Summary
Protein S (PS) is an anticoagulant plasma protein whose deficiency is associated with increased risk of venous thrombosis. PS directly inhibits thrombin generation by the blood coagulation pathways by several mechanisms, including by binding coagulation factors (F) Va and Xa. To identify PS sequences that mediate inhibition of FVa activity, antibodies and synthetic peptides based on PS sequence were prepared and employed in plasma coagulation assays, purified component prothrombinase assays, binding assays, and immunoblots. In the absence of activated protein C, monoclonal antibody (Mab) S4 shortened FXa-induced clotting in normal plasma but not in PS-depleted plasma. Mab S4 also blocked PS inhibition of FVa-dependent prothrombinase activity in purified component assays in the absence or presence of phospholipids and inhibited binding of PS to immobilized FVa. Epitope mapping identified N-terminal region residues 37–67 of PS as this antibody's epitope. A peptide representing PS residues 37–50 inhibited FVa-dependent prothrombinase activity in a noncompetitive manner, with 50% inhibition observed at 11 μM peptide, whereas a peptide with a D-amino acid sequence of 37–50 was ineffective. FVa, but not FXa, bound specifically to the immobilized peptide representing residues 37–50, and the peptide inhibited binding of FVa to immobilized PS. These data implicate PS residues 37–50 as a binding site for FVa that mediates, at least in part, the direct inhibition of FVa-dependent procoagulant activity by PS.
Purpose Patient-provider communication (PPC) is an important component of optimal patient care. Many factors influence the quality of PPC among cancer patients, however, there are conflicting data on the impact of patient race and education level on PPC. We sought to assess the effect of race and education level on PPC among a multiracial cohort of cancer survivors. Methods We conducted a survey of 360 cancer survivors. Data were collected on age, race, income, and education level. The survey assessed satisfaction with PPC and follow-up with cancer physician. Questions were answered on a 5-point response scale. We evaluated PPC using nonparametric analyses and built logistic regression models for satisfaction with follow-up care. Results Patients with a high school or lower education consistently rated questions of PPC more poorly than those who attained a higher level of education. No significant associations were detected between PPC and race. Results for perceived quality of care showed a similar disparity by education level. High school educated patients reported significantly lower satisfaction with quality of follow-up care compared with patients who attained Graduate level education (OR 3.50, 95% CI 1.37-8.94). Conclusion Our study demonstrated that education level, but not race, is associated with perception of communication and satisfaction with follow-up care. Patients who attained higher levels of education had higher PPC ratings and satisfaction with follow-up care. Our findings identify an opportunity for improvement in PPC through individualizing the delivery of health-related information with the goal of achieving optimal care of long-term cancer survivors.
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