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1. Diabetic Nephropathy Alters the Distribution of Circulating Angiogenic MicroRNAs Among Extracellular Vesicles, HDL, and Ago-2 (vol 68, pg 2287, 2019)

Author: Florijn, B.W., Duijs, J.M.G.J., Levels, J.H., Dallinga-Thie, G.M., Wang, Y.A., Boing, A.N., Yuana, Y.N., Stam, W., Limpens, R.W.A.L., Au, Y.W., Nieuwland, R., Rabelink, T.J., Reinders, M.E.J., Zonneveld, A.J. van, and Bijkerk, R.
Published: 2020

2. Cancer-ID: towards identification of cancer by tumor-derived extracellular vesicles in blood

Author: Rikkert, L G, Beekman, P, Caro, J, Coumans, F A W, Enciso Martinez, A, Jenster, G, Le Gac, S, Lee, W, Van Leeuwen, Ton G, Loozen, G B, Nanou, A, Nieuwland, R, Offerhaus, H L, Otto, C, Pegtel, D M, Piontek, M C, Van Der Pol, E, De Rond, L, Roos, W H, Schasfoort, R B M, Wauben, Marca, Zuilhof, H, Terstappen, Leon WMM, Celbiologie, and dB&C I&I
Subjects: Cell-Derived Microparticles, Electrochemistry, transmission electron microscopy 3, Surface Plasmon Resonance, Exosomes, Flow Cytometry, extracellular vesicles, Scanning electron microscopy, fluorescence microscopy, Atomic Force Microscopy, Raman spectrum analysis
Abstract: Extracellular Vesicles (EVs) have great potential as biomarkers since their composition and concentration in biofluids are disease state-dependent and their cargo can contain disease related information. Large tumor-derived EVs (tdEVs, > 1 μm) in blood from cancer patients are associated with poor outcome and changes in their number can be used to monitor therapy effectiveness. Whereas small tumor-derived EVs (
Published: 2020

3. Standardization of extracellular vesicle measurements by flow cytometry through vesicle diameter approximation

Author: van der Pol, E., Sturk, A., van Leeuwen, T., Nieuwland, R., Coumans, F., Mobarrez, F., Arkesteijn, G., Wauben, M., Siljander, P. R.M., Sánchez-López, V., Otero-Candelera, R., Ramón, L. A., Dolz, S., Vila, V., Mackman, N., Geddings, J., Mullier, F., Bailly, N., Han, J. Y., Kwaan, H. C., Weiss, I. M., Buzás, E. I., Pállinger, E., Harrison, P., Kraan, J., Hedley, B. D., LazoLangner, A., Enjeti, A., Norris, P. J., Paris, C., Susen, S., Bonnefoy, A., Delorme, I., Chandler, W. L., Hau, C., Aass, H. C.D., Connor, D., Wu, X., Dragovic, R., Uotila, L. M., Lacroix, R., Robert, S., Dep Infectieziekten Immunologie, LS Celbiologie-Algemeen, Sub General Pharmaceutics, Sub Algebra,Geometry&Mathem. Logic begr., LS Pharma, dB&C I&I, Hematology, Erasmus School of Economics, Medical Oncology, General Practice, Business Economics, ACS - Atherosclerosis & ischemic syndromes, CCA - Imaging and biomarkers, Biomedical Engineering and Physics, ACS - Microcirculation, Laboratory for General Clinical Chemistry, Laboratory Specialized Diagnostics & Research, Dep Infectieziekten Immunologie, LS Celbiologie-Algemeen, Sub General Pharmaceutics, Sub Algebra,Geometry&Mathem. Logic begr., LS Pharma, and dB&C I&I
Subjects: 0301 basic medicine, Materials science, Light, Platelet Function Tests, cell-derived microparticles, blood platelets, exosomes, 030204 cardiovascular system & hematology, Bead, Light scattering, Flow cytometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Calibration, Humans, Scattering, Radiation, Particle Size, Cell Size, Observer Variation, standardization, medicine.diagnostic_test, Vesicle, flow cytometry, Integrin beta3, Reproducibility of Results, Phycoerythrin, Hematology, Extracellular vesicle, Volumetric flow rate, 030104 developmental biology, chemistry, visual_art, visual_art.visual_art_medium, Polystyrene, extracellular vesicles, Biomarkers, Biomedical engineering
Abstract: Essentials Platelet extracellular vesicles (EVs) concentrations measured by flow cytometers are incomparable. A model is applied to convert ambiguous scatter units to EV diameter in nanometer. Most included flow cytometers lack the sensitivity to detect EVs of 600 nm and smaller. The model outperforms polystyrene beads for comparability of platelet EV concentrations. Summary: Background Detection of extracellular vesicles (EVs) by flow cytometry has poor interlaboratory comparability, owing to differences in flow cytometer (FCM) sensitivity. Previous workshops distributed polystyrene beads to set a scatter-based diameter gate in order to improve the comparability of EV concentration measurements. However, polystyrene beads provide limited insights into the diameter of detected EVs. Objectives To evaluate gates based on the estimated diameter of EVs instead of beads. Methods A calibration bead mixture and platelet EV samples were distributed to 33 participants. Beads and a light scattering model were used to set EV diameter gates in order to measure the concentration of CD61–phycoerythrin-positive platelet EVs. Results Of the 46 evaluated FCMs, 21 FCMs detected the 600–1200-nm EV diameter gate. The 1200–3000-nm EV diameter gate was detected by 31 FCMs, with a measured EV concentration interlaboratory variability of 81% as compared with 139% with the bead diameter gate. Part of the variation in both approaches is caused by precipitation in some of the provided platelet EV samples. Flow rate calibration proved essential because systems configured to 60 μL min−1 differed six-fold in measured flow rates between instruments. Conclusions EV diameter gates improve the interlaboratory variability as compared with previous approaches. Of the evaluated FCMs, 24% could not detect 400-nm polystyrene beads, and such instruments have limited utility for EV research. Finally, considerable differences were observed in sensitivity between optically similar instruments, indicating that maintenance and training affect the sensitivity.
Published: 2018

4. Randomized controlled trial protocol to investigate the antiplatelet therapy effect on extracellular vesicles (AFFECT EV) in acute myocardial infarction

Author: Gasecka, Alecja, Nieuwland, R, Budnik, Mateusz, Dignat-George, Francoise, EYILETEN, c, Harrison, Peter, HUCZEK, Z, KAPLON-CIESLICKA, A, Lacroix, Romaric, Opolski, Grzegorz, Pluta, Kacper, VAN DER POL, E, POSTULA, M, Leroyer, Aurelie S, SILJANDER, P, STURK, A, FILIPIAK, KJ, Medical University of Warsaw - Poland, University of Amsterdam [Amsterdam] (UvA), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Birmingham [Birmingham], and University of Helsinki
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

5. Randomized controlled trial protocol to investigate the antiplatelet therapy effect on extracellular vesicles (AFFECT EV) in acute myocardial infarction

Author: Gasecka, Alecja, Nieuwland, R, Budnik, Mateusz, Dignat-George, Francoise, EYILETEN, c, Harrison, Peter, HUCZEK, Z, KAPLON-CIESLICKA, A, Lacroix, Romaric, Opolski, Grzegorz, Pluta, Kacper, VAN DER POL, E, POSTULA, M, Leroyer, Aurelie S, SILJANDER, P, STURK, A, FILIPIAK, KJ, Medical University of Warsaw - Poland, University of Amsterdam [Amsterdam] (UvA), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Birmingham [Birmingham], and University of Helsinki
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

6. Randomized controlled trial protocol to investigate the antiplatelet therapy effect on extracellular vesicles (AFFECT EV) in acute myocardial infarction

Author: Gasecka, Alecja, Nieuwland, R, Budnik, Mateusz, Dignat-George, Francoise, EYILETEN, c, Harrison, Peter, HUCZEK, Z, KAPLON-CIESLICKA, A, Lacroix, Romaric, Opolski, Grzegorz, Pluta, Kacper, VAN DER POL, E, POSTULA, M, Leroyer, Aurelie S, SILJANDER, P, STURK, A, FILIPIAK, KJ, Medical University of Warsaw - Poland, University of Amsterdam [Amsterdam] (UvA), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Birmingham [Birmingham], and University of Helsinki
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

7. Plasma vesicle-associated mirnas as therapy response biomarkers in hodgkin lymphom

Author: Pegtel, D M., Drees, E., van Eijndhoven, M. A. J., Groenewegen, N. J., van Niele, S., Prins, R., Baglio, S. R., Zijlstra, J.M., van der Voorn, H., Libregts, S. F. W. M., Wauben, M. H., de Menezes, R. X., van Weering, J. R. T., Nieuwland, R., Diepstra, A., de Jong, D., and Stem Cell Aging Leukemia and Lymphoma (SALL)
Published: 2016

8. PLASMA VESICLE-ASSOCIATED miRNAs AS THERAPY RESPONSE BIOMARKERS IN HODGKIN LYMPHOMA

Author: Pegtel, D. M., Drees, E., Eijndhoven, M. A. J., Groenewegen, N. J., Niele, S., Prins, R., Baglio, S. R., Zijlstra, J. M., Voorn, H., Libregts, Sfwm, Wauben, M. H., Menezes, R. X., Weering, J. R. T., Nieuwland, R., Diepstra, A., Anke van den Berg, Jong, D., Pathology, CCA - Biomarkers, Hematology, Clinical genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pediatrics, and Surgery
Published: 2016

9. Standardization of microparticle enumeration across different flow cytometry platforms: results of a multicenter collaborative workshop

Author: Cointe, S, Judicone, C, Robert, S, Mooberry, M J, Poncelet, P, Wauben, M, Nieuwland, R, Key, N S, Dignat-George, F, Lacroix, R, LS Celbiologie-Algemeen, dB&C I&I, ACS - Amsterdam Cardiovascular Sciences, CCA -Cancer Center Amsterdam, Laboratory Specialized Diagnostics & Research, ACS - Microcirculation, Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), LS Celbiologie-Algemeen, and dB&C I&I
Subjects: 0301 basic medicine, Standardization, cell-derived microparticles, Neutrophils, Computer science, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, computer.software_genre, Sensitivity and Specificity, Extracellular vesicles, Plasma, 03 medical and health sciences, 0302 clinical medicine, Cellular origin, Enumeration, Humans, Particle Size, standardization, Plasma samples, Platelet Count, flow cytometry, Hematology, 030104 developmental biology, multicenter study, Multicenter study, Calibration, Data mining, extracellular vesicles, computer
Abstract: International audience; Essentials The clinical enumeration of microparticles (MPs) is hampered by a lack of standardization. A new strategy to standardize MP counts by flow cytometry was evaluated in a multicenter study. No difference was found between instruments using forward or side scatter as the trigger parameter. This study demonstrated that beads can be used as a standardization tool for MPs. Click to hear the ISTH Academy's webinar on microvesicles SUMMARY: Background Microparticles (MPs) are extracellular vesicles resulting from the budding of cellular membranes that have a high potential as emergent biomarkers; however, their clinical relevance is hampered by methodological enumeration concerns and a lack of standardization. Flow cytometry (FCM) remains the most commonly used technique with the best capability to determine the cellular origin of single MPs. However, instruments behave variably depending on which scatter parameter (forward (FSC) or side scatter (SSC)) provides the best resolution to discriminate submicron particles. To overcome this problem, a new approach, based on two sets of selected beads adapted to FSC or SSC-optimized instruments, was recently proposed to reproducibly enumerate platelet-derived MP counts among instruments with different optical systems. Objective The objective was to evaluate this strategy in an international workshop that included 44 laboratories accounting for 52 cytometers of 14 types. Methods/Results Using resolution capability and background noise level as criteria to qualify the instruments, the standardization strategy proved to be compatible with 85% (44/52) of instruments. All instruments correctly ranked the platelet MP (PMP) levels of two platelet-free plasma samples. The inter-laboratory variability of PMP counts was 37% and 28% for each sample. No difference was found between instruments using forward or side-scattered light as the relative sizing parameter. Conclusions Despite remaining limitations, this study is the first to demonstrate a real potential of bead-based strategies for standardization of MP enumeration across different FCM platforms. Additional standardization efforts are still mandatory to evaluate MPs' clinical relevance at a multicenter level.
Published: 2016

10. Single-step size exclusion chromatography enriches for plasma vesicle-associated miRNAs that are directly applicable for cancer biomarker discovery using small RNAseq

Author: Van Eijndhoven, M, Groenewegen, N, Van Weering, J, Nieuwland, R, De Jong, D, Zijlstra, J, Pegtel, M, Clinical genetics, NCA - Brain mechanisms in health and disease, Surgery, Hematology, CCA - Disease profiling, CCA - Imaging, Pathology, and CCA - Oncogenesis
Abstract: Introduction: Circulating microRNAs are generally believed to have biomarker potential for diagnosis, prognosis and monitoring of treatment response in multiple diseases, including cancer. Extracellular vesicles (EVs) are actively secreted by tumour cells and normal cells, and they encapsulate miRNAs, protecting them from degradation by RNases. Circulating miRNAs can also be associated with and protected by proteins and HDL; moreover, dying cells release biomolecules (i.e. RNA, DNA, protein) into circulation. The use of tumour-derived EV as biomarker has many advantages: 1) they reflect living tumour cells, 2) EV-associated miRNAs are stable in archived material, 3) EV-secreted miRNAs outnumber other types, 4) EV-associated miRNAs promote tumourigenic processes, 5) tumour vesicles carry proteins on their surface that trace them back to the tumour cells. Thus for circulating miRNA biomarker research it maybe of critical importance to isolate (tumour) EV from circulation. Methods: We performed size exclusion chromatography using sepharose CL-2B and commercially available qEV columns (iZON™) on 1.5 ml plasma to separate EV from protein/HDL. Results: Electron Microscopy showed the presence of EV in the vesicle fractions but not in the protein/HDL fractions. Particle analysis using qNano (iZON™) showed that the vesicle fractions are highly enriched in particles with a size-distribution that corresponds to the EM images. Moreover, western analysis showed the presenceof exosome-marker CD63in the vesicle fractions, but not the protein/HDL fractions. RNA was isolated using TRIzol from the EV and protein/HDL fractions separated by SEC, followed by RT-PCR. The EV fractions were highly enriched for vtRNA1-1, let7a and miR142-3p, whereas protein/HDL fractions are enriched for miR92a, miR21 and miR451. EV isolated using SEC contained sufficient RNA of suitable quality for screening using RNAseq. Classical Hodgkin lymphoma plasma EVs had a distinct smallRNA profile compared to healthy donor plasma EVs. We validated potential miRNA biomarker candidates by RT-PCR. Summary/conclusion: All together these results indicate that EVs isolated using SEC are useful for miRNA biomarker discovery in cancer patients.
Published: 2015

11. Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response

Author: van den Goor, J., Nieuwland, R., van den Brink, A., van Oeveren, W., Rutten, 27818, Tijssen, J., Eijsman, L., Rutten, P, Faculteit Medische Wetenschappen/UMCG, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Laboratory for Experimental Clinical Chemistry, and Cardiology
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, Surface Properties, SURGERY, coronary artery bypass grafting, HEPARIN-COATED CIRCUITS, Phospholipases A, BIOCOMPATIBILITY, law.invention, EXTRACORPOREAL CIRCUIT, Intraoperative Period, SECRETORY PHOSPHOLIPASE A(2), Coated Materials, Biocompatible, law, acute phase response, Cardiopulmonary bypass, Medicine, Humans, Derivation, Postoperative Period, Prospective Studies, Coronary Artery Bypass, Acute-Phase Reaction, Pancreatic elastase, Complement Activation, Aged, biology, Pancreatic Elastase, business.industry, Elastase, C-reactive protein, INFLAMMATORY RESPONSE, Acute-phase protein, General Medicine, Perioperative, Middle Aged, C-REACTIVE PROTEIN, Phospholipases A2, surgical procedures, operative, Trillium, Anesthesia, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, cardiopulmonary bypass, Perfusion
Abstract: Objective: In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated- (UMS), Carmeda(R)- (BPS) or Trillium(R)-coated oxygenators (BAS). Methods: Prospectively, 71 CABG patients were randomly allocated to one of the oxygenator groups (UMS: n = 25, BPS: n = 25 and BAS: n = 2 1). Terminal complement complexes (TCC) and elastase were determined in plasma samples collected before, during and after bypass. Secretory phospholipase A(2) (sPLA(2)) and C-reactive protein (CRP) were determined before and after bypass. Results: Demographic, CPB and clinical outcome data were similar for the three groups. TCC and elastase increased during CPB, and decreased thereafter. Significant differences between the groups were present in the levels of TCC at the end of CPB (P = 0.002) and at the first (P = 0.012) and second (P
Published: 2004

12. Prediction of venous thromboembolism in cancer patients by tissue factor dependent microparticle coagulant activity, biomarkers and a clinical score

Author: Kleinjan, A., Bossuyt, P., Cesarman-Maus, G., Di Nisio, M., Kamphuisen, P.W., Kramer, M., Mahé, I., Nanayakkara, P., Nieuwland, R., Otten, H.M., Stephanian, A., Büller, H.R., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: cancer patient, sampling, venous thromboembolism, heparin, chemotherapy, blood, antibody, death, thromboplastin, PADGEM protein, follow up, advanced cancer, coagulating agent, fibrin, human, hospital, randomized controlled trial (topic), thrombosis, plasma, risk, predictive value, weight, prediction, clinical study, biological marker, thrombin, blood clotting time, society, female, confidence interval, blood clotting factor 8, D dimer, hemostasis, bootstrapping, patient, laboratory, neoplasm
Abstract: Background: Cancer patients receiving chemotherapy in an ambulatory setting are at risk of venous thromboembolism (VTE). Randomized controlled trials have shown that thromboprophylaxis with lowmolecular- weight-heparin reduces the occurrence of VTE in cancer patients but the overall incidence of 4% is generally considered too low to justify thromboprophylaxis in all patients. A logical next step is to focus on tools for selecting cancer patients at the highest risk of VTE, in whom thromboprophylaxis is expected to have a more favorable risk-benefit ratio. Aim: We aimed to determine the performance of tissue factor (TF)- dependent microparticle coagulant activity in predicting VTE, and to compare it to that of the Khorana score, and previously evaluated biomarkers. Methods: In six hospitals blood was obtained from consenting ambulatory patients receiving chemotherapy for stage III or IV cancer. Patients were prospectively followed for 6 months for development of VTE. At inclusion, TF-dependent microparticle coagulant activity was measured in a fibrin generation test (FGT) on fresh plasma in the local laboratories. The outcome measure of this plasma recalcification test was the prolongation of the clotting time in the presence of antibody to factor VII/TF, expressed as percentage of the clotting time in the absence of antibody. The result was considered positive above 13%. Remaining plasma was frozen and stored for later central measurement of D-dimer, P-selectin, pro-thrombin fragment 1 + 2 (F1 + 2) and factor VIII; for these tests positivity cut-offs from the original publications were used. Clinical data were collected for calculation of the Khorana score, which assigns patients to three risk categories. Estimates of sensitivity and positive predictive value (PPV) were calculated, taking into account death as a competing risk, with 95% confidence intervals (CI) based on bootstrap re-sampling. Results: The prospective cohort has recruited 443 patients, with a mean age of 61 years, of which 49% women. In total, 23 patients developed VTE, after a mean time of 2.1 months (5.2%); 77 patients died, after a mean follow-up of 3.3 months (18%). Sensitivity was estimated at 61% (95% CI: 31-84%) for FGT, 84% (61-97) for D-dimer, 85% (56-96) for P-selectin, 44% (61-97) for factor VIII, and 70% (36-89) for F1 + 2. The positive predictive value was 4.7% (1.9-9.3%) for FGT, 6.9% (3.5-12) for D-dimer, 14% (4.8-27) for P-selectin, 11% (4.5-21) for factor VIII and 5.9% (2.4-12) for F1 + 2. A high Khorana score had a sensitivity of 63% (28-83) and PPV of 5.1% (1.6-12). None of the differences were statistically significant. Summary/Conclusions: There are no substantial differences in predictive performance between the studied biomarkers. None of the individual positive predictive values exceeded 15%. In this cohort of patients with advanced cancer, 18% died, which makes adjustment for death as competing risk of utmost importance. In our opinion single predictors will probably not solve the problem and combinations are likely to be helpful.
Published: 2013

13. Chemotherapy and anti-angiogenic drugs affect composition and coagulant phenotype of cell-derived vesicles in cancer patients

Author: Kleinjan, A., Verhoeff, J., Berckmans, R., Kunst, P., Van Doormaal, F., Di Nisio, M., Richel, D., Kamphuisen, P.W., Büller, H.R., Nieuwland, R., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: cancer patient, phenotype, cisplatin, bevacizumab, anticoagulant agent, chemotherapy, angiogenesis, blood, glioma, cetuximab, exosome, coagulating agent, vasculotropin receptor 1, fibrin, human, normal human, thrombosis, plasma, radiotherapy, cancer cell, endothelial microparticle, centrifugation, therapy, flow cytometry, membrane microparticle, gemcitabine, procoagulant, lung cancer, angiogenesis inhibitor, society, antiangiogenic therapy, hemostasis, patient, prognosis, neoplasm
Abstract: Background: The relationship between chemotherapy and circulating microparticles in patients with cancer is complex. First, release of cancer cell-derived microparticles may contribute to resistance of cancer cells to chemotherapy. Second, chemotherapy and angiogenesis inhibiting agents promote a prothrombotic state in cancer, and microparticles have been shown to exhibit both pro- and anticoagulant features. Aim: The aim of the present exploratory study was to determine the effects of therapy on the composition and coagulant activity of circulating vesicles. Methods: Blood was collected from 11 patients with glioma and 5 patients with lung cancer, at respectively 4 and 6 different time points before and after start of two different chemotherapy regimens. Age and sex matched healthy subjects (n = 11) were included for the glioma patients. In glioma patients, temozolamide was combined with bevacizumab, an anti-angiogenic agent. Patients with stage IIIB or IV lung cancer were treated with either cisplatin and gemcitabine, or with daily radiotherapy and cetuximab. Procoagulant activity was studied in a fibrin generation test. For some experiments, the coagulant activity of exosomes and other small types of vesicles in plasma was determined by removing microparticles by centrifugation. Numbers of endothelial and tumour-derived microparticles were determined by flow cytometry. Results: Treatment did not affect the overall procoagulant activity of vesicles in cancer patients (P = 0.39). Plasma of three patients had a detectable coagulant activity in the exosome fraction before therapy, compared to plasma from six patients after chemotherapy. Levels of endothelial microparticles (CD62E+) tended to increase in the glioma (P = 0.18), but not in lung cancer patients (P = 0.41). Baseline levels of microparticles exposing vascular endothelial growth factor receptor- 1 (VEGFR-1) were increased in cancer patients compared to healthy subjects (P = 0.012), and VEGFR-1-exposing microparticles decreased by 85% after anti-angiogenic therapy in glioma patients (P = 0.021). Finally, overall, no differences could be observed in the levels of mucine-exposing microparticles, except in two lung cancer patients which showed a clear increase two days after chemotherapy. Summary/Conclusion: In this small explorative study, chemotherapy and anti-angiogenic therapy lead to specific changes in the composition of circulating vesicles, especially with regard to endothelial- and tumour-derived microparticles. These changes are markedly different between the two patients groups and even between subjects within one group, suggesting that such microparticles may be associated with prognosis or response to treatment. At baseline, the procoagulant activity was mainly associated with microparticles, whereas after chemotherapy also a part of the procoagulant activity is associated with smaller vesicles (exosomes) in some patients, suggesting a role for such vesicles in the prothrombotic state after chemotherapy.
Published: 2013

