Protein-mediated boundary lubrication in arthroplasty.

Wear of articulated surfaces can be a major lifetime-limiting factor in arthroplasty. In the natural joint, lubrication is effected by the body's natural synovial fluid. Following arthroplasty, and the subsequent reformation of the synovial membrane, a fluid of similar composition surrounds the artificial joint. Synovial fluid contains, among many other constituents, a substantial concentration of the readily adsorbing protein albumin. The ability of human serum albumin to act as a boundary lubricant in joint prostheses has been investigated using a pin-on-disc tribometer. Circular dichroism spectroscopy was employed to follow the temperature- and time-dependent conformational changes of human serum albumin in the model lubricant solution. Effects of protein conformation and polymer surface hydrophilicity on protein adsorption and the resulting friction in the boundary lubrication regime have been investigated. Unfolded proteins preferentially adsorb onto hydrophobic polymer surfaces, where they form a compact, passivating layer and increase sliding friction-an effect that can be largely suppressed by rendering the substrate more hydrophilic. A molecular model for protein-mediated boundary friction is proposed to consolidate the observations. The relevance of the results for in vivo performance and ex vivo hip-joint testing are discussed.

Infectivity of scrapie prions bound to a stainless steel surface.

BACKGROUND: The transmissible agent of Creutzfeldt-Jakob disease (CJD) is not readily destroyed by conventional sterilization and transmissions by surgical instruments have been reported. Decontamination studies have been carried out thus far on solutions or suspensions of the agent and may not reflect the behavior of surface-bound infectivity. MATERIALS AND METHODS: As a model for contaminated surgical instruments, thin stainless-steel wire segments were exposed to scrapie agent, washed exhaustively with or without treatment with 10% formaldehyde, and implanted into the brains of indicator mice. Infectivity was estimated from the time elapsing to terminal disease. RESULTS: Stainless steel wire (0.15 x 5 mm) exposed to scrapie-infected mouse brain homogenate and washed extensively with PBS retained the equivalent of about 10(5) LD50 units per segment. Treatment with 10% formaldehyde for 1 hr reduced this value by only about 30-fold. CONCLUSIONS: The model system we have devised confirms the anecdotal reports that steel instruments can retain CJD infectivity even after formaldehyde treatment. It lends itself to a systematic study of the conditions required to effectively inactivate CJD, bovine spongiform encephalopathy, and scrapie agent adsorbed to stainless steel surfaces such as those of surgical instruments.

Fine genetic and comparative mapping of the deafness mutation Ames waltzer on mouse chromosome 10.

The Ames waltzer (av) mouse mutant is an autosomal recessive deafness mutation on mouse Chromosome 10. Previously, av had not been mapped relative to molecular markers. We have performed an intersubspecific backcross with Mus musculus castaneus and mapped microsatellite markers in this cross. Toothpick PCR on previously frozen tissue samples from offspring was used as an efficient strategy to screen a large number of animals quickly. In 1258 progeny tested we found three recombinants for each of the flanking markers D10Mit199 and D10Mit64. In addition, nine different genes (Ank3, Bcr, Gnaz, Tfam, Mif, Mmp11, Dcoh, Pyp, and Gstt2) were mapped and eliminated genetically as candidate genes for av. av had been discussed as a potential mouse model for the human deafness loci Usher syndrome type ID (USH1D) and DFNB12. Comparative mapping shows that av maps near an evolutionary break point and makes it unlikely that those loci are human homologues of av. A human homologue of av is predicted to lie either on 22q11.2 or on 10q21. The orientation of conserved linkage groups between these two human chromosomal regions relative to mouse Chromosome 10 was determined.