128 research outputs found

    Characterization of the reactivity of prothrombin-dependent anti-phospholipid antibodies with apoptotic cells

    No full text
    Anti-phospholipid antibodies (aPL) occur in patients with the anti-phospholipid syndrome, and are directed against various combinations of phospholipids and phospholipid-binding proteins (e.g., beta2-glycoprotein I and prothrombin). Lupus anticoagulants (LA), a subset of aPL, exhibit anticoagulant properties in vitro, but are strikingly procoagulant in vivo. We have previously demonstrated that some aPL bind specifically to apoptotic, but not viable, thymocytes in the presence of beta2-glycoprotein 1. Here, we demonstrate that prothrombin binds selectively to the surface of apoptotic Jurkat cells, and supports the binding of LA-positive murine monoclonal antibodies (mAb) and patient-derived IgG to apoptotic cells. Despite similar LA activity and reactivity with apoptotic cells, the mAb differed in affinity and specificity. One mAb was highly reactive with prothrombin alone, while the other required anionic phospholipid for elevated binding. These results demonstrate that aPL recognize multiple epitopes on apoptotic cells, suggesting that apoptotic antigens contribute to the induction and/or perpetuation of aPL

    A novel red blood cell substitute based on crosslinked hemoglobin, superoxide dismutase, and catalase /

    No full text
    Modified hemoglobin red blood cell substitutes have a number of potential areas of application. In some of these applications, it will be important to lessen the pro-oxidant effects of hemoglobin and potential free radical-mediated toxicity. This research introduces a novel modified hemoglobin that is based on intermolecularly crosslinking hemoglobin, superoxide dismutase and catalase (PolyHb-SOD-CAT) with the bifunctional agent, glutaraldehyde. Superoxide dismutase and catalase catalyze the breakdown of superoxide radical and hydrogen peroxide respectively. Studies of structural and functional parameters reveal that PolyHb-SOD-CAT retains superoxide dismutase and catalase enzymatic activity, and consists of a mixture of molecular species ranging in molecular size and protein composition. Circulation time studies of PolyHb-SOD-CAT in rats show that hemoglobin, superoxide dismutase and catalase possess longer circulatory half-lives as compared to the free forms of these proteins. Studies also show that PolyHb-SOD-CAT prevents the formation of methemoglobin, ferrylhemoglobin, hydroxyl radical, free iron, and lipid peroxidation. Ischemia-reperfusion studies using isolated perfused hindlimbs and intestine of rat show that PolyHb-SOD-CAT reduced the formation of hydroxyl radical compared to PolyHb. Altogether, these results suggest that PolyHb-SOD-CAT is a potentially safer modified hemoglobin oxygen carrier by virtue of its ability to detoxify reactive oxygen species, and reduced propensity to promote and participate in oxidative processes

    FemTech: A Feminist Technoscience Analysis

    No full text
    This research paper grapples with the oppressive consequences and liberatory possibilities of innovations in menstruation technologies enabled by the Fem- Tech industry. First, it discusses a feminist technoscience framework, tracing some progressions of feminist thought on technology. Then, it reviews popular discourse about FemTech and problematizes some of its implicit assumptions. Using FemTech as a starting point, the paper looks backward in time to some recent histories of menstrual technologies. Finally, it draws on Ursula Franklin’s 1985 discussion about the dichotomy of values that underlie that technological order and those that underlie the women’s world, wondering whether FemTech can serve as a bridge between them. In all, this paper explores how the “femi- nist” label is implicitly and explicitly tied up with FemTech and imagines what truly feminist menstrual technologies could accomplish

    Hemoglobin-based oxygen carriers: from mechanisms of toxicity and clearance to rational drug design

    Full text link
    Hemoglobin-based oxygen carriers (HBOCs) have been developed to support blood oxygen transport capacity during hemorrhagic shock, hemolysis and ischemic insult. Existing product candidates have demonstrated considerable efficacy in experimental animal models and in clinical trial subjects; however, severe adverse safety signals that appeared in recent phase II and phase III clinical trials involving certain HBOCs have in part hindered further development and licensing. Emerging insights into hemoglobin (Hb) toxicity as well as physiologic Hb scavengers such as haptoglobin and CD163 that are capable of detoxifying extracellular Hb in vivo suggest that alternative product candidates could be designed. Together with novel animal models and biomarkers tailored to monitor the effects of extracellular Hb, a new generation of HBOCs can be envisioned
    • …
    corecore