The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung

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1. Verfasser: Deppermann, Carsten 1985- (VerfasserIn)
Format: Abschlussarbeit Buch
Sprache:English
Veröffentlicht: Würzburg August 2015
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Datensatz im Suchindex

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adam_text CONTENTS CONTENTS III SUMMARY VI ZUSAMMENFASSUNG VII 1 INTRODUCTION 1 1.1 PLATELETS.................................................................................................................. 1 1.2 PLATELET ACTIVATION AND THROMBUS FORMATION............................................................. 2 1.3 PLATELET SIGNALING UPON ACTIVATION........................................................................... 3 1.4 MEGAKARYOCYTES................................................................................................... 7 1.4.1 MEGAKARYOPOIESIS..................................... 9 1.4.2 TRANSCRIPTION FACTORS IN MEGAKARYOPOIESIS................................................ 9 1.5 PLATELET G RA NU LE S.................................................................................................... 10 1.5.1 PLATELET GRANULE C O N TE N T............................................................................. 10 1.5.2 PLATELET GRANULE CONTENT IN NORMAL PHYSIOLOGY AND PATHOPHYSIOLOGY .... 11 1.5.3 BIOGENESIS OF PLATELET GRANULES.................................................................. 14 1.5.4 PLATELET SECRETION........................................................................................ 15 1.5.5 PLATELET GRANULE DISORDERS.......................................................................... 17 1.6 AIM OF THIS S TU D Y .................................................................................................... 16 2 MATERIALS AND METHODS 20 2.1 MATERIALS ............................................................................................................... 20 2.1.1 CHEMICALS AND REAGENTS............................................................................. 20 2.1.2 ANTIBODIES . ................................................................................................... 21 2.1.3 BUFFERS ...................................................................................................... 22 2.1.4 A NIM ALS...................................................................................................... 25 2.2 METHODS.................................................................................................................. 26 2.2.1 GENOTYPING OF MICE ................................................................................... 26 2.2.2 MOLECULAR BIOLOGY AND BIOCHEMISTRY . . . . .......................................... 28 2.2.3 IN VITRO ANALYSES OF PLATELET FUNCTION ......................................................... 29 2.2.4 IN VIVO ANALYSES OF PLATELET FUNCTION............................................................ 32 2.2.5 MK A N A LYSE S.............................................................................................. 34 2.2.6 ELECTRON MICROSCOPY.................................................................................. 35 2.2.7 H ISTOLO G Y.................................................................................................... 36 2.2.8 STATISTICAL DATA A N A LY S IS .............................................................................. 37 3 RESULTS 38 3.1 ANALYSIS OF MUND 3-4-DEFICIENT M IC E ..................................................................... 38 3.1.1 UNC13CT/ MICE DISPLAY UNALTERED PLATELET COUNTS AND GRANULE NUMBERS . . 38 3.1.2 ABROGATED ATP SECRETION AND AGGREGATION OF U N D 3DA P LA TE LE TS ............ 38 3.1.3 UNC13DA PLATELETS SHOW IMPAIRED P-SELECTIN EXPOSURE AND INTEGRIN ACTI VATION AFTER STIMULATION AND ADHESION TO COLLAGEN UNDER FLO W .................... 39 3.1.4 DEFECTIVE IN VIVO THROMBUS FORMATION AND HEMOSTASIS IN UNC13CTA MICE . 41 3.1.5 REDUCED INFARCT SIZE AND NO SIGNS OF HEMORRHAGE IN MUND 3-4-DEFICIENT MICE AFTER TM C A O ...................................................................................... 42 3.2 ANALYSIS OF NBEAL2-DEFICIENT M ICE ........................................................................... 46 3.2.1 NBEAL 2A MICE ARE MACROTHROMBOCYTOPENIC AND LACK -GRANULES IN MKS AND P LA TE LE TS ............................................................................................... 46 3.2.2 DEFECTIVE ADHESION AND AGGREGATE FORMATION OF NBEAL2A PLATELETS UNDER F L O W ............................................................................................................. 