14. Rhinovirus infection induces procoagulant changes in parallel with eosinophilic airway inflammation

Author: Majoor, C.J., Kamphuisen, P.W., Van De Pol, M.A., Meijers, J.C., Van Der Poll, T., Nieuwland, R., Johnston, S.L., Bel, E.H., Lutter, R., Van Der Sluijs, K.F., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: Rhinovirus, eosinophil count, antiplasmin, thrombin antithrombin complex, respiratory tract inflammation, hemostatic agent, von Willebrand factor, volunteer, lung, low drug dose, lung lavage, study design, thromboplastin, virus infection, pneumonia, inoculation, eosinophil, fibrin, coagulating agent, human, liquid, serotype, immunoassay, thrombosis, plasma, plasmin, risk, marker, limit of detection, plasminogen activator inhibitor 1, asthma, assay, procoagulant, thrombin, infection, respiratory tract diseases, drug therapy, respiratory virus, society, female, airway, inflammation, D dimer, hemostasis, eosinophil cationic protein, Rhinovirus infection, patient
Abstract: Background: Asthma exacerbations are frequently triggered by rhinovirus infections. Asthma itself is associated with activated coagulation and increased risk of venous thromboembolism1 and also respiratory viruses may activate hemostasis. Vice versa, a prothrombotic state in the lung can also induce or aggravate pulmonary inflammation. Aim: To determine whether rhinovirus infection and asthmatic airway inflammation act on the local and systemic hemostatic balance in patients in vivo. Methods: In a two-groups parallel study design 28 volunteers (14 patients with mild asthma (seven females, 19-26 years) and 14 healthy controls (13 females, 19-31 years)) were experimentalliy infected with low-dose rhinovirus serotype 16 (RV16). Patients with mild asthma were stable after discontinuation of their asthma medication 2 weeks prior to RV16 inoculation. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained 1 day before and 6 days after rhinovirus challange to evaluate several key markers of coagulation activation in plasma and BAL fluid, as well as the coagulant features of microparticles in BAL fluid. Thrombin-antithrombin complexes (TATc), von Willebrand factor (vWF), Plasmin-antiplasmin complexes (PAP), Plasminogen activator inhibitor type-1 (PAI-1), and eosinophil cationic protein (ECP) in plasma and BAL fluid were measured by immunoassay. Endogenous thrombin potential (ETP) was analysed using the Calibrated Automated Thrombogram® and tissue factor bearing microparticles, measured by fibrin generation test (FGT). Eosinophils were counted on cytospin preparations. Comparisons and correlations were performed by non-parametric testing. Results: In plasma, RV16 challange resulted in increased PAI-1 levels in patients with asthma after viral infection (26.5 ng/mL in patients with astma vs. 10.0 ng/mL in healthy controls, P = 0.01) and decreased PAP levels (318 vs. 534 ng/mL resp., P = 0.04). Changes in PAI-1 levels were significantly elevated in asthma than in control subjects (3.0 vs. -3.5 ng/L respectively, P = 0.024), while changes in TATc, D-dimer, vWF and ETP did not differ between both groups. In BAL fluid, the FGT shortened after viral infection in asthma (t = -1 day: 689s vs. t = 6 days: 516 s; P = 0.011), but not in healthy controls (t = -1 day: 695s vs. t = 6 days: 672 s; P = 0.79). The changes in TATc and PAP did not differ between both groups and vWF, D-dimer and PAI-1 were below the detection limit. Both FGT and TATc in BAL fluid correlated (Spearman) with eosinophil counts and ECP (r = -0.583 and -0.682 resp. for FGT and r = 0.535 and 0.619 resp. for TATc, all P
Published: 2013

15. Coagulant activity and cellular origin of circulating tissue factor exposing microparticles in cancer patients - two forms of TF-exposing microparticles

Author: Kleinjan, A., Boing, A. N., Di Nisio, M., Twint, D., Kamphuisen, P. W., Nanayakkara, P., Buller, H. R., Nieuwland, R., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: cancer patient, tumor cell, chemotherapy, blood, antibody, thromboplastin, metastasis, coagulating agent, fibrin, human, thrombosis, plasma, cancer cell, marker, limit of detection, flow cytometry, staining, citric acid, blood clotting time, thrombocyte, society, blood clotting factor 7, vein thrombosis, tumor marker, monocyte, hemostasis, patient, neoplasm
Abstract: Background: Because plasma of cancer patients presenting with venous thrombosis contains high numbers of tissue factor (TF)-exposing microparticles (TF-MP1), TF-MP have been causally linked to the occurrence of venous thrombosis in cancer patients. The relationship between numbers of TF-exposing MP and the TF-MP dependent coagulant activity, however, is unclear. In addition, to which extent TF-MP originate from cancer cells is also unknown. Aim: We investigated the relationship between TF-MP numbers and coagulant activity, and the cellular origin of circulating TF-MP in cancer patients. Methods: Citrate-anticoagulated blood was collected via a single blood withdrawal from cancer patients undergoing chemotherapy. The number of TF-MP was measured by flow cytometry and TF-MP coagulant activity was measured in a fibrin generation test (FGT) in the presence or absence of an inhibitory antibody to human factor VII. Patients were categorised as having a low or high number of TF-MP (≤ or > 95th percentile), and as having low or high TF-MP coagulant activity (≤ or > 13% TF-dependent prolongation of clotting time as determined by FGT). The cellular origin was determined by flow cytometry in those patients with number of TF-MP above the 95th percentile of the total cohort. Results: Of the total cohort of 209 cancer patients, 98 had metastasis (47%). Overall, no correlation was present between the numbers of TF-MP and the coagulant activity (r = 0.029, P = 0.69). When comparing patients with a high and low number of TF-MP, respectively three of the 12 (25%) and 60 of the 192 (31%) patients had high TFMP coagulant activity. Conversely, when comparing patients with high and low TF-MP coagulant activity, respectively only three of the 63 (4.8%) and nine of the 141 (6.4%) patients had a high number of TF-exposing MP. There was a marked variation between patients with regard to the cellular origin of the TF-MP. Of the 13 patients with high TF-MP numbers, the cellular origin of TF in five patients was variable and added up to above 100%; including 67% and 44% staining for two independent tumor markers, 66% for a platelet marker, and 59% for a monocyte marker (all medians). In the other eight patients, the origin of > 25% of TF-MP could be established, and most of these TF-MP originated from platelets and no tumor-derived vesicles were detectable. Summary/Conclusions: Because increased numbers of TF-MP and coagulant activity are almost mutually exclusive, we postulate that two forms of TF associated with MP circulate in cancer patients, a coagulant form which is present in minute quantities and below the detection limit of flow cytometry, and a non-coagulant form which is detectable by flow cytometry. Taken together, although at least part of the TFMP can derive from tumor cells, the cellular origin of circulating and coagulant TF-exposing MP in cancer patients remains to be elucidated.
Published: 2013

16. Cell-derived vasicles in health and disease

Author: Sturk, A., Nieuwland, R., Amsterdam Cardiovascular Sciences, Tytgat Institute for Liver and Intestinal Research, Cancer Center Amsterdam, and Laboratory for Experimental Clinical Chemistry
Published: 2012

17. Circulating Microparticles in Patients with Benign and Malignant Ovarian Tumors

Author: Rank, A., Liebhardt, S., Zwirner, J., Burges, A., Nieuwland, R., Toth, B., ACS - Amsterdam Cardiovascular Sciences, CCA -Cancer Center Amsterdam, and Laboratory Specialized Diagnostics & Research
Abstract: Background: Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. Patients and Methods: Microparticles from platelets/megakaryocytes, activated platelets and endothelial cells, tissue factor exposing microparticles and D-dinier values were examined in patients with newly diagnosed ovarian lesions before surgery, and were correlated with tumor histology. Results: Higher counts of CD63-positive microparticles were detected in patients with ovarian cancer [mean=276x10(6) (range: 64-948)/l; n=12] as compared to patients with benign ovarian tumors [146x10(6) (45-390)/l; n=21; p=0.014]. D-dimer values were also increased in patients with cancer [860 (180-4500) ng/l versus 280 (170-2720) ng/l; p=0.001]. Conclusion: Elevated levels of CD63-positive microparticles and D-dimer reflect the procoagulant phenotype of these patients. However, for the discrimination between benign and malignant ovarian tumors, measuring preoperative levels of microparticles does not seem to be helpful
Published: 2012

18. Platelet-Derived Microparticles

Author: Nieuwland, R., van der Pol, E., Gardiner, C., Sturk, A., Michelson, A. D., Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Laboratory for Experimental Clinical Chemistry, Other Research, Biomedical Engineering and Physics, and Tytgat Institute for Liver and Intestinal Research
Published: 2012

19. Vesiclepedia:A Compendium for Extracellular Vesicles with Continuous Community Annotation

Author: Kalra, H., Simpson, R.J., Ji, H., Aikawa, E., Altevogt, P., Askenase, P., Bond, V.C., Borras, F.E., Breakefield, X., Budnik, V., Buzas, E., Camussi, G., Clayton, A., Cocucci, E., Falcon-Perez, J.M., Gabrielsson, S., Gho, Y.S., Gupta, D., Harsha, H.C., Hendrix, A., Hill, A.F., Inal, J.M., Jenster, G., Kramer-Albers, E.M., Lim, S.K., Llorente, A., Lotvall, J., Marcilla, A., Mincheva-Nilsson, L., Nazarenko, I., Nieuwland, R., Nolte-'t Hoen, E.N.M., Pandey, A, Patel, T., Piper, M.G., Pluchino, S., Prasad, T.S., Rajendran, L., Raposo, G., Record, M., Reid, G.E., Sanchez-Madrid, F., Schiffelers, R.M., Siljander, P., Stensballe, A., Stoorvogel, W., Taylor, D., Thery, C., Valadi, H., van Balkom, B.W.M., Vazquez, J., Vidal, M., Wauben, M.H.M., Yanez-Mo, M., Zoeller, M., Mathivanan, S., Strategic Infection Biology, Dep Biochemie en Celbiologie, Sub Atmospheric physics and chemistry, dB&C I&I, LS Celbiologie-Algemeen, Urology, Medical Microbiology & Infectious Diseases, University of Zurich, Mathivanan, Suresh, Strategic Infection Biology, Dep Biochemie en Celbiologie, Sub Atmospheric physics and chemistry, dB&C I&I, LS Celbiologie-Algemeen, ACS - Amsterdam Cardiovascular Sciences, CCA -Cancer Center Amsterdam, and Laboratory Specialized Diagnostics & Research
Subjects: human proteinpedia, exosomal proteins, delivery-system, breast-milk, url decay, cells, microvesicles, update, rna, biogenesis, QH301-705.5, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), 610 Medicine & health, Apoptosis, Computational biology, 1100 General Agricultural and Biological Sciences, Biology, Vesiclepedia, Exosomes, Exosome, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Annotation, 0302 clinical medicine, SDG 3 - Good Health and Well-being, 1300 General Biochemistry, Genetics and Molecular Biology, 2400 General Immunology and Microbiology, Community Page, ExoCarta, Biology (General), Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), Biología y Biomedicina, 030304 developmental biology, Uncategorized, 0303 health sciences, General Immunology and Microbiology, General Neuroscience, Microvesicle, Research, 2800 General Neuroscience, Extracellular vesicle, 11359 Institute for Regenerative Medicine (IREM), Extracellular vesicles, Microvesicles, Compendium, Cell biology, Data sharing, Databases as Topic, 030220 oncology & carcinogenesis, General Agricultural and Biological Sciences, Extracellular Space
Abstract: Vesiclepedia is a community-annotated compendium of molecular data on extracellular vesicles., Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
Published: 2012

20. Microparticle tissue factor activity is increased in cancer patients prior to the development of venous thromboembolism

Author: Kleinjan, A., Van Doormaal, F.F., Berckmans, R.J., MacKman, N., Manly, D.A., Kamphuisen, P.W., Richel, D.J., Buller, H.R., Sturk, A., Nieuwland, R., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: marker, blood clotting factor 10a, cancer patient, thrombin antithrombin complex, venous thromboembolism, assay, procoagulant, society, blood clotting factor 7, thromboplastin, D dimer, hemostasis, follow up, cardiovascular diseases, fibrin, human, patient, normal human, phospholipid, thrombosis, neoplasm, risk
Abstract: Introduction: Cancer greatly increases the risk of venous thromboem-bolism (VTE). Here, we investigated the contribution of microparti-cle-dependent procoagulant activity to the prothrombotic state in these patients. Methods: In 43 cancer patients without VTE at entry and 22 healthy volunteers, markers of in vivo and microparticle-dependent coagulation were measured and patients were prospectively followed for 6 months for the development of VTE. Procoagulant activity of microparticles (MPs) was measured using a phospholipid dependent test (STA Procoag PLL), a factor Xa-generation assay (Xa-assay) with and without anti-tissue factor (TF), and a fibrin generation test (FGT) with and without anti-factor VII(a). Results: Markers of in vivo coagulation activation and total number of circulating MPs were elevated in cancer patients compared to controls (F1+2 246 vs. 156 pM, thrombin-antithrombin complexes 4.1 vs. 3.0 mg/L, D-dimer 0.76 vs. 0.22 mg/L and 5.53 x 106 vs. 3.37 x 106 microparticles per mL; all P
Published: 2011

21. The effect of common beta2-receptor haplotypes on catecholamine levels and hemostasis after standing up

Author: De Peuter, O.R., Meijers, J.C., Van Den Bogaard, B., Kim, Y.-S., Schaap, M.C., Nieuwland, R., Kok, W.E., Buller, H.R., Kamphuisen, P.W., and Vascular Ageing Programme (VAP)
Subjects: cardiovascular risk, haplotype, noradrenalin, nitrogen 13, thrombocyte activation, receptor, hemostatic agent, blood clotting factor, procoagulant, thrombin, aged, society, risk factor, catecholamine, blood clotting factor 8, catecholamine release, beta 2 adrenergic receptor, PADGEM protein, hemostasis, noradrenalin release, human, protein, thrombosis, plasma volume
Abstract: Introduction: Standing up increases the levels of several coagulation factors, partially due to a decrease in plasma volume. Whether this hemostatic response is additionally mediated by catecholamine release, is unknown. Furthermore, common haplotypes of the beta2- adrenergic receptor, which are associated with increased cardiovascular risk at older ages, may also affect catecholamine release and the hemostatic response. Methods: Catecholamine levels and hemostatic parameters were measured at rest and 10 min after standing up in healthy individuals, homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 (n = 24) haplotype. Mean age was 63 ± 1 years. Hemostatic parameters included coagulation factors, platelet activation by flow cytometric analysis of P-selectin and PAC-1 surface presentation, and endogenous thrombin potential (ETP). Results: Standing up resulted in an increase in the levels of catecholamine and clotting factors, notably factor VIII (116 ± 5% to 137 ± 5%, P
Published: 2011

22. The influence of carvedilol vs. metoprolol on sympathetic activity and hemostasis in patients with heart failure

Author: De Peuter, O.R., Kok, W. E., Verberne, H.J., Van Den Bogaard, B., Truijen, J., Schaap, M.C., Nieuwland, R., Meijers, J.C., Verheul, J.A., De Groot, C.A., Bakx, A.D., Somsen, G.A., Brewster, L.M., Buller, H.R., Kamphuisen, P.W., and Vascular Ageing Programme (VAP)
Subjects: haplotype, (3 iodobenzyl)guanidine, crossover procedure, iodine 123, receptor, heart failure, hemostatic agent, heart, carvedilol, von Willebrand factor, beta 2 adrenergic receptor, human, outcome assessment, thrombosis, risk, marker, nitrogen 13, beta adrenergic receptor blocking agent, thromboembolism, metoprolol, hyperactivity, society, hemostasis, patient, sympathetic tone, heart left ventricle ejection fraction
Abstract: Background: Carvedilol, a non-selective beta-blocker, may be more effective in reducing the risk of thromboembolic events in heart failure, compared to metoprolol, a selective beta-blocker (De Peuter et al., Eur J Heart Fail, in press/ISTH 2009). We hypothesized that carvedilol lowers this risk through more effective downregulation of the sympathetic hyperactivity and the associated prothrombotic state compared to metoprolol. This effect may be mediated through common haplotypes of the beta2-adrenergic receptor. Methods: In this prospective, randomized, open-label with blinded outcome assessments, crossover study, stable heart failure patients (left ventricular ejection fraction
Published: 2011

23. Apheresis platelet concentrates contain platelet-derived and endothelial cell-derived microparticles

Author: Rank, A., Nieuwland, R., Liebhardt, S., Iberer, M., Grützner, S., Toth, B., Pihusch, R., Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, and Laboratory for Experimental Clinical Chemistry
Abstract: Background and Objectives Microparticles (MP) are membrane vesicles with thrombogenic and immunomodulatory properties. We determined MP subgroups from resting platelets, activated platelets and endothelial cells in donors and apheresis platelet concentrates (PC). Material and Methods MP were double stained with annexin V and CD61 (platelet-derived MP; PMP), P-selectin or CD63 (MP from activated platelets) and CD144 plus E-selectin (endothelial cell-derived MP; EMP) and detected by flow cytometry in platelet donors (n = 36) and apheresis PC (n = 11; Trima (TM)). Results PC contained MP, mainly from resting platelets [93% (90-95)], and minor fractions of PMP from activated platelets [P-selectin+ or CD63+; 4 center dot 8% (3 center dot 2-7 center dot 7) and 2 center dot 6% (2 center dot 0-4 center dot 0)]. Compared to donors, levels of annexin V+ MP, PMP, P-selectin+ and CD63+ MP were 1 center dot 7-, 2 center dot 3-, 8 center dot 6- and 3 center dot 1-fold higher in PC (all P
Published: 2011

24. Measurement of procoagulant activity of microparticles by the fibrin generation test as a predictor for venous thrombosis in cancer patients

Author: Kleinjan, A., Van Doormaal, F.F., Berckmans, R.J., Di Nisio, M., Sturk, A., Kamphuisen, P.W., Nieuwland, R., Büller, H.R., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: cancer patient, receiver operating characteristic, prevalence, venous thromboembolism, membrane microparticle, assay, procoagulant, anticoagulant agent, blood clotting time, lung cancer, blood clotting factor 7, vein thrombosis, antibody, thromboplastin, hemostasis, follow up, fibrin, patient, thrombosis, neoplasm, plasma, breast, risk
Abstract: Background: Although in patients with cancer the risk of venous thromboembolism (VTE) is increased, the incidence is too low to routinely give prophylactic treatment. Procoagulant microparticles (MPs), especially tissue factor (TF)-bearing MPs, contribute to the risk of VTE in cancer patients. In the present study, we assessed the MP-associated procoagulant activity using a functional assay, the fibrin generation test (FGT), to identify cancer patients who will develop VTE. Methods: As an ongoing study, plasma was collected from cancer patients, mainly with stage III or IV pancreatic, gastro-intestinal, breast or lung cancer. The MP-associated procoagulant activity was determined via the FGT with the addition of an inhibitory antibody to factor VII. The prolongation of the clotting time in the presence of anti-factor VII is a measure for the contribution of TF-bearing MPs to the clotting time. Patients were followed up for 6 months. Preliminary results: 100 patients were included, of which 77 had complete follow-up. The first 43 patients were used to establish a cut-off value of the FGT. Receiver operating characteristics showed that a prolongation of the clotting time of 13% after addition of anti-factor VII, was the optimal cut-off value. In the entire group, 8 of 77 patients (10%) developed VTE, of which 7 could have been predicted by the FGT. Using this cut-off value, 23 patients (30%) had a FGT-result above the cut-off (positive test) and 54 patients had a FGT-result below the cut-off (negative test). The prevalence of VTE was 30% in the FGT-positive patients and 2% in the FGT-negative patients (sensitivity 88%, specificity 77%). Conclusion: The FGT seems an excellent predictor for VTE in cancer patients. The next step will be to test the efficacy of prophylactic anticoagulants in patients with cancer and a high thrombosis risk based on the FGT.
Published: 2010

25. Commercial SOI sensor technology

Author: van Zeijl, E., Schmits, R., van den Berg, J. H., Harmsma, P. J., Westerveld, W.J., Lagioia, M., Bodis, P., Ebeling, R. P., Nieuwland, R. A., and Yang, S.
Abstract: We present a platform for the deployment of SOI based sensors in commercialapplications. The platform is designed from a systems perspective and includes allaspects of a SOI sensor system, including sensor head itself, the communicationsinfrastructure and a customized interrogation system.
Published: 2010

26. Phospholipid-dependent clotting time is able to identify cancer patients with high levels of circulating microparticles

Author: Van Doormaal, F.F., Kleinjan, A., Buller, H.R., Kamphuisen, P., Berckmans, R.J., Nieuwland, R., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: normal distribution, cancer patient, velocity, lipocortin 5, digestive system cancer, pancreas cancer, blood, thromboplastin, gender, metastasis, normal human, phospholipid, thrombosis, plasma, breast, centrifugation, membrane microparticle, citric acid, assay, procoagulant, thrombin, blood clotting time, society, female, hemostasis, patient, neoplasm
Abstract: Introduction: Circulating procoagulant microparticles (MP) have been associated with a prothrombotic state in many diseases, including cancer. MP can enhance thrombin formation by exposing tissue factor (TF), the initiator of coagulation in vivo. Whether procoagulant TF is really exposed on circulating MP in cancer, however, is still debated. In addition, MP can also expose procoagulant phospholipids, which are essential for propagation of coagulation. In this study, we determined the contribution of circulating MP to phospholipid (PPL)-dependent coagulation in plasma samples from a heterogeneous group of cancer patients and compared them to healthy subjects. Methods: Citrate-anticoagulated blood was collected from healthy subjects (n = 85) and cancer patients (n = 50). The procoagulant activity of circulating MP was measured in fresh plasma using the STA procoag PPL assay (Diagnostica Stago). Results: The mean age of healthy subjects was 54 ± 12 years and 62% was female. The PPL-dependent clotting time (CTPPL) was 77.8 s ± 8.7 (mean ± SD, normal distribution), gender independent (P = 0.97) and not associated with age (r = 0.24, P = 0.83). Both removal of MP by high speed centrifugation or addition of annexin V strongly prolonged the CTPPL, indicating that MP are indeed the main source of PPL under these conditions. With regard to plasma samples from cancer patients, seven patients (14%) showed a faster CTPPL than controls (below 2.5 percentile). Five of these patients had metastatic disease (four gastrointestinal, one pancreatic cancer). The other two had local disease (one breast and one gastrointestinal cancer). Conclusions: The CTPPL is useful in identifying cancer patients with high levels of circulating procoagulant MP.
Published: 2009

