The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform

Peter N. Walsh - One of the best experts on this subject based on the ideXlab platform.

  • Molecular cloning of platelet Factor XI, an alternative splicing product of the Plasma Factor XI gene.
    Journal of Biological Chemistry, 1998
    Co-Authors: Scott K. Shore, Thikkavarapu Seshsmma, Omar Bagasra, Peter N. Walsh
    Abstract:

    Abstract Platelet Factor XI is associated with the platelet Plasma membrane and has an apparent M r(220,000 nonreduced, 55,000 reduced) different from that of Plasma Factor XI. However, the site of synthesis and the nature of platelet Factor XI are not known. Using reverse transcriptase polymerase chain reaction, 12 out of 13 exons (all except exon V) coding for mature Plasma Factor XI were amplified from human platelet mRNA. The sequence of each of these exons was identical to that of Plasma Factor XI. In situ amplification and hybridization of Factor XI mRNA was positive for exon III and negative for exon V in platelets and negative for both exons in other blood cells. By Northern hybridization, a Factor XI mRNA transcript of ∼1.9 kilobases was detected in megakaryocytic cells, and one of ∼2.1 kilobases was detected in liver cells. Factor XI cDNA was cloned from a megakaryocyte library and sequenced. Exon V was absent, and the splicing of exon IV to exon VI maintained the open reading frame without alteration of the amino acid sequence except for the deletion of amino acids Ala91–Arg144 within the amino-terminal portion of the Apple 2 domain. Thus, platelet Factor XI is an alternative splicing product of the Factor XI gene, localized to platelets and megakaryocytes but absent from other blood cells.

  • Tissue-Specific Expression of Functional Platelet Factor XI Is Independent of Plasma Factor XI Expression
    Blood, 1998
    Co-Authors: Chang-jun Hu, Frank A. Baglia, David C.b. Mills, Barbara A. Konkle, Peter N. Walsh
    Abstract:

    Abstract Platelet Factor XI is an alternatively spliced product of the Factor XI gene expressed specifically within megakaryocytes and platelets as an approximately 1.9-kb mRNA transcript (compared with ∼2.1 kb in liver cells) lacking exon V. Flow cytometry with an affinity-purified Factor XI antibody, with PAC1 antibody (to the GPIIb/IIIa complex on activated platelets), and with S12 antibody (to P-selectin, an α-granule membrane protein expressed on the platelet surface during secretion) on platelets activated with ADP, thrombin, thrombin receptor peptide (SFLLRN amide), or collagen at various concentrations exposed platelet Factor XI and PAC1 antibody binding in parallel. Unactivated platelets expressed approximately 40% of total platelet Factor XI but no PAC1 binding sites. Enhanced membrane exposure of platelet Factor XI is independent of α-granule secretion, because ADP and collagen exposed platelet Factor XI but no S12 binding sites. Platelets from four patients with Plasma Factor XI deficiency (<0.04 U/mL) had normal constitutive and activation-dependent expression of platelet Factor XI. Well-washed platelets from normal and from Factor XI-deficient donors incubated with low concentrations of thrombin (0.05 to 0.1 U/mL) corrected the clotting defect observed with Factor XI-deficient Plasma. Thus, functionally active platelet Factor XI is differentially expressed on platelet membranes in a tissue-specific manner both constitutively and in a concentration-dependent fashion by various agonists in the absence of detectable Plasma Factor XI.

  • Tissue-Specific Expression of Functional Platelet Factor XI Is Independent of Plasma Factor XI Expression
    Blood, 1998
    Co-Authors: Chang-jun Hu, Frank A. Baglia, David C.b. Mills, Barbara A. Konkle, Peter N. Walsh
    Abstract:

    Platelet Factor XI is an alternatively spliced product of the Factor XI gene expressed specifically within megakaryocytes and platelets as an approximately 1.9-kb mRNA transcript (compared with ∼2.1 kb in liver cells) lacking exon V. Flow cytometry with an affinity-purified Factor XI antibody, with PAC1 antibody (to the GPIIb/IIIa complex on activated platelets), and with S12 antibody (to P-selectin, an α-granule membrane protein expressed on the platelet surface during secretion) on platelets activated with ADP, thrombin, thrombin receptor peptide (SFLLRN amide), or collagen at various concentrations exposed platelet Factor XI and PAC1 antibody binding in parallel. Unactivated platelets expressed approximately 40% of total platelet Factor XI but no PAC1 binding sites. Enhanced membrane exposure of platelet Factor XI is independent of α-granule secretion, because ADP and collagen exposed platelet Factor XI but no S12 binding sites. Platelets from four patients with Plasma Factor XI deficiency (

Cihangir Erem - One of the best experts on this subject based on the ideXlab platform.

