No abstract

Caspase-8 has been implicated in signaling for apoptotic cell death and for certain nonapoptotic functions. However, knowledge of actual physiological or pathophysiological processes to which this enzyme contributes is lacking. Using a mouse model and employing the conditional knockout approach to delete the caspase-8 gene specifically in the liver, we found that caspase-8 deficiency in hepatocytes facilitates infection of the liver by Listeria monocytogenes, attenuates the hepatocyte proliferation wave during the first 48 hours after partial hepatectomy and, depending on the genetic background of the mice, prompts a chronic inflammatory response to the hepatectomy, as a result of which the proliferation of hepatocytes, although initially suppressed, might later be persistently enhanced, resulting in significant hepatomegaly. Conclusion: These findings indicate that caspase-8 participates in regulation of the cellular response to infection and injury and that it does so by affecting various cellular functions, including cell death, cell proliferation, and induction of inflammation. (HEPATOLOGY 2007;45:1014-1024

In the liver, the magnitude of the percentage change in SI induced by hypercapnia and hyperoxia reflects changes in total blood volume; whereas percentage change in SI values induced by hypercapnia from a negative to a positive value reflects relative changes in portal-to-arterial blood flow ratio.

In the yeast Sacchromyces cerevisiae, addition of glucose to starved cells triggers a transient rise in the intracellular level of cyclic AMP that induces a protein phosphorylation cascade. The glucose signal is processed by the Cdc25/Ras/adenylyl cyclase pathway, where the role of Cdc25 is to catalyse the GDP-GTP exchange on Ras. The molecular mechanisms involved in the regulation of the activity of Cdc25 are unknown. We report here the use of highly selective anti-Cdc25 antibodies to demonstrate that Cdc25 is a phospho protein and that in response to glucose it is hyperphosphorylated, within seconds, by the cyclic AMP-dependent protein kinase. It is also demonstrated that, concomitantly with hyperphosphorylation, Cdc25 partially relocalizes to the cytoplasm, reducing its accessibility to membrane-bound Ras. These results are of general significance because of the highly conserved sequence of Ras-guanyl nucleotide exchange factors from yeasts to mammals.

ABSTRACT. Deep vein thrombophlebitis (DVT) and septic pulmonary emboli (PE) are rare in children. The association of DVT and acute disseminated staphylococcal disease (DSD) during childhood has not been previously reported. We report 3 children who developed a triad of DVT, septic PE, and acute osteomyelitis with Staphylococcus aureus cultured from blood and bone. One child succumbed, while 2 survived following prolonged, morbid hospitalizations. The rapid clinical deterioration observed in these patients might be caused by the aggressiveness of staphylococcal infection combined with an ongoing showering of septic emboli from the ileo-femoral DVT. We suggest that infected DVT with septic PE had a pivotal role in the development of DSD in these children. The presence of this triad should prompt aggressive treatment with the appropriate antibiotics, anticoagulation, surgical drainage, and assisted ventilation when indicated. Pediatrics 2000;106(6). URL: http://www.pediatrics.org/cgi/content/full/106/6/e87; deep vein thrombophlebitis, disseminated staphylococcal disease, osteomyelitis, pediatric, septic pulmonary emboli.ABBREVIATIONS. DVT, deep vein thrombophlebitis; PE, pulmonary emboli; DSD, disseminated staphylococcal disease; WBC, white blood cell count. D eep vein thrombophlebitis (DVT) and septic pulmonary emboli (PE) rarely occur in children. The triad of DVT, septic pulmonary embolism, and acute osteomyelitis in children has not been emphasized in the literature or in any report of acute disseminated staphylococcal disease (DSD) in childhood. [1][2][3][4][5][6] The present report describes 3 children with this triad, 1 of whom died, while 2 survived after prolonged, complicated hospitalizations. Theories regarding the role of DVT in the development of DSD, diagnostic modalities, and appropriate therapies are discussed. CASE REPORTS Patient 1An 11-year-old previously healthy boy presented with left hip pain, fever (approaching 39.7°C), recurrent vomiting, and a generalized erythematous rash of 2 days duration. Physical examination showed an alert child: temperature, 39°C; heart rate, 188 beats/minute; respiratory rate, 32 breaths/minute; and blood pressure, 75/50 mm Hg. A diffuse erythematous rash was present over the extremities. Chest examination revealed crepitations over the left side. The left hip joint was tender with no evidence of local infection.Initial laboratory results included: hemoglobin, 12.6 g/dL; white blood cell count (WBC), 28 000/mm 3 with 80% polymorphonuclears; platelet count, 168 000/mm 3 ; prothrombin time, 24% (international normalized ratio: 2.2); and partial thromboplastin time, 42.8 seconds. The chest radiograph showed bilateral diffuse infiltrates (Fig 1). Ultrasonography of the left hip joint demonstrated intraarticular fluid and thickening of the joint capsule. A bone scan was consistent with osteomyelitis of the left proximal femur. Doppler ultrasound revealed thrombosis with partial occlusion of the left femoral vein (Fig 2). Blood cultures were drawn and intravenous administ...