bluuebunny/crossref_metadata_2025 huggingface dataset:
Body Lipids of Guinea Pigs Exposed to Different Dietary Fats from Mid-Gestation to 3 Months of Age
Authors: Gurr Michael I. , Robinson Paul , Kirtland Janet , Widdowson Elsie M.
Published: November 2008

Pregnant guinea pigs were fed one of three diets: a ‘control’ low-fat diet, or a high-fat diet containing maize oil or beef dripping. Offspring were reared on the same diet as their mothers and when they were 3 months old, the fatty acid compositions of the lipids of the adipose tissue, blood plasma, liver and muscle were analysed. The proportion of linoleic acid was elevated in both the storage triglycerides and the tissue phosphoglycerides of animals fed ‘maize’ diet whereas in the ‘beef’ group the proportion of oleic acid was significantly elevated compared with controls. A substantial part of these diet-induced changes in tissue fatty acid composition had occurred by the time the animal was born; only minor changes took place in the subsequent 3 months of feeding.
Enhancement of Intestinal Sugar Transport by Rats Fed Sucrose as Compared to Starch
Authors: Reiser Sheldon , Hallfrisch Judith , Putney John , Lev Frances
Published: November 2008

The weight and length of the small intestine and the intestinal transport of sugars and amino acids were determined in Wistar rats fed diets containing either 54% starch or sucrose ad libitum or in meals. The relative weight and length of the small intestine were greater after meal feeding than after ad libitum feeding. Regardless of the pattern of feeding, transport of 1 mM glucose, 1 mM α-methylglucose, 5 mM fructose, and 30 mM sucrose was significantly greater in sucrose-fed rats than in starch-fed rats. The transport of 30 mM maltose, 30 mM lactose, 1 mM leucine, and 1 mM lysine was not affected by diet. The pattern of feeding employed neither generally affected the transport rates of the sugars or amino acids nor modified the greater sugar transport exhibited by the sucrose-fed rats.
Risks and benefits of transcatheter thrombolytic therapy in patients with splanchnic venous thrombosis
Authors: Smalberg Jasper H. , Spaander Manon V. M. C. W. , Jie Kon-Siong G. , Pattynama Peter M. T. , van Buuren Henk R. , van den Berg Bart , Janssen Harry L. A. , Leebeek Frank W. G.
Published: November 2008

Transcatheter local thrombolytic therapy in patients with acute, extended splanchnic venous thrombosis is controversial. Here we present our single-center experience with transcatheter thrombolytic therapy in these patients. All consecutive patients (n=12) with acute,extended splanchnic venous thrombosis who underwent transcatheter thrombolytic therapy in our hospital, were included in this study. Thrombolytic therapy was successful for three thrombotic events and partially successful for four thrombotic events.Two patients developed minor procedure-related bleeding (17%).Six patients (50%) developed major procedure-related bleeding, with a fatal outcome in two. Transcatheter thrombolytic therapy in patients with acute, extended splanchnic vein thrombosis is found to be associated with a high rate of procedure-related bleeding. Therefore, thrombolysis should be reserved for patients in whom the venous flow cannot be restored by using conventional anticoagulant therapy or stent placement across the thrombosed vessel segment.

H.L.A. Janssen and F.W.G. Leebeek are both Clinical Fellows of the Netherlands Organisation for Scientific Research (NWO).
High glucose conditions induce upregulation of fractalkine and monocyte chemotactic protein-1 in human smooth muscle cells
Authors: Dragomir Elena , Manduteanu Ileana , Calin Manuela , Gan Ana , Stan Daniela , Koenen Rory , Weber Christian , Simionescu Maya
Published: November 2008

The major complication of diabetes mellitus is accelerated atherosclerosis that entails an inflammatory process, in which fractalkine and monocyte chemotactic protein-1 (MCP-1) play a key role.We investigated the effect of diabetes-associated high glucose (HG) on these chemokines and signalling mechanisms involved in human aortic smooth muscle cells (SMC). Exposure of SMC to HG resulted in an increase of fractalkine and MCP-1 expression and the activated mitogen-activated protein kinase (MAPK) signalling pathway, a process associated with elevated oxidative stress.Transfection with decoy oligodeoxynucleotides identified the involvement of transcription factors activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) in the observed up-regulation of chemokines. The MAPK inhibitors blocked the phosphorylation of IkBα and c-jun, indicating the role of MAPK in NF-κB and AP-1 activation in SMC under HG conditions.The up-regulation of MCP-1 and fractalkine was associated with increased adhesive interactions between HG-exposed SMC and monocytes. Treatment of HG-exposed SMC with peroxisome proliferator-activated receptors α (PPAR α ) activators (fenofibrate and clofibrate) resulted in a reduction of mRNA and protein expression of MCP-1 and fractalkine.In conclusion, HG upregulates the expression of fractalkine and MCP-1 in SMC leading to increased monocyte-SMC adhesive interactions by a mechanism involving activation of MAPK, activator protein-1 (AP-1) and NF-κB. The increased expression of these two pro-inflammatory chemokines and the ensuing increased adhesion between SMC and monocytes may trigger the inflammatory process associated with further vascular complications of diabetes.
Recombinant production of a hybrid plasminogen activator composed of surfactant protein B and low-molecular-weight urokinase
Authors: Ruppert Clemens , Mahavadi Poornima , Wygrecka Malgorzata , Weaver Timothy E. , Magdolen Viktor , Idell Steven , Preissner Klaus T. , Seeger Werner , Günther Andreas , Markart Philipp
Published: November 2008

