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CLINICAL SCIENCE |

Biochemistry of the White Blood Cell

Seymour Perry, MD
[+] Author Affiliations

Reprint requests to National Institutes of Health, Department of Health, Education, and Welfare, Bethesda, Md 20014 (Dr. Perry).


From the National Cancer Institute, National Institutes of Health, Bethesda, Md.


JAMA. 1964;190(10):918-925. doi:10.1001/jama.1964.03070230054017
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In spite of the numerous studies and a growing list of publications concerned with the biochemistry of the white blood cell (WBC), many fundamental problems still remain unsolved. There are a number of factors responsible for this situation, but the two most important ones concern the procurement of leukocytes, and the physical and chemical characteristics of the cells. Several methods for the separation of WBC's from red blood cells (RBC's) and platelets are now available but these do not provide for the isolation of leukocytes of uniform age within the myeloid series, or for the separation of granulocytes from lymphocytes. This is of particular importance in biochemical studies involving the cells of patients with chronic myelocytic leukemia (CML). It has been demonstrated that the concentration of many of the enzymatic and nonenzymatic constituents is different in granulocytes and lymphocytes, and that the levels change as the leukocyte matures.

In addition

REFERENCES

Warburg, O.: Metabolism of Tumors, translated by F. Dickens, London: Constable, 1930.
Seelich, F.: " Metabolism of Normal and Abnormal Leukocytes ," in Physiology and Pathology of Leukocytes , H. Braunsteiner, and F. Zucker, ed., New York: Grune & Stratton, Inc., 1962;, p 152.
Valentine, W.:  Metabolism of the Leukemic Leukocyte , Amer J Med 28:699, 1960;.
Beck, W.S.:  Control of Leukocyte Glycolysis , J Biol Chem 232:251-279 ( (May) ) 1958;.
Beck, W.S., and Valentine, W.N.:  Carbohydrate Metabolism of Leukocytes: A Review , Cancer Res 13:309, 1953;.
Beck, W.S.:  Leukocyte Glycolysis , Ann NY Acad Sci 75:4, 1958;.
Beck, W.S.:  Occurrence and Control of Phosphogluconate Oxidation Pathway in Normal and Leukemic Leukocytes , J Biol Chem 232:271-283 ( (May) ) 1958;.
Vanotti, A.: " Metabolic Pattern of Leukocytes Within the Circulation and Outside It ," Ciba Foundation Study Group 10, Biological Activity of the Leukocyte , Boston: Little, Brown & Co., 1961;, p 78.
Burk, D.; Laszlo, J.; and Wight, K.:  Comparative Metabolism of Normal Human Leukocytes , Fed Proc 18:199, 1959;.
Laszlo, J., et al:  Effects of Chemotherapeutic Agents on Metabolism of Human Acute Leukemic Cells in Vitro , Proc Soc Exper Biol Med 97:127, 1958;.
Munroe, J.F.; Shipp, J.C.; and Crevasse, L. E.:  Glucose Metabolism in Human Leukocytes From Patients With Diabetes Mellitus and Hypercholesterolemia , Clin Res 12:275, 1964;.
Kremer, W., and Perry, S.: To be published.
Karnovsky, M.L.: " Metabolic Shifts in Leukocytes During the Phagocytic Event ," in Ciba Foundation Study Group 10, Biological Activity of the Leukocyte , Boston: Little, Brown & Co., 1961;, p 60.
Sidbury, J.B. Jr., et al:  Glycogen in Erythrocytes of Patients With Glycogen Storage Disease , Pediatrics 27:103, 1961;.
VanderWende, C.; Miller, W.L.; and Glass, S.A.:  Glycogen Metabolism of Normal and Leukemic Leukocytes , Life Sci 3:223, 1964;.
Yunis, A.L., and Arimura, G.K.:  Enzymes of Glycogen Metabolism in White Blood Cells. Glycogen Phosphorylase in Normal and Leukemic Human Leukocytes , Cancer Res 24:489, 1964;.
