Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibody reagents were used to develop a sensitive enzyme-linked immunoassay for clinical measurement of circulating transferrin receptor. By using transferrin-bound receptor for the preparation of the immunologic reagents, we developed an assay that gives an identical dose-response curve with either free or transferrin-bound receptor. The mean concentration of circulating receptor in 82 normal male and female volunteers was 5.63 +/- 1.42 mg/L. The level was reduced significantly in patients with primary aplastic anemia and post-transplant aplasia (2.58 +/- 1.07 mg/L and 2.32 +/- 0.48 mg/L, respectively) and was sharply elevated in patients with hemolytic anemia and iron deficiency anemia (33.1 +/- 17 and 18.0 +/- 11.4 mg/L, respectively). Our assay values are approximately 20-fold higher than results published previously in a study that used an immunoradiometric assay. The disparity apparently relates to a difference in sensitivity of the latter assay for free and transferrin-bound receptor. Measurements of serum transferrin receptor provide a useful clinical index of either total or iron-deficiency erythropoiesis.
 ...
PMID:The clinical measurement of serum transferrin receptor. 267 98

Iron overload is found clinically in such conditions as hemochromatosis and sideroblastic anemia, and after long term repeated transfusion in aplastic anemia. An animal model of iron overload was successfully developed in rats and rabbits by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+-NTA). This procedure induced a diabetic state with hyperglycemia, ketonemia, glycosuria and ketonuria. Blood venesection on these rats reduced the iron load in the liver and pancreas, and ameliorated the general diabetic symptoms. A single injection of Fe3+-NTA in rats induced a temporary elevation in plasma iron concentration, lipid peroxidation in the perfused liver homogenate expressed by malondialdehyde (MDA) formation, blood GOT, GPT, ALP and gamma-GTP sequentially. Fe3+-NTA uptake in the liver caused membrane lipid peroxidation, and subsequently produced a transit liberation of liver cell enzymes, although the incorporated liver Fe3+-NTA was only 1% of the injected dosage (7.5 mg iron/kg BW) at 3 hr after injection. The direct toxic effect of Fe3+-NTA to living cells was examined using cultured normal rat liver parenchymal cells (RL-34). Marked cytolysis was found in cells exposed to more than 25 micrograms of iron through Fe3+-NTA/ml. At 50 micrograms iron of Fe3+-NTA/ml, most cells were lethally injured and the remaining cells were piled up and aggregated at 15 days. They grew on soft agar culture, and when inoculated subcutaneously to five newly born rats a subcutaneous tumor developed in all animals within three weeks. Lung metastases were found in three of five inoculated rats. A spin trapping technique with electron spin resonance (ESR) on Fe3+-NTA employing 5, 5-dimethyl-l-pyrroline-N-oxide (DMPO) yielded a spin adduct with three doublets (DMPO-Z) which corresponded to singlet oxygen. By ESR in the presence of H2O2, the Fe3+-NTA solution strongly generated hydroxyl radical. The production of active oxygen species by Fe3+-NTA solution may explain the toxicity and carcinogenicity of Fe3+-NTA. The majority of stainable iron in the iron overloaded tissue was hemosiderin (Hs). We tried to purify the Hs from multi-transfused human spleen by the method of Weir et al. The purified Hs did not show a DMPO-OH adducts in the presence of H2O2 and DMPO on ESR measurement. The Hs iron was solubilized with several biological ligands in an acidic state in the presence of a reducing reagent like glutathione. Solubilized Hs iron produced iron chelate complexes which resulted in OH radicals production in the presence of H2O2 in acidic conditions below pH 5.5.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Pathogenesis and mechanism of iron overload: ferric nitrilotriacetate, hemosiderin, active oxygen, and carcinogenesis]. 268 76

Iron deposits in the human labial minor salivary glands were examined in a series of 195 postmortem subjects. Iron deposits (hemosiderin granules) were found in 7 subjects (3.6%), and the major types of illness in these cases were liver cirrhosis with or without hepatoma, aplastic anemia and acute myelogenous leukemia. Three out of 7 subjects had a history of blood transfusion. Considerable quantities of hemosiderin granules were deposited within the cytoplasm of the acinar and ductal epithelial cells, and hemosiderin-laden cells were scattered in the interstitial connective tissue.
 ...
PMID:Iron deposits in the human labial minor salivary glands: a postmortem study. 273 86

