The long-term objectives and specific aims are to develop laboratory methods which will expand the ability of health professional to diagnose and assess nutritional status with respect to folic acid and vitamin B-12, deficiencies of which are the second and third most frequent causes of nutritional anemia. The research will focus particularly on how best to screen people over 50 for the earliest stages of developing pernicious anemia and how best to screen people with liver disease and/or iron defieciency and/or hemoglobinopathy for hidden foalte or vitamin B-12 deficiency before vitamin deficiency anemia develops, therby allowing vitamin B-12 or folate treatment before need for acute care or hospitalization develops. Current radioassay and microbiologic assay methodology for measuring serum levels of vitamin B-12 and folate, and red cell folate, which misses many cases, will be compared with newer methodologies, namely, measurements of percent saturation of transcobalamin II (TC II) with Cobalamin and cobalamin analogues, and non-competitive endogenous ligand radioassays which measure number of molecules bound (competitive assays use exogenous ligand to measure competition of various analogues of a vitamin with a standard). Two new and more sensitive modifications of radioassay for antibody to intrinsic factor in urine will also be evaluated for value in diagnosis of early pernicious anemia. The value of looking for subtle hypersegmentation in granules, and of doing deocyurindine (dU) suppression tests of peripheral blood lymphocytes as well as measuring percent saturation of TC II to diagnose deficiencies of vitamin B-12 and/or folate which are missed by finding normal serum and red cell vitamin B-12 and folate will be further studied, as will measurement of the quantity of the saturated component, as well as the value of new non-competitive endogenous ligand radioassays of folate in serum, red cells, and whole blood.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Nutrition Study Section (NTN)
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Mount Sinai School of Medicine
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New York
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Herbert, V (1990) Nutritional anemias in the elderly. Prog Clin Biol Res 326:203-27
Herbert, V; Fong, W; Gulle, V et al. (1990) Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B12 (cobalamin) absorption in patients with AIDS. Am J Hematol 34:132-9
Herzlich, B C; Ranginwala, M; Nawabi, I et al. (1990) Synergy of inhibition of DNA synthesis in human bone marrow by azidothymidine plus deficiency of folate and/or vitamin B12? Am J Hematol 33:177-83
Shaw, S; Jayatilleke, E; Herbert, V et al. (1989) Cleavage of folates during ethanol metabolism. Role of acetaldehyde/xanthine oxidase-generated superoxide. Biochem J 257:277-80
Das, K C; Herbert, V (1989) In vitro DNA synthesis by megaloblastic bone marrow: effect of folates and cobalamins on thymidine incorporation and de novo thymidylate synthesis. Am J Hematol 31:11-20
Shaw, S; Jayatilleke, E; Meyers, S et al. (1989) The ileum is the major site of absorption of vitamin B12 analogues. Am J Gastroenterol 84:22-6
Herbert, V (1988) Don't ignore low serum cobalamin (vitamin B12) levels. Arch Intern Med 148:1705-7
Herzlich, B; Herbert, V (1988) Depletion of serum holotranscobalamin II. An early sign of negative vitamin B12 balance. Lab Invest 58:332-7
Herbert, V (1987) The 1986 Herman award lecture. Nutrition science as a continually unfolding story: the folate and vitamin B-12 paradigm. Am J Clin Nutr 46:387-402
Herbert, V (1987) Recommended dietary intakes (RDI) of folate in humans. Am J Clin Nutr 45:661-70

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