bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Membrane Glycoproteins and the Interaction between Bovine Factor VIII Related Protein and Human Platelets
Authors: Solum Nils Olav , Hagen Inger , Gjemdal Torbjørn 
Published: July 2018

SummaryThe “GP I fraction” seen on polyacrylamide gel electrophoresis of reduced samples of whole normal platelets contains three glycopolypeptides corresponding to the integral membrane protein GP I (GP Ia), the easily solubilized membrane protein GPS (GP Ib, glycocalicin) and a granule-located glycoprotein.Freezing and thawing of platelets in tris-buffered saline leads to a lysis of platelets and platelet granules with the result that both GPS and the granule glycoprotein is found in the soluble fraction. The two glycoproteins can be separated by SDS polyacrylamide gel electrophoresis both in reduced and unreduced samples when urea and EDTA is incorporated into the gels. This permitted electrophoretic studies of GPS using the granule glycoprotein as a control and marker substance.A working hypothesis stating that the presence of GPS on the platelet surface is a prerequisite to the agglutination of human platelets with bovine factor VIII related protein, has been investigated. The hypothesis was supported by the observation that storage of platelets in tris-buffered saline at 4° C led to the elution of GPS and loss of agglutination, as was also the case when platelets were frozen and thawed in tris-buffered saline, or preincubated in 3 M KCl and resuspended in either tris-buffered saline or the EDTA-containing medium A. GPS was not, or only slightly, solubilized when platelets were frozen and thawed in the EDTA-containing medium and the resulting platelet ghosts still agglutinated.Platelets from 1 patient of the Bernard-Soulier type did not agglutinate with the bovine factor VIII-related protein, nor did the platelets contain GPS. An improved technique for the isolation of such platelets is described.
Insights into the Mechanism of Platelet Action through Studies at pH 5.3.
Authors: Mürer E. H , Stewart G. J 
Published: July 2018

SummaryIncubation of washed human platelets at pH 5.3 at 37° C induces a slow secretion of stored compounds. The secretion is 60% inhibited by metabolic inhibitors and blocked at 0° C.
The major changes in the metabolic adenine nucleotide levels in the platelets precede the secretion, which is accompanied by a drop in ADP and an increase in inosine and hypoxanthine. The incubation does not lead to significantly increased loss in cytoplasmic compounds from the platelets.Ultrastructural changes which accompany pH 5.3-induced secretion include a coalescence of cytoplasmic material in the center and a decrease in densely stained material in the periphery of the platelet. These changes are only seen by prolonged incubation (60 min). In the presence of 2 mM fluoride similar changes are seen after 3 min incubation. Other changes induced by fluoride, i. e. the formation of swollen areas in the periphery of the platelet are not induced by incubation at pH 5.3 alone.The metabolic changes seen by incubation at pH 5.3 are to a great degree reversible, even when secretion has been induced. Although secretion cannot be induced by incubation of platelets at pH 7.6 alone, pH 5.3-induced secretion continues at the higher pH. Whereas incubation at pH 5.3 in the cold does not induce secretion, incubation with 2 mM fluoride under these conditions will result in at least 50% secretion of stored compounds when pH and temperature are increased, indicating that fluoride has been taken up by the platelet by passive diffusion. This concentration of fluoride is below the threshold for induction of secretion at pH 7.6.In contrast to secretion induced by thrombin, and in agreement with the findings with fluoride, the calcium ionophore A 23187 is equally effective as inducer of secretion at pH 5.3 and at pH 7.6. This also agrees with the findings that when secretion has been “initiated” in the cold with thrombin at pH 7.4, the extrusion which takes place at higher temperature has a shift in pH optimum towards the acid pH and is only partially inhibited at pH 5.5, while the action of agents which effect platelet secretion from the outside, including added Ca++, is blocked below pH 6, and the induction effect of thrombin below pH 6.5.We propose that the agents which cause secretion at low pH have a direct intracellular effect, probably on the level of cytoplasmic Ca++, while the agents which are inhibited by the low pH act indirectly via external membrane sites.
Laboratory Evaluation and Clinical Characteristics of 2,132 Consecutive Unselected Patients with Venous Thromboembolism – Results of the Spanish Multicentric Study on Thrombophilia (EMET*-Study)
Authors: Mateo José , Oliver Artur , Borrell Montserrat , Sala Núria , Fontcuberta Jordi ,   EMET Group
Published: July 2018

