PubMed · 4180548
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
J R O'Brien. 1969-04-26. Arvin and platelets.. https://doi.org/10.1016/s0140-6736(69)91931-x
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.
A highly sensitive and rapid clinical method for the visualization of the multimeric structure of von Willebrand Factor in plasma and platelets is described. The method utilizes submerged horizontal agarose gel electrophoresis, followed by transfer of the von Willebrand Factor onto a polyvinylidine fluoride membrane, and immunolocalization and luminographic visualization of the von Willebrand Factor multimeric pattern. This method distinguishes type 1 from types 2A and 2B von Willebrand disease, allowing timely evaluation and classification of von Willebrand Factor in patient plasma. It also allows visualization of the unusually high molecular weight multimers present in platelets. There are several major advantages to this method including rapid processing, simplicity of gel preparation, high sensitivity to low concentrations of von Willebrand Factor, and elimination of radioactivity.
Two flow cytometric parameters are generally used to quantify platelet activation as measured by P-selectin (CD62) expression: percentage and mean channel fluorescence of CD62-positive platelets (%(+) and MCF(+), respectively). We describe a method for calculation of indices of platelet activation for positive (IPA(+)) and total (IPA(Sigma)) platelets, which reflect integrated amounts of CD62 expressed in these populations; IPA(+) is calculated as the product of %(+) and MCF(+), whereas IPA(Sigma) is exclusively determined by mean fluorescence of the total platelet population (MCF(Sigma)) and does not depend on %(+). We use these parameters to characterize human platelet activation in whole blood samples treated with varying human alpha-thrombin concentrations, mimicking the variations in platelet activation in a number of clinical settings. Multiparameter analysis of CD62 expression may be useful for selective diagnosis of disorders with systemic or localized platelet activation and for monitoring the clinical course of the disease and effect of therapeutic interventions.