bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular fibrinogen binding protein, Efb, from Staphylococcus aureus binds to platelets and inhibits platelet aggregation
Authors: Shannon Oonagh , Flock Jan-Ingmar 
Published: March 2004

Summary
S. aureus produces and secretes a protein, extracellular fibrinogen binding protein (Efb), which contributes to virulence in wound infection. We have shown here that Efb is a potent inhibitor of platelet aggregation. Efb can bind specifically to platelets by two mechanisms; 1) to fibrinogen naturally bound to the surface of activated platelets and 2) also directly to a surface localized component on the platelets. This latter binding of Efb is independent of fibrinogen. The specific binding of Efb to the putative receptor on the platelet surface results in a stimulated, non-functional binding of fibrinogen in a dose dependent manner, distinct from natural binding of fibrinogen to platelets. The natural binding of fibrinogen to GPIIb/IIIa on activated platelets could be blocked by a monoclonal antibody against this integrin, whereas the Efb-mediated fibrinogen binding could not be blocked. The enhanced Efb-dependent fibrinogen binding to platelets is of a nature that does not promote aggregation of the platelets; instead it inhibits aggregation. The anti-thrombotic action of Efb may explain the effect of Efb on wound healing, which is delayed in the presence of Efb.
Injection of recombinant activated factor VII can induce transient increase in circulating procoagulant microparticles
Authors: Hugel Bénédicte , Guillet Benoit , Trichet Catherine , Rafowicz Anne , Lambert Thierry , Freyssinet Jean-Marie , Dreyfus Marie , Proulle Valérie 
Published: March 2004

SummaryRecombinant activated factor VII (rFVIIa) is an effective haemostatic treatment in haemophiliacs with inhibitors. In vitro, FVIIa concentrations corresponding to those obtained with therapeutic doses of rFVIIa have been shown to induce normal thrombin generation and platelet activation in the absence of factors VIII or IX. To further study the in vivo haemostatic changes induced by rFVIIa, circulating procoagulant microparticles (MP) were measured in patients treated with discontinuous injections of Novoseven®. In 6 out of 15 patients, a transient peak of procoagulant MP was observed after injection, occurring 15 min to 2 h after infusion. It was composed primarily of platelet-derived MP and was of very short duration. This peak was not observed in haemophiliacs without inhibitor, who were treated with conventional replacement therapies. Our results provide further in vivo evidence that rFVIIa specifically activates platelets, either directly or as a consequence of a burst of thrombin generation that could account for its haemostatic efficacy.
Contribution of PAR-1, PAR-4 and GPIbα in intracellular signaling leading to the cleavage of the β3 cytoplasmic domain during thrombin-induced platelet aggregation
Authors: Dubois Christophe , Steiner Beat , Meyer Reigner Sylvie 
Published: March 2004

SummaryIntegrin αIIbβ3 plays a pivotal role in platelet aggregation by binding to fibrinogen. The β3 cytoplasmic domain of αIIbβ3 interacts with cytoskeletal and signaling proteins and is cleaved by µ-calpain, a calcium regulated cysteine protease. In the present study, we have investigated in more detail the cleavage of the β3 cytoplasmic domain during platelet aggregation induced by thrombin, TRAP-1 and TRAP-4. Our data show that β3 is cleaved in all three cases. The time course of β3 cleavage and the amount of cleaved β3 depends on the way platelets are activated and on the complete activation of µ-calpain, with a maximum of 90% of cleaved β3 obtained when thrombin is used. Furthermore, our results also show that the cleaved αIIbβ3 is mainly distributed in the Triton soluble fraction, indicating its inability to bind to the cytoskeleton. Interestingly, in the absence of GPIbα or following inhibition of thrombin binding to GPIbα, there is a reduction in the thrombin-induced calcium flux, β3 cleavage and µ-calpain activation. These results suggest that cleavage of the β3 cytoplasmic domain by µ-calpain might be an important step regulating the link between the cytoskeleton and αIIbβ3 during platelet aggregation, and that GPIbα could function as a cofactor for the complete activation of platelets by thrombin.
Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk
Authors: Hoekstra Tiny , Schouten Evert , Kluft Cees , Geleijnse Johanna 
Published: March 2004

