scholarly journals Platelet fibrinogen and vitronectin in Glanzmann thrombasthenia: evidence consistent with specific roles for glycoprotein IIb/IIIA and alpha v beta 3 integrins in platelet protein trafficking [see comments]

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2603-2610 ◽  
Author(s):  
BS Coller ◽  
U Seligsohn ◽  
SM West ◽  
LE Scudder ◽  
KJ Norton
Keyword(s):  
Protein Trafficking ◽  
Extracellular Proteins ◽  
Platelet Glycoprotein ◽  
Integrin Receptors ◽  
Vitronectin Receptor ◽  
Glanzmann Thrombasthenia ◽  
Platelet Protein ◽  
Individual Contributions ◽  
The Individual ◽  
Alpha V Beta 3

Abstract To assess the individual contributions of the platelet glycoprotein (GP) IIb/IIIa receptor and the alpha v beta 3 vitronectin receptor to platelet levels of fibrinogen and vitronectin, we analyzed the platelets from two groups of Glanzmann thrombasthenic patients: Iraqi- Jews, whose platelets lack both receptors, and Arab patients in Israel, whose platelets lack GPIIb/IIIa, but have normal or increased numbers of alpha v beta 3 vitronectin receptors. The platelets from both thrombasthenic groups had profound deficiencies of fibrinogen, but the defect in the Iraqi-Jewish patients' platelets appeared to be slightly more severe. This finding indicates that GPIIb/IIIa is the major determinant of platelet fibrinogen, presumably acting by receptor- mediated uptake, and that the alpha v beta 3 vitronectin receptor plays little or no role. Arab patients' platelets have normal amounts of platelet vitronectin, whereas Iraqi-Jewish patients' platelets have nearly five times as much vitronectin as control or Arab patients' platelets. To account for these data, we propose a working hypothesis in which vitronectin is synthesized in megakaryocytes and the alpha v beta 3 vitronectin receptor is involved in transport of the protein out of megakaryocytes and/or platelets. Collectively, these observations suggest that in addition to their recognized roles in cell adhesion and in the interaction of cells with extracellular proteins, integrin receptors may be important in protein trafficking into, and perhaps out of, platelets.

scholarly journals Platelet fibrinogen and vitronectin in Glanzmann thrombasthenia: evidence consistent with specific roles for glycoprotein IIb/IIIA and alpha v beta 3 integrins in platelet protein trafficking [see comments]

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2603-2610 ◽  
Author(s):  
BS Coller ◽  
U Seligsohn ◽  
SM West ◽  
LE Scudder ◽  
KJ Norton
Keyword(s):  
Protein Trafficking ◽  
Extracellular Proteins ◽  
Platelet Glycoprotein ◽  
Integrin Receptors ◽  
Vitronectin Receptor ◽  
Glanzmann Thrombasthenia ◽  
Platelet Protein ◽  
Individual Contributions ◽  
The Individual ◽  
Alpha V Beta 3

To assess the individual contributions of the platelet glycoprotein (GP) IIb/IIIa receptor and the alpha v beta 3 vitronectin receptor to platelet levels of fibrinogen and vitronectin, we analyzed the platelets from two groups of Glanzmann thrombasthenic patients: Iraqi- Jews, whose platelets lack both receptors, and Arab patients in Israel, whose platelets lack GPIIb/IIIa, but have normal or increased numbers of alpha v beta 3 vitronectin receptors. The platelets from both thrombasthenic groups had profound deficiencies of fibrinogen, but the defect in the Iraqi-Jewish patients' platelets appeared to be slightly more severe. This finding indicates that GPIIb/IIIa is the major determinant of platelet fibrinogen, presumably acting by receptor- mediated uptake, and that the alpha v beta 3 vitronectin receptor plays little or no role. Arab patients' platelets have normal amounts of platelet vitronectin, whereas Iraqi-Jewish patients' platelets have nearly five times as much vitronectin as control or Arab patients' platelets. To account for these data, we propose a working hypothesis in which vitronectin is synthesized in megakaryocytes and the alpha v beta 3 vitronectin receptor is involved in transport of the protein out of megakaryocytes and/or platelets. Collectively, these observations suggest that in addition to their recognized roles in cell adhesion and in the interaction of cells with extracellular proteins, integrin receptors may be important in protein trafficking into, and perhaps out of, platelets.

