Clinical correlation of brain MRI and MRS abnormalities in patients with Wilson disease.

BACKGROUND: The progression of Wilson disease (WD), a disorder of copper metabolism, can be arrested by chelation therapy. However, neurologic deficits may persist despite adequate treatment. MRI is used to assess patients with WD, but previous attempts to correlate clinical progression with the investigation findings have often been unsuccessful. OBJECTIVE: To identify MR visible markers that could help stratify disease severity and to clarify the mechanism of persistent neurologic deficit after treatment. METHODS: MRI and proton MR spectroscopy (1H-MRS) were performed in 17 patients with WD. MRI was assessed semiquantitatively and used to locate volumes of interest (voxels) in the striatum for 1H-MRS. RESULTS: MRI showed abnormalities predominantly confined to those patients with neurologic features of WD. The 1H spectra demonstrated a reduction of N-acetylaspartate and N-acetylaspartylglutamate (2.05 mM; p < 0.01) in those patients with neurologic features but not in patients without clinical neurologic involvement (0.42 mM; p > 0.1) in comparison with age-matched normal control subjects. Choline was also reduced in both patient groups (0.08 mM; p < 0.01) compared with age-matched controls. CONCLUSIONS: There may be a biochemical correlate of tissue-specific dysfunction in patients with Wilson disease who develop neurologic features. These changes appear to be present despite prior clinical improvement and may imply a need for additional treatment.

Enzymatic transformations in supersaturated substrate solutions: II. Synthesis of disaccharides via transglycosylation.

Enzymatic transglycosylation in supersaturated solutions of substrates was investigated using crude glycosidase preparations from barley, snail, and coffee beans. It was shown that the use of supersaturated glycoside solutions as media for transglycosylation reactions offers considerable advantages over conventional aqueous systems. These advantages include higher yields, more efficient use of the donor glycosides and improved volumetric productivity, especially in the case of poorly water-soluble substrates. The regioselectivity of the glycosylation was not significantly affected by high concentrations of acceptor glycosides. It was also shown that the regioselectivity of transfer could be directed towards secondary hydroxyl groups by the use of methyl 6-O-acetyl-alpha-galactopyranoside as acceptor. The value of these approaches was demonstrated by the synthesis of methyl 3- and 4-O-beta-D-galactopyranosyl-alpha-D-galactopyranosides and methyl 3-O-beta-D-galactopyranosyl-alpha-L-fucopyranoside on a preparative scale.