Williams, H.E.; Kendig, E.M.; and Field, J.B.:  Leukocyte Debranching Enzyme in Glycogen Storage Disease . J Clin Invest 42:656, 1963;.
Williams, H.E., and Field, J.B.:  Low Leukocyte Phosphorylase in Hepatic Phosphorylase Deficient Glycogen Storage Disease , J Clin Invest 40:1841, 1961;.
Malamos, B., et al:  In Vitro Incorporation of Acetate-1-C 14 into Normal and Leukemic Leukocyte Lipids , J Lipid Res 3:222, 1962;.
Kidson, C.:  Leukocyte Lipid Metabolism in Myeloproliferative States , Aust Ann Med 11:50, 1962;.
Kidson, C.:  Lipid Synthesis in Human Leukocytes in Acute Leukemia , Aust Ann Med 10:282, 1961;.
Kidson, C.:  Relation of Leukocyte Lipid Metabolism to Cell Age: Studies in Infective Leukocytosis , Brit J Exp Path 42:597, 1961;.
deDuve, C.: " Lysosomes, New Group of Cytoplasmic Particles ," in Subcellular Particles , T. Hayashi, ed., New York: Ronald Press, 1959;, p 128.
Hirsch, J.G.:  Cinemicrophotographic Observation on Granule Lysis in Polymorphonuclear Leukocytes During Phagocytosis , J Exp Med 116:827, 1962;.
Hirsch, J.G.; Bernheimer, A.W.; and Weissmann, G.:  Motion Picture Study of the Toxic Action of Streptolysins on Leukocytes , J Exp Med 118:223, 1963;.
Kaplow, L.S.:  Histochemical Procedure for Localizing and Evaluating Leukocyte Alkaline Phosphatase Activity in Smears of Blood and Marrow , Blood 10:1025, 1955;.
Valentine, W.N., and Beck, W.C.:  Biochemical Studies on Leukocytes, I. Phosphatase Activity in Health, Leukocytosis, and Myelocytic Leukemia , J Lab Clin Med 38:39, 1951;.
Peacock, A. C.; Brecher, G.; and Highsmith, E.M.:  Simplified Procedure for Quantitative Measurement of Alkaline Phospatase in White Blood Cells , Amer J Clin Path 29:80,1958;.
Wachstein, M.:  Alkaline Phosphatase Activity in Normal and Abnormal Human Blood and Bone Marrow , J Lab Clin Med 31:1, 1946;.
Valentine, W.N., et al:  Biochemical Studies in Chronic Myelocytic Leukemia, Polycythemia Vera, and Other Idiopathic Myeloproliferative Disorders , Blood 7:959, 1952;.
Beck, W.S., and Valentine, W.N.:  Biochemical Studies in Leukocytes. II. Phosphatase Activity in Chronic Lymphocytic Leukemia, Acute Leukemia and Miscellaneous Hematological Conditions , J Lab Clin Med 38:245, 1951;.
Valentine, W.N., et al:  Relationship of Leukocyte Alkaline Phosphatase to "Stress ," to ACTH, and to Adrenal 17-OH-Corticosteroids, J Lab Clin Med 49:723, 1957;.
Unpublished data.
Xefteris, E.. et al:  Leukocyte Alkaline Phosphatase in Busulfan Induced Remissions of Chronic Granulocytic Leukemia , Blood 18:202, 1961;.
Tanaka, K.R.; Valentine, W.N.; and Fredericks, R.E.:  Diseases or Clinical Conditions Associated With Low-Leukocyte Alkaline Phosphatase , New Eng J Med 262:912, 1960;.
Koler, R.D., et al:  Myeloproliferative Diseases. Diagnostic Value of Leukocyte Alkaline Phosphatase Test , Amer J Clin Path 30:295, 1958;.
