bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-Asparaginase and the effect of age on coagulation and fibrinolysis in childhood acute lymphoblastic leukemia
Authors: Hop Wim C. J. , van Kessel-Bakvis Carla , Stigter Rolinda , Pieters Rob , Appel Inge M. 
Published: July 2008

SummaryAlterations in haemostasis are frequently observed in children with acute lymphoblastic leukemia (ALL). It was the objective of this study to analyse age-related disturbances in coagulation and fibrinolysis parameters during the induction phase of the anti-leukemic treatment. Sixty-four children were classified by age into three groups (1–5, 6–10, 11–16 years), and studied during induction treatment of ALL including four weeks of dexamethasone, followed by two weeks tapering of dexamethasone during which 6,000 IU/m2 native L-Asparaginase (total 4 doses) was administered intravenously twice weekly. Blood samples were collected immediately before each L-Asparaginase infusion to analyze procoagulant (fibrinogen, factor [F] II, FV, FVII, F IX, F X) and anticoagulant factors (antithrombin [AT], protein C, protein S), parameters of thrombin generation (F1+2, TAT) and fibrinolysis (α2-antiplasmin, plasminogen, PA P , D-dimer). Children were in a hypercoagulable state after four weeks of dexamethasone due to upregulation of coagulation parameters. Upregulation was highest in the two youngest age groups. During L-Asparaginase treatment the 11– to 16-year- olds showed lower values in procoagulant and, even more, in anticoagulant factor levels compared to the younger children. Activation markers of thrombin generation and fibrinolysis did not change over time during the study period. Decreased synthesis of α2-antiplasmin and plasminogen during L-Asparaginase treatment resulted in less potential of clot lysis by plasmin in children older than 11 years of age. In conclusion, a more severe decline of anticoagulant and fibrinolytic parameters in children between 11 and 16 years of age underline that these children are at higher risk of thrombosis during ALL induction treatment.
Inhibitors and activation markers of the haemostatic system during hormone therapy: A comparative study of oral estradiol (2 mg)/ dydrogesterone and estradiol (2 mg)/ trimegestone
Authors: Brosnan Jeanette , Bonnar John , Conard Jacqueline , Kluft Cornelius , Hellgren Margareta , Norris Lucy A. 
Published: July 2008

SummaryEpidemiological studies have shown that hormone therapy (HT) increases the risk of venous thromboembolism in post menopausal women. The mechanism of this increased risk is unknown; however, activation of the haemostatic system is known to contribute to the pathogenesis of venous thromboembolism. In post-menopausal women the estrogen /progestogen composition of the HT can influence the level of haemostatic activation. It was the objective of this study to compare changes in inhibitors and activation markers of the haemostatic system in healthy post-menopausal women taking estradiol (2 mg) combined with dydrogesterone or a new progestin, trimegestone. A multicentre study of 186 women randomised to six months therapy with either estradiol (2 mg) +trimegestone (0.5 mg) or estradiol (2 mg) +dydrogesterone (10 mg) was performed. Antithrombin and protein S activity was decreased and activated protein C (APC) resistance, D-dimer and prothrombin fragment 1.2, were increased in both groups on treatment. Protein C activity was decreased and plasmin-antiplasmin complex was increased in the trimegestone group only. The increase in plasmin-antiplasmin complex and D-dimer was greater after six cycles of treatment in the trimegestone group compared with the dydro-gesterone group. In conclusion, decreased levels of inhibitors of blood coagulation and increased thrombin production were found in both groups however a greater increase in the levels of plasmin-antiplasmin complex and D-dimer was found in the tri-megestone group. This suggests an enhanced fibrinolytic response in this group. Further studies are required to determine the significance of this finding with respect to venous thrombosis risk.
Elevated plasma fibronectin levels associated with venous thromboembolism
Authors: Pecheniuk Natalie M. , Elias Darlene J. , Deguchi Hiroshi , Averell Patricia M. , Griffin John H. 
Published: July 2008