Intraalveolar fibrin deposition is commonly observed during acute inflammatory and chronic interstitial lung diseases and may contribute to impairment of surfactant function and gas exchange.We recently described a chemically cross-linked chimeric protein consisting of surfactant protein (SP)-B and urokinase (uPA) for targeting alveolar fibrin under conditions such as acute respiratory distress syndrome (ARDS) or lung fibrosis.We now investigated the feasibility of a recombinant production of a fusion protein encoding mature SP-B and uPA, termed SPUC. Four different SPUC proteins (N-term SP-B/C-term uPA, N-term uPA/C-term SP-B, each +/− His-tag) were prepared by cloning the cDNA encoding mature SP-B and low-molecular-weight uPA into the expression vector pcDNA3.1. CHO-cells were transfected with the constructs and the supernatant and cell lysates were analyzed for expression of SPUC.Using a chromogenic substrate assay uPA activity was found in supernatants and lysates of transfected cells with highest activities related to the N-term uPA/C-term SP-B (+/− His-tag) construct in supernatants 48h after transfection.Casein enzymography showed an enzymatically active fusion proteins with a molecular weight of ∼ 42 kDa in the supernatant of cells transfected with the N-term uPA/C-term SP-B (+/− His-tag) construct,but only a minor activity with the N-term SP-B/C-term uPA construct. The N-term uPA/C-term SP-B construct was also shown to possess higher resistance towards inhibition by plasminogen activator inhibitor-1.We conclude that recombinant production of a fusion protein consisting of mature SP-B and uPA is feasible, when the SP-B moiety is fused to the C-terminus of urokinase.
Enzymatically hydrolyzed low-density lipoprotein modulates inflammatory responses in endothelial cells
Authors: Fenske Dominic , Dersch Katrin , Lux Cornelia , Zipse Lisa , Suriyaphol Prapat , Dragneva Yolantha , Han Shan-Rui , Bhakdi Sucharit , Husmann Matthias
Published: November 2008

There is evidence that low-density lipoprotein (LDL) is modified by hydrolytic enzymes,and that the product (E-LDL) induces selective production of interleukin 8 (IL-8) in endothelial cells. Since nuclear factor-kappaB (NF-κB) is a major regulator of IL-8 transcription, we studied its activation in endothelial cells treated with E-LDL. Unexpectedly,the modified lipoprotein not only failed to activate NF-κB, but completely blocked its activation by tumour necrosis factor-alpha (TNF-α) in EA.hy926-cells, as assessed by electrophoretic mobility shift assays and immunofluorescence. Inhibition occurred upstream of NF-κB translocation, as inhibitor of NF-κB- (IκB)-phosphorylation was suppressed by E-LDL. In contrast to NF-κB,transcription factor activator protein-1 (AP-1) proved to be activated. Removal of free fatty acids present in E-LDL obliterated both activation of AP-1 and inhibition of NF-κB. Chromatin immunoprecipitation revealed that phosphorylated c-jun, but not NF-κBp65 bound to the natural IL-8 promoter. Production of endothelial IL-8 and simultaneous modulation of NF-κB in response to hydrolyzed LDL might serve to protect the vessel wall and promote silent removal of the insudated lipoprotein.
Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon
Authors: Brouwers Jacobus R. B. J. , Schalekamp Tom , Wilffert Bob , Beinema Maarten
Published: November 2008

Coumarin oral anticoagulant drugs have proven to be effective for the prevention of thromboembolic events. World-wide, warfarin is the most prescribed drug. In Europe, acenocoumarol and phenprocoumon are also administered. Yet it has been proven that variant alleles of theVKORC1 and CYP2C9 genotypes influence the pharmacokinetics and pharmacodynamics of these drugs. The combination of these two variant genotypes is a major cause of the inter-individual differences in coumarin anticoagulant drug dosage. Individuals who test positive for both variant genotypes are at increased risk of major bleeding. The impact of the CYP2C9 andVKORC1 genotype is most significant during the initial period of coumarin anticoagulant therapy. The effect ofVKORC1 allelic variants is relatively similar for all three VKAs. The CYP2C9 polymorphism is associated with delayed stabilisation for coumarin anticoagulants. The effects of CYP2C9 polymorphisms on the pharmacokinetics and anticoagulant response are least pronounced in the case of phenprocoumon. In the long term, patients using phenprocoumon have more often international normalised ratio (INR) values in the therapeutic range, requiring fewer monitoring visits. This leads us to conclude that in the absence of pharmacogenetic testing, phenprocoumon seems preferable for use in long-term therapeutic anti-coagulation. Pharmacogenetic testing before initiating coumarin oral anticoagulants may add to the safety of all coumarin anticoagulants especially in the elderly receiving multiple drugs.
Anti-apoptotic roles of plasminogen activator inhibitor-1 as a neurotrophic factor in the central nervous system
Authors: Koyanagi Satoru , Kuramoto Yukako , Kimura Masahiko , Oda Masatoshi , Kozako Tomohiro , Hayashida Satoru , Shimeno Hiroshi , Soeda Shinji
Published: November 2008

