Skip to main content
SpringerLink
Log in

Vitamin B12 and Folic Acid: Clinical and Pathophysiological Considerations

  • Chapter
Nutritional Elements and Clinical Biochemistry

Abstract

The last decade has brought new understanding to the pathophysiological mechanisms and biochemical interrelationships of vitamin B12 and folic acid and their role in DNA synthesis. The evolution of facts concerned with these vitamins continues to unfold in the meticulous fashion begun over 50 years ago (Kass, 1978) when it was recognized that pernicious anemia was a deficiency disease. Even such a momentous contribution at that time could not foretell the present promise to understand basic cellular processes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Allen, R. H., 1975, Human vitamin B12 transport proteins, in “Progress in Hematology” (E. B. Brown, ed.), pp. 57–84, Grune and Stratton, New York.

    Google Scholar 

  • Allen, R. H., and Majerus, P. W., 1972a, Isolation of vitamin B12-binding proteins using affinity chromatography. I. Preparation and properties of vitamin B12 Sepharose, J. Biol. Chem., 247:7695.

    Google Scholar 

  • Allen, R. H., and Majerus, P. W., 1972b, Isolation of vitamin B12-binding proteins using affinity chromatography. II. Purification and properties of a human granulocyte vitamin B12-binding protein, J. Biol. Chem., 247:7702.

    Google Scholar 

  • Allen, R. H., and Majerus, P. W., 1972c, Isolation of vitamin B12-binding proteins using affinity chromatography. III. Purification and properties of human plasma transcobalamin II, J. Biol. Chem., 247:7709.

    Google Scholar 

  • Allen, R. H., and Mehlman, C. S., 1973, Isolation of gastric vitamin B12 binding proteins using affinity chromatography. I. Purification and properties of human intrinsic factor, J. Biol. Chem., 248:3660.

    Google Scholar 

  • Alperin, J. B., Haggard, M. E., and Haynie, T. P., 1970, A study of vitamin B12 requirements in a patient with pernicious anemia and thyrotoxicosis; evidence of an increased need for vitamin B12 in the presence of hyperthyroidism, Blood, 36:632.

    Google Scholar 

  • Amess, J. A. L., Rees, G. M., Burman, J. F., Nancekieviel, D. G., and Mollin, D. L., 1978, Megalobastic haemopoiesis in patients receiving nitrous oxide, Lancet, 2:339.

    Google Scholar 

  • Ampola, M. G., Mahoney, M. J., Nakamura, E., and Tanaka, K., 1975, Prenatal therapy of a patient with vitamin-B12 responsive methylmalonic acidemia, New Engl. J. Med., 293:313.

    Google Scholar 

  • Angier, R. B., Boothe, J. H., Hutchings, B. L., Mowat, J. H., Semb, J., Stokstad, E. L. R., Subbarow, Y., Waller, C. W., Cosulich, D. B., Fahrenbach, M. J., Hultquist, M. E., Kuh, E., Northey, E. H., Seeger, D. R., Sickels, J. P., and Smith, J. M., Jr., 1945, Synthesis of a compound identical with the L. casei factor isolated from liver, Science, 102:227.

    Google Scholar 

  • Ardeman, S., and Chanarin, I., 1965, Steoids and Addisonian pernicious anemia, New Engl. J. Med., 273:1352.

    Google Scholar 

  • Ardeman, S., and Chanarin, I., 1966, Gastric intrinsic factor after partial gastrectomy, Gut, 7:217.

    Google Scholar 

  • Ardeman, S., Chanarin, I., Krafchik, B., and Singer, W., 1966, Addisonian pernicious anemia and intrinsic factor antibodies in thyroid disorders, Quart. J. Med., 35:421.

    Google Scholar 

  • Arvanitakis, C., Holmes, F. F., and Hearne, E., III, 1979, A possible association of pernicious anemia with neoplasia, Oncology, 36:127.

    Google Scholar 

  • Astaldi, G., 1960, Differentiation, proliferation and maturation of haematopoietic cells studied in tissue culture, in “Ciba Foundation Symposium on Haemopoiesis: Cell Production and its Regulation” (G. E. W. Wolstenholme and M. O’Connor, eds.), p. 60, Little, Brown and Co., Boston.

    Google Scholar 

  • Badenoch, J., Bedford, P. D., and Evans, J. R., 1955, Massive diverticulosis of the small intestine with steatorrhoea and megaloblastic anemia, Quart. J. Med., 24:321.

    Google Scholar 

  • Baker, S. J., 1972, Vitamin B12 and tropical sprue, Br. J. Haematol., 23 (Supplement):135.

    Google Scholar 

  • Baker, S. J., and DeMaeyer, E. M., 1979, Nutritional anemia: its understanding and control with special reference to the work of the World Health Organization, Amer. J. Clin. Nutr., 32:368.

    Google Scholar 

  • Baker, S. J., and Mathan, V. I., 1968, Syndrome of tropical sprue in South India, Amer. J. Clin. Nutr., 21:984.

    Google Scholar 

  • Baker, S. J., and Mathan, V. I., 1971, “Tropical Sprue and Megaloblastic Anaemia”, p. 189, Wellcome Trust, Churchill, London.

    Google Scholar 

  • Barker, H. A., 1967, Biochemical functions of corrinoid compounds, Biochem. J., 105:1.

    Google Scholar 

  • Barker, H. A., Weissbach, H., and Smyth, R. D., 1958, A coenzyme containing pseudovitamin B12, Proc. Natl. Acad. Science, U. S. A., 44:1093.

    Google Scholar 

  • Bar-Shany, S., and Herbert, V., 1967, Transplacentally acquired antibody to intrinsic factor with vitamin B12 deficiency, Blood, 30:777.

    Google Scholar 

  • Bash, R. I., and Rosner, F., 1979, Pernicious anemia in young black women, Arch. Intern. Med., 139:829.

    Google Scholar 

  • Baugh, C. M., Krumdieck, C. L., Baker, H. J., and Butterworth, C. E., Jr., 1971, Studies on the absorption and metabolism of folic acid. I. Folate absorption in the dog after exposure of isolated intestinal segments to synthetic pterolypolyglutamates of various chain lengths, J. Clin. Invest., 50:2009.

    Google Scholar 

  • Beck, W. S., 1977a, General considerations of megaloblastic anemias, in “Hematology” (W. J. Williams, E. Beutler, A. J. Erslev, and R. W. Rundles, eds.), Second Edition, pp. 300–307, McGraw-Hill, New York.

    Google Scholar 

  • Beck, W. S., 1977b, Vitamin B12 deficiency, in “Hematology” (W. J. Williams, E. Beutler, A. J. Erslev, and R. W. Rundles, eds.), Second Edition, pp. 307–334, McGraw-Hill, New York.

    Google Scholar 

  • Beck, W. S., 1977c, Folic acid deficiency, in “Hematology” (W. J. Williams, E. Beutler, A. J. Erslev, and R. W. Rundles, eds.), Second Edition, pp. 334–355, McGraw-Hill, New York.

    Google Scholar 

  • Begley, J. A., and Trachtenberg, A., 1979, An assay for intrinsic factor based on blocking of the R binder of gastric juice by cobamide, Blood, 53:788.

    Google Scholar 

  • Berk, L., Castle, W. B., Welch, A. D., Heinle, R. W., Anker, R., and Epstein, M., 1948, Observations on the etiologic relationship of achylia gastrica to pernicious anemia. X. Activity of vitamin B12 as food (extrinsic) factor, New Engl. J. Med., 239:911.

    Google Scholar 

  • Bernier, G., and Hines, J. D., 1967, Immunologic heterogeneity of autoantibodies in patients with pernicious anemia, New Engl. J. Med., 277:1386.

    Google Scholar 

  • Bertino, J. R., ed., 1971, Folate Antagonists as Chemotherapeutic Agents, Annals New York Acad. Science, 186:1.

    Google Scholar 

  • Bertino, J. R., Nixon, P. F., and Nahas, A., 1977, Mechanism of uptake of folate monoglutamates and their metabolism, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 178–187, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Bhat, P., Shantakumari, S., Rajan, D., Mathan, V. I., Kapadia, C. R., Swarnabai, C., and Baker, S. J., 1972, Bacterial flora of the gastrointestinal tract in southern Indian control subjects and patients with tropical sprue, Gastroenterology, 62:11.

    Google Scholar 

  • Bianchi, A., Chipman, D. W., Dreskin, A., and Rosenzweig, N. S., 1970, Nutritional folic acid deficiency with megaloblastic changes in the small bowel epithelium, New Engl. J. Med., 282:859.

    Google Scholar 

  • Blackburn, E. K., Callender, S. T., Dacie, J. V., Doll, R., Girdwood, R. H., Mollin, D. L., Saracci, R., Stafford, J. L., Thompson, R. B., Varadi, S., and Wetherley-Mein, G., 1968, Possible association between pernicious anaemia and leukemia: a prospective study of 1,625 patients with a note on the very high incidence of stomach cancer, Internat. J. Cancer, 3:163.

    Google Scholar 

  • Blakley, R. L., 1977, Folic acid biochemistry: present status and future direction, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 3–24, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D.C.

    Google Scholar 

  • Boger, W. P., Bayne, G. M., Wright, L. D., and Beck, G. D., 1957, Differential serum vitamin B12 concentrations in mothers and infants, New Engl. J. Med., 256:1085.

    Google Scholar 

  • Booth, C. C., and Mollin, D. L., 1959, The site of absorption of vitamin B12 in man, Lancet, 1:18.

    Google Scholar 

  • Booth, C. C., Tabaqchali, S., and Mollin, D. L., 1968, Comparison of stagnant-loop syndrome with chronic tropical sprue, Amer. J. Clin. Nutr., 21:1097.

    Google Scholar 

  • Branda, R. F., Moldow, C. F., MacArthur, J. R., Wintrobe, M. M., Anthony, B. K., and Jacob, H. S., 1978, Folate-induced remission in aplastic anemia with familial defect of cellular folate uptake, New Engl. J. Med., 298:469.

    Google Scholar 

  • Brandt, L. J., Bernstein, L. H., and Wagle, A., 1977, Production of vitamin B12 analogues in patients with small-bowel bacterial overgrowth, Ann. Intern. Med., 87:546.

    Google Scholar 

  • Brody, E. A., Estrén, S., and Herbert, V., 1966, Coexistent pernicious anemia and malabsorption in four patients: including one whose malabsorption disappeared with vitamin B12 therapy, Ann. Intern. Med., 64:1246.

    Google Scholar 

  • Buchanan, J. M., 1964, The function of vitamin B12 and folic acid coenzymes in mammalian cells, Medicine, 43:697.

    Google Scholar 

  • Buchanan, J. M., Elford, H. L., Loughlin, R. E., McDougall, B. M., and Rosenthal, S., 1964, The role of vitamin B12 in methyl transfer to homocysteine, Ann. New York Acad. Science, 112:756.

