38 results on '"Limido, L"'
Search Results
2. An atypical case of sporadic fatal insomnia
- Author
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Priano, L., Giaccone, G., Mangieri, M., Albani, G., Limido, L., Brioschi, A., Pradotto, L., Orsi, L., Mortara, P., Fociani, P., Mauro, A., and Tagliavini, F.
- Subjects
Insomnia -- Research ,Insomnia -- Physiological aspects ,Prion diseases -- Research ,Prion diseases -- Physiological aspects ,Health ,Psychology and mental health - Published
- 2009
3. A novel phenotype of sporadic Creutzfeldt-Jakob disease
- Author
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Giaccone, G., Di Fede, G., Mangieri, M., Limido, L., Capobianco, R., Suardi, S., Grisoli, M., Binelli, S., Fociani, P., Bugiani, O., and Tagliavini, F.
- Subjects
Creutzfeldt-Jakob disease -- Genetic aspects ,Creutzfeldt-Jakob disease -- Diagnosis ,Creutzfeldt-Jakob disease -- Case studies ,Prions -- Health aspects ,Prions -- Genetic aspects ,Phenotype -- Analysis ,Health ,Psychology and mental health - Published
- 2007
4. Studio clinico, neuropatologico e bio-molecolare della malattia di Creutzfeldt-Jakob associata a mutazione V210I del gene della proteina prionica
- Author
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FOGLIA C, NIGRO M, PUOTI, Gianfranco, PISCOSQUITO G, CANDELARESI P, GARGIULO MG, ANZILOTTI S, DI FEDE G, MANGIERI M, LIMIDO L, GIACCONE G, ROSSI G, TAGLIAVINI F, COTRUFO R., COPPOLA, Cinzia, Foglia, C, Nigro, M, Puoti, Gianfranco, Coppola, Cinzia, Piscosquito, G, Candelaresi, P, Gargiulo, Mg, Anzilotti, S, DI FEDE, G, Mangieri, M, Limido, L, Giaccone, G, Rossi, G, Tagliavini, F, and Cotrufo, R.
- Published
- 2009
5. The epsilon isoform of 14-3-3 protein is a component of the prion protein amyloid deposits of Gerstmann-Sträussler-Scheinker disease
- Author
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DI FEDE G., GIACCONE G., LIMIDO L., MANGERI M., SUARDI S., PUOTI, Gianfranco, MORBIN M., MAZZOLENI G., GHETTI B., TAGLIAVINI F., DI FEDE, G., Giaccone, G., Limido, L., Mangeri, M., Suardi, S., Puoti, Gianfranco, Morbin, M., Mazzoleni, G., Ghetti, B., and Tagliavini, F.
- Subjects
Amyloid ,Prion protein ,mental disorders ,14-3-3 ,Creutzfeldt-Jakob disease ,nervous system diseases - Abstract
The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic events, such as transduction pathway modulation, cell cycle control, and apoptosis. Seven isoforms have been identified that are abundant in the brain, preferentially localized in neurons. Remarkable increases in 14-3-3 are seen in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease (CJD), and it has been found in pathologic inclusions of several neurodegenerative diseases. Moreover, the zeta isoform has been detected in prion protein (PrP) amyloid deposits of CJD patients. To further investigate the cerebral distribution of 14-3-3 in prion-related encephalopathies, we carried out an immunohistochemical and biochemical analysis of brain tissue from patients with Gerstmann-Sträussler-Scheinker disease (GSS) and sporadic, familial and acquired forms of CJD, using specific antibodies against the seven 14-3-3 isoforms. The study showed a strong immunoreactivity of PrP amyloid plaques of GSS patients for the 14-3-3 epsilon isoform, but not for the other isoforms. The epsilon isoform of 14-3-3 was not found in PrP deposits of CJD. These results indicate that the epsilon isoform of 14-3-3 is a component of PrP amyloid deposits of GSS and suggest that this is the sole 14-3-3 isoform specifically involved in the neuropathologic changes associated with this disorder.
- Published
- 2007
6. Experimental Therapy with Quinacrine in Creutzfeldt-Jakob disease
- Author
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PUOTI, Gianfranco, GIACCONE G, TAGLIAVINI F, DE ANGELIS G, DI FEDE G, LIMIDO L, TUCCI C, SCALELLA G, MANGIERI M, BUGIANI O. AND COTRUFO R., Puoti, Gianfranco, Giaccone, G, Tagliavini, F, DE ANGELIS, G, DI FEDE, G, Limido, L, Tucci, C, Scalella, G, Mangieri, M, and Bugiani, O. AND COTRUFO R.
- Published
- 2004
7. SPORADIC CEREUTZFELDT-JAKOB DISEASE WITH MM1-TYPE PRION PROTEIN AND PLAQUES
- Author
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PUOTI, Gianfranco, LIMIDO L, COTRUFO R, DI FEDE G, TAGLIAVINI F., Puoti, Gianfranco, Limido, L, Cotrufo, R, DI FEDE, G, and Tagliavini, F.
- Published
- 2004
8. Creutzfeldt-Jakob disease (CJD) associated with V210I PRNP mutation: phenotypic and molecular genetic analysis
- Author
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PUOTI, Gianfranco, DI FEDE G, MANGIERI M, LIMIDO L, GIACCONE G, ROSSI G, COTRUFO R, BUGIANI O, TAGLIAVINI F., Puoti, Gianfranco, DI FEDE, G, Mangieri, M, Limido, L, Giaccone, G, Rossi, G, Cotrufo, R, Bugiani, O, and Tagliavini, F.
