Biology of erythropoietin

  • Graham Molineux
Part of the Milestones in Drug Therapy MDT book series (MDT)


Recombinant Human Erythropoietin Erythropoietin Gene Throid Cell Thropoietin Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Davis JM, Arakawa T, Strickland TW, Yphantis DA (1987) Characterization of recombinant human erythropoietin produced in Chinese hamster ovary cells. Biochemistry 26: 2633–2638PubMedGoogle Scholar
  2. 2.
    Law ML, Cai GY, Lin FK, Wei Q, Huang SZ, Hartz JH, Morse H, Lin CH, Jones C, Kao FT (1986) Chromosomal assignment of the human erythropoietin gene and its DNA polymorphism. Proc Natl Acad Sci USA 83: 6920–6924PubMedGoogle Scholar
  3. 3.
    D’Andrea AD, Lodish HF, Wong GG (1989) Expression cloning of the murine erythropoietin receptor. Cell 57: 277–285Google Scholar
  4. 4.
    Noguchi CT, Bae KS, Chin K, Wada Y, Schechter AN, Hankins WD (1991) Cloning of the human erythropoietin receptor gene. Blood 78: 2548–2556PubMedGoogle Scholar
  5. 5.
    Maouche L, Tournamille C, Hattab C, Boffa G, Cartron JP, Chretien S (1991) Cloning of the gene encoding the human erythropoietin receptor. Blood 78: 2557–2563PubMedGoogle Scholar
  6. 6.
    Wagner KF, Katschinski DM, Hasegawa J, Schumacher D, Meller B, Gembruch U, Schramm U, Jelkmann W, Gassmann M, Fandrey J (2001) Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin. Blood 97: 536–542CrossRefPubMedGoogle Scholar
  7. 7.
    Wu H, Liu X, Jaenisch R, Lodish HF (1995) Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 83: 59–67PubMedGoogle Scholar
  8. 8.
    Lin CS, Lim SK, D’Agati V, Costantini F (1996) Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis. Genes Dev 10: 154–164PubMedGoogle Scholar
  9. 9.
    Wu H, Lee SH, Gao J, Liu X, Iruela-Arispe ML (1999) Inactivation of erythropoietin leads to detects in cardiac morphogenesis. Development 126: 3597–3605PubMedGoogle Scholar
  10. 10.
    Yu X, Lin CS, Costantini F, Noguchi CT (2001) The human erythropoietin receptor gene rescues erythropoiesis and developmental defects in the erythropoietin receptor null mouse. Blood 98: 475–477PubMedGoogle Scholar
  11. 11.
    Jelkmann W (1992) Erythropoietin: Structure, control of production, and function. Physiol Rev 72: 449–489PubMedGoogle Scholar
  12. 12.
    Maxwell AP, Lappin TR, Johnston CF, Bridges JM, McGeown MG (1990) Erythropoietin production in kidney tubular cells. Br J Haematol 74: 535–539PubMedGoogle Scholar
  13. 13.
    Lim GB, Jeyaseelan K, Wintour EM (1994) Ontogeny of erythropoietin gene expression in the sheep fetus: effect of dexamethasone at 60 days of gestation. Blood 84: 460–466PubMedGoogle Scholar
  14. 14.
    Eckardt KU (1995) The ontogeny of the biological role and production of erythropoietin. J Perinat Med 23: 19–29PubMedGoogle Scholar
  15. 15.
    Wintour EM, Butkus A, Earnest L, Pompolo S (1996) The erythropoietin gene is expressed strongly in the mammalian mesonephric kidney. Blood 88: 3349–3353PubMedGoogle Scholar
  16. 16.
    Tan CC, Eckardt KU, Firth JD, Ratcliffe PJ (1992) Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia. Am J Physiol 263: F474–F481PubMedGoogle Scholar
  17. 17.
    Masuda S, Okano M, Yamagishi K, Nagao M, Ueda M, Sasaki R (1994) A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes. J Biol Chem 269: 19488–19493PubMedGoogle Scholar
  18. 18.
    Anagnostou A, Lee ES, Kessimian N, Levinson R, Steiner M (1990) Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci USA 87: 5978–5982PubMedGoogle Scholar
  19. 19.
    Conrad KP, Benyo DF, Westerhausen-Larsen A, Miles TM (1996) Expression of erythropoietin by the human placenta. FASEB J 10: 760–768PubMedGoogle Scholar
  20. 20.
    Marti HH, Wenger RH, Rivas LA, Straumann U, Digicaylioglu M, Henn V, Yonekawa Y, Bauer C, Gassmann M (1996) Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci 8: 666–676PubMedGoogle Scholar
  21. 21.