    Google Scholar 

  • Burger, R. L., Mehlman, C. S., and Allen, R. H., 1975, Human plasma R-type vitamin B12-binding proteins. I. Isolation and characterization of transcobalamin I, transcobalamin III and the normal granulocyte vitamin B12-binding protein, J. Biol. Chem., 250:7700.

    Google Scholar 

  • Burman, J. F., Mollin, D. L., Sourial, N. A., and Sladden, R. A., 1979, Inherited lack of transcobalamin II in serum and megaloblastic anemia: a further patient, Br. J. Haematol., 43:27.

    Google Scholar 

  • Burnier, E., Zwahlen, A., and Cruchard, A., 1976, Nonmalignant monoclonal immunoglobulinemia, pernicious anemia and gastric carcinoma. A model of immunologic dysfunction. Report of two cases and review of the literature, Amer. J. Med., 60:1019.

    Google Scholar 

  • Butterworth C. E., Baugh, C. M., and Krumdieck, C., 1969, A study of folate absorption and metabolism in man utilizing carbon-14-labeled polyglutamates synthesized by the solid phase method, J. Clin. Invest., 48:1131.

    Google Scholar 

  • Butterworth, C. E., Jr., Newman, A. J., and Krumdieck, C. L., 1974, Tropical sprue: a consideration of possible etiologic mechanisms with emphasis on pteroylpolyglutamate metabolism, Trans. Amer. Clin. Climatol. Assoc., 86:11.

    Google Scholar 

  • Carmel, R., 1975, Extreme elevation of serum transcobalamin I in patients with metastatic cancer, New Engl. J. Med., 292:282.

    Google Scholar 

  • Carmel, R., 1979, Macrocytosis, mild anemia and delay in the diagnosis of pernicious anemia, Arch. Intern. Med., 139:47.

    Google Scholar 

  • Carmel, R., and Herbert, V., 1967, Correctable intestinal defect of vitamin B12 absorption in pernicious anemia, Ann. Intern. Med., 67:1201.

    Google Scholar 

  • Carmel, R., and Herbert, V., 1969, Deficiency of vitamin B12 binding alpha globulin in two brothers, Blood, 33:1.

    Google Scholar 

  • Carmel, R., and Johnson, C. S., 1978, Racial patterns in pernicious anemia. Early age at onset and increased frequency of intrinsic factor antibody in black women, New Engl. J. Med., 298:647.

    Google Scholar 

  • Carmel, R., and Schurafa, M., 1977, Circulating immunoglobulin-transcobalamin I complex in patients with elevated serum vitamin B12 levels, Fed. Proc., 36:1121 (Abstract).

    Google Scholar 

  • Castle, W. B., 1929, Observations on etiologic relationship of achylia gastrica to pernicious anemia. I. Effect of administration to patients with pernicious anemia of contents of normal human stomach recovered after ingestion of beef muscle, Amer. J. Med. Science, 178:748.

    Google Scholar 

  • Castle, W. B., 1961, The Gordon Wilson Lecture, a century of curiosity about pernicious anemia, Trans. Amer. Clin. Climatol. Assoc., 73:53.

    Google Scholar 

  • Castle, W. B., and Townsend, W. C., 1929, Observations on etiologic relationship of achylia gastrica to pernicious anemia. II. Effect of administration to patients with pernicious anemia of beef muscle after incubation with normal human gastric juice, Amer. J. Med. Science, 178:764.

    Google Scholar 

  • Castle, W. B., Townsend, W. C., and Heath, C. W., 1930, Observations on etiologic relationship of achylia gastrica to pernicious anemia. III. Nature of reaction between normal human gastric juice and beef muscle leading to clinical improvement and increased blood formation similar to effect of liver feeding, Amer. J. Med. Science, 180:305.

    Google Scholar 

  • Castle, W. B., Heath, C. W., and Strauss, M., 1931, Observations on the etiologic relationship of achylia gastrica to pernicious anemia. IV. A biologic assay of the gastric secretion of patients with pernicious anemia having free hydrochloric acid and that of patients without anemia or with hypochromic anemia having no free hydrochloric acid, and of the role of intestinal impermeability to hematopoietic substances in pernicious anemia, Amer. J. Med. Science, 182:741.

    Google Scholar 

  • Castrén, O. M., and Rossi, R. R., 1970, Effect of oral contraceptives on serum folic acid content, J. Obstet. Gynaecol. Br. Commonw., 77:548.

    Google Scholar 

  • Chanarin, I., 1969, “The Megaloblastic Anaemias”, F. A. Davis, Co., Philadelphia, Blackwell Scientific Publications, Great Britain.

    Google Scholar 

  • Chanarin, I., 1970, Folate deficiency in the myeloproliferative disorders, Amer. J. Clin. Nutr., 23:855.

    Google Scholar 

  • Chanarin, I., 1972, Pernicious anaemia as an autoimmune disease, Br. J. Haematol., 23 (Supplement):101.

    Google Scholar 

  • Chanarin, I., and Perry, J., 1968, Metabolism of 5-methyltetrahydrofolate in pernicious anemia, Br. J. Haematol., 14:297.

    Google Scholar 

  • Chanarin, I., and Perry, J., 1977, Mechanisms in the production of megaloblastic anemia, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 156–168, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Chanarin, I., Perry, J., and Lumb, M., 1974, The biochemical lesion in vitamin B12 deficiency in man, Lancet, 1:1251.

    Google Scholar 

  • Chanarin, I., Rothman, D., and Berry, V., 1965, Iron deficiency and its relation to folic acid status in pregnancy. Results of a clinical trial, Br. Med. J., 1:480.

    Google Scholar 

  • Charache, P., Hodkinson, B. A., Lambiotte, B., and McIntyre, P. A., 1968, Genetic and auto-immune features of pernicious anemia. II. Effect of transplacental transfer of antibody to intrinsic factor, Johns Hopkins Med. J., 122:184.

    Google Scholar 

  • Christensen, J. M., Hippe, E., Olesen, H., Rye, M., Haber, E., Lee, L., and Thomsen, J., 1973, Purification of human intrinsic factor by affinity chromatography, Biochim. Biophys. Acta, 303:319.

    Google Scholar 

  • Colman, N., and Herbert, V., 1974, Evidence for granulocyte-related and liver-related folate binders in human serum, and renal glomerular filtration of folate binder, Clin. Res., 22:700 A (Abstract).

    Google Scholar 

  • Cook, G. C., Morgan, J. O., and Hoffbrand, A. V., 1974, Impairment of folate absorption by systemic bacterial infections, Lancet, 2:1416.

    Google Scholar 

  • Cooper, B. A., 1976, Megalobastic anaemia and disorders affecting utilization of vitamin B12 and folate in childhood, in “Clinics in Haematology, Megaloblastic Anaemia” (A. V. Hoffbrand, ed.), pp. 631–659, W. B. Saunders Co. Ltd., London.

    Google Scholar 

  • Cooper, B. A., 1977, Physiology of absorption of monoglutamyl folates from the gastrointestinal tract, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 188–197, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Cooper, B. A., and Castle, W. B., 1960, Sequential mechanisms in the enhanced absorption of vitamin B12 by intrinsic factor in the rat, J. Clin. Invest., 39:199.

    Google Scholar 

  • Cooper, B. A., and White, J. J., 1968, Absence of intrinsic factor from human portal plasma during 57Co B12 absorption in man, Br. J. Haematol., 14:73.

    Google Scholar 

  • Cooper, B. A., and Whitehead, V. M., 1978, Evidence that some patients with pernicious anemia are not recognized by radiodilution assay for cobalamin in serum, New Engl. J. Med., 299:816.

    Google Scholar 

  • Cooper, B. A., Cantlie, G. S. D., and Brunton, L., 1970, The case for folic acid supplements during pregnancy, Amer. J. Clin. Nutr., 23:848.

    Google Scholar 

  • Cooper, B. T., Holmes, G. K. T., and Cooke, W. T., 1978, Coeliac disease and immunological disorders, Br. Med. J., 1:537.

    Google Scholar 

  • Corcino, J., Waxman, S., and Herbert, V., 1970, Mechanism of triamterene-induced megaloblastosis, Ann. Intern. Med., 73:419.

    Google Scholar 

  • Corcino, J. J., Zalusky, R., Greenberg, M., and Herbert, V., 1971, Coexistence of pernicious anemia with chronic myeloid leukemia; an experiment of nature involving B12 metabolism, Br. J. Haematol., 20:511.

    Google Scholar 

  • Corcino, J. J., Coll, G., and Klipstein, F. A., 1975, Pteroylglutamic acid malabsorption in tropical sprue, Blood, 45:577.

    Google Scholar 

  • Corcino, J. J., Reisenauer, A. M., and Halsted, C. H., 1976, Jejunal perfusion of simple and conjugated folates in tropical sprue, J. Clin. Invest., 58:298.

    Google Scholar 

  • Cox, E. V., and White, A. M., 1962, Methylmalonic acid excretion: an index of vitamin B12 deficiency, Lancet, 2:853.

    Google Scholar 

  • Cox, E. V., Robertson-Smith, D., Small, M., and White, A. M., 1968, The excretion of propionate and acetate in vitamin B12 deficiency, Clin. Science, 35:123.

    Google Scholar 

  • da Costa, M., and Rothenberg, S. P., 1974, Appearance of a folate binder in leucocytes and serum of women who are pregnant or taking oral contraceptives, J. Lab. Clin. Med., 83:207.

    Google Scholar 

  • Dallman, P. R., 1974, Iron, vitamin E, and folate in the preterm infant, J. Pediatr., 95:742.

    Google Scholar 

  • Darby, W. J., Bridgforth, W. B., LeBrocquy, J., Clark, S. L. Jr., DeOlivera, J. D., Kevany, J., McGanity, W. J., and Perez, C., 1958, Vitamin B12 requirement of man, Amer. J. Med., 25:726.

    Google Scholar 

  • Das, K., and Herbert, V., 1976, Vitamin B12-folate interrelations, in “Clinics in Haematology, Megaloblastic Anaemia” (A. V. Hoffbrand, ed.), pp. 697–725, W. B. Saunders Co., Ltd., London.

    Google Scholar 

  • Davidson, G. P., and Townley, R. R. W., 1977, Structural and functional abnormalities of the small intestine due to nutritional folic acid deficiency in infancy, J. Pediat., 90:590.

    Google Scholar 

  • Davis, R. E., Stenhouse, N. S., and Woodliff, H. J., 1969, Serum folate levels in pregnancy, Med. J. Austral., 1:52.