  • blood coagulation fibrinolytic activity and lipid profile in subclinical thyroid disease subclinical hyperthyroidism increases Plasma Factor x activity
    Clinical Endocrinology, 2006
    Co-Authors: Cihangir Erem
    Abstract:

    BACKGROUND AND OBJECTIVES: Various abnormalities of coagulation and fibrinolysis occur in patients with thyroid diseases, and may range from subclinical laboratory abnormalities to clinically significant disorders of coagulation and, rarely, major haemorrhage or thromboembolism. The influence of subclinical hypothyroidism (SHypo) on haemostasis is controversial, both hypercoagulable and hypocoagulable states have been reported. A hypercoagulable state might be a risk Factor for thromboembolic disease in SHypo. On the other hand, subclinical hyperthyroidism (SCHyper) is associated with enhanced cardiovascular risk. In the English literature, there are no studies on changes in coagulation and fibriolytic status in subjects with SCHyper. Therefore, the aim of the present study was to investigate the markers of endogenous coagulation and fibrinolysis, and to evaluate the relationships between serum lipid profile and thyroid hormones and these haemostatic parameters in subclinical thyroid patients. DESIGN AND METHODS: Various haemostatic parameters were investigated in 30 patients with SHypo and 20 patients with SCHyper and compared to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, Factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these haemostatic parameters were examined. RESULTS: Compared with the control subjects, only FX activity was significantly increased in patients with SCHyper (P < 0.01). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in patients with SHypo compared with the control group (P < 0.001 and P < 0.01, respectively). TC levels were significantly higher in patients with SCHyper than in controls (P < 0.05). No differences could be found in coagulation/fibrinolysis parameters between subclinical hypothyroid patients and control subjects. In patients with SCHyper, serum TSH level was positively correlated with FX activity (r: 0.58, P < 0.01) and inversely correlated with PAI-1 (r: -0.55. P < 0.05). Serum TG levels were inversely correlated with Plasma activities of Factors V, VII, VIII, IX, X and vWF (r: -0.83, P < 0.001; r: -0.68, P < 0.05; r: -0.61, P < 0.05; r: -0.77, P < 0.01; r: -0.63, P < 0.05; r: -0.60, P < 0.05, respectively). Serum TC levels were positively correlated with Plasma fibrinogen levels (r: 0.72, P < 0.05). Serum HDL-C levels were positively correlated with protein S activity (r: 0.68, P < 0.05) and negatively correlated with F VII activity (r: -0.69, P < 0.05). Also, in patients with SHypo, serum TG levels were positively correlated with serum TSH levels (r: 0.42, P < 0.05), Plasma activities of Factors V, VII and X (r: 0.42, P < 0.05; r: 0.54, P < 0.01; r: 0.57, P < 0.01, respectively) and negatively correlated with Plasma fibrinogen levels (r: -0.41, P < 0.05). Serum TC levels were positively correlated with Factors V and X (r: 0.42, P < 0.05; r: 0.58, P < 0.01, respectively) and negatively correlated with t-PA Ag levels (r: -0.44, P < 0.05). Serum HDL-C levels were inversely correlated with F VII activity (r: -0.48, P < 0.05). INTERPRETATION AND CONCLUSIONS: Some differences were found in the haemostatic parameters and lipid profile between the subclinical thyroid patients and healthy controls. Increased Factor X activity in patients with subclinical hyperthyroidism represent a potential hypercoagulable state, which might augment the already existing risk for atheroscleroic complications. Also, subclinical hypothyroid patients exhibit a more atherogenic lipid profile compared with healthy individuals. Therefore, subclinical hypothyroidism is also associated with an increased risk of cardiovascular disease. However, thyroid hormones may play a role at different levels of the complex haemostatic system in subclinical thyroid disease.

