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Volume 21, Number 5—May 2015
CME ACTIVITY - Perspective

Recent US Case of Variant Creutzfeldt-Jakob Disease—Global Implications

Atul MaheshwariComments to Author , Michael Fischer, Pierluigi Gambetti, Alicia Parker, Aarthi Ram, Claudio Soto, Luis Concha-Marambio, Yvonne Cohen, Ermias D. Belay, Ryan A. Maddox, Simon Mead, Clay Goodman, Joseph S. Kass, Lawrence B. Schonberger, and Haitham M. Hussein
Author affiliations: Baylor College of Medicine, Houston, Texas, USA (A. Maheshwari, A. Parker, A. Ram, C. Goodman, J.S. Kass); Harris Health System, Houston (A. Maheshwari, A. Parker, A. Ram, J.S. Kass); Texas Department of State Health Services, Austin, Texas, USA (M. Fischer); Case Western Reserve University School of Medicine, Cleveland, Ohio, USA (P. Gambetti, Y. Cohen); University of Texas Medical School at Houston, Houston (C. Soto, L. Concha-Marambio); Universidad de los Andes, Santiago, Chile (L. Concha-Marambio); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (E.D. Belay, R.A. Maddox, L.B. Schonberger); University College London Institute of Neurology, London, UK (S. Mead); HealthPartners Clinics & Services, St. Paul, Minnesota, USA (H.M. Hussein)

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Figure 4

Results of biochemical testing of a US patient with variant Creutzfeldt-Jakob disease (vCJD). A) Immunoblot of vCJD patient and controls. All the PK-treated preparations show similar electrophoretic profiles characterized by 3 bands displaying different mobilities according to number of the linked sugar moieties. The samples from this case and another vCJD case used as positive control (third lane) show the overrepresentation of the diglycosylated band, whereas in sCJD cases, the monoglycosylate

Figure 4. Results of biochemical testing of a US patient with variant Creutzfeldt-Jakob disease (vCJD). A) Immunoblot of vCJD patient and controls. All the PK-treated preparations show similar electrophoretic profiles characterized by 3 bands displaying different mobilities according to number of the linked sugar moieties. The samples from this case and another vCJD case used as positive control (third lane) show the overrepresentation of the diglycosylated band, whereas in sCJD cases, the monoglycosylated band is the most prominent. In both vCJD cases, the unglycosylated band co-migrates with type 2 (sixth lane) as indicated by the type 1 and 2 controls. The PK-untreated preparation (first lane) is used as control of PK digestion. Total brain homogenate, antibody 3F4. B) PrPSc detection in urine by protein misfolding cyclic amplification (PMCA). A urine sample from the patient was processed as previously described (6), and the supernatant fraction was run in duplicate (S1, S2). Samples were subjected to 96 PMCA cycles in the presence of 10% TgHuM brain homogenate, used as the substrate for PMCA. PrPSc signal was assessed by Western blot after PK digestion. As a positive control, vCJD brain homogenate was spiked at 10−5, 10−7, and 10−9 dilutions into urine from a healthy person and processed at the same time and in the same manner for PMCA. Lane C, PMCA-negative control (no sample); lane H, urine from a healthy person; sCJD, urine from an sCJD patient. CJD, Creutzfeldt-Jakob disease; Contr, control; MonoGly, monoglycosylated; NBH, normal brain homogenate without PK treatment used as an electrophoretic migration marker; Pres, present; PK, proteinase K; PrPSc, scrapie prion protein; sCJD, sporadic CJD; Unglyc, unglycosylated.

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