ABSTRACT
BACKGROUND: It is well established that as a blood unit ages, fewer of the unit's red blood cells (RBCs) remain in circulation post-transfusion. The mechanism for clearance is not well defined. Phosphatidylethanolamine (PE) is a phospholipid that is primarily found on the inner leaflet of healthy cells, and is an important ligand for phagocytosis of dead cells when exposed. OBJECTIVES: The objective of the present study was to measure the change in PE exposure in donor RBCs over increasing storage ages using the novel PE-specific probe, duramycin. METHODS: Five adsol (AS-1) preserved RBC units were sampled weekly for 6 weeks and were labelled with duramycin. The percentage of PE exposed on red cells in each sample was determined using flow cytometry. Surface phosphatidylserine (PS) was evaluated for comparison. RESULTS: We found that RBCs in AS-preserved donor units increasingly exposed PE, from less than 1% in freshly processed RBCs, to nearly 20% at 42 days of storage and correlated with increased relative vesiculation or microparticle concentration and release of cell-free haemoglobin. By comparison, only 5% of cells exposed PS at 42 days. CONCLUSION: We conclude that exposure of PE in the RBC outer membrane was higher than that of PS during 42 days of storage and correlated significantly with increased vesiculation and release of haemoglobin.
Subject(s)
Blood Preservation , Cell-Derived Microparticles/metabolism , Cellular Senescence , Erythrocyte Membrane/metabolism , Phosphatidylethanolamines/metabolism , Female , Flow Cytometry/methods , Humans , Male , Time FactorsSubject(s)
Anemia, Sickle Cell/therapy , Blood Group Antigens/immunology , Erythrocyte Transfusion/methods , Adult , Black or African American , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/epidemiology , Baltimore , Blood Donors , Blood Group Antigens/genetics , Blood Group Incompatibility/etiology , Blood Group Incompatibility/prevention & control , Child , Erythrocyte Transfusion/adverse effects , Hospitals, University , Humans , Pathology, Molecular , Program DevelopmentABSTRACT
Noonan syndrome, a distinctive syndrome characterized by dysmorphism, cardiac abnormalities and developmental delay, has been associated with a number of malignancies, however, only a few cases of primary glial or glioneuronal neoplasms have been reported. We report here the case of an 18-year-old with Noonan syndrome who developed a rosette forming glioneuronal tumor of the posterior fossa. The tumor demonstrated strong pERK immunoreactivity, suggesting MAPK/ERK pathway activation. Molecular testing did not reveal BRAF rearrangements (fusion transcripts) by PCR or a BRAFV600E mutation by sequencing. We review the literature regarding the molecular pathogenesis of Noonan syndrome and primary brain tumors, and consider the intriguing link between their common molecular pathways.
