We designed poly(amidoamine) dendrimers with phenylalanine or leucine residues at their chain ends. Thereby, we achieved efficient gene transfection of cells through synergy of the proton sponge effect, which is induced by the internal tertiary amines of the dendrimer, and hydrophobic interaction by the hydrophobic amino acid residues in the dendrimer periphery. Dendrimers having 16, 29, 46, and 64 terminal phenylalanine residues were prepared by the reaction of the amine-terminated poly(amidoamine) G4 dendrimer and L-phenylalanine using condensing reagent 1,3-dicyclohexylcarbodiimide. Transfection activity of these phenylalanine-modified dendrimers for CV1 cells, an African green monkey kidney cell line, increased concomitant with the increasing number of the terminal phenylalanine residues, except for the dendrimer with 64 phenylalanine residues, which showed poor water solubility and hardly formed a complex with DNA at neutral pH. However, under weakly acidic conditions, the dendrimer with 64 phenylalanine residues formed a complex with DNA, thereby achieving highly efficient transfection. In contrast, the attachment of L-leucine residues was unable to improve the transfection activity of the parent dendrimer, probably because of the relatively lower hydrophobicity of this amino acid. The phenylalanine-modified dendrimer exhibited a higher transfection activity and a lower cytotoxicity than some widely used transfection reagents. For that reason, the phenylalanine-modified dendrimers are considered to be promising gene carriers.

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Positron emission tomographic (PET) data on local cerebral metabolic rates for glucose (LCMR) are reported for 32 regions of interest (ROI)s in cross-sectional studies on 57 patients with clinically diagnosed Alzheimer's disease (AD) and 20 neurologically normal controls, and in serial studies on 13 of the AD cases, including a familial, young-onset case where the diagnosis has been confirmed at autopsy. Extensive psychological testing was done on all the AD cases. Almost all cortical regions showed a significant decline in LCMR with age in the control subjects. There were the expected cortical metabolic deficits in AD and the serial studies showed a general increase in such deficits over time in 12 of the 13 cases. The regions showing the greatest declines with time in serial studies are the same as those showing the most severe deficiencies in cross-sectional studies. The young-onset case did not show a greater rate of metabolic decline than many of the older cases studied. Results on individual psychological tests tended to correlate with metabolic rates in multiple, rather than single, cortical regions, suggesting intact neuronal networks are required for good performance. The correlations with cortical metabolic activity found were of a sign indicating that the higher the metabolic rates and the better the left:right asymmetry index, the better was the performance. RESUME: Tomographic par emission de positrons utilisant le 18 F-fluorodeoxyglucose chez des cas presumement atteints de la maladie d'Alzheimer, dont 13 scans series Nous rapportons les donnces sur les taux m£taboliques cerebraux locaux d'utilisation du glucose (TMCL) determines au moyen de la tomographic par emission de positrons (PET) dans 32 regions d'interet, en etude transversale chez 57 patients avec un diagnostic clinique de maladie d'Alzheimer (MA) et 20 controles normaux au point de vue neurologique, en etude seriee chez 13 cas de MA, incluant un cas de MA familiale, a debut precoce, ou le diagnostic a ete confirme a l'autopsie. Tous les cas de MA ont &\€ soumis a une evaluation psychologique poussee. 11 existait une diminution significative du TMCL avec l'age chez les controles dans presque toutes les regions corticales. Les deficits metaboliques corticaux auxquels on s'attendait elaient presents dans la MA et les etudes seriees ont montre un accroissement general de ces deficits avec le temps chez 12 des 13 sujets. Les regions manifestant les plus hauts taux de progression des deficits avec le temps dans les efudes seYiees sont les memes que celles manifestant les deficits les plus seVeres dans les Etudes transversales. Le cas a d6but precoce ne montrait pas une diminution plus rapide du taux metabolique que plusieurs des cas plus ages qui ont efe Studies. Les resultats des epreuves psychologiques individuelles tendaient a etre en correlation avec les taux metaboliques dans plusieurs regions corticales plutot que dans une seule, suggerant que des reseaux neuronaux intacts sont requis pour fournir un bon rendement. Les correlat...

Postgraduate clinical training for dentists in Japan became mandatory in April 2006. Mandatory postgraduate clinical training for physicians has been criticized as having accelerated the imbalance in distribution of physicians. This suggests the danger that the same phenomenon might occur in distribution of dentists. It is also necessary to investigate the geographic distribution of dental trainees and practicing dentists in Japan. In this study, the number of dental trainees enrolled in each clinical training program and number that had actually received clinical training at each facility were compared by prefecture. The results suggest that disparities in the number of dental trainees among prefectures are being compensated for by movement across prefectural borders under the clinical training facilities-group system. Postgraduate dental trainees, however, showed a significantly greater imbalance in geographic distribution than practicing dentists. Continuation of the postgraduate clinical training for dentists under the existing system may accelerate this imbalance in distribution of dentists. To prevent this, practical measures should be taken in accordance with the coming review of the system, based on research regarding changes in geographic distribution of dental trainees.

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