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Creutzfeldt-Jakob Disease (creutzfeldt-jakob + disease)
Kinds of Creutzfeldt-Jakob Disease Selected AbstractsCreutzfeldt-Jakob Disease and haemophilia: assessment of riskHAEMOPHILIA, Issue 2000Evatt First page of article [source] Creutzfeldt-Jakob Disease in the Obstetric PatientJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 5 2005Randa Sperling Recent reports have indicated the presence of transmissible spongiform encephalopathy or Creutzfeldt-Jakob disease in the United States. This disease can occur as a rare, sporadic disease with no recognizable pattern of transmission or as a familial disease associated with prion protein gene mutations. This article discusses the presence of sporadic Creutzfeldt-Jakob disease in a woman who became pregnant early in the course of the disease and subsequent care pre- and postdelivery. [source] Variant Creutzfeldt-Jakob Disease: implications for the health care systemAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 4 2005R. A. Dunstan The recognition of the first cases of variant Creutzfeldt-Jakob Disease in the United Kingdom (UK) in 1996 and the realisation that this new disease represented the human form of the cattle disease BSE has prompted a considerable investment in research, particularly in the UK, Europe and the United States (US). Much has been learnt about this disease but much is still unknown. Infectivity is not destroyed by conventional sterilisation and disinfection treatment methods. This, combined with the widespread distribution throughout the lymphoid system as well as the central nervous system, raises the spectre of transmission through both surgical and ophthalmological procedures. Reports in 2004 of two likely transfusion-transmitted cases of vCJD suggest the probability of infection through blood transfusion and tissue transplantation. The risk of hospital-based and community-based transmission has not been quantified. To complicate matters even further, there is no suitable ante-mortem screening test or effective treatment for this fatal disease. The incubation period prior to onset of clinical disease is many years and there is good evidence for the existence of subclinical infection and infectivity during this stage. The extent of under-diagnosis and misdiagnosis is probably significant, adding to the risk of human-to-human transmission. [source] Failure of immunocompetitive capillary electrophoresis assay to detect disease-specific prion protein in buffy coat from humans and chimpanzees with Creutzfeldt-Jakob diseaseELECTROPHORESIS, Issue 5 2003Larisa Cervenakova Abstract The emergence of a new environmentally caused variant of Creutzfeldt-Jakob disease (vCJD), the result of food-born infection by the causative agent of bovine spongiform encephalopathy (BSE), has stimulated research on a practical diagnostic screening test. The immunocompetitive capillary electrophoresis (ICCE) assay has been reported to detect disease-specific, proteinase-resistant prion protein (PrPres) in the blood of scrapie-infected sheep. We have applied this method to blood from CJD-infected chimpanzees and humans. The threshold of detection achieved with our ICCE was 0.6 nM of synthetic peptide corresponding to the prion protein (PrP) C -terminus, and 2 nM of recombinant human PrP at the optimized conditions. However, the test was unable to distinguish between extracts of leucocytes from healthy and CJD-infected chimpanzees, and from healthy human donors and patients affected with various forms of CJD. Thus, the ICCE assay as presently performed is not suitable for use as a screening test in human transmissible spongiform encephalopathies (TSEs). [source] Creutzfeldt-Jakob disease: hopes for therapyEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2008M. Pocchiari No abstract is available for this article. [source] Cellular prion protein/laminin receptor: distribution in adult central nervous system and characterization of an isoform associated with a subtype of cortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2004Hasna Baloui Abstract The 67-kDa LR protein was originally discovered as a non-integrin laminin receptor. Several more recent in vitro studies demonstrated the function of 67-kDa LR and its related ,precursor' form 37-kDa LRP as receptors of cellular prion protein and their implication in abnormal prion protein propagation in vitro. In addition, expression of both proteins was shown to increase considerably in the brain of scrapie-infected mice and