scholarly journals Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel

Blood ◽  
1991 ◽  
Vol 77 (1) ◽  
pp. 75-83 ◽  
Author(s):  
BS Coller ◽  
DA Cheresh ◽  
E Asch ◽  
U Seligsohn
Keyword(s):  
Receptor Expression ◽  
Platelet Glycoprotein ◽  
Adhesion Assay ◽  
Integrin Receptors ◽  
Arab Population ◽  
Vitronectin Receptor ◽  
Glanzmann Thrombasthenia ◽  
And Function ◽  
Alpha V Beta 3 ◽  
Inhibition Studies

Glanzmann thrombasthenia is a rare, inherited disorder of the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) complex. We previously identified two distinct populations with this disorder in Israel, Iraqi-Jews and Arabs. The groups are indistinguishable in hemorrhagic symptoms and platelet GP IIB/IIIa receptor deficiency, but they differ in their platelet immunodetectable GP IIIa (beta 3), with the Iraqi-Jewish population expressing no detectable GP IIIa and the Arab population expressing small amounts. We have now examined the platelets of these two populations as well as normal platelets for the alpha v beta 3 vitronectin receptor. Normal platelets contained between approximately 50 to 100 alpha v beta 3 vitronectin receptors as judged by the binding of antibodies to both alpha v (LM142) and the intact alpha v beta 3 vitronectin receptor complex (LM609). In addition, normal platelets bound to immobilized vitronectin in the presence of 1 mmol/LMnCl2; the adhesion was mediated predominantly through GP IIb/IIIa, but with a distinct contribution by the alpha v beta 3 vitronectin receptor, as determined by monoclonal antibody inhibition studies. Iraqi-Jewish patients' platelets had a profound decrease in immunodetectable alpha v beta 3 vitronectin receptors, and their platelets did not adhere well to vitronectin. In contrast, Arab patients' platelets had normal or increased numbers of platelet alpha v beta 3 vitronectin receptors, and these receptors functioned well in the vitronectin adhesion assay, taking over much of the adhesion mediated by GP IIb/IIIa in normal platelets. These studies define further the heterogeneity of the molecular basis of Glanzmann thrombasthenia; they also have more widespread implications for understanding the synthesis and function of the beta 3 family of integrin receptors.

scholarly journals Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel

Blood ◽  
1991 ◽  
Vol 77 (1) ◽  
pp. 75-83 ◽  
Author(s):  
BS Coller ◽  
DA Cheresh ◽  
E Asch ◽  
U Seligsohn
Keyword(s):  
Receptor Expression ◽  
Platelet Glycoprotein ◽  
Adhesion Assay ◽  
Integrin Receptors ◽  
Arab Population ◽  
Vitronectin Receptor ◽  
Glanzmann Thrombasthenia ◽  
And Function ◽  
Alpha V Beta 3 ◽  
Inhibition Studies

Abstract Glanzmann thrombasthenia is a rare, inherited disorder of the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) complex. We previously identified two distinct populations with this disorder in Israel, Iraqi-Jews and Arabs. The groups are indistinguishable in hemorrhagic symptoms and platelet GP IIB/IIIa receptor deficiency, but they differ in their platelet immunodetectable GP IIIa (beta 3), with the Iraqi-Jewish population expressing no detectable GP IIIa and the Arab population expressing small amounts. We have now examined the platelets of these two populations as well as normal platelets for the alpha v beta 3 vitronectin receptor. Normal platelets contained between approximately 50 to 100 alpha v beta 3 vitronectin receptors as judged by the binding of antibodies to both alpha v (LM142) and the intact alpha v beta 3 vitronectin receptor complex (LM609). In addition, normal platelets bound to immobilized vitronectin in the presence of 1 mmol/LMnCl2; the adhesion was mediated predominantly through GP IIb/IIIa, but with a distinct contribution by the alpha v beta 3 vitronectin receptor, as determined by monoclonal antibody inhibition studies. Iraqi-Jewish patients' platelets had a profound decrease in immunodetectable alpha v beta 3 vitronectin receptors, and their platelets did not adhere well to vitronectin. In contrast, Arab patients' platelets had normal or increased numbers of platelet alpha v beta 3 vitronectin receptors, and these receptors functioned well in the vitronectin adhesion assay, taking over much of the adhesion mediated by GP IIb/IIIa in normal platelets. These studies define further the heterogeneity of the molecular basis of Glanzmann thrombasthenia; they also have more widespread implications for understanding the synthesis and function of the beta 3 family of integrin receptors.