SummaryThe habitual level of PAI-1 is influenced by many factors, of which obesity and insulin resistance are the most important. It is possible to reduce plasma PAI-1 by changes in life style, e.g. weight reduction and physical activity. Data on potential interactions between environmental and metabolic variables on one hand, and the 4G/5G-polymorphism on the other hand, are still scarce. It becomes more and more clear that PAI-1 may possibly not be a major (causal) factor in cardiovascular disease, but its role in inflammation deserves further attention. In the presence of the 4G-allele not only the PAI-1 response was more pronounced, but also the response of other acute-phase reactants, which implies that the increases of these reactants are secondary to the increase in PAI-1. A myocardial infarction also provokes an acute phase response. It can thus be hypothesized that the 4G-allele might exacerbate tissue injury during the acute phase after a myocardial infarction, and thereby negatively affect the prognosis.
Elevated coagulation factor VIII and the risk for recurrent early pregnancy loss
Authors: Dossenbach-Glaninger Astrid , van Trotsenburg Michael , Krugluger Walter , Dossenbach Martin , Oberkanins Christian , Huber Johannes , Hopmeier Pierre 
Published: March 2004

SummaryInherited and acquired thrombophilia are associated with recurrent pregnancy loss. Recently, an increased risk for thromboembolic disease was described for patients with elevated coagulation factor VIII, but it is unknown whether there is also an association to early pregnancy loss. We therefore evaluated the relation between recurrent early pregnancy loss and levels of coagulation factor VIII. We enrolled 49 unrelated Caucasian women with a history of 2 6 early pregnancy losses and 48 healthy controls, who had delivered at least one term infant and had never experienced pregnancy loss. We determined factor V Leiden-, G20210A prothrombin-, MTHFR C677Tand A1298Cgene mutations, levels of antithrombin, protein C, protein S, factor VIII, C-reactive protein and antiphospholipid antibodies. There was a significantly higher rate of pregnancy losses in women with Antiphospholipid Syndrome (p = 0.043). Furthermore, plasma levels of coagulation factor VIII were significantly higher in cases than in controls (130.5 IU/dl ± 25.4 vs 119.5 IU/dl ± 24.1; p = 0.032) and appeared independent of Creactive protein (R = 0.146, p = 0.323 in cases; R = 0.028, p = 0.850 in controls). The relative risk for recurrent pregnancy loss in women with factor VIII levels above 151 IU/dl (90th percentile of controls) was 2.5 (0.7 – 8.9, 95 percent confidence interval), for levels above 156 IU/dl (95th percentile of controls) 3.9 (0.8 – 20.0, 95 percent confidence interval). Elevated maternal plasma levels of coagulation factor VIII tend to be associated with an increased risk for recurrent early pregnancy loss.
Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score
Authors: Wurst Michael , Smolinski Mathias , Lorenz Stephan , Osika Alexandra , Olenik Daniela , Fiedler Fritz , Borggrefe Martin , Dempfle Carl-Erik 
Published: March 2004

SummaryThe overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.
The novel human platelet septin SEPT8 is an interaction partner of SEPT4
Authors: Bläser Susanne , Horn Julia , Würmell Paul , Bauer Heike , Strümpell Sandra , Nurden Paquita , Pagenstecher Axel , Busse Anja , Wunderle Daniela , Hainmann Ina , Zieger Barbara 
Published: March 2004