hamsters. While LRP/LR are thus likely to play important roles in neuronal cell adhesion, survival and homeostasis and during pathological disorders, little is known so far about their fine cellular distribution in adult central nervous system. Using immunocytochemistry and western blotting, we show here that the 67-kDa LR is the major receptor form in adult rat brain and spinal cord, expressed within the cytoplasm and at the plasma membrane of most neurons and in a subset of glial cells. The overall distribution of LR correlates well with that reported for laminin-1 but also with brain regions classically associated with prion-related neurodegeneration. In contrast to LR, the 37-kDa LRP form is much less abundant in adult than in postnatal central nervous system. Characterization of a novel antibody allowed us to study the distribution across tissues of cell membrane-associated LRP. Interestingly, this form is almost exclusively found on a subclass of parvalbumin-immunoreactive cortical interneurons known to degenerate during the early stages of Creutzfeldt-Jakob disease. Our demonstration of local differences in the expression of particular LRP/LR isoforms may be a first step towards unraveling their specific molecular interactions. [source] Human prion diseases: biology and transmission by bloodISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue 1 2006J. W. Ironside Human prion diseases are a group of rare fatal transmissible neurodegenerative disorders that occur in sporadic, acquired and familial forms. In 1996, a new type of human prion disease, variant Creutzfeldt-Jakob disease (vCJD), was first identified and has subsequently been identified in 10 additional countries. vCJD results from human exposure to the bovine spongiform encephalopathy (BSE) agent, most likely through the consumption of BSE-contaminated meat products. Unlike other human prion diseases, both infectivity and the disease-associated form of the prion protein are readily detected in lymphoid tissues in vCJD, suggesting that infectivity may also be present in blood. Three recent cases of apparent iatrogenic vCJD infection by blood transfusion have occurred in the UK, following red blood cell transfusions from asymptomatic donors who subsequently died from vCJD. The first and third cases resulted in a clinical illness identical to vCJD, while the second case was an asymptomatic infection only detected at autopsy. There are no current means of detecting vCJD infection in asymptomatic donors, so continuing surveillance is required in the UK and other countries to monitor the incidence of vCJD and further cases of secondary transmission by blood transfusion. [source] Methods of studying the planar distribution of objects in histological sections of brain tissueJOURNAL OF MICROSCOPY, Issue 3 2006R. A. ARMSTRONG Summary This article reviews the statistical methods that have been used to study the planar distribution, and especially clustering, of objects in histological sections of brain tissue. The objective of these studies is usually quantitative description, comparison between patients or correlation between histological features. Objects of interest such as neurones, glial cells, blood vessels or pathological features such as protein deposits appear as sectional profiles in a two-dimensional section. These objects may not be randomly distributed within the section but exhibit a spatial pattern, a departure from randomness either towards regularity or clustering. The methods described include simple tests of whether the planar distribution of a histological feature departs significantly from randomness using randomized points, lines or sample fields and more complex methods that employ grids or transects of contiguous fields, and which can detect the intensity of aggregation and the sizes, distribution and spacing of clusters. The usefulness of these methods in understanding the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Creutzfeldt-Jakob disease is discussed. [source] Creutzfeldt-Jakob Disease in the Obstetric PatientJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 5 2005Randa Sperling Recent reports have indicated the presence of transmissible spongiform encephalopathy or Creutzfeldt-Jakob disease in the United States. This disease can occur as a rare, sporadic disease with no recognizable pattern of transmission or as a familial disease associated with prion protein gene mutations. This article discusses the presence of sporadic Creutzfeldt-Jakob disease in a woman who became pregnant