Pharmacological Manipulation of 2,3 Diphosphoglycerate (2,3-Dpg) Levels in Human Erythrocytes

Abstract

studies specific g o a t a n t i -S and specific r a b b i t a n t i -F sera were shown t o b e adequate f o r q u a n t i f y i n g hemoglobins S and F i n mixed p r o p o r t i o n s s i m u l a t i n g those anticipated in newborn infants w i t h hemoglobin AS o r SS. To d a t e 107 c o r d b l o o d specimens from b l a c k infants have been t e s t e d f o r r e l a t i v e q u a n t i t i e s o f hemoglobins S and F. The mean relative q u a n t i t y o f F was 86.3% * 10.6 S.D. I n 1 5 o f t h e s e specimens S was d e t e c t e d with a mean relative q u a n t i t y o f 6.3% + 2.5 S.D. T h i s t e c h n i q u e p r e s e n t l y can s e r v e as a convenient s c r e e n i n g device w i t h i d e n t i f i c a t i o n o f SS among p o s i t i v e s by t h e more cmbersome agar g e l e l e c t r o p h o r e s i s t e c h n i q u e . Continuing work w i l l compare t h e p e r c e n t concordance between d i a g n o s e s o f AS and SS by these two methods. This study was designed t o determine the origin of SF and its turnover in t h e rat and in man. The concentrotion of SF was measured by radioimmunoassay. 5 9~e in SF during kinetic studies was measured after ultracentrifugal fractionation of plasma on o sucrose gradient, based on the greater molecular weight of ferritin compored with other iron containing components. After injection of heat-treated 5 9~e -~~~ in rats, peak labelling of SF fraction was a t 30 min; other 5 9~e in plosmo, primarily transferrin-bound, was maximally labelled a t 2 h. N o labelling of the SF fraction was detected after injection of 59~e-transferrin in mon or in the rat or after 59~e-hemoglobin-hoptoglobin in the rat. Purified rat liver 59~e-ferritin, injected intravenously in the rat, was removed by t h e liver a t an exponential rate with a half-life of 4 min. NEW ROLE FORThe turnover of SF in man was estimated by a n unusual approach, based on a n 8-fold higher concentration in t h e newborn compored with the adult. SF concentration was measured in 1 0 ml increments of blood removed during 1.5 -2.0 volume exchange transfusions of the newborn for hyperbilirvbinemia. The decrease in serum SF during the 1 h exchanges was slow and of small magnitude. The rote of synthesis of SF was computed t o correspond t o a half-life a s short a s 5 min. The rapid turnover of iron in SF, compared with tmnsferrin iron, suggests a quantitatively important role for SF in t h e transport of iron from the RE cell t o the liver. CESSATION O F THERAPY DURING REMISSION IN CHILDREN WITH ACUTE LYMPHOCYTIC LEUKEMIA (ALL). Joseph V. Simone, RhomesAur, Manuel Verzosa, Omar Hustu, and Donald Pinkel, St. Jude Children's Res. Hosp., Memphis, TN. Combination chemotherapy and preventive central nervous system (CNS) therapy for childhood ALL have resulted in 5-year leukemia-free survival in about one-half of the patients. However, the risk of side effects and fatal infection is significant so chemotherapy was stopped after 2-3 years of complete remission.Therapy was stopped in a total of 123 patients with ALL...