We investigated the effect of the histone deacetylase inhibitors (HDIs), trichostatin A and trapoxin A on leukemia cells and cell lines from the viewpoint of differentiation induction. TSA induced differentiation in erythroid cell lines by itself, whereas it synergistically enhanced the differentiation that was directed by all-trans retinoic acid (ATRA) or vitamin D3 in U937, HL60 and NB4 cells. The combined treatment of HDI with ATRA induced differentiation in ATRA-resistant HL60 and NB4 cells. The transcriptional expression during the treatment with HDI was examined in HL60, U937 and MEG-O1. Cell cycle-regulator genes (p21 waf1 and p16 INK4A ) were upregulated or constantly expressed, erythroid-specific genes (GATA-1, -globin) were silent or downregulated, and housekeeping genes (-actin and GAPDH) were constantly expressed. Twelve of 35 (34%) clinical samples from AML patients ranging from M0 to M7 also displayed both phenotypical and morphological changes by the treatment with TSA alone. HDIs are thus the potent inducer or enhancer of differentiation in acute myeloid leukemia and regulate transcription in an ordered manner.
Key message
Tension pneumomediastinum is a rare complication of interstitial pneumonia. This case shows computed tomography findings of the Macklin effect, in which air dissection along the bronchovascular interstitium caused by alveolar rupture leads to pneumomediastinum.
PURPOSE: Pleuroparenchymal fibroelastosis (PPFE) is a rare fibrosing lung disease with an upper lobe predilection. Its natural history and prognosis have not been fully elucidated because of the rarity and the heterogeneous etiologies of the fibrosis. Sleep often causes profound changes on the respiratory system, especially in patients with underlying chronic pulmonary diseases. Sleep-related hypoventilation syndromes (SRHS) are characterized by an abnormal increase in the arterial carbon dioxide partial pressure (PaCO2) and a decrease in the arterial oxygen partial pressure (PaO2) during sleep. SHRS is well known to be important in the development of hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD). SRHS in PPFE have, however, not been well documented. The aim of this study is to clarify the impact of SRHS on prognosis in PPFE.
METHODS:From January 2016 to July 2019, we retrospectively reviewed medical records of 393 consecutive patients undergoing transcutaneous carbon dioxide (PtCO2) monitoring during sleep. Among those, 126 patients (32%) were diagnosed as SRHS, which fulfilled American Academy of Sleep Medicine criteria.RESULTS: Among those patients with SRHS, 40 patients (31.7%) had COPD, followed by 30 patients (23.8%) with PPFE, 20 patients (15.8%) with idiopathic interstitial pneumonia (IPF) or non-specific interstitial pneumonia (NSIP), and 15 patients (11.9%) with chronic pulmonary aspergillosis (CPA). On the other hand, the prevalence of SRHS was the most common in PPFE (53.4%) followed by COPD (38.8%). Furthermore, PPFE with SRHS was significantly associated with poorer prognosis, compared with PPFE without SRHS (median survival: 270 days for with SRHS versus median not reached for without SRHS, p < 0.001).
CONCLUSIONS:The present study has demonstrated that in PPFE, SRHS might be one of the most common complications associated with poor outcome.CLINICAL IMPLICATIONS: Sleep-related hypoventilation syndrome might be a poor prognostic condition in PPFE.
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