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)

The present minireview summarizes recent developments in the field of DNA separations by capillary zone electrophoresis (CZE), as developed by our group. Separation of antisense oligonucleotides in sieving liquid polymers in isoelectric buffers is discussed first. It is shown that the use of isoelectric buffers permits very high voltage gradients (up to 1000 V cm-1) with much reduced transit times and increased resolution of all truncated and failed sequences. Oligonucleotides can also be analysed by zone electrophoresis against a stationary pH gradient (typically a pH 6.5-10 range): if injected at the alkaline end, the sample components experience stacking and zone sharpening due to modulation of charge as the oligonucleotides move along the pH gradient. Oligonucleotides having the same length, but differing by one single nucleotide in the chain, can be separated in free solution (i.e. in the absence of a sieving matrix) at strongly acidic pH values (pH 3.0-3.3) where charge differences due to base protonation are maximized. By working in free solution, it has also been possible to measure accurately the free mobility of DNAs, shown to reach a constant value of 3.75 +/- 0.04 10(-4) cm2 V-1 s-1 at 25 degrees C and in Tris-acetate-EDTA buffer, pH 8.3, above a critical length of ca. 400 base pairs. Finally, detection of point mutations in human genomic DNA is proven to be feasible in nonisocratic CZE, by running temperature-programmed CZE. The temperature gradient is activated within the capillary lumen by voltage ramps during the run, by exploiting joule effects. This technique has been proven to work for all point mutants, from low-, to intermediate-, to high-melters and has been applied to a number of point mutants in cystic fibrosis and thalassemia.
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PMID:Recent advances in capillary zone electrophoresis of DNA. 962 82

Patients with homozygous beta-thalassemia are chronically transfused and, if not assiduously chelated, are at risk for cardiac dysfunction. Available data suggest that even in optimally chelated patients, cardiac pathology is abnormal secondary to iron deposition, fibrosis, hypertrophy, and the structural effects of chronic anemia. Evidence of myopericarditis may also be found. Cardiac performance is usually only subtly affected, primarily with diastolic abnormalities not routinely detected on echocardiograms or nuclear scan. In poorly chelated patients, severe heart failure occurs and is easily predictable but invariably fatal, despite treatment with diuretics, vasodilators, inotropes, and antiarrhythmics. Based on successful prevention of heart failure with ACE inhibitors in other forms of cardiomyopathy, we suggest multicenter trials to explore methods to stabilize cardiac function in patients at risk for iron-induced heart disease. Long-term adverse effects of iron deposition, diastolic dysfunction, and abnormal hormone regulation need to be quantitated in patients reaching their third and fourth decades when the potential for ischemic cardiac disease could compound cardiac dysfunction.
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PMID:Diagnosis and management of iron-induced heart disease in Cooley's anemia. 966 46

We have developed a method for the separation and quantitation of human alpha-, beta-, and gamma-globins utilizing cellulose acetate electrophoresis. The relative rates of synthesis of globin chains in reticulocytes in peripheral blood is determined by: (i) incubating intact cells with [35S]methionine; (ii) preparing globin from the hemolysates; (iii) performing electrophoresis of the globin on cellulose acetate strips; and (iv) autoradiography or direct determination of the radioactivity incorporated into each globin chain. The method is simple and rapid, requires only small amounts of hemolysate (30 micrograms of globin), and provides excellent resolution and reproducible quantitation of alpha-, beta A-, beta S-, and gamma-globin chains for up to 24 peripheral blood samples at one time. Measurements by this method in patients with thalassemia variants and sickle-cell disorders correlate well with analysis of the same samples by carboxymethyl cellulose chromatography. This methodology may permit more widespread analysis of globin synthesis in the thalassemia syndromes and may also be useful in the analysis of globins synthesized from human globin mRNA in cell-free systems.
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PMID:Quantitation of human globin chain synthesis by cellulose acetate electrophoresis. 976 93

Different electrophoretic and chromatographic techniques are described in the literature for the estimation of HbA2 levels. We compared the fast protein liquid chromatography (FPLC) technique with the conventional cellulose acetate electrophoresis (CAE) used routinely in most laboratories. Ninety five individuals from high risk groups were screened for beta-thalassaemia trait by both the techniques. The cut-off value for the diagnosis of beta-thalassaemia trait by both the techniques was 3.8 per cent and 27 heterozygotes were identified. As both techniques gave comparable results, CAE could be the cost effective method of choice for routine screening for beta-thalassaemia trait.
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PMID:Comparison of FPLC with cellulose acetate electrophoresis for the diagnosis of beta-thalassaemia trait. 980 44

Screening of the university students for hemoglobinopathies detected 153 patients with various hemoglobin abnormalities; 69 with Hb AS, 3 with Hb S-beta-thalassemia, 4 with Hb S-alpha-thalassemia, 3 with hb SC, 1 with Hb SK, 1 with Hb CC, 38 with Hb AC, 1 with Hb A O Arab, 4 with Hb EE, 25 with Hb AE, 1 with Hb AD, 1 with Hb AI, 1 with beta-thalassemia major, and 1 with beta-thalassemia minor. The most grave disease was observed in a child with Hb S-beta-thalassemia and in a youth with beta-thalassemia major. The patterns of Hb SC disease varied. The majority of heterozygote carriers of Hb S, Hb C, Hb E, etc. were healthy. A total of 7000 students were screened by express electrophoresis on cellulose acetate films. more than 400 subjects with abnormal hemoglobins were detected, the most numerous of which were heterozygote carriers of Hb S (Hb AS).
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PMID:[Hemoglobinopathies in students at the Russian University of the Friendship of Peoples]. 1039 34

