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.
Purpose: Chronic obstructive pulmonary disease (COPD) is a worldwide problem because of its high prevalence and mortality. However, there is no fundamental treatment to ameliorate their pathological change in COPD lung. Recently, adipose-derived mesenchymal stem cells (ADSCs) have attracted attention in the field of regenerative medicine to repair damaged organs. Moreover, their utility in treating respiratory diseases has been reported in some animal models. However, the detailed mechanism by which ADSCs improve chronic respiratory diseases, including COPD, remains to be elucidated. We examined whether human ADSCs (hADSCs) ameliorated elastase-induced emphysema and whether hADSCs differentiated into alveolar epithelial cells in a murine model of COPD. Methods: Female SCID-beige mice (6 weeks old) were divided into the following four groups according to whether they received an intratracheal injection of phosphate-buffered saline or porcine pancreatic elastase, and whether they received an intravenous injection of saline or hADSCs 3 days after intratracheal injection; Control group, hADSC group, Elastase group, and Elastase-hADSC group. We evaluated the lung function, assessed histological changes, and compared gene expression between hADSCs isolated from the lung of Elastase-hADSC group and naïve hADSCs 28 days after saline or elastase administration. Results: hADSCs improved the pathogenesis of COPD, including the mean linear intercept and forced expiratory volume, in an elastase-induced emphysema model in mice. Furthermore, hADSCs were observed in the lungs of elastase-treated mice at 25 days after administration. These cells expressed genes related to mesenchymal-epithelial transition and surface markers of alveolar epithelial cells, such as TTF-1, β-catenin, and E-cadherin. Conclusion: hADSCs have the potential to improve the pathogenesis of COPD by differentiating into alveolar epithelial cells by mesenchymal-epithelial transition.
At the initiation of therapy, breathing regularity during wakefulness while wearing CPAP is an objective predictor of short-term CPAP adherence.
A 69-year-old man presented with upper airway symptoms, multiple lung nodules and masses, proteinuria and hematuria, and an increased level of proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA). Granulomatosis with polyangiitis (GPA) was diagnosed by a transbronchial lung biopsy. All of these symptoms were ameliorated and the level of PR3-ANCA declined following treatment with prednisolone and cyclophosphamide. The patient developed a headache 16 months after the onset of symptoms, and contrastenhanced magnetic resonance imaging showed the thickening of the dura mater, which suggested that hypertrophic pachymeningitis (HP) had developed as a complication of GPA. HP can be a unique complication of GPA at recurrence, and can occur without the relapse of other lesions or an increase in PR3-ANCA level.
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