    Stopka T, Zivny JH, Stopkova P, Prchal JF, Prchal JT (1998) Human hematopoietic progenitors express erythropoietin. Blood 91: 3766–3772PubMedGoogle Scholar
  22. 22.
    Maxwell PH, Osmond MK, Pugh CW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJ, Johnson MH, Ratcliffe PJ (1993) Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int 44: 1149–1162PubMedGoogle Scholar
  23. 23.
    Magnanti M, Gandini O, Giuliani L, Gazzaniga P, Marti HH, Gradilone A, Frati L, Agliano AM, Gassmann M (2001) Erythropoietin expression in primary rat Sertoli and peritubular myoid cells. Blood 98: 2872–2874CrossRefPubMedGoogle Scholar
  24. 24.
    Semenza GL, Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12: 5447–5454PubMedGoogle Scholar
  25. 25.
    Pugh CW, Tan CC, Jones RW, Ratcliffe PJ (1991) Functional analysis of an oxygen-regulated transcriptional enhancer lying 3′ to the mouse erythropoietin gene. Proc Natl Acad Sci USA 88: 10553–10557PubMedGoogle Scholar
  26. 26.
    Bunn HF, Poyton RO (1996) Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 76: 839–885PubMedGoogle Scholar
  27. 27.
    Galson DL, Tsuchiya T, Tendler DS, Huang LE, Ren Y, Ogura T, Bunn HF (1995) The orphan receptor hepatic nuclear factor 4 functions as a transcriptional activator for tissue-specific and hypoxia-specific erythropoietin gene expression and is antagonized by EAR3/COUP-TF1. Mol Cell Biol 15: 2135–2144PubMedGoogle Scholar
  28. 28.
    Ebert BL, Bunn HF (1998) Regulation of transcription by hypoxia requires a multiprotein complex that includes hypoxia-inducible factor 1, an adjacent transcription factor, and p300/CREB binding protein. Mol Cell Biol 18: 4089–4096PubMedGoogle Scholar
  29. 29.
    Goldberg MA, Gaut CC, Bunn HF (1991) Erythropoietin mRNA levels are governed by both the rate of gene transcription and post-transcriptional events. Blood 77: 271–277PubMedGoogle Scholar
  30. 30.
    Miranda CE, Scaro JL, Buys MC, Torrejon I, Martin B, Guerra L (1998) Urinary elimination of erythropoietin in patients under treatment with cytostatics drugs. Acta Physiol Pharmacol Ther Latinoam 48: 207–210PubMedGoogle Scholar
  31. 31.
    Chapel S, Veng-Pedersen P, Hohl RJ, Schmidt RL, McGuire EM, Widness JA (2001) Changes in erythropoietin pharmacokinetics following busulfan-induced bone marrow ablation in sheep: Evidence for bone marrow as a major erythropoietin elimination pathway. J Pharmacol Exp Ther 298: 820–824PubMedGoogle Scholar
  32. 32.
    Chapel SH, Veng-Pedersen P, Schmidt RL, Widness JA (2001) Receptor-based model accounts for phlebotomy-induced changes in erythropoietin pharmacokinetics. Exp Hematol 29: 425–431CrossRefPubMedGoogle Scholar
  33. 33.
    Marmont AM (1997) Erythropoietin: Biochemical characteristics, biologic effects, indications and results of use in hematology. Tumori 83: S3–S15PubMedGoogle Scholar
  34. 34.
    Broudy VC, Lin N, Brice M, Nakamoto B, Papayannopoulou T (1991) Erythropoietin receptor characteristics on primary human erythroid cells. Blood 77: 2583–2590PubMedGoogle Scholar
  35. 35.
    Constantinescu SN, Keren T, Socolovsky M, Nam H, Henis YI, Lodish HF (2001) Ligand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain. Proc Natl Acad Sci USA 98: 4379–4384CrossRefPubMedGoogle Scholar
  36. 36.
    Chen C, Sytkowski AJ (2001) Erythropoietin activates two distinct signaling pathways required for the initiation and the elongation of c-myc. J Biol Chem 276: 38518–38526PubMedGoogle Scholar
  37. 37.
    von Lindern M, Parren-van Amelsvoort M, van Dijk T, Deiner E, van den AE, Emst-de Vries S, Willems P, Beug H, Lowenberg B (2000) Protein kinase C alpha controls erythropoietin receptor signaling. J Biol Chem 275: 34719–34727Google Scholar
  38. 38.
    Frank SJ (2002) Receptor dimerization in GH and erythropoietin action — it takes two to tango, but how? Endocrinology 143: 2–10CrossRefPubMedGoogle Scholar
  39. 39.
    Cheung JY, Miller BA (2001) Molecular mechanisms of erythropoietin signaling. Nephron 87: 215–222CrossRefPubMedGoogle Scholar
  40. 40.