scholarly journals Postprenylation CAAX Processing Is Required for Proper Localization of Ras but Not Rho GTPases

2005 ◽  
Vol 16 (4) ◽  
pp. 1606-1616 ◽  
Author(s):  
David Michaelson ◽  
Wasif Ali ◽  
Vi K. Chiu ◽  
Martin Bergo ◽  
Joseph Silletti ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Protein Trafficking ◽  
Rho Gtpases ◽  
Ras Proteins ◽  
Rho Proteins ◽  
Carboxyl Methylation ◽  
C Terminus ◽  
Individual Contributions ◽  
The Individual ◽  
And Function

The CAAX motif at the C terminus of most monomeric GTPases is required for membrane targeting because it signals for a series of three posttranslational modifications that include isoprenylation, endoproteolytic release of the C-terminal– AAX amino acids, and carboxyl methylation of the newly exposed isoprenylcysteine. The individual contributions of these modifications to protein trafficking and function are unknown. To address this issue, we performed a series of experiments with mouse embryonic fibroblasts (MEFs) lacking Rce1 (responsible for removal of the –AAX sequence) or Icmt (responsible for carboxyl methylation of the isoprenylcysteine). In MEFs lacking Rce1 or Icmt, farnesylated Ras proteins were mislocalized. In contrast, the intracellular localizations of geranylgeranylated Rho GTPases were not perturbed. Consistent with the latter finding, RhoGDI binding and actin remodeling were normal in Rce1- and Icmt-deficient cells. Swapping geranylgeranylation for farnesylation on Ras proteins or vice versa on Rho proteins reversed the differential sensitivities to Rce1 and Icmt deficiency. These results suggest that postprenylation CAAX processing is required for proper localization of farnesylated Ras but not geranygeranylated Rho proteins.

scholarly journals Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but not alpha 6 beta 4 functions as a major receptor for fragment E8.

1990 ◽  
Vol 110 (6) ◽  
pp. 2145-2155 ◽  
Author(s):  
A Sonnenberg ◽  
C J Linders ◽  
P W Modderman ◽  
C H Damsky ◽  
M Aumailley ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Types ◽  
Integrin Subunit ◽  
Integrin Receptors ◽  
Cell Binding ◽  
Vitronectin Receptor ◽  
Beta 1 Integrin ◽  
Integrin Alpha 6 ◽  
Alpha V Beta 3 ◽  
Integrin Family