27. Hemostase anno 2008

Author: Nieuwland, R., Stroobants, A. K., Sturk, A., Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Laboratory for Experimental Clinical Chemistry, and Laboratory for General Clinical Chemistry
Published: 2008

28. Microparticles and thrombosis

Author: Boing, A. N., Sturk, A., Nieuwland, R., Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Other Research, Laboratory for Experimental Clinical Chemistry, and Laboratory for General Clinical Chemistry
Published: 2007

29. Complement activatie op micropartikels

Author: Biro, E., Nieuwland, R., Hack, C. E., Sturk, A., Other departments, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Laboratory for Experimental Clinical Chemistry, Landsteiner Laboratory, and Laboratory for General Clinical Chemistry
Published: 2007

30. Aspirine en clopidogrel resistentie

Author: Nieuwland, R., Sturk, A., Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Laboratory for Experimental Clinical Chemistry, and Laboratory for General Clinical Chemistry
Published: 2007

31. Platet-derived microparticles

Author: Nieuwland, R., Sturk, A., Michelson, A. D., Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Laboratory for Experimental Clinical Chemistry, and Laboratory for General Clinical Chemistry
Published: 2007

32. Platelet-derived microparticles

Author: Nieuwland, R., Sturk, A., Michelson, A. D., Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Laboratory for Experimental Clinical Chemistry, and Laboratory for General Clinical Chemistry
Published: 2006

33. Synovial microparticles from arthritic patients modulate chemokine and cytokine release by synoviocytes

Author: Berckmans, R.J., Nieuwland, R., Kraan, M.C., Schaap, M.C.L., Pots, D., Smeets, T.J.M., Sturk, A., Tak, P.P., and Faculteit der Geneeskunde
Published: 2005

34. Cellulaire micropartikels en vaatschade. II. Functionele eigenschappen en klinische betekenis

Author: Diamant, M., Tushuizen, M. E., Sturk, A., Nieuwland, R., Laboratory for Experimental Clinical Chemistry, Laboratory for General Clinical Chemistry, Amsterdam Cardiovascular Sciences, and Cancer Center Amsterdam
Abstract: Cellular microparticles support coagulation by exposure of negatively charged phospholipids and sometimes tissue factor. They are involved in inflammatory processes, the transfer of membrane antigens and bioactive molecules, and in the modulation of endothelial functions. Patients with disturbances in membrane vesiculation, leading to decreased numbers of circulating microparticles, present clinically with an increased bleeding tendency. In contrast, elevated numbers of microparticles are found in a great variety of diseases involving blood-vessel damage and hypercoagulability. Microparticles are also a major component of human atherosclerotic plaques. In view of their functional properties, cellular microparticles may be a missing link between cellular and plasmatic processes underlying atherosclerotic blood-vessel damage
Published: 2004

35. Cellulaire micropartikels en vaatschade. I. Structuur, detectie en ontstaanswijze

Author: Diamant, M., Tushuizen, M. E., Sturk, A., Nieuwland, R., Laboratory for Experimental Clinical Chemistry, Laboratory for General Clinical Chemistry, Amsterdam Cardiovascular Sciences, and Cancer Center Amsterdam
Abstract: In virtually all eukaryotic cells, activation and apoptosis lead to the formation of vesicles or microparticles by intracellular mechanisms which as yet are not completely understood. Flow cytometry, electron microscopy and ELISA techniques can be used to detect microparticles. Microparticles are a heterogeneous population and their numbers, cellular origin, composition and functional characteristics, both in vitro and in vivo, depend on the circumstances under which they were generated. Microparticles derived from various cells, primarily platelets but also lymphocytes, granulocytes, monocytes, erythrocytes and endothelial cells, are present in the circulation of healthy subjects. Elevated numbers of microparticles can be found in a wide variety of diseases, all of which are associated with hypercoagulability and blood-vessel damage, thus suggesting their role in the pathogenesis of vascular disease
Published: 2004

36. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation

Author: Rj, Berckmans, Nieuwland R, An, Böing, Fred Romijn, Ce, Hack, and Sturk A
Subjects: Enzyme Activation, Male, Membrane Lipids, Blood Cells, Reference Values, Thrombin, Humans, Endothelium, Vascular, Phosphatidylserines, Annexin A5, Particle Size, Flow Cytometry, Blood Coagulation
Abstract: We determined the numbers, cellular origin and thrombin-generating properties of microparticles in healthy individuals (n = 15). Microparticles, isolated from fresh blood samples and identified by flow cytometry, originated from platelets [237 x 10(6)/L (median; range 116-565)], erythrocytes (28 x 10(6)/L; 13-46), granulocytes (46 x 10(6)/L; 16-94) and endothelial cells (64 x 10(6)/L; 16-136). They bound annexin V, indicating surface exposure of phosphatidylserine, and supported coagulation in vitro. Interestingly, coagulation occurred via tissue factor (TF)-independent pathways, because antibodies against TF or factor (F)VII were ineffective. In contrast, in our in vitro experiments coagulation was partially inhibited by antibodies against FXII (12%, p = 0.006), FXI (36%, p0.001), FIX (28%, p0.001) or FVIII (32%, p0.001). Both the number of annexin V-positive microparticles present in plasma and the thrombin-generating capacity inversely correlated to the plasma concentrations of thrombin-antithrombin complex (r = -0.49, p = 0.072 and r = -0.77, p = 0.001, respectively), but did not correlate to prothrombin fragment F1+2 (r = -0.002, p = 0.99). The inverse correlations between the number of microparticles and their thrombin-forming capacity and the levels of thrombin-antithrombin complex in plasma may indicate that microparticles present in the circulation of healthy individuals have an anticoagulant function by promoting the generation of low amounts of thrombin that activate protein C. We conclude that microparticles in blood from healthy individuals support thrombin generation via TF- and FVII-independent pathways, and which may have an anticoagulant function.
Published: 2001

37. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation

Author: Berckmans, R. J., Nieuwland, R., Böing, A. N., Fred Romijn, Hack, C. E., Sturk, A., and Other departments
Abstract: We determined the numbers, cellular origin and thrombin-generating properties of microparticles in healthy individuals (n = 15). Microparticles, isolated from fresh blood samples and identified by flow cytometry, originated from platelets [237 x 10(6)/L (median; range 116-565)], erythrocytes (28 x 10(6)/L; 13-46), granulocytes (46 x 10(6)/L; 16-94) and endothelial cells (64 x 10(6)/L; 16-136). They bound annexin V, indicating surface exposure of phosphatidylserine, and supported coagulation in vitro. Interestingly, coagulation occurred via tissue factor (TF)-independent pathways, because antibodies against TF or factor (F)VII were ineffective. In contrast, in our in vitro experiments coagulation was partially inhibited by antibodies against FXII (12%, p = 0.006), FXI (36%, p
Published: 2001

38. Laboratoriumdiagnostiek van heparine-geïnduceerde trombocytopenie

Author: Biró, Éva, Nieuwland, R., Wester, J. P., Haas, F. J., Sturk, A., and Other departments
Published: 2000

39. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant

Author: Nieuwland, R., Berckmans, R.J., Rotteveel-Eijkman, R.C., Maquelin, K.N., Roozendaal, K.J., Janssen, P.G., ten Have, K., Eijsman, L., Hack, C.E., Sturk, A., and Faculteit der Geneeskunde
Published: 1997

40. Ticagrelor decreases concentrations of prothrombotic extracellular vesicles compared to clopidogrel

Author: Gasecka, A., Nieuwland, R., Budnik, M., Françoise DIGNAT-GEORGE, Eyileten, C., Harrison, P., Kaplon-Cieslicka, A., Lacroix, R., Opolski, G., Pol, E., Postula, M., Leroyer, A., Siljander, P., Sturk, A., and Filipiak, K.

41. Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

Author: Clayton A, Buschmann D, J. Brian Byrd, Drf, Carter, Cheng L, Compton C, Daaboul G, Devitt A, Jm, Falcon-Perez, Gardiner C, Gustafson D, Harrison P, and Nieuwland R

42. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis

Author: Nieuwland R, Rj, Berckmans, McGregor S, An, Böing, Fred Romijn, Rg, Westendorp, Ce, Hack, and Sturk A
Subjects: Adult, Blood Platelets, Male, Adolescent, Lipopolysaccharide Receptors, Thrombin, Infant, Disseminated Intravascular Coagulation, Blood Coagulation Factors, Thromboplastin, Meningococcal Infections, Child, Preschool, Sepsis, Humans, Thrombophilia, Female, Survivors, Particle Size, Child, Biomarkers, Granulocytes
Abstract: Patients with meningococcal sepsis generally suffer from disseminated intravascular coagulation (DIC). The aim of this study was to address whether these patients have elevated numbers of circulating microparticles that contribute to the development of DIC. Plasma samples from 5 survivors, 2 nonsurvivors, and 5 healthy volunteers were analyzed for the presence of microparticles by flow cytometry. Ongoing coagulation activation in vivo was quantified by enzyme-linked immunosorbent assay of plasma prothrombin fragment F(1 + 2), and procoagulant properties of microparticles in vitro were estimated by thrombin-generation assay. On admission, all patients had increased numbers of microparticles originating from platelets or granulocytes when compared with controls (P =.004 and P =.008, respectively). Patients had elevated levels of F(1 + 2) (P =.004), and their microparticles supported thrombin generation more strongly in vitro (P =.003) than those of controls. Plasma from the patient with the most fulminant disease course and severe DIC contained microparticles that expressed both CD14 and tissue factor, and these microparticles demonstrated extreme thrombin generation in vitro. We conclude that patients with meningococcal sepsis have elevated numbers of circulating microparticles that are procoagulant. These findings may suggest a novel therapeutic approach to combat clinical conditions with excessive coagulation activation.