early in the course of the disease and subsequent care pre- and postdelivery. [source] Variant Creutzfeldt-Jakob disease: An unfolding epidemic of misfolded proteinsJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 6 2002P Horby Abstract: Variant Creutzfeldt-Jakob disease (vCJD) is an emerging infectious disease believed to be the human manifestation of bovine spongiform encephalopathy (BSE). Variant CJD belongs to a family of human and animal diseases called transmissible spongiform encephalopathies (TSE). The pathogenesis of TSE is not fully understood, but a modified form of a normal cellular protein plays a central role. Current measures to control vCJD aim to prevent transmission of the infectious agent from animals to humans through food or pharmaceutical products and to prevent transmission from person to person via medical interventions. The anticipated development of preclinical diagnostic tests and treatments for vCJD will create new control options and difficult choices. [source] The first Japanese patient with variant Creutzfeldt-Jakob disease (vCJD)NEUROPATHOLOGY, Issue 6 2009Akiyo Shinde Eleven years after a brief visit to some European countries, a 48-year-old Japanese man developed writing difficulty, irritability and general fatigue. Then he complained of dysesthetic pains in his legs, for which benzodiazepines were prescribed. However, at the time pulvinar sign was retrospectively confirmed on brain MRI. Eighteen months after the onset, his gait became ataxic with rapid deterioration of mental status over the following several months. Thirty-one months after the onset, he became akinetic and mute with periodic synchronous discharges on EEG, and died at the age of 51. The total clinical course was approximately 43 months. Pathological examination revealed the characteristic alterations of spongiform encephalopathy, severe in the thalamus, moderate but widely spread in the cerebral cortices, and moderate in the cerebellum. Abundant amyloid plaques were easily identified in the cerebral cortex and the cerebellum on HE staining. Immunohistochemistry for abnormal prion protein (PrPsc) confirmed amyloid plaques in several forms, such as florid, uni- and multi-centric plaques as well as perineuronal and periaxonal deposits in the basal ganglia and synaptic patterns in the thalami. A Western blotting study identified type 2B protease-resistant PrP. This is the first Japanese patient who was definitely diagnosed as variant Creutzfeldt-Jakob disease (vCJD). The pathological findings were similar to those of previous reports of vCJD in the UK. However, the changes were much more severe both in degree and distribution, probably due to a longer duration of the illness than those in the UK. [source] MM2-cortical-type sporadic Creutzfeldt-Jakob disease with early stage cerebral cortical pathology presenting with a rapidly progressive clinical courseNEUROPATHOLOGY, Issue 6 2008Yoshiki Niimi We report the case of a 67-year-old man with MM2-cortical-type sporadic Creutzfeldt-Jakob disease (sCJD) with a rapidly progressive clinical course of 5 months. Initial symptoms were progressive memory disturbance and dementia. MRI revealed high signal-intensity lesions on diffusion-weighted images in the bilateral frontal and occipital cortices. Myoclonus and periodic sharp-wave complexes on the electroencephalogram were observed in the early disease stage. The clinical diagnosis was typical sCJD. Neuropathologic examination at autopsy showed widespread, characteristic cerebral neocortical involvement with large confluent vacuole-type spongiform change. Spongiform degeneration was also evident in the striatum and medial thalamus. In the cerebellar cortex, slight depletion of Purkinje neurons was evident without spongiform change in the molecular layer or apparent neuron loss in the granule cell layer. The inferior olivary nucleus showed slight hypertrophic astrocytosis without neuron loss. Prion protein (PrP) immunostaining showed widespread, characteristic perivacuolar-type PrP deposits with irregular plaque-like PrP deposits in the cerebral neocortex, striatum and medial thalamus. We believe this patient showed early-stage cerebral cortical pathology of MM2-cortical-type sCJD, which may provide clues regarding the pathologic progression of this rare sCJD subtype. Although MM2-cortical-type sCJD generally shows slow progression without myoclonus or periodic sharp-wave complexes, the present patient showed a rapidly progressive clinical course similar to that of MM1-type