scholarly journals The Interaction of Hemoglobin E With β Thalassemia: A Study of Hemoglobin Synthesis in a Family of Mixed Burmese and Iranian Origin

Blood ◽  
1973 ◽  
Vol 42 (5) ◽  
pp. 783-791 ◽  
Author(s):  
Robert Feldman ◽  
Ronald F. Rieder
Keyword(s):  
Bone Marrow ◽  
Specific Activity ◽  
Family Members ◽  
Hemoglobin F ◽  
Hemoglobin E ◽  
Hemoglobin Synthesis ◽  
Abnormal Hemoglobin ◽  
Thalassemia Trait ◽  
Mixed Origin

Abstract A 5-yr-old girl with hemoglobin E-β thalassemia was discovered in a family of mixed origin. The father is Iranian (β-thalassemia trait) and the mother is Burmese (hemoglobin-E trait). Hemoglobin synthesis was studied in vitro in the blood of the proposita and family members. In the subjects with hemoglobin E trait the ratio of the quantity of hemoglobin A to hemoglobin E was 3:1. However. the βA/βE synthesis ratio in reticulocytes was in the range of 1.5-2.18, and the specific activity of βE was 31%-49% greater than βA, suggesting instability of hemoglobin E with preferential destruction of abnormal hemoglobin. The blood of the proposita exhibited only hemoglobin F and hemoglobin E and reticulocytes and bone marrow showed no βA synthesis. This Iranian β-thalassemia gene is therefore of the β° type. The βE/α synthesis ratio (approximately 0.74) in blood of the proposita was similar to the βA/α ratio in mildly affected relatives with thalassemia trait. These results suggest that the severity of the hemoglobin E-β thalassemia syndrome is attributable to both instability and defective synthesis of hemoglobin E in association with absent βA synthesis due to a β° thalassemia gene.

scholarly journals The in Vitro Synthesis of Hemoglobin by Human Bone Marrow in Thalassemia

Blood ◽  
1965 ◽  
Vol 25 (6) ◽  
pp. 897-906 ◽  
Author(s):  
THOMAS F. NECHELES ◽  
MANFRED STEINER ◽  
MARIO BALDINI
Keyword(s):  
Bone Marrow ◽  
Thalassemia Major ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Hemoglobin F ◽  
In Vitro Synthesis ◽  
Apparent Increase ◽  
Hemoglobin Synthesis ◽  
Thalassemia Trait

Abstract 1. A technic has been described for the in vitro measurement of hemoglobin synthesis by human bone marrow. The rate of synthesis of individual hemoglobins may be investigated in this system. 2. This technic has been used to measure the rate of synthesis of hemoglobin from patients with both thalassemia trait and thalassemia major. Hemoglobin A synthesis was found to be reduced in both, and to a greater extent in thalassemia major. An apparent increase in the rate of synthesis of hemoglobin F was also noted.

scholarly journals In vitro stimulation of primate hemoglobin synthesis by L-thyroxine

Blood ◽  
1977 ◽  
Vol 49 (3) ◽  
pp. 407-413 ◽  
Author(s):  
JE Fuhr ◽  
N Gengozian ◽  
M Overton
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Leucine Incorporation ◽  
Hemoglobin Synthesis ◽  
Globin Chains ◽  
Stimulation Of ◽  
Marrow Cells

Abstract Bone marrow cells from adult and abortus primates (marmosets) were incubated in vitro to determine their responsiveness to L-thyroxine. 3H- leucine incorporation into purified globin chains was the parameter assayed to determine responsiveness. Bone marrow from spontaneously aborted animals consistently was stimulated by the presence of physiologic levels of L-thyroxine. Bone marrow cells from adult animals were unaffected by the hormone.

scholarly journals Brief Report: The Di Guglielmo Syndrome: Studies in Hemoglobin Synthesis

Blood ◽  
1967 ◽  
Vol 29 (4) ◽  
pp. 550-553 ◽  
Author(s):  
THOMAS F. NECHELES ◽  
WILLIAM DAMESHEK
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Clinical Course ◽  
Marrow Cell ◽  
Cell Suspensions ◽  
In Vitro Synthesis ◽  
Hemoglobin Synthesis ◽  
Heme Synthesis ◽  
Globin Synthesis

Abstract The in vitro synthesis of heme and globin has been studied in bone marrow cell suspensions obtained from five patients with Di Guglielmo syndrome. In all, a defect of heme synthesis was demonstrated, but globin synthesis was greatly reduced in only two of the five; in these two, the clinical course was a rapid one.

