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| 2. |
- Berge, Tone, et al.
(author)
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T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells
- 2010
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9761-
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Journal article (peer-reviewed)abstract
- BACKGROUND: The chemokine CXCL12/SDF-1alpha interacts with its G-protein coupled receptor CXCR4 to induce migration of lymphoid and endothelial cells. T cell specific adapter protein (TSAd) has been found to promote migration of Jurkat T cells through interaction with the G protein beta subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail. PRINCIPAL FINDINGS: We show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk). Presence of Itk Y511 was necessary to boost TSAd's effect on CXCL12 induced migration of Jurkat T cells. In addition, TSAd's ability to promote CXCL12-induced actin polymerization and migration of Jurkat T lymphocytes was dependent on the Itk-interaction site in the proline-rich region of TSAd. Furthermore, TSAd-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses. CONCLUSION: We propose that TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements.
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| 3. |
- Billnert, Robert, 1981, et al.
(author)
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New information on the characteristics of 1 in. x 1 in. cerium bromide scintillation detectors
- 2011
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 647:1, s. 94-99
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Journal article (peer-reviewed)abstract
- In view of highly demanded new and accurate data on prompt gamma-ray emission in nuclear fission a major part of investigations is directed towards the selection of suitable detector systems. Here we have studied a new type of crystal scintillation detectors made from cerium bromide (CeBr(3)). For the first time a full characterization of such a detector is presented in terms of energy resolution, pulse-height linearity, intrinsic activity and intrinsic timing resolution. In particular the latter one is very important for prompt fission gamma-ray studies, because the presence of fast neutrons, emitted in fission too, requires the time-of-flight method for their discrimination. The energy resolution has been found to be comparable to that of cerium-doped LaCl(3):Ce detectors at an efficiency comparable to the one of a LaBr(3):Ce detector of the same size. The intrinsic activity of the CeBr(3) crystal was observed to be much lower compared to lanthanum halide crystals. The intrinsic timing resolution of a coaxial 1 in. x 1 in. sized detector was measured relative to that of a previously characterized LaCl(3):Ce detector and found to be (326 +/- 7) Ps at (60)Co energies, which is in between those of a LaBr(3):Ce and a LaCl(3):Ce detector of same size.
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| 4. |
- Billnert, Robert, 1981, et al.
(author)
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Novel Scintillation Detectors for Prompt Fission γ-Ray Measurements
- 2012
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In: Physics Procedia. - : Elsevier BV. - 1875-3884 .- 1875-3892. ; 31, s. 29-34
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Conference paper (peer-reviewed)abstract
- In this work we present first results from measurements of prompt fission γ-rays from the spontaneous fission in 252Cf. New and accurate data on corresponding γ-rays from the reactions 235U(nth,f) and 239Pu(nth,f) are highly demanded for the modeling of new Generation-IV nuclear reactor systems. For these experiments we employed scintillation detectors made out of new materials (LaBr3, LaCl3 and CeBr3), whose properties were necessary to know in order to obtain reliable results. Hence, we have characterized these detectors. In all the important properties these detectors outshine sodium-iodine detectors that where used in the 1970s, when the existing data had been acquired. Our finding is that the new generation of scintillation detectors is indeed promising, as far as an improved precision of the demanded data is concerned.
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| 6. |
- De Caterina, R, et al.
(author)
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General mechanisms of coagulation and targets of anticoagulants (Section I) : Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2013
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In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:4, s. 569-579
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Journal article (peer-reviewed)abstract
- Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.
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| 7. |
- De Caterina, Raffaele, et al.
(author)
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New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes : ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease Position Paper
- 2012
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 59:16, s. 1413-1425
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Research review (peer-reviewed)abstract
- Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.
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| 8. |
- De Caterina, Raffaele, et al.
(author)
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Parenteral anticoagulants in heart disease : Current status and perspectives (Section II) Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2013
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In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:5, s. 769-786
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Journal article (peer-reviewed)abstract
- Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.
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| 9. |
- De Caterina, Raffaele, et al.
(author)
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Vitamin K antagonists in heart disease : Current status and perspectives (Section III)
- 2013
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In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1087-1107
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Journal article (peer-reviewed)abstract
- Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.
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