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)

Although the exact mechanism of positive inotropic action of cardiac glycosides is unknown, specific membrane bound proteins with high affinity for this group of drugs have been characterized. These "receptors" for cardiac glycosides have been measured quantitatively in cardiac tissue of humans and several species as well as in other tissues. The occupation of receptors by cardioactive steroids has been found to agree quantitatively with the drug effects in respect to inhibition of (Na+ + K+)-ATPase and in respect to positive inotropy (these experiments were performed in electrically stimulated contracting cardiac muscle). Changes in receptor concentration or receptor properties have been observed in hyperthyroidism, chronic hypokalaemia, thalassaemia or in acutely changed serum concentrations of K+, Ca++ and several drugs. These changes may be of great significance in patients treated with cardiac glycosides as their effects are not reflected by the serum concentration of cardiac glycosides. The understanding of drug-receptor-interactions on the molecular level--especially under the pathological conditions in the patient--will increase our diagnostic and therapeutic knowledge.
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PMID:[Quantitative aspects of specific binding of cardiac glycosides to membrane receptors]. 22 57

The sialic acid content of the human erythrocyte membrane is higher in homozygous beta-thalassemia than in heterozygous and healthy donors. Analysis of the difference by means of polyacrylamide gel electrophoresis in 1% sodium dodecyl sulphate and PAS staining failed to reveal significant variations in mobility and relative staining intensity of the main glycoprotein components, PAS-1, PAS-2 and PAS-3. The minor, although highly significant, changes which were recognized in the PAS pattern of beta-thalassemia patients compared with normal controls concerned the PAS-4 region and a shoulder trailing band PAS-2, which both increased in staining intensity relatively to the main sialocomponent PAS-1. Moreover, the shoulder was found to be more prominent in profiles from erythrocytes of blood group 0, in both normal and thalassemic subjects. The experimental data are discussed in the light of the presence of blood group ABH specific macroglycolipids in human erythrocytes (Dejter-Juszynski et al. 1978).
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PMID:Minor changes in the sodium dodecyl sulphate-gel electrophoresis periodic acid-Schiff-staining profiles of erythrocyte membranes in beta-thalassemia major. 55 3

Normal red blood cells, preincubated for 75 min with 1.15 mM menadione sodium bisulfite lose potassium and water on subsequent incubation at 37 degrees C for 24 h without menadione. The potassium loss is increased by addition of calcium and prevented by addition of glucose. Since normal red cells treated with menadione behave like untreated hypochromic cells, both from beta-thalassaemia or iron deficiency anaemia in respect to membrane permeability to potassium, it may be supposed that menadione induces in normal red cells an abnormality similar to that naturally occurring in hypochromic cells.
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PMID:Increased potassium permeability induced in vitro by menadione in normal human red cells. 84 Dec 69

Renal function studies were performed in 41 patients with sickle cell-beta thalassaemia (S/b thal) and compared to 14 normal controls and 8 sickle cell (SS) patients. Polyuria, hyposthenuria and mild proteinuria were common in both S/b thal and SS patients. A renal concentrating defect was manifest in all patients studied, and in 4 of the 7 S/b that patients tested, an abnormal acidification test was found. A statistically significant negative correlation (n = 19, r = -0.48, p less than 0.05) was noted between creatinine clearance (CCr) and age for the patients over 30 years. There was no correlation between hemoglobin and CCr; on the contrary, a statistically significant negative correlation was found between CCr and hemoglobin F (n = 29, r = -0.428, p less than 0.05) Our S/b thal and SS patients showed a decreased daily excretion of sodium, calcium, phosphate and magnesium and lower serum magnesium levels than the controls. One third of the S/b thal patients showed hyperuricosuria, and a statistically significant negative correlation was noted between serum uric acid and its fractional excretion in all S/b thal patients (n = 41, r = -0.450, p less than 0.01). Serum phosphate levels were independent of age. A statistically significant positive correlation was found between the tubular reabsorptive capacity for phosphate and the number of painful crises per year (n = 33, r = 0.836, p less than 0.001). We conclude that renal involvement in the double heterozygous state is as severe as in homozygous sickle cell disease.
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PMID:Renal involvement in sickle cell-beta thalassemia. 138 36

