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

A simple and reliable method, utilizing capillary electrophoresis in uncoated capillaries in acidic isoelectric buffers, is reported for screening for thalassemia and other defects on the synthesis of human globin chains. A solution of 50 mM iminodiacetic acid (pI 2.23), containing 7 M urea and 0.5% hydroxyethylcellulose (apparent pH 3.2) is used as background electrolyte for fast separation of heme-free, denatured globin (alpha, beta and gamma) chains. Due to the low conductivity of such a buffer, high voltage gradients (600 V/cm) can be applied, thus reducing the separation time to only a few minutes. It is additionally shown that inclusion of 2% surfactant (Tween 20) in the background electrolyte induces the splitting of the gamma chains into two zones, called Agamma and Ggamma, which represent the products of two genes coding for Ala or Gly as residue 136 of the chain.
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PMID:Human globin chain separation by capillary electrophoresis in acidic isoelectric buffers. 971 53

A patient originating from Iraq was referred to our laboratory upon suspicion of a hemoglobinopathy. Routine hematological tests revealed a microcytic and slightly anemic phenotype with an elevated HbA2 suggestive of beta-thalassemia. Samples were obtained for several members of the family which upon examination revealed highly heterogeneous phenotypes that prompted us to investigate the case further. Sequencing of the beta-globin gene and alpha cluster mapping in the propositus and his brother showed a previously undescribed beta-globin variant:Hb Iraq-Halabja, beta10(A7) Ala-->Val (GCC-->GTC), associated with beta0-thalassemia IVS-2 nt1 G-->A and either alpha-thal-2-3.7 kb deletion (brother), or alpha-globin gene triplication anti-3.7 kb type (propositus). Detailed functional studies of the variant gave a normal oxygenation curve, a normal heterotopic action of 2,3 DPG, and normal heat stability and isopropanol precipitation tests. The variant shows a clear difference in migration properties compared to normal beta-chain only when run on PAGE urea Triton. As expected, alpha/beta-globin mRNA ratios were influenced by the concomitant presence of an alpha-globin gene pathology and the beta0 thalassemia and not by the presence of the beta-globin variant which apparently is clinically silent.
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PMID:Hb Iraq-Halabja beta10 (A7) Ala-->Val (GCC-->GTC): a new beta-chain silent variant in a family with multiple Hb disorders. 1039 11

Sodium 4-phenylbutyrate (PBA), a short-chain fatty acid, has been approved to treat patients with urea cycle enzyme deficiencies and is being evaluated in the management of sickle cell disease, thalassemia, cancer, and cystic fibrosis (CF). Because relatively little is known about the effects of PBA on the expression and function of the wild-type CF transmembrane conductance regulator (wt CFTR), the goal of this study was to examine the effects of PBA and related compounds on wt CFTR-mediated Cl(-) secretion. To this end, we studied Calu-3 cells, a human airway cell line that expresses endogenous wt CFTR and has a serous cell phenotype. We report that chronic treatment of Calu-3 cells with a high concentration (5 mM) of PBA, sodium butyrate, or sodium valproate but not of sodium acetate reduced basal and 8-(4-chlorophenylthio)-cAMP-stimulated Cl(-) secretion. Paradoxically, PBA enhanced CFTR protein expression 6- to 10-fold and increased the intensity of CFTR staining in the apical plasma membrane. PBA also increased protein expression of Na(+)-K(+)-ATPase. PBA reduced CFTR Cl(-) currents across the apical membrane but had no effect on Na(+)-K(+)-ATPase activity in the basolateral membrane. Thus a high concentration of PBA (5 mM) reduces Cl(-) secretion by inhibiting CFTR Cl(-) currents across the apical membrane. In contrast, lower therapeutic concentrations of PBA (0.05-2 mM) had no effect on cAMP-stimulated Cl(-) secretion across Calu-3 cells. We conclude that PBA concentrations in the therapeutic range are unlikely to have a negative effect on Cl(-) secretion. However, concentrations >5 mM might reduce transepithelial Cl(-) secretion by serous cells in submucosal glands in individuals expressing wt CFTR.
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PMID:PBA increases CFTR expression but at high doses inhibits Cl(-) secretion in Calu-3 airway epithelial cells. 1051 10