sCJD. [source] Enhanced Aquaporin-4 immunoreactivity in sporadic Creutzfeldt-Jakob diseaseNEUROPATHOLOGY, Issue 4 2007Yasushi Iwasaki Aquaporin-4 (AQP-4) is a water channel protein located on the plasma membrane of astrocytes and is regulated under various conditions. In the present study, a series of brains with sporadic Creutzfeldt-Jakob disease (sCJD) were investigated to determine the possible contribution of AQP-4 in the development of sCJD pathology. Six cases of subacute spongiform encephalopathy (SSE) and four cases of panencephalopathic (PE)-type sCJD were included. Increased AQP-4 immunoreactivity compared to that in controls was observed in all sCJD patients, particularly in the cerebral neocortex and cerebellar cortex. AQP-4 immunoreactivity was present in the cell bodies and processes of protoplasmic astrocytes in SSE and around cell bodies and processes of hypertrophic astrocytes in PE-type sCJD. Analysis of serial sections showed the development of sCJD pathology, particularly in neocortical lesions, as follows: PrP deposition; spongiform change and gliosis; enhanced staining for AQP-4; hypertrophic astrocytosis; and neuronal loss and tissue rarefaction. Strong AQP-4 immunoreactivity was present in burnt-out lesions such as those of status spongiosus. These results indicate that increased AQP-4 expression in sCJD is an early pathologic event and appears to remain until the late disease stage. We suggest that increased expression of AQP-4 is a pathologic feature of sCJD. [source] Immunohistochemical studies of the PrPCJD deposition in Creutzfeldt-Jakob diseaseNEUROPATHOLOGY, Issue 2 2000Shinichiro Tanaka The PrPCJD deposition in eight brains of sporadic Creutzfeldt-Jakob disease (CJD) was examined immunohistochemically using both hydrolytic autoclaving and formic acid pretreatment in order to understand the pathogenesis of CJD. Synaptic-type PrP immunoreactivity was revealed in the gray matter in all cases and had a tendency to be weaker in devastated areas in cases with a longer duration of illness. However, in one particular case with numerous prion plaques, the degeneration was relatively mild while PrPCJD immunoreactivity was intense despite the longest duration of illness among the examined cases. Deep layer accentuation of PrPCJD immunoreactivity was observed in the cerebral cortices in most cases. This staining pattern, however, disappeared in a burnt-out lesion exhibiting status spongiosus. The granular layer was damaged mostly in the cerebellum of the advanced cases. PrPCJD and synaptophysin immunoreactivities decreased as the tissue degeneration progressed. Interestingly, the Purkinje cells had no positivity for PrPCJD in all cases, although the neurons in relatively preserved cerebellum showed apparent positivity for synaptophysin. In the Ammon's horn and subiculum the neurons were well preserved despite the marked immunoreactivity for PrPCJD in all cases, although some cases demonstrated severe spongiform change. Approximately half of the cases showed intracytoplasmic inclusion body-like immunoreactivity for PrPCJD in neurons of the dentate nucleus. These findings suggest that PrPCJD deposition may be an event that precedes neuronal degeneration evolving from deeper layers of the cerebral cortex. Although the Ammon's horn and subiculum showed striking PrPCJD deposition and spongiform change, neuronal loss did not take place, suggesting that deposited PrPCJD itself seems not to be directly harmful to the neurons. Some investigators have assumed that microglia activated by PrPCJD plays an important role in neuronal degeneration. Considering this, we speculate that microglia in the Ammon's horn and subiculum may have a unique characteristic of not responding to PrPCJD. [source] Creutzfeldt-Jakob disease with the V203I mutation and M129V polymorphism of the prion protein gene (PRNP) and a 17 kDa prion protein fragmentNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2010B-H. Jeong First page of article [source] Disease-specific particles without prion protein in prion diseases , phenomenon or epiphenomenon?