Search

Your search keyword '"Teisman A"' showing total 930 results
Start Over Author "Teisman A"
930 results on '"Teisman A"'

52. JNJ-67569762, A 2-Aminotetrahydropyridine-Based Selective BACE1 Inhibitor Targeting the S3 Pocket: From Discovery to Clinical Candidate

Author

Rombouts, Frederik J. R., primary, Kusakabe, Ken-ichi, additional, Alexander, Richard, additional, Austin, Nigel, additional, Borghys, Herman, additional, De Cleyn, Michel, additional, Dhuyvetter, Deborah, additional, Gijsen, Harrie J. M., additional, Hrupka, Brian, additional, Jacobs, Tom, additional, Jerhaoui, Soufyan, additional, Lammens, Lieve, additional, Leclercq, Laurent, additional, Tsubone, Koichi, additional, Ueno, Tatsuhiko, additional, Morimoto, Kenji, additional, Einaru, Shunsuke, additional, Sumiyoshi, Hirokazu, additional, Van den Bergh, An, additional, Vos, Ann, additional, Surkyn, Michel, additional, Teisman, Ard, additional, and Moechars, Diederik, additional

Published
2021
Full Text
View/download PDF

53. Governance of sustainability at airports: Moving beyond the debate between growth and noise

Author

Boons, Frank, Van Buuren, Arwin, and Teisman, Geert

Subjects
Airports -- Analysis, Sustainable urban development -- Analysis, Environmental issues, Geography
Abstract

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1477-8947.2010.01314.x Byline: Frank Boons (1), Arwin van Buuren (1), Geert Teisman (1) Keywords: Airports; Sustainable development; Complexity theory; Governance Abstract: Abstract Airports increasingly are contested areas where many sustainability aspects are relevant. Especially in cases where airport development and urban development coincide, the actors involved are engaged in decision-making processes where only a small subset of the broader scope of sustainability issues is discussed. In this article we use a conceptual framework building on complexity theory to shed light on this phenomenon and its consequences for the case of Schiphol Airport in The Netherlands. First, we analyze the systemic causes for the narrow debate about sustainability. We then use the framework to recommend ways forward to broaden the debate about the sustainable development of airports by creating the institutional space for a reflexive and collaborative dialogue. Author Affiliation: (1)Erasmus University Rotterdam, Department of Public Administration. Rotterdam, The Netherlands Article note: Frank Boons, Geert Teisman and Arwin van Buuren are with Erasmus University Rotterdam, Department of Public Administration. Rotterdam, The Netherlands. E-mail: boons@fsw.eur.nl, teisman@fsw.eur.nl and vanbuuren@fsw.eur.nl

Published
2010

59. Seizure-induced Torsades de pointes:In a canine drug-induced long-QT1 model

Author

David J. Gallacher, Ard Teisman, Mohamed Kreir, and Henk van der Linde

Subjects
medicine.medical_specialty, Long QT syndrome, Population, Torsades de pointes, Toxicology, Sudden death, QT interval, Epilepsy, Electrocardiography, Dogs, Seizures, Torsades de Pointes, Internal medicine, medicine, Repolarization, Animals, Humans, education, Pharmacology, education.field_of_study, business.industry, medicine.disease, Long QT Syndrome, Pharmaceutical Preparations, Ventricular fibrillation, Cardiology, business
Abstract

Introduction People with epilepsy are at heightened risk of sudden death compared to the general population. The leading cause of epilepsy-related premature mortality is a sudden unexpected death in epilepsy (SUDEP). The mechanism of SUDEP remains largely unresolved and the lack of preclinical models to study the potential mechanism underlying SUDEP is a problem. Method By combining electroencephalographic (EEG) and electrocardiogram (ECG) measurements within a well described LQT1 dog model, we investigated the effect of the proconvulsive compound pentylenetetrazol (PTZ), and its link to the induction of Torsades de Pointes (TdP). Results Pre-treatment with the potent and selective IKs blocker JNJ 282 induced a pronounced QT (QTc) prolongation in anaesthetized dogs (Long QT syndrome type 1 or LQT1 group) compared to dogs that were not treated (control group). Subsequent PTZ administration induced spiking on the EEG signal and seizures in both groups, but only R-on-T, salvo and TdP were observed in dogs of the LQT1 group. Conclusion Our results show that a proconvulsive drug can trigger TdP-like cardiac arrhythmias, in conditions of compromised repolarization in the heart (Iks blockade). In man, TdP arrythmia's can often lead to ventricular fibrillation (VF) and sudden death. This observation suggests that long QT-intervals (genetic or drug induced) could potentially be one of the risk factors for SUDEP in epileptic patients.

