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Table of Contents
Vol. 14, Suppl. 1, 2005
Issue release date: July 2005
Section title: Review
Open Access Gateway
Med Princ Pract 2005;14:2–14

Megaloblastosis: From Morphos to Molecules

Das K.C.a · Das M.b · Mohanty D.b · Jadaon M.M.a · Gupta A.a · Marouf R.a · Easow S.K.a
aHematology Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait; bInstitute of Immunohematology, Mumbai, India
email Corresponding Author

Dr. K.C. Das

Hematology Unit, Department of Pathology, Faculty of Medicine, Kuwait University

PO Box 24923, 13110 Safat (Kuwait)

Tel. +965 531 9476, Fax +965 533 8905



  1. Chanarin I: The Megaloblastic Anaemia, ed 3. Oxford, Blackwell Scientific Publications, 1990, pp 315–331.
  2. Wills L: Treatment of pernicious anaemia of pregnancy and ‘tropical anaemia’ with special reference to yeast extract as a curative agent. Br Med J 1931;1:1059–1064.

    External Resources

  3. Wills L: Treatment of pernicious anaemia, nutritional macrocytic anaemia and tropical sprue. Blood 1948;3:36–56.

    External Resources

  4. Chatterjea JB: Nutritional megaloblastic anaemia in tropical zones. Proc 11th Congr Int Soc Hematol, Sidney, 1966, pp 120–132.
  5. Das KC: Nutritional megaloblastic anaemia. Proc Symp Nutr Anemias, Plenary Sess 2, Meet Asian Pacific Div, Int Soc Hematol, Melbourne, 1971, pp 11–13.
  6. Herbert V: The five possible causes of all nutrient deficiency. Aust NZ J Med 1972;1:69–72.

    External Resources

  7. Das KC, Herbert V: Vitamin B12-folate interrelations. Clin Haematol 1976;5:997–725.
  8. Herbert V: The Megaloblastic Anemias, ed 1. New York, Grune and Stratton, 1959, p 1.
  9. Lee RG: Megaloblastic anemias: Disorders of impaired DNA synthesis; in Lee RG, Foester J, Lukens J, Parakevas JP, Rodgers GM (eds): Wintrobe’s Clinical Hematology, ed 10. Baltimore, Williams & Wilkins, 1999, pp 941–978.
  10. Das KC, Hoffbrand AV: Lymphocyte transformation in megaloblastic anaemias. Morphology and DNA synthesis. Br J Haematol 1970;19:459–468.
  11. Das KC, Herbert V: The lymphocyte as a marker of past nutritional status. Persistence of abnormal lymphocyte deoxyuridine (dU) suppression test and chromosomes in patients with past deficiency of folate and vitamin B12. Br J Haematol 1978;38:219–223.
  12. Metz J, Kelly A, Swett VC, Waxman S, Herbert V: Deranged DNA synthesis by bone marrow from vitamin B12-deficient humans. Br J Haematol 1968;14:575–592.
  13. Mohanty D, Das KC: Effect of folate deficiency on the reproductive organs of female Rhesus monkeys: A cytomorphological and cytokinetic study. J Nutr 1982;112:1505–1576.
  14. Johnson EM, Nelson MM, Monie IN: The composition of folate-deficient diet for rats. Anat Rec 1963;146:215.
  15. Dacie JV, Lewis SM: Practical Haematology, ed 8. London, Churchill Livingstone, 1995, pp 49–143.
  16. Das KC, Herbert V: In vitro DNA synthesis by megaloblastic bone marrow: Effect of folates and cobalamins on thymidine incorporation and de novo thymidylate synthesis. Am J Hematol 1989;31:11–20.
  17. Das KC, Manusselis C, Herbert V: In vitro DNA synthesis by bone marrow cells and PHA-stimulated lymphocytes. Suppression by non radioactive thymidine of the incorporation of 3H-deoxyuridine into DNA: Enhancement of incorporation when inadequate vitamin B12 and folate is corrected. Br J Haematol 1980;44:51–63.
  18. Das KC, Garewal G, Mohanty D: Derangement of DNA synthesis in erythroleukemia. Normal deoxyuridine suppression and impaired thymidine incorporation in bone marrow culture. Acta Haematol 1980;64:121–134.
  19. Das KC, Mohanty D, Garewal G: Cytogenetics in nutritional megaloblastic anaemia: Prolonged persistence of chromosomal abnormalities in lymphocytes after remission. Acta Haematol 1986;76:146–154.
  20. Sambrook J, Fritsch EF, Maniatis J: Molecular Cloning: A Laboratory Manual. New York, Cold Spring Harbor Laboratory Press, 1989, pp 1–25.
  21. Murray K: The acid extraction of histones from calf thymus deoxyribonucleoprotein. J Mol Biol 1966;15:409–419.
  22. Das KC, Kaufman RP, Gay H: Autoradiographic evidence of synthesis of an arginine-rich histone during spermatogenesis in Drosophila melanogaster. Nature 1964;204:1008–1009.
  23. Tidwell T, Allfrey VF, Mirsky AE: The methylation of histone during regeneration of the liver. J Biol Chem 1968;243:707–715.
  24. Gershey FL, Halett GW, Vidali G, Allfrey VG: Chemical studies on histone methylation. Evidence for the occurrence of 3-methyl-histidine in avian erythrocyte histone fraction. J Biol Chem 1969;244:4871–4877.
  25. Longo DL, Herbert V: Radioassay for serum and red cell folate. J Lab Clin Med 1976;87:138–151.
  26. Das KC, Manusselis, Herbert V: Determination of vitamin B12 (cobalamin) in serum and erythrocytes by radioassay and of holo-transcobalamin II ( holo-TC-II) and holo-haptocorrin (holo-TC1 and III) in serum by adsorbing holo-TC-II on microfine silica. J Nutr Biochem 1991;2:455–463.
  27. Kiossoglou, KA, Mitus WJ, Dameshek W: Chromosomal aberrations in pernicious anemia. Study of three cases before and after therapy. Blood 1965;5:662–682.