SummarySeptins are a family of GTP-binding proteins, which are essential for active membrane movement such as cytokinesis and vesicle trafficking. In non-dividing cells (such as platelets and neurons) septins are implicated in exocytosis. Platelets from a SEPT5 knockout mouse showed an altered serotonin secretion and platelet aggregation, suggesting that SEPT5 is involved in secretion in platelets. Septins form complexes consisting of multiple septin polypeptides. Using the yeast two-hybrid system we had demonstrated that SEPT5 partners with SEPT8.The aim of this study was to identify other interaction partners of the human platelet septin SEPT8. Using the yeast two-hybrid system with SEPT8 as bait protein we identified the human septin SEPT4 as an interaction partner of SEPT8. The interaction between SEPT4 and SEPT8 was confirmed by immunoprecipitation. Expression analysis revealed that SEPT4 is also expressed in human platelets. Thus, SEPT4 is the third described platelet septin besides SEPT5 and SEPT8.Transmission electron microscopy of platelets revealed that SEPT8 and SEPT4 are localized surrounding α-granules (as it had been shown for the septin SEPT5) suggesting that the three septins may be components of the septin complex in platelets and contribute in such a way to platelet biology. Activation of platelets by agonists resulted in the translocation of SEPT4 and SEPT8 to the platelet surface indicating a possible functional role of these proteins in platelet granular secretion.
Protective role of interleukin-6 in coagulatory and hemostatic disturbance induced by lipopolysaccharide in mice
Authors: Inoue Ken-ichiro , Yanagisawa Rie , Sakurai Miho , Shimada Akinori , Morita Takehito , Sato Masahiko , Yoshino Shin , Yoshikawa Toshikazu , Tohyama Chiharu , Takano Hirohisa 
Published: March 2004

SummaryAlthough the role of interleukin (IL)-6 in inflammatory diseases has been previously examined, its role in hemostasis, fibrinolysis, and coagulation during inflammation remains to be established. The present study elucidated the role of IL-6 in hemostatic and coagulatory changes during severe inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS: 1 mg/kg) using IL-6 null (-/-) mice. After LPS challenge, IL-6 (-/-) mice revealed significant prolongation of prothrombin time and activated partial thromboplastin time and a significant decrease in platelet counts as compared with wild type mice. LPS treatment induced marked pulmonary hemorrhage with neutrophilic inflammation in IL-6 (-/-) mice, in contrast, only mild neutrophilic infiltration in WT mice confirmed by macroscopic and histological findings.The protein levels of proinflammatory mediators, such as IL-1?, macrophage inflammatory protein (MIP)-1a., MIP-2, macrophage chemoattractant protein1, granulocyte/macrophage-colony-stimulating factor, and keratinocyte chemoattractant in the lungs were significantly greater in IL-6 (-/-) mice than in WT mice after LPS challenge. These results directly indicate that IL-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least partly, via the modulation of proinflammatory processes.
Pharmacogenetics of the CD14 endotoxin receptor polymorphism and progression of coronary atherosclerosis
Authors: Agema Willem , de Maat Moniek , Zwinderman Aeilko , Kastelein John , Rabelink Ton , van der Wall Ernst , Jukema J. Wouter 
Published: March 2004

SummaryAtherosclerosis is at least in part an inflammatory disease. CD14 is an endotoxin receptor that after binding of lipopolysaccharides evokes endothelial activation and secretion of several cytokines. A polymorphism of CD14 has been associated with myocardial infarction. We evaluated the role of the -159 T/C polymorphism in the promoter region of the CD14 gene in relation to severity and progression of coronary atherosclerosis and response to the HMG CoA reductase inhibitor pravastatin. We recruited patients from the multicenter double-blind randomized placebo controlled REGRESS trial and genotyped the -159T/C CD14 polymorphism. DNA and angiographic follow-up were available from 759 patients with objectivated coronary artery disease. We measured changes in mean segment diameter (MSD) and minimum obstruction diameter (MOD) with quantitative coronary angiography and noted the occurrence of major adverse cardiac events. The genotype distribution was 28% TT, 49% CT, 23% CC. We did not find any association between genotype and MSD and MOD at baseline, frequency of previous myocardial infarction, changes in MSD and MOD or major clinical events. Treatment with the HMG CoA reductase inhibitor pravastatin reduced progression of coronary atherosclerosis and adverse events equally for all genotypes. We conclude, that the -159T/C polymorphism in the CD14 monocyte receptor gene was not associated with progression of coronary atherosclerosis in this population nor did it influence the efficacy of pravastatin in the treatment of atherosclerosis.
Platelet-endothelial cell interaction in pulmonary microcirculation: the role of PARS
Authors: Kiefmann Rainer , Heckel Kai , Schenkat Sonja , Dörger Martina , Węsierska-Gądek Józefa , Goetz Alwin 
Published: March 2004

