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

Erythropoietic progenitors from bone marrow of patients with polycythemia vera (PV), secondary polycythemia (SP) and healthy subjects (HS) were cultured in plasma clot diffusion chambers in vivo. The chambers were inserted into the peritoneal cavities of rats, which 24 and 2 h before implantation received an injection of phenylohydrazine. Control experiments were done without erythropoietin (Epo) stimulation. Colonies after 2 and 7 days of culture were considered to be formed by mature erythropoietic progenitors (CFU-D-E) and burst forming cells (BFU-D-E), respectively. PV-erythroid progenitors, both BFU-D-E and CFU-D-E produced markedly more colonies than those from SP and HS, especially in experiments without Epo stimulation (p less than 0.01). The plating efficiency in SP was comparable to that noted in HS (p greater than 0.05). These results have led us to postulate that the study of erythroid progenitor clonal proliferation in plasma clot diffusion chamber can be helpful in the differential diagnosis of PV and SP, when other clinical and laboratory findings are not sufficiently convincing.
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PMID:Usefulness of the assessment of erythroid progenitors growth for differential diagnosis of primary and secondary polycythemias. 244 2

We recently reported the development of several monoclonal antibodies (MoAbs) to native human erythropoietin (Ep). In the present study we have used the two antibodies with highest affinity to develop a two-sided or sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ep in human serum. In this assay Ep is incubated in microtiter wells precoated with the first (IgE) anti-Ep antibody. Assay wells are then incubated with the second (IgG1) anti-Ep antibody, which is labeled noncovalently with the enzyme alkaline phosphatase (AP) by means of bispecific tetrameric antibody complexes consisting of IgG1 anti-Ep cross-linked to IgG1 anti-AP using rat MoAbs specific for mouse IgG1. Application of this noncovalent labeling procedure, in combination with substrate amplification, results in a detection sensitivity of 0.5 to 1.0 mU/sample (5 to 10 mU/mL), which makes this assay suitable for measuring normal serum Ep levels. The validity of this ELISA for quantitating Ep in biological fluids was demonstrated by the parallelism obtained between pure recombinant Ep dose-response curves and those obtained with plasma and serum from healthy donors and patients with various hematologic disorders. Normal plasma Ep levels detected with this ELISA ranged from 9 to 101 mU/mL with a mean of 32 +/- 23 (SD) mU/mL. Ep levels in sera from patients with polycythemia vera were in the low to normal range, whereas Ep levels in sera from patients with secondary polycythemia and patients with aplastic anemia were moderately to strongly elevated. These results demonstrate that the Ep-ELISA is a sensitive, reliable, and nonradioactive immunologic method for quantitating Ep levels and should prove useful in a variety of clinical and laboratory settings.
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PMID:An enzyme-linked immunosorbent assay for erythropoietin using monoclonal antibodies, tetrameric immune complexes, and substrate amplification. 247 3

Serum erythropoietin (Ep) was measured by radioimmunoassay before and 24 hours after therapeutic phlebotomies in patients with polycythemia vera (PV) and in normal subjects before and after phlebotomies of comparable volumes. In addition the in vivo oxygen affinity of hemoglobin (P50) was calculated, and red cell indices and 2,3 DPG values were measured. Paired t tests determined whether the differences between pre- and post--phlebotomy values were statistically significant. Blood hemoglobin (Hb) levels declined after phlebotomy, and generally continued to be at or above normal levels. Serum Ep increased after phlebotomy in both groups of subjects. The in vivo P50 value for patients with PV (29.4 +/- 0.4 mmHg) was significantly (p less than 0.005) greater than the normal value (27.2 +/- 0.5). Seven of the PV patients (5 males, 2 females) were restudied. Their Hb and hematocrit values were either normal or slightly higher than normal. The MCV for 4 males and 1 female was below normal. The MCHC was slightly lower than normal and reticulocytosis was not present. The male PV patients had greater than normal 2,3 DPG values and most had right-shifted P50 values. There was no correlation between 2,3 DPG values and P50 values. The female patients did not have 2,3 DPG values consistently greater than normal and their P50 values were not right shifted. These results showed that serum EP increased in response to small reductions in Hb even when subnormal Hb values were not produced. The reduced affinity of Hb in PV patients may explain earlier observations that patients with PV have lower levels of urinary or plasma Ep than normals with the same hematocrits.
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PMID:Serum erythropoietin and hemoglobin affinity for oxygen in patients phlebotomized for polycythemia vera. 248 92

