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

Five cases of HbH disease were discovered in a large family of American Blacks. Anaemia was mild with PCV ranging from 0.275 to 0.405. The amount of HbH was 2--6%. Studies of haemoglobin synthesis in peripheral blood reticulocytes demonstrated marked deficits in alpha globin production with an average alpha/beta ratio of 0.31 (range 0.22--0.36). Eighteen additional family members had evidence of thalassaemia trait and were provisionally classified as either alpha-thal-1 (average MCV 65.2 fl; range 59--70) or alpha-thal-2 (average MCV 79.6 fl; range 74--88). A subject with altha-thal-1 trait had an alpha/beta ratio of 0.56; the average for five cases of alpha-thal-2 was 0.73. One other family member was thought to be homozygous for alpha-thal-2 trait and exhibited an MCV of 65 fl with an alpha/beta ratio of 0.5. These data reconfirm that in Blacks with alpha thalassaemia the proportion of HbH is lower and the severity of anaemia is less than in certain other racial groups, e.g. Southeast Asians. However, the degree of hypochromia and microcytosis and the imbalance in alpha and beta globin synthesis appear to be similar in Blacks and other races. These results suggest that the milder clinical course of HbH disease in Blacks is not a result of greater alpha globin production in that population of thalassaemics.
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PMID:Alpha thalassaemia in American blacks: a study of a family with five cases of haemoglobin H disease. 42 29

Globin mRNAs were isolated from circulating reticulocytes both from rats carrying a homozygous, recessive mutation causing a severe thalassemia-like syndrome and from normal rats. After first identifying the rat globin chains as alpha or beta chains, the translational products primed by both polysomal and nonpolysomal mRNAs in wheat germ 30000 x g supernatant were analyzed: the ratio of alpha to beta globin mRNAs found in polysomes isolated from mutant rats is identical to the ratio of their products synthesized in vivo while the ratio of these mRNAs is quite different in the nonpolysomal fraction, the latter being enriched in alpha globin mRNA. No difference is found in the ratio of alpha and beta globin mRNAs in the polysomal and nonpolysomal RNA isolated from normal rats, both being identical to the ratio of their products synthesized in vivo. One third of the total amount of mRNA found in mutant cells is not in polysomes as compared to only 6 percent for the mRNA from normal lysates. These results suggest that a translational control mechanism is involved although the decreased globin synthesis in b/b anemia can not be fully accounted for by its operation.
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PMID:Rat b/b anemia: translation of normal and anemic globin mRNA in wheat-germ cell-free system. 100 56

A patient with homozygous beta thalassemia of German/Italian descent was found to be doubly heterozygous for the common IVS1-110 G----A mutation of the beta globin gene and for a novel C----T mutation of the proximal CACCC-box of the beta globin gene promoter at position -87 relative to the transcription start site (cap). Transcription analysis in an HeLa cell transfection assay indicated a 45% to 51% residual activity of the gene with the -87 C----T mutation relative to normal, further underlining the physiologic role of the affected promoter element. The finding of an only moderately reduced transcriptional activity of the beta globin gene with the -87 C----T mutation corresponds well with the clinical phenotype of the reported patient, which is characterized by a late onset of symptoms, moderate anemia, and normal physical development. The ethnically German mother of the propositus has minimal anemia with only slightly changed red blood cell indices, which can also be explained by the relatively high residual activity of the gene with the -87 C----T mutation.
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PMID:Thalassemia intermedia: moderate reduction of beta globin gene transcriptional activity by a novel mutation of the proximal CACCC promoter element. 201 42

Hematological and clinical data are presented for a young Malay patient with a homozygous (delta beta)zero-thalassemic condition. His red blood cells contained 100% fetal hemoglobin with alpha and G gamma chains only. Detailed gene mapping defined a large deletion with a 5' end between the Aha III and Apa I sites, some 200-400 bp 5' to the A gamma globin gene and a 3' end beyond sequences 17-18 kb 3' to the beta globin gene. This G gamma (A gamma delta beta)zero-type of thalassemia is different from all the other six types described before. Comparison of the hematological data of this patient with those of homozygotes for either the Sicilian or Spanish types of G gamma A gamma (delta beta)zero-thalassemia showed no differences; all homozygotes have a moderate anemia which is accentuated by the relatively high oxygen affinity of the Hb F containing erythrocytes.
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PMID:Homozygosity for a new type of G gamma (A gamma delta beta)zero-thalassemia in a Malaysian male. 242 78

Clinical, hematologic and hemoglobin composition data on the first case of Hb 0-Arab in association with beta 0-thalassemia in Yugoslavia are reported here. The propositus was a 26-years-old female from Strumica who was admitted to the hospital for several times because of anemia, hepatosplenomegaly, occasional abdominal pains, malaise and fatigue. Laboratory results presented: Hb 10.0 g/dl, RBC 3.84.10(12)/L, PCV 0.260 l/l, MCV 68 fl, MCH 26 pg, reticulocyte count 1.8%, anisopoikilocytosis, polychromasis, numerous target cells, total bilirubin 2.1 mg/dl, (indirect 1.7 mg/dl), serum-Fe 32.3 microM/L. A starch gel electrophoresis of hemolysate provided evidence for the presence of abnormal hemoglobin (approximately 85%) and Hb F (approximately 15%); the Hb A was absent. Familial screening showed her father was heterozygous for the abnormal hemoglobin, whereas the mother was heterozygous for beta-thalassemia. In vitro biosynthesis disclosed a total absence of beta globin and reduced synthesis of beta x x and gamma globin. The alpha/beta x + gamma-globin ratio was 1.77 (normal, 1.0 + 0.1). Amino acid analysis revealed that lysine substituted for glutamic acid at the position one hundred twenty-one of the beta chain (= Hb 0-Arab or beta 121 Glu----Lys).
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PMID:[Hemoglobin O Arab in interaction with beta 0-thalassemia]. 273 98

