bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biphasic effect of pioglitazone on isolated human endothelial progenitor cells: Involvement of peroxisome proliferator-activated receptor-γ and transforming growth factor-β1
Authors: Hristov Mihail , Gümbel Denis , Tejerina Teresa , Redondo Santiago , Weber Christian 
Published: June 2007

SummaryEndothelial progenitor cells (EPCs) have been implicated in vascular repair and found to be functionally impaired in patients with diabetes. We evaluated the effects of the anti-diabetic drug pioglitazone on human EPC function and the involvement of PPAR-γ and TGF-β1. EPCs in culture were characterized at day 7 by the development of colony-forming units (CFUs) and flow cytometry assessment of differentiation marker (DiI-ac-LDL/lectin, KDR and CD31). Adhesion on fibronectin and fibrinogen in flow was analyzed as functional parameter. Treatment with pioglitazone for 72 hours increased the number of EPC-CFUs, DiI-ac-LDL+/lectin+, CD31+ and KDR+ EPCs at 1 μM but not at 10 μM. Since pioglitazone did not significantly alter proliferation and apoptosis in cultured EPCs, the increase in EPC number was most likely attributable to augmented adhesion and differentiation. Indeed, pioglitazone increased EPC adhesion in flow at 1 μM, an effect prevented by PPAR-γ and β2-integrin blockade. In contrast, pioglitazone did not promote EPC adhesion at 10 μM; however, increased adhesion became evident by co-incubation with a blocking TGF-β1 antibody. As determined by ELISA, pioglitazone induced a persistent increase in TGF-β1 secretion only at 10 μM when a significantly elevated expression of endoglin, the accessory receptor forTGF-β1, was also observed. Taken together, pioglitazone exerts biphasic effects on the function of isolated EPCs, causing a PPAR-γ-dependent stimulation at 1 μM and a TGF-β1-mediated suppression at 10 μM. These results may help to define optimal therapeutic doses of pioglitazone for improving endothelial dysfunction.
High frequency of factor V Leiden in surgical patients with symptomatic venous thromboembolism despite prophylaxis
Authors: Baba-Ahmed Mohamed , Le Gal Grégoire , Couturaud Francis , Lacut Karine , Oger Emmanuel , Leroyer Christophe 
Published: June 2007

SummaryAmong candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control “EDITH” study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by theAmerican College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2–18). Prophylaxis was judged as adequate in 116 cases (88.5 %) and in 129 controls (87.2 %) (p = 0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p = 0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomaticVTE occurring after surgery despite prophylaxis.
Functional promoter polymorphism in the VKORC1 gene is no major genetic determinant for coronary heart disease in Northern Germans
Authors: Eddine El Mokhtari Nour , Ivandic Boris , Müller Jens , Schreiber Stefan , Watzka Matthias , Nebel Almut , Oldenburg Johannes 
Published: June 2007

SummaryRecently, the C-allele of polymorphism rs2359612 (VKORC1: c.283+837C>T) in the VKORC1 gene has been reported to represent a major risk factor for coronary heart disease (CHD), stroke, and aortic dissection in Chinese patients. VKOR activity itself is the rate-limiting step in gamma-carboxylation of vitamin K-dependent coagulation factors (factors II, VII, IX, X, protein C, S, and Z) and proteins of calcium metabolism (matrix Gla protein and osteocalcin). Gamma-carboxylation is essential for the biological activity of these proteins that have been previously hypothesised to play a role in the pathogenesis of atherosclerosis. It was the objective of this study to analyse the VKORC1 genotype frequency in patients with CHD and controls from Northern Germany and to investigate the association of VKORC1 and CHD risk in patients with an European background. CHD paients (n = 901) and healthy controls (n = 521) were part of the PopGen biobank. Case and control samples were matched for ethnic and geographic origin, age and gender. After typing German CHD patients and control individuals, no evidence for a statistically significant association was detected between VKORC1 genotype and CHD phenotype. Also stratification for gender and myocardial infarction yielded no significant results. In conclusion, the discrepant association findings in Chinese and German populations may be explained by ethnic differences in genetic and perhaps environmental predisposition, modifying the polygenic CHD phenotype by interacting withVKORC1 variants and thus conferring disease susceptibility in some populations, but not in others.
Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: Inhibitory effects on receptormediated uPA activity in vitro and in vivo
Authors: Pass Jesper , Jögi Annika , Lund Ida , Rønø Birgitte , Rasch Morten , Gårdsvoll Henrik , Lund Leif , Ploug Michael , Rømer John , Danø Keld , Høyer-Hansen Gunilla 
Published: June 2007