55 3.2.3 SEVERELY DEFECTIVE ARTERIAL THROMBUS FORMATION AND HEMOSTASIS IN NBEAL2- DEFICIENT M ICE............................................................................................... 57 3.2.4 NBEAL2A MICE ARE PROTECTED IN A MODEL OF ISCHEMIC STROKE ....................... 60 3.2.5 NBEAL2A MICE SHOW IMPAIRED DERMAL HEALING DUE TO REDUCED TGF-SS RE LEASE FROM MUTANT P LA TE LE TS........................................................................ 61 3.2.6 COMPARISON OF NBEAL2A AND HUMAN GPS PLATELETS AND M K S ................. 62 3.3 ANALYSIS OF MUND 3-4/NBEAL2-DEFICIENT M ICE ......................................................... 65 3.3.1 MACROTHROMBOCYTOPENIA BUT UNALTERED PLATELET GLYCOPROTEIN EXPRESSION IN UNC13CTA/NBEAL2A M ICE .............................................................................. 65 3.3.2 ABROGATED P-SELECTIN EXPOSURE AND REDUCED INTEGRIN ACTIVATION UPON STIM ULATION OF MUND 3-4/NBEAL2-DEFICIENT PLATELETS ........................................ 65 3.3.3 UNC13CTA/NBEAL2~A PLATELETS SHOW DEFECTIVE AGGREGATION, ADHESION TO COL LAGEN UNDER FLOW AND PS EXPOSURE ............................................................ 67 3.3.4 MUND 3-4/NBEAL2-DEFICIENT MICE DISPLAY IMPAIRED THROMBOSIS AND HEMOSTA SIS IN V IV O .................................................................................................... 69 3.3.5 U ND 3CTA/NBEAL2A MICE MAINTAIN VASCULAR INTEGRITY AT SITES OF LOCAL IN FLAMMATION BUT NOT ISCHEMIC STRO KE ............................................................ 69 4 DISCUSSION 73 4.1 PLATELET DENSE GRANULES IN THROMBOSIS, HEMOSTASIS AND STROKE............................. 73 4.2 PLATELET -GRANULES IN THROMBOSIS, HEMOSTASIS AND S TR O K E .................................. 74 4.2.1 THE NBEAL2A MOUSE AS A MODEL FOR THE GRAY PLATELET SYNDROM E .............. 77 4.2.2 THE ROLE OF NBEAL2 IN -GRANULE BIOGENESIS ........................................... 78 4.3 COMBINED DEFICIENCY OF PLATELET- AND DENSE GRANULE SECRETION............ .............. 79 4.4 CONCLUDING REMARKS AND O U TLO O K ........................................................................... 82 BIBLIOGRAPHY 84 5 APPENDIX 101 5.1 ABBREVIATIONS.............................................................................................................101 5.2 ACKNOWLEDGEMENTS.................................................................................................... 104 5.3 CURRICULUM V IT A E .......................................................................................................105 5.4 PUBLICATIONS............................................................................................................... 107 5.4.1 RESEARCH ARTICLES ........................................................................................... 107 5.4.2 SELECTED TALKS AND PRESENTATIONS..................................................................107 5.5 A FFID A VIT..................................................................................................................... 109 5.6 EIDESSTATTLICHE ERKLAERUNG .........................................................................................109
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physical viii, 109 Seiten Illustrationen, Diagramme 30 cm
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spellingShingle Deppermann, Carsten 1985-
The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung
Entzündung (DE-588)4014975-4 gnd
Thrombozyt (DE-588)4059964-4 gnd
Schlaganfall (DE-588)4052588-0 gnd
subject_GND (DE-588)4014975-4
(DE-588)4059964-4
(DE-588)4052588-0
(DE-588)4113937-9
title The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung
title_alt Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung
title_auth The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung
title_exact_search The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung
title_full The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung submitted by Carsten Deppermann from Frankfurt/Main, Germany
title_fullStr The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung submitted by Carsten Deppermann from Frankfurt/Main, Germany
title_full_unstemmed The role of platelet granules in thrombosis, hemostasis, stroke and inflammation = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung submitted by Carsten Deppermann from Frankfurt/Main, Germany
title_short The role of platelet granules in thrombosis, hemostasis, stroke and inflammation
title_sort the role of platelet granules in thrombosis hemostasis stroke and inflammation zur rolle der thrombozytengranula in thrombose hamostase schlaganfall und entzundung
title_sub = Zur Rolle der Thrombozytengranula in Thrombose, Hämostase, Schlaganfall und Entzündung
topic Entzündung (DE-588)4014975-4 gnd
Thrombozyt (DE-588)4059964-4 gnd
Schlaganfall (DE-588)4052588-0 gnd
topic_facet Entzündung
Thrombozyt
Schlaganfall
Hochschulschrift
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