The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
Daniel T Eitzman - One of the best experts on this subject based on the ideXlab platform.
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α galactosidase a deficiency leads to increased tissue Fibrin Deposition and thrombosis in mice homozygous for the factor v leiden mutation
Stroke, 2006Co-Authors: Yuechun Shen, Peter F Bodary, Fernando B Vargas, Jonathon W Homeister, David Gordon, Kristen A Ostenso, James A Shayman, Daniel T EitzmanAbstract:Background— Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to α-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature. Methods and Results— To examine a potential interaction between FvL and Gla deficiency in vivo, we analyzed tissue Fibrin Deposition in mice carrying combined mutations in FvL and Gla. Gla deficiency markedly increased tissue Fibrin Deposition in mice carrying the FvL mutation (0.33±0.03%; n=7) compared with FvL mutation (0.14±0.02%; n=10; P<0.0005). Conclusions— These observations demonstrate a synergistic interaction between Gla deficiency and FvL toward tissue Fibrin Deposition in mice. Concomitant mutations in these genes may increase the penetrance of vascular thrombotic events in humans.
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α-Galactosidase A Deficiency Leads to Increased Tissue Fibrin Deposition and Thrombosis in Mice Homozygous for the Factor V Leiden Mutation
Stroke, 2006Co-Authors: Yuechun Shen, Peter F Bodary, Fernando B Vargas, Jonathon W Homeister, David Gordon, Kristen A Ostenso, James A Shayman, Daniel T EitzmanAbstract:Background— Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to α-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature. Methods and Results— To examine a potential interaction between FvL and Gla deficiency in vivo, we analyzed tissue Fibrin Deposition in mice carrying combined mutations in FvL and Gla. Gla deficiency markedly increased tissue Fibrin Deposition in mice carrying the FvL mutation (0.33±0.03%; n=7) compared with FvL mutation (0.14±0.02%; n=10; P
Stephen T Smiley - One of the best experts on this subject based on the ideXlab platform.
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In situ assays demonstrate that interferon-gamma suppresses infection-stimulated hepatic Fibrin Deposition by promoting Fibrinolysis.
Journal of Thrombosis and Haemostasis, 2006Co-Authors: Isis K. Mullarky, Frank M. Szaba, Caylin G. Winchel, Michelle A. Parent, Lawrence W. Kummer, Lawrence L. Johnson, Nigel Mackman, Stephen T SmileyAbstract:Summary. Background: Inflammatory cytokines potently impact hemostatic pathways during infection, but the tissue-specific regulation of coagulation and Fibrinolysis complicates studies of the underlying mechanisms. Methods and Results: Here, we describe assays that quantitatively measuring prothrombinase (PTase), protein C-ase (PCase) and plasminogen activator (PA) activities in situ, thereby facilitating studies of tissue-specific hemostasis. Using these assays, we investigate the mechanisms regulating hepatic Fibrin Deposition during murine toxoplasmosis and the means by which interferon-gamma (IFN-γ) suppresses infection-stimulated Fibrin Deposition. We demonstrate that Toxoplasma infection upregulates hepatic PTase, PCase, and PA activity. Wild type and gene-targeted IFN-γ-deficient mice exhibit similar levels of infection-stimulated PTase activity. By contrast, IFN-γ-deficiency is associated with increased PCase activity and reduced PA activity during infection. Parallel analyses of hepatic gene expression reveal that IFN-γ-deficiency is associated with increased expression of thrombomodulin (TM), a key component of the PCase, increased expression of thrombin-activatable Fibrinolysis inhibitor (TAFI), a PC substrate, and reduced expression of urokinase PA (u-PA). Conclusions: These findings suggest that IFN-γ suppresses infection-stimulated hepatic Fibrin Deposition by suppressing TM-mediated activation of TAFI, thereby destabilizing Fibrin deposits, and concomitantly increasing hepatic u-PA activity, thereby promoting Fibrinolysis. We anticipate that further application of these in situ assays will improve our understanding of tissue-specific hemostasis, its regulation by cytokines, and its dysregulation during coagulopathy.