SummaryElevated plasma fibronectin levels occur in various clinical states including arterial disease. Increasing evidence suggests that atherothrombosis and venous thromboembolism (VTE) share common risk factors. To assess the hypothesis that high plasma fibronectin levels are associated with VTE, we compared plasma fibronectin levels in the Scripps Venous Thrombosis Registry for 113VTE cases vs. age and sex matched controls. VTE cases had significantly higher mean fibronectin concentration compared to controls (127% vs. 103%, p<0.0001); the difference was greater for idiopathic VTE cases compared to secondary VTE cases (133% vs. 120%, respectively). Using a cut-off of >90% of the control values, the odds ratio (OR) for association of VTE for fibronectin plasma levels above the 90th percentile were 9.37 (95% CI 2.73–32.2; p<0.001) and this OR remained significant after adjustment for sex, age, body mass index (BMI), factor V Leiden and prothrombin nt20210A (OR 7.60,95% CI 2.14–27.0; p=0.002). In particular, the OR was statistically significant for idiopathic VTE before and after these statistical adjustments. For the total male cohort, the OR was significant before and after statistical adjustments and was not significant for the total female cohort. In summary, our results suggest that elevated plasma fibronectin levels are associated with VTE especially in males, and extend the potential association between biomarkers and risk factors for arterial atherothrombosis and VTE.
Surgical evaluation of a recombinant factor VIII prepared using a plasma/albumin-free method: Efficacy and safety of Advate in previously treated patients
Authors: Shapiro Amy , Berntorp Erik , Pabinger Ingrid , Tarantino Michael , Retzios Antonio , Schroth Phillip , Ewenstein Bruce , Négrier Claude 
Published: July 2008

SummaryEvaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed recombinant FVIII (rAHF-PFM) administered by bolus or continuous infusion in haemophilia A patients undergoing surgery. Subjects ≥5 years of age with baseline FVIII:C ≤2%, and ≥150 prior FVIII exposure days were included in this prospective, international, open-label, uncontrolled clinical trial. rAHFPFM was administered perioperatively by bolus infusion (BI) or continuous infusion (CI) according to the standard use at the center to prevent bleeding complication. Both the surgeon and haematologist rated efficacy during hospitalization. Fifty-eight subjects underwent 65 surgical procedures (22 major haemor rhagic risk; 35 minor, 8 dental procedures). Bolus infusion was used exclusively in 47 procedures and continuous infusion, with or without supplemental bolus infusions, in 18.Haemostatic efficacy was assessed as excellent or good for 100% of intraoperative ratings (17 CI, 44 BI, 61 total procedures), and 100% of postoperative ratings performed at time of discharge (18 CI, 44 BI, 62 total procedures). Median total consumption of rAHF-PFM during hospitalization was 822 IU/kg/surgery with CI and 910 IU/kg/surgery with BI. Overall rAHF-PFM was well tolerated, and FVIII inhibitors were not detected. In conclusion, rAHF-PFM administered via continuous infusion or bolus injections is safe, non-immunogenic, and effective for perioperative hemostatic management in previously treated haemophilia A patients.
Plasminogen activator inhibitor type 2 inhibits cell surface associated tissue plasminogen activator in vitro
Authors: Lobov Sergei , Croucher David R. , Saunders Darren N. , Ranson Marie 
Published: July 2008

SummaryRegulation of cellular plasminogen activation is necessary for maintenance of tissue homeostasis. Despite increasing evidence for co-expression of tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type-2 (PAI-2;SERPINB2) under patho/physiological conditions, the inhibition of cell-bound tPAmediated plasminogen activation by PAI-2 has not been addressed. Here we show that PAI-2 can inhibit cell-bound tPA activity in vitro and thus prevent plasmin formation. We also examined the potential involvement in this inhibition of the annexin II heterotetramer (AIIt), one of the many well characterized cell-surface co/receptors for tPA and plasminogen that efficiently promotes plasminogen activation. This receptor was of interest because AIIt has also been shown to directly bind PAI-2. Characterization of these potential interactions using purified protein systems revealed that PAI-2 directly bound AIIt via the p11 (S100A10) subunit. However, PAI-2 prevented AIIt/tPA-mediated plasminogen activation by its classic serpin inhibitory activity rather than through competition with tPA/plasminogen for binding. Further analysis showed that PAI-2 inhibited cell bound tPA-induced plasmin activity in both an AIIt-dependent and -independent manner. These data open new possibilities for further investigations regarding the regulation of cellular plasmin generation in vivo, especially in tissues where PAI-2 and tPA may be co-expressed.
Adiponectin inhibits tissue factor expression and enhances tissue factor pathway inhibitor expression in human endothelial cells
Authors: Chen Yi-Jian , Zhang Li-Qun , Wang Guang-Ping , Zeng Hui , Lü Ben , Shen Xu-Liang , Jiang Zhi-Ping , Chen Fang-Ping 
Published: July 2008

SummaryTissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/ FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Adp inhibits inflammatory cytokine and adhesion molecules expression, and it can prevent endothelial dysfunction. In this study, we investigated the effects of Adp on tumor necrosis factor-α (TNF-α)-induced expression of TF and TFPI in human umbilical vein endothelial cells (HU-VECs), and the signaling transduction pathways involved. It was found that Adp significantly inhibited both TF protein expression and activity in TNF-α-stimulated HUVECs. In the meanwhile, it increased TFPI protein expression and activity for about two folds. Adp also inhibited TF mRNA expression induced by TNF-α, but had no effect on TFPI mRNA expression. The inhibitory effect of Adp onTNF-α-inducedTF expression was prevented by pretreatment with Rp-cAMPs, a PKA inhibitor. Adp increased intracellular cAMP content and PKA activity levels in a dose-dependent manner. Phosphorylation of IκB-α was decreased by Adp, but phosphorylation of p44/42MAPK, SAPK/ JNK, and p38MAPK were not affected. These results suggested that Adp inhibits TF expression through inhibition of a PKA dependent nuclear factor- κB (NF-κB) signaling pathway. It was also found that adiponectin promoted Akt and AMP-activated protein kinase phosphorylation. The inhibitory effect of Adp on TNF-α-induced TF synthesis was abrogated in part by pretreatment with the PI3kinase inhibitor LY 294002, suggesting that Akt activation might inhibit TF expression induced by TNF-α. The inhibitory effect of Adp is almost completely abrogated by inhibition of both the cAMP/PKA pathway and PI3K/Akt pathway. In conclusion, our data indicated that inhibition of NF-κB through stabilization of IκB-α and activation of Akt phosphorylation may mediate the inhibitory effect of Adp on TF expression; but the enhancement effect of Adp on the TFPI production might occur via translational rather than transcriptional regulation.
Transendothelial migration drives dissociation of plateletmonocyte complexes
Authors: Martins Paula A. , Mol Anita , Hordijk Peter L. , Zwaginga Jaap , van Gils Janine M. 
Published: July 2008

SummaryMonocytes and platelets are both crucially involved in atherogenesis. Importantly, activated platelets bound to circulating monocytes increase adhesion of the monocytes and thus mediate colocalization of both cell types at the vessel wall. We examined the fate of the platelets upon migration of these potentially pro-atherogenic platelet-monocyte complexes (PMC) across activated endothelium. Platelet-monocyte complex migration was studied both quantitatively by means of Transwell filters coated with endothelial cells, as well as qualitatively with different imaging techniques, and in the absence or presence of flow. Upon PMC transendothelial migration, platelets relocate with monocytic P-selectin glycoprotein ligand-1 (PSGL-1) to the rear of the monocyte, detach,and remain at the endothelial surface. Platelet dissociation appeared not to be due to reduced PSGL-1 expression or reduced platelet-binding capacity of the migrated monocytes. In addition, different endothelial matrix proteins with different platelet-binding capacities coated on the Transwell filter, instead of endothelial cells, did not affect PMC dissociation. In contrast, lowering the mechanical stress that PMC experience during transmigration prevented dissociation of platelets. In conclusion, PMC dissociate during transendothelial migration as a result of monocytic PSGL-1 redistribution and mechanical stress. PMC-mediated deposition of activated platelets at sites of vascular inflammation is likely relevant for cardiovascular disease progression or vascular regeneration.
Characterization of a novel mutation in the von Willebrand factor propeptide in a distinct subtype of recessive von Willebrand disease
Authors: Lanke Elsa , Kristoffersson Ann-Charlotte , Philips Malou , Holmberg Lars , Lethagen Stefan 
Published: July 2008

