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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression "congenital dyserythropoietic anemia" (CDA) has been used to characterize the kinetic and morphological aberrations in the proliferation and maturation compartment of erythropoiesis, occurring in a group of hereditary anemias of unknown pathogenesis. The main symptoms of these disorders are moderate or mild anemia, increased hemoglobin turnover, ineffectiveness of erythropoiesis, striking morphological aberrations of the erythroblasts and tendency to secondary hemochromatosis. To date, three types have emerged from this group that may be hereditary nosological entities. They are distinguished not only on a morphological basis, but also by different modes of inheritance and immunological properties of the red cell membrane. A number of additional cases or families have been described which could not be attributed to one of these three types. Comparative investigations of morphological, biochemical and immunological details in CDA on the one hand, and other forms of ineffective erythropoiesis (e.g. thalassemia, refractory anemia) on the other demonstrate the lack of specificity of many of the single changes observed in CDA. These changes may well be secondary phenomenon of intramedullary cell destruction brought about by different underlying pathogenetic mechanisms.
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PMID:[Dyserythropoiesis and dyserythropoietic anemias]. 120 18

The authors report on a 24-year old patient with Blackfan-Diamond syndrome who developed a Hodgkin's disease. This patient became transfusion-dependent at the age of 10, after an initial period of corticosensitivity, and after failure of androgens. He developed hemochromatosis despite from parenteral chelation therapy. He died of infectious complications 4 months after the diagnosis of Hodgkin's lymphoma. A review of the literature shows an increased incidence of malignancies in Blackfan-Diamond syndrome (three cases of leukemia), and in similar disease (thalassemia and sickle cell disease), but not in other patients with hemosiderosis (primitive hemochromatosis, end-stage renal failure under dialysis). Etiopathogenic hypotheses are discussed.
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PMID:[Blackfan-Diamond disease and malignancy: cause effect relationships?]. 133 66

A 64-year-old man was admitted due to ascites. Laboratory data showed hemoglobin 6.7 g/dl, mean corpuscular volume 82 fl, and ferritin 2,360 ng/ml. Liver biopsy showed hemochromatosis. The diagnosis of beta-thalassemia was suggested by a decreased ratio of beta/alpha-globin synthesis in vitro (0.26). Cloning of the beta-globin gene showed A-to-G mutation in the first base of the ATA box. He was confirmed to be homozygous for this specific allele by beta-gene complex analysis and analysis of Southern blot hybridization of the alpha- and beta-globin genes. His two sons were confirmed to be heterozygous for this allele.
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PMID:Beta(+)-thalassemia with hemochromatosis. 136 99

A patient with thalassemia minor (TM) is reported who ingested 80 g of alcohol/day and presented an important overload of iron with deposits and a hepatic iron ratio compatible with primary hemochromatosis. The results obtained from the study of histocompatibility antigens, clinical manifestations and family analysis discarded the possibility of two genetic diseases, beta-thalassemia and primary hemochromatosis, being concomitantly present in the same progeny. Thalassemia minor and alcoholic hepatopathy are considered as having acted together and being responsible for the iron overload. The relation between alcohol ingested, TM and iron deposits is discussed.
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PMID:[Thalassemia minor with iron overload: genetic and clinical study of a family]. 176 61

Since freshly obtained acute lymphoblastic leukemia (ALL) cells rarely replicate spontaneously in vitro in a sustained way, development of a useful clonogenic assay for ALL blast progenitors is dependent on identifying the cellular growth requirements. Thus, marrows from 25 ALL cases were cultured in methylcellulose to determine the optimal conditions for cell growth. Blast colonies were confirmed as leukemic by morphology, cytochemistry, surface markers, and cytogenetics. Irradiated (7000 rads) normal peripheral blood feeder cells were an absolute requirement and produced number-dependent increases in ALL colonies; added growth factors enhanced the feeder cell effect. ALL cell-feeder cell contact was essential since their physical separation in a two-layer culture system drastically interfered with colony growth. Feeder cells from various donors, including new and relapsed cases of ALL, yielded colony numbers that differed widely when tested on the same marrow with and without added growth factor; thus, identification of a "good" feeder cell donor was key to an optimal assay. Neither recombinant interleukin-2 nor recombinant GM-CSF had ALL growth-promoting properties when tested alone or in combination but in the presence of feeder cells they moderately enhanced the feeder cell effect. The most effective growth factors were derived from cells exposed to phytohemagglutinin (PHA) for 72 h. In order of magnitude for colony growth-promoting activity, PHA-T cell conditioned medium (CM) was more stimulatory than PHA-blast cell CM followed by PHA-leukocyte CM; removal of PHA from CM by affinity chromotography did not alter the results. The most potent PHA-TCM was prepared from T-cells from a phlebotomized hemochromatosis patient; PHA-TCM from transfused thalassemia patients and normal donors were less active. Concanavalin-A blast cell CM had modest colony promoting properties whereas CM prepared with other B-cell mitogens and supernatants from ALL blasts in liquid culture had none. Our studies illustrate the complex and fastidious growth needs of ALL cells. The data have allowed us to refine a clonogenic blast progenitor assay that should facilitate study of proliferative properties of B and T lineage leukemias. The assay could be adapted further for detection of residual leukemia cells in marrow samples used for autologous transplantation, and in patients during complete hematological "remission."
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PMID:Growth requirements for human acute lymphoblastic leukemia cells: refinement of a clonogenic assay. 304 51

