Original Article
Extraneural Pathologic Prion Protein in Sporadic Creutzfeldt–Jakob Disease
N Engl J Med 2003; 349:1812-1820November 6, 2003
- Abstract
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.
Media in This Article
Figure 1
Western Blot Analysis of Phosphotungstate-Precipitated Pathologic Prion Protein (PrPSc) from Spleen and Muscle Samples from Patients with Sporadic Creutzfeldt–Jakob Disease (sCJD).Figure 2
Histopathological Findings in the Cerebellum of Patients with Sporadic Creutzfeldt–Jakob Disease and Peripheral Pathologic Prion Protein (PrPSc).Article Activity
- Article
Prion diseases are characterized by degeneration of central nervous tissue associated with the replication of a transmissible agent, a prion.1 Prions are mainly composed of an abnormal, partially protease-resistant conformer (PrPSc) of a cellular protein (PrPC).2 Although tissue damage occurs only in the central nervous system, the accumulation of PrPSc and prion infectivity are not necessarily confined to neural tissue in all prion diseases. In scrapie in sheep, chronic wasting disease in deer, and numerous animal models of prion diseases, prions invade the lymphoreticular system.3 PrPSc has also been reported in the skeletal muscle of mice with experimentally induced prion disease.4
The most common prion disease in humans is Creutzfeldt–Jakob disease, which has been classified as sporadic, familial, iatrogenic, or variant. The causation of sporadic Creutzfeldt–Jakob disease is unclear, whereas biochemical, histopathological, and epidemiologic evidence suggests that the variant form results from the transmission of bovine spongiform encephalopathy prions to humans.5,6 PrPSc accumulates in tonsils7 and other lymphoreticular organs8 of patients with variant Creutzfeldt–Jakob disease,9 whereas the sporadic form of the disease is not thought to target the lymphoreticular system.10 The allegedly unique involvement of the lymphoreticular system in variant Creutzfeldt–Jakob disease serves as a diagnostic criterion to distinguish variant from sporadic Creutzfeldt–Jakob disease and is one of the principal pieces of evidence that these forms represent two distinct disease entities.6 Refinements in the sensitivity of the methods of detection11 prompted us to reinvestigate the distribution of PrPSc in humans with sporadic Creutzfeldt–Jakob disease.
Methods
Collection of Samples
We collected central nervous system, spleen, and muscle samples at autopsy from a cohort of Swiss patients who died between 1996 and 2002: 36 patients with prion disease (36 brain specimens, 32 muscle specimens, and 28 spleen specimens), 10 with Alzheimer's disease (10 muscle and 8 spleen samples), and 9 patients without neurologic disorders (9 muscle and 9 spleen samples). The utmost care was taken to avoid contamination of extraneural samples with central nervous system tissue. All tissues were processed according to established guidelines regarding safety and ethics.
Detection of PrPSc in Extraneural Tissues
All procedures were carried out in biosafety level 3 facilities with strict adherence to safety guidelines. The method of precipitation with the use of sodium phosphotungstic acid was adapted from published protocols.8 We prepared 10 percent tissue homogenates (weight per volume) in 2 percent sarkosyl in sterile phosphate-buffered saline using a RiboLyser (Hybaid). Cellular debris was removed by centrifugation at 80×g for one minute in a microcentrifuge. Occasional residual debris was removed by additional centrifugation at 2700×g for five minutes. Supernatants (500 μl) were mixed with equal volumes of 2 percent sarkosyl in phosphate-buffered saline and incubated for 10 minutes at 37°C. Benzonase (Benzon nuclease, Merck) and magnesium chloride were added (final concentration, 50 units per milliliter and 1 mmol per liter, respectively), and the mixture was incubated under constant agitation for 30 minutes at 37°C.
Samples were adjusted to a final concentration of 0.3 percent phosphotungstate, incubated at 37°C for 30 minutes under constant agitation, and centrifuged at 15,800×g for 30 minutes in a microcentrifuge. The pellets were resuspended in 20 μl of phosphate-buffered saline with 0.1 percent sarkosyl. Samples were adjusted to a final concentration of 20 μg of proteinase K per milliliter and incubated at 37°C for 30 minutes. Digestion was terminated by the addition of protease inhibitors (Complete protease inhibitor cocktail, Boehringer Mannheim). Samples were boiled in loading buffer (125 mM TRIS sodium chloride, 4 percent sodium dodecyl sulfate, 20 percent glycerol, and 0.02 percent bromophenol blue), subjected to electrophoresis in 12 percent TRIS–glycine gels, and blotted on nitrocellulose membranes. Membranes were blocked with 5 percent Topblock (Jura) in phosphate-buffered saline with 0.05 percent Tween and then incubated overnight with a monoclonal antibody against PrP (3F4; dilution 1:5000).12
The samples were then incubated with an alkaline-phosphatase–conjugated secondary antibody (1:20,000) and examined with use of 2-chlor-5-(4-methoxyspiro{1,2-dioxetan-3,2'-(5'-chlor) tricycl[3.3.1.13,7]decan}-4-yl)-1-phenylphosphate dinatrium salt chemiluminescent substrate (Amersham) and a VersaDoc digital imager (model 5000, Bio-Rad). Each blot included appropriate positive and negative controls (10 μg or 100 μg of brain homogenate from a patient with sporadic Creutzfeldt–Jakob disease or a patient without a prion disease added to 50 mg of muscle or spleen specimen from a patient without a prion disease). All analyses were carried out and all but six samples were examined at least twice by independent investigators. Samples were deemed positive if proteinase K–resistant diglycosylated, monoglycosylated, and unglycosylated bands with electrophoretic motility indicative of PrPSc were unambiguously identified.
Detection of PrPSc in Neural Tissues
Western blot analysis was carried out as described previously.13 PrP glycoforms were quantified with use of a Kodak image station (model 440) or a VersaDoc digital imager (model 5000), and patients were typed according to the size of the protease-resistant core PrP fragment14 and the prevalence of glycoforms.15,16
Genetic Analysis
Genomic DNA was extracted from frozen tissues. Polymerase chain reaction and analysis of the entire coding region of the prion protein gene (PRNP) were performed with use of standard techniques and software (SeqScape, Applied Biosystems). In addition, codon 129 polymorphisms were identified by restriction-fragment–length polymorphism analysis.17
Histologic Analysis
Tissue was fixed with 4 percent buffered formalin, inactivated by exposure to 98 percent formic acid for one hour, and embedded in paraffin. Sections (3 μm) were subjected to conventional staining and to immunostaining for glial fibrillary acid protein (Dako) and PrP (monoclonal antibody 3F4) after hydrolytic autoclaving.