Detailed gene mapping data are provided for members of a Yugoslavian and Canadian family with a thalassemia heterozygosity characterized by mild anemia with severe microcytosis and hypochromia, normal levels of Hb A2 and slightly raised Hb F levels. The condition in both families results from large deletions (minimally approximately 148 kb in the Yugoslavian family and minimally approximately 185 kb in the Canadian family), which include all functional and psi genes of the beta globin gene cluster. The Canadian propositus was a newborn baby who has been followed for nearly 2 years; severe anemia developed some 30-40 days after birth when the Hb F level was still 70%; recovery was evident at the age of 90 days when the Hb F level had decreased to 40%.
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PMID:Two new large deletions resulting in epsilon gamma delta beta-thalassemia. 313 75

We have analyzed the sequence of the beta globin gene of a chromosome that is linked to the occurrence of an inclusion body beta-thalassemia characterized in the heterozygote by moderate anemia, severe red cell abnormalities, splenomegaly, inclusion body formation, elevated Hb A2 levels, and an increased in vitro alpha/beta chain synthetic ratio. The data indicate a change in codon 114 from CTG (Leu) to -GG that resulted in a frameshift and the presumed synthesis of an abnormal beta chain that is 156 residues long with a completely different C-terminal amino acid sequence. The change in codon 114 gives a -GGGCCC- sequence that creates a new ApaI site; the resulting 2.6-kilobase fragment has been observed in all subjects with this thalassemia condition. Protein structural analyses failed to demonstrate any trace of the abnormal beta chain, even in reticulocytes and nucleated red cells that were isolated by density gradient centrifugation. The inclusion bodies appear to contain mainly normal alpha chains. It is assumed that the structure of the beta-Geneva chain prevents it from combining with normal alpha chains; this results in a rapid breakdown of the abnormal protein during the early stages of red cell maturation and an accumulation of free alpha chains.
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PMID:Inclusion body beta-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxy-terminus due to a modification in codon beta 114. 340 99

Using the spleen cells of mice infected with the anemia-inducing strain of Friend leukemia virus, an in vitro model system of erythropoiesis has been developed in which a homogeneous population of murine proerythroblasts terminally differentiates in response to erythropoietin (EP). The biochemical events involved in EP's capacity to maintain viability, induce hemoglobin production, and promote the development of the specialized erythrocyte membrane were studied during the 48-72 hour period required for proerythroblasts to differentiate into reticulocytes. The results show that EP increases glucose uptake and the syntheses of RNA and protein in the first few hours after exposure of the erythroblasts to the hormone. A coordinated production of heme, alpha and beta globin occurs later and peaks at about 48 hours. This peak corresponds to the time at which the majority of cells are undergoing enucleation and becoming reticulocytes. The syntheses of the erythrocyte membrane and membrane skeletal proteins are not coordinated, and multiple patterns of synthesis are found with respect to the time of EP exposure. A number of proteins are lost from the membrane fraction while the characteristic proteins of the mature erythrocyte become prominent in the membrane fraction of erythroid cells as they develop from reticulocytes into erythrocytes.
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PMID:Erythropoietin control of terminal erythroid differentiation: maintenance of cell viability, production of hemoglobin, and development of the erythrocyte membrane. 347 8

In two black families with the hereditary persistence of fetal hemoglobin (HPFH) gene there are eight A-F heterozygotes and two double heterozygotes for sickle cell trait and HPFH. These patients are clinically asymptomatic and have homogeneous acid elution smears. Measurement of globin chain synthesis in peripheral blood demonstrates balanced production of a alpha and non-alpha (beta plus gamma) chains. In these patients, the balance is achieved by increased gamma globin production and increased activity of the remaining beta globin allele. In two patients, one A-F and the other S-F there is also balanced globin synthesis in the bone marrow. In a double heterozygote for HPFH and beta-thalassemia, anemia (Hb: 11.5 g/100 ml) is associated with a moderate degree of globin chain imbalance. There is a correlation between balanced globin chain synthesis and the absence of anemia in patients with HPFH.
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PMID:Balanced globin chain synthesis in hereditary persistence of fetal hemoglobin. 484 53

The genetic polymorphism previously reported to be associated with the sickle-cell (beta S) gene in black U.S.A. citizens was studied in the population of two French West-Indies islands in order to evaluate its potential application to the antenatal diagnosis of sickle-cell anaemia. The polymorphism consists of a change in the DNA sequences located near the 3' end of the beta globin gene. The change can be detected by means of the restriction endonuclease Hpa I. When cellular DNA is digested with this enzyme, the beta globin gene is contained in a DNA fragment measuring either 7.6 or 13.0 kilobases (kb). In 70% of SS homozygous subjects in Martinique and 57% in Guadeloupe the beta S gene was carried by a 13.0 kb DNA fragment, whereas the normal beta A gene was carried by a 7.6 kb DNA fragment. This polymorphism would make it possible to detect the foetal beta S gene in the DNA of amniotic fluid cells by linkage analysis.
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PMID:[Antenatal diagnosis of sickle-cell anaemia by DNA analysis of amniotic fluid cells. A preliminary study in the French West-Indies (author's transl)]. 722 Mar 30


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