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Sample records for atypical scrapie phenotype

  1. Phenotype shift from atypical scrapie to CH1641 following experimental transmission in sheep.

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    Simmons, Marion M; Moore, S Jo; Lockey, Richard; Chaplin, Melanie J; Konold, Timm; Vickery, Christopher; Spiropoulos, John

    2015-01-01

    The interactions of host and infecting strain in ovine transmissible spongiform encephalopathies are known to be complex, and have a profound effect on the resulting phenotype of disease. In contrast to classical scrapie, the pathology in naturally-occurring cases of atypical scrapie appears more consistent, regardless of genotype, and is preserved on transmission within sheep homologous for the prion protein (PRNP) gene. However, the stability of transmissible spongiform encephalopathy phenotypes on passage across and within species is not absolute, and there are reports in the literature where experimental transmissions of particular isolates have resulted in a phenotype consistent with a different strain. In this study, intracerebral inoculation of atypical scrapie between two genotypes both associated with susceptibility to atypical forms of disease resulted in one sheep displaying an altered phenotype with clinical, pathological, biochemical and murine bioassay characteristics all consistent with the classical scrapie strain CH1641, and distinct from the atypical scrapie donor, while the second sheep did not succumb to challenge. One of two sheep orally challenged with the same inoculum developed atypical scrapie indistinguishable from the donor. This study adds to the range of transmissible spongiform encephalopathy phenotype changes that have been reported following various different experimental donor-recipient combinations. While these circumstances may not arise through natural exposure to disease in the field, there is the potential for iatrogenic exposure should current disease surveillance and feed controls be relaxed. Future sheep to sheep transmission of atypical scrapie might lead to instances of disease with an alternative phenotype and onward transmission potential which may have adverse implications for both public health and animal disease control policies.

  2. The natural atypical scrapie phenotype is preserved on experimental transmission and sub-passage in PRNP homologous sheep

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    Bellworthy Susan J

    2010-03-01

    Full Text Available Abstract Background Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries. Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. The first successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007. Results This study demonstrates that atypical scrapie has distinct clinical, pathological and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype. Conclusions Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage.

  3. Atypical scrapie isolates involve a uniform prion species with a complex molecular signature.

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    Dorothea R Götte

    Full Text Available The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d. To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338. The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research.

  4. Atypical scrapie isolates involve a uniform prion species with a complex molecular signature.

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    Götte, Dorothea R; Benestad, Sylvie L; Laude, Hubert; Zurbriggen, Andreas; Oevermann, Anna; Seuberlich, Torsten

    2011-01-01

    The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d)). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research.

  5. Neuroanatomical distribution of abnormal prion protein in naturally occurring atypical scrapie cases in Great Britain.

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    Moore, Sarah Jo; Simmons, Marion; Chaplin, Melanie; Spiropoulos, John

    2008-11-01

    Scrapie belongs to a group of diseases known as the transmissible spongiform encephalopathies or prion diseases. Two different categories of naturally occurring scrapie have been identified: classical scrapie, which was first recorded around 1750, and atypical scrapie or 'Nor-98', which was first identified in Norway in 1998. The molecular characteristics of atypical scrapie have been well defined, but detailed descriptions of the neuropathological phenotype are rare since the majority of cases have been detected through active surveillance programmes where only brainstem and cerebellum are collected for statutory diagnosis. In order to characterise the neuropathology of naturally occurring atypical scrapie in sheep, we examined multiple brain levels from 15 whole brains from field cases of atypical scrapie, both clinical suspects and fallen stock, collected in Great Britain between 2004 and 2006. We found that the distribution of disease-associated prion protein (PrP(Sc)) and vacuolation in atypical scrapie cases are very different to both classical scrapie and experimental bovine spongiform encephalopathy in sheep. Immunolabelling for PrP(Sc) is mild and restricted at the obex and more intense and widespread rostrally, particularly in the cerebellum, substantia nigra, thalamus and basal nuclei. Intracellular immunolabelling types are not seen, but distinctive white matter immunolabelling is widespread. Vacuolation associated with PrP(Sc) deposits was not observed in the brainstem neuroanatomical areas commonly affected in classical scrapie and bovine spongiform encephalopathy, but was instead most prominent in the cerebellar cortex and neocortex. This is the largest comprehensive descriptive study of atypical scrapie pathology to date, and provides baseline data against which other natural or experimental cases can be compared. It also reinforces the current recommendation to collect cerebellum in addition to brainstem to enable confident confirmation of this

  6. Diversity in neuroanatomical distribution of abnormal prion protein in atypical scrapie.

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    Alice Nentwig

    2007-06-01

    Full Text Available Scrapie is a transmissible spongiform encephalopathy (TSE in sheep and goats. In recent years, atypical scrapie cases were identified that differed from classical scrapie in the molecular characteristics of the disease-associated pathological prion protein (PrP(sc. In this study, we analyze the molecular and neuropathological phenotype of nine Swiss TSE cases in sheep and goats. One sheep was identified as classical scrapie, whereas six sheep, as well as two goats, were classified as atypical scrapie. The latter revealed a uniform electrophoretic mobility pattern of the proteinase K-resistant core fragment of PrP(sc distinct from classical scrapie regardless of the genotype, the species, and the neuroanatomical structure. Remarkably different types of neuroanatomical PrP(sc distribution were observed in atypical scrapie cases by both western immunoblotting and immunohistochemistry. Our findings indicate that the biodiversity in atypical scrapie is larger than expected and thus impacts on current sampling and testing strategies in small ruminant TSE surveillance.

  7. Characterization of PRNP and SPRN coding regions from atypical scrapie cases diagnosed in Poland.

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    Piestrzyńska-Kajtoch, Agata; Gurgul, Artur; Polak, Mirosław P; Smołucha, Grzegorz; Zmudziński, Jan F; Rejduch, Barbara

    2012-03-01

    Scrapie, a fatal transmissible spongiform encephalopathy (TSE) occurs in two phenotypes: classical and atypical. Many authors point out that the polymorphism of three codons (136, 154, 171) of the PRNP (PrP gene) is associated with a sheep susceptibility to classical scrapie. Until now, only one PRNP gene variant coding phenylalanine at codon 141 has been found to be associated with atypical scrapie. Another recently identified and interesting candidate gene for scrapie susceptibility in sheep is an SPRN gene coding for Shadoo protein (Sho). Sho is a highly interspecies conserved protein and an insertion/deletion (indel) found in a sheep Sho gene was associated with classical scrapie occurrence. Here we determined the polymorphism of PRNP and SPRN genes in nine atypical scrapie cases (six in native born sheep and three in imported sheep) and compared these results with a control group of healthy animals comprising six corresponding Polish sheep breeds. In atypical scrapie cases five PRNP diplotypes were identified: A(136)R(154)Q(171)/ARQ, AHQ/ARQ, ARR/ARQ, ARR/AHQ and AHQ/AHQ. The ARR/AHQ diplotype was found only in imported sheep. A previously unobserved SNP in PRNP (E224K) was also found in both atypical scrapie and in a few control animals. In the ORF of the SPRN gene, six SNPs and one indel were identified. None of these variations was exclusive for scrapie animals and they were probably, naturally occurring polymorphisms. Special attention was given to the 6-bp indel SPRN polymorphism which was previously associated with classical scrapie occurrence.

  8. Epidemiological and genetical differences between classical and atypical scrapie cases

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    Lühken, Gesine; Buschmann, Anne; Brandt, Horst; Eiden, Martin; Groschup, Martin; Erhardt, Georg

    2007-01-01

    International audience; The aim of this study was to analyze the epidemiology and prion protein (PrP) genetics in scrapie-affected sheep flocks in Germany. For this purpose, 224 German scrapie cases in sheep diagnosed between January 2002 and February 2006 were classified as classical or atypical scrapie and the amino acids at codons 136, 141, 154 and 171 were determined. Likewise, representative numbers of flock mates were genotyped. Significant epidemiological differences were observed betw...

  9. Atypical/Nor98 scrapie infectivity in sheep peripheral tissues.

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    Olivier Andréoletti

    Full Text Available Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrP(Sc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.

  10. Discrepant epidemiological patterns between classical and atypical scrapie in sheep flocks under French TSE control measures.

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    Fediaevsky, Alexandre; Gasqui, Patrick; Calavas, Didier; Ducrot, Christian

    2010-09-01

    The occurrence of secondary cases of atypical and classical scrapie was examined in 340 outbreaks of atypical and 296 of classical sheep scrapie detected in France during active surveillance programmes between 2002 and 2007. The prevalence of atypical scrapie in these flocks was 0.05% under selective culling and 0.07% under intensified monitoring i.e. not significantly different from that detected during active surveillance of the general population (P>0.5), whereas these figures were much higher for classical scrapie (3.67% and 0.25%, respectively, P<10(-5)). In addition the number of atypical scrapie cases per outbreak did not indicate clustering. The results suggest that atypical scrapie occurs spontaneously or is not particularly contagious, and that the control measures in force allowed appropriate control of classical scrapie but were not more efficient than active surveillance in detecting cases of atypical scrapie.

  11. Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections.

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    Chong, Angela; Kennedy, Iain; Goldmann, Wilfred; Green, Andrew; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-10-01

    Natural scrapie in sheep occurs in classical and atypical forms, which may be distinguished on the basis of the associated neuropathology and properties of the disease-associated prion protein on Western blots. First detected in 1998, atypical scrapie is known to have occurred in UK sheep since the 1980s. However, its aetiology remains unclear and it is often considered as a sporadic, non-contagious disease unlike classical scrapie which is naturally transmissible. Although atypical scrapie tends to occur in sheep of prion protein (PRNP) genotypes that are different from those found predominantly in classical scrapie, there is some overlap so that there are genotypes in which both scrapie forms can occur. In this search for early atypical scrapie cases, we made use of an archive of fixed and frozen sheep samples, from both scrapie-affected and healthy animals (∼1850 individuals), dating back to the 1960s. Using a selection process based primarily on PRNP genotyping, but also on contemporaneous records of unusual clinical signs or pathology, candidate sheep samples were screened by Western blot, immunohistochemistry and strain-typing methods using tg338 mice. We identified, from early time points in the archive, three atypical scrapie cases, including one sheep which died in 1972 and two which showed evidence of mixed infection with classical scrapie. Cases with both forms of scrapie in the same animal as recognizable entities suggest that mixed infections have been around for a long time and may potentially contribute to the variety of scrapie strains.

  12. Identification of the first case of atypical scrapie in Japan

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    IMAMURA, Morikazu; MIYAZAWA, Kohtaro; IWAMARU, Yoshifumi; MATSUURA, Yuichi; YOKOYAMA, Takashi; OKADA, Hiroyuki

    2016-01-01

    A Corriedale ewe was confirmed as the first atypical scrapie case during an active surveillance program for transmissible spongiform encephalopathies in small ruminants in Japan. The animal was homozygous for the AF141RQ haplotype of PRNP. The animal showed clinical neurological signs possibly due to listeriosis before culling. Western blot analysis showed an unusual multiple banded pattern with a low-molecular fragment at ~7 kDa. Histopathology revealed suppurative meningoencephalitis caused by listeriosis in the brainstem. Fine granular to globular immunostaining of disease-associated prion proteins was mainly detected in the neuropil of the spinal tract of the trigeminal nerve and in the white matter of the spinocerebellar tract. Based on these results, this case was conclusively diagnosed as atypical scrapie with encephalitic listeriosis. PMID:27616556

  13. Immunological characterization of abnormal prion protein from atypical scrapie cases in sheep using a panel of monoclonal antibodies

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    Gretzschel, A.; Buschmann, A.; Langeveld, J.P.M.; Groschup, M.H.

    2006-01-01

    After the implementation of an active surveillance programme for scrapie in sheep in the EU, the number of diagnosed classical scrapie cases rose sharply and a novel kind of so-called atypical scrapie case was discovered. These atypical scrapie cases display unusual features concerning the distribut

  14. Clinical findings in two cases of atypical scrapie in sheep: a case report

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    Chaplin Melanie

    2007-02-01

    Full Text Available Abstract Background Atypical scrapie is a recently recognised form of transmissible spongiform encephalopathy of sheep that differs from classical scrapie in its neuropathological and biochemical features. Most cases are detected in apparently healthy sheep and information on the clinical presentation is limited. Case presentation This report describes the clinical findings in two sheep notified as scrapie suspects and confirmed as atypical scrapie cases by immunohistochemistry and Western immunoblotting. Although both sheep displayed signs suggestive of a cerebellar dysfunction there was considerable variation in the individual clinical signs, which were similar to classical scrapie. Conclusion Any sheep presenting with neurological gait deficits should be assessed more closely for other behavioural, neurological and physical signs associated with scrapie and their presence should lead to the suspicion of scrapie.

  15. A descriptive study of the prevalence of atypical and classical scrapie in sheep in 20 European countries

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    Calavas Didier

    2008-06-01

    Full Text Available Abstract Background The development of active surveillance programmes for transmissible spongiform encephalopathies of small ruminants across Europe has led to the recent identification of a previously undetected form of ovine prion disease, 'atypical' scrapie. Knowledge of the epidemiology of this disease is still limited, as is whether it represents a risk for animal and/or public health. The detection of atypical scrapie has been related to the use of only some of the EU agreed rapid tests. Information about the rapid tests used is not, as yet, available from public reports on the surveillance of transmissible spongiform encephalopathies in small ruminants. We collected detailed results of active surveillance from European countries to estimate and to compare the prevalence of atypical scrapie and classical scrapie in sheep for each country stratified by each surveillance stream; healthy slaughtered and found dead adult sheep. Results From the 20 participating countries, it appeared that atypical scrapie was detected in Europe wherever the conditions necessary for its diagnosis were present. In most countries, atypical scrapie and classical scrapie occurred at low prevalence level. The classical scrapie prevalence estimates were more variable than those for atypical scrapie, which appeared remarkably homogeneous across countries, surveillance streams and calendar years of surveillance. Differences were observed in the age and genotype of atypical scrapie and classical scrapie cases that are consistent with previous published findings. Conclusion This work suggests that atypical scrapie is not rare compared to classical scrapie. The homogeneity of its prevalence, whatever the country, stream of surveillance or year of detection, contrasts with the epidemiological pattern of classical scrapie. This suggests that the aetiology of atypical scrapie differs from that of classical scrapie.

  16. Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein.

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    Wadsworth, Jonathan D F; Joiner, Susan; Linehan, Jacqueline M; Balkema-Buschmann, Anne; Spiropoulos, John; Simmons, Marion M; Griffiths, Peter C; Groschup, Martin H; Hope, James; Brandner, Sebastian; Asante, Emmanuel A; Collinge, John

    2013-11-01

    Public and animal health controls to limit human exposure to animal prions are focused on bovine spongiform encephalopathy (BSE), but other prion strains in ruminants may also have zoonotic potential. One example is atypical/Nor98 scrapie, which evaded statutory diagnostic methods worldwide until the early 2000s. To investigate whether sheep infected with scrapie prions could be another source of infection, we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of classical and atypical scrapie, sheep with experimental BSE, and cattle with BSE. We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods when mice were inoculated with classical or atypical scrapie prions. These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to naturally occurring prions of sheep than after exposure to epizootic BSE prions of ruminants.

  17. Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks

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    Minguijón Esmeralda

    2010-03-01

    Full Text Available Abstract Background Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases with similarities to the previously identified atypical scrapie cases termed Nor98. Case presentation Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8, their breed (all Latxa and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ. All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum. Conclusions This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country. Moreover, a new genotype (ALRQ/ALRH was found associated to atypical scrapie.

  18. Clinical examination protocol to detect atypical and classical scrapie in sheep.

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    Konold, Timm; Phelan, Laura

    2014-01-19

    The diagnosis of scrapie, a transmissible spongiform encephalopathy (TSEs) of sheep and goats, is currently based on the detection of disease-associated prion protein by post mortem tests. Unless a random sample of the sheep or goat population is actively monitored for scrapie, identification of scrapie cases relies on the reporting of clinical suspects, which is dependent on the individual's familiarization with the disease and ability to recognize clinical signs associated with scrapie. Scrapie may not be considered in the differential diagnosis of neurological diseases in small ruminants, particularly in countries with low scrapie prevalence, or not recognized if it presents as nonpruritic form like atypical scrapie. To aid in the identification of clinical suspects, a short examination protocol is presented to assess the display of specific clinical signs associated with pruritic and nonpruritic forms of TSEs in sheep, which could also be applied to goats. This includes assessment of behavior, vision (by testing of the menace response), pruritus (by testing the response to scratching), and movement (with and without blindfolding). This may lead to a more detailed neurologic examination of reporting animals as scrapie suspects. It could also be used in experimental TSE studies of sheep or goats to evaluate disease progression or to identify clinical end-point.

  19. A retrospective immunohistochemical study reveals atypical scrapie has existed in the United Kingdom since at least 1987.

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    Webb, Paul R; Powell, Linda; Denyer, Margaret; Marsh, Sarah; Weaver, Colin; Simmons, Marion M; Johns, Elizabeth; Sheehan, John; Horsfield, Peter; Lyth, Chris; Wilson, Christina; Long, Ann; Cawthraw, Saira; Saunders, Ginny C; Spencer, Yvonne I

    2009-11-01

    Atypical scrapie is a relatively recent discovery, and it was unknown whether it was a new phenomenon or whether it had existed undetected in the United Kingdom national flock. Before 1998, the routine statutory diagnosis of transmissible spongiform encephalopathy (TSE) in sheep relied on the presence of TSE vacuolation in the brainstem. This method would not have been effective for the detection of atypical scrapie. Currently, immunohistochemistry (IHC) and Western blot are commonly used for the differential diagnosis of classical and atypical scrapie. The IHC pattern of PrPd deposition in atypical scrapie is very different from that in classical scrapie using the same antibody. It is thus possible that because of a lack of suitable diagnostic techniques and awareness of this form of the disease, historic cases of atypical scrapie remain undiagnosed. Immunohistochemistry was performed on selected formalin-fixed, paraffin-embedded (FFPE) blocks of ovine brain from the Veterinary Laboratories Agency archives that were submitted for various reasons, including suspect neurological disorders, between 1980 and 1989. It was found that PrPd deposits in a single case were consistent with atypical scrapie. A method was developed to obtain a PrP genotype from FFPE tissues and was applied to material from this single case, which was shown to be AHQ/AHQ. This animal was a scrapie suspect from 1987, but diagnosis was not confirmed by the available techniques at that time.

  20. Detection of classical and atypical/Nor98 scrapie by the paraffin-embedded tissue blot method.

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    Wemheuer, W M; Benestad, S L; Wrede, A; Wemheuer, W E; Brenig, B; Bratberg, B; Schulz-Schaeffer, W J

    2009-05-30

    The paraffin-embedded tissue (PET) blot method was used to investigate sections of the central nervous system and lymphatic tissues from 24 cases of classical scrapie and 25 cases of atypical/Nor98 scrapie in sheep and four healthy control sheep. The PET blot detected deposits of PrP(Sc) in the brain tissue of all 49 sheep with scrapie but no PrP(Sc) labelling could be detected in the control sheep. By contrast, not all the atypical/Nor98 scrapie cases were detectable by immunohistochemistry. The high sensitivity of the PET blot method made it possible to observe that in some atypical/Nor98 cases, deposits of PrP(Sc) may be restricted to supratentorial brain structures and that the diagnosis may be missed when only testing the obex area, where deposits are common in classical scrapie, and the cerebellar structures, where deposits are considered to be common in atypical/Nor98 cases.

  1. A descriptive study of the prevalence of atypical and classical scrapie in sheep in 20 European countries.

    OpenAIRE

    Calavas Didier; Nöremark Maria; Tongue Sue C; Fediaevsky Alexandre; Ru Giuseppe; Hopp Petter

    2008-01-01

    Abstract Background The development of active surveillance programmes for transmissible spongiform encephalopathies of small ruminants across Europe has led to the recent identification of a previously undetected form of ovine prion disease, 'atypical' scrapie. Knowledge of the epidemiology of this disease is still limited, as is whether it represents a risk for animal and/or public health. The detection of atypical scrapie has been related to the use of only some of the EU agreed rapid tests...

  2. A Case–Control Study on the Origin of Atypical Scrapie in Sheep, France

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    Morignat, Eric; Ducrot, Christian; Calavas, Didier

    2009-01-01

    A matched case–control study (95 cases and 220 controls) was designed to study risk factors for atypical scrapie in sheep in France. We analyzed contacts with animals from other flocks, lambing and feeding practices, and exposure to toxic substances. Data on the prnp genotype were collected for some case and control animals and included in a complementary analysis. Sheep dairy farms had a higher risk for scrapie (odds ratio [OR] 15.1, 95% confidence interval [CI] 3.3–69.7). Lower risk was associated with organic farms (OR 0.15, 95% CI 0.02–1.26), feeding corn silage (OR 0.16, 95% CI 0.05–0.53), and feeding vitamin and mineral supplements (OR 0.6, 95% CI 0.32–1.14). Genetic effects were quantitatively important but only marginally changed estimates of other variables. We did not find any risk factor associated with an infectious origin of scrapie. Atypical scrapie could be a spontaneous disease influenced by genetic and metabolic factors. PMID:19402956

  3. Atypical disease phenotypes in pediatric ulcerative colitis

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    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...

  4. Transmissibility of atypical scrapie in ovine transgenic mice: major effects of host prion protein expression and donor prion genotype.

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    Jean-Noël Arsac

    Full Text Available Atypical scrapie or Nor98 has been identified as a transmissible spongiform encephalopathy (TSE that is clearly distinguishable from classical scrapie and BSE, notably regarding the biochemical features of the protease-resistant prion protein PrP(res and the genetic factors involved in susceptibility to the disease. In this study we transmitted the disease from a series of 12 French atypical scrapie isolates in a transgenic mouse model (TgOvPrP4 overexpressing in the brain approximately 0.25, 1.5 or 6x the levels of the PrP(ARQ ovine prion protein under the control of the neuron-specific enolase promoter. We used an approach based on serum PrP(c measurements that appeared to reflect the different PrP(c expression levels in the central nervous system. We found that transmission of atypical scrapie, much more than in classical scrapie or BSE, was strongly influenced by the PrP(c expression levels of TgOvPrP4 inoculated mice. Whereas TgOvPrP4 mice overexpressing approximately 6x the normal PrP(c level died after a survival periods of 400 days, those with approximately 1.5x the normal PrP(c level died at around 700 days. The transmission of atypical scrapie in TgOvPrP4 mouse line was also strongly influenced by the prnp genotypes of the animal source of atypical scrapie. Isolates carrying the AF(141RQ or AHQ alleles, associated with increased disease susceptibility in the natural host, showed a higher transmissibility in TgOvPrP4 mice. The biochemical analysis of PrP(res in TgOvPrP4 mouse brains showed a fully conserved pattern, compared to that in the natural host, with three distinct PrP(res products. Our results throw light on the transmission features of atypical scrapie and suggest that the risk of transmission is intrinsically lower than that of classical scrapie or BSE, especially in relation to the expression level of the prion protein.

  5. Review: A review on classical and atypical scrapie in caprine: Prion protein gene polymorphisms and their role in the disease.

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    Curcio, L; Sebastiani, C; Di Lorenzo, P; Lasagna, E; Biagetti, M

    2016-10-01

    Scrapie is a naturally occurring transmissible spongiform encephalopathy in sheep and goat. It has been known for ~250 years and is characterised by the accumulation of an abnormal isoform of a host-encoded prion protein that leads to progressive neurodegeneration and death. Scrapie is recognised in two forms, classical and atypical scrapie. The susceptibility to both types of scrapie is influenced by polymorphisms of the prion protein gene (PRNP). Sheep susceptibility or resistance to classical scrapie is strongly regulated by the polymorphisms at codons 136, 154 and 171 of the PRNP. The genetic role in atypical scrapie in sheep has been defined by polymorphisms at codons 141, 154 and 171, which are associated with different degrees of risk in the occurrence of the ovine disease. Progress has been achieved in the prevention of scrapie in sheep due to efficient genetic breeding programmes based on eradication and control of the disease. In Europe, the success of these programmes has been verified by applying eradication and genetic selection plans. In general terms, the ovine selection plans aim to eliminate and reduce the susceptible allele and to enrich the resistant allele ARR. During outbreaks all susceptible animals are slaughtered, only ARR/ARR resistant rams and sheep and semi-resistant females are preserved. In the occurrence of scrapie positive goats a complete cull of the flock (stamping out) is performed with great economic loss and severe risk of extinction for the endangered breeds. The ability to select scrapie-resistant animals allows to define new breeding strategies aimed to boost genetic progress while reducing costs during scrapie outbreaks. Allelic variants of PRNP can be protective for caprine scrapie, and the knowledge of their distribution in goats has become very important. Over the past few years, the integration of genetic information on goat populations could be used to make selection decisions, commonly referred to as genetic selection

  6. Quantitative estimation of genetic risk for atypical scrapie in French sheep and potential consequences of the current breeding programme for resistance to scrapie on the risk of atypical scrapie

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    Laurent Pascal

    2010-05-01

    Full Text Available Abstract Background Since 2002, active surveillance programmes have detected numerous atypical scrapie (AS and classical scrapie cases (CS in French sheep with almost all the PrP genotypes. The aim of this study was 1 to quantify the genetic risk of AS in French sheep and to compare it with the risk of CS, 2 to quantify the risk of AS associated with the increase of the ARR allele frequency as a result of the current genetic breeding programme against CS. Methods We obtained genotypes at codons 136, 141, 154 and 171 of the PRNP gene for representative samples of 248 AS and 245 CS cases. We used a random sample of 3,317 scrapie negative animals genotyped at codons 136, 154 and 171 and we made inferences on the position 141 by multiple imputations, using external data. To estimate the risk associated with PrP genotypes, we fitted multivariate logistic regression models and we estimated the prevalence of AS for the different genotypes. Then, we used the risk of AS estimated for the ALRR-ALRR genotype to analyse the risk of detecting an AS case in a flock homogenous for this genotype. Results Genotypes most at risk for AS were those including an AFRQ or ALHQ allele while genotypes including a VLRQ allele were less commonly associated with AS. Compared to ALRQ-ALRQ, the ALRR-ALRR genotype was significantly at risk for AS and was very significantly protective for CS. The prevalence of AS among ALRR-ALRR animals was 0.6‰ and was not different from the prevalence in the general population. Conclusion In conclusion, further selection of ALRR-ALRR animals will not result in an overall increase of AS prevalence in the French sheep population although this genotype is clearly susceptible to AS. However the probability of detecting AS cases in flocks participating in genetic breeding programme against CS should be considered.

  7. The interpretation of disease phenotypes to identify TSE strains following murine bioassay: characterisation of classical scrapie.

    Science.gov (United States)

    Beck, Katy E; Vickery, Christopher M; Lockey, Richard; Holder, Thomas; Thorne, Leigh; Terry, Linda A; Denyer, Margaret; Webb, Paul; Simmons, Marion M; Spiropoulos, John

    2012-11-01

    Mouse bioassay can be readily employed for strain typing of naturally occurring transmissible spongiform encephalopathy cases. Classical scrapie strains have been characterised historically based on the established methodology of assessing incubation period of disease and the distribution of disease-specific vacuolation across the brain following strain stabilisation in a given mouse line. More recent research has shown that additional methods could be used to characterise strains and thereby expand the definition of strain "phenotype". Here we present the phenotypic characteristics of classical scrapie strains isolated from 24 UK ovine field cases through the wild-type mouse bioassay. PrPSc immunohistochemistry (IHC), paraffin embedded tissue blots (PET-blot) and Western blotting approaches were used to determine the neuroanatomical distribution and molecular profile of PrPSc associated with each strain, in conjunction with traditional methodologies. Results revealed three strains isolated through each mouse line, including a previously unidentified strain. Moreover IHC and PET-blot methodologies were effective in characterising the strain-associated types and neuroanatomical locations of PrPSc. The use of Western blotting as a parameter to define classical scrapie strains was limited. These data provide a comprehensive description of classical scrapie strain phenotypes on isolation through the mouse bioassay that can provide a reference for further scrapie strain identification.

  8. Clinical Examination Protocol to Detect Atypical and Classical Scrapie in Sheep

    OpenAIRE

    Konold, Timm; Phelan, Laura

    2014-01-01

    The diagnosis of scrapie, a transmissible spongiform encephalopathy (TSEs) of sheep and goats, is currently based on the detection of disease-associated prion protein by post mortem tests. Unless a random sample of the sheep or goat population is actively monitored for scrapie, identification of scrapie cases relies on the reporting of clinical suspects, which is dependent on the individual's familiarization with the disease and ability to recognize clinical signs associated with scrapie. Scr...

  9. Different prion disease phenotypes result from inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain

    Directory of Open Access Journals (Sweden)

    Hawkins Steve AC

    2006-10-01

    Full Text Available Abstract Background Given the theoretical proposal that bovine spongiform encephalopathy (BSE could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c. inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic. Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990. Control groups comprised five cattle inoculated with sheep brain free from scrapie, five cattle inoculated with saline, and for comparison with BSE, naturally infected cattle and cattle i.c. inoculated with BSE brainstem homogenate from a parallel study. Phenotypic characterisation of the disease forms transmitted to cattle was conducted by morphological, immunohistochemical, biochemical and biological methods. Results Disease occurred in 16 cattle, nine inoculated with the pre-1975 inoculum and seven inoculated with the post-1990 inoculum, with four cattle still alive at 83 months post challenge (as at June 2006. The different inocula produced predominantly two different disease phenotypes as determined by histopathological, immunohistochemical and Western immunoblotting methods and biological characterisation on transmission to mice, neither of which was identical to BSE. Whilst the disease presentation was uniform in all scrapie-affected cattle of the pre-1975 group, the post-1990 inoculum produced a more variable disease, with two animals sharing immunohistochemical and molecular profile characteristics with animals in the pre-1975 group. Conclusion The study has demonstrated that cattle inoculated with different pooled scrapie sources can develop different prion disease phenotypes, which were not consistent with the phenotype of BSE of cattle and whose isolates did not have the strain typing characteristics of the BSE agent on transmission to mice.

  10. Diagnosis of the first cases of scrapie in Poland

    NARCIS (Netherlands)

    Polak, M.P.; Larska, M.; Langeveld, J.P.M.; Buschmann, A.; Groschup, M.H.; Zmudzinski, J.F.

    2010-01-01

    This is the first report of cases of scrapie in Poland. The disease was an atypical phenotype, diagnosed in two aged sheep which were found dead. Brainstem samples from both animals were positive on the applied ELISA rapid test, while the confirmatory immunoblot indicated abnormal banding patterns o

  11. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.

    Science.gov (United States)

    Wilson, Rona; Plinston, Chris; Hunter, Nora; Casalone, Cristina; Corona, Cristiano; Tagliavini, Fabrizio; Suardi, Silvia; Ruggerone, Margherita; Moda, Fabio; Graziano, Silvia; Sbriccoli, Marco; Cardone, Franco; Pocchiari, Maurizio; Ingrosso, Loredana; Baron, Thierry; Richt, Juergen; Andreoletti, Olivier; Simmons, Marion; Lockey, Richard; Manson, Jean C; Barron, Rona M

    2012-07-01

    The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

  12. Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics

    NARCIS (Netherlands)

    Cali, I.; Castellani, R.; Alshekhlee, A.; Cohen, Y.; Blevins, J.; Yuan, J.; Langeveld, J.P.M.; Parchi, P.; Safar, J.G.; Zou, W.Q.; Gambetti, P.

    2009-01-01

    Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrPSc) types

  13. Incidence of infection in Prnp ARR/ARR sheep following experimental inoculation with or natural exposure to classical scrapie.

    Directory of Open Access Journals (Sweden)

    Martin Jeffrey

    Full Text Available The prion protein gene (Prnp is highly influential in determining risk and susceptibility of sheep exposed to classical scrapie. Sheep homozygous for alanine at codon 136 and arginine at codons 154 and 171 (ARR/ARR of the Prnp gene are historically considered to be highly resistant to classical scrapie, although they form a significant fraction of cases of atypical scrapie. To date, experimental transmission of prions to ARR/ARR sheep has only been achieved with the BSE agent and mostly by the intracerebral route. We summarise here the results of six separate studies, in which 95 sheep of the ARR/ARR genotype were naturally exposed to (n = 18 or experimentally challenged with (n = 77 natural or experimental sources of classical scrapie by the oral, intra-intestinal, subcutaneous or intracerebral routes and allowed to survive for periods of up to 94 months post-infection. Only the intracerebral route resulted in disease and/or amplification of disease associated PrP (PrPd, and only in two of 19 sheep that survived for longer than 36 months. Discriminatory immunohistochemistry and Western blot confirmed the scrapie, non-BSE signature of PrPd in those two sheep. However, the neuropathological phenotype was different from any other scrapie (classical or atypical or BSE source previously reported in sheep of any Prnp genotype. These studies confirm the widely held view that ARR/ARR sheep are highly resistant to classical scrapie infection, at least within their commercial lifespan. Moreover, within the constraints of the present studies (only two infected sheep, these results do not support the suggestion that atypical scrapie or BSE are generated by adaptation or mutation of classical scrapie in sheep of resistant ARR/ARR genotype.

  14. Incidence of infection in Prnp ARR/ARR sheep following experimental inoculation with or natural exposure to classical scrapie.

    Science.gov (United States)

    Jeffrey, Martin; Martin, Stuart; Chianini, Francesca; Eaton, Samantha; Dagleish, Mark P; González, Lorenzo

    2014-01-01

    The prion protein gene (Prnp) is highly influential in determining risk and susceptibility of sheep exposed to classical scrapie. Sheep homozygous for alanine at codon 136 and arginine at codons 154 and 171 (ARR/ARR) of the Prnp gene are historically considered to be highly resistant to classical scrapie, although they form a significant fraction of cases of atypical scrapie. To date, experimental transmission of prions to ARR/ARR sheep has only been achieved with the BSE agent and mostly by the intracerebral route. We summarise here the results of six separate studies, in which 95 sheep of the ARR/ARR genotype were naturally exposed to (n = 18) or experimentally challenged with (n = 77) natural or experimental sources of classical scrapie by the oral, intra-intestinal, subcutaneous or intracerebral routes and allowed to survive for periods of up to 94 months post-infection. Only the intracerebral route resulted in disease and/or amplification of disease associated PrP (PrPd), and only in two of 19 sheep that survived for longer than 36 months. Discriminatory immunohistochemistry and Western blot confirmed the scrapie, non-BSE signature of PrPd in those two sheep. However, the neuropathological phenotype was different from any other scrapie (classical or atypical) or BSE source previously reported in sheep of any Prnp genotype. These studies confirm the widely held view that ARR/ARR sheep are highly resistant to classical scrapie infection, at least within their commercial lifespan. Moreover, within the constraints of the present studies (only two infected sheep), these results do not support the suggestion that atypical scrapie or BSE are generated by adaptation or mutation of classical scrapie in sheep of resistant ARR/ARR genotype.

  15. Influence of polymorphisms in the prion protein gene on the pathogenesis and neuropathological phenotype of sheep scrapie after oral infection.

    Science.gov (United States)

    González, L; Pitarch, J L; Martin, S; Thurston, L; Simmons, H; Acín, C; Jeffrey, M

    2014-01-01

    The prion protein gene (Prnp) plays a crucial role in the susceptibility of sheep to scrapie in terms of attack rate and/or incubation period. However, the influence of Prnp on the pathogenesis of the disease, specifically the involvement of tissues of the lymphoreticular system (LRS), pathways of neuroinvasion and neuropathological phenotypes, remains controversial. This study reports the onset and progression of disease-associated prion protein (PrP(d)) accumulation in the LRS and nervous tissues of sheep of six different Prnp genotypes infected by oral administration of the same mixed scrapie brain homogenate. Sheep homozygous for glutamine (Q) at codon 171 of PrP, with either valine (V) or alanine (A) at codon 136 (i.e. VRQ/VRQ, VRQ/ARQ and ARQ/ARQ), showed early and consistent PrP(d) accumulation in LRS tissues of the pharynx and gut. In contrast, LRS involvement was minimal, inconsistent and occurred late in the incubation period in sheep heterozygous for arginine (R) at codon 171 (i.e. VRQ/ARR and ARQ/ARR). Despite this difference, all five groups were susceptible to infection and developed clinical disease, albeit with significantly different incubation periods (shortest in VRQ/VRQ and longest in ARQ/ARR sheep). The remaining group of ARR/ARR homozygous sheep did not show evidence of infection at the end of the experiment or at previous predetermined time points. As for LRS tissues, the sites of initial PrP(d) accumulation in the brain were determined immunohistochemically. These were the same in all susceptible sheep (except for ARR/ARR sheep), regardless of their Prnp genotype which, together with an early and consistent accumulation of PrP(d) in circumventricular organs and a late or inconsistent involvement of the enteric and autonomic nervous system and of the spinal cord, suggests neuroinvasion occurring via the blood. The neuropathological phenotype (PrP(d) profile in the central nervous system) of clinically affected sheep was similar in the three V

  16. Diagnosis of the first cases of scrapie in Poland.

    Science.gov (United States)

    Polak, Miroslaw P; Larska, Magdalena; Langeveld, Jan P M; Buschmann, Anne; Groschup, Martin H; Zmudzinski, Jan F

    2010-10-01

    This is the first report of cases of scrapie in Poland. The disease was an atypical phenotype, diagnosed in two aged sheep which were found dead. Brainstem samples from both animals were positive on the applied ELISA rapid test, while the confirmatory immunoblot indicated abnormal banding patterns of protease resistant prion protein (PrP(res)). The genotypes of these sheep were ALRQ/ALHQ and ALRQ/ALRR. The absence of premonitory clinical signs, the advanced age of the affected sheep, the higher concentration of PrP(res) in the cerebellum relative to the obex, the unusual banding profile of the prion protein and its relatively low resistance to proteolytic degradation confirmed the diagnosis of atypical scrapie (Nor98-like) in both cases.

  17. Identical pathogenesis and neuropathological phenotype of scrapie in valine, arginine, glutamine/valine, arginine, glutamine sheep infected experimentally by the oral and conjunctival routes.

    Science.gov (United States)

    González, L; Pitarch, J L; Martin, S; Thurston, L; Moore, J; Acín, C; Jeffrey, M

    2014-01-01

    The pathogenesis of scrapie in sheep after natural or oral exposure to the infectious agent generally involves the early accumulation of disease-associated prion protein (PrP(d)) in the lymphoreticular system (LRS). This phase is followed by neuroinvasion, for which two routes, ascending neural and haematogenous, have been postulated. The present study reports the use of immunohistochemistry to track the tissue progression of PrP(d) deposition in sheep of a single, highly scrapie-susceptible PrP genotype administered by the oral or conjunctival routes. Regardless of the route of infection, the earliest detection of PrP(d) was in gut- and pharynx-associated LRS tissues. Subsequently, the brain became PrP(d) positive simultaneously with other LRS tissues, but before the spinal cord and peripheral nervous tissues of the enteric, parasympathetic and sympathetic systems. The sites of initial PrP(d) accumulation in the brain were the dorsal motor nucleus of the vagus and the hypothalamus and their related circumventricular organs (the area postrema and the median eminence, respectively). These were the same for both routes of infection. Rapid progression to clinical disease was observed in sheep infected orally or conjunctivally, with definite signs of scrapie recorded at around 6 and 8 months after infection, respectively. Longer incubation periods in sheep infected by the conjunctival route were probably due to them receiving a lower dose than those infected orally. Irrespective of the route of infection, clinically affected sheep showed the same pathological phenotype (PrP(d) profile) and PrP(d) distribution throughout the brain. The identical peripheral and central pathogenesis observed in sheep of both groups suggests early dissemination of the infectious agent in the bloodstream and a common neuroinvasion pathway. The late involvement of the enteric and autonomic nervous system supports a haematogenous route of infection to the brain.

  18. A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation.

    Science.gov (United States)

    Boutoleau-Bretonnière, Claire; Camuzat, Agnès; Le Ber, Isabelle; Bouya-Ahmed, Kawtar; Guerreiro, Rita; Deruet, Anne-Laure; Evrard, Christelle; Bras, José; Lamy, Estelle; Auffray-Calvier, Elisabeth; Pallardy, Amandine; Hardy, John; Brice, Alexis; Derkinderen, Pascal; Vercelletto, Martine

    2015-01-01

    SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. More recently, SQSTM1 mutations were identified in few families with frontotemporal dementia. We report a new family carrying SQSTM1 mutation and presenting with a clinical phenotype of speech apraxia or atypical behavioral disorders, associated with early visuo-contructional deficits. This study further supports the implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic spectrum associated with SQSTM1 mutations.

  19. Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype?

    Science.gov (United States)

    Verhoeven, Willem MA; Egger, Jos IM; Willemsen, Marjolein H; de Leijer, Gert JM; Kleefstra, Tjitske

    2012-01-01

    The 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep disturbances, communication deficits, and motor perseverations. Data on psychological dysfunctions are so far not available. Previous studies have suggested that the loss of one copy of the gene SH3 and multiple ankyrin repeat domains 3 (SHANK3) is related to the neurobehavioral phenotype. Additional genes proximal to SHANK3 are also likely to play a role in the phenotype of patients with larger deletions. The present paper describes two adult brothers with an identical 2.15 Mb 22qter (22q13.32q13.33) deletion, of whom the youngest was referred for evaluation of recurrent mood changes. In both patients, magnetic resonance imaging of the brain showed hypoplasia of the vermis cerebelli. Extensive clinical examinations led to a final diagnosis of atypical bipolar disorder, of which symptoms fully remitted during treatment with a mood stabilizer. In the older brother, a similar psychopathological picture appeared to be present, although less severe and with a later onset. It is concluded that the behavioral phenotype of the 22q13.3 deletion syndrome comprises absent or delayed speech and perseverations with associated autistic-like features, whereas its psychopathological phenotype comprises an atypical bipolar disorder. The latter may have implications for the treatment regime of the syndrome-related behavioral disturbances. PMID:22570549

  20. Comparison of two US sheep scrapie isolates supports identification as separate strains

    Science.gov (United States)

    Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) of sheep and goats. There are different strains of sheep scrapie that are associated with unique molecular, transmission, and phenotype characteristics, but very little is known about the potential presence of scrapie str...

  1. Genotyping and surveillance for scrapie in Finnish sheep

    Directory of Open Access Journals (Sweden)

    Hautaniemi Maria

    2012-07-01

    Full Text Available Abstract Background The progression of scrapie is known to be influenced by the amino acid polymorphisms of the host prion protein (PrP gene. There is no breeding programme for TSE resistance in sheep in Finland, but a scrapie control programme has been in place since 1995. In this study we have analysed PrP genotypes of total of 928 purebred and crossbred sheep together with the data of scrapie survey carried out in Finland during 2002–2008 in order to gain knowledge of the genotype distribution and scrapie prevalence in Finnish sheep. Results The ARQ/ARQ genotype was the most common genotype in all breeds studied. ARR allele frequency was less than 12% in purebred Finnish sheep and in most genotypes heterozygous for ARR, the second allele was ARQ. The VRQ allele was not detected in the Grey race sheep of Kainuu or in the Aland sheep, and it was present in less than 6% of the Finnish Landrace sheep. Leucine was the most prominent amino acid found in codon 141. In addition, one novel prion dimorphisms of Q220L was detected. During the scrapie survey of over 15 000 sheep in 2002–2008, no classical scrapie cases and only five atypical scrapie cases were detected. Conclusions The results indicate that the Finnish sheep populations have genetically little resistance to classical scrapie, but no classical scrapie was detected during an extensive survey in 2002–2008. However, five atypical scrapie cases emerged; thus, the disease is present in the Finnish sheep population at a low level.

  2. Phenotypic and Genotypic Characterization of Atypical Listeria monocytogenes and Listeria innocua Isolated from Swine Slaughterhouses and Meat Markets

    Directory of Open Access Journals (Sweden)

    Luisa Zanolli Moreno

    2014-01-01

    Full Text Available In the last decade, atypical Listeria monocytogenes and L. innocua strains have been detected in food and the environment. Because of mutations in the major virulence genes, these strains have different virulence intensities in eukaryotic cells. In this study, we performed phenotypic and genotypic characterization of atypical L. monocytogenes and L. innocua isolates obtained from swine slaughterhouses and meat markets. Forty strains were studied, including isolates of L. monocytogenes and L. innocua with low-hemolytic activity. The isolates were characterized using conventional phenotypic Listeria identification tests and by the detection and analysis of L. monocytogenes-specific genes. Analysis of 16S rRNA was used for the molecular identification of the Listeria species. The L. monocytogenes isolates were positive for all of the virulence genes studied. The atypical L. innocua strains were positive for hly, plcA, and inlC. Mutations in the InlC, InlB, InlA, PI-PLC, PC-PLC, and PrfA proteins were detected in the atypical isolates. Further in vitro and transcriptomic studies are being developed to confirm the role of these mutations in Listeria virulence.

