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C Vannier

Publications and source records attributed to C Vannier.

40 records · Page 3Linked to original sources
PubMed1976

Structural and topological homology between porcine intestinal and renal brush border aminopeptidase.

A method for the preparation of closed, right-side-out vesicles from the brush border membrane of the kidney proximal tubules is described. The aminopeptidase known to be bound to this membrane was investigated in order to compare its properties with those already reported for the intestinal enzyme. Both are composed of a hydrophilic, catalytically active part lying on the external side of the membrane and a short hydrophobic domain probably located in the N-terminal region of one of the subunits ensuring fixation to the lipid matrix. The enzyme were also found to be clinically similar. Moreover, a quantitative immunological technique showed that they contained 6 cross-reacting determinants, consistent with a very high degree of homology. Four of these determinants were accessible in the bound form of the enzymes in the region of the active site. The other two, probably related to the junction between the hydrophilic moiety and the hydrophobic anchor were completely masked in the bound form. The remainder (6 in the intestinal and 4 in the renal enzyme), were heterologous. The accessibility of two well determinants in this latter group was substantially reduced, perhaps by the proximity of the lipid and/or of other enzyme molecules.

Amino Acids↗
PubMed1975

Topological studies on the hydrolases bound to the intestinal brush border membrane. I. Solubilization by papain and Triton X-100.

Papain digestion of closed, right side out vesicles from pig, rat and rabbit jejunum brush border induces the release of the hydrolases bound to the membrane without grossly affecting the lipid bilayer limiting the vesicles. This observation definitely proves that intestinal hydrolases are surface components attached to the external side of the membrane. All proteins released by papain could be identified by electrophoresis and immunoelectrophoresis to already known intestinal hydrolases, with the exception of an unidentified substance strongly stained by the Schiff's reagent. The early observation that the aminopeptidase form released from pig bursh border by Triton X-100 is different from that released by papain was extended to other hydrolases from pig, rat and rabbit. In some cases, the Triton-released form could be converted by further proteolytic digestion into a new form similar to that liberated by papin. These facts may be related to the existence of hydrophobic anchors retaining the intestinal hydrolases to the membrane surface.

Animals↗
PubMedDate not supplied

The preclinical assessment of the risk for QT interval prolongation.

Some drugs have been reported to induce severe ventricular arrhythmias, including torsades de pointes, and have been responsible in some cases for sudden death of patients. Although the mechanisms of these arrhythmias are not well understood, they are often, but not always, associated with QT interval prolongation. Regulatory authorities (CPMP in Europe) have recently pointed out the necessity to assess most carefully the potential, especially of non-cardiovascular drugs, for QT interval prolongation. Different methodological approaches are presented in this paper and experimental protocols are suggested; limitations and advantages of the presently available in vitro and in vivo models are discussed. It appears that both in vitro and in vivo approaches are complementary. In particular it is pointed out that only the in vitro models using isolated cardiac tissues (Purkinje fibres or papillary muscles) enable assessment of the drug properties under low cardiac rhythm conditions. This model allows us to mimic pathological situations of long QT interval (such as acquired or congenital long QT syndrome) in which most of the major clinical problems are encountered. Finally, a strategy for the preclinical assessment of the potential of a molecule for QT interval prolongation is presented.

Animals↗