- Published
- 2003
9. MM2-Thalamic Creutzfeldt-Jacob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain
- Author
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Moda, F., Suardi, S., Di Fede, G., Indaco, A., Limido, L., Vimercati, C., Ruggerone, M., Campagnani, I., Langeveld, J.P.M., Terruzzi, A., Brambilla, A., Zerbi, P., Fociani, P., Bishop, T., Will, G.W., Manson, J.C., Giaccone, G., and Tagliavini, F.
- Subjects
prpsc types ,animal diseases ,brain ,scrapie ,coexistence ,degeneration ,Bacteriology, Host Pathogen Interaction & Diagnostics ,nervous system diseases ,cooccurrence ,classification ,variant ,mental disorders ,Bacteriologie, Host Pathogen Interactie & Diagnostiek ,sporadic fatal insomnia ,protein - Abstract
In CreutzfeldtJakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrPSc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrPSc are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrPSc. Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrPSc, a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form.
- Published
- 2012
10. Results of Sacral Nerve Modulation For the Treatment of Bladder Dysfunctions In Multiple Sclerosis Patients
- Author
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Andretta, E., Ostardo, E., Simeone, Claudio, Signorello, D., Pastorello, M., Campo, C., Limido, L., and Bastianello, P.
- Published
- 2009
11. Pre-symptomatic detection of prions by cyclic amplification of protein misfolding
- Author
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Castilla, Joaquín [0000-0002-2216-1361], Soto, Claudio, Anderes, L., Suardi, S., Cardone, Franco, Castilla, Joaquín, Frossard, M. J., Peano, S., Saa, P., Limido, L., Carbonatto, M., Ironside, James W., Torres, J. M., Pocchiari, M., Tagliavini, F., Castilla, Joaquín [0000-0002-2216-1361], Soto, Claudio, Anderes, L., Suardi, S., Cardone, Franco, Castilla, Joaquín, Frossard, M. J., Peano, S., Saa, P., Limido, L., Carbonatto, M., Ironside, James W., Torres, J. M., Pocchiari, M., and Tagliavini, F.
- Abstract
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders affecting humans and animals. At present, it is not possible to recognize individuals incubating the disease before the clinical symptoms appear. We investigated the effectiveness of the "Protein Misfolding Cyclic Amplification" (PMCA) technology to detect the protease-resistance disease-associated prion protein (PrPres) in pre-symptomatic stages. PMCA allowed detection of PrPres in the brain of pre-symptomatic hamsters, enabling a clear identification of infected animals as early as two weeks after inoculation. Furthermore, PMCA was able to amplify minute quantities of PrPres from a variety of experimental and natural TSEs. Finally, PMCA allowed the demonstration of PrPres in an experimentally infected cow 32 month post-inoculation, that did not show clinical signs and was negative by standard Western blot analysis. Our findings indicate that PMCA may be useful for the development of an ultra-sensitive diagnostic test to minimize the risk of further propagation of TSEs. © 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
- Published
- 2005
12. 276 Sacral nerve stimulation in non-obstructive urinary retention following surgery for deep endometriosis
- Author
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Pastorello, M., primary, Ballario, R., additional, Limido, L., additional, Andretta, E., additional, and Molon, A., additional
- Published
- 2012
- Full Text
- View/download PDF
13. A novel phenotype of sporadic Creutzfeldt-Jakob disease
- Author
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Giaccone, G, primary, Di Fede, G., additional, Mangieri, M., additional, Limido, L., additional, Capobianco, R., additional, Suardi, S., additional, Grisoli, M., additional, Binelli, S., additional, Fociani, P., additional, Bugiani, O., additional, and Tagliavini, F., additional
- Published
- 2009
- Full Text
- View/download PDF
14. Creutzfeldt-Jakob disease with a novel extra-repeat insertional mutation in the PRNP gene
- Author
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Pietrini, V., primary, Puoti, G., additional, Limido, L., additional, Rossi, G., additional, Di Fede, G., additional, Giaccone, G., additional, Mangieri, M., additional, Tedeschi, F., additional, Bondavalli, A., additional, Mancia, D., additional, Bugiani, O., additional, and Tagliavini, F., additional
- Published
- 2003
- Full Text
- View/download PDF
15. Evaluation of Quinacrine Treatment for Prion Diseases
- Author
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Barret, A., primary, Tagliavini, F., additional, Forloni, G., additional, Bate, C., additional, Salmona, M., additional, Colombo, L., additional, De Luigi, A., additional, Limido, L., additional, Suardi, S., additional, Rossi, G., additional, Auvré, F., additional, Adjou, K. T., additional, Salès, N., additional, Williams, A., additional, Lasmézas, C., additional, and Deslys, J. P., additional
- Published
- 2003
- Full Text
- View/download PDF
16. Creutzfeldt-Jakob disease with a novel extra-repeat insertional mutation in the PRNP gene
- Author
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Vladimiro Pietrini, Puoti, G., Limido, L., Rossi, G., Di Fede, G., Giaccone, G., Mangieri, M., Tedeschi, F., Bondavalli, A., Mancia, D., Bugiani, O., Tagliavini, F., Pietrini, V, Puoti, Gianfranco, Limido, L, Rossi, G, DI FEDE, G, Giaccone, G, Mangieri, M, Tedeschi, F, Bondavalli, A, Mancia, D, Bugiani, O, and Tagliavini, F.
