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)

Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Limb deformity and metaphyseal abnormalities in thalassaemia major. 774 45

The applications of isoelectric focusing in immobilized pH gradients in clinical chemistry and forensic analysis are reviewed. Strong emphasis is given to the separation of serum proteins, in particular alpha 1-acidic glycoprotein, acid phosphatase, alkaline phosphatase, alpha 1-antitrypsin, apolipoproteins, complement component, factor B, factor XIIIB, group-specific component, lecithin:cholesterol acyltransferase, phosphoglucomutase, prealbumin, protein C and transferrin. The analysis of human parotid salivary proteins is discussed and an assessment is given of the state of the art in thalassaemia screening.
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PMID:Isoelectric focusing in immobilized pH gradients: applications in clinical chemistry and forensic analysis. 193 87

This review delineates the subcellular distribution, biochemical characteristics, and metabolic functions of 5'-nucleotidase (5'NT), summarizes the analytical biochemistry of 5'NT, and assesses the clinical significance of 5'NT determinations in body fluids, cells, and tissues. Salient aspects of the clinical biochemistry of 5'NT, discussed herein, are as follows: (A) Serum 5'NT activity is generally elevated in hepatobiliary diseases, especially with intrahepatic obstruction, but, unlike serum alkaline phosphatase, serum 5'NT activity is not increased in infancy, childhood, pregnancy, or osteoblastic disorders. (B) In cancer patients, elevated serum 5'NT activity does not always indicate hepatobiliary involvement; in some cases, 5'NT may be released into serum from the primary tumor or local metastases. (C) Genetic deficiency of erythrocyte pyrimidine 5'NT activity is a common cause of hereditary non-spherocytic hemolytic anemia. (D) Acquired deficiency of erythrocyte pyrimidine 5'NT activity occurs in patients with beta-thalassemia and lead poisoning. (E) 5'NT activity is low in circulating monocytes, increases markedly upon their differentiation to tissue macrophages, and subsequently diminishes during macrophage activation. (F) Lymphocyte ecto-5'NT activity, a plasma membrane marker of cell maturation, is generally low in immunodeficiency states, and undergoes characteristic changes in patients with certain lymphomas and leukemias.
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PMID:The clinical biochemistry of 5'-nucleotidase. 218 4

The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta-thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity.
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PMID:Bone disease in children with homozygous beta-thalassemia. 230 56

The influence of the alpha-thalassaemia gene on the haematological, biochemical and clinical presentation of sickle cell anaemia (SCA) was investigated in Saudi patients with 1 or 2 alpha-gene deletions. The results were compared to the results obtained in SCA patients without alpha-thalassaemia. In SCA patients with 2 gene deletions (homozygous alpha-thalassaemia 2), the mean cell volume, mean cell haemoglobin and Hb F were significantly lower (p less than 0.05), while packed cell volume and Hb A2 level were considerably higher (p less than 0.05) than in the SCA patients without alpha-thalassaemia. RBC and haemoglobin were higher in the former group, but the difference was not statistically significant. Patients with 1 gene deletion had intermediate values. Among the biochemical parameters, the bilirubin level was highest in patients with 1 gene deletion. Triglyceride, cholesterol, creatinine and urea levels were lower in all SCA patients, while alkaline phosphatase (ALP) and transaminases were elevated. The increase in the levels of ALP, SGOT and SGPT was maximum in the SCA patients with 2 gene deletions, but except for SGOT, the increase was not statistically significant. The retrospective analysis of the clinical data revealed that SCA patients with alpha-thalassaemia had fewer complications and had received fewer blood transfusions than the patients without alpha-thalassaemia.
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PMID:Clinical manifestation and laboratory findings of sickle cell anaemia in association with alpha-thalassaemia in Saudi Arabia. 242 Jan 34

A highly specific enzyme-linked immunosorbent assay (ELISA) was developed for the rapid identification and quantification of hemoglobin C in hemolysates. The procedure involves coating the surface of microtiter wells with Hb C and then addition of monospecific rabbit antibodies that recognize the unique beta 6 GLU----LYS substitution in Hb C. Next, an antibody to rabbit gamma-globulin conjugated with alkaline phosphatase is added, followed by substrate; a yellow color is formed due to the enzymatic hydrolysis of the substrate, which can be measured spectrophotometrically. For quantification purposes, a hemolysate containing Hb C is introduced just prior to the addition of the Hb C antibody. This results in blocking the attachment of the anti-Hb C to the Hb C coated to the plastic surface. Upon addition of anti-rabbit gamma-globulin conjugate and substrate, there is a consequent reduction or elimination of color formation. Since the degree of diminution of color formation is dose-dependent, standard curves can be developed for quantification of Hb C in unknowns. Of the total hemoglobin, the amounts of Hb C in heterozygotes averaged 27.3 +/- 5.7% by ELISA and 25.1 +/- 3.9% by radioimmunoassay (RIA). In SC individuals the corresponding values were 30.2 +/- 10.1% by ELISA and 24.7 +/- 10.9% by RIA. In homozygotes, Hb C values averaged 83.2 +/- 4.2% by ELISA and 85.0 +/- 6.6% by RIA. Subjects with Hb C beta(+)-thalassemia had 66.5 +/- 3.7% Hb C as measured by ELISA and 63.5 +/- 9.1% as determined by RIA. The ELISA procedure offers distinct advantages for Hb C identification and quantification over other techniques in parameters such as specificity, sensitivity, and rapidity.
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PMID:Identification and quantification of Hb C with an enzyme-linked immunosorbent assay. 389 43

