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)

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

Serum half-lives for antipyrine were normal or shorter than normal in 19 subjects between 7 and 23 yr of age with beta-thalassemia major. The mean antipyrine serum half life (+/-SE) for the group as a whole was 8.5 +/- 0.6 hr. The mean antipyrine half-lives (t1/2) for the younger subjects were within the range reported for normal children, while the mean t1/2 for the older males approached the values reported for normal adult males. The mean t1/2 for the older females was shorter than has been reported for normal adult females. The mean apparent volume of distribution for antipyrine (+/-SE) in the subjects with thalassemia was 0.69 +/- 0.01 L/kg. Thus, total body water appears to be increased in thalassemia. The mean metabolic clearance rate for antipyrine (+/-SE) in the group as a whole (1.07 +/- 0.08 ml/min/kg) is substantially higher than the metabolic clearance rates for antipyrine reported in normal adults. Thus, the relatively short t1/2s of antipyrine in subjects with thalassemia are attributable to rapid rates of clearance of the drug. The data indicate that antipyrine clearance is unimpaired in patients with thalassemia despite evidence of liver damage and iron overload. Our study supports the proposition that hepatic microsomal hemoprotein synthesis is not adversely affected in homozygous beta-thalassemia.
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PMID:Antipyrin clearance in homozygous beta-thalassemia. 97 19

A defect in urine concentrating ability occurs in individuals with sickle cell trait (HbAS). This may result from intracellular polymerization of sickle hemoglobin (HbS) in erythrocytes, leading to microvascular occlusion, in the vasa recta of the renal medulla. To test the hypothesis that the severity of the concentrating defect is related to the percentage of sickle hemoglobin present in erythrocytes, urinary concentrating ability was examined after overnight water deprivation, and intranasal desmopressin acetate (dDAVP) in 27 individuals with HbAS. The HbAS individuals were separated into those who had a normal alpha-globin genotype (alpha alpha/alpha alpha), and those who were either heterozygous (-alpha/alpha alpha) or homozygous (-alpha/-alpha) for gene-deletion alpha-thalassemia, because alpha-thalassemia modulates the HbS concentration in HbAS. The urinary concentrating ability was less in the alpha alpha/alpha alpha genotype than in the -alpha/alpha alpha or -alpha/-alpha genotypes (P less than 0.05). After dDAVP, the urine osmolality was greater in patients with the -alpha/-alpha genotype than with the -alpha/alpha alpha genotype (882 +/- 37 vs. 672 +/- 38 mOsm/kg H2O) (P less than 0.05); patients with the -alpha/alpha alpha genotype had greater concentrating ability than individuals with a normal alpha-globin gene arrangement. There was an inverse linear correlation between urinary osmolality after dDAVP and the percentage HbS in all patients studied (r = -0.654; P less than 0.05). A linear correlation also existed for urine concentrating ability and the calculated polymerization tendencies for an oxygen saturation of 0.4 and O (r = -0.62 and 0.69, respectively). We conclude that the severity of hyposthenuria in HbAS is heterogeneous. It is determined by the amount of HbS polymer, that in turn is dependent upon the percentage HbS, which is itself related to the alpha-globin genotype.
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PMID:Effects of alpha-thalassemia and sickle polymerization tendency on the urine-concentrating defect of individuals with sickle cell trait. 175 55

The variable levels of HbF in sickle cell anemia reflect the heterogeneous genetic mix of the beta s-gene-cluster haplotypes and coinheritance of alpha-thalassemia-2 in American SS patients. Clinical severity is less when the level of HbF reaches 20% or 1.2 g/dl or more. The coinheritance of alpha-thalassemia-2 not only increases the intracellular red cell water but modifies the HbF level in accordance with the beta-cluster haplotype. In general, the SS patient with at least one Senegalese haplotype who does not have a CAR haplotype in trans, has a significantly greater probability of maintaining HbF above 20%. This is in part related to the genetic control of the G gamma HbF locus. Such a patient is protected from arteriolar vasculopathy and subsequent major organ destruction. Much of this but perhaps not all of the better health of patients with a Senegalese haplotype can be attributed to the elevation of G gamma HbF. The coinheritance of alpha-thalassemia-2 further decreases the risk of major morbidity of the soft tissues but increases the risk of avascular necrosis of the bony skeleton. Although these heterozygous Senegal patients are healthier, eventually most, in time, will show the deleterious effect of HbS as retinopathy and avascular necrosis usually beginning after age 30 and sickle nephropathy after age 40. Because of the age-specific effect, the onset of the sickle vasculopathy is delayed by nearly 20 years in the Sen/Ben patient with increased G gamma HbF as compared to those with a CAR haplotype or the homozygous Benin. Lifetime elevation of HbF above 20% modifies the severity of disease expression and provides relative protection to the patient with sickle cell anemia.
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PMID:The influence of fetal hemoglobin on the clinical expression of sickle cell anemia. 247 64