Results
We analyzed a total of 45 spleen specimens and 51 skeletal-muscle samples from 36 patients with histopathologically, biochemically, and genetically confirmed sporadic Creutzfeldt–Jakob disease (mean [±SD] age, 66.8±8.7 years; 20 men and 16 women); 10 patients with Alzheimer's disease (mean age, 76.2±4.6 years; 6 men and 4 women); and 9 patients without neurologic disease (mean age, 59±19.2 years; 5 men and 4 women). The age distribution, sex ratio, and duration of disease (mean, 5.0±4.6 months) of the cohort of patients with sporadic Creutzfeldt–Jakob disease did not differ significantly from those in published series.18
Accumulation of PrPSc in Spleen and Skeletal Muscle
Western blot analysis of protease-resistant prion protein after phosphotungstate precipitation showed PrPSc in 10 of 28 spleen samples and in 8 of 32 skeletal-muscle samples from the patients with sporadic Creutzfeldt–Jakob disease (Figure 1Figure 1
Western Blot Analysis of Phosphotungstate-Precipitated Pathologic Prion Protein (PrPSc) from Spleen and Muscle Samples from Patients with Sporadic Creutzfeldt–Jakob Disease (sCJD).). Three patients had PrPSc in both spleen and muscle (Table 1Table 1
Age at Onset and Duration of Disease in 15 Patients with Sporadic Creutzfeldt–Jakob Disease and Extraneural Pathologic Prion Protein (PrPSc).). Assays were repeated with independently homogenized tissue fragments: three spleen and three muscle samples always tested positive, whereas others yielded variable results (Table 1), possibly because of inhomogeneous peripheral distribution of PrPSc, as described previously.4,19 Control samples of spleen and muscle were assessed in parallel: none of them contained PrPSc (data not shown). Patients with PrPSc in spleen and patients without PrPSc in spleen did not differ significantly with respect to age (Table 2Table 2
Demographic Characteristics and Classification of Sporadic Creutzfeldt–Jakob Disease in Patients with and Those without Pathologic Prion Protein (PrPSc) in Spleen and Muscle Specimens.). However, patients with PrPSc only in spleen or in spleen or muscle or both had significantly longer intervals between the onset of clinical symptoms and death than did patients without extraneural PrPSc. Patients with PrPSc in muscle tended to be younger at death than patients without PrPSc in muscle (Table 2). None of the subgroups differed significantly with respect to the ratio of men to women.One patient with splenic PrPSc had received a cadaveric dura mater transplant more than 22 years before the onset of dementia. This case was deemed unlikely to represent iatrogenic transmission, since the incubation period would be longer than that in any other documented case of dura mater–associated transmission.20
Genetic Analysis of PRNP
We sequenced the entire open reading frame of PRNP from all patients with extraneural PrPSc and found no disease-associated mutations. The common methionine–valine polymorphism at codon 129 was analyzed in all 10 patients with splenic PrPSc and all 8 patients with muscle PrPSc as well as in 15 patients without splenic PrPSc and 21 patients without muscle PrPSc. We observed a tendency toward overrepresentation of heterozygosity for methionine and valine and homozygosity for valine among patients with splenic PrPSc, whereas the majority of patients with muscle PrPSc were homozygous for methionine (Table 2).
Histologic and Biochemical Analyses
Typical histopathological features of sporadic Creutzfeldt–Jakob disease, consisting of spongiform changes, neuronal loss, and gliosis, were present in all patients (Figure 2Figure 2
Histopathological Findings in the Cerebellum of Patients with Sporadic Creutzfeldt–Jakob Disease and Peripheral Pathologic Prion Protein (PrPSc).). The electrophoretic mobility of unglycosylated, protease-digested PrPSc (also called the core fragment size, which can be 21 kD for type 1 or 19 kD for type 2)14 allows for the stratification of Creutzfeldt–Jakob disease into subgroups with specific clinical features, which may be caused by different prion strains.6 A finer degree of stratification is attained by including information on the codon 129 genotype and patterns of cerebral deposition of PrPSc; accordingly, we assigned each patient in our series to one of seven proposed groups.18 This analysis indicated an overrepresentation of uncommon variants of sporadic Creutzfeldt–Jakob disease such as MM2C (homozygous for methionine, type 2, with cortical deposition) and MV2 (heterozygous, type 2) in patients with extraneural PrPSc (Table 2), suggesting that peripheral deposition of PrPSc may identify a biochemically or genetically unique subgroup of patients.Quantification of the relative prevalence of diglycosylated, monoglycosylated, and unglycosylated PrPSc is a further instrument for the biochemical characterization of PrPSc, which allows one to discriminate sporadic from variant Creutzfeldt–Jakob disease.16 This analysis did not uncover any unorthodox PrPSc glycotypes in patients with peripheral PrPSc (Figure 3Figure 3
Glycoform Profiles of Patients with Sporadic and Variant Creutzfeldt–Jakob Disease (CJD) According to the Presence or Absence of Peripheral Pathologic Prion Protein (PrPSc).): the distribution of brain glycotypes in patients with peripheral PrPSc was similar to that in other cohorts of patients with sporadic Creutzfeldt–Jakob disease.13 Distribution of PrPSc in Skeletal-Muscle Groups
Earlier studies in mice have shown that the PrPSc content may vary among muscle groups.4 In our series, the presence of PrPSc was not limited to specific muscle groups: PrPSc was found in four samples of pectoral muscle, two samples of psoas muscle, and two samples of intercostal muscle. It was absent in 10 pectoral-muscle specimens, 5 psoas-muscle specimens, 2 biceps-muscle specimens, and 4 intercostal-muscle specimens. In three patients without extraneural PrPSc, no information on the anatomical origin of muscle samples could be obtained.
