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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chinese patient with hemoglobin (Hb) H and Hb New York is described. Unlike classical Hb H disease, the additional beta New York chain defect resulted in a more marked alpha/beta-globin chain imbalance in this patient with only one alpha-gene, accounting for her severe anemia (3.4-6.8 g/dl) during the steady state.
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PMID:Combination of three alpha-globin gene loci deletions and hemoglobin New York results in a severe hemoglobin H syndrome. 382 56

Splenic erythroblasts of mice infected with the anemia-inducing strain of Friend virus can be isolated in large numbers with less than 5% contamination with other cell types. In short-term culture, the isolated cells will initiate globin synthesis and undergo other aspects of terminal differentiation only if erythropoietin (EP) is added to the medium. An early effect of the hormone on these cells is stimulation of total RNA synthesis. EP also causes initiation of transcription of the beta-globin genes after a lag period of 4 to 6 h. By 6 h, the transcription rate of beta-globin RNA is enhanced threefold, and by 12 h, it is nearly maximal at ca. 20 times the level of control cells which received no EP. Transcription rates of alpha and beta-globin genes are approximately equal to each other throughout the period of terminal differentiation. In the splenic erythroblasts, the chromatin structure in the vicinity of the beta-major globin gene was analyzed with two nucleases during these transcription rate changes. No S1 nuclease-hypersensitive site is detectable near the gene. The beta-major gene is quite sensitive to DNase I in comparison with the albumin gene; however, the level of sensitivity is the same before EP addition as it is during maximal gene transcription after EP addition. Also, a hypersensitive site near the 5' cap site of the beta-major gene is quantitatively equivalent both before and after EP addition. Analysis of cytosine methylation at two sites upstream from the gene showed no changes upon induction of beta-globin gene transcription by EP. Thus, the initiation of beta-globin transcription by EP appears to be at some step after chromatin structural alteration such as synthesis, release, or activation of a specific transcription initiation factor.
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PMID:Control of globin gene transcription by erythropoietin in erythroblasts from friend virus-infected mice. 399 Jun 88

Mice of the mutant haplotype (Hbbs2) produce a variant beta-s globin (beta-s2major) which can be distinguished from beta-smajor and beta-sminor by cellulose acetate electrophoresis and ion exchange chromatography. Mice homozygous for this mutation were used to study the relative quantities of the mutant beta-s2major and normal beta-sminor globins specified by the two adult beta-globin genes of the Hbbs2 haplotype during development. At 11.5 days of gestation, beta-s2major comprises under 20% and beta-sminor over 80% of the adult beta-globin. The relative level of beta-sminor decreases through fetal development; at birth beta-sminor represents 33.7% of the beta-globin. The adult value of 71.0% beta-s2major and 29.0% beta-sminor globin is expressed in mice 6 days after birth. In mildly anemia alpha-thalassemic heterozygotes (Hbab2(th)/Hbab;Hbbs2/Hbbs2) the level of beta-sminor globin increases from 29.0 to 37.9%, but beta-sminor is elevated only slightly (29.0 to 33.9%) in asymptomatic beta-thalassemic heterozygotes (Hbab/Hbab;Hbbd3(th)Hbbs2). The relative quantity of beta-sminor is increased significantly (29.0 to 41.4%) in doubly heterozygous alpha-thalassemic, beta-thalassemic mice (Hbab2(th)/Hbab;Hbbd3(th)/Hbbs2). The relative levels of expression of the beta 1s2major and beta 2sminor globin genes of Hbbs2/Hbbs2 mice correlates well with the expression of the beta 1dmajor and beta 2dminor globin genes of Hbbd/Hbbd mice during development and in response to hematological stress caused by thalassemia. Expression of the beta 1sminor globin gene should not have been affected by the ENU-induced base substitution in the beta 1smajor gene. Therefore, we propose that the beta 1sminor gene is also expressed in mice of the Hbbs haplotype. The results also indicated that the two adult beta-globin genes of the Hbbs2 and, presumably, of the Hbbs haplotypes are regulated independently as are the beta 1dmajor and beta 2dminor genes of the Hbbd and Hbbp haplotypes.
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PMID:Use of a new mouse beta-globin haplotype (Hbbs2) to study hemoglobin expression during development. 407 48