Concentration of iron in plasma, total iron-binding capacity (TIBC), and transferrin saturation are often determined by standard spectrophotometric methods, but iron concentration may be quantified by immunoprecipitation or, electrochemically, by controlled-potential coulometry. Because these iron assays do not all measure the same form(s) of iron, we studied subjects in various states of iron nutriture: normal adults, iron-deficient patients, thalassemia patients with unsaturated transferrin or oversaturated transferrin, and patients with idiopathic hemochromatosis. The spectrophotometric and coulometric methods detected essentially all non-heme iron in plasma; results correlated well but showed a negative bias toward the coulometric method. Results by an immunoprecipitation procedure, which measures only transferrin-bound iron, correlated well with those obtained coulometrically but were slightly higher than the latter. The characteristics of the various methods for iron must be understood by the clinical laboratory if diagnosis of iron disorders is to be accurate.
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PMID:Interpreting results of coulometry and immunoprecipitation in diagnosing iron disorders. 329 21

In 33 patients with thalassemia and idiopathic hemochromatosis, plasma ferritin protein levels ranged from 36 to 5,850 micrograms/L. The iron content of this ferritin as determined by immunoprecipitation ranged from undetectable amounts to 507 micrograms/L. The mean iron content of ferritin protein in those and other subjects with plasma ferritin concentrations of over 1,000 was 6.8% +/- 2.7%. Plasma transferrin was usually saturated with iron in patients with measurable ferritin iron, but exceptions occurred. In studies using electrophoretic separation, it was shown that some ferritin iron moved to transferrin during in vitro incubation, whereas exchange in the opposite direction was extremely limited. Because some plasma ferritin iron was measured by the standard colorimetric plasma iron determination, these observations (a) indicate that plasma ferritin contains a significant amount of iron (b) indicate that a significant proportion of nontransferrin iron in individuals with nontransferrin iron as detected by standard plasma iron and total iron-binding capacity measurements is due to the presence of ferritin, and (c) suggest that large amounts of ferritin iron may affect the saturation of plasma transferrin.
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PMID:Quantitation of ferritin iron in plasma, an explanation for non-transferrin iron. 335 90

The transferrin iron transport system, along with its procurement sites and delivery receptors, provides a highly effective means of satisfying internal iron requirements. Iron uptake by individual tissues is determined by their receptor number, by the relative amounts of monoferric and diferric transferrin in circulation, and by the amount of available iron in donor tissues. Although the modus operandi of this system under basal conditions has been characterized, its exquisite regulation remains an enigma. In some manner, the procurement of iron is determined by iron requirements. What seems to be an inappropriate behavior of the absorptive mechanism in thalassemia and certain other erythroid overload states may actually be life-saving in the absence of transfusion, since it results in higher levels of plasma iron and thereby higher levels of erythropoiesis. The definition of the regulatory mechanism in such conditions may well lead to an understanding of the molecular defect in idiopathic hemochromatosis.
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PMID:Transferrin: physiologic behavior and clinical implications. 608 33

Hemochromatosis is a syndrome which, when fully expressed, is manifested by melanoderma , diabetes mellitus, and liver cirrhosis, with iron overload involving parenchymal and reticuloendothelial cells in many organ systems. This clinical presentation may arise as a consequence of either hereditary or acquired abnormalities of iron overload, although the mechanisms are quite different. In hereditary hemochromatosis (also known as primary, or idiopathic, hemochromatosis), increased intestinal iron absorption leads to excessive accumulations of iron, throughout the body, particularly in parenchymal cells. In secondary forms of iron overload including transfusional hemosiderosis, alcoholic cirrhosis, thalassemia, sideroblastic anemia, and porphyria cutanea tarda, iron accumulates in the reticuloendothelial system initially, but with increasing amounts of total body iron, excessive iron deposits eventually accumulate in parenchymal cells throughout the body producing a picture indistinguishable from hereditary hemochromatosis. In this article, the course, prognosis, and therapy of iron overload will be reviewed in detail. Clinical and experimental data concerning the pathogenesis of the different forms of iron overload will be examined critically. In particular, information relating to possible abnormalities of reticuloendothelial function, intestinal mucosal iron transport, and alterations in serum and tissue isoferritin patterns in hereditary hemochromatosis will be analyzed, and possible directions for future research will be suggested. The mode of inheritance and linkage with the major histocompatibility (HLA) complex will be discussed. Theories on the pathogenesis of tissue damage by excess iron will be evaluated. Methods for measuring the extent of iron overload in clinical practice will be described, including measurements of serum iron, serum ferritin, iron absorption, cobalt excretion, desferrioxamine excretion, liver biopsy and tissue iron determinations, and HLA typing. Finally, unresolved problems in the understanding of the disease process, diagnosis, and therapy will be delineated.
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PMID:Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy. 637 41

Basic ferritin (liver-type) was measured in erythrocytes of subjects with alpha- and beta-thalassemia trait, thalassemia intermedia and Cooley's disease, and compared with normals and patients with abnormal iron metabolism without erythrocyte metabolic defect (iron deficiency anemia and idiopathic hemochromatosis). In all the thalassemic syndromes considered, erythrocyte ferritin was significantly higher than in normals (p less than 0.001) and increased progressively with the increasing 'severity' of the thalassemic disorder. In both thalassemic and non-thalassemic subjects, erythrocyte ferritin levels were related to body iron status, but in the thalassemic group, the increased erythrocyte ferritin values seemed also to be closely related to the intracellular metabolic abnormality. The severity of the defect in globin chain synthesis seemed to play an important role in determining ferritin accumulation in red cells of thalassemic subjects.
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PMID:Erythrocyte ferritin in thalassemia syndromes. 642 38


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