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 activities of orotate phosphoribosyl transferase (OPRT) and orotidine monophosphate decarboxylase (ODC) were significantly elevated (P less than 0.001) in erythrocytes (RBC) from five patients with prednisone-responsive congenital hypoplastic anaemia (CHA). (OPRT: patients - 10.1--64.2 nmol/h/10(9) RBC; controls - 2.8 +/- 0.3 (mean +/- SEM, n = 37); ODC: patients = 30--124 nmol/h/10(9) RBC; controls = 10.2 +/- 0.7 (mean SEM, n = 37).) Two patients had a less pronounced, but significant, increase of aspartate transcarbamylase activity and three patients had marginal increases of dihydroorotase activity. Dihydroorotate dehydrogenase activity was not detected in any CHA patient or control. In one patient prior to prednisone therapy, the OPRT and ODT activities were elevated 10-fold and remained elevated 3-fold after 16 months of therapy. An elevated enzyme pattern similar to that of RBC from CHA patients was observed in three parents of three CHA patients, but not in three parents of two other CHA patients. The activities of all five pyrimidine enzymes were normal for one patient with transient erythroblastopenia of childhood. In contrast, the activities of all the pyrimidine biosynthetic enzymes were elevated in blood from patients with a young RBC population: sickle cell anaemia, sickle-beta-thalassaemia, hereditary spherocytosis, and DiGuglielmo syndrome and from the newborn. It is postulated that factors which affect the activities of pyrimidine enzymes in CHA may also result in diminished erythropoiesis.
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PMID:Elevation of pyrimidine enzyme activities in the RBC of patients with congenital hypoplastic anaemia and their parents. 3 27

Interferon-gamma (IFN-gamma) has been shown to influence globin gene expression in cord blood and normal adult progenitor-derived erythroblasts. To explore the influence of IFN-gamma on fetal hemoglobin (HbF) synthesis in the hemoglobinopathies, erythroid progenitors (BFU-E, burst forming unit-erythroid) from patients with sickle cell anemia (SCA) and thalassemia were co-cultured with or without IFN-gamma. Hemoglobin content in progenitor-derived erythroblasts was assessed by radioligand assay (RIA). Co-culture of erythroid progenitors from 12 SCA patients with 200-400 U/ml of IFN-gamma resulted in a significant decrease in picograms of HbF and percent HbF per BFU-E-derived erythroblast. The mean decrease (+/- SEM) of picograms of HbF per cell and percent of HbF was by 42 +/- 9% and 35 +/- 8% of control cultures, respectively. Co-culture of erythroid progenitors from 10 patients with thalassemia major or thalassemia variant (HPFH/thalassemia, sickle/beta 0-thalassemia) with 200 U/ml IFN-gamma also resulted in a significant decrease in picograms and percent of HbF per BFU-E-derived erythroblast. IFN-gamma treatment also inhibited the enhancement in gamma-globin synthesis induced in culture by butyric acid. Erythroid progenitors from 2 patients with SCA, 1 patient with sickle/beta 0-thalassemia, and 1 patient with HbE/beta 0-thalassemia were co-cultured with IFN-gamma, L-alpha-amino-n-butyric acid, or both. HbF content (expressed as picograms HbF/cell) was decreased in samples co-cultured with IFN, increased in cultures with L-alpha-amino-n-butyric acid, but remained at control values in cultures treated with IFN plus L-alpha-amino-n-butyric acid. These data demonstrate that IFN-gamma is an environmental factor that influences gamma-globin gene expression in the beta hemoglobinopathies in vitro.
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PMID:Interferon-gamma modulates fetal hemoglobin synthesis in sickle cell anemia and thalassemia. 170 29