Beisel, W.R.; Benjamin, N.; and Austen, K.F.:  Absence of Leukocyte Alkaline Phosphatase in Hypophosphatasia , Blood 14:975, 1959;.
King, M.J.; Gillis, E.M.; and Baikie, A.G.:  Alkaline Phosphatase in Mongolism , Lancet 2:1302, 1962;.
Hardin, B., et al:  Studies on Sulfhydryl Content of Human Leukocytes and Erythrocytes , Amer J Med Sci 228:73, 1954;.
Code, C.F.:  Source in Blood of Histamine-Like Constituent , J Physiol 90:349, 1937;.
Code, C.F.:  Histamine-Like Activity of White Blood Cells , J Physiol 90:485, 1937;.
Valentine, W.N., et al:  Relationship of the Basophil to Blood Histamine in Man , Blood 10:154, 1955;.
Graham, H.T., et al:  Distribution of Histamine Among Leukocytes and Platelets , Blood 10:467, 1955;.
Hartmen, W.J.; Clark, W.G.; and Cyr, S.D.:  Histidine Decarboxylase Activity of Basophils From Chronic Myelogenous Leukemic Patients, Origin of Blood Histamine , Proc Soc Exper Biol Med 107:123, 1961;.
Jorpes, E.: Heparin in Treatment of Thrombosis , 2nd ed, London: Oxford University Press, 1946;, pp 59-66.
Ratnoff, O.D.: Bleeding Syndromes , Springfield, Ill: Charles C Thomas, 1960;, pp 111-113.
Riley, J.F.:  Functional Significance of Histamine and Heparin in Tissue Mast Cells , Ann NY Acad Sci 103:151-163 ( (Feb 26) ) 1963;.
Barnhart, M.I., and Riddle, J.M.:  Cellular Localization of Profibrinolysin (Plasminogen) , Blood 21:306, 1963;.
Schultz, J., and Kaminker, K.:  Myeloperoxidase of the Leukocyte of Normal Human Blood, I. Content and Localization , Arch Biochem 96:465-467 ( (March) ) 1962;.
Agner, K.:  Verdoperoxidase , Acta Physiol Scand 2:1, 1941;.
Schultz, J.; Shay, H.; and Gruenstein, M.:  Chemistry of Experimental Chloroma. I. Porphyrins and Peroxidases , Cancer Res 14:157, 1954;.
Baron, D.M., and Roberts, P.M.:  Sodium, Potassium, and Water Content of Isolated Normal Human Leukocytes , J Physiol 165:219, 1963;.
McNary, W.F., Jr.:  Histochemical Demonstration of Trace Metals in Leukocytes , J Histochem Cytochem 8:124, 1960;.
Rigas, D.A.:  Electrolyte, Nitrogen, and Water Content of Human Leukemic Leukocytes: Relation to Cell Maturity , J Lab Clin Med 58:234, 1961;.
Vallee, B.L.:  Biochemistry, Physiology, and Pathology of Zinc , Physiol Rev 39:443, 1959;.
Valentine, W.N.; Tanaka, K.R.; and Fredricks, R.E.:  Studies on Leukocyte Alkaline Phosphatase: Role of Zinc and Magnesium , J Lab Clin Med 55:303, 1960;.
Gibson, J.G. II, et al:  Studies of Zinc Content of Leukocytes in Myelogenous Leukemia , Acta Un Int Cancr 6:1102, 1950;.
Hammerstein, E., and Reichard, P.:  Pyrimidine Nucleosides as Precursors of Pyrimidines in Polynucleotides , J Biol Chem 183:105, 1950;.
Beck, W.S.:  Metabolic Functions of Vitamin B12 , New Eng J Med 266:708. 1962;.
Bertino, J.R., et al:  Studies on Normal and Leukemic Leukocytes. IV. Tetrahydrofolate-Dependent Enzyme Systems and Dihydrofolic Reductase , J Clin Invest 42:1899, 1963;.
