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)

A new mutant, hemoglobin Cowtown, has been found in a white man and his father, both of whom have erythrocytosis. The father had previously been treated with 32P for polycythemia vera. The abnormal hemoglobin is not detectable on electrophoresis in alkaline buffers, but it resolves distinctively on electrophoresis in citrate agar, pH 6.0; similarly, the abnormal beta-globin chain does not separate from beta-A in urea 2-mercaptoethanol buffers of pH 8.9, but it moves anodically to beta-A at pH 6.0. Peptide chromatography and amino acid analysis of the beta chain reveal that the C-terminal histidine residue (beta 146) has been replaced by leucine. Like several other hemoglobins substituted at this residue, Hb Cowtown has a high oxygen affinity and a diminished Bohr effect.
 ...
PMID:Hemoglobin Cowtown (beta 146 HC3 His-Leu): a mutant with high oxygen affinity and erythrocytosis. 4 11

Five smokers had erythrocyte masses sufficiently larger than normal to pose a problem in the differential diagnosis of polycythemia. Evaluation excluded lung disease, shunt physiology, hemoglobin with increased oxygen affinity, erythropoietin-producing tumor, renal disease, or polycythemia rubra vera as the primary cause of erythrocytosis in these patients. All were found to have levels of carboxyhemoglobin sufficient to cause clinically significant hypoxemia and to account for the increased erythrocyte masses. In two patients the erythrocytosis improved when they stopped smoking. Heavy smoking is a reversible cause of polycythemia and should be considered in the differential diagnosis of this problem.
 ...
PMID:Smoking as a cause of erythrocytosis. 23 31

Marrow specimens of patients with polycythemia vera rise to erythrocytic colonies in vitro without addition of erythropoietin to the culture. This behavior was never observed with marrow cells of normal subjects or secondary erythrocytosis. These results indicate that the sensitivity of some erythrocytic progenitor cells to erythropoietin is altered in polycythemia vera.
 ...
PMID:[Abnormal sensitivity to erythropoietin in the erythroblast precursors in Vaquez disease]. 40 38

We investigated the pathogenesis of isolated erythrocytosis of 14 yr duration in a 28-yr-old man. The increase in red cell mass was attributed to increased erythropoietin production. An extensive search for recognized causes of secondary erythrocytosis was unrevealing. Family members were found to be hematologically normal. After reduction of the circulating red cell mass by 20%, erythropoietin activity nearly quadrupled, thus suggesting a normal erythropoietin response to phlebotomy. When bone marrow cells of the patient were cultured in plasma clots in the absence of added erythropoietin, endogenous erythroid colony formation was observed, a pattern previously believed to be specific for polycythemia vera bone marrow cells. Our observations suggest that the erythrocytosis in this individual is best explained by an abnormal "servoregulatory" mechanism of erythropoietin production. In addition, this is the first instance in which the rule that endogenous erythroid colony formation is correlated with the diagnosis of polycythemia vera has not held.
 ...
PMID:Erythropoietin-dependent primary pure erythrocytosis. 44 59

During the last 12 years, 86 apparently primary polycythemias have been observed in subjects less than 40 years old. In twelve of them a non-suspected cause has been found (seven abnormalities of the hemoglobin function). In 43 cases, all males, the erythrocytosis (red cell volume more than 36 ml/kg) was pure and stable, without any complication; this "benign erythrocytosis" probably depicts extreme values of the normal distribution of the red cell mass. In 31 cases, the disease had criteria similar to those of polycythemia vera observed in older patients; in 12 of these cases, severe thrombo-embolic complications have been observed at the very beginning of the disease; however no further complication has been seen, when the patients were actively treated (phlebotomies or 32P); at the present time, no one of these cases did show transformation into acute leukemia, but the long-term prognosis (beyond 15 years) cannot yet been precisely drawn.
 ...
PMID:[Polycythemias of young subjects (author's transl)]. 55 80

A patient with classical polycythemia vera (PV) was found to have an inappropriately elevated serum erythropoietin (Ep) level. Investigations did not reveal any lesion or blood abnormality known to be associated with excessive Ep production and erythrocytosis. Sudden withdrawal of blood to reduce the Hb and Hct from 18.5 gm% and 56% to 13.6 gm% and 41.5%, respectively, resulted in an increment of serum Ep to abnormal level. With iron treatment there was a brisk return of Hb and Hct to prebleeding levels which was associated with reduction in the serum Ep. The inverse relationship between the Ep and Hb or Hct is inconsistent with the presence of excessive Ep-producing lesion. These results suggested that the threshold for Ep secretion from normal Ep-secreting tissue to Hb and Hct levels is set at an abnormal level. This patient's marrow cells when cultured in vitro in the absence of Ep, unlike other PV patients' (except one) marrow cells, did not grow erythroid colonies. In the presence of Ep, however, the colonies comparable to those formed from normal marrow cultures were obtained. These results suggested that his marrow erythropoietic cells were neither Ep independent nor Ep-hyperresponsive, as has been suggested by some investigators for erythropoiesis in PV. This patient presents phenomena that hitherto have not been reported.
 ...
PMID:Inappropriate erythropoietin secretion in polycythemia vera. 60 35