43. 40 EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author: Veitenhansl, M., Stegner, K., Hierl, F-X, Dieterle, C., Feldmeier, H., Gutt, B., Landgraf, R., Garrow, A. P., Vileikyte, L., Findlow, A., Waterman, C., Boulton, A. J. M., Shankhdhar, K., Shankhdhar, L., Shankhdhar, U., Petrova, N. L., Foster, A. V. M., Edmonds, M. E., Ferraresi, R., Caravaggi, C., Giglio, R., Cavaiani, P., Pogliaghi, I., Sommariva, E., Katz, I. A., Harlan, A., Miranda-Palma, B., Prieto-Sanchez, L., Armstrong, D. G., Bowker, J. H., Mizel, M. S., Cernea, S., Wohlgelernter, J., Kidron, M., Modi, P., Raz, I., Arbit, E., Nosek, L., Kapitza, C., Beckett, P., Gelfand, R., Goldberg, M., Heise, T., Testa, M. A., Turner, R. R., Hayes, J. F., Scranton, R. E., Simonson, D. C., Yang, Y-W, Hsu, Y-J, Naujok, O., Francini, F., Jorns, A., Tiedge, M., Lenzen, S., Abdel-Wahab, Y. H. A., Marenah, L., Orr, D. F., Shaw, C., Flatt, P. R., Chokkalingam, K., Mansell, P. I., Clausen, P., Ekbom, P., Damm, P., Feldt-Rasmussen, U., Nielsen, B., Mathiesen, E. R., Feldt-Rasmussen, B., Dewan, S., Da Silva, N., Ternan, P. Mc, Leong, K. S., Wilding, J. P. H., Asatiani, N., Kurashvili, R., Dundua, M., Shelestova, E., Pagava, K., Ramazashvili, M., Hod, M., Smirnov, S., Petersen, J. L. A., Justesen, T. I., Ringholm Nielsen, L., Muller, C., Hojlund, K., Wensaas, A., Kase, E. T., Aas, V., Rustan, A. C., Thoresen, G. H., Levin, K., Beck-Nielsen, H., Gaster, M., Im, S-S, Kang, S-Y, Kim, S-Y, Ahn, Y-H, Lihn, A. S., Schmoll, D., Werner, T., Kienitz, A., Meyer, M., Barthel, A., Ailett, F., Sutherland, C., Walther, R., Grempler, R., Sasson, S., Reich, R., Tenenbaum, T., Alpert, E., Anfossi, G., Russo, I., Traversa, M., Massucco, P., Mattiello, L., Doronzo, G., Trovati, M., Lally, S., Tan, C. Y., Owens, D., Tomkin, G. H., Porchay, I., Pean, F., Bellili, N., Betoulle, D., Balkau, B., Tichet, J., Marre, M., Fumeron, F., Group D.E.S.I.R., Chatellier, G., Alhenc-Gelas, F., Diabhycar, Study Group, Nichols, G. A., Brown, J. B., Hayes, R. P., Bowman, L., Drexel, H., Saely, C. H., Marte, T., Benzer, W., Langer, P., Hoefle, G., Moll, W., Aczel, S., Karagiannis, E., Lubben, G., Urquhart, R., Edwards, G., Bruce, S., Howlett, H. S. C., Cugnardey, N., Turner, K. C., Park, J-S, Fiedorek, F. T., Avogaro, A., Gallo, A., Pinton, P., Rizzuto, R., Murphy, E., Ceolotto, G., Caterson, I., Guy-Grand, B., Hill, J., Barone, M., Aiello, A., Allochis, G., Borzi, V., Cannata, F., Caronna, S., D Avanzo, A., Elli, R., Formoso, G., Paroli, A., Scardapane, R., Sorichetti, P., Tatti, P., Viviani, G., Santeusanio, F., Italian Repaglinide Study Group, Manzella, D., Grella, R., Abbatecola, A. M., Paolisso, G., Sondergaard, L. G., Monster, T. B. M., Johnsen, S. P., Olsen, M. L., Mclaughlin, J. K., Sorensen, H. T., Lervang, H. H., Rungby, J., Lyssenko, V., Fredriksson, J., Almgren, P., Anevski, D., Orho-Melander, M., Sjogren, M., Tuomi, T., Groop, L., Jaziri, R., Aubert, R., Tuomilehto, J., Hu, G., Jousilahti, P., Peltonen, M., Lindstrom, J., Laina, A., Alevizaki, M., Philippou, G., Souvatzoglou, A., Anastasiou, E., Alba, S., Metcalf, B. S., Voss, L. D., Jeffery, A. N., Wilkin, T. J., Gluimer, C., Colagiuri, S., Vistisen, D., Borch-Johnsen, K., Haynes, A., Bower, C., Bulsara, M. K., Jones, T. W., Davis, E. A., Mortensen, H. B., Hougaard, P., Holl, R., Swift, P., Pociot, F., Knip, M., Hansen, L., Szadkowska, A., Pietrzak, I., Zmyslowska, A., Wyka, K., Bodalski, J., Holl, R. W., Swift, R., Hougaard, R., Gerstl, E-M, Engelsberger, I., Rabl, W., Rosenbauer, J., Grobe, H., Hofer, S. E., Krause, U., DPV-Wiss-Study Group, Dabelea, D., Morgan, T., Pettitt, D. J., Dolan, L., Mayer-Davis, E. J., Pihoker, C., Hillier, T. A., Imperatore, G., Ruggiero, A., Hamman, R. E., Stylianou, A., Tentolouris, N., Perrea, D., Tselepis, A. D., Lourida, E., Kitsou, E., Katsilambros, N., Vedovato, M., Dodesini, A. R., Lepore, G., Tiengo, A., Trevisan, R., Penno, G., Miccoli, R., Pucci, L., Lucchesi, D., Bandinelli, S., Fotino, C., Triscornia, S., Baldassari, E., Del Prato, S., Reboldi, P., Santeusanio, E., Fuller, J., Langham, R. G., Gow, R. M., Zhang, Y., Kelly, D. J., Christensen, P. K., Parving, H-H, Gilbert, R. E., Chibalin, A. V., Zhong, Z., Kotova, O., Davidescu, A., Ehren, I., Ekberg, K., Wahren, J., Wassef, L., Buckley, A. J., Rooney, K. B., Briody, J., Thompson, M., Ozanne, S. E., Thompson, C. H., Chamson-Reig, A., Summers, K., Arany, E. J. R., Hill, D. J., Solerte, S. B., Gazzaruso, C., Locatelli, E., Precerutti, S., Schifino, N., Ferrari, E., Fioravanti, M., Phenekos, C. V., Ginis, A., Fragaki, I., Chalkiadaki, M., Tzioras, C., Powell, L. A., Mcguire, G. M., Jewhurst, V., Trimble, E. R., Rasmussen, B. M., Vessby, B., Uusitupa, M., Berglund, L., Pedersen, E., Riccardi, G., Rivellese, A. A., Tapsell, L., Hermansen, K., Kanwu, Study Group, Da Silva Xavier, G., Rutter, J., Rutter, G. A., Briaud, I. M., Lingohr, M. K., Dickson, L. M., Mccuaig, J. R., Lawrence, J. C., Rhodes, C. J., Wikstrom, J. D., Katzman, S. M., Shirihai, O. S., Yang, J., Deng, S., Wang, X., Hessner, M. J., Wu, J., Wong, R. K., Sukumvanich, S., Markman, J. F., Naji, A., Wolf, B. A., Gao, Z., Rubi, B., Del Arco, A., Satrustegui, J., Maechler, P., Del Guerra, S., Lupi, R., Bugliani, M., Sbrana, S., Torri, S., Boggi, U., Vistoli, F., Mosca, F., Marchetti, P., Rennings, A. J. M., Smits, P., Stewart, M. W., Tack, C. J. J., Li, L., Nystrom, T., Gutniak, M., Ahren, B., Holst, J., Sjoholm, A., Gomes, M. B., Cailleaux, S., Tibirica, E., Albertini, J-P, Chen, H., Mather, R., Valensi, P. E., Chisalita, S. I., Arnqvist, H. J., Kraenkel, N., Adams, V., Linke, A., Gielen, S., Schuler, G., Humbrecht, R., Cipollone, F., Iezzi, A., Fazia, M., Pini, B., Cucurullo, C., Cesare, D., Schmidt, A. M., Mazurek, T., Zang, L. F., Mannion, J., Diehl, J., Martin, J., Martella, A., Zalewski, A., Shi, Y., Otter, W., Winter, M., Doering, W., Standi, E., Schnell, O., Kragelund, C., Kober, L., Faber, J., Hildebrandt, P., Steffensen, R., Pankowska, E., Szypowska, A., Lipka, M., Herwig, J., Scholl-Schilling, G., Bohles, H., Robertson, K. J., Schonle, E., Gucev, Z., Mordhorst, L., Tamer, S. C., Gall, M-A, Ludvigsson, J., Hoogma, R. P. L., Hammond, P. J., Gomis, R., Kerr, D., Bruttomesso, D., Bouter, P., Wiefels, K. J., La Calle, H., Schweitzer, D. H., Pfohl, M., Torlone, E., Krinelke, L. G., 205-Nations Study Group, Conget, I., Storms, F., Rodriguez, J., Leperlier, C., Davies, M., At Lantus, Study Group, Peter, R., Luzio, S. D., Dunseath, G., Miles, A., Hare, B., Backx, K., Pauvaday, V., Owens, D. R., Caselli, A., Marfia, G. A., Battista, C., Veves, A., Spallone, V., Uccioli, L., Gonzalez, J. S., Peyrot, M. F., Rubin, R. R., Leventhal, H., Scheffler, N., Ulbrecht, J. S., Cavanagh, P. R., Boulton, A. J., Perrin, N. A., Oglesby, A., Bastyr, E. J., Ziegler, D., Siekierka-Kleiser, E., Meyer, B., Schweers, M., Selvarajah, D., Wilkinson, I. D., Emery, C. J., Shaw, P. J., Griffiths, P. D., Tesfaye, S., Obrosova, I. G., Arezzo, J., Phillips, K., Fidarestat Study Group, Gribble, F. M., Williams, L., Reimann, F., Iakoubov, R., Whiteside, C., Brubaker, P. L., Acitores, A., Gonzalez, N., Sancho, V., Valverde, I., Villanueva-Penacarrillo, M. L., Martin-Duce, A., Trigo, M. V., Arnes, L., Burkart, V., Ichino, N., Ohashi, A., Klein, B. S., Paxian, S., Schmid, R., Karlsen, A. E., Heding, P. E., Frobose, H., Ronn, S. G., Kruhoffer, M., Orntoft, T. F., Nerup, J., Mandrup-Poulsen, T., Billestrup, N., Cardozo, A. K., Ortis, F., Feng, Y-M, Rasschaert, J., Eylen, F., Storling, J., Herchuelz, A., Eizirik, D. L., Wang, H., Kouri, G., Wollheim, C. B., Ribaux, P., Hammar, E., Parnaud, G., Rouiller, D., Bosco, D., Halban, P., Midthjell, K., Carlsson, S., Grill, V., Lau, C., Farch, K., Glumer, C., Tetens, I., Jorgensen, T., Tillin, T., Forouhi, N., Mckeigue, P., Chaturvedi, N., Zethelius, B., Hales, C. N., Berne, C., Coleman, R. L., Stevens, R. J., Holman, R. R., Christensen, J. O., Sandbak, A., Lauritzen, T., Irwin, N., Gault, V. A., Green, B. D., Harriott, P., O Harte, F. P. M., Bouman, S. D., Urso, B., Brand, C. L., Rolin, B., Ribel, U., Schaffer, L., Maggs, D. G., Ceriello, A., Frias, J. P., Wang, Y., Ruggles, J. A., Kolterman, O. G., Piconi, L., Weyer, C., Want, L. L., Ratner, R. E., Uwaifo, G. I., Thornberry, N. A., Eiermann, G., Kim, D., Lankas, G., Leiting, B., Li, Z., Lyons, K., Petrov, A., Sinha Roy, R., Woods, A., Woods, J., Zhang, B. B., Fisher, M., Moller, D. E., Weber, A. E., Dreyer, M., Bellin, C., Schmitz, V., Roesen, R., Nescheret, A. P., Bose, A. K., Mocanu, M. M., Carr, R. D., Yellon, D. M., Manolopoulos, K., Born, S., Wagner, A., Jeziorska, M., Ben Drief, A., Bashir, M., Tomlinson, D., Malik, R. A., Zeymer, U., Schwarzmaier-D Assie, A., Petzinna, D., Chiasson, J-L, Stratton, I. M., Af Bjorkesten, C-G, Fagerudd, J., Rosengard-Barlund, M., Forsblom, C., Pettersson-Fernholm, K., Waden, J., Saraheimo, M., Ronnback, M., Thorn, L., Groop, P-H, Mollsten, A., Svensson, M., Kockum, I., Rudberg, S., Brismar, K., Dahlquist, G., Hovind, P., Hansen, T. K., Tarnow, L., Thiel, S., Jensen, B. R., Flyvbjerg, A., Kankova, K., Hertlova, M., Krusova, D., Schwenke, S., Ott, J., Thom, S. A. M., Mistry, P., Sjolie, A., Larsen, B., Witt, N., Hughes, A. D., Samira, H. H., Lahiry, S., Howlader, S. R., Parveen, S., Azad Khan, A. K., Clarke, P. M., Gray, A., Stevens, R., Holman, R., Phillips, L., Phillips, P. J., Chittleborough, C., Baldock, K., Taylor, A., North West Adelaide Health Study Team, Davis, W. A., Davis, T. M. E., Knuiman, M. W., Hendrie, D., Worthley, D., Nicolucci, A., Pellegrini, F., Berardis, G., Franciosi, M., Belfiglio, M., Rossi, M. C. E., Sacco, M., Valentini, M., Richardson, C. C., Jones, P., Persaud, S., Hussain, K., Clark, A., Christie, M. R., Gniuli, D., Hribal, M. L., Accili, D., Khan, M., Zervou, S., Cheung, L., Abouna, S., Ifandi, V., Pelengaris, S., Luco, R. F., Ferrer, J., Ma, D., Shield, J. P. H., Dean, W., Leclerc, I., Knauf, C., Burcelin, R., Kelsey, G., Powers, A. C., Shostak, A., Ferrara, N., Poffenberger, G., Jerome, W. G., Brissova, M., Geloneze, S. R., Tambascia, M. A., Pareja, J. C., Chaim, E., Silveira, H. V., Geloneze, B., Ravikumar, B., Carey, P. E., Snaar, J. E., Dheelchand, D., Cook, D. B., Neely, D., Taylor, G., Morris, P. G., Taylor, R., Stears, A. J., Masding, M. G., Wootton, S. A., Sandeman, D. D., Klimes, I., Wein, S., Gasperikova, D., Ukropec, J., Wiernsperger, N., Sebokova, E., Manco, M., Mingrone, G., Granato, L., Greco, A. V., Nanni, G., Castagneto, M., Vidal, H., Calvani, M., Ferrannini, E., Alvarsson, M., Sundkvist, G., Lager, I., Henricsson, M., Berntorp, K., Fernqvist-Forbes, E., Steen, L., Orn, T., Shutler, S., Bianchi-Biscay, M., Rosenstock, J., Sugimoto, D., Strange, P., Stewart, J., Soltes Rak, E., Dailey, G., Kloos, C., Muller, U., Samann, A., Femerling, M., Risse, A., Jecht, M., Haak, T., Garg, R., Lawrence, I. G., Akinsola, M. O., Davies, M. J., Mcnally, P. G., Garber, A. J., Kim, H., Draeger, E., Aydin, L., Sengul, A., Kurklu, A., Ucak, S., Basat, O., Seber, S., Altuntas, Y., Jin, J., Yu, Y., Yu, H., Zhang, X., Mattoo, V., Eckland, D., Widel, M., Duran, S., Fajardo, C., Strand, J., Knight, D., Oakley, D., Tan, M., Sato, A., Nagao, M., Aki, N., Nakagami, T., Iwamoto, Y., Zhou, Z., Li, X., Huang, G., Yan, X., Yang, L., Peng, J., Wang, J., Tan, S., Tang, W., Furnsinn, C., Brunmair, B., Wagner, L., Gras, F., Artwohl, M., Zierhut, B., Waldhausl, W., Shine, B. L., Hopkins, D., Anand, V., Lim, E., Raval, U., Sharp, P., Corder, R., Lipkin, D., Lahiri, A., Bartnik, M., Ryden, L., Ferrari, R., Malmberg, K., Pyorala, K., Simoons, M. L., Standl, E., Soler-Soler, J., Ohrvik, J., Euro Heart Survey Investigators, Bruce, D. G., Starkstein, S. E., Schauer, U. J. W., Astrup, A. S., Pietraszek, L., Nielsen, F. S., Rossing, P., Ali, S., Smidt, U. M., Yokoyama, H., Pavkov, M. E., Knowler, W. C., Bennett, P. H., Nelson, R. G., Lopez-Alba, A., Morcillo, L., Caballero, A., Montoya, L., Jimenez, A., Maceira, B., Lewis, J. B., Ravid, M., Wajman, A., Tadgell, C., Remuzzi, G., Hunsicker, L. G., Wessman, M., Taskinen, M-R, FinnDiane Study Group, Pugliese, G., Amadio, L., Menini, S., Oddi, G., Ricci, C., Iacobini, C., Pricci, F., Sorcini, M., Pesce, C., Migliaccio, E., Giorgio, M., Pelicci, P., Di Mario, U., Lassila, M., Jandeleit-Dahm, K., Seah, K. K., Calkin, A. C., Allen, T. J., Cooper, M. E., Lopes Faria, J. M., Cavakcanti, T. C., Silva, K. C., Ferrari, A. L., Lopes Faria, J. B., Cellek, S., Foxwell, N. A., Cotter, M. A., Cameron, N. E., Tennagels, N., Jordan, H., Stahl, P., Voss, M. D., Welte, S., Werner, U., Lehmann, R., Moeschel, K., Baumgartner, F., Oeckinghaus, A., Beck, A., Weigert, C., Hennige, A., Schleicher, E. D., Haring, H. U., Mussig, K., Staiger, H., Haring, H-U, Natalicchio, A., Laviola, L., Tullio, C., Renna, L., Giorgino, R., Giorgino, F., Falasca, M., Maffucci, T., Park, D., Kang, S., Song, J., Lee, D., Lee, Y., Hariharan, N., Kunselman, L., Gu, L., Sasseville, V., Harrity, T., Cheng, P. T. W., Pratley, R. E., Schweizer, A., Mills, D., Kim, T-H, Song, X-L, Poelje, P. D., Potter, S. C., Dang, Q., Fujitaki, J. M., Linemeyer, D. L., Landau, B. R., Erion, M. D., Pankop, M., Golay, A., Despres, J., Sjostrom, L., Lawlor, D. L., Legg, K. T., Ur, E., Houweling, S. T., Kleefstra, N., Meyboom-De Jong, B., Bilo, H. J. G., Schlomer, G. J., Meyer, G., Kasper, J., Muhlhauser, I., Young, B., Taylor, J., Friede, T., Hollis, S., Mason, J., Long, A., Gambling, T., Pauline, L., Burns, E., New, J., Gibson, M., Betteridge, D. J., Leiter, L. A., Audit, Investigators, Whitty, P. M., Eccles, M. P., Hawthorne, G., Grimshaw, J., Steen, I. N., Vanoli, A., Wood, L., Speed, C., Mcdowell, D., Rewers, M., Maahs, D., Wadwa, R., Eckel, R., Tracy, R., Pfutzner, A., Strotmann, H-J, Schulze, J., Hohberg, C., Pahler, S., Forst, T., Ambery, P. D., Sydall, H., Cooper, C., Dennison, E., Sayer, A. Aihie, Barker, D., Phillips, D., Lalic, N. M., Ostojic, M., Lalic, K., Zamaklar, M., Jotic, A., Ilic, M., Rajkovic, N., Lukic, L., Milicic, T., Verges, B., Zeller, M., Steg, P. G., Beer, J. C., Brisard, C., Brindisi, M. C., Dentan, G., Laurent, Y., Janin-Manificat, L., Makki, H., Ravisy, J., Cottin, Y., Ajjan, R. A., Grant, P. J., Futers, T. S., Brown, J. M., Carter, A. M., Rasmussen, M. S., Bruun, J. M., Pedersen, S. B., Richelsen, B., Dietze-Schroeder, D., Sell, H., Koenen, M., Eckel, J., Delporte, M-L L., Bauche, I. B., Brichard, S. M., Ait El Mkadem, S., Rezsohazy, R., Tsiotra, P. C., Tsigos, C., Gatsiou, C., Raptis, S. A., Walker, C. G., Bryson, J. M., Hancock, D. P., Caterson, I. D., Takahashi, N., Hatakeyama, H., Kasai, H., Gauthier, B. R., Iezzi, M., Fukuda, M., Duhamel, D. L., Ravier, M. A., Dufer, M., Neye, Y., Krippeit-Drews, P., Hennige, A. M., Sausbier, U., Arntz, C., Sausbier, M., Neuhuber, W., Ruth, P., Drews, G., Beauvois, M. C., Rolland, J-F, Jonas, J-C, Merezak, C., Henquin, J-C, Gilon, P., Jabin Gustafsson, A., Dzabic, M., Islam, M. S., Vaxillaire, M., Cheyssac, C., Dina, C., Vasseur-Delannoy, V., Lepretre, F., Siddiq, A., Froguel, P., Neve, B., Fernandez-Zapico, M. E., Ashkenazi-Katalan, V., Urrutia, R., Melloul, D., Froguel, R., Poulsen, P., Wojtaszewski, J., Richter, E., Vaag, A., Granhall, C., Renstrom, E., Luthman, H., Isomaa, B., Gloyn, A. L., Edghill, E. L., Pearson, E. R., Mackay, D. J. G., Temple, I. K., Noyes, K., Freedenberg, D., Gillespie, K. M., Lambert, A. P., Gale, E. A., Ellard, S., Hattersley, A. T., Fanelli, C. G., Porcellati, F., Rossetti, P., Busciantella, N. R., Billi, C., Burrin, D. G., Bolli, G. B., Bingham, E. M., Dunn, J., Sutcliffe-Goulden, J., Marsden, P., Amiel, S., Davis, R. E., Kennedy-Martin, T., Peters, J. R., Wittrup-Jensen, K. U., Mcewan, P., Morrissey, M., Currie, C. J., Akram, K., Pedersen-Bjergaard, U., Thorsteinsson, B., Pibernik-Okanovic, M., Peros, K., Begic, D., Szabo, S., Metelko, Z., Vlaiculescu, M. V., Calota, I., Busila, T., Bruckner, I., Giannakopoulou, D. F., Lindner, H. D., Hrachovinova, T., Fejfarova, V., Csemy, L., Malcomson, J., Campbell, M., Pandolfi, A., Giardinelli, A., Di Tomo, P., Di Silvestre, S., Di Fulvio, P., Capani, F., Consoli, A., Roesen, P., Patruno, A., Grilli, A., Capani, R., Felaco, M., Boner, G., Mccarroll, K., Brenner, B. M., Zeeuw, D., Kowey, P., Shahinfar, S., Crow, R. S., Iso, K., Kuboki, K., Tada, H., Yoshino, G., Schjoedt, K. J., Andersen, S., Distiller, L. A., Degenhardt, T. P., Szabo, J. R., Khalifah, R. G., Schotzinger, R. J., Achenbach, P., Knopff, A., Naserke, H., Ziegler, A. G., Bonifacio, E., Valera, L., Jardin, B., Roche, S., Lampasona, V., Pugniere, M., Roquet, F., Granier, C., Laune, D., Afifiyan, F., Cheung, R., Yantha, J., Jackowski, G., Dosch, H-M, Nakanishi, K., Kogawa, N., Komatsu, Y., Fontes, G., Imamura, T., Ilic, C., Puech, C., Ktorza, A., Bataille, D., Dalle, S., Sorensen, H., Fosgerau, K., Gelling, R. W., Nishimura, E., Andersen, B., Madsen, P., Lau, J., Streicher, R., Wagner, K., Vettermann, R., Potterat, O., Renard, E., Panteleon, A. E., Kolopp, M., Rebrin, K., Steil, G., Steil, G. M., Hariri, F., Darwin, C., Saad, M. F., Buckingham, B., Kunselman, B., Wong, L., Istoc, E., Leach, J., Purvis, R., Monfre, S. L., Fischer, J. S., Garg, S., Ahmann, A. J., Ruchti, T. L., Gandhi, G. Y., Nuttall, G. A., Mullany, C. J., Schaff, H. V., Williams, B. A., Rizza, R. A., Mcmahon, M. M., Gates, G., Mentel, J., Smith, R., Crook, J., Hosszufalusi, N., Vatay, A., Palik, E., Fust, G., Karadi, I., Romics, L., Panczel, P., Aurich, K., Voelker, U., Braun, A., Muller, U. A., Nguyen, L. L., Kriketos, A. D., Hancock, D., Denver, G. S., Uceyler, N., Schutt, M., Lesch, K-P, Mossner, R., Sommer, C., Seda, O., Liska, F., Kazdova, L., Sedova, L., Krenova, D., Zima, T., Tremblay, J., Kren, V., Hamet, P., Kloting, N., Follak, N., Kloting, I., Dessapt, C., Dei Cas, A., Baradez, M-O, Hayward, A., Thomas, S., Viberti, G., Gnudi, L., Gale, C. P., Jandeleit-Dahm, K. A. M., Thallas, V., Thomas, M. C., Candido, R., Burns, W. C., Forbes, J. M., Shymanskyy, I., Kuchmerovska, T., Klimenko, A., Jaeckel, E., Manns, M. P., Boehmer, H., Hedrich, H. J., Tellez, N., Montolio, M., Estimes, E., Rodriguez-Mulero, S., Soler, J., Montanya, E., Liu, Y., Chen, J., Rowlands, D., Chan, H., Simeonov, I. S., Anthony, K., Bingham, E., Marsden, P. K., Amiel, S. A., Malik, R. J. A., Zelaya, F., Williams, S., Brammer, M., Mountjoy, P. D., Bailey, S. J., Shaw, J. E., Sicree, R., Dunstan, D., Cameron, A., Zimmet, P. Z., Hewitt, S., Graff-Iversen, S., Assah, F. K., Fezeu, L., Kengne, A., Awah, P. K., Mbanya, J. N., Shu, J. A., Kamadjeu, R. K. K., Kiawi, E. C., Mbanya, J., Assah, F., Kerenyi, Z., Peterfalvi, A., Bosnyak, Z., Madarasz, E., Tabak, A. G., Szantho, J., Rakoczi, I., Tamas, G., Di