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P Pierre

Publications and source records attributed to P Pierre.

31 records · Page 2Linked to original sources

Molecular characterization of two functional domains of CLIP-170 in vivo.

CLIP-170 is a microtubule-binding protein isolated from HeLa cells that is involved in the interaction of endosomes with microtubules. The basic N-terminal domain of CLIP-170 binds to microtubules in vitro. To characterize further the functional domains of this cytoplasmic linker protein, we have transiently expressed intact and mutant forms of CLIP-170 in mammalian cells (HeLa and Vero cells) and show that the tandem repeat present in the N-terminal domain is essential for its binding to microtubules in vivo as previously found in vitro. With increasing levels of expression of CLIP-170, the sites with which the peripheral ends of microtubules interact enlarge, eventually forming large patches, which finally lead to the apparent bundling of microtubules. These patches do not form when the C-terminal domain is absent from the transfected protein. Modification of the microtubule-binding region, particularly of the tandem repeat motif, modulates the binding of CLIP-170 to microtubules. Overexpressed CLIP-170 appears neither to interact with nor to influence the organization of the intermediate filaments, and collapsing the network of intermediate filaments with microinjected antibodies against vimentin has no effect on the distribution of CLIP-170. These data suggest that CLIP-170 has at least two functional domains in vivo, an N-terminal microtubule-binding domain, and a C-terminal domain that is involved in the anchoring of microtubules to peripheral cytoplasmic structures.

Amino Acid Sequence↗

Interest and necessity of combined neuroradiological and neurosurgical treatment in some cases of dural arterio-venous fistulae.

The authors report 3 observations of dural arterio-venous fistula cured by combined neuroradiological and neurosurgical intervention. In the first case, the shunt affected the left lateral sinus. Repeated embolizations failed whilst intracranial hypertension developed, as a consequence of flux in the opposite lateral sinus and in the sagittal sinus. Surgical intervention, consisting in isolation of the transverse sinus, led to complete cure, after a one month delay. In the second case, the shunt was adjacent to the sagittal sinus, right parietal, and had led to an intracerebral haematoma, by rupture of an arterialized cortical vein. Embolizations alone could not cure the fistula which therefore had to be excised. In the third case, the shunt was located in the falx, at the parieto-occipital junction, and was responsible for arterialization of cerebral veins in the right parieto-occipital region. For this reason, after failure of endovascular treatment, the fistula was coagulated, with subsequent complete cure. These three cases illustrate the different types of drainage of such arterio-venous fistula, and their corresponding neurological symptoms and signs, complications and risks, that required a radical-not only clinical, but also anatomical-cure. This aim was achieved when embolizations were accompanied by direct surgical attack.

Adult↗

CLIP-170 links endocytic vesicles to microtubules.

Binding of endocytic carrier vesicles to microtubules depends on the microtubule-binding protein CLIP-170 in vitro. In vivo, CLIP-170 colocalizes with a subset of transferrin receptor-positive endocytic structures and, more extensively, with endosomal tubules induced by brefeldin A. The structure of CLIP-170 has been analyzed by cloning its cDNA. The predicted non-helical C- and N-terminal domains of the homodimeric protein are connected by a long coiled-coil domain. We have identified a novel motif present in a tandem repeat in the N-terminal domain of CLIP-170 that is involved in binding to microtubules. This motif is also found in the Drosophila Glued and yeast BIK1 proteins. These features, together with its very elongated structure, suggest that CLIP-170 belongs to a novel class of proteins, cytoplasmic linker proteins (CLIPs), mediating interactions of organelles with microtubules.

Amino Acid Sequence↗

Modulation of oral tolerance to ovalbumin by cholera toxin and its B subunit.

Oral administration to mice of ovalbumin (OVA), if given together with cholera toxin (CT) or its B subunit (CTB) prevented the hyporesponsiveness to OVA subsequently injected parenterally. Oral immunization with CT plus OVA or OVA plus CTB in fact primed the immune system, inducing a stronger response to a subsequent parenteral injection of OVA with complete Freund's adjuvant than in mice prefed only with OVA or with saline. Oral CT plus OVA also induced good serum IgG1 and IgA anti-OVA responses, with slightly (not significant) decreased IgG2a and IgG2b responses. Our in vivo findings agree well with earlier in vitro data from others, including CT inhibition of the Th1 CD4+ T cell subset and with CT effect on B cells (induction of LPS-stimulated IgM+ B cells to undergo increased switch differentiation to IgG1- and IgA-secreting cells).

Adjuvants, Immunologic↗

[IgA deficiency].

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Autoimmune Diseases↗

Ischemic stroke in patients under age 45.

Contrary to a common view, ischemic stroke under the age of 45 is not rare. In the Lausanne Stroke Registry, more than 10% of the patients were within this age limit. Overall, in Occidental countries the causes of stroke in the young adult do not really differ from those in the older individual; it is only the relative frequency of stroke that is not the same. Cardiac embolism, arterial dissection, and migraine represent the most common etiologic factors, while atherosclerosis is much more unusual. The etiologic aspects and their therapeutic implications justify an active investigative attitude in young adults with recent ischemic stroke. After the acute phase of stroke, prognosis is reasonable.

Adolescent↗

Neutralization of cholera toxin by rat IgA secretory antibodies induced by a free synthetic peptide.

Secretory immunoglobulin A (sIgA) is the major immunoglobulin in the bile of several species. They contribute to local immune defences of the gut. The protection against cholera toxin (CT) is due to the presence of specific sIgA in the bile and in the gut. We have already reported that oral administration of the peptide corresponding to the sequence 50-75 of cholera toxin B subunit elicits serum antibodies neutralizing CT activity, and that IgA and local protection are observed in the intestine of P50-75 orally immunized mice. In this study, we demonstrate the potential of this synthetic peptide as immunogen without carrier or adjuvant, not only in a strain known to be sensitive to CT, but also in an outbred one. Furthermore, this peptide stimulates the mucosal immunity, since we show that P50-75 induced-sIgA purified from rats bile and serum, are capable of neutralizing CT activity in the in vivo intestinal ligated loop test.

Animals↗

Cholera toxin neutralization: a comparison of purified serum IgG and biliary secretory IgA antibodies.

Rats were immunized three times with cholera toxin via the intraintestinal or intravenous route, and their respective biliary secretory IgA (sIgA) or serum IgG antibodies were affinity-purified on a cholera toxin immunoabsorbent. On a molar basis, the sIgA antibodies were roughly seven-fold more efficient than IgG antibodies in neutralizing cholera toxin in the ligated intestinal loop assay. Various explanations for this difference in neutralizing capacity are proposed.

Animals↗