Grunberg-Manago, M.:  Enzymatic Synthesis of Nucleic Acids , Ann Rev Biochem 31:301, 1962;.
Craddock, C.G., and Nakai, G.S.:  Leukemic Cell Proliferation as Determined by In Vitro Desoxyribonucleic Acid Synthesis , J Clin Invest 41:360, 1962;.
Scott, J.L.:  Human Leukocyte Metabolism In Vitro. I. Incorporation of Adenine-8-C14 and Formate-C14 Into Nucleic Acids of Leukemic Leukocytes , J Clin Invest 41:67, 1962;.
Gavosto, F.; Maraini, G.; and Pileri, A.:  Nucleic Acids and Protein Metabolism in Acute Leukemic Cells , Blood 16:1555,1960;.
Bianchi, P.A.:  Thymidine Phosphorylation and Deoxyribonucleic Acid Synthesis in Human Leukaemic Cells , Biochim Biophys Acta 55:547-549 ( (April 2) ) 1962;.
Silber, R.; Gabrio, B.W.; and Huennekens, F.M.:  Enzymatic Synthesis of Thymidylate by Leukocytes , Clin Res 10:207, 1962;.
Silber, R.:  Feedback Inhibition of Deoxyribonucleotide Interconversion in Human Leukocytes , J Clin Invest 43:1248, 1964;.
Smith, L.H., Jr.; Baker, F.A.; and Sullivan, M.:  Pyrimidine Metabolism in Man. II. Studies of Leukemic Cells , Blood 15:360, 1960;.
Bresnick, E., and Karajala, R.J.:  End-Product Inhibition of Thymidine Kinase Activity in Normal and Leukemic Human Leukocytes , Cancer Res 24:841, 1964;.
Frenster, J.H.; Best, W.R.; and Winzler, R.J.:  Metabolism of Human Leukocytes In Vitro. V. Inhibition by Human Serum of Formate and Glycine Incorporation , Proc Soc Exper Biol Med 98:887, 1958;.
Perry, S., and Marsh, J.C.:  Uptake of Tritiated Thymidine by Leukemic Cells: Effect of Various Leukocyte Preparations , Proc Soc Exp Biol Med 115:51, 1964;.
Craddock, C.G.:  Physiology of Granulocytic Cells in Normal and Leukemic States , Amer J Med 28:711, 1960;.
Walker, R.I., and Fowler, I.:  Culture In Vitro of Human Peripheral Blood Leukocytes After Granulocyte Removal , Clin Res 12:233, 1964;.
Marsh, J.C., and Perry, S.:  Thymidine Catabolism by Normal and Leukemic Human Leukocytes , J Clin Invest 43:267, 1964;.
Marsh, J.C., and Perry, S.:  Reduction of Thymine by Human Leukocytes , Arch Biochem Biophys 104:146, 1964;.
Rubini, J.R.:  Implications of Thymidine Phosphorylase in Tissues , Clin Res 12:230, 1964;.
Bessis, M.:  Use of Replacement Transfusion in Diseases Other Than Hemolytic Disease of Newborn , Blood 4:324, 1949;.
Bierman, H.R., et al: " Influence of Cellular Fractions of Whole Blood on Course of Acute Lymphocytic Leukemia ," in The Leukemias , J. Rebuck, ed., NY: Academic Pres, 1957;, p 301.
" Cures" for Leukemia , editorial, Brit Med J 1:129 ( (Jan 18) ) 1964;.
Bierman, H.R., et al:  Studies on Cross-Circulation in Man. I. Methods and Clinical Changes , Blood 6:487, 1951;.
Perry, S., and Moxley, J.: Unpublished data.
Swenseid, M.E.; Bethell, F.H.; and Bird, O.D.:  Concentration of Folic Acid in Leukocytes , Cancer Res 11:864, 1951;.
