Strict morphological criteria of CC coupled with assessment of the tumour cell/stroma relationship and the nuclear features facilitate discrimination between mucinous tumours of salivary gland.
High-resolution oligonucleotide array comparative genomic hybridization (aCGH) and spectral karyotyping (SKY) were applied to a panel of malignant mesothelioma (MMt) cell lines. SKY has not been applied to MMt before, and complete karyotypes are reported based on the integration of SKY and aCGH results. A whole genome search for homozygous deletions (HDs) produced the largest set of recurrent and non-recurrent HDs for MMt (52 recurrent HDs in 10 genomic regions; 36 non-recurrent HDs). For the first time, LINGO2, RBFOX1/A2BP1, RPL29, DUSP7, and CCSER1/FAM190A were found to be homozygously deleted in MMt, and some of these genes could be new tumor suppressor genes for MMt. Integration of SKY and aCGH data allowed reconstruction of chromosomal rearrangements that led to the formation of HDs. Our data imply that only with acquisition of structural and/or numerical karyotypic instability can MMt cells attain a complete loss of tumor suppressor genes located in 9p21.3, which is the most frequently homozygously deleted region. Tetraploidization is a late event in the karyotypic progression of MMt cells, after HDs in the 9p21.3 region have already been acquired.
lar endothelial injury is the major mechanism for multiorgan dysfunction in sepsis. Following this process, the permeability of the alveolar capillaries is augmented with subsequent increase in water content and acute respiratory distress syndrome (ARDS). Nevertheless, the role of alveolar epithelium is less known. Therefore, we examined alveolar fluid clearance (AFC) using isolated perfused rat lung model in septic rats without ARDS. Sepsis was induced by ligating and puncturing the cecum with a 21-gauge needle. AFC was examined 24 and 48 h later. The expression of Na-K-ATPase proteins was examined in type II alveolar epithelial cells (ATII) and basolateral membrane (BLM). The rate of AFC in control rats was 0.51 Ϯ 0.02 ml/h (means Ϯ SE) and decreased to 0.3 Ϯ 0.02 and 0.33 Ϯ 0.03 ml/h in 24 and 48 h after sepsis induction, respectively (P Ͻ 0.0001). Amiloride, significantly decreased AFC in sepsis; conversely, isoproterenol reversed the inhibitory effect of sepsis. The alveolar-capillary barrier in septic rats was intact; therefore the finding of increased extravascular lung water in early sepsis could be attributed to accumulation of protein-poor fluid. The expression of epithelial sodium channel and Na-K-ATPase proteins in whole ATII cells was not different in both cecal ligation and puncture and control groups; however, the abundance of Na-K-ATPase proteins was significantly decreased in BLMs of ATII cells in sepsis. Early decrease in AFC in remote sepsis is probably related to endocytosis of the Na-K-ATPase proteins from the cell plasma membrane into intracellular pools, with resultant inhibition of active sodium transport in ATII cells. acute respiratory distress syndrome; alveolar fluid clearance; active sodium transport; endocytosis SEPSIS AND RELATED SYSTEMIC inflammatory reaction is a lifethreatening disease that affects ϳ750,000 patients a year in the United States; the frequency is increasing, given an aging population with increasing numbers of patients with comorbid conditions (29). The acute respiratory distress syndrome (ARDS) is a common, devastating clinical syndrome of acute lung injury (ALI) that affects both medical and surgical patients. Sepsis that is not caused by pneumonia is associated with the highest risk of progression to ALI or ARDS (12, 42).Widespread vascular endothelial injury is thought to be the major mechanism for multiorgan dysfunction and ARDS in sepsis, thereby augmenting the permeability of alveolar capillaries with subsequent influx of protein-rich edema fluid into the air spaces (17).The resolution of both cardiogenic pulmonary edema and ARDS depends on the clearance of fluid from the alveolar space, a process that requires an intact, functional alveolar epithelium (22, 24). The primary driving force for alveolar fluid clearance (AFC) is the active transport of sodium from the alveolar space to the interstitium by alveolar epithelial type II cells (ATII cells) (2,21,23,34,36). Little is known about ATII function in sepsis. Therefore, we aimed to examine the effects of r...
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