- Subjects
Brain Chemistry ,Male ,Amyloid ,Heterozygote ,Tyrosine 3-Monooxygenase ,Prions ,Homozygote ,Immunoblotting ,Brain ,Electroencephalography ,tau Proteins ,Middle Aged ,Immunohistochemistry ,Polymerase Chain Reaction ,Creutzfeldt-Jakob Syndrome ,Prion Proteins ,14-3-3 Proteins ,Endopeptidases ,Mutation ,Humans ,Neurology (clinical) ,Protein Precursors - Abstract
—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 proteaseresistant PrP, similar to type 1 and type 2 of sCJD. The features suggest that this insertion is a pathogenic mutation.
17. Widespread distribution of PRPres in the brain and in peripheral tissues of an Italian patient with variant Creutzfeldt-Jakob disease (vCJD)
- Author
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Bugiani, O., Giaccone, G., Mangieri, M., Limido, L., Capobianco, R., Suardi, S., Di Fede, G., Carsana, L., Fociani, P., and Fabrizio Tagliavini
18. Experimental transmission of an atypical form of bovine spongiform encephalopathy
- Author
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Tagliavini, F., Capobianco, R., Casalone, C., Miccolo, C., Suardi, S., Mangieri, M., Limido, L., maria grazia bruzzone, Corona, C., Zanusso, G., Monaco, S., and Caramelli, M.
19. Experimental therapy with quinacrine in Creutzfeldt-Jakob disease
- Author
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Puoti, G., giorgio giaccone, Tagliavini, F., Angelis, G., Rossi, R., Limido, L., Tucci, C., Mangieri, M., and Cotrufo, R.
20. EXPERIMENTAL TRANMSISSION OF AN ATYPICAL FORM OF BOVINE SPONGIFORM ENCEPHALOPATHY.
- Author
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Tagliavini, F, Capobianco, R, Casalone, C, Miccolo, C, Suardi, S, Mangieri, M, Limido, L, Bruzzone, M G, Corona, C, Zanusso, G, Monaco, S, and Caramelli, M
- Published
- 2005
21. WIDESPREAD DISTRIBUTION OF PRPres IN THE BRAIN AND IN PERIPHERAL TISSUES OF AN ITALIAN PATIENT WITH VARIANT CREUTZFELDT-JAKOB DISEASE (vCJD).
- Author
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Bugiani, O, Giaccone, G, Mangieri, M, Limido, L, Capobianco, R, Suardi, S, Di Fede, G, Carsana, L, Fociani, P, and Tagliavini, F
- Published
- 2004
22. Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc
- Author
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Raffaella Capobianco, Giacomina Rossi, Silvia Suardi, Graziella Filippini, Roberto Cotrufo, Pietro Zerbi, Giuseppe Di Fede, Paolo Fociani, Michela Mangieri, Lucia Limido, Fabrizio Tagliavini, Gianfranco Puoti, Gabriella Marcon, Orso Bugiani, Giorgio Giaccone, Selina Iussich, Puoti, Gianfranco, Giaccone, G., Mangieri, M., Limido, L., Fociani, P., Zerbi, P., Suardi, S., Rossi, G., Iussich, S., Capobianco, R., DI FEDE, G., Marcon, G., Cotrufo, R., Filippini, G., Bugiani, O., Tagliavini, F., Puoti, G, Giaccone, G, Mangieri, M, Limido, L, Fociani, P, Zerbi, P, Suardi, S, Rossi, G, Iussich, S, Capobianco, R, DI FEDE, G, Marcon, Gabriella, Cotrufo, R, Filippini, G, and Bugiani, O
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Programmed cell death ,PrPSc Proteins ,animal diseases ,Blotting, Western ,Neuropathology ,Biology ,Creutzfeldt-Jakob Syndrome ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Degenerative disease ,medicine ,Humans ,Protein Isoforms ,Aged ,Aged, 80 and over ,Microglia ,Genetic heterogeneity ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Creutzfeldt-Jakob disease ,nervous system diseases ,Blot ,medicine.anatomical_structure ,nervous system ,Neurology ,Prion protein ,Western blot analysis ,Neuroglia ,Female ,Neurology (clinical) - Abstract
In prion-related encephalopathies, microglial activation occurs early and is dependent on accumulation of disease-specific forms of the prion protein (PrPSc) and may play a role in nerve cell death. Previously, we found that different types of PrPSc (i.e. type 1 and type 2) coexisted in approximately 25% of patients with sporadic Creutzfeldt-Jakob disease (CJD); and a close relationship was detected between PrPSc type, the pattern of PrP immunoreactivity, and extent of spongiform degeneration. To investigate whether microglial reaction is related to the biochemical type and deposition pattern of PrPSc, we carried out a neuropathologic and biochemical study on 26 patients with sporadic CJD, including all possible genotypes at codon 129 of the prion protein gene. By quantitative analysis, we demonstrated that strong microglial activation was associated with type 1 PrPSc and diffuse PrP immunoreactivity, whereas type 2 PrPSc and focal PrP deposits were accompanied by mild microglia reaction. These findings support the view that the phenotypic heterogeneity of sporadic CJD is largely determined by the physicochemical properties of distinct PrPSc conformers.