Huennekens, F.M., et al:  Antimetabolites in Chemotherapy of Leukemia , Exp Cell Res 9:441, 1963;.
Misra, D.K., et al:  Increased Dihydrofolate Reductase ACtivity as a Possible Basis of Drug Resistance in Leukaemia , Nature 189:39, 1961;.
Bertino, J.R., et al:  Increased Level of Dihydrofolic Reductase in Leukocytes of Patients Treated With Amethopterin , Nature 193:140, 1962;.
Davidson, J.R.:  Studies on Mechanism of Action of 6Mercaptopurine in Sensitive and Resistant L-1210 Leukemia In Vitro , Cancer Res 20:225, 1960;.
Brockman, R.W.:  Biochemical Aspects of Mercaptopurine Inhibition and Resistance , Cancer Res 23:1191, 1963;.
Brockman, R.W., and Anderson, E.P.:  Biochemistry of Cancer , Ann Rev Biochem 32:463, 1963;.
Cohen, S.S., et al:  Mode of Action of 5-Fluorouracil and Its Derivations , Proc Nat Acad Sci USA 44:1004, 1958;.

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Warburg, O.: Metabolism of Tumors, translated by F. Dickens, London: Constable, 1930.
Seelich, F.: " Metabolism of Normal and Abnormal Leukocytes ," in Physiology and Pathology of Leukocytes , H. Braunsteiner, and F. Zucker, ed., New York: Grune & Stratton, Inc., 1962;, p 152.
Valentine, W.:  Metabolism of the Leukemic Leukocyte , Amer J Med 28:699, 1960;.
Beck, W.S.:  Control of Leukocyte Glycolysis , J Biol Chem 232:251-279 ( (May) ) 1958;.
Beck, W.S., and Valentine, W.N.:  Carbohydrate Metabolism of Leukocytes: A Review , Cancer Res 13:309, 1953;.
Beck, W.S.:  Leukocyte Glycolysis , Ann NY Acad Sci 75:4, 1958;.
Beck, W.S.:  Occurrence and Control of Phosphogluconate Oxidation Pathway in Normal and Leukemic Leukocytes , J Biol Chem 232:271-283 ( (May) ) 1958;.
Vanotti, A.: " Metabolic Pattern of Leukocytes Within the Circulation and Outside It ," Ciba Foundation Study Group 10, Biological Activity of the Leukocyte , Boston: Little, Brown & Co., 1961;, p 78.
Burk, D.; Laszlo, J.; and Wight, K.:  Comparative Metabolism of Normal Human Leukocytes , Fed Proc 18:199, 1959;.
Laszlo, J., et al:  Effects of Chemotherapeutic Agents on Metabolism of Human Acute Leukemic Cells in Vitro , Proc Soc Exper Biol Med 97:127, 1958;.
Munroe, J.F.; Shipp, J.C.; and Crevasse, L. E.:  Glucose Metabolism in Human Leukocytes From Patients With Diabetes Mellitus and Hypercholesterolemia , Clin Res 12:275, 1964;.
Kremer, W., and Perry, S.: To be published.
Karnovsky, M.L.: " Metabolic Shifts in Leukocytes During the Phagocytic Event ," in Ciba Foundation Study Group 10, Biological Activity of the Leukocyte , Boston: Little, Brown & Co., 1961;, p 60.
Sidbury, J.B. Jr., et al:  Glycogen in Erythrocytes of Patients With Glycogen Storage Disease , Pediatrics 27:103, 1961;.
VanderWende, C.; Miller, W.L.; and Glass, S.A.:  Glycogen Metabolism of Normal and Leukemic Leukocytes , Life Sci 3:223, 1964;.
Yunis, A.L., and Arimura, G.K.:  Enzymes of Glycogen Metabolism in White Blood Cells. Glycogen Phosphorylase in Normal and Leukemic Human Leukocytes , Cancer Res 24:489, 1964;.
