Sensitivity of assays for the detection of HPA-1a antibodies: results of an international workshop demonstrating the impact of cation chelation from integrin αIIbβ3 on three widely used assays

Vox Sanguinis ◽  
2013 ◽  
Vol 105 (2) ◽  
pp. 167-173 ◽  
Author(s):  
D. L. Allen ◽  
P. Metcalfe ◽  
C. Kaplan ◽  
R. Kekomaki ◽  
M. de Haas ◽  
...  
Keyword(s):  
International Workshop ◽  
Integrin Αiibβ3 ◽  
The Impact

Impaired Platelet Function in Sept8-Deficient Mice In Vitro

2020 ◽  
Author(s):  
Kerstin Jurk ◽  
Katharina Neubauer ◽  
Victoria Petermann ◽  
Elena Kumm ◽  
Barbara Zieger
Keyword(s):  
Platelet Function ◽  
Thrombin Generation ◽  
Human Platelets ◽  
Platelet Surface ◽  
Integrin Αiibβ3 ◽  
Glycoprotein Vi ◽  
Fibrinogen Receptor ◽  
Static Conditions ◽  
The Impact

AbstractSeptins (Septs) are a widely expressed protein family of 13 mammalian members, recognized as a unique component of the cytoskeleton. In human platelets, we previously described that SEPT4 and SEPT8 are localized surrounding α-granules and move to the platelet surface after activation, indicating a possible role in platelet physiology. In this study, we investigated the impact of Sept8 on platelet function in vitro using Sept8-deficient mouse platelets. Deletion of Sept8 in mouse platelets caused a pronounced defect in activation of the fibrinogen receptor integrin αIIbβ3, α-granule exocytosis, and aggregation, especially in response to the glycoprotein VI agonist convulxin. In contrast, δ-granule and lysosome exocytosis of Sept8-deficient platelets was comparable to wild-type platelets. Sept8-deficient platelet binding to immobilized fibrinogen under static conditions was diminished and spreading delayed. The procoagulant activity of Sept8-deficient platelets was reduced in response to convulxin as determined by lactadherin binding. Also thrombin generation was decreased relative to controls. Thus, Sept8 is required for efficient integrin αIIbβ3 activation, α-granule release, platelet aggregation, and contributes to platelet-dependent thrombin generation. These results revealed Sept8 as a modulator of distinct platelet functions involved in primary and secondary hemostatic processes.

Murine Platelets Expressing a Polymorphism of Integrin β3 Associated with Acute Coronary Thrombosis in Humans.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3896-3896
Author(s):  
David A. Wilcox ◽  
Juan Fang ◽  
Bryon D. Johnson
Keyword(s):  
Platelet Function ◽  
Flow Cytometric Analysis ◽  
Thrombotic Complication ◽  
Homogeneous Population ◽  
Integrin Αiibβ3 ◽  
Integrin Β3 ◽  
Flow Cytometric ◽  
The Impact ◽  
Human Integrin