Quantification of PrPSc in Extraneural Organs
In order to estimate the relative concentration of PrPSc in extraneural organs, we compared the intensity of proteinase K–digested Western blot signals with calibration curves obtained by diluting brain homogenate from a patient with Creutzfeldt–Jakob disease with muscle or spleen homogenate from a patient without a prion disease. Despite considerable variations in individual spleen and muscle specimens, the signal intensity of peripheral PrPSc was generally similar to that obtained when 10 μg of brain homogenate from a patient with sporadic Creutzfeldt–Jakob disease was diluted with 50 mg of spleen or muscle from a patient without a prion disease (Figure 1). Therefore, we estimate that the levels of PrPSc in extraneural organs are lower by a factor of approximately 1×10–4 than those typically found in the central nervous system of patients with sporadic Creutzfeldt–Jakob disease.
Discussion
Previous studies did not detect PrPSc in the tonsils, spleen, lymph nodes,10 or appendix of patients with sporadic Creutzfeldt–Jakob disease.21 However, after a systematic search for PrPSc in extraneural organs of patients referred to the Swiss National Reference Center for Prion Diseases, we found that extraneural deposits of PrPSc are much more frequent in patients with sporadic Creutzfeldt–Jakob disease than previously thought. There may be several reasons why this fact was not previously recognized.
First, our series of patients is much larger than previous ones. Second, repeated homogenization of distinct fragments of extraneural organs identified substantial variations in the PrPSc content of these tissues. Generic problems related to the technical reproducibility of our results are unlikely to account for this variation, since control samples consisting of brain homogenate from a patient with sporadic Creutzfeldt–Jakob disease diluted with muscle or spleen homogenate from a patient without a prion disease did not have such variations (data not shown). Instead, the presence of variability suggests that the distribution of PrPSc is not homogeneous in single muscle fibers and single splenic germinal centers. This finding parallels the finding that prion infectivity titers vary in spleen22 and muscle4 samples from experimentally infected mice.
Third, PrPSc levels in spleen and muscle were lower than those in brain by a factor of 1×10–4: extraneural PrPSc was never detectable by plain Western blot analysis (data not shown) and could be visualized only after sodium phosphotungstic acid precipitation, an approach that increases the sensitivity of Western blot analysis by three orders of magnitude by preferentially precipitating PrPSc from tissue homogenates.8,11 Although this method is not suitable for use with very small biopsy specimens (less than 100 mg), it is ideal for situations in which sample size is not a limiting factor.
Previous studies suggested the presence of abnormal PrP in the skeletal muscle of patients with inclusion-body myositis.23 However, this may represent denervation-dependent up-regulation of PrPC transcription.24 In one patient with coincident sporadic Creutzfeldt–Jakob disease and inclusion-body myositis, we found PrPSc levels that were 103 times as high as the levels in our study cohort, possibly because the overexpression of PrPC in muscle facilitates the deposition of PrPSc (Kovacs G: personal communication).
Does the presence of peripheral PrPSc correlate with any specific genetic, biochemical, or clinical factors? When plotting the incidence of codon 129 polymorphisms (MM, MV, or VV [homozygous for valine]), PrPSc core-fragment sizes (type 1, 21 kD, and type 2, 19 kD), and histologic characteristics (plaque and plaque-like lesions [P], cortical or synaptic deposits [C], or thalamic deposits [T]), we observed several uncommon phenotypes in patients with peripheral PrPSc, such as MM2C and MV2. In addition, one patient with PrPSc in lymphoid organs who was homozygous for valine at codon 129 could not be classified according to any of the existing schemes.18,25 These features may represent a new phenotype with atypical clinical signs,26 which we have termed VV1P because of the presence of plaque-like deposits of PrP in the cerebellum and a PrPSc core-fragment size of 21 kD.
The relative ratios of PrPSc glycoforms are different in sporadic and variant Creutzfeldt–Jakob disease. Glycotype analysis failed to reveal features specific to patients with peripheral PrPSc, and none of them had the glycoform distribution associated with variant Creutzfeldt–Jakob disease. Patients with splenic PrPSc had significantly longer durations of disease than did those without splenic PrPSc. Assuming that prions arise primarily in the central nervous system of these patients, one might speculate that protracted disease increases the likelihood of spillover of cerebral PrPSc to extraneural areas.
Although the amount of PrPSc found in spleen and muscle samples from patients with sporadic Creutzfeldt–Jakob disease was much lower than levels in lymphoid organs of patients with variant Creutzfeldt–Jakob disease,7 and the infectivity of prions from these tissues awaits verification, our findings arouse concern about the possibility of iatrogenic transmission of sporadic Creutzfeldt–Jakob disease. Brown et al. reported that extraneural tissues of patients with spongiform encephalopathy (including hereditary forms and kuru) occasionally transmitted disease when inoculated into nonhuman primates.27 Infectivity was detected in 2 of 4 lung-tissue samples, 4 of 35 liver specimens, 5 of 28 kidney specimens, 3 of 31 spleen samples, and 3 of 15 lymph-node samples.27 Five attempts to transmit the disease through the inoculation of skeletal muscle were not successful, possibly because the sample size was insufficient, because the infectivity of the samples was not uniform, or because transmission from human to nonhuman primates is not always highly efficient.
The causation of sporadic Creutzfeldt–Jakob disease is unknown. Some allegedly sporadic cases may in reality have an iatrogenic origin, and surgery of any kind was found to constitute a mild risk factor for sporadic Creutzfeldt–Jakob disease.28 Extensive epidemiologic surveys did not substantiate any risk of blood-borne transmission,29 suggesting that the presence of PrPSc in lymphoid organs whose cellular constituents migrate to and from blood may not lead to substantial contamination of blood donations by prions.
Many patients with sporadic Creutzfeldt–Jakob disease are subjected to extensive neurologic examinations in the prodromal stages, often including electromyography and muscle biopsies. The finding that PrPSc is prevalent in skeletal muscle reinforces calls for the use of single-use needle electrodes and of special protocols for the sterilization of surgical instruments used for muscle biopsies.