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Infection-Stimulated Fibrin Deposition Controls Hemorrhage and Limits Hepatic Bacterial Growth during Listeriosis
Infection and immunity, 2005Co-Authors: Isis K. Mullarky, Frank M. Szaba, Michelle A. Parent, Lawrence W. Kummer, Lawrence L. Johnson, Kiera N. Berggren, Wangxue Chen, Stephen T SmileyAbstract:Bacterial infections are major causes of human mortality. The activation of coagulation pathways leading to the Deposition of insoluble Fibrin frequently accompanies bacterial infection, and much attention has focused upon the pathological attributes of infection-stimulated Fibrin Deposition. Nevertheless, here we present conclusive evidence that infection-stimulated Fibrin Deposition can perform critical protective functions during bacterial infection. Specifically, we demonstrate that coagulation-impaired Fibrin(ogen)-deficient mice, in comparison with genetically matched control mice, display increased mortality upon peritoneal infection with the gram-positive facultative intracellular bacterium Listeria monocytogenes. To distinguish effects of Fibrinogen from those of Fibrin, we treat wild-type mice with warfarin, an anticoagulant that suppresses Fibrin formation without impacting Fibrinogen levels. Warfarin treatment exacerbates listeriosis, suggesting that Fibrin is the key mediator of protection. With regard to the underlying protective mechanisms, we demonstrate that Fibrin(ogen) suppresses anemia, reduces hemorrhagic pathology, and limits bacterial growth during listeriosis. Despite confirming a prior report that Fibrin(ogen) promotes the peritoneal clearance of the extracellular bacterium Staphylococcal aureus, we demonstrate that Fibrin(ogen) plays little role in controlling peritoneal numbers of L. monocytogenes bacteria or the dissemination of L. monocytogenes bacteria from the peritoneal cavity. Rather, Fibrin(ogen) primarily limits the growth of these intracellular bacteria within hepatic tissue. While the pathological potential of excessive infection-stimulated Fibrin Deposition is well appreciated, our findings reveal that Fibrin can function protectively, via multiple mechanisms, during bacterial infection.
Majella Maher - One of the best experts on this subject based on the ideXlab platform.
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Placental prothrombin mRNA levels in APC resistance (APCR) women with increased placental Fibrin Deposition
Irish journal of medical science, 2013Co-Authors: S. Sedano-balbas, G Gaffney, Mark Lyons, Brendan Cleary, Margaret Murray, Majella MaherAbstract:We investigated the link between the mRNA of the procoagulant prothrombin in the placental tissue with the increased placental Fibrin Deposition associated with activated protein C resistance (APCR). Women with APCR were not found to produce higher levels of prothrombin transcript compared to women with a normal APC ratio. This indicates that accumulated Fibrin in the placenta is not the consequence of too much production of the procoagulant prothrombin transcript, but may be associated with altered function of other haemostatic factors interacting with APC in the placenta.
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Activated Protein C Resistance (APCR) and Placental Fibrin Deposition
Placenta, 2008Co-Authors: S. Sedano, G Gaffney, G. Mortimer, Mark Lyons, Brendan Cleary, Margaret Murray, Majella MaherAbstract:Abstract Activated protein C resistance (APCR) results in an ineffective anticoagulant response leading to an increased risk of thrombosis, particularly during pregnancy. Adverse pregnancy outcomes including pre-eclampsia (PET), intrauterine growth restriction (IUGR), recurrent miscarriage and placental abruption have been linked with thrombotic lesions compromising the utero-placental circulation. Using histological staining including Martius Scarlet Blue (MSB) and Haematoxylin and Eosin (H&E) and microscopy, we studied placental Fibrin Deposition and histological abnormalities in subjects ( n = 23) with APCR (APCR group), based on a ratio of less than or equal to 2.1 s with the Coatest ® classic test and subjects ( n = 11) with an APC ratio in the normal range, greater than 2.1 s (APCN group). Fibrin Deposition was significantly higher (3.3-fold) in the APCR group compared to the APCN group. An inverse correlation between APC ratio and placental Fibrin Deposition was determined for the study group. Histological abnormalities were more than 2-fold higher in the APCR group compared to the APCN group. Molecular screening identified common thrombophilic mutations, FVL and FII-G20210A in the APCR group but not in the APCN group.
Yuechun Shen - One of the best experts on this subject based on the ideXlab platform.