SummaryvonWillebrand factor (VWF) is a plasma protein that consists of a series of multimers of which the high-molecular-weight VWF multimers are the most potent in platelet adhesion and aggre-gation. The propeptide of theVWF (VWFpp) is known to be essential in the process of multimer assembly. Genetic studies were performed in a patient with a phenotype of vonWillebrand disease (VWD) characterized by very low plasma factorVIII and VWF levels and a VWF consisting of only a dimeric band and total absence of all multimers in plasma. The patient was found to be homozygous for the novel C570S mutation, caused by a 1709G>C transition in exon 14 of theVWF gene coding for the propeptide. Three asymptomatic relatives were found to be heterozygous. In-vitro mutagenesis and expression in COS-7 cells confirmed the detrimental effect of the mutation on VWF multimerization. Our findings show that the C570S mutation in the VWFpp abolishes multimerization of VWF. The mutation probably disrupts the normal configuration of the VWFpp, which is essential for correct orientation of the protomers and ultimately multimerization. The mutant amino acid is located in a region that is highly conserved across several species which underlines its critical role. This variant constitutes a distinct subtype of recessive 2AVWD with the exclusive presence of the dimeric form of VWF in plasma.
Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism
Authors: H.White Richard , Chan Wee-Shian , Zhou Hong , Ginsberg Jeffrey S. 
Published: July 2008

SummaryIt is not known whether women who develop venous throm-boembolism (VTE) during pregnancy have a higher or lower incidence of recurrent VTE than women with unprovokedVTE. The aim of the study was to compare the risk of recurrent VTE among women with pregnancy-associated VTE to women with unprovoked VTE. Hospital discharge data identified women age 18–46 years old with pregnancy-associated or unprovoked index VTE between 1994 and 2005. Risk of recurrent VTE was compared between six and 60 months after the index event using both age-matched comparison of disease-free survival and proportional hazard modelling, adjusting for age and other risk factors. The Kaplan-Meier incidence of recurrent VTE in 1085 women with pregnancy-associatedVTE was 5.8% versus 10.4% in 7625 women with unprovoked VTE (p=0.02). Twelve of 34 (35%) recurrent events in the pregnancy-associated group occurred during a subsequent pregnancy compared with 29 of 331 (8.7%) events in the unprovoked group (p<0.001).In the risk-adjusted multivariate model, women with pregnancy-associated VTE had a significantly lower risk of recurrent VTE (HR = 0.6, 95%CI=0.4–0.9). Overall, the incidence of recurrentVTE during subsequent pregnancies was higher in the pregnancy group, 21 of 465 (4.5%), than in the unprovoked group, 37 of 1353 (2.7%, RR=1.7, CI:1.0–2.8). Compared to women with unprovoked VTE, women with pregnancy-associated VTE had a significantly lower long-term risk of recurrent VTE but a higher risk of recurrent VTE during a subsequent pregnancy. These findings should be considered when decisions are made about VTE prophylaxis in women with a history of pregnancy-associated VTE.
More than one intracellular processing bottleneck delays the secretion of coagulation factor VII
Authors: Kristensen Claus , Steenstrup Thomas D. , Bolt Gert 
Published: July 2008

SummaryCoagulation factorVII (FVII) is a vitamin K-dependent glycoprotein that undergoes extensive post-translational modification prior to secretion. Secretion of FVII proteins from producer cells is a slow process. To identify bottlenecks for the transport of FVII through the secretory pathway of FVII-producing cells, we analysed the processing of intracellular FVII by pulse-chase of FVII producing CHO cells followed by radioimmuno precipitation, SDS-PAGE, and autoradiography. FVII was coprecipitated with GRP78 and vice versa for at least three hours after synthesis of the labelled FVII, suggesting that nascent FVII is retained in the endoplasmic reticulum (ER). Judged from barium citrate precipitation assay, gamma-carboxylation of the pulse-labelled FVII was a slow process requiring several hours and seemed to be the most important bottleneck in the intracellular processing of FVII. Nevertheless, FVII was not released from the cells immediately after gamma-carboxylation. Gamma-carboxylated FVII accumulated in the cells and migrated as a band with reduced mobility compared to uncarboxylated FVII. This shift in migration was caused by N-glycan processing in the Golgi complex. Thus, the release of FVII from producer cells is delayed by at least two bottlenecks. The major bottleneck appears to be gamma-carboxylation, which determines the rate of transport of FVII out of the ER. Another bottleneck retains FVII in the cells after processing of the N-glycans into complex chains. Cells with an intact gamma-carboxylation machinery appear to posses mechanisms that protect nascent FVII from intracellular degradation and keep FVII in the ER until it is gamma-carboxylated.
Incidence and causes of new-onset dyspnea in 3,719 patients treated with clopidogrel and aspirin combination after coronary stenting
Authors: Pokov Ilya , Kuliczkowski Wiktor , Vahabi Javad , Atar Dan , Serebruany Victor 
Published: July 2008