  3. Genomic and Phenotypic Analyses Reveal the Emergence of an Atypical Salmonella enterica Serovar Senftenberg Variant in China

    KAUST Repository

    Abd El Ghany, Moataz

    2016-05-25

    Human infections with Salmonella enterica subspecies enterica serovar Senftenberg are often associated with exposure to poultry flocks, farm environments, or contaminated food. The recent emergence of multidrug-resistant isolates has raised public health concerns. In this study, comparative genomics and phenotypic analysis were used to characterize 14 Salmonella Senftenberg clinical isolates recovered from multiple outbreaks in Shenzhen and Shanghai, China, between 2002 and 2011. Single-nucleotide polymorphism analyses identified two phylogenetically distinct clades of S. Senftenberg, designated SC1 and SC2, harboring variations in Salmonella pathogenicity island 1 (SPI-1) and SPI-2 and exhibiting distinct biochemical and phenotypic signatures. Although the two variants shared the same serotype, the SC2 isolates of sequence type 14 (ST14) harbored intact SPI-1 and -2 and hence were characterized by possessing efficient invasion capabilities. In contrast, the SC1 isolates had structural deletion patterns in both SPI-1 and -2 that correlated with an impaired capacity to invade cultured human cells and also the year of their isolation. These atypical SC1 isolates also lacked the capacity to produce hydrogen sulfide. These findings highlight the emergence of atypical Salmonella Senftenberg variants in China and provide genetic validation that variants lacking SPI-1 and regions of SPI-2, which leads to impaired invasion capacity, can still cause clinical disease. These data have identified an emerging public health concern and highlight the need to strengthen surveillance to detect the prevalence and transmission of nontyphoidal Salmonella species.

  4. p.Pro4Arg mutation in LMNA gene: a new atypical progeria phenotype without metabolism abnormalities.

    Science.gov (United States)

    Guo, Hong; Luo, Na; Hao, Fei; Bai, Yun

    2014-08-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a typical presenile disorder, with mutation in the LMNA gene. Besides HGPS, mutations in LMNA gene have also been reported in atypical progeroid syndrome (APS). The objective of the study was to investigate the phenotype and molecular basis of APS in a Chinese family. LMNA gene mutations were also reviewed to identify the phenotypic and pathogenic differences among APS. Two siblings in a non-consanguineous Chinese family with atypical progeria were reported. The clinical features were observed, including presenile manifestations such as bird-like facial appearance, generalized lipodystrophy involving the extremities and mottled hyperpigmentation on the trunk and extremities. A heterozygous mutation c.11C>G (p.Pro4Arg) of the LMNA gene was detected in the two patients. 28 different variants of the LMNA gene have been reported in APS families, spreading over almost all the 12 exons of the LMNA gene with some hot-spot regions. This is the first detailed description of an APS family without metabolism abnormalities. APS patients share most of the clinical features, but there may be some distinct features in different ethnic groups.

  5. Evidence for zoonotic potential of ovine scrapie prions.

    Science.gov (United States)

    Cassard, Hervé; Torres, Juan-Maria; Lacroux, Caroline; Douet, Jean-Yves; Benestad, Sylvie L; Lantier, Frédéric; Lugan, Séverine; Lantier, Isabelle; Costes, Pierrette; Aron, Naima; Reine, Fabienne; Herzog, Laetitia; Espinosa, Juan-Carlos; Beringue, Vincent; Andréoletti, Olivier

    2014-12-16

    Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

  6. Atypisk scrapie i Danmark

    DEFF Research Database (Denmark)

    Lind, Peter; Jensen, Tim Kåre; Mølbak, Lars

    2010-01-01

    Testningen af ca. 35.000 danske får og geder for TSE i perioden 2006-2010 har medført fund af syv tilfælde hos får, som alle er karakteriseret som atypisk scrapie......Testningen af ca. 35.000 danske får og geder for TSE i perioden 2006-2010 har medført fund af syv tilfælde hos får, som alle er karakteriseret som atypisk scrapie...

  7. Deconstructing "Atypical" Eating Disorders: an Overview of Emerging Eating Disorder Phenotypes.

    Science.gov (United States)

    Murray, Stuart B; Anderson, Leslie K

    2015-11-01

    Recent changes to the diagnostic framework of eating disorders (ED's) in DSM-5 were introduced to reduce the large preponderance of cases falling within the residual and undifferentiated category. However, current reports continue to illustrate overrepresentation of cases in this residual category, suggesting that clinical reality comprises more diverse ED psychopathology than is accounted for in the current diagnostic spectrum. However, with emerging evidence preliminarily delineating several additional distinct phenotypes, we aim to provide a narrative overview of emerging ED phenotypes which (i) are not currently located as a specific diagnostic category in diagnostic criteria for ED's, (ii) centrally feature ED psychopathology, and (iii) have emerging empirical evidence suggesting the distinct nature of the syndrome. A greater awareness of these emerging phenotypes will likely facilitate accurate diagnostic practice and may also serve to facilitate further empirical efforts.

  8. Minder BSE en scrapie

    NARCIS (Netherlands)

    Zijderveld, van F.G.

    2011-01-01

    De dierziekte BSE is gevaarlijk voor de mens. Onderzoekers van het Central Veterinary Institute (CVI) hebben daarom snelle diagnostische tests ontwikkeld en ingezet bij rundvee, schapen en geiten. Ook hebben ze ervoor gezorgd dat schapen minder vatbaar zijn voor de verwante prionziekte scrapie.

  9. Different mutations at V363 MAPT codon are associated with atypical clinical phenotypes and show unusual structural and functional features.

    Science.gov (United States)

    Rossi, Giacomina; Bastone, Antonio; Piccoli, Elena; Morbin, Michela; Mazzoleni, Giulia; Fugnanesi, Valeria; Beeg, Marten; Del Favero, Elena; Cantù, Laura; Motta, Simona; Salsano, Ettore; Pareyson, Davide; Erbetta, Alessandra; Elia, Antonio Emanuele; Del Sorbo, Francesca; Silani, Vincenzo; Morelli, Claudia; Salmona, Mario; Tagliavini, Fabrizio

    2014-02-01

    Microtubule-associated protein tau gene (MAPT) is one of the major genes linked to frontotemporal lobar degeneration, a group of neurodegenerative diseases clinically, pathologically, and genetically heterogeneous. In particular, MAPT mutations give rise to the subgroup of tauopathies. The pathogenetic mechanisms underlying the MAPT mutations so far described are the decreased ability of tau protein to promote microtubule polymerization (missense mutations) or the altered ratio of tau isoforms (splicing mutations), both leading to accumulation of hyperphosphorylated filamentous tau protein. Following a genetic screening of patients affected by frontotemporal lobar degeneration, we identified 2 MAPT mutations, V363I and V363A, leading to atypical clinical phenotypes, such as posterior cortical atrophy. We investigated in vitro features of the recombinant mutated tau isoforms and revealed unusual functional and structural characteristics such as an increased ability to promote microtubule polymerization and a tendency to form oligomeric instead of filamentous aggregates. Thus, we disclosed a greater than expected complexity of abnormal features of mutated tau isoforms. Overall our findings suggest a high probability that these mutations are pathogenic.

  10. Atypical sporadic CJD-MM phenotype with white matter kuru plaques associated with intranuclear inclusion body and argyrophilic grain disease.

    Science.gov (United States)

    Berghoff, Anna S; Trummert, Anita; Unterberger, Ursula; Ströbel, Thomas; Hortobágyi, Tibor; Kovacs, Gabor G

    2015-08-01

    We describe an atypical neuropathological phenotype of sporadic Creutzfeldt-Jakob disease in a 76-year-old man. The clinical symptoms were characterized by progressive dementia, gait ataxia, rigidity and urinary incontinence. The disease duration was 6 weeks. MRI did not show prominent atrophy or hyperintensities in cortical areas, striatum or thalamus. Biomarker examination of the cerebrospinal fluid deviated from that seen in pure Alzheimer's disease. Triphasic waves in the EEG were detected only later in the disease course, while 14-3-3 assay was positive. PRNP genotyping revealed methionine homozygosity (MM) at codon 129. Neuropathology showed classical CJD changes corresponding to the MM type 1 cases. However, a striking feature was the presence of abundant kuru-type plaques in the white matter. This rare morphology was associated with neuropathological signs of intranuclear inclusion body disease and advanced stage of argyrophilic grain disease. These alterations did not show correlation with each other, thus seemed to develop independently. This case further highlights the complexity of neuropathological alterations in the ageing brain.

  11. Transmission of scrapie prions to primate after an extended silent incubation period.

    Science.gov (United States)

    Comoy, Emmanuel E; Mikol, Jacqueline; Luccantoni-Freire, Sophie; Correia, Evelyne; Lescoutra-Etchegaray, Nathalie; Durand, Valérie; Dehen, Capucine; Andreoletti, Olivier; Casalone, Cristina; Richt, Juergen A; Greenlee, Justin J; Baron, Thierry; Benestad, Sylvie L; Brown, Paul; Deslys, Jean-Philippe

    2015-06-30

    Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

  12. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency

    Science.gov (United States)

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A.; Fliegauf, Manfred; Sayar, Esra H.; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S¸ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-01-01

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease—all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients. PMID:26476407

  13. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

    Science.gov (United States)

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A; Fliegauf, Manfred; Sayar, Esra H; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S Ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-12-20

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients.

  14. Epidemiological characteristics of classical scrapie outbreaks in 30 sheep flocks in the United Kingdom.

    Directory of Open Access Journals (Sweden)

    K Marie McIntyre

    Full Text Available Most previous analyses of scrapie outbreaks have focused on flocks run by research institutes, which may not reflect the field situation. Within this study, we attempt to rectify this deficit by describing the epidemiological characteristics of 30 sheep flocks naturally-infected with classical scrapie, and by exploring possible underlying causes of variation in the characteristics between flocks, including flock-level prion protein (PrP genotype profile. In total, the study involved PrP genotype data for nearly 8600 animals and over 400 scrapie cases.We found that most scrapie cases were restricted to just two PrP genotypes (ARQ/VRQ and VRQ/VRQ, though two flocks had markedly different affected genotypes, despite having similar underlying genotype profiles to other flocks of the same breed; we identified differences amongst flocks in the age of cases of certain PrP genotypes; we found that the age-at-onset of clinical signs depended on peak incidence and flock type; we found evidence that purchasing infected animals is an important means of introducing scrapie to a flock; we found some evidence that flock-level PrP genotype profile and flock size account for variation in outbreak characteristics; identified seasonality in cases associated with lambing time in certain flocks; and we identified one case that was homozygous for phenylalanine at codon 141, a polymorphism associated with a very high risk of atypical scrapie, and 28 cases that were heterozygous at this codon.This paper presents the largest study to date on commercially-run sheep flocks naturally-infected with classical scrapie, involving 30 study flocks, more than 400 scrapie cases and over 8500 PrP genotypes. We show that some of the observed variation in epidemiological characteristics between farms is related to differences in their PrP genotype profile; although much remains unexplained and may instead be attributed to the stochastic nature of scrapie dynamics.

  15. 9 CFR 54.22 - State scrapie certification boards.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false State scrapie certification boards. 54... SCRAPIE Scrapie Flock Certification Program § 54.22 State scrapie certification boards. An area... a State scrapie certification board for the purpose of coordinating activities for the Scrapie...

  16. Epilepsy phenotype associated with a chromosome 2q24.3 deletion involving SCN1A: Migrating partial seizures of infancy or atypical Dravet syndrome?

    Science.gov (United States)

    Lim, Byung Chan; Hwang, Hee; Kim, Hunmin; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Yum, Mi-Sun; Ko, Tae-Sung

    2015-01-01

    The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that map within this cluster has not been delineated. We presented five new cases with a chromosome 2q24.3 deletion involving SCN1A and investigated their epilepsy phenotype in relation to the extent of the deletion. Three cases with deletion of the whole sodium channel gene cluster (SCN3A, SCN2A, SCN1A, SCN9A, and SCN7A) exhibited a complex epilepsy phenotype that was atypical for Dravet syndrome and suggestive of migrating partial seizures of infancy: early seizure onset (before 2 months of age), severe developmental delay from seizure onset, multifocal interictal spikes, polymorphous focal seizures, and acquired microcephaly. Two cases with partial deletion of SCN1A and SCN9A and whole SCN1A deletion had an epilepsy phenotype of Dravet syndrome. A literature review of cases with chromosome 2q24.3 deletion revealed that, in most Dravet syndrome cases, it does not involve SCN2A and SCN3A, whereas a complex epilepsy phenotype that is shared with migrating partial seizures of infancy was associated with cases of deletion of the whole sodium channel gene cluster.

  17. Sheep Feed and Scrapie, France

    Science.gov (United States)

    Philippe, Sandrine; Ducrot, Christian; Roy, Pascal; Remontet, Laurent; Jarrige, Nathalie

    2005-01-01

    Scrapie is a small ruminant, transmissible spongiform encephalopathy (TSE). Although in the past scrapie has not been considered a zoonosis, the emergence of bovine spongiform encephalopathy, transmissible to humans and experimentally to sheep, indicates that risk exists for small ruminant TSEs in humans. To identify the risk factors for introducing scrapie into sheep flocks, a case-control study was conducted in France from 1999 to 2000. Ninety-four case and 350 control flocks were matched by location and main breed. Three main hypotheses were tested: direct contact between flocks, indirect environmental contact, and foodborne risk. Statistical analysis was performed by using adjusted generalized linear models with the complementary log-log link function, considering flock size as an offset. A notable effect of using proprietary concentrates and milk replacers was observed. The risk was heterogeneous among feed factories. Contacts between flocks were not shown to be a risk factor. PMID:16102318

  18. A distinct proteinase K resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak

    NARCIS (Netherlands)

    Bouzalas, I.; Lörtscher, F.; Dovas, C.; Oevermann, A.; Langeveld, J.P.M.; Papanastassopoulou, M.; Papadopoulos, O.; Zurbriggen, A.; Seuberlich, T.

    2011-01-01

    Considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (BSE). Here we report the in-depth molecular analysis of the proteinase K-resistant prion protein core fragment (PrPres

  19. Atypical Depression

    Science.gov (United States)

    Diseases and Conditions Atypical depression By Mayo Clinic Staff Any type of depression can make you feel sad and keep you from enjoying life. However, atypical depression — also called depression with atypical features — means that ...

  20. Prion protein and scrapie susceptibility

    NARCIS (Netherlands)

    Smits, M.A.; Bossers, A.; Schreuder, B.E.C.

    1997-01-01

    This article presents briefly current views on the role of prion protein (PrP) in Transmissible Spongiform Encephalopathies or prion diseases and the effect of PrP polymoryhisms on the susceptibility to these diseases, with special emphasis on sheep scrapie. The PrP genotype of sheep apears to be a

  1. Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains.

    OpenAIRE

    Kascsak, R J; Rubenstein, R; Merz, P A; Carp, R I; Robakis, N. K.; Wisniewski, H M; Diringer, H

    1986-01-01

    Scrapie-associated fibrils (SAFs) are abnormal filamentous structures that are uniquely associated with unconventional slow virus diseases. The antigenic relationships of SAFs from animals infected with four biologically distinct scrapie strains were investigated by using antisera raised to purified SAF proteins. Rabbit antisera were raised to SAFs isolated from mice infected with the ME7 scrapie strain and to SAFs isolated from hamsters infected with the 263K scrapie strain. A strong antigen...

  2. Sheep prions with molecular properties intermediate between classical scrapie, BSE and CH1641-scrapie

    NARCIS (Netherlands)

    Langeveld, J.P.M.; Jacobs, J.G.; Erkens, J.H.F.; Baron, T.; Andreoletti, O.; Yokoyama, T.; Keulen, van L.J.M.; Zijderveld, van F.G.; Davidse, A.; Hope, J.; Tang, Y.; Bossers, A.

    2014-01-01

    Efforts to differentiate bovine spongiform encephalopathy (BSE) from scrapie in prion infected sheep have resulted
    in effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptions
    that BSE, classical scrapie and CH1641–a rare scrapie variant–

  3. Biochemical and computational analyses of two phenotypically related GALT mutations (S222N and S135L that lead to atypical galactosemia

    Directory of Open Access Journals (Sweden)

    Benjamin Cocanougher

    2015-06-01

    Full Text Available Galactosemia is a metabolic disorder caused by mutations in the GALT gene [1,2]. We encountered a patient heterozygous for a known pathogenic H132Q mutation and a novel S222N variant of unknown significance [3]. Reminiscent of patients with the S135L mutation, our patient had loss of GALT enzyme activity in erythrocytes but a very mild clinical phenotype [3–8]. We performed splicing experiments and computational structural analyses to investigate the role of the novel S222N variant. Alamut software data predicted loss of splicing enhancers for the S222N and S135L mutations [9,10]. A cDNA library was generated from our patient׳s RNA to investigate for splicing errors, but no change in transcript length was seen [3]. In silico structural analysis was performed to investigate enzyme stability and attempt to understand the mechanism of the atypical galactosemia phenotype. Stability results are publicly available in the GALT Protein Database 2.0 [11–14]. Animations were created to give the reader a dynamic view of the enzyme structure and mutation locations. Protein database files and python scripts are included for further investigation.

  4. 9 CFR 54.10 - Tests for scrapie.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Tests for scrapie. 54.10 Section 54.10... COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES CONTROL OF SCRAPIE Scrapie Indemnification Program § 54.10 Tests for scrapie. (a) The Administrator may approve new tests for the...

  5. Early and late pathogenesis of natural scrapie infection in sheep

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Vromans, M.E.W.; Zijderveld, van F.G.

    2002-01-01

    The pathogenesis of scrapie infection was studied in sheep carrying the PrPVRQ/PrPVRQ genotype, which is associated with a high susceptibility for natural scrapie. The sheep were killed at sequential time points during a scrapie infection covering both the early and late stages of scrapie pathogenes

  6. Evidence of scrapie transmission via milk

    Directory of Open Access Journals (Sweden)

    Moore S Jo

    2008-04-01

    Full Text Available Abstract Background The risk of scrapie infection increases with increased duration and proximity of contact between sheep at lambing. Scrapie infectivity has not been detected in milk but cellular prion protein, the precursor of disease-associated prion protein PrPd, has been found in milk from ruminants. To determine whether milk is able to transmit scrapie, 18 lambs with a prion protein genotype associated with high susceptibility to scrapie (VRQ/VRQ were fed milk from twelve scrapie-affected ewes of the same genotype, and 15 VRQ/VRQ sheep reared on scrapie-free dams served as controls. Results Three lambs fed milk from scrapie-affected ewes were culled due to intercurrent diseases at 43, 44 and 105 days of age respectively, and PrPd was detected in the distal ileum of the first two lambs, whilst PrPd was not found in lymphoreticular tissues in the third lamb. A control lamb, housed in a separate pen and culled at 38 days of age, was also negative for PrPd in a range of tissues. Samples of recto-anal mucosa associated lymphoid tissue collected from the remaining 15 live lambs at seven months of age (between five to seven months after mixing were positive for PrPd in the scrapie milk recipients, whereas PrPd was not detected in the remaining 14 controls at that time. A subsequent sample collected from control lambs revealed PrPd accumulation in two of five lambs eight months after mixing with scrapie milk recipients suggestive of an early stage of infection via lateral transmission. By contrast, the control sheep housed in the same building but not mixed with the scrapie milk recipients were still negative for PrPd. Conclusion The presence of PrPd in distal ileum and rectal mucosa indicates transmission of scrapie from ewe to lamb via milk (or colostrum although it is not yet clear if such cases would go on to develop clinical disease. The high level of infection in scrapie-milk recipients revealed by rectal mucosal testing at approximately

  7. Scrapie e seu diagnóstico diferencial em ovinos no Mato Grosso do Sul Scrapie and differential diagnosis in sheep in Mato Grosso do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Héllen M. Martins

    2012-12-01

    Full Text Available Scrapie é uma doença infecciosa, neurodegenerativa fatal, causada pelo príon scrapie (PrPsc. Apresenta-se tanto na forma clássica em ovinos e caprinos geneticamente susceptíveis quanto na forma atípica em ovinos. A primeira notificação oficial do Brasil à Organização Mundial de Saúde Animal (OIE, um caso da forma clássica diagnosticado no Rio Grande do Sul ocorreu em 1985, mas a doença já havia sido diagnosticada no mesmo Estado em 1978. Este trabalho objetivou descrever dois surtos de Scrapie em ovinos em Mato Grosso do Sul (MS, Brasil e investigar, por meio de imuno-histoquímica (IHQ a presença de PrPsc no Sistema Nervoso Central (SNC de ovinos examinados entre 2003 e 2010. Na primeira parte observaram-se dois ovinos com sinais clínicos típicos de scrapie, detalhando-se os sinais neurológicos, dados epidemiológicos, histopatológicos e amostras teciduais em duplicata desses ovinos foram encaminhadas para realização de diagnóstico de Raiva e para diagnóstico IHQ para príon. Na segunda parte realizou-se levantamento de laudos de necropsia e diagnósticos histopatológicos de ovinos, no período de maio de 2003 a março de 2010. Amostras de sistema nervoso central de 51 casos foram selecionados, incluindo os dois já com diagnóstico de Scrapie mencionados acima; os tecido de todos esses ovinos foram submetidos à IHQ para detecção de proteína priônica. Os 49 ovinos avaliados apresentaram resultado negativo na IHQ para príon.Scrapie is a fatal neurodegenerative infectious disease, caused by the scrapie prion (PrPsc, that can both in the as the classic form in genetically susceptible sheep and goats and in the atypical form in sheep. The first official notification of scrapie from Brazil was made to the World Organization for Animal Health (OIE in 1985, in the state of Rio Grande do Sul, although the disease was first documented in this Brazilian state in 1978. The objective this paper was to describe two outbreaks

  8. Atypical pneumonia

    Science.gov (United States)

    Walking pneumonia; Community-acquired pneumonia - atypical ... Bacteria that cause atypical pneumonia include: Mycoplasma pneumonia is caused by the bacteria Mycoplasma pneumoniae . It often affects people younger than age 40. Pneumonia due ...

  9. Genome-Wide Association Studies Identify Two Novel BMP15 Mutations Responsible for an Atypical Hyperprolificacy Phenotype in Sheep

    Science.gov (United States)

    Demars, Julie; Fabre, Stéphane; Sarry, Julien; Rossetti, Raffaella; Gilbert, Hélène; Persani, Luca; Tosser-Klopp, Gwenola; Mulsant, Philippe; Nowak, Zuzanna; Drobik, Wioleta; Martyniuk, Elzbieta; Bodin, Loys

    2013-01-01

    Some sheep breeds are naturally prolific, and they are very informative for the studies of reproductive genetics and physiology. Major genes increasing litter size (LS) and ovulation rate (OR) were suspected in the French Grivette and the Polish Olkuska sheep populations, respectively. To identify genetic variants responsible for the highly prolific phenotype in these two breeds, genome-wide association studies (GWAS) followed by complementary genetic and functional analyses were performed. Highly prolific ewes (cases) and normal prolific ewes (controls) from each breed were genotyped using the Illumina OvineSNP50 Genotyping Beadchip. In both populations, an X chromosome region, close to the BMP15 gene, harbored clusters of markers with suggestive evidence of association at significance levels between 1E−05 and 1E−07. The BMP15 candidate gene was then sequenced, and two novel non-conservative mutations called FecXGr and FecXO were identified in the Grivette and Olkuska breeds, respectively. The two mutations were associated with the highly prolific phenotype (pFecXGr = 5.98E−06 and pFecXO = 2.55E−08). Homozygous ewes for the mutated allele showed a significantly increased prolificacy (FecXGr/FecXGr, LS = 2.50±0.65 versus FecX+/FecXGr, LS = 1.93±0.42, p<1E−03 and FecXO/FecXO, OR = 3.28±0.85 versus FecX+/FecXO, OR = 2.02±0.47, p<1E−03). Both mutations are located in very well conserved motifs of the protein and altered the BMP15 signaling activity in vitro using a BMP-responsive luciferase test in COV434 granulosa cells. Thus, we have identified two novel mutations in the BMP15 gene associated with increased LS and OR. Notably, homozygous FecXGr/FecXGr Grivette and homozygous FecXO/FecXO Olkuska ewes are hyperprolific in striking contrast with the sterility exhibited by all other known homozygous BMP15 mutations. Our results bring new insights into the key role played by the BMP15 protein in ovarian function and could

  10. Refractory Classical Hodgkin Lymphoma Presenting with Atypical Cutaneous Involvement and Diagnosis of ZZ Phenotype Alpha-1 Antitrypsin Deficiency

    Directory of Open Access Journals (Sweden)

    Mohamad Khawandanah

    2014-01-01

    Full Text Available Cutaneous Hodgkin lymphoma is a rare condition. Specific neoplastic involvement can be primary (confined to the skin or secondary to systemic involvement (metastatic. Cutaneous involvement by HL usually occurs late in the course and is associated with poor prognosis; however in some cases it can exhibit indolent behavior. Skin involvement with nonspecific cutaneous findings may represent a paraneoplastic syndrome. We describe a case of 46-year-old white male patient presented with rash and lymphadenopathy which led to the diagnosis of stage IVE mixed cellularity classical Hodgkin lymphoma with skin involvement. His disease was refractory to multiple lines of chemotherapy including (1 AVD (doxorubicin/bleomycin/dacarbazine, (2 brentuximab, and (3 bendamustine, he later achieved complete remission with (4 GCD (gemcitabine/carboplatin/dexamethasone salvage regimen. Bleomycin was not given secondary to poor pulmonary function tests. His treatment was complicated after AVD with multiple pneumothoraces which unmasked the diagnosis of ZZ phenotype alpha-1 antitrypsin (ATT deficiency. Simultaneous existence of Hodgkin lymphoma and ATT is rarely reported.

  11. Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

    Directory of Open Access Journals (Sweden)

    Timm eKonold

    2015-09-01

    Full Text Available Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial Protein Misfolding Cyclic Amplification (sPMCA have suggested that objects on a scrapie-affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing and other objects that sheep may rub against used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation sheep became infected when exposed to either a water trough (four out of five or to objects used for rubbing (four out of seven. This field furniture had been used by the scrapie-infected flock eight weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23 through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12 on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie-free.The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.

  12. Sheep prions with molecular properties intermediate between classical scrapie, BSE and CH1641-scrapie

    OpenAIRE

    Langeveld, Jan P. M.; Jacobs, Jorg G; Erkens, Jo H.F.; Baron, Thierry; Andreoletti, Olivier; Yokoyama, Takahashi; Van Keulen, Lucien J. M.; van Zijderveld, Fred G.; Davidse, Aart; Hope, Jim; Tang, Yue; Bossers, Alex

    2014-01-01

    Efforts to differentiate bovine spongiform encephalopathy (BSE) from scrapie in prion infected sheep have resulted in effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptions that BSE, classical scrapie and CH1641–a rare scrapie variant–could occur as mixtures. In field samples including those from fallen stock, triplex Western blotting analyses of variations in the molecular properties of the proteinase K resistant part of the disease‑as...

  13. Phenotypic variability in developmental coordination disorder: Clustering of generalized joint hypermobility with attention deficit/hyperactivity disorder, atypical swallowing and narrative difficulties.

    Science.gov (United States)

    Celletti, Claudia; Mari, Giorgia; Ghibellini, Giulia; Celli, Mauro; Castori, Marco; Camerota, Filippo

    2015-03-01

    Developmental coordination disorder (DCD) is a recognized childhood disorder mostly characterized by motor coordination difficulties. Joint hypermobility syndrome, alternatively termed Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly featuring generalized joint hypermobility (gJHM), musculoskeletal pain, and minor skin features. Although these two conditions seem apparently unrelated, recent evidence highlights a high rate of motor and coordination findings in children with gJHM or JHS/EDS-HT. Here, we investigated the prevalence of gJHM in 41 Italian children with DCD in order to check for the existence of recognizable phenotypic subgroups of DCD in relation to the presence/absence of gJHM. All patients were screened for Beighton score and a set of neuropsychological tests for motor competences (Movement Assessment Battery for Children and Visual-Motor Integration tests), and language and learning difficulties (Linguistic Comprehension Test, Peabody Picture Vocabulary Test, Boston Naming Test, Bus Story Test, and Memoria-Training tests). All patients were also screening for selected JHS/EDS-HT-associated features and swallowing problems. Nineteen (46%) children showed gJHM and 22 (54%) did not. Children with DCD and gJHM showed a significant excess of frequent falls (95 vs. 18%), easy bruising (74 vs. 0%), motor impersistence (89 vs. 23%), sore hands for writing (53 vs. 9%), attention deficit/hyperactivity disorder (89 vs. 36%), constipation (53 vs. 0%), arthralgias/myalgias (58 vs. 4%), narrative difficulties (74 vs. 32%), and atypical swallowing (74 vs. 18%). This study confirms the non-causal association between DCD and gJHM, which, in turn, seems to increase the risk for non-random additional features. The excess of language, learning, and swallowing difficulties in patients with DCD and gJHM suggests a wider effect of lax tissues in the development of the nervous system.

  14. Selective breeding for scrapie resistance in sheep

    Directory of Open Access Journals (Sweden)

    Cristina Santos Sotomaior

    2012-11-01

    Full Text Available It is well known that the susceptibility of sheep to scrapie is determined by the host’s prion protein gene (PRNP. PRNP polymorphisms at codons 136 (alanine, A/valine, V, 154 (histidine, H/arginine, R and 171 (glutamine, Q/histidine, H/arginine, R are the main determinants of sheep susceptibility/resistance to classical scrapie. There are four major variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programs have been developed in the European Union and the USA to increase the frequency of the resistant ARR allele while decreasing the frequency of the susceptible VRQ allele in sheep populations. In Brazil, little PRNP genotyping data are available for sheep, and thus far, no controlled breeding scheme for scrapie has been implemented. This review will focus on important epidemiological aspects of scrapie and the use of genetic resistance as a tool in breeding programs to control the disease.

  15. Surveillance and simulation of bovine spongiform encephalopathy and scrapie in small ruminants in Switzerland

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    Zurbriggen Andreas

    2010-04-01

    Full Text Available Abstract Background After bovine spongiform encephalopathy (BSE emerged in European cattle livestock in 1986 a fundamental question was whether the agent established also in the small ruminants' population. In Switzerland transmissible spongiform encephalopathies (TSEs in small ruminants have been monitored since 1990. While in the most recent TSE cases a BSE infection could be excluded, for historical cases techniques to discriminate scrapie from BSE had not been available at the time of diagnosis and thus their status remained unclear. We herein applied state-of-the-art techniques to retrospectively classify these animals and to re-analyze the affected flocks for secondary cases. These results were the basis for models, simulating the course of TSEs over a period of 70 years. The aim was to come to a statistically based overall assessment of the TSE situation in the domestic small ruminant population in Switzerland. Results In sum 16 TSE cases were identified in small ruminants in Switzerland since 1981, of which eight were atypical and six were classical scrapie. In two animals retrospective analysis did not allow any further classification due to the lack of appropriate tissue samples. We found no evidence for an infection with the BSE agent in the cases under investigation. In none of the affected flocks, secondary cases were identified. A Bayesian prevalence calculation resulted in most likely estimates of one case of BSE, five cases of classical scrapie and 21 cases of atypical scrapie per 100'000 small ruminants. According to our models none of the TSEs is considered to cause a broader epidemic in Switzerland. In a closed population, they are rather expected to fade out in the next decades or, in case of a sporadic origin, may remain at a very low level. Conclusions In summary, these data indicate that despite a significant epidemic of BSE in cattle, there is no evidence that BSE established in the small ruminant population in

  16. Sheep prions with molecular properties intermediate between classical scrapie, BSE and CH1641-scrapie.

    Science.gov (United States)

    Langeveld, Jan P M; Jacobs, Jorg G; Erkens, Jo H F; Baron, Thierry; Andréoletti, Olivier; Yokoyama, Takahashi; van Keulen, Lucien J M; van Zijderveld, Fred G; Davidse, Aart; Hope, Jim; Tang, Yue; Bossers, Alex

    2014-01-01

    Efforts to differentiate bovine spongiform encephalopathy (BSE) from scrapie in prion infected sheep have resulted in effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptions that BSE, classical scrapie and CH1641-a rare scrapie variant-could occur as mixtures. In field samples including those from fallen stock, triplex Western blotting analyses of variations in the molecular properties of the proteinase K resistant part of the disease‑associated form of prion protein (PrP(res)) represents a powerful tool for quick discrimination purposes. In this study we examined 7 deviant ovine field cases of scrapie for some typical molecular aspects of PrP(res) found in CH1641‑scrapie, classical scrapie and BSE. One case was most close to scrapie with respect to molecular mass of its non-glycosylated fraction and N-terminally located 12B2‑epitope content. Two cases were unlike classical scrapie but too weak to differentiate between BSE or CH1641. The other 4 cases appeared intermediate between scrapie and CH1641 with a reduced molecular mass and 12B2‑epitope content, together with the characteristic presence of a second PrP(res) population. The existence of these 2 PrP(res) populations was further confirmed through deglycosylation by PNGaseF. The findings indicate that discriminatory diagnosis between classical scrapie, CH1641 and BSE can remain inconclusive with current biochemical methods. Whether such intermediate cases represent mixtures of TSE strains should be further investigated e.g. in bioassays with rodent lines that are varying in their susceptibility or other techniques suitable for strain typing.

  17. Evidence of in utero transmission of classical scrapie in sheep.

    Science.gov (United States)

    Spiropoulos, John; Hawkins, Stephen A C; Simmons, Marion M; Bellworthy, Susan J

    2014-04-01

    Classical scrapie is one of the transmissible spongiform encephalopathies (TSEs), a group of fatal infectious diseases that affect the central nervous system (CNS). Classical scrapie can transmit laterally from ewe to lamb perinatally or between adult animals. Here we report detection of infectivity in tissues of an unborn fetus, providing evidence that in utero transmission of classical scrapie is also possible.

  18. Circulation of prions within dust on a scrapie affected farm.

    Science.gov (United States)

    Gough, Kevin C; Baker, Claire A; Simmons, Hugh A; Hawkins, Steve A; Maddison, Ben C

    2015-04-16

    Prion diseases are fatal neurological disorders that affect humans and animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs have a direct link to the transmission of disease. Using protein misfolding cyclic amplification we demonstrate that scrapie PrP(Sc) can be detected within circulating dusts that are present on a farm that is naturally contaminated with sheep scrapie. The presence of infectious scrapie within airborne dusts may represent a possible route of infection and illustrates the difficulties that may be associated with the effective decontamination of such scrapie affected premises.

  19. A three-generation family with terminal microdeletion involving 5p15.33-32 due to a whole-arm 5;15 chromosomal translocation with a steady phenotype of atypical cri du chat syndrome.

    Science.gov (United States)

    Elmakky, Amira; Carli, Diana; Lugli, Licia; Torelli, Paola; Guidi, Battista; Falcinelli, Cristina; Fini, Sergio; Ferrari, Fabrizio; Percesepe, Antonio

    2014-03-01

    Cri du chat syndrome is characterized by cat-like cry, facial dysmorphisms, microcephaly, speech delay, intellectual disability and slow growth rate, which are present with variable frequency. The typical cri du chat syndrome, due to 5p15.2 deletion, includes severe intellectual disability, facial dysmorphisms, neonatal hypotonia and pre- and post-natal growth retardation, whereas more distal deletions in 5p15.3 lead to cat-like cry and speech delay and produce the clinical picture of the atypical cri du chat syndrome, with minimal or absent intellectual impairment. In this article we report a three-generation family with an unbalanced whole arm translocation between chromosome 5 and 15 and a microdeletion of 5.5 Mb involving 5p15.33-32. By reporting the smallest terminal deletion of 5p15.3 described so far and by reviewing the literature we discuss the genotype/phenotype correlations of the distal region of the cri du chat syndrome. The previously described critical region for the speech delay may be narrowed down and microcephaly, growth retardation and dysmorphic facial features can be included in the phenotypic expression of the atypical cri du chat syndrome due to 5p15.3 deletions.

  20. Prion Protein Gene Variability in Spanish Goats. Inference through Susceptibility to Classical Scrapie Strains and Pathogenic Distribution of Peripheral PrPsc

    Science.gov (United States)

    Acín, Cristina; Martín-Burriel, Inmaculada; Monleón, Eva; Lyahyai, Jaber; Pitarch, José Luis; Serrano, Carmen; Monzón, Marta; Zaragoza, Pilar; Badiola, Juan José

    2013-01-01

    Classical scrapie is a neurological disorder of the central nervous system (CNS) characterized by the accumulation of an abnormal, partially protease resistant prion protein (PrPsc) in the CNS and in some peripheral tissues in domestic small ruminants. Whereas the pathological changes and genetic susceptibility of ovine scrapie are well known, caprine scrapie has been less well studied. We report here a pathological study of 13 scrapie-affected goats diagnosed in Spain during the last 9 years. We used immunohistochemical and biochemical techniques to discriminate between classical and atypical scrapie and bovine spongiform encephalopathy (BSE). All the animals displayed PrPsc distribution patterns and western blot characteristics compatible with classical scrapie. In addition, we determined the complete open reading frame sequence of the PRNP in these scrapie-affected animals. The polymorphisms observed were compared with those of the herd mates (n = 665) and with the frequencies of healthy herds (n = 581) of native Spanish goats (Retinta, Pirenaica and Moncaina) and other worldwide breeds reared in Spain (Saanen, Alpine and crossbreed). In total, sixteen polymorphic sites were identified, including the known amino acid substitutions at codons G37V, G127S, M137I, I142M, H143R, R151H, R154H, R211Q, Q222K, G232W, and P240S, and new polymorphisms at codons G74D, M112T, R139S, L141F and Q215R. In addition, the known 42, 138 and 179 silent mutations were detected, and one new one is reported at codon 122. The genetic differences observed in the population studied have been attributed to breed and most of the novel polymorphic codons show frequencies lower than 5%. This work provides the first basis of polymorphic distribution of PRNP in native and worldwide goat breeds reared in Spain. PMID:23580248

  1. Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrP(sc..

    Directory of Open Access Journals (Sweden)

    Cristina Acín

    Full Text Available Classical scrapie is a neurological disorder of the central nervous system (CNS characterized by the accumulation of an abnormal, partially protease resistant prion protein (PrP(sc in the CNS and in some peripheral tissues in domestic small ruminants. Whereas the pathological changes and genetic susceptibility of ovine scrapie are well known, caprine scrapie has been less well studied. We report here a pathological study of 13 scrapie-affected goats diagnosed in Spain during the last 9 years. We used immunohistochemical and biochemical techniques to discriminate between classical and atypical scrapie and bovine spongiform encephalopathy (BSE. All the animals displayed PrP(sc distribution patterns and western blot characteristics compatible with classical scrapie. In addition, we determined the complete open reading frame sequence of the PRNP in these scrapie-affected animals. The polymorphisms observed were compared with those of the herd mates (n = 665 and with the frequencies of healthy herds (n = 581 of native Spanish goats (Retinta, Pirenaica and Moncaina and other worldwide breeds reared in Spain (Saanen, Alpine and crossbreed. In total, sixteen polymorphic sites were identified, including the known amino acid substitutions at codons G37V, G127S, M137I, I142M, H143R, R151H, R154H, R211Q, Q222K, G232W, and P240S, and new polymorphisms at codons G74D, M112T, R139S, L141F and Q215R. In addition, the known 42, 138 and 179 silent mutations were detected, and one new one is reported at codon 122. The genetic differences observed in the population studied have been attributed to breed and most of the novel polymorphic codons show frequencies lower than 5%. This work provides the first basis of polymorphic distribution of PRNP in native and worldwide goat breeds reared in Spain.

  2. Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrP(sc.).

    Science.gov (United States)

    Acín, Cristina; Martín-Burriel, Inmaculada; Monleón, Eva; Lyahyai, Jaber; Pitarch, José Luis; Serrano, Carmen; Monzón, Marta; Zaragoza, Pilar; Badiola, Juan José

    2013-01-01

    Classical scrapie is a neurological disorder of the central nervous system (CNS) characterized by the accumulation of an abnormal, partially protease resistant prion protein (PrP(sc)) in the CNS and in some peripheral tissues in domestic small ruminants. Whereas the pathological changes and genetic susceptibility of ovine scrapie are well known, caprine scrapie has been less well studied. We report here a pathological study of 13 scrapie-affected goats diagnosed in Spain during the last 9 years. We used immunohistochemical and biochemical techniques to discriminate between classical and atypical scrapie and bovine spongiform encephalopathy (BSE). All the animals displayed PrP(sc) distribution patterns and western blot characteristics compatible with classical scrapie. In addition, we determined the complete open reading frame sequence of the PRNP in these scrapie-affected animals. The polymorphisms observed were compared with those of the herd mates (n = 665) and with the frequencies of healthy herds (n = 581) of native Spanish goats (Retinta, Pirenaica and Moncaina) and other worldwide breeds reared in Spain (Saanen, Alpine and crossbreed). In total, sixteen polymorphic sites were identified, including the known amino acid substitutions at codons G37V, G127S, M137I, I142M, H143R, R151H, R154H, R211Q, Q222K, G232W, and P240S, and new polymorphisms at codons G74D, M112T, R139S, L141F and Q215R. In addition, the known 42, 138 and 179 silent mutations were detected, and one new one is reported at codon 122. The genetic differences observed in the population studied have been attributed to breed and most of the novel polymorphic codons show frequencies lower than 5%. This work provides the first basis of polymorphic distribution of PRNP in native and worldwide goat breeds reared in Spain.

  3. Stability of murine scrapie strain 87V after passage in sheep and comparison with the CH1641 ovine strain.

    Science.gov (United States)

    González, Lorenzo; Chianini, Francesca; Hunter, Nora; Hamilton, Scott; Gibbard, Louise; Martin, Stuart; Dagleish, Mark P; Sisó, Sílvia; Eaton, Samantha L; Chong, Angela; Algar, Lynne; Jeffrey, Martin

    2015-12-01

    Breed- and prion protein (PRNP) genotype-related disease phenotype variability has been observed in sheep infected with the 87V murine scrapie strain. Therefore, the stability of this strain was tested by inoculating sheep-derived 87V brain material back into VM mice. As some sheep-adapted 87V disease phenotypes were reminiscent of CH1641 scrapie, transgenic mice (Tg338) expressing ovine prion protein (PrP) were inoculated with the same sheep-derived 87V sources and with CH1641. Although at first passage in VM mice the sheep-derived 87V sources showed some divergence from the murine 87V control, all the characteristics of murine 87V infection were recovered at second passage from all sheep sources. These included 100 % attack rates and indistinguishable survival times, lesion profiles, immunohistochemical features of disease-associated PrP accumulation in the brain and PrP biochemical properties. All sheep-derived 87V sources, as well as CH1641, were transmitted to Tg338 mice with identical clinical, pathological, immunohistochemical and biochemical features. While this might potentially indicate that sheep-adapted 87V and CH1641 are the same strain, profound divergences were evident, as murine 87V was unable to infect Tg338 mice but was lethal for VM mice, while the reverse was true for CH1641. These combined data suggest that: (i) murine 87V is stable and retains its properties after passage in sheep; (ii) it can be isolated from sheep showing a CH1641-like or a more conventional scrapie phenotype; and (iii) sheep-adapted 87V scrapie, with conventional or CH1641-like phenotype, is biologically distinct from experimental CH1641 scrapie, despite the fact that they behave identically in a single transgenic mouse line.

  4. Scrapie-associated prion protein accumulates in astrocytes during scrapie infection.

    OpenAIRE

    Diedrich, J F; Bendheim, P E; Kim, Y. S.; Carp, R. I.; Haase, A T

    1991-01-01

    In the course of scrapie, a transmissible spongiform encephalopathy caused by an unconventional agent, a normal cellular protein is converted to an abnormal form that copurifies with infectivity and aggregates to form deposits of amyloid. We have used immunocytochemistry and methods that enhance detection of amyloidogenic proteins to investigate the types of cells in the central nervous system which are involved in the formation of the abnormal scrapie-associated protein. We show that this pr...