SummaryAccumulation of platelets might contribute to acute lung injury during systemic inflammation. The aim of the study was to elucidate the role of the poly (ADP-ribose) synthetase, a nucleotide-polymerizising enzyme, in mediation of platelet-endothelial cell interaction through regulation of adhesion molecules within the pulmonary microcirculation during endotoxemia. We used in vivo fluorescence microscopy to quantify kinetics of fluorescently labeled erythrocytes and platelets in rabbit pulmonary arterioles and venules. Six hours after onset of endotoxin infusion we observed a massive interaction of platelets with the microvascular endothelial cells, whereas under control conditions, no platelet sequestration was measured. An up-regulation of P- and E-selectin was detected in lung tissue following endotoxin infusion by immunohistochemistry and Western blot analysis. Blockade of endothelial P-selectin with fucoidin resulted in a reduction of the endotoxin-induced platelet-endothelial cell interaction. Inhibition of poly (ADP-ribose) synthetase by 3-aminobenzamide inhibited the endotoxin-induced expression of endothelial P- and E-selectin and the subsequent recruitment of platelets. In summary, we provide first in vivo evidence that platelets accumulate in pulmonary microcirculation following endotoxemia. Poly (ADP-ribose) synthetase seems to mediate this platelet-endothelial cell interaction via P- and E-selectin expressed on the surface of microvascular endothelium.
Factor V Leiden and prothrombin G20210A mutations in young adults with cryptogenic ischemic stroke
Authors: Mira Yolanda , Vayá Amparo , Corella Dolores , Ferrando Fernando , Villa Piedad , Estellés Amparo , Aznar Justo 
Published: March 2004

SummaryThe association between factor V Leiden (FVL) and prothrombin G20210A (PT 20210) mutations and ischemic stroke remains controversial, particularly in young adults with cryptogenic stroke. Prevalence of FVL (4.1%) and PT 20210 (8.2%) mutations was assessed in 49 patients under 50 years with cryptogenic stroke and compared with controls. Odd ratio (OR) for cryptogenic stroke was 2.62 (95% CI, 0.49-13.95) for FVL and 3.75 (95% CI, 1.05-13.34) for PT 20210 and 3.28 (95% CI, 1,17-9.20) for some recognized genetic thrombophilic defect. Moreover, the OR for cryptogenic stroke in young women using oral contraceptives (OC) was 3.59 (95% CI, 1.28-10.5). When some genetic thrombophilic defect was associated with OC, the OR was much higher (OR: 14.27; 95% CI, 0.66-309.99). Our results suggest that in the Mediterranean populations the PT 20210 mutation, but not FV Leiden, is a risk factor for cryptogenic stroke in young adults. OC use is also a significant risk factor for cryptogenic stroke, which is increased in women with some genetic thrombotic risk factor.
A systematic review of the accuracy of ultrasound in the diagnosis of deep venous thrombosis in asymptomatic patients
Authors: Boissel Jean-Pierre , Cucherat Michel , Sonie Sandrine , Shah Nirav , Leizorovicz Alain , Kassaï Behrouz 
Published: March 2004

SummaryEvaluation of the accuracy of ultrasound has yielded heterogeneous results. Our objective was to summarize the evidence on the accuracy of ultrasound compared to venography in asymptomatic patients, taking into account the variation due to threshold differences. Searches of journal table of contents, computer databases (Medline, Embase, Biomed, Cochrane) and conference proceedings were performed. A study was eligible if it prospectively compared ultrasound to venography for the diagnosis of DVT in asymptomatic patients. Data of studies selected for inclusion were extracted independently by two authors. High quality studies with consecutive patient enrollment, blind evaluation of the two techniques, and absence of verification bias are summarized as Level 1, while those not fulfilling one or more of these criteria are considered Level 2. Original study authors were contacted to confirm accuracy and to provide missing data. A pooled estimate of the accuracy of ultrasound was obtained according to the method of Moses and coworkers. This method gives a summary diagnostic odds ratio (DOR). The DOR is a single indicator of test performance. It varies between 0 and infinity and exceeds 1, only when ultrasound is more often positive in patients with DVT relative to those without DVT. Higher DOR indicates better discriminatory test performance. Thirty one studies were rated as potentially unbiased and graded as Level 1.The mean prevalence of DVT as determined by venography was 22%. In Level 1 studies, the odds of positive ultrasound in proximal veins was 379 times higher (95% confidence limits 65, 2,200) and in distal veins 32 times higher (7.5, 135) among patients with DVT than those without. Our results suggest that, particularly for proximal veins, ultrasound is accurate for the diagnosis of DVT in asymptomatic postoperative orthopedic patients. More research is needed in other clinical settings.
Lower limb venous haemodynamic impairment on dependency: quantification and implications for the “economy class” position
Authors: Knaggs Alison , Sonecha Tans , Zervas Vasileios , Jenkins Michael , Wolfe John , Delis Konstantinos 
Published: March 2004