Abstract Inheritance of a naturally occurring polymorphism of the human integrin β3-subunit at amino acid 33 causes a change from Leu to Pro that has been implicated as a risk factor for thrombotic complication in humans. It is unclear; however, if Pro (also known as the platelet alloantigen PlA2 form of β3) can alter integrin activation to significantly affect platelet function in vivo, since some clinical studies do not corroborate the initial findings. Since PlA2 is a frequent variant of β3 expressed on 28% of platelets from Americans the impact of this genetic variation on platelet function could have widespread clinical relevance; therefore, we developed a murine model to determine if expression of this common polymorphism of human integrin β3 can increase platelet function and lead to an increased propensity for thrombosis within a homogeneous population of mice. This model eliminates issues arising from variation in the genetic make-up, physical environment, and/or lifestyles of humans and allows for in vivo analysis not possible with human subjects. To accomplish this, cDNA encoding each form of the human β3-subunit was subcloned into an HIV type-1 lentivirus-derived vector under the transcriptional control of the human αIIb gene promoter to direct synthesis of β3 specifically to the megakaryocyte lineage. Bone marrow was isolated from β3-deficient mice and transduced with β3 virions encoding either the PlA1 or PlA2 form of human β3, and then transplanted into lethally irradiated β3-deficient littermates. Flow cytometric analysis demonstrated stable expression of the hybrid murine/human αIIbβ3 integrin complex on the surface of circulating platelets. Immunoanalysis using monoclonal antibodies and human serum that react specifically with the PlA1 or PlA2 confirmed the identity of each alloantigen of human β3. The lentivirus contained a second transgene encoding a drug-selectable marker (P140K MGMT) that was used for in vivo enrichment of transduced cells in mice treated with two regimens of cytotoxic reagents, O6-BG/BCNU. Flow cytometric analysis showed that use of drug-selection resulted in increased expression of the integrin αIIbβ3 complex to equal levels on nearly 100% of platelets using either form of human β3. Similar to platelets from normal mice, platelets expressing each PlA form of β3 could be induced to form aggregates ex vivo upon treatment with a cocktail of physiological agonists of platelet activation (adenosine diphosphate, epinephrine and the thrombin receptor activating peptide). These results demonstrate the feasibility for targeting expression of altered forms of the human integrin β3-subunit to murine platelets and pave the way for future studies to examine and compare the effect of integrin αIIbβ3 structure on platelet function and thrombosis in vivo.

scholarly journals 3. Quo Vadis the Contemporary Music Criticism? (The First International Workshop of Journalism in Kalv, Sweden. Reflection, Orientation, Persuasion)

2020 ◽  
Vol 19 (1) ◽  
pp. 17-20
Author(s):  
Luminiţa Duţică
Keyword(s):  
Rural Population ◽  
Contemporary Music ◽  
International Workshop ◽  
Music Criticism ◽  
Music Journalism ◽  
Quo Vadis ◽  
To Come ◽  
The Impact ◽  
First Time

AbstractAnnually, in Kalv is organized one of Sweden’s most innovative festivals for Contemporary Music. For the first time, on 8-11 August 2019 took place a workshop in Music Journalism field. In this study we intend to show working methods used in Western Journalism and the impact of current music on the cultural level Kalv’s rural population. Together with the mentor Andreas Engström from Berlin, we attended concerts, seminars, we interviewed more artists and musicians across the globe, also we wrote different texts, essays and chronicles for publication. To conclude, organising a Musical Journalism Workshop during a festival of contemporary music is a commendable initiative which plays a major role in getting acquainted and gaining a better understanding of the compositional intentions of present-day creators. We will be happy to come back here, in a world at once picturesque and post-modern owing to these unforgettable musical encounters.

scholarly journals Risk Factors for Childhood Leukemia: Radiation and Beyond

2021 ◽  
Vol 9 ◽  
Author(s):  
Janine-Alison Schmidt ◽  
Sabine Hornhardt ◽  
Friederike Erdmann ◽  
Isidro Sánchez-García ◽  
Ute Fischer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Mouse Models ◽  
Environmental Risk ◽  
Childhood Leukemia ◽  
Background Radiation ◽  
Lymphoblastic Leukemia ◽  
International Workshop ◽  
Experimental Studies ◽  
The Impact

Childhood leukemia (CL) is undoubtedly caused by a multifactorial process with genetic as well as environmental factors playing a role. But in spite of several efforts in a variety of scientific fields, the causes of the disease and the interplay of possible risk factors are still poorly understood. To push forward the research on the causes of CL, the German Federal Office for Radiation Protection has been organizing recurring international workshops since 2008 every two to three years. In November 2019 the 6th International Workshop on the Causes of CL was held in Freising and brought together experts from diverse disciplines. The workshop was divided into two main parts focusing on genetic and environmental risk factors, respectively. Two additional special sessions addressed the influence of natural background radiation on the risk of CL and the progress in the development of mouse models used for experimental studies on acute lymphoblastic leukemia, the most common form of leukemia worldwide. The workshop presentations highlighted the role of infections as environmental risk factor for CL, specifically for acute lymphoblastic leukemia. Major support comes from two mouse models, the Pax5+/− and Sca1-ETV6-RUNX1 mouse model, one of the major achievements made in the last years. Mice of both predisposed models only develop leukemia when exposed to common infections. These results emphasize the impact of gene-environment-interactions on the development of CL and warrant further investigation of such interactions — especially because genetic predisposition is detected with increasing frequency in CL. This article summarizes the workshop presentations and discusses the results in the context of the international literature.

