A Meckel's diverticulum presenting as pyogenic liver abscesses.

Meckel's diverticula are the most common congenital malformation of the small intestine. The condition is rarely symptomatic and is usually an incidental finding during surgery. Bleeding in children and obstruction in adults are the most common symptomatic presentations. Our case involves a 50-year-old man with multiple pyogenic liver abscesses due to a Meckel's diverticulum. The abscesses were percutaneously drained and the diverticulum was eventually resected. Pyogenic liver abscess is a very rare presentation of a Meckel's diverticulum. The diverticulum in our case appeared to have a thickened wall on imaging but no signs of acute inflammation were present on the CT scan or noticed intraoperatively. It was presumed to be the possible source as all other possibilities were ruled out. Ultimately, the surgical pathology revealed acute inflammation and focal abscess. We propose that elective resection of a Meckel's diverticulum should be considered in the setting of pyogenic liver abscess with no other identifiable source.

Mechanical force-activated phospholipase D is mediated by Galpha12/13-Rho and calmodulin-dependent kinase in renal epithelial cells.

The renal glomerulus, the site of plasma ultrafiltration, is exposed to mechanical force in vivo arising from capillary blood pressure and fluid flow. Studies of cultured podocytes demonstrate that they respond to stretch by altering the structure of the actin cytoskeleton, but the mechanisms by which physical force triggers this architectural change and the signaling pathways that lead to generation of second messengers are not defined. In the present study, we found that in renal epithelial cells [podocytes and Madin-Darby canine kidney (MDCK) cells], application of mechanical force to the cell surface through fibronectin-coated ferric beads and exposure of the cells to magnetic force lead to Rho translocation and actin cytoskeleton reorganization. This application of force recruited Rho and filamentous actin (F-actin) to bead loci and subsequently stimulated phospholipase D (PLD), a downstream effector of Rho. Using MDCK cells that stably express regulators of G protein-signaling (RGS) proteins [RGS4 attenuates Galpha(i) and Galpha(q), and the p115RhoGEF-RGS domain (p115-RGS) attenuates Galpha(12/13)] to define the signaling pathway, we found that mechanical force induced Galpha(12/13)-Rho activation and increased F-actin to stimulate PLD activity. The activation can be partially prevented by the C(3) exoenzyme. Pretreatment of the cells with chemical inhibitors of several kinases showed that calmodulin-dependent kinase is also involved in stretch-induced PLD activation by a separate pathway. Taken together, our data demonstrate that in cultured podocytes and MDCK cells, mechanical force leads to actin cytoskeleton reorganization and PLD activation. The signaling pathways for PLD activation involve Galpha(12/13)/Rho/F-actin and calmodulin-dependent kinase.

Role of ceramide in Ca2+-sensing receptor-induced apoptosis.

Increased extracellular Ca(2+) ([Ca(2+)](o)) can damage tissues, but the molecular mechanisms by which this occurs are poorly defined. Using HEK 293 cell lines that stably overexpress the Ca(2+)-sensing receptor (CaR), a G protein-coupled receptor, we demonstrate that activation of the CaR leads to apoptosis, which was determined by nuclear condensation, DNA fragmentation, caspase-3 activation, and increased cytosolic cytochrome c. This CaR-induced apoptotic pathway is initiated by CaR-induced accumulation of ceramide which plays an important role in inducing cell death signals by distinct G protein-independent signaling pathways. Pretreatment of wild-type CaR-expressing cells with pertussis toxin inhibited CaR-induced [(3)H]ceramide formation, c-Jun phosphorylation, and caspase-3 activation. The ceramide accumulation, c-Jun phosphorylation, and caspase-3 activation by the CaR can be abolished by sphingomyelinase and ceramide synthase inhibitors in different time frames. Cells that express a nonfunctional mutant CaR that were exposed to the same levels of [Ca(2+)](o) showed no evidence of activation of the apoptotic pathway. In conclusion, we report the involvement of the CaR in stimulating programmed cell death via a pathway involving GTP binding protein alpha subunit (Galpha(i))-dependent ceramide accumulation, activation of stress-activated protein kinase/c-Jun N-terminal kinase, c-Jun phosphorylation, caspase-3 activation, and DNA cleavage.