- Published
- 2005
23. The behavioural features of fatal familial insomnia: A new Italian case with pathological verification
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Lucia Limido, V. Garibotto, Mauro Manconi, Stefano F. Cappa, Luigi Ferini-Strambi, D Perani, Fabrizio Tagliavini, Sandro Iannaccone, Giorgio Giaccone, Marco Zucconi, Alessandra Marcone, Alberto Raggi, Michele Zamboni, Raggi, A, Perani, DANIELA FELICITA L., Giaccone, G, Iannaccone, S, Manconi, M, Zucconi, M, Garibotto, V, Marcone, A, Zamboni, M, Limido, L, Tagliavini, F, FERINI STRAMBI, Luigi, and Cappa, STEFANO FRANCESCO
- Subjects
Fatal familial insomnia ,medicine.medical_specialty ,musculoskeletal, neural, and ocular physiology ,Thalamus ,Sleep regulation ,Brain ,General Medicine ,Middle Aged ,medicine.disease ,Insomnia, Fatal Familial ,Non-rapid eye movement sleep ,nervous system diseases ,Italy ,mental disorders ,medicine ,Humans ,Female ,Wakefulness ,Presentation (obstetrics) ,Radionuclide Imaging ,Psychology ,Psychiatry ,Pathological ,psychological phenomena and processes - Abstract
We report a new, pathologically verified Italian case of fatal familial insomnia, whose clinical presentation was characterised by complex behavioural disturbances, suggesting wakefulness/NREM/REM combinations.
- Published
- 2009
24. Inter-laboratory assessment of PrPSc typing in creutzfeldt-jakob disease: a Western blot study within the NeuroPrion Consortium
- Author
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Silvio Notari, Stéphane Haïk, Herbert Budka, Petra Weber, Thomas Ströbel, Lucia Limido, Hans A. Kretzschmar, Agustín Rodríguez, James W. Ironside, Isidre Ferrer, Fabrizio Tagliavini, Mark Head, Heinz Schimmel, Piero Parchi, Jean Jacques Hauw, Parchi P., Notari S., Weber P., Schimmel H., Budka H., Ferrer I., Haik S., Hauw J.J., Head M.W., Ironside J.W., Limido L., Rodriguez A., Strobel T., Tagliavini F., and Kretzschmar H.A.
- Subjects
PrPSc Proteins ,animal diseases ,Blotting, Western ,Disease ,Computational biology ,Creutzfeldt-Jakob Syndrome ,Pathology and Forensic Medicine ,Molecular typing ,Western blot ,medicine ,Humans ,Typing ,Prion protein ,Inter-laboratory ,Research Articles ,Brain Chemistry ,medicine.diagnostic_test ,business.industry ,General Neuroscience ,Strain typing ,Laboratories, Hospital ,Virology ,nervous system diseases ,Neurology (clinical) ,Spongiform encephalopathy ,business - Abstract
Molecular typing is of considerable importance for the surveillance and epidemiology of human transmissible spongiform encephalopathies (TSEs). It relies on the detection of distinct protease-resistant prion protein (PrP Sc ) core fragments that differ in molecular mass and/or glycoform ratio. In this collaborative study, we tested the inter-laboratory agreement in TSE molecular typing. Sixteen characterized brain specimens from sporadic TSEs and variant Creutzfeldt-Jakob disease (vCJD) cases were distributed blindly to seven laboratories for molecular characterization by a defined protocol and classification. Agreement between laboratories in the classification of samples was excellent. In particular, there were no differences in the distinction between PrP Sc type 1, type 2A, and type 2B with one exception, which eventually was identified as a case with types 1 and 2 co-occurrence. This shows that the general technique and particular classification system used here are robust and represent a reliable basis for diagnostic and epidemiologic purposes. The subtle further distinction of subtypes among type 1 and type 2 groups requires high-sensitivity gel electrophoresis protocols that are unsuitable for routine diagnostic needs and must be reserved for research investigations. Further research is necessary on the identification and significance of co-occurrence of PrP Sc types 1 and 2 within one brain.
- Published
- 2008
25. Brain protein preservation largely depends on the postmortem storage temperature: implications for study of proteins in human neurologic diseases and management of brain banks: a BrainNet Europe Study
- Author
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Rosa Blanco, Gabriel Santpere, Hans A. Kretzschmar, Lucia Limido, Berta Puig, Giorgio Giaccone, Margarita Carmona, Susana Boluda, Bjarne Krebs, Herbert Budka, Jeanne E. Bell, Rosaria Strammiello, Thomas Arzberger, Piero Parchi, Isidre Ferrer, Thomas Ströbel, Ferrer I., Santpere G., Arzberger T., Bell J., Blanco R., Boluda S., Budka H., Carmona M., Giaccone G., Krebs B., Limido L., Parchi P., Puig B., Strammiello R., Strobel T., and Kretzschmar H.
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Frontal cortex ,Time Factors ,Postmortem delay ,Brain bank ,Postmortem tissue sample ,Blotting, Western ,Protein degradation ,Human brain tissue ,Protein preservation ,Pathology and Forensic Medicine ,Andrology ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,medicine ,Humans ,Electrophoresis, Gel, Two-Dimensional ,Aged ,Gel electrophoresis ,Brain Chemistry ,Tissue Survival ,business.industry ,Temperature ,Brain ,Proteins ,Reduced intensity ,General Medicine ,Middle Aged ,Blot ,Europe ,Neurology ,Postmortem Changes ,Female ,Neurology (clinical) ,Tissue Preservation ,business - Abstract
The present study was designed to reveal protein modifications in control cases related with postmortem delay and temperature of storage in 3 paradigms in which the same postmortem tissue sample (frontal cortex) was frozen a short time after death or stored at 1°C, 4°C, or room temperature and then frozen at -80°C at different intervals. No evidence of protein degradation as revealed with monodimensional gel electrophoresis and Western blotting was observed in samples artificially stored at 1°C and then frozen at different intervals up to 50 hours after death. However, the levels of several proteins were modified in samples stored at 4°C and this effect was more marked in samples stored at room temperature. Two-dimensional gel electrophoresis and mass spectrometry further corroborated these observations and permitted the identification of other proteins vulnerable or resistant to postmortem delay. Finally, gel electrophoresis and Western blotting of sarkosyl-insoluble fractions in Alzheimer disease showed reduced intensity of phospho-tau-specific bands with postmortem delay with the effects being more dramatic when the brain samples were stored at room temperature for long periods. These results emphasize the necessity of reducing the body temperature after death to minimize protein degradation. © 2007 American Association of Neuropathologists, Inc.
