Background & Aims: Protein is secreted into bile via several independent pathways. The aim of this study was to investigate whether these pathways are influenced by secretion of biliary lipid.
Methods: Protein secretion and biliary lipid output were studied in wild-type mice (+/+), heterozygotes (+/-), and homozygotes (-/-) for mdr2 gene disruption.
QTL mapping experiments involve many animals to be genotyped and performance tested. Consequently, experimental designs need to be optimized to minimize the costs of data collection and genotyping. The present study has analyzed the power and efficiency of experiments with two or three-generation family structures containing full-sib families, half-sib families, or both.
View Article and Find Full Text PDFIt is generally accepted that gallbladder mucin (GBM) plays an important role in the pathogenesis of cholesterol gallstone (ChG) disease. However, it remains unclear whether ChG patients have higher GBM concentrations than controls. Discrepant findings regarding biliary mucin concentrations may be due to methodological problems with the assays commonly used.
View Article and Find Full Text PDFBackground & Aims: Gallstones consist of calcium salts and cholesterol crystals, arrayed on a matrix of gallbladder mucin (GBM), and regulatory proteins like calcium-binding protein (CBP). To determine if interactions between CBP and GBM follow a biomineralization scheme, their mutual binding and effects on CaHPO4 precipitation were studied.
Methods: Binding of CBP to GBM was assessed by inhibition of the fluorescence of the complex of GBM with bis-1,8-anilinonaphthalene sulfonic acid (bis-ANS).
A potential bias in estimation of inbreeding depression when using pedigree relationships to assess the degree of homozygosity for loci under selection is indicated. A comparison of inbreeding coefficients based on either pedigree or genotypic frequencies indicated that, as a result of selection, the inbreeding coefficient based on pedigree might not correspond with the random drift of allelic frequencies. Apparent differences in average levels of both inbreeding coefficients were obtained depending on the genetic model (additive versus dominance, initial allelic frequencies, heritability) and the selection system assumed (no versus mass selection).
View Article and Find Full Text PDFThe association of unconjugated bilirubin (UCB) with amorphous calcium phosphate was studied in vitro. To this end UCB, solubilized in different micellar bile salt solutions, was incubated with freshly prepared calcium phosphate precipitate. It was demonstrated that amorphous calcium phosphate (ACP) rapidly binds and precipitates UCB in a dose-dependent way.
View Article and Find Full Text PDFBackground & Aims: Hypersecretion of gallbladder mucin has been proposed as a pathogenic factor in gallstone formation. We investigated whether mucin secretion is modulated by biliary constituents using normal, well-differentiated dog gallbladder epithelial cells.
Methods: Model biles or bile salts were applied to monolayers of epithelial cells.
The distribution of phospholipid and cholesterol between the vesicular and micellar phases in bile plays an important role in the formation of cholesterol gallstones. Conventional analytical procedures to determine the distribution are potentially unreliable because they disturb the distribution of these compounds between the two phases. In this work, we circumvent this problem by using NMR.
View Article and Find Full Text PDFIn this study, the interaction of mucin and concanavalin A-binding proteins isolated from human bile with cholesterol/phospholipid vesicles was investigated. Using resonance energy transfer assays originally developed by Struck, Hoekstra and Pagano [(1981) Biochemistry 20, 4093-4099], no significant protein-induced fusion or aggregation of vesicles was demonstrated. Instead of fusion, these proteins induced destabilization of cholesterol/phospholipid vesicles, as monitored by release of entrapped carboxyfluorescein.
View Article and Find Full Text PDFDisruption of the mdr2 gene in mice leads to a complete absence of phospholipid from bile (Smit, J. J. M.