Congestive heart failure is the most common cause of death in young adults with thalassaemia major. In the present study we compared atrial natriuretic peptide levels (ANP) in 30 asymptomatic patients with thalassaemia major (aged 16.6 +/- 6.4 years), normal left ventricular diastolic cavity dimension and systolic function, with 30 aged and sex matched normal control subjects. ANP levels were significantly higher in patients with thalassaemia major compared to controls (93.9 +/- 26.3 pg.ml-1 vs 51.8 +/- 26.5 pg.ml-1; P < 0.001). Plasmatic renin activity, aldosterone, urinary sodium and catecholamine levels at basal conditions did not differ significantly in these two groups (ns). Blood volume stimulation (blood transfusion) in thalassaemic patients was followed by an increase of mean ANP values (93.9 +/- 26.3 to 109.1 +/- 40.5 pg.ml-1; P < 0.03). ANP basal levels above two standard deviations of the mean values obtained in normal control subjects were considered as abnormal and found to be in close correlation with the presence of diastolic dysfunction of the left ventricle identified by Doppler echocardiography. The method has a 57% sensitivity and a 91% specificity for revealing pre-clinical cardiac involvement (P < 0.02). Although a longer observation period is necessary in order to define the clinical and prognostic significance of these data, our results show that an increase in ANP basal values is present in asymptomatic patients with thalassaemia major. This suggests initial myocardial involvement, while ANP response to volume overload is maintained.
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PMID:Cardiac involvement in thalassaemia major: altered atrial natriuretic peptide levels in asymptomatic patients. 139 10

In thalassemia erythrocyte cation permeability is increased, but the increment in ATPase-dependent cation pumps maintains normal concentrations of Ca++, Na+ and K+. In this study we investigated erythrocyte concentrations of Mg++ in heterozygous beta-thalassemia and in microcytic sideropenic anemia. Twenty-five healthy controls, 40 heterozygous beta-thalassemics and 25 patients with sideropenic anemia were studied. Erythrocyte Mg++ was assayed either by atomic absorption or by standard laboratory methods. Erythrocyte Mg++ was significantly lower in the beta-thalassemia group than in the other two groups (p less than 0.001). Serum magnesium was significantly lower in sideropenic anemia patients than in beta-thalassemics and in controls (p less than 0.01), whereas these latter two groups showed similar values. Our results suggest that the increment in ATPase-dependent cation pumps is not sufficient to maintain normal erythrocyte Mg++ concentrations in heterozygous beta-thalassemia. In sideropenic anemia cation permeability is not increased, therefore erythrocyte Mg++ is normal. Low serum Mg++ levels in sideropenic anemia could be explained by a primary Mg++ deficit associated with sideropenia.
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PMID:Serum and erythrocyte levels of magnesium in microcytosis: comparison between heterozygous beta-thalassemia and sideropenic anemia. 166 66

To study the potential of multivariate classification methods in order to obtain more insight into abnormal laboratory data from patients with sickle cell disease, we investigated standard haematological and clinical chemical variables of 18 controls and 37 apparently healthy persons with heterozygous sickle cell disease (Hb AS), all women, using both univariate and multivariate classification methods. In the univariate method, those with Hb AS showed decreased serum log aspartate aminotransferase (log AST) activity, mean corpuscular volume and mean corpuscular haemoglobin (MCH) and increased sodium concentration. The multivariate method identified sodium, potassium, urea, uric acid, log AST, alanine aminotransferase and MCH as the variables that produced maximal separation between persons with Hb As and controls. It increased the 'non-error rate' for classification of persons with Hb AS by 16.4% compared with classification based on the variable, MCH, that produced maximal separation by the univariate method. The frequency distribution of percentage Hb S in the Hb AS group proved bimodal with maximal separation at 37.0% Hb S. The subgroup with 37.0% or less (n = 16) was considered to have concomitant heterozygous alpha-thalassaemia-2. In the univariate method the subgroup characterized by greater than 37.0% Hb S (n = 21) had increased serum sodium and uric acid concentrations, perhaps related to sickle cell nephropathy, whereas the subgroup with less than or equal to 37% Hb S did not. The multivariate method added information to the univariate method by additionally identifying abnormalities in serum potassium and urea concentrations in the former subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potential of descriptive linear discriminant analysis for studying clinical chemical and haematological data from persons with heterozygous sickle cell disease. 189 49