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2007P. P. Liberski The search for the cause of transmissible spongiform encephalopathies (TSEs) has a long and tortuous history. In a recent paper, 25-nm virus-like particles were identified that were consistently observed in cell cultures infected with Creutzfeldt-Jakob disease (CJD) and scrapie; they are similar to, or even identical with, the virus-like tubulovesicular structures (TVS) found in experimental scrapie as early as in 1968, and subsequently in all naturally occurring and experimentally induced TSEs. These particles have been viewed with caution by the scientific community because of the unverified or uninterpretable record of virus-like structures reported over the years in TSEs. TVS are spherical or tubular particles of approximate diameter 25,37 nm. They are smaller than synaptic vesicles, but larger than many particulate structures of the central nervous system, such as glycogen granules. Their electron density is higher compared with synaptic vesicles, and in experimental murine scrapie, they form paracrystalline arrays. None of these observations distinguish between TVS as an entity critical to the infectious process, or as a highly specific ultrastructural epiphenomenon, but their consistent presence in all TSEs demands further research. [source] Anaesthesia for patients with Creutzfeldt-Jakob disease.ANAESTHESIA, Issue 7 2003A practical guide No abstract is available for this article. [source] Identification of polymorphisms in the ovine Shadow of prion protein (SPRN) gene and assessment of their effect on promoter activity and susceptibility for classical scrapieANIMAL GENETICS, Issue 2 2010E. Lampo Summary Shadow of prion protein (SPRN) is an interesting candidate gene thought to be involved in prion pathogenesis. In humans, an association has already been discovered between mutations in SPRN and the incidence of variant and sporadic Creutzfeldt-Jakob disease. However, in sheep, the effect of mutations in SPRN is largely unknown. Therefore, we analysed the presence of mutations in the entire ovine SPRN gene, their association with scrapie susceptibility and their effect on SPRN promoter activity. In total, 26 mutations were found: seven in the promoter region, four in intron 1, seven in the coding sequence and eight in the 3, untranslated region. The mutations detected in the coding sequence and the promoter region were subsequently analysed in more detail. In the coding sequence, a polymorphism causing a deletion of two alanines was found to be associated with susceptibility for classical scrapie in sheep. Furthermore, a functional analysis of deletion constructs of the ovine SPRN promoter revealed that the region 464 to 230 bp upstream of exon 1 (containing a putative AP-2 and putative Sp1 binding sites) is of functional importance for SPRN transcription. Six mutations in the SPRN promoter were also found to alter the promoter activity in vitro. However, no association between any of these promoter mutations and susceptibility for classical scrapie was found. [source] Human prion strain selection in transgenic mice,ANNALS OF NEUROLOGY, Issue 2 2010Kurt Giles DPhil Objective: Transgenic (Tg) mice expressing chimeras of mouse and human prion proteins (PrPs) have shorter incubation periods for Creutzfeldt-Jakob disease (CJD) prions than mice expressing full-length human PrP. Increasing the sequence similarity of the chimeric PrP to mouse PrP, by reverting human residues to mouse, resulted in a Tg line, denoted Tg22372, which was susceptible to sporadic (s) CJD prions in ,110 days. Methods: Mice expressing chimeric mouse/human PrP transgenes were produced. The mice were inoculated intracerebrally with extracts prepared from the brains of patients who died of CJD. Onset of neurological dysfunction marked the end of the incubation time. After sacrifice of the Tg mice, their brains were analyzed for PrPSc and neuropathological changes. Results: Reversion of 1 additional residue (M111V) resulted in a new Tg line, termed Tg1014, susceptible to sCJD prions in ,75 days. Tg1014 mice also have shorter incubation periods for variant (v) CJD prions, providing a more tractable model for studying this prion strain. Transmission of vCJD prions to Tg1014 mice resulted in 2 different strains, determined by neuropathology and biochemical analysis, which correlated with the length of the incubation time. One strain had the biochemical, neuropathological, and transmission characteristics, including longer incubation times, of the inoculated vCJD strain; the second strain produced a phenotype resembling that of sCJD prions including relatively shorter incubation periods. Mice with intermediate incubation periods for vCJD prions had a mixture of the 2 strains. Both strains were serially transmitted in Tg1014 mice, which led to further reduction in incubation periods. Conversion of vCJD-like to sCJD-like strains was favored in Tg1014 mice more than in the Tg22372 line. The single