Williams, H.E.; Kendig, E.M.; and Field, J.B.:  Leukocyte Debranching Enzyme in Glycogen Storage Disease . J Clin Invest 42:656, 1963;.
Williams, H.E., and Field, J.B.:  Low Leukocyte Phosphorylase in Hepatic Phosphorylase Deficient Glycogen Storage Disease , J Clin Invest 40:1841, 1961;.
Malamos, B., et al:  In Vitro Incorporation of Acetate-1-C 14 into Normal and Leukemic Leukocyte Lipids , J Lipid Res 3:222, 1962;.
Kidson, C.:  Leukocyte Lipid Metabolism in Myeloproliferative States , Aust Ann Med 11:50, 1962;.
Kidson, C.:  Lipid Synthesis in Human Leukocytes in Acute Leukemia , Aust Ann Med 10:282, 1961;.
Kidson, C.:  Relation of Leukocyte Lipid Metabolism to Cell Age: Studies in Infective Leukocytosis , Brit J Exp Path 42:597, 1961;.
deDuve, C.: " Lysosomes, New Group of Cytoplasmic Particles ," in Subcellular Particles , T. Hayashi, ed., New York: Ronald Press, 1959;, p 128.
Hirsch, J.G.:  Cinemicrophotographic Observation on Granule Lysis in Polymorphonuclear Leukocytes During Phagocytosis , J Exp Med 116:827, 1962;.
Hirsch, J.G.; Bernheimer, A.W.; and Weissmann, G.:  Motion Picture Study of the Toxic Action of Streptolysins on Leukocytes , J Exp Med 118:223, 1963;.
Kaplow, L.S.:  Histochemical Procedure for Localizing and Evaluating Leukocyte Alkaline Phosphatase Activity in Smears of Blood and Marrow , Blood 10:1025, 1955;.
Valentine, W.N., and Beck, W.C.:  Biochemical Studies on Leukocytes, I. Phosphatase Activity in Health, Leukocytosis, and Myelocytic Leukemia , J Lab Clin Med 38:39, 1951;.
Peacock, A. C.; Brecher, G.; and Highsmith, E.M.:  Simplified Procedure for Quantitative Measurement of Alkaline Phospatase in White Blood Cells , Amer J Clin Path 29:80,1958;.
Wachstein, M.:  Alkaline Phosphatase Activity in Normal and Abnormal Human Blood and Bone Marrow , J Lab Clin Med 31:1, 1946;.
Valentine, W.N., et al:  Biochemical Studies in Chronic Myelocytic Leukemia, Polycythemia Vera, and Other Idiopathic Myeloproliferative Disorders , Blood 7:959, 1952;.
Beck, W.S., and Valentine, W.N.:  Biochemical Studies in Leukocytes. II. Phosphatase Activity in Chronic Lymphocytic Leukemia, Acute Leukemia and Miscellaneous Hematological Conditions , J Lab Clin Med 38:245, 1951;.
Valentine, W.N., et al:  Relationship of Leukocyte Alkaline Phosphatase to "Stress ," to ACTH, and to Adrenal 17-OH-Corticosteroids, J Lab Clin Med 49:723, 1957;.
Unpublished data.
Xefteris, E.. et al:  Leukocyte Alkaline Phosphatase in Busulfan Induced Remissions of Chronic Granulocytic Leukemia , Blood 18:202, 1961;.
Tanaka, K.R.; Valentine, W.N.; and Fredericks, R.E.:  Diseases or Clinical Conditions Associated With Low-Leukocyte Alkaline Phosphatase , New Eng J Med 262:912, 1960;.
Koler, R.D., et al:  Myeloproliferative Diseases. Diagnostic Value of Leukocyte Alkaline Phosphatase Test , Amer J Clin Path 30:295, 1958;.
Beisel, W.R.; Benjamin, N.; and Austen, K.F.:  Absence of Leukocyte Alkaline Phosphatase in Hypophosphatasia , Blood 14:975, 1959;.