Chang-jun Hu - One of the best experts on this subject based on the ideXlab platform.

  • Tissue-Specific Expression of Functional Platelet Factor XI Is Independent of Plasma Factor XI Expression
    Blood, 1998
    Co-Authors: Chang-jun Hu, Frank A. Baglia, David C.b. Mills, Barbara A. Konkle, Peter N. Walsh
    Abstract:

    Abstract Platelet Factor XI is an alternatively spliced product of the Factor XI gene expressed specifically within megakaryocytes and platelets as an approximately 1.9-kb mRNA transcript (compared with ∼2.1 kb in liver cells) lacking exon V. Flow cytometry with an affinity-purified Factor XI antibody, with PAC1 antibody (to the GPIIb/IIIa complex on activated platelets), and with S12 antibody (to P-selectin, an α-granule membrane protein expressed on the platelet surface during secretion) on platelets activated with ADP, thrombin, thrombin receptor peptide (SFLLRN amide), or collagen at various concentrations exposed platelet Factor XI and PAC1 antibody binding in parallel. Unactivated platelets expressed approximately 40% of total platelet Factor XI but no PAC1 binding sites. Enhanced membrane exposure of platelet Factor XI is independent of α-granule secretion, because ADP and collagen exposed platelet Factor XI but no S12 binding sites. Platelets from four patients with Plasma Factor XI deficiency (<0.04 U/mL) had normal constitutive and activation-dependent expression of platelet Factor XI. Well-washed platelets from normal and from Factor XI-deficient donors incubated with low concentrations of thrombin (0.05 to 0.1 U/mL) corrected the clotting defect observed with Factor XI-deficient Plasma. Thus, functionally active platelet Factor XI is differentially expressed on platelet membranes in a tissue-specific manner both constitutively and in a concentration-dependent fashion by various agonists in the absence of detectable Plasma Factor XI.

  • Tissue-Specific Expression of Functional Platelet Factor XI Is Independent of Plasma Factor XI Expression
    Blood, 1998
    Co-Authors: Chang-jun Hu, Frank A. Baglia, David C.b. Mills, Barbara A. Konkle, Peter N. Walsh
    Abstract:

    Platelet Factor XI is an alternatively spliced product of the Factor XI gene expressed specifically within megakaryocytes and platelets as an approximately 1.9-kb mRNA transcript (compared with ∼2.1 kb in liver cells) lacking exon V. Flow cytometry with an affinity-purified Factor XI antibody, with PAC1 antibody (to the GPIIb/IIIa complex on activated platelets), and with S12 antibody (to P-selectin, an α-granule membrane protein expressed on the platelet surface during secretion) on platelets activated with ADP, thrombin, thrombin receptor peptide (SFLLRN amide), or collagen at various concentrations exposed platelet Factor XI and PAC1 antibody binding in parallel. Unactivated platelets expressed approximately 40% of total platelet Factor XI but no PAC1 binding sites. Enhanced membrane exposure of platelet Factor XI is independent of α-granule secretion, because ADP and collagen exposed platelet Factor XI but no S12 binding sites. Platelets from four patients with Plasma Factor XI deficiency (

Robert R Montgomery - One of the best experts on this subject based on the ideXlab platform.

  • a conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of Plasma Factor viii
    Blood, 2014
    Co-Authors: Scot A Fahs, Matthew T Hille, Hartmut Weiler, Robert R Montgomery
    Abstract:

    The cellular source of coagulation Factor VIII (FVIII) remains controversial. Like many coagulation proteins, FVIII is produced in the liver, and FVIII synthesis has long been associated with hepatocytes. But extrahepatic synthesis also occurs, and mounting evidence suggests that hepatocytes are not responsible for FVIII production. To determine the tissue that synthesizes FVIII, we developed a Cre/lox-dependent conditional knockout (KO) model in which exons 17 and 18 of the murine Factor VIII gene (F8) are flanked by loxP sites, or floxed (F8F). In cells expressing Cre-recombinase, the floxed sequence is deleted, resulting in F8F→KO gene inactivation. When F8F mice were crossed with various tissue-specific Cre strains, we found that hepatocyte-specific F8-KO mice are indistinguishable from controls, whereas efficient endothelial-KO models display a severe hemophilic phenotype with no detectable Plasma FVIII activity. A hematopoietic Cre model was more equivocal, so experimental bone marrow transplantation was used to examine hematopoietic FVIII synthesis. FVIIInull mice that received bone marrow transplants from wild-type donors were still devoid of Plasma FVIII activity after hematopoietic donor cell engraftment. Our results indicate that endothelial cells are the predominant, and possibly exclusive, source of Plasma FVIII.

