cAMP Response Element Binding Protein Is Required for Differentiation of Respiratory Epithelium during Murine Development

The cAMP response element binding protein 1 (Creb1) transcription factor regulates cellular gene expression in response to elevated levels of intracellular cAMP. Creb1−/− fetal mice are phenotypically smaller than wildtype littermates, predominantly die in utero and do not survive after birth due to respiratory failure. We have further investigated the respiratory defect of Creb1−/− fetal mice during development. Lungs of Creb1−/− fetal mice were pale in colour and smaller than wildtype controls in proportion to their reduced body size. Creb1−/− lungs also did not mature morphologically beyond E16.5 with little or no expansion of airway luminal spaces, a phenotype also observed with the Creb1−/− lung on a Crem−/− genetic background. Creb1 was highly expressed throughout the lung at all stages examined, however activation of Creb1 was detected primarily in distal lung epithelium. Cell differentiation of E17.5 Creb1−/− lung distal epithelium was analysed by electron microscopy and showed markedly reduced numbers of type-I and type-II alveolar epithelial cells. Furthermore, immunomarkers for specific lineages of proximal epithelium including ciliated, non-ciliated (Clara), and neuroendocrine cells showed delayed onset of expression in the Creb1−/− lung. Finally, gene expression analyses of the E17.5 Creb1−/− lung using whole genome microarray and qPCR collectively identified respiratory marker gene profiles and provide potential novel Creb1-regulated genes. Together, these results demonstrate a crucial role for Creb1 activity for the development and differentiation of the conducting and distal lung epithelium

Radical perineal prostatectomy and early continence: outcomes after 120 cases

PURPOSE: Evaluate the results of urinary continence on patients who had undergone radical perineal prostatectomy (RPP) for clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed the continence data of 120 patients with pathology of cT1-cT2N0M0 prostate cancer and who had undergone RPP. Continence was assessed on the day of catheter removal, at the end of the first and third month, and the first year postoperatively. The patients who were continent immediately after catheter removal were classified in the group of “immediately continent” while the patients who became continent during the 3 postoperative months were classified as “early continent.” RESULTS: Mean duration of catheterization was 10 (10-25) days. Of 120 patients, 44 (36.7%) were immediately continent. At the end of the first and third months, 65 (54.1%) and 87 (72.5%), respectively, were early continent. At the one-year follow-up, 95.3% of 107 cases whose one-year follow-up data were available were continent. When the relationship between patients’ age and continence was analyzed, it was found that the early continence rates were 77.7% (7/9), 73.3% (33/45), 73.4% (36/49), and 64.7% (11/17) in the groups of = 49, 50-59, 60-69, and = 70 years, respectively (p = 0.68). CONCLUSIONS: The majority of patients who underwent RPP rapidly regained continence within 3 months. RPP is an exceptional alternative approach for radical surgery in the treatment of localized prostate cancer

Patterns of peroxidative ethane emission from submerged rice seedlings indicate that damage from reactive oxygen species takes place during submergence and is not necessarily a post-anoxic phenomenon

Contains fulltext : 36303pub.pdf (publisher's version ) (Closed access)Using ethane as a marker for peroxidative damage to membranes by reactive oxygen species (ROS) we examined the injury of rice seedlings during submergence in the dark. It is often expressed that membrane injury from ROS is a post-submergence phenomenon occurring when oxygen is re-introduced after submergence-induced anoxia. We found that ethane production, from rice seedlings submerged for 24-72 h, was stimulated to 4-37 nl gFW(-1), indicating underwater membrane peroxidation. When examined a week later the seedlings were damaged or had died. On de-submergence in air, ethane production rates rose sharply, but fell back to less than 0.1 nl gFW(-1) h(-1) after 2 h. We compared submergence-susceptible and submergence-tolerant cultivars, submergence starting in the morning (more damage) and in the afternoon (less damage) and investigated different submergence durations. The seedlings showed extensive fatality whenever total ethane emission exceeded about 15 nl gFW(-1). Smaller amounts of ethane emission were linked to less extensive injury to leaves. Partial oxygen shortage (O-2 levels < 1%) imposed for 2 h in gas phase mixtures also stimulated ethane production. In contrast, seedlings under anaerobic gas phase conditions produced no ethane until re-aerated: then a small peak was observed followed by a low, steady ethane production. We conclude that damage during submergence is not associated with extensive anoxia. Instead, injury is linked to membrane peroxidation in seedlings that are partially oxygen deficient while submerged. On return to air, further peroxidation is suppressed within about 2 h indicating effective control of ROS production not evident during submergence itself