    Google Scholar 

  • Day, P. L., Mims, V., Totter, J. R., Stokstad, E. L. R., Hutchings, B. L., and Sloane, N. H., 1945, Successful treatment of vitamin M deficiency in monkey with highly purified Lactobacillus casei factor, J. Biol. Chem., 157:423.

    Google Scholar 

  • Deacon, R., Perry, J., Lumb, M., Chanarin, I., Mintz, B., Halsey, M. J., and Nunn, J. F., 1978, Selective inactivation of vitamin B12 in rats by nitrous oxide, Lancet, 2:1023.

    Google Scholar 

  • Deller, D. J., and Witts, L. J., 1962, Changes in the blood after partial gastrectomy with special reference to vitamin B12. I. Serum vitamin B12, haemoglobin, serum iron and bone marrow, Quart. J. Med., 31:71.

    Google Scholar 

  • Deller, D. J., Richards, W. C. D., and Witts, L. J., 1962, Changes in the blood after partial gastrectomy with special reference to vitamin B12. II. The cause of the fall in serum vitamin B12 Quart. J. Med., 31:89.

    Google Scholar 

  • Dellipiani, A. W., Samson, R. R., and Girdwood, R. H., 1968, The uptake of vitamin B12 by E. coli. Possible significance in relation to the blind loop syndrome, Amer. J. Digest. Dis., 13:718.

    Google Scholar 

  • De Oliviera, J. E. D., 1979, The stone that the builders rejected, Am. J. Clin. Nutr., 32:1566.

    Google Scholar 

  • Deren, J. J., Arora, B., Toskes, P. P., Hansell, J., and Sibinga, M. S., 1973, Malabsorption of crystalline vitamin B12 in cystic fibrosis, New Engl. J. Med., 288:949.

    Google Scholar 

  • Doig, A., Girdwood, R. H., Duthie, J. J. R., and Knox, J. D. E., 1957, Response of megaloblastic anemia to prednisolone, Lancet, 2:966.

    Google Scholar 

  • Donaldson, R. M., Jr., 1968, Significance of small bowel bacteria, Am. J. Clin. Nutr., 21:1088.

    Google Scholar 

  • Donaldson, R. M., Jr., 1978, “Serum B12” and the diagnosis of cobalamin deficiency, New Engl. J. Med., 299:827.

    Google Scholar 

  • Doscherholmen, A., and Swaim, W. R., 1973, Impaired assimilation of egg Co57 vitamin B12 in patients with hypochlorhydria and achlorhydria and after gastric resection, Gastroenterology, 64:913.

    Google Scholar 

  • Doscherholmen, A., Hagen, P. S., and Olin, L., 1959, Delay of absorption of radiolabeled cyanocobalamin in the intestinal wall in the presence of intrinsic factor, J. Lab. Clin. Med., 54:434.

    Google Scholar 

  • Druskin, N. S., Waller, M. H., and Bonagura, L., 1962, Anticonvulsant associated megaloblastic anemia. Response to 25 micorogm of folic acid administered by mouth daily, New Engl. J. Med., 267:483.

    Google Scholar 

  • Eastwood, D. W., Green, C. D., Lamdin, M. A., and Gardner, R., 1963, Effect of nitrous oxide on the white cell count in leukemia, New Engl. J. Med., 268:297.

    Google Scholar 

  • Editorial, 1978, Nitrous Oxide and the bone-marrow, Lancet, 2:613.

    Google Scholar 

  • Engel, A. G., and Stickney, J. M., 1972, Pernicious anemia and polycythemia vera in one patient, Arch. Intern. Med., 109:168.

    Google Scholar 

  • Erbe, R. W., 1975, Inborn errors of folate metabolism, second of two parts, New Engl. J. Med., 293:807.

    Google Scholar 

  • Farrell, M., Farrell, A., Murphy, C., and Dundon, S., 1979, Pernicious anemia in an eleven-year-old male, Acta Haematol., 61:175.

    Google Scholar 

  • Finch, C. A., Coleman, D. H., Motulsky, A. G., Donohue, D. M., and Reiff, R. H., 1956, Erythrokinetics in pernicious anemia, Blood, 11:807.

    Google Scholar 

  • Fink, B. R., Shepard, T. H., and Blandau, R. J., 1967, Teratogenic activity of nitrous oxide, Nature, 214:146.

    Google Scholar 

  • Finkler, A. E., and Hall, C. A., 1967, Nature of the relationship between vitamin B12 binding and cell uptake, Arch. Biochem. and Biophys., 120:79.

    Google Scholar 

  • Fisher, J. M., and Taylor, K. B., 1965, A comparison of autoimmune phenomena in pernicious anemia and chronic atrophic gastritis, New Engl. J. Med., 272:499.

    Google Scholar 

  • Franklin, J. L., and Rosenberg, I. H., 1973, Impaired folic acid absorption in inflammatory bowel disease; effects of salicylazosulfapyridine (azulfidine), Gastroenterology, 64:517.

    Google Scholar 

  • Fraser, K. J., 1969, Multiple myeloma and pernicious anemia, Med. J. Austral., 1:298.

    Google Scholar 

  • Frater-Schröder, M., Hitzig, W. H., and Bütler, R., 1979, Studies on transcobalamin (TC). 1. Detection of TC II isoproteins in normal serum, Blood, 53:193.

    Google Scholar 

  • Frei, E., III, Jaffe, N., Tattersall, M. H. N., Pitman, S., and Parker, L., 1975, New approaches to cancer chemotherapy with methotrexate, New Engl. J. Med., 292:846.

    Google Scholar 

  • Frenkel, E. P., 1973, Abnormal fatty acid metabolism in peripheral nerves of patients with pernicious anemia, J. Clin. Invest., 52:1237.

    Google Scholar 

  • Frenkel, E. P., and Kitchens, R. L., 1977, Applicability of an enzymatic quantitation of methylmalonic, propionic and acetic acids in normal and megaloblastic states, Blood, 49:125.

    Google Scholar 

  • Friedman, P. A., Shia, M. A., and Wallace, J. K., 1977, A saturable high affinity binding site for transcobalamin II-vitamin B12 complexes in human placental membrane preparations, J. Clin. Invest., 59:51.

    Google Scholar 

  • Gardner, F. H., 1956, Observations on the cytology of gastric epithelium in tropical sprue, J. Lab. Clin. Med., 47:529.

    Google Scholar 

  • Gardner, F. H., 1958, Tropical sprue, New Engl. J. Med., 258:791, 835.

    Google Scholar 

  • Garrido-Pinson, G. C., Turner, M. D., Crookston, J. H., Samloff, I. M., Miller, L. L., and Segal, H. L., 1966, Studies of human intrinsic factor auto-antibodies, J. Immunol., 97:897.

    Google Scholar 

  • Gerson, C. D., Cohen, N., Hepner, G. W., Brown, N., Herbert, V., and Janowitz, H. D., 1971, Folic acid absorption in man: enhancing effect of glucose, Gastroenterology, 61:224.

    Google Scholar 

  • Glass, G. B. J., 1974, “Gastric Intrinsic Factor and Other Vitamin B12 Binders, Biochemistry, Physiology and Relation to Vitamin B12 Metabolism”, George Thieme, Stuttgart.

    Google Scholar 

  • Gilliam, J. N., and Cox, A. J., 1973, Epidermal changes in vitamin B12 deficiency, Arch. Dermatol., 107:231.

    Google Scholar 

  • Gimpert, E., Jakob, M., and Hitzig, W. H., 1975, Vitamin B12 transport in blood. Congenital deficiency of transcobalamin II, Blood, 45:71.

    Google Scholar 

  • Goetsch, C., 1962, An evaluation of aminopterin as an abortifacient;. Am. J. Obstet. Gynecol., 83:1474.

    Google Scholar 

  • Goldberg, L. S., Barnett, E. V., and Desai, R., 1967, Effect of transplacental transfer of antibody to intrinsic factor, Pediatrics, 40:851.

    Google Scholar 

  • Gompertz, D., 1971, The metabolic effects of an impaired methylmalonyl CoA mutase, in “The cobalamins” (H. R. V. Arnstein, and R. J. Wrighton, eds.), p. 101, Churchill Livingstone, Edinburgh.

    Google Scholar 

  • Gorbach, S. L., Banwell, J. G., Jacobs, B., Chatterjee, B. D., Mitra, R., Sen, N. N., and Mazumber, D. N. G., 1970, Tropical sprue and malnutrition in West Bengal. I. Intestinal microflora and absorption, Am J. Clin. Nutr., 23:1545.

    Google Scholar 

  • Gottlieb, C., Lau, K.-S., Wasserman, L. R., and Herbert, V., 1965, Rapid charcoal assay for intrinsic factor (IF), gastric juice, unsaturated B12 binding capacity, antibody to IF, and serum unsaturated B12 binding capacity, Blood, 25:875.

    Google Scholar 

  • Gräsbeck, R., 1959, Influence of some specific group inhibitors on rat intrinsic factor, Acta Physiol. Scand., 45:116.

    Google Scholar 

  • Gräsbeck, R., 1960, Physiology and pathology of vitamin B12 absorption, distribution and excretion, Advan. Clin. Chem., 3:299.

    Google Scholar 

  • Gräsbeck, R., 1969, Intrinsic factor and the other vitamin B12 transport proteins, in “Progress in Hematology”, Vol. VI (E. B. Brown and C. V. Moore, eds.), pp. 233–260, Grune and Stratton, New York.

    Google Scholar 

  • Gräsbeck, R., 1975, Absorption and transport of vitamin B12, Br. J. Haematol., 31 (Supplement):103.

    Google Scholar 

  • Gräsbeck, R., Gordin, R., Kantero, I., and Kuhlbäck, B., 1960, Selective vitamin B12 malabsorption and proteinuria in young people, Acta Med. Scand., 167:289.

    Google Scholar 

  • Gräsbeck, R., Simons, K., and Sinkkonen, I., 1966, Isolation of intrinsic factor and its probable degradation product, as their vitamin B12 complexes, from human gastric juice, Biochem. Biophys. Acta, 127:47.

    Google Scholar 

  • Greipp, P. R., 1978, Hyperpigmentation syndromes (Diffuse hypermelanosis), Arch. Intern. Med., 138:356.

    Google Scholar 

  • Guest, J. R., Friedman, S., Woods, D. D., and Smith, E. L., 1962, A methyl analogue of cobamide coenzyme in relation to methionine synthesis by bacteria, Nature, 195:340.

    Google Scholar 

  • Guest, J. R., Foster, M. A., and Woods, D. D., 1964, Methyl derivatives of folic acid as intermediates in the methylation of homocysteine by Escherichia coli, Biochem. J., 92:488.

    Google Scholar 

  • Gutteridge, J. M. C., and Wright, E. B., 1970, A simple and rapid thin layer technique for the detection of methylmalonic acid in urine, Clin. Chim. Acta, 27:289.