A Novel Nr4a1GFP Reporter System Reveals That Nr4a1 Expression Identifies Long-Term Hematopoietic Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2339-2339
Author(s):  
Ruben Land ◽  
Trevor Barlowe ◽  
Shwetha Manjunath ◽  
Sophie Eiger ◽  
Matthew Gross ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Conflicts Of Interest ◽  
Family Members ◽  
Reporter System ◽  
Hematopoietic Stem ◽  
And Function

Abstract Abstract 2339 Recent studies have highlighted the importance of the NR4A nuclear receptor family (Nur77 (Nr4a1), Nurr1 (Nr4a3), Nor1 (Nr4a2)) in the regulation of hematopoiesis. In murine models, NR4A gene deficiencies lead to aberrant proliferation of hematopoietic stem cells, and can lead to acute myeloid leukemia (AML). NR4A gene deficiencies also appear to be a feature in human AML cells. In order to better understand the pattern of expression and function of NR4A family members during normal hematopoiesis, we have developed a novel reporter mouse where the Nr4a1 promoter drives GFP expression (Nr4a1GFP). Our analyses reveal a hierarchy in Nr4a1 expression among bone marrow hematopoietic stem cells: long-term (LT) HSC's (CD150+CD48-LSKs) express the highest levels of Nr4a1GFP, more mature HSC's and multilineage progenitor populations (CD150+CD48+ and CD150-CD48+ LSKs) express intermediate levels, and common myeloid progenitors (CMLs, defined as Lin-c-kit+sca-1-) express no Nr4a1GFP. Interestingly, circulating LSK's in the spleen express Nr4a1GFP at higher levels than their bone marrow counterparts. In support of data suggesting that Nr4a family members regulate quiescence, we find that 1) all hematopoietic stem cells that remain in the bone marrow after acute (36h) 5-FU treatment express Nr4a1GFP, 2) Nr4a1GFP expression decreases among circulating splenic LSKs 48 hours after treatment with PolyI:C, and 3) Nr4a1GFP expression increases markedly when stem cells are cultured in vitro under conditions that promote quiescence. We will use this novel system to more directly address the role of Nr4a1 expression in hematopoiesis by evaluating the cell cycle status and defining the reconstitution potential of HSC's on the basis of their Nr4a1GFP expression. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparison of the Action of 3H-Thymidine and Hydroxyurea on Testosterone-treated Hemopoietic Stem Cells

Blood ◽  
1972 ◽  
Vol 40 (2) ◽  
pp. 198-203 ◽  
Author(s):  
J. W. Byron
Keyword(s):  
Bone Marrow ◽  
Testosterone Propionate ◽  
Specific Activity ◽  
High Specific Activity ◽  
Cytotoxic Action ◽  
Mouse Bone Marrow ◽  
Onset Of Action ◽  
Normal Bone ◽  
Increased Sensitivity

Abstract The treatment of mice with a single, subcutaneous injection of either testosterone propionate or of 5β-dihydrotestosterone results in an increase in the sensitivity of spleen colony-forming cells (CFU-S) to the cytocidal action of high specific activity 3H-TdR. The effect is still present 24 hr after treatment. By 1 hr after exposure in vitro to 2.4 x 10-8M testosterone hydrogen succinate (THS), CFU-S from mouse bone marrow similarly become more sensitive to 3H-TdR. Sensitivity to the cytotoxic action of 10-3M hydroxyurea (HU) also increases. Compared with 3H-TdR sensitivity, however, there is a delay in the onset of sensitivity to HU. The lag is shortened if HU is added 1 hr after the addition of THS. The increased sensitivity of CFU-S to HU is prevented by deoxyribonucleoside, i.e., unlabeled thymidine, and the change during the first hour in 3H-TdR sensitivity is unaltered by the presence of HU. From these data, it is suggested that CFU-S from normal bone marrow contain precursors for DNA synthesis, e.g., deoxyribonucleotides. On the assumption that the action of HU is to inhibit the formation of deoxyribonucleotides from ribonucleotides, the delay in the onset of action of HU may depend on the exhaustion of such pools. It is postulated that CFU-S responding to THS are held up in a stage of the cell cycle close to the G1-S boundary.

