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OCR for page 259
PLATE 2-1 Depiction of the three-dimensional structure of the intact human prion
protein, PrP (23-230~. The a-helices are orange, the p-sheets blue. The segments
with nonregular secondary structure within the C-te'lllinal domain are yellow. Yellow
dots represent the flexibly disordered tail composed of residues 23-121. Reprinted
from Zahn et al. (2000) with permission from Proceedings of the National Academy
of the United States (2000~. Copyright 2000, Proceedings of the National Academy
of the United States.
OCR for page 260
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PLATE 2-2 Hypothetical models of PrP 27-30, the pro/ease-resistant segment of
PrPSc. (a) Three PrP 27-30 polypeptide models scaled and positioned to reflect the
presumed structure of the crystal in the background. Each polypeptide has three p-
sheet regions (blue) and two a-helices (red). The background is an electron micrograph
of a two-dimensional crystal of PrP 27-30 after image processing. (b) A side view of
the hypothesized structure of a short segment of a scrapie-associated fibril. Multiple
sets of PrP 27-30 polypeptide trimers, viewed from above in (a), are stacked here to
form part of a rod-shaped fibril.
SOURCES: electron micrograph: H. Wille, Institute for Neurodegenerative Diseases,
University of California, San Francisco, July 2003; models: C. Govaerts, Department
of Cellular and Molecular Pharmacology, University of California, San Francisco,
July 2003.
OCR for page 261
Normal sCJ :) vCUD
PLATE 4-1 The results of hematoxylin and eosin (HOE) staining (top row) and of
immunohistochemical staining (IHC) of PrP (bottom row) are visible in
microphotography of human brain tissue from a normal brain, the brain of a patient
with sCID, and the brain of a patient with vCID. Top row: The white spaces in sCTD
and vCID tissue are vacuoles, a sign of neurodegeneration described as spongiform.
In sCTD, the vacuoles are minute and evenly distributed; by contrast, in vCID, they
are relatively large and mainly clustered around plaques in formations commonly
called florid plaques or daisy plaques the hallmark of vCID. Bottom row: The IHC
technique used on these tissues stains PrP brown and removes PrPC, hence the absence
of staining in normal tissue. The fine, ubiquitous brown stain in sCID tissue indicates
a fairly even distribution of PrPSC, whereas the spotty, intense brown stains in vCJD
tissue reflect an uneven distribution of the protein, whichhas accumulated in plaques.
SOURCE: I. Ironside, National CID Surveillance Center, Edinburgh, and P. Gambetti,
National Prion Disease Pathology Surveillance Center, Cleveland, Ohio, September
2003.
OCR for page 262
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