Bartolo, P., Valpiani, G., Di Martino, M., Scaramuzza, A., Saragoni, S., Degli Esposti, E., Gudbjornsdottir, S., Cederholm, J., Nilsson, P., Eliasson, B., Miettinen, M. E., Miettinen, J., Nan, H. R., Dong, Y., Gao, W., Sun, B., Wang, N., Fu, F., Shi, H., Ding, M., Lorenzo, C., Serrano-Rios, M., Martinez-Larrad, M. T., Gonzalez-Sanchez, J. L., Seclen, S., Villena, A., Gonzalez-Villalpando, C., Williams, K., Stern, M. P., Haffner, S. M., Sakurai, M., Miura, K., Kita, Y., Takamura, T., Ota, T., Ishizaki, M., Morikawa, Y., Nakagawa, H., Szybinski, Z., Szurkowska, M., Mardarowicz, G., Lopatynski, J., Gilis-Januszewska, A., Szafraniec, K., Nicer, T., Kwon, H-S, Lee, J-H, Lee, H-J, Park, Y-M, Choi, Y-H, Kim, S-R, Jang, S-A, Song, B-R, Yoon, K-H, Kim, H-S, Lee, W-C, Cha, B-Y, Lee, K-W, Son, H-Y, Kang, S-K, Jorgensen, M. E., Moustgaard, H., Bjerregaard, P., Ebara, F., Dunstan, D. W., Salmon, J., Owen, N., Cameron, A. J., Welborn, T. A., Armstrong, T., Jolley, D., Galtier, F., Deschamps, V., Borys, J-M, Lasfargues, G., Andre, P., Born, C., Royer, B., Wilpart, E., Cailleau, M., Eschwege, E., Timar, R. Z., Serban, V., Vlad, A. R., Diaconu, L. F., Rosu, M., Olari, O., Sima, A. C., Qiao, Q., Chappuis, B., Diem, P., Christ, E. R., Iafusco, D., Prisco, F., Gemma, C., Mattera, S., Sanges, M., Menneila, C., Sommese, L., Jarosz-Chobot, P., Polanska, J., Feltbower, R. G., Mckinney, P. A., Stephenson, C. R., Bodansky, H. J., Icks, A., Du Prel, J-B, Grabert, M., Giani, G., Kyvik, K. O., Skytthe, A., Ioacara, S., Farcasiu, E., Bradescu, O., Guja, C., Scutaru, G., Savu, O., Ionescu-Tirgoviste, C., Ola, T. O., Hawa, M. I., Buzzetti, R., Scherbaum, W., Kolb, H., Thivolet, C., Hunter, S., Hadden, D., Guntram, S., Leiva, A., Mauricio, D., Pozzilli, P., Leslie, R. D. G., Benediktsson, R., Jonsdottir, A. M., Einarsdottir, A. S., Reynisdottir, I., Aspelund, T., Grant, S. F. A., Thorleifsson, G., Sigurdsson, G., Stefansson, K., Gudnason, V., Wollitzer, A. O., Jovanovic, L., Lobo, P. E., Marti, M. L., Preiti, M. C., Urdaneta, R. F., Juarez, S. S., Schober, E., Thon, A., Rami, B., Hofer, S., Tringham, J. R., Buyukbese, M. A., Sakamoto, Y., Inoue, Y., Matsumoto, H., Oono, K., Tokumasa, Y., Gorter, K. J., Janssen, P. G. H., Stolk, R. P., Hessen, P. A. W., Rutten, G. E. H., Niedermayer, D., Murro, A., Geloneze, S., Coghi, C., Federici, M. Orsini, Benedetti, M. Massi, Koehler, C., Henkel, E., Temelkova-Kurktschiev, T., Stier, U., Ott, P., Siegert, G., Bergmann, S., Hanefeld, M., Leonhardt, W., Sayeed, M. A., Mahtab, H., Khanam, P. A., Banu, A., Rashid, M. A., Mulnier, H., Seaman, H., Lovell, D., Soedamah-Mathu, S., Colhoun, H., Lawrenson, R., Diehm, C., Lange, S., Darius, H., Pittrow, D., Haberl, R., Stritzky, B., Tepohl, G., Allenberg, J. R., Trampisch, H-J, Soinio, M., Marniemi, J., Laakso, M., Lehto, S., Ronnemaa, T., Ito, C., Sasaki, H., Ishida, S., Maeda, R., Barengo, N. C., Lakka, T. A., Kohler, C., Benke, I., Raccah, D., Bailleau, C., Vexiau, P., Vaur, L., Aydin, N., Topsever, P., Filiz, T. M., Dayan, A., Bulgurlu, S., Gebeloglu, N., Demirtunc, R., Dagar, A., Skliros, E., Sotiropoulos, A., Vassibosis, A., Xipnitos, C., Liva, E., Chronopoulos, I., Merkouris, P., Skourtis, S., Pappas, S., Charbonnel, B., Baigts, F., Dumenil, V., Paillasson, S., Baleydier, A., Hanaire, H., Sert, C., Chabrier, G., Rodier, M., Fontaine, P., Kim, J-I, Miyake, Y., Sakai, T., Takamatsu, K., Tomioka, Y., Sugano, H., Murao, S., Shimizu, I., Unwin, N. C., Nag, S., Roglic, G., Connolly, V., Roper, N., Goodwin, J., Kelly, W., Lervang, H-H, Thomsen, R. W., Hundborg, H. H., Schonheyder, H. C., Khalangot, M. D., Gang, H., Tajima, N., Bianchi, C., Giovannitti, M. G., Pellegrini, G., Caricato, F., Bertolotto, A., Corfini, M., Guzder, R., Gatling, W., Byrne, C., Varillas, V. F., Boronat, M., Carrillo, A., La Roche, F., Ojeda, A., Lopez, Y., Marrero, D., Novoa, J., Shahidul Alam Khan, A. K. M., Thaware, P. K., Gangat, I., Howlett, T. A., Jenum, A. K., Holme, I., Birkeland, K. I., Sourij, H., Stoschitzky, K., Klein, W., Roth, M., Dittrich, P., Wascher, T. C., Hilding, A., Eriksson, A-K, Agardh, E. E., Efendic, S., Ostenson, C-G, Levitt, N. S., Bradshaw, D., Salzsieder, E., Freyse, E-J, Rutscher, A., Heinke, P., Augstein, P., Makino, H., Kainou, Y., Konoue, E., Ohno, K., Ebisui, O., Fujii, Y., Kondo, S., Fujiyama, M., Tanaka, K., Takemoto, K., Kida, K., Onuma, Y., Osawa, H., Tuomilehto-Wolf, E., Kinnunen, L., Laine, A-P, Kokko, T., Kakko, T., Hermann, R., Veijola, R., Simell, O., Ilonen, J., Guglielmi, C., Galgani, A., Beretta Anguissola, G., D Avola, D., Bakhtadze, E., Weiss, H., Hedrich, H-J, Wedekind, D., Bilbao, J. R., San Pedro, J. I., Vitoria, J. C., Martul, P., Castano, L., Badenhoop, K., Ramos Lopez, E., Usadel, K. H., Wagner, A. M., Cloos, P. A. C., Stahlhut, M., Bergholdt, R., Ramos, E., Taxvig, C., Vella, A., Smyth, D., Cooper, J. D., Undlien, D. E., Ronningen, K. S., Savage, D. A., Dunger, D. B., Strachan, D. P., Ring, S. M., Todd, J. A., Mironczuk, K., Kretowski, A., Kinalska, I., Nutland, S., Guja, L., Nielsen, L. B., Gammeltoft, S., Schwarz, P. E. H., Towers, W. G., Fischer, S., Mcrae, J. F., Willis, J. A., Scott, R. S., Potter, H. C., Merriman, T. R., Frampton, C. M., George, P. M., Spranger, J., Mohlig, M., Hoffmann, K., Muller, S., Osterhoff, M., Ristow, M., Boeing, H., Pfeiffer, A. F. H., Li, Y., Fisher, E., Burwinkel, B., Schrezenmeir, J., Mager, U., Pulkkinen, L., Lindi, V., Xiu, L. L., Sui, Y., Weng, J. P., Kalis, M., Cilio, C. M., Olde, B., Owman, C., Groop, L. C., Leveen, P., Da Ros, R., Assaloni, R., Maier, A., Quagliaro, L., Zuodar, G., Zakja, E., Gu, H. F., Nordman, S., Brookes, A. J., Prince, J. A., Helwig, U., Rubin, D., Hampe, J., Schreiber, S., Folsch, U. R., Doring, F., Porzio, O., Massa, O., Cunsolo, V., Hansen, T., Njolstad, P. R., Terrinoni, A., Melino, G., Federici, M., Colombo, C., Federici, G., Barbetti, F., Herder, C., Bongardt, F., Schopfer, A., Rathmann, W., Martin, S., Holle, R., Thorand, B., Wichmann, H. E., Koenig, W., Illig, T., Kora, Group, Blasiak, J., Arabski, M., Krupa, R., Wozniak, K., Dabrowski, J., Kasznicki, J., Zurawska, M., Drzewoski, J. S., Kose, H., Matsumoto, K., Wilke, B., Kerr-Bayles, L. J., Walder, K., Civitarese, A., Jowett, J., Curran, J., Elliott, K., Trevaskis, J., Bishara, N., Wanyonyi, S., Sanigorski, A. M., Zimmet, P., Blangero, J., Kissebah, A., Collier, G. R., Carlsson, E., Arner, P., Ridderstrale, M., Nitz, I., Lindner, I., Suzuki, S., Hinokio, Y., Hirai, M., Yamada, T., Yoshizumi, S., Tanizawa, Y., Matsutani, A., Ishihara, H., Takahashi, K., Katagiri, H., Oka, Y., Nam, M., Hong, S. B., Kim, H. J., Ahn, C. W., Kim, Y. S., Lee, H. C., Zeggini, E., Parkinson, J., Groves, C. J., Frayling, T. M., Hitman, G. A., Walker, M., Sampson, M., Levy, J. C., Weedon, M. N., Wiltshire, S., Owen, K. R., Halford, S., Mccarthy, M. I., Shehadeh, N., Bakri, D., Gershoni-Baruch, R., Yasuda, K., Okada, T., Sunaga, Y., Kajimoto, Y., Shibasaki, T., Kaburagi, Y., Kadowaki, T., Estalella, I., Rica, I., Vazquez, J. A., Mody, Spanish Group Of, Andrade, P., Den Ouweland, J. M. W., Maassen, J. A., Huoponen, K., Savontaus, M-L, Dimitrijevic Sreckovic, V. S., Djordjevic, P. B., Popovic, S. S., Gostiljac, D., Canovic, F., Sreckovic, B. M., Colak, E., Obrenovic, R., Milic, G., Glisic, B., Etemadi, A., Saadat, N., Azizi, F., Tsur, A., Cohen, Y., Yerushalmi, Y., Wainstein, J., Israel Diabetes Research Group (IDRG), Norberg, M., Eriksson, J. W., Lindahl, B., Andersson, C., Rolandsson, O., Stenlund, H., Weinehall, L., Lecomte, P. J., Vol, S., Caces, E., Chabrolle, C., Halimi, J-M, Nijpels, G., Dekker, J. M., Bouter, L. M., Heine, R. J., Lobner, K., Mollenhauer, U., Baumgarten, A., Com, E., Sargin, M., Karadeniz, S., Suleymanoglu, Y., Pekcanli, N., Yilmaz, T., Cicero, A. F. G., Dormi, A., Miconi, A., D Addato, S., Laghi, L., Brillante, R., Bernardi, R., Grandi, E., Gaddi, A. V., Jones, M., Lacey, L., Bergenheim, K., Yamagata, F., Yamakoshi, M., Takahashi, M., Kawazu, S., Festa, A., Hanley, A. J. G., Otvos, J. D., Goff, D. C., Wajngot, A., Cerasi, E., Baumert, J., Schneider, A., Lowel, H., Roussel, R., Muller-Brandes, C., Ballmann, M., Nahrlich, L., Thalhammer, G., Nastoll, M., Schwarz, J., Johne, U., Erfurth, M., Luddeke, H-J, Liebl, A., Kotowa, W., Maclaine, G., Evers, T., Pontiroli, A. E., Pizzocri, P., Paganelli, M., Folli, F., Lee, K., Jung, D-S, Park, M-K, Henriksen, J. E., Durck, T. T., Rasmussen, M., Weghuber, D., Roden, M., Tura, A., Pacini, G., Bischof, M., Widhalm, K., Sharp, G. W. G., Shanmugam, G., Straub, S. G., Michael, D., Chow, R., Regazzi, R., Gerona, R., Martin, T. F. J., Waselle, L., Tomas, A., Min, L., Pessin, J. E., Halban, P. A., Bjorklund, A., Ma, Z., Portwood, N., Parton, L. E., Smith, E. R., Diraison, F., Tsuboi, T., Lehtihet, M., Webb, D-L, Honkanen, R. E., Knoch, K-P, Meisterfeld, R., Bergert, H., Kolpe, M., Altkruger, A., Saeger, H-D, Solimena, M., Haspel, D., Aguilar-Bryan, L., Bryan, J., Ullrich, S., Berchtold, S., Ranta, F., Seebohm, G., Alexander, D., Wulff, P., Kuhl, D., Lang, F., Speier, S., Yang, S-B, Rose, T., Rupnik, M., Varadi, A., Mitchell, K. J., Schwappach, B., Bleck, C., Wienbergen, A., Rustenbeck, I., Vieira, E., Gylfe, E., Seissler, J., Wohlrab, U., Schmiegelt, D., Ruetter, R., Herten, M., Lechner, A., Nolan, A. L., Blacken, R. A., Habener, J. F., Gao, R., Ustinov, J., Korsgren, O., Mikkola, M., Lundin, K., Otonkoski, T., Jahr, H., Bieback, K., Kern, S., Brendel, C., Brendel, M. D., Bretzel, R. G., Taniguchi, S., Ohgawara, H., Tsuchiya, K., Tsuchiya, M., Okochi, H., Kelter, A-R, Dohrmann, C., Austen, M., Aicher, B., Maedler, K., Schumann, D. M., Iwakura, Y., Donath, M. Y., Peter, A., Opel, A., Seufert, J., Fernandez, E., Serradas, P., Martin, M. A., Plachot, C., Bailbe, D., Gangnerau, M. N., Gavete, M. L., Fajardo, S., Escriva, F., Portha, B., Alvarez, C., Lipsett, M., Jamal, A-M, Hanley, S., Castellarin, M., Rosenberg, L., Bhushan, A., Georgia, S., Calderari, S., Gangnerau, M-N, Meile, M-J, Miettinen, P. J., Palgi, J., Virkamaki, A., Ferris, W. F., Campbell, S. C., Armstrong, L., Hole, N., Lako, M., Macfarlane, W. M., Barbera, A., Altirriba, J., Nadal, B., Larsen, M. O., Gotfredsen, C. F., Holst, J. J., Reusens, B., Sparre, T., Kalbe, L., Leunda, A., Orntoft, T., Remade, C., Dasilva Xavier, G., Motakis, E., Nason, G. P., Leibiger, B., Berggren, P-O, Leibiger, I. B., Uhles, S., Moede, T., Welters, H. J., Senkel, S., Erdmann, S., Thomas, H., Morgan, N. G., Irminger, J-C, Rickenbach, K., Donath, M., Rouiller, D. G., Taylor, J. P., Jackson, D. A., Chan, S. L. F., Dezaki, K., Watanabe, M., Hosoda, H., Kangawa, K., Yada, T., Kuhnen, P., Laubner, K., Hernandez, R., Silvestre, R. A., Egido, E. M., Chatenet, D., Leprince, J., Chartrel, N., Vaudry, H., Marco, J., Zhang, F., Zhang, Q., Tengholm, A., Thore, S., Costes, S., Longuet, C., Broca, C., Baltrusch, S., Dyachok, O., Thams, P., Anwar, M. R., Capito, K., Radu, R. G., Fujimoto, S., Mukai, E., Shimono, D., Nabe, K., Shimodahira, M., Kominato, R., Aramaki, Y., Yamada, Y., Seino, Y., Giroix, M. H., Agascioglu, E., Courtois, P., Malaisse, W. J., Sener, A., Piquer, S., Barcelo-Batllori, S., Julia, M., Li, J., Li, X. J., Lou, M., Zhang, J., Zhou, Q., Zhao, G. Z., Webb, G. C., Dalal, S., Garcia, C., Saxena, P., Houk, M., Nenquin, M., Abdel-Ghany, M., Miele, C., Romano, C., Corbo, V., Maitan, M. A., Andreozzi, F., Ungaro, P., Oriente, F., Raciti, G. A., Formisano, P., Beguinot, F., Mcclenaghan, N. H., Mccluskey, J. T., Patterson, S., Efanov, A., Sewing, S., Bokvist, K., Gromada, J., Frederiksen, A. L., Juhl, C. B., Schwarts, M., Schmitz, O., Andersen, P. H., Valeri, C., Castelli, M. D., Bonfante, R., Beyan, H., Elouil, H., Khaldi, M. Z., Evangelista, S., Zeender, E., Berney, T., Schumann, D., Franklin, I., Sergeev, P., Chervonsky, A. V., Wollheim, C., Nyblom, H., Ahmed, M., Bergsten, P., Sol, E-R, Kharroubi, I., Ladriere, L., Cnop, M., Moffitt, J. H., Fielding, B., Currie, J., Staiger, K., Brandhorst, D., Winter, D., Kellerer, M., Oprescu, A. I., Naassan, A., Klimentova, T., Constantin, S. A., Tang, C., Uchino, H., Lam, L., Wheeler, M. B., Fantus, G. I., Giacca, A., Ortsater, H., Sundsten, T., Youshikawa, H., Winzell, M. S., Montrone, C., Martemucci, S., Perrini, S., Caccioppoli, C., Grassetti, D., Scipioni, A., Dotta, F., Yamamoto, N., Tsunekawa, S., Ito, Y., Oiso, Y., Miura, Y., Niki, I., Scrocchi, L. A., Ha, K. B. N., Wang, F., Chen, Y., Wu, L., Fraser, P. E., Yermen, B., Lilla, V., Kaminski, A., Mathe, Z., Dupraz, P., Zbinden, M., Filo, A., Bucher, P., Rinsch, C., Thorens, B., Pepper, M. S., Estilles, E., Sigrist, S., Rieger, L., Mandes, K., Bohbot, A., Pinget, M., Kessler, L., Parab, P. B., Katdare, M. R., Galande, S., Saha, B., Yoshida, A., Satoh, J., Homo-Dekarche, F., Coulaud, J., Durant, S., Drexhage, H. A., Mabley, J. G., Deb, A., Wallace, R., Pacher, P., Elder, R. H., Szabo, C., Schlosser, M., Mentel, R., Moya-Suri, V., Wassmuth, R., Gurtler, L., Ankelo, M., Westerlund, A., Blomberg, K., Hinkkanen, A. E., Popova, V. V., Gruzov, M. A., Afanasyeva, V. V., Kulikovskaya, A. V., Melnichenko, S. V., Mankovsky, B. N., Zak, K. P., Koczwara, K., Warncke, K., Kawasaki, E., Imagawa, A., Uchigata, Y., Kobayashi, M., Abiru, N., Yamasaki, H., Eguchi, K., Chrul, S., Polakowska, E., Heinrich, A., Walter, M., Pitocco, D., Visalli, N., Crino, A., Costantino, F., Manfrini, S., Spera, S., Suraci, C., Patera, P., Matteoli, M. C., Schiaffini, R., Ghirlanda, G., Leotta, S., Imdiab, Group, Hatziagelaki, E., Tsiavou, A., Degiannis, D., Chaidaroglou, A., Manginas, A., Koniavitou, K., Desai, M., Williams, A. J. K., Horton, V. A., Bingley, P. J., Cull, C. A., Citarrella, R., Richiusa, P., Mattina, A., Criscimanna, A., Mantione, L., Bronte, V., Pizzolanti, G., Galluzzo, A., Giordano, C., Giulietti, A., Stoffels, K., Overbergh, L., Mathieu, C., Bilgic, S., Aktas, E., Salman, F., Yillar, G., Yilmaz, M., Deniz, G., Valorani, G. M., Imdiab, G., Pozzilli, R., Weets, I., Truyen, I., Verschraegen, I., Auwera, B., Schepper, J., Dorchy, H., Lebrethon, M-C, Gaal, L., Rooy, P., Pipeleers, D. G., Gorus, F. K., Belgian Diabetes Registry (Brussels, Belgium), Shtandel, S. A., Atramentova, L. A., Karachentsev, Y. I., Kravchun, N. A., Koval, S. N., Poltorak, V. V., Levchenko, T. P., Snegurakaya, I. A., Miloslavskiy, D. K., Bojko, V. V., Resnik, L. A., Chico, A., Rojas, I., Novials, A., Bendlova, B., Vcelak, J., Vankova, M., Sramkova, D., Samalikova, P., Kvasnickova, H., Vondra, K., Petrone, A., Vania, A., Zavarella, S., Alemanno, I., Di Cola, S., Ribaudo, M. C., Leonetti, F., Angel, B., Carrasco, E., Santos, J., Albala, C., Oyarzun, A., Perez-Bravo, F., Petry, C. J., Ong, K. K., Michelmore, K., Artigas, S., Wingate, D. L., Zegher, F., Ibanez, L., Prestle, J., Adomeit, A., Hammer, E., Zieher, T., Missler, B., Appl, T., Schindler, M., Brodbeck, K., Machicao, F., Haring, H., Just, M., Fargeman, N., Knudsen, J., Quint, M., Tschank, G., Korn, M., Henriksen, E. J., Dokken, B. B., Sloniger, J. A., Dorig, J., Quarre, L., Piatkiewicz, P., Taton, J., Czech, A., Gorski, A., Jebens, E., Brennesvik, E. O., Ktori, C., Ruzzin, J., Shepherd, P. R., Jensen, J., Lakka, H-M, Rankinen, T., Leon, A. S., Skinner, J. S., Wilmore, J. H., Rao, D. C., Bouchard, C., Vendrell, J. J., Chacon, M. R., Garcia-Espana, A., Fernandez-Real, J., Gutierrez, C., Richart, C., Takeshita, Y., Shimizu, A., Hamaguchi, E., Kaneko, S., Hrebicek, J., Orel, M., Lichnovska, R., Gwozdziewiczova, S., Chlup, R., Faturos, I., Tournis, S., Fotinakis, P., Thomakos, P., Manousaki, M., Leontsini, D., Taxildaris, K., Mitrakou, A., Kim, S., Hur, K., Shim, W., Ahn, C., Cho, Y., Lim, S., Kim, K., Lee, H., Cha, B., Beregszaszi, M., Chevenne, D., Sebag, G., Kerdanet, M., Huet, F., Polak, M., Lacombe, D., Paoli, A., Levy-Marchal, C., Mokhort, T., Shishko, E., Shepelkevich, A., Benito, M., Arribas, M., Valverde, A. M., Menghini, R., Marchetti, V., Cardellini, M., Sbraccia, P., Lauro, D., Lauro, R., Ali, A. T., Penny, C., Merwe, M-T, Paiker, J. E., Psaras, G., Ekram, F., Crowther, N. J., Musri, M. M., Corominola, H., Casamitjana, R., Parrizas, M., Renstrom, F., Buren, J., Park, C., Park, Y., Lee, G., Kang, E., Kim, K-S, Sanchez-Margalet, V., Gonzalez-Yanes, C., Diaz-Troya, S., Rodriguez Fonseca, F., Mcnamara, M. R. J., Boschetti, N., Schmid, D., Spinas, G. A., Trub, T., Niessen, M., Kuhlmann, J., Neumann-Haefelin, C., Belz, U., Juretschke, H-P, Kramer, W., Herling, A. W., Markova, I., Oliyarnyk, O., Cahova, M., Manders, R. J. F., Koopman, R., Zorenc, A. H. G., Keizer, H. A., Loon, L. J. C., Straczkowski, M., Kowalska, I., Dzienis-Straczkowska, S., Nikolajuk, A., Gorska, M., Zabielski, P., Baranowski, M., Gorski, J., Tack, C. J., Haan, J., Klomp, D., Heerschap, A., Corpeleijn, E., Budzinski, R. M., Stengele, I., Schuler, M., Selzle, N., Lehmann-Lintz, T., Heckel, A., Vavrinkova, H., Meskhishvili, E., Furier, S. M., Parkes, H. A., Cooney, G. J., Alemzadeh, R., Tushaus, K. M., Nencioni, S., Giovannitti, G., Longo, V., Vries, R., Kerstens, M. N., Tol, A., Dullaart, R. P. F., Mcbride, R., Denke, M. A., Pearson, T., Battisti, W. P., Brady, W. E., Palmisano, J., Tuzova, O. V., Wahl, H. G., Hong, Q., Luz, K., Xu, G., Schmulling, R. M., Liebich, H. M., Oomen, P. H. N., Hattori, H., Smit, A. J., Scheek, L. M., Thomaseth, K., Lajoix, A-D, Gauthey, A., Dietz, S., Jahannault, C., Manteghetti, M., Petit, P., Gross, R., Quynh, N. T. T., Floren, A., Langel, U., Gedulin, B. R., Smith, P., Prickett, K. S., Tryon, M., Barnhill, S., Yeoh, T., Young, A. A., Hiles, R., Carpenter, T., Serota, D., Schafer, K., Ross, P., Nelson, D., Rebelatto, M., Ikeda, H., Nagashima, K., Tsukiyama, K., Todo, T., Trombetta, M., Boselli, L., Cali, A., Cretti, A., Monauni, T., Bifari, F., Bonora, E., Muggeo, M., Bonadonna, R. C., Gredal, C., Rosenfalck, A., Dejgaard, A., Hilsted, J., Rudovich, N. N., Rochlitz, H. J., Ritzel, R. A., Butler, A. E., Butler, P. C., Murphy, M. J., Korner, A., Csillag, J., Pinter, A., Cameron, N., Toman, M., Gray, I. P., Vielwerth, S. E., Rinnov, A., Jensen, R. B. B., Juul, A., Uitterlinden, P., Bruining, G. J., Lamberts, S. W., Rasmussen, E., Malis, C., Ekstrom, C., Arne, A., James, J. L., Thomas, P., Cavan, D. C., Owona, A. M., Ozaki, R., So, W., Tong, P., Chan, M., Wong, G., Cockram, C., Chan, J., Redemann, N. H., Gotz, B., Lahm, P., Mader, G., Tadayyon, M., Oh, Y., Schippmann, V., Kluge, R., Bornstein, S. R., Scherbaum, W. A., Joost, H-G, Bae, H. Y., Kim, S. Y., Lee, B. R., Vertigan, H., Carroll, D., Griffiths, L., Coghlan, M. P., Freeman, S., Toffolo, G., Dalla