Published
2021

60. The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells

Author

Alain J. Labro, Alaerts Maaike, Dieter V. Van de Sande, Dirk J. Snyders, David J. Gallacher, Luc Leybaert, Ivan Kopljar, Hua Rong Lu, Ard Teisman, and Loeys Bart

Subjects
0301 basic medicine, Patch-Clamp Techniques, Kir2.1, Biophysics, Giant Cells, Biochemistry, Membrane Potentials, In vitro model, input resistance, 03 medical and health sciences, Technical Report, 0302 clinical medicine, action potential, Whole cell patch-clamp, Medicine and Health Sciences, Myocytes, Cardiac, Induced pluripotent stem cell, Biology, Membrane potential, Syncytium, Chemistry, electrophysiology, Cell biology, Electrophysiology, 030104 developmental biology, Potassium, Stem cell, 030217 neurology & neurosurgery, Input resistance
Abstract

Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression of the Kir2.1 potassium channel that generates the I-K1 current. However, most RMP recordings are obtained from isolated hSC/hiPSC-CMs whereas in a more native setting these cells are interconnected with neighboring cells by connexin-based gap junctions, forming a syncytium. Hereby, these cells are electrically connected and the total pool of I-K1 increases. Therefore, the input resistance (Ri) of interconnected cells is lower than that of isolated cells. During patch clamp experiments pipettes need to be well attached or sealed to the cell, which is reflected in the seal resistance (Rs), because a nonspecific ionic current can leak through this pipette-cell contact or seal and balance out small currents within the cell such as I-K1. By recording the action potential of isolated hSC-CMs and that of hSC-CMs cultured in small monolayers, we show that the RMP of hSC-CMs in monolayer is approximately -20 mV more hyperpolarized compared to isolated cells. Accordingly, adding carbenoxolone, a connexin channel blocker, isolates the cell that is patch clamped from its neighboring cells of the monolayer and depolarizes the RMP. The presented data show that the recorded RMP of hSC-CMs in a syncytium is more negative than that determined from isolated hSC/hiPSC-CMs, most likely because the active pool of Kir2.1 channels increased.

Published
2021

61. Tools for professional practice to facilitate business model development and market adoption of improved bioP2methane technology

Author

Smit, Annet Jantien and Teisman, Joline

Subjects
Energy(All), Groen Gas, Energietransitie, Alternative Gasses And Hybrid Fuels, Energy Transition, Professional Practice &Amp; Society, New Business Models, New Economics, Labour Market And Legal Aspects In The Energy Sector, Biomethaan, Life Sciences undefined Renewable Energy, Business Models, Green Gas, No Hanze Research Focus Area Applicable, Energie (Alles), Alternatieve Gassen En Hybride Brandstoffen, Nieuwe Economie, Werk En Juridische Aspecten In De Energiesector, Bedrijfsmodellen
Published
2020

62. Over de boeg van een akkoord

Author

Spekkink, W. (Wouter), Teisman, G.R. (Geert), Muller, S. (Sam), Buuren, M.W. (Arwin) van, Spekkink, W. (Wouter), Teisman, G.R. (Geert), Muller, S. (Sam), and Buuren, M.W. (Arwin) van

Abstract

Dit essay beschrijft een praktijk van lokaal klimaatbeleid, waarin beleid in de vorm van een klimaatakkoord met ruim 100 partijen tot stand komt. In plaats van dat de gemeente beleid afkondigt, maken partijen dit samen. Werkt dat, hoe werkt dat en wat kunnen we ervan leren? We gingen op zoek naar de kracht van de aanpak en hoe partijen die kracht hebben gevonden. De volgende vraag was daarbij leidend: _‘Wat zijn de opbrengsten van de werkwijze rond het Rotterdams Klimaatakkoord, welke dilemma’s deden zich voor en welke lessen kan een initiërende gemeente (als Rotterdam) daaruit trekken?’_

Published
2021

69. Time for a Fully Integrated Nonclinical–Clinical Risk Assessment to Streamline QT Prolongation Liability Determinations: A Pharma Industry Perspective

Author

Vargas, Hugo M., primary, Rolf, Michael G., additional, Wisialowski, Todd A., additional, Achanzar, William, additional, Bahinski, Anthony, additional, Bass, Alan, additional, Benson, Charles T, additional, Chaudhary, Khuram W., additional, Couvreur, Nicolas, additional, Dota, Corina, additional, Engwall, Michael J, additional, Michael Foley, C., additional, Gallacher, David, additional, Greiter‐Wilke, Andrea, additional, Guillon, Jean‐Michel, additional, Guth, Brian, additional, Himmel, Herbert M., additional, Hegele‐Hartung, Christa, additional, Ito, Maki, additional, Jenkinson, Stephen, additional, Chiba, Katsuyoshi, additional, Lagrutta, Armando, additional, Levesque, Paul, additional, Martel, Eric, additional, Okai, Yoshiko, additional, Peri, Ravikumar, additional, Pointon, Amy, additional, Qu, Yusheng, additional, Teisman, Ard, additional, Traebert, Martin, additional, Yoshinaga, Takashi, additional, Gintant, Gary A., additional, Leishman, Derek J., additional, and Valentin, Jean‐Pierre, additional

Published
2020
Full Text
View/download PDF

72. Employing complexity: complexification management for locked issues

Author

Geert Teisman, Hans Joosse, and Public Administration

Subjects
Wicked problem, Computer science, Complexification (Lie group), 05 social sciences, 0506 political science, Management Information Systems, Path dependency, Risk analysis (engineering), Management of Technology and Innovation, Public management, 0502 economics and business, 050602 political science & public administration, Line (text file), 050203 business & management
Abstract

In line with wicked problem literature, we argue that public management based on ordering societal issues to make them controllable and solvable (simplification) can be initially attractive, but in the long-term ineffective. We elaborate on an alternative management mode of increasing the complexity of both the problem and the approach to deal with the problem (complexification). Based on an in-depth case-study about transforming Utrecht Central Station (the Netherlands), we present complexification as a management strategy to revitalize processes that got locked by simplification management. Path-dependency shows up as a weakness of simplification, and path-creation as a strength of complexification.

