Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We cultured marrow and peripheral blood erythropoietic precrusors in methylcellulose clonal assay and measured the synthetic rates of HbA, A2, F, and S in patients with and without sickle cell anemia. Hb was labeled with 14C-amino acid in culture, separated by slab gel isoelectric focusing techniques, and quantitated by autoradiographic methods. Comparison of marrow late (CFU-E) and early (BFU-E) precursors from patients without hemoglobinopathies showed that preferential synthesis of HbF is limited to early precursors. Simultaneous examinations of Hb synthesis by blood and marrow early erythropoietic precursors confirmed the similarity of the biosynthetic capabilities of the precursors from the two sources. Increasing concentrations of erythropoietin (Ep) in culture corresponded with increases in the percentages of HbF synthesized by blood BFU-E of normal individuals. HbF biosynthesis by blood BFU-E from sickle cell anemia patients was significantly higher than that synthesized by nonanemic individuals and showed significant individual variations. HbF synthesis in patients with sickle cell anemia was partially dependent on Ep concentrations in culture. Cell culture of circulating erythropoietic precursors in man appears to provide a unique tool for studying the control mechanisms of Hb synthesis in man.
 ...
PMID:Augmentation of fetal hemoglobin (HbF) synthesis in culture by human erythropoietic precursors in the marrow and peripheral blood: studies in sickle cell anemia and nonhemoglobinopathic adults. 71 66

The absence of any response to the administration of recombinant human erythropoietin (rHuEpo) is exceptional in uremic patients with anemia. Initial "nonresponders" generally respond to higher doses of the hormone. However, a small number of patients may remain unresponsive. The most common cause of limited response is mild to moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Another common cause of resistance is the presence of an overt or, more often, an unrecognized inflammatory state, including acute or chronic infection. Marked aluminum overload and severe hyperparathyroidism also have been shown to induce resistance in at least some patients. Other factors may contribute to the severity of anemia and hence increase rHuEpo requirements, such as acute or chronic hemolytic conditions or blood loss, folate deficiency, hemoglobinopathies, and still poorly defined uremic toxins. In patients who show a resistance to the effect of the recombinant hormone, these should be sought and eliminated, if possible.
 ...
PMID:Modulating factors in the hematopoietic response to erythropoietin. 192 86

We report a case of erythrocytosis in a patient with end-stage renal failure on chronic hemodialysis. The patient with polycystic kidney disease had an average Hb level of 10 g/dl while on hemodialysis for 3 years. He developed erythrocytosis (Hb 17.6 g/dl) following a cadaveric renal transplantation. No signs suggesting polycythemia vera were found. Nonrenal causes of secondary erythrocytosis such as anoxia, hemoglobinopathies or tumors were excluded. Angiography showed renal artery occlusion of the native kidney. Serum erythropoietin level was 85 U/l (normal 52 +/- 31 U/l) as measured by 3H-thymidine uptake. It is suggested that ischemia caused by the renal artery thrombosis stimulated the erythropoietin production in the native polycystic kidney.
 ...
PMID:Erythrocytosis associated with renal artery thrombosis in a patient with polycystic kidney disease on hemodialysis. 211 27

The administration of recombinant human erythropoietin (rHuEPO) to anemic hemodialysis patients is usually followed by a rapid increase in hemoglobin. Initial 'nonresponders' may either respond to higher doses of rHuEPO or rarely may remain totally unresponsive. Schematically, one can distinguish between a state of relative and absolute resistance to the action of the hormone. The most common causes of resistance are iron deficiency, aluminium overload, episodes of infection or other inflammatory processes, probably severe hyperparathyroidism, acute or chronic hemolytic conditions, acute or chronic blood loss, folate deficiency, and hemoglobinopathies in exceptional instances. Antibody formation against rHuEPO or marrow fibrosis secondary to rHuEPO treatment can be discarded as potential causes of resistance.
 ...
PMID:Resistance to recombinant human erythropoietin in hemodialysis patients. 226 Jun 16

The absolute adult and fetal hemoglobin (HbF) contents of the erythroid cells derived from the differentiation of normal human and simian erythroid progenitors and of the peripheral blood erythroid burst-forming units (BFU-E) of patients with nondeletion hemoglobinopathies have been measured with a sensitive radioligand immunoassay. The HbF content varied between 0.13 and 2.96 pg/cell, representing between 0.7% and 19.6% of the total hemoglobin with a mean value of 7.0%. The absolute content of HbF was indistinguishable in the well-hemoglobinized progeny of marrow erythroid colony-forming units, marrow or blood BFU-E, or of mixed colony-forming units. The term HbF program refers to this inherent capacity to produce fetal hemoglobin (HbF) in the erythroid cells derived from these progenitors in vitro. The HbF content of marrow erythroblasts as determined by the same radioligand immunoassay was similar to that found in the peripheral blood, suggesting that the switch off of gamma-chain production occurs after the erythroid colony-forming unit stage of maturation. Increasing concentrations of a crude erythropoietin-containing preparation induced higher numbers of erythroid colonies, which were larger in size, but the HbF program was unaffected. In contrast to the hemoglobin accumulation in human progenitor-derived colonies, simian progenitor-derived colonies produced considerably more HbF, and the amount of HbF was strongly influenced by progenitor maturity. Assays of the HbF content of erythroblasts derived from culture of the peripheral blood BFU-E of patients with nondeletion hemoglobinopathies and their parents showed that the HbF program in the progenitors of such patients is highly variable. Some produce only a slight excess of HbF in progenitor-derived erythroblasts, whereas others have extraordinarily high HbF programs. The molecular basis of this variability is presently unknown.
 ...
PMID:Determination of the hemoglobin F program in human progenitor-derived erythroid cells. 258 Aug 59

