Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of mast cell growth factor (MGF) was studied on erythropoietin (Epo)-dependent and Epo-independent ("spontaneous") erythroid colony formation in patients with polycythemia vera (PV). MGF stimulated both Epo-dependent and Epo-independent erythroid colony formation from PV peripheral blood progenitor cells in vitro at a dose similar to normal erythroid progenitor. In addition, evidence was obtained that the stimulating effect of MGF was a direct effect on the erythroid progenitor and independent of serum. Antibodies against interleukin-1 (IL-1), IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and Epo could not abolish the enhancing effect of MGF. This was also supported by the finding that sorted CD34+ cells could be stimulated by MGF in the presence and absence of Epo. Finally, it was demonstrated that the spontaneous erythroid colony formation could not be ascribed to spontaneous release of MGF in the culture medium since anti-MGF did not affect the colony numbers. In conclusion, MGF has a direct stimulatory effect, independent of serum, on both Epo-dependent and Epo-independent erythroid colony formation in PV.
 ...
PMID:Recombinant human mast cell growth factor supports erythroid colony formation in polycythemia vera in the presence and absence of erythropoietin and serum. 768 83

No conference of consensus was previously held in France, in the field of hematology. We decided to study the polycythemias, since it is a disease of relatively large frequency (about 1-2/100,000/year) relatively well defined, but in which initial evaluation, choice of treatment, quality or survey need really a consensus. Since the definition given in 1975 by the Polycythemia Vera Study Group (PVSG), some examinations became obsolete, and new ones (erythropoietin, stem cell culture) did appear, so that it seems useful to re-define the criteria of the disease. On another hand, the financial problems of our health systems make necessary do define what biological tests are really useful. As the vascular complications are the main risk of these patients, it would be useful to define what type of study is necessary for predicting the risk and also what preventive treatment could be advised. Such a study has presently never been done. Many questions still remain un-solved concerning the treatment. Beyond which age are the advantages of 32 P higher than the risk of leukemia? Is the chemotherapy by hydroxyurea or vercyte as easy to use than it is perhaps too often said? What is the best treatment, able to delay the development of myelofibrosis? The problem of survey is also, often, badly solved. What is the part of the specialist and that of the private physician?
 ...
PMID:Is a clinical consensus possible for the polycythaemic patients? 803 28

A few simple, low-priced, outpatient investigations, including an upper abdominal ultrasonography, a measurement of the arterial oxygen saturation and, in some cases, a leukocyte alkaline phosphatase score (LAP) suffice to find out the etiology of an increased red cell mass in most patients. The diagnosis of polycythemia vera (PV) could be accepted in patients with an increased red cell mass if the spleen is enlarged and if the arterial oxygen saturation is normal, although the latter measurement may not be required in typical cases. If the spleen is not enlarged, the diagnosis of PV could be accepted if, in addition, the leukocyte or thrombocyte count is increased. An elevated LAP score also points to the diagnosis of PV, provided fever or inflammation are not present. If, at that stage, an etiologic diagnosis has not been made, smoker's polycythemia should be considered and excluded. The next step should include a serum erythropoietin assay and culture of erythroid stem cells before performing investigations aimed at ruling out the many conditions associated with secondary polycythemia.
 ...
PMID:Biological and radiological investigations in patients with an increased red blood cell mass: Which are needed? Which are useful? which are unnecessary? 803 33

In vivo and in vitro bioassays, radio immunoassays (RIA), enzyme linked immunoassays (ELISA) and immunoradiometric assays (IRMA) have been applied to measure serum erythropoietin (Epo) levels. Results are expressed in international units (IU). In vivo bioassays are time consuming, expensive and not sensitive enough to measure the amount of Epo in normal sera. Nevertheless, this test remains the standard of comparison for the other new assays. Immunologic technics are specific, sensitive, reproducible, easy to perform, rapid and are now preferred for the measurement of Epo. Published values for non anemic human range from 6 to 32 IU/l. In the search of etiology of a polycythemia, the results of usual investigations to class the polycythemia either as primitive (P. vera) or secondary are often inconclusive. In these situations, measurement of serum Epo could be of value for accurate a differential diagnosis. However the results of the literature and our personal experience, show that the serum Epo level does not discriminate with an absolute fiability between Polycythemia Vera and secondary polycythemia because of a great overlap between the two groups.
 ...
PMID:Determination of serum erythropoietin. Its value in the differential diagnosis of polycythemias. 803 36