An increased incidence of diabetes mellitus and glucose intolerance has been reported in thalassaemia major treated with a high transfusion programme (HTP). To investigate beta-cell function, serum immunoreactive insulin (IRI), C-peptide (CP) and glucose were measured fasting and at 3, 6 and 10 min after i.v. administration of 1 mg glucagon in 20 thalassaemia patients treated by many transfusions and in nine healthy control subjects. Fasting C-peptide concentrations (mean +/- SEM) were higher in the thalassaemic group (2.15 +/- 0.17 ng/ml) than in the controls (1.41 +/- 0.13 ng/ml). After stimulation with glucagon, C-peptide concentrations were consistently higher (P less than 0.01) by approximately 50% in the thalassaemic than in the control group (5.29 +/- 0.31 vs 3.36 +/- 0.21 ng/ml, at 3 min; 5.22 +/- 0.30 vs 3.53 +/- 0.21 ng/ml at 6 min and 4.69 +/- 0.27 vs 3.30 +/- 0.17 ng/ml after 10 min). Plasma IRI concentrations increased in both groups after glucagon stimulation but were not significantly different. The glucose values were approximately 15% higher at each sampling time in the thalassaemic group than those of the normal subjects. It is concluded that disturbances in carbohydrate metabolism in thalassaemia major treated with HTP are the consequence of hepatic cirrhosis which accompanies secondary haemosiderosis, and possibly iron deposition in the beta-cells of the pancreas.
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PMID:A study of beta-cell function after glucagon stimulation in thalassaemia major treated by high transfusion programme. 332 97

We studied the electrophoretic pattern of hemoglobin (Hb) and red blood cell indices in 128 women divided into four groups: group I, 36 nonanemic hyperthyroid women, divided in two subgroups: 36 with untreated hyperthyroidism (subgroup IA) and 9 made euthyroid by antithyroid drug therapy (subgroup IB); group II, 12 nonanemic women with untreated hypothyroidism; group III, 30 women known to be heterozygous for beta-thalassemia; and group IV, 50 healthy women. The mean (+/- SEM) HbA2 level was higher (P less than 0.001) in subgroup IA (3.21 +/- 0.06%) than in subgroup IB (2.42 +/- 0.09%) and group IV (2.48 +/- 0.04%), but lower (P less than 0.001) than in group III (5.26 +/- 0.12%). The mean HbA2 level was lower (P less than 0.001) in group II (1.99 +/- 0.08%) than in group IV. Hb fetal was detectable in eight patients of subgroup IA and undetectable in subgroup IB and groups II and IV. The mean cellular volume was lower (P less than 0.001) in subgroup IA than in other nonanemic groups. The mean cellular volume was higher (P less than 0.001) in group II than in group IV. Follow-up of nine patients who became euthyroid with treatment showed the normalization of these erythrocyte parameters. These results suggest that thyroid hormones can modulate the synthesis of delta- and gamma-globin chains.
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PMID:Influence of thyroid status on hemoglobin A2 expression. 619 Aug 36

Pulmonary function tests were performed in 12 thalassemia patients on a hypertransfusion program (age 18.4 +/- 2.6 SEM years) to determine the presence of any abnormalities of lung function. These included spirometry, expiratory flow rates, body plethysmography, single-breath nitrogen washout, single breath carbon monoxide diffusing capacity, and arterial blood gases. Only one patient had normal pulmonary function. Arterial hypoxemia was present in ten of 12 patients at rest. The total lung capacity (TLC) was normal. The residual volume was abnormally increased in five of 12 patients. The slope of phase III of single breath nitrogen washout curve was abnormal in five of 12 patients, but the closing volume was normal. The maximal expiratory flow rate at 60% total lung capacity was decreased in four of 12 patients, suggesting the presence of small airway disease. The single breath carbon monoxide diffusing capacity was normal in all patients. These pulmonary function abnormalities did not correlate with age or the cumulative amount of iron via blood transfused. The small airway obstruction, hyperinflation; and hypoxemia observed in thalassemia patients on a hypertransfusion program may result from the basic disease, iron deposition in the lungs, or other factors.
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PMID:Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program. 736 14