- Published
- 2007
26. MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.
- Author
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Moda F, Suardi S, Di Fede G, Indaco A, Limido L, Vimercati C, Ruggerone M, Campagnani I, Langeveld J, Terruzzi A, Brambilla A, Zerbi P, Fociani P, Bishop MT, Will RG, Manson JC, Giaccone G, and Tagliavini F
- Subjects
- Adult, Animals, Glial Fibrillary Acidic Protein metabolism, Humans, Mice, Mice, Transgenic, Young Adult, Creutzfeldt-Jakob Syndrome genetics, Creutzfeldt-Jakob Syndrome pathology, Creutzfeldt-Jakob Syndrome transmission, Polymorphism, Genetic genetics, Prions genetics, Prions metabolism, Thalamus metabolism, Thalamus pathology
- Abstract
In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form., (© 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.)
- Published
- 2012
- Full Text
- View/download PDF
27. Inter-laboratory assessment of PrPSc typing in creutzfeldt-jakob disease: a Western blot study within the NeuroPrion Consortium.
- Author
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Parchi P, Notari S, Weber P, Schimmel H, Budka H, Ferrer I, Haik S, Hauw JJ, Head MW, Ironside JW, Limido L, Rodriguez A, Ströbel T, Tagliavini F, and Kretzschmar HA
- Subjects
- Brain Chemistry, Humans, Blotting, Western methods, Blotting, Western standards, Creutzfeldt-Jakob Syndrome classification, Laboratories, Hospital standards, PrPSc Proteins analysis
- Abstract
Molecular typing is of considerable importance for the surveillance and epidemiology of human transmissible spongiform encephalopathies (TSEs). It relies on the detection of distinct protease-resistant prion protein (PrP(Sc)) core fragments that differ in molecular mass and/or glycoform ratio. In this collaborative study, we tested the inter-laboratory agreement in TSE molecular typing. Sixteen characterized brain specimens from sporadic TSEs and variant Creutzfeldt-Jakob disease (vCJD) cases were distributed blindly to seven laboratories for molecular characterization by a defined protocol and classification. Agreement between laboratories in the classification of samples was excellent. In particular, there were no differences in the distinction between PrP(Sc) type 1, type 2A, and type 2B with one exception, which eventually was identified as a case with types 1 and 2 co-occurrence. This shows that the general technique and particular classification system used here are robust and represent a reliable basis for diagnostic and epidemiologic purposes. The subtle further distinction of subtypes among type 1 and type 2 groups requires high-sensitivity gel electrophoresis protocols that are unsuitable for routine diagnostic needs and must be reserved for research investigations. Further research is necessary on the identification and significance of co-occurrence of PrP(Sc) types 1 and 2 within one brain.
- Published
- 2009
- Full Text
- View/download PDF
28. The behavioural features of fatal familial insomnia: A new Italian case with pathological verification.
- Author
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Raggi A, Perani D, Giaccone G, Iannaccone S, Manconi M, Zucconi M, Garibotto V, Marcone A, Zamboni M, Limido L, Tagliavini F, Ferini-Strambi L, and Cappa SF
- Subjects
- Brain diagnostic imaging, Brain physiopathology, Female, Humans, Insomnia, Fatal Familial physiopathology, Italy, Middle Aged, Radionuclide Imaging, Brain pathology, Insomnia, Fatal Familial pathology, Insomnia, Fatal Familial psychology
- Abstract
We report a new, pathologically verified Italian case of fatal familial insomnia, whose clinical presentation was characterised by complex behavioural disturbances, suggesting wakefulness/NREM/REM combinations.
- Published
- 2009
- Full Text
- View/download PDF
29. A novel phenotype of sporadic Creutzfeldt-Jakob disease.
- Author
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Giaccone G, Di Fede G, Mangieri M, Limido L, Capobianco R, Suardi S, Grisoli M, Binelli S, Fociani P, Bugiani O, and Tagliavini F
- Abstract
An atypical case of sporadic Creutzfeldt-Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrP(Sc)) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype.