Erythropoietic activity is known to be closely associated with marrow iron uptake. A modification of the standard measure of plasma iron turnover has been developed in which erythron transferrin uptake (ETU) rather than iron uptake has been calculated. The ETU has the advantage of providing a parameter of erythroid marrow activity independent of change produced by plasma iron and transferrin saturation. Measurements in 80 patients with anemia were compared to the normal value of 60 +/- 12 mumol/L whole blood/d. The mean ETU for ten patients with severe aplastic anemia and for six patients with pure red-cell aplasia were 12 +/- 8 and 12 +/- 11 mumol/L whole blood/d, respectively. In ten transfusion-dependent patients with renal failure under dialysis therapy, the mean value was 35 +/- 11, while ten other dialyzed patients who were transfusion independent had a mean ETU of 73 +/- 21 mumol/L whole blood/d. Sixteen patients with hemolytic anemia had an average ETU of 400 +/- 130, while 28 patients with ineffective erythropoiesis had a mean value of 474 +/- 147 mumol/L whole blood/d. While patients with hypoproliferative anemia showed no relation between the severity of anemia and ETU, those with hyperproliferative erythroid marrow showed increasing values as the anemia became more severe. Sequential measurements in patients with aplastic anemia under treatment and in thalassemic patients under transfusion therapy showed the value of this measurement in monitoring the effects of treatment on erythroid marrow activity. It is concluded that the measurement of ETU provides a more direct ferrokinetic evaluation of erythroid activity in anemic states.
 ...
PMID:Erythroid marrow function in anemic patients. 309 23

Conventional ferrokinetic studies were done in patients with idiopathic hemochromatosis, secondary siderosis of the liver and iron overload in consequence of sideroblastic or aplastic anaemia. By means of the isotope 59Fe we determined the clearance of radioiron from the plasma, the plasma iron turnover, the utilization of iron by the erythropoesis and the iron uptake by the liver. The later value showed a good correlation with the iron content of the liver determined by atomic absorption spectrometry as well in patients with hemochromatosis as in patients with secondary siderosis of the liver. The 59Fe uptake by the liver was normal in treated hemochromatosis. There was no correlation between the degree of the iron overload and the 59Fe uptake by the liver in patients with anaemia.
 ...
PMID:[Ferrokinetic studies with Fe-59 in idiopathic hemochromatosis and other forms of iron overload]. 324 50

Analysis of radioactive iron kinetics was performed using a multi-compartment model on a series of 300 patients having either a quantitative (aplasia, haemolysis, iron deficiency) or qualitative (dyserythropoiesis, agnogenic myeloid metaplasia) anomaly of iron metabolism. Calculations were performed using a mammillary model of iron metabolism. The study demonstrated that the flux of iron from the plasma to the exchangeable compartment was a constant fraction of the global iron flux, equal to 15%, in those cases without dyserythropoiesis. This suggested that a constant correction for calculations of iron flux from the slope of the initial portion of the radioactive iron elimination curve may be applied to calculations of haemoglobin production and to the movements of iron to its exchangeable pools. Contrary to previously published information, the exchange of iron between the plasma and the exchangeable pools was not related to circulating iron levels when the other parameters were held constant. In the patients with aplastic anaemia the iron flux was diminished, but never eliminated, demonstrating that the exchangeable compartment was not solely erythroblastic, but included non-erythroid transferrin receptors. In dyserythropoietic states and myelofibrosis, the iron flux from the plasma was elevated, indicating that an important fraction of radio-iron leaves the plasma and then returns, without participating in effective erythropoiesis as determined by the appearance in the circulation of labelled viable red blood cells. The determination of this movement permitted the measurement of ineffective erythropoiesis.
 ...
PMID:Radio-iron kinetic studies in anaemia and the measurement of dyserythropoiesis. 341 96