Published
2020

75. Discovery of an Extremely Potent Thiazine-Based β-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose

Author

Yasuyoshi Iso, Naoki Kanegawa, Vijay Urmaliya, Kazuki Fujimoto, Kazuo Komano, Ard Teisman, An Van Den Bergh, Herman Borghys, Hisanori Ito, Shuhei Yoshida, Shigeru Ando, Yasuto Kido, Nigel E. Austin, Naoya Asada, Shinji Suzuki, Kenji Nakahara, Ken-ichi Kusakabe, Eriko Matsuoka, Harrie J.M. Gijsen, Gaku Sakaguchi, Genta Tadano, Yoshinori Yamano, Tamio Fukushima, Takahiko Yamamoto, Deborah Dhuyvetter, and Kouki Fuchino

Subjects
Male, Liver toxicity, Drug Evaluation, Preclinical, Thiazines, Pharmacology, 01 natural sciences, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Mice, Dogs, In vivo, Thiazine, Alzheimer Disease, mental disorders, Drug Discovery, Amyloid precursor protein, Animals, Humans, Protease Inhibitors, Volume concentration, 030304 developmental biology, Cytochrome P-450 CYP2C9, 0303 health sciences, Amyloid beta-Peptides, biology, Half-life, Brain, Heart, Haplorhini, 0104 chemical sciences, Rats, 010404 medicinal & biomolecular chemistry, chemistry, Liver, biology.protein, β secretase, Molecular Medicine, Trough level, Female, Amyloid Precursor Protein Secretases, Half-Life
Abstract

Genetic evidence points to deposition of amyloid-β (Aβ) as a causal factor for Alzheimer's disease. Aβ generation is initiated when β-secretase (BACE1) cleaves the amyloid precursor protein. Starting with an oxazine lead 1, we describe the discovery of a thiazine-based BACE1 inhibitor 5 with robust Aβ reduction in vivo at low concentrations, leading to a low projected human dose of 14 mg/day where 5 achieved sustained Aβ reduction of 80% at trough level.

Published
2019

76. Assessing Drug-Induced Long QT and Proarrhythmic Risk Using Human Stem-Cell-Derived Cardiomyocytes in a Ca2+ Imaging Assay: Evaluation of 28 CiPA Compounds at Three Test Sites

Author

Jennifer B. Pierson, Armando Lagrutta, Holly Clouse, Michael Furniss, Ivan Kopljar, Frederick Sannajust, Ralf Kettenhofen, Haoyu Zeng, Hua Rong Lu, Karel Van Ammel, Fetene Tekle, Ard Teisman, Jin Zhai, Liang Guo, and David J. Gallacher

Subjects
0301 basic medicine, Drug, Risk, media_common.quotation_subject, Torsades de pointes, 030204 cardiovascular system & hematology, Pharmacology, Toxicology, QT interval, Afterdepolarization, 03 medical and health sciences, 0302 clinical medicine, Emerging Technologies, Methods, and Models, Medicine, Myocyte, Humans, Myocytes, Cardiac, Cells, Cultured, media_common, Proarrhythmia, Dose-Response Relationship, Drug, business.industry, Stem Cells, Arrhythmias, Cardiac, medicine.disease, In vitro, Long QT Syndrome, 030104 developmental biology, Calcium, business, Plate reader
Abstract

The goal of this research consortium including Janssen, MSD, Ncardia, FNCR/LBR, and Health and Environmental Sciences Institute (HESI) was to evaluate the utility of an additional in vitro assay technology to detect potential drug-induced long QT and torsade de pointes (TdP) risk by monitoring cytosolic free Ca2+ transients in human stem-cell-derived cardiomyocytes (hSC-CMs). The potential proarrhythmic risks of the 28 comprehensive in vitro proarrhythmia assay (CiPA) drugs linked to low, intermediate, and high clinical TdP risk were evaluated in a blinded manner using Ca2+-sensitive fluorescent dye assay recorded from a kinetic plate reader system (Hamamatsu FDSS/µCell and FDSS7000) in 2D cultures of 2 commercially available hSC-CM lines (Cor.4U and CDI iCell Cardiomyocytes) at 3 different test sites. The Ca2+ transient assay, performed at the 3 sites using the 2 different hSC-CMs lines, correctly detected potential drug-induced QT prolongation among the 28 CiPA drugs and detected cellular arrhythmias-like/early afterdepolarization in 7 of 8 high TdP-risk drugs (87.5%), 6 of 11 intermediate TdP-risk drugs (54.5%), and 0 of 9 low/no TdP-risk drugs (0%). The results were comparable among the 3 sites and from 2 hSC-CM cell lines. The Ca2+ transient assay can serve as a user-friendly and higher throughput alternative to complement the microelectrode array and voltage-sensing optical action potential recording assays used in the HESI-CiPA study for in vitro assessment of drug-induced long QT and TdP risk.

