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Search Results: 1 - 10 of 160474 matches for " Andrew F. Ducruet "
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De Novo Glioblastoma in the Territory of a Prior Middle Cerebral Artery Infarct
Teresa J. Wojtasiewicz,Andrew F. Ducruet,Sonal S. Noticewala,Peter Canoll,Guy M. McKhann II
Case Reports in Neurological Medicine , 2013, DOI: 10.1155/2013/356526
Abstract: We report a case of a patient who developed glioblastoma in the territory of a previous infarction. Two years after an ischemic stroke, the patient presented with a cystic, necrotic, and heterogeneously enhancing mass. Open biopsy and debulking of the mass with histological analysis revealed the mass to be glioblastoma. Though several cases of posttraumatic GBM have been reported, this is the first proposed case of GBM after an ischemic stroke. From this case, we suggest that the ischemic stroke, like other forms of cortical injury, may predispose to glioblastoma formation. 1. Introduction Previous reports have suggested that glioblastoma (GBM) may arise from areas of gliosis resulting from traumatic brain injury, chronic abscess, or surgical resection [1–4]. The process of reactive gliosis that follows such injuries may increase the chance of malignant transformation. The mechanisms underlying this process remain unclear. Here, we present a patient who developed GBM two years after an ischemic infarction. We propose that this GBM developed in the region of previous infarction and review the existing evidence of posttraumatic tumorigenesis. 2. Case Report 2.1. Initial Presentation A 73-year-old woman with a history of mechanical aortic valve replacement and atrial fibrillation, maintained on warfarin, initially presented with acute left-sided hemiparesis and a right gaze deviation in the setting of a subtherapeutic prothrombin time/international normalized ratio (PT/INR). Head computed tomography (CT) revealed loss of differentiation of the grey-white junction in the right insula and lateral basal ganglia with densities in the right middle cerebral artery (MCA) and right internal carotid artery (ICA) (Figure 1(a)). Concurrent CT angiography (CTA) revealed an occlusion of the supraclinoid segment of the right ICA extending to the M1 segment of the MCA (Figure 1(b)). Despite intravenous tissue plasminogen activator (tPa), intra-arterial urokinase, and attempted mechanical thrombectomy, her occlusion remained. Figure 1: Imaging of initial ischemic stroke. (a) CT without contrast, showing dense right MCA (white solid arrow) and loss of differentiation of the grey-white junction on the right. (b) CT angiography, revealing occlusion of the right MCA (white solid arrow). (c) CT without contrast, showing subsequent hemorrhagic transformation of the infarct. Serial head CT scans obtained over the next several days revealed an evolving right MCA territory infarction extending to the right temporal pole, frontal operculum, and basal ganglia, as well as a
Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest
Brad E. Zacharia,Zachary L. Hickman,Bartosz T. Grobelny,Peter A. DeRosa,Andrew F. Ducruet,E. Sander Connolly
Mediators of Inflammation , 2009, DOI: 10.1155/2009/124384
Abstract: Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.
Complement Inhibition Promotes Endogenous Neurogenesis and Sustained Anti-Inflammatory Neuroprotection following Reperfused Stroke
Andrew F. Ducruet, Brad E. Zacharia, Sergey A. Sosunov, Paul R. Gigante, Mason L. Yeh, Justin W. Gorski, Marc L. Otten, Richard Y. Hwang, Peter A. DeRosa, Zachary L. Hickman, Paulina Sergot, E. Sander Connolly
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038664
Abstract: Background and Purpose The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points. Methods To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA). Results Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point. Conclusions Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke.
Ports et routes maritimes dans le monde (1890-1925)
César Ducruet
M@ppemonde , 2012,
Incheon, vitrine de la Corée du Sud et masque de Séoul
César Ducruet
M@ppemonde , 2007,
Abstract: Le gouvernement sud-coréen actuel a pour ambition de donner à la ville portuaire d'Incheon un nouveau visage, celui d'une ville globale, grace à une gigantesque zone franche. Les contraintes rencontrées à différentes échelles obligent à poser la question de la possibilité pour Incheon d'arriver à un véritable rayonnement international. Malgré l'ampleur des aménagements entrepris, qui visent aussi à diminuer l'hypertrophie de Séoul, Incheon ne peut prétendre dépasser son r le de porte d'entrée de la capitale, dont les fonctions mondiales déjà profondément ancrées dans le système urbain coréen
Structures et dynamiques spatiales des villes portuaires: du local au mondial
César Ducruet
M@ppemonde , 2005,
Abstract: More than other cities, port cities must constantly adapt to a rapidly changing international trade environment. This adaptation is spurred by their ties to both maritime and land networks and by specific spatio-functional relations between cities and ports, from the local to the global level. For comparative purposes, this paper proposes a new way to interpret the basic structures and trends underlying these complex, and sometimes contradictory, ties.
L’archipel nord-coréen: transition économique et blocages territoriaux
César Ducruet,Stanislas Roussin
M@ppemonde , 2007,
Abstract: L’une des caractéristiques récentes de la Corée du Nord est le manque manifeste d’intégration territoriale, en contradiction croissante avec la volonté d’ouverture économique. Dans un environnement mondialisé, le faible co t et la qualité de sa main-d’ uvre, l’abondance des ressources naturelles, et une situation stratégique entre la Corée du Sud, le Japon et leurs voisins continentaux immédiats comme la Chine et la Russie, sont autant d’atouts qui devraient permettre la mise en uvre des réformes et la relance de l’économie. Tandis que la plupart des travaux précédents se basent sur les facteurs politiques externes pour expliquer les difficultés rencontrées (isolement d à la disparition du bloc de l’Est, embargo imposé par les états-Unis et le Japon), cet article privilégie les facteurs spatiaux internes. L’examen successif de structures spatiales fondamentales montre que la déconnexion croissante entre les différentes provinces, conséquence d’un long déclin économique et de la dégradation des infrastructures, serait une contrainte majeure avec laquelle les projets de développement du pays sont confrontés, au-delà des aspects purement politiques.