Erythroid progenitor cells isolated from patients with polycythemia vera (PV) proliferate and differentiate in methylcellulose in the absence of exogenous erythropoietin (EPO). To investigate the potential role of the erythropoietin receptor (EPO-R) in the pathogenesis of PV, we cultured bone marrow-derived or peripheral blood-derived erythroid progenitors in the presence of neutralizing monoclonal antibodies (MoAbs) specific for EPO or EPO-R. Mononuclear cells were obtained from 9 healthy adults and 9 PV patients by Ficoll-Hypaque gradients and cultured with or without EPO in methylcellulose for 12 days under standard or serum-free conditions. Neutralizing anti-EPO and anti-EPO-R MoAbs, added to cultures at day 0, caused dose-dependent growth inhibition of all normal burst-forming units-erythroid (BFU-E) derived from health adult controls. The MoAbs had no effect on the growth of nonerythroid progenitor cells under the same culture conditions. In contrast, neutralizing antibodies distinguished two classes of BFU-E derived from PV patients. Class I BFU-E from PV patients were EPO-dependent. These progenitors, like those derived from healthy adults, had normal EPO dose-dependent growth characteristics and showed a normal period of EPO requirement in vitro that extended 6 days after the initiation of culture. These results indicate that EPO exerts its critical effect early during erythroid differentiation; the addition of neutralizing antibodies to normal progenitors after 6 days had no effect on the subsequent size or maturation of the colonies. Class II BFU-E from PV patients were EPO-independent. They proliferated and differentiated even in the presence of high concentrations of neutralizing anti-EPO or anti-EPO-R MoAbs. We conclude that the class II BFU-E from PV patients are independent of free EPO.
 ...
PMID:Anti-erythropoietin (EPO) receptor monoclonal antibodies distinguish EPO-dependent and EPO-independent erythroid progenitors in polycythemia vera. 808 Oct

A 42-year-old Caucasian male with sporadic primary polycythemia has been followed by us for 13 years. During the time of observation, his hemoglobin had been stable, and he has never had an elevated white count or platelet count or any other stigmata of polycythemia vera (PV). Both of his parents, his three children, and all siblings have been hematologically normal. The in vitro culture of erythroid progenitors revealed an absence of autonomous erythropoietin (Epo)-independent erythroid colonies but demonstrated a marked increase in the sensitivity of erythroid progenitors to Epo. We have undertaken a study designed to determine whether a mutation in the Epo receptor (Epo-R) gene could cause the polycythemia phenotype seen in either dominant or recessive primary polycythemia described by us and others, or in polycythemia vera. We have sequenced the cytoplasmic positive and negative regulatory domains of the Epo-R genomic DNA, and a transversion of C to T in nucleotide 6148 was found in one of the patient's chromosomes. This mutation is located in the negative regulatory domain and results in a change from proline to serine (P488S). We have subsequently analyzed more than 40 chromosomes from unrelated normal subjects, as well as autosomal dominant, recessive, and sporadic primary polycythemia and polycythemia vera subjects. In no instance was the same or any other mutation in the Epo-R found. To determine if this Epo-R mutation is a cause of increased sensitivity of erythroid progenitors to erythropoietin, Ba/F3 cells (interleukin-3-dependent murine lymphoid line) were transfected with normal and mutated Epo-R cDNA, rendering the transfected cells viable and able to proliferate in Epo. Transfectants with wild-type and mutant Epo-R cDNA exhibited no difference in the presence of Epo. More recently, we were able to obtain DNA from the seven family members of the propositus and found that the nonpolycythemic mother and one of the siblings have the same Epo-R mutation. We conclude that this first described mutation of Epo-R encountered in humans does not appear on its own to explain the polycythemia phenotype; however, the possibility that it may interact with some other acquired or congenital abnormality in generating the polycythemia phenotype cannot be excluded.
 ...
PMID:Mutation in the negative regulatory element of the erythropoietin receptor gene in a case of sporadic primary polycythemia. 817 75

Serum erythropoietin (Epo) concentrations were measured by radioimmunoassay (RIA) in normal, polycythemic, and anemic dogs and cats. The serum Epo concentration in normal dogs (n = 25) ranged from 7 to 37 mU/mL (median, 20 mU/mL); and in normal cats (n = 11) ranged from 9 to 38 mU/mL (median, 18 mU/mL). Polycythemic animals (PCV > 55% in dogs, > 45% in cats) were classified as those with primary (polycythemia vera), secondary, or polycythemia of uncertain etiology. Dogs with polycythemia vera (PV, n = 8) had a median serum Epo concentration in the normal range (17 mU/mL); cats with PV (n = 7) also had a median serum Epo concentration that was within the normal range (10 mU/mL). In the category of secondary polycythemias, dogs (n = 7) (median, 30.7 mU/mL) and cats (n = 2) had normal Epo concentrations. The median serum Epo concentration was significantly decreased (P < .05) in dogs with PV compared with dogs with secondary polycythemias. The median serum Epo concentrations in dogs (n = 13) and cats (n = 5) with anemias not due to chronic renal disease were significantly increased (P < .05) compared with normal dogs and cats. In cats with anemias due to chronic renal disease (n = 5) the median serum Epo concentration was not significantly different from normal cats. The measurement of the serum EPO concentration may be useful in assessment of anemia or polycythemia but the overlap of values with the normal range in all groups evaluated limit its diagnostic use.
 ...
PMID:Serum erythropoietin concentrations measured by radioimmunoassay in normal, polycythemic, and anemic dogs and cats. 784 80

