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...

We report here that compound heterozygosity for hemoglobin Korle-Bu (HbKB) and HbC (j36 Glu + Lys) is associated with moderate chronic hemolytic anemia with microcytosis. To understand the pathogenesis of this syndrome, we have studied the effect of Hb Korle-Bu (KB = 873 Asp + Asn) on the crystallization of HbC. We have previously established that fetal Hb (HbF) inhibits the crystallization of ...

Interferons have the ability to enhance or diminish the expression of specific genes and have been shown to affect the proliferation of certain cells. Here, the effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblas...

Adult erythroid progenitors produce significantly higher fetal hemoglobin (HbF) levels in cultures containing fetal calf serum (FCS) and erythropoietin (Ep) than in vivo. The precise mechanisms for this increased HbF production in culture have not been elucidated. We examined HbF biosynthesis by enriched human progenitors in serum-free (SF) culture. We measured globin chain biosynthesis by comb...

Erythrocyte dehydration is an important feature of sickle cell disease, leading to increased sickle hemoglobin polymerization and decreased red blood cell survival. Substantial in vivo dehydration appears to occur in reticulocytes or in an even younger subset of reticulocytes that are positive for transferrin receptor. Previous studies have suggested both sickling-dependent and sickling-indepen...

We have studied the effect of transforming growth factor beta (TGFbeta) on erythropoiesis in cultures from adult peripheral blood, using flow cytometric enumeration of fetal hemoglobin (HbF)-containing cells. TGFbeta caused a dramatic increase in the proportions of cells that accumulated HbF together with adult hemoglobin (HbA) (F+A+ cells). This highly significant (P <.0001) increase in F+ cel...

Diamond-Blackfan anemia (DBA) is a congenital macrocytic anemia characterized by severely reduced erythroid precursors with normal megakaryocytic and granulocytic differentiation.1 There is also reticulocytopenia and increased red blood cell (RBC) fetal hemoglobin (HbF).1 About 25% of patients harbor a mutation on chromosome 19 that involves the gene encoding ribosomal protein S19.1 Many patien...

Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocy...

higher MetHb values in the presence of HbF. For MetHb concentrations of 15% or less, i.e., values most likely to be encountered clinically with NO therapy, the Corning 270, in agreement with the study carried out previously (5), was unaffected by the presence of HbF in the umbilical cord sample (P 5 0.7380). By contrast, the Chiron 800 showed a constant error to significantly higher MetHb (P 5 ...

Preeclampsia (PE) complicates 3-8% of all pregnancies and manifests clinically as hypertension and proteinuria in the second half of gestation. The pathogenesis of PE is not fully understood but recent studies have described the involvement of cell-free fetal hemoglobin (HbF). Hypothesizing that PE is associated with prolonged hemolysis we have studied the response of the cell-free Hb- and heme...