  5. Role of PRNP S127 allele in experimental goat infection with classical caprine scrapie

    Science.gov (United States)

    Classical scrapie is a transmissible spongiform encephalopathy that affects domestic goats and sheep. Experimental inoculation studies in sheep confirmed that classical caprine scrapie can readily transmit to sheep. Therefore, even if current scrapie eradication measures are successful in sheep, goa...

  6. A novel deletion mutation in IL2RG gene results in X-linked severe combined immunodeficiency with an atypical phenotype.

    Science.gov (United States)

    Mou, Wenjun; He, Jianxin; Chen, Xi; Zhang, Hui; Ren, Xiaoya; Wu, Xunyao; Ni, Xin; Xu, Baoping; Gui, Jingang

    2017-01-01

    Severe combined immunodeficiency (SCID) is the most serious disorder among primary immunodeficiency diseases threatening children's life. Atypical SCID variant, presenting with mild reduced T cells subsets, is often associated with infection susceptibility but poor clinical diagnosis. The atypical X-SCID patient in the present study showed a mild clinical presentation with a T(low)NK(+)B(+) immunophenotype. The patient has reduced T- cell subpopulations with a subdued thymic output measured by sjTRECs. Further analysis showed that T cells maintained a normal proliferation and a broad Vβ repertoire. NK cells, however, exhibited a skewed development toward immature CD3(-)CD16(+)CD56(-) cells. Genetic analysis revealed a novel deletion at nucleotide 52 in exon 1 of IL2RG gene. Sequence alignment predicted a truncated IL2RG protein missing signal peptide derived from a possible alternative reading frame. The novel mutation in IL2RG gene identified in our study may help the early diagnosis of atypical X-SCID.

  7. Atypical Cities

    Science.gov (United States)

    DiJulio, Betsy

    2011-01-01

    In this creative challenge, Surrealism and one-point perspective combine to produce images that not only go "beyond the real" but also beyond the ubiquitous "imaginary city" assignment often used to teach one-point perspective. Perhaps the difference is that in the "atypical cities challenge," an understanding of one-point perspective is a means…

  8. Caprine prion gene polymorphisms are associated with decreased incidence of classical scrapie in goat herds in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Goldmann Wilfred

    2011-10-01

    Full Text Available Abstract The application of genetic breeding programmes to eradicate transmissible spongiform encephalopathies in goats is an important aim for reasons of animal welfare as well as human food safety and food security. Based on the positive impact of Prnp genetics on sheep scrapie in Europe in the past decade, we have established caprine Prnp gene variation in more than 1100 goats from the United Kingdom and studied the association of Prnp alleles with disease phenotypes in 150 scrapie-positive goats. This investigation confirms the association of the Met142 encoding Prnp allele with increased resistance to preclinical and clinical scrapie. It reveals a novel association of the Ser127 encoding allele with a reduced probability to develop clinical signs of scrapie in goats that are already positive for the accumulation of disease-specific prion protein in brain or periphery. A United Kingdom survey of Prnp genotypes in eight common breeds revealed eleven alleles in over thirty genotypes. The Met142 encoding allele had a high overall mean allele frequency of 22.6%, whereas the Ser127 encoding allele frequency was considerably lower with 6.4%. In contrast, a well known resistance associated allele encoding Lys222 was found to be rare (0.9% in this survey. The analysis of Prnp genotypes in Mexican Criollas goats revealed nine alleles, including a novel Phe to Leu substitution in codon 201, confirming that high genetic variability of Prnp can be found in scrapie-free populations. Our study implies that it should be feasible to lower scrapie prevalence in goat herds in the United Kingdom by genetic selection.

  9. Caprine prion gene polymorphisms are associated with decreased incidence of classical scrapie in goat herds in the United Kingdom.

    Science.gov (United States)

    Goldmann, Wilfred; Ryan, Kelly; Stewart, Paula; Parnham, David; Xicohtencatl, Rosa; Fernandez, Nora; Saunders, Ginny; Windl, Otto; González, Lorenzo; Bossers, Alex; Foster, James

    2011-10-31

    The application of genetic breeding programmes to eradicate transmissible spongiform encephalopathies in goats is an important aim for reasons of animal welfare as well as human food safety and food security. Based on the positive impact of Prnp genetics on sheep scrapie in Europe in the past decade, we have established caprine Prnp gene variation in more than 1100 goats from the United Kingdom and studied the association of Prnp alleles with disease phenotypes in 150 scrapie-positive goats. This investigation confirms the association of the Met142 encoding Prnp allele with increased resistance to preclinical and clinical scrapie. It reveals a novel association of the Ser127 encoding allele with a reduced probability to develop clinical signs of scrapie in goats that are already positive for the accumulation of disease-specific prion protein in brain or periphery. A United Kingdom survey of Prnp genotypes in eight common breeds revealed eleven alleles in over thirty genotypes. The Met142 encoding allele had a high overall mean allele frequency of 22.6%, whereas the Ser127 encoding allele frequency was considerably lower with 6.4%. In contrast, a well known resistance associated allele encoding Lys222 was found to be rare (0.9%) in this survey. The analysis of Prnp genotypes in Mexican Criollas goats revealed nine alleles, including a novel Phe to Leu substitution in codon 201, confirming that high genetic variability of Prnp can be found in scrapie-free populations. Our study implies that it should be feasible to lower scrapie prevalence in goat herds in the United Kingdom by genetic selection.

  10. Experimental infection of meadow voles (Microtus pennsylvanicus) with sheep scrapie

    Science.gov (United States)

    Carlson, CM; Schneider, Jay R.; Pedersen, Janice C.; Heisey, Dennis M.; Johnson, Christopher J.

    2015-01-01

    Meadow voles (Microtus pennsylvanicus) are permissive to chronic wasting disease (CWD) infection, but their susceptibility to other transmissible spongiform encephalopathies (TSEs) is poorly characterized. In this initial study, we intracerebrally challenged 6 meadow voles with 2 isolates of sheep scrapie. Three meadow voles acquired a TSE after the scrapie challenge and an extended incubation period. The glycoform profile of proteinase K-resistant prion protein (PrP(res)) in scrapie-sick voles remained similar to the sheep inocula, but differed from that of voles clinically affected by CWD. Vacuolization patterns and disease-associated prion protein (PrP(Sc)) deposition were generally similar in all scrapie-affected voles, except in the hippocampus, where PrP(Sc) staining varied markedly among the animals. Our results demonstrate that meadow voles can acquire a TSE after intracerebral scrapie challenge and that this species could therefore prove useful for characterizing scrapie isolates.

  11. Experimental infection of meadow voles (Microtus pennsylvanicus) with sheep scrapie.

    Science.gov (United States)

    Carlson, Christina M; Schneider, Jay R; Pedersen, Joel A; Heisey, Dennis M; Johnson, Christopher J

    2015-01-01

    Meadow voles (Microtus pennsylvanicus) are permissive to chronic wasting disease (CWD) infection, but their susceptibility to other transmissible spongiform encephalopathies (TSEs) is poorly characterized. In this initial study, we intracerebrally challenged 6 meadow voles with 2 isolates of sheep scrapie. Three meadow voles acquired a TSE after the scrapie challenge and an extended incubation period. The glycoform profile of proteinase K-resistant prion protein (PrP(res)) in scrapie-sick voles remained similar to the sheep inocula, but differed from that of voles clinically affected by CWD. Vacuolization patterns and disease-associated prion protein (PrP(Sc)) deposition were generally similar in all scrapie-affected voles, except in the hippocampus, where PrP(Sc) staining varied markedly among the animals. Our results demonstrate that meadow voles can acquire a TSE after intracerebral scrapie challenge and that this species could therefore prove useful for characterizing scrapie isolates.

  12. Advanced survival models for risk-factor analysis in scrapie

    OpenAIRE

    2007-01-01

    Because of the confounding effects of long incubation duration and flock management, accurate epidemiological studies of scrapie outbreaks are difficult to carry out. In this study, 641 Manech red-faced sheep from six scrapie-affected field flocks in Pyrénées Atlantiques, France, were monitored for clinical scrapie over a 6–9 year period. Over this period, 170 scrapie clinical cases were recorded and half of the culled animals were submitted for post-mortem transmissible spongiform encephalop...

  13. A Targeted Survey for Scrapie in Jos Plateau State, Nigeria

    OpenAIRE

    Nwankiti, O. O.; Ikeh, E. I.; Arowolo, O. A.; Nwankiti, A. J.; M. O. Odugbo; T. Seuberlich

    2013-01-01

    Scrapie, a disease of sheep and goats with a progressive course and fatal outcome, has not been identified in Nigeria. Anecdotal scrapie reports by livestock workers abound. Livestock diseases like scrapie form huddles in livestock economics of countries. For 8 months we surveyed for scrapie targeting emergency/casualty slaughter sheep and goats in Jos, Nigeria. We clinically examined 510 sheep and 608 goats of local breeds, aged from 12 months to 5 years. In total 31 (5.10%) goats and no she...

  14. Scrapie strain-specific interactions with endogenous murine leukaemia virus.

    Science.gov (United States)

    Carp, R I; Meeker, H C; Caruso, V; Sersen, E

    1999-01-01

    The finding that a senescence-accelerated mouse (SAMP8) shows early brain ageing, with histopathological changes resembling those seen in scrapie, combined with the discovery of high levels of endogenous murine leukaemia virus (MuLV) in brains of SAMP8 mice prompted us to examine the effect of scrapie infection on MuLV titres in this strain and in one of its progenitors, the AKR strain. Three scrapie strains (ME7, 22L and 139A) that had a comparatively short incubation period in SAMP8 and AKR mice caused an increase in brain MuLV titres that was scrapie strain-specific: in each mouse strain, the greatest effect was with 1 39A, and the least with ME7. The 22A scrapie strain, which has a long incubation period in SAMP8 mice, did not affect MuLV titres in brains of this mouse strain. Previous analyses of scrapie incubation periods in AKR, SAMP8 and another strain derived from an AKR cross (SAMR1) showed an inverse relationship between brain MuLV titres and scrapie incubation periods. This finding, combined with the effect of scrapie on MuLV titres, suggests an interaction between the scrapie infectious process and MuLV replication.

  15. 9 CFR 54.9 - Waiver of requirements for scrapie control pilot projects.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Waiver of requirements for scrapie... CONTROL OF SCRAPIE Scrapie Indemnification Program § 54.9 Waiver of requirements for scrapie control pilot projects. The Administrator may waive the following requirements of this part for participants in a...

  16. Strain typing of classical scrapie by transgenic mouse bioassay using protein misfolding cyclic amplification to replace primary passage.

    Directory of Open Access Journals (Sweden)

    Katy E Beck

    Full Text Available According to traditional murine bioassay methodology, prions must be serially passaged within a new host before a stable phenotype, and therefore a strain, can be assigned. Prions often transmit with difficulty from one species to another; a property termed the transmission barrier. Transgenic mouse lines that over express prion protein (PrP genes of different species can circumvent the transmission barrier but serial passages may still be required, particularly if unknown strains are encountered. Here we sought to investigate whether protein misfolding cyclic amplification (PMCA, an in-vitro method of PrP(Sc replication, could be used to replace serial passage of VRQ/VRQ classical scrapie isolates undergoing strain typing in ovine transgenic tg338 mice. Two classical scrapie field isolates that do not readily transmit to wild-type mice underwent bioassay in tg338 mice pre- and post- PMCA and the phenotype of disease in inoculated mice was compared. For one of the sources investigated, the PMCA product gave rise to the same disease phenotypes in tg338 mice as traditional bioassay, as indicated by lesion profile, IHC analysis and Western blot, whilst the second source produced phenotypic characteristics which were not identical with those that arose through traditional bioassay. These data show that differences in the efficiency of PMCA as a strain-typing tool may vary between ovine classical scrapie isolates and therefore suggest that the ability of PMCA to replace serial passage of classical scrapie in tg338 mice may depend on the strain present in the initial source.

  17. Fluorescence spectroscopy of the retina from scrapie-infected mice.

    Science.gov (United States)

    Bose, Sayantan; Schönenbrücher, Holger; Richt, Jürgen A; Casey, Thomas A; Rasmussen, Mark A; Kehrli, Marcus E; Petrich, Jacob W

    2013-01-01

    Recently, we have proposed that the fluorescence spectra of sheep retina can be well correlated with the presence or absence of scrapie. Scrapie is the most widespread TSE (transmissible spongiform encephalopathy) affecting sheep and goats worldwide. Mice eyes have been previously reported as a model system to study age-related accumulation of lipofuscin, which has been investigated by monitoring the increasing fluorescence with age covering its entire life span. The current work aims at developing mice retina as a convenient model system to diagnose scrapie and other fatal TSE diseases in animals such as sheep and cows. The objective of the research reported here was to determine whether the spectral features are conserved between two different species namely mice and sheep, and whether an appropriate small animal model system could be identified for diagnosis of scrapie based on the fluorescence intensity in retina. The results were consistent with the previous reports on fluorescence studies of healthy and scrapie-infected retina of sheep. The fluorescence from the retinas of scrapie-infected sheep was significantly more intense and showed more heterogeneity than that from the retinas of uninfected mice. Although the structural characteristics of fluorescence spectra of scrapie-infected sheep and mice eyes are slightly different, more importantly, murine retinas reflect the enhancement of fluorescence intensity upon infecting the mice with scrapie, which is consistent with the observations in sheep eyes.

  18. Epidemiological analysis of data for scrapie in Great Britain

    NARCIS (Netherlands)

    Hagenaars, T.H.J.; Donnelly, C.; Ferguson, N.M.

    2006-01-01

    In recent years, the control or eradication of scrapie and any other transmissible spongiform encephalopathies (TSEs) possibly circulating in the sheep population has become a priority in Britain and elsewhere in Europe. A better understanding of the epidemiology of scrapie would greatly aid the dev

  19. 78 FR 25943 - Changes to Scrapie Flock Certification Program

    Science.gov (United States)

    2013-05-03

    ... Animal and Plant Health Inspection Service Changes to Scrapie Flock Certification Program AGENCY: Animal... giving notice of changes to the Scrapie Flock Certification Program (SFCP), a voluntary program for sheep and goat flock owners who wish to reduce and/or eliminate the risk of introducing classical...

  20. A Targeted Survey for Scrapie in Jos Plateau State, Nigeria

    Directory of Open Access Journals (Sweden)

    O. O. Nwankiti

    2013-01-01

    Full Text Available Scrapie, a disease of sheep and goats with a progressive course and fatal outcome, has not been identified in Nigeria. Anecdotal scrapie reports by livestock workers abound. Livestock diseases like scrapie form huddles in livestock economics of countries. For 8 months we surveyed for scrapie targeting emergency/casualty slaughter sheep and goats in Jos, Nigeria. We clinically examined 510 sheep and 608 goats of local breeds, aged from 12 months to 5 years. In total 31 (5.10% goats and no sheep were clinically suspicious for scrapie. Caudal brainstem tissues of suspect animals collected postmortem were analyzed for the disease specific form of the prion protein, PrPSc, using Bio-Rad’s TeSeE ELISA rapid test kit. No sample was positive for scrapie. Fluorescent antibody test for rabies and H&E staining on samples were carried out for differential diagnosis. These showed no pathological lesions indicative for neurological disease. While our findings do not exclude the presence of scrapie in Jos, we demonstrate that targeted sampling of small ruminants for neuroinfectious disease is feasible in developing countries, pointing to the possibility of implementing such a monitoring scheme in Nigeria to prevent economic losses in small ruminant livestock as scrapie caveats from endemic countries have shown.

  1. The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks.

    OpenAIRE

    Baylis, M.; Houston, Fiona; Goldmann, W.; Hunter, N.; McLean, A.R.

    2000-01-01

    The amino-acid sequence of the PrP protein plays an important role in determining whether sheep are susceptible to scrapie. Although the genetics of scrapie susceptibility are now well understood, there have been few studies of the PrP gene at the population level, especially in commercially farmed sheep. Here we describe the PrP genetic profiles of the breeding stock of four UK sheep flocks, comprising nearly 650 animals in total. Two flocks had been scrapie affected for about eight years an...

  2. Norwegian farmers' vigilance in reporting sheep showing scrapie-associated signs

    OpenAIRE

    Jarp Jorun; Vatn Synnøve; Hopp Petter

    2007-01-01

    Abstract Background Scrapie is a chronic neurodegenerative disease affecting small ruminants and belongs to the transmissible spongiform encephalopathies. Scrapie is considered a serious animal disease and it has been notifiable in Norway since 1965. The clinical signs of scrapie might be vague and the farmers, if familiar with the signs of scrapie, are often in the best position for detecting scrapie suspects. In 2002, an anonymous questionnaire survey was conducted in order to assess Norweg...

  3. Scrapie : in vitro- and in vivo-separation of infectivity and scrapie-associated fibrils (SAFs)

    NARCIS (Netherlands)

    Braig, Henk Ronald

    1995-01-01

    The sheep and goat disease scrapie adapted to hamsters was studied as a model for unconventionals low virus diseases which are rare, fatal, spongiform encephalopathies of animals and man characterized by sometimes extreme long incubation periods, an apparent absence of any host immune reaction, and

  4. Advanced survival models for risk-factor analysis in scrapie. : PrP genotype influence on scrapie infection risk and incubation period.

    OpenAIRE

    Corbière, Fabien; Barillet, Francis; Andréoletti, Olivier; Fidelle, Francis; Laphitz-Bordet, Nathalie; Schelcher, François; Joly, Pierre

    2007-01-01

    International audience; Because of the confounding effects of long incubation duration and flock management, accurate epidemiological studies of scrapie outbreaks are difficult to carry out. In this study, 641 Manech red-faced sheep from six scrapie-affected field flocks in Pyr?es Atlantiques, France, were monitored for clinical scrapie over a 6-9 year period. Over this period, 170 scrapie clinical cases were recorded and half of the culled animals were submitted for post-mortem transmissible...

  5. Replication of the Scrapie Agent in Ocular Neural Tissues

    Science.gov (United States)

    Buyukmihci, Ned; Rorvik, Marie; Marsh, Richard F.

    1980-02-01

    Optic nerves and retinas removed from hamsters experimentally inoculated with the scrapie agent contain a high titer of infectivity. Ophthalmoscopic examination of these animals revealed gross lesions of retinopathy as early as 3 weeks before the onset of clinical signs of brain degeneration. These results suggest that the scrapie agent may spread centrifugally in nerve fibers after intracerebral inoculation and that the scrapie-associated retinopathy seen in hamsters is directly induced by the agent rather than the result of retrograde degeneration from central neural damage.

  6. Iron and iron/manganese ratio in forage from Icelandic sheep farms: relation to scrapie

    Directory of Open Access Journals (Sweden)

    Jóhannesson T

    2006-08-01

    Full Text Available Abstract This study was undertaken in order to examine whether any connection existed between the amounts of iron in forage and the sporadic occurrence of scrapie observed in certain parts of Iceland. As iron and manganese are considered antagonistic in plants, calculation of the Fe/Mn ratios was also included by using results from Mn determination earlier performed in the same samples. Forage samples (n = 170 from the summer harvests of 2001–2003, were collected from 47 farms for iron and manganese analysis. The farms were divided into four categories: 1. Scrapie-free farms in scrapie-free areas (n = 9; 2. Scrapie-free farms in scrapie-afflicted areas (n = 17; 3. Scrapie-prone farms (earlier scrapie-afflicted, restocked farms (n = 12; 4. Scrapie-afflicted farms (n = 9. Farms in categories 1 and 2 are collectively referred to as scrapie-free farms. The mean iron concentration in forage samples from scrapie-afflicted farms was significantly higher than in forage samples from farms in the other scrapie categories (P = 0.001. The mean Fe/Mn ratio in forage from scrapie-afflicted farms was significantly higher than in forage from scrapie-free and scrapie-prone farms (P

  7. Glycidol degrades scrapie mouse prion protein.

    Science.gov (United States)

    Yamamoto, M; Horiuchi, M; Ishiguro, N; Shinagawa, M; Matsuo, T; Kaneko, K

    2001-09-01

    Agents of transmissible spongiform encephalopathy (prion) are known to be extremely resistant to physicochemical inactivation procedures such as heat, radiation, chemical disinfectants such as detergents, alcohols, glutaraldehyde, formalin, and so on. Because of its remarkable resistance, it is difficult to inactivate prion. Chemical inactivation seems to be a practical method because it is applicable to large or fixed surfaces and complicated equipment. Here, three epoxides: beta-propiolactone, propylene oxide, and glycidol (GLD) were examined of their inactivation ability against scrapie-mouse prion protein (PrP(Sc)) under various conditions of chemical concentration, incubation time, and temperature. Among these chemicals, GLD worked most effectively and degraded PrP into small fragments. As a result of the bioassay, treatment with 3% GLD for 5 hr and 5% GLD for 2, 5 hr or 12 hr at room temperature prolonged the mean incubation time by 44, 30, 110 and 73 days, respectively. From dose-incubation time standard curve, the decrease in infectivity titers were estimated as 10(3) or more. Therefore, degradation of PrP(Sc) by GLD decreased the scrapie infectivity. It is also suggested that pH and salt concentrations influence the effect of GLD. Although further study is necessary to determine the optimal condition, GLD may be a potential prion disinfectant.

  8. A C-terminal protease-resistant prion fragment distinguishes ovine "CH1641-like" scrapie from bovine classical and L-Type BSE in ovine transgenic mice.

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    Thierry Baron

    Full Text Available The protease-resistant prion protein (PrP(res of a few natural scrapie isolates identified in sheep, reminiscent of the experimental isolate CH1641 derived from a British natural scrapie case, showed partial molecular similarities to ovine bovine spongiform encephalopathy (BSE. Recent discovery of an atypical form of BSE in cattle, L-type BSE or BASE, suggests that also this form of BSE might have been transmitted to sheep. We studied by Western blot the molecular features of PrP(res in four "CH1641-like" natural scrapie isolates after transmission in an ovine transgenic model (TgOvPrP4, to see if "CH1641-like" isolates might be linked to L-type BSE. We found less diglycosylated PrP(res than in classical BSE, but similar glycoform proportions and apparent molecular masses of the usual PrP(res form (PrP(res #1 to L-type BSE. However, the "CH1641-like" isolates differed from both L-type and classical BSE by an abundant, C-terminally cleaved PrP(res product (PrP(res #2 specifically recognised by a C-terminal antibody (SAF84. Differential immunoprecipitation of PrP(res #1 and PrP(res #2 resulted in enrichment in PrP(res #2, and demonstrated the presence of mono- and diglycosylated PrP(res products. PrP(res #2 could not be obtained from several experimental scrapie sources (SSBP1, 79A, Chandler, C506M3 in TgOvPrP4 mice, but was identified in the 87V scrapie strain and, in lower and variable proportions, in 5 of 5 natural scrapie isolates with different molecular features to CH1641. PrP(res #2 identification provides an additional method for the molecular discrimination of prion strains, and demonstrates differences between "CH1641-like" ovine scrapie and bovine L-type BSE transmitted in an ovine transgenic mouse model.

  9. A C-terminal protease-resistant prion fragment distinguishes ovine "CH1641-like" scrapie from bovine classical and L-Type BSE in ovine transgenic mice.

    Science.gov (United States)

    Baron, Thierry; Bencsik, Anna; Vulin, Johann; Biacabe, Anne-Gaëlle; Morignat, Eric; Verchere, Jérémy; Betemps, Dominique

    2008-08-29

    The protease-resistant prion protein (PrP(res)) of a few natural scrapie isolates identified in sheep, reminiscent of the experimental isolate CH1641 derived from a British natural scrapie case, showed partial molecular similarities to ovine bovine spongiform encephalopathy (BSE). Recent discovery of an atypical form of BSE in cattle, L-type BSE or BASE, suggests that also this form of BSE might have been transmitted to sheep. We studied by Western blot the molecular features of PrP(res) in four "CH1641-like" natural scrapie isolates after transmission in an ovine transgenic model (TgOvPrP4), to see if "CH1641-like" isolates might be linked to L-type BSE. We found less diglycosylated PrP(res) than in classical BSE, but similar glycoform proportions and apparent molecular masses of the usual PrP(res) form (PrP(res) #1) to L-type BSE. However, the "CH1641-like" isolates differed from both L-type and classical BSE by an abundant, C-terminally cleaved PrP(res) product (PrP(res) #2) specifically recognised by a C-terminal antibody (SAF84). Differential immunoprecipitation of PrP(res) #1 and PrP(res) #2 resulted in enrichment in PrP(res) #2, and demonstrated the presence of mono- and diglycosylated PrP(res) products. PrP(res) #2 could not be obtained from several experimental scrapie sources (SSBP1, 79A, Chandler, C506M3) in TgOvPrP4 mice, but was identified in the 87V scrapie strain and, in lower and variable proportions, in 5 of 5 natural scrapie isolates with different molecular features to CH1641. PrP(res) #2 identification provides an additional method for the molecular discrimination of prion strains, and demonstrates differences between "CH1641-like" ovine scrapie and bovine L-type BSE transmitted in an ovine transgenic mouse model.

  10. Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Schreuder, B.E.C.; Meloen, R.H.; Mooij-Harkes, G.; Vromans, M.E.W.; Langeveld, J.P.M.

    1996-01-01

    The scrapie-associated form of the prion protein (PrP(Sc)) accumulates in the brain and lymphoid tissues of sheep with scrapie. In order to assess whether detecting PrP(Sc) in lymphoid tissue could he used as a diagnostic test for scrapie, we studied the localization and distribution of PrP(Sc) in v

  11. 9 CFR 79.7 - Waiver of requirements for scrapie control pilot projects.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Waiver of requirements for scrapie... PRODUCTS SCRAPIE IN SHEEP AND GOATS § 79.7 Waiver of requirements for scrapie control pilot projects. (a) The Administrator may waive the following requirements of this part for participants in a...

  12. 9 CFR 79.4 - Designation of scrapie-positive animals, high-risk animals, exposed animals, suspect animals...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Designation of scrapie-positive... (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCRAPIE IN SHEEP AND GOATS § 79.4 Designation of scrapie-positive..., noncompliant flocks, and source flocks; notice to owners. (a) Designation. A designated scrapie...

  13. Analysis of host genetic control of scrapie-induced obesity.

    Science.gov (United States)

    Carp, R I; Callahan, S M; Yu, Y; Sersen, E

    1993-01-01

    The potential for induction of obesity during the preclinical phase of scrapie disease in mice was previously shown to be a function of both the strain of scrapie and the strain of inbred mouse. In the present study, host control of obesity induction by a scrapie strain was examined to determine if the effect were dependent on a single gene or multiple genes. The approach used was assessment of the pattern of weight induction in F1 and F2 crosses of parental inbred mouse strains that did or did not show a weight increase with a specific scrapie strain. Analyses of these data indicated that the induction of obesity was controlled by multiple host genes. In an unrelated observation, there was a correlation between the incubation period of a strain of scrapie in F2 generation mice and their coat color, i.e., the average incubation period of yellow-brown mice was significantly less than those of either black or white mice.

  14. Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination.

    Science.gov (United States)

    Carp, R I; Callahan, S M; Sersen, E A; Moretz, R C

    1984-01-01

    Several inbred strains of mice were injected with different scrapie agents and their total body weight was monitored throughout the incubation period. As a control, mice were injected with normal mouse brain homogenate. For most combinations of scrapie agent and mouse strain, weights during the preclinical phase were similar to or lower than the average weight of controls. For some combinations there was a significant increase in weight (compared to controls) during the latter part of the preclinical phase of disease. The effect was dependent on both agent and mouse strain, i.e., in some cases a mouse strain showed the increase with one scrapie agent but not another and some scrapie agents caused the increase in one inbred strain of mouse but not in another strain. The increase in weight was due to accumulations of fat rather than a generalized increase in weight of various organs. With one mouse strain (SJL), there was increased vacuolation seen in the hypothalamus of mice injected with scrapie agents that showed the increase in weight compared to the lesion intensity with an agent which did not cause the weight increase.

  15. Synthetic scrapie infectivity: interaction between recombinant PrP and scrapie brain-derived RNA.

    Science.gov (United States)

    Simoneau, Steve; Thomzig, Achim; Ruchoux, Marie-Madeleine; Vignier, Nicolas; Daus, Martin L; Poleggi, Anna; Lebon, Pierre; Freire, Sophie; Durand, Valerie; Graziano, Silvia; Galeno, Roberta; Cardone, Franco; Comoy, Emmanuel; Pocchiari, Maurizio; Beekes, Michael; Deslys, Jean-Philippe; Fournier, Jean-Guy

    2015-01-01

    The key molecular event in human cerebral proteinopathies, which include Alzheimer's, Parkinson's and Huntington's diseases, is the structural conversion of a specific host protein into a β-sheet-rich conformer. With regards to this common mechanism, it appears difficult to explain the outstanding infectious properties attributed to PrP(Sc), the hallmark of another intriguing family of cerebral proteinopathies known as transmissible spongiform encephalopathies (TSE) or prion diseases. The infectious PrP(Sc) or "prion" is thought to be composed solely of a misfolded form of the otherwise harmless cellular prion protein (PrP(c)). To gain insight into this unique situation, we used the 263K scrapie hamster model to search for a putative PrP(Sc)-associated factor that contributes to the infectivity of PrP(Sc) amyloid. In a rigorously controlled set of experiments that included several bioassays, we showed that originally innocuous recombinant prion protein (recPrP) equivalent to PrP(c) is capable of initiating prion disease in hamsters when it is converted to a prion-like conformation (β-sheet-rich) in the presence of RNA purified from scrapie-associated fibril (SAF) preparations. Analysis of the recPrP-RNA infectious mixture reveals the presence of 2 populations of small RNAs of approximately 27 and 55 nucleotides. These unprecedented findings are discussed in light of the distinct relationship that may exist between this RNA material and the 2 biological properties, infectivity and strain features, attributed to prion amyloid.

  16. Extended scrapie incubation time in goats singly heterozygous for PRNP S146 or K222.

    Science.gov (United States)

    White, Stephen N; Reynolds, James O; Waldron, Daniel F; Schneider, David A; O'Rourke, Katherine I

    2012-06-10

    Scrapie is the transmissible spongiform encephalopathy (TSE) of sheep and goats, and scrapie eradication in sheep is based in part on strong genetic resistance to classical scrapie. Goats may serve as a scrapie reservoir, and to date there has been no experimental inoculation confirming strong genetic resistance in goats. Two prion protein variants (amino acid substitutions S146 and K222) in goats have been significantly underrepresented in scrapie cases though present in scrapie-exposed flocks, and have demonstrated low cell-free protein conversion efficiency to the disease form (PrP(D)). To test degree of genetic resistance conferred in live animals with consistent exposure, we performed the first oral scrapie challenge of goats singly heterozygous for either PRNP S146 or K222. All N146-Q222 homozygotes became clinically scrapie positive by an average of 24months, but all S146 and K222 heterozygotes remain scrapie negative by both rectal biopsy and clinical signs at significantly longer incubation times (Pscrapie, suggesting these alleles do not confer complete resistance in the heterozygous state but rather extend incubation. The oral challenge results presented here confirm extended incubation observed in a recent intracerebral challenge of K222 heterozygotes, and to our knowledge provide the first demonstration of extended incubation in S146 heterozygotes. These results suggest longer relevant trace-back histories in scrapie-eradication programs for animals bearing these alleles and strengthen the case for additional challenge experiments in both homozygotes to assess potential scrapie resistance.

  17. Genetic resistance to scrapie infection in experimentally challenged goats.

    Science.gov (United States)

    Lacroux, Caroline; Perrin-Chauvineau, Cécile; Corbière, Fabien; Aron, Naima; Aguilar-Calvo, Patricia; Torres, Juan Maria; Costes, Pierrette; Brémaud, Isabelle; Lugan, Séverine; Schelcher, François; Barillet, Francis; Andréoletti, Olivier

    2014-03-01

    In goats, several field studies have identified coding mutations of the gene encoding the prion protein (I/M142, N/D146, S/D146, R/Q211, and Q/K222) that are associated with a lower risk of developing classical scrapie. However, the data related to the levels of resistance to transmissible spongiform encephalopathies (TSEs) of these different PRNP gene mutations are still considered insufficient for developing large-scale genetic selection against scrapie in this species. In this study, we inoculated wild-type (WT) PRNP (I142R154R211Q222) goats and homozygous and/or heterozygous I/M142, R/H154, R/Q211, and Q/K222 goats with a goat natural scrapie isolate by either the oral or the intracerebral (i.c.) route. Our results indicate that the I/M142 PRNP polymorphism does not provide substantial resistance to scrapie infection following intracerebral or oral inoculation. They also demonstrate that H154, Q211, and K222 PRNP allele carriers are all resistant to scrapie infection following oral exposure. However, in comparison to WT animals, the H154 and Q211 allele carriers displayed only moderate increases in the incubation period following i.c. challenge. After i.c. challenge, heterozygous K222 and a small proportion of homozygous K222 goats also developed the disease, but with incubation periods that were 4 to 5 times longer than those in WT animals. These results support the contention that the K222 goat prion protein variant provides a strong but not absolutely protective effect against classical scrapie.

  18. Norwegian farmers' vigilance in reporting sheep showing scrapie-associated signs

    Directory of Open Access Journals (Sweden)

    Jarp Jorun

    2007-12-01

    Full Text Available Abstract Background Scrapie is a chronic neurodegenerative disease affecting small ruminants and belongs to the transmissible spongiform encephalopathies. Scrapie is considered a serious animal disease and it has been notifiable in Norway since 1965. The clinical signs of scrapie might be vague and the farmers, if familiar with the signs of scrapie, are often in the best position for detecting scrapie suspects. In 2002, an anonymous questionnaire survey was conducted in order to assess Norwegian sheep farmers' vigilance of scrapie. Results Although the potential detection of a scrapie-positive animal would lead to the destruction of the sheep flock concerned, almost all the farmers (97 % expressed their willingness to report scrapie suspects. This was most certainly dependent on the Government taking the economic responsibility for the control programme as nearly all the farmers responded that this was an important condition. Listeriosis is relatively common disease in Norwegian sheep and a differential diagnosis for scrapie. In a multinomial logistic regression the reporting behaviour for non-recovering listeriosis cases, used as a measurement of willingness to report scrapie, was examined. The reporting of non-recovering listeriosis cases increased as the knowledge of scrapie-associated signs increased, and the reporting behaviour was dependent on both economic and non-economic values. Conclusion The results indicate that in 2002 almost all sheep farmers showed willingness to report any scrapie suspects. Nevertheless there is an underreporting of scrapie suspects and the farmers' awareness and hence their vigilance of scrapie could be improved. Furthermore, the results suggest that to ensure the farmers' compliance to control programmes for serious infectious diseases, the farmers' concerns of non-economic as well as economic values should be considered.

  19. Glutathione peroxidase (GPX activity in blood of ewes on farms in different scrapie categories in Iceland

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    Eiríksson Tryggvi

    2008-06-01

    Full Text Available Abstract Background Preliminary studies indicated decreased glutathione peroxidase (GPX activity in blood of ewes on scrapie-afflicted farms. Other studies have shown decreased GPX activity in brain of prion-infected mice and in prion-infected cells in vitro. The aim of this study was to examine the GPX activity in blood as well as the distribution of GPX-activity levels from ewes on farms in scrapie-afflicted areas in Iceland. Methods Blood samples were collected from 635 ewes (non-pregnant [n = 297] and pregnant [n = 338] on 40 farms in scrapie-afflicted areas during the years 2001–2005, for analysis of GPX activity. The farms were divided into three categories: 1. Scrapie-free farms (n = 14; 2. Scrapie-prone farms (earlier scrapie-afflicted, restocked farms (n = 12; 3. Scrapie-afflicted farms (n = 14. For comparison, 121 blood samples were also collected from non-pregnant ewes on one farm (farm A in a scrapie-free area (scrapie never registered. Chi-square test was used to test for normal distribution of GPX-results, and Kruskal-Wallis test to compare GPX-results between categories. Results The GPX-results appeared to be biphasically distributed in ewes in all three scrapie categories and on farm A. The presumptive breaking point was about 300 units g Hb-1. About 30–50% of the GPX-results from ewes in all three scrapie categories were below 300 units g Hb-1 but only about 13% of the GPX-results from ewes on farm A. The mean GPX activity was highest on farm A, and was significantly lower on scrapie-prone farms than on scrapie-free or scrapie-afflicted farms (non-pregnant and pregnant ewes: P Conclusions 1 the distribution of GPX-results in blood of Icelandic ewes apparently has a biphasic character; 2 the GPX-results were higher in ewes on one farm in a scrapie-free area than in ewes on farms in the scrapie-afflicted areas; 3 GPX-activity levels were significantly lowest on earlier scrapie-afflicted, restocked farms, which might have a

  20. Evidence in sheep for pre-natal transmission of scrapie to lambs from infected mothers.

    Science.gov (United States)

    Foster, James D; Goldmann, Wilfred; Hunter, Nora

    2013-01-01

    Natural scrapie transmission from infected ewes to their lambs is thought to occur by the oral route around the time of birth. However the hypothesis that scrapie transmission can also occur before birth (in utero) is not currently favoured by most researchers. As scrapie is an opportunistic infection with multiple infection routes likely to be functional in sheep, definitive evidence for or against transmission from ewe to her developing fetus has been difficult to achieve. In addition the very early literature on maternal transmission of scrapie in sheep was compromised by lack of knowledge of the role of the PRNP (prion protein) gene in control of susceptibility to scrapie. In this study we experimentally infected pregnant ewes of known PRNP genotype with a distinctive scrapie strain (SSBP/1) and looked for evidence of transmission of SSBP/1 to the offspring. The sheep were from the NPU Cheviot flock, which has endemic natural scrapie from which SSBP/1 can be differentiated on the basis of histology, genetics of disease incidence and strain typing bioassay in mice. We used embryo transfer techniques to allow sheep fetuses of scrapie-susceptible PRNP genotypes to develop in a range of scrapie-resistant and susceptible recipient mothers and challenged the recipients with SSBP/1. Scrapie clinical disease, caused by both natural scrapie and SSBP/1, occurred in the progeny but evidence (including mouse strain typing) of SSBP/1 infection was found only in lambs born to fully susceptible recipient mothers. Progeny were not protected from transmission of natural scrapie or SSBP/1 by washing of embryos to International Embryo Transfer Society standards or by caesarean derivation and complete separation from their birth mothers. Our results strongly suggest that pre-natal (in utero) transmission of scrapie may have occurred in these sheep.

  1. Transcriptomic determinants of scrapie prion propagation in cultured ovine microglia

    Science.gov (United States)

    While infection by scrapie prions is dependent on expression of cellular prion protein (PrP-C), other factors must play a role since not all cells that express equivalent levels of PrP-C are permissive to infection. The aim of this study was to determine the cellular factors associated with permissi...

  2. hTERT-immortalized ovine microglia propagate natural scrapie isolates

    Science.gov (United States)

    Scrapie is a transmissible fatal neurodegenerative disease of sheep that is caused by a novel infectious agent called a prion. The study of prions under controlled culture conditions is crucial to advancing knowledge regarding prion processes of replication and accumulation within cells. Unfortunate...

  3. hTERT-immortalized ovine microglia propagate natural scrapie isolates.

    Science.gov (United States)

    Muñoz-Gutiérrez, Juan F; Schneider, David A; Baszler, Timothy V; Greenlee, Justin J; Nicholson, Eric M; Stanton, James B

    2015-02-16

    Ex vivo propagation of natural prion isolates (i.e., propagated solely in the natural host) is crucial for the characterization and study of transmissible spongiform encephalopathies (TSEs). Several well-established, prion-permissive cell culture systems are available; however, only a few cell lines are permissive to natural prion isolates and these cells are not pathophysiologically relevant (e.g., renal epithelium and fibroblast-like cells). Therefore, a pathophysiologically relevant cell line derived from a natural TSE host could be used for propagation of natural prion isolates. In this study, ovine brain macrophages (microglia) were immortalized by transfection with the human telomerase reverse transcriptase (hTERT) gene to identify cell lines (hTERT-microglia) permissive to natural scrapie prion isolates. Following transfection, hTERT-microglia were passaged up to 100 times and their lifespan was significantly longer compared to parental cells (Fisher's exact test, Pscrapie isolates (i.e., derived from brain homogenates of sheep infected with scrapie). Prion infectivity and partial protease resistance of the prion protein were maintained in hTERT-microglia. Comparisons between scrapie-permissive and non-permissive hTERT-microglia sublines revealed that overall quantity of the normal cellular prion protein was not associated with prion permissiveness. The use of hTERT-microglia in future TSE studies may be more germane to the characterization of the cellular and subcellular pathophysiology of natural scrapie prion isolates and to investigate host-specific factors involved in prion replication.

  4. Eradication of scrapie with selective breeding: are we nearly there?

    Directory of Open Access Journals (Sweden)

    Davidse Aart

    2010-05-01

    Full Text Available Abstract Background Following EU decision 2003/100/EC Member States have recently implemented sheep breeding programmes to reduce the prevalence of sheep with TSE susceptible prion genotypes. The present paper investigates the progress of the breeding programme in the Netherlands. The PrP genotype frequencies were monitored through time using two sets of random samples: one set covers the years 2005 to 2008 and is taken from national surveillance programme; the other is taken from 168 random sheep farms in 2007. The data reveal that although the level of compliance to the breeding programme has been high, the frequency of susceptible genotypes varies substantially between farms. The 168 sheep farms are a subset of 689 farms participating in a postal survey inquiring about management and breeding strategies. This survey aimed to identify how much these strategies varied between farms, in order to inform assessment of the expected future progress towards eradication of classical scrapie. Results On the one hand, we found that compliance to the national breeding program has been high, and the frequency of resistant genotypes is expected to increase further in the next few years. On the other hand, we observed a large variation in prevalence of the scrapie resistant PrP genotype ARR between farms, implicating a large variation of genetic resistance between farms. Substantial between-flock differences in management and breeding strategies were found in the postal survey, suggesting considerable variation in risk of scrapie transmission between farms. Conclusions Our results show that although there has been a good progress in the breeding for scrapie resistance and the average farm-level scrapie susceptibility in the Netherlands has been significantly reduced, still a considerable proportion of farms contain high frequencies of susceptible genotypes in their sheep population. Since 2007 the breeding for genetic resistance is voluntarily again, and

  5. Histopathological studies of "CH1641-like" scrapie sources versus classical scrapie and BSE transmitted to ovine transgenic mice (TgOvPrP4.

    Directory of Open Access Journals (Sweden)

    Anna Bencsik

    Full Text Available The possibility of the agent causing bovine spongiform encephalopathy (BSE infecting small ruminants is of serious concern for human health. Among scrapie cases, the CH1641 source in particular appears to have certain biochemical properties similar to the BSE strain. In France, several natural scrapie cases were identified as "CH1641-like" natural scrapie isolates in sheep and goats. The Tg(OvPrP4 mouse line expressing the ovine prion protein is a sensitive model for studying and identifying strains of agents responsible for scrapie and BSE. This model is also very useful when studying specific scrapie source CH1641, known to be not transmissible to wild-type mice despite the similarity of some of its biochemical properties to those of the BSE strain. As it is important to be able to fully distinguish CH1641 from BSE, we herein report the histopathological data from CH1641 scrapie transmission experiments compared to specific cases of "CH1641-like" natural scrapie isolates in sheep, murine scrapie strains and BSE. In addition to the conventional vacuolar lesion profile approach and PrP(d brain mappings, an innovative differential PET-blot analysis was introduced to classify the different strains of agent and revealed the first direct concordance between ways of grouping strains on the basis of PrP(d biochemical characteristics.

  6. Histopathological studies of "CH1641-like" scrapie sources versus classical scrapie and BSE transmitted to ovine transgenic mice (TgOvPrP4).

