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The reaction with two tyrosine nitration reagents, peroxynitrite and tetranitromethane was used to probe two conformational isomers of recombinant hamster prion protein. Results revealed that tyrosine nitration has identified two specific regions of the normal prion protein isoform that undergo a change in chemical environment upon conversion to a structure that is enriched in [beta]-sheet.

Prion diseases or transmissible spongiform encephalopathies are characterized histopathologically by the accumulation of prion protein (PrP) ranging from diffuse deposits to amyloid plaques. Moreover, pathologic PrP isoforms ([PrP.sup.Sc]) are detected by immunoblot analysis and used both as diagnostic markers of disease and as indicators of the presence of infectivity in tissues. It is not known which forms of PrP are associated with infectivity. To address this question, we performed bioassays using human brain extracts from two cases with phenotypically distinct forms of familial prion disease (Gerstmann-Straussler-Scheinker P102L). Both cases had PrP accumulations in the brain, but each had different [PrP.sup.sc] isoforms. Only one of the brains had spongiform degeneration. Tissue from this case transmitted disease efficiently to transgenic mice (Tg PrP101LL), resulting in spongiform encephalopathy. In contrast, inoculation of tissue from the case with no spongiform degeneration resulted in almost complete absence of disease transmission but elicited striking PrP-amyloid deposition in several recipient mouse brains. Brains of these mice failed to transmit any neurological disease on passage, but PrP-amyloid deposition was again observed in the brains of recipient mice. These data suggest the possible isolation of an infectious agent that promotes PrP amyloidogenesis in the absence of a spongiform encephalopathy. Alternatively, the infectious agent may be rendered nonpathogenic by sequestration in amyloid plaques, or PrP amyloid can seed amyloid accumulation in the brain, causing a proteinopathy that is unrelated to prion disease. Formation of PrP amyloid may therefore not necessarily be a reliable marker of transmissible spongiform encephalopathy infectivity. amyloid | Gerstmann-Straussler-Scheinker transmissible spongiform encephalopathy | neurodegeneration

Creutzfeldt-Jakob disease (CJD) surveillance relies on autopsy and neuropathologic evaluation. The 1990-2000 CJD autopsy rate in California was 21%. Most neurologists were comfortable diagnosing CJD (83%), but few pathologists felt [...]

Byline: A. Harder* (1), A. Gregor* (2), T. Wirth (3), F. Kreuz (4), W. J. Schulz-Schaeffer (5), O. Windl (6), M. Plotkin (7), H. Amthauer (7), K. Neukirch (6), H. A.. Kretzschmar (6), T. Kuhlmann (1), R. Braas (2), H. H. Hahne (2), K. Jendroska (8) Keywords: fatal familial insomnia; FFI; literature review; human prion disease Abstract: Abstract. Fatal familial insomnia (FFI) is a prion disease exhibiting the PRNP D178N/129M genotype. Features of this autosomal dominant illness are progressive insomnia, dysautonomia, myoclonus, cognitive decline and motor signs associated with thalamic nerve cell loss and gliosis. In contrast to the new variant of Creutzfeldt-Jakob disease (vCJD) the onset of FFI is in middle to late adulthood. We report two male patients who belong to a large German FFI kindred. They were examined clinically, and postmortem neuropathological examination was carried out in collaboration with the German reference centre for prion disease. Additionally, the prion protein gene (PRNP) was analysed. To identify further patients with disease onset under 30 years of age a comprehensive literature review was carried out. Two male patients presented with typical symptoms of FFI at the age of 23 and 24 years. In their kindred, the age of onset has never before been under 44 years of age. Our literature review identified five additional early onset cases who died at age 21 to 25 years. In all 22 reviewed FFI families the median manifestation age was 49.5 years. Although phenotypic variability of FFI is common, age of onset under 30 years has been considered to be a hallmark of vCJD with a mean manifestation at 27 years of age. Our findings underline that in addition to vCJD, FFI must be considered in cases of young-onset prion disease. This has considerable impact on clinical management and genetic counselling. Author Affiliation: (1) Institute of Neuropathology, Charite Humboldt University, Augustenburger Platz 1, 13353, Berlin, Germany (2) German Military Hospital, Berlin, Germany (3) Clinics of Erlabrunn GmbH, Erlabrunn, Germany (4) Institute of Clinical Genetics, Medical Faculty, Carl Gustav Carus Technical University Dresden, Dresden, Germany (5) Institute of Neuropathology, University Gottingen, Gottingen, Germany (6) Institute of Neuropathology, Ludwig Maximilians University Munich, CJD Surveillance, Munich, Germany (7) Dept. of Radiology, Charite Humboldt University, Berlin, Germany (8) Dept. of Neurology, Charite Humboldt University, Berlin, Germany Article History: Registration Date: 01/01/2004 Received Date: 10/07/2003 Accepted Date: 19/01/2004 Article note: * These two authors contributed equally

