Chronic cerebral ischemia may accelerate clinicopathological changes in Alzheimer's disease. We have examined whether chronic cerebral hypoperfusion accelerates amyloid beta deposition in amyloid protein precursor transgenic (APP-Tg) mouse. At 5, 8, and 11 months of age, C57Bl/6J male mice overexpressing a mutant form of the human APP bearing the both Swedish (K670N/M671L) and the Indiana (V717F) mutations (APPSwInd) and their litterrmates were subjected to either sham operation or bilateral carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm (short-period group). One month after the sham operation or BCAS, these animals were examined by immunohistochemistry for glial fibrillary acidic protein, amyloid beta(1-40) (Abeta(1-40)), amyloid beta(1-42) (Abeta(1-42)), as well as Western blotting and filter assay for Abeta. Another batch of the littermates of APPSwInd mice were subjected to either sham operation or BCAS at 3 months and were examined in the same manner after survival for 9 months (long-period group). In the BCAS-treated group, the white matter was rarefied and astroglia was proliferated. Amyloid beta(1-40) immunoreactivity was found in a few axons in the white matter after BCAS, whereas Abeta(1-42) was accumulated in the scattered cortical neurons and the axons at ages of 6 months and thereafter in the short- and long-period groups. In the neuropil, both Abeta(1-40) and Abeta(1-42) were deposited in the sham-operated and BCAS-treated mice at ages of 9 and 12 months. There were no differences between the short-period group at ages of 12 months and the long-period group. Filter assay showed an increase of Abeta fibrils in the extracellular enriched fraction. Taken together, chronic cerebral hypoperfusion increased Abeta fibrils and induced Abeta deposition in the intracellular compartment and, therefore, may accelerate the pathological changes of Alzheimer's disease.

Enantiomeric esterifications and transesterifications catalyzed by hydrolytic enzymes in nonaqueous media, pioneered by our group and others, are emerging as a method of choice for facile kinetic resolution of racemic alcohols, acids, and other derivatives.' In organic solvents, it is also well established that hydrolases can catalyze the reactions of aminolysis, thiotransesterification, and oximolysis in addition to the aforementioned reactions.' Based on these knowledges, it occurred to us that the kinetic resolution of racemic amines, thiols, and oximes might be possible by the same strategy. In this paper, we wish to report the first successful enzymatic resolution of racemic amines.'Our first choice of enzyme was lipases, which are successfully used for the resolution of alcohols.' In order to find the enzyme for an enantioselective amidation reaction, we examined 15 commercially available lipases4 as a catalyst for the reaction between trifluoroethyl butyrate and the enantiomers of a-methylbenzylamine' in anhydrous n-octane.6 Among them, lipases from Candida cylindracea, Pseudomonas sp., Mucor sp., porcine pancreas, and Chromobacterium viscosum exhibited significant catalytic activity. However, the ratios of the initial rates for S and R isomers (VJV,) were 0.88,0.94, 1.0, 1.5, and 0.66, respectively, and no lipase tested showed substantial enantioselectivity.Protease subtilisin Carlsberg is known to catalyze the amide (peptide) bond formation between carboxylic acid esters and amines in anhydrous organic solvents.' Moreover, a recent study of our group unveiled that the enantioselectivity of this enzyme is greatly affected by the hydrophobicity of the reaction medium.' Encouraged by these findings, we used subtilisin as a catalyst for the aforementioned reaction and examined the dependency of the selectivity factor (VJ V,) on the solvent. As seen in

Reversible posterior leukoencephalopathy syndrome (RPLS) is caused by various heterogeneous factors, the commonest being hypertension, followed by nonhypertensive causes such as eclampsia, renal diseases and immunosuppressive therapy. Patients with RPLS exhibit bilateral white and gray matter abnormalities in the posterior aspects of the cerebral hemispheres. However, this syndrome may affect the brainstem predominantly, and these cases are designated as hypertensive brainstem encephalopathy. We present here two patients with reversible brainstem encephalopathy: one with hypertension and the other without hypertension. These patients presented with swelling and diffuse hyperintensities of the brainstem in fluid-attenuated inversion-recovery (FLAIR) and T2-weighted MRI, but with relatively mild clinical symptoms. They recovered without major neurological deficits, but had residual lacunar lesions in the pons. Reversible brainstem encephalopathy with characteristic MRI features was found in both hypertensive and nonhypertensive patients. These patients were diagnosed with a brainstem variant of RPLS, which is potentially fully reversible after an adequate treatment, and therefore should be carefully differentiated from other brainstem disease conditions.

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