SummaryThe experimental oral antiplatelet agent AZD6140 causes dyspnea in randomized trials. Whether clopidogrel may also cause dyspnea remains controversial. We sought to define the incidence and causes of dyspnea in a large post-percutaneous coronary intervention (PCI) cohort based on open-labeled consecutive registry analysis of in-hospital charts and discharge diagnoses. Data were collected at six-month follow-up by means of telephone interviews or returned questionnaires during outpatient visits. Patients undergoing coronary stent implantation were loaded with 600 mg clopidogrel followed by 75 mg/daily in combination with 75–325 mg of aspirin daily for at least six months. Data from 3,719 patients were analyzed. Dyspnea was diagnosed in 157 (4.2%) patients caused by chronic obstructive pulmonary disease (n=43 or 27% of the dyspnea group), heart failure (n=30 or 19%), cancer (n=22 or 14%), pneumonia (n=17 or 11%); asthma (n=8 or 5%), pulmonary hypertension (n=8 or 5%);pericarditis (n=5 or 3%);cardiac arrhythmias (n=4 or 2.5%); pleural effusion (n=1), pulmonary embolism (n=1), anxiety (n=1), or unknown (n=17,or 11%).The incidence of dyspnea at six months in a post-stent cohort treated with aspirin and clopidogrel is low (4.2%). The majority of patients with dyspnea (140/157) exhibit a distinct underlying disease or condition, in contrast to only 17 patients (0.45% of total cohort) in whom the pathogenesis of dyspnea remained unidentified. These data closely match the frequency of dyspnea that was observed in the CAPRIE trial, suggesting that therapy with clopidogrel, and/or aspirin holds very small (if any) risk for dyspnea.
Cherchez les femmes: Were the yahad Celibates?
Authors: Regev Eyal 
Published: July 2008

AbstractThis article challenges the consensual view that the yahad were a celibate group by raising the following arguments: (1) The silence of the Community Rule regarding women and family cannot attest to celibacy, since there are no passages in the scrolls which refer to celibacy; (2) The passage in CD 7:3–10 should not be regarded as alluding to the celibacy of the yahad; (3) Comparisons with early-modern sects attest to the centrality of celibacy in the group ideology, hence it is impossible that celibacy was self-understood; (4) 4Q502 Ritual of Marriage mentions marriage, reproduction and children, and bears several lexical affinities with 1QS and other compositions of the yahad. Therefore, it should be related to the yahad. Consequently, the sweeping identification of the yahad with the (mainly celibate) Essenes seems problematic.
B'ym (Isa 11:15) = (Bīt-)Bahiān: Resolving an Ancient Crux
Authors: Demsky Aaron 
Published: July 2008

AbstractBa'yâm in Isaiah 11:15 is the Hebrew form of the dynastic eponym Bahiān, and refers in Isaiah to the head waters of the river Habur, also called the river Gozan.
PROCLAIMING THE CRUCIFIED CHRIST IN A BROKEN WORLD: An Asian Perspective
Authors: Chandrakantan A.J.V. 
Published: July 2008

AbstractThis article originally delivered as a keynote address at the IAMS Tenth International Conference in Hammanskraal, South Africa, is a passionate call to attend to the atrocities being committed against Tamils in the "broken world" of contemporary Sri Lanka. As the author puts it: "Disbelief and forgetfulness are the weapons of those who are opposed to humanity therefore to God. Forgetfulness is the antidote to truth and truthfulness of memory. Looking at this indescribable suffering of the innocent I have often felt that we all live in a world that has become unresponsive to the cries of the poor and under privileged. Such an attitude calls for solidarity among the victims and the oppressed. We also live in a world where a common agenda seems to unite all those who have chosen to be the enemies of humanity. It is our duty to fight this mute silence of the world with the power of the WORD. We should allow the word of Truth about the poor and innocent about voiceless women, men and children, to seek refuge and self-exile. Let us speak this word to the powers that be. All that we carry with us now is the memory of our life and that of the death of our fellow Tamils."