Published
2019

77. Abstracts of papers and posters Pharmacological Meeting

Author

Adan, Roger A. H., Peter, J., Burbach, H., Gispen, Willem -Hendrik, Bax, Willem A., Saxena, Pramod R., Beenen, O. H. M., Pfaffendorf, M., van Zwieten, P. A., Biewenga, G. Ph., Nicastia, A. J., Haenen, G. R. M. M., Bast, A., Bouwknecht, J. A., Molewijk, H. E., van der Poel, A. M., Mos, J., Olivier, B., Broersen, L. M., Heinsbroek, R. P. W., de Bruin, J. P. C., Brouwers, D. L., Nelissen-Vrancken, H. J. M. G., Smits, J. F. M., Bruning, T. A., Kemme, M. J. B., Chang, P. C., Muizert, Y., Buckley, Theresa L., Nijkamp, Frans P., Cappendijk, S. L. T., Duval, S. Y., De Vries, R., Dzoljic, M. R., Compaan, J. C., Groenink, L., van der Gugten, J., Cox, E. H., van Hemert, A. G. N., de Jong, E., Danhof, M., Crijns, F. R. L., Wolffenbuttel, B. H. R., van Essen, H., Boudier, H. A. J. Struijker, Dam, J. P. M., Doornekamp, F. N. G., Velema, E., Post, M. J., Borst, C., de Boer, J., Meurs, H., Bottone, A. E., Koopal, M., Visser, J. C., Zaagsma, J., de Lannoy, L. M., Danser, A. H. J., Bouhuizen, A. M. B., Schoemaker, R. G., Saxena, P. R., Schalekamp, M. A. D. H., de Vlieger, J. F., van den Wijngaard, P., Koster, A. Sj., Buckley, T. L., Wilting, J., van Heuven-Nolsen, D., Nijkamp, F., Du, X. Y., Bos, E., Dubois, E. A., Vermeulen, R. J., Janssen, A. F. M., van Royen, E. A., Gaillard, P. J., de Boer, A. G., Breimer, D. D., Garrelds, I. M., de Graaf-in't Veld, C., van Wijk, R. Gerth, Zijlstra, F. J., Gerrits, Mirjam A. F. M., Patkina, Nadezda, Zvartau, Edwin E., van Ree, Jan M., Gho, B. C. G., Verdouw, P. D., Gingras, M. A., Cools, A. R., Gommans, J., Hijzen, T., Maes, R. A., Verdouw, P. M., Herremans, A. H. J., Hijzen, T. H., Slangen, J. L., Hoiting, B. H., Schuiling, M., Elzinga, C. R. S., Hoogstraate, A. J., Verhoef, J., Schrijvers, A. H. G. J., Pijpers, A., van Leengoed, L. A. M. G., Verheijden, J. H. M., Junginger, H. E., Boddé, H. E., Hüsken, B. C. P., Joordens, R. J. E., Kalkman, E. A. J., Bilgin, M. Y., Kam, K. L., Kraneveld, A. D., Muis, T., Nijkamp, F. P., Madretsma, G. S., van Dijk, A. P. M., Wilson, J. H. P., Mohede, C. M., Van Oosterhout, J. M., Niikamp, F. P., Nestby, P., Visser, D., Wardeh, G., Hogenboom, F., Mulder, A. H., Schoffelmeer, A. N. M., Oosting, J., Struijker Boudier, H. A. J., Janssen, B. J. A., Passier, P. C. J. J., Verluyten, M. J. A., Drexler, H., Daemen, M. J. A. P., Hashjin, Gudarz Sadeghi, Henricks, Paul A. J., Folkerts, Gert, Shirmohammadi, Mahnaz, Niikamp, Frans P., Santing, R. E., Olymulder, C. G., van der Molen, K., Scheerens, Heleen, Van Loveren, Henk, Sipma, H., den Hertog, A., Nelemans, A., Smit, J., Coppes, R. P., Tintelen, E. J. J. v., Roffel, A. F., Smit, M. J., Leurs, Rob, Timmerman, H., Stam, W. B., Avezaat, C. J. J., Stolte, J., Schiffers, P. M. H., Boudier, H. A. J. Struyker, ten Berge, R. E. J., Krikke, M., Teisman, B. C. H., Tjon, G. H. K., Michiels, N., Voorn, P., van Bergen, P., De Wildt, D. J., Versteeg, D. H. G., van den Tweel, M. C., Bloemen, P. G. M., Henricks, P. A. J., Engels, F., Blomjous, F. J., van der Geest, R., van Laar, T., Roos, R. A. C., van de Velde, M. J., van Kats, J. P., Sassen, L. M. A., Polak, M. P. J., Derkx, F. H. M., van Kesteren, C. A. M., Lamers, J. M. J., van Heugten, H. A. A., van Meeteren, N. L. U., Frankhuyzen-Sierevogel, A., Brakkee, J. H., Wiegant, V. M., Gispen, W. H., Vroom, M. B., van Wezel, H. B., Timmenga, E. J. F., van der Horst, C. M. A. M., Winkler Prins, E. A., Zwavelina, J., Maas, A., Zhang, J., Zwaveling, J., Jansen, F. P., Mochizuki, T., Yamatodani, A., Masereeuw, R., Moons, W. M., Russel, F. G. M., van de Meent, H., van den Berg, C., Wemer, J., Vleeming, W., Kasbergen, C. M., van der Aa, E. M., Wouterse, A. C., Peereboom-Stegeman, J. H. J. Copius, Hessel, E. M., Van Oosterhout, A. J. M., de Bie, J. J., Hofman, G., and Van Loveren, H.

