In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to ...screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification-unlike those for population screening programs, which are currently well regulated-are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies.
Abstract The rise in prevalence of obesity, diabetes, metabolic syndrome, and fatty liver disease has been linked to increased consumption of fructose-containing foods or beverages. Our aim was to ...compare the effects of moderate consumption of fructose-containing and non-caloric sweetened beverages on feeding behavior, metabolic and serum lipid profiles, and hepatic histology and serum liver enzymes, in rats. Behavioral tests determined preferred (12.5–15%) concentrations of solutions of agave, fructose, high fructose corn syrup (HFCS), a combination of HFCS and Hoodia (a putative appetite suppressant), or the non-caloric sweetener Stevia ( n = 5/gp). HFCS intake was highest, in preference and self-administration tests. Groups ( n = 10/gp) were then assigned to one of the sweetened beverages or water as the sole source of liquid at night (3 nights/wk, 10 wks). Although within the normal range, serum cholesterol was higher in the fructose and HFCS groups, and serum triglycerides were higher in the Agave, HFCS, and HFCS/Hoodia groups (vs. water-controls, p < 0.05). Liver histology was normal in all groups with no evidence of steatosis, inflammation, or fibrosis; however serum alanine aminotransferase was higher in the fructose and HFCS groups (vs. water-controls, p < 0.05). Serum inflammatory marker levels were comparable among Stevia, agave, fructose, HFCS, and water-consuming groups, however levels of IL-6 were significantly lower in association with the ingestion of Hoodia. There were no differences in terminal body weights, or glucose tolerance assessed by 120-min IVGTTs performed at the end of the 10-week regimen. We conclude that even moderate consumption of fructose-containing liquids may lead to the onset of unfavorable changes in the plasma lipid profile and one marker of liver health, independent of significant effects of sweetener consumption on body weight.
An understanding of fluid flow, mass transport and isotopic exchange in fractured rock is required to understand the origin of several geological processes including hydrothermal mineral deposits. ...The numerical model HydroGeoSphere simulates 3D advection, molecular diffusion, mechanical dispersion and isotopic exchange in a discretely fractured porous media, and can be used to better understand the processes of mass transport and isotopic exchange in fractured rocks. Study of ¹⁸O isopleth patterns for different types of fractures and fracture networks with a range of structural complexity and hydraulic properties shows that fracture properties and geometry control mass transport and isotopic exchange. The hydraulic properties, as well as the density, spacing, and connectivity of fractures determine the isotopic patterns. Asymmetries in the geometry of oxygen isotope patterns could be used to determine the direction of hydrothermal fluid flow.
Background & 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. Mucin secretion was studied by measuring the secretion of
3H
N-acetyl-
d-glucosamine-labeled glycoproteins.
Results:
Model biles with different cholesterol saturation indices increased mucin secretion by the cells to an average 251% after 5 hours of incubation (
P < 0.01). Mucin secretion remained elevated during a 24-hour period, suggesting a sustained effect on mucin secretion. There was no relation between the cholesterol or phospholipid concentration and the extent of stimulation of mucin secretion. Taurocholate caused a dose-dependent increase in mucin secretion, suggesting that bile salt was the bile component responsible for the stimulatory effect. At a concentration of 0.5 mmol/L, only the more hydrophobic bile salts taurochenodeoxycholate and taurodeoxycholate, but not the hydrophylic bile salts taurocholate and tauroursodeoxycholate, stimulated mucin secretion (
P < 0.01).
Conclusions:
Bile salts play an important role in the regulation of mucin secretion. A shift in the bile salt composition of bile towards the more hydrophobic bile salts may cause mucin hypersecretion, thereby initiating cholesterol gallstone formation.
Epithelial cells, isolated from a normal dog pancreatic duct, were grown on collagen-coated culture inserts suspended above a feeder layer of myofibroblasts. The cells were examined by transmission ...electron microscopy, immunohistochemistry, cytogenetics, and flow cytometry. In addition, the constitutive and agonist-stimulated mucin secretion of these cells was studied using a 3HN-acetyl-D-glucosamine labeling assay, and the stimulation of intracellular cAMP was measured. Cells grown on inserts with a feeder layer developed into confluent monolayers consisting of strictly polarized columnar epithelial cells with prominent microvilli, intercellular junctions, and normal chromosomal characteristics. They could be passaged repeatedly without a detectable alteration in their morphology. The cells could also be grown on organotypic cultures, resulting in further differentiated cells simulating in vivo morphology. Immunohistochemistry demonstrated the presence of carbonic anhydrase II in these cells. Cells treated with vasoactive intestinal peptide, epinephrine, and dibutyryl-cAMP demonstrated a marked increase in mucin secretion compared with controls. In parallel experiments, VIP and epinephrine significantly increased intracellular cAMP. In conclusion we have developed a pancreatic epithelial cell preparation with morphology, cytokinetics, chromosomal, and DNA analyses characteristic of normal cells. Similar to normal columnar epithelial cells, these pancreatic duct cells secreted mucin constitutively and responded to agonist by increasing secretion via a cAMP-mediated pathway. They also contained carbonic anhydrase, which indicates that the cells are capable of secreting bicarbonate.