A scanning electron microscopy study of liver changes has been carried out in three patients affected by beta-thalassemia intermedia (BTI). Applying a new osmium maceration method, recently developed in our laboratory, we had the opportunity to obtain, at SEM, tridimensional images of intra and extracellular structures. Other than the previously reported lesions in BTI, we observed the following pathological findings: disarrangement of the cell structure by a high number of hemosiderin loaded lysosomes; alterations in shape and in diameter of the nuclear pores; presence of apoptotic bodies scattered among the parenchymal cells; deposition of collagen fibers in the space of Disse to form a perihepatocytic dam; enlargement of the sinusoidal endothelial cell fenestrae of the sieve plate. By complete digestion of liver cells, we evidenced a diffuse pericellular fibrosis, made up of interlacing fibrils. Our study evidences some not yet reported morphological lesions in BT. Since patients affected by BTI do not need blood transfusions, these lesions could be considered intrinsic of the disease.
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PMID:A 3D study of intra and extracellular structures of liver in beta-thalassemia intermedia: an OsO4 maceration analysis. 906 44

Serum levels of the vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D, and of osteocalcin, C-terminal parathyroid hormone and other biochemical indices related to bone metabolism, were determined in two groups of patients with beta-thalassaemia aged 5-10 years (summer 7.8 +/- 0.4 years, mean +/- SEM, and winter 7.7 +/- 0.4 years, group A, n = 15) and 11-23 years (16.6 +/- 0.9 and 15.7 +/- 0.9 years in summer and winter, respectively, group B, n = 22). Emphasis was given to populations of school and adolescent ages and to the seasons of summer and winter when vitamin D status demonstrates the widest extremes. The mean serum levels of 25-hydroxyvitamin D in patients aged 5-10 years did not differ from those of controls during both seasons studied. In contrast, in the age group 11-23 years these levels were found to be lower in patients than in controls both in winter (10.6 +/- 0.9 ng/ml vs 15.0 +/- 2.0 ng/ml, p < 0.05) and summer (20.2 +/- 2.1 ng/ml vs 27.1 +/- 2.0 ng/ml, p < 0.05). The serum concentrations of 24,25-dihydroxyvitamin D were lower in the thalassaemic patients than in controls in both age groups and both seasons. In the patients under 10 years of age the mean values of this metabolite in winter were 1.06 +/- 0.17 ng/ml vs 1.68 +/- 0.20 ng/ml in the respective controls (p < 0.05), and in summer 1.44 +/- 0.11 ng/ml vs 2.35 +/- 0.36 ng/ml in controls (p < 0.05). In the group of patients aged 11-23 years, the mean levels of 24,25-dihydroxyvitamin D were in winter 0.65 +/- 0.12 ng/ml vs 1.12 +/- 0.19 ng/ml (p < 0.05) in controls and in summer 1.34 +/- 0.12 ng/ml vs 1.84 +/- 0.20 ng/ml (p < 0.05). The 1,25-dihydroxyvitamin D concentrations in both thalassaemic patient groups were significantly no different from those in the respective control groups. Serum osteocalcin, C-terminal parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase levels in the patients studied were not significantly different from those in controls, except for calcium and phosphate in the older group. In the older group of thalassaemic patients, serum calcium was lower than in the controls (2.26 +/- 0.03 vs 2.37 +/- 0.03 mmol/l, p < 0.05) in summer and serum phosphate higher than in the controls in winter (1.47 +/- 0.05 mmol/l vs 1.27 +/- 0.06 mmol/l, p < 0.05).
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PMID:Vitamin D metabolites (25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D) and osteocalcin in beta-thalassaemia. 920 93

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), and interferon-gamma (IFN-gamma) were estimated by conventional ELISA kits in 60, 42, and 58 Thai patients, respectively, with beta(o)-thalassemia HbE and found to be above the normal range in 13%, 21%, and 33% of the patients, respectively. Using high-sensitivity ELISA systems, an additional 10 beta(o)-thal/HbE patients were compared with 9 controls for concentrations of circulating TNF-alpha and IL-1beta, and 9 and 5 patients, respectively, but only 1 and none of the controls, respectively, showed values above the normal ranges. In patients with abnormally high IFN-gamma levels, basal hemoglobin values were significantly lower than in those with normal levels of the cytokine (mean +/- SEM: 6.03+/-0.24 vs. 7.08+/-0.18, p < 0.05), although circulating concentrations of soluble transferrin receptors (sTrF) and absolute reticulocyte counts were similar in the two groups. Patients with raised or normal levels of TNF-alpha, IL-1alpha, or IL-1beta had similar basal hemoglobin values. In a phagocytosis assay, monocytes of patients with raised serum levels of IFN-gamma showed significantly more attached or ingested IgG-coated red cells than those of patients with normal concentrations of the cytokine (mean +/- SEM: 192+/-22 vs. 140+/-14 per 100 monocytes, p < 0.05). Moreover, in 3 of 4 of the former patients, the number of attached or ingested IgG-coated red cells per 100 monocytes was above the 95% reference limit for the latter patients. The results suggest that IFN-gamma aggravates the anemia of beta(o)-thal/HbE by activating mononuclear phagocytes for destruction of red cells but not by inhibiting erythropoiesis. The elevated serum levels of TNF-alpha and IL-1 could contribute to complications of the disease, such as cachexia and thromboembolic phenomena.
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PMID:Serum levels of tumor necrosis factor-alpha, interleukin-1, and interferon-gamma in beta(o)-thalassemia/HbE and their clinical significance. 1009 Mar 95

