Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteolytic degradation of labelled pyromycyl polypeptides was investigated in human intact erythroid cells derived from the bone marrow of eight non-thalassaemic patients and the peripheral blood of eleven thalassaemics (eight splenectomized beta thalassaemia heterozygotes and three sickle-cell beta thalassaemics). These abnormal polypeptides are rapidly degraded to soluble trichloroacetic-acid (TCA) fragments with a half-life of 12 min both in bone marrow and peripheral blood. This comes very close to the half-life reported for the puromycyl peptide degradative system in rabbit reticulocytes (15 min). The relationship of the present proteolytic system to the ATP-dependent one, described in rabbit reticulocytes, and to that responsible for the free alpha-chain degradation in beta thalassaemia is discussed.
 ...
PMID:Rapid proteolysis of puromycyl peptides in non-thalassaemic and thalassaemic erythroid cells. 643 47

Erythrocyte protoporphyrin (EP) was measured in 50 normal control subjects, 22 iron-responsive anemic subjects, and in 106 patients with thalassemic diseases. All normal subjects had EP of less than 80 micrograms/dL red blood cells, whereas all iron-deficiency subjects had EP of more than 80 micrograms/dL red blood cells. Six of 22 heterozygotes for thalassemias had elevated EP, and all of these had transferrin iron saturation of less than 16%, reflecting a complicating iron deficiency. Among 52 patients with beta-thalassemia/hemoglobin (Hb) E disease, 26.9% had elevated EP levels, and among 32 patients with Hb H disease, 40.6% had elevated EP. These elevated EP levels were associated with transferrin iron saturation between 18 and 44%. In none of the thalassemic patients with transferrin iron saturation above 44% was EP elevated. These findings suggest that elevation of EP in some thalassemic patients causally is related to iron supply inadequate for the massively expanded erythropoiesis. This relative iron deficiency in thalassemia occurs at a transferrin iron saturation level usually considered to be normal. These relationships demonstrate the need for an increased iron supply in patients with erythroid marrow hyperplasia, if erythropoiesis is to proceed at maximal rates.
 ...
PMID:Increased red blood cell protoporphyrin in thalassemia: a result of relative iron deficiency. 646 95

To perform a systematic analysis of beta-thalassemia genes among Chinese, we have determined the DNA haplotype in the beta-globin gene region of 37 Chinese beta-thalassemia chromosomes. Only four haplotypes were found. Blot hybridization analysis of erythroid RNA from patients homozygous for haplotypes 1, 2, and 3 demonstrated different patterns, suggesting that a different mutation was associated with each haplotype. The mutation associated with haplotype 1 was a C----T substitution at IVS-2, position 654. This mutation produces a new donor splice site and leads to formation of a beta-globin RNA with an insertion of 73 nucleotides. The mutation associated with haplotype 2 was a nucleotide insertion of A between codons 71 and 72, which results in a frameshift and premature termination of beta-globin synthesis. Haplotype analysis suggests that these two mutations may account for up to 85% of beta-thalassemia genes in this ethnic group. The haplotype 3 gene contained a transcriptional "TATA" box mutation that has been previously reported. Oligonucleotide hybridization demonstrated that the mutation associated with haplotype 4 was the same IVS-1 position 5 substitution commonly observed among beta-thalassemia genes in Asian Indians. Since haplotype 4 of Chinese differs at polymorphic sites on either side of the IVS-1 position 5 mutation from the haplotype associated with this mutation in Indians, the mutation presumably arose independently in these two populations.
 ...
PMID:beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects. 658 31

The influence of splenectomy on erythroid burst colony formation by peripheral blood mononuclear cells from 10 patients (four with hereditary spherocytosis, two with beta-thalassaemia major, two with Hodgkin's disease and two with idiopathic thrombocytopenic purpura) was studied. In every instance splenectomy was followed by a lowering of blood BFU-E. The post-splenectomy levels ranged from 0 to 30% of the preoperative levels. Mononuclear cells from the spleens of eight patients were cultured and found to contain numerous BFU-E. The total quantity of BFU-E in the whole blood and in the spleen of the patients was generally of the same order of magnitude. The number of splenic BFU-E did not correlate with spleen size. Splenic BFU-E differed from peripheral blood BFU-E in that they were more sensitive to erythropoietin (Ep) and in that they failed to respond to burst promoting activity (BPA) produced by preincubating the spleen mononuclear cells with phytohaemagglutinin M (PHA). In contrast, media conditioned by PHA-treated spleen cells contained BPA active on peripheral blood BFU-E from normal individuals. These data suggest that the spleen may have an influence on the numbers and functional properties of BFU-E.
 ...
PMID:The relationship between human spleen and blood erythroid burstforming units (BFU-E). 668 75

A variable rate of iron loading, reaching toxic levels in some patients, was seen in a series of non-transfused patients with beta thalassaemia intermedia or sideroblastic anaemia. The degree of anaemia was a poor guide to the risk of iron overload. However the extent of erythroid hyperplasia, judged by ferrokinetic studies or more simply by bone marrow aspiration, was useful in predicting both the rate of iron loading and the need for iron chelation therapy.
 ...
PMID:Iron absorption in non-transfused iron loading anaemias: prediction of risk for iron loading, and response to iron chelation treatment, in beta thalassaemia intermedia and congenital sideroblastic anaemias. 672 53