SummaryThe role of stasis in venous disease is undisputed, yet surprisingly, its haemodynamic quantitation remains largely undefined. We investigated the phenomenon of venous stasis in the lower limb upon sitting and standing and project its implications to economy class aircraft passengers. 26 normal limbs, 13 subjects, age 29-54, selected after duplex, plethysmography and ABPI, had peak[Vpeak], mean[Vmean] and minimum[Vmin] velocities, volumeflow[Qvenous], pulsatility index [PIvenous] and diameter obtained on horizontal, sitting (as in economy aircraft seats) and standing with duplex, at popliteal, femoral[FV] and common femoral[CFV]veins [differences in median %]. Vpeak, Vmean and Qvenous decreased from horizontal to sitting in the CFV [57%, 71%, 31%, respectively], FV [51%, 70%, 34%] and popliteal [31%, 58%, 42%] (all, p<.001). Vpeak, Vmean and Qvenous decreased further from sitting to standing in the CFV [26%, 44%, 25%, respectively], FV [21%, 42%, 27%] and popliteal [14%, 42%, 20%] (all, p <.001). Diameter, Vmin and PIvenous increased from horizontal to sitting in the CFV [50%, 63%, 38%, respectively], FV [39%, 23%, 66%] and popliteal [21%, 14%, 84%] (all, p <.001)]. Diameter, Vmin and PIvenous increased further from sitting to standing in CFV [10%, 22%, 19%, respectively; p ≤.004], FV [12%, 68%, 2%[ns]; p <.001)] and popliteal [14%, 50%, 24%; p ≤.017]. In all postures: Vpeak, Vmean, Qvenous and diameter at CFV exceeded FV (p <.025) and popliteal (p <.001) ones; also those at FV exceeded the popliteal ones (p ≤.003), except for the diameter on horizontal. Vmin in popliteal was higher than in CFV (p ≤.003) or FV (p <.025), on horizontal and standing. PIvenous in CFV was lower than in FV or popliteal (p <.025) on sitting. Right to left differences nonsignificant. [Wilcoxon+Bonferroni test: significance at p <.025] A shift from horizontal to sitting generates a most significant attenuation in Qvenous, Vpeak and Vmean linked to a reciprocal increase in Vmin, PIvenous and vein diameter, with further exacerbation on standing. Vpeak, Vmean and Qvenous decline with distance from groin enhancing venous stasis in the periphery. By restricting activation of the natural venous pumps, sitting cramped during long flights may protract the status of haemodynamic stagnation sustained on dependency which paired with marked venous dilatation generates a milieu that may promote thrombogenesis.
A review of the therapeutic uses of thrombin
Authors: Bradshaw Ralph , Gabriel Don , Ortel Thomas , Lawson Jeffrey , Mann Kenneth , Lundblad Roger 
Published: March 2004

SummaryThrombin is the product of the hemostatic response essential to the conversion of fibrinogen to fibrin. In addition, it is also responsible for the aggregation of blood platelets in the formation of the “platelet plug” as well as the activation of factor VIII, factor V, factor XI, factor XIII and protein C. The action of thrombin is not confined to the hemostatic response as it also has a critical function in the wound healing process by stimulating ‘mitogenic’ events through interaction with cell surface receptors. In this review, we consider the various biological activities of thrombin as they relate to current therapeutic use. While there has been considerable interest in the development of fibrin sealant products, there has been considerably less interest in documenting the continuing use of thrombin as a therapeutic. The use of thrombin for topical hemostasis and the treatment of pseudoaneurysms will be discussed in detail. It is concluded that the use of thrombin as a drug will not only continue but also will significantly increase. However, the availability of a safe human thrombin preparation will be critical for the continued use of thrombin as a therapeutic.