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 the analysis of a beta-thalassaemia gene involving three bases in codons 4/5 and 6 (ACT CCT GAG-> ACA TCT TAG) in a confirmed carrier whose child had beta-thalassaemia major. The fragment of the gene carrying the mutation was detected by denaturing gradient gel electrophoresis (DGGE) using GC clamped primers, followed by direct sequencing. DGGE analysis indicated that one gene was the wild type (normal) while the sequence changes observed were all in the other gene causing beta-thalassaemia major in the child. This confirms a single case report from Lucknow (UP) and adds to the beta-thalassaemia mutations identified in the beta-globin gene in India and will help in the thalassaemia control programme.
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PMID:A beta-thalassaemia allele with 3 base substitution in codons 4/5 & 6 (ACT CCT GAG-> ACA TCT TAG) detected by denaturing gradient gel electrophoresis & sequencing. 1079 90

A case of hemoglobin H disease in combination with hemoglobin Constant Spring and a beta-globin chain variant is reported in a 3-yr-old Thai girl. On routine cellulose acetate electrophoresis, one abnormal band in addition to the hemoglobins A, A2, H, Bart's and Constant Spring was detected. The amount of this abnormal band movement towards more anodic to the hemoglobin A was 35.7%. DNA analysis of the alpha-globin gene cluster by polymerase chain reaction (PCR) revealed a combination of defects caused by the SEA-type alpha-thalassemia 1 and the alpha-Constant Spring gene. Analysis of beta-globin gene by PCR and DNA sequencing also detected the heterozygosity for the GGC-GAC mutation at codon 56, leading to a substitution of aspartic acid for glycine resulting in the hemoglobin J Bangkok. The hematologic data of this unusual case of hemoglobin H disease are presented and compared with two compound heterozygotes for hemoglobin J Bangkok and alpha-thalassemia 1 found in the patient's father and grandfather. A simple DNA assay based on an allele-specific PCR for rapid diagnosis of the hemoglobin J Bangkok is also described.
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PMID:Atypical hemoglobin H disease in a Thai patient resulting from a combination of alpha-thalassemia 1 and hemoglobin Constant Spring with hemoglobin J Bangkok heterozygosity. 1142 10

We report a new unstable variant identified in three carriers of a family from East Sicily; it was named Hb Bronte after the place from which the family originated. DNA sequencing from nucleotides -181 to +894 (alpha1) and to +884 (alpha2) revealed a GTG-->GGG substitution at codon 93 of the alpha2-globin gene. The MCV and MCH values were at the lower end of the normal range in the carriers. On cation exchange high performance liquid chromatography (HPLC), the Hb A2 level was apparently increased to around 6%, and a small abnormal peak (0.3-0.4%) was detected after Hb A2. Two abnormal bands were detected by cellulose acetate electrophoresis: a major band (about 3-4%) migrated between Hb A and Hb F; a minor band (<1%) migrated between Hb A2 and carbonic anhydrase. Normal values of Hb A2 were detected by DEAE microchromatography. On reversed phase HPLC the variant chain was not detected, and most likely it was eluted with the alpha chain peak. The isopropanol stability test was very slightly positive in the carriers. Hemolytic symptoms were absent with the exception of indirect bilirubin, which was at high borderline in 2/3 carriers. In biosynthesis in vitro, the specific activity of the alpha chains was much higher than that of the beta-globin chains, and the alpha/beta biosynthetic ratio in the mother and proband was of the beta-thalassemia (thal) type (2.24 and 2.54, respectively). Time course experiments showed that the increase of the 3H-specific activity of the peak containing normal and variant alpha chains was not linear and was much higher than that of beta chains; moreover, the alpha/beta biosynthetic ratio varied during the 2 hours incubation.
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PMID:Hb Bronte or alpha93(FG5)Val-->Gly: a new unstable variant of the alpha2-globin gene, associated with a mild alpha(+)-thalassemia phenotype. 1290 99

There is a description of an observation of patient N., aged 29, (a student of Russian University for Peoples' Friendship and a citizen of Tanzania) suffering from sickle-cell anemia--SCA--(HbSS), homozygous type, which was detected at screening of abnormal Hb by electrophoresis on the cellulose acetate strips. The results of clinical-and-biological examinations of the patients are described. The patient had anemia (Hb 98-83 g/L); thrombotic (pain) crises with dark urination were periodically observed. HbS accounted for the bulwark (98%) of Hb, while small fractions of Hb (HbF and HbA2) were within the normal limits. This was a comparatively mild form of the disease; the patient had minor changes in the heart and lungs with other internal bodies being intact. Patient N. received, from childhood, an appropriate therapy including antibiotics, folic acid, analgesics etc. Obviously, this provides for an explanation to that he lived up to 29 years, withstood the acclimatization in Russia and could get education. A comparison of the clinical-and-laboratory indices of patient N. with the data of patients with SCA of other types (HbS-thalassemia, HbSC and HbSK) is presented.
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PMID:[Sickle cell anemia (HBSS) in an adult patient from Tanzania]. 1291 Jun 40


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