SummaryBinding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR, potentiates plasminogen activation and localizes it to the cell surface. Focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. The interaction between uPA and uPAR therefore represents a potential target for anti-invasive cancer therapy. Inhibitors of the human uPA-uPAR interaction have no effect in the murine system. To enable in-vivo studies in murine cancer models we have now generated murine monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR-deficient mice with recombinant muPAR and screened for antibodies, which inhibit the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2, interfered with the interaction between muPAR and the amino-terminal fragment of muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell binding experiments using radiolabelled mATF, the maximal inhibition obtained with mR1 was 85% while that obtained with mR2 was 50%. The IC50 value for mR1 was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax toxins, requiring cell-bound muPA activity for its cytotoxity, a ~50% rescue of the cells could be obtained by addition of mR1. Importantly, in-vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice treated with a lethal dose of uPA-activatable anthrax toxins.
Venous thromboembolism during pregnancy or postpartum: Findings from the RIETE Registry
Authors: Blanco-Molina Angeles , Trujillo-Santos Javier , Criado Juan , Lopez Luciano , Lecumberri Ramón , Gutierrez Reyes , Monreal Manuel ,   for the RIETE Investigators
Published: June 2007

SummaryVenous thromboembolism (VTE) occurs infrequently during pregnancy, and issues concerning its natural history, prevention and therapy remain unresolved. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we compared the clinical characteristics and outcome for all enrolled pregnant and postpartum women with acuteVTE, and all non-pregnant women in the same age range. Up to May 2005, 11,630 patients were enrolled in RIETE, of whom 848 (7.3%) were women aged < 47 years. Of them, 72 (8.5%) were pregnant, 64 (7.5%) postpartum. Pregnant women presented less often with symptomatic pulmonary embolism (11%) than non-pregnant women (39%). VTE developed during the first trimester in 29 (40%) pregnant patients; in the second in 13; in the third in 30. Thrombophilia tests were m Venous thromboembolism (VTE) occurs infrequently during pregnancy, and issues concerning its natural history, prevention and therapy remain unresolved. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we compared the clinical characteristics and outcome for all enrolled pregnant and postpartum women with acuteVTE, and all non-pregnant women in the same age range. Up to May 2005, 11,630 patients were enrolled in RIETE, of whom 848 (7.3%) were women aged < 47 years. Of them, 72 (8.5%) were pregnant, 64 (7.5%) postpartum. Pregnant women presented less often with symptomatic pulmonary embolism (11%) than non-pregnant women (39%). VTE developed during the first trimester in 29 (40%) pregnant patients; in the second in 13; in the third in 30. Thrombophilia tests were m
Parnaparin, a low-molecular-weight heparin, prevents P-selectindependent formation of platelet-leukocyte aggregates in human whole blood
Authors: Di Fabio Giovannina , Barbanti Miriam , de Gaetano Giovanni , Benedetta Donati Maria , Cerletti Chiara , Maugeri Norma 
Published: June 2007