    Koury MJ, Bondurant MC (1990) Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science 248: 378–381PubMedGoogle Scholar
  41. 41.
    Koury MJ, Bondurant MC (1990) Control of red cell production: The roles of programmed cell death (apoptosis) and erythropoietin. Transfusion 30: 673–674CrossRefPubMedGoogle Scholar
  42. 42.
    Spivak JL, Pham T, Isaacs M, Hankins WD (1991) Erythropoietin is both a mitogen and a survival factor. Blood 77: 1228–1233PubMedGoogle Scholar
  43. 43.
    Krantz SB (1991) Erythropoietin. Blood 77: 419–434PubMedGoogle Scholar
  44. 44.
    Udupa KB, Reissmann KR (1980) Stimulation of erythroblast formation in suspension cultures of murine marrow by a factor in normal mouse serum, and its relationship to erythropoietin. Exp Hematol 8: 1106–1113PubMedGoogle Scholar
  45. 45.
    Cynshi O, Satoh K, Higuchi M, Imai N, Kawaguchi T, Hirashima K (1990) Effects of recombinant human erythropoietin on anaemic W/Wv and Sl/Sld mice. Br J Haematol 75: 319–324PubMedGoogle Scholar
  46. 46.
    Pharr PN, Hofbauer A, Worthington RE, Longmore GD (2000) Residual erythroid progenitors in W/W mice respond to erythropoietin in the absence of steel factor signals. Int J Hematol 72: 178–185PubMedGoogle Scholar
  47. 47.
    Kapur R, Zhang L (2001) A novel mechanism of cooperation between c-Kit and erythropoietin receptor. Stem cell factor induces the expression of Stat5 and erythropoietin receptor, resulting in efficient proliferation and survival by erythropoietin. J Biol Chem 276: 1099–1106CrossRefPubMedGoogle Scholar
  48. 48.
    Rice L, Ruiz W, Driscoll T, Whitley CE, Tapia R, Hachey DL, Gonzales GF, Alfrey CP (2001) Neocytolysis on descent from altitude: A newly recognized mechanism for the control of red cell mass. Ann Intern Med 134: 652–656PubMedGoogle Scholar
  49. 49.
    Rice L, Alfrey CP (2000) Modulation of red cell mass by neocytolysis in space and on Earth. Pflugers Arch 441: R91–R94PubMedGoogle Scholar
  50. 50.
    Trial J, Rice L, Alfrey CP (2001) Erythropoietin withdrawal alters interactions between young red blood cells, splenic endothelial cells, and macrophages: An in vitro model of neocytolysis. J Investig Med 49: 335–345PubMedGoogle Scholar
  51. 51.
    Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM (1986) Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 2: 1175–1178PubMedGoogle Scholar
  52. 52.
    Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987) Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med 316: 73–78PubMedGoogle Scholar
  53. 53.
    Adamson JW, Eschbach JW (1990) Treatment of the anemia of chronic renal failure with recombinant human erythropoietin. Annu Rev Med 41: 349–360CrossRefPubMedGoogle Scholar
  54. 54.
    Anonymous (1991) Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients. The US Recombinant Human Erythropoietin Predialysis Study Group. Am J Kidney Dis 18: 50–59Google Scholar
  55. 55.
    Chmielewski CM (1995) Case study of the anemic patient: epoetin alfa — focus on erythrokinetics. ANNA J 22: 420–423PubMedGoogle Scholar
  56. 56.
    Beguin Y (1996) Erythropoietin and the anemia of cancer. Acta Clin Belg 51: 36–52PubMedGoogle Scholar
  57. 57.
    Ludwig H, Fritz E (1998) Anemia of cancer patients: Patient selection and patient stratification for epoetin treatment. Semin Oncol 25: 35–38PubMedGoogle Scholar
  58. 58.
    Ludwig H, Fritz E (1998) Anemia in cancer patients. Semin Oncol 25: 2–6PubMedGoogle Scholar
  59. 59.
    Bron D, Meuleman N, Mascaux C (2001) Biological basis of anemia. Semin Oncol 28: 1–6CrossRefPubMedGoogle Scholar
  60. 60.
    Ludwig H, Pecherstorfer M, Leitgeb C, Fritz E (1993) Recombinant human erythropoietin for the treatment of chronic anemia in multiple myeloma and squamous cell carcinoma. Stem Cells 11: 348–355PubMedGoogle Scholar
  61. 61.
    DeGowin RL, Gibson DP (1979) Erythropoietin and the anemia of mice bearing extramedullary tumor. J Lab Clin Med 94: 303–311PubMedGoogle Scholar
  62. 62.
