PubMed · 4895043
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
R Marx. 1969. [Preface].. https://pubmed.ncbi.nlm.nih.gov/4895043/
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.
Explore the source record for details and available documents.
Concentrations of danazol in patient plasma and red blood cells (RBC) were assayed over a 6-month period in 75 patients on danazol therapy using a high-pressure liquid chromatography (HPLC) method more reliable than previous radioimmunoassay (RIA) methods. It was found that plasma danazol rose regularly for 15 days after the beginning of treatment, reaching a steady state plateau of 175 +/- 76 ng/ml in 20 patients on normal dose, and less for lower dose schedules. After stopping danazol, concentrations declined to near zero in a similar time frame. RBC concentrations on a packed volume basis were similar to plasma levels. However, the membrane ghosts of RBC contained about 50% of the total RBC danazol, implying about 100-fold higher concentration in membranes than in plasma. Similar distributions were obtained in vitro with both RBC and platelets, and were confirmed by 14-C-labeled danazol. These findings tend to support the hypothesis that the benefits of danazol in immune disorders may be attributable in part to its intercalation in the lipid bilayer of the plasma membrane, altering antigen/receptor expression to modulate immune reactions. This hypothesis was first suggested when it was observed that the RBC of patients on danazol therapy showed morphological changes and increased resistance to osmotic lysis. It was later shown that danazol in vitro reduces binding of autoantibodies, and protects against complement-mediated lysis, suggesting direct action of danazol on the membranes. This hypothesis is discussed, and danazol's effect in protecting against complement-mediated lysis is described.