SummaryParnaparin, a low-molecular-weight heparin (LMWH), prevents platelet activation and interaction with polymorphonuclear leukocyte (PMN) in a washed cell system. The in-vitro effect of parnaparin was studied here on platelet-PMN aggregates formed with more physiologic approaches in whole blood, in parallel with unfractionated heparin and enoxaparin, another LMWH. Citrated blood from healthy subjects was stimulated: i) from passage through the “Platelet Function Analyzer” (PFA-100), a device that exposes blood to standardized high shear flow through collagen/ADP cartridges; ii) by collagen and ADP (2 and 50 µg/ml, respectively) added in combination under stirring in an aggregometer cuvette; iii) with recombinant Tissue Factor, to generate thrombin concentrations able to activate platelets without inducing blood clotting, or iv) the Thrombin Receptor Activating Peptide-6 (TRAP-6). Platelet P-selectin and platelet-PMN aggregates were measured by flow cytometry upon stimulation of blood. Fibrinogen binding to platelets and markers of PMN activation were also detected. Platelet P-selectin expression and platelet-PMN aggregate formation were induced in all four activation conditions tested. Parnaparin prevented in a concentration-dependent manner (0.3–0.8 IUaXa/ml) the expression of P-selectin and the formation of mixed aggregates, while the two reference heparin preparations had a much weaker effect. Platelet fibrinogen binding and PMN activation markers (fibrinogen binding, CD11b and CD40) were also prevented by parnaparin. These data extend in more physiological systems of platelet activation, the anti-inflammatory profile of parnaparin, previously reported in washed cells. The greater effect of parnaparin, as compared to the reference heparins, could be due to chemico-physical differences possibly unrelated to their anticoagulant effect.
Calcium-binding sites of the thrombin-thrombomodulin-protein C complex: Possible implications for the effect of platelet factor 4 on the activation of vitamin K-dependent coagulation factors
Authors: Yang Likui , Rezaie Alireza 
Published: June 2007

SummaryThe Ca2+-dependence of protein C activation by thrombin in complex with thrombomodulin (TM) containing chondroitin sulfate (CS) exhibits saturation at ~0.5–1 mM Ca2+, but withTM lacking CS, it has a distinct optimum at ~0.1 mM Ca2+. Since the substrate protein C has multiple Ca2+-binding sites, and the cofactor TM also interacts with Ca2+, the basis for differences in Ca2+ effect on protein C activation by thrombin in complex with TM containing or lacking CS is not known. In this study, by using full-length and Gla-domainless mutants of protein C whose activation by thrombin is independent of either Ca2+ or both Ca2+ and TM, we demonstrate that i) the Ca2+ occupancy of a high-affinity binding site in TM is essential for the high-affinity interaction of the cofactor with thrombin, ii) the Ca2+ occupancy of a binding site (KD ~50 μM) in the catalytic domain of protein C is required for the substrate recognition by the thrombin-TM complex, however, at this concentration of Ca2+ the Gla domain of protein C is not folded properly and thus interacts with exosite-2 of thrombin in complex with TM that lacks CS but not withTM that contains CS, and finally iii) platelet factor 4 can nonspecifically interact with the Gla domain of protein C and other coagulation factors to influence their activation only at subphysiological concentrations of Ca2+.
Characterisation of five factor XI mutations
Authors: Dai Letian , Clarke John , Bolton-Maggs Paula , Savidge Geoffrey , Alhaq Anwar , Mitchell Michael 
Published: June 2007