    Science.gov (United States)

    Bencsik, Anna; Baron, Thierry

    2011-01-01

    The possibility of the agent causing bovine spongiform encephalopathy (BSE) infecting small ruminants is of serious concern for human health. Among scrapie cases, the CH1641 source in particular appears to have certain biochemical properties similar to the BSE strain. In France, several natural scrapie cases were identified as "CH1641-like" natural scrapie isolates in sheep and goats. The Tg(OvPrP4) mouse line expressing the ovine prion protein is a sensitive model for studying and identifying strains of agents responsible for scrapie and BSE. This model is also very useful when studying specific scrapie source CH1641, known to be not transmissible to wild-type mice despite the similarity of some of its biochemical properties to those of the BSE strain. As it is important to be able to fully distinguish CH1641 from BSE, we herein report the histopathological data from CH1641 scrapie transmission experiments compared to specific cases of "CH1641-like" natural scrapie isolates in sheep, murine scrapie strains and BSE. In addition to the conventional vacuolar lesion profile approach and PrP(d) brain mappings, an innovative differential PET-blot analysis was introduced to classify the different strains of agent and revealed the first direct concordance between ways of grouping strains on the basis of PrP(d) biochemical characteristics.

  7. Scrapie-specific pathology of sheep lymphoid tissues.

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    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases often result in accumulation of disease-associated PrP (PrP(d in the lymphoreticular system (LRS, specifically in association with follicular dendritic cells (FDCs and tingible body macrophages (TBMs of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrP(d was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrP(d within endosomes and lysosomes. In addition, TBMs showed PrP(d in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrP(d is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrP(d/cell membrane interactions occur in different cell types.

  8. Selectie tegen gevoeligheid voor scrapie met behoud van genetische variatie = Selection against scrapie susceptibility while maintaining within breed genetic variation

    NARCIS (Netherlands)

    Windig, J.J.; Hoving, A.H.

    2009-01-01

    In 2007 is de nationale regelgeving, gericht op selectie tegen scrapie gevoeligheid, gewijzigd. De verplichte inzet van ARR/ARR rammen is beëindigd. In dit rapport geven we een algemeen advies hoe het beste tegen scrapiegevoeligheid kan worden geselecteerd. In dit kader is ook een themadag over fokk

  9. Enhancement of immunohistochemical staining of scrapie proteins and immune cells within lymph nodes of early scrapie-infected sheep.

    Science.gov (United States)

    Furr, Annissa; Knudsen, David; Hildreth, Michael B; Young, Alan J

    2011-08-31

    Transmissible spongiform encephalopathies (TSE) are a group of fatal neurodegenerative diseases that affect animals as well as humans. The oldest of these diseases is Scrapie seen in sheep. Scrapie is caused by an altered form (PrP(sc)), capable of inducing "self-replication" of the normal host prion protein (PrP(c)). There is currently no universal standard for antigen retrieval when using immunohistochemistry to simultaneously stain the PrP(c) protein and other cellular markers. The use of formalin-fixed tissue creates a challenge by concealing the antigenic sites where an antibody would bind, and lengthy antigen retrieval methods must be applied in order to facilitate staining. Further complicating sheep tissue immunohistochemistry is a significant lack of commercial antibodies to sheep cell markers available in research. Here we developed a novel immunohistochemical technique using trypsin, formic acid, and hydrated autoclaving using citraconic anhydride buffer to increase sensitivity of staining for scrapie proteins and immune cell subsets. This allowed us to stain and identify cells within lymphoid tissue associated with early lymphoid pathogenesis in scrapie.

  10. Accumulation of Cholesterol Esters in ex vivo Lymphocytes from Scrapie-susceptible Sheep and in Scrapie-infected Mouse Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Alessandra Pani

    2007-01-01

    Full Text Available Our studies on the role of cholesterol homeostasis in the pathogenesis of scrapie in sheep, revealed abnormal accumulation of cholesterol esters in brains and in ex vivo skin fibroblasts from genetically scrapie-susceptible, as compared to sheep with resistant genotype. We now report that PBMCs isolated from scrapie-susceptible sheep, as well as mouse neuroblastoma cell lines persistently infected with two different mouse-adapted strains of scrapie, showed similar alterations with up to 3-fold higher cholesterol ester levels than their resistant or uninfected counterparts. Treatments with drugs that interfere with intracellular cholesterol metabolism strongly reduced accumulation of cholesterol esters in scrapie-infected cell lines, whereas had significantly lower, or no effect, in uninfected cell line. These data add support to our hypothesis that accumulation of cholesterol esters may represent a biological marker of susceptibility to prion infection and a potential molecular target for prion inhibitors.

  11. Sensitivity and specificity of a commercial BSE kit for the detection of ovine scrapie.

    Science.gov (United States)

    Yamamoto, Takuji; Ushiki-Kaku, Yuko; Yokoyama, Takashi; Hattori, Shunji

    2013-06-01

    To examine the sensitivity of a commercially available bovine spongiform encephalopathy (BSE) kit (NippIBL) for the detection of ovine scrapie, 50 scrapie-positive ovine samples from the UK, and 54 scrapie-negative ovine samples from Japan were obtain and tested using this kit. The sensitivity and specificity of NippIBL for ovine samples were 96% and 100%, respectively. The detection limit of the abnormal isoform of prion protein (PrP(Sc) ) of NippIBL was examined using diluted scrapie-positive samples. The sensitivity of NippIBL to ovine scrapie was 3-10 times superior to that of another commercial BSE diagnosis kit. Thus, the NippIBL kit proved more effective for the detection of ovine scrapie.

  12. Atypical charles bonnet syndrome.

    Science.gov (United States)

    Arun, Priti; Jain, Rajan; Tripathi, Vaibhav

    2013-10-01

    Charles Bonnet syndrome (CBS) is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  13. NOVEL ATYPICAL ANTIPSYCHOTIC AGENTS

    Directory of Open Access Journals (Sweden)

    Vijay Vinay

    2011-05-01

    Full Text Available Antipsychotics are a group of drugs commonly but not exclusively used to treat psychosis. Antipsychotic agents are grouped in two categories: Typical and Atypical antipsychotics. The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. The first atypical anti-psychotic medication, clozapine, was discovered in the 1950s, and introduced in clinical practice in the 1970s. Both typical and atypical antipsychotics are effective in reducing positive and negative symptoms of schizophrenia. Blockade of D2 receptor in mesolimbic pathway is responsible for antipsychotic action. Typical antipsychotics are not particularly selective and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects. Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2-receptor binding and high ratio of serotonin type 2 (5-HT2-receptor binding to D2. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, narcoleptic malignant syndrome, and hyperprolactinemia. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs and tardive dyskinesia (TD.

  14. Diagnosis and PrP genotype target of scrapie in clinically healthy sheep of Massese breed in the framework of a scrapie eradication programme.

    Science.gov (United States)

    Vascellari, M; Aufiero, G M; Nonno, R; Agrimi, U; Vaccari, G; Basilicata, L; Falcaro, C; Mancin, M; Marcon, S; Mutinelli, F

    2005-10-01

    The application of a selective culling programme in two scrapie affected flocks of Massese breed sheep is described. The genetic susceptibility of this breed and the sensitivity of different diagnostic methods in the pre-clinical diagnosis of scrapie were also investigated. Overall, 2,068 clinically healthy sheep underwent PrP genotyping, providing the basis for selective culling. The prevalence of scrapie infection was investigated in susceptible sheep by two independent diagnostic methods. All the sheep older than 18 months (n = 620) were tested by Prionics Check Western rapid test on the obex, with a prevalence of infection of 3.9%. Furthermore, 385 sheep underwent immunohistochemistry (IHC) on retropharyngeal lymph node (RPLN), with a prevalence of infection of 5.2%. Overall, 32 sheep were diagnosed with pre-clinical scrapie. Of these, 31 were positive by Western blot on the spleen, 29 by IHC on the RPLN and tonsil, 28 by IHC on the obex, 24 by rapid test, and only 18 by IHC on the third eyelid. All the scrapie positive sheep were of the ARQ/ARQ, ARQ/AHQ or ARQ/VRQ genotypes. No significant differences in scrapie prevalence were observed among these genotypes. The estimated risk of the three targeted alleles was also similar, suggesting that in this breed the VRQ allele was not at higher risk for scrapie, compared to the ARQ and AHQ alleles.

  15. PrP(Sc) detection and infectivity in semen from scrapie-infected sheep.

    Science.gov (United States)

    Rubenstein, Richard; Bulgin, Marie S; Chang, Binggong; Sorensen-Melson, Sharon; Petersen, Robert B; LaFauci, Giuseppe

    2012-06-01

    A scrapie-positive ewe was found in a flock that had been scrapie-free for 13 years, but housed adjacent to scrapie-positive animals, separated by a wire fence. Live animal testing of the entire flock of 24 animals revealed seven more subclinical scrapie-positive ewes. We hypothesized that they may have contracted the disease from scrapie-positive rams used for breeding 4 months prior, possibly through the semen. The genotypes of the ewe flock were highly scrapie-susceptible and the rams were infected with the 'Caine' scrapie strain having a short incubation time of 4.3-14.6 months in sheep with 136/171 VQ/VQ and AQ/VQ genotypes. PrP(Sc) accumulates in a variety of tissues in addition to the central nervous system. Although transmission of prion diseases, or transmissible spongiform encephalopathies, has been achieved via peripheral organ or tissue homogenates as well as by blood transfusion, neither infectivity nor PrP(Sc) have been found in semen from scrapie-infected animals. Using serial protein misfolding cyclic amplification followed by a surround optical fibre immunoassay, we demonstrate that semen from rams infected with a short-incubation-time scrapie strain contains prion disease-associated-seeding activity that generated PrP(Sc) in sPMCA (serial protein misfolding cyclic amplification). Injection of the ovinized transgenic mouse line TgSShpPrP with semen from scrapie-infected sheep resulted in PrP(Sc)-seeding activity in clinical and, probably as a result of the low titre, non-clinical mouse brain. These results suggest that the transmissible agent, or at least the seeding activity, for sheep scrapie is present in semen. This may be a strain-specific phenomenon.

  16. Lipid profiles in brains from sheep with natural scrapie.

    Science.gov (United States)

    Rosa, Antonella; Scano, Paola; Incani, Alessandra; Pilla, Federica; Maestrale, Caterina; Manca, Matteo; Ligios, Ciriaco; Pani, Alessandra

    2013-01-01

    Prion diseases are fatal neurodegenerative disorders affecting many mammals, ovine scrapie being the archetypal prion disease. Several independent studies in murine and cell-based models of scrapie have highlighted the presence of a link between prion generation and lipid alterations; yet, no data on natural disease are available. In this study we investigated levels of total lipids and cholesterol as well as profiles of fatty acids in brain homogenates from symptomatic and asymptomatic scrapie-infected sheep vs. healthy sheep, all belonging to the same flock. Lipid extracts were analyzed by means of gas chromatography and high performance liquid chromatography. Data of fatty acids were submitted to multivariate statistical analysis to give a picture of the brain lipid profiles of sheep. Interestingly, results revealed abnormalities in the brain fatty acid unsaturation of infected/symptomatic animals. Significant reduction of monoene 18:1 n-9 was detected in brain lipids from infected/symptomatic sheep, as compared to healthy and infected/asymptomatic animals, and this alteration occurred in combination with a significant increase in 18:0 level. The unsupervised Principal Component Analysis showed that infected/symptomatic and healthy sheep samples lie in two different regions of the plot, infected/asymptomatic lie mostly next to healthy. The increase of cerebral saturated fatty acids provides a rough indication of presumed alterations in lipid raft domains of nervous cells during scrapie, suggesting that they may exist in a notable viscous liquid-ordered state. Such physicochemical alteration would have a profound impact on the raft thermodynamic properties, its spatial organization, and signal transduction, all potentially relevant for prion generation.

  17. Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia.

    Science.gov (United States)

    Muñoz-Gutiérrez, Juan F; Pierlé, Sebastián Aguilar; Schneider, David A; Baszler, Timothy V; Stanton, James B

    2016-01-01

    Susceptibility to infection by prions is highly dependent on the amino acid sequence and host expression of the cellular prion protein (PrPC); however, cellular expression of a genetically susceptible PrPC is insufficient. As an example, it has been shown in cultured cells that permissive and resistant sublines derived from the same parental population often have similar expression levels of PrPC. Thus, additional cellular factors must influence susceptibility to prion infection. The aim of this study was to elucidate the factors associated with relative permissiveness and resistance to scrapie prions in cultured cells derived from a naturally affected species. Two closely related ovine microglia clones with different prion susceptibility, but no detectable differences in PrPC expression levels, were inoculated with either scrapie-positive or scrapie-negative sheep brainstem homogenates. Five passages post-inoculation, the transcriptional profiles of mock and infected clones were sequenced using Illumina technology. Comparative transcriptional analyses identified twenty-two differentially transcribed genes, most of which were upregulated in poorly permissive microglia. This included genes encoding for selenoprotein P, endolysosomal proteases, and proteins involved in extracellular matrix remodeling. Furthermore, in highly permissive microglia, transforming growth factor β-induced, retinoic acid receptor response 1, and phosphoserine aminotranspherase 1 gene transcripts were upregulated. Gene Set Enrichment Analysis identified proteolysis, translation, and mitosis as the most affected pathways and supported the upregulation trend of several genes encoding for intracellular proteases and ribosomal proteins in poorly permissive microglia. This study identifies new genes potentially involved in scrapie prion propagation, corroborates results from other studies, and extends those results into another cell culture model.

  18. 76 FR 43649 - Notice of Request for Extension of Approval of an Information Collection; Scrapie in Sheep and...

    Science.gov (United States)

    2011-07-21

    ... Collection; Scrapie in Sheep and Goats; Interstate Movement Restrictions and Indemnity Program AGENCY: Animal... indemnity program to control the spread of scrapie. DATES: We will consider all comments that we receive on... regulations to control the spread of scrapie, contact Dr. Diane Sutton, Senior Staff Veterinarian,...

  19. The time-course of a scrapie outbreak

    Directory of Open Access Journals (Sweden)

    Stevenson Emily

    2006-06-01

    Full Text Available Abstract Background Because the incubation period of scrapie has a strong host genetic component and a dose-response relationship, it is possible that changes will occur during an outbreak, especially in the genotypes of cases, age-at-onset of disease and, perhaps, the clinical signs displayed. We investigated these factors for a large outbreak of natural scrapie, which yielded sufficient data to detect temporal trends. Results Cases occurred mostly in two genotypes, VRQ/VRQ and VRQ/ARQ, with those early in the outbreak more likely to be of the VRQ/VRQ genotype. As the epidemic progressed, the age-at-onset of disease increased, which reflected changes in the genotypes of cases rather than changes in the age-at-onset within genotypes. Clinical signs of cases changed over the course of the outbreak. As the epidemic progressed VRQ/VRQ and VRQ/ARQ sheep were more likely to be reported with behavioural changes, while VRQ/VRQ sheep only were less likely to be reported with loss of condition. Conclusion This study of one of the largest scrapie outbreaks in the UK allowed investigation of the effect of PrP genotype on other epidemiological parameters. Our analysis indicated that, although age-at-onset and clinical signs changed over time, the observed changes were largely, but not exclusively, driven by the time course of the PrP genotypes of cases.

  20. An economic evaluation of preclinical testing strategies compared to the compulsory scrapie flock scheme in the control of classical scrapie.

    Science.gov (United States)

    Boden, Lisa; Handel, Ian; Hawkins, Neil; Houston, Fiona; Fryer, Helen; Kao, Rowland

    2012-01-01

    Cost-benefit is rarely combined with nonlinear dynamic models when evaluating control options for infectious diseases. The current strategy for scrapie in Great Britain requires that all genetically susceptible livestock in affected flocks be culled (Compulsory Scrapie Flock Scheme or CSFS). However, this results in the removal of many healthy sheep, and a recently developed pre-clinical test for scrapie now offers a strategy based on disease detection. We explore the flock level cost-effectiveness of scrapie control using a deterministic transmission model and industry estimates of costs associated with genotype testing, pre-clinical tests and the value of a sheep culled. Benefit was measured in terms of the reduction in the number of infected sheep sold on, compared to a baseline strategy of doing nothing, using Incremental Cost Effectiveness analysis to compare across strategies. As market data was not available for pre-clinical testing, a threshold analysis was used to set a unit-cost giving equal costs for CSFS and multiple pre-clinical testing (MT, one test each year for three consecutive years). Assuming a 40% within-flock proportion of susceptible genotypes and a test sensitivity of 90%, a single test (ST) was cheaper but less effective than either the CSFS or MT strategies (30 infected-sales-averted over the lifetime of the average epidemic). The MT strategy was slightly less effective than the CSFS and would be a dominated strategy unless preclinical testing was cheaper than the threshold price of £6.28, but may be appropriate for flocks with particularly valuable livestock. Though the ST is not currently recommended, the proportion of susceptible genotypes in the national flock is likely to continue to decrease; this may eventually make it a cost-effective alternative to the MT or CSFS.

  1. An economic evaluation of preclinical testing strategies compared to the compulsory scrapie flock scheme in the control of classical scrapie.

    Directory of Open Access Journals (Sweden)

    Lisa Boden

    Full Text Available Cost-benefit is rarely combined with nonlinear dynamic models when evaluating control options for infectious diseases. The current strategy for scrapie in Great Britain requires that all genetically susceptible livestock in affected flocks be culled (Compulsory Scrapie Flock Scheme or CSFS. However, this results in the removal of many healthy sheep, and a recently developed pre-clinical test for scrapie now offers a strategy based on disease detection. We explore the flock level cost-effectiveness of scrapie control using a deterministic transmission model and industry estimates of costs associated with genotype testing, pre-clinical tests and the value of a sheep culled. Benefit was measured in terms of the reduction in the number of infected sheep sold on, compared to a baseline strategy of doing nothing, using Incremental Cost Effectiveness analysis to compare across strategies. As market data was not available for pre-clinical testing, a threshold analysis was used to set a unit-cost giving equal costs for CSFS and multiple pre-clinical testing (MT, one test each year for three consecutive years. Assuming a 40% within-flock proportion of susceptible genotypes and a test sensitivity of 90%, a single test (ST was cheaper but less effective than either the CSFS or MT strategies (30 infected-sales-averted over the lifetime of the average epidemic. The MT strategy was slightly less effective than the CSFS and would be a dominated strategy unless preclinical testing was cheaper than the threshold price of £6.28, but may be appropriate for flocks with particularly valuable livestock. Though the ST is not currently recommended, the proportion of susceptible genotypes in the national flock is likely to continue to decrease; this may eventually make it a cost-effective alternative to the MT or CSFS.

  2. Identification of prion protein gene polymorphisms in goats from Italian scrapie outbreaks

    NARCIS (Netherlands)

    Acutis, P.L.; Bossers, A.; Priem, J.; Riina, M.V.; Peletto, S.; Mazza, M.; Casalone, C.; Forloni, G.; Ru, G.; Caramelli, M.

    2006-01-01

    Susceptibility to scrapie in sheep is influenced by polymorphisms of the prion protein (PrP) gene, whereas no strong association between genetics and scrapie has yet been determined in goats due to the limited number of studies on these animals. In this case¿control study on 177 goats from six Itali

  3. Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep

    NARCIS (Netherlands)

    Thuring, C.M.A.; Keulen, van L.J.M.; Langeveld, J.P.M.; Vromans, M.E.W.; Zijderveld, van F.G.; Sweeney, T.

    2005-01-01

    Sheep are susceptible experimentally to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between scrapie and BSE infection. The objectives of

  4. Selection for scrapie resistance decreased inbreeding rates in two rare sheep breeds in the Netherlands

    NARCIS (Netherlands)

    Windig, J.J.; Hoving-Bolink, A.H.; Hiemstra, S.J.

    2010-01-01

    An attempt to balance selection intensity and conservation of genetic diversity was made in the national program for breeding for scrapie resistance in the Netherlands. The ARR allele is associated with resistance to scrapie. In the Netherlands a breeding program was started on a voluntary basis in

  5. Selection for scrapie resistance and simultaneous restriction of inbreeding in the rare sheep breed "Mergellander"

    NARCIS (Netherlands)

    Windig, J.J.; Meuleman, H.; Lansbergen, L.M.T.E.

    2007-01-01

    Scrapie is a fatal infectious neurodegenerative disease for which susceptibility is associated with polymorphisms in the ovine prion protein (PrP) gene. Scrapie-eradication programmes are based on eliminating the susceptible VRQ allele and/or breeding for the resistant ARR allele. In rare breeds or

  6. Quantitating PrP polymorphisms present in prions from heterozygous scrapie-infected sheep

    Science.gov (United States)

    Scrapie is a prion (PrPSc) disease of sheep. The incubation period of sheep scrapie is strongly influenced by polymorphisms at positions 136, 154, and 171 of a sheep’s normal cellular prion protein (PrPC). Chymotrypsin was used to digest sheep recombinant PrP to identify a set of characteristic pept...

  7. Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da

    Energy Technology Data Exchange (ETDEWEB)

    Bellinger-Kawahara, C.G.; Kempner, E.; Groth, D.; Gabizon, R.; Prusiner, S.B.

    1988-06-01

    Scrapie is a degenerative neurologic disease in sheep and goats which can be experimentally transmitted to laboratory rodents. Considerable evidence suggests that the scrapie agent is composed largely, if not entirely, of an abnormal isoform of the prion protein (PrPSc). Inactivation of scrapie prions by ionizing radiation exhibited single-hit kinetics and gave a target size of 55,000 +/- 9000 mol wt. The inactivation profile was independent of the form of the prion. Scrapie agent infectivity in brain homogenates, microsomal fractions, detergent-extracted microsomes, purified amyloid rods, and liposomes exhibited the same inactivation profile. Our data are consistent with the hypothesis that the infectious particle causing scrapie contains approximately 2 PrPSc molecules.

  8. PrP-associated resistance to scrapie in five highly infected goat herds.

    Science.gov (United States)

    Corbière, Fabien; Perrin-Chauvineau, Cécile; Lacroux, Caroline; Costes, Pierrette; Thomas, Myriam; Brémaud, Isabelle; Martin, Samuel; Lugan, Séverine; Chartier, Christophe; Schelcher, François; Barillet, Francis; Andreoletti, Olivier

    2013-01-01

    The PrP gene polymorphisms at codons 142 (I/M), 154 (R/H), 211 (R/Q), 222 (Q/K) and 240 (S/P) and their association with susceptibility to classical scrapie infection were investigated in five French goat herds displaying a high disease prevalence (>10%). On the basis of PrP(Sc) detection in the central nervous system and in various lymphoid tissues, 301 of 1343 goats were found to be scrapie infected. The statistical analyses indicated that while P(240) mutation had no direct impact on scrapie infection risk, the H(154), Q(211) and K(222) mutations were associated with high resistance to scrapie. The M(142) mutated allele was associated with a limited protection level against the disease. These results further reinforce the view that, like in sheep, the control and eradication of classical scrapie through the selection of certain PrP alleles could be envisaged in commercial goat population.

  9. Atypical Optic Neuritis.

    Science.gov (United States)

    Gaier, Eric D; Boudreault, Katherine; Rizzo, Joseph F; Falardeau, Julie; Cestari, Dean M

    2015-12-01

    Classic demyelinative optic neuritis is associated with multiple sclerosis and typically carries a good prognosis for visual recovery. This disorder is well characterized with respect to its presentation and clinical features by baseline data obtained through the optic neuritis treatment trial and numerous other studies. Atypical optic neuritis entails clinical manifestations that deviate from this classic pattern of features. Clinical signs and symptoms that deviate from the typical presentation should prompt consideration of less common etiologies. Atypical features to consider include lack of pain, simultaneous or near-simultaneous onset, lack of response to or relapse upon tapering from corticosteroids, or optic nerve head or peripapillary hemorrhages. The most important alternative etiologies to consider and the steps towards their respective diagnostic evaluations are suggested for these atypical features.

  10. A case-control study on scrapie in Norwegian sheep flocks.

    Science.gov (United States)

    Hopp, P; Ulvund, M J; Jarp, J

    2001-10-11

    Scrapie first was detected in indigenous sheep in Norway in 1981, and from 1995 to 1997 an increase in the number of flocks with scrapie cases was recorded. These flocks were mainly in one geographical region. A study to identify risk factors for scrapie was conducted. The study had three frequency-matched controls selected for every case within the same Veterinary District. A questionnaire was submitted to 176 sheep flocks (42 had been scrapie flocks). The data obtained by the questionnaire were linked to data collected from governmental and industry registers. After imputing missing data using single random imputation, the statistical analysis was performed using multivariable conditional logistic regression. Purchase of female sheep from scrapie flocks, sharing of rams, or sharing of pastures between different flocks were the risk factors associated with the occurrence of scrapie. Of factors potentially sustaining and promoting the infection in the flock, number of winter-fed sheep, number of buildings for housing sheep, rams and ewes shared room during mating period and increase in the flock size were associated with scrapie. We interpret these findings to show that factors involving transfer of sheep between flocks or direct contact between sheep of different flocks are important for the spread of scrapie. Management factors are important for the development of scrapie. However, it was not possible to discriminate between the different management factors in this study at the flock level. Also, factors indicating awareness and interest of the farmer (as well as willingness to contact a veterinarian for diseased sheep) were related to the detection of scrapie in the flock.

  11. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo;

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class...

  12. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

    Science.gov (United States)

    Harmancı, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; Coşkun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Lee, Tong Ihn; Abraham, Brian J.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Omay, S. Bülent; Baranoski, Jacob; Baran, Burçin; Carrión-Grant, Geneive; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander O.; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A.; Günel, Murat

    2017-01-01

    Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets. PMID:28195122

  13. Atypical charles bonnet syndrome

    Directory of Open Access Journals (Sweden)

    Priti Arun

    2013-01-01

    Full Text Available Charles Bonnet syndrome (CBS is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  14. Prions in milk from ewes incubating natural scrapie.

    Directory of Open Access Journals (Sweden)

    Caroline Lacroux

    2008-12-01

    Full Text Available Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrP(Sc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 microg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species.

  15. Prions in milk from ewes incubating natural scrapie.

    Science.gov (United States)

    Lacroux, Caroline; Simon, Stéphanie; Benestad, Sylvie L; Maillet, Séverine; Mathey, Jacinthe; Lugan, Séverine; Corbière, Fabien; Cassard, Hervé; Costes, Pierrette; Bergonier, Dominique; Weisbecker, Jean-Louis; Moldal, Torffin; Simmons, Hugh; Lantier, Frederic; Feraudet-Tarisse, Cécile; Morel, Nathalie; Schelcher, François; Grassi, Jacques; Andréoletti, Olivier

    2008-12-01

    Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrP(Sc) accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 microg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species.

  16. The scrapie disease process is unaffected by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, H.; Farquhar, C.F.; McConnell, I.; Davies, D. (AFRC MRC Neuropathogenesis Unit, Edinburgh (England))

    1989-01-01

    The incubation period of scrapie, its degenerative neuropathology and the replication of its causal unconventional virus are all tightly controlled parameters of the experimental disease in mice. Each parameter can vary depending on the strain and dose of virus, on the route of infection, and on the host genotype. Exposure to whole-body gamma-irradiation from Cesium 137 has no effect on the progress or development of the disease, based on the three independent indices of incubation period, neuropathology, or infectibility by high or low doses of virus. These results are based on an extensive series of experiments in many mouse strains and are consistent using different strains (ME7, 22A, 79A, 87V) and doses of virus, routes of infection, timing and dose of radiation (3-15 Gy) administered as single or fractionated exposures with or without bone-marrow (b.m.) replacement therapy. Levels of infection in the spleen are unaltered after lethal whole-body irradiation of the scrapie-infected host, despite several-fold reductions in tissue mass due to the loss of proliferating myeloid and lymphoid precursor cells and their progeny. Contrary to our earlier suggestion, scrapie infection with the 22A virus does not reduce the effectiveness of post-exposure bone-marrow replacements to recolonize an infected host after repeated ionizing radiation totalling 15Gy. This work narrows the search for the candidate cells and biosynthetic systems which replicate the virus in the lymphoreticular and central nervous systems. Many programmed cellular events are radiation sensitive but protein synthesis is extremely radioresistant.

  17. Identification of a Protein that Purifies with the Scrapie Prion

    Science.gov (United States)

    Bolton, David C.; McKinley, Michael P.; Prusiner, Stanley B.

    1982-12-01

    Purification of prions from scrapie-infected hamster brain yielded a protein that was not found in a similar fraction from uninfected brain. The protein migrated with an apparent molecular size of 27,000 to 30,000 daltons in sodium dodecyl sulfate polyacrylamide gels. The resistance of this protein to digestion by proteinase K distinguished it from proteins of similar molecular weight found in normal hamster brain. Initial results suggest that the amount of this protein correlates with the titer of the agent.

  18. The placenta shed from goats with classical scrapie is infectious to goat kids and lambs.

    Science.gov (United States)

    Schneider, David A; Madsen-Bouterse, Sally A; Zhuang, Dongyue; Truscott, Thomas C; Dassanayake, Rohana P; O'Rourke, Katherine I

    2015-08-01

    The placenta of domestic sheep plays a key role in horizontal transmission of classical scrapie. Domestic goats are frequently raised with sheep and are susceptible to classical scrapie, yet potential routes of transmission from goats to sheep are not fully defined. Sparse accumulation of disease-associated prion protein in cotyledons casts doubt about the role of the goat's placenta. Thus, relevant to mixed-herd management and scrapie-eradication efforts worldwide, we determined if the goat's placenta contains prions orally infectious to goat kids and lambs. A pooled cotyledon homogenate, prepared from the shed placenta of a goat with naturally acquired classical scrapie disease, was used to orally inoculate scrapie-naïve prion genotype-matched goat kids and scrapie-susceptible lambs raised separately in a scrapie-free environment. Transmission was detected in all four goats and in two of four sheep, which importantly identifies the goat's placenta as a risk for horizontal transmission to sheep and other goats.

  19. Persistence of ovine scrapie infectivity in a farm environment following cleaning and decontamination.

    Science.gov (United States)

    Hawkins, Steve A C; Simmons, Hugh A; Gough, Kevin C; Maddison, Ben C

    2015-01-24

    Scrapie of sheep/goats and chronic wasting disease of deer/elk are contagious prion diseases where environmental reservoirs are directly implicated in the transmission of disease. In this study, the effectiveness of recommended scrapie farm decontamination regimens was evaluated by a sheep bioassay using buildings naturally contaminated with scrapie. Pens within a farm building were treated with either 20,000 parts per million free chorine solution for one hour or were treated with the same but were followed by painting and full re-galvanisation or replacement of metalwork within the pen. Scrapie susceptible lambs of the PRNP genotype VRQ/VRQ were reared within these pens and their scrapie status was monitored by recto-anal mucosa-associated lymphoid tissue. All animals became infected over an 18-month period, even in the pen that had been subject to the most stringent decontamination process. These data suggest that recommended current guidelines for the decontamination of farm buildings following outbreaks of scrapie do little to reduce the titre of infectious scrapie material and that environmental recontamination could also be an issue associated with these premises.

  20. Characterization of atypical Aeromonas salmonicida by different methods

    DEFF Research Database (Denmark)

    Austin, B.; Austin, D.A.; Dalsgaard, Inger;

    1998-01-01

    Fifty two isolates of atypical Aeromonas salmonicida, recovered from a wide range of hosts and geographical locations, were heterogeneous in terms of molecular and phenotypic characteristics, and represented taxa which could not be accommodated by the current classification of four subspecies...

  1. [In vitro modification of the morphology and the growth of cells infected with scrapie (author's transl)].

    Science.gov (United States)

    Markovits, P; Dormont, D; Maunoury, R; Delamarche, C; Delpech, A; Dianoux, L; Latarjet, R

    1982-02-15

    Seven cell lines originated either in brains or in neuroblastomas of Mice, were infected with Scrapie. After 12 to 16 in vitro passages, 6 lines out of 7 showed changes of their morphology, and of their growth, resembling those occurring in the course of a malignant transformation. The Scrapie infected cells acquired the capacity to form 2 to 4 times more colonies in liquid medium than the controls, and to develop large tridimensional colonies in semisolid medium. The role of Scrapie in these changes is discussed.

  2. Apomorphine-induced circling behaviour in hamsters following unilateral injection of scrapie gent in the striatum.

    Science.gov (United States)

    Gorde, J M; Bert, J; Gambarelli, D; Tamalet, J

    1981-03-10

    Twenty golden hamsters received a microinjection of scrapie agent into the left striatum. At different times after inoculation animals were injected intraperitoneally with apomorphine, a direct dopamine receptor agonist. Two types of effects developed simultaneously, starting at about 80 days after infection. First, apomorphine induced a rotational behaviour which showed a progressive destruction of the striatal neurones at the site of injection. This suggest a local spread of scrapie agent by cell to cell transfer in the striatum. Secondly, the clinical signs of scrapie developed, indicating a more widespread distribution of agent throughout the brain.

  3. Bovine Spongiform Encephalopathy: Atypical Pros and Cons

    Science.gov (United States)

    Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that affect several mammalian species including human beings. Four animal TSE agents have been reported: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink encephalopath...

  4. Toxicological Evaluation of Anti-Scrapie Trimethoxychalcones and Oxadiazoles

    Directory of Open Access Journals (Sweden)

    CLAUDIA P. FIGUEIREDO

    2015-08-01

    Full Text Available An altered form of the cellular prion protein, the PrPScor PrPRes, is implicated in the occurrence of the still untreatable transmissible spongiform encephalopathies. We have previously synthesized and characterized aromatic compounds that inhibit protease-resistant prion protein (PrPRes accumulation in scrapie-infected cells. These compounds belong to different chemical classes, including acylhydrazones, chalcones and oxadiazoles. Some of the active compounds were non-toxic to neuroblastoma cells in culture and seem to possess drugable properties, since they are in agreement with the Lipinski´s rule of 5 and present desirable pharmacokinetic profiles as predicted in silico. Before the evaluation of the in vivo efficacy of the aromatic compounds in scrapie-infected mice, safety assessment in healthy mice is needed. Here we used Swiss mice to evaluate the acute toxicity profile of the six most promising anti-prionic compounds, the 2,4,5-trimethoxychalcones (J1, J8, J20 and J35 and the 1,3,4-oxadiazoles (Y13 and Y17. One single oral administration (300 mg/kg of J1, J8, J20, J35, Y13 and Y17 or repeated intraperitoneal administration (10 mg/kg, 3 times a week, for 4 weeks of J1, J8 and J35, did not elicit toxicity in mice. We strongly believe that the investigated trimethoxychalcones and oxadiazoles are interesting compounds to be further analyzed in vivo against prion diseases.

  5. Atypical presentations of neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Douglas Sato

    2011-10-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4 has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks.

  6. Childhood Learning Disabilities and Atypical Dementia: A Retrospective Chart Review.

    Directory of Open Access Journals (Sweden)

    Alon Seifan

    Full Text Available To further our understanding of the association between self-reported childhood learning disabilities (LDs and atypical dementia phenotypes (Atypical Dementia, including logopenic primary progressive aphasia (L-PPA, Posterior Cortical Atrophy (PCA, and Dysexecutive-type Alzheimer's Disease (AD.This retrospective case series analysis of 678 comprehensive neuropsychological assessments compared rates of self-reported LD between dementia patients diagnosed with Typical AD and those diagnosed with Atypical Dementia. 105 cases with neuroimaging or CSF data available and at least one neurology follow-up were identified as having been diagnosed by the neuropsychologist with any form of neurodegenerative dementia. These cases were subject to a consensus diagnostic process among three dementia experts using validated clinical criteria for AD and PPA. LD was considered Probable if two or more statements consistent with prior LD were documented within the Social & Developmental History of the initial neuropsychological evaluation.85 subjects (Typical AD n=68, Atypical AD n=17 were included in the final analysis. In logistic regression models adjusted for age, gender, handedness, education and symptom duration, patients with Probable LD, compared to patients without Probable LD, were significantly more likely to be diagnosed with Atypical Dementia vs. Typical AD (OR 13.1, 95% CI 1.3-128.4. All three of the L-PPA cases reporting a childhood LD endorsed childhood difficulty with language. By contrast, both PCA cases reporting Probable childhood LD endorsed difficulty with attention and/or math.In people who develop dementia, childhood LD may predispose to atypical phenotypes. Future studies are required to confirm whether atypical neurodevelopment predisposes to regional-specific neuropathology in AD and other dementias.

  7. [Trials of in vitro propagation of the scrapie agent in mouse nerve cells].

    Science.gov (United States)

    Markovits, P; Dormont, D; Delpech, B; Court, L; Latarjet, R

    1981-11-02

    We attempted to propagate the Scrapie agent in vitro in glia and neuroblastoma cells of Mice. Four out of seven assays of infection were positive, i.e. after several passages in vitro yielding at most a 10(9) fold final dilution of the original material, the extracts of each of the four cultures, when injected intracerebrally into CD1 Mice, produced a deadly disease displaying the clinical and pathological signs characteristic of Scrapie.

  8. Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep.

    Science.gov (United States)

    Thuring, C M A; van Keulen, L J M; Langeveld, J P M; Vromans, M E W; van Zijderveld, F G; Sweeney, T

    2005-01-01

    Sheep are susceptible experimentally to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between scrapie and BSE infection. The objectives of this study were to determine whether (1) PrPSc accumulates in biopsy samples of the tonsil or third eyelid, or both, of BSE-infected sheep before the appearance of clinical disease, and (2) such samples from BSE- and scrapie-infected sheep differ in respect of PrPSc accumulations. Homozygous ARQ sheep (n = 10) were dosed orally at 4-5 months of age with a brain homogenate from BSE-infected cattle. Third eyelid and tonsillar biopsy samples were taken at macrophages (TBMs) between BSE- and scrapie-infected sheep were detected with anti-peptide antibodies directed towards amino acids 93-106 of the ovine prion protein: thus, PrPSc appeared as single granules in TBMs of tonsillar sections from BSE-infected sheep, whereas clusters of PrPSc granules were observed within TBMs in the tonsils of scrapie-infected sheep. In contrast, antibodies against epitopes situated N- and C-terminally from the 93-106 region of the ovine prion protein revealed no differences between BSE- and scrapie-infected sheep in terms of PrPSc granules in TBMs.

  9. Inactivation of the Scrapie agent by ultraviolet irradiation in the presence of chlorpromazine

    Energy Technology Data Exchange (ETDEWEB)

    Dees, C.; Wade, W.F.; German, T.L.; Marsh, R.F. (Wisconsin Univ., Madison (USA). Dept. of Veterinary Science)

    1985-04-01

    The sensitivity of the scrapie agent to u.v. inactivation was found to be related to the purity of the tissue preparation. Scrapie infectivity associated with membrane vesicles was unaffected when irradiated with 10/sup 4/ J/m/sup 2/. Irradiation of more highly purified preparations from detergent-extracted CsCl gradient fractions reduced scrapie infectivity from 10sup(7.8) log/sub 10/ LD/sub 50/ per ml to as low as 10sup(4.5). Sensitivity of membrane-associated scrapie infectivity to inactivation by u.v. irradiation could be increased by addition of chlorpromazine, a phenthiazine antipsychotic which penetrates lipid bilayers and induces single-strand breaks in nucleic acids under irradiation. Chlorpromazine without irradiation, and a semiquinone protein-binding radical of chlorpromazine, failed to decrease scrapie infectivity by themselves. A closely related phenthiazine antipsychotic, trifluoperazine, which does not bind to nucleic acids, did not reduce scapie infectivity. These findings suggest that the target of u.v. radiation for inactivation of scrapie infectivity in the presence of chlorpromazine is an essential nucleic acid.

  10. The limits of test-based scrapie eradication programs in goats.

    Science.gov (United States)

    Corbière, Fabien; Chauvineau-Perrin, Cécile; Lacroux, Caroline; Lugan, Séverine; Costes, Pierrette; Thomas, Myriam; Brémaud, Isabelle; Chartier, Christophe; Barillet, Francis; Schelcher, François; Andréoletti, Olivier

    2013-01-01

    Small ruminant post-mortem testing programs were initially designed for monitoring the prevalence of prion disease. They are now considered as a potential alternative to genetic selection for eradicating/controlling classical scrapie at population level. If such policy should be implemented, its success would be crucially dependent on the efficiency of the surveillance system used to identify infected flocks. In this study, we first determined the performance of post-mortem classical scrapie detection in eight naturally affected goat herds (total n = 1961 animals) according to the age at culling. These results provided us with necessary parameters to estimate, through a Monte Carlo simulation model, the performance of scrapie detection in a commercial population. According to this model, whatever the number of tests performed, post mortem surveillance will have limited success in identifying infected herds. These data support the contention that scrapie eradication programs relying solely on post mortem testing in goats will probably fail. Considering the epidemiological and pathological similarities of scrapie in sheep and goats, the efficiency of scrapie surveillance in both species is likely to be similar.

  11. Atypical aging in Down syndrome.

    Science.gov (United States)

    Zigman, Warren B

    2013-01-01

    At present, there may be over 210,000 people with Down syndrome (DS) over the age of 55 in the United States (US) who have significant needs for augmented services due to circumstances related to ordinary and/or pathological aging. From 1979 through 2003, the birth prevalence of DS rose from 9.0 to 11.8 (31.1%) per 10,000 live births in 10 representative US regions. This increase, largely due to women conceiving after age 35, portends an ever-growing population of people with DS who may be subject to pathogenic aging. Whereas Trisomy 21 is one of the most widespread genetic causes of intellectual disability (ID), it still is one of the least understood of all genetic ID syndromes. While longevity in people with DS has improved appreciably in as modest a period as 30 years, age-specific risk for mortality still is considerably increased compared both with other people with ID or with the typically developing population. The penetrance of the phenotype is widely distributed, even though a consistent genotype is assumed in 95% of the cases. Some, but not all body systems, exhibit signs of premature or accelerated aging. This may be due to both genetic and epigenetic inheritance. We now know that the long-term outcome for people with DS is not as ominous as once contemplated; a number of people with DS are living into their late 60s and 70s with few if any major signs of pathogenic aging. Alzheimer's disease (AD), a devastating disease that robs a person of their memory, abilities and personality, is particularly common in elder adults with DS, but is not a certainty as originally thought, some 20% to 30% of elder adults with DS might never show any, or at most mild signs of AD. DS has been called a mature well-understood syndrome, not in need of further research or science funding. We are only beginning to understand how epigenetics affects the phenotype and it may be feasible in the future to alter the phenotype through epigenetic interventions. This chapter is

  12. [Atypical presentation of preeclampsia].

    Science.gov (United States)

    Ditisheim, A; Boulvain, M; Irion, O; Pechère-Bertschi, A

    2015-09-09

    Preeclampsia is a pregnancy-related syndrome, which still represents one of the major causes of maternal-fetal mortality and morbidity. Diagnosis can be made difficult due to the complexity of the disorder and its wide spectrum of clinical manifestations. In order to provide an efficient diagnostic tool to the clinician, medical societies regularly rethink the definition criteria. However, there are still clinical presentations of preeclampsia that escape the frame of the definition. The present review will address atypical forms of preeclampsia, such as preeclampsia without proteinuria, normotensive preeclampsia, preeclampsia before 20 weeks of gestation and post-partum preeclampsia.

  13. Cloning of a Gene Whose Expression is Increased in Scrapie and in Senile Plaques in Human Brain

    Science.gov (United States)

    Wietgrefe, S.; Zupancic, M.; Haase, A.; Chesebro, B.; Race, R.; Frey, W.; Rustan, T.; Friedman, R. L.

    1985-12-01

    A complementary DNA library was constructed from messenger RNA's extracted from the brains of mice infected with the scrapie agent. The library was differentially screened with the objectives of finding clones that might be used as markers of infection and finding clones of genes whose increased expression might be correlated with the pathological changes common to scrapie and Alzheimer's disease. A gene was identified whose expression is increased in scrapie. The complementary DNA corresponding to this gene hybridized preferentially and focally to cells in the brains of scrapie-infected animals. The cloned DNA also hybridized to the neuritic plaques found with increased frequency in brains of patients with Alzheimer's disease.

  14. PRNP genetic variability and molecular typing of natural goat scrapie isolates in a high number of infected flocks.

    Science.gov (United States)

    Fragkiadaki, Eirini G; Vaccari, Gabriele; Ekateriniadou, Loukia V; Agrimi, Umberto; Giadinis, Nektarios D; Chiappini, Barbara; Esposito, Elena; Conte, Michela; Nonno, Romolo

    2011-09-30

    One hundred and four scrapie positive and 77 negative goats from 34 Greek mixed flocks were analysed by prion protein gene sequencing and 17 caprine scrapie isolates from 11 flocks were submitted to molecular isolate typing. For the first time, the protective S146 variant was reported in Greece, while the protective K222 variant was detected in negative but also in five scrapie positive goats from heavily infected flocks. By immunoblotting six isolates, including two goat flockmates carrying the K222 variant, showed molecular features slightly different from all other Greek and Italian isolates co-analysed, possibly suggesting the presence of different scrapie strains in Greece.