Man, C., Basu, R., Rizza, R., Cobelli, C., Bertoldo, A., Price, J., Mathis, C. A., Mason, N. S., Holt, D., Kelley, C., Mckolanis, T. M., Kelley, D. E., Whyte, M., Jackson, N., Beale, R., Treacher, D., Carroll, P., Jones, R. H., Umpleby, M., Jaquet, D., Boiko, J., Rigal, O., Czernichow, P., Qvisth, V., Hagstrom-Toft, E., Moberg, E., Bolinder, J., Sjostrand, M., Strindberg, L., Lonnroth, P., Mick, D. D., Sumarac-Dumanovic, M., Cvijovic, G. M., Kendereski, A., Pejkovic, D., Zoric, S., Casanueva, F. F., Dieguez, C. C., Singh, R. J., Basu, A., Chittilapilly, E. G., Johnson, M. C., Abdallah, B. M., Shubeska Stratrova, S., Svendsen, O. L., Dhatariya, K. K., Bigelow, M. L., Nair, K. S., Lundgren, M., Ruge, T., Myrnas, T., Gimeno, R. E., Suri, V., Li, D., Huard, C., Martine PUGNIERE, Vettore, M., Sironi, A. M., Gastaldelli, A., Mari, A., Ciociaro, D., Buzzigoli, E., Pettiti, M., Positano, V., Lombardi, M., Radziuk, J., Pye, S., Brehm, A. R., Krssak, M., Bernroider, E., Anderwald, C., Nowotny, P., Cline, G., Shulman, G. I., Kotsa, K., Papazisi, A., Spanopoulos, I., Giovos, I., Suzuki, A., Sobajima, H., Naruse, S., Kitagawa, M., Ishiguro, H., Futakuchi, S., Goto, H., Hines, G., Kennedy, I., Matthews, D., Levy, J., Radikova, Z., Koska, J., Ksinantova, L., Imrich, R., Huckova, M., Vigas, M., Wallace, T. M., Matthews, D. R., Rajala, U., Hiltunen, L., Keinanen-Kiukaanniemi, S., Noh, J-H, Kim, D-J, Choi, N-H, Lee, B-W, Chung, J-H, Min, Y-K, Lee, M-S, Kim, K-W, Lee, M-K, Byrne, C. D., Holt, H. B., Phillips, D. I. W., Wood, P. J., Darekar, A. A., Astrup, A., Gross, S., Matthies, K., Weck, M., Malinska, H., Beifort, R. S., Berria, R., Defronzo, R., Cusi, K., Gorshunska, M. Y., Karachenzev, Y. I., Lopez-Bermejo, A., Pratt, K. L., Hwa, V., Recasens, M., Broch, M., Vendrell, J., Rosenfeld, R. G., Fernandez-Real, J. M., Ricart, W., Grunnet, L., Pedersen, B. K., Franke, B., Fleming, S., Lemke, N., Laue, C., Pfeuffer, M., Lecube, A., Hernandez, C., Genesca, J., Garcia, L., Francisco, G., Simo, R., Kraml, P. J., Syrovatka, P., Brunerova, L., Smejkalova, V., Potockova, J., Andel, M., Leshchenko, Z., Poltorack, V., Krasova, N., Gladkih, A., Yang, K., Chamson, A., Thyssen, S. M., Rojo Llobet, A. M., Christoffersen, B. O., Raun, K., Fledelius, C., Svendsen, O., Vinterby, A., Golozoubova, V., Afonso, R. A., Ribeiro, R. T., Macedo, M. P., Guarino, M. P., Yang, G., Kurita, S., Misu, H., Akahori, H., Cerf, M. E., Nkomo, X. I., Muller, C. J., Du Toit, D. F., Louw, J., Wolfe-Coote, S. A., Nikishin, P., Zagayko, A., Taylor, K. D., Guo, X., Langefeld, C. D., Cur, J., Jinagouda, S., Bowden, D., Hokanson, J., Rotter, J. I., Liew, C. F., Wise, S. D., Yeo, K. P., Teng, C. H., Lee, K. O., Fisher, F. M., Trujillo, M. E., Hanif, W., Mcternan, P. G., Barnett, A. H., Scherer, P. E., Kumar, S., Kaltenbach, S., Stumvoll, M., Mlynarski, W., Andrzejewski, W., Shojaee-Moradie, F., Das, S., Stolinski, M., Jefferson, W., Cramb, R., Shahmanesh, M., Lyngso, D., Simonsen, L., Bulow, J., Meinardi, J. R., Sluiter, W. J., Wolffenbuttel, B. H. R., Bonnet, F., Guebre-Egziabher, F., Rabasa, R., Laville, M., Gosby, A. K., Maloney, C. A., Haering, H-U, Patarrao, R. S., Lautt, W. W., Correia, N. C., Santos, A. I., Leite, V., Boavida, J. M., Nanwei, T. N. W., Bobbioni-Harsch, E., Lehmann, T., Sztajzel, J., Morel, P., Huber, O., Chassot, G., Assimacopoulos-Jeannet, F., Gedulin, G., Baron, A., Hendrickx, H., Lane, J., Coverly, J., Simcox, J., Stocks, J., Brown, L., Beha, A., Juretschke, P., Gerl, M., Klebach, M., Biemer-Daub, G., Perez-Del-Pulgar, S., Zorzano, A., Heinsbroek, A. C. M., D Alessio, D., Dijk, G., Tornero, M. P., Bailey, C. J., Mack, C. M., Wilson, J. K., Parkes, D. G., Kusunoki, M., Sakakibara, F., Kato, K., Okabayashi, N., Nakamura, T., Miyata, T., Habu, S., Nakamura, R., Nakasone, Y., Yasaka, T., Ishihara, R., Morikawa, R., Otake, K., Nakaya, Y., Ruzickova, J., Rossmeisl, M., Flachs, P., Sponarova, J., Prazak, T., Matejkova, O., Kopecky, J., Gram, D. X., Liu, W., Bodvarsdottir, T., Hansen, J. B., Sturis, J., Kern, W., Hallschmid, M., Benedict, C., Schultes, B., Born, J., Fehm, H. L., Westerbacka, J., Lammi, K., Hakkinen, A-M, Rissanen, A., Yki-Jarvinen, H., Mayr, P., Mertl-Roetzer, M., Lauster, F., Pohl, M., Lerch, M., Haslbeck, M., Eriksen, J., Rahlfs, V. W., Serhiyenko, V. A., Serhiyenko, A. A., Serhiyenko, L. M., Radulian, G., Vladica, M., Panaite, C., Balas, B., Derosa, G., Dumas, A., Fiorito, A., Prieto, P. G., Cancelas, J., Loba, J., Czupryniak, L., Bialasiewicz, P., Pawlowski, M., Nowak, D., Dupuy, O., Le Berre, J. P., Bordier, L., Rousseau, C., Mayaudon, H., Bauduceau, B., Bossi, A. C., Meregalli, G., Balini, A., Berzi, D., Cremonesi, B., Cerrato, D., Rezzani, C., Tumiati, M., Han, K., Min, K., Kim, E., Ahn, K., Ahn, H., Arguelles, I., Forga, L., Izquierdo, M., Gorostiaga, E., Fuentes, C., Ibanez, J., Rivero, A., Baynes, K., Pentecost, C., Bell, J. D., Thomas, E. L., Jackson, N. C., Umpleby, A. M., Kuhl, J., Ruderman, N. B., Musi, N., Goodyear, L. J., Patti, M. E., Thorell, A., Nygren, J., Ljungkvist, O., Degerblad, M., Stahle, A., Brismar, T. B., Saha, A. K., Bavenholm, P. N., Aydemir, D., Kiran, B., Unal, M., Okumus, N., Kayserilioglu, A., Perkins, J., Salman, S., Ozer, E., Kayserilioǧlu, A., Dinccaǧ, N., Tikkanen, H., Lakka, T., Macdonald, A. L., Harrison, M., Dickinson, H., Bone, A. J., Watt, P. W., Ostergard, T., Short, K., Saltin, B., Nair, K., Di Mauro, M., Papalia, G., Battiato, R., Giuffrida, D., Boemi, G., Castellino, P., Akter, S., Akhter, A., Pervin, T., Ahmed, S., Ahmed, K. R., Saleh, F., Chaudhury, H. S., Tankova, T., Dakovska, G., Lazarova, M., Dakovska, L., Kirilov, G., Koev, D., Torgerson, J. S., Hauptman, J., Boldrin, M., Shi, Y-F, Pan, C-Y, Gao, Y., Lindgarde, F., Broom, I., Takeda, H., Oana, F., Matsuzawa, A., Hashizume, H., Akahane, S., Howlett, H. C. S., Cornes, M., Lund, S. S., Poulsen, G., Frandsen, M., Pedersen, O., Pankiv, V. I., Yngen, M., Hjemdahl, P., Wallen, N. H., Florow, D., Leyck Dieken, M. G., Kitahara, Y., Mine, T., Konya, H., Hamaguchi, T., Satani, K., Umehara, A., Ishikawa, T., Kohri, K., Hasegawa, Y., Suehiro, A., Kakishita, E., Namba, M., Wang, F. N., Liao, Z. H., Yao, B., Li, Y. B., Hu, G. L., Belcher, G., Mariz, S., Tan, M. H., Moules, I., Pfutzner, A. H., Butzer, R., Langenfeld, M., Koder, C., Cooper, M., Majali, K. Al, Adiseshiah, M., Betteridge, J., Pratipanawatr, T., Chotmongkol, R., Kanhasura, S., Pratipanawatr, W., Miyazaki, Y., Matsuda, M., Defronzo, R. A., Nagasawa, T., Kuroda, J., Dey, D., Chovatia, M., Nag, A., Pandey, B., Nag, B., Thomas, L., Krauth, M., Allgauer, S., Besenfelder, U., Dennenmoser, J., Moon, C-K, Chae, S-H, Kim, M-H, Jo, Y-Y, Shin, J-S, Ahn, S-K, Lee, H-W, Lee, S-J, Panadero Moya, A., Rodriguez, E., Gonzalo, A., Sanchez-Vilar, O., Lara, J. I., Rovira, A., Otto, C., Otto, B., Goke, B., Parhofer, K. G., Juurinen, L., Tiikkainen, M., Graner, M., Bajaj, M., Suraamornkul, S., Argon, D., Canbek, E., Schofl, C., Franzen, C., Gregg, R. E., Swaminathan, A., Frost, C., Nepal, S., Raymond, R., Mosqueda-Garcia, R., Johns, D., Gilmore, K., Perriello, G., Pampanelli, S., Di Pietro, C., Rinaldi, T., Brunetti, P., Oshinyemi, K., Garcia, S., Curtis, P., Zambanini, A., Home, P. D., Pocock, S., Dargie, H., Komajda, M., Jones, N. P., Record, Study Group, Munscher, C., Potthoff, F., Golbach, U., Weidenhammer, J., Kusterer, K., Lundershausen, R., O Neill, M. C., Goldstein, B. J., Wooddell, M. J., Strow, L. J., Waterhouse, B. R., Cobitz, A. R., Wyne, K. L., Porter, L. E., Weston, W. M., Chen, T., James, R. E., Kravitz, B. G., Pinkowski, D., Ruxer, J., Mozdzan, M., Siejka, A., Kaiser, M., Hauser, C., Jacober, S. J., Zagar, A. J., Althouse, S. K., Pinaire, J. A., Becker, R. H. A., Frick, A. D., Rave, K., Moses, R., Ways, K., Krones, R., Basir, S., Klein, C., Sawicki, P. T., Rotella, C. M., Pala, L., Dicembrini, I., Mannucci, E., Annuzzi, G., Natale, C., Bozzetto, L., Patti, L., Cipriano, P., Campaigne, B., Malone, J. K., Bai, S., Reviriego, J., Augendre-Ferrante, B., Schreiber, S. A., Schneider, K., Schweitzer, M-A, Fach, E-M, Busch, K., Karimi Anderesi, Z., Hoe, Study Group, Dunseath, G. J., Sengul, A. M., Haupt, A., Eckert, H., Schweitzer, M. A., Peiker, J., Fritsche, A., Janka, H. U., Plewe, G., Kliebe-Frisch, C., Maxeiner, S., Teng, L., Chan, C., Ernest, C. S., Skrivanek, Z., Brodows, R. G., Soon, D., Pan, C. Y., Chung, K-D, Russmann, A., Ryysy, L., Hanninen, J., Hulme, S., Kauppinen-Makelin, R., Lahdenpera, S., Lehtonen, R., Levanen, H., Nikkia, K., Tulokas, T., Virtamo, H., Vahatalo, M., Fulcher, G. R., Lavalle-Gonzalez, F., Soon, D. K. W., La Pena, A., Lim, M., Scholtz, H. E., Derezinski, T., Gerber, R. A., Hauber, A. B., Bolinder, B., Johnson, F. R., Boehm, B. O., Keiding, J., Home, P., Raastam, J., Moller, M. K., Parkner, T., Chen, J-W, Jorgensen, C., Smedegaard, J., Christiansen, J. S., Mcdougall, A., Fitch, M., Nelson, G., Mueller, U. A., Saemann, A., Ishii, H., Iburi, T., Furuya, M., Yamagami, K., Sekine, O., Yamashiro, S., Ishibashi, R., Tsujii, S., Sauriol, L., Lescrauwaet, B., Heckmann, B., Helbig, C., Franke, I., Schiel, R., Oguzhan, B., Gursoy, N., Turkish Diabetes Centers Study Group, Gutierrez, E., Garcia, P., Rokeya, B., Hossain, M. E., Ali, L., Ivanova, O. V., Gorbenko, N. I., Gladkich, A. I., Leshchenko, Z. A., Gorbenko, N., Ivanova, O., Gorbenko, K., Blase, E., Taylor, K., Nguyen, T., Su, G., Gao, H-Y, Carr, E., Wintle, M., Fineman, M., Calara, F., Han, J., Aisporna, M., Zabala, E., Fehse, F., Trautmann, M. E., Halseth, A. E., Nauck, M. A., Kendall, D. M., Riddle, M. C., Zhuang, D., Kim, D. D., Fineman, M. S., Baron, A. D., Buse, J., Henry, R., Ratner, R., Linnebjerg, H., Kothare, P., Ernest, C. Nd, Atkins, M., Trautmann, M., Bjerre Knudsen, L., Voss, P. V., Nauck, M., Hompesch, M., Filipczak, R., Le, T. T. D., Nielsen, L., Zdravkovic, M., Gumprecht, J., Deacon, C. F., Plamboeck, A., Guivarch, P-H, Dreyfus, J-F, Mathi, S., Castaigne, J-P, Drucker, D. J., Kruger, D., Burrell, T., Gloster, M., Crean, J., Herrmann, K., Maggs, D., Kolterman, O., Kovatchev, B., Cox, D. J., Mccall, A., Whitehouse, F., Kovatchev, B. P., Chapman, I., Parker, B., Doran, S., Feinle-Bisset, C., Wishart, J., Lush, C., Mcintyre, S., Deckhut, D., Horowitz, M., El-Ouaghlidi, A., Rehring, E., Holmes, D., Sallas, W. M., He, Y. L., Watson, C., Ligueros-Saylan, M., Foley, J. E., Narayanan, S., Thomas, A., Shah, D., Gopalan, B., Vakkalanka, S., Arch, J., Ryskjar, J., Krarup, T., Madsbad, S., Vilsboll, T., Ciani, S., Bardini, G., Pezzatini, A., Cappadona, A., Bodvarsdottir, T. B., Joergensen, M. S., Jensen-Holm, H. B., Kristensen, L., Kanstrup, A. B., Mckillop, A. M., Duffy, N., Lindsay, J. R., Bell, P. M., Hansen, B. S., Gronemann, S., Wilken, M., Herman, G. A., Zhao, P-L, Dietrich, B., Golor, G., Schrodter, A., Keymeulen, B., Lasseter, K. C., Kipnes, M. S., Hilliard, D., Tanen, M., Smet, M., Dyck, K., Tanaka, W., Gottesdiener, K. M., Wagner, J. A., Hoffmann, T., V Horsten, S., Demuth, H-U, Paule, S. G., Myers, M. A., Nikolovski, B., Fujiwara, H., Hosokawa, M., Fukuda, K., Nishi, Y., Fujita, Y., Yamada, K., Ueda, N., Jones-Leone, A. R., Yu, T., Barilla, D., He, Y-L, Ho, Y., Foley, J., Makrilakis, K., Panagiotakos, D. B., Dimosthenopoulos, C., Ioannidis, I., Chrysohoou, C., Pitsavos, C., Kuo, S-W, Levendal, R-A, Frost, C. L., Poonsatha, S., Jones, G., Fahey, R., Collier, G., Hoa, N. K., Norberg, A., Liepinsh, E., Phan, D. V., Thuan, N. D., Jornvall, H., Sillard, R., Ostenson, C. G., Tessari, P., Kiwanuka, E., Cristini, M., Zaramella, M., Enslen, M., Garcia-Rodenas, C., Yazawa, M., Imai, Y., Ohmura, E., Tsuchida, A., Matsuda, A., Hosaka, D., Horie, H., Ichita, M., Hisano, Y., Woodhead, S., Xu, W., Chen, X. H., Cavalot, F. L., Bonomo, K., Perna, P., Bacillo, E., Salacone, P., Gallo, M., Gaia, E., Vinik, A. I., Yu, D., Heise, M. A., Freed, M. I., Aguilera, E., Pellitero, S., Naf, S., Bendtzen, K., Nicoletti, F., Hahn, J-U, Bochnig, S., Koenig, H., Sporleder, B., Maisonneuve, P., Lowenfels, A. B., Kerner, W., Lankisch, P. G., Thai, A. C., Mohan, V., Khalid, B. A. K., Yeo, J. P., Asdiab, Study Group, Gasiorowska, A., Talar-Wojnarowska, R., Malecka-Panas, E., Schindler, K., Rieger, A., Gmeinhart, B., Schlembacher, K., Merz, P., Ludvik, B., Muller, N., Rodriguez, F. U., Aas, A-M, Seljeflot, I., Huang, C., Biswas, N., Hashimoto, N., Kamatani, Y., Suzuki, Y., Yagui, K., Saito, Y., Iwai, R., Takahashi, H., Yoshida, S., Skowronski, M., Zozulinska, D., Juszczyk, J., Wierusz-Wysocka, B., Bohles, H. J., Peterkova, V. A., Kuraeva, T. L., Scherbacheva, L. N., Andrianova, E. A., Maximova, V. P., Titovich, E. V., Danne, T., Bittner, C., Hanaire-Broutin, H., Schumicki, D-M, Souhami, E., Morrison, G., Purewal, T. S., Weston, P. J., Smahelova, A., Rusavy, Z., Koznarova, R., Loykova, V., Belobradkova, J., Devries, J. H., Retnakaran, R., Hochman, J., Melki, V., Zinman, B., Corbi, S., Costanza, F., Fioriti, E., Cappa, M., Jaron, M., Martinek, V., Piechatzek, R., Klaff, L., Prager, R., Robinson, A., Penfornis, A., Garg, S. K., Thomas, R., Selam, J. L., Sola-Gazagnes, A., Vitacolonna, E., Canonico, V., Fabietti, P., Iorio, M., Orsini Federici, M., Timi, A., Massi Benedetti, M., Sarti, E., Ashwell, S. G., Gebbie, J., Siebenhofer, A., Plank, J., Berghold, A., Horvath, K., Mrak, P., Jeitler, K. J., Pieber, T. R., Heller, S., Gottlieb, P., Paul, J., Chase, P., Menditto, L., Antuna, R., Grimaldi, A., Brun, J-M, Vialettes, B., Halimi, S., Dubroca, I., Blayo, A., Gomez-Peralta, F., Santos-Mazo, E., Payeras-Mas, F., Abreu-Padin, C., Santos-Palacios, S., Salvador-Rodriguez, J., Burge, M. R., Schroeder, E., Witthaus, E., Johnston, P., Bradley, C., Kudva, Y. C., Jenkins, G., Pons, G., Quandt, L., Gebel, J., Vogelsang, D., Smith, S., Isley, W., Russell-Jones, D., Maier, C., Mustapic, D., Schuster, E., Luger, A., Eher, R., Rubesova, I., Pelikanova, T., Skibova, J., Sanz, F. J., Ampudia-Blasco, F. J., Gabaldon, J., Catala, M., Carmena, R., Heinemann, L., Kronshage, B., Ward, K., Sass, D., Essenpreis, M., Voelkel, D., Lodwig, V., Nguyen, M., Mondok, A., Friedrich, C., Caduff, A., Totonelli, A., Longhitano, S., Agro, F., Edelman, S. V., Morrison, Z., Velazquez, F., Howard, S., Banks, R., Berger, B., Burian, P., Nilsson, K. A., Karlen, M., Rylander, E., Blonde, L., Freemantle, N., Ross, S. A., Duhot, D., Eggertsen, R., Hobbs, F. D. R., Martinez, L., Stridde, E., Skyler, J. S., Tusek, C., Stephan, J-A, Krasner, A., Landschulz, W. H., Sha, S., Bott, S., Bergenstal, R. M., Damge, C., Ubrich, N., Kaltenbacher, M-C, Maincent, P., Wutte, A., Bock, G., Balent, B., Midtgaard, A., Ronn, B. B., Pieber, T., Edgerton, D. S., Cherrington, A. D., Neal, D. W., Scott, M., Glass, D., Bowen, L. E., Wilson, W., Hobbs, C. H., Leach, C., Sivakumaran, S., Strack, T. R., Meyts, P., Aladdin, H., Palsgaard, J., Theede, A-M, Sajid, W., Hinrichsen, J., Klaproth, B., Lademann, J., Ostergaard, J., Andersen, A. S., Boss, A. H., Cheatham, W. W., Pfuetzner, A., Larbig, M., Forst, S., Abdollahnia, R., Grenningloh, M., Leatherdale, B., Bartley, E., Schwartz, S. L., Buchea, O., Shin, J., Hoss, U., Shah, R., Endo, T., Hata, S., Yamazaki, H., Hernandez Campos, S., Busciantella Ricci, N., Kaufman, F., Halvorson, M., Carpenter, S., Cooper, K., Mueller, J., Wasen, H., Brumberg, J., Rduch, K., Mertens, S., Reess, F., Renz, H., Maran, A., Sparacino, G., Pavanini, A., Corazza, S., Crepaldi, M., Poscia, A., Acosta, D., Salcedo, D., Delgado, E., Hawkins, F., Parramon, M., Mesa, J., Parhimovich, R. M., Darko, D. A., Odusanya, P. O. T., Pullen, F., Hopkins, D. F., Mukherjee, S., Child, D. F., Redkin, Y. A., Dreval, A. A., Bogomolov, V. V., Dreval, A. V., Ostgren, C. J., Grodzinsky, E., Lindstrom, K., Borgquist, L., Fegan, G., Hamliton, P., Mccrimmon, R. J., Evans, M. L., Fan, X., Ding, Y., Sherwin, R., Boomsma, F., Pramming, S., Fischer, B. M., Soydan, N., Eckhard, M., Saar, P., Kreuder, J., Linn, T., Holstein, A., Plaschke, A., Ptak, M., Egberts, E-H, El-Din, J., Kirchheiner, J., Hoashi, S., Khamis, A., Kilbane, M. T., Cannon, D. E., Gribben, A. P., Firth, R. G. R., Kinsley, B. T., Cranston, I. C., Galan, B. E., Mol, P., Wennekes, L., Due-Andersen, R., Lundkvist, J., Jonsson, L., Mukhopadhyay, B., Deans, K. A., Kesson, C. M., Jendrike, N., Buck, H., Abicht, A., Haug, C., Freckmann, G., Warren, R. E., Sommerfield, A. J., Allen, K. V., Deary, I. J., Frier, B. M., Hoi-Hansen, T., Wu, A., Holtman, V., Plaschke, A. J., Tenberken, O., Maurer, H. H., Al-Zakwani, I., Bullano, M. F., Baron, J. J., Willey, V. J., Nattrass, M., Kurtzhals, P., Colding-Jorgensen, M., Riddle, M., Massi-Benedetti, M., Murray, F., Lin, Z., Kolendorf, K., Prasek, M., Philotheou, A., Javashvili, L., Virsaladze, D., Kajaia, N., Raposo, J. F., Pratas, S., Fernandes, C., Valadas, C., Duarte, R., Gardete-Correia, L., Boavida, J., Locatelli, M., Patera, I. P., Bottazzo, G. F., Hadjidakis, D., Mylonakis, A., Raptis, A., Papaefstathiou, A., Hedman, C. A., Frystyk, J., Fridell, K., Jonsson, A., Lindstrom, T., Saito, M., Eto, M., Kaku, K., Stotzka, M., Stein, G., Prince, M. J., Kulzer, B., Scholze, A., Hermanns, N., Kubiak, T., Starostina, E. G., Shavrikova, E. P., Furuhashi, N., Hirose, T., Kuroda, M., Kimura, M., Ishizawa, M., Sarui, H., Takeda, N., Furuta, T., Drewelow, S., Lindloh, C., Paddison, C. A. M., Faimalie, M., Flett, R. A., Micheletti, S., Perelli Cippo, P., Mantovani, L. G., Su, M., Trento, M., Bajardi, M., Passera, P., Miselli, V., Tomalino, M., Borgo, E., Cavallo, F., Porta, M., Miclea, S., Bogatean, M., Hancu, N. D., Leppert, K., Rittmeier, H., Hancu, N., Mchorney, C., Myers, J., Reinecker, H., Meier, J. J., Gallwitz, B., Askenas, M., Vollmer, K., Schmidt, W. E., Kyrou, I., Souvatzoglou, E., Cseh, K., Baranyi, E., Kaszas, E., Szocs, A., Melczer, Z., Sikter, M., Szenthe, P., Hajos, P., Pogatsa, G., Winkler, G., Pardo, I. C. G., Barros-Filho, A. A., Jahan, S., Huq, F., Biswas, K. B., Chowdhury, T. A., Khan, A. R., Ritterath, C., Talai Rad, N., Siegmund, T., Heinze, T., Henrich, W., Siebert, G., Dudenhausen, J., Buhling, K., Kautzky-Willer, A., Mustafa, S., Winzer, C., Vukovich, T., Shaat, N., Ekelund, M., Lernmark, A., Ivarsson, S., Zmudzinska, M., Bronisz, A., Pufal, M., Junik, R., Beran, D. H., Toledano, Y., Giveon, S., Kahan, E., Aycheh, S., Guttman, N., Jaffe, A., Alberti, H., Boudriga, N., Nabli, M., Jaiveer, S., Jaiveer, P. K., Lee, J. D., Shaikh, S., Gopinath, A., Morrissey, J. R., Patel, V., Lenz, M., Dvoynishnikova, O. M., Mayorov, A. Y., Galstyan, G. R., Antsiferov, M. B., Dedov, I. I., Rybarczyk, M., Scalone, L., Palmer, A. J., Morgutti, M., Valentine, W. J., Renaudin, C., Roze, S., Morsanutto, A., Berto, P., Lopatriello, S., Voinovich, D., Gelisio, R., Brandie, M., Russ, W., Greiner, R. A., Rubio