Play it, Jen

Every good movie has a piano player somewhere in the background--
sometimes seen, usually unseen.
Seldom really noticed.
The feeling, the very soul of a scene, is created by that person tinkering at the keys.
It has been said, "All the world's a stage."
Well then...Play it, Jen.

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Location: Over Yonder, Missouri

I'm a California Native transplanted to the Missouri Ozarks. I've learned how to chase cows in high heels and load hay faster than you can say "Coco Chanel." These are some of our pictures and stories of living in a land with breath-taking beauty and adventure around every bend.

Sunday, August 20, 2006

The next challenge in pediatric cholestasis: deciphering the pathogenesis of biliary atresia.

Entrez PubMed
Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and The University of Cincinnati College of Medicine, OH, USA.

Cholestasis is a common presenting symptom of liver disease in infants. Chief among diseases presenting as neonatal cholestasis is biliary atresia, the most common cause of chronic liver disease in children, but little is known about the pathogenesis of this disease. In search for the molecular basis of biliary atresia, we began two areas of investigation. In the first, we interrogated the hepatic transcriptome of children with biliary atresia and found an interferon-gamma (IFNgamma)-rich proinflammatory footprint at the time of diagnosis. To directly explore if IFNgamma plays an important role in biliary injury and obstruction, we used a mouse model of experimental biliary atresia and found that inactivation of the murine Ifngamma gene decreases the tropism of lymphocytes to neonatal bile ducts and prevents the inflammatory obstruction of the duct lumen. Further analysis of the extrahepatic biliary tract also outlined a broader network of proinflammatory genes at the onset and during progression to duct obstruction, with the time-specific activation of IFNgamma-, apoptosis-, and complement-driven networks. In the second approach, we searched for molecular profiles that differentiate clinical forms of biliary atresia by analyzing the hepatic transcriptome of age-matched subjects at the time of diagnosis. We found a preliminary profile that differentiates the embryonic from the perinatal forms of biliary atresia. The profile contained the differential activation of genes involved in epigenetic mechanisms of disease. Collectively, these studies provide new insight into pathogenesis of biliary atresia and identify potential therapeutic targets to foster long-term outcome with the native liver.

PMID: 16819397 [PubMed - in process]


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