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At least 19 recordsLinked to original sources
PubMed1979

On the chromatographic heterogeneity of human fetal hemoglobin.

Minor fetal hemoglobins in red cell hemolysates of newborn and adults with elevated levels of Hb F have been separated and quantitated by Biorex 70 column chromatography. In addition to Hb F1, other minor hemoglobin zones eluting before F1, pre-F1, and after F1, post-f1 have been observed. The relative amounts of the two pre-F1 zones and F1 are higher in the red cells of adults with 97--100% Hb F (homozygous hereditary persistence of fetal hemoglobin, homozygous deltabeta-thalassemia and homozygous beta0-thalassemia) than in the red cells of an adult with homozygous beta+-thalassemia with 66% Hb F, a child with a trisomy-D-13 having 38% Hb F, and in two newborn. Hb F was glycosylated in vitro with [14C]glucose or [14C] glucose 6-phosphate, and was acetylated using chicken reticulocyte lysate or a crude acetyltransferase preparation isolated from the same lysate with [14C]acetyl-CoA as substrate. Chromatographic analyses indicated that the Hb F1 zone can be formed both by glycosylation and acetylation of Hb F, and that pre-F1 zones can be products of the reaction of Hb F with phosphorylated glycolytic intermediates. Biosynthesis of minor hemoglobins in reticulocytes was studied with [14C]leucine in the presence and absence of cycloheximide and by pulse-chase. The resulting data indicate that Hb F1 synthesis is dependent upon Hb F synthesis and that the posttranslational modification may take place at an early stage in Hb F synthesis.

Acetylation↗
PubMed1976

Oxygen equilibrium characteristics of adult and fetal hemoglobin of Japanese monkey (Macaca fuscata).

Adult hemoglobin and fetal hemoglobin were obtained from Japanese monkey (Macaca fuscata) and their oxygen equilibrium characteristics were studied. (1) The oxygen affinity of fetal hemoglobin was higher than that of adult hemoglobin both in the presence and absence of 2,3-diphosphoglycerate. The presence of diphosphoglycerate lowers the oxygen affinity of adult hemoglobin much greater than does that of HbF and the diphosphoglycerate levels of red cells of adult and newborn monkeys are about the same. (2) The intensity of the Bohr effect, as expressed by -deltalogP50/deltapH, at pH 7.4 was in the order of fetal hemoglobin-diphosphoglycerate greater than adult hemoglobin-diphosphoglycerate greater than fetal hemoglobin greater than adult hemoglobin.

Animals↗
PubMed1979

The synthesis of fetal hemoglobin types in red blood cells and in BFU-E derived colonies from peripheral blood of patients with sickle cell anemia, beta+ - and delta beta-thalassemia, various forms of hereditary persistence of fetal hemoglobin, normal adults and newborn.

The biosynthesis of two types of human fetal hemoglobin (Hb F), namely Hb F with G gamma chains having glycine in position 136 and Hb F with A gamma chains having alanine in position 136, was studied in blood samples and in cultures of erythroid precursors from blood of patients with different hemoglobinopathies. High pressure liquid chromatography (HPLC) was adapted to allow the separation of the methionyl-containing tryptic peptides G gamma T-15 and A gamma T-15 (which include the Gly leads to Ala polymorphism at position 136) from a digest of microquantitites of 35S-methionyl labelled Hb F. This method was sensitive enough to quantitate the relative production of the G ygamma and A gamma chains by erythroid colonies derived from cloned Burst Forming Units (bfu-e) which were cultured for 16 days on methylcellulose. The production of Hb F in these colonies was generally higher than the level of Hb F in blood except for subjects with the G gamma A gamma-HPFH heterozygosity. The G gamma to A gamma ratio in the Nb F produced in cultures of cells from G gamma delta beta-thalassemia or G gamma-HPFH heterozygotes was lower and that from A gamma-HPFH heterosygotes was higher than the ratios in the Hb F of the corresponding peripheral blood cells. Mixtures of G gamma and A gamma chains were present in cell cultures of SS patients, beta+-thalassemia homozygotes and G gamma A gamma-HPFH heterozygotes in a ratio similar to that in the Hb F of mature red cells. These data suggest that erythroblasts in BFU-E derived colonies reactivate all available gamma chain structural genes, both in cis and in trans to the abnormal determinant. Hb F biosynthesis by adult blood samples concerns primarily the G gamma chains. This was particularly striking for blood samples in which erythroblasts were absent and the biosynthesis took place in fetal reticulocytes. Thus, the F-retuculocytes in blood of A gamma-HPFH heterozygotes with about 5% Hb F of the A gamma type produced primarily Hb F with G gamma chains. Similar differences were observed for G gamma A gamma-HPFH heterozygotes and, less strinkingly, for SS patients. A satisfactory explanation for this observation has not yet been obtained.

