UMLS:C0002871 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0002871 (anemia)
52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum albumin gastric loss was estimated from the measurement of non-dialysable radioactivity of the gastric juice after intravenous injection of radioiodinated serum albumin (RISA). Immunochemical quantitation of serum albumin was performed in some of the samples. In the control group, the mean gastric clearance of albumin was 1.71 ml per hour with a range of 0.41 to 4.41 ml per hour. This represented a gastric loss of 1.9 gram of albumin per day and 11% of the daily degradation of albumin. There was no significant change in the gastric albumin loss after stimulating the gastric secretion. No significant difference in the gastric albumin leakage was found between normal subjects and patients with gastric or duodenal ulcer. IN PERNICIOUS ANAEMIA ALBUMIN LOSS INTO THE STOMACH WAS GREATER (MEAN: 3.72 ml per hour; SD 1.52 ml) than in the normal group and accounted for the greater albumin fractional catabolic rate. This fact had never been proved before. In both patients with giant rugae of the gastric mucosa the gastric clearance of serum albumin was also increased. It is concluded first that albumin is not secreted by the chief and parietal cells of the mucosa and probably passes through the gastric wall between the cells of the mucosa, perhaps during the exfoliation of the surface epithelial cells, and secondly that the stomach is one of the sites of serum albumin breakdown, a fact that supports the view that the gastrointestinal tract plays a major role in the catabolism of serum albumin.
...
PMID:Gastric clearance of serum albumin in normal man and in certain gastroduodenal disorders. 421 Jan 83

ANEMIA CAUSES A CHANGE IN THE TYPE OF CIRCULATING HEMOGLOBIN IN GOATS AND CERTAIN SHEEP: HbA (alpha(2)beta(2) (A)) is replaced by HbC (alpha(2)beta(2) (C)). We have isolated globin mRNA from erythroid cells of anemic and nonanemic animals to investigate the mechanism whereby anemia causes this switch. To study several stages in transition from beta(A) to beta(C) synthesis, active globin mRNA was isolated from bone marrow cells, as well as from reticulocytes. By assaying these globin mRNAs in a rabbit reticulocyte cell-free system, we have demonstrated that the switch from beta(A) to beta(C) globin synthesis is mediated via a change in functional globin mRNA.
...
PMID:Hemoglobin switching in sheep and goats: change in functional globin messenger RNA in reticulocytes and bone marrow cells. 450 88

This investigation is concerned with the kinetics of the reciprocal relationship between sheep hemoglobin (Hb) A and Hb C formation in response to anemia. The relative synthesis of the hemoglobin types was assessed at various times in bone marrow erythroid cells incubated in vitro with (59)Fe. The changeover from Hb A to Hb C formation lagged by about 3 days behind the development of anemia and was complete within about 11 days. After recovery from anemia the reciprocal change back to preanemic conditions proceeded at a much slower rate, Hb C formation gradually declining to unmeasurable levels over about 25 days. Infusions of plasma with high erythropoietin titre induced the formation of relatively large quantities of Hb C in erythroid cells of nonanemic sheep, demonstrating the central importance of a humoral mechanism in the change of expression of the hemoglobin genes. THE FOLLOWING CONCLUSIONS WERE DRAWN: hemoglobin phenotype is determined at a stem cell level. Erythroid stem cells appear to undergo gradual renewal. The identity of the plasma factor which induces Hb C formation is not yet known; it is not present in plasma from nonanemic sheep, and its production is not dependent upon hemoglobin genotype. If the plasma factor turns out to be erythropoietin, then this hormone must have an important influence on the pool of erythroid stem cells.
...
PMID:Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype. 567 11