    Zarrabi MH, Lysik R, DiStefano J, Zucker S (1977) The anaemia of chronic disorders: Studies of iron reutilization in the anaemia of experimental malignancy and chronic inflammation. Br J Haematol 35: 647–658PubMedGoogle Scholar
  63. 63.
    Leng HM, Albrecht CF, Kidson SH, Folb PI (1999) Erythropoietin production in anemia associated with experimental cancer. Exp Hematol 27: 806–810CrossRefPubMedGoogle Scholar
  64. 64.
    Fisher JW, Roh BL (1964) Influence of alkylating agents on kidney erythropoietin production. Cancer Res 24: 983–988PubMedGoogle Scholar
  65. 65.
    Magid E, Hansen P (1966) The erythropoietin content of plasma from sheep treated with nitrogen mustard. Scand J Clin Lab Invest 18: 347–352PubMedGoogle Scholar
  66. 66.
    Barcelo AC, Bozzini CE (1982) Erythropoietin formation during hypoxia in mice with impaired responsiveness to erythropoietin induced by irradiation or 5-fluorouracil injection. Experientia 38: 504–505PubMedGoogle Scholar
  67. 67.
    Zucker S, Friedman S, Lysik RM (1974) Bone marrow erythropoiesis in the anemia of infection, inflammation, and malignancy. J Clin Invest 53: 1132–1138PubMedGoogle Scholar
  68. 68.
    Lockner D (1966) Iron absorption and serum erythropoietin concentration in patients with cancer of the uterine cervix. Acta Med Scand 180: 651–655PubMedGoogle Scholar
  69. 69.
    Schreuder WO, Ting WC, Smith S, Jacobs A (1984) Testosterone, erythropoietin and anaemia in patients with disseminated bronchial cancer. Br J Haematol 57: 521–526PubMedGoogle Scholar
  70. 70.
    Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak JL (1990) Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 322: 1689–1692PubMedGoogle Scholar
  71. 71.
    Smith DH, Goldwasser E, Vokes EE (1991) Serum immunoerythropoietin levels in patients with cancer receiving cisplatin-based chemotherapy. Cancer 68: 1101–1105PubMedGoogle Scholar
  72. 72.
    Greendyke RM, Sharma K, Gifford FR (1994) Serum levels of erythropoietin and selected other cytokines in patients with anemia of chronic disease. Am J Clin Pathol 101: 338–341PubMedGoogle Scholar
  73. 73.
    Ponchio L, Beguin Y, Farina G, Pedrazzoli P, Pedrotti C, Poggi G, Rosti V, Bergamaschi G, Battistel V, Cazzola M (1992) Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia. Haematologica 77: 494–501PubMedGoogle Scholar
  74. 74.
    Ozguroglu M, Arun B, Demir G, Demirelli F, Mandel NM, Buyukunal E, Serdengecti S, Berkarda B (2000) Serum erythropoietin level in anemic cancer patients. Med Oncol 17: 29–34PubMedGoogle Scholar
  75. 75.
    Groopman JE, Itri LM (1999) Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst 91: 1616–1634CrossRefPubMedGoogle Scholar
  76. 76.
    Corazza F, Beguin Y, Bergmann P, Andre M, Ferster A, Devalck C, Fondu P, Buyse M, Sariban E (1998) Anemia in children with cancer is associated with decreased erythropoietic activity and not with inadequate erythropoietin production. Blood 92: 1793–1798PubMedGoogle Scholar
  77. 77.
    Itri LM (2002) The use of epoetin alfa in chemotherapy patients: A consistent profile of efficacy and safety. Semin Oncol 29: 81–87PubMedGoogle Scholar
  78. 78.
    Dame C, Bartmann P, Wolber E, Fahnenstich H, Hofmann D, Fandrey J (2000) Erythropoietin gene expression in different areas of the developing human central nervous system. Brain Res. Dev Brain Res 125: 69–74PubMedGoogle Scholar
  79. 79.
    Morishita E, Masuda S, Nagao M, Yasuda Y, Sasaki R (1997) Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 76: 105–116PubMedGoogle Scholar
  80. 80.
    Cerami A (2001) Beyond erythropoiesis: novel applications for recombinant human erythropoietin. Semin Hematol 38: 33–39CrossRefPubMedGoogle Scholar
  81. 81.
    Buemi M, Allegra A, Corica F, Floccari F, D’Avella D, Aloisi C, Calapai G, Iacopino G, Frisina N (2000) Intravenous recombinant erythropoietin does not lead to an increase in cerebrospinal fluid erythropoietin concentration. Nephrol Dial Transplant 15: 422–423PubMedGoogle Scholar
  82. 82.
    Cerami A, Brines ML, Ghezzi P, Cerami CJ (2001) Effects of epoetin alfa on the central nervous system. Semin Oncol 28: 66–70CrossRefPubMedGoogle Scholar
  83. 83.
    Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C, Itri LM, Cerami A (2000) Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 97: 10526–10531CrossRefPubMedGoogle Scholar
  84. 84.
    Shingo T, Sorokan ST, Shimazaki T, Weiss S (2001) Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci 21: 9733–9743PubMedGoogle Scholar
  85. 85.
    Yu X, Shacka JJ, Eells JB, Suarez-Quian C, Przygodzki RM, Beleslin-Cokic B, Lin CS, Nikodem VM, Hempstead B, Flanders KC et al. (2002) Erythropoietin receptor signalling is required for normal brain development. Dev Suppl 129: 505–516Google Scholar
  86. 86.
    Alafaci C, Salpietro F, Grasso G, Sfacteria A, Passalacqua M, Morabito A, Tripodo E, Calapai G, Buemi M, Tomasello F (2000) Effect of recombinant human erythropoietin on cerebral ischemia following experimental subarachnoid hemorrhage. Eur J Pharmacol 406: 219–225CrossRefPubMedGoogle Scholar
  87. 87.
    Grasso G (2001) Neuroprotective effect of recombinant human erythropoietin in experimental subarachnoid hemorrhage. J Neurosurg Sci 45: 7–14PubMedGoogle Scholar
  88. 88.
    Grasso G, Buemi M, Alafaci C, Sfacteria A, Passalacqua M, Sturiale A, Calapai G, De Vico G, Piedimonte G, Salpietro FM et al. (2002) Beneficial effects of systemic administration of recombinant human erythropoietin in rabbits subjected to subarachnoid hemorrhage. Proc Natl Acad Sci USA 99: 5627–5631CrossRefPubMedGoogle Scholar
  89. 89.
    Campana WM, Myers RR (2001) Erythropoietin and erythropoietin receptors in the peripheral nervous system: Changes after nerve injury. FASEB J 15: 1804–1806PubMedGoogle Scholar
  90. 90.
    Kapiteijn K, Koolwijk P, Van Der WR, Helmerhorst F, Kooistra T, Van Hinsbergh VW (2001) Steroids and cytokines in endometrial angiogenesis. Anticancer Res 21: 4231–4242PubMedGoogle Scholar
  91. 91.
    Carlini RG, Reyes AA, Rothstein M (1995) Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int 47: 740–745PubMedGoogle Scholar
  92. 92.
    Barrett JD, Zhang Z, Zhu JH, Lee DB, Ward HJ, Jamgotchian N, Hu MS, Fredal A, Giordani M, Eggena P (1998) Erythropoietin upregulates angiotensin receptors in cultured rat vascular smooth muscle cells. J Hypertens 16: 1749–1757CrossRefPubMedGoogle Scholar
  93. 93.
    Akimoto T, Kusano E, Inaba T, Iimura O, Takahashi H, Ikeda H, Ito C, Ando Y, Ozawa K, Asano Y (2000) Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway. Kidney Int 58: 269–282CrossRefPubMedGoogle Scholar
  94. 94.
    Vaziri ND (2001) Cardiovascular effects of erythropoietin and anemia correction. Curr Opin Nephrol Hypertens 10: 633–637CrossRefPubMedGoogle Scholar
  95. 95.
    Macdougall IC (2001) Role of uremic toxins in exacerbating anemia in renal failure. Kidney Int Suppl 78: S67–S72Google Scholar
  96. 96.
    Macdougall IC, Cooper A (2002) The inflammatory response and epoetin sensitivity. Nephrol Dial Transplant 17: 48–52PubMedGoogle Scholar
  97. 97.
    Voulgarelis M, Kokori SI, Ioannidis JP, Tzioufas AG, Kyriaki D, Moutsopoulos HM (2000) Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin. Ann Rheum Dis 59: 217–222CrossRefPubMedGoogle Scholar
  98. 98.
    Tzioufas AG, Kokori SI, Petrovas CI, Moutsopoulos HM (1997) Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus: correlation with anemia. Arthritis Rheum 40: 2212–2216PubMedGoogle Scholar
  99. 99.
    Sipsas NV, Kokori SI, Ioannidis JP, Kyriaki D, Tzioufas AG, Kordossis T (1999) Circulating autoantibodies to erythropoietin are associated with human immunodeficiency virus type 1-related anemia. J Infect Dis 180: 2044–2047CrossRefPubMedGoogle Scholar
  100. 100.
    Kuramochi S, Ikawa Y, Todokoro K (1990) Characterization of murine erythropoietin receptor genes. J Mol Biol 216: 567–575CrossRefPubMedGoogle Scholar
  101. 101.
