The Addenbrooke's Cognitive Examination Revised is as effective as the original to detect dementia in a French-speaking population.

INTRODUCTION: This paper presents the validation of the French version of the Addenbrooke's Cognitive Examination Revised (ACE-R). METHODS: The variability of the 3 versions of the ACE-R (A, B and C), performed by the same observer, hence mainly 2 or 3 times on 119 patients showing no progression, was first calculated by Cronbach's alpha coefficient, t test and linear regression. The alpha coefficients of the 3 versions were obtained showing that the ACE-R versions can be considered as one, and an analysis of the interobserver variability was performed by Cohen's kappa coefficient, t test and linear regression on 12 patients. Eventually, we performed a receiver operating characteristic (ROC) analysis to compare the sensitivities and specificities to detect dementia of the ACE, the ACE-R and Mini Mental State Examination on 319 consecutive patients. RESULTS: The ROC areas of sensitivities and specificities of the ACE and ACE-R were very similar. Two cutoffs were identified at 83/100 and 89/100 with a specificity to normality of 98.6% if the ACE-R score was ≥83 and a sensitivity to dementia of 98.4% if the ACE-R score was ≤89. CONCLUSION: ACE-R in French is as reliable and valid as the original version to detect dementia.

A short phosphodiester window is sufficient to direct RNase H-dependent RNA cleavage by antisense peptide nucleic acid.

The potential pharmacologic benefits of using peptide nucleic acid (PNA) as an antisense agent are tempered by its incapacity to activate RNase H. The mixed backbone oligonucleotide (ON) (or gapmer) approach, in which a short internal window of RNAse H-competent residues is embedded within an RNase H-incompetent ON has not been applied previously to PNA because PNA and DNA hybridize to RNA with very different helical structures, creating structural perturbations at the two PNA-DNA junctions. It is demonstrated here for the first time that a short internal phosphodiester window within a PNA is sufficient to evoke the RNase H-dependent cleavage of a targeted RNA and to abrogate translation elongation in a well-characterized in vitro assay.

Inhibition of a DNA-helicase by peptide nucleic acids.

Bis-peptide nucleic acid (bis-PNA) binding results in D-loop formation by strand displacement at complementary homopurine stretches in DNA duplexes. Transcription and replication in intact cells is mediated by multienzymatic complexes involving several proteins other than polymerases. The behaviour of the highly stable clamp structure formed by bis-PNAs has thus far been studied with respect to their capacity to arrest RNA polymerases. Little attention has been given to their recognition and processing by DNA helicases. In this report we have investigated the inhibitory effect of a bis-PNA on the DNA-helicase activity of the well characterized herpes simplex type I UL9 protein. Unwinding by UL9 of a synthetic substrate is significantly inhibited by a bis-PNA and the addition of the ICP8 protein, which increases UL9 processivity, does not relieve this inhibition.

Pharmacokinetics of oligonucleotides in cell culture.

Synthetic oligonucleotides offer interesting perspectives for the regulation of gene expression in normal and pathological situations. Poor uptake in many cell types, inadequate intracellular compartmentalization, often fragmentary knowledge of intracellular behaviour and mechanism of action, and lack of specificity remain major challenges. These limitations strongly urge the design of new oligonucleotide analogues and more efficient antisense strategies. Present achievements and perspectives for further developments will be discussed with emphasis on cell delivery and intracellular fate.