SummaryPrevious studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2,132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinoge-nemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfib-rinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% Cl 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and in 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% Cl 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% Cl 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78,95% Cl 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.
Increased Tissue Factor Pathway Inhibitor (TFPI) and Coagulation in Patients with Insulin-dependent Diabetes mellitus
Authors: Leurs Paul B , van Oerle Rene , Wolffenbuttel Bruce H R , Hamulyak Karly 
Published: July 2018

SummaryRecently, we found an increase in tissue factor pathway inhibitor (TFPI) activity in patients with insulin-dependent diabetes mellitus (IDDM). This increase in TFPI activity could be the result of increased thrombin formation and/or altered binding of TFPI to glycosaminoglycans. We studied TFPI activity (chromogenic assay) in relation to prothrombin F1+2 fragments and endogenous thrombin potential (ETP), in 46 IDDM patients, and 18 age and sex-matched healthy controls. Prothrombin, antithrombin and thrombomodulin were also determined. In IDDM patients, TFPI activity and F1+2 levels were significantly higher, while ETP, prothrombin antigen levels, and antithrombin activity were lower as compared to the controls. In IDDM patients with microalbuminuria, a manifestation of generalized angiopathy, TFPI activity, F1+2 and thrombomodulin levels were higher than in patients with only retinopathy or patients without complications. No correlation between TFPI activity, F1+2 levels and thrombomodulin was found, while TFPI activity was negatively correlated with ETP (r = -0.27). Microalbuminuria was significantly correlated with TFPI activity (r = 0.46), F1+2 (r = 0.56), and thrombomodulin (r = 0.52). In TFPI-depleted plasma, ETP increased, indicating that ETP is affected by TFPI. In conclusion, the increase in TFPI activity in IDDM patients may not be considered to be a reaction on a procoagulant state. It is hypothesized that vascular damage, leading to alterations in glycosaminoglycans, is in part responsible for the changes in TFPI activity, F1+2 levels and ETP.
Ventilation-Perfusion Lung Scanning and the Diagnosis of Pulmonary Embolism: Improvement of Observer Agreement by the Use of a Lung Segment Reference Chart
Authors: Lensing Anthonie W A , van Beek Edwin J R , Demers Christine , Tiel-van Buul Monique M C , Yakemchuk Valerie , van Dongen Annemarie , Coates Geoffrey , Ginsberg Jeffrey S , Hirsh Jack , ten Cate Jan Wouter , Büller Harry R 
Published: July 2018