Plasminogen activator inhibitor-1 (PAI-1), a member of the ser-pin gene family, is the primary inhibitor of urokinase-type and tissue-type PA s.PA I-1 plays an important role in the process of peripheral tissue remodeling and fibrinolysis through the regulation of PA activity. This serpin is also produced in brain tissues and may regulate the neural protease sequence in the central nervous system (CNS), as it does in peripheral tissues. In fact, PA I-1 mRNA is up-regulated in mouse brain after stroke.The serpin activity of PA I-1 helps to prevent tissue-type PA -induced neuron death.However, we have previously found that PAI-1 has a novel biological function in the CNS: the contribution to survival of neurites on neurons. In neuronally differentiated rat pheochromocytoma (PC-12) cells, a deficiency of PA I-1 in vitro caused a significant reduction in Bcl-2 and Bcl-XL mRNAs and an increase in Bcl-XS and Bax mRNAs.The change in the balance between mRNA expressions of the anti- and pro-apoptotic Bcl-2 family proteins promoted the apoptotic sequence: cas-pase-3 activation, cytochrome c release from mitochondria and DNA fragmentation. Our results indicate that PA I-1 has an antiapoptotic role in neurons.PAI-1 prevented the disintegration of the formed neuronal networks by maintaining or promoting neuroprotective signaling through the MAPK/ ERK pathway, suggesting that the neuroprotective effect of PAI-1 is independent of its action as a protease inhibitor. This review discusses the neuroprotective effects of PA I-1 in vitro, together with the relevant data from other laboratories. Special emphasis is placed on its action on PC-12 cells.
Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins
Authors: Kruithof Egbert K. O.
Published: November 2008

Elevated plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1), also named serpin E1, are encountered in patients with thrombophilia, atherosclerosis, septicemia and the metabolic syndrome and may be associated with an increased risk of complications. Expression of PAI-1 is increased by inflammatory stimuli and decreased by statins, drugs widely used in patients with cardiovascular disease. Increased expression of PAI-1 by inflammatory stimuli is mediated by a large variety of signal transduction pathways, which include the NF-κB and MAP kinase pathways. The downregulating effect of statins on PAI-1 expression is dependent on the inhibition of Rho family proteins and may involve an activation of PI-3 kinase/Akt signaling pathways. In this review we summarize the findings on the effect of inflammation and statins on PAI-1 expression.
Integration of non-SMAD and SMAD signaling in TGF-β1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells
Authors: Samarakoon Rohan , Higgins Paul J.
Published: November 2008

Overexpression of plasminogen activator inhibitor-1 (SER-PINE1, PAI-1), the major physiological inhibitor of pericellular plasmin generation, is a significant causative factor in the progression of vascular disorders (e.g. arteriosclerosis, thrombosis, perivascular fibrosis) as well as a biomarker and a predictor of cardiovascular-disease associated mortality. PAI-1 is a temporal/ spatial regulator of pericellular proteolysis and ECM accumulation impacting, thereby, vascular remodeling, smooth muscle cell migration, proliferation and apoptosis. Within the specific context of TGF-β1-initiated vascular fibrosis and neointima formation, PAI-1 is a member of the most prominently expressed subset of TGF-β1-induced transcripts. Recent findings implicate EGFR/pp60c-src
→MEK/ERK1/2 and Rho/ROCK→SMAD2/3 signaling in TGF-β1-stimulated PAI-1 expression in vascular smooth muscle cells. The EGFR is a direct upstream regulator of MEK/ERK1/2 while Rho/ROCK modulate both the duration of SMAD2/3 phosphorylation and nuclear accumulation. E-box motifs (CACGTG) in the PE1/PE2 promoter regions of the human PAI-1 gene, moreover, are platforms for a MAP kinase-directed USF subtype switch (USF-1→USF-2) in response to growth factor addition suggesting that the EGFR→MEK/ERK axis impacts PAI-1 expression, at least partly, through USF-dependent transcriptional controls. This paper reviews recent data suggesting the essential cooperativity among the EGFR→MAP kinase cascade, the Rho/ROCK pathway and SMADs in TGF-β1-initiated PAI-1 expression. The continued clarification of mechanistic controls on PAI-1 transcription may lead to new targeted therapies and clinically-relevant options for the treatment of vascular diseases in which PAI-1 dysregulation is a major underlying pathogenic feature.
Modulation of tissue factor and tissue factor pathway inhibitor-1 by neutrophil proteases
Authors: Steppich Birgit A. , Seitz Isabell , Busch Gabi , Stein Andreas , Ott Ilka
Published: November 2008