SummaryA large scale factor XI (FXI) mutation screening program identified a number of novel candidate mutations and previously reported mutations and polymorphisms. Five potential missense mutations were selected for further study; these included two novel missense mutations – Met-18Ile (p.Met1Ile) and Met102Thr (p.Met120Thr), two previously reported missense mutations – Tyr133Ser (Tyr151Ser) and Thr575Met (Thr593Met), and one amino acid substitution previously reported as a polymorphism – Arg378Cys (Arg396Cys). The substitutions were recreated by the site-directed mutagenesis of a FXI cDNA and stably expressed in a BHK-570 cell line. Subsequent analysis of both the conditioned media and cell lysates showed that three of the substitutions, Met-18Ile, Met102Thr andTyr133Ser, prevented secretion of the mutated protein from the transfected cell line, resulting in a cross-reactive material negative (CRM-) phenotype. The remaining two mutants, Thr575Met and Arg378Cys, secreted significant levels of FXI into the conditioned media; however, these mutant FXIs were shown to have negligible factor IX activation activity in an APTT based assay. These results confirmed all five of the missense mutations as being causative of factor XI deficiency, despite one having been previously reported as a polymorphism (Arg378Cys) and one (Tyr133Ser) as a mild mutation – FXI:C 38 U/dl in a homozygous patient.
Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from isolated peripheral blood mononuclear cells
Authors: Kierulf Peter , Sandset Per , Klingenberg Olav , Joø Gunn , Godal Hans , Skjønsberg Ole , Jensen Torstein 
Published: June 2007

SummaryFibrinogen in plasma includes three main fractions; high-molecular- weight (HMW) -fibrinogen, low-molecular-weight (LMW) -fibrinogen, and very-low-molecular-weight (LMW`) -fibrinogen. During acute-phase conditions, plasma fibrinogen levels and the HMW-/LMW-fibrinogen ratio increase rapidly due to increased synthesis of HMW-fibrinogen. The consequences of elevated plasma fibrinogen levels and local deposition of fibrin in inflammatory tissues observed during acute-phase conditions are not clear.We wanted to investigate proinflammatory effects of fibrinogen and fibrin on peripheral blood mononuclear cells (PBMC) as reflected by altered mRNA expression and synthesis of the proinflammatory cytokines IL-6,TNF- α and IL-1 β, and to explore the significance of altered HMW-/LMW-fibrinogen ratio. PBMC were isolated from whole blood using Lymphoprep® . HMW-fibrinogen was separated from unfractioned fibrinogen by ammonium sulphate precipitation. Cells were incubated with unfractioned fibrinogen, HMW-fibrinogen or fibrin. Cytokine levels in cell lysates were determined using ELISA assays. Real-time PCR was used for mRNA quantification. We found that fibrinogen significantly increased mRNA levels, and induced synthesis of the proinflammatory cytokines IL-6 and TNF- α in PBMC in a dose dependent manner. Median (25, 75 percentile) IL-6 and TNF- α concentrations were 12 (5, 40) pg/ ml and 16 (0,61) pg/ml,respectively.Median mRNA quantity was increased 12.3– (6.6, 48.6) and 1.7– (1.5, 6.5) fold for IL-6 and TNF- α compared to controls.The stimulatory effect of unfractioned fibrinogen was not significantly different from HMW-fibrinogen. Fibrinogen and fibrin were equally effective in promoting cytokine synthesis from PBMC.The results support that fibrin and fibrinogen may actively modulate the inflammatory process by inducing synthesis of proinflammatory cytokines from PBMC.
Rivaroxaban for thromboprophylaxis after orthopaedic surgery: Pooled analysis of two studies
Authors: Eriksson Bengt , Bauer Kenneth , Borris Lars , Dahl Ola , Gent Michael , Haas Sylvia , Homering Martin , Huisman Menno , Kakkar Ajay , Kälebo Peter , Kwong Louis , Misselwitz Frank , Turpie Alexander , Fisher William 
Published: June 2007

SummaryRivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N=722), and one in patients undergoing total knee replacement (TKR; N=621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5–9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1–24.4% of per-protocol patients receiving rivaroxaban 5–60 mg, and 27.8% receiving enoxaparin (n=914). There was a flat dose response relationship between rivaroxaban and total VTE (p=0.39). Major bleeding (safety population, n=1,317) increased dose-dependently with rivaroxaban (p<0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5–20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery.
Eosinophilic synovitis of the tarsocrural joint in a horse
Authors: Climent F. , Cuenca R. , Prades M. , Carmona J. U. 
Published: June 2007