The role of erythropoietin (EP) in polycythemia vera (PV) is controversial, with some experiments suggesting that erythroid progenitors in PV are exquisitely sensitive to EP and EP dependent, and others suggesting that PV progenitors are EP independent. We have examined the characteristics of the EP receptor (EP-R) on erythroid colony-forming cells (ECFC) from patients with PV. In contrast to normal ECFC, which have two classes of EP-R, with 20% showing high affinity (Kd = 0.13 nM; range, 0.04-0.20 nM) and the remainder lower affinity (Kd = 0.37 nM; range, 0.28-0.57 nM), PV ECFC show a single class of 851 low affinity EP-R with Kd = 0.72 nM (range, 0.36-0.85 nM). ECFC from patients with secondary (EP driven) polycythemia or anemia show two classes of EP-R (Kd = 0.18 and 1.10 nM, respectively). Attempts to remove tightly bound EP from putative high affinity EP-R in PV did not reveal any higher affinity receptors. Determination of molecular size by crosslinking showed two proteins of 90 and 100 kD similar to those seen with normal EP-R. These studies indicate the PV ECFC have EP-R that are structurally similar to normal EP-R but lack the higher binding affinity for EP.
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PMID:Erythropoietin receptors in polycythemia vera. 255 27

Megakaryocyte colony formation, as identified by conventional techniques, was observed in precursor cell cultures from peripheral blood in 8 of 20 consecutive patients with diagnosis of myeloproliferative disease (4/11 patients with polycythemia vera, 3/5 with essential thrombocythemia, 1/2 with primary osteomyelofibrosis and 2 with a myeloproliferative syndrome not further assessable), but not in 50 healthy controls (p less than 0.0001). 7 cultures showed spontaneous erythroid colonies, but were negative for megakaryocyte colonies. Megakaryocyte colony formation was independent of added erythropoietin, plasma or human leukocyte-conditioned medium, but was dependent on the presence of accessory cells. The cells in megakaryocyte colonies had the characteristic morphology of megakaryocytes and stained positively with the IIIa/IIb monoclonal anti-platelet antibody. Thus, megakaryocyte colony formation by precursor cells from peripheral blood in the absence of exogenous stimulating factors seems to be a phenomenon specific for myeloproliferative disease. Differential diagnosis of thrombocythemia may be facilitated by demonstration of endogenous megakaryocyte colony formation, which does not occur in secondary disease.
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PMID:Endogenous megakaryocyte colonies from peripheral blood in precursor cell cultures of patients with myeloproliferative disorders. 265 91

To further define the growth factors required for the in vitro proliferation of erythroid progenitors in polycythemia vera (PV), we have compared the ability of interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to support the growth of erythropoietin (Epo)-dependent and -independent erythroid colony formation. By using nonadherent mononuclear cells from peripheral blood, Epo-dependent colony formation was enhanced by IL-3 and GM-CSF in PV patients. Comparable results were obtained with normal erythroid progenitors. Augmenting effects of IL-3 and GM-CSF were observed on spontaneous erythroid colony formation, i.e., erythroid colony formation in the absence of exogenous supplied Epo. This was not due to a small amount of Epo in the culture media because an anti-Epo antibody did not prevent endogenous colony formation, nor did it prevent the enhancing effects of IL-3. Finally it was observed that in contrast to IL-3, monocyte depletion was required for the enhancing effects of GM-CSF on erythroid colony formation. These results provide evidence that endogenous colony formation in PV is independent of Epo but can be augmented by IL-3 or GM-CSF.
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PMID:In polycythemia vera human interleukin 3 and granulocyte-macrophage colony-stimulating factor enhance erythroid colony growth in the absence of erythropoietin. 267 32