amino acid difference therefore appears to offer selective pressure for propagation of the sCJD-like strain. Interpretation: These 2 Tg mouse lines provide relatively rapid models to study human prion diseases as well as the evolution of human prion strains. ANN NEUROL 2010;68:151,161 [source] Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein,ANNALS OF NEUROLOGY, Issue 2 2010Wen-Quan Zou MD Objective: The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV). Methods: Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics. Results: Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3 129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with "variably protease-sensitive prionopathy" (VPSPr). None of the subjects had mutations in the PrP gene coding region. Interpretation: Because all 3 129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Sträussler-Scheinker disease. ANN NEUROL 2010;68:162,172 [source] Clinical diagnosis and differential diagnosis of CJD and vCJD,APMIS, Issue 1 2002Inga Zerr The most widely distributed form of transmissible spongiform encephalopathy, sporadic Creutzfeldt-Jakob disease, typically affects patients in their sixties. Rapidly progressive dementia is usually followed by focal neurological signs and typically myoclonus. The disease duration in sporadic CJD is shorter than in variant CJD (6 months and 14 months, respectively). The clinical diagnosis in sporadic CJD is supported by the detection of periodic sharp and slow wave complexes in the electroencephalogram, hyperintense signals in basal ganglia on magnetic resonance imaging and elevated levels of neuronal proteins in the cerebrospinal fluid (such as 14-3-3). In contrast to the sporadic form, hyperintense signals in the posterior thalamus ("pulvinar sign") are seen in variant CJD. Following recent developments in diagnostic premortem techniques, clinical criteria for probable sporadic and probable variant CJD were established. Clinicopathological studies on sporadic CJD revealed different phenotypes which are characterized by neuropathological lesion profile, clinical syndrome, codon 129 genotype and type of proteinase K-resistant core of the prion protein. Alzheimer's disease and Lewy body dementia are the most frequent differential diagnoses in sporadic CJD in elderly patients, whereas chronic inflammatory disorders of the central nervous system have to be considered in younger patients. [source] Improved infection control in the prevention of variant Creutzfeldt-Jakob disease in Australia: costs and benefitsAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 6 2004Trang Vu Objective: To evaluate the costs and benefits of infection control strategies to prevent the transmission of variant Creutzfeldt-Jakob disease (vCJD) in ophthalmic surgery in Australia. Methods: The reduction in the risk of iatrogenic transmission of vCJD from feasible infection control strategies was calculated using decision analytic models. A static model calculated the direct secondary transmission for surgical eye procedures, and a simple dynamic model estimated the change in the risk of a subsequent sustained epidemic over the longer term. The expected number of vCJD infections, their cost of care and years of life lost and the estimated cost of strategies included the direct costs of infection control measures were calculated taking a health system perspective. Results: The dynamic model (Markov process) predicted that from a hypothetical pool of as many as 100 primary vCJD cases there would be less than five iatrogenic infections in the next 30 years. If there are fewer than five primary cases the model predicted no secondary cases of vCJD. The costs of providing care for a vCJD case is estimated to be about 50,000, subject to considerable uncertainty. The minimum cost for using a partial infection control strategy to prevent an iatrogenic infection is likely to be in the order of several millions of dollars. Conclusions: Substantial public health investment would need to be made in order to reduce a low risk of iatrogenic transmission of vCJD. Given the likely number of cases of iatrogenic infection, and the order of magnitude of the costs of caring for cases of vCJD, it may be difficult to justify the high cost of risk reduction strategies. [source] Immunohistochemistry for the Prion Protein: Comparison of Different Monoclonal Antibodies in Human Prion Disease SubtypesBRAIN PATHOLOGY, Issue 1 2002Gábor G. Kovács MD Demonstration of the abnormal form of the prion protein (PrP) in the brain confirms the