    Maeda Y, Sakaguchi M, Naiki Y, Sumimoto Y, Miyatake JI, Matsuda M, Hasegawa H, Kanamaru A (2001) Possible involvement of soluble erythropoietin receptor in resistance to erythropoietin in patients with renal anemia. Am J Nephrol 21: 426CrossRefPubMedGoogle Scholar
  102. 102.
    Hercberg S, Preziosi P, Galan P (2001) Iron deficiency in Europe. Public Health Nutr 4: 537–545PubMedGoogle Scholar
  103. 103.
    Bayoumeu F, Subiran-Buisset C, Baka NE, Legagneur H, Monnier-Barbarino P, Laxenaire MC (2002) Iron therapy in iron deficiency anemia in pregnancy: Intravenous route versus oral route. Am J Obstet Gynecol 186: 518–522CrossRefPubMedGoogle Scholar
  104. 104.
    Stoves J, Inglis H, Newstead CG (2001) A randomized study of oral versus intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin. Nephrol Dial Transplant 16: 967–974PubMedGoogle Scholar
  105. 105.
    Wen D, Boissel JP, Tracy TE, Gruninger RH, Mulcahy LS, Czelusniak J, Goodman M, Bunn HF (1993) Erythropoietin structure-function relationships: High degree of sequence homology among mammals. Blood 82: 1507–1516PubMedGoogle Scholar
  106. 106.
    David RB, Blom AK, Sjaastad OV, Harbitz I (2001) The porcine erythropoietin gene: cDNA sequence, genomic sequence and expression analyses in piglets. Domest Anim Endocrinol 20: 137–147CrossRefPubMedGoogle Scholar
  107. 107.
    Arai M, Darman J, Lewis A, Yamamoto JK, Darmen J (2000) The use of human hematopoietic growth factors (rhGM-CSF and rhEPO) as a supportive therapy for FIV-infected cats. Vet Immunol Immunopathol 77: 71–92PubMedGoogle Scholar
  108. 108.
    Manire CA, Rhinehart HL (2000) Use of human recombinant erythropoietin for the treatment of non-regenerative anemia in a rough-toothed dolphin (Steno bredanensis). J Zoo Wildl Med 31: 157–163PubMedGoogle Scholar
  109. 109.
    McKeever KH (1996) Erythropoietin: a new form of blood doping in horses. In: J Wade (ed.): Proceedings of the 11th International Conference of Racing Analysts and Veterinarians. R and W Press, Newmarket, UK, 79–84Google Scholar
  110. 110.
    Catania MA, Marciano MC, Parisi A, Sturiale A, Buemi M, Grasso G, Squadrito F, Caputi AP, Calapai G (2002) Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils. Eur J Pharmacol 437: 147–150CrossRefPubMedGoogle Scholar
  111. 111.
    Grasso G, Passalacqua M, Sfacteria A, Conti A, Morabito A, Mazzullo G, De VG, Buemi M, Macri B, Tomasello F (2002) Does administration of recombinant human erythropoietin attenuate the increase of S-100 protein observed in cerebrospinal fluid after experimental subarachnoid hemorrhage? J Neurosurg 96: 565–570PubMedGoogle Scholar
  112. 112.
    Chapel SH, Veng-Pedersen P, Schmidt RL, Widness JA (2000) A pharmacodynamic analysis of erythropoietin-stimulated reticulocyte response in phlebotomized sheep. J Pharmacol Exp Ther 295: 346–351PubMedGoogle Scholar
  113. 113.
    Piercy RJ, Swardson CJ, Hinchcliff KW (1998) Erythroid hypoplasia and anemia following administration of recombinant human erythropoietin to two horses. J Am Vet Med Assoc 212: 244–247PubMedGoogle Scholar
  114. 114.
    Sifakis S, Angelakis E, Vardaki E, Koumantaki Y, Matalliotakis I, Koumantakis E (2001) Erythropoietin in the treatment of iron deficiency anemia during pregnancy. Gynecol Obstet Invest 51: 150–156CrossRefPubMedGoogle Scholar
  115. 115.
    Eckardt KU (2001) After 15 years of success — perspectives of erythropoietin therapy. Nephrol Dial Transplant 16: 1745–1749PubMedGoogle Scholar
  116. 116.
    Oster W, Herrmann F, Gamm H, Zeile G, Lindemann A, Muller G, Brune T, Kraemer HP, Mertelsmann R (1990) Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration. J Clin Oncol 8: 956–962PubMedGoogle Scholar
  117. 117.
    Abels R (1993) Erythropoietin for anaemia in cancer patients. Eur J Cancer 29A: S2–S8PubMedGoogle Scholar
  118. 118.