- Published
- 2009
- Full Text
- View/download PDF
30. The efficacy of tetracyclines in peripheral and intracerebral prion infection.
- Author
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De Luigi A, Colombo L, Diomede L, Capobianco R, Mangieri M, Miccolo C, Limido L, Forloni G, Tagliavini F, and Salmona M
- Subjects
- Animals, Cricetinae, Male, Mesocricetus, Brain Diseases drug therapy, Prion Diseases drug therapy, Tetracyclines therapeutic use
- Abstract
We have previously shown that tetracyclines interact with and reverse the protease resistance of pathological prion protein extracted from scrapie-infected animals and patients with all forms of Creutzfeldt-Jakob disease, lowering the prion titre and prolonging survival of cerebrally infected animals. To investigate the effectiveness of these drugs as anti-prion agents Syrian hamsters were inoculated intramuscularly or subcutaneously with 263K scrapie strain at a 10(-4) dilution. Tetracyclines were injected intramuscularly or intraperitoneally at the dose of 10 mg/kg. A single intramuscular dose of doxycycline one hour after infection in the same site of inoculation prolonged median survival by 64%. Intraperitoneal doses of tetracyclines every two days for 40 or 44 days increased survival time by 25% (doxycycline), 32% (tetracycline); and 81% (minocycline) after intramuscular infection, and 35% (doxycycline) after subcutaneous infection. To extend the therapeutic potential of tetracyclines, we investigated the efficacy of direct infusion of tetracyclines in advanced infection. Since intracerebroventricular infusion of tetracycline solutions can cause overt acute toxicity in animals, we entrapped the drugs in liposomes. Animals were inoculated intracerebrally with a 10(-4) dilution of the 263K scrapie strain. A single intracerebroventricular infusion of 25 microg/20 microl of doxycycline or minocycline entrapped in liposomes was administered 60 days after inoculation, when 50% of animals showed initial symptoms of the disease. Median survival increased of 8.1% with doxycycline and 10% with minocycline. These data suggest that tetracyclines might have therapeutic potential for humans.
- Published
- 2008
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- View/download PDF
31. Nestin, PDGFRbeta, CXCL12 and VEGF in glioma patients: different profiles of (pro-angiogenic) molecule expression are related with tumor grade and may provide prognostic information.
- Author
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Maderna E, Salmaggi A, Calatozzolo C, Limido L, and Pollo B
- Subjects
- Adult, Aged, Brain Neoplasms mortality, Brain Neoplasms pathology, Female, Glioma chemistry, Glioma mortality, Glioma pathology, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Staging, Nestin, Prognosis, Brain Neoplasms chemistry, Chemokine CXCL12 analysis, Glioma blood supply, Intermediate Filament Proteins analysis, Nerve Tissue Proteins analysis, Receptor, Platelet-Derived Growth Factor beta analysis, Vascular Endothelial Growth Factor A analysis
- Abstract
Angiogenesis is a key event in the natural progression of gliomas. Nestin, a marker for multipotential neuroepithelial stem cells, is detected in neuroepithelial tumors and in proliferating endothelial cells (ECs) and is involved in the early stages of lineage commitment, proliferation and differentiation. Nestin expression is correlated with proangiogenic chemokines (CXCL12 and its receptor CXCR4) and growth factors (VEGF, PDGF-B and its receptor PDGFRbeta). VEGF expression upregulates CXCR4 on endothelial cells, binding the chemokine SDF1/CXCL12 (Stromal Derived Factor) that has a role on angiogenesis and chemotaxis of endothelial cells; PDGF (platelet-derived growth factor) and PDGFRbeta are also crucial by increasing the expression of VEGF. We performed a retrospective study on the presence and role of nestin-expressing cells in 102 patients with glioma, relating the findings to VEGF, CXCL12, PDGFRbeta expression and to clinical outcome (time to tumor progression-TTP and survival time-ST). Our results suggest that in gliomas the detection of proliferating ECs expressing nestin correlates to histological malignancy grade and clinical outcome. Also, the expression of CXCL12 in low-grade gliomas was the only factor associated with a significantly shorter TTP, suggesting a role of this chemokine in angiogenic shift and/or disease progression.
- Published
- 2007
- Full Text
- View/download PDF
32. Conversion of the BASE prion strain into the BSE strain: the origin of BSE?
- Author
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Capobianco R, Casalone C, Suardi S, Mangieri M, Miccolo C, Limido L, Catania M, Rossi G, Di Fede G, Giaccone G, Bruzzone MG, Minati L, Corona C, Acutis P, Gelmetti D, Lombardi G, Groschup MH, Buschmann A, Zanusso G, Monaco S, Caramelli M, and Tagliavini F
- Subjects
- Animals, Brain metabolism, Cattle, Encephalopathy, Bovine Spongiform classification, Mice, Mice, Inbred C57BL, Mice, Transgenic, PrPC Proteins metabolism, PrPSc Proteins metabolism, Encephalopathy, Bovine Spongiform etiology, Encephalopathy, Bovine Spongiform transmission, PrPC Proteins isolation & purification, PrPSc Proteins isolation & purification
- Abstract
Atypical neuropathological and molecular phenotypes of bovine spongiform encephalopathy (BSE) have recently been identified in different countries. One of these phenotypes, named bovine "amyloidotic" spongiform encephalopathy (BASE), differs from classical BSE for the occurrence of a distinct type of the disease-associated prion protein (PrP), termed PrP(Sc), and the presence of PrP amyloid plaques. Here, we show that the agents responsible for BSE and BASE possess different biological properties upon transmission to transgenic mice expressing bovine PrP and inbred lines of nontransgenic mice. Strikingly, serial passages of the BASE strain to nontransgenic mice induced a neuropathological and molecular disease phenotype indistinguishable from that of BSE-infected mice. The existence of more than one agent associated with prion disease in cattle and the ability of the BASE strain to convert into the BSE strain may have important implications with respect to the origin of BSE and spongiform encephalopathies in other species, including humans.