King, M.J.; Gillis, E.M.; and Baikie, A.G.:  Alkaline Phosphatase in Mongolism , Lancet 2:1302, 1962;.
Hardin, B., et al:  Studies on Sulfhydryl Content of Human Leukocytes and Erythrocytes , Amer J Med Sci 228:73, 1954;.
Code, C.F.:  Source in Blood of Histamine-Like Constituent , J Physiol 90:349, 1937;.
Code, C.F.:  Histamine-Like Activity of White Blood Cells , J Physiol 90:485, 1937;.
Valentine, W.N., et al:  Relationship of the Basophil to Blood Histamine in Man , Blood 10:154, 1955;.
Graham, H.T., et al:  Distribution of Histamine Among Leukocytes and Platelets , Blood 10:467, 1955;.
Hartmen, W.J.; Clark, W.G.; and Cyr, S.D.:  Histidine Decarboxylase Activity of Basophils From Chronic Myelogenous Leukemic Patients, Origin of Blood Histamine , Proc Soc Exper Biol Med 107:123, 1961;.
Jorpes, E.: Heparin in Treatment of Thrombosis , 2nd ed, London: Oxford University Press, 1946;, pp 59-66.
Ratnoff, O.D.: Bleeding Syndromes , Springfield, Ill: Charles C Thomas, 1960;, pp 111-113.
Riley, J.F.:  Functional Significance of Histamine and Heparin in Tissue Mast Cells , Ann NY Acad Sci 103:151-163 ( (Feb 26) ) 1963;.
Barnhart, M.I., and Riddle, J.M.:  Cellular Localization of Profibrinolysin (Plasminogen) , Blood 21:306, 1963;.
Schultz, J., and Kaminker, K.:  Myeloperoxidase of the Leukocyte of Normal Human Blood, I. Content and Localization , Arch Biochem 96:465-467 ( (March) ) 1962;.
Agner, K.:  Verdoperoxidase , Acta Physiol Scand 2:1, 1941;.
Schultz, J.; Shay, H.; and Gruenstein, M.:  Chemistry of Experimental Chloroma. I. Porphyrins and Peroxidases , Cancer Res 14:157, 1954;.
Baron, D.M., and Roberts, P.M.:  Sodium, Potassium, and Water Content of Isolated Normal Human Leukocytes , J Physiol 165:219, 1963;.
McNary, W.F., Jr.:  Histochemical Demonstration of Trace Metals in Leukocytes , J Histochem Cytochem 8:124, 1960;.
Rigas, D.A.:  Electrolyte, Nitrogen, and Water Content of Human Leukemic Leukocytes: Relation to Cell Maturity , J Lab Clin Med 58:234, 1961;.
Vallee, B.L.:  Biochemistry, Physiology, and Pathology of Zinc , Physiol Rev 39:443, 1959;.
Valentine, W.N.; Tanaka, K.R.; and Fredricks, R.E.:  Studies on Leukocyte Alkaline Phosphatase: Role of Zinc and Magnesium , J Lab Clin Med 55:303, 1960;.
Gibson, J.G. II, et al:  Studies of Zinc Content of Leukocytes in Myelogenous Leukemia , Acta Un Int Cancr 6:1102, 1950;.
Hammerstein, E., and Reichard, P.:  Pyrimidine Nucleosides as Precursors of Pyrimidines in Polynucleotides , J Biol Chem 183:105, 1950;.
Beck, W.S.:  Metabolic Functions of Vitamin B12 , New Eng J Med 266:708. 1962;.
Bertino, J.R., et al:  Studies on Normal and Leukemic Leukocytes. IV. Tetrahydrofolate-Dependent Enzyme Systems and Dihydrofolic Reductase , J Clin Invest 42:1899, 1963;.
Grunberg-Manago, M.:  Enzymatic Synthesis of Nucleic Acids , Ann Rev Biochem 31:301, 1962;.