Our results suggest that muscle and lymph-node biopsies can be used as diagnostic procedures for sporadic Creutzfeldt–Jakob disease. Because of the unambiguous and extremely specific nature of the immunochemical detection of PrPSc, any positive results would firmly establish the diagnosis of Creutzfeldt–Jakob disease without the need for more invasive procedures. However, the diagnostic sensitivity of the detection of PrPSc in muscle-biopsy specimens is likely to be low, since less than one third of our patients were positive for PrPSc in muscle. We did not detect PrPSc in one muscle-biopsy specimen obtained because of suspected vasculitis 10 weeks before death in a patient with Creutzfeldt–Jakob disease (data not shown). The sensitivity of prion detection is likely to improve soon, in view of the considerable refinements in the technique that are being reported.30
In contrast to previous reports, our study focused on a homogeneous, narrowly defined group of patients. All the patients had died of sporadic Creutzfeldt–Jakob disease in Switzerland between 1996 and 2002. On the other hand, there has been an alarming increase in the incidence of Creutzfeldt–Jakob disease in Switzerland.13 Although the causes of this epidemiologic shift are not clear, the etiologic process of sporadic Creutzfeldt–Jakob disease in our cohort may differ from that in cohorts in other countries. It will therefore be important to extend the present study to additional countries, in order to determine whether our observations apply to all cases of sporadic Creutzfeldt–Jakob disease.
The Swiss Reference Center for Prion Diseases is funded by the Swiss Federal Office of Public Health. Dr. Glatzel is supported by a career development award (Forschungskredit) of the University of Zurich.
Dr. Glatzel and Mr. Abela contributed equally to the article.
We are indebted to all the referring physicians; to Ivan Hegyi, Marco Prinz, and Judith Gottwein for assistance with tissue collection; to Mauri Peltola for technical help; to Lorenz Amsler for help with statistical analysis; to Johannes Streffer for sequencing; to Thorsten Lührs for proposing the use of triangular glycoplots; to Klaus Hess for critical reading of the manuscript; to Prionics for providing laboratory space; and to the University Hospital of Zurich for a generous infrastructural grant enabling the creation of the Swiss CJD tissue collection.
Source Information
From the Institute of Neuropathology and National Reference Center for Prion Diseases, University Hospital of Zurich, Zurich, Switzerland.
Address reprint requests to Dr. Aguzzi at the Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland, or at adriano@pathol.unizh.ch.
- References
References
1
Prusiner SB . Prions. Proc Natl Acad Sci U S A 1998;95:13363-13383
CrossRef | Web of Science | Medline2
Prusiner SB ,McKinley MP ,Bowman KA , et al. Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 1983;35:349-358
CrossRef | Web of Science | Medline3
Aguzzi A ,Montrasio F ,Kaeser PS . Prions: health scare and biological challenge. Nat Rev Mol Cell Biol 2001;2:118-126
CrossRef | Web of Science | Medline4
Bosque PJ ,Ryou C ,Telling G , et al. Prions in skeletal muscle. Proc Natl Acad Sci U S A 2002;99:3812-3817
CrossRef | Web of Science | Medline5
Bruce ME ,Will RG ,Ironside JW , et al. Transmissions to mice indicate that `new variant' CJD is caused by the BSE agent. Nature 1997;389:498-501
CrossRef | Web of Science | Medline6
Hill AF ,Desbruslais M ,Joiner S , et al. The same prion strain causes vCJD and BSE. Nature 1997;389:448-50, 526
CrossRef | Web of Science | Medline7
Hill AF ,Zeidler M ,Ironside J ,Collinge J . Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 1997;349:99-100
CrossRef | Web of Science | Medline8
Wadsworth JDF ,Joiner S ,Hill AF , et al. Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immunoblotting assay. Lancet 2001;358:171-180
CrossRef | Web of Science | Medline9
Will RG ,Ironside JW ,Zeidler M , et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:921-925
CrossRef | Web of Science | Medline10
Hill AF ,Butterworth RJ ,Joiner S , et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999;353:183-189
CrossRef | Web of Science | Medline11
Safar J ,Wille H ,Itri V , et al. Eight prion strains have PrP(Sc) molecules with different conformations. Nat Med 1998;4:1157-1165
CrossRef | Web of Science | Medline12
Kascsak RJ ,Rubenstein R ,Merz PA , et al. Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol 1987;61:3688-3693
Web of Science | Medline13
Glatzel M ,Rogivue C ,Ghani A ,Streffer JR ,Amsler L ,Aguzzi A . Incidence of Creutzfeldt-Jakob disease in Switzerland. Lancet 2002;360:139-141
CrossRef | Web of Science | Medline14
Parchi P ,Castellani R ,Capellari S , et al. Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996;39:767-778
CrossRef | Web of Science | Medline15
Collinge J ,Sidle KC ,Meads J ,Ironside J ,Hill AF . Molecular analysis of prion strain variation and the aetiology of `new variant' CJD. Nature 1996;383:685-690
CrossRef | Web of Science | Medline16
Wadsworth JD ,Hill AF ,Joiner S ,Jackson GS ,Clarke AR ,Collinge J . Strain-specific prion-protein conformation determined by metal ions. Nat Cell Biol 1999;1:55-59
CrossRef | Web of Science | Medline17
Windl O ,Giese A ,Schulz-Schaeffer W , et al. Molecular genetics of human prion diseases in Germany. Hum Genet 1999;105:244-252
CrossRef | Web of Science | Medline18
Parchi P ,Giese A ,Capellari S , et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999;46:224-233