The involvement of integrins in mediating interaction of cells to well-characterized proteolytic fragments (P1, E3, and E8) of laminin was assessed by antibody blocking studies. Cell adhesion to fragment P1 was affected by mAbs against the integrin beta 1 and beta 3 subunits and furthermore could be prevented completely by a synthetic peptide containing the Arg-Gly-Asp sequence. Because the beta 3 antibody-sensitive cell lines expressed the vitronectin receptor (alpha v beta 3) at high levels, the involvement of this receptor in cell adhesion to P1 is strongly suggested. Integrin-mediated cell adhesion to E3 is of low affinity and was inhibited by antibodies against the integrin beta 1 subunit. In contrast, adhesion of some cell types to E3 was not or only partially sensitive to inhibition by anti-integrin subunit antibodies. Cell adhesion to E8 was blocked completed by integrin alpha 6 or beta 1 antibodies. The alpha 6-specific antibody did not inhibit cell adhesion to E3 or P1. Furthermore, the antibody only blocked adhesion to laminin of those cells that adhered exclusively to the E8 fragment. In addition, expression of alpha 6 beta 1 was closely correlated with the ability of cells to bind to the E8 fragment of laminin. These results indicate that the alpha 6 beta 1 integrin is a specific receptor for the E8 fragment of laminin. Many cell types expressed, instead of or in addition to alpha 6 beta 1 the recently described integrin alpha 6 beta 4. Although the ligand of alpha 6 beta 4 was not identified, it must be different from that of alpha 6 beta 1, because cells that express alpha 6 beta 4, but not alpha 6 beta 1, do not adhere to E8, and cell adhesion to E8 was specifically blocked by beta 1 specific antibodies. In conclusion, the data indicate that distinct integrin receptors belonging to the beta 1 or beta 3 subfamily are involved in adhesion of cells to the various laminin fragments. Adhesion to E3 may also be brought about by other receptor molecules, possibly proteoglycans, not belonging to the integrin family.

Binding of Abciximab to αVβ3 and Activated αMβ2 Receptors: With a Review of Platelet-Leukocyte Interactions

1999 ◽  
Vol 82 (08) ◽  
pp. 326-336 ◽  
Author(s):  
Barry Coller
Keyword(s):  
Cardiovascular Disease ◽  
The Other ◽  
Platelet Glycoprotein ◽  
Inhibit Platelet Aggregation ◽  
Integrin Receptors ◽  
Antithrombotic Agent ◽  
Vitronectin Receptor ◽  
Pathologic Processes ◽  
Derivatives Of

IntroductionMurine monoclonal antibody 7E3, as well as the derivatives of 7E3 used in vivo [7E3-F(ab’)2, 7E3 Fab’, mouse/human chimeric 7E3 Fab (c7E3 Fab; abciximab; ReoPro™)], inhibit platelet aggregation induced by physiologic and pathologic agonists by binding to the platelet glycoprotein (GP) IIb/IIIa receptor.1,2 This biological activity formed the basis of its development as an antithrombotic agent to prevent and treat plateletmediated ischemic cardiovascular disease. During its development, 7E3 was reported to also react with two other integrin receptors, the αVβ3 “vitronectin” receptor (CD51/CD61)3,4 and at least one activation-dependent conformation of the αMβ2 or “Mac-1” receptor (CD11b/CD18).5 Whereas both αVβ3 and αMβ2 have been implicated in a number of different physiologic and pathologic processes, it is possible that some effects of abciximab are due to its reactivity with one or the other of these receptors. Moreover, the reactivity of abciximab with these receptors opens up the possibility that abciximab, or other agents that inhibit these receptors, may be useful in preventing or treating disorders in which these receptors play a role. This review will address these issues.

A Handbook to Eddic Poetry: Myths and Legends of Early Scandinavia, ed. Carolyne Larrington, Judy Quinn, and Brittany Schorn. Cambridge: Cambridge University Press, 2016, xii, 413 pp., 12 b/w ill.

Mediaevistik ◽  
2018 ◽  
Vol 31 (1) ◽  
pp. 366-366
Author(s):  
Albrecht Classen
Keyword(s):  
Old Norse ◽  
Entire Volume ◽  
Cambridge University ◽  
Critical Studies ◽  
Individual Contributions ◽  
The Many ◽  
The Individual ◽  
Made In ◽  
Scandinavian Literature

Eddic poetry constitutes one of the most important genres in Old Norse or Scandinavian literature and has been studied since the earliest time of modern-day philology. The progress we have made in that field is impressive, considering the many excellent editions and translations, not to mention the countless critical studies in monographs and articles. Nevertheless, there is always a great need to revisit, to summarize, to review, and to digest the knowledge gained so far. The present handbook intends to address all those goals and does so, to spell it out right away, exceedingly well. But in contrast to traditional concepts, the individual contributions constitute fully developed critical article, each with a specialized topic elucidating it as comprehensively as possible, and concluding with a section of notes. Those are kept very brief, but the volume rounds it all off with an inclusive, comprehensive bibliography. And there is also a very useful index at the end. At the beginning, we find, following the table of contents, a list of the contributors, unfortunately without emails, a list of translations and abbreviations of the titles of Eddic poems in the Codex Regius and then elsewhere, and a very insightful and pleasant introduction by Carolyne Larrington. She briefly introduces the genre and then summarizes the essential points made by the individual authors. The entire volume is based on the Eddic Network established by the three editors in 2012, and on two workshops held at St. John’s College, Oxford in 2013 and 2014.