    Google Scholar 

  • Hakami, N., Neiman, P. E., Canellos, G. P., and Lazerson, J., 1971, Neonatal megaloblastic anemia due to inherited transcobalamin II deficiency in two siblings, New Engl. J. Med., 285:1163.

    Google Scholar 

  • Hall, C. A., 1971, Vitamin B12-binding proteins of man, Ann. Intern. Med., 75:297.

    Google Scholar 

  • Hall, C. A., 1973, Congenital disorders of vitamin B12 transport and their contribution to concepts, Gastroenterology, 65:684.

    Google Scholar 

  • Hall, C. A., and Finkler, A. E., 1969, Vitamin B12-binding protein in polycythemia vera plasma, J. Lab. Clin. Med., 73:60.

    Google Scholar 

  • Hall, C. A., Hitzig, W. H., Green, P. D., and Begley, J. A., 1979, Transport of therapeutic cyanocobalamin in the congenital deficiency of transcobalamin (TC II), Blood, 53:251.

    Google Scholar 

  • Halpern, R., Halpern, B. C., Stea, B., Dunlap, A., Conklin, K., Clark, B., Ashe, H., Sperling, L., Halpern, L. A., Hardy, D., and Smith, R. A., 1977, Pterin-6-aldehyde. A cancer cell catabolite: identification and application in diagnosis and treatment of human cancer, Proc. Soc. Nat. Acad. Sci. U. S. A., 74:587.

    Google Scholar 

  • Halsted, C. H., Griggs, R. C., and Harris, J. W., 1967, The effect of alcoholism on the absorption of folic acid (3H-PGA) evaluated by plasma levels and urine excretion, J. Lab. Clin. Med., 69:116.

    Google Scholar 

  • Halsted, C. H., Robles, E. A., and Mezey, E., 1971, Decreased jejunal uptake of labeled folic acid (3-PGA) in alcoholic patients: roles of alcohol and nutrition, New Engl. J. Med., 285:701.

    Google Scholar 

  • Halsted, C. H., Robles, E. A., and Mezey, E., 1973, Intestinal malabsorption in folate-deficient alcoholics, Gastroenterology, 64:526.

    Google Scholar 

  • Harker, L. A., and Finch, C. A., 1969, Thrombokinetics in man, J. Clin. Invest., 48:963.

    Google Scholar 

  • Hart, R. J., Jr., and McCurdy, P. R., 1971, Pernicious anemia in Negroes. Ann. Intern. Med., 74:448.

    Google Scholar 

  • Haurani, F. I., 1973, Vitamin B12 and the megaloblastic development, Science, 182:78.

    Google Scholar 

  • Heinrich, H. C., 1964, Metabolic basis of the diagnosis and therapy of vitamin B12 deficiency, Seminar. Hematol., 1:199.

    Google Scholar 

  • Helman, N., 1973, Macrocytosis and cigarette smoking, Ann. Intern. Med., 79:287.

    Google Scholar 

  • Hepner, G. W., Booth, C. C., Cowan, J., Hoffbrand, A. V., and Mollin, D. L., 1968, Absorption of crystalline folic acid in man, Lancet, 2:302.

    Google Scholar 

  • Herbert, V., 1959, Mechanism of intrinsic factor action in everted sacs of rat small intestine, J. Clin. Invest., 38:102.

    Google Scholar 

  • Herbert, V., 1962a, Experimental nutritional folate deficiency in man, Trans. Assoc. Am. Physicians, 75:307.

    Google Scholar 

  • Herbert, V., 1962b, Minimal daily adult folate requirement, Arch. Intern. Med., 110:649.

    Google Scholar 

  • Herbert, V., 1963, A palatable diet for producing experimental folate deficiency in man, Am. J. Clin. Nutr., 12:17.

    Google Scholar 

  • Herbert, V., 1968, Megaloblastic anemia as a problem in world health, Am. J. Clin. Nutr., 21:1115.

    Google Scholar 

  • Herbert, V., 1970a, Introduction to the “nutritional anemias”, Seminar. Hematol., 2:2.

    Google Scholar 

  • Herbert, V., 1970b, Symposium, Folic acid deficiency. I. Introduction, Am. J. Clin. Nutr., 23:841.

    Google Scholar 

  • Herbert, V., 1972a, Metformin and B12 malabsorption, Ann. Intern. Med., 76:140.

    Google Scholar 

  • Herbert, V., 1972b, Malabsorption syndrome secondary to B12 deficiency, in “Hematopoietic and Gastrointestinal Investigations with Radionuclides” (J. A. Gilson, W. M. Smoak, and M. B. Weinstein, eds.), pp. 287–293, C. C. Thomas, Springfield, Ill.

    Google Scholar 

  • Herbert, V., 1972c, Detection of malabsorption of vitamin B12 due to gastric or intestinal dysfunction, Seminar. Nucl. Med., 2:220.

    Google Scholar 

  • Herbert, V., 1973, The five possible causes of all nutrient deficiency; illustrated by deficiencies of vitamin B12 and folic acid, Am. J. Clin. Nutr., 26:77.

    Google Scholar 

  • Herbert, V., 1975, Drugs effective in megaloblastic anemias. Vitamin B12 and folic acid, in “The Pharmacological Basis of Therapeutics” Fifth Edition (L. S. Goodman and A. Gilman, eds.), pp. 1324–1349, MacMillan Co., New York.

    Google Scholar 

  • Herbert, V., 1979, Megaloblastic anemias, in “Cecil, Textbook of Medicine” (P. B. Beeson, W. McDermott, Jr., and J. B. Wyngaarden, eds.), pp. 1719–1729, W. B. Saunders, Co., Philadelphia.

    Google Scholar 

  • Herbert, V., and Castle, W. B., 1961, Divalent cation and pH dependence of rat intrinsic factor action in everted sacs and mucosal homogenates of rat small intestine, J. Clin. Invest., 40:1978.

    Google Scholar 

  • Herbert, V., and Das, K. C., 1976, The role of vitamin B12 and folic acid in hemato- and other cell-poiesis, in “Vitamins and Hormones, Advances in Research and Applications”, Vol. 34, (P. L. Munson, E. Diczfalusy, J. Glover, and R. E. Olson, eds.), pp. 1–30, Academic Press, New York.

    Google Scholar 

  • Herbert, V., and Jacob, E., 1974, Destruction of vitamin B12 by ascorbic acid, J. Am. Med. Assoc., 230:241.

    Google Scholar 

  • Herbert, V., and Zalusky, R., 1962, Interrelation of vitamin B12 and folic acid metabolism: folic acid clearance studies, J. Clin. Invest., 41:1263.

    Google Scholar 

  • Herbert, V., Zalusky, R., and Davidson, C. S., 1963, Correlation of folate deficiency with alcoholism and associated macrocytosis, anemia, and liver disease, Ann. Intern. Med., 58:977.

    Google Scholar 

  • Herbert, V., Streiff, R. R., and Sullivan, L. W., 1964, Notes on vitamin B12 absorption: autoimmunity and childhood pernicious anemia; relation of intrinsic factor to blood group substance, Medicine, 43:679.

    Google Scholar 

  • Herbert, V., Tisman, G., Go, L. T., and Brenner, L., 1973, The dU suppression test using 125I-UdR to define biochemical megaloblastosis, Br. J. Haematol., 24:713.

    Google Scholar 

  • Hermos, J. A., Adams, W. H., Lui, Y. K., Sullivan, L. W., and Trier, J. S., 1972, Mucosa of the small intestine in folate-deficient alcoholics, Ann. Intern. Med., 76:957.

    Google Scholar 

  • Heyssel, R. M., Bozian, R. C., Darby, W. J., and Bell, M. C., 1966, Vitamin B12 turnover in man: the assimilation of vitamin B12 from natural foodstuff by man and estimates of minimal daily dietary requirements, Am. J. Clin. Nutr., 18:176.

    Google Scholar 

  • Hibbard, E. D., and Smithells, R. W., 1965, Folic acid metabolism and human embryopathy, Lancet, 1:1254.

    Google Scholar 

  • Higginbotham, M. C., Sweetman, L., and Nyhan, W. L., 1978, A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities of a vitamin B12-deficient breast-fed infant of a strict vegetarian, New Engl. J. Med., 299:317.

    Google Scholar 

  • Hild, D., 1969, Folate losses from the skin in exfoliative dermatitis, Arch. Intern. Med., 123:51.

    Google Scholar 

  • Hines, J. D., 1966, Megaloblastic anemia in adult vegan, Am. J. Clin. Nutr., 19:260.

    Google Scholar 

  • Hines, J. D., Hoffbrand, A. V., and Mollin, D. L., 1967, The hematologic complications following partial gastrectomy. A study of 292 patients, Am. J. Med., 43:555.

    Google Scholar 

  • Hoedemaker, P. J., Abels, J., Wachters, J. J., Arends, A., and Nieweg, H. O., 1964, Investigations about the site of production of Castle’s gastric intrinsic factor, Lab. Invest., 13:1394.

    Google Scholar 

  • Hoffbrand, A. V., 1970, Folate deficiency in premature infants, Arch. Dis. Child., 45:441.

    Google Scholar 

  • Hoffbrand, A. V., 1975, Synthesis and breakdown of natural folates (folate polyglutamates), in “Progress in Hematology”, Vol. IX, (E. B. Brown, ed.), pp. 85–105, Grune and Stratton, New York.

    Google Scholar 

  • Hoffbrand, A. V., Chanarin, I., Kremenchuzky, S., Szur, L., Waters, A. H., and Mollin, D. L., 1968, Megaloblastic anaemia in myelosclerosis, Quart. J. Med., 37:493.

    Google Scholar 

  • Hoffbrand, A. V., Tripp, E., Lavoié, A., 1977, Folate polyglutamate synthesis and breakdown in human cells, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 110–121, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Hooper, D. C., Alpers, D. H., Burger, R. L., Mehlman, C. S., and Allen, R. H., 1973, Characterization of ileal vitamin B12 binding using homogeneous human and hog intrinsic factors, J. Clin. Invest., 52:3074.

    Google Scholar 

  • Hoppner, K., Lampi, B., and Smith, D. C., 1977, Data on folacin activity in foods: availability, applications, and limitations, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 69–81, Food and Nutrition Board, National Research Council, Washington, D. C.

    Google Scholar 

  • Horton, M. A., and Oliver, R. T. D., 1976, HLA and pernicious anemia, New Engl. J. Med., 294:396.

    Google Scholar 

  • Huennekens, F. M., 1966, Biochemical functions and interrelationships of folic acid and vitamin B12, in “Progress in Hematology” Vol. 5, (E. B. Brown, and C. V. Moore, eds.), pp. 83–104, Grune and Stratton, New York.

