, Segel GB, Lichtman MA. Phorbol ester restores L-system amino acid transport of B lymphocytes in chronic lymphocytic leukemia. J Clin Invest. 1988 Jan; 81(1):32-8.

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Costa-Casnellie MR, Segel GB, Cragoe EJ, Lichtman MA. Characterization of the Na+/H+ exchanger during maturation of HL-60 cells induced by dimethyl sulfoxide. J Biol Chem. 1987 Jul 5; 262(19):9093-7.

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Costa-Casnellie MR, Segel GB, Lichtman MA. Signal transduction in human monocytes: relationship between superoxide production and the level of kinase C in the membrane. J Cell Physiol. 1986 Dec; 129(3):336-42.

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Segel GB, Simon W, Lichtman MA. Variables influencing the timing of marrow transplantation in patients with chronic myelogenous leukemia. Blood. 1986 Nov; 68(5):1055-64.

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Scully SP, Segel GB, Lichtman MA. Relationship of superoxide production to cytoplasmic free calcium in human monocytes. J Clin Invest. 1986 Apr; 77(4):1349-56.

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Costa-Casnellie MR, Segel GB, Lichtman MA. Concanavalin A and phorbol ester cause opposite subcellular redistribution of protein kinase C. Biochem Biophys Res Commun. 1985 Dec 31; 133(3):1139-44.

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Segel GB, Tometsko AM, Lichtman MA. Y+- and L-system amino acid transport in normal and chronic lymphocytic leukemia lymphocytes: photoinhibition by fluoronitrophenylazide. Arch Biochem Biophys. 1985 Nov 1; 242(2):347-54.

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Segel GB, Ryan DH, Lichtman MA. Ecto-nucleotide triphosphatase activity of human lymphocytes: studies of normal and CLL lymphocytes. J Cell Physiol. 1985 Sep; 124(3):424-32.

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Abboud CN, Scully SP, Lichtman AH, Brennan JK, Segel GB. The requirements for ionized calcium and magnesium in lymphocyte proliferation. J Cell Physiol. 1985 Jan; 122(1):64-72.

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Scully SP, Segel GB, Lichtman MA. Calcium exchange and ionized cytoplasmic calcium in resting and activated human monocytes. J Clin Invest. 1984 Aug; 74(2):589-99.

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Segel GB, Simon W, Lichtman MA. Multicomponent analysis of amino acid transport in human lymphocytes. Diminished L-system transport in chronic leukemic B lymphocytes. J Clin Invest. 1984 Jul; 74(1):17-24.

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Segel GB, Simon W, Lichtman MA. A multicomponent analysis of amino acid transport systems in human lymphocytes. 1. Kinetic parameters of the A and L systems and pathways of uptake of naturally occurring amino acids in blood lymphocytes. J Cell Physiol. 1983 Sep; 116(3):372-8.

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Lichtman AH, Segel GB, Lichtman MA. The role of calcium in lymphocyte proliferation. (An interpretive review). Blood. 1983 Mar; 61(3):413-22.

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Scully SP, Segel GB, Lichtman MA. Plasma membrane vesicles prepared from unadhered monocytes: characterization of calcium transport and the calcium ATPase. Cell Calcium. 1982 Dec; 3(6):515-30.

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Segel GB, Lichtman MA. Decreased L-system for amino acid transport in chronic lymphocytic leukemic lymphocytes. J Biol Chem. 1982 Aug 25; 257(16):9255-7.

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Lichtman AH, Segel GB, Lichtman MA. Effects of trifluoperazine and mitogenic lectins on calcium ATPase activity and calcium transport by human lymphocyte plasma membrane vesicles. J Cell Physiol. 1982 May; 111(2):213-7.

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Segel GB, Simon W, Lichtman AH, Lichtman MA. The activation of lymphocyte plasma membrane (Na,K)-ATPase by EGTA is explained better by zinc than calcium chelation. J Biol Chem. 1981 Jul 10; 256(13):6629-32.