Summary
Objective. To test the hypothesis that the systematic use of a lung segment reference chart can improve the inter- and intra-observer agreement for the interpretation of ventilation-perfusion lung scans.
Design. A randomized trial.
Study population. Ventilation-perfusion lung scans were obtained in a series of 220 consecutive patients with clinically suspected pulmonary embolism.
Intervention. Ventilation-perfusion scans were randomly allocated to one of two series each consisting of 110 ventilation-perfusion lung scans. The first series of lung scans was interpreted according to the routine diagnostic approach, and the second series was interpreted with the mandatory use of a lung segment reference chart on which observed ventilation and perfusion defects were drawn. The two nuclear medicine physicians agreed a priori on the diagnostic criteria of the classification scheme.
Measurements. Lung scans were classified as normal, non-high probability, or high probability for pulmonary embolism. The extent of disagreement between the nuclear medicine physicians (inter-observer disagreement) and the lack of internal consistency of each nuclear medicine physician (intra-observer disagreement) was assessed by the percentage disagreement and by kappa statistic.
Results. Inter-observer disagreement which was 20% in the first series, decreased significantly in the second series to 7%; P = 0.003. Intra-observer disagreement for the first series was 10% and 22% for the nuclear medicine physicians, respectively. Intra-observer disagreement for the second series of lung scans decreased significantly for one nuclear medicine physician (intra-observer disagreement, 0%; P <0.01), whereas intra-observer disagreement was reduced to 10% for the other nuclear medicine physician (P = 0.09).
Conclusion. Inter- and intra-observer disagreement were significantly reduced when two nuclear medicine specialists interpreted ventilation-perfusion lung scans according to the routine diagnostic approach plus the use of a lung segment reference chart. The use of the lung segment reference chart for the interpretation of lung scans is likely to improve the management of patients with clinically suspected pulmonary embolism.
Activation of Coagulation and Fibrinolysis Following OKT3 Administration to Renal Transplant Recipients: Association with Distinct Mediators
Authors: Raasveld Maarten H M , Hack C Erik , ten Berge Ineke J M 
Published: July 2018

SummaryTreatment with OKT3 induces cytokine release and activates the complement system. Since both phenomena may affect coagulation and fibrinolysis we studied these systems in 8 renal transplant recipients during OKT3 treatment. In 8 of 9 patients a similar pattern was observed: plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-α2-antiplasmin-complex levels were increased as compared to pretreatment levels (p <0.05) at 15 min after the first OKT3 dose and reached peak values at 1 h. No significant changes were observed upon subsequent OKT3 administrations or in a control group of 8 patients. In one patient upon the first OKT3 administration only complement activation, and no cytokine release was observed, whereas plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-α2-antiplasmin-complex levels increased only at 15 min.In conclusion, we demonstrate a biphasic activation of coagulation and fibrinolysis upon the first OKT3 dose; the initial phase seems to be associated with complement activation, the later phase with cytokine release.
Immunoglobulin Fractions Isolated from Patients with Antiphospholipid Antibodies Prevent the Inactivation of Factor Va by Activated Protein C on Human Endothelial Cells
Authors: Borrell Montserrat , Sala Nuria , de Castellarnau Conxita , Lopez Silvia , Gari Merce , Fontcuberta Jordi 
Published: July 2018

SummaryWe studied the effect of purified immunoglobulins (Ig) from 21 patients with antiphospholipid antibodies (aPL) on factor Va degradation by activated protein C (aPC) on cultured human umbilical vein endothelial cells (HUVEC). Sera from patients were tested on an ELISA aPL assay to determine the isotype with aPL activity. HUVEC were incubated with purified IgG or IgM fraction from controls or patients. Activated PC and factor Va were then added and factor Va degradation was measured after several reaction times. 13 of 14 IgM and 8 of 10 IgG from patients showed an inhibitory effect on factor Va degradation by aPC when compared with control Ig. We also observed the same inhibitory effect with patients’ Ig on studying the degradation of factor Va by aPC in a purified system containing aPC, protein S and phospholipids. These results suggest that aPL antibodies disturb the anticoagulant activity of aPC, which may contribute to the thrombotic tendency of these patients.
A Rapid Monoclonal Antibody-Based Enzyme Immunoassay (EIA) for the Quantitative Determination of Soluble Fibrin in Plasma
Authors: Nieuwenhuizen W , Hoegee-De Nobel E , Laterveer R 
Published: July 2018