diagnosis of human prion disease (PrD). Using immunohistochemistry, we have compared ten monoclonal antibodies in PrD subtypes including sporadic and variant Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Alzheimer's disease (AD), and control brains. CJD subgroups were determined using Western blot analysis for the protease-resistant PrP type in combination with sequencing to determine the genotype at the methionine/valine polymorphism at codon 129 of the prion protein gene. None of the antibodies labeled given subgroups exclusively, but the intensity of immunoreactivity varied among morphologically distinct types of deposit. Fine granular or synaptic PrP deposits stained weakly or not at all with antibodies against the N-terminus of PrP, and were visible in one case only with 12F10 and SAF54. Coarser and plaque type deposits were immunolabeled with all antibodies. The immunostaining patterns appear characteristic for the disease subgroups. Labeling of certain neurons in all cases irrespective of disease, and staining at the periphery and/or throughout the senile plaques of AD patients were also noted. Antibodies such as 6H4 and 12F10 failed to give this type of labeling and are therefore less likely to recognise non-pathological PrP material in immunohistochemistry. [source] Striatal [123I] FP-CIT SPECT demonstrates dopaminergic deficit in a sporadic case of Creutzfeldt,Jakob diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009M. Ragno Background,,, The frequent occurrence of movement disorders such as myoclonus, parkinsonism and dystonia, strongly suggests an involvement of the dopaminergic system in sporadic Creutzfeldt-Jakob disease (sCJD), but this issue has not been specifically addressed yet. Methods,,, We report a patient who after a sub-acute focal clinical onset, developed the full clinical picture of probable sCJD. Given the early unilateral right extrapyramidal rigidity, the patient was assessed by single-photon emission computed tomography of the dopamine transporter (DAT) using [123I] FP-CIT. Results,,, DAT-scan demonstrated reduced values of presynaptic receptorial trace in the putamen, particularly on the left side, consistent with functional putaminal dopaminergic presynaptic alteration. Conclusions,,, The present observation emphasizes the possible role of DAT imaging studies in the investigation of the pathogenesis of movement disorders in CJD. [source] Unraveling the mysteries of protein folding and misfoldingIUBMB LIFE, Issue 12 2008Heath Ecroyd Abstract This mini-review focuses on the processes and consequences of protein folding and misfolding. The latter process often leads to protein aggregation and precipitation with the aggregates adopting either highly ordered (amyloid fibril) or disordered (amorphous) forms. In particular, the amyloid fibril is discussed because this form has gained considerable notoriety due to its close links to a variety of debilitating diseases including Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jakob diseases, and type-II diabetes. In each of these diseases a different protein forms fibrils, yet the fibrils formed have a very similar structure. The mechanism by which fibrils form, fibril structure, and the cytotoxicity associated with fibril formation are discussed. The generic nature of amyloid fibril structure suggests that a common target may be accessible to treat amyloid fibril-associated diseases. As such, the ability of some molecules, for example, the small heat-shock family of molecular chaperone proteins, to inhibit fibril formation is of interest due to their therapeutic potential. © 2008 IUBMB IUBMB Life, 60(12): 769,774, 2008 [source] The ,Malbouffe' Saga La Saga de la ,Malbouffe' Die Saga von ,Malbouffe"EUROCHOICES, Issue 1 2007Alain Rérat summary The ,Malbouffe' Saga After the end of the Second World War, a marked increase in animal and plant production was observed in France, little by little considered by consumers to be obtained at the expense of product quality. The pejorative term ,malbouffe' soon emerged, in connection not only with the hygiene of food, but also with its organoleptic and technological characteristics. This article focuses on food safety in France, with special attention paid to the incidence of toxi-infections and food contaminations of biological and chemical origin. The Mad Cow outbreak is reviewed, along with its consequences for human health in the form of new variant Creutzfeldt-Jakob's disease. It is emphasized that food-related human mortality , almost exclusively