  15. Characteristics of 263K scrapie agent in multiple hamster species.

    Science.gov (United States)

    Meade-White, Kimberly D; Barbian, Kent D; Race, Brent; Favara, Cynthia; Gardner, Don; Taubner, Lara; Porcella, Stephen; Race, Richard

    2009-02-01

    Transmissible spongiform encephalopathy (TSE) diseases are known to cross species barriers, but the pathologic and biochemical changes that occur during transmission are not well understood. To better understand these changes, we infected 6 hamster species with 263K hamster scrapie strain and, after each of 3 successive passages in the new species, analyzed abnormal proteinase K (PK)-resistant prion protein (PrPres) glycoform ratios, PrPres PK sensitivity, incubation periods, and lesion profiles. Unique 263K molecular and biochemical profiles evolved in each of the infected hamster species. Characteristics of 263K in the new hamster species seemed to correlate best with host factors rather than agent strain. Furthermore, 2 polymorphic regions of the prion protein amino acid sequence correlated with profile differences in these TSE-infected hamster species.

  16. Isolation of a Defective Prion Mutant from Natural Scrapie

    Science.gov (United States)

    Migliore, Sergio; Cosseddu, Gian Mario; Pirisinu, Laura; Riccardi, Geraldina; Nonno, Romolo

    2016-01-01

    It is widely known that prion strains can mutate in response to modification of the replication environment and we have recently reported that prion mutations can occur in vitro during amplification of vole-adapted prions by Protein Misfolding Cyclic Amplification on bank vole substrate (bvPMCA). Here we exploited the high efficiency of prion replication by bvPMCA to study the in vitro propagation of natural scrapie isolates. Although in vitro vole-adapted PrPSc conformers were usually similar to the sheep counterpart, we repeatedly isolated a PrPSc mutant exclusively when starting from extremely diluted seeds of a single sheep isolate. The mutant and faithful PrPSc conformers showed to be efficiently autocatalytic in vitro and were characterized by different PrP protease resistant cores, spanning aa ∼155–231 and ∼80–231 respectively, and by different conformational stabilities. The two conformers could thus be seen as different bona fide PrPSc types, putatively accounting for prion populations with different biological properties. Indeed, once inoculated in bank vole the faithful conformer was competent for in vivo replication while the mutant was unable to infect voles, de facto behaving like a defective prion mutant. Overall, our findings confirm that prions can adapt and evolve in the new replication environments and that the starting population size can affect their evolutionary landscape, at least in vitro. Furthermore, we report the first example of “authentic” defective prion mutant, composed of brain-derived PrPC and originating from a natural scrapie isolate. Our results clearly indicate that the defective mutant lacks of some structural characteristics, that presumably involve the central region ∼90–155, critical for infectivity but not for in vitro replication. Finally, we propose a molecular mechanism able to account for the discordant in vitro and in vivo behavior, suggesting possible new paths for investigating the molecular bases of

  17. Rapid and discriminatory diagnosis of scrapie and BSE in retro-pharyngeal lymph nodes of sheep

    Directory of Open Access Journals (Sweden)

    van Zijderveld Fred G

    2006-06-01

    Full Text Available Abstract Background Diagnosis based on prion detection in lymph nodes of sheep and goats can improve active surveillance for scrapie and, if it were circulating, for bovine spongiform encephalopathy (BSE. With sizes that allow repetitive testing and a location that is easily accessible at slaughter, retropharyngeal lymph nodes (RLN are considered suitable organs for testing. Western blotting (WB of brain homogenates is, in principle, a technique well suited to both detect and discriminate between scrapie and BSE. In this report, WB is developed for rapid diagnosis in RLN and to study biochemical characteristics of PrPres. Results Optimal PrPres detection in RLN by WB was achieved by proper tissue processing, antibody choice and inclusion of a step for PrPresconcentration. The analyses were performed on three different sheep sources. Firstly, in a study with preclinical scrapie cases, WB of RLN from infected sheep of VRQ/VRQ genotype – VRQ represents, respectively, polymorphic PrP amino acids 136, 154, and 171 – allowed a diagnosis 14 mo earlier compared to WB of brain stem. Secondly, samples collected from sheep with confirmed scrapie in the course of passive and active surveillance programmes in the period 2002–2003 yielded positive results depending on genotype: all sheep with genotypes ARH/VRQ, VRQ/VRQ, and ARQ/VRQ scored positive for PrPres, but ARQ/ARQ and ARR/VRQ were not all positive. Thirdly, in an experimental BSE study, detection of PrPres in all 11 ARQ/ARQ sheep, including 7 preclinical cases, was possible. In all instances, WB and IHC were almost as sensitive. Moreover, BSE infection could be discriminated from scrapie infection by faster electrophoretic migration of the PrPres bands. Using dual antibody staining with selected monoclonal antibodies like 12B2 and L42, these differences in migration could be employed for an unequivocal differentiation between BSE and scrapie. With respect to glycosylation of PrPres, BSE cases

  18. Atypical Vitamin B-6 Deficiency A Rare Cause of Unexplained Neonatal and Infantile Epilepsies

    DEFF Research Database (Denmark)

    Baumgart, A.; von Spiczak, S.; Verhoeven-Duif, N. M.;

    2014-01-01

    . We identified 1 patient with an epilepsy phenotype resembling Dravet syndrome and likely pathogenic mutations in ALDH7A1. Presenting features were highly atypical of pyridoxine-dependent epilepsy, including febrile seizures, response to anticonvulsive drugs, and periods of seizure freedom without...... pyridoxine treatment. "Hidden" vitamin B-6 deficiencies might be rare but treatable causes of unexplained epilepsy extending beyond the classical phenotypes....

  19. Apparent reduction of ADAM10 in scrapie-infected cultured cells and in the brains of scrapie-infected rodents.

    Science.gov (United States)

    Chen, Cao; Lv, Yan; Zhang, Bao-Yun; Zhang, Jin; Shi, Qi; Wang, Jing; Tian, Chan; Gao, Chen; Xiao, Kang; Ren, Ke; Zhou, Wei; Dong, Xiao-Ping

    2014-12-01

    It has been described that A disintegrin and metalloproteinase (ADAM10) may involve in the physiopathology of prion diseases, but the direct molecular basis still remains unsolved. In this study, we confirmed that ADAM10 was able to cleave recombinant human prion protein in vitro. Using immunoprecipitation tests (IP) and immunofluorescent assays (IFA), reliable molecular interaction between the native cellular form of PrP (PrP(C)) and ADAM10 was observed not only in various cultured neuronal cell lines but also in brain homogenates of healthy hamsters and mice. Only mature ADAM10 (after removal of its prodomain) molecules showed the binding activity with the native PrP(C). Remarkably more prion protein (PrP)-ADAM10 complexes were detected in the membrane fraction of cultured cells. In the scrapie-infected SMB cell model, the endogenous ADAM10 levels, especially the mature ADAM10, were significantly decreased in the fraction of cell membrane. IP and IFA tests of prion-infected SMB-S15 cells confirmed no detectable PrP-ADAM10 complex in the cellular lysates and PrP-ADAM10 co-localization on the cell surface. Furthermore, we demonstrated that the levels of ADAM10 in the brain homogenates of scrapie agent 263K-infected hamsters and agent ME7-infected mice were also almost diminished at the terminal stage, showing time-dependent decreases during the incubation period. Our data here provide the solid molecular basis for the endoproteolysis of ADAM10 on PrP molecules and interaction between ADAM10 and PrP(C). Obvious loss of ADAM10 during prion infection in vitro and in vivo highlights that ADAM10 may play essential pathophysiological roles in prion replication and accumulation.

  20. Quantitative detection and biological propagation of scrapie seeding activity in vitro facilitate use of prions as model pathogens for disinfection.

    Directory of Open Access Journals (Sweden)

    Sandra Pritzkow

    Full Text Available Prions are pathogens with an unusually high tolerance to inactivation and constitute a complex challenge to the re-processing of surgical instruments. On the other hand, however, they provide an informative paradigm which has been exploited successfully for the development of novel broad-range disinfectants simultaneously active also against bacteria, viruses and fungi. Here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model pathogens for disinfection. We used specifically adapted serial protein misfolding cyclic amplification (PMCA for the quantitative detection, on steel wires providing model carriers for decontamination, of 263K scrapie seeding activity converting normal protease-sensitive into abnormal protease-resistant prion protein. Reference steel wires carrying defined amounts of scrapie infectivity were used for assay calibration, while scrapie-contaminated test steel wires were subjected to fifteen different procedures for disinfection that yielded scrapie titre reductions of ≤10(1- to ≥10(5.5-fold. As confirmed by titration in hamsters the residual scrapie infectivity on test wires could be reliably deduced for all examined disinfection procedures, from our quantitative seeding activity assay. Furthermore, we found that scrapie seeding activity present in 263K hamster brain homogenate or multiplied by PMCA of scrapie-contaminated steel wires both triggered accumulation of protease-resistant prion protein and was further propagated in a novel cell assay for 263K scrapie prions, i.e., cerebral glial cell cultures from hamsters. The findings from our PMCA- and glial cell culture assays revealed scrapie seeding activity as a biochemically and biologically replicative principle in vitro, with the former being quantitatively linked to prion infectivity detected on steel wires in vivo. When combined, our in vitro assays provide an alternative to titrations of biological

  1. Quantitative detection and biological propagation of scrapie seeding activity in vitro facilitate use of prions as model pathogens for disinfection.

    Science.gov (United States)

    Pritzkow, Sandra; Wagenführ, Katja; Daus, Martin L; Boerner, Susann; Lemmer, Karin; Thomzig, Achim; Mielke, Martin; Beekes, Michael

    2011-01-01

    Prions are pathogens with an unusually high tolerance to inactivation and constitute a complex challenge to the re-processing of surgical instruments. On the other hand, however, they provide an informative paradigm which has been exploited successfully for the development of novel broad-range disinfectants simultaneously active also against bacteria, viruses and fungi. Here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model pathogens for disinfection. We used specifically adapted serial protein misfolding cyclic amplification (PMCA) for the quantitative detection, on steel wires providing model carriers for decontamination, of 263K scrapie seeding activity converting normal protease-sensitive into abnormal protease-resistant prion protein. Reference steel wires carrying defined amounts of scrapie infectivity were used for assay calibration, while scrapie-contaminated test steel wires were subjected to fifteen different procedures for disinfection that yielded scrapie titre reductions of ≤10(1)- to ≥10(5.5)-fold. As confirmed by titration in hamsters the residual scrapie infectivity on test wires could be reliably deduced for all examined disinfection procedures, from our quantitative seeding activity assay. Furthermore, we found that scrapie seeding activity present in 263K hamster brain homogenate or multiplied by PMCA of scrapie-contaminated steel wires both triggered accumulation of protease-resistant prion protein and was further propagated in a novel cell assay for 263K scrapie prions, i.e., cerebral glial cell cultures from hamsters. The findings from our PMCA- and glial cell culture assays revealed scrapie seeding activity as a biochemically and biologically replicative principle in vitro, with the former being quantitatively linked to prion infectivity detected on steel wires in vivo. When combined, our in vitro assays provide an alternative to titrations of biological scrapie

  2. Differential immunoreactivity of goat derived scrapie following in vitro misfolding versus mouse bioassay.

    Science.gov (United States)

    Madsen-Bouterse, Sally A; Zhuang, Dongyue; O'Rourke, Katherine I; Schneider, David A

    2012-07-13

    The protein misfolding cyclic amplification (PMCA) assay allows for detection of prion protein misfolding activity in tissues and fluids from sheep with scrapie where it was previously undetected by conventional western blot and immunohistochemistry assays. Studies of goats with scrapie have yet to take advantage of PMCA, which could aid in discerning the risk of transmission between goats and goats to sheep. The aim of the current study was to adapt PMCA for evaluation of scrapie derived from goats. Diluted brain homogenate from scrapie-infected goats (i.e., the scrapie seed, PrP(Sc)) was subjected to PMCA using normal brain homogenate from ovinized transgenic mice (tg338) as the source of normal cellular prion protein (the substrate, PrP(C)). The assay end-point was detection of the proteinase K-resistant misfolded prion protein core (PrP(res)) by western blot. Protein misfolding activity was consistently observed in caprine brain homogenate diluted 10,000-fold after 5 PMCA rounds. Epitope mapping by western blot analyses demonstrated that PrP(res) post-PMCA was readily detected with an N-terminus anti-PrP monoclonal antibody (P4), similar to scrapie inoculum from goats. This was in contrast to limited detection of PrP(res) with P4 following mouse bioassay. The inverse was observed with a monoclonal antibody to the C-terminus (F99/97.6.1). Thus, brain homogenate prepared from uninoculated tg338 served as an appropriate substrate for serial PMCA of PrP(Sc) derived from goats. These observations suggest that concurrent PMCA and bioassay with tg338 could improve characterization of goat derived scrapie.

  3. Characterization of mesenchymal stem cells in sheep naturally infected with scrapie.

    Science.gov (United States)

    Mediano, Diego R; Sanz-Rubio, David; Bolea, Rosa; Belén, Marín; Vázquez, Francisco J; Remacha, Ana R; López-Pérez, Oscar; Fernández-Borges, Natalia; Castilla, Joaquin; Zaragoza, Pilar

    2015-12-01

    Mesenchymal stem cells (MSCs) can be infected with prions and have been proposed as in vitro cell-based models for prion replication. In addition, autologous MSCs are of interest for cell therapy in neurodegenerative diseases. To the best of our knowledge, the effect of prion diseases on the characteristics of these cells has never been investigated. Here, we analysed the properties of MSCs obtained from bone marrow (BM-MSCs) and peripheral blood (PB-MSCs) of sheep naturally infected with scrapie — a large mammal model for the study of prion diseases. After three passages of expansion, MSCs derived from scrapie animals displayed similar adipogenic, chondrogenic and osteogenic differentiation ability as cells from healthy controls, although a subtle decrease in the proliferation potential was observed. Exceptionally, mesenchymal markers such as CD29 were significantly upregulated at the transcript level compared with controls. Scrapie MSCs were able to transdifferentiate into neuron-like cells, but displayed lower levels of neurogenic markers at basal conditions, which could limit this potential .The expression levels of cellular prion protein (PrPC) were highly variable between cultures, and no significant differences were observed between control and scrapie-derived MSCs. However, during neurogenic differentiation the expression of PrPC was upregulated in MSCs. This characteristic could be useful for developing in vitro models for prion replication. Despite the infectivity reported for MSCs obtained from scrapie-infected mice and Creutzfeldt–Jakob disease patients, protein misfolding cyclic amplification did not detect PrPSc in BM- or PB-MSCs from scrapie-infected sheep, which limits their use for in vivo diagnosis for scrapie.

  4. Factors influencing temporal variation of scrapie incidence within a closed Suffolk sheep flock.

    Science.gov (United States)

    González, Lorenzo; Dagleish, Mark P; Martin, Stuart; Finlayson, Jeanie; Sisó, Sílvia; Eaton, Samantha L; Goldmann, Wilfred; Witz, Janey; Hamilton, Scott; Stewart, Paula; Pang, Yvonne; Steele, Philip; Reid, Hugh W; Chianini, Francesca; Jeffrey, Martin

    2012-01-01

    Several studies have shown that transmission of natural scrapie can occur vertically and horizontally, and that variations in scrapie incidence between and within infected flocks are mostly due to differences in the proportion of sheep with susceptible and resistant PRNP genotypes. This report presents the results of a 12-year period of scrapie monitoring in a closed flock of Suffolk sheep, in which only animals of the ARQ/ARQ genotype developed disease. Among a total of 120 of these, scrapie attack rates varied between birth cohorts from 62.5 % (5/8) to 100 % (9/9), and the incidence of clinical disease among infected sheep from 88.9 % (8/9) to 100 % (in five birth cohorts). Susceptible sheep born to scrapie-infected ewes showed a slightly higher risk of becoming infected (97.2 %), produced earlier biopsy-positive results (mean 354 days) and developed disease at a younger age (median 736 days) than those born to non-infected dams (80.3 %, 451 and 782 days, respectively). Taken together, this was interpreted as evidence of maternal transmission. However, it was also observed that, for the birth cohorts with the highest incidence of scrapie (90-100 %), sheep born to infected and non-infected dams had a similar risk of developing scrapie (97.1 and 95.3 %, respectively). Compared with moderate-attack-rate cohorts (62.5-66.7 %), high-incidence cohorts had greater numbers of susceptible lambs born to infected ewes, suggesting that increased rates of horizontal transmission in these cohorts could have been due to high levels of environmental contamination caused by infected placentas.

  5. Immunohistochemical studies of scrapie archival material from Irish ARQ/ARQ sheep for evidence of bovine spongiform encephalopathy-derived disease

    NARCIS (Netherlands)

    Sharpe, A.; McElroy, M.; Langeveld, J.P.M.; Bassett, H.; O'Donoghue, A.M.; Sweeney, T.

    2005-01-01

    Since scrapie and bovine spongiform encephalopathy (BSE) in sheep are clinicopathologically indistinguishable, BSE in sheep may have been misdiagnosed as scrapie. Disease-specific prion protein (PrPd) patterns in archival tissues of 38 Irish ARQ/ARQ sheep diagnosed as scrapie-affected were compared

  6. Atypical manifestations of leptospirosis.

    Science.gov (United States)

    Rajapakse, Senaka; Rodrigo, Chaturaka; Balaji, Krishan; Fernando, Sumadhya Deepika

    2015-05-01

    Leptospirosis is an illness with a wide spectrum of clinical manifestations and severe illness affects nearly all organ systems. Serious and potentially life-threatening clinical manifestations of acute leptospirosis are caused by both direct tissue invasion by spirochaetes and by the host immune responses. In its severe form, leptospirosis can cause multi-organ dysfunction and death in a matter of days. Therefore it is critical to suspect and recognize the disease early, in order to initiate timely treatment. While the classical presentation of the disease is easily recognized by experienced clinicians practising in endemic regions, rarer manifestations can be easily missed. In this systematic review, we summarize the atypical manifestations reported in literature in patients with confirmed leptospirosis. Awareness of these unusual manifestations would hopefully guide clinicians towards early diagnosis.

  7. 9 CFR 54.11 - Approval of laboratories to run official scrapie tests and official genotype tests.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Approval of laboratories to run official scrapie tests and official genotype tests. 54.11 Section 54.11 Animals and Animal Products ANIMAL... laboratories to run official scrapie tests and official genotype tests. (a) State, Federal, and...

  8. Evaluation of two commercial, rapid, ELISA kits testing or scrapie in retro-pharyngeal lymph nodes in sheep

    NARCIS (Netherlands)

    Kittelberger, R.; McIntuyre, L.; Watts, S.; MacDiarmid, S.; Hannah, M.J.; Jenner, J.; Bueno, R.; Swainsbury, R.; Langeveld, J.P.M.; Keulen, van L.J.M.; Zijderveld, van F.G.; Wemheuer, W.M.; Richt, J.A.; Sorenson, S.J.; Pigott, C.J.; O'Keefe, J.S.

    2014-01-01

    AIMS: To estimate the number of cases of scrapie that would occur in sheep of different prion protein (PrP) genotypes if scrapie was to become established in New Zealand, and to compare the performance of two commercially available, rapid ELISA kits using ovine retro-pharyngeal lymph nodes (RLN) fro

  9. Scrapie prevalence in sheep of susceptible genotype is declining in a population subject to breeding for resistance

    NARCIS (Netherlands)

    Hagenaars, T.H.J.; Melchior, M.B.; Bossers, A.; Davidse, A.; Engel, B.; Zijderveld, van F.G.

    2010-01-01

    Background - Susceptibility of sheep to scrapie infection is known to be modulated by the PrP genotype of the animal. In the Netherlands an ambitious scrapie control programme was started in 1998, based on genetic selection of animals for breeding. From 2002 onwards EU regulations required intensive

  10. Classical natural ovine scrapie prions are detected in practical volumes of blood by lamb and transgenic mouse bioassay

    Science.gov (United States)

    In vitro ligand-based immunoassay studies revealed abnormal isoforms of prion protein (PrP-Sc) are primarily associated with B lymphocytes of scrapie-infected sheep. Our recent study also demonstrated efficient transmission of scrapie to lambs following a transfusion of B lymphocytes isolated from 5...

  11. Lack of relationship between Visna/maedi infection and scrapie resistance genetic markers

    Directory of Open Access Journals (Sweden)

    Eider Salazar

    2014-06-01

    Full Text Available The relationship between Visna/maedi virus (VMV antibody status and scrapie genetic resistance of 10,611 Rasa Aragonesa sheep from 17 flocks in Aragón (Spain was investigated. The fifteen most common PRNP gene haplotypes and genotypes were identified and the genotypes were classified into the corresponding scrapie risk groups (groups 1 to 5. ARQ (93.3% and ARR (31.8% were the most common haplotypes and ARQ/ARQ (56% and ARR/ARQ (25.6% were the most common genotypes. The frequencies of scrapie risk groups 1, 2, 3, 4 and 5 were 3.3%, 27.3%, 63.5%, 1.2% and 4.8%, respectively. Overall Visna/maedi seroprevalence was 53% and flock seroprevalence ranged between 21-86%. A random effects logistic regression model indicated that sheep VMV serological status (outcome variable was not associated with any particular scrapie risk group. Instead, VMV seropositivity progressively increased with age, was significantly greater in females compared to males and varied between flocks. The absence of a relationship between VMV infection and scrapie genotypes is important for VMV control and specifically for sheep participating in an ELISA-based Visna/maedi control program.

  12. Investigation of a Simple Model for Within-Flock Transmission of Scrapie.

    Science.gov (United States)

    Hagenaars, Thomas J; Windig, Jack J

    2015-01-01

    Genetic control programs for scrapie in sheep build on solid knowledge of how susceptibility to scrapie is modulated by the prion protein genotype at the level of an individual sheep. In order to satisfactorily analyze the effectivity of control programs at the population level, insight is needed at the flock level, i.e., how the grouping of sheep in flocks affects the population-level transmission risk. In particular, one would like to understand how this risk is affected by between-flock differences in genotype frequency distribution. A first step is to model the scrapie transmission risk within a flock as a function of the flock genotype profile. Here we do so by estimating parameters for a model of within-flock transmission using genotyping data on Dutch flocks affected by scrapie. We show that the data are consistent with a relatively simple transmission model assuming horizontal transmission and homogeneous mixing between animals. The model expresses the basic reproduction number for within-flock scrapie as a weighted average of genotype-specific susceptibilities, multiplied by a single overall transmission parameter. The value of the overall transmission parameter may vary between flocks to account for random between-flock variation in non-genetic determinants such as management practice. Here we provide an estimate of its mean value and variation for Dutch flocks.

  13. Active surveillance for scrapie in the Netherlands: effect of a breeding programme on the prevalence of scrapie in sheep (2002-2010)? = Acht jaar actieve scrapie-surveillance in Nederland: het effect van het fokprogramma op de prevalentie van schrapie bij het schaap (2002-2010)

    NARCIS (Netherlands)

    Melchior, M.B.; Hagenaars, T.H.J.; Davidse, A.; Keulen, van L.J.M.; Bossers, A.; Zijderveld, van F.G.

    2011-01-01

    The susceptibility of sheep to scrapie is modulated by the prion protein (PrP) genotype of the animal. An ambitious voluntary scrapie control programme was started in the Netherlands in 1998, based on selection of rams with theARR/ARR genotype for breeding. This programme was followed by an obligato

  14. Atypical Odontalgia (Phantom Tooth Pain)

    Science.gov (United States)

    ... atypical facial pain, phantom tooth pain, or neuropathic orofacial pain, is characterized by chronic pain in a ... such as a specialist in oral medicine or orofacial pain. The information contained in this monograph is ...

  15. Atypical GTPases as drug targets.

    Science.gov (United States)

    Soundararajan, Meera; Eswaran, Jeyanthy

    2012-01-01

    The Ras GTPases are the founding members of large Ras superfamily, which constitutes more than 150 of these important class of enzymes. These GTPases function as GDP-GTP-regulated binary switches that control many fundamental cellular processes. There are a number of GTPases that have been identified recently, which do not confine to this prototype termed as "atypical GTPases" but have proved to play a remarkable role in vital cellular functions. In this review, we provide an overview of the crucial physiological functions mediated by RGK and Centaurin class of multi domain atypical GTPases. Moreover, the recently available atypical GTPase structures of the two families, regulation, physiological functions and their critical roles in various diseases will be discussed. In summary, this review will highlight the emerging atypical GTPase family which allows us to understand novel regulatory mechanisms and thus providing new avenues for drug discovery programs.

  16. Atypical Light Curves

    CERN Document Server

    Steenwyk, Steven D; Molnar, Lawrence A

    2013-01-01

    We have identified some two-hundred new variable stars in a systematic study of a data archive obtained with the Calvin-Rehoboth observatory. Of these, we present five close binaries showing behaviors presumably due to star spots or other magnetic activity. For context, we first present two new RS CVn systems whose behavior can be readily attribute to star spots. Then we present three new close binary systems that are rather atypical, with light curves that are changing over time in ways not easily understood in terms of star spot activity generally associated with magnetically active binary systems called RS CVn systems. Two of these three are contact binaries that exhibit gradual changes in average brightness without noticeable changes in light curve shape. A third system has shown such large changes in light curve morphology that we speculate this may be a rare instance of a system that transitions back and forth between contact and noncontact configurations, perhaps driven by magnetic cycles in at least o...

  17. Detection of prions in the faeces of sheep naturally infected with classical scrapie

    Directory of Open Access Journals (Sweden)

    Terry Linda A

    2011-05-01

    Full Text Available Abstract Classical scrapie is a naturally transmitted prion disease of sheep and goats. Contaminated environments may contribute to the spread of disease and evidence from animal models has implicated urine, blood, saliva, placenta and faeces as possible sources of the infection. Here we sought to determine whether sheep naturally infected with classical scrapie shed prions in their faeces. We used serial protein misfolding cyclic amplification (sPMCA along with two extraction methods to examine faeces from sheep during both the clinical and preclinical phases of the disease and showed amplification of PrPSc in 7 of 15 and 14 of 14 sheep respectively. However PrPSc was not amplified from the faeces of 25 sheep not exposed to scrapie. These data represent the first demonstration of prion shedding in faeces from a naturally infected host and thus a likely source of prion contamination in the environment.

  18. A Rare Case: Atypical Measles

    OpenAIRE

    Ümmü Sena Sarı; Figen Kaptan

    2016-01-01

    Atypical measles has been described in persons who were exposed to wild measles virus several years after they were immunized with killed measles vaccine. Occasionally, it can be caused by live measles vaccines also. It is a clinical picture different from typical measles. In this report, an adult patient with a history of immunization, who presented with high fever, maculopapular rash starting at the palms and soles, and pneumonia, is presented. Atypical measles that was ...

  19. Cyclodextrins inhibit replication of scrapie prion protein in cell culture.

    Science.gov (United States)

    Prior, Marguerite; Lehmann, Sylvain; Sy, Man-Sun; Molloy, Brendan; McMahon, Hilary E M

    2007-10-01

    Prion diseases are fatal neurodegenerative disorders that are caused by the conversion of a normal host-encoded protein, PrP(C), to an abnormal, disease-causing form, PrP(Sc). This paper reports that cyclodextrins have the ability to reduce the pathogenic isoform of the prion protein PrP(Sc) to undetectable levels in scrapie-infected neuroblastoma cells. Beta-cyclodextrin removed PrP(Sc) from the cells at a concentration of 500 microM following 2 weeks of treatment. Structure activity studies revealed that antiprion activity was dependent on the size of the cyclodextrin. The half-maximal inhibitory concentration (IC(50)) for beta-cyclodextrin was 75 microM, whereas alpha-cyclodextrin, which possessed less antiprion activity, had an IC(50) of 750 microM. This report presents cyclodextrins as a new class of antiprion compound. For decades, the pharmaceutical industry has successfully used cyclodextrins for their complex-forming ability; this ability is due to the structural orientation of the glucopyranose units, which generate a hydrophobic cavity that can facilitate the encapsulation of hydrophobic moieties. Consequently, cyclodextrins could be ideal candidates for the treatment of prion diseases.

  20. Summarization of scrapie%羊痒病概述

    Institute of Scientific and Technical Information of China (English)

    韩彩霞; 吴长德; 赵德明

    2005-01-01

    羊痒病(scrapie)是传染性海绵状脑病(TSE)的原型,目前在世界许多地方流行.该病是绵羊的一种缓慢发展的致死性中枢神经系统变性疾病,能引起绵羊和山羊中枢神经系统发生退化变性,病羊具有中枢神经系统变性、空泡化、星形胶质细胞增生等特点,病羊表现为共济失调、痉挛、麻痹、衰弱和严重的皮肤瘙痒,病畜死亡率达100%.该病是由正常的朊蛋白(FrPc)发生错误折叠而变成异常的蛋白形式(PrPsc)引起的.

  1. Prenatal transmission of scrapie in sheep and goats: A case study for veterinary public health

    Directory of Open Access Journals (Sweden)

    D.B. Adams

    2016-11-01

    Full Text Available Unsettled knowledge as to whether scrapie transmits prenatally in sheep and goats and transmits by semen and preimplantation embryos has a potential to compromise measures for controlling, preventing and eliminating the disease. The remedy may be analysis according to a systematic review, allowing comprehensive and accessible treatment of evidence and reasoning, clarifying the issue and specifying the uncertainties. Systematic reviews have clearly formulated questions, can identify relevant studies and appraise their quality and can summarise evidence and reasoning with an explicit methodology. The present venture lays a foundation for a possible systematic review and applies three lines of evidence and reasoning to two questions. The first question is whether scrapie transmits prenatally in sheep and goats. It leads to the second question, which concerns the sanitary safety of artificial breeding technologies, and is whether scrapie transmits in sheep and goats by means of semen and washed or unwashed in vivo derived embryos. The three lines of evidence derive from epidemiological, field and clinical studies, experimentation, and causal reasoning, where inferences are made from the body of scientific knowledge and an understanding of animal structure and function. Evidence from epidemiological studies allow a conclusion that scrapie transmits prenatally and that semen and embryos are presumptive hazards for the transmission of scrapie. Evidence from experimentation confirms that semen and washed or unwashed in vivo derived embryos are hazards for the transmission of scrapie. Evidence from causal reasoning, including experience from other prion diseases, shows that mechanisms exist for prenatal transmission and transmission by semen and embryos in both sheep and goats.

  2. Propagation of ovine prions from "poor" transmitter scrapie isolates in ovine PrP transgenic mice.

    Science.gov (United States)

    Thackray, Alana M; Hopkins, Lee; Lockey, Richard; Spiropoulos, John; Bujdoso, Raymond

    2012-02-01

    Ovine prion strains have typically been identified by their transmission properties, which include incubation time and lesion profile, in wild type mice. The existence of scrapie isolates that do not propagate in wild type mice, defined here as "poor" transmitters, are problematic for conventional prion strain typing studies as no incubation time or neuropathology can be recorded. This may arise because of the presence of an ovine prion strain within the original inoculum that does not normally cross the species barrier into wild type mice or the presence of a low dose of an infectious ovine prion strain that does. Here we have used tg59 and tg338 mouse lines, which are transgenic for ovine ARQ or VRQ PrP, respectively, to strain type "poor" transmitter ovine scrapie isolates. ARQ and VRQ homozygous "poor" transmitter scrapie isolates were successfully propagated in both ovine PrP transgenic mouse lines. We have used secondary passage incubation time, PrPSc immunohistochemistry and molecular profile, to show that different prion strains can be isolated from different "poor" transmitter samples during serial passage in ovine PrP transgenic mice. Our observations show that poor or inadequate transmissibility of some classical scrapie isolates in wild type mice is associated with unique ovine prion strains in these particular sheep scrapie samples. In addition, the analysis of the scrapie isolates used here revealed that the tg338 mouse line was more versatile and more robust at strain typing ovine prions than tg59 mice. These novel observations in ovine PrP transgenic mice highlight a new approach to ovine prion strain typing.

  3. White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation.

    Science.gov (United States)

    Greenlee, Justin J; Smith, Jodi D; Kunkle, Robert A

    2011-10-11

    Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. The purpose of this experiment was to determine susceptibility of white-tailed deer to the agent of scrapie after intracerebral inoculation and to compare clinical signs and lesions to those reported for chronic wasting disease (CWD). Deer (n = 5) were inoculated with 1 mL of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. A non-inoculated deer was maintained as a negative control. Deer were observed daily for clinical signs of disease and euthanized and necropsied when unequivocal signs of scrapie were noted. One animal died 7 months post inoculation (pi) due to intercurrent disease. Examinations of brain tissue for the presence of the disease-associated abnormal prion protein (PrP(Sc)) by western blot (WB) and immunohistochemistry (IHC) were negative whereas IHC of lymphoid tissues was positive. Deer necropsied at 15-22 months pi were positive for scrapie by IHC and WB. Deer necropsied after 20 months pi had clinical signs of depression and progressive weight loss. Tissues with PrP(Sc) immunoreactivity included brain (at levels of cerebrum, hippocampus, colliculus, cerebellum, and brainstem), trigeminal ganglion, neurohypophysis, retina, spinal cord, and various lymphoid tissues including tonsil, retropharyngeal and mesenteric lymph nodes, Peyer's patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation. To further test the susceptibility of white-tailed deer to scrapie these experiments will be repeated with a more natural route of inoculation.

  4. Prion protein gene polymorphism and genetic risk evaluation for scrapie in all Turkish native sheep breeds.

    Science.gov (United States)

    Meydan, H; Yüceer, B; Degirmenci, R; Özkan, M M; Yildiz, M A

    2012-08-01

    The aim of this study was to identify the prion protein (PrP) gene polymorphism in a total of 1,110 healthy sheep from 18 Turkish native sheep breeds. There were nine alleles and 22 genotypes observed based on codons 136, 154, and 171 of the PrP gene. The ARQ allele was predominant for all breeds. The most resistant allele to scrapie, ARR, was present in all breeds. The VRQ allele, associated with the highest susceptibility to scrapie, was detected at low frequencies in İvesi (0.06), Kıvırcık (0.021), Sakız (0.010), Karayaka (0.011), Çine Çaparı (0.012), and Güneykaraman (0.017). In general, the ARQ/ARQ genotype was predominant in all breeds. The most resistant genotype to scrapie, ARR/ARR, was found with the frequency lower than 0.180. The most susceptible genotype, VRQ/VRQ, was found in only Kıvırcık. The TRR and TRH alleles and the genotypes of ARR/TRR, ARR/ARK, and ARH/TRH have been found for the first time in Turkish native sheep breeds. According to these results, all breeds belong to risk group R3 followed by R2. It is propounded that the susceptibility to scrapie increased from eastern to western part of Turkey. Our findings of Turkish native sheep breeds with PrP gene polymorphisms will assist the sheep breeding program for selection of scrapie resistance genotypes to reduce the risk of scrapie.

  5. Prenatal transmission of scrapie in sheep and goats: A case study for veterinary public health

    Science.gov (United States)

    Adams, D.B.

    2016-01-01

    Unsettled knowledge as to whether scrapie transmits prenatally in sheep and goats and transmits by semen and preimplantation embryos has a potential to compromise measures for controlling, preventing and eliminating the disease. The remedy may be analysis according to a systematic review, allowing comprehensive and accessible treatment of evidence and reasoning, clarifying the issue and specifying the uncertainties. Systematic reviews have clearly formulated questions, can identify relevant studies and appraise their quality and can summarise evidence and reasoning with an explicit methodology. The present venture lays a foundation for a possible systematic review and applies three lines of evidence and reasoning to two questions. The first question is whether scrapie transmits prenatally in sheep and goats. It leads to the second question, which concerns the sanitary safety of artificial breeding technologies, and is whether scrapie transmits in sheep and goats by means of semen and washed or unwashed in vivo derived embryos. The three lines of evidence derive from epidemiological, field and clinical studies, experimentation, and causal reasoning, where inferences are made from the body of scientific knowledge and an understanding of animal structure and function. Evidence from epidemiological studies allow a conclusion that scrapie transmits prenatally and that semen and embryos are presumptive hazards for the transmission of scrapie. Evidence from experimentation confirms that semen and washed or unwashed in vivo derived embryos are hazards for the transmission of scrapie. Evidence from causal reasoning, including experience from other prion diseases, shows that mechanisms exist for prenatal transmission and transmission by semen and embryos in both sheep and goats. PMID:27928518

  6. Evidence for co-infection of ovine prion strains in classical scrapie isolates.

    Science.gov (United States)

    Thackray, A M; Lockey, R; Beck, K E; Spiropoulos, J; Bujdoso, R

    2012-01-01

    The diversity of strains of ovine prions within classical scrapie isolates was investigated by transmission studies in wild type mice. To determine the maximum diversity of prion strains present in each ovine scrapie isolate examined, isolates from mice having the shortest and longest incubation times for terminal disease after primary inoculation were passaged serially. Serial passage of ARQ/ARQ scrapie isolates in RIII mice revealed the ME7 prion strain in mice with short incubation times for terminal prion disease and the 87A strain in those mice with long incubation times. Serial passage of VRQ/VRQ scrapie isolates in RIII mice led to emergence of the 221C prion strain in mice with short incubation times and a variant of the 221C strain in those mice with long incubation times. RIII mice with short incubation times had higher levels of total and proteinase K-resistant PrP(Sc) compared with those RIII mice with long incubation times, while mice with long incubation times had large aggregates and plaques of PrP(Sc). ME7 PrP(Sc) differed in stability compared with the 87A prion strain, while PrP(Sc) associated with 221C had similar stability to that of the 221C variant. Serial passage in VM mice led to identification of ME7 and 87V in the same scrapie isolate. The data show that different prion strains can emerge from the same ovine scrapie isolate following serial passage in wild type mice and that the transmission properties of these strains correlate with distinct patterns of PrP(Sc) deposition.

  7. Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie.

    Science.gov (United States)

    Gibbs, C J; Gajdusek, D C; Latarjet, R

    1978-01-01

    The titers of several preparations of kuru. Creutzfeldt-Jacob disease, and scrapie viruses were reduced by only 1/10th or less by high doses of gamma radiation of 50 kGy and by only 1/10th-1/1000th or less for 200 kGy. This unusual radiation resistance of the two human viruses further links them with the scrapie virus and suggests that the genetic information of all three viruses is considerably smaller than that of any other known viruses of mammals. PMID:104301

  8. Clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie

    Directory of Open Access Journals (Sweden)

    Toutain Pierre-Louis

    2011-06-01

    Full Text Available Abstract Background The retina is part of the diencephalon in a peripheral location and may be involved in prion diseases. Retinal function and structural changes were assessed in naturally scrapie-affected red face Manech ewes presenting the classical signs of the disease, and clinically healthy age-matched subjects for controls. Ophthalmic examination was done prior to electroretinography (ERG, which was carried out under conditions that allowed photopic and scotopic activities to be assessed. Histomorphometry of the inner and outer retinal layers was performed post-mortem, and retinas were also examined for evidence of abnormal prion protein (PrPSc accumulation and glial fibrillary acidic protein (GFAP upregulation as a marker of gliosis. Scrapie status was determined by examination of brain tissue Results Ocular reflexes and ophthalmoscopy did not reveal any difference between scrapie affected and control animals. Although the light-and dark-adapted ERG responses of both rod-and cone-mediated functions had a similar waveform in scrapie-affected and control sheep, a significant reduction in the amplitude of the ERG a-and b-waves was observed in affected animals compared to controls. These functional alterations were correlated with a substantial loss of cells in the outer nuclear layer (ONL, lengthening and disorganization in photoreceptor segments, and substantial reduction in cellularity and thickness of the inner nuclear layer (INL. The degenerative changes in the INL and ONL were most marked in the central and paracentral areas of the scrapie retinas, and were accompanied in all scrapie retinas by PrPSc deposition in the ganglion cell and synaptic layers. GFAP immunoreactivity was mainly increased in the ganglion cell and inner plexiform layers. Conclusions No appreciable fundoscopic changes were observed in the scrapie-affected ewes although reproducible changes in retinal function as measured by ERG were observed in these animals. The

  9. Altered lymphocyte proliferation and innate immune function in scrapie 139A- and ME7-infected mice.

    Science.gov (United States)

    Cho, In Soo; Spinner, Daryl S; Kascsak, Richard J; Meeker, H Cliff; Kim, Bo Sook; Park, Seung Yong; Schuller-Levis, Georgia; Park, Eunkyue

    2013-06-01

    Lymphoid organs play an important role in prion disease development and progression. While the role of lymphoid organs and changes in immune-related genes have been extensively investigated in scrapie-infected animals, innate immunity has not. Previous studies examined lymphocyte function in scrapie-infected C3H/HeJ mice, which exhibit defects in lipopolysaccharide (LPS) response now known to result from a mutation in Toll-like receptor (TLR) 4. We examined immune function in scrapie-infected CD1 mice, which are LPS responders. Lymphocyte proliferation from CD1 mice infected with either 139A or ME7 scrapie was measured in response to concanavalin (Con) A or LPS at 1 and 3 months after infection. Following LPS exposure, mice infected 3 months with ME7, but not 139A, demonstrated significantly decreased lymphocyte proliferation compared to controls. After Con A exposure, lymphocyte proliferation in scrapie-infected mice did not differ from controls. Gender-specific comparison of lymphocyte proliferation showed significant decreases in mitogenic responses in females infected 3 months with either 139A or ME7, compared to controls. Males infected for 3 months with ME7, but not 139A, showed significantly decreased proliferation after lymphocyte exposure to LPS, but not Con A. Neither gender showed changes in lymphocyte proliferation after 1 month of scrapie infection. Innate immune activation of peritoneal macrophages was determined via production of nitric oxide (NO), IL-6, and TNF-α after exposure to TLR ligands. TNF-α and IL-6 production were reduced in macrophages from females infected with either scrapie strain for 3 months, while NO production after TLR agonist plus IFN-γ exposure was decreased in both females and males infected for 3 months with 139A, compared to ME7. These data demonstrated altered innate immunity, suggesting hormonal and/or other gender-specific regulation may contribute to gender differences in some immune functions. Our data demonstrate

  10. Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

    Science.gov (United States)

    Filali, Hicham; Martin-Burriel, Inmaculada; Harders, Frank; Varona, Luis; Lyahyai, Jaber; Zaragoza, Pilar; Pumarola, Martí; Badiola, Juan J.; Bossers, Alex; Bolea, Rosa

    2011-01-01

    The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed. PMID:21629698

  11. Report of outbreaks of classical scrapie in Dorper sheep and associated prion protein gene polymorphisms in affected flocks.

    Science.gov (United States)

    de Andrade, Caroline Pinto; de Oliveira, Eduardo Conceição; Leal, Juliano Souza; de Almeida, Laura Lopes; de Castro, Luiza Amaral; da Silva, Sergio Ceroni; Driemeier, David

    2015-08-01

    Scrapie is an infectious neurodegenerative disease affecting sheep and goats, related with conformational alteration of an isoform of the prion protein that leads to deposition and aggregation in the host's central nervous system. Occurrence of the natural disease can be influenced by host genetic factors, such as a single nucleotide polymorphism of the prion protein gene. This study reports three scrapie-affected Dorper flocks located on three different farms in Brazil. The objective of this study was to analyze these three flocks using scrapie diagnostics, combining histology, immunohistochemistry, genotyping, and western blot assays. For immunohistochemistry, 192 sheep were selected and 308 sheep blood samples were taken for genotyping. A total of 22 sheep were scrapie positive by immunohistochemistry. Of these, four presented clinical signs and had scrapie immunoreactivity at the obex in western blot assays. The sheep without clinical signs were positive in lymphoid organs, such as the third eyelid and rectal mucosa. The major genotypes found on the flocks were ARQ/ARQ, ARQ/ARR, and ARQ/VRQ for codons 136, 154, and 171. Most of the sheep were considered to be at moderate to high risk, based on risk groups for developing scrapie. Some blood samples were sequenced, and polymorphisms were identified in other codons, such as 127, 142, and 143. Our data demonstrate the importance of preclinical scrapie diagnosis in Brazilian sheep, as most of the affected sheep showed no clinical signs, and emphasize the relevance of genotyping other Dorper sheep to determine the genotypic profile of the breed.