Published
1994
Full Text
View/download PDF

78. Abstracts of papers and posters

Author

Anthonio, R. L., Willemsen, A. T. M., Visser, T., van Waarde, A., Elzinga, P., Weemaes, A., Meeder, J. G., Pruim, J., Visser, G., Blanksma, P. K., Vaalburg, W., Bloemen, P. G. M., Henricks, P. A. J., van Bloois, L., van den Tweel, M. C., Nijkamp, F. P., Crommelin, D. J. A., Storm, G., de Boer, A. H., Winter, H. M. I., Lerk, C. F., de Boer, J., Meurs, H., Bottone, A. E., Koopal, M., Visser, J. C., Zaagsma, J., Borger P., Kauffman H. F., Vijgen J. L. J., Postma D. S., Vellenga E., Buckley, Theresa L., Buikema, H., van Gilst, W. H., van Veldhuisen, D. J., de Smet, B. J. G. L., Scholtens, E., Lie, K. I., Wesseling, H., Cheung, P. K., Dijkhuis, F. W. D., Bakker, W. W., Visser, J., Coopes, R. P., Benthem, L., van der Leest, J., Roffel, A. F., Coppes, R. P., Zeilstra, L. J. W., Vissink, A., Konings, A. W. T., Dijkstra, M., Veld, G. In't, Müller, M., van den Berg, G. J., Kuipers, F., Vonk, R. J., Elsinga, P. H., Franssen, E. J. F., van der Graaf, W. T. A., de Vries, E. G. E., Visser, G. M., Vos, M. G., Braker, A. H., Visser, T. J., Visser, G. M., Engels, F., van Houwelingen, A. H., van de Velde, M. J., Gansevoort, R. T., Sluiter, W. J., Hemmelder, M. H., de Zeeuw, D., de Jong, P. E., Gelissen, H. P. M. M., Henning, R. H., Epema, A. H., van Eekeren, J., Hennis, P. J., Den Hertog, A., de Graaf, S. S. N., Kellie, S. J., Bloemhof, H., Johnston, I., Besser, M., Chaseling, R. W., Ouvrier, R. A., Uqes, D. R. A., De Haan, A., Geerligs, H. J., Huchshorn, J. P., Van Scharenburg, G. J. M., Wilschut, J., Haas, M., Kluppel, C. A., Meijer, D. K. F., Moolenaar, F., Heerdink, Eibert R., Leufkens, Hubert G., Herings, Ron M. C., Stricker, Bruno H. Ch., Bakker, Albert, Heesen W. F., Beltman F. W., Smit A. J., May J. F., Meyboom-de Jong B., Duin, M., van den Akker, J., te Pas, M. F. W., van Popta, J. P., Nelemans, S. A., van der Linde, H. J., de Boer, A., Sturmans, F., Hessel, E. M., Van Oosterhout, A. J. M., Hofstra, C. L., Garssen, J., van Loveren, H., Savelkoul, H. F. J., Hoekstra, Y., Weersink, E. J. M., de Jong, J. W., van der Belt-Gritter, B., Jonkman, Lisa M., Kemner, Chantal, Koelega, Harry S., van Engeland, Herman, Verbaten, Marinus N., Kalivianakis, M., Zijlstra, I., Verkade, H. J., Elzinga, H., Stellaard, F., Kamps, J. A. A. M., Swart, P. J., Morselt, H., Scherphof, G. L., Kenemans, J. L., Lorist, M. M., Koopen, N. R., Kraneveld, A. D., Koster, A. Si., Kuipers, M. E., Groenink, M., Huisman, H., Schuitemaker, H., Lau, H. S., van den Broek, I. J. P. M., van Dijk, A., Oostinga, J., Porsius, A. J., Lin, Y., Havinga, R., Meijer, R. J., van der Mark, Th. W., Koëter, G. H., Michels, A. A., Nguyen, V. -T., Bensaude, O., Kampinga, H. H., Mohede, Inge C. M., Van Antoon J. M., Molema, Grietje, Edgington, Thomas S., Thorpe, Philip E., Olinga, P., Sandker, G. W., Slooff, M. J. H., Merema, M. T., Groothuis, G. M. M., Hofman, G., Van Ark, I., Paulussen, J. J. C., Fischer, M. J. E., de Mol, N. J., Janssen, L. H. M., Peters, E. Th. J., van der Werf, G. Th., Haaijer-Ruskamp, F. M., Pinto, Yigal M., Rooks, Gerrit, Grandjean, Jean G., Ebels, Tjark, Schunkert, H., Redegeld, Frank A., Garssen, Johan, van Loveren, Henk, Rigter, Irma M., van Groningen, Muck, Boks, Gertjan J., Tollenaere, Jan P., Trollope, Keith I., Vinter, Jeremy G., Hashjin, Gudarz Sadeghi, Folkerts, Gert, van de Loo, Peet G. F., Santing, R. E., Olymulder, C. G., van der Molen, K., Pasman, Y., Scheerens, Heleen, Van Loveren, Henk, Seppenwoolde-Waasdorp, T. J. A., de Boer, P., Van Engelen, H. M. J., Thijssen, J. H. H., Maes, R. A. A., Smit, J., Smit, J. W., Steen, H., Steurs, M. H., Kuks, P. F. M., Leusink, J. A., Szabó, Balázs M., Crijns, Harry J. G. M., Wiesfeld, Ans C. P., Talsma, H., Borchert, J. C. H., van Steenbergen, M. J., Hennink, W. E., Teeuw, K. B., Cromheecke, H., Schreudering, A., Teisman, B. C. H., Maselbas, W., Wolters-Keulemans, G. T. P., Tieleman, R. G., de Langen, C. D. J., Bel, K., Crijns, H. J. G. M., Grandjean, J., Wijffels, M., Klimp, A. H., van de Meer, P. F., Allessie, M. A., van Patot, H. A. Tissot, de Jongh, B. M., Tuininga, Y. S., Brouwer, J., Haaksma, J., Man in't Veld, A. J., Blomjous, F. J., Vingerhoeds, M. H., Belliot, S. O., Haisma, H. J., Visscher, C. A., Huisman, R. M., Navis, G. J., de Vlieger, J. F., van den Wijngaard, P., Wilting, J., van Heuven-Nolsen, D., Voors, A. A., van Brussel, B. L., Plokker, H. W. M., Van Waardenburg R. C. A. M., Meijer, Prins J., De Vries, C., Mulder N. H., Wierenga, P. K., Wilschut J., Schoen P., and Bron R.

