460 resultados para CT complex


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Using the yeast two-hybrid system, we identified the mu 2 subunit of the clathrin adaptor complex 2 as a protein interacting with the C-tail of the alpha 1b-adrenergic receptor (AR). Direct association between the alpha 1b-AR and mu 2 was demonstrated using a solid phase overlay assay. The alpha 1b-AR/mu 2 interaction occurred inside the cells, as shown by the finding that the transfected alpha 1b-AR and the endogenous mu 2 could be coimmunoprecipitated from HEK-293 cell extracts. Mutational analysis of the alpha 1b-AR revealed that the binding site for mu 2 does not involve canonical YXX Phi or dileucine motifs but a stretch of eight arginines on the receptor C-tail. The binding domain of mu 2 for the receptor C-tail involves both its N terminus and the subdomain B of its C-terminal portion. The alpha 1b-AR specifically interacted with mu 2, but not with the mu 1, mu 3, or mu 4 subunits belonging to other AP complexes. The deletion of the mu 2 binding site in the C-tail markedly decreased agonist-induced receptor internalization as demonstrated by confocal microscopy as well as by the results of a surface receptor biotinylation assay. The direct association of the adaptor complex 2 with a G protein-coupled receptor has not been reported so far and might represent a common mechanism underlying clathrin-mediated receptor endocytosis.

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Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21-specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05). These signals were confirmed in a replication cohort of 92 DS-CHD cases and 80 DS-without CHD (nominal P-value 0.0022). Furthermore, CNV analyses using a customized chromosome 21 aCGH of 135K probes in 55 DS-AVSD and 53 DS-without CHD revealed three CNV regions associated with AVSD risk (FDR ≤ 0.05). Two of these regions that are located within the previously identified CHD region on chromosome 21 were further confirmed in a replication study of 49 DS-AVSD and 45 DS- without CHD (FDR ≤ 0.05). One of these CNVs maps near the RIPK4 gene, and the second includes the ZBTB21 (previously ZNF295) gene, highlighting the potential role of these genes in the pathogenesis of CHD in DS. We propose that the genetic architecture of the CHD risk of DS is complex and includes trisomy 21, and SNP and CNV variations in chromosome 21. In addition, a yet-unidentified genetic variation in the rest of the genome may contribute to this complex genetic architecture.

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In this study we investigated the variations of the maximal activities of the rate-controlling glycolytic enzymes (i.e., hexokinase, HK; phosphofructokinase, PFK; pyruvate kinase, PK) and of the pyruvate-dehydrogenase complex (PDHc) during the early embryogenesis of Xenopus laevis (from cleavage through hatching). All the enzymatic assays, using different coupled reactions, were performed spectrophotometrically on cytosolic and mitochondrial fractions. The maximal HK activity increases markedly from neurulation onwards, PFK activity presents a peak around gastrulation, PK activity remains relatively constant throughout the period studied and the highest PDHc activity is observed during cleavage. The specific activities display the same temporal pattern. Furthermore, in the sequence of reactions by which glucose is degraded to form acetyl-CoA, the maximal activities of PFK and PK are not limiting while those of HK and PDHc could be rate-limiting at relatively late developmental stages (hatching).

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For the past decade, PET and PET/CT have been widely studied for myocardial perfusion imaging. Several studies demonstrated the incremental value of PET for the diagnostic and prognostic assessment of patients with coronary artery disease. Moreover, PET allows for non-invasively quantifying myocardial blood flow and myocardial flow reserve, that both are recognized as surrogate marker of cardiac event free survival. By enabling the exploration of epicardial disease and the microvasculature, PET constitutes a unique tool to study pathophysiogical mechanisms leading to atherosclerosis genesis. The recent emergence of high-tech hybrid machines may even provide further incremental information about coronary function and morphology. By taking the best of each modality, a better assessment of patients with coronary artery disease is expected. (C) 2011 Elsevier Masson SAS. All rights reserved.