In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi32P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo. he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the inital discovery of this type of hemoglobinopathy came 27 yr after the introduction of 32P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to 32P. The exposed population should be cosely followed, since this will likely permit assessment of the risk of 32P-induced leukemia in a nonneoplastic condition.
 ...
PMID:32P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima. 66 62

We performed in vitro culture studies examining the interaction of erythropoietin with red cell progenitors in polycythemia vera. Bone marrow was obtained from five patients with typical disease and from five healthy volunteers, and assayed for erythroid colony formation (CFU-E) by the methylcellulose technique. In cultures without added erythropoietin, a mean eightfold greater cloning efficiency was noted with the polycythemia vera marrows, as compared to normal. There was prominent stimulation of colony formation by erythropoietin, and the shape of the erythropoietin dose-response cruves appeared to be similar in both patients and controls. Anti-erythropoietin antibody reduced the number of CFU-E in cultures not containing added erythropoietin, but did not eliminate them. Dexamethasone (10(-9) M) caused a consistent increase in CFU-E in the patients' cultures. These studies provide evidence for functional erythropoietin and glucocorticosteroid receptor mechanisms on erythroid precursors in polycythemia vera. The observations are consistent with a concept of this disease as a disorder of hematopoietic stem cells in which peripheral erythrocytosis is caused by an expanded erythroid progenitor compartment which maintains responsiveness to hormonal modulation.
 ...
PMID:Polycythemia vera: hormonal modulation of erythropoiesis in vitro. 83 49

We found primary erythrocytosis in two male siblings with hematologically normal parents. To clarify the abnormalities in erythropoiesis, we studied erythropoietin production in the older sibling as well as in vivo and in vitro responses of bone marrow to various stimuli. His erythropoietin excretion after a 1000-ml phlebotomy increased by 0 to 11 units per day. In liquid-suspension culture, erythropoiesis was prominently augmented by erythropoietin and unstimulated erythropoiesis was greater and more prolonged than normal. Numbers of erythroid colonies rose in methylcellulose culture without exogenous erythropoietin, and cloning increased with added erythropoietin. Anti-erythropoietin antibody substantially decreased erythropoiesis in vitro. Increased bone-marrow erythropoiesis was also demonstrated in murine diffusion chambers. The principal abnormality in this familial erythrocytosis appears to be a greatly expanded erythropoietic precursor pool that is responsive to erythropoietin in vitro and in vivo. This abnormality is analogous to the functional erythropoietic defect in typical polycythemia vera.
 ...
PMID:Erythropoiesis in familial erythrocytosis. 85 May 18

Three families with polycythemia inherited through apparently different modes are described. Secondary causes of polycythemia were ruled out. Erythropoietin (EPO) levels were normal or low, even after phlebotomy. In vitro erythroid colony growth in standard assay cultures containing EPO was normal; however, in the absence of added EPO, a few progenitors from most of the affected individuals were able to generate recognizable colonies of mature erythroblasts, although these were smaller and proportionately less numerous than seen in polycythemia vera (PV). To search for EPO-receptor changes as a possible pathophysiologic mechanism, we examined, by Southern blot analysis, genomic DNA samples from affected and nonaffected family members, as well as three patients with PV. Two different probes, derived from the human EPO-receptor, were used. We found no evidence for chromosomal rearrangements or gene amplification in hereditary polycythemia or PV patients. Further, no nucleotide sequences were found that were homologous to the Friend spleen focus-forming virus glycoprotein gp55, which has been shown to bind to and activate the murine EPO-receptor. Functional studies examining number and binding affinity of the EPO-receptor on erythroid progenitors from three hereditary polycythemia patients demonstrated no abnormalities. We conclude that the mechanism(s) for the erythrocytosis in familial and congenital polycythemia and in PV may not involve the EPO-receptor and, therefore, may result from alterations of postreceptor responses.
 ...
PMID:Familial and congenital polycythemia in three unrelated families. 131 90


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