Constitutive dimerization of glycoprotein VI (GPVI) in resting platelets is essential for binding to collagen and activation in flowing blood

The platelet collagen receptor glycoprotein VI (GPVI) has been suggested to function as a dimer, with increased affinity for collagen. Dissociation constants (K(d)) obtained by measuring recombinant GPVI binding to collagenous substrates showed that GPVI dimers bind with high affinity to tandem GPO (Gly-Pro-Hyp) sequences in collagen, whereas the markedly lower affinity of the monomer for all substrates implies that it is not the collagen-binding form of GPVI. Dimer binding required a high density of immobilized triple-helical (GPO)(10)-containing peptide, suggesting that the dimer binds multiple, discrete peptide helices. Differential inhibition of dimer binding by dimer-specific antibodies, m-Fab-F and 204-11 Fab, suggests that m-Fab-F binds at the collagen-binding site of the dimer, and 204-11 Fab binds to a discrete site. Flow cytometric quantitation indicated that GPVI dimers account for ~29% of total GPVI in resting platelets, whereas activation by either collagen-related peptide or thrombin increases the number of dimers to ~39 and ~44%, respectively. m-Fab-F inhibits both GPVI-dependent static platelet adhesion to collagen and thrombus formation on collagen under low and high shear, indicating that pre-existing dimeric GPVI is required for the initial interaction with collagen because affinity of the monomer is too low to support binding and that interaction through the dimer is essential for platelet activation. These GPVI dimers in resting circulating platelets will enable them to bind injury-exposed subendothelial collagen to initiate platelet activation. The GPVI-specific agonist collagen-related peptide or thrombin further increases the number of dimers, thereby providing a feedback mechanism for reinforcing binding to collagen and platelet activation

Retrospective cohort study of rough-surface titanium implants with at least 25 years’ function

Abstract Background The longitudinal clinical outcomes over decades contribute to know potential factors leading to implant failure or complications and help in the decision of treatment alternatives. Methods The cases of all patients who received dental implants treated with titanium plasma-sprayed surfaces and whose prostheses were set in the period 1984–1990 at seven private practices were retrospectively analyzed. The cumulative survival rate, the cumulative incidence of peri-implantitis, and the complication-free prosthesis rate were calculated with Kaplan-Meier survival curves, and the factors’ influence on implant survival rate and the incidence of peri-implantitis were determined by a single factor in univariate analyses and multivariate analyses. Results A total of 223 implants and 106 prostheses were applied to 92 patients, and approx. 62% of the implants and patients dropped out over the 25 years following their treatment. The cumulative survival rates of the implants at 10, 15, and 25 years were 97.4, 95.4, and 89.8%, respectively. A significant difference was observed in the implant position. The cumulative incidences of peri-implantitis at 10, 15, and 25 years were 15.3, 21.0, and 27.9%, respectively. Significant differences were observed in the gender, implant type, and width of keratinized mucosa around the implant. The cumulative survival rates of mechanical complication-free prostheses at 10, 15, and 25 years were 74.9, 68.8, and 56.4%, respectively. The difference in the type of prosthesis resulted in significant differences. Conclusions The high rate of dropout during follow-up indicates the difficulty of determining long-term (> 25 years) prognoses. The gender, location, and width of keratinized mucosa affected the development of peri-implantitis, resulting in late failures. Implant-supported overdentures were frequently repaired. Tooth implant-supported prostheses are not recommended for long-term survival