scholarly journals In vitro stimulation of primate hemoglobin synthesis by L-thyroxine

Blood ◽  
1977 ◽  
Vol 49 (3) ◽  
pp. 407-413
Author(s):  
JE Fuhr ◽  
N Gengozian ◽  
M Overton
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Leucine Incorporation ◽  
Hemoglobin Synthesis ◽  
Globin Chains ◽  
Stimulation Of ◽  
Marrow Cells

Bone marrow cells from adult and abortus primates (marmosets) were incubated in vitro to determine their responsiveness to L-thyroxine. 3H- leucine incorporation into purified globin chains was the parameter assayed to determine responsiveness. Bone marrow from spontaneously aborted animals consistently was stimulated by the presence of physiologic levels of L-thyroxine. Bone marrow cells from adult animals were unaffected by the hormone.

scholarly journals Hemopoietic stress and fetal hemoglobin synthesis: comparative studies in vivo and in vitro

Blood ◽  
1979 ◽  
Vol 54 (5) ◽  
pp. 1176-1181 ◽  
Author(s):  
J DeSimone ◽  
P Heller ◽  
JG Adams
Keyword(s):  
Bone Marrow ◽  
Comparative Studies ◽  
Fetal Hemoglobin ◽  
Erythroid Cells ◽  
Hemoglobin Synthesis

Abstract Baboons exposed to acute hemolytic stres increase their production of fetal hemoglobin (HbF). Although the maximal in vivo HbF levels attained in 5 treated animals varied from 6.4% to 34.8%, their cultured bone marrow erythroid cells reverted to the fetal pattern of hemoglobin synthesis. These data suggest that HbF synthesis is modulated by the interaction of inhibiting and promoting factors, which is different among animals in vivo but equal in the cultures of their bone marrow erythroid cells.

scholarly journals Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1172-1176 ◽  
Author(s):  
Kesinee Chotivanich ◽  
Rachanee Udomsangpetch ◽  
Kovit Pattanapanyasat ◽  
Wirongrong Chierakul ◽  
Julie Simpson ◽  
...  
Keyword(s):  
Selectivity Index ◽  
Red Cells ◽  
The Other ◽  
Protective Effects ◽  
Parasite Invasion ◽  
Hemoglobin E ◽  
Balanced Polymorphism ◽  
Erythrocyte Invasion ◽  
Abnormal Hemoglobin

Hemoglobin E is very common in parts of Southeast Asia. The possible malaria protective effects of this and other inherited hemoglobin abnormalities prevalent in Thailand were assessed in a mixed erythrocyte invasion assay. In vitro, starting at 1% parasitemia,Plasmodium falciparum preferentially invaded normal (HbAA) compared to abnormal hemoglobin (HbH, AE, EE, HCS, β-thalassemia E) red cells (HRBCs). The median (range) ratio of parasitization of HRBCs (n = 109) compared to the controls of different major blood groups was 0.40 (0.08, 0.98), less than half that of the normal red cells (NRBCs) compared to their controls 0.88 (0.53, 1.4;P = .001). The median (range) parasitemia in the HRBCs was 2% (0.1%-9%) compared to 5.2% (1.2%-16.3%) in the NRBCs (P = .001). The proportion of the RBC population that is susceptible to malaria parasite invasion can be described by a selectivity index (SI; observed number of multiply invaded RBCs/number predicted). The heterozygote AE cells differed markedly from all the other cells tested with invasion restricted to approximately 25% of the RBCs; the median (range) SI was 3.8 (1-15) compared with 0.75 (0.1-0.9) for EE RBCs (P < .01). Despite their microcytosis, AE cells are functionally relatively normal in contrast to the RBCs from the other hemoglobinopathies studied. These findings suggest that HbAE erythrocytes have an unidentified membrane abnormality that renders the majority of the RBC population relatively resistant to invasion by P falciparum. This would not protect from uncomplicated malaria infections but would prevent the development of heavy parasite burdens and is consistent with the “Haldane” hypothesis of heterozygote protection against severe malaria for hemoglobin E.

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