CrossRef | Web of Science | Medline19
Blattler T ,Brandner S ,Raeber AJ , et al. PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain. Nature 1997;389:69-73
CrossRef | Web of Science | Medline20
Nakamura Y ,Yanagawa H ,Kitamoto T ,Sato T . Epidemiologic features of 65 Creutzfeldt-Jakob disease patients with a history of cadaveric dura mater transplantation in Japan. Epidemiol Infect 2000;125:201-205
CrossRef | Web of Science | Medline21
Joiner S ,Linehan J ,Brandner S ,Wadsworth JD ,Collinge J . Irregular presence of abnormal prion protein in appendix in variant Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 2002;73:597-598
CrossRef | Web of Science | Medline22
Klein MA ,Kaeser PS ,Schwarz P , et al. Complement facilitates early prion pathogenesis. Nat Med 2001;7:488-492
CrossRef | Web of Science | Medline23
Askanas V ,Bilak M ,Engel WK ,Alvarez RB ,Tome F ,Leclerc A . Prion protein is abnormally accumulated in inclusion-body myositis. Neuroreport 1993;5:25-28
CrossRef | Web of Science | Medline24
Zanusso G ,Vattemi G ,Ferrari S , et al. Increased expression of the normal cellular isoform of prion protein in inclusion-body myositis, inflammatory myopathies and denervation atrophy. Brain Pathol 2001;11:182-189
CrossRef | Web of Science | Medline25
Hill AF ,Joiner S ,Wadsworth JD , et al. Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 2003;126:1333-1346
CrossRef | Web of Science | Medline26
Rossetti AO ,Glatzel M ,Aguzzi A ,Janzer R ,Bogousslavsky J . Clinical and radiological mimicry of vCJD in a valine homozygous PrP(Sc) type 1 sCJD patient. J Neurol 2003;250:491-493
CrossRef | Web of Science | Medline27
Brown P ,Gibbs CJ Jr ,Rodgers-Johnson P , et al. Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 1994;35:513-529
CrossRef | Web of Science | Medline28
Collins S ,Law MG ,Fletcher A ,Boyd A ,Kaldor J ,Masters CL . Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet 1999;353:693-697
CrossRef | Web of Science | Medline29
Aguzzi A . Prion diseases, blood and the immune system: concerns and reality. Haematologica 2000;85:3-10
Web of Science | Medline30
Aguzzi A ,Heikenwalder M . Prion diseases: cannibals and garbage piles. Nature 2003;423:127-129
CrossRef | Web of Science | Medline
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J. A. Edgeworth, A. Sicilia, J. Linehan, S. Brandner, G. S. Jackson, J. Collinge. (2011) A standardized comparison of commercially available prion decontamination reagents using the Standard Steel-Binding Assay. Journal of General Virology 92:3, 718-726
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A. PEDEN, L. McCARDLE, M. W. HEAD, S. LOVE, H. J. T. WARD, S. N. COUSENS, D. M. KEELING, C. M. MILLAR, F. G. H. HILL, J. W. IRONSIDE. (2010) Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 16:2, 296-304
CrossRef15
Gianpietro Bondiolotti, Giuseppe Rossoni, Maria Puricelli, Elena Formentin, Barbara Lucchini, Giorgio Poli, Wilma Ponti, Silvio R. Bareggi. (2010) Changes in sympathetic activity in prion neuroinvasion. Neurobiology of Disease 37:1, 114-117
CrossRef16
Rhiannon L. C. H. Huzarewich, Christine G. Siemens, Stephanie A. Booth. (2010) Application of “omics” to Prion Biomarker Discovery. Journal of Biomedicine and Biotechnology 2010, 1-15
CrossRef17
Sílvia Sisó, Lorenzo González, Martin Jeffrey. (2010) Neuroinvasion in Prion Diseases: The Roles of Ascending Neural Infection and Blood Dissemination. Interdisciplinary Perspectives on Infectious Diseases 2010, 1-16
CrossRef18
Glaucia N.M. Hajj, Tiago G. Santos, Zanith S.P. Cook, Vilma R. Martins. (2009) Developmental expression of prion protein and its ligands stress-inducible protein 1 and vitronectin. The Journal of Comparative Neurology 517:3, 371-384
CrossRef19
F. Cardone, A. Thomzig, W. Schulz-Schaeffer, A. Valanzano, M. Sbriccoli, H. Abdel-Haq, S. Graziano, S. Pritzkow, M. Puopolo, P. Brown, M. Beekes, M. Pocchiari. (2009) PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice infected orally with bovine spongiform encephalopathy. Journal of General Virology 90:10, 2563-2568
CrossRef20
Mario Nuvolone, Adriano Aguzzi, Mathias Heikenwalder. (2009) Cells and prions: A license to replicate. FEBS Letters 583:16, 2674-2684
CrossRef21
Jasmin Naderi, Christian Bernreuther, Nicole Grabinski, Charles T. Putman, Birgit Henkel, Gordon Bell, Markus Glatzel, Karim R. Sultan. (2009) Plasminogen Activator Inhibitor Type 1 Up-Regulation Is Associated with Skeletal Muscle Atrophy and Associated Fibrosis. The American Journal of Pathology 175:2, 763-771
CrossRef22
Gianluigi Zanusso, Sergio Ferrari, Diego Benedetti, Marco Sbriccoli, Nicola Rizzuto, Salvatore Monaco. (2009) Different Prion Conformers Target the Olfactory Pathway in Sporadic Creutzfeldt-Jakob Disease. Annals of the New York Academy of Sciences 1170:1, 637-643
CrossRef23
Ed M Choi, Michael D Geschwind, Camille Deering, Kristen Pomeroy, Amy Kuo, Bruce L Miller, Jiri G Safar, Stanley B Prusiner. (2009) Prion proteins in subpopulations of white blood cells from patients with sporadic Creutzfeldt–Jakob disease. Laboratory Investigation 89:6, 624-635
CrossRef24
Haiyun Zhou, Xiangmei Zhou, Mohammed Kouadir, Zhongqiu Zhang, Xiaomin Yin, Lifeng Yang, Deming Zhao. (2009) Induction of macrophage migration by neurotoxic prion protein fragment. Journal of Neuroscience Methods 181:1, 1-5
CrossRef25
