In this study, we documented the clinical features of patients who had obstructive sleep apnea (OSA) and coexisting asthma and assessed the safety of nocturnal nasal continuous positive airway pressure (nCPAP) therapy on the stability of asthma. Nine patients (8 men and 1 woman) with asthma and OSA confirmed on all-night sleep study were studied. All patients suffered from frequent nocturnal asthma attacks, resulting in hospitalizations and respiratory arrests in 3. All patients had symptoms of heavy snoring, nocturnal choking, frequent sleep arousals, and excessive daytime sleepiness. They recorded their daily peak expiratory flow rates (PEFR) in the mornings and evenings, before and after bronchodilator in three 2-wk periods consisting of control, nCPAP, and control. During the period of nCPAP therapy, all patients recorded improvement in their PEFR. The mean prebronchodilator and postbronchodilator PEFR for the 9 patients were significantly higher during nCPAP therapy than during both control periods. This study confirms that nCPAP therapy can be used safely in treating patients with OSA and coexisting asthma. Furthermore, nCPAP treatment improves the asthma control and, in particular, the nocturnal attacks in this group of patients. These results also suggest that recurrent upper airway obstruction and snoring may be important triggering mechanisms of nocturnal asthma attacks.
The D-type cyclins promote progression through the G 1 phase of the cell cycle and may provide a link between growth factors and the cell cycle machinery. We determined the nucleotide sequence of the 5-flanking region of the human cyclin D2 and cyclin D3 genes and identified the transcription start sites. Analysis of the upstream sequences required for transcription of the cyclin D2 and cyclin D3 genes in continuously dividing cells revealed marked differences in their regulatory elements. In the cyclin D2 gene positive elements were localized between positions ؊306 and ؊114 relative to the ATG codon at ؉1. Additional positive elements were localized between ؊444 and ؊345, whereas sequences that reduced transcription were identified between nucleotides ؊1624 and ؊892. In the cyclin D3 gene all of the positive elements required for maximal transcription were localized between nucleotides ؊366 and ؊167, and no negative elements were found. The activities of a reporter gene linked to the upstream regulatory sequences of the cyclin D2 gene but not the cyclin D3 gene were induced when starved cells were serum stimulated. This suggests that although the abundance of both the cyclin D2 and cyclin D3 mRNAs is increased by serum stimulation, only the cyclin D2 gene is up-regulated at the transcriptional level. Sequences between nucleotides ؊306 and ؊1624 of the cyclin D2 gene were necessary for serum inducibility.
Abundant evidence suggests that growth factors are important mediators of non-small cell lung cancer (NSCLC) growth. Although multiple growth factors have been found to be produced by NSCLC tissues, little is known about possible differences in growth factor expression between malignant and adjacent normal lung tissues. Variation in growth factor expression between normal and malignant lung tissues could be potentially useful diagnostically and therapeutically. In studies reported here, the expression of the angiogenic growth factor pleiotrophin (PTN) and homolog midkine (MK) was assessed in resected normal and malignant lung tissues. Primers specific for the two growth factors were used to amplify reverse transcriptase-produced DNA copies of RNA transcripts harvested from the tissues. This analysis revealed that all normal lung tissues examined (n = 17) expressed PTN but only two expressed MK. Conversely, all of the resected lung cancers (n = 20) expressed MK but only one expressed PTN. These results demonstrated a striking reciprocal expression pattern of MK and PTN in normal versus malignant lung tissue.
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