Published
1994
Full Text
View/download PDF

79. Use of microdialysis for monitoring sympathetic and parasympathetic innervation of heart in conscious rats

Author

Cremers, T.I.F.H., Teisman, A.C.H., Van Gilst, W.H., and Westerink, B.H.C.

Subjects
Dialysis -- Methods, Heart -- Innervation, Neural transmission -- Measurement, Biological sciences
Abstract

Research shows that microdialysis can be used to monitor sympathetic and parasympathetic innervation in rat heart performance. Experiments designed to probe the heart of moving male albino rats for biochemicals norepinephrine and acetylcholine using microdialysis techniques are described. Norepinephrine and acetylcholine perfusion data is illustrated.

Published
1997

81. Employing Complexity: Complexification Management for Locked Issues

Author

Joosse-Bil, J.A. (Hans), Teisman, G.R. (Geert), Joosse-Bil, J.A. (Hans), and Teisman, G.R. (Geert)

Abstract

In line with wicked problem literature, we argue that public management based on ordering societal issues to make them controllable and solvable (simplification) can be initially attractive, but in the long-term ineffective. We elaborate on an alternative management mode of increasing the complexity of both the problem and the approach to deal with the problem (complexification). Based on an in-depth casestudy about transforming Utrecht Central Station (the Netherlands), we present complexification as a management strategy to revitalize processes that got locked by simplification management. Path-dependency shows up as a weakness of simplification, and path-creation as a strength of complexification.

Published
2020
Full Text
View/download PDF

82. Employing complexity:complexification management for locked issues

Author

Joosse, Hans, Teisman, Geert, Joosse, Hans, and Teisman, Geert

Abstract

In line with wicked problem literature, we argue that public management based on ordering societal issues to make them controllable and solvable (simplification) can be initially attractive, but in the long-term ineffective. We elaborate on an alternative management mode of increasing the complexity of both the problem and the approach to deal with the problem (complexification). Based on an in-depth case-study about transforming Utrecht Central Station (the Netherlands), we present complexification as a management strategy to revitalize processes that got locked by simplification management. Path-dependency shows up as a weakness of simplification, and path-creation as a strength of complexification.