During systemic inflammation, neutrophil activation is accompanied by endothelial cell damage and hypercoagulability. Activated neutrophils release serine proteases that participate in tissue injury.We sought to investigate the effects of neutrophil proteases on proinflammatory and procoagulant changes in endothelial cells.The effects of elastase (HNE), cathepsin G (CG), and proteinase 3 (PR3) on expression of tissue factor (TF) and tissue factor pathway inhibitor-1 (TFPI) were examined in human umbilical vein endothelial cells. Flow cytometry demonstrated that these proteases proteolytically degraded endothelial cell-bound TFPI. TFPI mRNA expression was reduced by HNE and CG. PR3, but not HNE or CG, increased surface expression of TF and TF mRNA.Yet, increased TF expression did not enhance TF activity suggesting induction of encrypted TF. Using antibodies and siRNA to inhibit and silence PAR-1 and PAR-2, we observed that PR3 upregulation of TF is at least in part mediated by PAR-1.Although CG and HNE cleaved PAR-1, antibody reactivity to the PAR-1 hirudin-like sequence demonstrated inactivating cleavage, accounting for the selective ability of PR3 to induce PAR-1-mediated procoagulant effects.This was supported by induction of p42/44 MAPK by PR3. In conclusion, PR3 degradation of TFPI increases the procoagulant activity of endothelial cells. Release of PR3 after neutrophil activation may represent an important step in neutrophil-mediated vascular injury.
Transcriptional regulation of the plasminogen activator inhibitor type 1 – with an emphasis on negative regulation
Authors: Nagamine Yoshikuni
Published: November 2008

By inhibiting plasminogen activators uPA and tPA, inducing uPAuPAR internalization and interfering with the interaction between extracellular matrix protein vitronectin and αvβ3 integrin, plasminogen activator inhibitor type 1 (PAI-1) is active in the regulation of various biological processes involving extracellular proteolysis and tissue remodeling. PAI-1 is expressed in many cell types under the control of a variety of signals, depending on cell type. The most prominent and important of these signals are TGFβ, hypoxia and insulin. Although the signaling pathways were largely elucidated, recent investigations have revealed more complicated aspects. The pathways interact at the level of both transcription factors and regulatory elements on the promoter. Furthermore, the engagement of negative factors in these pathways has been shown to be important, adding complexity and versatility to PAI-1 gene regulation.
Heparin-induced thrombocytopenia (HIT): Clinical and economic outcomes
Authors: Piovella Chiara , Fanikos John , Labreche Matthew , Lin Jay , Goldhaber Samuel Z. , Baroletti Steven
Published: November 2008

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction that occurs following exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH).HIT with thrombosis (HITT) can cause devastating venous thromboembolism or arterial clots, prolonged hospitalization, and increased costs. To explore the economic and clinical implications of HIT and HITT, we initiated a single-center patient registry. In this report, we describe patient characteristics, comorbidities, management strategies, clinical outcomes, and costs. We enrolled 349 hospitalized patients with an enzyme immunoassay-confirmed diagnosis of HIT over a 40-month period. Patients were assessed for the primary outcome of 30-day mortality, as well as baseline characteristics, development of thrombosis, and the economic impact of HIT. The primary outcome measure was 30-day mortality and occurred in 58 (16.6%) patients, 40 (15.3%) in the HIT group versus 18 (20.7%) in the HITT group (p=0.25).The frequency of HIT was greater in patients exposed to UFH than in patients exposed to LMWH (0.8% vs. 0.2%, respectively, p<0.001). Both HIT and HITT patients who were exposed to UFH had higher hospital costs than those exposed to LMWH ($113,100 vs. $56,352, respectively, p<0.001). HIT remains an important clinical problem with a high mortality rate and significant cost, regardless of development of thrombosis. Prospective controlled trials need to be conducted to determine the optimal strategy to reduce the frequency of HIT.
Melanoma cell adhesion can be blocked by heparin in vitro: Suggestion of VLA-4 as a novel target for antimetastatic approaches
Authors: Simonis Dirk , Bendas Gerd , Fritzsche Juliane
Published: November 2008

The clinical benefit of heparin in cancer patients to prolong survival can be attributed to non-anticoagulant mechanisms. Since adhesion molecules are crucially involved in tumour cell metastasis, their inhibition offers an attractive approach for interfering with the metastatic cascade. Heparin is known to attenuate metastasis in a selectin-dependent manner and possessesa variety of additional effects that are thought to influence tumour cell dissemination, proliferation, and angiogenesis. We investigated the adhesion behaviour of B16F10 melanoma cells in vitro regarding selectin- and VLA-4/VCAM-1-mediated binding to get an insight into underlying mechanisms of melanoma cell metastasis. We show that B16F10 cells display binding ability to P- and L-selectin as well as to isolated platelets. In contrast, B16F10 cells did not adhere to immobilized P-selectin under flow. This contributes to recent findings that elucidate a major role of platelet P-selectin for microemboli formation and thus, facilitating metastasis. In contrast, B16F10 cells adhered to endothelial cells under flow, which could partly be inhibited by a function-blocking anti-VCAM-1 mAb. To emphasizeVCAM-1 function, we analyzed cell adhesion at immobilizedVCAM-1 and observed an integrin dependency. Inhibition experiments reveal that heparin influences VLA-4-mediated binding pathways. By a combination of different techniques we prove that the site of heparin action is ratherVLA-4 thanVCAM-1.To our knowledge, this is the first time that heparin is shown to interfere with theVLA-4/VCAM-1 interaction leading to the suggestion of a novel heparin target. Our results may contribute to the understanding of how heparin exerts its anti-metastatic activity.
Thrombotic events in high risk patients are predicted by evaluating different pathways of platelet function
Authors: Marcucci Rossella , Paniccia Rita , Giusti Betti , Fedi Sandra , Antonucci Emilia , Buonamici Piergiovanni , Antoniucci David , Gensini Gian , Abbate Rosanna , Gori Anna
Published: November 2008

