Characterization of novel platelet and endothelial cell target antigens in a family with genetic susceptibility to autoimmunity.

This report describes a French Canadian family whose members exhibit a high incidence of allo- and autoantibodies to antigens present on both platelets and endothelial cells. This is correlated with various HLA specificities known to be associated with autoimmunity, such as A1, B8, DR3, and, in some cases, with clinical disorders, including nephritis, hypertension, and thrombocytopenia. Immunoblot analysis using platelet and endothelial cell lysates showed serum antibodies to a 75 kDa endothelial cell surface polypeptide and to polypeptides with apparent mass of 115 kDa and 26 kDa found on both platelets and endothelial cells. This 115 kDa internal platelet protein was also found in a variety of other cell types, such as mononuclear cells, and increased following cell activation. Monoclonal antibody immunobilization assays were used to characterize the 26 kDa polypeptide; in three of the four patients tested, an antibody to leukocyte differentiation antigen CD9 was identified. The asymptomatic child of the propositus also exhibited an autoantibody against an 80 kDa platelet protein which was sensitive to thrombin digestion, suggesting that this polypeptide may be platelet glycoprotein V. In addition, P1A1 alloantibody was identified in one sister who had given birth to a severely thrombocytopenic boy and who herself had a severe vascular rejection to a cadaver kidney 2 years prior to this study. The propositus also developed hypertensive renal disease following a pregnancy and became dialysis dependent. Thus, members of this family have developed a variety of antibodies, particularly to platelet and endothelial cell antigens. Some subjects have remained asymptomatic in spite of having autoantibodies. However, others have been seriously ill, and their immune response to these antigens is believed to have played a role in the pathogenesis of their neonatal alloimmune thrombocytopenic purpura, hypertensive renal disease, renal graft rejection, and thrombocytopenia.     

The Role of Attachment in Body Weight and Weight Loss in Bariatric Patients

Purpose

The aim of this study is to explore the role of attachment styles in obesity.

Material and Methods

The present study explored differences in insecure attachment styles between an obese sample waiting for bariatric surgery (n = 195) and an age, sex and height matched normal weight control group (n = 195). It then explored the role of attachment styles in predicting change in BMI 1 year post bariatric surgery (n = 143).

Results

The bariatric group reported significantly higher levels of anxious attachment and lower levels of avoidant attachment than the control non-obese group. Baseline attachment styles did not, however, predict change in BMI post surgery.

Conclusion

Attachment style is different in those that are already obese from those who are not. Attachment was not related to weight loss post surgery.

     

In Vitro and Computational Thrombosis on Artificial Surfaces With Shear Stress

Implantable devices in direct contact with flowing blood are associated with the risk of thromboembolic events. This study addresses the need to improve our understanding of the thrombosis mechanism and to identify areas on artificial surfaces susceptible to thrombus deposition. Thrombus deposits on artificial blood step transitions are quantified experimentally and compared with shear stress and shear rate distributions using computational fluid dynamics (CFD) models. Larger steps, and negative (expanding) steps result in larger thrombus deposits. Fitting CFD results to experimental deposit locations reveals a specific shear stress threshold of 0.41 Pa or a shear rate threshold of 54 s^?1 using a shear thinning blood viscosity model. Thrombosis will occur below this threshold, which is specific to solvent‐polished polycarbonate surfaces under in vitro coagulation conditions with activated clotting time levels of 200–220 s. The experimental and computational models are valuable tools for thrombosis prediction and assessment that may be used before proceeding to clinical trials and to better understand existing clinical problems with thrombosis.     

Cholestasis induces apoptosis in mice cardiac cells: the possible role of nitric oxide and oxidative stress

Background/Aims: Acute cholestasis is associated with cardiovascular complications. The purpose of the present study was to investigate the effect of cholestasis on heart apoptosis and the involvement of nitric oxide (NO) and oxidative stress in the possible altered apoptosis of cholestatic hearts. Methods: Cholestasis was induced by bile duct–ligation, and sham‐operated mice served as controls. Three days after the surgery, heart tissues were evaluated for apoptosis and the level of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been studied in cardiac tissues. The role of treatment with l ‐NAME, a non‐selective inhibitor of NO synthase, or with d ‐NAME, an inactive isomer of l ‐NAME, on cholestatic and sham cardiac apoptosis, level of MDA and CAT, SOD and GSHPx activities was also investigated. The content of NO in cardiac tissue was also determined. Results: Cholestatic hearts showed structural abnormalities and increased apoptosis compared with sham hearts. Treatment with l ‐NAME, but not d ‐NAME, improved both structural abnormalities and enhanced apoptosis of cholestatic hearts. Cholestatic hearts also had an increased level of MDA and decreased activities of CAT and GSHPx, which were not modified by d ‐NAME treatment. By l ‐NAME treatment, the level of MDA decreased and activities of CAT, GSHPx and SOD increased in BDL mice. The content of NO was higher in cholestatic cardiac tissue, which was decreased by l ‐NAME treatment. Conclusion: In conclusion, apoptosis in cholestatic heart might have occurred because of NO overproduction, which could induce oxidative stress in the heart of cholestatic mice.