The survival of erythrocytes (RBC) is shortened in uremia, and it has been shown that calcium influx into RBC evoked crenation and increased their rigidity. The high blood levels of parathyroid hormone (PTH) may augment entry of calcium into RBC and hence affect their integrity. We examined the effect of PTH on osmotic fragility of human RBC and investigated the mechanisms through which PTH interacts with RBC. Both the amino-terminal (1-34) PTH and the intact (1-84) PTH, but not the carboxy-terminal (53-84) PTH, produced significant increases in osmotic fragility. This effect was abolished by prior inactivation of the hormone. There was a dose-response relationship between both moieties of PTH and the increase in osmotic fragility. This action of PTH required calcium, was mimicked by calcium ionophore, and was partially blocked by verapamil. PTH caused significant influx of (45)Ca into RBC, which was not associated with potassium leak. The hormone did not affect water content of RBC. Scanning electron microscopy revealed that the incubation of RBC with PTH was associated with the appearance of membrane filamentous extensions, which anchor RBC together. Inhibition of glycolytic activity of RBC with NaF or inhibition of Na-K-activated ATPase with ouabain did not abolish the effect of PTH on osmotic fragility. PTH did not stimulate RBC Na-K-activated ATPase or Mg-dependent ATPase but caused marked and significant stimulation of Ca-activated ATPase. The basal activity of the RBC adenylate cyclase was low and PTH produced only a modest stimulation of this enzyme. Both cyclic AMP and dibutyryl cyclic AMP had no effect on osmotic fragility. THE DATA INDICATE THAT: (a) the RBC is a target organ for PTH, (b) the hormone increases osmotic fragility of RBC, and (c) this effect of PTH is due to enhanced calcium entry into RBC. We suggest that the increased calcium influx may affect the spectrin-actin of the cytoskeletal network of the RBC and may alter the stability and integrity of the cell membrane. This action of PTH on the RBC could be, at least in part, responsible for the shortened survival of RBC in uremia, and assign a new role for PTH in the pathogenesis of the anemia of uremia.
...
PMID:Effect of parathyroid hormone on osmotic fragility of human erythrocytes. 628 9