Terres, C., Pablos, P., Smith, I. C., Wittrup-Jensen, K., Morgan, C. L., Tsutskiridze, L., Haag, B., Delbuono, B., Silva, C., Fox, A., Padilla, V., Naraine, K., Cypryk, K., Szymczak, W., Szosland, K., Sobczak, M., Zawodniak-Szalapska, M., Lewinski, A., Schvarcz, E., Lindqvist, A., Stenninger, E., Ostlund, I., Aman, J., Lapolla, A., Dalfra, M., Di Benedetto, A., Dolci, M., Franzetti, I., Masotti, M., Napoli, A., Salietti, G., Santini, C., Tortul, C., Di Cianni, G., Popow, C., Waldhor, T., Horn, W., Biermann, E., Rihl, J., Riedl, M., Kastner, P., Kollmann, A., Pusch, W., Schreier, G., Hearnshaw, H. M., Lowe, P., Griffiths, F. E., Stapperfend, M. C., Baehring, T. U., Cosson, E., Benchimol, M., Carbillon, L., Paries, J., Lormeau, B., Valensi, P., Pharisien, I., Tourel, E., Uzan, M., Attali, J-R, Zabarovskaya, Z. V., Mulyarchik, O. V., Shepelkevich, A. P., Barsukov, A. N., Guseva, T. K., Begum, K., Haque, L., Bokor, A., Rigo, J., Garamvolgyi, Z., Pusztai, P., Somogyi, A., Hanson, U., Nystrom, L., Blohmo, G., Ekbom-Schnell, A., Ostman, J., Persson, B., Parretti, E., Cioni, R., Marzari, C., Masin, M., Scarselli, G., Mello, G., Seghieri, G., Bellis, A., Anichini, R., Alviggi, L., Franconi, F., Breschi, C. M., Dworacka, M., Wender-Ozegowska, E., Winiarska, H., Macugowska, M., Zawiejska, A., Bobkiewicz-Kozlowska, T., Pietryga, M., Brazert, J., Bousboulas, S., Politakis, P., Papadimitriou, P., Lyu, R., Yin, D. D., Green, A., Kristensen, J. K., Rodriguez-Saldana, J., Clark, C. M. Jr, Morales Teresa, M., Escorza-Dominguez, A. B., Ortiz-Gress, A. A., Monroy-Mayorga, A., Mejia-Pedraza, B. J., Seeliger, S., Kaiser, J., Muller, E., Maxion-Bergemann, S., Bergemann, R., Goertz, A., Shearer, A., Bagust, A., Schoeffski, O., Mayorov, A., Shestakova, M., Antsiferov, M., Balabolkin, M., Chugunova, L., Shamkhalova, M., Zaytseva, N., Naumenkova, I., Brevnova, N., Dedov, I., Tsibina, L., Rosak, C., Petzoldt, R., Stammer, H., Dehmel, B., Seidel, D. K., Roth, W., Fennenkotter, U., Gottschall, V., Kanatsuka, A., Lauenborg, J., Mathiesen, E., Hornnes, P., Wagner, O. F., Zajdenverg, L., Halfoun, V. L. C., Oliveira, J. E. P., Lencioni, C., Volpe, L., Chatzianagnostou, K., Cuccuru, I., Ghio, A., Pardini, E., Salvadorini, M., Saltiki, A., Korakovouni, A., Stavrianos, H., Zapanti, E., Antsaklis, A., Pithova, P., Sporna, M., Bustani, R., Todd, D. M., Lawrence, I., Guerrero, R., Vazquez, M., Amaya, M., Dios, E., Quijada, D., Garcia-Hernandez, N., Astorga, R., Gandhi, R. A., Jayawarna, C., Fernando, D. J. S., Hill, R. P., Lloyd-Mostyn, R. H., Thomson, G. A., Rewers, A., Bothner, J., Klingensmith, G., Sysoyeva, O., Karlovich, N., Rankins, D., Wellard, M., Werther, G., Northam, E., Kordonouri, O., Haberland, H., Hauschild, M., Kapellen, T., Kraft, V., Wiemann, D., Lange, K., Witte, D. R., Fuller, J. H., Eurodiab Pcs, Group, Laude, D., Dabire, H., Hadj Brahim, F., Papanas, N., Papatheodorou, K., Christakidis, D., Papazoglou, D., Giassakis, G., Piperidou, H., Monastiriotis, H., Maltezos, E., Barrett, C., Serghides, H., Tindali, H., Kelly, F., Chiheb, S., Chen, Q., Brahimi, M., Cynober, L., Delaporte, C., Scionti, L., Conti, M., Vermigli, C., Galimberti, G., Cazzetta, G., Bosi, E., Sugimoto, K., Shoji, M., Yasujima, M., Suda, T., Yagihashi, S., Mabley, J., Zsengeller, Z., Charniauskaya, T., Abatan, O. I., Kimura, I., Tsuneki, H., Hara, S., Sasaki, K., Nangle, M. R., Gibson, T. M., Yorek, M. A., Hirooka, H., Stevens, M. J., Tarhzaoui, K., Cohen-Boulakia, F., Smith, G., Lestrade, R., Behar, A., Komori, H., Oi, K., Takahashi, D., Kunitou, T., Moroi, M., Philips, J-C, Marchand, M., Geronooz, I., Scheen, A. J., Gambardella, S., Ciampittiello, G., Bracaglia, D., Cicconetti, E., Gigli, F., Verri, C., Baroni, A., Frontoni, S., Szabo, M., German, M., Farkas, L., Szentendrei, D., Maiello, M. R., Mandica, S., Morganti, R., Menzinger, G., Bernardi, L., Aso, Y., Wakabayashi, S., Takebayashi, K., Takemura, Y., Inukai, T., Kalter-Leibovici, O., Lifshitz, A., Yerushalmy, Y., Stern, E., Ogawa, K., Nanjo, K., Kawamori, R., Katayama, S., Shirai, M., Fonseca, V., Seftel, A., Denne, J., Fredlund, P., Buvat, J., Schmitt, H., Ahlen, H., Varanese, L., Lips, J., Hoekstra, J. B. L., Banga, J-D, Legros, J-J, Lufuma, M., Bouter, K. P., Fan, L. F., Lu, J. M., Zheng, Y. G., Zhang, X. Q., Spruce, M. C., Jones, C., Coppini, D. V., Lavery, L. A., Holtz-Neiderer, K., Mohler, M. J., Wendel, C. S., Nixon, B. P., Jurado, J., Bataller, F., Dorca, A., Garcia, F., Brossa, N., Barnera, T., Pou Torello, J. M., Bregovski, V. B., Karpova, I. A., Hedetoft, C., Rasmussen, A., Fabrin, J., Driver, V. R., Thoms, T. L., Jeffcoate, W. J., Monaghan, J., Game, F. L., Dalla Noce, S., Cimmino, M., Caruso, S., Manes, C., Mikoudi, K., Sossidou, E., Pigas, G., Karagianni, D., Skoutas, D., Fotiadis, S., Pruna, S., Eroshkin, I. A., Vasiljev, Y. G., Udovichenko, O. V., Udovichenko, A. E., Bondarenko, O. N., Dang, C. N., Prasad, Y. D. M., Anwar, R., Thomas, G., Malik, R., Lobmann, R., Motzkau, M., Pittasch, D., Lehnert, H., Piaggesi, A., Marsocci, A., Fanara, M. G., Rizzo, L., Palumbo, F., Campi, F., Tedeschi, A., Scatena, A., Goretti, C., Baicchi, U., Chipchase, S., Treece, K., Pound, N., Hill, N. R., Cyganek, K., Mirkiewicz-Sieradzka, B., Malecki, M., Wolkow, P., Skupien, J., Naskalska, A., Sieradzki, J., Tapp, R. J., Tonkin, A. M., Harper, A., Mccarty, D. J., Soderberg, S., Taylor, H. R., Chitson, P., Alberti, G. K. M., Sheetz, M. J., Aiello, L. P., Davis, M. D., Milton, R. C., Arora, V., Hu, K., Girach, A., Vignati, L., Tyrberg, M., Melander, A., Lindblad, U., Giannarelli, R., Coppelli, A., Sartini, M., Aragona, M., Fletcher, E. L., Ninkovic, S., Foster, L. E., Jones, D., Gooyer, T., Stitt, A., Vingrys, A. J., Wilkinson-Berka, J. L., Lewandowska, A. B., Randeva, H. S., Komorowski, J., Lewandowski, K. C., Jurowski, P., Sankar, S., Gos, R., Kowluru, R. A., Odenbach, S., Shinn, S., Oh, Y-S, Kim, J., Agardh, C-D, Hultberg, B., Agardh, E., Segura, R. M., Fonollosa, A., Berrone, E., Beltramo, E., Solimine, C., Ubertalli, A., Islam, N., Esteve, E., Fernandez, M., Recas, I., Mauri, S., Biarnes, F., Junca, E., Fernadez-Real, J., Rossner, S., Stenlof, K., Levy, B., Perry, B., Fitchet, M., Chrysos, G., Kamaratos, A., Lepeniotis, G., Kokkoris, S., Varytimiadis, K., Stasini, F., Mikros, S., Gianneli, D., Tryfinopoulou, K., Melidonis, A., Nikolopoulou, C., Harley, K., Ryder, R., De, P, Vannieuwenhoven, F. A., Rossing, K., Oliver, N., Goldschmeding, R., Jacobsen, P. K., Tan, F., Liew, S., Mukherjee, J. J., Lim, P., Frojdo, S., Sjolind, L., Parkkonen, M., Makinen, V., Tikellis, C., Nieuwenhoven, F. A. V., Macisaac, R. J., Tsalamandris, C., Mcneil, K. J., Panaiotopoulos, S., Smith, T. J., Ho, M., Matthews, P. G., Jerums, G., Hut, H., Den Meiracker, A. H., Nakhjavani, M., Behjati, J., Esteghamati, A., Esfahanian, F., Aghamohamadzadeh, N., Abbasi, M., Kohnert, K-D, Zander, E., Krabbe, S., Stehouwer, C. D., Schalkwijk, C. G., Saraheimo, M. T., Krarup Hansen, T., Teppo, A-M, Ebeling, P., Hansen, B. V., Abdella, N. A., Mojiminiyi, O. A., Al Dahi, W. A., Al Mohammedi, H., Al Jebely, S., Neugebauer-Baba, S., Baba, T., Ohashi, H., Nakajima, S., Hesselmann, C., Watanabe, T., Nargis, M., Zaid, R. B., Voronko, O. E., Shestakova, M. V., Shamkhalova, M. S., Tchugunova, L. A., Vikulova, O. K., Nosikov, V. V., Liu, L., Zheng, T., Li, M., Zhang, R., Xiang, K., Hadjadj, S., Jeunemaitre, X., Vervoort, G., Veldman, B., Berden, J., Wetzels, J., Singh, B. M., Holland, M. R., Baskar, V., Oh, J., Seo, J., Choi, K., Baik, S., Choi, D., Kim, N., Matsumoto, S., Suetsugu, M., Matsutomo, R., Pisarczyk-Wiza, D., Banaszak, A., Wysocki, H., Usui, H., Shikata, K., Okada, S., Ogawa, D., Yozai, K., Kido, Y., Nagase, R., Ohga, S., Tone, A., Sasaki, M., Wada, J., Unno, Y., Horiuchi, S., Mclennan, S. V., Kamarinos, M., Kelly, D., Waltham, M., Dy, V., Yue, D., Langham, R., Gilbert, R., Zdychova, J., Komers, R., Cresci, B., Giannini, S., Manuelli, C., Giunti, S., Pinach, S., Ianni Palarchio, A., Arnaldi, L., Vittone, F., Camussi, G., Cavallo Perin, P., Gruden, G., Marshall, S. M., Jones, S. E., White, K. E., Brizzi, M., Dentelli, P., Rosso, A., Calvi, C., Gambino, R., Cassader, M., Salvidio, G., Deferrari, G., Pegoraro, L., Pagano, G., Cavallo-Perin, P., Oates, R., Ellery, C., Beebe, D., Coutcher, J., Qian, Y-Z, Lowe, V., Appleton, T., Raunig, D., O Neil, S., Mylari, B., Amazonas, R. B., Fujita, A., Doi, A., Matsuno, S., Okamoto, K., Matsumoto, E., Furuta, H., Nishi, M., Tsuno, T., Taniguchi, H., Bessho, H., Wasen, E., Isoaho, R., Mattila, K., Vahlberg, T., Kivela, S-L, Irjala, K., Rigalleau, V., Lasseur, C., Perlemoine, C., Barthes, N., Raffaitin, C., Chauveau, P., Combe, C., Baillet-Blanco, L., Beauvieux, M-C, Gin, H., Heinrich, S., Steiner, T., Ott, U., Holdass, H., Fellstrom, B., Jardine, A., Staffler, B., Logan, J. O., Gimpelewicz, C., Stanciu, C. C., Pena, C. M., Serafinceanu, C. C., Gonzalez-Posada, J. M., Hernandez, D., Perez-Tamajo, L., Lo, A. J., Herna Alarco, M., Meneses, M., Barsotti, M., Rizzo, G., Schmauss, S., Havrdova, T., Saudek, F., Boucek, P., Adamec, M., Invitti, C., Gilardini, L., Parati, G., Mazzilli, G., Pontiggia, B., Sartorio, A., Lutgers, H. L., Groenier, K. H., Zasadzinska, G., Saryusz-Wolska, M., Temelkova-Kurktschiev, T. S., Kurktschiev, D. P., Majdrakova, I., Varbanova, T., Todorova, B., Bajo-Martinez, A., Bernal, E., Sanchez, O., Ugalde-Canitrot, A., Sanchez-Largo, E., Coca-Robinot, D., Fabregate, R., Calbacho, M., Marquez, J., Saban-Ruiz, J., Penesova, A., Cizmarova, E., Blazicek, P., Jongh, R. T., Serne, E. H., Ijzerman, R. G., Vries, G., Stehouwer, C. D. A., Poulsen, P. L., Andersen, N. H., Knudsen, S. T., Helleberg, K., Mogensen, C. E., Walus, M., Idzior-Walus, B., Sztefko, K., Cieslik, G., Fedak, D., Wozniakiewicz, E., Lin, S. D., Guo, M. Y., Lin, C. J., Liu, X. C., Francisco, M-M J., Rodriguez-Rosas, H., Peiro-Martinez, I., Macias-Batista, A., Harte, A. L., Rodriguez-Cuenca, S., Valsamakis, G., Chetty, R., Anderson, L. A., Roca, P., Matyka, K., Lasalle, J., Hershon, K., Berman, L., Gibson, E., Gillen, D., Maroni, J., Simmons, D., Hiukka, A., Forder, P., Leinonen, E., Hilden, H., Fruchart, J., Fruchart, J-C, Keech, A., Farnier, M., Freeman, M., Macdonell, G., Perevozskaya, I., Mitchel, Y., Gumbiner, B., Didangelos, T. P., Athyros, V. G., Mikhailidis, D. P., Papageorgiou, A. A., Bouloukos, V. I., Pehlivanidis, A. N., Symeonidis, A. N., Elisaf, M., Mckenney, J., Insull, W. Jr, Lewin, A., Maccubbin, D., Lee, M., Kush, D., Schuster, H., Barter, P. J., Stender, S., Cheung, R. C., Bonnet, J., Morrell, J. M., Watkins, C., Kallend, D., Stalenhoef, A. F. H., Ballantyne, C. M., Murin, J., Tonstad, S., Rose, H., Wilpshaar, W., Jenkins, A., Karschimkus, C., Dragicevic, G., Rowley, K., Wolthers, T., Best, J. D., Voet, B., Murdoch, S. J., Marcovina, S. M., Chen, H. C., Brunzell, J. D., Caparevic, Z. V., Kostic, N. D., Ilic, S. M., Sartore, G., Piarulli, F., Cantaro, S., Reitano, R., Fiore, C., Marin, R., Bassan, S., Manzato, E., Fedele, D., Solini, A., Santini, E., Thornalley, P. J., Babaei-Jadidi, R., Karachalias, N., Kupich, C., Ahmed, N., Fowler, A. E., Baker, A. R., Starczynski, J., O Hare, P., Szepietowska, B., Szelachowska, M., Puch, U., Glebocka, A., Quinn, D. W., Da Silva, N. F., Mcternan, C. L., Bonser, R. S., Mcternan, P., Dimitriou, K., Apostolou, O., Kontela, E., Devangelio, E., Gould, E. M., Serri, O., Roussin, A., Buithieu, J., Mamputu, J-C, Renier, G., Giordanetti, S., Amici, E., Poggi, G., Turpini, C., Fratino, P., Garzaniti, A., Yin, D., Banu, I., Roman, G., Negrean, M., Bala, C. G., Nita, C., Kistorp, C., Gustafsson, F., Chong, A., Lip, G., Galatius, S., Shearer, A. T., Ari, N., Sahilli, M., Ceylan-Isik, A., Ozansoy, G., Karasu-Yilmaz, C., Matteucci, E., Rosada, J., Pallini, M., Evangelista, I., Cassetti, G., Giusti, C., Giampietro, O., Capaldo, B., Galderisi, M., Cicala, S., Turco, A., Imbroinise, A., Nosso, G., D Errico, A., Divitiis, O., Klimontov, V. V., Korolyova, E. A., Jeltova, L. I., Bondar, I. A., Tarkun, I., Arslan, B., Canturk, Z., Tarkun, P., Agacdiken, A., Komsuoglu, B., Meneveau, N., Pierre-Justin, E., Alsayed, M., Sabbah, R., Paulin, S., Marcu, S., Tauveron, I., Zimmermann, C., Schiele, F., Seronde, M-E, Vautrin, P., Lusson, J-R, Thieblot, P., Bernard, Y., Mistry, A., Pye, M. P., Peovska, I., Maksimovic Pavlovic, J., Vavlukis, M., Pop Gorceva, D., Bosevski, M., Scognamiglio, R., Negut, C., Kreutzenberg, S., Madonna, R., Caterina, R., Willerson, J. T., Geng, Y-J, Vahsen, S., Ledwig, D., Ramrath, S., Frantz, S., Schmidt, I., Calvillo, L., Dienesch, C., Elbing, I., Bischoff, H., Ertl, G., Bauersachs, J., Davydov, A. L., Mkrtum Yan, A. M., Baranova, L. Y., Ikeda, Y., Suehiro, T., Osaki, F., Ota, K., Arii, K., Kumon, Y., Hashimoto, K., Doney, A. S. F., Fischer, B., Morris, A. D., Palmer, C. N. A., Ahn, Y-M, Lee, B-C, Kim, S-I, Byun, S-H, Ahn, S-Y, Doo, H-K, Pagnin, E., Calo, L. A., Fadini, G., Kubaszek, A., Chai, S., Chai, Q., Rasmussen, L., Ledet, T., Wogensen, L., Lengyel, C., Varro, A., Virag, L., Magyar, J., Biro, T., Jost, N., Skoumal, R., Nanasi, P., Toth, M., Horkay, F., Papp, J. G., Zacharopoulou, O., Athanaselis, S., Tsokos, N., Doupis, J., Psallas, M., Cokkinos, D., Pavlatos, S., Liatis, S., Akhobadze, T., Dzneladze, L., Samarguliani, I., Taskiran, M., Rasmussen, V., Rasmussen, B., Jensen, G. B., Fisher, A. A., Petrovsky, N., Davis, M. W., Srikusalanukul, W., Budge, M. M., Trifunovic-Zamaklar, D. D., Zivkovic, M., Jelic, V., Vukomanovic, G., Ristic, A. D., Seferovic, P. M., Costa, J. V., Duarte, S., Manley, S. E., Sailesh, S., Venkataraman, A., Haider, Y., Groza, I., Oprean, M., Ardelean, A., Morosanu, A., Darkow, T., Vanderplas, A., Mamas, M. A., Mcelduff, P., Burns, J., Edwards, R., Fitchet, A., Young, R. J., Gibson, J. M., New, J. P., Lichiardopol, R., Niculescu, N., Totora, A., Pencea, C., Tomescu, I., Cinteza, M., Manicardi, V., Coscelli, C., Navazio, A., Catellani, E., Michelini, M., Dall Asta, D., Guberti, A., Piazza, A., Gasparini, E., Pantaleoni, M., Guiducci, U., Manari, A., Sejil, S., Janand-Delenne, B., Avierinos, J-F, Habib, G., Labastie, N., Vague, P., Lassmann-Vague, V., Luzniak, P., Wojciechowska Luzniak, A., Zairis, M., Lyras, A., Patsourakos, N., Tsirimbis, V., Foussas, S., Lupon, J., Urrutia, A., Herreros, J., Gonzalez, B., Coll, R., Altimir, S., Prats, M., Valle, V., Abreu-Padi, C., Rabago, G., Ivanova, L. A., Brasacchio, D., Calkin, A., Jandeleit-Dahm, K. A., Harno, E., Keenan, A. K., Li, H. L., Yu, Y. R., Lu, Z. M., Zhang, X. E., Ke, L., Liu, H., Zhang, X. X., Jeong, I-K, Chae, M-K, Choi, M-H, Yoo, H-J, Kim, C. D., Yun, M. R., Na, M. A., Kang, Y. H., Kong, O. N., Son, S. M., Kim, I. J., Kim, Y. K., Tanaka, N., Hosoi, M., Matsuyama, Y., Fukumoto, M., Yamakita, T., Yoshioka, K., Ishii, T., Sato, T., Fujii, S., Aoki, T., Shibata, T., Mizutani, N., Suzuki, J-Y, Fowelin, J. H. R., Samuelsson, P., Brandrup-Wogsen, G., Okumura, K., Tokmakova, A. Y., Staroverova, D. N., Antcieferov, M. B., Shutichina, I. V., Kuntchevich, G. I., Vriesendorp, T. M., Morelis, Q. J., Legemate, D. A., Schaper, F., Mainas, E. I., Gkioulmpasanis, I., Panagiotou, I., Vassilikos, G., Skorda, L., Sidira, M., Christoforidou, M., Alaveras, A., Artikis, V., Evdemon, E., Lechleitner, M., Koch, T., Ebenbichler, C., Sturm, W., Moretti, L., Moruzzo, D., Boldrini, E., Pandolfo, C., Kameyama, M., Iwasa, R., Cho, M-H, Nam, J-Y, Kim, C-S, Kim, D-M, Ahn, C-W, Cha, B-S, Lim, S-K, Kim, K-R, Lee, H-C, Huh, K-B, Kaplar, M., Paragh, G., Erdei, A., Csongradi, E., Garai, I., Varga, J., Galuska, L., Udvardy, M., Higa, M., Kaneko, Y., Hiroi, N., Koziarska, D., Nowacki, P., Majkowska, L., Wojciechowska-Luzniak, A., Tushuizen, M. E., Nieuwland, R., Snoeck, D. P., Sturk, A., Diamant, M., Aguiar, L. G. K., Bahia, L., Villela, N., Laflor, C., Conde, C., Bottino, D., Dorigo, D., Bouskela, E., Pu, S., Yu, H. L., Luo, Z. T., Lam, K. S. L., Dan, Q., Xu, A., Shen, J., Cheng, K., Xu, J. Y. U., Thamer, C., Stefan, N., Haap, M., Heller, E., Tschritter, O., Prado, A., Ortiz, A., Ybarra, J., Gich, I., Pou, J. M., Ehren, M., Meyer, M. F., Roggenland, D., Reinsen, B., Klein, H. H., Rittig, K., Stock, J., Kocher, B., Balletshofer, B., Lee, J., Shon, H. S., Chung, D. S., Nakatani, Y., Matsuhisa, M., Kaneto, H., Hatazaki, M., Yoshiuchi, K., Katakami, N., Kawamori, D., Ohtoshi, K., Sakamoto, K., Matsuoka, T-A, Ozawa, K., Ogawa, S., Hori, M., Yamasaki, Y., Zitouni, K., Harry, D., Nourooz-Zadeh, J., Betteridge, J. D., Earle, K. A., Rasmussen, L. M., Olesen, P., Franco, L., Corvaja, C., Semplicini, A., Rosen, P., Lee, I-K, Kim, M-J, Park, K-G, Jung, E-D, Shin, D-W, Jo, S-R, Obuobie, K., Prakash, P. K., Hanna, F. W., Evans, M., Lazarus, J., Varadhan, L., Gurushankar, J., James, D., Sheikh, S., Gaede, P., Li, H., Zou, D., Lee, S. J., Choi, M. G., Kim, D. S., Kim, T. W., Vilarrasa, N., Perez-Maraver, M., Mena, E., Perez, D., Setti, G., Buckingham, R., Urbancic, V., Stefanovska, A., Bernjak, A., Azman-Juvan, K., Kocijancic, A., Glowania, A., Filters, T. S., Fosmark, D. S., Torjesen, P. A., Kilhovd, B., Berg, T. J., Sandvik, L., Hanssen, K. F., Mentink, C. J. A., Kilhovd, B. K., Kuchmerovska, T. M., Shymanskyy, I. O., Donchenko, G. V., Stepanenko, S. P., Klimenko, A. P., Park, J., Maingrette, F., Deng, H. C., Lindenmair, A., Waldhausl, W. K., Freudenthaler, A., Baumgartner-Parzer, S. M., Nizheradze, K., Khoruzhenko, A., Tronko, N., Sheu, W. H. H., Ou, H-C, Shen, H-M, Lin, T-M, Wu, H-S, Yang, C-H, Mogylnytska, L., Mankovsky, B., Schmoelzer, I., Davies, J. I., Band, M., Morris, A., Struthers, A. D., Prazny, M., Skrha, J., Kasalova, Z., Neelotpol, S., Jahan, P., Kauschke, S. G., Harrop, C. A., Schafer, A., Widder, J., Eigenthaler, M., Walter, U., Uchimura, I., Ikebukuro, M., Kaibara, M., Hirata, M., Helal, R., Pervin, F., Khan, A. K. A., Yang, X., Jansson, P-A, Nagaev, I., Jack, M. M., Carvalho, E., Sunnerhagen, K. Stibrant, Cam, M. C., Cushman, S. W., Smith, U., Creely, S. J., Farmer, J., Creely, S., Gustafson, B., Kusminski, C. M., Krusinova, E., Wohl, P., Klementova, M., Lanska, V., Mcdougall, C., Thomas, S. J., Kelly, I., Abbas, Z. G., Lutale, J. K., Archibald, L. K., Karunajeewa, H., Stingemore, N., Stuccio, G., Mcgechie, D., Muller, L. M. A., Hak, E., Goudzwaard, W. L., Montorsi, F., Homering, M., Sprenger, K., Goldstein, I., Asnaghi, V., Ferrari, G., Rastaldi, M., Gabellini, D., Antonio, G., Maestroni, A., Ruggieri, D., Luzi, L., Piemonti, L., Zerbini, G., Anafaroglu, I., Tutuncu, N. B., Sultana, M., Siddiqua, N., Iwasaki, T., Nakajima, A., Yoneda, M., Mukasa, K., Tanaka, S., and Sekihara, H.