In five patients with sickle beta-thalassemia there was balanced alpha- and beta-globin synthesis in the bone marrow and decreased total beta-chain synthesis relative to that of alpha-chain in the peripheral blood. These findings are similar to those in patients with simple beta-thalassemia trait. Despite a range of hemoglobin concentrations from 6.8 to 12.5 g/100 ml in the patients with sickle thalassemia, there was no evidence of a significant excess of alpha-chains in the red cells of the bone marrow which could contribute to the hemolysis and anemia. In patients heterozygous for beta-thalassemia the capacity to synthesize beta-chain decreases more rapidly than that for alpha-chain. In nonthalassemic subjects the rates of beta- and alpha-chain synthesis decrease equally as the red cell matures. The beta(S)- and beta(A)-chains serve as convenient markers for globin synthesis due to the nonthalassemic and thalassemic alleles in patients with sickle beta-thalassemia. The unbalanced globin synthesis in the peripheral blood of these patients is explained by the decrease in relative synthesis of beta(S)-chain, in comparison with that of alpha-chain. This instability is not present in sickle cell trait. The beta(A)-chain synthesis was only unstable in the two patients who had the most marked anemia. The major mechanism for achieving balanced globin production in the bone marrow in the presence of one thalassemic gene appears to be increased synthesis of beta-chain due to the nonthalassemic allele. In addition, there may be a decrease of total alpha-chain synthesis in some patients.
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PMID:Synthesis of globin chains in sickle -thalassemia. 468 90

In gamma-beta-thalassaemia, human gamma- and beta-globin gene expression is suppressed; this results in a severe anaemia in newborns which subsequently develops into a beta-thalassaemia syndrome in adult life. This hereditary disease is now shown to be the result of a deletion of at least 40,000 base pairs of the gammadeltabeta-globin gene locus. The gamma- and delta-globin genes are deleted in the affected chromosome but, surprisingly, the beta-globin gene is still present, together with a large segment of the DNA sequences flanking the gene on its 5'-side and the entire region on the 3'-side of the gene. Hence, a deletion of DNA far from the beta-globin gene results in the suppression of its activity.
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PMID:gamma-beta-Thalassaemia studies showing that deletion of the gamma- and delta-genes influences beta-globin gene expression in man. 615 59

Levels of fetal hemoglobin (HbF) bearing reticulocytes (F reticulocytes) range from 2% to 50% in patients with sickle cell (SS) anemia. To learn whether any portion of such variation in F cell production is regulated by loci genetically separable from the beta-globin gene cluster, percentages of F reticulocytes were compared in 59 sib pairs composed solely of SS members, including 40 pairs from Jamaica and 19 from the United States. We reasoned that differences in F reticulocyte levels might arise (1) from any of several kinds of artifact, (2) via half-sib status, or (3) because one or more genes regulating F cell production segregate separately from beta S. We minimized the role of artifact by assay of fresh samples from 84 SS individuals, including both members of 38 sib pairs. In 78 of the 84 subjects, serial values for percent F reticulocytes fell within 99.9% confidence limits or were alike by t test (P greater than or equal to .05). This left 32 sib pairs for which F reticulocyte levels in each member were reproducible. When sib-sib comparisons were limited to these 32 pairs, percentages of F reticulocytes were grossly dissimilar within 12 Jamaican and 3 American sibships. Within them, the probability that sibs were alike was always less than or equal to .005 and usually less than or equal to 10(-4). We next minimized the contribution of half-sibs among Jamaicans by a combination of paternity testing and sib-sib comparison of beta-globin region DNA restriction fragment length polymorphisms, especially among discordant pairs. We thereafter concluded that at least seven to eight Jamaican pairs were composed of reproducibly discordant full sibs. There is thus little doubt that there are genes regulating between-patient differences in F cell production that are separate from the beta-globin gene cluster. Still unanswered is (1) whether or not these genes are actually linked to beta S, (2) why F reticulocyte levels in Americans tend to be lower than in Jamaicans, and (3) whether or not differences in F cell production among SS patients are regulated by several major loci or by only one.
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PMID:Production of F cells in sickle cell anemia: regulation by a genetic locus or loci separate from the beta-globin gene cluster. 620 72