Published
2020

83. Chronic drug-induced effects on contractile motion properties and cardiac biomarkers in human induced pluripotent stem cell-derived cardiomyocytes

Author

Petra Vinken, David J. Gallacher, Ivan Kopljar, Nick Goeminne, Ard Teisman, Hua Rong Lu, Ilse Van den Wyngaert, An De Bondt, and Bruce Damiano

Subjects
0301 basic medicine, Pharmacology, Cardiotoxicity, business.industry, Video microscopy, Pre-clinical development, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, In vivo, Troponin I, Myocyte, Biomarker (medicine), Medicine, business, Induced pluripotent stem cell, 030217 neurology & neurosurgery
Abstract

Background and Purpose In the pharmaceutical industry risk assessments of chronic cardiac safety liabilities are mostly performed during late stages of preclinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. Experimental Approach Video microscopy-based motion field imaging was applied to evaluate the chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs. In parallel, the release of cardiac troponin I (cTnI), heart fatty acid binding protein (FABP3) and N-terminal pro-brain natriuretic peptide (NT-proBNP) was analysed from cell medium, and transcriptional profiling of hiPS-CMs was done at the end of the experiment. Key Results Different cardiotoxic drugs altered the contractile motion properties of hiPS-CMs together with increasing the release of cardiac biomarkers. FABP3 and cTnI were shown to be potential surrogates to predict cardiotoxicity in hiPS-CMs, whereas NT-proBNP seemed to be a less valuable biomarker. Furthermore, drug-induced cardiotoxicity produced by chronic exposure of hiPS-CMs to arsenic trioxide, doxorubicin or panobinostat was associated with different profiles of changes in contractile parameters, biomarker release and transcriptional expression. Conclusion and Implications We have shown that a parallel assessment of motion field imaging-derived contractile properties, release of biomarkers and transcriptional changes can detect diverse mechanisms of chronic drug-induced cardiac liabilities in hiPS-CMs. Hence, hiPS-CMs could potentially improve and accelerate cardiovascular de-risking of compounds at earlier stages of drug discovery. Linked Articles This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc

Published
2017
Full Text
View/download PDF

91. Crystal Structure of BACE1 in complex with N-{3-[(4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-thiazin-4-yl]-4-fluorophenyl}-5-(fluoromethoxy)pyrazine-2-carboxamide

Author

Anan, K., primary, Iso, Y., additional, Oguma, T., additional, Nakahara, K., additional, Suzuki, S., additional, Yamamoto, T., additional, Matsuoka, E., additional, Ito, H., additional, Sakaguchi, G., additional, Ando, S., additional, Morimoto, K., additional, Kanegawa, N., additional, Kido, Y., additional, Kawachi, T., additional, Fukushima, T., additional, Teisman, A., additional, Urmaliya, V., additional, Dhuyvetter, D., additional, Borghys, H., additional, Austin, N., additional, Bergh, A.V.D., additional, Verboven, P., additional, Bischoff, F., additional, Gijsen, H.J.M., additional, Yamano, Y., additional, and Kusakabe, K.I., additional

Published
2020
Full Text
View/download PDF

94. Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking

Author

Hua Rong Lu, David J. Gallacher, Karel Van Ammel, Ivan Kopljar, Fetene Tekle, Ard Teisman, and Martin Otava

Subjects
0301 basic medicine, Drug, Risk, Scoring system, Drug-Related Side Effects and Adverse Reactions, media_common.quotation_subject, hERG, Induced Pluripotent Stem Cells, cardiomyocytes, Biology, Hazard analysis, Bioinformatics, drug discovery and development, arrhythmia, Biochemistry, Article, 03 medical and health sciences, stem cells, Drug Discovery, Genetics, Humans, Myocytes, Cardiac, Calcium Signaling, drug screening, Adverse effect, Induced pluripotent stem cell, lcsh:QH301-705.5, health care economics and organizations, media_common, lcsh:R5-920, Drug discovery, Reproducibility of Results, Cell Biology, Reference Standards, 3. Good health, Pre-clinical development, 030104 developmental biology, lcsh:Biology (General), biology.protein, torsade de pointes, cardiac safety, pharmacology, lcsh:Medicine (General), Algorithms, Developmental Biology, cardiac hazard
Abstract

Summary Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known cardiac adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into cardiac de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used the calcium transient screening assay in hiPSC-CMs to develop a hazard score system for cardiac electrical liabilities. Tolerance interval calculations and evaluation of different classes of cardio-active drugs enabled us to develop a weighted scoring matrix. This approach allowed the translation of various pharmacological effects in hiPSC-CMs into a single hazard label (no, low, high, or very high hazard). Evaluation of 587 internal NCEs and good translation to ex vivo and in vivo models for a subset of these NCEs highlight the value of the cardiac hazard scoring in facilitating the selection of compounds during early drug safety screening., Highlights • Scoring system identifies different degrees of cardiac hazard • Can be applied within R&D to cardiac safety screening of NCEs • Controls and reference drugs are essential for development of scoring matrix • Analysis can be applied to other in vitro drug safety assays, Kopljar and colleagues developed a scoring system to evaluate the potential cardiac hazard of drugs using a hiPSC-CM-based screening assay. This approach allows translation of various pharmacological responses in hiPSC-CMs into a single hazard label. Early evaluation of thousands of new chemical entities within drug discovery and development should enhance the development of new drugs with a favorable cardio-safety profile.