Aplastic anaemia affects the entire bone marrow. Current methods of assessment of bone marrow function, like bone marrow biopsy or peripheral blood examination are either invasive or inadequate and cannot be expected to represent fully the changes in the entire bone marrow tissue. This prospective study was undertaken to develop and standardise a new Nuclear Medicine technique called 'Dynamic Bone marrow Imaging'. Eleven patients and ten controls were studied. Serial images of the pelvis were obtained in frame mode following intravenous injection of 185-370 mBq of 99mTc S. Colloid, and an index, called the Bone Marrow Uptake Index (P) was calculated by taking into consideration the time activity curve obtained over the iliac crest. This was followed by static imaging of the entire bone marrow in all cases. It was possible to obtain excellent information regarding topographic distribution of bone marrow as well as detect early changes in bone marrow function following treatment. An attempt was also made to correlate bone marrow cellularity as obtained by bone marrow biopsy with the results of dynamic bone marrow scintigraphy. On the basis of the encouraging results obtained in the present study, the authors feel that dynamic bone marrow imaging is an excellent technique for the objective evaluation of bone marrow in aplastic anaemia. Aplastic anaemia affects the entire bone marrow tissue. Although much progress has been made in the management of this disease, many aspects of it await better understanding. There is almost total lack of knowledge regarding the distribution of functioning marrow in various phases of aplastic anaemia, such as in relapse and remission. Current methods of assessment of marrow function rely mainly on bone marrow biopsy and peripheral blood examination. Bone marrow biopsy is invasive and cannot be expected to represent fully the changes in the entire tissue. Changes in peripheral blood picture lag behind the changes in the bone marrow. Thus, there is a need for an investigation which is safe, simple, sensitive, non invasive and capable of assessing the global function of bone marrow. Radio-nuclide imaging of bone marrow requires labelling of one or more components of this widely dispersed tissue. The reticuloendothelial and erythropoietic components can be labelled with radio-colloids and radio-iron respectively. Experimental studies have shown that the reticuloendothelial and erythropoietic elements are invariably found together in the marrow and have similar distribution. This report is based on a prospective study of bone marrow function in patients with aplastic anaemia, using 99mTc. Sulphur colloid.
 ...
PMID:Marrow uptake index (MUI): a quantitative scintigraphic study of bone marrow in aplastic anaemia. 343 29

To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects (p less than 0.01). Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of 125I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast.
 ...
PMID:Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias. 360 65

A 32 year old woman with severe aplastic anaemia required frequent transfusions and consequently developed hyperferrioxaemia (54 microMol/l) and hyperferritinaemia (1,700 ng/ml). For the treatment of transfusion siderosis she was given 18 high dose courses each comprising 35 g of desferrioxamine. Because of pre-existing thrombocytopenia (platelet count 5 X 10(9)/l) the iron chelating agent was given by continuous intravenous infusion over 3 1/2 days. High dose desferrioxamine had to be abandoned because of severe bone pain. The desferrioxamine infusions achieved a negative iron balance, iron loss after each infusion being 100 to 200 mg in the urine and 400 mg in the faeces. Serum iron and ferritin concentrations fell almost to normal. This report shows that faecal iron excretion must be taken into account in assessing the balance of iron input and output during desferrioxamine treatment.
 ...
PMID:High dosage desferrioxamine therapy in a female patient with acquired aplastic anaemia and transfusion siderosis. 363 32

Serum transferrin receptors were measured by a sandwich radioimmunoassay procedure in patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia. The mean circulating transferrin receptor concentration of normal subjects and patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia are 253 +/- 82 ng/mL, 730 +/- 391 ng/mL, 1,426 +/- 1,079 ng/mL, and 182 +/- 39 ng/mL, respectively. The values for those with iron deficiency anemia and autoimmune hemolytic anemia were significantly higher than that of normal controls and the values for those with aplastic anemia were lower than that of normal controls. After iron supplementation in iron deficiency anemia, the serum transferrin receptor values increased twofold over those of pretreatment values. This increase parallels an increase in peripheral reticulocytes. Therefore, the number of circulating transferrin receptors in anemic patients may reflect the level of bone marrow erythropoiesis and is a potentially useful new index for red cell production.
 ...
PMID:Serum transferrin receptor as a new index of erythropoiesis. 367 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>