Adult↗
PubMed1979

Fetal hemoglobin (HbF) synthesis in baboons, Papio cynocephalus. Analysis of fetal and adult hemoglobin synthesis during fetal development.

Fetal hemoglobin (HbF) and adult hemoglobin (HbA) synthesis was studied in fetal baboons, Papio cynocephalus, to determine the normal pattern of hemoglobin production during fetal development. Fetuses ranging from 53 to 180 days gestation (term gestation 184 days) were used. Erythroid cells were incubated with 3H-L-leucine, and the rates of globin chain synthesis and the distribution of radioactivity into hemoglobin intermediates and completed hemoglobin molecules were determined. Gamma chain synthesis accounted for approximately 97% of the total nonalpha chain synthesis up to 140 days gestation; beta chain synthesis accounted for the remainder. After 140 days gestation, approximately equal quantities of gamma and beta chain were synthesized in the bone marrow. Prior to 140 days gestation, total alpha chain synthesis was 30% greater than total non-alpha chain synthesis, while there was balanced chain synthesis after 140 days gestation. During the period of excess alpha chain synthesis, fetal erythrocytes contained a large pool of alpha-hemoglobin (alpha chain with heme attached) molecules uncombined with beta or gamma chains. In view of the possibility that alpha chains may have a lower affinity for gamma chains than beta chains, excess alpha chain synthesis may be required to maintain low levels of free gamma chains.

Animals↗
PubMed1978

Mouse fetal hemoglobin.

Using isoelectric focusing, a fetal hemoglobin was found in the peripheral blood of C57BL/6 fetal mouse during the 14 to 20 days gestational period. In acid-urea polyacrylamide gel the pattern of this fetal hemoglobin was different from that of the adult hemoglobin. The mouse fetal hemoglobin was differentiated from the mouse adult hemoglobin by immunodiffusion reaction. It suggests that there is a transient fetal hemoglobin in the C57BL/6 mouse during gestational age.

Animals↗
PubMed1977

[Fetal hemoglobin in acute leukemias].

The question of fetal hemoglobin synthesis reactivation is a current topic both from the aspect of the genetic regulation of synthesis and from the aspect of the disorder of erythropoiesis in malignant diseases. The author presents the results of the quantitative determination of fetal hemoglobin in 84 children suffering from acute leukemias. The quantitation of HbF was performed by the method of alkalide-naturation and values of hemoglobin A2 by celulose-acetate electrophoresis. In acute lymphoblastic leukaemias fetal hemoglobin has been increased in 59% of the patients and in acute nonlymphoblastic leukaemias in 72% of the patients. The highest values of fetal hemoglobin were about 20%. The author considers that presence of fetal hemoglobin in these diseases cannot be a marker for estimation of remission and aggravation of the disease.

Acute Disease↗
PubMed1979

Cellular regulation of hemoglobin switching: evidence for inverse relationship between fetal hemoglobin synthesis and degree of maturity of human erythroid cells.

To investigate whether the level of maturity of human erythroid cells influences the expression of the fetal hemoglobin program, we studied the relative production of fetal (Hb F) and adult (Hb A) hemoglobins during the maturation of erythroid clones produced in vitro by adult or neonatal erythroid stem cells. In both the adult and the neonatal cell cultures, clones composed of immature erythroblasts showed a significantly higher Hb F/Hb A ratio compared to the mature clones. Culture conditions enhancing erythroid cell maturity (such as an increase in the level of erythropoietin or culture time) decreased the relative synthesis of Hb F in the maturing erythroid cells. Direct immunofluorescence studies demonstrated earlier production of Hb F compared with Hb A during maturation of adult-origin HbF-synthesizing clones. The findings show that the final expression of Hb F is influenced by the degree of maturity of the terminally differentiated cells and suggest that, in addition to regulation at the level of erythroid stem cells, there is control of Hb F expression during erythroblast maturation. The inverse relationship between Hb F expression and level of cell maturity suggests that a regulatory mechanism operating throughout the process of erythroid stem cell differentiation/erythroblast maturation decreases the potential of Hb F expression as the development of the erythroid cell advances.

Adult↗
PubMed1976

Regulation of the beta- and delta-hemoglobin genes. A family with hereditary persistent fetal hemoglobin and beta-thalassemia.