SummarySoluble fibrin is considered as a molecular marker for intravascular fibrin formation, and impending thrombotic events. Most of the existing assays are less suitable for routine clinical applications and their specificity may be limited.We have developed a sandwich-type EIA with a fibrin-specific MoAb described by us before (Proc Natl Acad Sci 1989; 86: 8951) as the capture antibody. An other MoAb (G8; Thromb Haemostas 1988; 60: 415) with an epitope in the carboxyl-terminal sections of the fibrin α-chains, was labeled with peroxidase and used as the tagging antibody. The EIA is calibrated against plasma spiked with known concentrations of soluble fibrin. The time-to-result of the EIA is only 1.5 h. Concentrations as low as 0.5 µg soluble fibrin/ml plasma are readily measurable. Heparin has no effect on the results. Fibrinogen and fibrin(ogen) degradation products are not detected. The values of fibrinopeptide A and soluble fibrin values found with the “COA-SET soluble fibrin” assay correlated well with the soluble fibrin values found with our EIA i.e. r = 0.998 and 0.984, respectively. The run-to-run variabilities were 7.9% and 6.6% for samples with low and high soluble fibrin concentrations, respectively. The within-run variabilities were 2.5, 1.8, 4.0 and 4.6% for samples with 1, 0.5, 0.25 and 0.125 µg soluble fibrin/ml, respectively.The sensitivity, specificity, accuracy and short time-to-result make our EIA suitable for routine clinical applications and the monitoring of the effectivity of heparinization.
Typ-2-Diabetes und Migranten: Menschen aus verschiedenen Sprach- und Kulturräumen
Authors: Berger Faize 
Published: July 2018

AbstractMigrants are more likely, earlier and more severely affected by type 2 diabetes than the native population. Prevalence, incidence and mortality in this population group, whose proportion of the total population continues to grow, are increased by a factor of 2 – even stronger depending on ethnicity, country of origin, gender and socio-economic conditions. This makes it necessary to pay special attention to this group.
Genomic analysis reveals multiple mismatches between biological and management units in yellowfin tuna (Thunnus albacares)
Authors: Mullins Rachel B , McKeown Niall J , Sauer Warwick H H , Shaw Paul W 
Published: July 2018

AbstractThe South African (SAF) yellowfin tuna (Thunnus albacares) fishery represents a potential example of misalignment between management units and biological processes. The SAF fishery spans an operational stock with a boundary at 20°E, either side of which fish are considered part of Atlantic or Indian Ocean regional stocks. However, the actual recruitment of fish from Atlantic and Indian Ocean spawning populations into SAF waters is unknown. To address this knowledge gap, genomic analysis (11 101 SNPs) was performed on samples from Atlantic and Indian Ocean spawning sites, including SAF sites spanning the current stock boundary. Outlier loci conferred high discriminatory power to assignment tests and revealed that all SAF fish were assigned to the Indian Ocean population and that no Atlantic Ocean fish appeared in the SAF samples. Additionally, several Indian Ocean migrants were detected at the Atlantic spawning site demonstrating asymmetric dispersal and the occurrence of a mixed-stock fishery in Atlantic waters. This study highlights both the spatial inaccuracy of current stock designations and a misunderstanding of interactions between the underlying biological units, which must be addressed in light of local and global declines of the species. Specifically, the entire SAF fishery must be managed as part of the Indian Ocean stock.
Celiac Disease: Against the Grain in Gastroenterology
Authors: Zhu Julie , Mulder Chris J J , Dieleman Levinus A 
Published: July 2018

AbstractThe incidence of celiac disease has risen quickly and has a worldwide distribution in Europe, North and South America, Asia, the Middle East and Africa. This is attributed in part to increased availability in screening but also to the fast-rising gluten consumption and perhaps unknown environmental factors. In daily practice, this means that more subclinical cases and very young and elderly patients are diagnosed. The pathogenesis of celiac disease is a T-cell driven process initiated by gluten, leading to increased intestinal permeability and villous atrophy. The process requires HLA genotypes DQ2, DQ8 or both. Additional non-HLA alleles have been identified in genome-wide association studies. Serological testing, followed by duodenal biopsies, are still required to confirm the diagnosis. Advances are in the making for novel biomarkers to monitor disease and for pharmacological support of celiac disease. Medical costs and patient-perceived disease burden remain high in celiac disease, which point to the need for ongoing research in drug development to improve quality of daily life. Drugs undergoing phase I and phase II clinical trials include intraluminal therapies and vaccines to restore immune tolerance. These therapies aim to reduce symptoms and mucosal injuries as adjunct therapies to a gluten-free diet.
The Israeli Raid Against the PLO Headquarters in Tunis—1985
Authors: Pobjie Erin , Declercq Fanny , Van Steenberghe Raphaël 
Published: July 2018

