Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal-recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and associated with mutations ...

Pneumonia remains the leading cause of infectious deaths and yet fundamentally new conceptual models underlying its pathogenesis have not emerged. Patients and mice with bacterial pneumonia have marked elevations of cardiolipin in lung fluid, a rare, mitochondrial-specific phospholipid that potently disrupts surfactant function. Intratracheal cardiolipin in mice recapitulates the clinical Users...

OBJECTIVES Familial intrahepatic cholestasis 1 (FIC1) deficiency is caused by a mutation in the ATP8B1 gene. Partial external biliary diversion (PEBD) is pursued to improve pruritus and arrest disease progression. Our aim is to describe clinical variability after PEBD in FIC1 disease. METHODS We performed a single-center, retrospective review of genetically confirmed FIC1 deficient patients w...

Progressive familial intrahepatic cholestasis type 2 (PFIC 2) results from mutations in ABCB11 gene coding bile salt export pump (BSEP). Medical treatment is usually unsuccessful and surgery intervention is necessary. Partial external biliary diversion (PEBD) is regarded as the first choice of surgical treatment. Ileal exclusion (IE) is an alternative operation if external stoma is not tolerate...

Bile secretion is a fundamental function of the liver of all vertebrates and is generated by ATP-dependent transport proteins at the canalicular membrane of hepatocytes, particularly by the bile salt export pump BSEP. To determine the evolutionary origin and structure-function relationship of this transport mechanism, a liver cDNA library from the marine skate Raja erinacea, a 200 million-year-...

Mammalian bile acids (BAs) are oxidized metabolites of cholesterol whose amphiphilic properties serve in lipid and cholesterol uptake. BAs also act as hormone-like substances that regulate metabolism. The Caenorhabditis elegans clk-1 mutants sustain elevated mitochondrial oxidative stress and display a slow defecation phenotype that is sensitive to the level of dietary cholesterol. We found tha...

The rod-shaped fission yeast Schizosaccharomyces pombe, which undergoes cycles of monopolar-to-bipolar tip growth, is an attractive organism for studying cell-cycle regulation of polarity establishment. While previous research has described factors mediating this process from interphase cell tips, we found that division site signaling also impacts the re-establishment of bipolar cell growth in ...

BACKGROUND AND OBJECTIVE Rapidly establishing the cause of neonatal cholestasis is an urgent matter. The aim of this study was to report on the prevalence and mortality of the diverse disorders causing neonatal cholestasis in an academic center in Germany. METHODS Clinical chemistry and cause of disease were retrospectively analyzed in 82 infants (male n = 42, 51%) that had presented with neo...