    Google Scholar 

  • Huennekens, F. M., DiGirolamo, P. M., Fujii, K., Jacobsen, D. W., and Vitols, K. S., 1976, B12-methionine synthetase as a potential target for cancer chemotherapy, Adv. Enzyme Regul., 14:187.

    Google Scholar 

  • Huntsman, R. G., 1974, Treatment of sickle-cell disease, Trans. Roy. Soc. Trop., Med. Hygiene, 68:80.

    Google Scholar 

  • Imerslund, O., 1960, Idiopathic chronic megaloblastic anemia in children, Acta Pediat., 49 (Supplement 119):1.

    Google Scholar 

  • Ingeberg, S., and Stoffersen, E., 1979, Platelet dysfunction in patients with B12 deficiency, Acta Haematol., 61:75.

    Google Scholar 

  • Irvine, W., 1963, Gastric antibodies studied by fluorescence microscopy, Quart. J. Med., 48:427.

    Google Scholar 

  • Irvine, W., 1965, Immunologic aspects of pernicious anemia, New Engl. J. Med., 273:432.

    Google Scholar 

  • IUPAC-IUB, 1966, Tentative Rules, nomenclature and symbols for folic acid and related compounds. Nomenclature of corrinoids, J. Biol. Chem., 241:2991.

    Google Scholar 

  • IUPAC-IUB, 1974, The nomenclature of corrinoids (1973 Recommendations), Biochemistry, 13:1555.

    Google Scholar 

  • Jacob, E., and Glass, G. B. J., 1969, The participation of complement in the parietal cell antigen-antibody reaction in pernicious anaemia and atrophic gastritis, Clin. Exper. Immunol., 5:141.

    Google Scholar 

  • Jacob, E., and Glass, G. B. J., 1971, Localization of intrinsic factor and complement-fixing intrinsic factor-intrinsic factor antibody complex in parietal cell of man, Clin. Exper. Immunol., 8:517.

    Google Scholar 

  • Jacob, E., Herbert, V., Burger, R. L., and Allen, R. H., 1977, Atypical plasma factor associated with bronchogenic carcinoma and complexing with R-type vitamin B12-binding proteins, New Engl. J. Med., 296:915.

    Google Scholar 

  • Jacobson, E. D., Chodos, R. B., and Faloon, W. W., 1960, An experimental malabsorption syndrome induced by neomycin, Am. J. Med., 28:524.

    Google Scholar 

  • Jandl, J. H., and Greenberg, M. S., 1959, Bone marrow failure due to relative nutritional deficiency in Cooley’s hemolytic anemia, New Engl. J. Med., 260:461.

    Google Scholar 

  • Jeffries, G. H., 1965, Recovery of gastric mucosal structure and function in pernicious anemia during prednisone therapy. Gastroenterology, 48:371.

    Google Scholar 

  • Jeffries, G. H., and Sleisenger, M. H., 1965, Studies of parietal cell antibody in pernicious anemia, J. Clin. Invest., 44:2021.

    Google Scholar 

  • Johns, D. G., and Bertino, J. R., 1965, Folates and megaloblastic anemia: a review, Clin. Pharmacol. Ther., 6:372.

    Google Scholar 

  • Jones, C. C., 1973, Megaloblastic anemia associated with long-term tetracycline therapy, report of a case, Ann. Intern. Med., 78:910.

    Google Scholar 

  • Kaplan, H. S., and Rigler, L. G., 1945, Pernicious anemia and carcinoma of the stomach. Autopsy studies concerning their interrelationship, Am. J. Med. Sci., 209:339.

    Google Scholar 

  • Kass, L., 1968, A clockface chromatin pattern in the intermediate megaloblast of vitamin B12 or folate deficiency, Blood, 32:711.

    Google Scholar 

  • Kass, L., 1976a, Unusual morphologic abnormalities of megaloblasts in pernicious anemia and folate deficiency, Am. J. Clin. Pathol., 65:195.

    Google Scholar 

  • Kass, L., 1976b, Pernicious Anemia, Vol. VII in “Major Problems in Internal Medicine” (L. H. Smith, Jr., ed.), W. B. Saunders, Co., Philadelphia.

    Google Scholar 

  • Kass, L., 1978, William B. Castle and intrinsic factor, Ann. Intern. Med., 89:983.

    Google Scholar 

  • Katz, M., and Cooper, B. A., 1974, Solubilized receptor for vitamin B12-intrinsic factor complex from human intestine, Br. J. Haematol., 26:569.

    Google Scholar 

  • Katz, M., Lee, S. K., and Cooper, B. A., 1972, Vitamin B12 malabsorption due to a biologically inert intrinsic factor, New Engl. J. Med., 287:425.

    Google Scholar 

  • Katz, M., Mehlman, C. S., and Allen, R. H., 1974, Isolation and characterization of an abnormal human intrinsic factor, J. Clin. Invest., 53:1274.

    Google Scholar 

  • Killmann, S. A., 1964, Effect of deoxyuridine on incorporation of tritiated thymidine; difference between normoblasts and megaloblasts, Acta Med. Scand., 175:483.

    Google Scholar 

  • Kiossoglou, K. A., Mitus, W. J., and Dameshek, W., 1965, Chromosomal aberrations in pernicious anemia. Study of three cases before and after therapy, Blood, 25:662.

    Google Scholar 

  • Kitay, D. Z., 1969, Folic acid deficiency in pregnancy. On the recognition, pathogenesis, consequences, and therapy of the deficiency state in human reproduction, Am. J. Obstet. Gynecol., 104:1067.

    Google Scholar 

  • Kitay, D. Z., and Marshall, J. S., 1968, Remission of folic acid deficiency in pregnancy, Am. J. Obstet. Gynecol., 102:297.

    Google Scholar 

  • Klipstein, F. A., 1968, Progress in gastroenterology: tropical sprue, Gastroenterology, 54:275.

    Google Scholar 

  • Klipstein, F. A., 1972, Folate in tropical sprue, Br. J. Haematol., 23 (Supplement):119.

    Google Scholar 

  • Klipstein, F. A., Samloff, I. M., and Schenk, E. A., 1966, Tropical sprue in Haiti, Ann. Intern. Med., 64:575.

    Google Scholar 

  • Klipstein, F. A., Holdeman, L. V., Corcino, J. J., and Moore, W. E. C., 1973, Enterotoxigenic intestinal bacteria in tropical sprue, Ann. Intern. Med., 79:632.

    Google Scholar 

  • Kolhouse, J. F., Kondo, H., Allen, N. C., Podell, E., and Allen, R. H., 1978, Cobalamin analogues are present in human plasma and can mask cobalamin deficiency because current radioisotope dilution assays are not specific for true cobalamin, New Engl. J. Med., 299:785.

    Google Scholar 

  • Krumdieck, C. L., Cornwell, P. E., Thompson, R. W., and White, W. E., Jr., 1977, Studies on the biological role of folic acid polyglutamates, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 25–42, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Lane, G. A., Nahrwold, M. L., Tait, A. R., Taylor, M. D., Beaudoin, A. R., Cohen, P. J., 1979, Nitrous oxide is teratogenic: xenon is not!, Anesthesiol., 51 (Supplement No. 3S):S260.

    Google Scholar 

  • Lanzkowsky, P., Erlandson, M. E., and Bezan, A. I., 1969, Isolated defect of folic acid absorption associated with mental retardation and cerebral calcification, Blood, 34:452.

    Google Scholar 

  • Larrabee, A. R., Rosenthal, S., Cathou, R. E., and Buchanan, J. M., 1961, A methylated derivative of tetrahydrofolate as an intermediate of methionine synthesis, J. Am. Chem. Soc., 83:4094.

    Google Scholar 

  • Larrabee, A. R., Rosenthal, S., Cathou, R. E., and Buchanan, J. M., 1963, Enzymatic synthesis of the methyl group of methionine. IV. Isolation, charaterization and role of 5-methyltetrahydrofolate, J. Biol. Chem., 238:1025.

    Google Scholar 

  • Larsson, S. O., 1962, Myeloma and pernicious anemia, Acta Med. Scand., 172:195.

    Google Scholar 

  • Lassen, H. C. A., Henriksen, E., Neukirch, F., and Kristensen, H. S., 1956, Treatment of tetanus: severe bone-marrow depression after prolonged nitrous oxide anaesthesia, Lancet, 1:527.

    Google Scholar 

  • Lawson, D. H., Murray, R. M., and Parker, J. L. W., 1972, Early mortality in the megaloblastic anaemias, Quart. J. Med., 41:1.

    Google Scholar 

  • Layzer, R. B., 1978, Myeloneuropathy after prolonged exposure to nitrous oxide, Lancet, 2:1227.

    Google Scholar 

  • Leevy, C. M., Cardi, L., Frank, O., Gellene, R., and Baker, H., 1965, Incidence and significance of hypovitaminemia in a randomly selected municipal hospital population, Am. J. Clin. Nutr., 17:259.

    Google Scholar 

  • Levine, P. H., 1973, A qualitative platelet defect in severe vitamin B12 deficiency, Ann. Intern. Med., 78:533.

    Google Scholar 

  • Lewis, S. M., and Verwilghen, R. L., 1973, Dyserythropoiesis and dyserythropoietic anemias, in “Progress in Hematology”, Vol. VIII (E. B. Brown, ed.), Grune and Stratton, Inc., New York.

    Google Scholar 

  • Lillie, R. S., 1914, The action of various anaesthetics in suppressing cell-division in sea-urchin eggs, J. Biol. Chem., 17:121.

    Google Scholar 

  • Lindebaum, J., Pezzimenti, J. F., and Shea, N., 1974, Small-intestinal function in vitamin B12 deficiency, Ann. Intern. Med., 80:326.

    Google Scholar 

  • Linnell, J. C., Matthews, D. M., Mudd, S. H., Uhlendorf, B. W., and Wise, I. J., 1976, Cobalamins in fibroblasts cultured from normal control subjects and patients with methylmalonic aciduria, Ped. Res., 10:179.

    Google Scholar 

  • London, I. M., and West, R., 1950, The formation of bile pigment in pernicious anemia, J. Biol. Chem., 184:359.

    Google Scholar 

  • Loughlin, R. E., Elford, H. L., and Buchanan, J. M., 1964, Enzymatic synthesis of the methyl group of methionine. VII. Isolation of a cobalamin-containing transmethylase (5-methyItetrahydrofolate-homocysteine) from mammalian liver, J. Biol. Chem., 239:2889.

    Google Scholar 

  • Lowe, W. C., 1976, Hypogammaglobulinemia, pernicious anemia. With carcinomas of urinary bladder and lung, New York State J. Med., 76:926.

    Google Scholar 

  • Luhby, A. L., Eagle, F. J., Roth, E., and Cooperman, J. M., 1961, Relapsing megaloblastic anaemia in an infant due to a specific defect in gastrointestinal absorption of folic acid, Am. J. Dis. Child., 102:482 (Abstract).