Extramedullary hematopoiesis (EMH) is observed in people suffering from severe anemia of prolonged duration and appears to be a compensatory mechanism for disturbed medullary hematopoiesis. The hemoglobinopathies (such as thalassemia, spherocytosis, and sickle cell disease), neoplastic diseases such as leukemia and lymphoma, and others, including myelofibrosis and osteitis fibrosa cystica, are associated with EMH. These diseases and their resultant anemia have in common the ability to stimulate erythropoietin production, which in turn may stimulate hematopoiesis in organs of mesenchymal origin. The liver and spleen are the most common sites of EMH; however, other sites, including the falx cerebri, thoracic cavity, retroperitoneal area and pelvis have been reported. When present, intrathoracic EMH is most frequently associated with thalassemia. Spinal cord compression and hemothorax have also been reported as complications of intrathoracic EMH.
 ...
PMID:Asymptomatic intrathoracic extramedullary hematopoiesis: a report of three cases. 262 Nov 1

Hydroxyurea (HU), an inhibitor of DNA synthesis, has been shown to increase fetal hemoglobin (HbF) levels in patients with sickle cell anemia and in some patients with beta-thalassemia. However, until now there have not been good in vitro model systems that simulate this effect for study of the molecular and cellular mechanism(s) involved in perturbing the normal ontogeny of the globin genes. We analyzed the cellular effects of HU using a two-phase liquid culture procedure (Fibach et al: Blood 73:100, 1989) in which human peripheral blood-derived progenitor cells undergo proliferation and differentiation. HU was found to have multiple effects on these cultured cells: (1) an increase in the proportion of HbF produced; (2) a decrease in cell number due to inhibition of cell proliferation; (3) an increase in hemoglobin content per cell (mean corpuscular hemoglobin [MCH]); and (4) an increase in cell size (mean corpuscular volume). The extent of these effects was related to the HU dose and time of addition. When added to cell cultures from normal individuals, 4 days following their exposure to erythropoietin (EPO), 100 mumol/L HU caused a 1.3- to 3.5-fold increase in the proportion of HbF, from 0.4% to 5.2% (mean 1.6) in untreated to 1.5% to 8.2% (mean 3.1) in HU-treated cultures and a 45% +/- 10% increase in MCH but only a 25% +/- 7% decrease in cell number on day 13. Cultures of cells derived from five patients with sickle cell anemia have shown a twofold to fivefold increase in the percentage of Hb F following addition of HU while four patients with beta-thalassemia showed a 1.3- to 6.2-fold increase. We believe that this primary cell culture procedure should prove useful in studying the cellular and molecular mechanisms of pharmacologic induction of HbF and might provide a valuable predictive assay system for evaluation of the response of individual patients with hemoglobinopathies to HU and similar agents.
 ...
PMID:Hydroxyurea increases fetal hemoglobin in cultured erythroid cells derived from normal individuals and patients with sickle cell anemia or beta-thalassemia. 768 Sep 23

We have examined whether the secretion of erythropoietin (Epo) from genetically modified cells could represent an alternative to repeated injections of the recombinant hormone for treating chronic anemias responsive to Epo. Primary mouse skin fibroblasts were transduced with a retroviral vector in which the murine Epo cDNA is expressed under the control of the murine phosphoglycerate kinase promoter. "Neo-organs" containing the genetically modified fibroblasts embedded into collagen lattices were implanted into the peritoneal cavity of mice. Increased hematocrit (> 80%) and elevated serum Epo concentration (ranging from 60 to 408 milliunits/ml) were observed in recipient animals over a 10-month observation period. Hematocrit values measured in recipient mice varied according to the number of implanted Epo-secreting fibroblasts (ranging from 2.5 to 20 x 10(6)). The implantation of neo-organs containing Epo-secreting fibroblasts appeared, therefore, as a convenient method to achieve permanent in vivo delivery of the hormone. We estimated that the biological efficacy of the approach may be relevant for the treatment of human hemoglobinopathies.
 ...
PMID:Sustained delivery of erythropoietin in mice by genetically modified skin fibroblasts. 772 39

Cytokines play key roles in the control of hemopoiesis and immunity. As they become available in increasing quantities and purity through improved recombinant technology, cytokines hold great clinical promise. This article focuses on recent clinical experience with a wide variety of cytokines. For example, newer uses of recombinant human erythropoietin include treatment of anemia of prematurity, AIDS, and some hemoglobinopathies. The myeloid-stimulating factors have established a niche in the treatment of chemotherapy-induced neutropenias and as an adjunct to bone marrow transplantation. Combinations of cytokines that act at different levels of hemopoietic proliferation are being evaluated for the treatment of other causes of neutropenia and thrombocytopenia and also as biologic response modifiers.
 ...
PMID:The use of cytokines in children. 820 76

The mechanism of resistance to recombinant human erythropoietin (EPO) in hemodialysis patients with hemoglobinopathy is not yet fully understood. Poor responses to EPO have been reported in anemic dialysis patients with sickle cell disease and thalassemia. We present the first case of a hemodialysis patient with EPO resistance and hemoglobin J-Meinung, which is initially found by hemoglobin electrophoresis and finally proven by molecular genetic analysis. Additionally, the patient was diagnosed as having chronic active hemolysis with hallmarks of splenomegaly, an increased serum bilirubin and reticulocyte index, and a reduced haptoglobin level. We discuss the possible mechanisms and proper treatment options in such patients with a poor response to EPO.
 ...
PMID:Resistance to recombinant erythropoietin in a hemodialysis patient with heterozygous hemoglobinopathy J-Meinung. 915 14


1 2 3 4 Next >>