Calcium and phosphate metabolism were studied in 22 patients with homozygous thalassemia. The overall results showed no significant difference for serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone, or 25-hydroxyvitamin D between thalassemic and control children. However, during the winter, serum 25-hydroxycholecalciferol levels were very significantly decreased in thalassemic children. A study of the hands showed thin metacarpal cortices related to increased resorption. Histomorphometric study of four iliac bone biopsies showed normal osteoclastic resorption and decreased bone formation. Prussian blue staining and x-ray electron microprobe analysis showed iron deposits inside the bone. Whether this finding is critical in the pathogenesis of the bone disease in unknown.
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PMID:Calcium phosphate metabolism and bone disease in patients with homozygous thalassemia. 705 21

We describe a rapid, automated method for direct detection of known single-base changes in genomic DNA. Fluorescence-based DNA minisequence analysis is employed in a template-dependent reaction which involves a single nucleotide extension of an oligonucleotide primer by the correct fluorescently-tagged dideoxynucleotide chain terminator. Detection following electrophoresis on denaturing acrylamide gels is facilitated by alkaline phosphatase treatment of reaction products after extension followed by isopropanol precipitation of the dye-tagged, single-base-extended primer to remove unincorporated deoxynucleotides. Fluorescence analysis of the incorporated dye tag reveals the identity of the template nucleotide immediately 3' to the primer site. This technique does not require radioactivity or biotinylated PCR product, relies on the incorporation of a single dideoxynucleotide terminator to extend the primer by one nucleotide and takes advantage of the sensitivity of fluorescent terminators developed for automated DNA sequence analysis. As a demonstration, we have applied the assay to human genomic DNA for detection of the sickle mutation in the beta-globin gene, and have also examined feasibility for simultaneous delineation using a multiplex-like strategy in a single gel-lane of some of the most common beta-thalassemia mutations in the Mediterranean basin.
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PMID:Fluorescence-based DNA minisequence analysis for detection of known single-base changes in genomic DNA. 747 10

Homozygous beta-thalassemia is a severe hereditary disorder associated with osteopenia. Recently it was suggested that thalassemia minor may be a risk factor for osteoporosis. The purpose of the present study was to investigate this suggestion. Bone mineral status was assessed in 22 premenopausal women and 21 men with beta-thalassemia minor. In vivo neutron activation analysis was applied to measure hand-bone phosphorus (HBP), single-photon absorptiometry to measure forearm bone mineral content (BMC), and dual-energy X-ray absorptiometry to measure spinal bone mineral density (BMD). Comparison of the HBP, BMC, and BMD values with those of sex- and age-matched healthy subjects without the beta-thalassemia trait failed to indicate a statistically significant difference for either sex group. Concerning the biochemical markers of bone metabolism that were studied (serum calcium, phosphate, alkaline phosphatase, osteocalcin, and parathyroid hormone, and 3-h fasting urine calcium-to-urine creatinine ratio) no difference was observed between the study subjects and matched controls. In conclusion, the present study showed that subjects with beta-thalassemia minor are not at risk for osteoporosis.
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PMID:Bone minerals in beta-thalassemia minor. 766 42

The homozygous form of beta-thalassemia, the most common single gene disorder, is treated by red cell transfusion therapy. Following transfusion, the chelator, deferoximine, is administered to patients to remove excess iron. However, when this drug is given to young children, metaphyseal dysplasia and abnormalities of linear growth are frequently observed. To explore the notion that deferoximine interferes with endochondral growth by chelating zinc, we examined the effect of the drug on chondrocytes maintained in long-term culture. We found that deferoximine caused a dose-dependent inhibition of a wide range of functions including cell proliferation, protein synthesis (and possibly under-hydroxylation of type X collagen), and mineral deposition. Directly relevant to the mineralization process was the observation that the drug dramatically lowered the activity of alkaline phosphatase, a zinc-requiring enzyme. To test the hypothesis that enzyme inhibition was due to chelation of zinc by deferoximine, the cell culture medium was supplemented with excess zinc. However, this treatment did not overcome the deferoximine-dependent change in enzyme activity. We next examined the possibility that deferoximine, in the presence of ascorbate, could form a free radical system that would serve to inactivate the enzyme. Using alkaline phosphatase extracted from chick cartilage, we noted that the activity of the phosphatase was markedly reduced in the presence of deferoximine and ascorbate. These effects were consistant with the notion that deferoximine and ascorbate can act as a prooxidant couple. This conclusion was confirmed when we measured the oxidative activities of the system using nitrobule tetrazolium and cytochrome c. Indeed, we noted that deferoximine markedly activates the autocatalytic oxidation of ascorbate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of deferoximine on chondrocyte alkaline phosphatase activity: proxidant role of deferoximine in thalassemia. 857 42


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