- Published
- 2007
- Full Text
- View/download PDF
33. The epsilon isoform of 14-3-3 protein is a component of the prion protein amyloid deposits of Gerstmann-Sträussler-Scheinker disease.
- Author
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Di Fede G, Giaccone G, Limido L, Mangieri M, Suardi S, Puoti G, Morbin M, Mazzoleni G, Ghetti B, and Tagliavini F
- Subjects
- 14-3-3 Proteins analysis, 14-3-3 Proteins immunology, Antibody Specificity, Biomarkers analysis, Biomarkers metabolism, Brain pathology, Brain physiopathology, Creutzfeldt-Jakob Syndrome pathology, Creutzfeldt-Jakob Syndrome physiopathology, Diagnosis, Differential, Gerstmann-Straussler-Scheinker Disease pathology, Gerstmann-Straussler-Scheinker Disease physiopathology, Humans, Immunohistochemistry, Neurons metabolism, Neurons pathology, Plaque, Amyloid pathology, Predictive Value of Tests, 14-3-3 Proteins metabolism, Brain metabolism, Creutzfeldt-Jakob Syndrome metabolism, Gerstmann-Straussler-Scheinker Disease metabolism, Plaque, Amyloid metabolism, Prions metabolism
- Abstract
The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic events, such as transduction pathway modulation, cell cycle control, and apoptosis. Seven isoforms have been identified that are abundant in the brain, preferentially localized in neurons. Remarkable increases in 14-3-3 are seen in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease (CJD), and it has been found in pathologic inclusions of several neurodegenerative diseases. Moreover, the zeta isoform has been detected in prion protein (PrP) amyloid deposits of CJD patients. To further investigate the cerebral distribution of 14-3-3 in prion-related encephalopathies, we carried out an immunohistochemical and biochemical analysis of brain tissue from patients with Gerstmann-Sträussler-Scheinker disease (GSS) and sporadic, familial and acquired forms of CJD, using specific antibodies against the seven 14-3-3 isoforms. The study showed a strong immunoreactivity of PrP amyloid plaques of GSS patients for the 14-3-3 epsilon isoform, but not for the other isoforms. The epsilon isoform of 14-3-3 was not found in PrP deposits of CJD. These results indicate that the epsilon isoform of 14-3-3 is a component of PrP amyloid deposits of GSS and suggest that this is the sole 14-3-3 isoform specifically involved in the neuropathologic changes associated with this disorder.
- Published
- 2007
- Full Text
- View/download PDF
34. Brain protein preservation largely depends on the postmortem storage temperature: implications for study of proteins in human neurologic diseases and management of brain banks: a BrainNet Europe Study.
- Author
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Ferrer I, Santpere G, Arzberger T, Bell J, Blanco R, Boluda S, Budka H, Carmona M, Giaccone G, Krebs B, Limido L, Parchi P, Puig B, Strammiello R, Ströbel T, and Kretzschmar H
- Subjects
- Aged, Alzheimer Disease pathology, Blotting, Western methods, Brain pathology, Brain Chemistry physiology, Electrophoresis, Gel, Two-Dimensional methods, Europe, Female, Humans, Male, Middle Aged, Time Factors, Tissue Preservation, Alzheimer Disease metabolism, Brain metabolism, Postmortem Changes, Proteins metabolism, Temperature, Tissue Survival physiology
- Abstract
The present study was designed to reveal protein modifications in control cases related with postmortem delay and temperature of storage in 3 paradigms in which the same postmortem tissue sample (frontal cortex) was frozen a short time after death or stored at 1 degrees C, 4 degrees C, or room temperature and then frozen at -80 degrees C at different intervals. No evidence of protein degradation as revealed with monodimensional gel electrophoresis and Western blotting was observed in samples artificially stored at 1 degrees C and then frozen at different intervals up to 50 hours after death. However, the levels of several proteins were modified in samples stored at 4 degrees C and this effect was more marked in samples stored at room temperature. Two-dimensional gel electrophoresis and mass spectrometry further corroborated these observations and permitted the identification of other proteins vulnerable or resistant to postmortem delay. Finally, gel electrophoresis and Western blotting of sarkosyl-insoluble fractions in Alzheimer disease showed reduced intensity of phospho-tau-specific bands with postmortem delay with the effects being more dramatic when the brain samples were stored at room temperature for long periods. These results emphasize the necessity of reducing the body temperature after death to minimize protein degradation.
- Published
- 2007
- Full Text
- View/download PDF
35. Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc.
- Author
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Puoti G, Giaccone G, Mangieri M, Limido L, Fociani P, Zerbi P, Suardi S, Rossi G, Iussich S, Capobianco R, Di Fede G, Marcon G, Cotrufo R, Filippini G, Bugiani O, and Tagliavini F
- Subjects
- Adult, Aged, Aged, 80 and over, Blotting, Western, Creutzfeldt-Jakob Syndrome metabolism, Creutzfeldt-Jakob Syndrome pathology, Female, Humans, Immunohistochemistry, Male, Middle Aged, Protein Isoforms metabolism, Creutzfeldt-Jakob Syndrome physiopathology, Microglia pathology, PrPSc Proteins metabolism
- Abstract
In prion-related encephalopathies, microglial activation occurs early and is dependent on accumulation of disease-specific forms of the prion protein (PrPSc) and may play a role in nerve cell death. Previously, we found that different types of PrPSc (i.e. type 1 and type 2) coexisted in approximately 25% of patients with sporadic Creutzfeldt-Jakob disease (CJD); and a close relationship was detected between PrPSc type, the pattern of PrP immunoreactivity, and extent of spongiform degeneration. To investigate whether microglial reaction is related to the biochemical type and deposition pattern of PrPSc, we carried out a neuropathologic and biochemical study on 26 patients with sporadic CJD, including all possible genotypes at codon 129 of the prion protein gene. By quantitative analysis, we demonstrated that strong microglial activation was associated with type 1 PrPSc and diffuse PrP immunoreactivity, whereas type 2 PrPSc and focal PrP deposits were accompanied by mild microglia reaction. These findings support the view that the phenotypic heterogeneity of sporadic CJD is largely determined by the physicochemical properties of distinct PrPSc conformers.