Abstract
This chapter examines the Israeli raid against the Palestine Liberation Organisation (PLO) headquarters in Tunis in 1985. It first sets out the facts and context of the raid, the positions of the main protagonists (Israel and Tunisia) and the reactions of third States and international organizations. The chapter then analyses the legal issues raised by the incident under international law as it stood at the time, and its impact on the jus ad bellum. The 1985 raid was an early example of a claimed right to exercise self-defence in response to attacks committed by non-state actors without those attacks being attributable to the state on whose territory the action in self-defence takes place. However, it is argued that this incident left unsettled whether or not such a right was accepted at the time.
Changes in the sensitivity of solar p-mode frequency shifts to activity over three solar cycles
Authors: Howe R , Chaplin W J , Davies G R , Elsworth Y , Basu S , Broomhall A-M 
Published: July 2018

Abstract
Low-degree solar p-mode observations from the long-lived Birmingham Solar-Oscillations Network (BiSON) stretch back further than any other single helioseismic data set. Results from BiSON have suggested that the response of the mode frequency to solar activity levels may be different in different cycles. In order to check whether such changes can also be seen at higher degrees, we compare the response of medium-degree solar p modes to activity levels across three solar cycles using data from Big Bear Solar Observatory, Global Oscillation Network Group, Michelson Doppler Imager, and Helioseismic and Magnetic Imager, by examining the shifts in the mode frequencies and their sensitivity to solar activity levels. We compare these shifts and sensitivities with those from radial modes from BiSON. We find that the medium-degree data show small but significant systematic differences between the cycles, with solar Cycle 24 showing a frequency shift about 10 per cent larger than Cycle 23 for the same change in activity as determined by the 10.7 cm radio flux. This may support the idea that there have been changes in the magnetic properties of the shallow subsurface layers of the Sun that have the strongest influence on the frequency shifts.
A Stronger Role for the European Supervisory Authorities in the EU27
Authors: Busch Danny 
Published: July 2018

Abstract
The chapter addresses two topics that are crucial to achieving more supervisory convergence in the European Union 27 (EU-27): (1) a more pan-European governance or decision-making structure of the European Supervisory Authorities (ESAs); and (2) more direct supervisory powers to the ESAs, particularly (but not exclusively) to the European Securities and Markets Authority (ESMA). These topics are analysed and discussed within the framework of the Commission's public consultation on the functioning of the ESAs; the Commission proposal of 29 June 2017 for a Regulation on a pan-European Personal Pension Product; the Commission's FinTech consultation of 23 March 2017; and the Commission proposal of 13 June 2017 to amend the European Market Infrastructure Regulation and the ESMA, which aims to introduce a more pan-European approach to central counterparties supervision.
OTC Derivatives Clearing, Brexit, and the CMU
Authors: Ferrarini Guido , Trasciatti Davide 
Published: July 2018

Abstract
This chapter contributes to the debate on the future of European over-the-counter (OTC) clearing and relevant infrastructures in light of the Capital Markets Union and its re-configuration after Brexit. It begins by introducing some basic notions about clearing dynamics. It then analyses the available divorce options between the EU and the UK once Article 50 has been triggered, and their impact on clearing particularly in light of the European Market Infrastructure Regulation's equivalence regime. Next, it examines the worst-case scenario that would materialize if UK central counterparties (CCPs) were excluded from the single market, and considers possible network strategies that CCPs could adopt to remedy the consequences of Brexit.