{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:32:05Z","timestamp":1789205525523,"version":"build-2803163510"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,12,10]],"date-time":"2010-12-10T00:00:00Z","timestamp":1291939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anonymous screening of lymphoreticular tissues removed during routine surgery has been applied to estimate the UK population prevalence of asymptomatic vCJD prion infection. The retrospective study of Hilton <jats:italic>et al<\/jats:italic>(<jats:italic>J Pathol<\/jats:italic> 2004; 203: 733\u2013739) found accumulation of abnormal prion protein in three formalin\u2010fixed appendix specimens. This led to an estimated UK prevalence of vCJD infection of \u223c1 in 4000, which remains the key evidence supporting current risk reduction measures to reduce iatrogenic transmission of vCJD prions in the UK. Confirmatory testing of these positives has been hampered by the inability to perform immunoblotting of formalin\u2010fixed tissue. Animal transmission studies offer the potential for \u2018gold standard\u2019 confirmatory testing but are limited by both transmission barrier effects and known effects of fixation on scrapie prion titre in experimental models. Here we report the effects of fixation on brain and lymphoreticular human vCJD prions and comparative bioassay of two of the three prevalence study formalin\u2010fixed, paraffin\u2010embedded (FFPE) appendix specimens using transgenic mice expressing human prion protein (PrP). While transgenic mice expressing human PrP 129M readily reported vCJD prion infection after inoculation with frozen vCJD brain or appendix, and also FFPE vCJD brain, no infectivity was detected in FFPE vCJD spleen. No prion transmission was observed from either of the FFPE appendix specimens. The absence of detectable infectivity in fixed, known positive vCJD lymphoreticular tissue precludes interpreting negative transmissions from vCJD prevalence study appendix specimens. In this context, the Hilton <jats:italic>et al<\/jats:italic> study should continue to inform risk assessment pending the outcome of larger\u2010scale studies on discarded surgical tissues and autopsy samples. Copyright \u00a9 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2821","type":"journal-article","created":{"date-parts":[[2010,11,11]],"date-time":"2010-11-11T08:17:13Z","timestamp":1289463433000},"page":"511-518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study"],"prefix":"10.1002","volume":"223","author":[{"given":"Jonathan DF","family":"Wadsworth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Dalmau\u2010Mena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Joiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M","family":"Linehan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"O'Malley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Brandner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel A","family":"Asante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W","family":"Ironside","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Hilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,10]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)91412-9"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/383685a0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/38925"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/39057"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf653"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05128-4"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.048660"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2007.02.010"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2009.09.018"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-3-4"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.18.10248"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/66.1.161"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.21.10106-10112.2001"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2510-2517.2002"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-008-0035-8"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2004.0017"},{"key":"e_1_2_7_18_2","unstructured":"SEAC. 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