Effect of atorvastatin on plasma apoE metabolism in patients with combined hyperlipidemia

Atorvastatin, a synthetic HMG-CoA reductase inhibitor used for the treatment of hyperlipidemia and the prevention of coronary artery disease, significantly lowers plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. It also reduces total plasma triglyceride and apoE concentrations. In view of the direct involvement of apoE in the pathogenesis of atherosclerosis, we have investigated the effect of atorvastatin treatment (40 mg/day) on in vivo rates of plasma apoE production and catabolism in six patients with combined hyperlipidemia using a primed constant infusion of deuterated leucine. Atorvastatin treatment resulted in a significant decrease (i.e., 30-37%) in levels of total triglyceride, cholesterol, LDL-C, and apoB in all six patients. Total plasma apoE concentration was reduced from 7.4 +/- 0.9 to 4.3 +/- 0.2 mg/dl (-38 +/- 8%, P < 0.05), predominantly due to a decrease in VLDL apoE (3.4 +/- 0.8 vs. 1.7 +/- 0.2 mg/dl; -42 +/- 11%) and IDL/LDL apoE (1.9 +/- 0.3 vs. 0.8 +/- 0.1 mg/dl; -57 +/- 6%). Total plasma lipoprotein apoE transport (i.e., production) was significantly reduced from 4.67 +/- 0.39 to 3.04 +/- 0.51 mg/kg/day (-34 +/- 10%, P < 0.05) and VLDL apoE transport was reduced from 3.82 +/- 0.67 to 2.26 +/- 0.42 mg/kg/day (-36 +/- 10%, P = 0.057). Plasma and VLDL apoE residence times and HDL apoE kinetic parameters were not significantly affected by drug treatment. Percentage decreases in VLDL apoE concentration and VLDL apoE production were significantly correlated with drug-induced reductions in VLDL triglyceride concentration (r = 0.99, P < 0.001; r = 0.88, P < 0.05, respectively, n = 6). Our results demonstrate that atorvastatin causes a pronounced decrease in total plasma and VLDL apoE concentrations and a significant decrease in plasma and VLDL apoE rates of production in patients with combined hyperlipidemia.     

Effect of somatocrinin and a somatostatin antiserum on duodenal and gastric growth in the rat

This study examines the effects of somatocrinin (GRF) and somatostatin antiserum (ASS), jointly and separately on gastric and duodenal growth. 24-day-old rats received twice daily SC injections of saline or GRF (4 and 20 micrograms X kg-1) for 14 days. ASS was given IP every 2 days. Alone, GRF increased gastric fundus weight concomitantly with DNA, RNA and protein contents producing hyperplasia and hypertrophy within this gland. Alone, ASS increased RNA and protein cellular concentrations. Joint ASS and GRF treatment stabilized the weight and protein content of the fundus, while reducing RNA contents as well as RNA and protein concentrations. GRF alone caused significant increments in duodenal weight and protein content suggesting cellular hypertrophy. Growth hormone, gastrin, cholecystokinin and secretin may be considered as putative mediators of these trophic effects.     

Two distinct TL-like molecular subsets defined by monoclonal antibodies on the surface of human thymocytes with different expression on leukemia lines

Monoclonal antibodies reacting with TL-like class I antigens expressed on the surface of human thymocytes and some T leukemia lines were found to define three independent epitopic clusters, two of which could be shown to reside on serologically distinct molecular subsets by a solid-phase radioimmunoassay as well as by sequential immunoprecipitation. Both molecular subsets consist of a 49-K heavy chain associated with a beta-2 microglobulin light chain. Thymocytes expressed similar amounts of the two molecular subsets, while on T leukemia lines the amount of these two molecular subsets varied from line to line.     