Patients with polycythaemia and normal controls have been studied to establish and subsequently test non-conventional criteria for the diagnosis of primary polycythaemia (primary proliferative polycythaemia, polycythaemia vera) as compared with conventional Polycythaemia Vera Study Group (PVSG) assessment. One criterion was erythroid colony formation from peripheral blood in a serum-free system, assayed alone and with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha interferon (alpha-IFN) (Dudley et al. 1990). The remaining criteria were non-culture associated and comprised platelet distribution width (PDW), platelet nucleotide ratio (ATP:ADP), serum erythropoietin and clinical evidence of ischaemic vascular disease. The combination of culture associated and non-culture associated variables, by use of a simple additive scoring system, gave no false positive and only 6% false negative results in distinguishing primary polycythaemia from other polycythaemias and normal controls in those (34 patients Group A) used in its derivation. Testing the scoring system in a newly presenting group (25 patients Group B) was highly satisfactory with no false positives and only a few false negative results (14%). Use of these non-conventional criteria should allow more confident diagnosis of primary polycythaemia, where conventional clinical and laboratory assessment is inconclusive.
 ...
PMID:Primary polycythaemia: diagnosis by non-conventional positive criteria. 824 12

The discovery of high hemoglobin and hematocrit values in a patient necessitates the determination of the red blood cell mass in order to confirm the absolute character of the polycythemia. If a true polycythemia is confirmed, its etiology must then be established. The diagnostic approach of polycythemia is presented in this paper. It is illustrated by a case presentation in which a polycythemia secondary to a renal carcinoma is discussed. Erythrocytosis is a classical, albeit rare manifestation of this type of tumor, and has the advantage of allowing early detection. Thus, it permits a prompt treatment plan, thereby improving the prognosis of such a neoplasia. The usefulness of a serum level of erythropoietin (EPO) is subsequently discussed. The diagnostic value of EPO remains controversial because of the overlapping values recorded amongst healthy patients, patients with polycythemia vera and others with secondary polycythemia. Finally, we discuss the presence of substances in paraneoplastic polycythemias whose biological activity is close to that of EPO. However, this molecules of a different structure would not be detected by the radioimmunoassay used to measure erythropoietin level.
 ...
PMID:[Secondary polycythemias: the role of erythropoietin]. 827 12

We have investigated the question of erythropoietin (Epo) hypersensitivity versus Epo independence as the basis for the endogenous erythroid bursts (EEBs) that develop in cultures without added Epo from hematopoietic cells of polycythemia vera (PV) patients. Using an improved serum-free (SF) medium containing interleukin (IL)-3, but no insulin-like growth factor-1 (IGF-1), and devoid of contaminants that influence erythropoiesis, we compared circulating normal and PV early erythroid progenitors (BFU-E) with respect to their responses in vitro to recombinant human (rHu) Epo. Cultures were seeded with Ficoll-Hypaque density-separated peripheral blood (PB) mononuclear cells (MNCs), and erythroid bursts, together with their component colonies of > or = 50 cells, were scored in situ at 13 to 16 days of culture. The Epo dose-response curve of BFU-E from PV patients was found to be statistically indistinguishable from that of normal subjects. This observation provides compelling evidence against the Epo-hypersensitivity hypothesis. In the complete SF medium minus Epo, the sensitivity of BFU-E to IGF-1 was much greater in PV than in normals, the dose-response curve being shifted to the left by at least 2 orders of magnitude. These data show that the erythroid progenitor cell response in PV is hypersensitive to IGF-1, and independent of Epo. The data also emphasize the importance of truly SF medium conditions for assessment of progenitor cell sensitivities to recombinant growth factors. Depletion of adherent cells totally prevented erythroid burst formation by normal circulating progenitors, but did not prevent the hypersensitive response to IGF-1 of such cells from PV patients. Hence, again unlike its normal counterpart, the progenitor cell response in PV appears to be independent of adherent cell control.
 ...
PMID:Circulating erythroid progenitors in polycythemia vera are hypersensitive to insulin-like growth factor-1 in vitro: studies in an improved serum-free medium. 827 28


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