地理研究 , 2011, DOI: 10.11821/yj2011030002
Abstract: 集装箱技术的传播深刻影响了港口体系的发展,集装箱港口体系的理论模型重点解析该技术对港口体系空间时序过程的影响机制。基于相关研究进展的回顾与评述,根据港口发展的新现象与新机制,综合Hayuth和Notterboom的理论模型,介绍了集装箱港口体系的最新理论,将其分为前集装箱化、技术试验、巩固集中化、枢纽港中心化、扩散化与离岸枢纽、港口区域化等六个时序阶段,对各阶段的发展特征进行了刻画和解析,并从枢纽港本地约束、集装箱航运模式、物流资源整合、内陆配送网络与干港、政府宏观调控和港口建设市场化等角度揭示了扩散化与离岸枢纽、港口区域化两个最新阶段的发展机制。并以长江三角洲作为案例进行实证,详细解析了长江三角洲集装箱港口体系的演化过程,重点是发展变化与内在机理,验证了本文的集装箱港口体系模型,探讨了该区域可能面临的发展趋势。
Bayesian classification of residues associated with protein functional divergence: Arf and Arf-like GTPases
Andrew F Neuwald
Biology Direct , 2010, DOI: 10.1186/1745-6150-5-66
Abstract: The mcBPPS sampler classified sequences within the entire P-loop GTPase class into multiple categories by identifying those evolutionarily-divergent residues most likely to be responsible for functional specialization. Here I focus on categories of residues that most distinguish various Arf/Arl GTPases from other GTPases. This identified residues whose specific roles have been previously proposed (and in some cases corroborated experimentally and that thus serve as positive controls), as well as several categories of co-conserved residues whose possible roles are first hinted at here. For example, Arf/Arl/Sar GTPases are most distinguished from other GTPases by a conserved aspartate residue within the phosphate binding loop (P-loop) and by co-conserved residues nearby that, together, can form a network of salt-bridge and hydrogen bond interactions centered on the GTPase active site. Residues corresponding to an N-[VI] motif that is conserved within Arf/Arl GTPases may play a role in the interswitch toggle characteristic of the Arf family, whereas other, co-conserved residues may modulate the flexibility of the guanine binding loop. Arl8 GTPases conserve residues that strikingly diverge from those typically found in other Arf/Arl GTPases and that form structural interactions suggestive of a novel interswitch toggle mechanism.This analysis suggests specific mutagenesis experiments to explore mechanisms underlying GTP hydrolysis, nucleotide exchange and interswitch toggling within Arf/Arl GTPases. More generally, it illustrates how the mcBPPS sampler can complement traditional evolutionary analyses by providing an objective, quantitative and statistically rigorous way to explore protein functional-divergence in molecular detail. Because the sampler classifies the input sequences at the same time, it can be used to generate subgroup profiles, in which functionally-divergent categories of residues are annotated automatically.This article was reviewed by Frank Eisenhaber,
The glycine brace: a component of Rab, Rho, and Ran GTPases associated with hinge regions of guanine- and phosphate-binding loops
Andrew F Neuwald
BMC Structural Biology , 2009, DOI: 10.1186/1472-6807-9-11
Abstract: Bayesian analysis of divergent patterns within a multiple alignment of Ras-like GTPase sequences identifies a structural component, termed here the glycine brace, as the feature that most distinguishes Rab, Rho/Rac, Ran and (to some degree) Ras family GTPases from other Ras-like GTPases. The glycine brace consists of four residues: An aromatic residue that forms a stabilizing CH-π interaction with a conserved glycine at the start of the guanine-binding loop; a second aromatic residue, which is nearly always a tryptophan, that likewise forms stabilizing CH-π and NH-π interactions with a glycine at the start of the phosphate-binding P-loop; and two other residues (typically an aspartate and a serine or threonine) that, together with a conserved buried water molecule, form a network of interactions connecting the two aromatic residues.It is proposed that the two glycine residues function as hinges and that the glycine brace influences guanine nucleotide binding and release by interacting with these hinges.Rab [1], Rho/Rac [2] and Ran [3,4] GTPases regulate diverse cellular processes including vesicle trafficking, cytoskeletal dynamics, cell polarity, membrane fusion, chromosome segregation, and nuclear transport. These proteins are a subgroup of the extended Ras-like superfamily of GTPases [5] (termed here the Ras-like GTPases), which function as signaling pathway on-off switches and which also include Arf, Arf-like (Arl), and Sar GTPases and α subunits of heterotrimeric G proteins. Given an appropriate upstream signal, Ras-like GTPases are turned 'on' by binding to GTP, resulting in their association with various 'effectors' that propagate the incoming signal to downstream components. Guanine nucleotide exchange factors (GEFs) facilitate this process by mediating the exchange of GTP for GDP. Ras-like GTPases are turned off upon hydrolysis of GTP to GDP, which results in termination of the signal and a shutting off of the pathway. GTPase activating proteins (GAPs) faci
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