Creutzfeldt-Jakob disease with a novel extra-repeat insertional mutation in the PRNP gene.

The authors investigated two unrelated patients with Creutzfeldt-Jakob disease (CJD) with clinical features of sporadic CJD (sCJD) carrying one extra octapeptide repeat in the prion protein (PrP) gene (PRNP). A synaptic type PrP distribution throughout the cerebral gray matter and plaque-like PrP deposits in the subcortical gray structures were detected immunocytochemically. The different patterns of PrP deposition were associated with distinct types of protease-resistant PrP, similar to type 1 and type 2 of sCJD. The features suggest that this insertion is a pathogenic mutation.

[The mechanism of impulse initiation: high-resolution epicardial pace-mapping in rat heart]. / Meccanismo di insorgenza del battito stimolato: misura del potenziale epicardico ad alta risoluzione spaziale nel cuore di ratto.

UNLABELLED: Simulations of cardiac tissue bidomain model indicate that point cathodal stimulation gives rise to a dog-bone depolarized region (virtual cathode) extending across fibers, limited by two symmetric hyperpolarized regions (virtual anode) extending along fibers. These predictions were experimentally confirmed by optical mapping studies of transmembrane potentials while no direct validation is reported at the extracellular level. The present study aims at defining the influence of the virtual cathode on extracellular potentials by means of high-density epicardial mapping. METHODS: Epicardial potentials were measured in seven exposed rat hearts by means of a 11 x 11 electrode array with 360 x 540 microns resolution. Cathodal current pulses, 100-200 microA intensity and 1 ms duration, to avoid superposition of stimulus and activation potentials, were delivered from one of the electrode array and unipolar potentials were measured from all other electrodes. RESULTS AND DISCUSSION: a) During stimulus, negative equipotential lines were elliptic along fibers, as expected, but for a 2 mm circular region at the pacing site. b) During 1-2 ms interval between stimulus offset and start of activation, equipotential lines became elliptic across fibers in the presence of the region directly excited by the stimulus field. Start of activation was either symmetric with isochrones initially circular around the pacing site and then elliptic along fibers, or asymmetric initiating at only one side of the pacing site across fibers with isochrones elliptic along fibers. In the latter case, the wave front was blocked through the refractory region directly excited by the stimulus field, subdivided into two wings which collided and merged at the opposite side, giving rise to a plane wave front propagating across fibers away from the pacing site. CONCLUSIONS: High spatial resolution epicardial potential mapping reveals the existence of the virtual cathode and its influence on impulse initiation and conduction. The unexpected existence of a region of conduction block at the pacing site, due to spatial asymmetry of normal cardiac tissue which enhances activation threshold at one of the two sides of the virtual cathode, is intriguing since it is one of the requirements for reentry of conduction in the presence of a circuit with decreased conduction velocity and short duration of refractory period.