ERYTHROPOIETIN (EPO): Erythropoietin (EPO) is a hormone that promotes the proliferation and differentiation of erythroid progenitor cells and regulates the number of erythrocytes in peripheral blood. EPO is produced mainly by the kidneys, and transcription of the EPO gene is promoted by a reduction in the oxygen concentration in the blood. The existence of EPO was suggested near the end of the 19th century by the discovery that hypoxia increases the production of red blood cells. EPO was identified as a serum factor in the 1950s, and in 1970 Miyake and coworkers succeeded in purifying it by using the urine of patients with aplastic anemia as a starting material. The human EPO gene was cloned in 1985 using a partial amino acid sequence from this purified EPO, and it is well known that recombinant EPO is currently used as a drug to treat anemia associated with chronic renal failure and other illnesses. ACTION OF EPO: When human bone marrow cells are cultured in a semisolid medium containing EPO, they form small erythroblast colonies in five to seven days, and by day 10 large erythroblast colonies appear that resemble fireworks ("burst" colonies). The original cells in the former colonies are called colony forming units-erythroid (CFU-E) or late-stage erythroblast progenitor cells and in the latter colonies they are called burst forming units-erythroid (BFU-E) or early-stage erythroblast progenitor cells. As shown in Figure 1, red blood cells are produced through differentiation from stem cells to BFU-E, CFU-E, and erythroblasts. Although EPO acts on both BFU-E and CFU-E cells, CFU-E cells show greater sensitivity to EPO, and other factors such as stem cell factor (SCF), interleukin (IL)-3, IL-4, and granulocyte macrophage colony-stimulating factor (GM-CSF) must be present together with EPO for BFU-E cell proliferation. In erythroblasts beyond the CFU-E stage, sensitivity to EPO decreases as the cells mature. THE EPO RECEPTOR AND THE CYTOKINE RECEPTOR FAMILY: The EPO receptor gene was cloned by D'Andrea and coworkers in 1989 from murine erythroleukemia cells [1]. It became clear that the EPO receptor belongs to the cytokine receptor family that comprises receptors for the various interleukins, GM-CSF, granulocyte colony-stimulating factor (G-CSF), growth hormone and prolactin. The special characteristic of this family of receptors is that they are switched on (i.e., the receptor is activated) and transduce signals to the interior of the cell by the formation of homo- or hetero-oligomers (dimers or trimers). Moreover, hetero-oligomers of these receptors share a common receptor subunit. As shown in Figure 2, the IL-3, IL-5 and GM-CSF receptors have a common &bgr; subunit, and their ligand specificity is determined by the &agr; subunit. In the same manner, the IL-6, LIF and oncostatin M (OSM) receptors all share gp130, which is the &bgr; subunit of the IL-6 receptor. The IL-2, IL-4 and IL-7 receptors all share the &ggr; subunit of the IL-2 receptor. All the above receptors are activated by the formation of hetero-oligomers, but the G-CSF receptor, EPO receptor, and growth hormone receptor are activated by the formation of homodimers of the same types of molecules [2]. We can see that groups of cytokines such as the interleukins that affect a relatively wide range of cells and have redundant biological activity create this redundancy through the common use of a single receptor subunit. On the other hand, EPO and G-CSF act with high specificity on a relatively limited range of cells, so it was probably unnecessary for their receptors to share one of the subunits. EPO RECEPTOR AND JAK2 KINASE: The signal for cellular proliferation and differentiation into erythroblasts is thought to originate at the EPO receptor. The cytoplasmic domain of the EPO receptor can be divided into two major regions. Roughly half of the cytoplasmic domain, the part lying nearest the plasma membrane, is required for generating the signals for proliferation and differentiation such as the induction of globin synthesis [3, 4]. The remaining half is not required for this signaling, and, conversely, it acts to dampen the signals. It is known that a tyrosine kinase called JAK2 associates with the region near the plasma membrane, undergoes autophosphorylation, and phosphorylates the EPO receptor, and a transcription factor called a STAT [5]. It is thought that JAK2 plays an important role in promoting cellular proliferation. The STAT is activated by the phosphorylation, and it then translocates to the nucleus, recognizes a specific base sequence in the promoter region of its target gene, and initiates transcription. At present, we know that the STAT whose activation is mediated by the EPO receptor is STAT5, and the target genes are CIS [6], which has an SH2 domain (a molecular structure that recognizes a phosphorylated tyrosine) and OSM [7], which is a pleiotropic cytokine. However, activation of STAT5 and activation of the target genes are not unique to the EPO receptor, and they also occur with the IL-2 and IL-3 receptors. Moreover, the JAK2 substrate that is directly linked to cellular proliferation is still unknown. At present, studies are under way to determine the transcription factors specific to EPO and their target genes, as well as the substrates of JAK2. RECEPTOR PHOSPHORYLATION AND CESSATION OF THE SIGNAL: On the other hand, tyrosine phosphorylation of the receptor is necessary at the cytoplasmic tail region far from the plasma membrane, and the signal transduction pathway that originates with this phosphorylated tyrosine and is mediated by proteins with SH2 domains becomes activated. First, a GTP/GDP exchange factor called SOS, which is mediated by Shc and Grb2, migrates to the plasma membrane and converts a ras protein to its GTP form. The activated ras protein then activates the Raf-MAP kinase kinase-MAP kinase cascade, and ultimately initiates the transcription of oncogenes such as c-fos and c-jun. An enzyme called PI3 kinase binds to the tyrosine phosphorylation site of the receptor and a second messenger is born. It is known that this pathway is a requirement for DNA synthesis in certain types of fibroblasts. However, these signal transduction pathways are not unique to the EPO receptor, and they are also activated by most growth factor receptors, so they are not necessarily required for EPO-induced proliferation. Conversely, the tyrosine phosphatase SH-PTP1 (also called HCP) that has an SH2 domain and is specific to blood cells associates with the tyrosine phosphorylation site of the receptor and promotes the dephosphorylation of JAK2. In other words, the role of SH-PTP1 is to stop generation of the signal [8]. Therefore, in mutations lacking this cytoplasmic tail region of the receptor far from the plasma membrane, the receptors do not undergo tyrosine phosphorylation, JAK2 activation continues for a longer period of time, and thus the signal is generated more efficiently. In fact, in one patient with a mild case of familial erythrocytosis a mutation was discovered in which the C-terminus of the EPO receptor was missing 70 amino acids [9]. This was a dominant genetic trait, and the patient's erythroblasts showed an increased sensitivity to EPO. In this family the impairment was not severe enough to be called an illness, and in fact it is said that this patient was proficient enough athletically to compete for a gold medal at the Olympics. More specifically, the reason that athletes undergo training at high altitudes is to boost EPO production because of the lower oxygen partial pressure, and this brings about the desired effect of sustained athletic capability due to a resultant increase in red blood cells. However, the same effect has occurred naturally in this athlete thanks to accelerated receptor capability.
...
PMID:Physician Education: The Erythropoietin Receptor and Signal Transduction. 1038 12

