R Lee

Recently, the ligand for c-mpl, a member of the family of cytokine receptors, was cloned and found to be a physiologic regulator of platelet homeostasis. We report that megakaryocyte growth and development factor (MGDF, thrombopoietin [TPO], c-mpl ligand ) induces differentiation in a majority of mpl-transfected 32D cells, while interleukin (IL)-3 is exclusively mitogenic in this system. MGDF differentiation, as measured by decreased proliferation, changes in cellular morphology, increased adherence, and downregulation of very late antigen (VLA)-4, is dominant over IL-3 proliferation. MGDF induces tyrosine-phosphorylation of mpl, JAK2, SHC, SHPTP-1 (HCP, motheaten) and SHPTP-2 (Syp, PTP-1D) within 30 seconds of stimulation, as well as of vav and MAPK with slightly delayed kinetics. A fraction of mpl and JAK2 is preassociated, and the stoichiometry of this complex is unaltered by cytokine stimulation. After MGDF stimulation, we detect interactions among SHC, grb2, SHPTP-1, SHPTP-2, and the mpl/JAK2 complex. IL-3 induces phosphorylation of the above proteins with the exception of mpl and also causes weak JAK1 phosphorylation. Although similar in composition, the MGDF- and IL-3-induced complexes of signal transducers appear to be assembled in different configurations, especially with respect to SHPTP-2. Both MGDF and IL-3 induce tyrosine phosphorylation of STAT3 (APRF) and STAT5 (MGF), with MGDF favoring STAT3 while IL-3 predominantly causes STAT5 phosphorylation. In addition, some proteins become tyrosine-phosphorylated in response to MGDF only, suggesting that we may have detected differentiation-specific signal transducers. These include a number of high-molecular-weight proteins (140 to 200 kD) and one 28-kD protein that becomes tyrosine-phosphorylated only briefly.

Objective ST segment elevation myocardial infarction (STEMI) is associated with significant mortality leading to loss of productive life years, especially in younger patients. This study aims to compare the characteristics and outcomes of young versus older patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) to help focus public health efforts in STEMI prevention. Methods Data from the Coronary Care Unit database of the National University Hospital, Singapore from July 2015 to June 2019 were reviewed. Patients were divided into young ( Results Of the 1818 consecutive patients with STEMI who underwent PPCI, 465 (25.6%) were Conclusion Young patients with STEMI are more often smokers, of Indian ethnicity and had family history of IHD, although cardiometabolic risk factors are also prevalent. Mortality is lower, but not negligible, among the young patients with STEMI. Public health efforts are needed to reduce the prevalence of these risk factors among the constitutionally susceptible population.