Abstract Plant-virus-based vaccines have emerged as a promising avenue in vaccine development. This report describes the engineering of an innovative vaccine platform using the papaya mosaic virus ...(PapMV) capsid protein (CP) as a carrier protein and a C-terminal fused hepatitis C virus (HCV) E2 epitope as the immunogenic target. Two antigen organizations of the PapMV-based vaccines were tested: a virus-like-particle (VLP; PapMVCP-E2) and a monomeric form (PapMVCP27–215 -E2). While the two forms of the vaccine were both shown to be actively internalized in vitro in bone-marrow-derived antigen presenting cells (APCs), immunogenicity was demonstrated to be strongly dependent on antigen organization. Indeed, C3H/HeJ mice injected twice with the multimeric VLP vaccine showed a long-lasting humoral response (more than 120 days) against both the CP and the fused HCV E2 epitope. The antibody profile (production of IgG1, IgG2a, IgG2b, IgG3) suggests a Th1/Th2 response. Immunogenicity of the PapMV vaccine platform was not observed when the monomer PapMVCP-E2 was injected. These results demonstrate for the first time the potential of the PapMV vaccine platform and the critical function of multimerization in its immunogenicity.
Hepatitis C virus core protein plays an important role in the assembly and packaging of the viral genome. We have studied the structure of the N-terminal half of the core protein (C82) which was ...shown to be sufficient for the formation of nucleocapsid-like particle (NLP)
in vitro and in yeast. Structural bioinformatics analysis of C82 suggests that it is mostly unstructured. Circular dichroism and structural NMR data indicate that C82 lacks secondary structure. Moreover, NMR relaxation data shows that C82 is highly disordered. These results indicate that the N-terminal half of the HCV core protein belongs to the growing family of intrinsically unstructured proteins (IUP). This explains the tendency of the hepatitis C virus core protein to interact with several host proteins, a well-documented characteristic of IUPs.
These studies investigated the growth characteristics and functional properties of isolated canine pancreatic ductal epithelial cells. Cells were isolated from the accessory pancreatic duct and ...cultured by using three conditions: on vitrogen-coated petri dishes with fibroblast conditioned medium (nonpolarized); in vitrogen-coated Transwells above a fibroblast feeder layer (polarized); or as organotypic rafts above a fibroblast-embedded collagen layer (polarized). Growth characteristics, transepithelial resistances, and carbonic anhydrase and cyclic adenosine monophosphate (AMP) responses were evaluated. Under polarized conditions, the cells grew as monolayers with columnar epithelial characteristics. The monolayers developed high transepithelial resistance and became impervious to the passage of horseradish peroxidase. Epithelial growth factor (EGF) (2 ng/ml) stimulated ductal cell growth and accelerated the formation of a high-resistance monolayer. Forskolin (10 microM) rapidly decreased transepithelial resistance. Carbonic anhydrase activity, which was lower in nonpolarized compared with polarized conditions, was stimulated by carbachol (175 microM). Secretin, however, did not stimulate carbonic anhydrase activity in these cells. Although secretin stimulated adenylyl cyclase activity in early-passage cells, this response was lost in later-passage cells. Both vasoactive intestinal polypeptide (VIP; 1 microM) and forskolin (10 microM) consistently increased adenylyl cyclase activity. Isolated canine pancreatic ductal epithelial cells proliferate in vitro, develop high-resistance epithelial monolayers, and respond to stimuli that activate adenylyl cyclase. These cells should provide a useful model for regulatory studies of ductal cell functions.
The enantiomers of the related substances methamphetamine, ephedrine, pseudoephedrine and methcathinone were determined by both gas chromatography after derivatization and by nuclear magnetic ...resonance using a chiral solvating agent. For GC the substances were derivatized with (
R)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA) to give diasteromeric derivatives. Resolution (baseline) of at least 1.6 was obtained between all derivatives. NMR determination of the enantiomers was conducted in a chiral environment by the addition of the chiral solvating agent, (
R)-(+)-1,1′-bi-2-naphthol, to NMR solutions of the substances. Racemization of methcathinone was demonstrated to be facile by exposure to alkaline solutions for varying periods of time. Enantiomeric ratios of some products derived from the oxidation of ephedrine were determined.
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