Byline: Arnaud Gacouin (1), Sylvain Lavoue (1), Thomas Signouret (1), Arnaud Person (1), Marie Dit Dinard (2), Nathalie Shpak (3), Remi Thomas (1) Keywords: Coma Toxic leucoencephalopathy Spongiform leucoencephalopathy Heroin intoxication Abstract: Objective.. To describe the clinical course and imaging findings in a young man who developed a spongiform leucoencephalopathy from heroin-vapour inhalation, and to discuss the treatments which may have contributed to the unexpected favourable outcome in this case. Design.. Case report. Setting.. Intensive care unit of a university teaching hospital. Patient.. A patient who developed a near fatal toxic leucoencephalopathy with impressive clinical recovery and reversible white matter changes on imaging. Measurements and results.. Successive computed tomography scans and magnetic resonance imaging over 7 months showed evolution from bilateral extensive involvement of the cerebral white matter to almost complete resolution accompanied by the development of periventricular lesions suggestive of necrosis. Despite the fact that the patient had stretching spasms for several days, the outcome was favourable with prolonged supportive care and antioxidant therapy by ubiquinone (coenzyme Q). Conclusion.. This case demonstrates that prolonged intensive care is of paramount importance in patients with spongiform leucoencephalopathy after inhalation of heated heroin, that abnormalities of cerebral white matter may be slowly regressive, and supports the use of coenzyme Q in severe forms of the disease. Author Affiliation: (1) Service des maladies infectieuses et de reanimation medicale, CHU Rennes, Hopital Pontchaillou, Rue Henri Le Guilloux-35033, Rennes, France (2) Service de Pharmacologie, CHU Rennes, France (3) Service de medecine physique et de readaptation, CHRU Rennes, France Article History: Received Date: 23/04/2002 Accepted Date: 23/01/2003 Article note: Electronic Publication

Byline: Albert Saiz (1), Carlos Nos (2), Jordi Yague (4), Angela Dominguez (3), Francesc Graus (1), Pilar Munoz (5) Keywords: Key words Creutzfeldt-Jakob disease; prion disease; 14-3-3 brain protein; prion protein gene; codon 129 genotype Abstract: The 14-3-3 assay in the CSF has a high predictive value for the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). Our objective was to analyse the trends in mortality and incidence rates of CJD in Catalonia, an autonomous community of Spain, setting the cut off point the date when the 14-3-3 assay was incorporated to our CJD surveillance system. Only definite and probable cases according to the criteria adapted from Masters and colleagues were included for the analysis. Familial cases were excluded after genetic analysis of the PrP gen. We found a quasi three-fold increase in the incidence and mortality rates for CJD after introduction of the 14-3-3 assay in our surveillance system in 1997 as compared with the period 1993--1996. Our findings suggest an improvement of case ascertainment in part due to the introduction of the 14-3-3 assay in the surveillance system. Author Affiliation: (1) Service of Neurology, Hospital Clinic, Villarroel 170, 0836 Barcelona, Spain Tel.: 3493-2275414 Fax: 3493-2275783 e-mail: asaiz@clinic.ub.es, ES (2) Clinical Neuroimmunology Unit, Hospitals Vall D'Hebron, Barcelona, Spain, ES (3) General Directorate of Public Health, Department of Health and Social Security, Generalitat de Catalunya, Barcelona, Spain, ES (4) Service of Immunology, Institut d'Investigacio Biomedica August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain, ES (5) Department of Statistics and Operational Research, Universitat Politecnica de Catalunya, Barcelona, Spain, ES Article note: Received: 30 June 2000 / Received in revised form: 19 January 2001 / Accepted: 24 January 2001

The sequence-dependent transmission barrier between hamster and mouse are determined. The findings suggest that the binding surface between the seed and monomer in the seeding reaction depends on the amino acid sequence of the seed.

RESEARCH A fatal neurodegenerative prion disease may now be easier to diagnose thanks to a urine test described last month (N. Engl. J. Med. 371, 530-539, 2014). The test made [...]

Author(s): Laura Bonetta [1] US scientists and government officials have been paying close attention to the bovine spongiform encephalopathy (BSE) crisis in Britain. 'It has enormous ramifications for the US [...]