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CD8+ cytotoxic T lymphocyte (CTL) can recognize and kill target cells that express only a few cognate major histocompatibility complex class I-peptide (pMHC) complexes. To better understand the molecular basis of this sensitive recognition process, we studied dimeric pMHC complexes containing linkers of different lengths. Although dimers containing short (10-30-A) linkers efficiently bound to and triggered intracellular calcium mobilization and phosphorylation in cloned CTL, dimers containing long linkers (&gt; or = 80 A) did not. Based on this and on fluorescence resonance energy transfer experiments, we describe a dimeric binding mode in which two T cell receptors engage in an anti-parallel fashion two pMHC complexes facing each other with their constant domains. This binding mode allows integration of diverse low affinity interactions, which increases the overall binding and, hence, the sensitivity of antigen recognition. In proof of this, we demonstrated that pMHC dimers containing one agonist and one null ligand efficiently activate CTL, corroborating the importance of endogenous pMHC complexes in antigen recognition.

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BACKGROUND AND PURPOSE: Knowledge of cerebral blood flow (CBF) alterations in cases of acute stroke could be valuable in the early management of these cases. Among imaging techniques affording evaluation of cerebral perfusion, perfusion CT studies involve sequential acquisition of cerebral CT sections obtained in an axial mode during the IV administration of iodinated contrast material. They are thus very easy to perform in emergency settings. Perfusion CT values of CBF have proved to be accurate in animals, and perfusion CT affords plausible values in humans. The purpose of this study was to validate perfusion CT studies of CBF by comparison with the results provided by stable xenon CT, which have been reported to be accurate, and to evaluate acquisition and processing modalities of CT data, notably the possible deconvolution methods and the selection of the reference artery. METHODS: Twelve stable xenon CT and perfusion CT cerebral examinations were performed within an interval of a few minutes in patients with various cerebrovascular diseases. CBF maps were obtained from perfusion CT data by deconvolution using singular value decomposition and least mean square methods. The CBF were compared with the stable xenon CT results in multiple regions of interest through linear regression analysis and bilateral t tests for matched variables. RESULTS: Linear regression analysis showed good correlation between perfusion CT and stable xenon CT CBF values (singular value decomposition method: R(2) = 0.79, slope = 0.87; least mean square method: R(2) = 0.67, slope = 0.83). Bilateral t tests for matched variables did not identify a significant difference between the two imaging methods (P >.1). Both deconvolution methods were equivalent (P >.1). The choice of the reference artery is a major concern and has a strong influence on the final perfusion CT CBF map. CONCLUSION: Perfusion CT studies of CBF achieved with adequate acquisition parameters and processing lead to accurate and reliable results.