Xiangzhu Xiao, Leticia Miravalle, Jue Yuan, John McGeehan, Zhiqian Dong, Robert Wyza, Gregory T. MacLennan, Alan M. Golichowski, Geoff Kneale, Nicholas King, Qingzhong Kong, Salvatore Spina, Ruben Vidal, Bernardino Ghetti, Karen Roos, Pierluigi Gambetti, Wen-Quan Zou. (2009) Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease. The American Journal of Pathology 174:5, 1602-1608
CrossRef26
Mathias Heikenwalder, Michael O. Kurrer, Ilan Margalith, Jan Kranich, Nicolas Zeller, Johannes Haybaeck, Magdalini Polymenidou, Matthias Matter, Juliane Bremer, Walker S. Jackson, Susan Lindquist, Christina J. Sigurdson, Adriano Aguzzi. (2008) Lymphotoxin-Dependent Prion Replication in Inflammatory Stromal Cells of Granulomas. Immunity 29:6, 998-1008
CrossRef27
S. Brandner, J. Whitfield, K. Boone, A. Puwa, C. O'Malley, J. M. Linehan, S. Joiner, F. Scaravilli, I. Calder, M. P. Alpers, J. D. F. Wadsworth, J. Collinge. (2008) Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease. Philosophical Transactions of the Royal Society B: Biological Sciences 363:1510, 3755-3763
CrossRef28
Laura J. Vella, Deanne L.V. Greenwood, Roberto Cappai, Jean-Pierre Y. Scheerlinck, Andrew F. Hill. (2008) Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid. Veterinary Immunology and Immunopathology 124:3-4, 385-393
CrossRef29
Wandong Zhang, Jun Wu, Yan Li, Robert C. Carke, Tom Wong. (2008) The In Vitro Bioassay Systems for the Amplification and Detection of Abnormal Prion PrPSc in Blood and Tissues. Transfusion Medicine Reviews 22:3, 234-242
CrossRef30
Yasmine Aguib, Sabine Gilch, Carmen Krammer, Alexa Ertmer, Martin H. Groschup, Hermann M. Schätzl. (2008) Neuroendocrine cultured cells counteract persistent prion infection by down-regulation of PrPc. Molecular and Cellular Neuroscience 38:1, 98-109
CrossRef31
F. Díaz-San Segundo, N. Sevilla, J.P. Gutiérrez, A. Brun. (2008) Altered lymphocyte homeostasis after oral prion infection in mouse. Veterinary Immunology and Immunopathology 122:3-4, 204-215
CrossRef32
J. D. F. Wadsworth, S. Joiner, J. M. Linehan, M. Desbruslais, K. Fox, S. Cooper, S. Cronier, E. A. Asante, S. Mead, S. Brandner, A. F. Hill, J. Collinge. (2008) Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice. Proceedings of the National Academy of Sciences 105:10, 3885-3890
CrossRef33
Hester J. T. Ward, Dawn Everington, Simon N. Cousens, Blaire Smith-Bathgate, Michelle Gillies, Katy Murray, Richard S. G. Knight, Peter G. Smith, Robert G. Will. (2008) Risk factors for sporadic Creutzfeldt-Jakob disease. Annals of Neurology 63:3, 347-354
CrossRef34
Gabor G. Kovacs, Herbert Budka. (2008) Prion Diseases: From Protein to Cell Pathology. The American Journal of Pathology 172:3, 555-565
CrossRef35
Adriano Aguzzi, Christina Sigurdson, Mathias Heikenwaelder. (2008) Molecular Mechanisms of Prion Pathogenesis. Annual Review of Pathology: Mechanisms of Disease 3:1, 11-40
CrossRef36
Alexander H Peden, Mark W Head, Michael Jones, Ian MacGregor, Marc Turner, James Ironside. (2008) Advances in the development of a screening test for variant Creutzfeldt–Jakob disease. Expert Opinion on Medical Diagnostics 2:2, 207-219
CrossRef37
Mathias Heikenwalder, Christian Federau, Lotta von Boehmer, Petra Schwarz, Mareike Wagner, Nicolas Zeller, Johannes Haybaeck, Marco Prinz, Burkhard Becher, Adriano Aguzzi. (2007) Germinal center B cells are dispensable in prion transport and neuroinvasion. Journal of Neuroimmunology 192:1-2, 113-123
CrossRef38
Gauthier Dorban, Valérie Defaweux, Caroline Demonceau, Sylvain Flandroy, Pierre-Bernard Lerberghe, Nandini Falisse-Poirrier, Joëlle Piret, Ernst Heinen, Nadine Antoine. (2007) Interaction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure. Virchows Archiv 451:6, 1057-1065
CrossRef39
Mathias Heikenwalder, Christian Julius, Adriano Aguzzi. (2007) Prions and peripheral nerves: A deadly rendezvous. Journal of Neuroscience Research 85:12, 2714-2725
CrossRef40
C. Pollera, G. Bondiolotti, E. Formentin, M. Puricelli, P. Mantegazza, S. Bareggi, G. Poli, W. Ponti. (2007) Plasma Noradrenalin as Marker of Neuroinvasion in Prion Diseases. Veterinary Research Communications 31:S1, 249-252
CrossRef41
Mourad Tayebi, Clive Bate, Simon Hawke, Alun Williams. (2007) A role for B lymphocytes in anti-infective prion therapies?. Expert Review of Anti-infective Therapy 5:4, 631-638
CrossRef42
Kevin Goggin, Cyntia Bissonnette, Catherine Grenier, Leonid Volkov, Xavier Roucou. (2007) Aggregation of cellular prion protein is initiated by proximity-induced dimerization. Journal of Neurochemistry 102:4, 1195-1205
CrossRef43
Markus Geissen, Susanne Krasemann, Jakob Matschke, Markus Glatzel. (2007) Understanding the natural variability of prion diseases. Vaccine 25:30, 5631-5636
CrossRef44
Adriano Aguzzi, Mathias Heikenwalder, Magdalini Polymenidou. (2007) Insights into prion strains and neurotoxicity. Nature Reviews Molecular Cell Biology 8:7, 552-561
CrossRef45
A. J. Smith, D. Hurrell, J. Bagg, S. McHugh, H. Mathewson, M. Henry. (2007) A method for surveying instrument decontamination procedures in general dental practice. BDJ 202:8, E20-E20
CrossRef46
Michael Beekes, Patricia A. McBride. (2007) The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies. FEBS Journal 274:3, 588-605
CrossRef47
Adriano Aguzzi. (2006) Prion diseases of mammals: epidemiology, genetics, and pathogenesis. Rendiconti Lincei 17:4, 355-376
CrossRef48
Stéphanie Chasseigneaux, Stéphane Haïk, Isabelle Laffont-Proust, Olivier De Marco, Martine Lenne, Jean-Philippe Brandel, Jean-Jacques Hauw, Jean-Louis Laplanche, Katell Peoc’h. (2006) V180I mutation of the prion protein gene associated with atypical PrPSc glycosylation. Neuroscience Letters 408:3, 165-169
CrossRef49
