Aquablation of the Prostate for Symptomatic Benign Prostatic Hyperplasia: Early Results.

Aquablation is a novel technique for the surgical management of bladder outlet obstruction secondary to benign prostatic hyperplasia. Following first-in-man studies, a multicenter trial was conducted with results now out to 1 year. Aquablation resulted in a mean International Prostate Symptom Score improvement of 16 points (p < 0.01) and a mean maximum urinary flow rate increase from 8.7 to 18.3 ml/s (p < 0.01) at 12 months. Due to the precise prostate mapping, aquablation has also demonstrated favorable sexual and urinary outcomes with no new erectile dysfunction, retrograde ejaculation, or urinary incontinence as often experienced with other techniques. These improvements in functional outcomes at 12 months confirm that aquablation is a safe and effective alternative for BPH treatment.

The equilibrium unfolding pathway of a (beta/alpha)8 barrel.

The (beta/alpha)(8) barrel is the most commonly occurring fold among enzymes. A key step towards rationally engineering (beta/alpha)(8) barrel proteins is to understand their underlying structural organization and folding energetics. Using misincorporation proton-alkyl exchange (MPAX), a new tool for solution structural studies of large proteins, we have performed a native-state exchange analysis of the prototypical (beta/alpha)(8) barrel triosephosphate isomerase. Three cooperatively unfolding subdomains within the structure are identified, as well as two partially unfolded forms of the protein. The C-terminal domain coincides with domains reported to exist in four other (beta/alpha)(8) barrels, but the two N-terminal domains have not been observed previously. These partially unfolded forms may represent sequential intermediates on the folding pathway of triosephosphate isomerase. The methods reported here should be applicable to a variety of other biological problems involving protein conformational changes.

Rapid mapping of protein structure, interactions, and ligand binding by misincorporation proton-alkyl exchange.

Understanding protein conformation, interactions, and ligand binding is essential to all biological inquiry. We report a novel biochemical technique, called misincorporation proton-alkyl exchange (MPAX), that can be used to footprint protein structure at single amino acid resolution. MPAX exploits translational misincorporation of cysteine residues to generate probes for physical analysis. We apply MPAX to the triosephosphate isomerase (beta/alpha)(8) barrel, accurately determining its substrate-binding site, a protein-protein interaction surface, the solvent-accessible protein surface, and the stability of the barrel. Because MPAX requires only microgram quantities of material and is not limited by protein size, it is ideally suited for proteins not amenable to conventional structural methods, such as membrane proteins, partially folded or insoluble proteins, and large protein complexes.