  12. The oral secretion of infectious scrapie prions occurs in preclinical sheep with a range of PRNP genotypes.

    Science.gov (United States)

    Gough, Kevin C; Baker, Claire A; Rees, Helen C; Terry, Linda A; Spiropoulos, John; Thorne, Leigh; Maddison, Ben C

    2012-01-01

    Preclinical sheep with the highly scrapie-susceptible VRQ/VRQ PRNP genotype secrete prions from the oral cavity. In order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of PRNP genotypes and analyzed by serial protein misfolding cyclic amplification (sPMCA). Prions were detected in buccal swabs from scrapie-exposed sheep of genotypes linked to high (VRQ/VRQ and ARQ/VRQ) and low (ARR/VRQ and AHQ/VRQ) lymphoreticular system involvement in scrapie pathogenesis. For both groups, the level of prion detection was significantly higher than that for scrapie-resistant ARR/ARR sheep which were kept in the same farm environment and acted as sentinel controls for prions derived from the environment which might contaminate the oral cavity. In addition, sheep with no exposure to the scrapie agent did not contain any measurable prions within the oral cavity. Furthermore, prions were detected in sheep over a wide age range representing various stages of preclinical disease. These data demonstrate that orally available scrapie prions may be a common feature in sheep incubating scrapie, regardless of the PRNP genotype and any associated high-level accumulation of PrP(Sc) within lymphoreticular tissues. PrP(Sc) was present in buccal swabs from a large proportion of sheep with PRNP genotypes associated with relatively low disease penetrance, indicating that subclinical scrapie infection is likely to be a common occurrence. The significance of positive sPMCA reactions was confirmed by the transmission of infectivity in buccal swab extracts to Tg338 mice, illustrating the likely importance of orally available prions in the horizontal transmission of scrapie.

  13. In vitro amplification of ovine prions from scrapie-infected sheep from Great Britain reveals distinct patterns of propagation

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    Thorne Leigh

    2012-11-01

    Full Text Available Abstract Background Protein misfolding cyclic amplification (PMCA is a method that facilitates the detection of prions from many sources of transmissible spongiform encephalopathy (TSE. Sheep scrapie represents a unique diversity of prion disease agents in a range of susceptible PRNP genotypes. In this study PMCA was assessed on a range of Great Britain (GB sheep scrapie isolates to determine the applicability to veterinary diagnosis of ovine TSE. Results PrPSc amplification by protein misfolding cyclic amplification (PMCA was assessed as a diagnostic tool for field cases of scrapie. The technique was initially applied to thirty-seven isolates of scrapie from diverse geographical locations around GB, and involved sheep of various breeds and PRNP genotypes. All samples were amplified in either VRQ and/or ARQ PrPC substrate. For PrPSc from sheep with at least one VRQ allele, all samples amplified efficiently in VRQ PrPC but only PrPSc from ARH/VRQ sheep amplified in both substrates. PrPSc from ARQ/ARQ sheep displayed two amplification patterns, one that amplified in both substrates and one that only amplified in ARQ PrPC. These amplification patterns were consistent for a further 14/15 flock/farm mates of these sheep. Furthermore experimental scrapie strains SSBP1, Dawson, CH1641 and MRI were analysed. SSBP1 and Dawson (from VRQ/VRQ sheep amplified in VRQ but not ARQ substrate. MRI scrapie (from ARQ/ARQ sheep nor CH1641 did not amplify in ARQ or VRQ substrate; these strains required an enhanced PMCA method incorporating polyadenylic acid (poly(A to achieve amplification. Conclusions PrPsc from 52 classical scrapie GB field isolates amplified in VRQ or ARQ or both substrates and supports the use of PMCA as a rapid assay for the detection of a wide range of ovine classical scrapie infections involving multiple PRNP genotypes and scrapie strains.

  14. EU-approved rapid tests for bovine spongiform encephalopathy detect atypical forms: a study for their sensitivities.

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    Daniela Meloni

    Full Text Available Since 2004 it become clear that atypical bovine spongiform encephalopthies (BSEs exist in cattle. Whenever their detection has relied on active surveillance plans implemented in Europe since 2001 by rapid tests, the overall and inter-laboratory performance of these diagnostic systems in the detection of the atypical strains has not been studied thoroughly to date. To fill this gap, the present study reports on the analytical sensitivity of the EU-approved rapid tests for atypical L- and H-type and classical BSE in parallel. Each test was challenged with two dilution series, one created from a positive pool of the three BSE forms according to the EURL standard method of homogenate preparation (50% w/v and the other as per the test kit manufacturer's instructions. Multilevel logistic models and simple logistic models with the rapid test as the only covariate were fitted for each BSE form analyzed as directed by the test manufacturer's dilution protocol. The same schemes, but excluding the BSE type, were then applied to compare test performance under the manufacturer's versus the water protocol. The IDEXX HerdChek ® BSE-scrapie short protocol test showed the highest sensitivity for all BSE forms. The IDEXX® HerdChek BSE-scrapie ultra short protocol, the Prionics®--Check WESTERN and the AJ Roboscreen® BetaPrion tests showed similar sensitivities, followed by the Roche® PrionScreen, the Bio-Rad® TeSeE™ SAP and the Prionics®--Check PrioSTRIP in descending order of analytical sensitivity. Despite these differences, the limit of detection of all seven rapid tests against the different classes of material set within a 2 log(10 range of the best-performing test, thus meeting the European Food Safety Authority requirement for BSE surveillance purposes. These findings indicate that not many atypical cases would have been missed surveillance since 2001 which is important for further epidemiological interpretations of the sporadic character of

  15. [Therapy for atypical facial pain].

    Science.gov (United States)

    Ishida, Satoshi; Kimura, Hiroko

    2009-09-01

    Atypical facial pain is a pain in the head, neck and the face, without organic causes. It is treated at departments of physical medicine, such as dental, oral and maxillofacial surgery, otolaryngology, cerebral surgery, or head and neck surgery. In primary care, it is considered to be a medically unexplained symptom (MUS), or a somatoform disorder, such as somatization caused by a functional somatic syndrome (FSS) by psychiatrists. Usually, patients consult departments of physical medicine complaining of physical pain. Therefore physicians in these departments should examine the patients from the holistic perspective, and identify organic diseases. As atypical facial pain becomes chronic, other complications, including psychiatric complaints other than physical pain, such as depression may develop. Moreover, physical, psychological, and social factors affect the symptoms by interacting with one another. Therefore, in examining atypical facial pain, doctors specializing in dental, oral and maxillofacial medicine are required to provide psychosomatic treatment that is based on integrated knowledge.

  16. Detection of PrPres in Genetically Susceptible Fetuses from Sheep with Natural Scrapie

    Science.gov (United States)

    Garza, María Carmen; Fernández-Borges, Natalia; Bolea, Rosa; Badiola, Juan José; Castilla, Joaquín; Monleón, Eva

    2011-01-01

    Scrapie is a transmissible spongiform encephalopathy with a wide PrPres dissemination in many non-neural tissues and with high levels of transmissibility within susceptible populations. Mechanisms of transmission are incompletely understood. It is generally assumed that it is horizontally transmitted by direct contact between animals or indirectly through the environment, where scrapie can remain infectious for years. In contrast, in utero vertical transmission has never been demonstrated and has rarely been studied. Recently, the use of the protein misfolding cyclic amplification technique (PMCA) has allowed prion detection in various tissues and excretions in which PrPres levels have been undetectable by traditional assays. The main goal of this study was to detect PrPres in fetal tissues and the amniotic fluid from natural scrapie infected ewes using the PMCA technique. Six fetuses from three infected pregnant ewes in an advanced clinical stage of the disease were included in the study. From each fetus, amniotic fluid, brain, spleen, ileo-cecal valve and retropharyngeal lymph node samples were collected and analyzed using Western blotting and PMCA. Although all samples were negative using Western blotting, PrPres was detected after in vitro amplification. Our results represent the first time the biochemical detection of prions in fetal tissues, suggesting that the in utero transmission of scrapie in natural infected sheep might be possible. PMID:22194786

  17. Classical scrapie prions in ovine blood are associated with B lymphocytes and platelets-rich plasma

    Science.gov (United States)

    Classical scrapie is a naturally occurring fatal brain disease of sheep and goats which is caused by prions, a novel class of infectious agent, and is accompanied by the accumulation of abnormal isoforms of prion protein (PrP-Sc) in certain neural and lymphoid tissues. Although collection of a blood...

  18. Intraepithelial and interstitial deposition of pathological prion protein in kidneys of scrapie-affected sheep.

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    Ciriaco Ligios

    Full Text Available Prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by Transmissible Spongiform Encephalopathy (TSE. The presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated PrP(Sc. We collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of PrP(Sc from distinct, geographically separated flocks. By performing Western blot, PET blot analysis and immunohistochemistry we found intraepithelial (cortex, medulla and papilla and occasional interstitial (papilla deposition of PrP(Sc in kidneys of scrapie-affected sheep. Interestingly, glomerula lacked detectable signals indicative of PrP(Sc. PrP(Sc was also detected in kidneys of subclinical sheep, but to significantly lower degree. Depending on the stage of the disease the incidence of PrP(Sc in kidney varied from approximately 27% (subclinical to 73.6% (clinical in naturally scrapie-affected sheep. Kidneys from flocks without scrapie outbreak were devoid of PrP(Sc. Here we demonstrate unexpectedly frequent deposition of high levels of PrP(Sc in ovine kidneys of various flocks. Renal deposition of PrP(Sc is likely to be a pre-requisite enabling prionuria, a possible co-factor of horizontal prion-transmission in sheep.

  19. Manipulation of PrPres production in scrapie-infected neuroblastoma cells

    NARCIS (Netherlands)

    Bate, C.; Langeveld, J.P.M.; Williams, A.

    2004-01-01

    In the present study the accumulation of protease resistant prion protein (PrPres) in scrapie-infected neuroblastoma cells (ScN2a cells) was shown to be dependent on culture conditions. The highest levels of PrPres were found in slow growing cells. Further increases in PrPres accumulation were obser

  20. A single step multiplex immunofluorometric assay for differential diagnosis of BSE and scrapie

    NARCIS (Netherlands)

    Tang, Y.; Thorne, J.; Whatling, K.L.; Jacobs, J.G.; Langeveld, J.P.M.; Sauer, M.

    2010-01-01

    Although there is no evidence that the European sheep population has been infected with bovine spongiform encephalopathy (BSE), distinguishing this from scrapie is paramount, given the association between BSE exposure and the human transmissible spongiform encephalopathy (TSE), variant Creutzfeldt–J

  1. A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation

    Science.gov (United States)

    Classical scrapie is a form of transmissible spongiform encephalopathies (TSE) affecting domestic goats and sheep and disease is characterized by the accumulation of abnormal conformational isoform (PrP-Sc) of normal cellular prion protein (PrP-C) in the central nervous system and, in most cases, ly...

  2. New insight into the nature of scrapie from old radiation results

    Energy Technology Data Exchange (ETDEWEB)

    Alper, T.

    1993-02-01

    The author examines a modification of the infectious plasma membrane hypothesis put forward to by Gibbons and Hunter (1967) to explain the transmission of Scrapie and discusses radiation experiments in the light of the target theory, carried out to estimate the size of the transmitting agent of the disease. (UK).

  3. Detection of PrPres in genetically susceptible fetuses from sheep with natural scrapie.

    Directory of Open Access Journals (Sweden)

    María Carmen Garza

    Full Text Available Scrapie is a transmissible spongiform encephalopathy with a wide PrPres dissemination in many non-neural tissues and with high levels of transmissibility within susceptible populations. Mechanisms of transmission are incompletely understood. It is generally assumed that it is horizontally transmitted by direct contact between animals or indirectly through the environment, where scrapie can remain infectious for years. In contrast, in utero vertical transmission has never been demonstrated and has rarely been studied. Recently, the use of the protein misfolding cyclic amplification technique (PMCA has allowed prion detection in various tissues and excretions in which PrPres levels have been undetectable by traditional assays. The main goal of this study was to detect PrPres in fetal tissues and the amniotic fluid from natural scrapie infected ewes using the PMCA technique. Six fetuses from three infected pregnant ewes in an advanced clinical stage of the disease were included in the study. From each fetus, amniotic fluid, brain, spleen, ileo-cecal valve and retropharyngeal lymph node samples were collected and analyzed using Western blotting and PMCA. Although all samples were negative using Western blotting, PrPres was detected after in vitro amplification. Our results represent the first time the biochemical detection of prions in fetal tissues, suggesting that the in utero transmission of scrapie in natural infected sheep might be possible.

  4. Presence of an acute phase response in sheep with clinical classical scrapie

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    Meling Siv

    2012-07-01

    Full Text Available Abstract Background Work with experimental scrapie in sheep has been performed on-site for many years including studies on PrPSc dissemination and histopathology of organs and tissues both at preclinical and clinical stages. In this work serum was sampled at regular intervals from lambs which were infected immediately after birth and from parallel healthy controls, and examined for acute phase proteins. In contrast to earlier experiments, which extensively studied PrPSc dissemination and histopathology in peripheral tissues and brain, this experiment is focusing on examination of serum for non-PrPSc markers that discriminates the two groups, and give insight into other on-going processes detectable in serum samples. Results There was clear evidence of an acute phase response in sheep with clinical scrapie, both experimental and natural. All the three proteins, ceruloplasmin, haptoglobin and serum amyloid A, were increased at the clinical stage of scrapie. Conclusion There was evidence of a systemic measurable acute phase response at the clinical terminal end-stage of classical scrapie.

  5. A single step multiplex immunofluorometric assay for differential diagnosis of BSE and scrapie.

    Science.gov (United States)

    Tang, Yue; Thorne, Jemma; Whatling, Kirsty; Jacobs, Jorg G; Langeveld, Jan; Sauer, Maurice J

    2010-04-30

    Although there is no evidence that the European sheep population has been infected with bovine spongiform encephalopathy (BSE), distinguishing this from scrapie is paramount, given the association between BSE exposure and the human transmissible spongiform encephalopathy (TSE), variant Creutzfeldt-Jakob disease. The capability to differentially diagnose TSEs in sheep is thus essential in order to safeguard the food chain and human health. Biochemical methods for differentiating BSE and scrapie are largely reliant on assessment by Western blot (WB) analysis of the abnormal disease associated prion protein PrP(D) following partial proteolytic digestion. WB banding patterns obtained using a panel of antibodies enable different strain specific conformations of PrP(D) to be distinguished. This approach provides a robust confirmatory test but one which is not appropriate for high throughput screening. A simple, one step, bead array flow cytometry based multiplex immunofluorometric assay has been developed which is suitable for simultaneous screening and confirmation. Using a combination of antibodies directed towards three PrP epitopes enabled differential diagnosis of scrapie and BSE. Proof of principle studies indicated a high predictive value (100%) when applied to brain samples from control animals, BSE infected cattle and sheep naturally infected with scrapie or experimentally infected with BSE.

  6. Lesion profiling at primary isolation in RIII mice is insufficient in distinguishing BSE from classical scrapie.

    Science.gov (United States)

    Beck, Katy E; Chaplin, Melanie; Stack, Michael; Sallis, Rosemary E; Simonini, Sarah; Lockey, Richard; Spiropoulos, John

    2010-03-01

    Primary isolation of bovine spongiform encephalopathy (BSE) in RIII mice generates a lesion profile believed to be reproducible and distinct from that produced by classical scrapie. This profile, which is characterized by peaks at gray matter areas 1, 4 and 7 (dorsal medulla, hypothalamus and septal nuclei), is used to diagnose BSE on primary isolation. The aim of this study was to investigate whether the BSE agent could be present in sheep diagnosed with classical scrapie, using lesion profiles in RIII mice as a discriminatory method. Sixty-two positive scrapie field cases were collected from individual farms between 1996 and 1999 and bioassayed in RIII mice. Fifty-five of these isolates transmitted successfully to at least one mouse. Of the 31 that produced adequate data to allow lesion profile analysis, 10 showed a consistent profile with peaks at brain areas 1, 4 and 7. All inocula for this subgroup were derived from sheep of genotype ARQ/ARQ. While the 1-4-7-scrapie profile exhibited similarities to BSE in RIII mice at primary isolation, it was distinguishable based on histopathology, immunohistochemistry and cluster analysis. We conclude that caution should be taken to distinguish this profile from BSE and that additional parameters should be considered to reach a final diagnosis.

  7. Rapid and discriminatory diagnosis of scrapie and BSE in retro-pharyngeal lymph nodes of sheep

    NARCIS (Netherlands)

    Langeveld, J.P.M.; Jacobs, J.G.; Erkens, J.H.F.; Bossers, A.; Zijderveld, van F.G.; Keulen, van L.J.M.

    2006-01-01

    Background Diagnosis based on prion detection in lymph nodes of sheep and goats can improve active surveillance for scrapie and, if it were circulating, for bovine spongiform encephalopathy (BSE). With sizes that allow repetitive testing and a location that is easily accessible at slaughter, retroph

  8. Medulla oblongata transcriptome changes during presymptomatic natural scrapie and their associaition with prion-related lesions.

    NARCIS (Netherlands)

    Filali, H.; Martin-Burriel, I.; Harders, F.; Varona, L.; Serrano, C.; Acín, C.; Badiola, J.J.; Bossers, A.; Bolea, R.

    2012-01-01

    Background The pathogenesis of natural scrapie and other prion diseases is still poorly understood. Determining the variations in the transcriptome in the early phases of the disease might clarify some of the molecular mechanisms of the prion-induced pathology and allow for the development of new bi

  9. Scrapie strains retain their distinctive characteristics following passages of homogenates from different brain regions and spleen.

    Science.gov (United States)

    Carp, R I; Meeker, H; Sersen, E

    1997-01-01

    The molecular basis of differences among scrapie strains is unknown. The prion theory posits that there are differences in the conformation of the host protease-resistant protein (PrP) molecules and that these differences are responsible for scrapie strains. A corollary of this theory is that the origin of host PrP variation resides in different neuronal cell types. To assess this concept, preparations from three brain regions (cerebrum, cerebellum and olfactory bulb) and from spleen were passaged in C57BL mice by intracerebral injection. After three passages of three scrapie strains in this manner, homogenates of each brain region and spleen were tested for several of the characteristics that distinguish the three strains: (1) the rank order of incubation periods in C57BL mice, (2) induction of obesity in SJL mice and (3) comparative incubation periods in mice with three genotypes for the scrapie incubation period marker. Analysis revealed that virtually all of the criteria that distinguished the three strains prior to passages of the three brain regions and spleen were retained after this series of passages. This finding argues against cellular-based PrP differences providing a basis for strain specificity.

  10. Scrapie e seu diagnóstico diferencial em ovinos no Mato Grosso do Sul

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    Héllen M. Martins

    2012-12-01

    Full Text Available Scrapie é uma doença infecciosa, neurodegenerativa fatal, causada pelo príon scrapie (PrPsc. Apresenta-se tanto na forma clássica em ovinos e caprinos geneticamente susceptíveis quanto na forma atípica em ovinos. A primeira notificação oficial do Brasil à Organização Mundial de Saúde Animal (OIE, um caso da forma clássica diagnosticado no Rio Grande do Sul ocorreu em 1985, mas a doença já havia sido diagnosticada no mesmo Estado em 1978. Este trabalho objetivou descrever dois surtos de Scrapie em ovinos em Mato Grosso do Sul (MS, Brasil e investigar, por meio de imuno-histoquímica (IHQ a presença de PrPsc no Sistema Nervoso Central (SNC de ovinos examinados entre 2003 e 2010. Na primeira parte observaram-se dois ovinos com sinais clínicos típicos de scrapie, detalhando-se os sinais neurológicos, dados epidemiológicos, histopatológicos e amostras teciduais em duplicata desses ovinos foram encaminhadas para realização de diagnóstico de Raiva e para diagnóstico IHQ para príon. Na segunda parte realizou-se levantamento de laudos de necropsia e diagnósticos histopatológicos de ovinos, no período de maio de 2003 a março de 2010. Amostras de sistema nervoso central de 51 casos foram selecionados, incluindo os dois já com diagnóstico de Scrapie mencionados acima; os tecido de todos esses ovinos foram submetidos à IHQ para detecção de proteína priônica. Os 49 ovinos avaliados apresentaram resultado negativo na IHQ para príon.

  11. Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

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    Dassanayake Rohana P

    2011-11-01

    Full Text Available Abstract Background Classical scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats characterized by cellular accumulation of abnormal isoforms of prion protein (PrPSc in the central nervous system and the follicles of peripheral lymphoid tissues. Previous studies have shown that the whole blood and buffy coat blood fraction of scrapie infected sheep harbor prion infectivity. Although PrPSc has been detected in peripheral blood mononuclear cells (PBMCs, plasma, and more recently within a subpopulation of B lymphocytes, the infectivity status of these cells and plasma in sheep remains unknown. Therefore, the objective of this study was to determine whether circulating PBMCs, B lymphocytes and platelets from classical scrapie infected sheep harbor prion infectivity using a sheep bioassay. Results Serial rectal mucosal biopsy and immunohistochemistry were used to detect preclinical infection in lambs transfused with whole blood or blood cell fractions from preclinical or clinical scrapie infected sheep. PrPSc immunolabeling was detected in antemortem rectal and postmortem lymphoid tissues from recipient lambs receiving PBMCs (15/15, CD72+ B lymphocytes (3/3, CD21+ B lymphocytes (3/3 or platelet-rich plasma (2/3 fractions. As expected, whole blood (11/13 and buffy coat (5/5 recipients showed positive PrPSc labeling in lymphoid follicles. However, at 549 days post-transfusion, PrPSc was not detected in rectal or other lymphoid tissues in three sheep receiving platelet-poor plasma fraction. Conclusions Prion infectivity was detected in circulating PBMCs, CD72+ pan B lymphocytes, the CD21+ subpopulation of B lymphocytes and platelet-rich plasma of classical scrapie infected sheep using a sheep bioassay. Combining platelets with B lymphocytes might enhance PrPSc detection levels in blood samples.

  12. Changes in HSP gene and protein expression in natural scrapie with brain damage

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    Serrano Carmen

    2011-01-01

    Full Text Available Abstract Heat shock proteins (Hsp perform cytoprotective functions such as apoptosis regulation and inflammatory response control. These proteins can also be secreted to the extracellular medium, acting as inflammatory mediators, and their chaperone activity permits correct folding of proteins and avoids the aggregation of anomalous isoforms. Several studies have proposed the implication of Hsp in prion diseases. We analysed the gene expression and protein distribution of different members of the Hsp27, Hsp70, and Hsp90 families in the central nervous system of sheep naturally infected with scrapie. Different expression profiles were observed in the areas analysed. Whereas changes in transcript levels were not observed in the cerebellum or medulla oblongata, a significant decrease in HSP27 and HSP90 was detected in the prefrontal cortex. In contrast, HSP73 was over-expressed in diencephalons of scrapie animals. Western blotting did not reveal significant differences in Hsp90 and Hsp70 protein expression between scrapie and control animals. Expression rates identified by real-time RT-PCR and western blotting were compared with the extent of classical scrapie lesions using stepwise regression. Changes in Hsp gene and protein expression were associated with prion protein deposition, gliosis and spongiosis rather than with apoptosis. Finally, immunohistochemistry revealed intense Hsp70 and Hsp90 immunolabelling in Purkinje cells of scrapie sheep. In contrast, controls displayed little or no staining in these cells. The observed differences in gene expression and protein distribution suggest that the heat shock proteins analysed play a role in the natural form of the disease.

  13. Medulla oblongata transcriptome changes during presymptomatic natural scrapie and their association with prion-related lesions

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    Filali Hicham

    2012-08-01

    Full Text Available Abstract Background The pathogenesis of natural scrapie and other prion diseases is still poorly understood. Determining the variations in the transcriptome in the early phases of the disease might clarify some of the molecular mechanisms of the prion-induced pathology and allow for the development of new biomarkers for diagnosis and therapy. This study is the first to focus on the identification of genes regulated during the preclinical phases of natural scrapie in the ovine medulla oblongata (MO and the association of these genes with prion deposition, astrocytosis and spongiosis. Results A custom microarray platform revealed that 86 significant probes had expression changes greater than 2-fold. From these probes, we identified 32 genes with known function; the highest number of regulated genes was included in the phosphoprotein-encoding group. Genes encoding extracellular marker proteins and those involved in the immune response and apoptosis were also differentially expressed. In addition, we investigated the relationship between the gene expression profiles and the appearance of the main scrapie-associated brain lesions. Quantitative Real-time PCR was used to validate the expression of some of the regulated genes, thus showing the reliability of the microarray hybridization technology. Conclusions Genes involved in protein and metal binding and oxidoreductase activity were associated with prion deposition. The expression of glial fibrillary acidic protein (GFAP was associated with changes in the expression of genes encoding proteins with oxidoreductase and phosphatase activity, and the expression of spongiosis was related to genes encoding extracellular matrix components or transmembrane transporters. This is the first genome-wide expression study performed in naturally infected sheep with preclinical scrapie. As in previous studies, our findings confirm the close relationship between scrapie and other neurodegenerative diseases.

  14. Atypical moles: diagnosis and management.

    Science.gov (United States)

    Perkins, Allen; Duffy, R Lamar

    2015-06-01

    Atypical moles are benign pigmented lesions. Although they are benign, they exhibit some of the clinical and histologic features of malignant melanoma. They are more common in fair-skinned individuals and in those with high sun exposure. Atypical moles are characterized by size of 6 mm or more at the greatest dimension, color variegation, border irregularity, and pebbled texture. They are associated with an increased risk of melanoma, warranting enhanced surveillance, especially in patients with more than 50 moles and a family history of melanoma. Because an individual lesion is unlikely to display malignant transformation, biopsy of all atypical moles is neither clinically beneficial nor cost-effective. The ABCDE (asymmetry, border irregularity, color unevenness, diameter of 6 mm or more, evolution) mnemonic is a valuable tool for clinicians and patients to identify lesions that could be melanoma. Also, according to the "ugly duckling" concept, benign moles tend to have a similar appearance, whereas an outlier with a different appearance is more likely to be undergoing malignant change. Atypical moles with changes suggestive of malignant melanoma should be biopsied, using an excisional method, if possible.

  15. Resistance to classical scrapie in experimentally challenged goats carrying mutation K222 of the prion protein gene.

    Science.gov (United States)

    Acutis, Pier Luigi; Martucci, Francesca; D'Angelo, Antonio; Peletto, Simone; Colussi, Silvia; Maurella, Cristiana; Porcario, Chiara; Iulini, Barbara; Mazza, Maria; Dell'atti, Luana; Zuccon, Fabio; Corona, Cristiano; Martinelli, Nicola; Casalone, Cristina; Caramelli, Maria; Lombardi, Guerino

    2012-02-01

    Susceptibility of sheep to scrapie, a transmissible spongiform encephalopathy of small ruminants, is strongly influenced by polymorphisms of the prion protein gene (PRNP). Breeding programs have been implemented to increase scrapie resistance in sheep populations; though desirable, a similar approach has not yet been applied in goats. European studies have now suggested that several polymorphisms can modulate scrapie susceptibility in goats: in particular, PRNP variant K222 has been associated with resistance in case-control studies in Italy, France and Greece. In this study we investigated the resistance conferred by this variant using a natural Italian goat scrapie isolate to intracerebrally challenge five goats carrying genotype Q/Q 222 (wild type) and five goats carrying genotype Q/K 222. By the end of the study, all five Q/Q 222 goats had died of scrapie after a mean incubation period of 19 months; one of the five Q/K 222 goats died after 24 months, while the other four were alive and apparently healthy up to the end of the study at 4.5 years post-challenge. All five of these animals were found to be scrapie negative. Statistical analysis showed that the probability of survival of the Q/K 222 goats versus the Q/Q 222 goats was significantly higher (p = 0.002). Our study shows that PRNP gene mutation K222 is strongly associated with resistance to classical scrapie also in experimental conditions, making it a potentially positive target for selection in the frame of breeding programs for resistance to classical scrapie in goats.

  16. Scrapie diagnosis in a goat and four Santa Inês sheep from the same herd in Brazil

    Directory of Open Access Journals (Sweden)

    J.S. Leal

    2015-12-01

    Full Text Available Scrapie is a fatal and progressive transmissible spongiform encephalopathy (TSE of natural occurrence in sheep and goats. The suspicion of scrapie may be based on clinical signs; however, the detection of pathological features of the prionic protein (PrP in target tissues is necessary to diagnose the disease. The presence of an abnormal protein form (PrPSc in lymphoreticular and nervous tissues is an important characteristic in diagnosis. This paper reports a case of scrapie in a flock of 55 Suffolk crossbred sheep, 19 Santa Inês sheep and 21 goats in the Mato Grosso state, midwestern Brazil. The animals were euthanized after the confirmation of a scrapie case with clinical signs in a Suffolk sheep in the same farm. Samples of brainstem at the level of the obex and lymphoid issues like palatine tonsils, mesenteric lymph nodes, third eyelid fixed in formalin 10% were processed for histological examination. Histological examination with hematoxylin and eosin did not show any microscopic changes in samples. Immunohistochemistry (IHC examination to detect anti-prion PrPSc was performed in lymphoid tissues. Scrapie diagnosis was confirmed based on IHC positive results for PrPSc in lymphoid tissues of a crossbreed goat and four Santa Inês sheep, without any clinical scrapie signs. IHC showed positive staining in at least three lymphoid germinal centers in goat mesenteric lymph node, palatine tonsil, and third eyelid samples. The mesenteric lymph node, and tonsil samples of all sheep showed positive immunostaining, and only one sheep showed positive staining in lymphoid follicles in the third eyelid. Scrapie diagnosis using IHC in fixed samples of lymphoreticular tissue is technically feasible to detect the disease in both goats and sheep, as a form of pre-clinical diagnosis. The results indicate that the herd was infected by a sheep coming from another herd where scrapie had been diagnosed before.

  17. Resistance to classical scrapie in experimentally challenged goats carrying mutation K222 of the prion protein gene

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    Acutis Pier Luigi

    2012-02-01

    Full Text Available Abstract Susceptibility of sheep to scrapie, a transmissible spongiform encephalopathy of small ruminants, is strongly influenced by polymorphisms of the prion protein gene (PRNP. Breeding programs have been implemented to increase scrapie resistance in sheep populations; though desirable, a similar approach has not yet been applied in goats. European studies have now suggested that several polymorphisms can modulate scrapie susceptibility in goats: in particular, PRNP variant K222 has been associated with resistance in case-control studies in Italy, France and Greece. In this study we investigated the resistance conferred by this variant using a natural Italian goat scrapie isolate to intracerebrally challenge five goats carrying genotype Q/Q 222 (wild type and five goats carrying genotype Q/K 222. By the end of the study, all five Q/Q 222 goats had died of scrapie after a mean incubation period of 19 months; one of the five Q/K 222 goats died after 24 months, while the other four were alive and apparently healthy up to the end of the study at 4.5 years post-challenge. All five of these animals were found to be scrapie negative. Statistical analysis showed that the probability of survival of the Q/K 222 goats versus the Q/Q 222 goats was significantly higher (p = 0.002. Our study shows that PRNP gene mutation K222 is strongly associated with resistance to classical scrapie also in experimental conditions, making it a potentially positive target for selection in the frame of breeding programs for resistance to classical scrapie in goats.

  18. Classical natural ovine scrapie prions detected in practical volumes of blood by lamb and transgenic mouse bioassays.

    Science.gov (United States)

    Dassanayake, Rohana P; Truscott, Thomas C; Zhuang, Dongyue; Schneider, David A; Madsen-Bouterse, Sally A; Young, Alan J; Stanton, James B; Davis, William C; O'Rourke, Katherine I

    2015-01-01

    Scrapie is diagnosed antemortem in sheep by detecting misfolded isoforms of prion protein (PrP(Sc)) in lymphoid follicles of the rectal mucosa and nictitating membranes. Assay sensitivity is limited if (a) the biopsy is collected early during disease development, (b) an insufficient number of follicles is collected, or (c) peripheral accumulation of PrP(Sc) is reduced or delayed. A blood test would be convenient for mass live animal scrapie testing. Currently approved techniques, however, have their own detection limits. Novel detection methods may soon offer a non-animal-based, rapid platform with detection sensitivities that rival the prion bioassay. In anticipation, we sought to determine if diseased animals could be routinely identified with a bioassay using B lymphocytes isolated from blood sample volumes commonly collected for diagnostic purposes in small ruminants. Scrapie transmission was detected in five of six recipient lambs intravenously transfused with B lymphocytes isolated from 5~10 mL of blood from a naturally scrapie-infected sheep. Additionally, scrapie transmission was observed in 18 ovinized transgenic Tg338 mice intracerebrally inoculated with B lymphocytes isolated from 5~10 mL of blood from two naturally scrapie-infected sheep. Based on our findings, we anticipate that these blood sample volumes should be of diagnostic value.

  19. In vitro Expression in Eukaryotic Cells of a Prion Protein Gene Cloned from Scrapie-Infected Mouse Brain

    Science.gov (United States)

    Caughey, Byron; Race, Richard E.; Vogel, Mari; Buchmeier, Michael J.; Chesebro, Bruce

    1988-07-01

    It has been proposed that the causative agent of scrapie represents a class of infectious particle that is devoid of nucleic acid and that an altered form of the endogenous prion protein (PrP) is the agent. However, it has been difficult to exclude the possibility that PrP purified from scrapie tissues might be contaminated with a more conventional viral agent. To obtain PrP uncontaminated by scrapie-infected tissues, PrP cDNA cloned from a scrapie-infected mouse brain was expressed in mouse C127 cells in vitro. mRNA and protein encoded by the cloned PrP gene were identified. The expressed PrP polypeptides appeared to be glycosylated and were released from the cell surface into the medium. Homogenates of the cells expressing the cloned PrP gene were inoculated into susceptible mice but failed to induce clinical signs of scrapie. Thus, either PrP is not the transmissible agent of scrapie or the expressed PrP requires additional modification to be infectious.

  20. Transcriptional profiling of peripheral lymphoid tissue reveals genes and networks linked to SSBP/1 scrapie pathology in sheep.

    Science.gov (United States)

    Gossner, Anton; Roupaka, Sofia; Foster, Jim; Hunter, Nora; Hopkins, John

    2011-12-15

    Transmissible spongiform encephalopathies (TSEs) are slow and progressive neurodegenerative diseases of humans and animals. The major target organ for all TSEs is the brain but some TSE agents are associated with prior accumulation within the peripheral lymphoid system. Many studies have examined the effects of scrapie infection on the expression of central nervous system (CNS) genes, but this study examines the progression of scrapie pathology in the peripheral lymphoid system and how scrapie infection affects the transcriptome of the lymph nodes and spleen. Infection of sheep with SSBP/1 scrapie resulted in PrP(Sc) deposition in the draining prescapular lymph node (PSLN) by 25 days post infection (dpi) in VRQ/VRQ genotype sheep and 75 dpi in tonsils and spleen. Progression of PrP(Sc) deposition in VRQ/ARR animals was 25 dpi later in the PSLN and 250 dpi later in spleen. Microarray analysis of 75 dpi tissues from VRQ/VRQ sheep identified 52 genes in PSLN and 37 genes in spleen cells that showed significant difference (P ≤ 0.05) between scrapie-infected and mock-infected animals. Transcriptional pathway analysis highlighted immunological disease, cell death and neurological disease as the biological pathways associated with scrapie pathogenesis in the peripheral lymphoid system. PrP(Sc) accumulation of lymphoid tissue resulted in the repression of genes linked to inflammation and oxidative stress, and the up-regulation of genes related to apoptosis.

  1. Clinical Heterogeneity of Atypical Pantothenate Kinase-Associated Neurodegeneration in Koreans

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    Jae-Hyeok Lee

    2016-01-01

    Full Text Available Objective Neurodegeneration with brain iron accumulation (NBIA represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. Methods We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN. Results Four subtypes of NBIA including PKAN (n = 30, PLA2G6-related neurodegeneration (n = 2, beta-propeller protein-associated neurodegeneration (n = 1, and aceruloplasminemia (n = 1 have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG. Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. Conclusions We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.

  2. Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

    DEFF Research Database (Denmark)

    Lindquist, Suzanne Granhøj; Nielsen, Jørgen Erik; Stokholm, Jette

    2008-01-01

    Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a fam...

  3. Comparison of strategies for substantiating freedom from scrapie in a sheep flock

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    Ducrot Christian

    2009-04-01

    Full Text Available Abstract Background The public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led European animal health authorities to launch large screening and genetic selection programmes. If demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. In this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapie. Classical approaches, based on surveys designed to detect disease presence, do not account for scrapie specificities: the genetic variations of susceptibility and the absence of live diagnostic test routinely available. Adapting these approaches leads to a paradoxical situation in which a greater amount of testing is needed to substantiate disease freedom in genetically resistant flocks than in susceptible flocks, whereas probability of disease freedom is a priori higher in the former than in the latter. The goal of this study was to propose, evaluate and compare several qualification strategies for demonstrating a flock is free from scrapie. Results A probabilistic framework was defined that accounts for scrapie specificities and allows solving the preceding paradox. Six qualification strategies were defined that combine genotyping data, diagnostic tests results and flock pedigree. These were compared in two types of simulated flocks: resistant and susceptible flocks. Two strategies allowed demonstrating disease freedom in several years, for the majority of simulated flocks: a strategy in which all the flock animals are genotyped, and a strategy in which only founders animals are genotyped, the flock pedigree being known. In both cases, diagnostic tests are performed on culled animals. The less costly strategy varied according to the genetic context (resistant or susceptible and to the relative costs of a genotyping exam and of a

  4. Atypical Steatocystoma Multiplex with Calcification

    Science.gov (United States)

    Rahman, Muhammad Hasibur; Islam, Muhammad Saiful; Ansari, Nazma Parvin

    2011-01-01

    A 60-year-old male reported to us with an atypical case of giant steatocystoma multiplex in the scrotum with calcification. There was no family history of similar lesions. Yellowish, creamy material was expressed from a nodule during punch biopsy. The diagnosis was based on clinical as well as histological findings. Successful surgical excision was done to cure the case without any complications. PMID:22363850

  5. Atypical Centrioles During Sexual Reproduction

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    Tomer eAvidor-Reiss

    2015-04-01

    Full Text Available Centrioles are conserved, self-replicating, microtubule-based 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, the proximal centriole-like structure (PCL. We also discuss another type of atypical centriole, the zombie centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology.

  6. Atypical Imaging Appearances of Meningioma

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    Ahmad Soltani shirazi

    2009-01-01

    Full Text Available "nIntroduction: Meningiomas are the commonest primary non-glial intracranial tumors. The diagnosis is usually correctly established on characteristic imaging appearances. Atypical meningiomas may be difficult to diagnose because of their similarity to other brain tumors. This paper presents one case of atypical meningioma, misdiagnosed primarily as glioblastoma multiforms (GBM by radiological techniques. "nCase report: A 15-year-old girl presented with a severe intermittent generalized headache that on occasion localized to retro-orbital and vertex. Other manifestations were blurred vision, photophobia, diplopia, weakness and clumsiness of the right hand. The result of systemic and neurological examinations was normal, except for a positive right hand drift test. MRI showed a large lobulated mass with peripheral edema, central necrosis and a heterogenous enhancement at the central part of the parietal lobe inducing to subfalcian herniation. Glioblastoma multiforms (GBM was misdiagnosed for the patient on the basis of MRI appearance. Pathology evaluation was compatible with meningioma (WHO grade I to II. The patient was operated and discharged with minimal right hand weakness. Physiotherapy was recommended to improve the remaining problems. "nConclusion: Atypical meningiomas may mimic other intracranical brain lesions and may cause misdiagnosis. It is important to be aware of these features in order to avoid misdiagnosis. "n"n  

  7. INCREASING FOOD CHAIN SECURITY FOR SCRAPIE BY MARKER ASSISTED SELECTION IN SHEEP POPULATIONS

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    VIORICA COŞIER

    2013-12-01

    Full Text Available Romania, by its genetic found made up of over 7.4 millions sheep and 1.8 millionsyoung sheep exported in EU countries, represents an important mark in bothEuropean and World sheep breeding sector, in last years marked by many ESSTcenters. The apparition of this disease and its high risk of danger for reared effectiveconstraint EEC countries to interfere by law regulations concerning scrapie controland stopping disease spreading. In our country, controls identified the presence ofscrapie in livestock. The international reference laboratories post mortem certifiedthe presence of disease. Immunohistochemical detection of PrPSc is a standarddiagnostic method for sheep scrapie. By immunohistochemistry (IHC, PrPSc isdetected in lymphoid tissues during preclinical and clinical disease. Aftergenotypization at PrnP locus, the marker assisted selection is compulsory, and flocksinclude only genotypes with high disease resistance.

  8. INCREASING FOOD CHAIN SECURITY FOR SCRAPIE BY MARKER ASSISTED SELECTION IN SHEEP POPULATIONS

    Directory of Open Access Journals (Sweden)

    COŞIER VIORICA

    2007-01-01

    Full Text Available Romania, by its genetic found made up of over 7.4 millions sheep and 1.8 millionsyoung sheep exported in EU countries, represents an important mark in bothEuropean and World sheep breeding sector, in last years marked by many ESSTcenters. The apparition of this disease and its high risk of danger for reared effectiveconstraint EEC countries to interfere by law regulations concerning scrapie controland stopping disease spreading. In our country, controls identified the presence ofscrapie in livestock. The international reference laboratories post mortem certifiedthe presence of disease. Immunohistochemical detection of PrPSc is a standarddiagnostic method for sheep scrapie. By immunohistochemistry (IHC, PrPSc isdetected in lymphoid tissues during preclinical and clinical disease. Aftergenotypization at PrnP locus, the marker assisted selection is compulsory, and flocksinclude only genotypes with high disease resistance.

  9. Distribution of Peripheral PrPSc in Sheep with Naturally Acquired Scrapie

    Science.gov (United States)

    Garza, María Carmen; Monzón, Marta; Marín, Belén; Badiola, Juan José; Monleón, Eva

    2014-01-01

    Accumulation of prion protein (PrPSc) in the central nervous system is the hallmark of transmissible spongiform encephalopathies. However, in some of these diseases such as scrapie or chronic wasting disease, the PrPSc can also accumulate in other tissues, particularly in the lymphoreticular system. In recent years, PrPSc in organs other than nervous and lymphoid have been described, suggesting that distribution of this protein in affected individuals may be much larger than previously thought. In the present study, 11 non-nervous/non-lymphoid organs from 16 naturally scrapie infected sheep in advanced stages of the disease were examined for the presence of PrPSc. Fourteen infected sheep were of the ARQ/ARQ PRNP genotype and 2 of the VRQ/VRQ, where the letters A, R, Q, and V represent the codes for amino-acids alanine, arginine, glutamine and valine, respectively. Adrenal gland, pancreas, heart, skin, urinary bladder and mammary gland were positive for PrPSc by immunohistochemistry and IDEXX HerdChek scrapie/BSE Antigen EIA Test in at least one animal. Lung, liver, kidney and skeletal muscle exhibited PrPSc deposits by immunohistochemistry only. To our knowledge, this is the first report regarding the presence of PrPSc in the heart, pancreas and urinary bladder in naturally acquired scrapie infections. In some other organs examined, in which PrPSc had been previously detected, PrPSc immunolabeling was observed to be associated with new structures within those organs. The results of the present study illustrate a wide dissemination of PrPSc in both ARQ/ARQ and VRQ/VRQ infected sheep, even when the involvement of the lymphoreticular system is scarce or absent, thus highlighting the role of the peripheral nervous system in the spread of PrPSc. PMID:24828439

  10. Scrapie affects the maturation cycle and immune complex trapping by follicular dendritic cells in mice.

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    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrP(d accumulations in the brain and lymphoreticular system (LRS. Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrP(d accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs and tingible body macrophages (TBMs. Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrP(d plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrP(d accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrP(d. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrP(d accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function.