Hematological data and globin synthesis studies in 8 alpha-thalassemic children whose parents are from various regions in the Middle East are reported. All patients were devoid of Hb H. 5 of them had mild anemia, hypochromia and microcytosis and their blood alpha-/non-alpha-globin radioactivity ratios ranged between 0.56 and 0.75. The other 3 patients were hematologically normal with blood radioactivity ratios between 0.77 and 0.88. Bone marrow studies showed balanced globin chain synthesis for 6 of the patients and relatively more alpha-globin synthesis than in the blood for the remaining 2. The decrease in the relative synthesis of alpha-globin on erythroid cell maturation may relate to the molecular basis of alpha-thalassemia in the Middle East.
 ...
PMID:Balanced bone marrow globin synthesis in mideastern alpha-thalassemia. 677 46

Nucleated bone marrow cells from normal individuals and from three patients with homozygous beta+-thalassemia were pulse-labeled with tritiated nucleosides. The processing of the newly synthesized globin mRNA precursors was monitored by inhibiting additional transcription with actinomycin D for 30 min. Human beta-globin mRNA is derived from its precursor via a series of reactions that generate processing intermediates. In nonthalassemic cells the precursor is processed efficiently to mature mRNA during the chase. In contrast, in beta+-thalassemic cells the processing of beta-globin RNA is defective. In one patient the beta-globin mRNA precursor turns over during the chase, but some of the intermediate RNAs accumulate and are not processed to mRNA. In two other patients a large fraction of the precursor and intermediate RNAs is not processed to mRNA. The alpha-globin mRNA precursor and intermediates are processed efficiently to mRNA-sized molecules in thalassemic and normal cells. The reduction in the rate of beta-globin but not alpha-globin RNA processing accounts for the alpha/beta globin mRNA imbalance in thalassemic erythroid cells. We discuss the possibility that the genetic lesions in beta+-thalassemia are at splicing signal sites within intervening sequences of the beta-globin gene.
 ...
PMID:Processing of human beta-globin mRNA precursor to mRNA is defective in three patients with beta+-thalassemia. 693 79

Three types of mice with globin gene mutations, called 352HB, 27HB, and Hbath-J, appear to be true animal models of human thalassemia. Expression of the alpha-globin genes in three stocks of mice, each one heterozygous for one of the alpha-globin mutations, was examined at the polypeptide, RNA, and DNA levels. alpha-Globin polypeptide chains, relative to beta-globin chains in heterozygous thalassemic mice, are present at approximately 80% of normal. The ratios of alpha-globin to beta-globin RNA sequences are also 75-80% of normal, exactly reflecting the alpha-globin to beta-globin chain ratios. In the case of mutant 352HB, at least one alpha-globin gene is deleted. Thalassemic mouse erythroid cells appear to compensate partially for the loss of half of their alpha-globin genes.
 ...
PMID:Three mouse models of human thalassemia. 694 54

We have developed a method that permits rapid identification of the consequences of mutations that alter beta-globin RNA processing in erythroid cells. S1 nuclease mapping techniques were used to analyze total bone marrow RNA obtained fron 15 patients who are clinically homozygous for beta-thalassemia and from 5 patients with erythroid hyperplasia from other causes. This analysis was facilitated by the use of single-stranded uniformly labeled DNA probes of high specific activity that were prepared by using recombinant phage M13-beta-globin DNA templates. Two abnormalities of RNA processing were found to occur with high frequency in these patients. Nine thalassemic patients were found to have increased levels of an RNA species that retains all sequences transcribed from intervening sequence 1, implying the presence of mutations that decrease the correct splicing of this intron. Seven of 15 thalassemic patients were found to have an abnormally processed RNA species that retains 19 nucleotides transcribed from the 3' end of intron 1; this abnormality is caused by the G leads to A substitution in intron 1 that is known to create an alternative splice acceptor site.
 ...
PMID:RNA processing errors in patients with beta-thalassemia. 695 87

In mild beta thalassemia hemoglobin levels are much higher than in severe beta thalassemia, yet black patients with the mild syndrome are as deficient in beta chain synthesis as severe thalassemia patients. The following studies were undertaken to determine if differences in the precipitation of excess alpha chain distinguishes these two groups of beta thalassemia homozygotes. The percentages of radioactive globin chain bound to erythroid cell stroma were determined in mild and severe thalassemia patients. Only the cells of splenectomized severe patients contained large amounts of stroma-bound globin radioactivity, the percentages in five such patients ranging from 6.7 to 13.9 (mean = 9.9). In four splenectomized patients with mild thalassemia the percentages ranged from 1.0 to 3.5 (mean = 1.9; p less than 0.005). This is the first observed difference in globin chain metabolism between these two groups of patients.
 ...
PMID:Soluble and stroma-bound globin chains in mild and severe beta thalassemia. 714 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>