A higher rate of clinical events in poor clopidogrel and/or aspirin responders was documented by using different methods to measure platelet function, but no conclusive data about the appropriate methodology to explore platelet reactivity are available.A total of 746 patients included in the cohort of the RECLOSE trial who had successful drug-eluting stent implantation were assessed for post-treatment residual platelet reactivity (RPR) in platelet-rich plasma by 10 µM adenosine 5’-diphosphate (ADP),1 mM arachidonic acid (AA) and 2 µg/ml collageninduced platelet aggregation and in whole blood by the PFA-100 system. At six-month follow-up, RPR by two stimuli (ADP and AA or ADP and collagen) and by three stimuli (ADP,AA and collagen) is significantly associated with higher percentage of primary (definite or probable stent thrombosis) and secondary cardiac mortality and stent thrombosis) end-points than RPR by ADP,AA, collagen and PFA-100 system.According to the primary and secondary end points, the specificity values for RPR identified by two (ADP and AA: 94%;ADP and collagen: 97%) and three stimuli were higher with respect to RPR by ADP (88%), or RPR by AA (83%) or RPR by collagen (90%).The positive likelihood ratio values of RPR by three stimuli (9.55) or of RPR by ADP and collagen (8.08) were higher than those of RPR by ADP (2.59), byAA (2.05), by collagen (4.73), or by PFA-100 (2.63).This prospective study documents that the evaluation of platelet reactivity addressed to identify patients at risk of thrombotic events on dual antiplatelet treatment has to be carried out by methods able to explore different pathways.
Biobanks and the search for predictive biomarkers of local and systemic outcome in atherosclerotic disease
Authors: Hurks Rob , Peeters Wouter , Derksen Wouter , Hellings Willem , Hoefer Imo , Moll Frans , de Kleijn Dominique , Pasterkamp Gerard
Published: November 2008

Multiple risk factors have been associated with progression of atherosclerosis. To identify the individual patient who is at risk for disruption of a vulnerable plaque, leading to a cardiovascular event, remains a major challenge. Current screening methods, based on traditional risk factors, do not allow risk stratification on an individual level. The discovery of new biomarkers would aid in identifying specific patient groups at risk for adverse cardiovascular events due to atherosclerotic disease progression. The current definition of the vulnerable plaque, e.g. atheromatous inflammatory plaque with a thin fibrous cap, has been based on cross-sectional post-mortem studies. The predictive value of these histological characteristics of the vulnerable plaque is likely to be low, because they are also frequently observed at multiple locations in symptomatic and asymptomatic patients. The Athero-express study follows a new concept to search for the atherosclerotic patient who may suffer from adverse events. In this study, we investigate the predictive value of local plaque composition for adverse events in other vascular territories, regarding the plaque as a concentrated expression of this systemic disease. First results from this longitudinal biobank study show that the local plaque hides strong predictive value for cardiovascular events elsewhere in the vascular tree. Longitudinal biobank studies will facilitate the identification of novel local plaque markers. The search for the plaque protein signature that is predictive for adverse events might enable patient stratification that will allow individualized tailor made medicine and subsequently guide the choice for therapeutic interventions.
Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor-1 (PAI-1) expression: Lessons from the liver
Authors: Dimova Elitsa Y. , Kietzmann Thomas
Published: November 2008

Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type plasminogen activators. Enhanced levels of PAI-1 are found in PAI-1 patients with type 2 diabetes mellitus which is associated with a dysbalance in glucose and lipid homeostasis. Especially a defective insulin response in the liver contributes to the development of hyperglycemia, dyslipidemia and peripheral insulin resistance and may contribute to hepatic overexpression of PAI-1 in diabetes type 2. Furthermore,a substantial upregulation of PAI-1 expression has also been shown in a variety of liver injury models.Thus, the liver appears to be not only a major site of PAI-1 synthesis in response to hormonal changes, but also in response to a variety of other pathological events. PAI-1 expression in liver largely depends on activation of signalling pathways and transcriptional regulators which may be the basis fora new level of cross-talk between different signalling pathways and thus may represent attractive therapeutic candidates.This article will primarily focus on the regulation of PAI-1 expression in liver cells and discuss potential cross-talks between metabolic, hormonal and environmental signals.
Polymorphisms in the protein C gene as risk factor for venous thrombosis
Authors: Doggen Carine , Vos Hans , Reitsma Pieter , Rosendaal Frits , Pomp Elisabeth
Published: November 2008

Protein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.
The ‘PAI-1 paradox’ in vascular remodelling
Authors: Bonello Steve , Diebold Isabel , Kraicun Damir , Görlach Agnes
Published: November 2008