Kathleen E. Brummel-ziedins - One of the best experts on this subject based on the ideXlab platform.

  • Thrombin generation in rheumatoid arthritis: Dependence on Plasma Factor composition
    Thrombosis and Haemostasis, 2020
    Co-Authors: Anetta Undas, Matthew Gissel, Beata Kwasny-krochin, Piotr Gluszko, Kenneth Mann, Kathleen E. Brummel-ziedins
    Abstract:

    SummaryGrowing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on Plasma Factor/inhibitor composition. Plasma Factor (F) compositions (II, V, VII, VIII, IX, X), antithrombin and free tissue Factor pathway inhibitor (TFPI) from 46 consecutive RA patients with no cardiovascular events (39 female, 7 male, aged 57 [range, 23–75] years; DAS28 [Disease Activity Score] 5.2 ± 1.1) were compared with those obtained in age- and sex-matched apparently healthy controls. Using each individual’s Plasma coagulation protein composition, tissue Factor- initiated thrombin generation was assessed both computationally and empirically. RA patients had higher fibrinogen (4.18 [IQR 1.09] vs. 2.56 [0.41] g/l, p<0.0001), FVIII (226 ± 40 vs. 113 ± 15%, p<0.001), PC (107 [16] vs. 100 [14]%, p<0.001), and free TFPI levels (22.3 [2.2] vs. 14.7 [2.1] ng/ml, p<0.001). DAS28, but not age, RA duration, or C-reac- tive protein, was associated with FV, FVIII, FIX, FX, antithrombin, and free TFPI (r from 0.27 to 0.48, p<0.05). Intergroup comparison of computational thrombin generation profiles showed that in RA patients, maximum thrombin levels (p=0.01) and the rate of thrombin formation (p<0.0001) were higher, whereas the initiation phase of thrombin generation (p<0.0001) and the time to maximum thrombin levels (p<0.0001) were longer. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. Simulations of thrombin formation suggest that blood Plasma composition, i.e. a marked increase in FVIII, somewhat counterbalanced by free TFPI, contributes to the prothrombotic phenotype in RA patients.

  • Thrombin generation in chronic obstructive pulmonary disease: dependence on Plasma Factor composition.
    Thrombosis Research, 2011
    Co-Authors: Anetta Undas, Miłosz Jankowski, Przemysław Kaczmarek, Krzysztof Sładek, Kathleen E. Brummel-ziedins
    Abstract:

    Background Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for thromboembolic events. We investigated thrombin generation profiles in COPD patients and their dependence on Plasma Factor/inhibitor composition.

  • Plasma Factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular events
    Thrombosis Research, 2010
    Co-Authors: Matthew Gissel, Anetta Undas, Kenneth G. Mann, Agnieszka Slowik, Kathleen E. Brummel-ziedins
    Abstract:

    Introduction More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether Plasma Factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events.

  • Thrombin generation in rheumatoid arthritis: dependence on Plasma Factor composition
    Thrombosis and Haemostasis, 2010
    Co-Authors: Anetta Undas, Matthew Gissel, Beata Kwasny-krochin, Piotr Głuszko, Kenneth G. Mann, Kathleen E. Brummel-ziedins
    Abstract:

    Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on Plasma Factor/inhibitor composition. Plasma Factor (F) compositions (II, V, VII, VIII, IX, X), antithrombin and free tissue Factor pathway inhibitor (TFPI) from 46 consecutive RA patients with no cardiovascular events (39 female, 7 male, aged 57 [range, 23–75] years; DAS28 [Disease Activity Score] 5.2 ± 1.1) were compared with those obtained in age- and sex-matched apparently healthy controls. Using each individual’s Plasma coagulation protein composition, tissue Factor-initiated thrombin generation was assessed both computationally and empirically. RA patients had higher fibrinogen (4.18 [IQR 1.09] vs. 2.56 [0.41] g/l, p