Jeremy D. Isaacs, Rebecca J. Ingram, John Collinge, Daniel M. Altmann, Graham S. Jackson. (2006) The Human Prion Protein Residue 129 Polymorphism Lies Within a Cluster of Epitopes for T Cell Recognition. Journal of Neuropathology and Experimental Neurology 65:11, 1059-1068
CrossRef50
J. Pedro-Cuesta, M. J. Bleda, A. Rábano, M. Cruz, H. Laursen, K. Mølbak, A. Siden, . (2006) Classification of surgical procedures for epidemiologic assessment of sporadic Creutzfeldt-Jakob Disease transmission by surgery. European Journal of Epidemiology 21:8, 595-604
CrossRef51
P. E. Hewitt, C. A. Llewelyn, J. Mackenzie, R. G. Will. (2006) Creutzfeldt–Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study. Vox Sanguinis 91:3, 221-230
CrossRef52
Adriano Aguzzi, Mathias Heikenwalder. (2006) Pathogenesis of prion diseases: current status and future outlook. Nature Reviews Microbiology 4:10, 765-775
CrossRef53
H. Murdoch, D. Taylor, J. Dickinson, J.T. Walker, D. Perrett, N.D.H. Raven, J.M. Sutton. (2006) Surface decontamination of surgical instruments: an ongoing dilemma. Journal of Hospital Infection 63:4, 432-438
CrossRef54
Marty T Lehto, Harry E Peery, Neil R Cashman. (2006) Current and future molecular diagnostics for prion diseases. Expert Review of Molecular Diagnostics 6:4, 597-611
CrossRef55
Constanze Riemer, Theresa Bamme, Simon Wing Fai Mok, Michael Baier. (2006) 3‐Methyl‐4‐Chlorophenol for Prion Decontamination of Medical Devices • . Infection Control and Hospital Epidemiology 27:7, 778-780
CrossRef56
Adriano Aguzzi, Markus Glatzel. (2006) Prion infections, blood and transfusions. Nature Clinical Practice Neurology 2:6, 321-329
CrossRef57
Adriano Aguzzi. (2006) Prion diseases of humans and farm animals: epidemiology, genetics, and pathogenesis. Journal of Neurochemistry 97:6, 1726-1739
CrossRef58
G. Gossrau, B. Herting, S. Möckel, A. Kempe, R. Koch, H. Reichmann, J. B. Lampe. (2006) Analysis of the polymorphic prion protein gene codon 129 in idiopathic Parkinson’s disease. Journal of Neural Transmission 113:3, 331-337
CrossRef59
Neil A. Mabbott, G. Gordon MacPherson. (2006) Prions and their lethal journey to the brain. Nature Reviews Microbiology 4:3, 201-211
CrossRef60
Alexander H. Peden, Diane L. Ritchie, Mark W. Head, James W. Ironside. (2006) Detection and Localization of PrPSc in the Skeletal Muscle of Patients with Variant, Iatrogenic, and Sporadic Forms of Creutzfeldt-Jakob Disease. The American Journal of Pathology 168:3, 927-935
CrossRef61
Larisa Cervenakova, Oksana Yakovleva, Carroll McKenzie. (2006) Protease-resistant Prion Protein in Lymphoreticular Tumors of Variant Creutzfeldt-Jakob Disease Mice. Emerging Infectious Diseases 12:3, 511-513
CrossRef62
Josef Finsterer, Ellen Gelpi. (2006) Creatine Kinase Elevation in Creutzfeldt-Jakob Disease. Gerontology 52:4, 264-266
CrossRef63
David A Hilton. (2006) Pathogenesis and prevalence of variant Creutzfeldt-Jakob disease. The Journal of Pathology 208:2, 134-141
CrossRef64
C. J. Sigurdson, A. Aguzzi. 2006. Prion diseases. , 309-331.
CrossRef65
Christopher A. Ludlam, Marc L. Turner. (2006) Managing the risk of transmission of variant Creutzfeldt Jakob disease by blood products. British Journal of Haematology 132:1, 13-24
CrossRef66
Ptolemaios G. Sarrigiannis, Robin P. Kennett, Simon Read, Maria E. Farrugia. (2006) Single-fiber EMG with a concentric needle electrode: Validation in myasthenia gravis. Muscle & Nerve 33:1, 61-65
CrossRef67
Gianluigi Zanusso, Salvatore Monaco. (2005) Molecular mechanisms of human prion diseases. Drug Discovery Today: Disease Mechanisms 2:4, 511-518
CrossRef68
J. W. Ironside, D. L. Ritchie, M. W. Head. (2005) Phenotypic variability in human prion diseases. Neuropathology and Applied Neurobiology 31:6, 565-579
CrossRef69
A. Smith, S. Letters, A. Lange, D. Perrett, S. McHugh, J. Bagg. (2005) Residual protein levels on reprocessed dental instruments. Journal of Hospital Infection 61:3, 237-241
CrossRef70
Steven J. Collins, Victoria Lewis, Marcus W Brazier, Andrew F. Hill, Victoria A. Lawson, Genevieve M. Klug, Colin L. Masters. (2005) Extended period of asymptomatic prion disease after low dose inoculation: Assessment of detection methods and implications for infection control. Neurobiology of Disease 20:2, 336-346
CrossRef71
S Letters, A J Smith, S McHugh, J Bagg. (2005) A study of visual and blood contamination on reprocessed endodontic files from general dental practice. British Dental Journal 199:8, 522-525
CrossRef72
R. A. Dunstan, M. P. Alpers. (2005) Variant Creutzfeldt-Jakob Disease: implications for the health care system. Australian and New Zealand Journal of Public Health 29:4, 308-312
CrossRef73
Janet M. Barletta, Daniel C. Edelman, W.E. Highsmith, Niel T. Constantine. (2005) Detection of ultra-low levels of pathologic prion protein in scrapie infected hamster brain homogenates using real-time immuno-PCR. Journal of Virological Methods 127:2, 154-164
CrossRef74
V. Galvani, R. R. Rupreht, V. Č. Šerbec, B. Vidan-Jeras. (2005) Genetic risk factors associated with Creutzfeld-Jakob disease in Slovenians and a rapid typing for PRNP codon 129 single nucleotide polymorphism. Transfusion Medicine 15:3, 197-207
CrossRef75
Will Hueston, Cory M. Bryant. (2005) Transmissible Spongiform Encephalopathies. Journal of Food Science 70:5, R77-R87
CrossRef76
Charles Weissmann, Adriano Aguzzi. (2005) Approaches to Therapy of Prion Diseases. Annual Review of Medicine 56:1, 321-344
CrossRef77
Adriano Aguzzi, Mathias Heikenwalder. (2005) Prions, Cytokines, and Chemokines: A Meeting in Lymphoid Organs. Immunity 22:2, 145-154