We have studied a 41-year-old black male with the simultaneous occurrence of hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia, and his two postadolescent sons, each heterozygous for one of the traits. The son heterozygous for beta-thalassemia had an elevated Hb A2, but the index case did not. The data from this pedigree indicate that the delta-allele trans to the beta-thalassemia gene was reponsible for the increased delta-chain production. Evidence from other cases of combination HPFH and beta-thalassemia indicates that regulation of the beta- and delta-chain production in beta-thalassemia is heterogeneous with respect to mechanism.

Adolescent↗
PubMed1979

Fetal hemoglobin: in vivo stimulation by D-thyroxine in adult marmosets.

Reactivation of fetal hemoglobin gene expressions was studied in new-world monkeys (marmosets). After a series of intraperitoneal injections of D-thyroxine, fetal hemoglobin production was increased in three experimental animals. Control animals were unaffected by the injection of the solvent. Because the percentage of cells containing fetal hemoglobin exceeded the total percentage of fetal hemoglobin, it was concluded that thyroid hormone influenced the synthesis of fetal hemoglobin rather than the development of a population of fetal cells.

Animals↗
PubMed1977

Modification of the acid elution technique for quantitation of fetal hemoglobin in individual erythrocytes.

A modification of the acid elution procedure for the demonstration of fetal hemoglobin in red cells using fast green stain is described. This technique not only permits improved visual estimation of the amount of fetal hemoglobin in red cells, but allows for the direct quantitation of fetal hemoglobin content of individual cells, using a scanning and integrating microdensitometer. As an application of this method, the distribution of fetal hemoglobin in populations of red cells of individuals was determined. Distributions were examined in sickle cell anemia patients with different proportions of fetal hemoglobin.

Anemia, Sickle Cell↗
PubMed1975

Oxidation-reduction potentials of human fetal hemoglobin and gamma chains. Effects of blocking sulfhydryl groups.

The oxidation-reduction equilibrium of the gamma chains of human fetal hemoglobin (Hb F) has been studied and compared with that of the alpha and beta chains of human adult hemoglobin (Hb A). The effects of the sulfhydryl (--SH) reagents, iodoacetate, iodoacetamide, and p-mercuribenzoate (PMB), on the three kinds of chains and on Hb F have been compared. The midpoint potentials (E-m) of all three sorts of chains are lower than those of tetrameric hemoglobin A or F. The E-m values of alpha chains are the lowest, E-m = 0.049 volt at 6 degrees, and are unaffected by pH change or by PMB treatment, at least from pH 6 to 8. The E-m values of beta-SH chains are higher; E-m = 0.102 volt at pH 7, decreasing to 0.050 volt at pH 8, both at 6 degrees. These results agree with those of Banerjee and Cassoly ((1969) J. Mol. Biol. 42, 337-349). They reported no effect of PMB on beta chains, but we find that 2 eq of PMB/chain raise E--M to 0.139 volt at pH 7 at 6 degrees, chiefly as the result of reaction at beta-93, not at beta-112. Carboxymethylation at beta-93 has an insignificant effect compared with that of PMB. The oxidation-reduction potential of gamma chains is similar to that of beta chains. E-m = 0.098 volt at pH 7 at 6 degrees, decreasing to 0.064 at pH 8 and 0.010 at pH 9. The effects of --SH reagents, reacting at position gamma-93 (the only --SH group present in gamma chains), are essentially the same as those seen with beta chains. The oxidation-reduction potential of Hb F is almost identical with that of Hb A, except for being 0.008 volt lower at pH 6 at 6 degrees. This agrees with the results reported by Flohe and Uehleke ((1966) Life Sci. 5, 1041-1045). PMB or iodoacetamide treatment lowers E-m by 0.02 to 0.03 volt, depending on the pH, from 6 to 9, in much the same way as previously reported for Hb A(Brunori, M., Taylor, J.F., Antonini, E., Wyman, J., and Rossi-Fanelli, A. (1967) J. Biol. Chem. 242, 2295-2300). The "residual oxidation Bohr effect" noted in Hb F can be attributed to the oxidation Bohr effect of the gamma chains. The apparent pK of the heme-linked water molecule was found at 25 degrees to be, for Hb F, 8.1; for gamma-SH chains, 7.85; for gamma-PMB chains, 8.35; and for gamma chains treated with iodoacetate, 7.80. Sedimentation coefficients, s-20, w, at a protein concentration of 5 mg/ml, were found to be, for fetal hemoglobin 4.09, for iodoacetamide-treated fetal hemoglobin 4.04, for PMB-treated fetal hemoglobin 3.41, for fetal gamma-SH chains 4.25, and for fetal gamma-PMB chains 3.08.