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Effect of alpha-galactosidase A deficiency on FV leiden Fibrin Deposition and thrombosis in mice
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi, 2009Co-Authors: Yuechun Shen, Ru-li Cai, Jie-zhen Pan, Xiao-ming WangAbstract:OBJECTIVE To evaluate the effect of alpha-galactosidase A (Gla) deficiency on FV Leiden (FVL) associated thrombosis in vivo. METHODS To generate the mice carrying mutations in Gla and FVL and analyze the tissue Fibrin Deposition in organs and thrombosis. RESULTS In the presence of FVL, Gla deficiency greatly increased tissue Fibrin Deposition compared with that in wild-type [Gla(-/0) FV(Q/Q) vs. Gla(+/0) FV(Q/Q) = (0.24 +/- 0.07)% vs. (0.086 +/- 0.049)%, P < 0.0001; Gla(-/-) FV(Q/Q) vs. Gla(+/+) FV(Q/Q) = (0.32 +/- 0.03)% vs. (0.06 +/- 0.005)%, P < 0.05]. With Gla deficiency, the number of thrombi on organ sections in FVL mice was significantly increased [(Gla(-/-) FV(Q/Q) and Gla(-/0) FV(Q/Q)) vs. (Gla(+/+) FV(Q/Q) and Gla(+/0) FV(Q/Q)) = 1.9 +/- 0.7 vs. 0.3 +/- 0.1, P < 0.05]. CONCLUSIONS Gla deficiency could be an important genetic modifier for the enhanced thrombosis associated with FVL.
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α galactosidase a deficiency leads to increased tissue Fibrin Deposition and thrombosis in mice homozygous for the factor v leiden mutation
Stroke, 2006Co-Authors: Yuechun Shen, Peter F Bodary, Fernando B Vargas, Jonathon W Homeister, David Gordon, Kristen A Ostenso, James A Shayman, Daniel T EitzmanAbstract:Background— Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to α-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature. Methods and Results— To examine a potential interaction between FvL and Gla deficiency in vivo, we analyzed tissue Fibrin Deposition in mice carrying combined mutations in FvL and Gla. Gla deficiency markedly increased tissue Fibrin Deposition in mice carrying the FvL mutation (0.33±0.03%; n=7) compared with FvL mutation (0.14±0.02%; n=10; P<0.0005). Conclusions— These observations demonstrate a synergistic interaction between Gla deficiency and FvL toward tissue Fibrin Deposition in mice. Concomitant mutations in these genes may increase the penetrance of vascular thrombotic events in humans.
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α-Galactosidase A Deficiency Leads to Increased Tissue Fibrin Deposition and Thrombosis in Mice Homozygous for the Factor V Leiden Mutation
Stroke, 2006Co-Authors: Yuechun Shen, Peter F Bodary, Fernando B Vargas, Jonathon W Homeister, David Gordon, Kristen A Ostenso, James A Shayman, Daniel T EitzmanAbstract:Background— Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to α-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature. Methods and Results— To examine a potential interaction between FvL and Gla deficiency in vivo, we analyzed tissue Fibrin Deposition in mice carrying combined mutations in FvL and Gla. Gla deficiency markedly increased tissue Fibrin Deposition in mice carrying the FvL mutation (0.33±0.03%; n=7) compared with FvL mutation (0.14±0.02%; n=10; P
Kingsley Yin - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of gamma interferon decreases bacterial load in peritonitis by accelerating peritoneal Fibrin Deposition and tissue repair.
Infection and immunity, 2003Co-Authors: Gang Qiu, Elizabeth Gribbin, Kathryn Harrison, Neil Sinha, Kingsley YinAbstract:Bowel perforation can lead to significant bacterial spillage, which may then cause septic peritonitis, characterized by a systemic inflammatory response and organ dysfunction. There are several reports that have shown that the development of peritoneal adhesions is dependent on inflammatory cytokine levels and that these adhesions can reduce bacterial spread, possibly by sealing off the cecum in the cecal ligation and puncture (CLP) model of septic peritonitis. There have not, however, been any studies that have utilized a strategy to accelerate tissue repair in order to seal off the injured cecum and reduce bacterial spread as well as ameliorate systemic inflammation. In the present study, we demonstrate that the administration of anti-gamma interferon (IFN-γ) antibody (1.2 mg/kg of body weight, intravenously) accelerated tissue repair via increased Fibrin Deposition 12 and 24 h after CLP in rats. This increase in Fibrin Deposition was associated with peritoneal adhesion 24 h after CLP and a reduction in bacterial load compared to the bacterial load of rats given irrelevant antibody. Plasma Fibrin levels, however, were not altered after IFN-γ antibody administration, suggesting that the inhibition of IFN-γ activity specifically increased Fibrin Deposition to the site of injury. Furthermore, plasma interleukin-6, used as a marker of systemic inflammatory response, was reduced in CLP rats given IFN-γ antibody compared to that found in those given irrelevant antibody. These results suggest that the early inhibition of IFN-γ activity in the CLP model is beneficial by accelerating Fibrin Deposition in cecal tissue to prevent bacterial spread and reduce the systemic inflammatory response. Importantly, increased Fibrin Deposition in the ceca was not associated with increased plasma Fibrin whereas the latter may have detrimental effects associated with coagulation disorders.