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L'athérosclérose est un processus inflammatoire chronique à l'origine des accidents cardiovasculaires qui constitue l'une des premières causes de mortalité en France. L'inflammation est le facteur essentiel dans l'initiation, la progression et l'instabilité des lésions athéromateuses à l'origine des accidents aigus. Les données récentes suggèrent que l'activation des récepteurs nucléaires PPAR (Peroxysome-Proliferator Activated Receptor) par des ligands pharmacologiques prévient le développement et la progression de l'athérosclérose et diminue de manière importante la mortalité cardiovasculaire. À côté de ces traitements pharmacologiques, l'exercice physique prévient aussi la mortalité cardiovasculaire de manière significative. L'objectif de notre premier travail a été d'explorer les effets de l'exercice physique de natation, sur le déve¬loppement des lésions athéromateuses d'une part et d'autre part, sur l'expression des récepteurs nucléaires PPAR. Nos résultats montrent que l'exercice physique de natation diminue la progression de l'athérosclérose et stimule l'expression des PPAR-γ vasculaires. De manière intéressante, lorsque le PPAR-γ est inhibé avec l'antagoniste BADGE, les effets antiathérogènes de l'exercice physique sont abolis. L'hypertension est à l'origine des complications graves telles que la rupture de plaque d'athérosclérose. L'objectif de notre deuxième travail a été d'explorer l'implication des PPAR dans la progression et la stabilité des lésions athéromateuses chez des souris ApoE-/- hypercholestérolemiques et hypertendues (2K1C), soumises à des exercices physiques (volontaire ou imposé) ou traités avec le telmisartan, un antihypertenseur. Nos résultats montrent que l'exercice physique possède différents mécanismes protecteurs. De manière similaire, l'exercice physique favorise la stabilité de lésions athéromateuses de manière comparable au traitement pharmacologique. De plus, nos résultats montrent que les souris traitées avec l'exercice imposé ou le telmisartan présentent un mécanisme comparable qui permet de réduire significativement l'expression des cytokines pro-inflammatoire et d'activer les PPAR-γ vasculaires. L'exercice volontaire favorise l'expression des marqueurs des macrophages alternatifs M2 et des cytokines anti-inflammatoires (CD 206, IL-1 Ra). L'exercice volontaire diminue significativement l'extension des lésions athéromateuses de manière comparable au telmisartan. Ces résultats montrent que l'exercice physique volontaire et l'exercice physique imposé ont deux mécanismes d'actions distincts. De plus, la surexpression des M2 en réponse à l'exercice volontaire modifie la balance inflammatoire en faveur des M2. Ce renversement de la balance au profit des macrophages alternatifs M2 est significativement corrélé à la diminution de la progression des lésions athéromateuses. Les exercices imposé et volontaire possèdent des mécanismes d'action distincts. L'exercice soumis diminue l'expression des cytokines pro-inflammatoires tandis que l'exercice volontaire augmente l'expression des cytokines anti-inflammatoires et favorise un phénotype anti-inflammatoire des macrophages M2 qui s'accompagne d'une réduction des lésions athéromateuses. - Atherosclerosis is a complex inflammatory process, leading cause of morbidity and mortality in France. Inflammation is essential in initiation, progression and atherosclerosis plaque destabilization leading to acute cardiovascular events. Recent studies suggest that pharmacological PPAR activation prevents ΑΤΗ développement and progression and decreased cardiovascular mortality. Compared to pharmacological treatment, physical exercise also significantly prevents cardiovascular mortality. The aim of the first study was to investigate the influence of physical exercise on ATS development and PPAR expression in arterial wall. Our results had shown that physical exercise decrease ΑΤΗ progression and increase PPAR-γ expression in arterial wall. Interestingly, PPAR-γ inhibition with BADGE, a PPAR-γ antagonist abolishes these antiatherogenic effects. Hypertension increase ΑΤΗ complication such as plaque rupture. The aim of the second study were to inves¬tigate PPAR-γ implication in progression and stabilization of ΑΤΗ lesions in hypercholesterolemic and hypertensive ApoE-/- mice (2K1C) submitted to different exercises (voluntary wheel running and submitted treadmill running) or treated with telmisartan an anti-hypertensive drug. Our results shown that, physical exercise prevents ATS cardiovascular events by several mechanisms. Similarly to telmisartan, physical exercises stabilize ΑΤΗ lesion. Moreover results shown that, submitted exercise and telmisartan have an comparable mechanism. In fact, they significantly decrease pro-inflammatory cytokines expression and in the same time activated PPAR-γ expression in arterial wall. Contrary to submitted exercise, voluntary exercises increases expression of anti-inflammatory cytokines IL-1ra and increase M2 marker CD206. These results suggest that voluntary and submitted exercise have two different mechanism of action. Moreover, M2 surexpression in response to voluntary exercise shift the inflammatory balance in favor to M2. Further, this change of balance in favor to M2, is significantly correlated to decrease of ΑΤΗ progression. Voluntary exercises significantly decreases ΑΤΗ progression in the same levels like telmisartan treatment. Voluntary and submitted exercise has two different mechanisms, submitted exercise decrease proinflammatory cytokines expression whereas voluntary exercise increase anti-inflammatory cytokines expression and promote an anti-inflammatory phenotype of macrophages M2. The shift of M1/M2 balance towards M2 decreases atherosclerosis progression.

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Amphibole fractionation in the deep roots of subduction-related magmatic arcs is a fundamental process for the generation of the continental crust. Field relations and geochemical data of exposed lower crustal igneous rocks can be used to better constrain these processes. The Chelan Complex in the western U. S. forms the lowest level of a 40-km thick exposed crustal section of the North Cascades and is composed of olivine websterite, pyroxenite, hornblendite, and dominantly by hornblende gabbro and tonalite. Magmatic breccias, comb layers and intrusive contacts suggest that the Chelan Complex was build by igneous processes. Phase equilibria, textural observations and mineral chemistry yield emplacement pressures of similar to 1.0 GPa followed by isobaric cooling to 700 degrees C. The widespread occurrence of idiomorphic hornblende and interstitial plagioclase together with the lack of Eu anomalies in bulk rock compositions indicate that the differentiation is largely dominated by amphibole. Major and trace element modeling constrained by field observations and bulk chemistry demonstrate that peraluminous tonalite could be derived by removing successively 3% of olivine websterite, 12% of pyroxene hornblendite, 33% of pyroxene hornblendite, 19% of gabbros, 15% of diorite and 2% tonalite. Peraluminous tonalite with high Sr/Y that are worldwide associated with active margin settings can be derived from a parental basaltic melt by crystal fractionation at high pressure provided that amphibole dominates the fractionation process. Crustal assimilation during fractionation is thus not required to generate peraluminous tonalite.