    Silverberg DS, Wexler D, Sheps D, Blum M, Keren G, Baruch R, Schwartz D, Yachnin T, Steinbruch S, Shapira I et al. (2001) The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: A randomized controlled study. J Am Coll Cardiol 37: 1775–1780CrossRefPubMedGoogle Scholar
  119. 119.
    Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, Leibovitch E, Brosh D, Laniado S, Schwartz D, Yachnin T et al. (2000) The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol 35: 1737–1744CrossRefPubMedGoogle Scholar
  120. 120.
    Rogiers P, Zhang H, Leeman M, Nagler J, Neels H, Melot C, Vincent JL (1997) Erythropoietin response is blunted in critically ill patients. Intensive Care Med 23: 159–162CrossRefPubMedGoogle Scholar
  121. 121.
    Corwin HL (2001) Anemia in the critically ill: The role of erythropoietin. Semin Hematol 38: 24–32CrossRefPubMedGoogle Scholar
  122. 122.
    Olivieri NF (1995) Erythropoietin therapy in inherited anemias (thalassemia and sickle cell disease). Int J Ped Hematol/Oncol 2: 105–116Google Scholar
  123. 123.
    al Khatti A, Umemura T, Clow J, Abels RI, Vance J, Papayannopoulou T, Stamatoyannopoulos G (1988) Erythropoietin stimulates F-reticulocyte formation in sickle cell anemia. Trans Assoc Am Physicians 101: 54–61Google Scholar
  124. 124.
    Rachmilewitz EA, Goldfarb A, Dover G (1991) Administration of erythropoietin to patients with beta-thalassemia intermedia: A preliminary trial. Blood 78: 1145–1147PubMedGoogle Scholar
  125. 125.
    Rund D, Rachmilewitz E (2000) New trends in the treatment of beta-thalassemia. Crit Rev Oncol Hematol 33: 105–118PubMedGoogle Scholar
  126. 126.
    Shaskey DJ, Green GA (2000) Sports haematology. Sports Med 29: 27–38CrossRefPubMedGoogle Scholar
  127. 127.
    Paul RE, Doerig C, Brey PT (2000) Erythropoiesis and molecular mechanisms for sexual determination in malaria parasites. IBUMB Life 49: 245–248Google Scholar
  128. 128.
    Fischl M, Galpin JE, Levine JD, Groopman JE, Henry DH, Kennedy P, Miles S, Robbins W, Starrett B, Zalusky R (1990) Recombinant human erythropoietin for patients with AIDS treated with zidovudine. N Engl J Med 322: 1488–1493PubMedGoogle Scholar
  129. 129.
    Henry DH, Beall GN, Benson CA, Carey J, Cone LA, Eron LJ, Fiala M, Fischl MA, Gabin SJ, Gottlieb MS (1992) Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials. Ann Intern Med 117: 739–748PubMedGoogle Scholar
  130. 130.
    Sheiban E, Gershon H (1993) Recognition and sequestration of young and old erythrocytes from young and elderly human donors: In vitro studies. J Lab Clin Med 121: 493–501PubMedGoogle Scholar
  131. 131.
    Carbonell-Estrany X, Figueras-Aloy J (2001) Anaemia of prematurity: Treatment with erythropoietin. Early Hum Dev 65: S63–S67PubMedGoogle Scholar
  132. 132.
    Cerami A, Brines M, Ghezzi P, Cerami C, Itri LM (2002) Neuroprotective properties of epoetin alfa. Nephrol Dial Transplant 17Suppl 1: 8–12PubMedGoogle Scholar
  133. 133.
    Wolcott DL, Marsh JT, La Rue A, Carr C, Nissenson AR (1989) Recombinant human erythropoietin treatment may improve quality of life and cognitive function in chronic hemodialysis patients. Am J Kidney Dis 14: 478–485PubMedGoogle Scholar
  134. 134.
    Nissenson AR (1992) Epoetin and cognitive function. Am J Kidney Dis 20: 21–24PubMedGoogle Scholar
  135. 135.
    Vaziri ND (2000) Vascular effects of erythropoietin and anemia correction. Semin Nephrol 20: 356–363PubMedGoogle Scholar
  136. 136.
    Laupacis A, Fergusson D (1998) Erythropoietin to minimize perioperative blood transfusion: A systematic review of randomized trials. The International Study of Peri-operative Transfusion (ISPOT) Investigators. Transfus Med 8: 309–317CrossRefPubMedGoogle Scholar
  137. 137.
    Goodnough LT, Skikne B, Brugnara C (2000) Erythropoietin, iron, and erythropoiesis. Blood 96: 823–833PubMedGoogle Scholar
  138. 138.
    Birgegard G, Sandhagen B (2001) Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood cells. Scand J Clin Lab Invest 61: 337–340PubMedGoogle Scholar
  139. 139.
