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From: TSS ()
-------- Original Message -------- ------------------------------------------------------------------------ (PRLEAP.COM) CJD Aware! is a North Carolina-based, information Although Creutzfeldt-Jakob disease is a rare, neurological disorder, CJD Aware! has a CJD information packet with informational http://www.prleap.com/pr/4591/ Christy Brom ================ -------- Original Message -------- Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD Date: Thu, 28 Nov 2002 10:23:43 -0000 From: "Asante, Emmanuel A" To: Dear Terry, I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention. Thank you for your interest in the paper. In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc. I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes. Emmanuel Asante <> ____________________________________ Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now) ____________________________________ snip... full text ; http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm THE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger ] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [||] , Dominique Dormont*, and Jean-Philippe Deslys* et al, that The agent responsible http://www.pnas.org/cgi/content/full/041490898v1 Characterization of two distinct prion strains http://vir.sgmjournals.org/cgi/content/abstract/85/8/2471 Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Wadsworth JD, Joiner S, Hill AF, Campbell TA, Desbruslais M, Luthert PJ, Collinge J. MRC Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, W2 1PG, London, UK. BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) has a pathogenesis distinct from other forms of human prion disease: disease-related prion protein (PrP(Sc)) is readily detectable in lymphoreticular tissues. Quantitation of risk of secondary transmission, and targeting of risk reduction strategies, is limited by lack of knowledge about relative prion titres in these and other peripheral tissues, the unknown prevalence of preclinical vCJD, and a transmission barrier which limits the sensitivity of bioassay. We aimed to improve immunoblotting methods for high sensitivity detection of PrP(Sc) to investigate the distribution of PrP(Sc) in a range of vCJD tissues. METHODS: We obtained tissues at necropsy from four patients with neuropathologically confirmed vCJD and from individuals without neurological disease. Tissues were analysed by sodium phosphotungstic acid precipitation of PrP(Sc) and western blotting using high sensitivity enhanced chemiluminescence. FINDINGS: We could reliably detect PrP(Sc) in the equivalent of 50 nL 10% vCJD brain homogenate, with a maximum limit of detection equivalent to 5 nl. PrP(Sc) could be detected in tissue homogenates when present at concentrations 10(4)-10(5) fold lower than those reported in brain. Tonsil, spleen, and lymph node were uniformly positive for PrP(Sc) at concentrations in the range of 0.1-15% of those found in brain: the highest concentrations were consistently seen in tonsil. PrP(Sc) was readily detected in the retina and proximal optic nerve of vCJD eye at levels of 2.5 and 25%, respectively of those found in brain. Other peripheral tissues studied were negative for PrP(Sc) with the exception of low concentrations in rectum, adrenal gland, and thymus from a single patient with vCJD. vCJD appendix and blood (Buffy coat fraction) were negative for PrP(Sc) at this level of assay sensitivity. INTERPRETATION: We have developed a highly sensitive immunoblot method for detection of PrP(Sc) in vCJD tissues that can be used to provide an upper limit on PrP(Sc) concentrations in peripheral tissues, including blood, to inform risk assessment models. Rectal and other gastrointestinal tissues should be further investigated to assess risk of iatrogenic transmission via biopsy instruments. Ophthalmic surgical instruments used in procedures involving optic nerve and the posterior segment of the eye, in particular the retina, might represent a potential risk for iatrogenic transmission of vCJD. Tonsil is the tissue of choice for diagnostic biopsy and for population screening of surgical tissues to assess prevalence of preclinical vCJD infection within the UK and other populations. PMID: 11476832 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11476832 Gabor G. Kovacs, MD PhD 1 2, Elisabeth Lindeck-Pozza, MD 1, Leila 1Institute of Neurology, University of Vienna, and Austrian Reference 2National Institute of Psychiatry and Neurology, Budapest, Hungary 3Department of Pathology, School of Medicine, Federal University of Rio 4Department of Neurology, School of Medicine, Federal University of Rio 5Department of Neurology, School of Medicine, Federal University of Sao 6Institute of Neuropathology, University Hospital of Zürich, Zürich, email: Herbert Budka (h.budka@akh-wien.ac.at *Correspondence to Herbert Budka, Institute of Neurology, AKH 4J, Funded by: European Union (EU) Project; Grant Number: TSELAB QLK2-CT-2002-81523 EU Concerted Action PRIONET; Grant Number: QLK2-2000-CT-00837 Abstract Pathologicalprion protein (PrPSc) is the hallmark of prion diseases ------------------------------------------------------------------------ Received: 16 June 2003; Revised: 11 September 2003; Accepted: 11 Digital Object Identifier (DOI) 10.1002/ana.10813 About DOI http://www3.interscience.wiley.com/cgi-bin/abstract/106598055/ABSTRACT NINDS Inclusion Body Myositis Information Page http://www.ninds.nih.gov/disorders/inclusion_body_myositis/inclusion_body_myositis.htm 107 Vet Pathol 42:107 108 (2005) Letters to the Editor Editor: Absence of evidence is not always evidence of absence. In the article Failure to detect prion protein (PrPres) by immunohistochemistry in striated muscle tissues of animals experimentally inoculated with agents of transmissible spongiform encephalopathy, recently published in Veterinary Pathology (41:78 81, 2004), PrPres was not detected in striated muscle of experimentally infected elk, cattle, sheep, and raccoons by immunohistochemistry (IHC). Negative IHC, however, does not exclude the presence of PrPSc. For example, PrPres was detected in skeletal muscle in 8 of 32 humans with the prion disease, sporadic Creutzfeldt-Jakob disease (CJD), using sodium phosphotungstic acid (NaPTA) precipitation and western blot.1 The NaPTA precipitation, described by Wadsworth et al.,3 concentrates the abnormal isoform of the prion, PrPres, from a large tissue homogenate volume before western blotting. This technique has increased the sensitivity of the western blot up to three orders of magnitude and could be included in assays to detect PrPres. Extremely conspicuous deposits of PrPres in muscle were detected by IHC in a recent case report of an individual with inclusion body myositis and CJD.2 Here, PrPres was detected in the muscle by immunoblotting, IHC, and paraf- fin-embedded tissue blot. We would therefore caution that, in addition to IHC, highly sensitive biochemical assays and bioassays of muscle are needed to assess the presence or absence of prions from muscle in experimental and natural TSE cases. Christina Sigurdson, Markus Glatzel, and Adriano Aguzzi Institute of Neuropathology University Hospital of Zurich Zurich, Switzerland References 1 Glatzel M, Abela E, et al: Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 349(19):1812 1820, 2003 2 Kovacs GG, Lindeck-Pozza E, et al: Creutzfeldt-Jakob disease and inclusion body myositis: abundant diseaseassociated prion protein in muscle. Ann Neurol 55(1): 121 125, 2004 3 Wadsworth JDF, Joiner S, et al: Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immuno-blotting assay. Lancet 358:171 180, 2001.../// ALL animals for human/animal consumption must be tested for TSE. ALL human TSEs must be made reportable Nationally and Internationally... ######### https://listserv.kaliv.uni-karlsruhe.de/warc/bse-l.html ##########
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