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Rapid response to : Madan M Rehani and Manorma Berry Radiation doses in computed tomography BMJ 2000; 320: 593-594

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This study demonstrates that the expression of the phenol UDP-glucuronosyltransferase 1 gene (UGT1A1) is regulated at the transcriptional level by thyroid hormone in rat liver. Following 3,5, 3'-triiodo-L-thyronine (T3) stimulation in vivo, there is a gradual increase in the amount of UGT1A1 mRNA with maximum levels reached 24 h after treatment. In comparison, induction with the specific inducer, 3-methylcholanthrene (3-MC), results in maximal levels of UGT1A1 mRNA after 8 h of treatment. In primary hepatocyte cultures, the stimulatory effect of both T3 and 3-MC is also observed. This induction is suppressed by the RNA synthesis inhibitor actinomycin D, indicating that neither inducer acts at the level of mRNA stabilization. Indeed, nuclear run-on assays show a 3-fold increase in UGT1A1 transcription after T3 treatment and a 6-fold increase after 3-MC stimulation. This transcriptional induction by T3 is prevented by cycloheximide in primary hepatocyte cultures, while 3-MC stimulation is only partially affected after prolonged treatment with the protein synthesis inhibitor. Together, these data provide evidence for a transcriptional control of UGT1A1 synthesis and indicate that T3 and 3-MC use different activation mechanisms. Stimulation of the UGT1A1 gene by T3 requires de novo protein synthesis, while 3-MC-dependent activation is the result of a direct action of the compound, most likely via the aromatic hydrocarbon receptor complex.

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The implementation of new techniques of imaging in the daily practice of the radiation oncologist is a major advance in these last 10 years. This allows optimizing the therapeutic intervals and locoregional control of the disease while limiting side effects. Among them, positron emission tomography (PET) offers an opportunity to the clinician to obtain data relative to the tumoral biological mechanisms, while benefiting from the morphological images of the computed tomography (CT) scan. Recently hybrid PET/CT has been developed and numerous studies aimed at optimizing its use in the planning, the evaluation of the treatment response and the prognostic value. The choice of the radiotracer (according to the type of cancer and to the studied biological mechanism) and the various methods of tumoral delineation, require a regular update to optimize the practices. We propose throughout this article, an exhaustive review of the published researches (and in process of publication) until December 2011, as user guide of PET/CT in all the aspects of the modern radiotherapy (from the diagnosis to the follow-up): biopsy guiding, optimization of treatment planning and dosimetry, evaluation of tumor response and prognostic value, follow-up and early detection of recurrence versus tumoral necrosis. In a didactic purpose, each of these aspects is approached by primary tumoral location, and illustrated with representative iconographic examples. The current contribution of PET/CT and its perspectives of development are described to offer to the radiation oncologist a clear and up to date reading in this expanding domain.

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Eight patients with colloid cysts of the third ventricle were examined with CT and MR. In six, surgical resection was performed and the material was subjected to histologic evaluation; the concentrations of trace elements were determined by particle-induced X-ray emission. Stereotaxic aspiration was performed in two. The investigation showed that colloid cysts are often iso- or hypodense relative to brain on CT (5/8), but sometimes have a center of increased density. Increased density did not correlate with increased concentration of calcium or other metals but did not correlate with high cholesterol content. Colloid cysts appear more heterogeneous on MR (6/8) than on CT (3/8), despite a homogeneous appearance at histology. High signal on short TR/TE sequences is correlated with a high cholesterol content. A marked shortening of the T2 relaxation time is often noticed in the central part of the cyst. Analysis of trace elements showed that this phenomenon is not related to the presence of metals with paramagnetic effects. Our analysis of the contents of colloid cysts does not support the theory that differing metallic concentrations are responsible for differences in MR signal intensity or CT density. We did find that increased CT density and high MR signal correlated with high cholesterol content.