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polycythemia/prolina
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Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline.
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A classic physiologic response to hypoxia in humans is the up-regulation of the ERYTHROPOIETIN (EPO) gene, which is the central regulator of red blood cell mass. The EPO gene, in turn, is activated by hypoxia inducible factor (HIF). HIF is a transcription factor consisting of an alpha subunit
Molecular responses and chromosomal aberrations in patients with polycythemia vera treated with peg-proline-interferon alpha-2b.
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Fifty-one polycythemia vera (PV) patients were enrolled in the phase I/II clinical study PEGINVERA to receive a new formulation of pegylated interferon alpha (peg-proline-IFNα-2b, AOP2014/P1101). Peg-proline-IFNα-2b treatment led to high response rates on both hematologic and molecular levels.
Postrenal transplant erythrocytosis: a possible role for testosterone, angiotensin I-converting enzyme, and N-acetyl-seryl-aspartyl-lysyl-proline: reply to Kessler et al.
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A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove.
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The molecular basis of the erythrocytosis group of red cell disorders is incompletely defined. Some cases are due to dysregulation of erythropoietin (Epo) synthesis. The hypoxia inducible transcription factor (HIF) tightly regulates Epo synthesis. HIF in turn is regulated through its alpha subunit,
Hemoglobin North Chicago (beta 36 [C2] proline----serine): a new high affinity hemoglobin.
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Hemoglobin North Chicago, beta 36 [C2] Pro----Ser is a new high oxygen affinity hemoglobin variant. It was discovered in a 52-year-old male with erythrocytosis since age 20 who had been treated with different regimens for polycythemia vera including several courses of 32P. The variant is
Biochemical characterization of human prolyl hydroxylase domain protein 2 variants associated with erythrocytosis.
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Prolyl hydroxylase domain proteins (PHD isozymes 1-3) regulate levels of the alpha-subunit of the hypoxia inducible factor (HIF) through proline hydroxylation, earmarking HIFalpha for proteosome-mediated degradation. Under hypoxic conditions, HIF stabilization leads to enhanced transcription and
Hemoglobin brigham (alpha2Abeta2100 Pro--Leu). Hemoglobin variant associated with familial erythrocytosis.
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Erythrocytosis associated with the presence of a hemoglobin with increased oxygen affinity has been reported for 10 hemoglobin variants, most of which demonstrate altered electrophoretic mobility. Several members of a family were found to have erythrocytosis, and both the whole blood and the
Polycythemia and paraganglioma with a novel somatic HIF2A mutation in a male.
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Recently, a new syndrome of paraganglioma, somatostatinoma, and polycythemia has been discovered (known as Pacak-Zhuang syndrome). This new syndrome, with somatic HIF2A gain-of-function mutations, has never been reported in male patients. We describe a male patient with Pacak-Zhuang syndrome who
Mutation in the negative regulatory element of the erythropoietin receptor gene in a case of sporadic primary polycythemia.
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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,
Mutations in the VHL gene in sporadic apparently congenital polycythemia.
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The congenital polycythemic disorders with elevated erythropoietin (Epo) have been until recently an enigma, and abnormality in the hypoxia-sensing pathway has been hypothesized as a possible mechanism. The tumor suppressor von Hippel-Lindau (VHL) participates in the hypoxia-sensing pathway, as it
New syndrome of paraganglioma and somatostatinoma associated with polycythemia.
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OBJECTIVE
The occurrence of ≥ two distinct types of tumors, one of them paraganglioma (PGL), is unusual in an individual patient, except in hereditary cancer syndromes.
METHODS
Four unrelated patients were investigated, with thorough clinical evaluation. Plasma and tissue catecholamines and
Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2alpha gain-of-function mutation.
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The hypoxia-inducible factors (HIFs; isoforms HIF-1α, HIF-2α, HIF-3α) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash
Hemoglobin Milledgeville (alpha 44 (CD2) Pro leads to Leu): a new variant with increased oxygen affinity.
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Hemoglobin Milledgeville, a new hemoglobin structural variant, was identified in three members of a black American family. The oxygen affinity of blood and hemoglobin samples from the affected individuals was markedly increased (p50 O2 of whole blood 11-15 mmHg at 37 degrees C, pH 7.4), and the
Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.
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Family members from four generations were found to have polycythemia and increased whole blood O2 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by
Hemoglobin Crete (beta 129 ala leads to pro): a new high-affinity variant interacting with beta o -and delta beta o -thalassemia.
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Hemoglobin Crete, beta129 (h7)ala leads to pro, is a new mutant hemoglobin (Hb) with high oxygen affinity that was discovered in a Greek family in various combinations with beta- and deltabeta-thalassemia. The propositus, who presented an unusual clinical picture of an "overcompensated" hemolytic
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