The pathogenesis of podagra.

Precipitation of crystals from solution is a relatively simple phenomenon that should be explained by changes in concentration, temperature, pH, or other local factors. Which of these factors determines the preferential precipitation of urate crystals at the base of the big toe? Podagra correlates with degenerative joint disease of the toe, often follows abuse of the feet, and classically occurs in the middle of the night. These characteristics suggest that crystals may form in resolving synovial effusions. The urate concentration must transiently rise in such an effusion because water will leave the joint space twice as fast as urate. If the local concentration surpasses the solubility of urate, crystals will form that may than induce acute podagra.     

Synovial permeability in rheumatoid arthritis.

In patients with rheumatoid arthritis, as well as in persons with other kinds of synovitis, proteins enter the knee joint more rapidly than in normal individuals (P less than 0.001). The rheumatoid synovium, however, is less permeable to small molecules (tritiated water, P less than 0.02; urate, P less than 0.05; and glucose, P less than 0.002) than is the normal joint lining. This difference is explained if rheumatoid microvascular changes enhance synovial permeability to proteins while coexisting interstitial changes diminish synovial permeability to smaller molecules.     

STUDIES ON PROTEIN FOLDING,UNFOLDING AND FLUCTUATIONS BY COMPUTER SIMULATION III. Effect of Short-Range Interactions

The theoretical model of proteins on the two-dimensional square lattice, introduced previously, is extended to include the specific short-range interactions. Attractive long-range interactions with various specificities and non-specific repulsive long-range interactions in the form of self-avoidance of the polymer chain are also operative in the model. Dynamics of the model protein is studied by a Monte Carlo method. The short-range interactions are found to accelerate the folding and unfolding transitions. Non-specific part of the attractive long-range interactions have a competing effect of decelerating the transitions. When the short-range interactions are weighted beyond a certain extent over the attractive long-range interactions, the all-or-none character of the folding and unfolding transitions is destroyed. How the destruction proceeds is quantitatively expressed in terms of the S-H curves. The limiting case of dominance of the specific short-range interactions over the attractive long-range interactions is studied in detail. The lattice polymer in this limit does not behave like a globular protein at all. This observation leads to a reexamination of the currently popular notion of the dominance of the short-range interactions. A new concept of consistency is proposed to replace it. Possible mechanisms of the acceleration of the transitions by the specific short-range interactions are discussed.