    Google Scholar 

  • Mackenzie, I. L., and Donaldson, R. M., Jr., 1972, Effect of divalent cations and pH on intrinsic factor-mediated attachment of vitamin B12 to intestinal microvillous membranes, J. Clin. Invest., 51:2465.

    Google Scholar 

  • Magnus, E. M., 1977, Plasma conjugase activity in health and disease, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 147–151, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Mahmud, K., Ripley, D., and Doscherholmen, A., 1971, Vitamin B12 absorption tests. Their unreliability in postgastrectomy states, J. Am. Med. Assoc., 216:1167.

    Google Scholar 

  • Mahoney, M. J., Hart, A. C., Steen, V. D., and Rosenberg, L. E., 1975, Methylmalonic acidemia: biochemical heterogeneity in defects of 5′-deoxyadenosylcobalamin synthesis, Proc. Natl. Acad. Science, U. S. A., 72:2799.

    Google Scholar 

  • Mann, J. G., Brown, W. R., and Kern, F., Jr., 1970, The subtle and variable clinical expressions of gluten-induced enteropathy (adult celiac disease, nontropical sprue) an analysis of twentyone cases, Am. J. Med., 48:357.

    Google Scholar 

  • Marcoullis, G., Parmentier, Y., and Nicolas, J.-P., 1979, Blocking and binding type antibodies against all major vitamin B12-binders in a pernicious anaemia serum, Br. J. Haematol., 43:15.

    Google Scholar 

  • Mathan, V. I., Babior, B. M., and Donaldson, R. M. J., 1974, Kinetics of the attachment of intrinsic factor-bound cobamides to ileal receptors, J. Clin. Invest., 54:598.

    Google Scholar 

  • Mayersdorf, A., Streiff, R. R., Wilder, B. J., and Hammer, R. H., 1971, Folic acid and vitamin B12 alterations in primary and secondary epileptic foci induced by metallic cobalt powder, Neurology, 21:418 (Abstract).

    Google Scholar 

  • McIntyre, R. O., Sullivan, L. W., Jeffries, G. H., and Silver, R. H., 1965, Pernicious anamia in childhood, New Engl. J. Med., 272:981.

    Google Scholar 

  • McPhedran, P., Barnes, M. G., Weinstein, J. S., and Robertson, J. S., 1973, Interpretation of electronically determined macrocytosis, Ann. Intern. Med., 78:677.

    Google Scholar 

  • Menzies, R. C., Crossen, P. E., Fitzgerald, P. H., and Gunz, F. W., 1966, Cytogenetic and cytochemical studies on marrow cells in B12 and folate deficiency, Blood, 28:581.

    Google Scholar 

  • Metz, J., 1970, Folate deficiency conditioned by lactation, Am. J. Clin. Nutr., 23:843.

    Google Scholar 

  • Metz, J., Randall, T. W., and Kniep, C. H., 1961, Addisonian pernicious anemia in young Bantu females, Br. Med. J., 1:178.

    Google Scholar 

  • Miller, D. R., Bloom, G. E., Streiff, R. R., LoBuglio, A. F., and Diamond, L. K., 1966, Juvenile “congenital” pernicious anemia: clinical and immunological studies, New Engl. J. Med., 275:978.

    Google Scholar 

  • Milunsky, A., 1976, Prenatal diagnosis of genetic disorders, New Engl. J. Med., 295:377.

    Google Scholar 

  • Minot, G. R., and Castle, W. B., 1935, The interpretation of reticulocyte reactions: their value in determining the potency of therapeutic materials, especially in pernicious anemia, Lancet, 2:319.

    Google Scholar 

  • Minot, G., and Murphy, W. P., 1926, Treatment of pernicious anemia by a special diet, J. Am. Med. Assoc., 87:470.

    Google Scholar 

  • Mitchell, H. K., Snell, E. E., and Williams, R. J., 1941, The concentration of “folic acid”, J. Am. Chem. Soc., 63:228.

    Google Scholar 

  • Mollin, D. L., and MacGibbon, B. H., 1972, Sideroblastic and megaloblastic anaemias, Br. J. Haematol., 23 (Supplement):147.

    Google Scholar 

  • Myhre, E., 1964a, Studies on megaloblasts in vitro. I. Proliferation and destruction of nucleated red cells in pernicious anemia before and during treatment with vitamin B12, Scand. J. Clin. Lab. Invest., 16:307.

    Google Scholar 

  • Myhre, E., 1964b, Studies on megaloblasts in vitro. II. Maturation of nucleated red cells in pernicious anemia before and during treatment with vitamin B12, Scand. J. Clin. Lab. Invest., 16:320.

    Google Scholar 

  • Nathan, D. G., and Gardner, F. H., 1962, Erythroid cell maturation and hemoglobin synthesis in megaloblastic anemia, J. Clin. Invest., 41:1086.

    Google Scholar 

  • National Nutrition Survey in California, Termination of Contract Report, 1971, California State Department of Public Health, Berkeley, California, November.

    Google Scholar 

  • NRC/NAS, 1974, “Recommended Dietary Allowances”, Eighth Revised Edition, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Necheles, T. F., and Snyder, L. M., 1970, Malabsorption of folate polyglutamates associated with oral contraceptive therapy, New Engl. J. Med., 282:858.

    Google Scholar 

  • Nixon, P. F., and Bertino, J. R., 1970, Interrelationships of vitamin B12 and folate in man, Am. J. Med., 48:555.

    Google Scholar 

  • Nixon, P. F. and Bertino, J. R., 1972, Impaired utilization of serum folate in pernicious anemia. A study with radiolabeled 5-methyltetrahydrofolate, J. Clin. Invest., 51:1431.

    Google Scholar 

  • Nunn, J. F., Sturrock, J. E., and Howell, A., 1976, The effect of inhalation anesthetics on division of bone marrow cells in vitro, Br. J. Anesth., 48:75.

    Google Scholar 

  • Nutrition Reviews, 1979, Altered immune responses in zinc deficiency in rodents, Nutrition Reviews, 37:234.

    Google Scholar 

  • Nybert, W., 1960, The influence of Diphyllobothrium latum on the vitamin B12-intrinsic factor complex. I. In vivo studies with Schilling test technique, Acta Med. Scand., 167:185.

    Google Scholar 

  • O’Brien, J. S., 1962, The role of the folate coenzymes in cellular division: a review, Cancer Res., 22:267.

    Google Scholar 

  • Ogbuawa, O., Trowell, J., Williams, J. T., Bradley, C., Archer, J., and Henry, W. L., 1978, Hyperpigmentation of pernicious anemia in blacks, Arch. Intern. Med., 138:388.

    Google Scholar 

  • Oliver, R. A. M., and Baker, G. P., 1969, Juvenile pernicious anemia and hypothyroidism, a family study, Br. Med. J., 2:27.

    Google Scholar 

  • O’Malley, B. W., and Means, A. R., 1974, Female steroid hormones and target cell nuclei, Science, 183:610.

    Google Scholar 

  • Osler, W., 1919, Observations on the severe anaemias of pregnancy and the post-partum state, Br. Med. J., 1:1.

    Google Scholar 

  • Pereira, S. M., and Baker, S. J., 1966, Haematologic studies in kwashiorkor, Am. J. Clin. Nutr., 18:413.

    Google Scholar 

  • Pfiffner, J. J., Binkley, S. B., Bloom, E. S., Brown, R. A., Bird, O. D., and Emmett, A. D., 1943, Isolation of antianemia factor-(vitamin Bc) in crystalline form from liver, Science, 97:404.

    Google Scholar 

  • Pincus, J. H., Reynolds, E. H., and Glaser, G. H., 1972, Subacute combined system degeneration with folate deficiency, J. Am. Med. Assoc., 221:496.

    Google Scholar 

  • Pinkhas, J., Ben-Bassat, M., and De Vries, A., 1973, Death in anticonvulsant-induced megaloblastic anemia, J. Am. Med. Assoc., 224:246.

    Google Scholar 

  • Powsner, E. R., and Berman, L., 1965, Human bone marrow chromosomes in megaloblastic anemia, Blood, 26:784.

    Google Scholar 

  • Prasad, A. S., Miale, A., Farid, Z., Sandstead, H. H., Schulert, A. R., and Darby, W. J., 1963, Biochemical studies on dwarfism, hypogonadism and anemia, Arch. Intern. Med., 111:407.

    Google Scholar 

  • Pritchard, J. A., Whalley, P. J., and Scott, D. E., 1969, The influence of maternal folate and iron deficiencies on intrauterine life, Am. J. Obstet. Gynecol., 104:388.

    Google Scholar 

  • Pritchard, J. A., Scott, D. E., and Whalley, P. J., 1971, Maternal folate deficiency and pregnancy wastage. IV. Effects of folic acid supplements, anticonvulsants and oral contraceptives, Am. J. Obstet. Gynecol., 109:341.

    Google Scholar 

  • Reizenstein, P. G., 1959, Excretion of non-labeled vitamin B12 in man, Acta Med. Scand., 165:313.

    Google Scholar 

  • Reizenstein, P., Ek, G., and Matthews, C. M. E., 1966, Vitamin B12 kinetics in man. Implications on total-body-B12-determinations, human requirements and normal and pathological cellular B12 uptake, Phys. Med. Biol., 11:295.

    Google Scholar 

  • Retief, F. P., Heyns, A. du P., Oosthuizen, M., and van Reenen, O. R., 1977, Aspects of folate metabolism in renal failure, Br. J. Haematol., 36:405.

    Google Scholar 

  • Reynolds, E. H., 1968, Mental effects of anticonvulsants and folate metabolism, Brain, 91:197.

    Google Scholar 

  • Reynolds, E. H., 1971, Anticonvulsant drugs, folic acid metabolism, frequency and psychiatric illness, Psychiatr. Neurol. Neurochir., 74:167.

    Google Scholar 

  • Reynolds, E. H., 1973, Anticonvulsants, folic acid, and epilepsy, Lancet, 1:1376.

    Google Scholar 

  • Reynolds, E. H., 1976, Neurological aspects of folate and vitamin B12 metabolism, in “Clinics in Haematology, Megaloblastic Anemia”, Vol. 5, No. 3, (A. V. Hoffbrand, ed.), pp. 661–696, W. B. Saunders, Co., Ltd., London.

    Google Scholar 

  • Rickes, E. L., Brink, N. G., Koniuszy, F. R., Wood, T. R., and Folkers, K., 1948, Crystalline vitamin B12, Science, 107:396.

    Google Scholar 

  • Rickles, F. R., Klipstein, F. A., Tomasini, J., Corcino, J. J., and Maldonado, N., 1972, Long-term follow-up of antibiotic-treated tropical sprue, Ann. Intern. Med., 76:203.