During a study of clinical and laboratory features in 83 patients with sickle cell disease in the Netherlands, serum creatinine, sodium, potassium, uric acid and osmolality were determined and reported for 65: 39 with homozygous sickle cell (SS) disease, 5 with beta degrees thalassaemia (S beta degrees thal), with sickle cell beta + thalassaemia (S beta degrees + thal) and 17 with sickle cell haemoglobin C (SC) disease. Data on history of hyposthenuria was unreliable. Haematuria was reported in 6 (7%) of the 83 patients. Four of the six patients with a history of haematuria, two of whom had elevated creatinine levels, had SS disease. Lower mean levels of serum sodium and higher levels of serum potassium were observed in SS's than in the other genotypes (p less than 0.001). Hyperkalaemia of greater than 5 mmol/l was seen in 50% of SS disease cases and in 33% of paediatric SC disease cases. Some high potassium levels must be ascribed to in vitro haemolysis. The rate of hyperuricaemia ranged from 24% to 40% among the various genotypes. Clinical gout was not observed.
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PMID:Renal and electrolyte profile in steady state sickle cell disease: observations in patients with sickle cell disease in The Netherlands. 276 58

Using a highly sensitive method for the determination of red cell densities (Percoll-Stractan continuous isopyknic gradients), we find that, in adults, this parameter varies with sex and race. Whites have red cell densities (expressed as mean corpuscular hemoglobin concentration [MCHC]) that are, on the average, 0.7 gm/dl higher than those in blacks (the difference of the means has p less than 2 x 10(-7]. White men have, on the average, 0.6 gm/dl higher MCHC than white women (the difference of the means has p less than 6 x 10(-5]. We find a strong correlation between all red cell densities and intracellular K+ and a slightly weaker correlation between red cell density and intracellular Na+ + K+. Men have an average intraerythrocytic K+ that is approximately 4.5 mmol/L of red cells less than that of women among whites as well as blacks (p less than 10(-5) and p less than 9 x 10(-4), respectively). Blacks have significantly higher plasma ferritin levels than do whites (in addition to the sex difference). Future work will have to dissect the possible causes of these differences, which include the high incidence of deletional alpha-thalassemia (-a/aa) among blacks, menstruation, hormonal effects, and the red cell transport and volume regulation differences between sexes and races. Whatever the cause of the sex and racial differences reported here, they are bound to affect the pathophysiologic expression of genetic red cell diseases that are particularly sensitive to the MCHC, such as the sickle cell syndromes.
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PMID:Red cell density is sex and race dependent in the adult. 341 Nov 95

It has been suggested that the less severe anemia that exists in patients with sickle cell anemia who also have alpha-thalassemia is related to an effect on the sickling of erythrocytes. To test this hypothesis, we used as a measure of sickling the change in sickle erythrocyte sodium and potassium content that occurs during deoxygenation. Sickle cells from individuals with four, three, or two alpha-globin genes were deoxygenated, and the change in monovalent cation content measured to determine whether a relationship exists between alpha-globin gene number and sickling. In samples of cells depleted of irreversibly sickled cells, the alpha-globin gene number was directly related to the magnitude of mean cation change and inversely related to the ratio of membrane surface area to cell volume. These data indicate that alpha-thalassemia is associated with a diminished degree of sickling in individuals with sickle cell anemia. They also suggest that excess cell membrane may play a role in this protective effect.
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PMID:Monovalent cation changes in sickle erythrocytes: a direct reflection of alpha-globin gene number. 400 25


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