The extent of intracellular polymerization of hemoglobin S, leading to loss of erythrocyte deformability and eventual morphological sickling, is primarily determined by oxygen saturation and intracellular hemoglobin concentration and composition. Epidemiological analysis of sickle cell disease severity among the sickle syndromes and studies of the biophysics of intracellular polymerization were used to estimate the potential clinical benefit of various therapeutic strategies. These strategies include those designed to increase deoxyhemoglobin S solubility; to increase erythrocyte volume or water content, thereby reducing the intracellular hemoglobin concentration; or, most recently, to decrease the proportion of hemoglobin S by increasing the amount of non-S hemoglobin. Increasing levels of hemoglobin F is of particular interest due to its "sparing" effect in inhibiting polymerization, the well-characterized epidemiological associations of high levels of hemoglobin F with reduced disease severity, and recent studies of drug-induced increases in hemoglobin F. Our analyses of equilibrium polymer formation at physiological oxygen saturation values suggest that small decreases in polymer formation at intermediate levels of hemoglobin F may give rise to a small decrease in anemia (as associated with homozygous alpha-thalassemia coexistent with sickle cell anemia), but that greater reductions in polymer formation may be necessary to effect a significant improvement in disease severity. Current studies of hydroxyurea-induced increases of hemoglobin F give cautious optimism that therapeutically useful levels may be attainable.
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PMID:Intracellular polymerization. Disease severity and therapeutic predictions. 247 66

Patients with Hb SC disease were found to have microcytic and hyperchromic red cell indices despite mild reticulocytosis. Iron deficiency anemia was ruled out by the finding of normal serum ferritin levels. In order to determine whether the microcytosis was due to coexistent alpha-thalassemia, restriction endonuclease mapping was performed on genomic DNA extracted from peripheral blood leukocytes. Patients with Hb SC disease had microcytic indices despite the presence of a full complement of four alpha-genes (alpha alpha/alpha alpha), suggesting that the microcytosis may be due to cellular dehydration (or xerocytosis), since the mean corpuscular hemoglobin concentration in Hb SC disease patients was significantly higher than in controls. This possibility was investigated further by the determination of RBC cation content. RBC Na levels were similar in SC and normal red cells. Hb SC RBCs, however, had significantly reduced K levels. These findings show that RBC cation content, and thus cell water, is decreased in Hb SC disease. The decreased RBC K level in the presence of normal cellular Na concentration suggests selective K loss that is not due to inhibition of the Na K pump. Ouabain-insensitive K+ efflux was increased to four times normal in SC cells. Cell dehydration was confirmed by the demonstration of increased high-density RBCs on discontinuous Stractan density gradients and by osmotic gradient ektacytometry. Cellular dehydration and its sequelae were worse in CC erythrocytes and milder in AC cells than in Hb SC red cells. Taken together, these data indicate that in Hb SC disease the RBCs are severely dehydrated and typically microcytic and hyperchromic. Hb SC RBCs seem to be dehydrated due to selective K loss. These findings suggest a functional interrelationship between Hb SC, the red cell membrane, and cation regulation.
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PMID:The xerocytosis of Hb SC disease. 294 42

