C A Spek

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..Thirty-three percent of patients with long-term use of antiretroviral treatment had hsCRP levels above 3 mg/L, which is strongly associated with cardiovascular disease in HIV-uninfected individuals...

..It is concluded that HNF-6 is a major determinant of protein C gene activity. Moreover, this is the first report describing the putative involvement of HNF-6 and of an HNF-6 binding site in human pathology...

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..We therefore conclude that the FV Leiden allele has no effect in murine colitis and we thus question the importance of activated blood coagulation in the etiology or pathogenesis of IBD...

..These advances in our knowledge of TF function will improve our understanding of several pathophysiological conditions, and may expand the therapeutic options available for their treatment...

..These data suggest that peripheral blood cells are of negligible importance in LPS-induced production of inflammatory mediators in vivo and that LPS may activate genes via a CD14-independent pathway that is slower and less efficient...

..After 12 h the baseline difference in TF activity was re-established. TF deficiency reduces cytokine production in vitro, but an enhanced induction of TF during murine endotoxemia eliminates this effect in vivo...

..Indeed, both clinical and experimental animal data suggest that a heterozygous FVL genotype might protect against the lethal consequences of sepsis. We sought to confirm the survival advantage of heterozygous FVL mice in septic disease...

..Our previous findings indicated that the TF:FVIIa complex activates signal transducer and activator of transcription (STAT) signaling, leading to cell survival in TF-transfected baby hamster kidney (BHK) cells...

..This may be a critical element in the assessment of ischemia-reperfusion effects of specific anticoagulant therapy...

..Overall, we thus show that endogenous APC is essential for immune-mediated cancer cell elimination...

..The role of the intrinsic pathway of coagulation in the pathogenesis of sepsis has not been explored yet...

..In this study, we therefore assessed the effect of inhaled rhAPC in a murine model of acute lung injury...

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..Fibrin content of the tumors was not affected by LMWH. It is concluded that effects of anticoagulants are dependent on cancer cell type and are correlated with their CD24 and PAR-1 expression...

..06) in this model for DIC. CONCLUSIONS: These results demonstrate the significance of blood coagulation in the progression of DIC and hint at a beneficial role for LMWH anticoagulation in the management of DIC...

..How this progress in the understanding of TF associated signal transduction may generate answers as to the mechanism through which TF exerts it pleiotropic effects will be focus of this review...

..CONCLUSIONS: These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does not play an important role in the antibacterial host defense in this murine model...

..This reduced rate of thrombus formation was attenuated by hyperglycemia. Together, these data establish a discrete but clear contribution of hyperglycemia in experimental arterial thrombosis...

..Fibrin deposition and thus inhibition of fibrin formation by anticoagulants do not seem to affect tumour development in this model...

..In conclusion, we have established that hypoxia is translated into a hedgehog response through HIF-1alpha and this mechanism is likely to be responsible for the hedgehog response observed in various ischaemia models...

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..These data establish a function for the previously described arachidonic acid-dependent Hh pathway in a developmentally relevant model system...

..Taken together, these results support the notion that, beyond its role in coagulation, FXa-dependent PAR-2 cleavage might play a role in the progression of tissue fibrosis and remodeling...

..Thus, Hh seems to exert a dualistic action in cardiac ischemia in which high exogenous levels are able to foster tissue repair and endogenous Hh seems to be deleterious...

..This study aimed to define differential immune responses in association with clinical outcomes by gene expression profiling of a selected panel of inflammatory genes in whole blood samples from children with severe dengue infections...

..Here, we propose that FXa-induced PAR(2) activation has an important role in orchestrating intestinal inflammatory and fibroproliferative responses, and that PAR(2) might provide a novel therapeutic target for the management of IBD...

..The current review focuses on blood coagulation factor Xa and summarizes the variety of cellular functions induced by factor Xa-driven PAR-2 activation and the subsequent consequences for tissue repair and hepatic fibrosis...

..Targeting FXa may be an exciting new therapeutic strategy in the treatment of (fibro)proliferative diseases for which current treatment options are limited...

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..Taken together, these results suggest an important role for PAR-2 in the development of pulmonary fibrosis, and the inhibition of the PAR-2-coagulation axis may provide a novel therapeutic approach to treat this devastating disease...

..It discusses the APC pathway as a potential novel target to influence cancer progression, but it also points to several limitations of APC administration in the setting of cancer cell metastasis...

..Many in vitro studies have focused on gene expression in influenza-infected leukocytes, lung tissue or cell lines. However, knowledge of in vivo gene expression in these compartments is limited...