  11. Distribution of peripheral PrP(Sc in sheep with naturally acquired scrapie.

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    María Carmen Garza

    Full Text Available Accumulation of prion protein (PrPSc in the central nervous system is the hallmark of transmissible spongiform encephalopathies. However, in some of these diseases such as scrapie or chronic wasting disease, the PrPSc can also accumulate in other tissues, particularly in the lymphoreticular system. In recent years, PrPSc in organs other than nervous and lymphoid have been described, suggesting that distribution of this protein in affected individuals may be much larger than previously thought. In the present study, 11 non-nervous/non-lymphoid organs from 16 naturally scrapie infected sheep in advanced stages of the disease were examined for the presence of PrPSc. Fourteen infected sheep were of the ARQ/ARQ PRNP genotype and 2 of the VRQ/VRQ, where the letters A, R, Q, and V represent the codes for amino-acids alanine, arginine, glutamine and valine, respectively. Adrenal gland, pancreas, heart, skin, urinary bladder and mammary gland were positive for PrPSc by immunohistochemistry and IDEXX HerdChek scrapie/BSE Antigen EIA Test in at least one animal. Lung, liver, kidney and skeletal muscle exhibited PrPSc deposits by immunohistochemistry only. To our knowledge, this is the first report regarding the presence of PrPSc in the heart, pancreas and urinary bladder in naturally acquired scrapie infections. In some other organs examined, in which PrPSc had been previously detected, PrPSc immunolabeling was observed to be associated with new structures within those organs. The results of the present study illustrate a wide dissemination of PrPSc in both ARQ/ARQ and VRQ/VRQ infected sheep, even when the involvement of the lymphoreticular system is scarce or absent, thus highlighting the role of the peripheral nervous system in the spread of PrPSc.

  12. Evidence of effective scrapie transmission via colostrum and milk in sheep

    OpenAIRE

    Konold, T.; Moore, SJ; Bellworthy, SJ; Terry, LA; Thorne, L.; Ramsay, A.; Salguero, FJ; Simmons, MM; Simmons, HA

    2013-01-01

    Background: Evidence for scrapie transmission from VRQ/VRQ ewes to lambs via milk was first reported in 2008 but in that study there were concerns that lateral transmission may have contributed to the high transmission rate observed since five control lambs housed with the milk recipients also became infected. This report provides further information obtained from two follow-up studies, one where milk recipients were housed separately after milk consumption to confirm the validity of the high...

  13. Differential gene expression and apoptosis markers in presymptomatic scrapie affected sheep.

    Science.gov (United States)

    Hedman, Carlos; Lyahyai, Jaber; Filali, Hicham; Marín, Belén; Serrano, Carmen; Monleón, Eva; Moreno, Bernardino; Zaragoza, Pilar; Badiola, Juan José; Martín-Burriel, Inmaculada; Bolea, Rosa

    2012-09-14

    Neuronal loss is one of the characteristics of scrapie neuropathology. Previous analysis of brains from sheep naturally infected with scrapie that were in a terminal stage did not detect a clear induction of apoptosis, although molecular changes were evidenced. As neuronal death could be occurring early in scrapie, we developed a neuropathological and gene expression study of sheep infected with scrapie in a presymptomatic stage. The histopathology, immunolabelling of PrP(Sc), Bax and activated caspase-3, and the analysis of the expression of 7 genes involved in the regulation of the mitochondrial pathway of apoptosis were investigated in the following 4 central nervous system areas: medulla oblongata, diencephalon, frontal cortex and cerebellum. Moreover, TUNEL and NeuN immunolabelling was performed in the medulla oblongata. The PrP(Sc) immunolabelling in the four areas, as well as a neuropil spongiform change, were more evident in the terminal stage than in presymptomatic animals. Cytoplasmic Bax immunostaining was observed in the presymptomatic medulla oblongata. In contrast to symptomatic animals, the immunostaining was not extended to the hypothalamus, indicating the progression of Bax induction during the course of the disease. Although neither caspase-3 immunostaining nor the TUNEL technique detected neurons with apoptosis, NeuN-immunolabelled cell counting determined that presymptomatic animals have already suffered neuronal loss in a lower or equal degree than symptomatic animals. Finally, the gene expression profiles indicated that the mitochondrial pathway of apoptosis was activated with higher intensity in presymptomatic animals than in symptomatic sheep and confirmed the implication of genes such as BAX or AIF in the disease.

  14. Distribution of peripheral PrP(Sc) in sheep with naturally acquired scrapie.

    Science.gov (United States)

    Garza, María Carmen; Monzón, Marta; Marín, Belén; Badiola, Juan José; Monleón, Eva

    2014-01-01

    Accumulation of prion protein (PrPSc) in the central nervous system is the hallmark of transmissible spongiform encephalopathies. However, in some of these diseases such as scrapie or chronic wasting disease, the PrPSc can also accumulate in other tissues, particularly in the lymphoreticular system. In recent years, PrPSc in organs other than nervous and lymphoid have been described, suggesting that distribution of this protein in affected individuals may be much larger than previously thought. In the present study, 11 non-nervous/non-lymphoid organs from 16 naturally scrapie infected sheep in advanced stages of the disease were examined for the presence of PrPSc. Fourteen infected sheep were of the ARQ/ARQ PRNP genotype and 2 of the VRQ/VRQ, where the letters A, R, Q, and V represent the codes for amino-acids alanine, arginine, glutamine and valine, respectively. Adrenal gland, pancreas, heart, skin, urinary bladder and mammary gland were positive for PrPSc by immunohistochemistry and IDEXX HerdChek scrapie/BSE Antigen EIA Test in at least one animal. Lung, liver, kidney and skeletal muscle exhibited PrPSc deposits by immunohistochemistry only. To our knowledge, this is the first report regarding the presence of PrPSc in the heart, pancreas and urinary bladder in naturally acquired scrapie infections. In some other organs examined, in which PrPSc had been previously detected, PrPSc immunolabeling was observed to be associated with new structures within those organs. The results of the present study illustrate a wide dissemination of PrPSc in both ARQ/ARQ and VRQ/VRQ infected sheep, even when the involvement of the lymphoreticular system is scarce or absent, thus highlighting the role of the peripheral nervous system in the spread of PrPSc.

  15. PrP genotype frequencies and risk evaluation for scrapie in dairy sheep breeds from southern Italy.

    Science.gov (United States)

    Martemucci, Giovanni; Iamartino, Daniela; Blasi, Michele; D'Alessandro, Angela Gabriella

    2015-12-01

    Concerns regarding scrapie in sheep breeding have increased in the last few decades. The present study was carried out in dairy sheep breeds from southern Italy. In order to find breeding animals resistant to scrapie, the PrP genes of 1,205 animals from entire flocks of dairy native Apulian Leccese and Altamurana breeds, and Sicilian Comisana breed, were analysed for polymorphisms at codons 136, 154, and 171 related to scrapie resistance/susceptibility. The Altamurana breed was considered as two populations (Alt-Cav and Alt-Cra-Zoe), based on presumed cross-breeding. A total of five alleles and ten different genotypes were found. The ARQ allele was predominant for all breeds followed by ARR, the most resistant allele to scrapie, which was highly prevalent in Comisana (50%) and in native Alt-Cav (42.4%). The VRQ allele, associated with the highest susceptibility to scrapie, was detected at not negligeable levels in allocthonous Comisana (3.5%), at a low frequency (0.2%) in native Leccese and Alt-Cra-Zoe, while it was absent in Alt-Cav. The frequencies of PrP genotypes with a very low susceptibility risk to scrapie (R1) was higher in Comisana and Alt-Cav. The most susceptible genotype, ARQ/VRQ, was found only in Comisana. Within the Altamurana breed, there were notable differences between Alt-Cav and Alt-Cra-Zoe sheep. The Alt-Cav was characterised by the absence of VRQ and AHQ alleles and by the higher frequency of the ARR/ARR genotype (18.7%). Breeding programs, mainly in endangered breeds such as Altamurana, should be conducted gradually, combining resistance to scrapie, maintenance of genetic variability, and production.

  16. A bovine cell line that can be infected by natural sheep scrapie prions.

    Science.gov (United States)

    Oelschlegel, Anja M; Geissen, Markus; Lenk, Matthias; Riebe, Roland; Angermann, Marlies; Schatzl, Herman; Schaetzl, Hermann; Groschup, Martin H

    2015-01-01

    Cell culture systems represent a crucial part in basic prion research; yet, cell lines that are susceptible to prions, especially to field isolated prions that were not adapted to rodents, are very rare. The purpose of this study was to identify and characterize a cell line that was susceptible to ruminant-derived prions and to establish a stable prion infection within it. Based on species and tissue of origin as well as PrP expression rate, we pre-selected a total of 33 cell lines that were then challenged with natural and with mouse propagated BSE or scrapie inocula. Here, we report the successful infection of a non-transgenic bovine cell line, a sub-line of the bovine kidney cell line MDBK, with natural sheep scrapie prions. This cell line retained the scrapie infection for more than 200 passages. Selective cloning resulted in cell populations with increased accumulation of PrPres, although this treatment was not mandatory for retaining the infection. The infection remained stable, even under suboptimal culture conditions. The resulting infectivity of the cells was confirmed by mouse bioassay (Tgbov mice, Tgshp mice). We believe that PES cells used together with other prion permissive cell lines will prove a valuable tool for ongoing efforts to understand and defeat prions and prion diseases.

  17. A bovine cell line that can be infected by natural sheep scrapie prions.

    Directory of Open Access Journals (Sweden)

    Anja M Oelschlegel

    Full Text Available Cell culture systems represent a crucial part in basic prion research; yet, cell lines that are susceptible to prions, especially to field isolated prions that were not adapted to rodents, are very rare. The purpose of this study was to identify and characterize a cell line that was susceptible to ruminant-derived prions and to establish a stable prion infection within it. Based on species and tissue of origin as well as PrP expression rate, we pre-selected a total of 33 cell lines that were then challenged with natural and with mouse propagated BSE or scrapie inocula. Here, we report the successful infection of a non-transgenic bovine cell line, a sub-line of the bovine kidney cell line MDBK, with natural sheep scrapie prions. This cell line retained the scrapie infection for more than 200 passages. Selective cloning resulted in cell populations with increased accumulation of PrPres, although this treatment was not mandatory for retaining the infection. The infection remained stable, even under suboptimal culture conditions. The resulting infectivity of the cells was confirmed by mouse bioassay (Tgbov mice, Tgshp mice. We believe that PES cells used together with other prion permissive cell lines will prove a valuable tool for ongoing efforts to understand and defeat prions and prion diseases.

  18. Effect of chemicals, heat, and histopathologic processing on high-infectivity hamster-adapted scrapie virus.

    Science.gov (United States)

    Brown, P; Rohwer, R G; Green, E M; Gajdusek, D C

    1982-05-01

    High-titered (greater than 10(10) LD50 [50% lethal dose[/g) preparations of scrapie virus-infected hamster brain were subjected to inactivation by various chemicals, autoclaving, and histopathologic processing. Sodium hypochlorite, which reduced infectivity by approximately 4 log LD50/g of brain (99.99%), was somewhat superior to sodium metaperiodate and clearly superior to chlorine dioxide, Lysol (National Laboratories, Montvale, N.J.), iodine, potassium permanganate, and hydrogen peroxide. Most inactivation occurred within 15-30 min of exposure to a chemical, and little if any additional inactivation occurred after 1 hr. Brains processed for histopathologic examination (formalin fixation followed by dehydration in methanol, clearing in chloroform, and embedding in paraffin) retained greater than or equal to 6.8 log LD50/g of the infectivity present in unprocessed control tissues (9.6 log LD50/g). One hour in an autoclave at 121 C reduced the titer of scrapie virus by approximately 7.5 log LD50/g of brain but left 2.5 log LD50/g of residual infectivity. A combination of exposure to chemicals and autoclaving may be necessary to sterilize high-titered scrapie virus-infected tissue.

  19. Gene expression alterations in brains of mice infected with three strains of scrapie

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    Race Richard E

    2006-05-01

    Full Text Available Abstract Background Transmissible spongiform encephalopathies (TSEs or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD in humans, bovine spongiform encephalopathy (BSE in cattle, chronic wasting disease (CWD in deer and elk, and scrapie in sheep, and experimental mice. To gain insights into TSE pathogenesis, we made and used cDNA microarrays to identify disease-associated alterations in gene expression. Brain gene expression in scrapie-infected mice was compared to mock-infected mice at pre-symptomatic and symptomatic time points. Three strains of mouse scrapie that show striking differences in neuropathology were studied: ME7, 22L, and Chandler/RML. Results In symptomatic mice, over 400 significant gene expression alterations were identified. In contrast, only 22 genes showed significant alteration in the pre-symptomatic animals. We also identified genes that showed significant differences in alterations in gene expression between strains. Genes identified in this study encode proteins that are involved in many cellular processes including protein folding, endosome/lysosome function, immunity, synapse function, metal ion binding, calcium regulation and cytoskeletal function. Conclusion These studies shed light on the complex molecular events that occur during prion disease, and identify genes whose further study may yield new insights into strain specific neuropathogenesis and ante-mortem tests for TSEs.

  20. Treatment options for atypical optic neuritis

    Directory of Open Access Journals (Sweden)

    Amina Malik

    2014-01-01

    Full Text Available Context: Optic neuritis (ON is defined as inflammation of the optic nerve and can have various etiologies. The most common presentation in the US is demyelinating, or "typical" ON, usually associated with multiple sclerosis. This is in contrast to "atypical" causes of ON, which differ in their clinical presentation, management, and prognosis. These atypical cases are characterized by lack of eye pain, exudates, and hemorrhages on exam, very severe, bilateral or progressive visual loss, or with failure to recover vision. Aims: The aim was to describe the clinical presentations of atypical ON and their treatments. Settings and Design: Review article. Materials and Methods: Literature review. Results: Types of atypical ON identified include neuromyelitis optica, autoimmune optic neuropathy, chronic relapsing inflammatory optic neuropathy, idiopathic recurrent neuroretinitis, and optic neuropathy associated with systemic diseases. Atypical ON usually requires corticosteroid treatment and often will require aggressive immunosuppression. Conclusions: Unlike demyelinating ON, atypical ON requires treatment to preserve vision.

  1. Comparison of detergent and protease enzyme combinations for the detection of scrapie-associated fibrils from the central nervous system of sheep naturally affected with scrapie.

    Science.gov (United States)

    Stack, M J; Aldrich, A M; Davis, L A

    1997-02-01

    Standardized samples of tissue from the central nervous system of four sheep naturally affected with scrapie and from four healthy control sheep were subjected to a centrifugal extraction technique used to obtain scrapie-associated fibrils; the latter were then demonstrated by negative-contrast transmission electron microscopy. This regime was used to evaluate the fibril yield obtained from the 25 possible combinations of five different detergents and five different proteolytic enzymes. N-lauroylsarcosine detergent was found to be the most efficient detergent for all five enzymes, followed by sulphabetaine 3-14. Sodium dodecyl sulphate detergent was successful only in combination with a subtilisin Carlsberg enzyme. Octylglucoside and nonidet P40 detergents did not produce fibrils with any of the enzymes. Proteinase K was the least efficient of the five enzymes when used in combination with N-lauroylsarcosine; subtilisin Carlsberg, clostripain, pronase and trypsin enzymes all gave higher fibril yields. A combination of N-lauroylsarcosine detergent and subtilisin Carlsberg proteolytic enzyme gave the highest fibril yield.

  2. Scrapie infectivity is quickly cleared in tissues of orally-infected farmed fish

    Directory of Open Access Journals (Sweden)

    Faoro Franco

    2006-06-01

    Full Text Available Abstract Background Scrapie and bovine spongiform encephalopathy (BSE belongs to the group of animal transmissible spongiform encephalopathy (TSE. BSE epidemic in the UK and elsewhere in Europe has been linked to the use of bovine meat and bone meals (MBM in the feeding of cattle. There is concern that pigs, poultry and fish bred for human consumption and fed with infected MBM would eventually develop BSE or carry residual infectivity without disease. Although there has been no evidence of infection in these species, experimental data on the susceptibility to the BSE agent of farm animals other than sheep and cow are limited only to pigs and domestic chicken. In the framework of a EU-granted project we have challenged two species of fish largely used in human food consumption, rainbow trout (Oncorhynchus mykiss and turbot (Scophthalmus maximus, with a mouse-adapted TSE strain (scrapie 139A, to assess the risk related to oral consumption of TSE contaminated food. In trout, we also checked the "in vitro" ability of the pathological isoform of the mouse prion protein (PrPSc to cross the intestinal epithelium when added to the mucosal side of everted intestine. Results Fish challenged with a large amount of scrapie mouse brain homogenate by either oral or parenteral routes, showed the ability to clear the majority of infectivity load. None of the fish tissues taken at different time points after oral or parenteral inoculation was able to provoke scrapie disease after intracerebral inoculation in recipient mice. However, a few recipient mice were positive for PrPSc and spongiform lesions in the brain. We also showed a specific binding of PrPSc to the mucosal side of fish intestine in the absence of an active uptake of the prion protein through the intestinal wall. Conclusion These results indicate that scrapie 139A, and possibly BSE, is quickly removed from fish tissues despite evidence of a prion like protein in fish and of a specific binding of Pr

  3. The evolution of the prevalence of classical scrapie in sheep in Great Britain using surveillance data between 2005 and 2012.

    Science.gov (United States)

    Arnold, Mark; Ortiz-Pelaez, Angel

    2014-11-01

    After the decline of the Bovine Spongiform Encephalopathy (BSE) epidemic in Great Britain (GB), scrapie remains the most prevalent animal Transmissible Spongiform Encephalopathy (TSE) present in GB. A number of control measures have been implemented for classical scrapie, and since 2005 there has been a large reduction in the number of observed cases. The objective of this study is to estimate two measures of disease frequency using up to date surveillance data collected during and after the implementation of different control measures established since 2004, and breeding for resistance schemes that ran from 2001 until 2009. This would enable an assessment of the effectiveness of both the breeding for resistance programme and the compulsory eradication measures in reducing the prevalence of scrapie in GB. Evaluation of the sensitivity of the rapid post-mortem test for scrapie indicated that it detected scrapie in the last 25% of the incubation period. A back-calculation model was developed to estimate the prevalence of infection at animal and flock-level. The results of the model indicated a mean drop of infection prevalence of 31% each year, leading to a 90% drop in infection prevalence between 2005, with an estimate of 5737 infected sheep in GB in 2012. The risks of classical scrapie infection in animals with genotypes of National Scrapie Plan Types I-IV (all other genotypes), relative to Type V (all genotypes containing V136 R154 Q171 and not A136 R154 R171), were estimated to be: 0, 0.0008, 0.07, and 0.21 respectively. The model estimated a very low rate of reporting of clinical suspects and a large decline from 2007 of the probability of a sheep being reported as a clinical suspect. The model also estimated that the expected number of sheep holdings with classical scrapie in 2012 was 215 (95% confidence interval: 33-437), out of a total of approximately 72,000 sheep holdings in GB. Model estimates indicate that the prevalence in 2012 has dropped to 10% of that

  4. Morphological changes in atypical bird's foot trefoil plants obtained during genetic transformation by agrobacterium

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    Nikolić Radomirka R.

    2003-01-01

    Full Text Available Atypical plants of bird's foot trefoil (Lotus corniculatus L., Bokor cv showing altered morphological characters that deviate from a normal phenotype were found after plant regeneration from transformed tissue. It had been obtained by genetic transformation of root sections of seedlings using Agrobacterium tumefaciens vector LBA4404/pBI121 on a medium supplemented with 0.2 mg I-1 BAP. The transformants 2b arid 4a were found to have a greatly atypical habit, including shortened internodes, elongated leaves, regular leaf arrangement along the stem and thicker leaves. Inheritance of altered characters was observed in the first progeny generation, and their genetic origin was considered.

  5. A Bayesian framework to assess the potential for controlling classical scrapie in sheep flocks using a live diagnostic test.

    Science.gov (United States)

    Gryspeirt, Aiko; Gubbins, Simon

    2013-09-01

    Current strategies to control classical scrapie remove animals at risk of scrapie rather than those known to be infected with the scrapie agent. Advances in diagnostic tests, however, suggest that a more targeted approach involving the application of a rapid live test may be feasible in future. Here we consider the use of two diagnostic tests: recto-anal mucosa-associated lymphatic tissue (RAMALT) biopsies; and a blood-based assay. To assess their impact we developed a stochastic age- and prion protein (PrP) genotype-structured model for the dynamics of scrapie within a sheep flock. Parameters were estimated in a Bayesian framework to facilitate integration of a number of disparate datasets and to allow parameter uncertainty to be incorporated in model predictions. In small flocks a control strategy based on removal of clinical cases was sufficient to control disease and more stringent measures (including the use of a live diagnostic test) did not significantly reduce outbreak size or duration. In medium or large flocks strategies in which a large proportion of animals are tested with either live diagnostic test significantly reduced outbreak size, but not always duration, compared with removal of clinical cases. However, the current Compulsory Scrapie Flocks Scheme (CSFS) significantly reduced outbreak size and duration compared with both removal of clinical cases and all strategies using a live diagnostic test. Accordingly, under the assumptions made in the present study there is little benefit from implementing a control strategy which makes use of a live diagnostic test.

  6. Cell-surface expression of PrPC and the presence of scrapie prions in the blood of goats.

    Science.gov (United States)

    Dassanayake, Rohana P; Schneider, David A; Herrmann-Hoesing, Lynn M; Truscott, Thomas C; Davis, William C; O'Rourke, Katherine I

    2012-05-01

    Although host-encoded prion protein (PrP(C)) expression in ovine PBMCs and prion infectivity in scrapie-infected sheep blood have been demonstrated, such studies have not been reported in goats. Therefore, this study characterized cell-surface expression of PrP(C) on PBMC subsets derived from normal goats and sheep, by flow cytometry, and determined prion infectivity in blood from a scrapie-infected goat using a transfusion bioassay in goat kids. Cell-surface PrP(C) expression was detected on all subsets of goat PBMCs. The highest PrP(C) cell-surface expression was found in CD2(+) T lymphocytes in goats. Transmission of infection was detected in all three recipients who received whole blood from a goat with classical scrapie. It was concluded that caprine PBMCs express PrP(C) similarly to sheep but with relative differences among PBMCs subsets, and that blood-borne infectious prions can be detected in scrapie-infected goats. Thus, similar to sheep, goat blood may be a suitable diagnostic target for the detection of scrapie infection.

  7. Allelic variants at codon 146 in the PRNP gene show significant differences in the risk for natural scrapie in Cypriot goats.

    Science.gov (United States)

    Ortiz-Pelaez, A; Georgiadou, S; Simmons, M M; Windl, O; Dawson, M; Arnold, M E; Neocleous, P; Papasavva-Stylianou, P

    2015-04-01

    Previous studies have shown the association between the polymorphisms serine (S) or aspartic acid (D) at codon 146 of the PRNP gene and resistance to scrapie. All goats aged >12 months (a total of 1075 animals) from four herds with the highest prevalence of scrapie in the country were culled and tested, of which 234 (21·7%) were positive by either the rapid test or immunohistochemistry (IHC) for any of the tissues tested. The odds of scrapie infection occurring in NN146 goats was 101 [95% credible interval (CrI) 19-2938] times higher than for non-NN146 or unknown genotypes. IHC applied to lymphoreticular tissue produced the highest sensitivity (94%, 95% CrI 90-97). The presence of putatively resistant non-NN146 alleles in the Cypriot goat population, severely affected by scrapie, provides a potential tool to reduce/eradicate scrapie provided that coordinated nationwide breeding programmes are implemented and maintained over time.

  8. Short-term study of the uptake of PrPSc by the Peyer’s patches in hamsters after oral exposure to scrapie

    DEFF Research Database (Denmark)

    Bergström, Ann-Louise; Jensen, Tim Kåre; Heegaard, Peter M. H.;

    2006-01-01

    The disease-associated prion protein (PrPSc) has been detected in the ileal Peyer's patches of lambs as early as one week after oral exposure to scrapie. In hamsters, the earliest reported time of PrPSc detection in the Peyer's patches after oral exposure to scrapie is 69 days post......-infection. To evaluate the acute uptake of inoculum and to investigate whether the Peyer's patches constitute the primary site of entry for scrapie after oral exposure, hamsters were each exposed orally to 1 ml of a 10% brain homogenate from hamsters in the terminal stage of infection with the 263 K strain...... of the scrapie agent. PrPSc was demonstrated in the Peyer's patches only a few days after exposure, i.e., much earlier than previously reported. This study Supports the view that the Peyer's patches constitute at least one of the primary entry sites of PrPSc after oral exposure to scrapie....

  9. Atypical Manifestation of Vestibular Schwannoma

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    Webster, Guilherme

    2013-09-01

    Full Text Available Introduction: Vestibular schwannoma (also known as acoustic neuroma is a benign tumor whose cells are derived from Schwann sheaths, which commonly occurs from the vestibular portion of the eighth cranial nerve. Furthermore, vestibular schwannomas account for ∼8% of intracranial tumors in adults and 80 to 90% of tumors of the cerebellopontine angle. Its symptoms are varied, but what stands out most is a unilateral sensorineural hearing loss, with a low index of speech recognition. Objective: Describe an atypical manifestation of vestibular schwannoma. Case Report: The 46-year-old woman had vertigo and binaural hearing loss and fullness, with ear, nose, and throat examination suggestive of cochlear injury. After 6 months, the patient developed worsening of symptoms and onset of right unilateral tinnitus. In further exams the signs of cochlear damage remained, except for the vestibular test (hyporeflexia. Magnetic resonance imaging showed an expansive lesion in the right cerebellopontine angle. Discussion: This report warns about the atypical manifestations of vestibular schwannoma, which must always be remembered in investigating and diagnosing hearing loss.

  10. Mouse-adapted scrapie strains 139A and ME7 overcome species barrier to induce experimental scrapie in hamsters and changed their pathogenic features

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    Shi Qi

    2012-03-01

    Full Text Available Abstract Background Transmissible spongiform encephalopathy (TSE diseases are known to be zoonotic diseases that can infect different kinds of animals. The transmissibility of TSE, like that of other infectious diseases, shows marked species barrier, either being unable to infect heterologous species or difficult to form transmission experimentally. The similarity of the amino acid sequences of PrP among species is believed to be one of the elements in controlling the transmission TSE interspecies. Other factors, such as prion strains and host's microenvironment, may also participate in the process. Methods Two mouse-adapted strains 139A and ME7 were cerebrally inoculated to Golden hamsters. Presences of scrapie associate fibril (SAF and PrPSc in brains of the infected animals were tested by TEM assays and Western blots dynamically during the incubation periods. The pathogenic features of the novel prions in hamsters, including electrophoretic patterns, glycosylating profiles, immunoreactivities, proteinase K-resistances and conformational stabilities were comparatively evaluated. TSE-related neuropathological changes were assayed by histological examinations. Results After long incubation times, mouse-adapted agents 139A and ME7 induced experimental scrapie in hamsters, respectively, showing obvious spongiform degeneration and PrPSc deposits in brains, especially in cortex regions. SAF and PrPSc in brains were observed much earlier than the onset of clinical symptoms. The molecular characteristics of the newly-formed PrPSc in hamsters, 139A-ha and ME7-ha, were obviously distinct from the original mouse agents, however, greatly similar as that of a hamster-adapted scrapie strain 263 K. Although the incubation times and main disease signs of the hamsters of 139A-ha and ME7-ha were different, the pathogenic characteristics and neuropathological changes were highly similar. Conclusions This finding concludes that mouse-adapted agents 139A and ME7

  11. Atypical Presentation of Atypical Teratoid Rhabdoid Tumor in a Child

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    Y. T. Udaka

    2013-01-01

    Full Text Available Atypical Teratoid Rhabdoid Tumor (ATRT is a rare malignant intracranial neoplasm more commonly diagnosed in young children. The authors report the case of an 11-year-old boy with a long standing history of slowly progressive weight loss, fatigue, and weakness over 1.5 years whose magnetic resonance imaging revealed a large heterogeneous enhancing dorsally exophytic lower brainstem mass. Examination revealed extreme cachexia, gaze-evoked nystagmus, dysphagia, dysarthria, bilateral dysmetria, and global weakness without ambulation. The protracted history and neuroimaging features were most suggestive of a low grade glioma. However, pathology revealed a hypercellular tumor with large hyperchromatic nucleoli and loss of INI-1 staining on immunohistochemistry consistent with a diagnosis of an ATRT. The child died shortly after surgery due to complications from his brainstem infiltrative disease. This case illustrates the diverse presentation of ATRT in childhood that can clinically and radiographically mimic that of low grade glioma.

  12. Scrapie Agent (Strain 263K can transmit disease via the oral route after persistence in soil over years.

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    Bjoern Seidel

    Full Text Available The persistence of infectious biomolecules in soil constitutes a substantial challenge. This holds particularly true with respect to prions, the causative agents of transmissible spongiform encephalopathies (TSEs such as scrapie, bovine spongiform encephalopathy (BSE, or chronic wasting disease (CWD. Various studies have indicated that prions are able to persist in soil for years without losing their pathogenic activity. Dissemination of prions into the environment can occur from several sources, e.g., infectious placenta or amniotic fluid of sheep. Furthermore, environmental contamination by saliva, excrements or non-sterilized agricultural organic fertilizer is conceivable. Natural transmission of scrapie in the field seems to occur via the alimentary tract in the majority of cases, and scrapie-free sheep flocks can become infected on pastures where outbreaks of scrapie had been observed before. These findings point to a sustained contagion in the environment, and notably the soil. By using outdoor lysimeters, we simulated a contamination of standard soil with hamster-adapted 263K scrapie prions, and analyzed the presence and biological activity of the soil-associated PrP(Sc and infectivity by Western blotting and hamster bioassay, respectively. Our results showed that 263K scrapie agent can persist in soil at least over 29 months. Strikingly, not only the contaminated soil itself retained high levels of infectivity, as evidenced by oral administration to Syrian hamsters, but also feeding of aqueous soil extracts was able to induce disease in the reporter animals. We could also demonstrate that PrP(Sc in soil, extracted after 21 months, provides a catalytically active seed in the protein misfolding cyclic amplification (PMCA reaction. PMCA opens therefore a perspective for considerably improving the detectability of prions in soil samples from the field.

  13. Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of scrapie.

    Science.gov (United States)

    Greenlee, Justin J; Kunkle, Robert A; Richt, Jürgen A; Nicholson, Eric M; Hamir, Amir N

    2014-01-01

    Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. The purpose of this study was to compare the survival time and PrPSc tissue distribution in sheep with highly resistant and highly susceptible PRNP genotypes after intracranial inoculation of the agent of scrapie. Five sheep each of genotype VRQ/VRQ, VRQ/ARR or ARQ/ARR were inoculated. Sheep were euthanized when clinical signs of scrapie became severe. Clinical signs, microscopic lesions, and western blot profiles were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the 171 polymorphic site with VRQ/VRQ sheep surviving 18 months, whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively. Labeling of PrPSc by immunohistochemistry revealed similar accumulations in central nervous system tissues regardless of host genotype. Immunoreactivity for PrPSc in lymphoid tissue was consistently abundant in VRQ/VRQ, present but confined to tonsil or retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep. The results of this study demonstrate the susceptibility of sheep with the ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in lymphoid tissue.

  14. Atypical presentations of celiac disease

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    Balasa Adriana Luminita

    2016-08-01

    Full Text Available In this study we evaluated the association of celiac disease in 81 children with autoimmune disease and genetic syndromes over a two years periods (January 2014 to July 2016 in Pediatric Clinic in Constanta. Because the extraintestinal symptoms are an atypical presentation of celiac disease we determined in these children the presence of celiac disease antibodies: Anti-tissue Transglutaminase Antibody IgA and IgA total serum level as a screening method followeds in selective cases by Anti-tissue Transglutaminase Antibody IgG, anti-endomysial antibodies, deamidated gliadin antibodies IgA and IgG and intestinal biopsia. In our study 8 patients had been diagnosed with celiac disease with extraintestinal symptoms, of which 4 with type 1 diabetes, 1 patient with ataxia, 2 patients with dermatitis herpetiformis and 1 patient with Down syndrome that associate also autoimmune thyroiditis, alopecia areata, enamel hypoplasia.

  15. Atypical BSE in Germany--proof of transmissibility and biochemical characterization.

    Science.gov (United States)

    Buschmann, A; Gretzschel, A; Biacabe, A-G; Schiebel, K; Corona, C; Hoffmann, C; Eiden, M; Baron, T; Casalone, C; Groschup, Martin H

    2006-10-31

    Intensive active surveillance has uncovered two atypical German BSE cases in older cattle which resemble the two different atypical BSE phenotypes that have recently been described in France (designated H-type) and Italy (designated L-type or BASE). The H-type is characterized by a significantly higher molecular size, but a conventional glycopattern of the proteinase K treated abnormal prion protein (PrP(Sc)), while the L-type PrP(Sc) has only a slightly lower molecular size and a distinctly different glycopattern. In this paper we describe the successful transmission of both German atypical BSE cases to transgenic mice overexpressing bovine PrP(C). Upon challenge with the L-type, these mice developed BSE after a substantially shorter incubation period than any classical BSE transmission using these mice to date. In contrast, the incubation period was distinctly prolonged when these mice were challenged with the H-type. PrP(Sc) accumulated in the brains of these mice were of the same atypical BSE type that had been used for the transmission. These atypical cases suggest the possible existence of sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in the UK could have also been initiated by an intraspecies transmission from a sporadic BSE case.

  16. Pseudoarthrosis in atypical femoral fracture: case report.

    Science.gov (United States)

    Giannotti, S; Bottai, V; Dell'Osso, G; De Paola, G; Ghilardi, M; Guido, G

    2013-11-01

    Atypical femoral fractures can be subsequent to a long-term biphosphonates treatment; they have a high frequency of delayed healing. The authors describe a femoral pseudoarthrosis of an atypical fracture treated with intramedullary nailing in a female after prolonged alendronate therapy. Atypical femoral fractures can be subsequent to a long-term biphosphonates treatment even if, in the literature, there is no clarity on the exact pathogenetic mechanism. The Task Force of the American Society for Bone and Mineral Research described the major and minor features to define atypical fractures and recommends that all the five major features must be present while minor features are not necessary. Another controversial aspect regarding the atypical femoral fractures is the higher frequency of the delayed healing that can be probably related to a suppressed bone turnover caused by a prolonged period of bisphosphonates treatment. This concept could be corroborated by the Spet Tc exam. In the case of a pseudoarthrosis, there is not a standardization of the treatment. In this report, the authors describe a femoral pseudoarthrosis of an atypical fracture treated with intramedullary nailing in a female after prolonged alendronate therapy; the patient was studied with clinical, bioumoral end SPECT-Tc exam of both femurs. Many studies show the relationship between bisphosphonates and the presence of atypical fractures. These fractures should be monitored more closely due to the risk of nonunion and they require considering an initial treatment with pharmacological augmentation to reduce the complications for the patient and the health care costs.

  17. Bisphosphonate-associated atypical subtrochanteric femur fracture.

    Science.gov (United States)

    Wolin, Ely A; Banks, Kevin P; Vroman, Penny J

    2015-03-01

    Bisphosphonates help prevent progressive bone mineralization loss and subsequent osteoporotic fractures. However, long-term bisphosphonate therapy paradoxically increases the risk of a unique injury called an atypical subtrochanteric femur fracture. Despite this, the benefits of bisphosphonates outweigh the risks, because far more pathologic fractures are prevented than induced. The early identification of atypical subtrochanteric femur fractures is important as there is high associated morbidity and mortality. We describe a case of a 76-y-old woman with a completed bisphosphonate-associated atypical subtrochanteric femur fracture.

  18. Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent.

    Science.gov (United States)

    Choi, S I; Ju, W K; Choi, E K; Kim, J; Lea, H Z; Carp, R I; Wisniewski, H M; Kim, Y S

    1998-09-01

    Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease of sheep and other animals. Clinical symptoms of prion diseases are characterized by a long latent period, followed by progressive ataxia, tremor, and death. To study the induction of neurodegeneration during scrapie infection, we have analyzed the activities of various antioxidant enzymes and mitochondrial enzymes in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected brains. The activities of glutathione peroxidase and glutathione reductase were increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might result in increasing oxidative stress in the mitochondria of infected brain; this concept is supported by our findings of a high level of lipid peroxidation, and low levels of ATPase and cytochrome c oxidase activity in the infected cerebral mitochondria. In addition, structural abnormalities of mitochondria have been observed in the neurons of hippocampus and cerebral cortex of infected brain. These results suggest that mitochondrial dysfunction caused by oxidative stress gives rise to neurodegeneration in prion disease.

  19. Cell surface expression of PrP-c and the presence of scrapie prions in the blood of goats

    Science.gov (United States)

    Classical scrapie is a naturally occurring fatal brain disease of goats and sheep which is caused by prions, a novel class of infectious agent, and is accompanied by the accumulation of abnormal isoforms of prion protein (PrP-Sc) in certain neural and lymphoid tissues. Although collection of a blood...

  20. Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles

    Science.gov (United States)

    The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (I...

  1. Accumulation of PrP-Sc in hemal nodes of naturally and experimentally scrapie-infected sheep

    Science.gov (United States)

    Classical scrapie is a naturally occurring fatal disease of sheep and goats which is caused by prions, a novel class of infectious agent. Infection is accompanied by accumulation of abnormal isoforms of the prion protein (PrP-Sc) in certain neural and lymphoid tissues. Hemal nodes, which are unique ...

  2. Caprine prion genen polymorphisms are associated with decreased incidence of classical scrapie in goat herds in the United Kingdom.

    NARCIS (Netherlands)

    Goldmann, W.; Ryan, K.; Stewart, P.; Parnham, D.; Xicohtencatl, R.; Fernandez, N.; Saunders, G.; Windl, O.; Gonzalez, L.; Bossers, A.

    2011-01-01

    The application of genetic breeding programmes to eradicate transmissible spongiform encephalopathies in goats is an important aim for reasons of animal welfare as well as human food safety and food security. Based on the positive impact of Prnp genetics on sheep scrapie in Europe in the past decade

  3. Relationships between PrPSc stability and incubation time for United States scrapie strains in a natural host system

    Science.gov (United States)

    Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP**C) into a beta-rich conformer (PrP**Sc) that accumulates into higher-order structures in the brain and other ti...

  4. Discrimination between scrapie and bovine spongiform encephalopathy in sheep by molecular size, immunoreactivity, and glycoprofile of prion protein

    NARCIS (Netherlands)

    Thuring, C.M.A.; Erkens, J.H.F.; Jacobs, J.G.; Bossers, A.; Keulen, van L.J.M.; Garssen, G.J.; Zijderveld, van F.G.; Ryder, S.J.; Groschup, M.H.; Sweeney, T.; Langeveld, J.P.M.

    2004-01-01

    A procedure for discrimination between scrapie and bovine spongiform encephalopathy (BSE) in sheep is of importance for establishing whether BSE has entered the sheep population. Since BSE has not yet been found in sheep at the farm level, such discrimination procedures can be developed only with ex

  5. Inoculation of Scrapie with the Self-Assembling RADA-Peptide Disrupts Prion Accumulation and Extends Hamster Survival

    Science.gov (United States)

    Intercerebral inoculation of 263K Scrapie brain homogenate (PrPsc) with a self-assembling RADA-peptide (RADA) significantly delayed disease onset and increased hamster survival. Time of survival was dependent on the dose of RADA and pre-incubation with PrPsc prior to inoculation. RADA treatment resu...

  6. Enzymatic formulation capable of degrading scrapie prion under mild digestion conditions.

    Directory of Open Access Journals (Sweden)

    Emeka A Okoroma

    Full Text Available The prion agent is notoriously resistant to common proteases and conventional sterilisation procedures. The current methods known to destroy prion infectivity such as incineration, alkaline and thermal hydrolysis are harsh, destructive, environmentally polluting and potentially hazardous, thus limit their applications for decontamination of delicate medical and laboratory devices, remediation of prion contaminated environment and for processing animal by-products including specified risk materials and carcases. Therefore, an environmentally friendly, non-destructive enzymatic degradation approach is highly desirable. A feather-degrading Bacillus licheniformis N22 keratinase has been isolated which degraded scrapie prion to undetectable level of PrP(Sc signals as determined by Western Blot analysis. Prion infectivity was verified by ex vivo cell-based assay. An enzymatic formulation combining N22 keratinase and biosurfactant derived from Pseudomonas aeruginosa degraded PrP(Sc at 65 °C in 10 min to undetectable level -. A time-course degradation analysis carried out at 50 °C over 2 h revealed the progressive attenuation of PrP(Sc intensity. Test of residual infectivity by standard cell culture assay confirmed that the enzymatic formulation reduced PrP(Sc infectivity to undetectable levels as compared to cells challenged with untreated standard scrapie sheep prion (SSBP/1 (p-value = 0.008 at 95% confidence interval. This novel enzymatic formulation has significant potential application for prion decontamination in various environmentally friendly systems under mild treatment conditions.

  7. The evaluation of exposure risks for natural transmission of scrapie within an infected flock

    Directory of Open Access Journals (Sweden)

    Davis Andrew

    2009-10-01

    Full Text Available Abstract Background Although the epidemiology of scrapie has been broadly understood for many years, attempts to introduce voluntary or compulsory controls to eradicate the disease have frequently failed. Lack of precision in defining the risk factors on farm has been one of the challenges to designing control strategies. This study attempted to define which parts of the annual flock management cycle represented the greatest risk of infection to naive lambs exposed to the farm environment at different times. Results In VRQ/VRQ lambs exposed to infected sheep at pasture or during lambing, and exposed to the buildings in which lambing took place, the attack rate was high and survival times were short. Where exposure was to pasture alone the number of sheep affected in each experimental group was reduced, and survival times were longer and related to length of exposure. Conclusion At the flock level, eradication and control strategies for scrapie must take into account the need to decontaminate buildings used for lambing, and to reduce (or prevent the exposure of lambs to infected sheep, especially in the later stages of incubation, and at lambing. The potential for environmental contamination from pasture should also be considered. Genotype selection may still prove to be the only viable tool to prevent infection from contaminated pasture, reduce environmental contamination and limit direct transmission from sheep to sheep.

  8. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice.

    Science.gov (United States)

    Choi, Hong-Seok; Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min; Park, Jeong-Ho; Kim, Jae-Il; Carp, Richard I; Choi, Eun-Kyoung; Kim, Yong-Sun

    2014-05-30

    Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the neuropathological changes associated with prion disease.

  9. Perturbation of the Secondary Structure of the Scrapie Prion Protein Under Conditions that Alter Infectivity

    Science.gov (United States)

    Gasset, Maria; Baldwin, Michael A.; Fletterick, Robert J.; Prusiner, Stanley B.

    1993-01-01

    Limited proteolysis of the scrapie prion protein (PrPSc) generates PrP 27-30, which polymerizes into amyloid. By attenuated total reflection-Fourier transform infrared spectroscopy, PrP 27-30 polymers contained 54% β-sheet, 25% α-helix, 10% turns, and 11% random coil; dispersion into detergent-lipid-protein-complexes preserved infectivity and secondary structure. Almost 60% of the β-sheet was low-frequency infrared-absorbing, reflecting intermolecular aggregation. Decreased low-frequency β-sheet and increased turn content were found after SDS/PAGE, which disassembled the amyloid polymers, denatured PrP 27-30, and diminished scrapie infectivity. Acid-induced transitions were reversible, whereas alkali produced an irreversible transition centered at pH 10 under conditions that diminished infectivity. Whether PrPSc synthesis involves a transition in the secondary structure of one or more domains of the cellular prion protein from α-helical, random coil, or turn into β-sheet remains to be established.

  10. Assessment of inbreeding resulting from selection for scrapie resistance: a model for rare sheep breeds.

    Science.gov (United States)

    Brown, C; Orford, M; Tzamaloukas, O; Mavrogenis, A P; Miltiadou, D

    Inbreeding in a small population of Chios sheep undergoing intense selection for the PrP gene was assessed 10 years after the beginning of a scrapie resistance selection programme. Inbreeding in this stock, already under selection for production traits, was analysed by using pedigree records containing 10,492 animals from 1968 to 2008, and also by genotyping 192 individuals with a panel of 15 microsatellites. Genetic markers indicated a loss of heterozygosity (FIS over all loci was 0.059) and allelic diversity (mean effective number of alleles was 3.075±0.275). The annual rate of inbreeding increased significantly after the start of the scrapie resistance programme, ΔF=0.005 compared with ΔF=0.001 before 1999, and was subjected to several genetic bottlenecks, mainly due to the low initial frequency of resistant animals. However, the mean individual inbreeding coefficient estimated from the pedigree - in this closed stock resembling the case of a rare breed - stood at the level of 4.5 per cent, five generations after the implementation of selection for the PrP gene. The inbreeding coefficient estimated by genetic markers was 4.37 per cent, implying that such a marker panel could be a useful and cost-effective tool for estimating inbreeding in unrecorded populations.

