Kinetic Studies of Lipid Exchanges in Red Cell Membranes in Hereditary High Red Cell Membrane Phosphatidylcholine Hemolytic Anemia : Reference to the Abnormal Accumulation of Phosphatidylcholine in These Membranes

The pathogenesis of the accumulation of phosphatidylcholine (PC) in red cell membranes of the patients with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) was studied utilizing 14C-PC and 14C-lyso-PC. The uptake of 14C-PC was not significantly different in the red cell membranes with HPCHA from that in normal controls and obstructive jaundice in whom red cell membrane PC and free cholesterol (FC) were elevated to the same extent as that in HPCHA. The efflux of 14C-PC with HPCHA was slightly decreased, in comparison with that in the normal controls and obstructive jaundice. The most striking data were obtained in the uptake of 14C-lyso-PC by the red cells of the HPCHA patients, showing more than two fold increase when compared with that in the normal control. The conversion of 14C-lyso-PC to 14C-PC was increased in comparison with that in the normal controls and obstructive jaundice. In summary, the exact cause of the abnormal accumulation of PC through increased uptake of lyso-PC, followed by the increased conversion of lyso-PC to PC is unknown. In obstructive jaundice of an acquired origin, some compensatory mechanism may exist to prevent the further accumulation of lipids in the red cell membranes

Quality of life and physical/psychosocial factors in children and adolescents with orthostatic intolerance

Background　Orthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI. Methods　A cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9-15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examined using multiple linear regression. Results　Pediatric patients with OI had significantly lower QOL scores than healthy children in both elementary (50.7 +/- 13.5 vs. 67.9 +/- 13.4, p Conclusions　These results suggest that the assessment of QOL, including both physical and psychosocial aspects, especially school factors, needs to be implemented earlier in children and adolescents with OI

Desensitization of delayed-type hypersensitivity in mice: suppressive environment

The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2) activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH) 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment

Human bone marrow VCAM-1+ macrophages provide a niche for reactive and neoplastic erythropoiesis

Resident bone marrow macrophages provide a microenvironment for erythropoiesis, forming erythroblastic islands (EBIs) via adhesion molecules. In this study, we examined vascular cell adhesion molecule-1 (VCAM-1) expression in human bone marrow specimens using immunohistochemistry. VCAM-1 was strongly expressed in CD169+ macrophages in EBIs and weakly in sinusoidal vascular endothelial cells. In reactive erythropoiesis, including hemolytic and megaloblastic anemia, the extended cytoplasm of VCAM-1+ CD169+ macrophages circumscribed the erythroid cells. The strong affinity between VCAM-1+ macrophages and erythroid cells was also observed in polycythemia vera (PV), essential thrombocythemia (ET), and chronic myelogenous leukemia (CML). VCAM-1 density was significantly higher in PV than in ET and CML (p < 0.001), and correlated with blood erythrocyte count in all three neoplasms (p < 0.001). In ET, the VCAM-1 density was higher in cases with the JAK2 mutation than with the CALR mutation. In myelodysplastic syndrome with erythroid predominance but unclear EBI formation, punctate VCAM-1+ cytoplasmic processes of macrophages were seen between erythroblasts, similar to those seen between granulocytic precursors in CML, suggesting incomplete contact of VCAM-1+ macrophages with dysplastic erythroid cells. These results suggest that VCAM-1+ macrophages create a niche for reactive and neoplastic erythropoiesis and may be a therapeutic target in PV

A new perfusion culture method with a self-organized capillary network

A lack of perfusion has been one of the most significant obstacles for three-dimensional culture systems of organoids and embryonic tissues. Here, we developed a simple and reliable method to implement a perfusable capillary network in vitro. The method employed the self-organization of endothelial cells to generate a capillary network and a static pressure difference for culture medium circulation, which can be easily introduced to standard biological laboratories and enables long-term cultivation of vascular structures. Using this culture system, we perfused the lumen of the self-organized capillary network and observed a flow-induced vascular remodeling process, cell shape changes, and collective cell migration. We also observed an increase in cell proliferation around the self-organized vasculature induced by flow, indicating functional perfusion of the culture medium. We also reconstructed extravasation of tumor and inflammatory cells, and circulation inside spheroids including endothelial cells and human lung fibroblasts. In conclusion, this system is a promising tool to elucidate the mechanisms of various biological processes related to vascular flow