Published
2018

96. Trifluoromethyl Dihydrothiazine‐Based β‐Secretase (BACE1) Inhibitors with Robust Central β‐Amyloid Reduction and Minimal Covalent Binding Burden

Author

Anan, Kosuke, primary, Iso, Yasuyoshi, additional, Oguma, Takuya, additional, Nakahara, Kenji, additional, Suzuki, Shinji, additional, Yamamoto, Takahiko, additional, Matsuoka, Eriko, additional, Ito, Hisanori, additional, Sakaguchi, Gaku, additional, Ando, Shigeru, additional, Morimoto, Kenji, additional, Kanegawa, Naoki, additional, Kido, Yasuto, additional, Kawachi, Tomoyuki, additional, Fukushima, Tamio, additional, Teisman, Ard, additional, Urmaliya, Vijay, additional, Dhuyvetter, Deborah, additional, Borghys, Herman, additional, Austin, Nigel, additional, Van Den Bergh, An, additional, Verboven, Peter, additional, Bischoff, Francois, additional, Gijsen, Harrie J. M., additional, Yamano, Yoshinori, additional, and Kusakabe, Ken-ichi, additional

Published
2019
Full Text
View/download PDF

97. Crystal Structure of BACE1 in complex with N-{3-[(4R,5R,6R)-2-amino-5-fluoro-4,6-dimethyl-5,6-dihydro-4H-1,3-thiazin-4-yl]-4-fluorophenyl}-5-(fluoromethoxy)pyrazine-2-carboxamide

Author

Tadano, G., primary, Komano, K., additional, Yoshida, S., additional, Suzuki, S., additional, Nakahara, K., additional, Fuchino, K., additional, Fujimoto, K., additional, Matsuoka, E., additional, Yamamoto, T., additional, Asada, N., additional, Ito, H., additional, Sakaguchi, G., additional, Kanegawa, N., additional, Kido, Y., additional, Ando, S., additional, Fukushima, T., additional, Teisman, A., additional, Urmaliya, V., additional, Dhuyvetter, D., additional, Borghys, H., additional, Bergh, A.V.D., additional, Austin, N., additional, Gijsen, H.J.M., additional, Yamano, Y., additional, Iso, Y., additional, and Kusakabe, K.I., additional

Published
2019
Full Text
View/download PDF

98. Discovery of an Extremely Potent Thiazine-Based β-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose

Author

Tadano, Genta, primary, Komano, Kazuo, additional, Yoshida, Shuhei, additional, Suzuki, Shinji, additional, Nakahara, Kenji, additional, Fuchino, Kouki, additional, Fujimoto, Kazuki, additional, Matsuoka, Eriko, additional, Yamamoto, Takahiko, additional, Asada, Naoya, additional, Ito, Hisanori, additional, Sakaguchi, Gaku, additional, Kanegawa, Naoki, additional, Kido, Yasuto, additional, Ando, Shigeru, additional, Fukushima, Tamio, additional, Teisman, Ard, additional, Urmaliya, Vijay, additional, Dhuyvetter, Deborah, additional, Borghys, Herman, additional, Van Den Bergh, An, additional, Austin, Nigel, additional, Gijsen, Harrie J. M., additional, Yamano, Yoshinori, additional, Iso, Yasuyoshi, additional, and Kusakabe, Ken-ichi, additional

Published
2019
Full Text
View/download PDF

99. Assessing Drug-Induced Long QT and Proarrhythmic Risk Using Human Stem-Cell-Derived Cardiomyocytes in a Ca2+ Imaging Assay: Evaluation of 28 CiPA Compounds at Three Test Sites

Author

Lu, Hua Rong, primary, Zeng, Haoyu, additional, Kettenhofen, Ralf, additional, Guo, Liang, additional, Kopljar, Ivan, additional, van Ammel, Karel, additional, Tekle, Fetene, additional, Teisman, Ard, additional, Zhai, Jin, additional, Clouse, Holly, additional, Pierson, Jennifer, additional, Furniss, Michael, additional, Lagrutta, Armando, additional, Sannajust, Frederick, additional, and Gallacher, David J, additional

Published
2019
Full Text
View/download PDF

100. PPPs: torn between two lovers: like the star-crossed experiment in Utrecht in the 1990s discussed in this article, PPPs may be doomed to fail. They mix two value patterns and organisational principles that cannot easily be combined. New management strategies are required to cross the 'borders'

Author

Teisman, Geert and Klijn, Erik-Hans

Subjects
Utrecht, Netherlands (Province) -- Economic policy, Public-private sector cooperation -- Management, Public-private sector cooperation -- Case studies, Company business management, Business, Business, international, Economics
Abstract

Public private partnerships (PPPs) are emerging internationally, as is well documented in this EBF debate. But growing co-operation between public and private parties is blurring the orderly distinction between what [...]

Published
2004

Catalog

Books, media, physical & digital resources
See catalog results