Craddock, C.G., and Nakai, G.S.:  Leukemic Cell Proliferation as Determined by In Vitro Desoxyribonucleic Acid Synthesis , J Clin Invest 41:360, 1962;.
Scott, J.L.:  Human Leukocyte Metabolism In Vitro. I. Incorporation of Adenine-8-C14 and Formate-C14 Into Nucleic Acids of Leukemic Leukocytes , J Clin Invest 41:67, 1962;.
Gavosto, F.; Maraini, G.; and Pileri, A.:  Nucleic Acids and Protein Metabolism in Acute Leukemic Cells , Blood 16:1555,1960;.
Bianchi, P.A.:  Thymidine Phosphorylation and Deoxyribonucleic Acid Synthesis in Human Leukaemic Cells , Biochim Biophys Acta 55:547-549 ( (April 2) ) 1962;.
Silber, R.; Gabrio, B.W.; and Huennekens, F.M.:  Enzymatic Synthesis of Thymidylate by Leukocytes , Clin Res 10:207, 1962;.
Silber, R.:  Feedback Inhibition of Deoxyribonucleotide Interconversion in Human Leukocytes , J Clin Invest 43:1248, 1964;.
Smith, L.H., Jr.; Baker, F.A.; and Sullivan, M.:  Pyrimidine Metabolism in Man. II. Studies of Leukemic Cells , Blood 15:360, 1960;.
Bresnick, E., and Karajala, R.J.:  End-Product Inhibition of Thymidine Kinase Activity in Normal and Leukemic Human Leukocytes , Cancer Res 24:841, 1964;.
Frenster, J.H.; Best, W.R.; and Winzler, R.J.:  Metabolism of Human Leukocytes In Vitro. V. Inhibition by Human Serum of Formate and Glycine Incorporation , Proc Soc Exper Biol Med 98:887, 1958;.
Perry, S., and Marsh, J.C.:  Uptake of Tritiated Thymidine by Leukemic Cells: Effect of Various Leukocyte Preparations , Proc Soc Exp Biol Med 115:51, 1964;.
Craddock, C.G.:  Physiology of Granulocytic Cells in Normal and Leukemic States , Amer J Med 28:711, 1960;.
Walker, R.I., and Fowler, I.:  Culture In Vitro of Human Peripheral Blood Leukocytes After Granulocyte Removal , Clin Res 12:233, 1964;.
Marsh, J.C., and Perry, S.:  Thymidine Catabolism by Normal and Leukemic Human Leukocytes , J Clin Invest 43:267, 1964;.
Marsh, J.C., and Perry, S.:  Reduction of Thymine by Human Leukocytes , Arch Biochem Biophys 104:146, 1964;.
Rubini, J.R.:  Implications of Thymidine Phosphorylase in Tissues , Clin Res 12:230, 1964;.
Bessis, M.:  Use of Replacement Transfusion in Diseases Other Than Hemolytic Disease of Newborn , Blood 4:324, 1949;.
Bierman, H.R., et al: " Influence of Cellular Fractions of Whole Blood on Course of Acute Lymphocytic Leukemia ," in The Leukemias , J. Rebuck, ed., NY: Academic Pres, 1957;, p 301.
" Cures" for Leukemia , editorial, Brit Med J 1:129 ( (Jan 18) ) 1964;.
Bierman, H.R., et al:  Studies on Cross-Circulation in Man. I. Methods and Clinical Changes , Blood 6:487, 1951;.
Perry, S., and Moxley, J.: Unpublished data.
Swenseid, M.E.; Bethell, F.H.; and Bird, O.D.:  Concentration of Folic Acid in Leukocytes , Cancer Res 11:864, 1951;.
Huennekens, F.M., et al:  Antimetabolites in Chemotherapy of Leukemia , Exp Cell Res 9:441, 1963;.
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CME Course for:


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To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
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NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
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