Vascular remodelling isa complex phenomenon associated with restructuring of the vessel wall as a consequence of disruption of vascular homeostasis. Alterations of the vascular wall have been linked to a variety of cardiovascular disorders including atherosclerosis, vascular injury and pulmonary hypertension. Plasminogen activator inhibitor-1 (PAI-1) is a member of the serpin (serine proteinase inhibitor) family and acts as an important inhibitor of fibrinolysis by interfering with the plasminogen system. In addition to its anti-fibrinolytic effects, PAI-1 appears to modulate cellular responses linked to vascular remodelling. Since PAI-1 levels have been shown to be altered in various disorders associated with vascular remodelling of the systemic and pulmonary vascular bed, this serpin may playa pivotal role in the pathogenesis of these diseases.
Competing Jurisdictions Between MERCOSUR and WTO
Authors: Lavranos Nikolaos , Vielliard Nicolas
Published: November 2008

The wider issues raised by the Brazilian Tyres case are discussed in this contribution. Regarding the institutional aspects, this case examines the difficulties between regional dispute settlement systems and the global WTO dispute settlement system. In particular, the WTO Appellate Body showed no deference towards the prior report of the MERCOSUR Arbitral Tribunal. Indeed, the WTO Appellate Body is espousing a supremacy of WTO law – not only vis-à-vis regional dispute settlement bodies, but also regarding WTO panels. It is argued that this attitude is not sustainable in the light of the increasing proliferation of international courts and tribunals, which inevitably results into disputes being adjudicated by different courts and tribunals at different levels. Regarding the substantive aspects, this case is a prime example of the difficulties of balancing non-trade interests and trade interests. At the end, trade interests superseded the nontrade interests. It is argued that the way Article XX GATT has been interpreted and applied by the WTO Appellate Body leaves states insufficient room to address urgent environmental and health problems by restricting trade. It is argued that in this case Brazil's non-trade interests should have been given preference over the trade interests of the EC and Uruguay.
A Question of Definition – The Concept of Internal Armed Conflict in the Swedish Aliens Act
Authors: Magnusson Jennie
Published: November 2008

Fleeing the horrors of an internal armed conflict constitutes a ground for subsidiary protection under the Qualification Directive and in the Swedish Aliens Act. However, what is to be defined as such a conflict is disputed. This is obvious within the European context from the inconsistent interpretations of for example the situation in Iraq amongst Member States. In Sweden, the Migration Court of Appeal established the situation in Iraq as severe, but as not amounting to an armed conflict. In France and Great Britain however, Iraq is regarded as such a conflict. The argument of this article is that the concept of internal armed conflict in the Swedish Aliens Law is incoherent and inadequate. This is due to the fact that the Swedish interpretation is based upon international humanitarian law, a law which provides an unclear and anachronistic concept of internal armed conflict.
Negotiating Boundaries of Social Belonging
Authors: Getrich Christina M.
Published: November 2008

Second-generation Mexican youth in San Diego actively engaged with the immigrant rights movement by participating in protests they organized and orchestrated in spring 2006. The protests highlighted the encounter—and clashing—of different categories of immigrant social belonging in U.S. society. State-oriented constructions of social belonging clashed with the teens' own notions of belonging developed in relation to the lived experiences of members of their social circles. The teens generally constructed their own boundaries of belonging to be more inclusive of “contributing” immigrants; however, they also internalized—and self-defensively rearticulated—negative messages about immigrant “illegality.” The teens' engagement with the immigrant rights movement demonstrated they were not merely “partial” citizens, as youth are typically portrayed. Rather, the teens had their own ways of navigating extant categories of belonging and articulating messages about cultural citizenship. The protests were ultimately transformative for the teens because they were both consciousness-raising and identity affirming.
Transesterification of Waste Olive Oil by Candida Lipase
Authors: Xiangping Shen  , Vasudevan Palligarnai T.
Published: November 2008

Biodiesel was produced by transesterification of waste olive oil with methanol and Novozym®435. The effect of the molar ratio of methanol to triolein, mode of methanol addition, reaction temperature, and mixing speed on biodiesel yield was determined. The effect of different acyl acceptors and/or solvents on biodiesel yield was also evaluated. Finally, the efficacy of Novozym®435 was determined by reusing the enzyme after washing it with a solvent.
Top Management Team Behavioral Integration and the Performance of Service Organizations
Authors: Carmeli Abraham
Published: November 2008

The call for more extensive research regarding the role of processes within top management teams (TMTs) in organizational functioning is addressed in this study. The focus is on the service sector, which according to recent estimations accounts for more than 60% of the total economic activity in most Organization for Economic Cooperation and Development countries and examines the relationship between TMT behavioral integration and multiple performance measures of service organizations. Results from survey data of TMTs from 96 organizations show that TMT behavioral integration is positively associated with both human resource performance and economic performance. The relationship between TMT behavioral integration and service quality and development was only marginally significant.
Ethical Failure Under the Agency Logic
Authors: du Plessis Charl J. A.
Published: November 2008

Progressive responses to recent failures in corporate ethical behavior advocate the complete separation of the chairman of the board and the CEO and the elevation of strategic planning, risk management, and financial certification to an independent board. Such proposals follow a linear path from the same agency logic that underpinned previously insufficient corporate governance reforms. After identifying problems associated with the agency logic, this article proposes its replacement with a new value logic, based on stakeholder theory, where empowerment of legitimate stakeholders and active board discourse become preferred mechanisms for a framework of ethical conduct within the firm.
Effectiveness of Decision Aids
Authors: Leatherman Sheila , Warrick Louise
Published: November 2008