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Lichtman AH, Segel GB, Lichtman MA. Calcium transport and calcium-ATPase activity in human lymphocyte plasma membrane vesicles. J Biol Chem. 1981 Jun 25; 256(12):6148-54.

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Segel GB, Cokelet GR, Lichtman MA. The measurement of lymphocyte volume: importance of reference particle deformability and counting solution tonicity. Blood. 1981 May; 57(5):894-9.

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Quastel MR, Segel GB, Lichtman MA. The effect of calcium chelation on lymphocyte monovalent cation permeability, transport and concentration. J Cell Physiol. 1981 May; 107(2):165-70.

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Segel GB, Lichtman MA. Amino acid transport in human lymphocytes: distinctions in the enhanced uptake with PHA treatment or amino acid deprivation. J Cell Physiol. 1981 Feb; 106(2):303-8.

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Segel GB. Membrane alterations in lymphocyte proliferation. Am J Pediatr Hematol Oncol. 1981; 3(4):433-8.

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Segel GB, Lichtman MA. The apparent discrepancy of ouabain inhibition of cation transport and of lymphocyte proliferation is explained by time-dependency of ouabain binding. J Cell Physiol. 1980 Jul; 104(1):21-6.

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Segel GB, Lukacher A, Gordon BR, Lichtman MA. Glucocorticoid suppression of human lymphocyte DNA synthesis: influence of phytohemagglutinin concentration. J Lab Clin Med. 1980 Apr; 95(4):624-32.

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Lichtman AH, Segel GB, Lichtman MA. Total and exchangeable calcium in lymphocytes: effects of PHA and A23187. J Supramol Struct. 1980; 14(1):65-75.

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Lichtman AH, Segel GB, Lichtman MA. An ultrasensitive method for the measurement of human leukocyte calcium: lymphocytes. Clin Chim Acta. 1979 Oct 1; 97(2-3):107-21.

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Segel GB, Simon W, Lichtman MA. Regulation of sodium and potassium transport in phytohemagglutinin-stimulated human blood lymphocytes. J Clin Invest. 1979 Sep; 64(3):834-41.

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Segel GB, Kovach G, Lichtman MA. Sodium-potassium adenosine triphosphatase activity of human lymphocyte membrane vesicles: kinetic parameters, substrate specificity, and effects of phytohemagglutinin. J Cell Physiol. 1979 Jul; 100(1):109-17.

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Segel GB, Androphy EJ, Lichtman MA. Increased ouabain-sensitive glycolysis of lymphocytes treated with phytohemagglutinin: relationship to potassium transport. J Cell Physiol. 1978 Dec; 97(3 Pt 2 Suppl 1):407-12.

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Gordon BR, Segel GB, Brennan JK, Lichtman MA. Effect of molecular modification on the inhibition of lymphocyte blastogenesis by cardiac glycosides. Blood. 1978 Mar; 51(3):497-505.

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Segel GB, Lichtman MA. The effect of method on the measurement of K+ concentration in PHA-treated human blood lymphocytes. Exp Cell Res. 1978 Mar 1; 112(1):95-102.

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Segel GB, Lichtman MA. Decreased membrane potassium permeability and transport in human chronic leukemic and tonsillar lymphocytes. J Cell Physiol. 1977 Nov; 93(2):277-84.

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Ganick DJ, Segel GB, Chamberlain J, Hirsch L, Klemperer MR. The effects of splenectomy and glucocorticoids on survival and hepatic uptake of damaged red cells in the mouse. Am J Hematol. 1977; 2(4):365-73.

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Segel GB, Lichtman MA. Potasssium transport in human blood lymphocytes treated with phytohemagglutinin. J Clin Invest. 1976 Dec; 58(6):1358-69.