- Published
- 2005
- Full Text
- View/download PDF
36. Pre-symptomatic detection of prions by cyclic amplification of protein misfolding.
- Author
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Soto C, Anderes L, Suardi S, Cardone F, Castilla J, Frossard MJ, Peano S, Saa P, Limido L, Carbonatto M, Ironside J, Torres JM, Pocchiari M, and Tagliavini F
- Subjects
- Animals, Brain metabolism, Cricetinae, Goats, Humans, Mesocricetus, Mice, Sheep, Prions isolation & purification, Protein Folding
- Abstract
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders affecting humans and animals. At present, it is not possible to recognize individuals incubating the disease before the clinical symptoms appear. We investigated the effectiveness of the "Protein Misfolding Cyclic Amplification" (PMCA) technology to detect the protease-resistance disease-associated prion protein (PrP(res)) in pre-symptomatic stages. PMCA allowed detection of PrP(res) in the brain of pre-symptomatic hamsters, enabling a clear identification of infected animals as early as two weeks after inoculation. Furthermore, PMCA was able to amplify minute quantities of PrP(res) from a variety of experimental and natural TSEs. Finally, PMCA allowed the demonstration of PrP(res) in an experimentally infected cow 32 month post-inoculation, that did not show clinical signs and was negative by standard Western blot analysis. Our findings indicate that PMCA may be useful for the development of an ultra-sensitive diagnostic test to minimize the risk of further propagation of TSEs.
- Published
- 2005
- Full Text
- View/download PDF
37. Sporadic Creutzfeldt-Jakob disease with MM1-type prion protein and plaques.
- Author
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Puoti G, Limido L, Cotrufo R, Di Fede G, and Tagliavini F
- Subjects
- Cerebellum chemistry, Frontal Lobe chemistry, Humans, PrPSc Proteins genetics, PrPSc Proteins isolation & purification, Cerebellum pathology, Creutzfeldt-Jakob Syndrome pathology, Frontal Lobe pathology, Immunoblotting methods, PrPSc Proteins classification
- Published
- 2004
- Full Text
- View/download PDF
38. Tetracyclines affect prion infectivity.
- Author
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Forloni G, Iussich S, Awan T, Colombo L, Angeretti N, Girola L, Bertani I, Poli G, Caramelli M, Grazia Bruzzone M, Farina L, Limido L, Rossi G, Giaccone G, Ironside JW, Bugiani O, Salmona M, and Tagliavini F
- Subjects
- Animals, Brain metabolism, Cattle, Creutzfeldt-Jakob Syndrome etiology, Cricetinae, Disease Models, Animal, Doxycycline analogs & derivatives, Doxycycline pharmacology, Encephalopathy, Bovine Spongiform etiology, Endopeptidase K metabolism, Gentamicins pharmacology, Guanidines pharmacology, Humans, Isothiocyanates pharmacology, Mesocricetus, PrPSc Proteins metabolism, PrPSc Proteins pathogenicity, Protein Denaturation, Scrapie etiology, Anti-Bacterial Agents pharmacology, PrPSc Proteins drug effects, Tetracycline pharmacology
- Abstract
Prion diseases are transmissible neurodegenerative disorders of humans and animals for which no effective treatment is available. Conformationally altered, protease-resistant forms of the prion protein (PrP) termed PrP(Sc) are critical for disease transmissibility and pathogenesis, thus representing a primary target for therapeutic strategies. Based on previous findings that tetracyclines revert abnormal physicochemical properties and abolish neurotoxicity of PrP peptides in vitro, we tested the ability of these compounds to interact with PrP(Sc) from patients with the new variant of Creutzfeldt-Jakob disease (vCJD) and cattle with bovine spongiform encephalopathy (BSE). The incubation with tetracycline hydrochloride or doxycycline hyclate at concentrations ranging from 10 microM to 1 mM resulted in a dose-dependent decrease in protease resistance of PrP(Sc). This finding prompted us to investigate whether tetracyclines affect prion infectivity by using an animal model of disease. Syrian hamsters were injected intracerebrally with 263K scrapie-infected brain homogenate that was coincubated with 1 mM tetracycline hydrochloride, 1 mM doxycycline hyclate, or vehicle solution before inoculation. Hamsters injected with tetracycline-treated inoculum showed a significant delay in the onset of clinical signs of disease and prolonged survival time. These effects were paralleled by a delay in the appearance of magnetic-resonance abnormalities in the thalamus, neuropathological changes, and PrP(Sc) accumulation. When tetracycline was preincubated with highly diluted scrapie-infected inoculum, one third of hamsters did not develop disease. Our data suggest that these well characterized antibiotics reduce prion infectivity through a direct interaction with PrP(Sc) and are potentially useful for inactivation of BSE- or vCJD-contaminated products and prevention strategies.
- Published
- 2002
- Full Text
- View/download PDF
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