The ability of erythroid cultures to distinguish among myeloproliferative disorders was examined. We studied 14 patients with polycythemia vera (PV), 11 with chronic myelogenous leukemia (CML), four with non-PV erythrocytosis, two with agnogenic myeloid metaplasia, as well as three normal fetuses and greater than 25 normal adults. Endogenous, i.e. grew without added erythropoietin, bone marrow CFU-E-derived colonies were observed in all but one PV patient. However, endogenous blood BFU-E-derived bursts were observed in only eight of 14 PV patients. Endogenous erythroid colonies were not seen in cultures from any normal adults or fetuses, or patients with CML, erythrocytosis, or myeloid metaplasia. In PV, relative HbF synthesis was always greater in cultures without erythropoietin, while in cultures from all other patients relative HbF synthesis was similar to that observed in cultures from normal individuals. We conclude that PV and CML are distinguishable in culture since CML patients do not have endogenous growth. Most important, endogenous bone marrow CFU-E-derived colonies are the only consistently unique observation in patients with PV, and endogenous CFU-E- and BFU-E-derived colonies and bursts are not uniformly observed in PV blood cultures. In-vitro studies of erythropoiesis to confirm the diagnosis of PV, therefore, require marrow when endogenous colonies and bursts are absent from blood cultures.
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PMID:Comparison of erythroid progenitor cell growth in vitro in polycythemia vera and chronic myelogenous leukemia: only polycythemia vera has endogenous colonies. 271 48

The development of highly specific antibodies against recombinant human erythropoietin (EPO) has recently made the accurate radioimmunological measurement of serum levels of this hormone possible. In this study we determined the serum-EPO levels in 100 healthy volunteers, in 54 patients suffering from polycythemia vera and in 51 patients with secondary polyglobulia. The mean levels for the healthy group were found to be 11.3 +/- 3.4 mU/ml in females and 8.0 +/- 3.2 mU/ml in males. Patients with polycythemia vera had serum-EPO levels of 4.3 mU/ml, while those with secondary polyglobulia had significantly higher levels averaging 30.3 mU/ml (p less than 0.0001). However, an overlapping of serum-EPO values in the range between 10 and 20 mU/ml occasionally occurs. Our results show that measurement of the serum-EPO level can be useful in the differential diagnosis of polyglobulias. Additionally, sequential EPO level measurements after phlebotomy and after hemorrhage show a pronounced increase in serum-EPO in secondary polyglobulia, while in polycythemia vera the level only increases slightly.
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PMID:[Serum erythropoietin levels: a new diagnostic tool?]. 274 Jun 73

The accurate radioimmunological measurement of serum erythropoietin (EPO) levels has only been possible since the development of highly specific antibodies directed against recombinant human EPO. In the present study, we determined the serum EPO levels in 100 healthy volunteers and in over 300 patients with anemias and hyperglobulinemia of various causes. In the healthy group, the females had levels of 11.3 +/- 3.4 mU/ml, while the males had levels of 8 +/- 3.2 mU/ml. The serum EPO concentrations were inversely related to the degree of anemia in patients with nonrenal anemias, while predialysis patients with renal anemias showed only partially such a tendency. Hemodialysis patients exhibited EPO-levels that were inadequately low relative to the degree of anemia. Patients with hyperglobulinemia had significantly higher serum EPO-levels than healthy individuals and polycythemia vera patients, the latter having particularly low serum EPO levels. Our results show that the determination of serum EPO levels can be of value in the differential diagnosis of hyperglobulinemia. Finally, sequential measurements document fluctuating serum EPO-levels after gastrointestinal hemorrhages and in patients with iron deficiency anemias receiving iron substitution. The probable reason for this phenomenon seems to be the intermittent utilisation of the hormone by EPO-sensitive erythropoietic precursor cells.
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PMID:[Serum erythropoietin levels in several diseases]. 291 82

Based on an analysis of the data pertaining to changes in the level of erythropoietin, chalones and stress hormones in the blood of patients with polycythemia vera after bloodletings and cytapheresis it is concluded that chalones participate in the development of a remission owing to the inhibition of the clone of mutant cells. The role of stress hormones is reduced to the potentiation of the effect of chalones, that of erythropoietin to the triggering of the proliferation of the cellular clone.
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PMID:[Physiological methods of treatment of patients with polycythemia vera]. 293 50


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