DNA polymorphisms are normal inherited variations in DNA that can often be used to document the inheritance of genes that produce disease. In this report we summarize our experience with prenatal diagnosis in 95 pregnancies in which the fetus was at risk for a hemoglobinopathy; the diagnosis was performed with use of DNA polymorphisms located so near the beta-globin gene that they are inherited along with that gene. Of the 95 pregnancies, 57 involved fetuses at risk for sickle-cell anemia, 32 fetuses at risk for beta-thalassemia, and 6 fetuses at risk for other beta-chain hemoglobinopathies. Diagnosis was achieved solely by analysis of DNA polymorphisms in cells recovered by amniocentesis in 82 cases (86 per cent) and was completed by fetoscopy and fetal-blood study in an additional 6 cases (6 per cent). Prenatal diagnosis was proved correct in all 78 cases that have been available for confirmation to date. Our experience demonstrates that DNA polymorphisms can be useful for the prenatal diagnosis of genetic diseases in which the basic defect cannot be directly detected.
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PMID:Prenatal diagnosis using DNA polymorphisms. Report on 95 pregnancies at risk for sickle-cell disease or beta-thalassemia. 630 Jun 77

Sickle-cell anemia results from an A leads to T transversion in the second nucleotide of codon 6 of the beta-globin gene. We now report an uncommon beta-thalassemia gene that contains a deletion of this nucleotide. Thus, one mutation (GAG leads to GTG) produces sickle-cell anemia, while the other (GAG leads to GG) eliminates beta-globin production. These data establish that different alterations affecting one specific nucleotide can produce either an abnormal hemoglobin or beta-thalassemia. Moreover, the nucleotide sequence comprising codons 6-8 of the beta-globin gene appears to be particularly susceptible to mutations affecting nucleotide number.
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PMID:beta-Thalassemia due to a deletion of the nucleotide which is substituted in the beta S-globin gene. 631 Sep 91

Previous studies of the Hpa I cleavage site-sickle cell hemoglobin gene linkage in various African populations suggested that the sickle gene arose independently more than once. In the present study we have performed restriction endonuclease haplotype analysis for the beta-globin-like gene cluster from four separate geographic areas in Africa, all of which possess the sickle gene. In Benin (Central West Africa) and Algeria (Arab North Africa) all chromosomes carrying the sickle gene possess an identical haplotype as defined by 11 different polymorphic restriction endonuclease sites within the 60-kilobase region of the beta-globin-like gene cluster. In the Central African Republic (Bantu-speaking Africa) and in Senegal (Atlantic West Africa) a very large proportion of the sickle gene chromosomes were associated with a haplotype specific for each country. Thus, three different haplotypes are shown to be associated with the sickle gene in Africa, and each is present at a very high frequency in geographically separate regions. Since the three haplotypes differ from each other by at least three sites residing both 5' and 3' to a putative hot spot for recombination, it is most likely that the sickle gene arose at least three times on separate preexisting chromosomal haplotypes. This may have implications for a better understanding of the variable nature of the expression of sickle cell anemia, because clinically relevant sequences (for example, gamma-globin gene regulatory sequences responsive to anemia) might be linked polymorphically to these haplotypes.
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PMID:Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. 658 11

Mouse bone marrow cells infected in vitro with the anemia strain of Friend leukemia virus from large clusters (bursts) of erythroblasts after 5 days in culture in methylcellulose medium. Two types of erythroblast populations can be isolated from bursts of infected cells by manipulation of the culture conditions. One type of erythroblast, which is obtained when erythropoietin (EP) is added to the culture, has proliferated and undergoes differentiation to become an erythrocyte. The second type of erythroblast, which is obtained when no EP is added to the culture, is the product of extensive proliferation, but it fails to undergo the terminal stages of erythroblast differentiation. Comparisons of these two types of erythroblasts demonstrate that specific EP effects include changes in the nucleus, cytoplasm, and membrane of the treated cells. Those events of erythroid differentiation shown to be directed by EP were extrusion of the nucleus from the erythroblast, induction of uroporphyrinogen I synthetase activity, increased iron incorporation into protoporphyrin, synthesis of alpha- and beta-globin polypeptides due largely to increased mRNA production, and synthesis and incorporation of spectrin into the cell membrane. In this system, EP promotes these effects without observable stimulation of progenitor proliferation in addition to that caused by the virus alone. Thus, the role of EP in terminal erythrocyte differentiation is not simply that of an erythroid-specific mitogen.
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PMID:Specific differentiation events induced by erythropoietin in cells infected in vitro with the anemia strain of Friend virus. 695 15


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