Clustering of vitronectin and RGD peptides on microspheres leads to engagement of integrins on the luminal aspect of endothelial cell membrane

In previous work (Conforti et al, Blood 80:437, 1992), we have shown that integrins in endothelial cells (EC) are not polarized to the basal cell membrane, but are also exposed on the apical cell surface, in contact with blood. Therefore, endothelial integrins might be available for binding circulating plasma proteins. However soluble plasma vitronectin (vn) bound very poorly to EC apical surface and this interaction was unaffected by Arg-Gly-Asp (RGD) peptides or an anti- alpha v beta 3 serum. In contrast, beads (diameter, 4.5 microns) coupled with plasma vn associated to EC apical surface in a time- and concentration-dependent way. Addition of antibodies directed to vn, alpha v beta 3, and RGD-containing peptides blocked the interaction of vn beads with EC. In contrast, heparin and antibodies directed to alpha v beta 5 and beta 1 integrin chain had no effect. Beads coupled with Gly-Arg-Gly-Asp-Ser-Pro bound to the EC surface, but not those coupled with Gly-Arg-Gly-Glu-Ser-Pro. This interaction was blocked by alpha v beta 3 antibodies and RGD peptides, but not by alpha v beta 5 antibody. Overall, these results indicate that luminal alpha v beta 3 retains its binding capacity for surface-linked vn and RGD-containing ligands, but binding is observed only when the ligand is offered in a clustered, multivalent form. We propose that when vn or RGD-containing proteins are bound to circulating cells, they can act as bridging molecules by promoting adhesion of the cells to the endothelium via apical integrins.     

Differences in coagulant and fibrinolytic activities of cultured human endothelial cells derived from omental tissue microvessels and umbilical veins

Large vessel and microvascular endothelial cells were compared in their capacity to synthesize and secrete coagulant and fibrinolytic factors. Human omental tissue microvascular endothelial cells (HOTMEC) and human umbilical vein endothelial cells (HUVEC) were isolated, grown to confluency under identical conditions, and studied in primary cultures. After an incubation period of 12 hours in serum-free medium, the conditioned medium of confluent HOTMEC contained 100-fold higher levels of tissue plasminogen activator (tPA) antigen than that of HUVEC. The conditioned media as well as the lysates of both cell types did not contain any free tPA activity, but the free plasminogen activator inhibitor capacity was found intracellularly as well as extracellularly. Although von Willebrand factor was detected in both cell types by immunofluorescence, measurable amounts were only found in HUVEC using an enzyme-linked immunosorbent assay. The kinetics of protein C activation by thrombin on the surface of once-passaged cells were identical for HOTMEC and HUVEC. The present study indicates that cultivated HOTMEC produce larger quantities of tPA than HUVEC do, possess smaller amounts of von Willebrand factor than HUVEC do, and express thrombomodulin for protein C activation as effectively as HUVEC.     

Some Theoretical Underpinnings of Knowledge Translation

A careful analysis of the definition of knowledge translation highlights the importance of the judicious translation of research into practice and policy. There is, however, a considerable gap between research and practice. Closing the research-to-practice gap involves changing clinical practice, a complex and challenging endeavor. There is increasing recognition that efforts to change practice should be guided by conceptual models or frameworks to better understand the process of change. The authors conducted a focused literature search, developed inclusion criteria to identify planned action theories, and then extracted data from each theory to determine the origins, examine the meaning, judge the logical consistency, and define the degree of generalizability, parsimony, and testability. An analysis was conducted of the concepts found in each theory, and a set of action categories was developed that form the phases of planned action. Thirty-one planned action theories were identified that formed the basis of the analyses. An Access database was created, as well as a KT Theories User's Guide that synthesizes all the planned change models and theories, identifies common elements of each, and provides information on their use. There are many planned change models and frameworks with many common elements and action categories. Whenever any planned change model is used, change agents should consider documenting their experiences with the model so as to advance understanding of how useful the model is and to provide information to others who are attempting a similar project.     

Percutaneous transluminal angioplasty of infrapopliteal vessels: preliminary results and technical considerations

Infrapopliteal balloon angioplasty was performed in 11 patients facing reconstructive surgery for limb salvage. Twelve separate sessions of angioplasty were performed, during which 15 of 16 diseased tibial runoff vessels were successfully dilated. Three complications occurred during percutaneous transluminal angioplasty (PTA). One was related to the concomitant use of a thrombolytic agent to open a femoropopliteal bypass graft and not related to the angioplasty itself. No limbs were lost as a result of complications. The procedure was a technical success in nine of 12 cases (75%) and an initial clinical success in eight of the nine that were technically successful (89%). Follow-up ranged from 1 to 22 months. Six of the nine cases (67%) remained clinically successful during this period. Preliminary results suggest that infrapopliteal PTA is a safe and effective alternative to surgical reconstruction in selected patients.     

Risk of ovarian failure and fertility preserving methods in girls and adolescents with a malignant disease

Girls and young women suffering from a malignant disease that requires treatment with chemo- and/or radiotherapy are at risk of losing fertility. The most significant risk factors are age and type of treatment given. Preserving fertility is of high priority to both the young patient and her parents. This article reviews the effect of chemo- and radiotherapy on gonadal function, and thus fertility, and offers different fertility preserving methods based on the literature. Cryopreservation of ovarian tissue is a possible way of preserving fertility in this group of patients in the future.