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O Muller

Publications and source records attributed to O Muller.

10 recordsLinked to original sources
PubMed1992

Erythropoietin induces the tyrosine phosphorylation of its own receptor in human erythropoietin-responsive cells.

Using the human erythropoietin-responsive hematopoietic cell line UT-7, we showed that erythropoietin (Epo) rapidly and specifically induced the tyrosine phosphorylation of its own receptor (M(r) 75,000) and increased the tyrosine phosphorylation of other proteins of M(r) 140,000, 120,000, 95,000, 60,000, 57,000, and 42,000. Neither granulocyte-macrophage colony-stimulating factor, interleukin 3, interleukin 6, nor the kit ligand induced the phosphorylation of the M(r) 75,000 receptor protein, although these growth factors induced the phosphorylation of other proteins. Cross-linking experiments using 125I-Epo indicated that the UT-7 cells expressed three Epo receptor subunits, of M(r) 100,000, 85,000, and 75,000, among which only the M(r) 75,000 subunit was tyrosine-phosphorylated following activation with Epo.

Blotting, Western↗
PubMed1991

Multimeric structure of the membrane erythropoietin receptor of murine erythroleukemia cells (Friend cells). Cross-linking of erythropoietin with the spleen focus-forming virus envelope protein.

In erythroleukemia cells infected with the polycythemia strain of the Friend virus complex, erythropoietin could be cross-linked mainly to a protein of 63 kDa when using disuccinimidyl suberate. In contrast, erythropoietin in other erythroleukemia cells cross-linked to two proteins of 85 and 100 kDa. When native erythropoietin receptor complexes were immunoprecipitated, the 63-kDa erythropoietin-cross-linked protein could be precipitated both by antibodies directed against the intracellular part of the cloned chain of the erythropoietin receptor and by antibodies directed against the envelope proteins of the Friend virus. However, after denaturation of the complexes, the 63-kDa protein was only precipitated by antibodies directed against the envelope proteins of the Friend virus. Enzymatic deglycosylation confirmed that erythropoietin was cross-linked with the envelope protein of the defective virus and bidimensional diagonal gel electrophoresis analyses showed that some of the erythropoietin cross-linked envelope proteins were dimerized by disulfide bonds. Thus, the main erythropoietin-receptor complex in the plasma membrane of these cells consisted of a molecule of the cloned chain of the erythropoietin receptor noncovalently associated with one or two disulfide-bonded molecule(s) of the envelope protein of the defective virus. Moreover, our results also showed that the viral envelope protein associated with the cloned chain of the erythropoietin receptor at a site distinct from the erythropoietin binding site.

Animals↗
PubMed1990

Solubilization and hydrodynamic characteristics of the erythropoietin receptor. Evidence for a multimeric complex.

In order to study the erythropoietin receptor in its native state, we solubilized erythropoietin-receptor complexes from spleen cell membranes of mice infected with the anemia strain of Friend virus using mild detergents. Among 11 tested detergents, Triton X-100 and Lubrol PX were the most effective. Triton X-100 was therefore selected for this study. The solubilized complexes appeared to be well representative of the total membrane receptor population as indicated by cross-linking experiments and affinity measurements. The hydrodynamic characteristics of the complexes were determined by gel filtration chromatography and ultracentrifugation through sucrose gradients prepared with H2O or D2O. Although erythropoietin-receptor-detergent complexes exhibited some heterogeneity, we determined the following minimal hydrodynamic values: sedimentation coefficient (s20,w): 11.7 +/- 0.8 S, Stokes radius: 7.7 +/- 0.2 nm, partial specific volume: 0.774 +/- 0.017 ml/g, giving a molecular mass of 458 +/- 66 kDa. The contribution of the detergent was estimated to be 28% from the measured partial specific volume, giving an estimated molecular mass of 330 +/- 48 kDa for the erythropoietin-receptor complex. The minimal molecular mass value was significantly greater than those obtained by polyacrylamide gel electrophoresis under denaturing conditions, strongly suggesting that the erythropoietin receptors were present as multimeric complexes. The nature of these complexes is discussed. Beside this major component our results revealed the presence of higher-molecular-mass erythropoietin binding components. We also demonstrated that erythropoietin-receptor complexes could be precipitated with anti-erythropoietin antibodies. This property should greatly improve the purification of erythropoietin receptors.

Animals↗
PubMed1990

Glycosylation of the murine erythropoietin receptor.

Murine erythropoietin-responsive Rauscher Red 5-1.5 cells were used to determine the contribution of glycosylation to the size and function of the erythropoietin receptor. The half life of the receptors was determined to be 4 h. The number of receptors was not significantly decreased in cells treated for 48 h with inhibitors of glycosylation (tunicamycin, glucosamine or swainsonine) and their affinity was slightly enhanced in tunicamycin- or glucosamine-treated cells. Erythropoietin was cross-linked with two proteins of 104 and 86 kDa. Their molecular masses were not significantly reduced in cells treated with the glycosylation inhibitors. When immunoprecipitated cross-linked receptors were digested with endoglycosidases, the molecular masses of both proteins were only slightly modified giving values of 100 and 82 kDa. Thus we can conclude that the proteins cross-linked to erythropoietin are very weakly glycosylated.

Alkaloids↗
PubMed1988

Epoprostenol (prostacyclin) in unstable angina.

The purpose of this randomized, double-blind multicenter trial was to investigate the potential therapeutic effect of epoprostenol (prostacyclin, PGI2) in patients with unstable angina, as compared with placebo, and to investigate the safety of this agent. Of the 184 patients enrolled, 28 did not fit the study criteria; of the remaining 156 patients, 30 received prostacyclin in an open-label fashion. In the double-blind portion of the study, 63 patients each received prostacyclin or placebo. The drug or its vehicle was infused intravenously up to 5 ng/kg/min dose for 72 hours with a tapering off period for the last 12 hours. Both treatment groups from the double-blind portion were comparable in regard to the demographic data, length of infusion, and total dose received. There were no significant differences between the placebo and prostacyclin group in the following clinical endpoints: levels of cardiac enzymes throughout hospitalization period (with the exception of lower SGOT level in the prostacyclin group at day 2), and severity of angina (throughout the study), and at the end of the study (day 30). The number of patients who had congestive heart failure, new myocardial infarction, balloon pump insertion, coronary artery bypass grafting, or percutaneous coronary angioplasty was similar in both groups. Similar results in regard to the efficacy endpoints were also apparent in the prostacyclin group that was treated under open-label fashion. There was also no difference in the New York Heart Association (NYHA) functional status at the end of the double-blind study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Etiology of portal vein thrombosis in adults. A prospective evaluation of primary myeloproliferative disorders.

In a prospective study of 33 adults with portal vein thrombosis unrelated to a liver tumor, we have assessed the prevalence of primary myeloproliferative disorders using conventional criteria and cultures of bone marrow progenitor cells. A primary myeloproliferative disorder was documented in 14 patients investigated at the time of recognition of portal vein thrombosis. Among these 14 patients, the main clue to the presence of the myeloproliferative disorder was (a) the observation of suggestive abnormalities of peripheral blood cell counts in 4 patients; (b) characteristic findings at bone marrow biopsy or determination of total red cell volume in 3 patients; and (c) formation of "spontaneous" erythroid colonies in cultures of bone marrow progenitor cells in erythropoietin-poor medium in 7 patients. In 2 other patients, agnogenic myeloid metaplasia with myelosclerosis of apparently recent onset developed 5 yr after recognition of portal vein thrombosis. In conclusion, primary myeloproliferative disorders--in a full-blown or latent form, or at an early stage--are a major cause of portal vein thrombosis.

Blood Cell Count↗
PubMed1988

Changes in coronary haemodynamics and myocardial metabolism at rest and during exercise after a cardiotonic drug (prenalterol) in patients with coronary artery disease.

To elucidate the myocardial metabolic and haemodynamic effects of an inotropic drug in patients with coronary artery disease (CAD) without evident congestive heart failure (CHF), the acute effects of prenalterol were studied in nine patients. Patients with documented CAD by leftsided cardioangiography and end-diastolic pressure greater than 15 mm Hg were included in the study. They were examined at rest and during supine exercise at a level just below their anginal threshold before and after prenalterol. At rest, rate pressure product (RPP) increased by 40% (P less than 0.01), cardiac index rose 20% (P less than 0.01), cardiac venous flow (CVF) increased by 18% (P less than 0.05), and myocardial oxygen consumption (MVO2) increased by 20% (P less than 0.05) after prenalterol administration. Despite a decrease in mean pulmonary capillary venous pressure (PCV) of 40% (P less than 0.01), myocardial lactate extraction fell significantly (P less than 0.01) and lactate production was observed in three of nine patients compared to before prenalterol administration. During exercise, RPP increased by 20% (P less than 0.01), cardiac index remained unchanged, CVF increased by 25% (NS) and MVO2 showed a tendency to an increase (NS) after prenalterol administration. Mean PCV pressure decreased by 30% (P less than 0.01). Myocardial lactate extraction was markedly reduced during exercise (P less than 0.01) and five of nine patients showed lactate production compared to that before prenalterol administration. Thus, despite a decrease in left ventricular filling pressure, increased myocardial oxygen demand occurred after acute administration of prenalterol. Prenalterol and probably similar inotropic drugs should be used cautiously in patients with CAD without clinical evidence of congestive heart failure.

Catheterization, Swan-Ganz↗
PubMed1987

Biochemical analyses of murine erythropoietin from plasma and from cloned erythroleukemia cells.

The hydrophobicity, ionic charges, degrees of glycosylation, and Western blot patterns of murine plasma erythropoietin and erythropoietin produced by clones of two murine erythroleukemic cell lines (IW32 and NN10) were compared. Erythropoietins from these different sources exhibited a number of similarities in their biochemical properties: identical retention on DEAE Affigel blue column and similar apparent molecular weights (30-36 kDa) in Western blot analysis. However, differences were also observed: heterogeneous binding to different lectin columns and varied retention on a phenyl Sepharose column. The data thus confirm that these murine plasma erythropoietins have biochemical properties in common with previously studied erythropoietins from humans or sheep. The major difference between erythropoietins secreted by erythroleukemic cell lines and other molecules belonging to the same family appears to be related to their glycosylation.

Animals↗
PubMedDate not supplied

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