Hemoglobin's physiologic properties depend on the orderly assembly of its subunits in erythropoietic cells. The biosynthesis of alpha- and beta-globin polypeptide chains is normally balanced. Heme rapidly binds to the globin subunit, either during translation or shortly thereafter. The formation of the alpha beta-dimer is facilitated by electrostatic attraction of a positively charged alpha-subunit to a negatively charged beta-subunit. The alpha beta-dimer dissociates extremely slowly. The difference between the rate of dissociation of alpha beta- and alpha gamma-dimers with increasing pH explains the well-known alkaline resistance of Hb F. Two dimers combine to form the functioning alpha 2 beta 2-tetramer. This model of hemoglobin assembly explains the different levels of positively charged and negatively charged mutant hemoglobins that are encountered in heterozygotes and the effect of alpha-thalassemia and heme deficiency states in modifying the level of the variant hemoglobin as well as Hb A2. Electrostatic interactions also affect the binding of hemoglobin to the cytoplasmic surface of the red cell membrane and may underlie the formation of target cells. Enhanced binding of positively charged variants such as S and C trigger a normally dormant pathway for potassium and water loss. Thus, the positive charge on beta c is responsible for the two major contributors to the pathogenesis of Hb SC disease: increased proportion of Hb S and increased intracellular hemoglobin concentration. It is likely that electrostatic interactions play an important role in the assembly of a number of other multisubunit macromolecules, including membrane receptors, cytoskeletal proteins, and DNA binding proteins.
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PMID:Subunit assembly of hemoglobin: an important determinant of hematologic phenotype. 353 23

It might appear that the Fe3+ ion would be particularly useful as an agent for enhancing contrast in NMR images since it has a relatively large magnetic moment and occurs in vivo in a variety of forms. Moreover, the concentration of Fe3+ changes locally in certain disease states (e.g., beta-thalassemia) and in trauma (formation of methemoglobin), and can be altered in the gastrointestinal tract by the ingestion of readily available dietary supplements. However, the Fe3+ ion is insoluble above pH approximately 4, and soluble chelate and protein complexes of Fe3+ tend to sequester the ions from solvent; hence, the efficacy of Fe3+ ions for relaxing water protons ought to be low under typical physiological conditions. We report the magnetic field dependence of the relaxation rate of solvent protons (NMRD profiles) for solutions of a variety of Fe3+ complexes to demonstrate the phenomenology relevant to NMR imaging. From these data we make some estimates to show that, despite the low relaxation rates of solvent protons in solutions of Fe3+ complexes, certain observed changes in image contrast are consistent, quantitatively, with inferences that can be drawn from solution data.
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PMID:Magnetic field dependence of solvent proton relaxation in aqueous solutions of Fe3+ complexes. 393 11

A series of polymers bearing hydroxamic acid-terminated side chains were prepared for the purpose of developing new iron chelators for treating iron overload in beta-thalassemia (Cooley's anemia) and other iron diseases. The polymers are for the most part amino acid amide derivatives of acrylic and methacrylic acid with the terminal carboxyl group converted to the hydroxamic acid. The polymers are generally water soluble and sequester iron(III) avidly. The polymeric iron chelators were assayed via a mouse screen for activity in removing iron. Iron overloaded mice were administered i.p. the iron chelator over a 7-day period. Urine and feces were collected and the iron content measured by atomic absorption. At the end of the treatment period the mice were sacrificed and the livers and spleens were homogenized and examined for iron content. The results were compared with similar data obtained for the iron chelator drug desferrioxamine as a standard. Four of the polymers prepared exhibited strong activity, as good or better than desferrioxamine in iron removal capability. The four polymers are the polyacroloyl and polymethacryloyl derivatives of beta-alanine with the side chain carboxyls converted to the N'--H or N'--CH3 hydroxamic acids. Of these four the polyacryloyl N'--CH3 derivative exhibited superior behavior, being 3 to 5 times as effective as desferrioxamine at the lower dose level. None of the four polymers produced toxic signs and the administration was accompanied by little or no pain response.
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PMID:Evaluation of polymeric hydroxamic acid iron chelators for treatment of iron overload. 397 22

According to several hematological and anthropological studies the formation of hyperostosis spongiosa orbitae can be attributed to different types of anemias. Since especially in Central Italy the different forms of thalassemia as well as Plasmodium vivax, Plasmodium malariae and Plasmodium falciparum have been rather vastly distributed a study of this trait (differentiating between degrees of expression) on a population sample (125 males, 80 females) including adult, mature and senile skulls has been carried out (anatomical series of the medical faculty of the University of Siena ). However, the high incidence of this trait, though rather weakly expressed (male 56.8%, female 70.0%), and clearly classifiable in three degrees of expression also indicates the existence of other factors involved. Among these factors the nutritional ones could be excluded because this region was scarcely populated and rich in nutritional resources. On the other hand, the low content of Fe and Cl anions in the water could be made up with the assumption of foods abounding for these elements.
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PMID:Frequencies of cribra orbitalia in central Italy (19th century) under special consideration of their degrees of expression. 637 79


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