Employee Surveys and Sensing

2020 ◽  
Keyword(s):  
Organizational Performance ◽  
Employee Engagement ◽  
Computational Linguistics ◽  
Full Range ◽  
Organization Culture ◽  
Employee Survey ◽  
Passive Data ◽  
Individual Contributions ◽  
Action Taking ◽  
The Individual

This volume comprises 27 chapters focused on the design and execution of employee survey programs. These chapters reflect the latest advances in technology and analytics and a pervasive emphasis on driving organizational performance and effectiveness. The individual chapters represent the full range of survey-related topics, including design, administration, analysis, feedback, and action-taking. The latest methodological trends and capabilities are discussed including computational linguistics, applications of artificial intelligence, and the use of qualitative methods such as focus groups. Extending beyond traditional employee surveys, contributions include the role of passive data collection as an alternative or supplement in a comprehensive employee listening system. Unique contextual factors are discussed including the use of surveys in a unionized environment. Individual contributions also reflect increasing stakeholder concerns for the protection of privacy among other ethical considerations. Finally, significant clarifications to the literature are provided on the use of surveys for measuring organization culture, strategic climate, and employee engagement.

Knowledge First

2017 ◽  
Author(s):  
J. Adam Carter ◽  
Emma C. Gordon ◽  
Benjamin W. Jarvis
Keyword(s):  
Philosophy Of Mind ◽  
Theoretical Background ◽  
Contemporary Research ◽  
Timothy Williamson ◽  
Research Themes ◽  
New Directions ◽  
Individual Contributions ◽  
The Individual

In this introductory chapter, the volume’s editors provide a theoretical background to the volume’s topic and a brief overview of the papers included. The chapter is divided into five parts: Section 1 explains the main contours of the knowledge-first approach, as it was initially advanced by Timothy Williamson in Knowledge and its Limits. In Sections 2–3, some of the key philosophical motivations for the knowledge-first approach are reviewed, and several key contemporary research themes associated with this approach in epistemology, the philosophy of mind and elsewhere are outlined and briefly discussed. The volume’s papers are divided into two broad categories: foundational issues and applications and new directions. Section 4 discusses briefly the scope and aim of the volume as the editors have conceived it, and Section 5 offers an overview of each of the individual contributions in the volume.

scholarly journals Of Visions and Visionaries: Information and Communication Technologies (ICT) in China

2021 ◽  
Vol 50 (1) ◽  
pp. 3-11
Author(s):  
Barbara Schulte ◽  
Marina Svensson
Keyword(s):  
Information And Communication Technologies ◽  
Communication Technologies ◽  
Special Issue ◽  
Empirical Reality ◽  
Information And Communication ◽  
Individual Contributions ◽  
State Governance ◽  
Different Dimensions ◽  
Chinese State ◽  
The Individual

This special issue approaches information and communication technologies (ICT) visions and their realisation/implementation at various levels, among different actors and from various perspectives. Conceptually, we distinguish three different dimensions, even though those overlap in the individual contributions as well as in empirical reality – namely ideational, instrumental, and relational. The different contributions address both visions formulated by the Chinese state and by individual actors such as entrepreneurs. Even though the conditions for the use of ICT in China are deeply affected by state governance, this governance is in no way tantamount to one single government. As this issue’s contributions show, state attempts at building a stable cyber-governance are in need of allies and, depending on the allies’ visions and other, competitive visions, the outcomes of these dynamics are seldom truthful realisations of one original grand masterplan.

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