We report three children with tubulointerstitial renal failure following leptospirosis. All had acute nonoliguric renal failure with mild hypocalemia and mild metabolic acidosis. Maximum blood urea nitrogen (BUN) and creatinine were 217 and 7.1 mg/dl, respectively, on the 6th day of disease, and no patient required dialysis. They presented with acute febrile illness and dehydration, and required intravenous fluid supplements. Myalgia, vomiting, and bleeding were found in two children. Abdominal pain, arthralgia, diarrhea, and conjunctival suffusion were found in one child. Only one child, who had an underlying disease of beta-thalassemia/Hb E, had jaundice, hepatosplenomegaly, anemia, and thrombocytopenia. Penicillin treatment was given in one case. All recovered, with normal renal function. The leptospirosis complement fixation test was used to confirm diagnosis. L. batavia was considered the etiologic agent in two of the children.
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PMID:Tubulointerstitial renal failure in childhood leptospirosis. 1053 63

Beta-thalassemia, by its high frequency and its heterogeneity, constitutes a real problem of health in Tunisia. Prenatal diagnosis by DNA analysis represents the only reality for couples at risk. The denaturant gradient (urea and formamide) on polyacrylamide gel electrophoresis has been performed in our laboratory, using psoralen as chemical clamps. This method is simple, reliable, safe, rapid, without radioactivity and has a reasonable cost (chemical clamps). Even if it needs an informatic modelization in other laboratories, this method seems to be adapted to our economic and work conditions and to the molecular heterogeneity of the Tunisian beta-thalassemia. We present the results of an epidemiological molecular study on 75 patients with beta-thalassemia and the results of ten prenatal diagnosis. The molecular lesions codon 39 (C-T) and IVS1 nt2 (T-G) are the most frequent in our study. This technical approach provides genetic counselling for at risk families by offering prenatal diagnosis (reducing as possible the cost and the delay of the result) after prealable family study and identification of the mutation(s).
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PMID:[Molecular analysis and prenatal diagnosis of beta-thalassemia: about our experience in central Tunisia]. 1093 46

In dialysis patients beta-thalassemia is a cause of resistance to erythropoietin (EPO). The aim of the present study is to evaluate the relationship between the amount of circulating anomalous hemoglobin chain and EPO resistance in hemodialysis. Ten hemodialyzed patients with beta-thalassemia minor were studied. The mean hemoglobin level was 9.22 +/- 0.91 g/dl, the HbA2 ranging between 5.6 and 6.8%; the weekly EPO dose was 13,500 +/- 7,185 IU/week and significantly correlated with HbA2 (r = 0.965; p = 0.0001). When stratifying patients in two groups according to HbA2 level (LOW <6%, n = 4; HIGH >6%, n = 6; HbA2 levels, respectively, 5.7 +/- 0.1 and 6.4 +/- 0.3 g/dl, p = 0.002), it was evidenced that the need of EPO was 13,200 +/- 3,033 IU/week in LOW and 36,167 +/- 13,060 IU/week in HIGH (p < 0.001). The EPO Resistance Index in the two groups was 13.4 +/- 4.1 IU/kg BW/week/g Hb in LOW and 21.9 +/- 10.0 in HIGH (p < 0.05). No differences were evidenced between the two groups regarding age, dialysis, body weight, serum levels of urea nitrogen, creatinine, albumin, C-reactive protein, aluminum, ferritin, transferrin and parathyroid hormone. In conclusion, in patients with beta-thalassemia minor on chronic hemodialysis, the amount of anomalous hemoglobin chain directly correlate with EPO dose, strongly indicating the magnitude of resistance to erythropoietin.
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PMID:Relationship between resistance to erythropoietin and high anomalous hemoglobin levels in hemodialysis patients with beta-thalassemia minor. 1458 79

This paper demonstrates the diagnosis of beta-thalassemia by capillary electrophoresis in conjunction with laser-induced fluorescence using poly(ethylene oxide) (PEO) solutions in the presence of electroosmotic flow (EOF). During the electrophoretic separation, PEO solution entered a capillary from the anodic vial by EOF. The separation of a mixture of the polymerase chain reaction (PCR) products (330 and 334 base pairs) from a healthy person and a beta-thalassemia patient was accomplished within 15 min at 15 kV using 1.5% PEO containing 2 M urea at 30 degrees C. The electropherogram patterns instead of migration times were used to diagnose beta-thalassemia, with an accuracy of 100% for the analyses of 11 blood samples from suspected patients. After injecting a large volume of the mixture to the capillary filled with 800 mM Tris-borate buffer (pH 10.0), the DNA fragments stacked due to increases in viscosity and sieving when migrating into 1.5% PEO solution. As a result of improved sensitivity, only 15 PCR cycles were required when using 500 ng of DNA templates. The results shown in this study indicate the potential of this simple, rapid, and cost-effective method for the diagnosis of beta-thalassemia.
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PMID:Fast and sensitive diagnosis of thalassemia by capillary electrophoresis. 1511 99

Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under conditions associated with cystic fibrosis and liver injury. In the present study, we evaluated the neuroprotective effect of 4-PBA on cerebral ischemic injury. Pre- or post-treatment with 4-PBA at therapeutic doses attenuated infarction volume, hemispheric swelling, and apoptosis and improved neurological status in a mouse model of hypoxia-ischemia. Moreover, 4-PBA suppressed ER-mediated apoptosis by inhibiting eukaryotic initiation factor 2alpha phosphorylation, CCAAT/enhancer-binding protein homologous protein induction, and caspase-12 activation. In neuroblastoma neuro2a cells, 4-PBA reduced caspase-12 activation, DNA fragmentation, and cell death induced by hypoxia/reoxygenation. It protected against ER stress-induced but not mitochondria-mediated cell death. Additionally, 4-PBA inhibited the expression of inducible nitric-oxide synthase and tumor necrosis factor-alpha in primary cultured glial cells under hypoxia/reoxygenation. These results indicate that 4-PBA could protect against cerebral ischemia through inhibition of ER stress-mediated apoptosis and inflammation. Therefore, the multiple actions of 4-PBA may provide a strong effect in treatment of cerebral ischemia, and its use as a chemical chaperone would provide a novel approach for the treatment of stroke.
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PMID:Sodium 4-phenylbutyrate protects against cerebral ischemic injury. 1522 15

Hemoglobin (Hb) chains have been analyzed traditionally by cellulose acetate electrophoresis after sample extraction with acetone and denaturation with concentrated urea in order to detect thalassemia (Thal). A few capillary electrophoresis (CE) methods have been also described for separation of Hb chains also after sample extraction. We describe a CE method for analysis of Hb chains without sample preparation. Red blood cells were diluted (hemolyzed) in water and injected directly onto the capillary. The separation was performed in concentrated phosphate buffer at pH 12.6 and 2.15. Under these conditions of pH and buffer concentration, the chains were denatured and separated from the heme during electrophoresis. The common variants of the beta-chains, such as beta(S), beta(C), and beta(E), are also separated from each other. The intact Hb molecule is analyzed using the same sample and CE conditions but in an arginine-Tris buffer, pH 8.6. The data from the three separations are used to complement each other for interpretation of the presence of Hb variants and for thalassemia. The main advantages of this method are simplicity and speed. This method illustrates the flexibility and simplicity of the CE for analysis of the hemoglobinopathies.
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PMID:Simplified hemoglobin chain detection by capillary electrophoresis. 1569 Apr 30

Thalassemia is a systematic disease in which the renal involvement has not yet been scrupulously studied. In a cross-sectional study, the renal findings of 50 cases of thalassemia intermedia (group 1) were compared to 58 patients with thalassemia major (group 2). Blood urea nitrogen, serum creatinine, uric acid, calcium, phosphorus, urinalysis, and ultrasonographical findings were evaluated. Mean age was 18 +/- 3.0 in group 1 and 17 +/- 3.5 years in group 2. The mean of serum ferritin levels was 871 +/- 81.8 ng/ml in group 1 vs. 3503 +/- 201 ng/ml in thalassemia major (p > 5) was observed among 19 children (17.6%); 17 of them were in group 1. In contrast, children with thalassemia major had significantly higher serum creatinine (0.89 +/- 0.18 vs. 0.59 +/- 0.37 mg/dl, p < 0.05) and blood urea nitrogen values (12.14 +/- 5.58 vs. 13.85 +/- 3.54 mg/dl, p < 0.05). We conclude that significant renal involvement is not a frequent complication in children and young adults suffering from thalassemia. Hyperuricemia and microscopic hematuria are more common in thalassemia intermedia than thalassemia major. Microscopic hematuria in thalassemia intermedia might be related to either hypercalciuria or hyperuricosuria.
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PMID:Comparative evaluation of renal findings in Beta-thalassemia major and intermedia. 1831 Aug 68


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