Increased interest in health care consumerism has created an environment conducive to growth in the use of decision aids (DAs) to support patient decision making. The authors review the research literature published within the past 5 years that assesses the effects of DAs in the areas of screening and treatment. Multiple measures are used to evaluate the effectiveness of DAs, with mixed evidence of impacts. To date, most evidence from screening studies suggests that DAs are effective in increasing knowledge and are acceptable to patients, but patient uptake of screening has been mixed. Among treatment studies, there is some, but limited, evidence showing impact of DAs on immediate and long-term decisional conflict, patient satisfaction, and quality of life. Few studies provide assessment of impact on health outcomes, quality of care, utilization, or costs, all areas likely to be of growing interest to private purchasers, insurers, and public programs.
Impact of Targeted Financial Incentives on Personal Health Behavior
Authors: Sutherland Kim , Christianson Jon B. , Leatherman Sheila
Published: November 2008

Over the past decade, there has been a substantial increase in the use of financial incentives by private employers and public programs to encourage healthy behaviors, wellness activities, and use of preventive services. The research evidence regarding the effectiveness of this approach is reviewed, summarizing relevant findings from literature reviews and from recent evaluations. The article concludes that financial incentives, even relatively small incentives, can influence individuals' health-related behaviors. However, the findings regarding health promotion and wellness are based primarily on analyses of a limited number of private sector initiatives, whereas the evidence regarding preventive services is based on evaluations of initiatives sponsored predominantly by public programs and directed at low-income populations. In either case, there are several important limitations in the ability of the published findings to provide clear guidance for public program administrators or private purchasers seeking to design and implement effective incentive programs.
The Economics of Utility, Agency, Theory, and Human Resource Development
Authors: Azevedo Ross E. , Akdere Mesut
Published: November 2008

The problem and the solution . Rational self-interest economic behavior of individuals may lead to undesirable outcomes for the institution. The principal—agent problem and its potential solutions deal with the ways that organizations must pay close attention in the relationships to optimize their physical and human resources for organizational success. Human resource development can play a significant role in facilitating a positive principal—agent relationship.
Economics of Social Capital: Implications for Organizational Performance
Authors: Akdere Mesut , Roberts Paul B.
Published: November 2008

The problem and the solution. The role of social interactions and relationships at the individual, group/team, and organizational levels is becoming increasingly significant in today's workplace. Relationships in an organization may provide some unplanned opportunities, and social capital is considered a new tool with which to increase organizational performance. As a relatively new concept, social capital is still at the exploratory stage for human resource development professionals and researchers. However, social capital has yet to be explored from an economics perspective. This article aims to examine the economics of social capital and the implications for organizational performance.
Critique of the critical incident technique
Authors: Sharoff Leighsa
Published: November 2008

The CIT is a practical and efficient methodology that encourages participants to tell their story; with happenings that are memorable events in participants' lives. It is a form of story-telling, as participants share their singular experience as a story to the researcher. It is a qualitative, systematic, open-ended technique for educing descriptive data from participants as well as being an effective naturalistic tool for focusing participants' on a specific event. The CIT is a user-friendly instrument that can foster reflection and promote personal expression. The development of the CIT to generate indicators of specific happenings relative to research questions demonstrates the technique's suppleness and emphasises the capability of this methodology in nursing research. As nurses learn more about this methodology and its application to the study of nurses and nursing care, they will begin to comprehend how simple and effortless this technique is to use. The CIT can be developed to conform to any area of nursing and provide a more comprehensive awareness of what nurses do and the needs of our clients.
That Damned Mob of Scribbling Siblings: The American Romance as Anti-novel in The Power of Sympathy and Pierre
Authors: Dill Elizabeth
Published: November 2008

In “That Damned Mob of Scribbling Siblings: The American Romance as Anti-Novel in The Power of Sympathy and Pierre,” Elizabeth Dill discusses the eruption of genre chaos in early and mid-nineteenth century American works of fiction. In order to do so, she considers the connections between two much-disputed incest romances, William Hill Brown's The Power of Sympathy (1789) and Herman Melville's Pierre; or, The Ambiguities (1852). Dill's interpretations show how both books refuse to fit into any genre category. The romantic yearnings of the sibling lovers in both books, Dill suggests, constitute a radical love that requires a radical language, so radical, in fact, that silence is often portrayed as the most rebellious of all forms of communication. In her readings of the two texts, then, Dill analyzes how silence in aberrant scenes of romance articulates an unspoken and unspeakable language of love. Dill thus presents the silences of these texts as revolutionary spaces. Within those spaces, Brown and Melville locate an erosion of certainty that the texts posit as an American ideal.
Science, Nature Work, and the Kinaesthetic Body in Cather and Stein
Authors: Raine Anne
Published: November 2008