PICK-1: a scaffold protein that interacts with Nectins and JAMs at cell junctions

Nectin adhesion molecules are involved in the early steps of cell junction formation. Later during the polarisation process, Nectins are components of epithelial adherens junctions where they are indirectly associated with the E-cadherin/Catenins complex via the adaptator AF-6. To have a better understanding of Nectin-based cell junctions, we looked for some new Nectins' partners. We demonstrate that the scaffold molecule PICK-1, involved in the clustering of junctional receptors in synaptic junctions, interacts directly with Nectins in a PSD-95/Dlg/ZO-1 domain-dependent manner and is localised at adherens junctions in epithelial cells. Finally, we observed that protein interacting with C-kinase-1 (PICK-1) also interacts directly with the junctional adhesion molecules, and we suggest that PICK-1 could be involved in the regulation of both adherens and tight junctions in epithelial cells.     

Synthesis of 3'-O2-(azaheterocycle)-thymidines

The synthesis of 3'-O2-(azaheterocycle)-thymidines is presented from 1-thia-3-aza- 1,3-butadiene precursors (N-thioacylamidines). A variety of heterocycles is accessible using the dienic, the electrophilic or the nucleophilic reactivity of these thia-azabutadiene systems. 3'-O2-(azaheterocycle)-thymidine analogues are regarded as potential substrates to interfere with the DNA-polymerization process.     

Oligomerization of Escherichia coli enterotoxin b through its C-terminal hydrophobic alpha-helix

Using a chemical cross-linker and gel electrophoresis or a dot blot overlay assay, we studied protein-protein interaction of STb toxin, a 48-residue amphiphilic polypeptide causing intestinal disorders. For the first time, we report on the oligomerization property of STb. This enterotoxin forms hexamers and heptamers in a temperature-independent fashion in presence or absence of its receptor (sulfatide) anchored in a 50-nm liposome or as a free molecule. Full STb structure integrity is necessary for its oligomerization as this process is not observed under reducing conditions in the presence of beta-mercaptoethanol. STb treatment with tetramethylurea (TMU) and different detergents prevented oligomerization. Site-directed mutagenesis decreasing overall STb hydrophobicity in the hydrophobic alpha-helix resulted in the incapacity to form oligomers. Taken together, these data suggest that the C-terminal hydrophobic alpha-helix corresponds to the domain of STb-STb inter-binding where hydrophobic interaction is involved.     

The effect of jugular or abomasal infusion of amino acids on milk yield in lactating cows fed a protein deficient diet

The influence of first-pass splanchnic metabolism was investigated by comparing the response of 5 lactating cows to an infusion of an amino acid mixture into the abomasum or a jugular vein over 5 d according to a complete block design. The basal diet and the amino acid infusion provided 71% and 14% of crude protein requirements, respectively. The jugular infusion increased (P = 0.01) milk yield by 0.80 kg in comparison to the abomasal infusion, but milk protein yield was not altered. The jugular infusion tended to increase (P = 0.06) the arterial concentration of total essential amino acids by 11% relatively to the abomasal infusion. Mammary plasma flow and net fluxes of amino acids and glucose were not affected by the infusion sites. Variations in essential amino acid concentrations suggest that splanchnic metabolism alters peripheral delivery of amino acids but the recirculation of amino acids within the animal decreased the impact of the first-pass splanchnic metabolism on lactational performances.     

Recovering Power in Association Mapping Panels with Variable Levels of Linkage Disequilibrium

Association mapping has permitted the discovery of major QTL in many species. It can be applied to existing populations and, as a consequence, it is generally necessary to take into account structure and relatedness among individuals in the statistical model to control false positives. We analytically studied power in association studies by computing noncentrality parameter of the tests and its relationship with parameters characterizing diversity (genetic differentiation between groups and allele frequencies) and kinship between individuals. Investigation of three different maize diversity panels genotyped with the 50k SNPs array highlighted contrasted average power among panels and revealed gaps of power of classical mixed models in regions with high linkage disequilibrium (LD). These gaps could be related to the fact that markers are used for both testing association and estimating relatedness. We thus considered two alternative approaches to estimating the kinship matrix to recover power in regions of high LD. In the first one, we estimated the kinship with all the markers that are not located on the same chromosome than the tested SNP. In the second one, correlation between markers was taken into account to weight the contribution of each marker to the kinship. Simulations revealed that these two approaches were efficient to control false positives and were more powerful than classical models.