Adult↗
PubMed1977

Effects of testosterone and estradiol on ratios of adult to fetal hemoglobin in cell cultures of human fetal liver.

The effects of testosterone and 17beta-estradiol on the synthesis of fetal and adult hemoglobins have been studied using a short-term primary cell culture system of human fetal liver at midgestation. There was a significant 23% increase in incorporation of 59Fe into adult hemoglobin relative to the total after the addition of 5 X 10(-8)M testosterone. 17beta-Estradiol (10(-6)M) lowered the incorporation of 59Fe by 21%. beta-Globin chain synthesis, measured as 3H- or 14C-leucine incorporation into globin chains, was identical in control and testosterone-treated cells and only slightly lower when 17beta-estradiol was added. For this reason the observed changes in adult hemoglobin resulting from the action of testosterone and 17beta-estradiol are caused by an indirect effect either in the final hemoglobin assembly or by small changes in the gamma/alpha-chain ratio which may be undetected by the methodology used.

Cells, Cultured↗
PubMed1978

Semiquantitative computerized image analysis of fetal hemoglobin distribution patterns in sickle cell anemia and its variants.

Computerized, semiquantitative image analysis of 2913 erythrocytes from 29 young patients with sickle cell anemia and its variants was conducted utilizing a modified method for determination of fetal hemoglobin distribution by an acid elution procedure. Histograms of eight arbitrary levels of staining intensity, proportional to fetal hemoglobin levels, were analyzed in relationship to both computer-generated, mathematical parameters of erythrocytic shape abnormalities and clinical parameters of disease severity. Shifts in fetal hemoglobin distribution were observed in analysis of sequential specimens. An inverse correlation was observed between angularity of erythrocytes and their individual fetal hemoglobin content (p less than or equal to 0.05). A positive correlation was noted between growth percentiles and percentage erythrocyte ghosts by acid elution (p less than or equal to 0.01).

Anemia, Sickle Cell↗
PubMed1976

Absence of messenger RNA and gene DNA for beta-globin chains in hereditary persistence of fetal hemoglobin.

The relative amounts of alpha-amd beta-globin mRNA and globin gene DNA were measured in reticulocyte RNA and lymphocyte DNA of an individual with homozygous hereditary persistence of fetal hemoglobin whose red blood cells contain 100% fetal hemoglobin (hb F: alpha2gamma2.) Molecular hybridization assays used as probes full-length DNA copies of human alpha- and beta-globin messenger RNA. The results of these hybridization assays demonstrated the expected amounts of alpha-globin mRNA and gene DNA, but absence of beta-globin mRNA and absence of beta-globin gene DNA. In the individual studied, hereditary persistence of fetal hemoglobin is associated with total deletion of the beta-globin structural gene.

Child↗
PubMed1977

An unusual case of leukemia with high fetal hemoglobin: demonstration of abnormal hemoglobin synthesis localized in a red cell clone.

A high level of fetal hemoglobin was found in an 8-yr-old boy without any hematologic disorders except for a moderate anemia. The absence of hemoglobin abnormalities in the parents led us to suspect a latent malignant disease that, on follow-up, was confirmed to be myelomonocytic leukemia. Hemoglobin biosynthetic studies provided evidence of unbalanced synthesis of globin subunits by reticulocytes, while the production of non-alpha chains was equal to that of alpha chains in bone marrow cells. The expression of red cell antigen i was increased, while those of I, A, and A1 antigens were found to decrease progressively. Two populations of erythrocytes, A-positive and A-negative, were distinguished and could be separated by differential agglutination. Unbalanced globin chain synthesis, increased fetal hemoglobin, and antigenic changes of the membrane were shown to be restricted to the A-negative population. The biologic data were not entirely consistent with a genuine reversion to fetal erythropoiesis. The question remains of a polychromosomal lesion of either quiescent F cells or adult stem cells.

ABO Blood-Group System↗
PubMed1977

Fetal hemoglobin and alpha-fetoprotein in various malignancies.

Fetal hemoglobin (HbF) concentrations were measured by a radial immunodiffusion assay in 233 patients with various malignancies. In 96 of these, alpha-fetoprotein (AFP) was also measured by radioimmunoassay. The concentration of HbF exceeded 2 SDs above the normal mean in 39 of 233 patients, most notably in patients with leukemia, lymphomas, multiple myeloma and testicular tumors. The proportion of HbF was not correlated with the total hemoglobin concentration or with serum AFP concentration.

Fetal Hemoglobin↗