scholarly journals Correction to Vol. 26, No. 2, Supplement 2

2005 ◽  
Vol 26 (3) ◽  
pp. 318-318
Keyword(s):  
International Workshop ◽  
Department Of Education ◽  
Education For All ◽  
International Institute ◽  
Global Citizens ◽  
The People ◽  
Production Error ◽  
Food And Nutrition ◽  
The Impact ◽  
Nutritional Sciences

“Proceedings of the International Workshop on Articulating the Impact of Nutritional De. ciencies on the Education for All Agenda,” Osman M. Galal, Charlotte G. Neumann, and Judie Hulett, guest editors The following acknowledgments were omitted from the above-referenced supplement due to a production error in the Food and Nutrition Bulletin Bulletin's editorial's office. The editors regret this oversight. Acknowledgments The guest editors of this supplement express gratigratitude for the unique opportunity to coordinate this tude workshop and our sincere appreciation of the encouragement and interest from the people who made this agement effort possible. Geoffrey Garrett UCLA International Institute Educating Global Citizens Allen Roberts US Department of Education Grant to the James S. Coleman African Studies Center, UCLA Edmond Keller Globalization Research Center – Africa, UCLA Mark Wahlqvist International Union of Nutritional Sciences (IUNS) Zoë Boutilier The Micronutrient Initiative Linda Rosenstock Dean UCLA School of Public Health Montague W. Demment Global Livestock CRSP, University of California, Davis (USAID) We are also indebted to our colleagues who made our visiting scholars feel at home and provided invaluable service to the workshop through their assistance and very hard work. Susan Silah Mary Vardazarian Ritesh Mistry Parisa Mirzadehgan

scholarly journals Enhanced Integrin Activation of PLD2-Deficient Platelets Accelerates Inflammation after Myocardial Infarction

2020 ◽  
Vol 21 (9) ◽  
pp. 3210 ◽  
Author(s):  
Aglaia Maria Klose ◽  
Meike Klier ◽  
Simone Gorressen ◽  
Margitta Elvers
Keyword(s):  
Myocardial Infarction ◽  
Plasma Levels ◽  
Ischemia Reperfusion ◽  
Scar Formation ◽  
Border Zone ◽  
Myocardial Ischemia And Reperfusion ◽  
Integrin Αiibβ3 ◽  
Tnf Α ◽  
The Impact ◽  
Deficient Mice

Background: Phospholipase (PL)D1 is crucial for integrin αIIbβ3 activation of platelets in arterial thrombosis and TNF-α-mediated inflammation and TGF-β-mediated collagen scar formation after myocardial infarction (MI) in mice. Enzymatic activity of PLD is not responsible for PLD-mediated TNF-α signaling and myocardial healing. The impact of PLD2 in ischemia reperfusion injury is unknown. Methods: PLD2-deficient mice underwent myocardial ischemia and reperfusion (I/R). Results: Enhanced integrin αIIbβ3 activation of platelets resulted in elevated interleukin (IL)-6 release from endothelial cells in vitro and enhanced IL-6 plasma levels after MI in PLD2-deficient mice. This was accompanied by enhanced migration of inflammatory cells into the infarct border zone and reduced TGF-β plasma levels after 72 h that might account for enhanced inflammation in PLD2-deficient mice. In contrast to PLD1, TNF-α signaling, infarct size and cardiac function 24 h after I/R were not altered when PLD2 was deleted. Furthermore, TGF-β plasma levels, scar formation and heart function were comparable between PLD2-deficient and control mice 21 days post MI. Conclusions: The present study contributes to our understanding about the role of PLD isoforms and altered platelet signaling in the process of myocardial I/R injury.

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