44. Gifts in fluid: Function of tissue factor and coagulation factor VII in human body fluids

Author: Hu, Y., van Leeuwen, Ton, van Noorden, Ron, Nieuwland, Rienk, Thaler, Johannes, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Biomedical Engineering and Physics, Other Research, CCA - Cancer biology and immunology, CCA - Cancer Treatment and Quality of Life, Graduate School, van Leeuwen, A.G.J.M., van Noorden, C.J.F., Nieuwland, R., Thaler, J., and Faculteit der Geneeskunde
Abstract: Cells release small particles, which are called extracellular vesicles (EVs). EVs are present in human body fluids, but their function is unknown. We investigated why normal human body fluids contain EVs, and how such EVs may play a role in physiology. We show that EVs present in human milk and other body fluids expose a protein called tissue factor (TF). TF triggers the clotting of blood, which helps to stop bleeding and reduces the risk of infection. The presence of these TF-exposing EVs in milk explains observations from the 1930-ies that bleeding can be stopped by applying milk-soaked gauzes. The blood clotting activity of milk survives conditions simulating the infants’ gastric and pancreatic digestion, suggesting that milk may possibly contribute to gastrointestinal haemostasis in infants. We also show that measuring the ability of human milk to trigger blood plasma clotting may be useful to evaluate milk pasteurization, a procedure applied when milk is stored in hospital biobanks. Furthermore, we demonstrate that EVs in amniotic fluid, milk, saliva and urine expose not only TF but also its ligand, coagulation factor VII (FVII). In fact, the presence of the complex of TF and FVII on EVs explains why EVs efficiently trigger blood clotting. The complex of TF and FVII also has non-haemostatic functions such as regulation of epithelial permeability, and we provide evidence that FVII, present in amniotic fluid, may interact with TF present on fetal epithelial cells, and we show that this interaction may play a role in regulating epithelial permeability. Taken together, this thesis contributes to our understanding how EVs present in body fluids may contribute to protection by promoting haemostasis and regulation of epithelial permeability.
Published: 2022

45. Gently down the stream: Detection of extracellular vesicles by flow cytometry

Author: de Rond, Leonie, van Leeuwen, A.G.J.M., Sturk, A., Coumans, F.A.W., Nieuwland, R., Faculteit der Geneeskunde, van Leeuwen, Ton G. J. M., Sturk, Guus, Coumans, Frank A. W., Nieuwland, Rienk, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, and CCA - Imaging and biomarkers
Abstract: Cells release extracellular vesicles (EVs) into their environment for protection, waste removal, and intercellular communication. As a result, body fluids contain EVs, which are particles with a phospholipid membrane that range in diameter from 30 to 1,000 nm. The molecular composition of an EV depends on the origin and status (e.g. resting, activated, apoptotic) of the releasing cell. The concentration and composition of EVs in body fluids therefore changes with disease, making EVs potential biomarkers. To use EVs as biomarker, there is a need for a technique suitable for clinical application that can 1) detect particles as small as EVs, 2) distinguish EVs from non-EV particles, 3) identify the cellular origin of single EVs, and 4) measure the concentration of EVs in a way that allows comparison between instruments and institutes. Flow cytometry has a high potential to fulfil these requirements. The aim of this thesis is to improve the detection and characterization of single EVs by flow cytometry, to eventually allow the use of EVs as biomarkers in a clinical setting. To that end, this thesis includes methods to 1) lower the scatter detection limit for EVs of a commercial flow cytometer, 2) distinguish EVs from non-EV particles using their refractive index, and 3) compare data from different flow cytometers by applying a calibration method. Scatter detection in flow cytometry is thereby ready to study the biomarker potential of EVs in a clinical setting. Less
Published: 2020

46. Creatine kinase and cardiovascular disease

Author: Horjus, D.J., Middeldorp, Saskia, Sturk, Guus, Nieuwland, Rienk, Vascular Medicine, ACS - Microcirculation, ACS - Pulmonary hypertension & thrombosis, Amsterdam Reproduction & Development, Graduate School, Experimental Vascular Medicine, Middeldorp, S., Sturk, A., Nieuwland, R., and Faculteit der Geneeskunde
Abstract: Dit proefschrift onderzoekt de rol van creatine kinase (CK) in cardiovasculaire ziekten. CK is een belangrijk enzym in het energie metabolisme van de cel door het katalyseren van het chemische evenwicht: creatinefosfaat + adenosinedifosfaat (ADP) ↔ creatine + adenosinetrifosfaat (ATP). Door het faciliteren van het cellulaire energie metabolisme bevordert CK de contractiliteit van o.a. skeletspieren, de hartspier en gladde spiercellen rondom vaten. Daarnaast wordt ook gedacht dat het de zoutretentie in de nier, tevens een energie consumerend proces, bevordert. Een hoge CK activiteit vergroot hierdoor de kans op hoge bloeddruk. Naast het intracellulaire effect van CK onderzoeken we het effect van het CK dat uit de cel is gelekt en actief is in de bloedbaan (het plasma). Een hoge plasma CK activiteit remt, door het wegvangen van ADP, de bloedplaatjesactivatie en -aggregatie. Gezien het feit dat geactiveerde bloedplaatjes tevens een belangrijke ondersteunende functie hebben in de secundaire hemostase, onderzoeken we ook of plasma CK invloed heeft op de secundaire hemostase. Allereerst wordt in deel I onderzocht of beïnvloeding van de CK activiteit een bloeddrukverlagend effect zou kunnen hebben en dus een mogelijke rol binnen de behandeling van hypertensie. Deel II beschrijft de associatie tussen CK en bloeddruk tijdens en na de zwangerschap. Tevens bestuderen we in dit deel de associatie tussen CK en hypertensieve zwangerschapsaandoeningen. De invloed van CK op de primaire en secundaire hemostase wordt in het derde deel onderzocht door middel van zowel een in vitro studie als een grote populatie studie.
Published: 2019

47. Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author: Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Urology, Pathology, Medical Oncology, Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University School of Medicine [Baltimore], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department for Molecular Biology and Nanobiotechnology, National Institute of chemitry, Slovenia, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Centre for Sustainable Tropical Fisheries and Aquaculture, James Cook University (JCU), Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Departamento de Ciências Biológicas, Universidade do Porto = University of Porto, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy] (Laboratory of Cellular Therapy), Università degli Studi di Modena e Reggio Emilia (UNIMORE), Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Center for Cooperative Research in Biosciences (CIC bioGUNE), Partner site Munich, German Centre for Infection Research (DZIF), Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Psychiatry, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Dalhousie University [Halifax], Department of Biology, Molecular Cell Biology, University of Mainz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg (GU), Universidad de Alicante, École supérieure du professorat et de l'éducation - Académie de Créteil (UPEC ESPE Créteil), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Antwerp (UA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Research Institute, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Veterinary Disease Biology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Biologie et Pathologie du Neurone (Brain-C), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics, American University, University of Pretoria [South Africa], Ecole des Ingénieurs de la Ville de Paris (EIVP), Universitat Pompeu Fabra [Barcelona] (UPF), Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Istituto Ortopedico Rizzoli, Department of Molecular Therapeutics, The Scripps Research Institute, Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], University Medical Center [Utrecht], University of Toronto, Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Federal University of Sao Paulo (Unifesp), Functional Genomics / Genómica Funcional [Montevideo], Institut Pasteur de Montevideo, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università degli Studi di Perugia (UNIPG), Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University of California [San Francisco] (UCSF), University of California-University of California, University of Vermont [Burlington], Peking University [Beijing], Shandong Agricultural University (SDAU), State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR, (Institute of Chinese Medical Sciences), Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], INSERM, Institut Curie, INCa [INCA-11548], French National Research Agency [ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043], SIDACTION [17-1-AAE-1138], Fondation ARC [PGA1 RF20180206962, PJA 20171206453], NIDA [DA040385, DA047807], Ministry of Education, NIA [AG057430], NIMH [MH118164], Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Biotechnology and Biological Sciences Research Council (BBSRC)-Aberystwyth University, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), The Scripps Research Institute [La Jolla, San Diego], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Università degli Studi di Perugia = University of Perugia (UNIPG), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), ANR-17-CE09-0025,MADNESS,Une approche microfluidique générique pour la qualification des nanoparticules biologiques(2017), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Laboratory Specialized Diagnostics & Research, Radiotherapie, RS: GROW - R2 - Basic and Translational Cancer Biology, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Università degli studi di Torino (UNITO), Universidade do Porto, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Toronto [Canada], Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto [Porto], Ghent University [Belgium] (UGENT), FEMTO-ST Institute, Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-CNRS : UMR6174, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Johannes Gutenberg - University of Mainz (JGU), Université Catholique de Louvain (UCL), Universitat Pompeu Fabra [Barcelona], Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Réactions et Génie des Procédés (LRGP), Fiocruz Minas - René Rachou Research Center / Instituto René Rachou, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Functional Genomics Unit, Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Vermont College of Medicine [Burlington, VT, USA], Extracellular Vesicles, Molecular and Integrative Biosciences Research Programme, Thery, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin-Smith, G. K., Ayre, D. C., Bach, J. -M., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., Beckham, C., Bedina Zavec, A., Benmoussa, A., Berardi, A. C., Bergese, P., Bielska, E., Blenkiron, C., Bobis-Wozowicz, S., Boilard, E., Boireau, W., Bongiovanni, A., Borras, F. E., Bosch, S., Boulanger, C. M., Breakefield, X., Breglio, A. M., Brennan, M. A., Brigstock, D. R., Brisson, A., Broekman, M. L. D., Bromberg, J. F., Bryl-Gorecka, P., Buch, S., Buck, A. H., Burger, D., Busatto, S., Buschmann, D., Bussolati, B., Buzas, E. I., Byrd, J. B., Camussi, G., Carter, D. R. F., Caruso, S., Chamley, L. W., Chang, Y. -T., Chaudhuri, A. D., Chen, C., Chen, S., Cheng, L., Chin, A. R., Clayton, A., Clerici, S. P., Cocks, A., Cocucci, E., Coffey, R. J., Cordeiro-da-Silva, A., Couch, Y., Coumans, F. A. W., Coyle, B., Crescitelli, R., Criado, M. F., D'Souza-Schorey, C., Das, S., de Candia, P., De Santana, E. F., De Wever, O., del Portillo, H. A., Demaret, T., Deville, S., Devitt, A., Dhondt, B., Di Vizio, D., Dieterich, L. C., Dolo, V., Dominguez Rubio, A. P., Dominici, M., Dourado, M. R., Driedonks, T. A. P., Duarte, F. V., Duncan, H. M., Eichenberger, R. M., Ekstrom, K., EL Andaloussi, S., Elie-Caille, C., Erdbrugger, U., Falcon-Perez, J. M., Fatima, F., Fish, J. E., Flores-Bellver, M., Forsonits, A., Frelet-Barrand, A., Fricke, F., Fuhrmann, G., Gabrielsson, S., Gamez-Valero, A., Gardiner, C., Gartner, K., Gaudin, R., Gho, Y. S., Giebel, B., Gilbert, C., Gimona, M., Giusti, I., Goberdhan, D. C. I., Gorgens, A., Gorski, S. M., Greening, D. W., Gross, J. C., Gualerzi, A., Gupta, G. N., Gustafson, D., Handberg, A., Haraszti, R. A., Harrison, P., Hegyesi, H., Hendrix, A., Hill, A. F., Hochberg, F. H., Hoffmann, K. F., Holder, B., Holthofer, H., Hosseinkhani, B., Hu, G., Huang, Y., Huber, V., Hunt, S., Ibrahim, A. G. -E., Ikezu, T., Inal, J. M., Isin, M., Ivanova, A., Jackson, H. K., Jacobsen, S., Jay, S. M., Jayachandran, M., Jenster, G., Jiang, L., Johnson, S. M., Jones, J. C., Jong, A., Jovanovic-Talisman, T., Jung, S., Kalluri, R., Kano, S. -I., Kaur, S., Kawamura, Y., Keller, E. T., Khamari, D., Khomyakova, E., Khvorova, A., Kierulf, P., Kim, K. P., Kislinger, T., Klingeborn, M., Klinke, D. J., Kornek, M., Kosanovic, M. M., Kovacs, A. F., Kramer-Albers, E. -M., Krasemann, S., Krause, M., Kurochkin, I. V., Kusuma, G. D., Kuypers, S., Laitinen, S., Langevin, S. M., Languino, L. R., Lannigan, J., Lasser, C., Laurent, L. C., Lavieu, G., Lazaro-Ibanez, E., Le Lay, S., Lee, M. -S., Lee, Y. X. F., Lemos, D. S., Lenassi, M., Leszczynska, A., Li, I. T. S., Liao, K., Libregts, S. F., Ligeti, E., Lim, R., Lim, S. K., Line, A., Linnemannstons, K., Llorente, A., Lombard, C. A., Lorenowicz, M. J., Lorincz, A. M., Lotvall, J., Lovett, J., Lowry, M. C., Loyer, X., Lu, Q., Lukomska, B., Lunavat, T. R., Maas, S. L. N., Malhi, H., Marcilla, A., Mariani, J., Mariscal, J., Martens-Uzunova, E. S., Martin-Jaular, L., Martinez, M. C., Martins, V. R., Mathieu, M., Mathivanan, S., Maugeri, M., Mcginnis, L. K., Mcvey, M. J., Meckes, D. G., Meehan, K. L., Mertens, I., Minciacchi, V. R., Moller, A., Moller Jorgensen, M., Morales-Kastresana, A., Morhayim, J., Mullier, F., Muraca, M., Musante, L., Mussack, V., Muth, D. C., Myburgh, K. H., Najrana, T., Nawaz, M., Nazarenko, I., Nejsum, P., Neri, C., Neri, T., Nieuwland, R., Nimrichter, L., Nolan, J. P., Nolte-'t Hoen, E. N. M., Noren Hooten, N., O'Driscoll, L., O'Grady, T., O'Loghlen, A., Ochiya, T., Olivier, M., Ortiz, A., Ortiz, L. A., Osteikoetxea, X., Ostegaard, O., Ostrowski, M., Park, J., Pegtel, D. M., Peinado, H., Perut, F., Pfaffl, M. W., Phinney, D. G., Pieters, B. C. H., Pink, R. C., Pisetsky, D. S., Pogge von Strandmann, E., Polakovicova, I., Poon, I. K. H., Powell, B. H., Prada, I., Pulliam, L., Quesenberry, P., Radeghieri, A., Raffai, R. L., Raimondo, S., Rak, J., Ramirez, M. I., Raposo, G., Rayyan, M. S., Regev-Rudzki, N., Ricklefs, F. L., Robbins, P. D., Roberts, D. D., Rodrigues, S. C., Rohde, E., Rome, S., Rouschop, K. M. A., Rughetti, A., Russell, A. E., Saa, P., Sahoo, S., Salas-Huenuleo, E., Sanchez, C., Saugstad, J. A., Saul, M. J., Schiffelers, R. M., Schneider, R., Schoyen, T. H., Scott, A., Shahaj, E., Sharma, S., Shatnyeva, O., Shekari, F., Shelke, G. V., Shetty, A. K., Shiba, K., Siljander, P. R. -M., Silva, A. M., Skowronek, A., Snyder, O. L., Soares, R. P., Sodar, B. W., Soekmadji, C., Sotillo, J., Stahl, P. D., Stoorvogel, W., Stott, S. L., Strasser, E. F., Swift, S., Tahara, H., Tewari, M., Timms, K., Tiwari, S., Tixeira, R., Tkach, M., Toh, W. S., Tomasini, R., Torrecilhas, A. C., Tosar, J. P., Toxavidis, V., Urbanelli, L., Vader, P., van Balkom, B. W. M., van der Grein, S. G., Van Deun, J., van Herwijnen, M. J. C., Van Keuren-Jensen, K., van Niel, G., van Royen, M. E., van Wijnen, A. J., Vasconcelos, M. H., Vechetti, I. J., Veit, T. D., Vella, L. J., Velot, E., Verweij, F. J., Vestad, B., Vinas, J. L., Visnovitz, T., Vukman, K. V., Wahlgren, J., Watson, D. C., Wauben, M. H. M., Weaver, A., Webber, J. P., Weber, V., Wehman, A. M., Weiss, D. J., Welsh, J. A., Wendt, S., Wheelock, A. M., Wiener, Z., Witte, L., Wolfram, J., Xagorari, A., Xander, P., Xu, J., Yan, X., Yanez-Mo, M., Yin, H., Yuana, Y., Zappulli, V., Zarubova, J., Zekas, V., Zhang, J. -Y., Zhao, Z., Zheng, L., Zheutlin, A. R., Zickler, A. M., Zimmermann, P., Zivkovic, A. M., Zocco, D., Zuba-Surma, E. K., dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms
Subjects: ectosome, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, Histology, Cell Biology, [SDV]Life Sciences [q-bio], size-exclusion, Medicine and Health Sciences, CELL-DERIVED MICROPARTICLES, FIELD-FLOW FRACTIONATION, requirements, circulating, ComputingMilieux_MISCELLANEOUS, Manchester Cancer Research Centre, lcsh:Cytology, PROSTATE-CANCER, microparticle, Cell interaction, microvesicle, chromatography, Position Paper, guideline, Life Sciences & Biomedicine, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, MEMBRANE-VESICLES, FETAL BOVINE, Ectosomes, Exosomes, Extracellular Vesicles, Guidelines, Microparticles, Microvesicles, Minimal Information Requirements, Reproducibility, Rigor, Standardization, CIRCULATING MICROPARTICLES, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ddc:570, exosome, SURFACE-PLASMON RESONANCE, ddc:610, lcsh:QH573-671, Biology, Interacció cel·lular, Science & Technology, ResearchInstitutes_Networks_Beacons/mcrc, Cell membranes, HUMAN URINARY EXOSOMES, PREANALYTICAL PARAMETERS, minimal information requirement, SIZE-EXCLUSION CHROMATOGRAPHY, 1182 Biochemistry, cell and molecular biology, extracellular vesicle, Human medicine, Membranes cel·lulars
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Published: 2018

48. Detection of extracellular vesicles: size does matter

Author: van der Pol, Edwin, van Leeuwen, Ton, Sturk, A., Nieuwland, R., Faculteit der Geneeskunde, van Leeuwen, Ton G. J. M., Sturk, Guus, Nieuwland, Rienk, Other Research, and Biomedical Engineering and Physics
Abstract: Cells release small sacks filled with fluid, which are called "extracellular vesicles". The diameter of extracellular vesicles (EV) typically ranges from 30 nm to 1 µm. Because cells release EV into their environment, our body fluids contain numerous EV. Cells release EV to remove waste and to transport cargo to other cells. Since the size, concentration, cellular origin, and composition of EV in body fluids change during disease, EV have promising clinical applications, such as diagnosis of cancer. However, clinical applications of EV are not realized yet, because currently used detection techniques lack the sensitivity to detect the majority of EV. The aim of this thesis is to improve the detection of EV by (1) obtaining insights into physical properties of EV, and (2) gaining a profound understanding of techniques to detect EV. This thesis explains why the reported concentrations of EV in human blood plasma differ 100,000,000-fold. In addition, this thesis shows that flow cytometry detects large vesicles and swarms of smaller vesicles, which both are counted as a single event signal. The relationship between light scattering and the diameter of EV is modelled using Mie theory to demonstrate that a currently widely applied standardization procedure for EV detection selects EV and cells with a diameter of 800-2,400 nm instead of the envisioned 500-900 nm. Furthermore, a method based on nanoparticle tracking analysis is developed to determine the size and refractive index of single EV and other nanoparticles.
Published: 2015

49. Venous thrombosis in cancer patients: Prediction, diagnosis and management

Author: Kleinjan, A., Büller, H.R., Kamphuisen, P.W., Nieuwland, R., Di Nisio, M., and Faculteit der Geneeskunde
Subjects: sense organs
Published: 2013

50. Postprandial dysmetabolism and cell-derived microparticles as cardiovascular risk factors in metabolic syndrome and type 2 diabetes mellitus

Author: Tushuizen, M.E., Diamant, M., Sturk, A., Nieuwland, R., Diamant, Michaela, Internal medicine, and ICaR - Circulation and metabolism
Published: 2012

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