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Segel GB, Lichtman MA, Gordon BR, MacPherson JL, Nusbacher J. Plateletpheresis residues: a source of large quantities of human blood lymphocytes. Transfusion. 1976 Sep-Oct; 16(5):455-9.

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Segel GB, Lichtman MA, Hollander MM, Gordon BR, Klemperer MR. Human lymphocyte potassium content during the initiation of phytohemagglutinin-induced mitogenesis. J Cell Physiol. 1976 May; 88(1):43-8.

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Segel GB, Gordon BR, Lichtman MA, Hollander MM, Klemperer MR. Exodus of 42K+ and 86Rb+ from rat thymic and human blood lymphocytes exposed to phytohemagglutinin. J Cell Physiol. 1976 Mar; 87(3):337-43.

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Klemperer MR, Ganick D, Shigeoka A, Lee H, Segel G. Attempted treatment of a child with metastatic neuroblastoma employing syngeneic marrow transplantation. Transplantation. 1976 Feb; 21(2):161-4.

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Dutcher PO, Segel GB, Feig SA, Miller DR, Klemperer MR. Cation transport and its altered regulations in human stomatocytic erythrocytes. Pediatr Res. 1975 Dec; 9(12):924-7.

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Klausner MA, Hirsch LJ, Leblond PF, Chamberlain JK, Klemperer MR, Segel GB. Contrasting splenic mechanisms in the blood clearance of red blood cells and colloidal particles. Blood. 1975 Dec; 46(6):965-76.

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Segel GB, Hollander MM, Gordon BR, Klemperer MR, Lichtman MA. A rapid phytohemagglutinin induced alteration in lymphocyte potassium permeability. J Cell Physiol. 1975 Oct; 86(2 PT 2 SUPPL 1):327-35.

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Segel GB, Feig SA, Glader BE, Muller A, Dutcher P, Nathan DG. Energy metabolism in human erythrocytes: the role of phosphoglycerate kinase in cation transport. Blood. 1975 Aug; 46(2):271-8.

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Feig SA, Segel GB, Kern KA, Osher AB, Schwartz RH. Erythrocyte transport function in cystic fibrosis. Pediatr Res. 1974 May; 8(5):594-7.

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Gordesky SE, Marinetti GV, Segel GB. The interaction of 1-fluoro-2,4-dinitrobenzene with amino-phospholipids in membranes of intact erythrocytes, modified erythrocytes, and erythrocytes ghosts. J Membr Biol. 1973; 14(3):229-42.

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Bennett JM, Klemperer MR, Segel GB. Survival prediction based on morphology of lymphoblasts. Recent Results Cancer Res. 1973; 43:23-7.

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Segel GB, Feig SA, Mentzer WC, McCaffrey RP, Wells R, Bunn HF, Shohet SB, Nathan DG. Effects of urea and cyanate on sickling in vitro. N Engl J Med. 1972 Jul 13; 287(2):59-64.

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Gordesky SE, Marinetti GV, Segel GB. Differences in the reactivity of phospholipids with FDNB in normal RBC, sickle cells and RBC ghosts. Biochem Biophys Res Commun. 1972 Jun 9; 47(5):1004-9.

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Feig SA, Segel GB, Shohet SB, Nathan DG. Energy metabolism in human erythrocytes. II. Effects of glucose depletion. J Clin Invest. 1972 Jun; 51(6):1547-54.

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Segel GB, Feig SA, Baehner RL, Nathan DG. Fluorometric analysis of glycolytic intermediates and pyridine nucleotides in peripheral blood cells. J Lab Clin Med. 1971 Dec; 78(6):969-76.

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Nathan DG, Segel GB. Pathophysiology of common hemolytic syndromes. Postgrad Med. 1971 Oct; 50(4):179-85.

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Gelfand EW, Abramson N, Segel GB, Nathan DG. Buffy-coat observations and red-cell antibodies in acquired hemolytic anemia. N Engl J Med. 1971 Jun 3; 284(22):1250-2.

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