Gonadotropin (Gn) replacement therapy using HCG plus HU-FSH was administered to 24 patients affected by beta-thalassaemia major with hypogonadotropic hypogonadism aged 18-40 years (25.2 +/- 5.4 yr, m +/- SEM). The age range at the start of treatment was 14.5-24.5 years (16.7 +/- 2.6 yr); the mean duration of Gn treatment was 8.6 +/- 3.9 years (range 1-15.2 yr). Gn therapy was begun with HCG alone, the dosage being initially 500 IU twice a week and then increased to a maximum of 3000 IU twice a week, according to the individual serum testosterone levels obtained. HU-FSH (75 IU twice a week) was added to initiate spermatogenesis in all cases when the HCG-induced testosterone serum levels normalized. The duration of HU-FSH treatment ranged from 1-2 years and then therapy was continued with HCG alone. In nine patients Gn therapy was discontinued after 6-14 years and was replaced by testosterone depot therapy, 75-100 mg i.m. twice a month, for a period ranging from 1-1.5 years. Using Gn therapy, the testosterone levels normalized. The compliant patients obtained good virilization and normal sexual function; testicular volume increased within the normal adult range and spermatogenesis was achieved. When Gn therapy was replaced by testosterone-depot therapy, a marked decrease in testicular volume and sperm count was observed, but the patients complied better and showed a slight increase in coarse hair. In conclusion gonadotropins are an effective replacement therapy for male hypogonadism in thalassaemic patients. If we consider the advantages and disadvantages of this therapy, the former seem to outweigh the latter. Finally, it should be emphasized that physicians caring for these patients must foster compliance during frequent check-ups and examinations.
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PMID:Hormonal replacement therapy with HCG and HU-FSH in thalassaemic patients affected by hypogonadotropic hypogonadism. 1009 Nov 62

The optimal regimen of intravenous deferoxamine for iron overload in high-risk homozygous beta-thalassemia is unknown because only short-term follow-up has been described in small patient groups. We report the outcome over a 16-year period of a continuous 24-hour deferoxamine regimen, with dose adjustment for serum ferritin, delivered via 25 indwelling intravenous lines for 17 patients. Treatment indications were cardiac arrhythmias, left ventricular dysfunction, gross iron overload, and intolerability of subcutaneous deferoxamine. Cardiac arrhythmias were reversed in 6 of 6 patients, and the left ventricular ejection fraction improved in 7 of 9 patients from a mean (+/- SEM) of 36 +/- 2% to 49 +/- 3% (P =.002, n = 9). The serum ferritin fell in a biphasic manner from a pretherapy mean of 6281 +/- 562 microg/L to 3736 +/- 466 microg/L (P =.001), falling rapidly and proportionally to the pretreatment ferritin (r(2) = 0.99) for values >3000 microg/L but falling less rapidly below this value (at 133 +/- 22 microg/L/mo). The principal catheter-related complications were infection and thromboembolism (1. 15 and 0.48 per 1000 catheter days, respectively), rates similar to other patient groups. Only one case of reversible deferoxamine toxicity was observed (retinal) when the therapeutic index was briefly exceeded. An actuarial survival of 61% at 13 years with no treatment-related mortality provides evidence of the value of this protocol. (Blood. 2000;95:1229-1236)
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PMID:Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia. 1066 95


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