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Journal Article
Research Support, Non-U.S. Gov't
Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease.
New England Journal of Medicine 2003 November 7
BACKGROUND: In patients with sporadic Creutzfeldt-Jakob disease, pathologic disease-associated prion protein (PrPSc) has been identified only in the central nervous system and olfactory-nerve tissue. Understanding the distribution of PrPSc in Creutzfeldt-Jakob disease is important for classification and diagnosis and perhaps even for prevention.
METHODS: We used a highly sensitive method of detection--involving the concentration of PrPSc by differential precipitation with sodium phosphotungstic acid, which increased the sensitivity of Western blot analysis by up to three orders of magnitude--to search for PrPSc in extraneural organs of 36 patients with sporadic Creutzfeldt-Jakob disease who died between 1996 and 2002.
RESULTS: PrPSc was present in the brain tissue of all patients. In addition, we found PrPSc in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrPSc in both spleen and muscle specimens. Patients with extraneural PrPSc had a significantly longer duration of disease and were more likely to have uncommon molecular variants of sporadic Creutzfeldt-Jakob disease than were patients without extraneural PrPSc.
CONCLUSIONS: Using sensitive techniques, we identified extraneural deposition of PrPSc in spleen and muscle samples from approximately one third of patients who died with sporadic Creutzfeldt-Jakob disease. Extraneural PrPSc appears to correlate with a long duration of disease.
METHODS: We used a highly sensitive method of detection--involving the concentration of PrPSc by differential precipitation with sodium phosphotungstic acid, which increased the sensitivity of Western blot analysis by up to three orders of magnitude--to search for PrPSc in extraneural organs of 36 patients with sporadic Creutzfeldt-Jakob disease who died between 1996 and 2002.
RESULTS: PrPSc was present in the brain tissue of all patients. In addition, we found PrPSc in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrPSc in both spleen and muscle specimens. Patients with extraneural PrPSc had a significantly longer duration of disease and were more likely to have uncommon molecular variants of sporadic Creutzfeldt-Jakob disease than were patients without extraneural PrPSc.
CONCLUSIONS: Using sensitive techniques, we identified extraneural deposition of PrPSc in spleen and muscle samples from approximately one third of patients who died with sporadic Creutzfeldt-Jakob disease. Extraneural PrPSc appears to correlate with a long duration of disease.
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