5-Azacytidine and several of its analogues are known to inhibit DNA methylation, alter gene expression, and inhibit cell growth. We report a Phase II study in which we investigated the antineoplastic activity of 5,6-dihydro-5-azacytidine and its induction of fetal hemoglobin synthesis when given by a 5-day continuous i.v. infusion of 1650 mg/m2/day that was repeated every 21 days. Fetal hemoglo...

During development, human beta-globin locus regulation undergoes two critical switches, the embryonic-to-fetal and fetal-to-adult hemoglobin switches. To define the role of the fetal (A)gamma-globin promoter in switching, human beta-globin-YAC transgenic mice were produced with the (A)gamma-globin promoter replaced by the erythroid porphobilinogen deaminase (PBGD) promoter (PBGD(A)gamma-YAC). A...

T HE RATIO OF CARBON MONOXIDE ( CO) to oxygen bound by hemoglobin A is 217 times greater than the ratio of these gas tensions in the equilibrium medium.’ This report shows that hemoglobin F has less preferential binding of CO over 02 than hemoglobin A. Because of this difference between adult and fetal hemoglobin the diffusion gradient for CO across the placenta can not be equated with the diff...

The human globin genes are among the most extensively characterized in the human genome, yet the details of the molecular events regulating normal human hemoglobin switching and the potential reactivation of fetal hemoglobin in adult hematopoietic cells remain elusive. Recent discoveries demonstrate physical interactions between the beta locus control region and the downstream structural gamma-...

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Methemoglobinemia is a dyshemoglobinemia characterized by cyanosis and reduced oxygen saturation with increased methemoglobin values. The etiology may be congenital or acquired, the latter being more common. We report case of full-term neonate who presented transient methemoglobinemia caused mutation in gamma chain fetal hemoglobin.

To determine the influence of cell cycle-specific agents on primate hematopoiesis and fetal hemoglobin production, two juvenile cynomolgus monkeys (Macaca fascicularis) were repeatedly bled to maintain their hemoglobins at approximately 6.5 g/dl and fetal hemoglobin levels at 3-5%. Six separate 5-d courses of hydroxyurea at 100 mg/kg per d were then administered over the next 200 d while phlebo...

A rationale for clinical trials of hydroxyurea (HU) treatment in sickle cell disease is that the agent increases red blood cell (RBC) fetal hemoglobin content. However, an additional effect of HU is to raise the mean corpuscular volume (MCV). To investigate the action of HU in a species that makes no electrophoretically distinguishable fetal hemoglobin, we treated dogs with the drug and compare...

Macaca nemestrina have two fetal hemoglobins which differ in the structures of their .y chains. Thus animals of this species, like man, appear to possess duplicate y-chain loci. In this study, the ontogenesis of hemoglobins in M. nemestrina was followed in animals ranging in age from the 60th day of gestation to adulthood. Fetuses in the 60th day of gestation had the two fetal hemoglobins and a...