due to biological contaminations , represented only 647 cases in 1995, i.e., 0.12 per cent of the overall mortality rate. The main contaminants were Salmonella, whose number is steadily decreasing, and Campylobacter, but parasite and phycotoxic risks are increasing. Mortality due to chemical contaminants is very low i.e., 10 cases or 0.002 per cent of overall mortality These contaminants, either accidental (dioxin, hydrocarbons, radioactive isotopes) or unavoidable (residues from phytochemicals, fertilisers) may be at the source of acute or chronic intoxications with sometimes unknown consequences. Nevertheless, food safety in France does not merit the spiteful term ,malbouffe'. Nach dem Ende des Zweiten Weltkriegs war in Frankreich im Bereich der Tier- und Pflanzenproduktion ein deutlicher Zuwachs zu beobachten, welcher in den Augen der Verbraucher zunehmend auf Kosten der Produktqualität erreicht wurde. Der abwertende Begriff ,Malbouffe" (in etwa ,schlechtes Essen") entstand bald darauf nicht nur im Hinblick auf die Nahrungsmittelhygiene, sondern auch in Bezug auf die organoleptischen und technologischen Eigenschaften der Nahrungsmittel. Dieser Beitrag konzentriert sich auf die Nahrungsmittelsicherheit in Frankreich unter besonderer Berücksichtigung der aufgetretenen Infektionen durch Giftstoffe und der Kontamination von Nahrungsmitteln biologischen und chemischen Ursprungs. Der BSE-Ausbruch und dessen Auswirkungen auf die Gesundheit des Menschen in Form von einer neuen Variante der Creutzfeldt-Jakob-Krankheit werden noch einmal betrachtet. Es wird hervor gehoben, dass die nahrungsmittelbedingte Sterblichkeit bei Menschen, die nahezu ausschließlich auf biologische Kontaminationen zurückzuführen ist, 1995 bei nur 647 Fällen lag, d.h. bei 0,12 Prozent der gesamten Sterblichkeitsrate. Die Nahrungsmittel wurden hauptsächlich durch Salmonellen (die Anzahl dieser Fälle nimmt kontinuierlich ab) und Campylobacter kontaminiert, die parasitären und phykotoxischen Risiken nehmen jedoch zu. Die auf chemische Kontaminationen zurückzuführende Sterblichkeit ist sehr gering und macht zehn Fälle oder 0,002 Prozent der gesamten Sterblichkeitsrate aus. Bei diesen Kontaminationen, die entweder zufällig herbei geführt werden (durch Dioxin, Kohlenwasserstoff, radioaktive Isotope) oder unvermeidbar sind (durch Rückstände pfl anzenchemischer Substanzen, Düngemittel), könnte es sich um die Ursache für akute oder chronische Vergiftungen handeln, welche zum Teil unbekannte Konsequenzen nach sich ziehen. Dennoch hat die Nahrungsmittelsicherheit in Frankreich den verächtlichen Begriff ,Malbouffe" nicht verdient. Après la fi n de la deuxième guerre mondiale, l'agriculture française a connu une augmentation spectaculaire des rendements des productions animale et végétale, rapidement accusée d'avoir été obtenue aux dépens de la qualité des produits consommés. Ainsi est apparue le terme barbare de «malbouffe», lié dans l'esprit des consommateurs, non seulement aux qualités hygiéniques de l'alimentation, mais également à ses caractéristiques sensorielles, voire technologiques. Ce rapport se focalise uniquement sur la salubrité alimentaire en France, soulignant, en particulier, l'évolution de l'incidence des toxi-infections et des contaminations alimentaires d'origine biologique et chimique. Après avoir rappelé l'épizootie de la vache folle (1000 cas en France depuis 1996 et actuellement en cours d'extinction) et de ses conséquences sur la santé humaine (nouvelle variante de la maladie de Creutzfeldt-Jakob) limitées actuellement à 13 cas mortels dans notre pays, ce rapport précise que la mortalité humaine liée à l'alimentation , presque totalement due à des contaminations biologiques - ne représentait en 1995 que 647 cas, i.e. 0.12% de la mortalité générale. Pour l'essentiel, ces contaminants sont des salmonelles, en baisse constante, et des campylobacter, mais on peut craindre la progression des risques parasitaires et phycotoxiques, encore réduits actuellement. La mortalité liée aux contaminants chimiques est très faible (10 cas, i.e. 0.002% de la mortalité générale); mais ces contaminants -qu'ils soient accidentels (dioxine, hydrocarbures, isotopes radio-actifs,) ou inévitables (résidus de phytosanitaires, d'engrais,)- peuvent être à l'origine de crises aiguës ou d'intoxications chroniques dont on ne connaît pas toujours les implications. Néanmoins, dans l'ensemble, la salubrité alimentaire en France ne mérite nullement la connotation malveillante du terme «malbouffe». [source] | |||||||||||||||||||||||||