PRINCIPAL CARDIOVASCULAR COMPLICATIONS IN END STAGE RENAL DISEASE: Cardiovascular diseases are the leading causes of morbidity and mortality in end stage renal disease patients. Very often, complications observed are left ventricular hypertrophy and various forms of arterial degenerative lesions involving coronary arteries, less frequently pericarditis and calcifying valvulopathy are diagnosed. THE REASONS ARE COMPLEX: Risk factors can be either specific of uremia per se such as anemia, overhydration, fistula or the same as in the general population. Hemodynamic alterations including tensile stress or blood flow play a major role associated to various locally or generally generated substances whose role remains currently to be determined. THEIR TREATMENTS: Treatments of cardiovascular complications are not specific in this end stage renal disease population but are more often the treatment of the etiology: reduction of fistula blood flow, increase of hemoglobin, best control of weight gain between two hemodialysis sessions or blood pressure control.
...
PMID:[Cardiac anomalies in chronic renal failure]. 1070 11

FREQUENT IN THE CASE OF CANCER: According to a European multicentre study on 15 000 cancer patients, the percentage of anaemia exceeded 66% during the development of solid tumours and 72% during development of malignant tumours. The lowest levels of haemoglobin were correlated with the lowest performance status, however no treatment had been prescribed for anaemia in the majority of patients. MULTIPLE MYELOMAS AND LYMPHOMAS: The frequency of anaemia appeared just as high during these malignant affections and the correlation between haemoglobin levels and performance status was just as clear. Likewise, around one half of the anaemic patients had not been treated in an adapted or efficient manner. SIGNIFICANCE OF ANEMIA DURING LYMPHOMAS: It appeared that the anaemia of Hodgkin's disease, related to the inflammation, was correlated with shorter survival, whereas the anaemia of non-hodgkin lymphoma, related to medullar infiltration, generally affected the complete rate of response.
...
PMID:[Epidemiological data on anaemia during malignant affections]. 1453 1

IMPROVED QUALITY OF LIFE WITH EPOETIN BETA: In a study against a placebo, there was evidence that the quality of life scores were significantly improved in patients treated with epoetin beta, whether they exhibited a solid tumour or a malignant lymphoma. The same was noted in children with cancer exhibiting severe neoplasia and treated with chemotherapy. The efficacy and tolerance to treatment were equivalent, whatever the administration regimen. IN PATIENTS SUFFERING FROM MYELODYSPLASTIC SYNDROMES: A particular entity among malignant blood diseases, myelodysplastic syndromes are at the origin of anaemia against which repeated transfusions and growth factors are proposed with varying results and disadvantages, and against which erythropoietin may be moderately effective (a mean of 25% in non-selected cohorts of patients). DEPENDING ON THE PROTOCOLS OF ERYTHROPOIETIN ADMINISTRATION IN CASES OF MYELODYSPLASTIC SYNDROMES: Recombinant human erythropoietin, irrespective of its concentration in myelodysplastic cell culture, does not appear capable of restoring normal erythropoiesis. The influence of prolonged treatment is not admitted by all. The effects of the addition of growth factors (notably G-CSF) are obvious but some are controversial because of the costs and the prolonged duration of such treatments.
...
PMID:[The benefits of treatment with recombinant human erythropoietin in cancer patients]. 1453 3

THE DEBATE: Although some believe that rHu-EPO should not be widely used in malignant affections, others think that because of the varied impact of these anaemia, its wider use should be recommended. FOR A TARGET USE: Various observations (influence of the degree of extension of the myelomas to the skeleton and response to specific treatment in the case of myeloma, whatever the haemoglobin concentration, degree of prevention of rHu-EPO chemo-induced anaemia) are in favour of its use in selected patients. FOR A WIDER USE: The benefits of treatment with rHu-EPO are not limited to the symptomatology of anaemia but extend to its potential complications in the most fragile patients. Other than the risks of infection, the heavy costs of transfusions must also be taken into account.
...
PMID:[rHU-EPO in cancer patients. Target or wider use?]. 1453 5

THE HEMOLYTIC ANEMIAS OF UNKNOWN CAUSE CAN BE SEPARATED INTO TWO MAIN GROUPS: (1) those produced by a defect in cell structure, which is usually hereditary, and (2) those due to a hemolysin of immune-body type.The hemolytic anemias associated with hypersensitivity to drugs and disease processes such as leukemia are less well understood and need further investigation. Splenectomy is the only effective treatment in congenital hemolytic jaundice and in acquired hemolytic anemia; the operation should be carried out promptly in most cases. Transfusion may be used in all varieties of hemolytic disease and is the only effective form of therapy in sickle-cell anemia and paroxysmal nocturnal hemoglobinuria.
...
PMID:Hemolytic anemias recent advances in diagnosis and treatment. 1811 27

1 2 Next >>