A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. Case presentation: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. Conclusions: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

El pintor navarro Juan Ochoa de Arín (1600-1652) y su producción en Gipuzkoa

Investigación realizada dentro del Programa de Formación y Perfeccionamiento de Personal Investigador del Gobierno Vasco (2010-2013).

Juan Antonio de Zamacola: vida, obra y concepción esteticomusical

Tesis doctoral originalmente defendida en la Universidad de Deusto el 29-09-2000

Diseño e implementación de una herramienta web para el análisis y ayuda para la toma de decisiones de tecnologías de acceso.

[EN]Nowadays the use of web applications is a routine not only for companies but also for anyone interested in them. Thus, this market has risen hugely since the introduction of The Internet in our daily lives. Everyone has experienced the moment when you have to choose an access service and you do not know which one to select. At that moment, it is when this web application comes into action. It provides a useful interface in order to choose between access services as well as an analysis tool for the different access technologies in the market. Written in Java language, this web application is as simple as it can be, offering a complete interface that meets the needs of everyone, from the people at home to the largest company.

Carta enviada por Juan Bueso Roda a Justo Garate en 1939

1 carta (manuscrita) ; 225x330 mm

Las industrias prehistóricas del yacimiento de San Juan (Castro Urdiales, Cantabria) y su contextualización cronológica y cultural

[ES] El análisis directo de los ajuares lítico y óseo que se conservan del yacimiento de San juan, nos induce a plantear una hipótesis principal, según la cual la ocupación prehistórica del depósito debió producirse fundamentalmente durante el Aziliense, aunque no puede descartarse un origen anterior, en las últimas fases del Magdaleniense.

Copia del documento de la Jefatura del Sector de Ochandiano del Ejército Vasco, firmado por Juan Ibarrola, dando cuenta de la distribución de un batallón

Fecha: 31 de marzo de 1937 / Unidad de ínstalación: Carpeta Rectorado - D-1 / Nº de pág.: 2 (manuscritas)

Systematic and evolutionary studies of the terrestrial gastropods Helicoidea and Pyramidula

178 p.