UCL University College London Eprints
UCL Eprints collects the work of UCL researchers and makes it freely available over the web, helping the worldwide scholarly community to discover UCL research. Institutional repositories like UCL Eprints complement the traditional academic publishing and scholarly communications processes. They raise the visibility of research and help to maximise its impact. UCL researchers are encouraged to deposit a copy of each journal article, conference paper, working paper, and any other research output, in the UCL Eprints at the earliest opportunity, ensuring that their research reaches as wide an audience as possible.
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Shaping of adaptive immune responses to soluble protein antigens by pathogen-associated molecular patterns. - Durand, V.M.M.
Invading organisms are detected by the innate immune system, through the recognition of conserved microbial structures. Innate responses are known to influence the development of adaptive immune responses, which are crucial for preventing infection and eliminating pathogens. Characterising the signals that initiate the induction of efficient cellular and humoral adaptive immune responses is particularly relevant for the rational design of new vaccines. The aims of this study were first to assess the ability of a broad range of conserved microbial stimuli to induce CD8+ T cells responses by cross-priming and enhance antibody responses against exogenous soluble protein antigens, and secondly...
Protein Kinase C - Binding partners and phosphorylation. - Durgan, J.
Protein Kinase C (PKC) comprises a family of phospholipid-dependent Ser/Thr kinases, implicated in a broad array of cellular processes. PKC activity is subject to a complex network of regulatory inputs, including co-factor binding, phosphorylation and protein-protein interaction. In addition, the chronic activation of PKC frequently leads to its down-regulation this process may be intrinsic to the tumour promoting activity of the phorbol esters. The aim of this work was to investigate the regulation of the novel PKC-e isoform by binding partners and phosphorylation, with a particular focus on the process of agonist-induced degradation. A yeast 2-hybrid screen was performed using...
Role of the fibrinolytic system in experimental allergic encephalomyelitis. - East, E.
The immunopathology of multiple sclerosis (MS), a disease of the central nervous system (CNS), is characterised by widespread inflammation, focal demyelination and axonal degeneration. As a result of early disturbances in the blood brain barrier (BBB), serum proteins, including fibrin(ogen) enter into the CNS. Up-regulation of components of the plasminogen activator (fibrinolytic) system correlates with onset of inflammation and migration of leucocytes into the brain parenchyma. Significant upregulation of plasminogen and plasminogen activator inhibitor-1 (PAI-1), and an accumulation of fibrin D-dimer was found during neuroinflammation, in the established mouse model of MS, chronic relapsing experimental allergic encephalomyelitis (CREAE) induced with...
From global corruption paradigm to the study of informal practices: outsiders vs. insiders/ От глобальной коррупционной парадигмы к изучению неформальных практик: различие в подходах аутсайдеров и инсайдеров - Ledeneva, AV; Barsukova, S
В статье представлен сравнительный анализ двух подходов: коррупционной парадигмы как взгляда аутсайдеров, применяющих универсальные суждения к разным обществам, и анализа неформальных практик, реконструирующего взгляд инсайдеров, их понимание мотивов и смыслов коррупционных практик. Коррупционная парадигма, получившая широкое распространение в 1990-е годы, базируется на трех предположениях: коррупцию можно четко определить, измерить и преодолеть. Такой подход лежит в основе международных мониторингов и стимулирует активную антикоррупционную политику. В статье систематизирована критика коррупционной парадигмы. Сделан вывод о том, что провалы антикоррупционных кампаний связаны не столько с дефицитом политической воли, сколько с недостаточностью знаний о социокультурной укорененности коррупции, предложены пути интеграции коррупционной парадигмы с традицией изучения...
Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. - Jalan, R; Saliba, F; Pavesi, M; Amoros, A; Moreau, R; Ginès, P; Levesque, E; Durand, F; Angeli, P; Caraceni, P; Hopf, C; Alessandria, C; Rodriguez, E; Solis-Muñoz, P; Laleman, W; Trebicka, J; Zeuzem, S; Gustot, T; Mookerjee, R; Elkrief, L; Soriano, G; Cordoba, J; Morando, F; Gerbes, A; Agarwal, B; Samuel, D; Bernardi, M; Arroyo, V; CANONIC study investigators of the EASL-CLIF Consortium,
Acute-on-chronic liver failure (ACLF) is a frequent syndrome (30% prevalence), characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. This study develops and validates a specific prognostic score for ACLF patients.
The brain in acute on chronic liver failure. - Wright, G; Sharifi, Y; Jover-Cobos, M; Jalan, R
Acute-on-chronic liver failure (ACLF) is a newly defined clinical entity with significant morbidity and mortality (~40-90% at 1 year dependent on need for organ support at presentation). It defines a presentation with acute severe liver injury, often with multiorgan dysfunction, on a background of previously known or unknown cirrhosis. In its severest form, it is almost indistinguishable from acute liver failure, as similarly in around 5% may rapidly progress to intracranial hypertension and cerebral oedema culminating in coma and/or death. Our understanding of such cerebral sequelae is currently limited to clinical observation, though our knowledge base is rapidly expanding since...
Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury. - Garcia-Martinez, R; Noiret, L; Sen, S; Mookerjee, R; Jalan, R
In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury.
Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. - Jalan, R; Fernandez, J; Wiest, R; Schnabl, B; Moreau, R; Angeli, P; Stadlbauer, V; Gustot, T; Bernardi, M; Canton, R; Albillos, A; Lammert, F; Wilmer, A; Mookerjee, R; Vila, J; Garcia-Martinez, R; Wendon, J; Such, J; Cordoba, J; Sanyal, A; Garcia-Tsao, G; Arroyo, V; Burroughs, A; Ginès, P
Bacterial infections are very common and represent one of the most important reasons of progression of liver failure, development of liver-related complications, and mortality in patients with cirrhosis. In fact, bacterial infections may be a triggering factor for the occurrence of gastrointestinal bleeding, hypervolemic hyponatremia, hepatic encephalopathy, kidney failure, and development of acute-on-chronic liver failure. Moreover, infections are a very common cause of repeated hospitalizations, impaired health-related quality of life, and increased healthcare costs in cirrhosis. Bacterial infections develop as a consequence of immune dysfunction that occurs progressively during the course of cirrhosis. In a significant proportion of patients, infections...
Plasma cytokine concentrations in dogs with a congenital portosystemic shunt. - Kilpatrick, S; Gow, AG; Foale, RD; Tappin, SW; Carruthers, H; Reed, N; Yool, DA; Woods, S; Marques, AI; Jalan, R; Mellanby, RJ
Congenital portosystemic shunts (cPSS) are a well-recognised vascular anomaly in dogs. Recent studies have shown an association between inflammation and hepatic encephalopathy (HE), which is a common clinical syndrome in dogs with a cPSS. Pro-inflammatory cytokines such as interleukin (IL)-6 and tumour necrosis factor (TNF)-α are frequently increased in the plasma of human patients with liver disease and have been implicated in the development of HE. In the current study, plasma concentrations of IL-2, IL-6, IL-8 and TNF-α were measured using a multiplex electrochemiluminescence immunoassay in 36 dogs with a cPSS and compared to 25 healthy dogs. There were no...
Hyperammonemia and systemic inflammatory response syndrome predicts presence of hepatic encephalopathy in dogs with congenital portosystemic shunts. - Tivers, MS; Handel, I; Gow, AG; Lipscomb, VJ; Jalan, R; Mellanby, RJ
Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS...
Treatment of hyperammonemia in liver failure. - Jover-Cobos, M; Khetan, V; Jalan, R
Hyperammonemia is thought to be central in the pathophysiology of hepatic encephalopathy in patients suffering from liver failure. The purpose of this article is to explore existing treatment options that help lower ammonia levels in patients and alleviate symptoms of hepatic encephalopathy.
Two-photon targeted patching and electroporation in vivo. - Häusser, M; Margrie, TW
By combining patch-clamp methods with two-photon microscopy, it is possible to target recordings to specific classes of neurons in vivo. Here we describe methods for imaging and recording from the soma and dendrites of neurons identified using genetically encoded probes such as green fluorescent protein (GFP) or functional indicators such as Oregon Green BAPTA-1. Two-photon targeted patching can also be adapted for use with wild-type brains by perfusing the extracellular space with a membrane-impermeable dye to visualize the cells by their negative image and target them for electrical recordings, a technique termed "shadowpatching." We discuss how these approaches can be...
Target-specific effects of somatostatin-expressing interneurons on neocortical visual processing. - Cottam, JC; Smith, SL; Häusser, M
A diverse array of interneuron types regulates activity in the mammalian neocortex. Two of the most abundant are the fast-spiking, parvalbumin-positive (PV(+)) interneurons, which target the axosomatic region of pyramidal cells, and the somatostatin-positive (SOM(+)) interneurons, which target the dendrites. Recent work has focused on the influence of PV(+) and SOM(+) interneurons on pyramidal cells. However, the connections among PV(+) and SOM(+) interneurons are poorly understood and could play an important role in cortical circuitry, since their interactions may alter the net influence on pyramidal cell output. We used an optogenetic approach to investigate the effect of SOM(+) interneurons on...
Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies. - Lynfield, R; Davey, R; Dwyer, DE; Losso, MH; Wentworth, D; Cozzi-Lepri, A; Herman-Lamin, K; Cholewinska, G; David, D; Kuetter, S; Ternesgen, Z; Uyeki, TM; Lane, HC; Lundgren, J; Neaton, JD; INSIGHT Influenza Study Group,
Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients.