A B S T R A C T The pathogenesis of the increased erythrocytosis and extramedullary erythropoiesis observed in infants of diabetic mothers (IDM) has been obscure. In the present studies, IDM were found to have elevated umbilical plasma erythropoietin (Ep) concentrations by radioimmunoassay. 22 of 61 IDM (36%) had levels above the range of28 nonasphyxiated, appropriately grown normal infants. In 16 controls and 20 IDM, plasma Ep correlated directly with plasma insulin (P < 0.001, r = 0.73). To investigate this relationship further, a chronic rhesus model was studied with continuous fetal hyperinsulinemia for 21 d in utero in the last third ofpregnancy. In five experimental fetuses, plasma insulin levels averaged 4,210 ,u.U/ml at delivery, whereas plasma Ep was above the range of six controls. In addition, the experimental fetuses had elevated reticulocyte counts in umbilical cord blood. The mechanism for the increased plasma Ep associated with hyperinsulinemia in the fetus is unexplained but may be mediated by fetal hypoxia.

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Taking all these results into consideration, it seems that although the overall outcome for patients with DLBCL is decided by a combination of different clinical and biologic variables, the expression of some of these cell-cycle regulator proteins appears to be specifically associated with the different clinical features of tumors.

One of the obvious uses which may be made of a tracer in biological studies is the determination of rates. Zilversmitt and associates (1) and more recently London (2) have called attention to this use of a tracer. Only when the isotope can be added without effectively changing the amount or concentration of material in a steady state system can such an application be made. Not until recently has radio iron been available which had sufficiently high specific activity to tag plasma iron without changing its concentration. The amount of iron leaving and entering the plasma would be significant in determining an abnormal turnover rate in some other system of the body containing iron, for example, the red cells. The present theory of iron metabolism conceives of plasma as a pool into which iron is returned before being resynthesized into the complex organic substances, hemoglobin, myoglobin, cytochromes, peroxidases, and ferritin which are so important to body function. Since the approximate normal rate of turnover of red cell iron is known, and since the major portion of this element in the body resides in the red cells, it would be expected that abnormalities in this rate would be directly reflected in plasma iron turnover rates. This paper concerns the plasma iron and red cell iron turnover data on 75 human subjects who were given amounts of iron which did not alter the steady state systems. It is shown that such turnover rates do, indeed, agree with the clinical and laboratory data concerning normal red cell life, abnormal rates of destruction and abnormal rates of formation of red cells. It is believed that the data ascertained from the type of study described here are of value

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