Clinical use of bone marrow mesenchymal stem cells (BMMSCs) holds great promise for regenerative medicine in intractable lung diseases, such as lung fibrosis or acute respiratory distress syndrome. However, a severe obstacle to the clinical application of BMMSC transplantation is the time-consuming, laborious processes required for cell culture. In order to evaluate the clinical applicability of BMMSC transplantation, we tested whether engraftment of minimally cultured BMMSCs ameliorates progressive fibrotic lung injury.Differences between murine BMMSCs cultured for 2 h (2-h adherent BMMSCs) and conventionally (9-day) cultured BMMSCs were examined in vitro. The effects of grafting either type of BMMSCs on fibrotic lung injury were then assessed by transfer experiments in a murine bleomycin-induced lung fibrosis model, in which donor cells were administered 3 days after challenge.2-h adherent BMMSCs were smaller, less granular, possessed higher proliferative capacity and expressed higher levels of several stem cell markers and chemokine receptors than 9-day cultured BMMSCs, but lower type I procollagen, a-smooth muscle actin, tumour necrosis factor-b and oncogenic transcription factor c-Myc, suggesting that they may be advantageous for cellbased therapy compared with 9-day cultured BMMSCs. Grafting 2-h adherent BMMSCs ameliorated inflammatory and fibrotic lung disorders, and reduced mortality equally well or better than 9-day cultured BMMSCs.Minimally cultured BMMSCs can substitute for conventionally cultured BMMSCs and will be a promising cell source for the treatment of acute fibrotic lung injury.
Sleeping in the light has effects like that of a stressor as it is associated with neuroexcitation, SDB, and resting breathing irregularity in healthy volunteers. These findings may be relevant to many sleep disorders associated with poor sleep hygiene.
Recent studies have advocated the genotypic and phenotypic delineation of a novel Ewing's sarcoma histologic variant showing epithelial features defined as "adamantinoma-like Ewing's sarcoma". We described an 18-year-old girl with a primary small round-cell sarcoma of the right tibia showing polyphenotypic differentiation with epithelioid features. The neoplastic cells had mainly round or oval nuclei with fine chromatin with a portion of epithelial arrangements. The immunohistochemical analysis showed the epithelial markers of cytokeratin 5/6/18, AE1/AE3, and cytokeratin high molecular weight were stained especially in the foci with epithelioid features, as well as MIC2, S100, and NSE. The diagnosis of the lesion was confirmed as Ewing's sarcoma by the presence of the EWS-FLI1 fusion transcript, and could be defined as the so-called "adamantinoma-like Ewing's sarcoma". After wide excision and high-dose chemotherapy with peripheral blood stem cell transfusion, the patient has been well and continuously event-free for 3 years since the initial diagnosis.
Study Objectives: Obstructive sleep apnea (OSA) can be severe and present in higher numbers during rapid eye movement (REM) than nonrapid eye movement (NREM) sleep; however, OSA occurs in NREM sleep and can be predominant. In general, ventilation decreases an average 10% to 15% during transition from wakefulness to sleep, and there is variability in just how much ventilation decreases. As dynamic changes in ventilation contribute to irregular breathing and breathing during NREM sleep is mainly under chemical control, our hypothesis is that patients with a more pronounced reduction in ventilation during the transition from wakefulness to NREM sleep will have NREM-predominant rather than REM-predominant OSA. Methods: A retrospective analysis of 451 consecutive patients (apnea-hypopnea index [AHI] > 5) undergoing diagnostic polysomnography was performed, and breath-tobreath analysis of the respiratory cycle duration, tidal volume, and estimated minute ventilation before and after sleep onset were examined. Values were calculated using respiratory inductance plethysmography. The correlation between the percent change in estimated minute ventilation during wakesleep transitions and the percentage of apnea-hypopneas in NREM sleep (%AHI in NREM; defi ned as (AHI-NREM) / [(AHI-NREM) + (AHI-REM)] × 100) was the primary outcome. Results: The decrease in estimated minute ventilation during wake-sleep transitions was 15.0 ± 16.6% (mean ± standard deviation), due to a decrease in relative tidal volume. This decrease in estimated minute ventilation was signifi cantly correlated with %AHI in NREM (r = −0.222, p < 0.01). 1,2 In general, upper airway obstruction and hypopnea is in REM sleep when upper airway muscle tonus is decreased as compared to nonrapid eye movement (NREM) sleep. However, OSA occurring predominantly in NREM sleep or equally in a numeric manner in both REM and NREM sleep is also encountered in clinical practice; neither prevalence nor mechanisms driving the relative distribution of REM and NREM events have been considered in any detail. In NREM sleep, detailed physiologic studies detect dynamic changes in ventilatory control during state transitions, which are considered to induce irregular breathing, and lead to obstructive apnea and/or hypopnea. [3][4][5][6][7] Detailed studies in REM sleep are absent, leaving an opportunity for the clinical polysomnogram to inform not only REM-predominant OSA but the possibility of NREM predominant OSA as well. ConclusionsVentilation decreases an average of 10% to 15% during the transition from wakefulness to sleep due mainly to a decrease in tidal volume; however, the literature reports substantial
These data suggest that DNA-PK activity might play a major role in the radioadaptive response following pre-irradiation at a low dose-rate.
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