This essay reads Stein and Cather's early autobiographical fictions as part of a complex negotiation of the gendered divide between the professionalizing sciences and the feminized field of “nature work.” Intrigued yet unsatisfied by scientific accounts of human consciousness as biological process, and wary of entanglement in popular associations of women's nature work with maternal sentiment and feminine virtue, Stein and Cather sought to modernize their “feel for mother earth” by rewriting it in unsentimental and authoritatively modern terms. To that end, both writers adapted notions of rhythm and kinaesthetic performance that originated in the new sciences of psychology and anthropology and were popularized by artists and intellectuals such as Isadora Duncan and Mary Austin. Using Duncan and the opera singer Olive Fremstad as models, Stein and Cather developed rhythmic conceptions of artistic production that sought to reconcile the modern scientific view of human interiority with a modernist celebration of human creative agency, and at the same time to distance themselves from women's nature work while continuing the nature worker's task of drawing attention to the vital continuity between human and nonhuman nature. Read in this light, their work reveals a shared and gendered ambivalence about science and nature that in many ways anticipates our own.
Development of a Collagen Hydrogel with High Mechanical Strength by a Simple Orientation Method for Triple-helix
Authors: Hongo Chizuru , Matsusaki Michiya , Nishida Kohji , Akashi Mitsuru
Published: November 2008

Collagen hydrogels with oriented triple-helix were fabricated simply via the axial orientation of a dense collagen solution onto a glass plate and cross-linking. The orientation of the collagen triple-helix in the gels was clearly confirmed by X-ray diffraction measurements. The tensile strength of the oriented collagen gels in parallel was twofold higher than that of non-oriented gels as a control. Our collagen gels with oriented triple-helix can be useful as novel scaffolds in the tissue engineering field.
Remarkable Support Effects of Gallium Compounds on the Activity and Selectivity of Ru Metal Catalyst for Liquid-phase Citral Hydrogenation
Authors: Nishiyama Hiroshi , Takeuchi Junichi , Hayase Hiroshi , Saito Nobuo , Inoue Yasunobu
Published: November 2008

Various types of p-block metal oxides and nitrides were employed as catalyst supports for Ru metal in liquid-phase citral hydrogenation. Compounds containing Ga3+ ions, in particular GaOOH, were found to exhibit remarkable support effects on the enhancement of catalytic activity and reaction selectivity for the production of α,β-unsaturated alcohols (nerol and geraniol).
An Efficient One-pot Three-component Reaction to Produce 1,4-Disubstituted-1,2,3-triazoles Catalyzed by a Dicopper-substituted Silicotungstate
Authors: Yamaguchi Kazuya , Kotani Miyuki , Kamata Keigo , Mizuno Noritaka
Published: November 2008

The dicopper-substituted γ-Keggin silicotungstate with bis-μ-1,1-azido ligands TBA4H2[γ-SiW10O36Cu2(μ-1,1-N3)2] (TBA = tetrabutylammonium) could act as an effective homogeneous precatalyst for the one-pot synthesis of various kinds of 1,4-disubstituted-1,2,3-triazole derivatives from organic halides, NaN3, and alkynes.
Photoluminescence and Electroluminescence Characteristics of 3,3′-Dicyano-[7,7′-biindolizine]-1,1′,2,2′-tetracarboxylic Acid 1,2-Diethyl 1′,2′-Dimethyl Ester
Authors: Matsushima Toshinori , Kimura Ryosuke , Asahara Masahiro , Murata Hideyuki
Published: November 2008

We investigated photoluminescence (PL) and electroluminescence (EL) characteristics of 3,3′-dicyano-[7,7′-biindolizine]-1,1′,2,2′-tetracarboxylic acid 1,2-diethyl 1′,2′-dimethyl ester (Et2Me2-biInd). We found that Et2Me2-biInd has efficient blue PL and a multilayer organic light-emitting diode doped with Et2Me2-biInd exhibits a relatively high EL efficiency of 1.8±0.1%.
Self-assembly TiO2 Hierarchical Hollow Microspheres with Rutile Nanorods by Template-free Hydrothermal Method
Authors: Zhang Yanfeng , Feng Xiaohui , Liu Hui , Wang Cici , Liu Jingze , Wei Yu
Published: November 2008

Hierarchical TiO2 hollow microspheres composed of rutile nanorods were directly prepared by a simple, efficient, facile, and template-free hydrothermal method with TiCl4 solution in the presence of hydrochloric acid.
Adsorption of Carbon Dioxide on Amine-modified MSU-H Silica in the Presence of Water Vapor
Authors: Hiyoshi Norihito , Yogo Katsunori , Yashima Tatsuaki
Published: November 2008

Mesoporous MSU-H silica modified with 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane showed high capacity of 3.08 mmol·g−1 for carbon dioxide adsorption under 15 kPa of carbon dioxide and 12 kPa of water vapor at 333 K.
Preparation of Monodispersed ZnO Nanoparticles via Thermal Growth-inhibitive Action of Polyethyleneimine (PEI) at Low Temperature
Authors: Kim Ki Seok , Kim Sang Mook , Jung Gun Young
Published: November 2008

An effective wet-chemical method to produce highly monodispersed ZnO nanoparticles (4–6 nm diameters) is presented. A thermal growth-inhibitive phenomenon of ZnO precursor by PEI was employed to generate monodispersed nanoparticles at low temperature (40 °C) and to improve the nanoparticle properties in terms of both size distribution and crystallinity.