SummaryEosinophilic synovitis (ES) is a rare disease described in human and veterinary medicine. Only three cases have been reported in the horse. A case of tarsocrural synovitis in an Hispano-Arabian gelding is presented in this report. The patient presented with severe joint effusion and lameness of the right tarsocrural joint on admission. Synovial fluid analysis revealed an increased WBC of 12800 leukocytes/microliter with 76% of eosinophils. Lavage of the diseased joint and medical treatment with antibiotics and non-steroidal anti-inflammatory drugs produced remission of the clinical problem.
Construction and characterization of a full-length cDNA library for the wheat stripe rust pathogen (Puccinia striiformis f. sp. tritici)
Authors: Ling Peng , Wang Meinan , Chen Xianming , Campbell Kimberly Garland 
Published: June 2007

Abstract

Background

Puccinia striiformis is a plant pathogenic fungus causing stripe rust, one of the most important diseases on cereal crops and grasses worldwide. However, little is know about its genome and genes involved in the biology and pathogenicity of the pathogen. We initiated the functional genomic research of the fungus by constructing a full-length cDNA and determined functions of the first group of genes by sequence comparison of cDNA clones to genes reported in other fungi.

Results
A full-length cDNA library, consisting of 42,240 clones with an average cDNA insert of 1.9 kb, was constructed using urediniospores of race PST-78 of P. striiformis f. sp. tritici. From 196 sequenced cDNA clones, we determined functions of 73 clones (37.2%). In addition, 36 clones (18.4%) had significant homology to hypothetical proteins, 37 clones (18.9%) had some homology to genes in other fungi, and the remaining 50 clones (25.5%) did not produce any hits. From the 73 clones with functions, we identified 51 different genes encoding protein products that are involved in amino acid metabolism, cell defense, cell cycle, cell signaling, cell structure and growth, energy cycle, lipid and nucleotide metabolism, protein modification, ribosomal protein complex, sugar metabolism, transcription factor, transport metabolism, and virulence/infection.

Conclusion
The full-length cDNA library is useful in identifying functional genes of P. striiformis.
Neointimal hyperplasia persists at six months after sirolimus-eluting stent implantation in diabetic porcine
Authors: Zhang Qi , Lu Lin , Pu LiJin , Zhang RuiYan , Shen Jie , Zhu ZhengBing , Hu Jian , Yang ZhenKun , Chen QiuJin , Shen WeiFeng 
Published: June 2007

Abstract

Background
Observational clinical studies have shown that patients with diabetes have less favorable results after percutaneous coronary intervention compared with the non-diabetic counterparts, but its mechanism remains unclear. The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process.

Methods
Diabetic porcine model was created with an intravenous administration of a single dose of streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation served as controls (control group). At 6 months, the degree of neointimal hyperplasia was determined by repeat coronary angiography, intravascular ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-α protein level in the aortic intima was evaluated by Western blotting, and TNF-α, interleukin (IL)-1β and IL-6 mRNA levels were assayed by reverse transcription and polymerase chain reaction.

Results
The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were comparable between the two groups. At 6-month follow-up, the degree of in-stent restenosis (40.4 ± 24.0% vs. 20.2 ± 17.7%, p < 0.05), late lumen loss (0.33 ± 0.19 mm vs. 0.10 ± 0.09 mm, p < 0.001) by quantitative angiography, percentage of intimal hyperplasia in the stented area (26.7 ± 19.2% vs. 7.3 ± 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 ± 0.76 mm2 vs. 0.41 ± 0.18 mm2, p < 0.05) by histological examination were significantly exacerbated in the diabetic group than those in the controls. Significant increases in TNF-α protein and TNF-α, IL-1β and IL-6 mRNA levels were observed in aortic intima in the diabetic group.

Conclusion
Neointimal hyperplasia persisted at least up to 6 months after SES implantation in diabetic porcine, which may be partly related to an exaggerated inflammatory response within the blood vessel wall. Our results provide theoretical support for potential direct beneficial effects of anti-diabetic and anti-inflammation medications in reducing the risk of restenosis after stenting.