    Google Scholar 

  • Riddell, E. M., and Davidson, R. J. L., 1968, Coexistence of pernicious anaemia and acute erythraemic myelosis, J. Clin. Path., 21:590.

    Google Scholar 

  • Rose, M. S., Chanarin, I., Doniach, D., Brostoff, J., and Ardeman, S., 1970, Intrinsic-factor antibodies in absence of pernicious anaemia: 3–7 year follow-up, Lancet, 2:9.

    Google Scholar 

  • Rosenberg, L. E., 1969, Inherited aminoacidopathies demonstrating vitamin dependency, New Engl. J. Med., 281:145.

    Google Scholar 

  • Rosenberg, I., 1975, Folate absorption and malabsorption, New Engl. J. Med., 293:1303.

    Google Scholar 

  • Rosenberg, I. H., 1976, Absorption and malabsorption of folates, in “Clinics in Haematology, Megaloblastic Anaemia”, Vol. 5, No. 3, (A. V. Hoffbrand, ed.), pp. 589–618, W. B. Saunders, Co., Ltd., London.

    Google Scholar 

  • Rosenberg, I. H., 1977, Role of intestinal conjugase in the control of the absorption of polyglutamyl folates, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 136–146, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Rosenberg, I. H., and Godwin, H. A., 1971, The digestion and absorption of dietary folate, Gastroenterology, 60:445.

    Google Scholar 

  • Rosenberg, I. H., Streiff, R. R., Godwin, H. A., and Castle, W. B., 1969, Absorption of polyglutamic folate: participation of deconjugating enzymes of the intestinal mucosa, New Engl. J. Med., 280:985.

    Google Scholar 

  • Rosenberg, H., Orkin, F. K., and Springstead, J., 1979, Abuse of nitrous oxide, Anesth. Analg., 58:104.

    Google Scholar 

  • Rothenberg, S. P., Da Costa, M., and Fischer, G., 1977, Use and significance of folate binders, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 82–97, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Rothman, D., 1970, Folic acid in pregnancy, Am. J. Obstet. Gynecol., 108:149.

    Google Scholar 

  • Rucker, R. W., and Harrison, G. M., 1973, Vitamin B12 deficiency in cystic fibrosis, New Engl. J. Med., 289:329.

    Google Scholar 

  • Samson, D. C., Swisher, S. N., Christian, R. M., and Engel, G. L., 1952, Cerebral metabolic disturbance and delirium in pernicious anemia, Arch. Intern. Med., 90:4.

    Google Scholar 

  • Sando, M. J. W., and Lawrence, J. R., 1958, Bone marrow depression following treatment with protracted nitrous-oxide anaesthesia, Lancet, 1:588.

    Google Scholar 

  • Santiago-Borrero, P. J., Santini, R., Jr., Pérez-Santiago, E., Maldonado, N., Millan, S., and Coll-Camález, G., 1973, Congenital isolated defect of folic acid absorption, J. Pediat., 92:450.

    Google Scholar 

  • Santini, R., Jr., Berger, F. M., Berdasco, G., Sheehy, T. W., Aviles, J., and Davila, I., 1962, Folic acid activity in Puerto Rican Foods, J. Am. Dietet. Assoc., 41:562.

    Google Scholar 

  • Santini, R., Millan, S., and Santiago-Borrero, P. J., 1973, Additional information on congenital defect in absorption of folic acid, J. Pediat., 83:345.

    Google Scholar 

  • Sauberlich, H. E., 1977, Detection of folic acid deficiency in populations, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 213–231, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Sauer, H., and Wilmanns, W., 1977, Cobalamin dependent methionine synthesis and methyl-folate-trap in human vitamin B12 deficiency, Br. J. Haematol., 36:189.

    Google Scholar 

  • Schade, S. G., Feick, P., Muckerheide, M., and Schilling, R. F., 1966, Occurrence in gastric juice of antibody to a complex of intrinsic factor and vitamin B12, New Engl. J. Med., 275:528.

    Google Scholar 

  • Schade, S., Abels, J., Schilling, R. F., Feick, P., and Muckerheide, M., 1967, Studies on antibody to intrinsic factor, J. Clin. Invest., 46:615.

    Google Scholar 

  • Schilling, R. F., 1953, Intrinsic factor studies. II. The effect of gastric juice on the urinary excretion of radioactivity after oral administration of radioactive vitamin B12, J. Lab. Clin. Med., 42:860.

    Google Scholar 

  • Schneerson, J. M., and Gazzard, B. G., 1977, Reversible malabsorption caused by methyldopa, Br. Med. J., 2:1456.

    Google Scholar 

  • Schwartz, M., 1958, Intrinsic factor-inhibiting substance in serum of orally treated patients with pernicious anaemia, Lancet, 2:61.

    Google Scholar 

  • Sheehy, T., and Dempsey, H., 1970, Methotrexate therapy for Plasmodium vivax malaria, J. Am. Med. Assoc., 214:109.

    Google Scholar 

  • Shin, Y. S., Williams, M. A., Stokstad, E. L. R., 1972, Identification of folic acid compounds in rat liver, Biochim. Biophys. Res. Commun., 47:35.

    Google Scholar 

  • Shulman, R., 1972, The present status of vitamin B12 and folic acid deficiency in psychiatric illness, Canad. Psychiatr. Assoc. J., 17:205.

    Google Scholar 

  • Silber, R., and Moldow, C. F., 1970, The biochemistry of B12-mediated reactions in man, Am. J. Med., 48:549.

    Google Scholar 

  • Silink, M., Reddel, R., Bethal, M., and Rowe, P. B., 1975, γ-Glutamyl hydroxylase (conjugase), J. Biol. Chem., 250:5982.

    Google Scholar 

  • Smith, E. L., 1965, “Vitamin B12” 3rd Edition, Wiley, New York.

    Google Scholar 

  • Smith, E. L., and Parker, L. F. J., 1948, Purification of anti-pernicious anaemia factor, Biochem. J. 43:viii (Abstract).

    Google Scholar 

  • Snell, E. E., and Peterson, W. H., 1940, Growth factors for bacteria. X. Additional factors required by certain lactic acid bacteria, J. Bacteriol., 39:273.

    Google Scholar 

  • Solanki, D. L., Jacobson, R. J., McKibbon, J., and Green, R., 1978, Racial patterns in pernicious anemia, New Engl. J. Med., 298:1365.

    Google Scholar 

  • Spector, R., 1977, Vitamin homeostasis in the central nervous system, New Engl. J. Med., 296:1393.

    Google Scholar 

  • Spector, R., and Lorenzo, A. V., 1975, Folate transport by the choroid plexus in vitro, Science, 187:540.

    Google Scholar 

  • Spencer, J. D., Raasch, F. O., and Trefny, F. A., 1976, Halothane abuse in hospital personnel, J. Am. Med. Assoc., 235:1034.

    Google Scholar 

  • Stadtman, T. C., 1971, Vitamin B12, biochemical studies elucidate the role of this complex molecule in diverse metabolic processes, Science, 171:859.

    Google Scholar 

  • Stebbins, R., and Bertino, J. R., 1976, Megaloblastic anaemia produced by drugs, in “Clinics in Haematology, Megaloblastic Anaemia”, Vol. 5, No. 3, (A. V. Hoffbrand, ed.), pp. 619–630, W. B. Saunders Co., Ltd., London.

    Google Scholar 

  • Stenman, U.-H., 1971, Isoelectric focusing of R-type vitamin B12-binding proteins, Scand. J. Clin. Lab. Invest., 27 (Supplement 116):26.

    Google Scholar 

  • Stephens, M. E. M., Craft, I., Peters, T. J., and Hoffbrand, A. V., 1972, Oral contraceptives and folate metabolism, Clin. Science, 42:405.

    Google Scholar 

  • Stokstad, E. L. R., 1943, Some properties of a growth factor for Lactobacillus casei, J. Biol. Chem., 149:573.

    Google Scholar 

  • Stokstad, E. L. R., Shin, Y. S., and Tamura, T., 1977, Distribution of folate forms in food and folate availability, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 56–68, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Stone, M. L., 1968, Effects on the fetus of folic acid deficiency in pregnancy, Clin. Obstet. Gynecol., 11:1143.

    Google Scholar 

  • Stone, M. L., Luhby, A. L., Feldman, R., Gordon, M., and Cooperman, J. M., 1967, Folic acid metabolism in pregnancy, Am. J. Obstet. Gynecol., 99:638.

    Google Scholar 

  • Streiff, R. R., 1970a, Folic acid deficiency anemia, Seminar. Hematol., 7:23.

    Google Scholar 

  • Streiff, R. R., 1970b, Folate deficiency and oral contraceptives, J. Am. Med. Assoc., 214:105.

    Google Scholar 

  • Streiff, R. R., and Greene, B., 1970, Drug inhibition of folate conjugase, Clin. Res., 18:418 (Abstract).

    Google Scholar 

  • Strickland, G. T., and Kostinas, J. E., 1970, Folic acid deficiency in malaria, Clin. Res., 18:418 (Abstract).

    Google Scholar 

  • Sturrock, J. E., and Nunn, J. F., 1974, Effect of anaesthesia on DNA synthesis in Chinese hamster fibroblasts, Br. J. Anaesth., 46:316.

    Google Scholar 

  • Sturrock, J. E., and Nunn, J. F., 1975, Mitosis in mammalian cells during exposure to anesthetics, Anesth., 43:21.

    Google Scholar 

  • Sullivan, L. W., 1970a, Vitamin B12 metabolism and megaloblastic anemia, Seminar. Hematol., 7:6.

    Google Scholar 

  • Sullivan, L. W., 1970b, Differential diagnosis and management of the patient with megaloblastic anemia, Am. J. Med., 48:609.

    Google Scholar 

  • Sullivan, L. W., and Herbert, V., 1964, Suppression of hematopoiesis by ethanol, J. Clin. Invest., 43:2048.

    Google Scholar 

  • Sullivan, L. W., and Herbert, V., 1965, Studies on the minimun daily requirement for vitamin B12: hematopoietic response for 0.1 microgram of coenzyme B12 and comparison of their relative potency, New Engl. J. Med., 272:340.

    Google Scholar 

  • Sullivan, L. W., Herbert, V., and Castle, W. B., 1963, In vitro assay for human intrinsic factor, J. Clin. Invest., 42;1443.

    Google Scholar 

  • Swanson, V. L., Wheby, M. S., and Bayless, T. M., 1966, Morphologic effects of folic acid and vitamin B12 on jejunal lesion of tropical sprue, Am. J. Path. 49:167.

    Google Scholar 

  • Sweetman, L., Weyler, W., Shafai, T., Young, P. E., and Nyhan, W. L., 1979, Prenatal diagnosis of propionic acidemia, J. Am. Med. Assoc., 242:1048.