View Article and Find Full Text PDFThe mouse mdr2 gene (and its human homologue MDR3, also called MDR2) encodes a P-glycoprotein that is present in high concentration in the bile canalicular membrane of hepatocytes. The 129/OlaHsd mice with a homozygous disruption of the mdr2 gene (-/- mice) lack this P-glycoprotein in the canalicular membrane. These mice are unable to secrete phospholipids into bile, showing an essential role for the mdr2 P-glycoprotein in the transport of phosphatidylcholine across the canalicular membrane.
View Article and Find Full Text PDFThere is a discrepancy between in vitro cholesterol dissolving efficacy of methyl-tert-butyl ether (MTBE) and ethyl propionate and cholesterol gall stone dissolution in vivo. This study investigated whether the presence of bile changes the cholesterol dissolving capacity of MTBE and ethyl propionate. The addition of dimethylsulphoxide to MTBE or ethyl propionate was also studied to discover if it improves the dissolving capacity for cholesterol gall stones.
View Article and Find Full Text PDFHuman bile contains cholesterol crystallization-stimulating proteins that can be isolated by concanavalin A-Sepharose chromatography. In the past few years an increasing number of different pronucleating proteins have been identified in the concanavalin A-binding fraction. In this study we attempted to estimate the relative contribution of a number of these proteins to total concanavalin A-binding pronucleating activity.
View Article and Find Full Text PDFBackground: The main disadvantage of endoscopic insertion of an endoprosthesis is the tendency of the stent to clog after a few months. In this study we determined the role of bile viscosity in stent clogging.
Methods: Sixty patients were stented with 10 Fr 11-cm stents.
Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid exchange between vesicles and micelles were monitored in a model bile system.
View Article and Find Full Text PDFThe objective of this study was to estimate trends in inbreeding in Dutch Black and White dairy cattle. A pedigree file for 4 280 588 cattle born after 1965 was used. In the early 1970s, Holstein-Friesian was introduced, gradually replacing Dutch Friesian.
View Article and Find Full Text PDF1. Human gallbladder mucin has been implicated as playing a role in the pathogenesis of gallstones. In previous studies no differences have been found in the content or composition of mucins derived from control bile or cholesterol gallstone bile.
View Article and Find Full Text PDF1. Human gallbladder mucin has been implicated to play a role in gallstone disease. In spite of this fact relatively little is known about the structure of human gallbladder mucin.
View Article and Find Full Text PDFTwo types of P-glycoprotein have been found in mammals: the drug-transporting P-glycoproteins and a second type, unable to transport hydrophobic anticancer drugs. The latter is encoded by the human MDR3 (also called MDR2) and the mouse mdr2 genes, and its tissue distribution (bile canalicular membrane of hepatocytes, B cells, heart, and muscle) suggests a specialized metabolic function. We have generated mice homozygous for a disruption of the mdr2 gene.
View Article and Find Full Text PDFJ Anim Breed Genet
January 1993
The relationship between the inbreeding coefficient and characteristics of DNA fingerprints is described to show opportunities of using DNA fingerprinting in assessing the inbreeding coefficient in populations with unknown pedigree. Characteristics studied include the number of bands per individual and the average level of bandsharing among individuals in a population. Conceptually simple functions relating allelic frequencies, inbreeding coefficient, and DNA fingerprint characteristics are derived.
View Article and Find Full Text PDFSelf-expanding metal stents are claimed to prolong biliary-stent patency, although no formal comparative trial between plastic and expandable stents has been done. In a prospective randomised trial, we assigned 105 patients with irresectable distal bile-duct malignancy to receive either a metal stent (49) or a straight polyethylene stent (56). Median patency of the first stent was significantly prolonged in patients with a metal stent compared with those with a polyethylene stent (273 vs 126 days; p = 0.
View Article and Find Full Text PDFIt has been hypothesized that bile acids and fatty acids promote colon cancer. A proposed mechanism is a lytic effect of these surfactants on colonic epithelium, resulting in a compensatory proliferation of colonic cells. To investigate the first step of this hypothesis, we studied the lytic activity of fatty acids and physiological mixtures of fatty acids and bile acids.
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