..Second, to create a simple scoring rule implementing PCT values. Third, to determine and compare associations of CRP and PCT with clinical outcomes...

..In order to identify patients warranting critical care as quickly as possible, we investigated the value of PTX3 as a biomarker for disease severity in patients presenting with fever at the emergency department...

..In conclusion, endogenous APC limits cancer cell extravasation because of S(1)P(1)-mediated VE-cadherin-dependent vascular barrier enhancement...

..We tested in humans whether activation of peripheral leukocytes in reaction to the administration of recombinant human C-reactive protein (rhCRP) may provide a mechanism for infectious diseases to promote atherosclerotic disease...

..Overall, our results establish a link between the coagulation cascade and angiogenesis during fibrosis...

..These results suggest that, beyond its role in blood coagulation, FXa plays a key role in cancer cell migration. They also shed light on an unexpected role of PAR-1, which appears to be a Janus-like receptor in cancer cell biology...

..In addition, we discuss the relationship between blood coagulation and cancer biology focusing on the potential role of PAR-induced modulation of cell survival, apoptosis and tumor growth...

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..Salmeterol is a beta2-adrenoreceptor agonist used in the treatment of obstructive pulmonary disease. Salmeterol inhibits inflammatory responses by neutrophils and mononuclear cells in vitro and in mouse models of lung inflammation in vivo...

..These data support the hypothesis that an inflammatory response involving leucocytes plays a role in the pathogenesis of myocardial infarction...

..In this review, we will discuss these phenomena in more detail and hypothesize on their role in TF-driven metastasis...

..Inhibition of the tissue factor (TF)/factor (F) VIIa pathway has been shown to attenuate the activation of coagulation and to prevent death in a primate model of sepsis caused by gram-negative bacteria...

..Finally, we demonstrated for the first time that TF/FVIIa-signal transduction is dependent on G12/G13 class G proteins...

..In summary, our data clearly indicate that endotoxin-induced coagulation and inflammation are strongly influenced by blood cell-derived tissue factor...

..Finally, TF:FVIIa-induced FXa generation dramatically increased cell survival. We propose that FVIIa-induced cell survival may explain why overexpression of TF is associated with successful metastasis...

..This can be an advantage compared to hypothesis-free whole genome screens where large numbers of differentially expressed genes can obscure functional interpretation...

..Dissecting the molecular interactions at the onset and progression of DIC might therefore help to elucidate the fundamental consequences of DIC, possibly contributing to better diagnostic tools and more effective therapeutic options...

..These results suggest that different hemostatic responses during endotoxemia may proceed via CD14-dependent and -independent pathways...

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..These results demonstrate for the first time that EP is a compound with combined anti-inflammatory and anticoagulant effects...

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..Overall we confirm that, beyond its role in blood coagulation, FXa plays a key role in cell migration and we unravel a new mechanism of PAR-1-mediated inhibition of migration via Rho and Src dependent pathways...

..We thus provide evidence that beyond its role in blood coagulation, FXa plays a key role in cellular processes in which Bim is the central player in determining cell survival...

..In conclusion, lipopolysaccharide differentially influences the toll-like receptor mRNA expression profile in human alveolar macrophages in vivo...

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..These results uncover an important role for PAR-4 in the Shwartzman reaction and suggest that inhibition of PAR-4 signaling in neutrophils could be protective in systemic inflammation and DIC...

..The underlying mechanisms are still not clear but it has been suggested that LMWHs (at least in part) limit metastasis by preventing cancer cell-induced destruction of the endothelial glycocalyx...

..The recent evidence for this emerging insight will be the subject of this review...

..In this study, we investigated expression and function of the NR4A nuclear receptor family, comprising Nur77 (NR4A1, TR3), Nurr1 (NR4A2), and NOR-1 (NR4A3) in human macrophages...

..These atypical features make Hedgehog physiology unique in biology and may explain why this field has attracted such significant attention...

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..This overview presents current insight in how the main coagulation factors might induce inflammation...

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..These data confirm and extend the finding that a functional deficiency in TM results in enhanced thrombus formation in a murine model of carotid artery thrombosis and support a role for TM defects in arterial thrombotic disease...

..The results could suggest that the BE expression profile is closer related to normal squamous esophagus then to EA. In addition, several uniquely expressed genes are identified...

..Here, we review the role of APC in the body natural defense against sepsis and discuss the mechanism by which APC might act at a cellular level...

..No longer would LDL merely be bad news for the progression of atherosclerotic plaques, as it also conveys a revascularization and tissue salvage signal in the form of hedgehog...