    Google Scholar 

  • Swenseid, M. E., Bethell, F. H., and Bird, O. D., 1951, The concentration of folic acid in leukocytes: observations on normal subjects and persons with leukemia, Cancer Res., 11:864.

    Google Scholar 

  • Taguchi, H., Laundy, M., Reid, C., Reynolds, E. H., and Chanarin, I., 1977, The effect of anticonvulsant drugs on thymidine and deoxyribosenucleic acid synthesis by human marrow cells, Br. J. Haematol., 36:81.

    Google Scholar 

  • Tamura, T., and Stokstad, E. L. R., 1973, The availability of food folate in man, Br. J. Haematol., 25:513.

    Google Scholar 

  • Tamura, T., Shane, B., Baer, M. T., King, J. C., Margen, S., and Stokstad, E. L. R., 1978, Absorption of mono- and polyglutamyl folates in zinc-depleted man, Am. J. Clin. Nutr., 31:1984.

    Google Scholar 

  • Taylor, K. B., 1965, The localization of gastric intrinsic factor, Gastroenterology, 48:853 (Abstract).

    Google Scholar 

  • Taylor, K. B., 1976, Immune aspects of pernicious anaemia and atrophic gastritis, in “Clinics in Haematology, Megaloblastic Anaemia”, Vol. 5, No. 3, (A. V. Hoffbrand, ed.), pp. 497–519, W. B. Saunders, Co., Ltd., London.

    Google Scholar 

  • Taylor, K. B., and Morton, J. A., 1958, An antibody to Castle’s intrinsic factor, Lancet, 1:29.

    Google Scholar 

  • Ternberg, J. L., and Eakin, R. E., 1949, Erythein and apoerythein and their relation to the antipernicious anemia principle, J. Am. Chem. Soc., 71:3858.

    Google Scholar 

  • Thiersch, J. B., 1952, Therapeutic abortions with a folic acid antagonist, 4, aminopteroylglutamic acid (4-amino PGA) administered by the oral route, Am. J. Obstet. Gynecol., 63:1298.

    Google Scholar 

  • Thorn, S. R., 1979, Effects of anesthetic gases and helium on microbial growth, Clin. Res., 27:607A (Abstract).

    Google Scholar 

  • Thorn, G. W., Forsham, P. H., Frawley, R. F., Hill, S. R., Jr., Toche, M., Staehelin, D., and Wilson, D. L., 1950, The clinical usefulness of ACTH and cortisone, New Engl. J. Med., 242:865.

    Google Scholar 

  • Toepfer, E. W., Zook, E. G., Orr, M. L., and Richardson, L. R., 1951, “Folic Acid Content of Foods”, Agric. Handbook No. 29, U.S. Dept. Agric., Washington, D. C.

    Google Scholar 

  • Toskes, P. P., and Deren, J. J., 1972, The role of the pancreas in vitamin B12 absorption: studies of vitamin B12 absorption in partially pancreatectomized rats, J. Clin. Invest., 51:216.

    Google Scholar 

  • Toskes, P. P., and Deren, J. J., 1973, Vitamin B12 absorption and malabsorption, Gastroenterology, 65:662.

    Google Scholar 

  • Toskes, P. P., Hansell, J., Cerda, J., and Deren, J. J., 1971, Vitamin B12 malabsorption in chronic pancreatic insufficiency, New Engl. J. Med., 284:627.

    Google Scholar 

  • Toskes, P. P., Deren, J. J. and Conrad, M. E., 1973, Trypsin-like nature of the pancreatic factor that corrects vitamin B12 malabsorption associated with pancreatic dysfunction, J. Clin. Invest., 52:1660.

    Google Scholar 

  • Trudeil, J. R., Hong, K., O’Neil, J. R., and Cohen, E. N., 1979, Metabolism of nitrous oxide by human and rat intestinal contents, Anesthesiology, 51 (Supplement 38):S258.

    Google Scholar 

  • Tso, S. C., 1976, Significance of subnormal red-cell folate in thalassemia, J. Clin. Path., 29:140.

    Google Scholar 

  • van Dommelen, C. K. V., Slagboom, G., Meester, G. T., and Wadman, S. K., 1963, Reversible hypogammaglobulinemia in cyanocobalamin (vitamin B12) deficiency, Acta Med. Scand., 174:193.

    Google Scholar 

  • van Niekirk, W. A., 1966, Cervical cytological abnormalities caused by folic acid deficiency, Acta Cytol., 10:67.

    Google Scholar 

  • Vilter, R. W., Horrigan, D., Mueller, J. F., Jarrold, T., Vilter, C. F., Hawkins, V., and Seaman, A., 1950, Studies on the relationships of vitamin B12, folic acid, thymine, uracil and methyl group donors in persons with pernicious anemia and related megaloblastic anemias, Blood, 5:695.

    Google Scholar 

  • Visuri, K., and Gräsbeck, R., 1973, Human intrinsic factor, isolation by improved conventional methods and properties of the preparation, Biochim. Biophys. Acta, 310:508.

    Google Scholar 

  • Von der Lippe, G., 1977, Absorption of vitamin B12 in chronic pancreatic insufficiency, Scand. J. Gastroenterology, 12:257.

    Google Scholar 

  • Waslien, C. I., 1977, Folacin requirement of infants, in “Folic Acid Biochemistry and Physiology in Relation to the Human Nutrition Requirement, Proceedings of a Workshop on Human Folate Requirements, Washington, D. C., June 2–3, 1975”, pp. 232–246, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D. C.

    Google Scholar 

  • Waxman, S., and Gilbert, H. S., 1973, A tumor-related vitamin B12 binding protein in adolescent hepatoma, New Engl. J. Med., 289:1053.

    Google Scholar 

  • Waxman, S., Corcino, J., and Herbert, V., 1970a, Aggravation or initiation of megaloblastosis by amino acids in the diet, J. Am. Med. Assoc., 214:101.

    Google Scholar 

  • Waxman, S., Corcino, J. J., and Herbert, V., 1970b, Drugs, toxins, and dietary amino acids affecting vitamin B12 or folic acid absorption or utilization, Am. J. Med., 48:599.

    Google Scholar 

  • West, R., and Reisner, E. H., Jr., 1949, Treatment of pernicious anemia with crystalline vitamin B12, Am. J. Med., 6:643.

    Google Scholar 

  • Whitehead, V. M., and Cooper, B. A., 1977, Failure of radiodilution assay for vitamin B12 to detect deficiency in some patients, Blood, 50 (Supplement 1):99.

    Google Scholar 

  • Whitehead, N., Reyner, F., and Lindenbaum, J., 1973, Megaloblastic changes in the cervical epithelium, association with oral contraceptive therapy and reversal with folic acid, J. Am. Med. Assoc., 226:1421.

    Google Scholar 

  • Whiteside, M. G., Ungar, B., and Cowling, D. C., 1968, Iron, folic acid, and vitamin B12 levels in normal pregnancy and their influence on birth weight and duration of pregnancy, Med. J. Austral., 1:338.

    Google Scholar 

  • Wickramasinghe, S. N., and Longland, J. E., 1974, Assessment of deoxyuridine suppression test in diagnosis of vitamin B12 or folate deficiency, Br. Med. J., 3:148.

    Google Scholar 

  • Wickramasinghe, S. N., and Pratt, J. R., 1970, Myelocyte proliferation in pernicious anaemia, Acta Haematol., 44:37.

    Google Scholar 

  • Wickramasinghe, S. N., Chalmers, D. G., and Cooper, E. H., 1967, Disturbed proliferation of erythropoietic cells in pernicious anaemia, Nature, 215:189.

    Google Scholar 

  • Wickramasinghe, S. N., Cooper, E. H., and Chalmers, D. G., 1968, A study of erythropoiesis by combined morphologic, quantitative, cytochemical and autoradiographic methods, Blood, 31:304.

    Google Scholar 

  • Williams, H. H., Erickson, B. N., Bernstein, S., Hummel, F. C., and Macy, I. G., 1937, The lipid and mineral distribution of the serum and erythrocytes in pernicious anemia, J. Biol. Chem., 118:599.

    Google Scholar 

  • Williams, R. B., Mills, C. F., and Davidson, R. J. L., 1973, Relationships between zinc deficiency and folic acid status of the rat, Proc. Nutr. Soc., 32:2A (Abstract).

    Google Scholar 

  • Wills, L., 1931, Treatment of “pernicious anemia of pregnancy” and “tropical anaemia”, Br. Med. J., 1:1059.

    Google Scholar 

  • Wills, L., 1932, Tropical macrocytic anaemia, Proc. Roy. Soc. Med., 25:1720.

    Google Scholar 

  • Wills, L., 1933, The nature of the haemopoietic factor in marmite, Lancet, 1:1283.

    Google Scholar 

  • Wintrobe, M. M., Cartwright, G. E., Palmer, J. G., Kuhns, W. J., and Samuels, L. T., 1951, Effect of corticotropin and cortisone on the blood in various disorders in man, Arch. Intern. Med., 88:310.

    Google Scholar 

  • WHO, Nutritional Anaemias, Report of a WHO group of experts, 1972, WHO Technical Report Series No. 503.

    Google Scholar 

  • Young, V. R., and Scrimshaw, N. S., 1979, Genetic and biological variability in human nutrient requirements, Am. J. Clin. Nutr., 32:486.

    Google Scholar 

  • Zarafonetis, C. J. D., Overman, R. L., and Molthan, L., 1957, Unique sequence of pernicious anemia, polycythemia and acute leukemia, Blood, 12:1011.

    Google Scholar 

  • Zittoun, R., Zittoun, J., Seignalet, J., and Dausset, J., 1975, HL-A and pernicious anemia, New Engl. J. Med., 293:1324.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Arkansas State Department of Health, Bureau of Cancer and Special Services, Little Rock, Arkansas, USA

    Ruth C. Steinkamp M.D. (Former Director)

Authors
  1. Ruth C. Steinkamp M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Pathology, Biochemistry, and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Marge A. Brewster

  2. Metabolic Laboratory, Arkansas Children’s Hospital, Little Rock, Arkansas, USA

    Marge A. Brewster

  3. Department of Biochemistry, Division of Laboratory Medicine, Department of A therosclerosis and Thrombosis Research, Division of Research, Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Herbert K. Naito

  4. Department of Chemistry, Cleveland State University, Cleveland, Ohio, USA

    Herbert K. Naito

Rights and permissions

Reprints and permissions

Copyright information

© 1980 Plenum Press, New York

About this chapter

Cite this chapter

Steinkamp, R.C. (1980). Vitamin B12 and Folic Acid: Clinical and Pathophysiological Considerations. In: Brewster, M.A., Naito, H.K. (eds) Nutritional Elements and Clinical Biochemistry. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3168-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-3168-1_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3170-4

  • Online ISBN: 978-1-4613-3168-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation