Automated bone marrow analysis using the CD4000 automated haematology analyser

At present, bone marrow analysis is performed microscopically, but is time consuming and labour intensive. No automated methods have been successfully applied to classification of bone marrows cells because automated blood cell analysers have been incapable of identifying erythroblasts. The present study was designed to evaluate automated analysis of bone marrow aspirates with the CELL-DYN 4000 (CD4000) haematology analyser, which enables automated determination of erythroblast counts in both the normal mode (haemolytic time; 11.5s) and the resistant RBC mode (34.0s). The percentages of subpopulations including lymphocytes, neutrophils and erythroblasts were obtained with the CD4000, and as a reference, differential counts by microscopic observation of May–Grünwald–Giesa-stained films of bone marrow aspirates were performed (n=98). Significant correlations (P < 0.01) between the results obtained with the two methods were observed for total nucleated cell count and lymphocytes, neutrophils, erythroblasts and myeloid/erythroid (M/E) ratio. However, there were biases in the average percentages of erythroblasts, lymphocytes and M/E ratio obtained using the normal mode with the CD4000 toward values lower than those obtained with the microscopic method. Using the RBC resistant mode with the CD4000, the average percentages of erythroblasts, lymphocytes and M/E ratio approximated those obtained with the microscopic method. In conclusion, the CD4000 in resistant RBC mode is more useful for analysis of bone marrow aspirates than is the normal mode, because the former better approximates the M/E ratio than the latter

Topoisomerase IIIβ Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice

Topoisomerase IIIβ (Top3β), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3β with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3β on neuro-behavior using newly generated Top3β deficient (Top3β−/−) mice. We found that Top3β−/− mice showed decreased anxiety and depression-like behaviors. The lack of Top3β was also associated with changes in circadian rhythm. In addition, a clear expression of Top3β was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3β−/− mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3β is essential for normal brain function and behavior in mice and that Top3β could be an interesting target to study neuropsychiatric disorders in humans