CrossRef78
Nicole C. Kaneider, Arthur Kaser, Stefan Dunzendorfer, Herbert Tilg, Josef R. Patsch, Christian J Wiedermann. (2005) Neurokinin-1 receptor interacts with PrP106–126-induced dendritic cell migration and maturation. Journal of Neuroimmunology 158:1-2, 153-158
CrossRef79
Christina Sigurdson, Magdalini Polymenidou, Adriano Aguzzi. (2005) Reconstructing Prions: Fibril Assembly from Simple Yeast to Complex Mammals. Neurodegenerative Diseases 2:1, 1-5
CrossRef80
(2005) Variant Creutzfeldt-Jakob Disease. Transfusion Medicine and Hemotherapy 32:3-4, 227-236
CrossRef81
Larisa Cervenakova, Paul Brown. (2004) Advances in screening test development for transmissible spongiform encephalopathies. Expert Review of Anti-infective Therapy 2:6, 873-880
CrossRef82
Giovanna Mallucci, John Collinge. (2004) Update on Creutzfeldt-Jakob disease. Current Opinion in Neurology 17:6, 641-647
CrossRef83
Oksana Yakovleva, Anna Janiak, Carroll McKenzie, Lisa McShane, Paul Brown, Larisa Cervenakova. (2004) Effect of protease treatment on plasma infectivity in variant Creutzfeldt-Jakob disease mice. Transfusion 44:12, 1700-1705
CrossRef84
G
bor G Kov
CrossRef85
Reza H. Dabaghian, Philip P. Mortimer, Jonathan P. Clewley. (2004) Prospects for the development of pre-mortem laboratory diagnostic tests for Creutzfeldt-Jakob disease. Reviews in Medical Virology 14:6, 345-361
CrossRef86
Markus Glatzel. (2004) Testing for prions: a novel protocol for vCJD prevalence studies. The Lancet 364:9441, 1196-1197
CrossRef87
Claudio Soto. (2004) Diagnosing prion diseases: needs, challenges and hopes. Nature Reviews Microbiology 2:10, 809-819
CrossRef88
J. W. Ironside, M. W. Head. (2004) Variant Creutzfeldt-Jakob disease: risk of transmission by blood and blood products. Haemophilia 10:s4, 64-69
CrossRef89
Adam Frosh, Lorraine C Smith, Carl J Jackson, Jacqueline M Linehan, Sebastian Brandner, Jonathan DF Wadsworth, John Collinge. (2004) Analysis of 2000 consecutive UK tonsillectomy specimens for disease-related prion protein. The Lancet 364:9441, 1260-1262
CrossRef90
Adriano Aguzzi, Christina J. Sigurdson. (2004) Antiprion immunotherapy: to suppress or to stimulate?. Nature Reviews Immunology 4:9, 725-736
CrossRef91
Herbert Budka. (2004) Concern about Mad Cow Disease: End of the beginning, or beginning of the end?. Wiener Klinische Wochenschrift 116:15-16, 505-507
CrossRef92
Alexander H Peden, Mark W Head, L Ritchie Diane, E Bell Jeanne, W Ironside James. (2004) Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. The Lancet 364:9433, 527-529
CrossRef93
Adriano Aguzzi, Mathias Heikenwalder, Gino Miele. (2004) Progress and problems in the biology, diagnostics, and therapeutics of prion diseases. Journal of Clinical Investigation 114:2, 153-160
CrossRef94
Jacqueline Janka, Frank Maldarelli. (2004) Prion diseases: Update on mad cow disease, variant creutzfeldt-jakob disease, and the transmissible spongiform encephalopathies. Current Infectious Disease Reports 6:4, 305-315
CrossRef95
Hisako Furukawa, Katsumi Doh-ura, Kensuke Sasaki, Toru Iwaki. (2004) Accumulation of prion protein in muscle fibers of experimental chloroquine myopathy: in vivo model for deposition of prion protein in non-neuronal tissues. Laboratory Investigation 84:7, 828-835
CrossRef96
O Andréoletti, S Simon, C Lacroux, N Morel, G Tabouret, A Chabert, S Lugan, F Corbière, P Ferré, G. Foucras, H. Laude, F. Eychenne, J Grassi, F Schelcher. (2004) PrPSc accumulation in myocytes from sheep incubating natural scrapie. Nature Medicine 10:6, 591-593
CrossRef97
Adriano Aguzzi, Gino Miele. (2004) Recent advances in prion biology. Current Opinion in Neurology 17:3, 337-342
CrossRef98
Achim Thomzig, Walter Schulz-Schaeffer, Christine Kratzel, Jessica Mai, Michael Beekes. (2004) Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie. Journal of Clinical Investigation 113:10, 1465-1472
CrossRef99
Lynne M. Sehulster. (2004) Prion Inactivation and Medical Instrument Reprocessing: Challenges Facing Healthcare Facilities • . Infection Control and Hospital Epidemiology 25:4, 276-279
CrossRef100
Stephen P. Oliver. (2004) Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease. Foodborne Pathogens and Disease 1:1, 65-72
CrossRef101
(2004) Extraneural Pathologic Prion Protein. New England Journal of Medicine 350:7, 732-733
Full Text102
Adriano Aguzzi, Markus Glatzel. (2004) vCJD tissue distribution and transmission by transfusion—a worst-case scenario coming true?. The Lancet 363:9407, 411-412
CrossRef103
Markus Glatzel, Olivier Giger, Harald Seeger, Adriano Aguzzi. (2004) Variant Creutzfeldt–Jakob disease: between lymphoid organs and brain. Trends in Microbiology 12:2, 51-53
CrossRef104
C Herzog, N Salès, N Etchegaray, A Charbonnier, S Freire, D Dormont, J-P Deslys, CI Lasmézas. (2004) Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection. The Lancet 363:9407, 422-428
CrossRef105
Adriano Aguzzi, Marina Bentivoglio, Giovanni Berlucchi, Maurizio Brunori, Krister Kristensson, Alfredo Margreth, Giuseppe Scalabrino, Catia Sorgato, Mario Stefanini, Tullio Pozzan. (2003) Discussione Generale e Conclusione dei Lavori. Rendiconti Lincei 14:4, 339-348
CrossRef106
Markus Glatzel, Peter M Ott, Thomas Linder, Jan O Gebbers, Arnold Gmür, Werner Wüst, Gerhard Huber, Holger Moch, Michael Podvinec, Bernhard Stamm, Adriano Aguzzi. (2003) Human prion diseases: epidemiology and integrated risk assessment. The Lancet Neurology 2:12, 757-763
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