    Westenfelder C, Baranowski RL (2000) Erythropoietin stimulates proliferation of human renal carcinoma cells. Kidney Int 58: 647–657CrossRefPubMedGoogle Scholar
  140. 140.
    Acs G, Acs P, Beckwith SM, Pitts RL, Clements E, Wong K, Verma A (2001) Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Res 61: 3561–3565PubMedGoogle Scholar
  141. 141.
    Stone P (2002) The measurement, causes and effective management of cancer-related fatigue. Int J Palliat Nurs 8: 120–128PubMedGoogle Scholar
  142. 142.
    Casadevall N (1995) Cellular mechanism of resistance to erythropoietin. Nephrol Dial Transplant 10Suppl 6: 27–30PubMedGoogle Scholar
  143. 143.
    Horl WH (1999) Is there a role for adjuvant therapy in patients being treated with epoetin? Nephrol Dial Transplant 14Suppl 2: 50–60PubMedGoogle Scholar
  144. 144.
    Besarab A, Frinak S, Yee J (1999) An indistinct balance: The safety and efficacy of parenteral iron therapy. J Am Soc Nephrol 10: 2029–2043PubMedGoogle Scholar
  145. 145.
    Allen DA, Breen C, Yaqoob MM, Macdougall IC (1999) Inhibition of CFU-E colony formation in uremic patients with inflammatory disease: role of IFN-gamma and TNF-alpha. J Investig Med 47: 204–211PubMedGoogle Scholar
  146. 146.
    Le Meur Y, Lorgeot V, Comte L, Szelag JC, Aldigier JC, Leroux-Robert C, Praloran V (2001) Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: Relationship with erythropoietin requirements. Am J Kidney Dis 38: 510–517PubMedGoogle Scholar
  147. 147.
    Gallucci MT, Lubrano R, Meloni C, Morosetti M, Manca DV, Scoppi P, Palombo G, Castello MA, Casciani CU (1999) Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients. Clin Nephrol 52: 239–245PubMedGoogle Scholar
  148. 148.
    Rosenlof K, Fyhrquist F, Tenhunen R (1990) Erythropoietin, aluminium, and anaemia in patients on haemodialysis. Lancet 335: 247–249CrossRefPubMedGoogle Scholar
  149. 149.
    Glaspy J, Cavill I (1999) Role of iron in optimizing responses of anemic cancer patients to erythropoietin. Oncology (Huntingt) 13: 461–473Google Scholar
  150. 150.
    Gadducci A, Cosio S, Fanucchi A, Genazzani AR (2001) Malnutrition and cachexia in ovarian cancer patients: Pathophysiology and management. Anticancer Res 21: 2941–2947PubMedGoogle Scholar
  151. 151.
    Del Mastro L, Gennari A, Donati S (1999) Chemotherapy of non-small-cell lung cancer: Role of erythropoietin in the management of anemia. Ann Oncol 10Suppl 5: S91–S94PubMedGoogle Scholar
  152. 152.
    Tzioufas AG, Kokori SI, Petrovas CI, Moutsopoulos HM (1997) Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus: Correlation with anemia. Arthritis Rheum 40: 2212–2216PubMedGoogle Scholar
  153. 153.
    Vannucchi AM, Bosi A, Grossi A, Guidi S, Saccardi R, Bacci P, Lombardini L, Rossi-Ferrini P (1993) The use of erythropoietin in the treatment of post-bone marrow transplantation anemia. Int J Artif Organs 16Suppl 5: 8–12PubMedGoogle Scholar
  154. 154.
    Andriani A, Bibas M, Callea V, De Renzo A, Chiurazzi F, Marceno R, Musto P, Rotoli B (1996) Autoimmune hemolytic anemia during alpha interferon treatment in nine patients with hematological diseases. Haematologica 81: 258–260PubMedGoogle Scholar
  155. 155.
    Jose Gomez MI, Gonzalez DD, Mellado Pena MJ, Garcia Miguel MJ, Garcia Rodriguez MC, Cilleruelo Ortega MJ, Martinez ZR, Fernandez CP, Martin FP (1992) Long-term follow-up study of 35 children with AIDS treated with zidovudine (AZT). (Spanish). An Esp Pediatr 36: 98–108PubMedGoogle Scholar
  156. 156.
    Bertero MT, Caligaris-Cappio F (1997) Anemia of chronic disorders in systemic autoimmune diseases. Haematologica 82: 375–381PubMedGoogle Scholar
  157. 157.
    Fisch P, Handgretinger R, Schaefer HE (2000) Pure red cell aplasia. Br J Haematol 111: 1010–1022CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2003

Authors and Affiliations

  • Graham Molineux
    • 1
  1. 1.Amgen Inc.Thousand OaksUSA

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