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  28. Heath CW: Cytogenetic observations in vitamin B12 and folate deficiency. Blood 1966;27:800–815.
  29. Das KC: Nutritional megaloblastosis. Symp Nutr Anaemias. Proc Second Congr Asian Pacific Div, Int Soc Haematol, New Delhi, 1976, pp 14–15.
  30. Hoffbrand AV, Pegg AE: Base composition of normal and megaloblastic bone marrow DNA. Nat New Biol 1972;235:187–188.
  31. Khobta A, Carlo-Stella C, Capranico G: Specific histone patterns and acetylase/deacetylase activity at the breakpoint-cluster region of the human MLL gene. Cancer Res 2004;64:2656–2662.
  32. Zhao J: Coordination of DNA synthesis and histone gene expression during normal cell cycle progression and after DNA damage. Cell Cycle 2004;3:695–697.
  33. Norbury CJ, Zhivolovsky B: DNA damage- induced apoptosis. Oncogene 2004;23:2797–2808.
  34. Wang C, Fu M, Pestell RG: Histone acetylation/deacetylation as a regulator of cell cycle gene expression. Methods Mol Biol 2004;241:207–216.
  35. McLaughlin F, La Thangue NB: Histone deacetylase inhibitors open new doors in cancer therapy. Biochem Pharmacol 2004;68:1139–1144.
  36. Ingram CF, Davidoff AN, Marais F, Sherman GG, Mendelow BV: Evaluation of DNA analysis for evidence of apoptosis in megaloblastic anaemia. Br J Haematol 1997;96:576–583.
  37. Koury MJ, Price JO, Hicks GG: Apoptosis in megaloblastic anemia occurs during DNA synthesis p53-independent, nucleoside-reversible mechanism. Blood 2000;96:3249–3255.
  38. Gu L, Wu J, Qiu L, Jennings CD, Li GM: Involvement of DNA mismatch repair infolate deficiency-induced apoptosis small star, filled. J Nutr Biochem 2002;13:355–363.
  39. Li GM, Presnell SR, Gu I: Folate deficiency, mismatch repair-independent apoptosis and human disease. J Nutr Biochem 2003;14:568–575.
  40. Das KC, Easow SK, Jadaon M, Das M, Mohanty D: The development of megaloblastosis is a species-restricted phenomenon. 9th Annu Health Sci Poster Conf, Kuwait, April 19–21, 2004, p 284.