Monika R. Leonard

Learn More
BACKGROUND & AIMS Helicobacter spp are common inhabitants of the hepatobiliary and gastrointestinal tracts of humans and animals and cause a variety of well-described diseases. Recent epidemiologic results suggest a possible association between enterohepatic Helicobacter spp and cholesterol cholelithiasis, chronic cholecystitis, and gallbladder cancer. To(More)
Cholesterol gallstone formation is a response to interactions between multiple genes and environmental stimuli. To determine the subset of cholesterol gallstone susceptibility (Lith) genes possessed by strains CAST/Ei (susceptible) and 129S1/SvImJ (resistant), we conducted quantitative trait locus (QTL) analyses of an intercross between these strains.(More)
Using model systems, we explored a potential function of hepatic phosphatidylcholine transfer protein to extract biliary-type phosphatidylcholines from intracellular membranes (e.g., smooth endoplasmic reticulum) and deliver them to canalicular plasma membranes where biliary secretion occurs. We measured transfer rates of parinaroyl phosphatidylcholine, a(More)
The molecular pathogenesis of cystic fibrosis (CF) liver disease is unknown. This study investigates its earliest pathophysiological manifestations employing a mouse model carrying DeltaF508, the commonest human CF mutation. We hypothesized that, if increased bile salt spillage into the colon occurs as in the human disease, then this should lead to a(More)
A complex genetic basis determines the individual predisposition to develop cholesterol gallstones in response to environmental factors. We employed quantitative trait locus/loci (QTL) analyses of an intercross between inbred strains CAST/Ei (susceptible) and DBA/2J (resistant) to determine the subset of gallstone susceptibility (Lith) genes these strains(More)
Gallstones are frequent in patients with cystic fibrosis (CF). These stones are generally "black" pigment (i.e., Ca bilirubinate) with an appreciable cholesterol admixture. The pathophysiology and molecular mechanisms for this "mixed" gallstone in CF are unknown. Here we investigate in a CF mouse model with no overt liver or gallbladder disease whether(More)
To predict bile salt-membrane interactions physiologically, we used an immobilized artificial membrane HPLC column that contains dimyristoyl-phosphatidylcholine molecules covalently linked to silica microspheres. Using a 90% aqueous (10% acetonitrile) mobile phase, 22 species of bile salts and 4 species of fusidates were eluted. Glycine conjugates displayed(More)
The molecular pathogenesis of cystic fibrosis (CF) liver disease is unknown. This study investigates its earliest pathophysiologic manifestations employing a mouse model carrying ∆F508, the commonest human CF mutation. We hypothesized that, if increased bile salt spillage into the colon occurs as in the human disease, this should lead to a hydrophobic bile(More)
UNLABELLED BACKGROUND; Decreased gallbladder smooth muscle (GBSM) contractility is a hallmark of cholesterol gallstone disease, but the interrelationship between lithogenicity, biliary stasis, and inflammation are poorly understood. We studied a mouse model of gallstone disease to evaluate the development of GBSM dysfunction relative to changes in bile(More)
Freudenberg F, Leonard MR, Liu SA, Glickman JN, Carey MC. Pathophysiological preconditions promoting mixed “black” pigment plus cholesterol gallstones in a F508 mouse model of cystic fibrosis. Am J Physiol Gastrointest Liver Physiol 299: G205–G214, 2010. First published April 29, 2010; doi:10.1152/ajpgi.00341.2009.—Gallstones are frequent in patients with(More)