  11. White blood cell-based detection of asymptomatic scrapie infection by ex vivo assays.

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    Sophie Halliez

    Full Text Available Prion transmission can occur by blood transfusion in human variant Creutzfeldt-Jakob disease and in experimental animal models, including sheep. Screening of blood and its derivatives for the presence of prions became therefore a major public health issue. As infectious titer in blood is reportedly low, highly sensitive and robust methods are required to detect prions in blood and blood derived products. The objectives of this study were to compare different methods--in vitro, ex vivo and in vivo assays--to detect prion infectivity in cells prepared from blood samples obtained from scrapie infected sheep at different time points of the disease. Protein misfolding cyclic amplification (PMCA and bioassays in transgenic mice expressing the ovine prion protein were the most efficient methods to identify infected animals at any time of the disease (asymptomatic to terminally-ill stages. However scrapie cell and cerebellar organotypic slice culture assays designed to replicate ovine prions in culture also allowed detection of prion infectivity in blood cells from asymptomatic sheep. These findings confirm that white blood cells are appropriate targets for preclinical detection and introduce ex vivo tools to detect blood infectivity during the asymptomatic stage of the disease.

  12. Antigen retrieval using sodium hydroxide for prion immunohistochemistry in bovine spongiform encephalopathy and scrapie.

    Science.gov (United States)

    Okada, H; Sato, Y; Sata, T; Sakurai, M; Endo, J; Yokoyama, T; Mohri, S

    2011-05-01

    Formalin-fixed and paraffin wax-embedded (FFPE) tissue sections are usually used for histopathological and immunohistochemical analyses in prion diseases in animals and man. However, formalin fixation cross-links proteins, reducing disease-associated prion protein (PrP(Sc)) immunolabelling. To detect PrP(Sc) in animals naturally affected with bovine spongiform encephalopathy (BSE) and scrapie, we applied minimal pretreatment with sodium hydroxide (NaOH). This simple pretreatment, combined with enzymatic digestion using proteinase K (PK), was equally effective in the detection of PrP(Sc) in FFPE tissue, and superior in terms of speed, compared with the usual autoclaving method. The most effective results, without any section loss, were obtained with 10 μg/ml PK in phosphate buffered saline containing 0.1% Triton-X at room temperature for 10 min and 150 mM NaOH at 60 °C for 10 min. By this simple procedure, PrP(Sc) was visualized in the brain of animals with BSE and scrapie using a range of anti-PrP primary antibodies.

  13. On the question of proportionality of the count of observed Scrapie cases and the size of holding

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    Del Rio Vilas Victor J

    2009-05-01

    Full Text Available Abstract Background The present paper investigates the question of a suitable basic model for the number of scrapie cases in a holding and applications of this knowledge to the estimation of scrapie-affected holding population sizes and adequacy of control measures within holding. Is the number of scrapie cases proportional to the size of the holding in which case it should be incorporated into the parameter of the error distribution for the scrapie counts? Or, is there a different – potentially more complex – relationship between case count and holding size in which case the information about the size of the holding should be better incorporated as a covariate in the modeling? Methods We show that this question can be appropriately addressed via a simple zero-truncated Poisson model in which the hypothesis of proportionality enters as a special offset-model. Model comparisons can be achieved by means of likelihood ratio testing. The procedure is illustrated by means of surveillance data on classical scrapie in Great Britain. Furthermore, the model with the best fit is used to estimate the size of the scrapie-affected holding population in Great Britain by means of two capture-recapture estimators: the Poisson estimator and the generalized Zelterman estimator. Results No evidence could be found for the hypothesis of proportionality. In fact, there is some evidence that this relationship follows a curved line which increases for small holdings up to a maximum after which it declines again. Furthermore, it is pointed out how crucial the correct model choice is when applied to capture-recapture estimation on the basis of zero-truncated Poisson models as well as on the basis of the generalized Zelterman estimator. Estimators based on the proportionality model return very different and unreasonable estimates for the population sizes. Conclusion Our results stress the importance of an adequate modelling approach to the association between holding

  14. Atypical imaging appearances of intracranial meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    O' Leary, S. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Adams, W.M. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Parrish, R.W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Mukonoweshuro, W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom)]. E-mail: William.mukonoweshuro@phnt.swest.nhs.uk

    2007-01-15

    Meningiomas are the commonest primary, non-glial intracranial tumours. The diagnosis is often correctly predicted from characteristic imaging appearances. This paper presents some examples of atypical imaging appearances that may cause diagnostic confusion.

  15. Atypical presentations of Wolframs syndrome

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    S Saran

    2012-01-01

    Full Text Available Background: Wolfram syndrome is a rare hereditary or sporadic neurodegenerative disorder also known as DIDMOAD. The classically described presentation is of insulin-dependent diabetes, followed by optic atrophy, central diabetes insipidus, and sensory neural deafness. Also included are less well-described presentations of Wolframs syndrome. We here present three cases of atypical presentation of this syndrome. Case 1: A 15-year-old boy with insulin-dependent diabetes was presented for evaluation of depressive symptoms associated with suicidal tendency. Neuropsychiatric manifestations are described with Wolframs syndrome, and wolframin gene, in recessive inheritance, is associated with psychiatric illnesses without other manifestations of Wolframs syndrome. Case 2: A 17-year-old diabetic boy on insulin with good control of blood sugar presented for evaluation of delayed puberty. Central hypogonadism and other anterior pituitary hormone dysfunctions are the less publicized hormone dysfunctions in Wolframs syndrome. Case 3: A 23-year-old female who was on insulin for diabetes for the past 14 years, got admitted for evaluation of sudden loss of vision. This patient had developed a vitreous hemorrhage and, on evaluation, was found to have optic atrophy, sensory neural hearing loss, and diabetes insipidus, and presented differently from the gradual loss of vision described in Wolframs syndrome. Conclusion: Wolframs syndrome being a multisystem degenerative disorder can have myriad other manifestations than the classically described features. Neuropsychiatric manifestations, depression with suicidal risk, central hypogonadism, and secondary adrenal insufficiency are among the less well-described manifestations of this syndrome.

  16. Emergence of a novel bovine spongiform encephalopathy (BSE) prion from an atypical H-type BSE

    OpenAIRE

    2016-01-01

    The H-type of atypical bovine spongiform encephalopathy (H-BSE) was serially passaged in bovinized transgenic (TgBoPrP) mice. At the fourth passage, most challenged mice showed a typical H-BSE phenotype with incubation periods of 223 ± 7.8 days. However, a different phenotype of BSE prion with shorter incubation periods of 109 ± 4 days emerged in a minor subset of the inoculated mice. The latter showed distinct clinical signs, brain pathology, and abnormal prion protein profiles as compared t...

  17. ATYPICAL ANTIPSYCHOTICS FROM SCRATCH TO THE PRESENT

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    Ashish Chauhan*, Amit Mittal, Pradeep Kumar Arora

    2013-01-01

    Full Text Available Mental illness constitutes the second-largest disease burden in the United States. Psychosis is one of the most common and severe mental illnesses. It is an extremely devastating condition characterised by delusions, hallucinations, distortion of thoughts and deteriorating social functioning experiences. Psychosis in all human societies has approximately same incidence of occurrence as in accordance to “anthropo-parity principle.” It has large economic impact on various aspects of cognition, health, and quality of life which has devastated effects on its sufferers and facing them large economic burden. Psychosis (Schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyper-stimulation of dopamine function in the brain, particularly in the mesolimbic pathway. Consequences of antipsychotic treatment are far reaching and expensive. Detrimental extrapyramidal side effects associated with conventional antipsychotics and non-compliance among patients limits long term treatment with conventional antipsychotics. It gives rise to a new class, atypical antipsychotics owning low propensity to cause EPS, efficacy against refractory cases and better control over negative symptoms, better tolerance and compliance along with lower relapse rate and safer adverse effect profile. Atypical antipsychotics have revolutionized the treatment of psychosis, now being the treatment of choice for patients with psychosis. The positive therapeutic experience with the atypical antipsychotics in the treatment of psychosis and their favourable effects outweighs their unfavourable adverse effects. Though atypical antipsychotics are widely prescribed in the treatment of schizophrenia, however not a single atypical antipsychotic drug having any exceptional efficacy and safety profile. Thus, there is still a lot of research needed to be carried out in the development of novel atypical antipsychotics. This review is comprehensive appraisal about

  18. Association of an indel polymorphism in the 3'UTR of the caprine SPRN gene with scrapie positivity in the central nervous system.

    Science.gov (United States)

    Peletto, Simone; Bertolini, Silvia; Maniaci, Maria Grazia; Colussi, Silvia; Modesto, Paola; Biolatti, Cristina; Bertuzzi, Simone; Caramelli, Maria; Maurella, Cristiana; Acutis, Pier Luigi

    2012-07-01

    The aim of this study was to analyse the SPRN genes of goats from several scrapie outbreaks in order to detect polymorphisms and to look for association with scrapie occurrence, by an unmatched case-control study. A region of the caprine SPRN gene encompassing the entire ORF and a fragment of the 3'UTR revealed a total of 11 mutations: 10 single-nucleotide polymorphisms and one indel polymorphism. Only two non-synonymous mutations occurring at very low incidence were identified. A significant association with scrapie positivity in the central nervous system was found for an indel polymorphism (602_606insCTCCC) in the 3'UTR. Bioinformatics analyses suggest that this indel may modulate scrapie susceptibility via a microRNA-mediated post-transcriptional mechanism. This is the first study to demonstrate an association between the SPRN gene and goat scrapie. The identified indel may serve as a genetic target other than PRNP to predict disease risk in future genetics-based scrapie-control approaches in goats.

  19. Human variant Creutzfeldt-Jakob disease and sheep scrapie PrP(res) detection using seeded conversion of recombinant prion protein.

    Science.gov (United States)

    Orrú, Christina D; Wilham, Jason M; Hughson, Andrew G; Raymond, Lynne D; McNally, Kristin L; Bossers, Alex; Ligios, Ciriaco; Caughey, Byron

    2009-08-01

    The pathological isoform of the prion protein (PrP(res)) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. Previously we showed that the quaking-induced conversion (QuIC) assay can detect sub-femtogram levels of PrP(res) in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (CSF) samples from normal and scrapie-infected hamsters. We now report the adaptation of the QuIC reaction to prion diseases of medical and agricultural interest: human variant Creutzfeldt-Jakob disease (vCJD) and sheep scrapie. PrP(res)-positive and -negative brain homogenates from humans and sheep were discriminated within 1-2 days with a sensitivity of 10-100 fg PrP(res). More importantly, in as little as 22 h we were able to distinguish CSF samples from scrapie-infected and uninfected sheep. These results suggest the presence of prions in CSF from scrapie-infected sheep. This new method enables the relatively rapid and sensitive detection of human CJD and sheep scrapie PrP(res) and may facilitate the development of practical preclinical diagnostic and high-throughput interference tests.

  20. Development of an assay to determine single nucleotide polymorphisms in the prion gene for the genetic diagnosis of relative susceptibility to classical scrapie in sheep.

    Science.gov (United States)

    Johnson, Mary Lynn; Evoniuk, Jessica M; Stoltenow, Charles L; O'rourke, Katherine I; Redmer, Dale A

    2007-01-01

    The objective of this study was to develop a reliable Taqman 5' Nuclease Assay for genotyping sheep for scrapie susceptibility. The sheep prion gene contains 2 single nucleotide polymorphisms (SNPs) that may mediate resistance to classical scrapie, one at codon 136, alanine (A) or valine (V), and another at codon 171, arginine (R) or glutamine (Q). The R allele appears to confer resistance to classical scrapie, with the AA(136) RR(171) genotype the most resistant to scrapie and QR(171) only rarely infected in the US sheep population. The Assays by Design protocol was used for development of probes and primers for codon 136 and Primer Express for codon 171. Commercially available kits were used to isolate genomic DNA from blood or muscle. For validation, 70 SNP determinations for each codon were compared to commercial testing with an error rate of less than 1%. Then, 935 samples from blood (n = 818) and muscle (n = 117) were tested for both codons with 928 successful determinations and only 7 samples (scrapie-resistant. This new Taqman 5' Nuclease SNP genotyping assay is accurate, easy to perform, and useful in the study of classical scrapie in sheep and its prevention through selective breeding programs to eliminate highly susceptible animals.

  1. Analysis of the incubation periods, induction of obesity and histopathological changes in senescence-prone and senescence-resistant mice infected with various scrapie strains.

    Science.gov (United States)

    Carp, R I; Meeker, H; Sersen, E; Kozlowski, P

    1998-11-01

    The similarity in histopathological changes seen in scrapie-infected mice and in an uninfected senescence-accelerated mouse strain led to a study in which the mouse strain that is prone to senescence (SAMP8), a strain that is resistant to senescence (SAMR1) and a progenitor strain (AKR) of these two strains were infected with three different scrapie strains, ME7, 139A and 22L. For each scrapie strain, the incubation period was shortest in AKR mice and longest in SAMR1 mice. The induction of obesity was a function of scrapie strain and not mouse strain; ME7 caused obesity in all mouse strains, whereas the average weights of mice injected with 139A and 22L did not differ significantly from mice injected with homogenates of normal mouse brain. The pattern of vacuolation seen in the brain of each mouse strain was primarily dependent on the scrapie strain injected. There were, in general, similarities to the patterns induced in other inbred strains; e.g. ME7 caused extensive forebrain vacuolation, 22L caused prominent vacuolation in the cerebellum, and the 139A strain induced characteristic white matter vacuolation. Vacuolation was also seen in the medulla and midbrain of SAMP8 mice injected with normal mouse brain, which is consistent with the occurrence of accelerated ageing changes in the brain of this strain. Further analysis of the differences among these mouse strains should provide information relating to the observed differences in scrapie incubation periods.

  2. Clinical Presentation of Atypical Genital Herpes

    Institute of Scientific and Technical Information of China (English)

    李俊杰; 梁沛杨; 罗北京

    2002-01-01

    Objective: To make a clinical analysis on the basis of 36cases of atypical genital herpes (GH) patients. Methods: Thirty-six cases of atypical GH were diagnosedclinically, and their case histories, symptoms and signs wererecorded in detail and followed up. Polymerase chain reaction(PCR) was adopted for testing HSV2-DNA with cotton-tippedswabs. Enzyme-linked immuno sorbent assay (ELISA) forserum anti-HSV2-IgM was done to establish a definfiivediagnosis. Other diagnoses were excluded at the same time bytesting for related pathogens including fungi, Chlamydia,Mycoplasma, Treponema pallidum, gonococci, Trichomonas,etc. Results: The main clinical manifestations of atypical GHwere: (1) small genital ulcers; (2) inflammation of urethralmeatus; (3) nonspecific genital erythema; (4) papuloid noduleson the glands; (5) nonspecific vaginitis. Twenty-three cases(64%) tested by PCR were HSV2-DNA sera-positive, and 36cases (100 %) anti-HSV2-IgM sera-positive by ELISA. Conclusion: atypical HSV is difficult to be diagnosed. Butthe combination of PCR and ELIAS will be helpful to thediagnosis of atypical HSV.

  3. [Atypical presentation of Klinefelter syndrome].

    Science.gov (United States)

    Sanz Marcos, N; Turón Viñas, A; Ibáñez Toda, L

    2013-08-01

    Klinefelter syndrome (KS) is the most common sex chromosomal abnormality and is associated with hypergonadotropic hypogonadism as an endocrine disorder. The phenotype is characterized by tall stature, abdominal adiposity and small testicles, and often appears after puberty.We report two cases of SK. The first patient is a 2-year-old boy with short stature who received growth hormone therapy. Because of non-progressive puberty, an evaluation of the reproductive axis was performed, showing increased basal gonadotropins. The karyotype (48 XXYY) confirmed the presence of KS. The second patient is an 8 year-old boy in whom peripheral precocious puberty was suspected. Laboratory tests showed high chorionic gonadotropin levels, and a chest CT scan revealed a mediastinal mass. The karyotype in peripheral blood disclosed a 48 XXYY formula (KS).Short stature does not exclude SK. In patients with a mediastinal mass and neurobehavioral deficits, KS should be suspected.

  4. Explaining the heterogeneous scrapie surveillance figures across Europe: a meta-regression approach

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    Ru Giuseppe

    2007-06-01

    Full Text Available Abstract Background Two annual surveys, the abattoir and the fallen stock, monitor the presence of scrapie across Europe. A simple comparison between the prevalence estimates in different countries reveals that, in 2003, the abattoir survey appears to detect more scrapie in some countries. This is contrary to evidence suggesting the greater ability of the fallen stock survey to detect the disease. We applied meta-analysis techniques to study this apparent heterogeneity in the behaviour of the surveys across Europe. Furthermore, we conducted a meta-regression analysis to assess the effect of country-specific characteristics on the variability. We have chosen the odds ratios between the two surveys to inform the underlying relationship between them and to allow comparisons between the countries under the meta-regression framework. Baseline risks, those of the slaughtered populations across Europe, and country-specific covariates, available from the European Commission Report, were inputted in the model to explain the heterogeneity. Results Our results show the presence of significant heterogeneity in the odds ratios between countries and no reduction in the variability after adjustment for the different risks in the baseline populations. Three countries contributed the most to the overall heterogeneity: Germany, Ireland and The Netherlands. The inclusion of country-specific covariates did not, in general, reduce the variability except for one variable: the proportion of the total adult sheep population sampled as fallen stock by each country. A large residual heterogeneity remained in the model indicating the presence of substantial effect variability between countries. Conclusion The meta-analysis approach was useful to assess the level of heterogeneity in the implementation of the surveys and to explore the reasons for the variation between countries.

  5. Membrane toxicity of abnormal prion protein in adrenal chromaffin cells of scrapie infected sheep.

    Science.gov (United States)

    McGovern, Gillian; Jeffrey, Martin

    2013-01-01

    Transmissible spongiform encephalopathies (TSEs) or prion diseases are associated with accumulations of disease specific PrP (PrP(d)) in the central nervous system (CNS) and often the lymphoreticular system (LRS). Accumulations have additionally been recorded in other tissues including the peripheral nervous system and adrenal gland. Here we investigate the effect of sheep scrapie on the morphology and the accumulation of PrP(d) in the adrenal medulla of scrapie affected sheep using light and electron microscopy. Using immunogold electron microscopy, non-fibrillar forms of PrP(d) were shown to accumulate mainly in association with chromaffin cells, occasional nerve endings and macrophages. PrP(d) accumulation was associated with distinctive membrane changes of chromaffin cells including increased electron density, abnormal linearity and invaginations. Internalisation of PrP(d) from the chromaffin cell plasma membrane occurred in association with granule recycling following hormone exocytosis. PrP(d) accumulation and internalisation from membranes is similarly associated with perturbations of membrane structure and trafficking in CNS neurons and tingible body macrophages of the LRS. These data suggest that a major toxic effect of PrP(d) is at the level of plasma membranes. However, the precise nature of PrP(d)-membrane toxicity is tissue and cell specific suggesting that the normal protein may act as a multi-functional scaffolding molecule. We further suggest that the co-localisation of PrP(d) with exocytic granules of the hormone trafficking system may provide an additional source of infectivity in blood.

  6. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

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    Choi, Hong-Seok [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Park, Jeong-Ho [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Jae-Il [Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737 (Korea, Republic of); Carp, Richard I. [New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 (United States); Choi, Eun-Kyoung, E-mail: ekchoi@hallym.ac.kr [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Yong-Sun, E-mail: yskim@hallym.ac.kr [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of)

    2014-05-30

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  7. Evaluation of the possible transmission of BSE and scrapie to gilthead sea bream (Sparus aurata.

    Directory of Open Access Journals (Sweden)

    Evgenia Salta

    Full Text Available In transmissible spongiform encephalopathies (TSEs, a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrP(Sc of the host-encoded cellular prion protein (PrP(C. While the precise mechanism of the PrP(C to PrP(Sc conversion is not understood, it is clear that host PrP(C expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish. Here we show that while gilthead sea bream (Sparus aurata orally challenged with brain homogenates prepared either from a BSE infected cow or from scrapie infected sheep developed no clinical prion disease, the brains of TSE-fed fish sampled two years after challenge did show signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs. Remarkably, the deposits developed much more rapidly and extensively in fish inoculated with BSE-infected material than in the ones challenged with the scrapie-infected brain homogenate, with numerous deposits being proteinase K-resistant. These plaque-like aggregates exhibited congophilia and birefringence in polarized light, consistent with an amyloid-like component. The neurodegeneration and abnormal deposition in the brains of fish challenged with prion, especially BSE, raises concerns about the potential risk to public health. As fish aquaculture is an economically important industry providing high protein nutrition for humans and other mammalian species, the prospect of farmed fish being contaminated with infectious mammalian PrP(Sc, or of a prion disease developing in farmed fish is alarming and requires further evaluation.

  8. Evaluation of the possible transmission of BSE and scrapie to gilthead sea bream (Sparus aurata).

    Science.gov (United States)

    Salta, Evgenia; Panagiotidis, Cynthia; Teliousis, Konstantinos; Petrakis, Spyros; Eleftheriadis, Eleftherios; Arapoglou, Fotis; Grigoriadis, Nikolaos; Nicolaou, Anna; Kaldrymidou, Eleni; Krey, Grigorios; Sklaviadis, Theodoros

    2009-07-28

    In transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrP(Sc)) of the host-encoded cellular prion protein (PrP(C)). While the precise mechanism of the PrP(C) to PrP(Sc) conversion is not understood, it is clear that host PrP(C) expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish. Here we show that while gilthead sea bream (Sparus aurata) orally challenged with brain homogenates prepared either from a BSE infected cow or from scrapie infected sheep developed no clinical prion disease, the brains of TSE-fed fish sampled two years after challenge did show signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs. Remarkably, the deposits developed much more rapidly and extensively in fish inoculated with BSE-infected material than in the ones challenged with the scrapie-infected brain homogenate, with numerous deposits being proteinase K-resistant. These plaque-like aggregates exhibited congophilia and birefringence in polarized light, consistent with an amyloid-like component. The neurodegeneration and abnormal deposition in the brains of fish challenged with prion, especially BSE, raises concerns about the potential risk to public health. As fish aquaculture is an economically important industry providing high protein nutrition for humans and other mammalian species, the prospect of farmed fish being contaminated with infectious mammalian PrP(Sc), or of a prion disease developing in farmed fish is alarming and requires further evaluation.

  9. Accumulation and dissemination of prion protein in experimental sheep scrapie in the natural host

    Directory of Open Access Journals (Sweden)

    Warner Richard

    2009-02-01

    Full Text Available Abstract Background In order to study the sites of uptake and mechanisms of dissemination of scrapie prions in the natural host under controlled conditions, lambs aged 14 days and homozygous for the VRQ allele of the PrP gene were infected by the oral route. Infection occurred in all lambs with a remarkably short and highly consistent incubation period of approximately 6 months. Challenge of lambs at approximately eight months of age resulted in disease in all animals, but with more variable incubation periods averaging significantly longer than those challenged at 14 days. This model provides an excellent system in which to study the disease in the natural host by virtue of the relatively short incubation period and close resemblance to natural infection. Results Multiple sites of prion uptake were identified, of which the most important was the Peyer's patch of the distal ileum. Neuroinvasion was detected initially in the enteric nervous system prior to infection of the central nervous system. At end stage disease prion accumulation was widespread throughout the entire neuraxis, but vacuolar pathology was absent in most animals that developed disease at 6–7 months of age. Conclusion Initial spread of detectable PrP was consistent with drainage in afferent lymph to dependent lymph nodes. Subsequent accumulation of prions in lymphoid tissue not associated with the gut is consistent with haematogenous spread. In addition to macrophages and follicular dendritic cells, prion containing cells consistent with afferent lymph dendritic cells were identified and are suggested as a likely vehicle for carriage of prions from initial site of uptake to the lymphoreticular system, and as potential carriers of prion protein in blood. It is apparent that spongiform change, the characteristic lesion of scrapie and other prion diseases, is not responsible for the clinical signs in sheep, but may develop in an age dependent manner.

  10. Detection of prion protein particles in blood plasma of scrapie infected sheep.

    Directory of Open Access Journals (Sweden)

    Oliver Bannach

    Full Text Available Prion diseases are transmissible neurodegenerative diseases affecting humans and animals. The agent of the disease is the prion consisting mainly, if not solely, of a misfolded and aggregated isoform of the host-encoded prion protein (PrP. Transmission of prions can occur naturally but also accidentally, e.g. by blood transfusion, which has raised serious concerns about blood product safety and emphasized the need for a reliable diagnostic test. In this report we present a method based on surface-FIDA (fluorescence intensity distribution analysis, that exploits the high state of molecular aggregation of PrP as an unequivocal diagnostic marker of the disease, and show that it can detect infection in blood. To prepare PrP aggregates from blood plasma we introduced a detergent and lipase treatment to separate PrP from blood lipophilic components. Prion protein aggregates were subsequently precipitated by phosphotungstic acid, immobilized on a glass surface by covalently bound capture antibodies, and finally labeled with fluorescent antibody probes. Individual PrP aggregates were visualized by laser scanning microscopy where signal intensity was proportional to aggregate size. After signal processing to remove the background from low fluorescence particles, fluorescence intensities of all remaining PrP particles were summed. We detected PrP aggregates in plasma samples from six out of ten scrapie-positive sheep with no false positives from uninfected sheep. Applying simultaneous intensity and size discrimination, ten out of ten samples from scrapie sheep could be differentiated from uninfected sheep. The implications for ante mortem diagnosis of prion diseases are discussed.

  11. Membrane toxicity of abnormal prion protein in adrenal chromaffin cells of scrapie infected sheep.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are associated with accumulations of disease specific PrP (PrP(d in the central nervous system (CNS and often the lymphoreticular system (LRS. Accumulations have additionally been recorded in other tissues including the peripheral nervous system and adrenal gland. Here we investigate the effect of sheep scrapie on the morphology and the accumulation of PrP(d in the adrenal medulla of scrapie affected sheep using light and electron microscopy. Using immunogold electron microscopy, non-fibrillar forms of PrP(d were shown to accumulate mainly in association with chromaffin cells, occasional nerve endings and macrophages. PrP(d accumulation was associated with distinctive membrane changes of chromaffin cells including increased electron density, abnormal linearity and invaginations. Internalisation of PrP(d from the chromaffin cell plasma membrane occurred in association with granule recycling following hormone exocytosis. PrP(d accumulation and internalisation from membranes is similarly associated with perturbations of membrane structure and trafficking in CNS neurons and tingible body macrophages of the LRS. These data suggest that a major toxic effect of PrP(d is at the level of plasma membranes. However, the precise nature of PrP(d-membrane toxicity is tissue and cell specific suggesting that the normal protein may act as a multi-functional scaffolding molecule. We further suggest that the co-localisation of PrP(d with exocytic granules of the hormone trafficking system may provide an additional source of infectivity in blood.

  12. Neuroleptic malignant syndrome induced by atypical antipsychotics.

    Science.gov (United States)

    Farver, Debra K

    2003-01-01

    A review of the English literature confirms that neuroleptic malignant syndrome (NMS) occurs with both traditional and atypical antipsychotic medications. Published reports of NMS induced by the traditional antipsychotics have given the practitioner valuable information on the prevention and treatment of this adverse effect. Case reports have also been published concerning NMS and clozapine, risperidone, olanzapine and quetiapine. By evaluating the case reports of atypical antipsychotic-induced NMS, valuable information may be obtained concerning similarities or differences from that induced by the traditional antipsychotics. The case reports of NMS with atypical antipsychotics were evaluated for diagnosis, age/sex of patient, risk factors, antipsychotic doses and duration of use, symptoms of NMS, and clinical course.

  13. [Atypical antipsychotic-induced weight gain].

    Science.gov (United States)

    Godlewska, Beata R; Olajossy-Hilkesberger, Luiza; Marmurowska-Michałowska, Halina; Olajossy, Marcin; Landowski, Jerzy

    2006-01-01

    Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.

  14. Atypical RNAs in the coelacanth transcriptome.

    Science.gov (United States)

    Nitsche, Anne; Doose, Gero; Tafer, Hakim; Robinson, Mark; Saha, Nil Ratan; Gerdol, Marco; Canapa, Adriana; Hoffmann, Steve; Amemiya, Chris T; Stadler, Peter F

    2014-09-01

    Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome. Surprisingly, the majority of the circularizing and trans-connecting splice junctions are unique to atypical forms, that is, are not used in normal isoforms.

  15. The abnormal isoform of the prion protein accumulates in late-endosome-like organelles in scrapie-infected mouse brain.

    Science.gov (United States)

    Arnold, J E; Tipler, C; Laszlo, L; Hope, J; Landon, M; Mayer, R J

    1995-08-01

    The prion encephalopathies are characterized by accumulation in the brain of the abnormal form PrPsc of a normal host gene product PrPc. The mechanism and site of formation of PrPsc from PrPc are currently unknown. In this study, ME7 scrapie-infected mouse brain was used to show, both biochemically and by double-labelled immunogold electron microscopy, that proteinase K-resistant PrPsc is enriched in subcellular structures which contain the cation-independent mannose 6-phosphate receptor, ubiquitin-protein conjugates, beta-glucuronidase, and cathepsin B, termed late endosome-like organelles. The glycosylinositol phospholipid membrane-anchored PrPc will enter such compartment for normal degradation and the organelles may therefore act as chambers for the conversion of PrPc into infectious PrPsc in this murine model of scrapie.

  16. [From the Scrapie syndrome of sheep and goat to the mad cow disease - the history of the discovery of prion].

    Science.gov (United States)

    Liu, Rui; Weng, Yi

    2009-05-01

    Since the discovery of Scrapie Syndrome in sheep and goats in 1730, there emerged a series of diseases such as Creutzfeldt-Jakob disease, kuru disease and mad cow disease etc. In the research of kuru disease, the American scientist D. Carlteton Gajdusek found a new virus without the characteristic of DNA and RNA, which was awarded the Nobel Prize in physiology in 1976. Since then another American scientist, Stanley B. Prusiner, found a new virus-prion, taking protein as the genetic medium, which was awarded the Nobel prize in physiology and medicine in 1997. The discovery of prion is a great landmark in the research of life science, which laid a theoretical foundation for people to conquer a series of diseases such as Scrapie syndrome in sheep and goats, Creutzfeldt-Jakob disease, kuru disease and mad cow disease etc.

  17. Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats.

    Science.gov (United States)

    Foster, J D; Parnham, D; Chong, A; Goldmann, W; Hunter, N

    2001-02-10

    This paper compares the dinical signs, histopathology, detection of PrPSc protein and PrP genetics of the transmission of BSE to sheep and goats, with the effects of the transmission of natural scrapie from a brain homogenate from a single sheep. After intracerebral and oral inoculations there were similarities in the clinical signs due to the two sources of infection, but there were differences in pathology at the end stage of disease and in the genotypes of the sheep which succumbed to the challenges. The incubation period of BSE was associated with the sheep PrP codon 171 genotype, but the natural scrapie source, despite inducing disease only in known susceptible genotypes, showed no clear association with PrP genotype.

  18. Chronic wasting disease and atypical forms of BSE and scrapie are not transmissible to mice expressing wild-type levels of human PrP

    Science.gov (United States)

    The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle TSEs can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several new TSEs in shee...

  19. Disruption of glycosylation enhances ubiquitin-mediated proteasomal degradation of Shadoo in Scrapie-infected rodents and cultured cells.

    Science.gov (United States)

    Zhang, Jin; Guo, Yan; Xie, Wu-Ling; Xu, Yin; Ren, Ke; Shi, Qi; Zhang, Bao-Yun; Chen, Cao; Tian, Chan; Gao, Chen; Dong, Xiao-Ping

    2014-06-01

    Shadoo (Sho) is an N-glycosylated glycophosphatidylinositol-anchored protein that is expressed in the brain and exhibits neuroprotective properties. Recently, research has shown that a reduction of Sho levels may reflect the presence of PrPSc in the brain. However, the possible mechanism by which prion infection triggers down-regulation of Sho remains unclear. In the present study, Western blot and immunohistochemical assays revealed that Sho, especially glycosylated Sho, declined markedly in the brains of five scrapie agent-infected hamsters and mice at the terminal stages. Analyses of the down-regulation of Sho levels with the emergence of PrPSc C2 proteolytic fragments did not identify close association in all tested scrapie-infected models. To further investigate the mechanism of depletion of Sho in prion disease, a Sho-expressing plasmid with HA tag was introduced into a scrapie-infected cell line, SMB-S15, and its normal cell line, SMB-PS. Western blot assay revealed dramatically decreased Sho in SMB-S15 cells, especially its glycosylated form. Proteasome inhibitor MG132 reversed the decrease of nonglycosylated Sho, but had little effect on glycosylated Sho. N-acetylglucosamine transferase inhibitor tunicamycin efficiently reduced the glycosylations of Sho and PrPC in SMB-PS cells, while two other endoplasmic reticulum stress inducers showed clear inhibition of diglycosylated PrPC, but did not change the expression level and profile of Sho. Furthermore, immunoprecipitation of HA-Sho illustrated ubiquitination of Sho in SMB-S15 cells, but not in SMB-PS cells. We propose that the depletions of Sho in scrapie-infected cell lines due to inhibition of glycosylation mediate protein destabilization and subsequently proteasome degradation after modification by ubiquitination.

  20. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

    Directory of Open Access Journals (Sweden)

    Fiona Houston

    Full Text Available Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE, which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock. The unusually long observation period (6-8 years for most, but up to 12 years for others allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of

  1. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

    Science.gov (United States)

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6-8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  2. Adaptation and evaluation of a rapid test for the diagnosis of sheep scrapie in samples of rectal mucosa.

    Science.gov (United States)

    González, Lorenzo; Horton, Robert; Ramsay, Drew; Toomik, Reet; Leathers, Valerie; Tonelli, Quentin; Dagleish, Mark P; Jeffrey, Martin; Terry, Linda

    2008-03-01

    In recent publications, it was shown that disease-associated prion protein (PrP(d)) accumulates in the lymphoid tissue of the rectal mucosa of a high proportion of scrapie-infected sheep at clinical and preclinical stages, regardless of several host factors; PrP(d) can also be detected in biopsy specimens of rectal mucosa, with an increased probability proportional to age or incubation period and with an efficiency almost identical to that of tonsil biopsies. Rectal biopsies have the advantages of providing higher numbers of lymphoid follicles and of being simpler to perform, which makes them suitable for scrapie screening in the field. In biopsy samples, PrP(d) could be demonstrated by immunohistochemical (IHC) and Western immunoblotting methods, and the purpose of the present study was to optimize and evaluate a "rapid test" for the diagnosis of scrapie in rectal biopsy samples. The HerdChek CWD (chronic wasting disease) antigen EIA (enzyme immunoassay) test was chosen and, once optimized, provided specificity and sensitivity figures of 99.2% and 93.5%, respectively, compared with IHC results in the same samples obtained at a postmortem. The sensitivity of the assay increased from 82.1%, when a single rectal mucosa sample was tested to 99.4% for those sheep in which 3 or more samples were analyzed. Similarly, sensitivity values of the HerdChek CWD antigen EIA test on biopsy samples increased from 95% to 100% for sheep subjected to 1 or 2 sequential biopsies 4 months apart, respectively. Thus, a preclinical diagnosis of scrapie in live sheep can be achieved by a combination of a simple sampling procedure, which can be repeated several times with no detrimental effect for the animals, and a rapid and efficient laboratory method.

  3. Isolation of cDNAs of scrapie-modulated RNAs by subtractive hybridization of a cDNA library.

    OpenAIRE

    1988-01-01

    We have developed a subtractive cloning procedure based on the hybridization of single-stranded cDNA libraries constructed in pi H3M, a vector containing the phage M13 origin of replication. We have used this strategy to isolate three transcripts whose abundance is increased in scrapie-infected brain. DNA sequence analysis showed that they represent glial fibrillary acidic protein, metallothionein II, and the B chain of alpha-crystallin; the latter two may represent a response to stress.

  4. Proteinase K-resistant material in ARR/VRQ sheep brain affected with classical scrapie is composed mainly of VRQ prion protein.

    Science.gov (United States)

    Jacobs, J G; Bossers, A; Rezaei, H; van Keulen, L J M; McCutcheon, S; Sklaviadis, T; Lantier, I; Berthon, P; Lantier, F; van Zijderveld, F G; Langeveld, J P M

    2011-12-01

    Classical scrapie is a prion disease in sheep and goats. In sheep, susceptibility to disease is genetically influenced by single amino acid substitutions. Genetic breeding programs aimed at enrichment of arginine-171 (171R) prion protein (PrP), the so-called ARR allele, in the sheep population have been demonstrated to be effective in reducing the occurrence of classical scrapie in the field. Understanding the molecular basis for this reduced prevalence would serve the assessment of ARR adaptation. The prion formation mechanism and conversion of PrP from the normal form (PrP(C)) to the scrapie-associated form (PrP(Sc)) could play a key role in this process. Therefore, we investigated whether the ARR allele substantially contributes to scrapie prion formation in naturally infected heterozygous 171Q/R animals. Two methods were applied to brain tissue of 171Q/R heterozygous sheep with natural scrapie to determine the relative amount of the 171R PrP fraction in PrP(res), the proteinase K-resistant PrP(Sc) core. An antibody test differentiating between 171Q and 171R PrP fragments showed that PrP(res) was mostly composed of the 171Q allelotype. Furthermore, using a novel tool for prion research, endoproteinase Lys-C-digested PrP(res) yielded substantial amounts of a nonglycosylated and a monoglycosylated PrP fragment comprising codons 114 to 188. Following two-dimensional gel electrophoresis, only marginal amounts (scrapie-infected animals. This is suggestive of a poor adaptation of classical scrapie to this resistance allele under these natural conditions.

  5. Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion.

    Science.gov (United States)

    Dassanayake, Rohana P; Orrú, Christina D; Hughson, Andrew G; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A; Knowles, Donald P; Schneider, David A

    2016-03-01

    Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200  mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10(- )3 dilution within 15  h. Our findings indicate that RT-QuIC was at least 10,000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples.

  6. Accumulation of pathological prion protein PrPSc in the skin of animals with experimental and natural scrapie.

    Directory of Open Access Journals (Sweden)

    Achim Thomzig

    2007-05-01

    Full Text Available Prion infectivity and its molecular marker, the pathological prion protein PrP(Sc, accumulate in the central nervous system and often also in lymphoid tissue of animals or humans affected by transmissible spongiform encephalopathies. Recently, PrP(Sc was found in tissues previously considered not to be invaded by prions (e.g., skeletal muscles. Here, we address the question of whether prions target the skin and show widespread PrP(Sc deposition in this organ in hamsters perorally or parenterally challenged with scrapie. In hamsters fed with scrapie, PrP(Sc was detected before the onset of symptoms, but the bulk of skin-associated PrP(Sc accumulated in the clinical phase. PrP(Sc was localized in nerve fibres within the skin but not in keratinocytes, and the deposition of PrP(Sc in skin showed no dependence from the route of infection and lymphotropic dissemination. The data indicated a neurally mediated centrifugal spread of prions to the skin. Furthermore, in a follow-up study, we examined sheep naturally infected with scrapie and detected PrP(Sc by Western blotting in skin samples from two out of five animals. Our findings point to the skin as a potential reservoir of prions, which should be further investigated in relation to disease transmission.

  7. Susceptibility of GT1-7 cells to mouse-passaged field scrapie isolates with a long incubation.

    Science.gov (United States)

    Miyazawa, Kohtaro; Okada, Hiroyuki; Iwamaru, Yoshifumi; Masujin, Kentaro; Yokoyama, Takashi

    2014-01-01

    A typical feature of scrapie in sheep and goats is the accumulation of disease-associated prion protein. Scrapie consists of many strains with different biological properties. Nine natural sheep scrapie cases were transmitted to wild-type mice and mouse-passaged isolates were classified into 2 types based on incubation time: short and long. These 2 types displayed a distinct difference in their pathology. We attempted to transmit these mouse-passaged isolates to 2 murine cell lines (GT1-7 and L929) to compare their properties. All of the isolates were transmitted to L929 cells. However, only mouse-passaged field isolates with a long incubation time were transmitted to GT1-7 cells. This specific susceptibility of GT1-7 cells was also confirmed with a primary-passaged isolate that was not completely adapted to the new host species. Characterization of the mechanisms of the specific susceptibility of GT1-7 cells to isolates with a long incubation time may lead to a greater understanding of the differences among prion strains.

  8. Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Nielsen, J.E.; Stokholm, J.

    2008-01-01

    BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic...... features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer......'s disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense...

  9. A macroprolactinoma becoming resistant to cabergoline and developing atypical pathology

    Science.gov (United States)

    Farah, George; Fathelrahman, Ahmed; Cudlip, Simon; Ansorge, Olaf; Karavitaki, Niki; Grossman, Ashley B

    2016-01-01

    Summary Pituitary adenomas are a common intracranial neoplasm, usually demonstrating a benign phenotype. They can be classified according to pathological, radiological or clinical behaviour as typical, atypical or carcinomas, invasive or noninvasive, and aggressive or nonaggressive. Prolactinomas account for 40–60% of all pituitary adenomas, with dopamine agonists representing the first-line treatment and surgery/radiotherapy reserved for drug intolerance/resistance or in neuro-ophthalmological emergencies. We present the case of a 62-year-old man with an apparently indolent prolactin-secreting macroadenoma managed with partial resection and initially showing a biochemical response to cabergoline. Five years later, the tumour became resistant to cabergoline, despite a substantial increase in dosage, showing rapid growth and causing worsening of vision. The patient then underwent two further transsphenoidal operations and continued on high-dose cabergoline; despite these interventions, the tumour continued enlarging and prolactin increased to 107 269 U/L. Histology of the third surgical specimen demonstrated features of aggressive behaviour (atypical adenoma with a high cell proliferation index) not present in the tumour removed at the first operation. Subsequently, he was referred for radiotherapy aiming to control tumour growth. Learning points: The development of secondary resistance to dopamine agonists (DAs) is a serious sign as it may be associated with de-differentiation of the prolactinoma and thus of aggressive or malignant transformation. Significant de-differentiation of the adenoma documented on consecutive histologies suggests a possible transition to malignancy. A combination of histological ‘alarm’ features associated with persistent growth and escape from DAs treatment in recurrent adenomas should alert clinicians and demands close follow-up. A multidisciplinary approach by pathologists, endocrinologists and neurosurgeons is essential. PMID

  10. Figurative language processing in atypical populations: The ASD perspective

    Directory of Open Access Journals (Sweden)

    Mila eVulchanova

    2015-02-01

    Full Text Available This paper is intended to provide a critical overview of experimental and clinical research documenting problems in figurative language processing in atypical populations with a focus on the Autistic Spectrum. Research in the comprehension and processing of figurative language in autism invariably documents problems in this area. The greater paradox is that even at the higher end of the spectrum or in the cases of linguistically talented individuals with Asperger syndrome, where structural language competence is intact, problems with extended language persist. If we assume that figurative and extended uses of language essentially depend on the perception and processing of more concrete core concepts and phenomena, the commonly observed failure in atypical populations to understand figurative language remains a puzzle.Various accounts have been offered to explain this issue, ranging from linking potential failure directly to overall structural language competence (Brock et al., 2008; Norbury, 2005 to right-hemispheric involvement (Gold and Faust, 2010. We argue that the dissociation between structural language and figurative language competence in autism should be sought in more general cognitive mechanisms and traits in the autistic phenotype (e.g., in terms of weak central coherence, Vulchanova et al., 2012b, as well as failure at on-line semantic integration with increased complexity and diversity of the stimuli (Coulson and van Petten, 2002. This perspective is even more compelling in light of similar problems in a number of conditions, including both acquired (e.g., Aphasia and developmental disorders (Williams Syndrome. This dissociation argues against a simple continuity view of language interpretation.

  11. Biochemical and molecular studies of atypical nevi

    NARCIS (Netherlands)

    Nieuwpoort, Arno Frans van

    2011-01-01

    The results obtained in this thesis suggest that the most explicit differences between normal and atypical melanocytes are subtle changes in pigment biosynthesis and the functioning of the antioxidant system. Impairment of the antioxidant system and increased levels of pheomelanin result in increase

  12. Non-diabetic atypical necrobiosis lipoidica

    Directory of Open Access Journals (Sweden)

    Mittal R

    1994-01-01

    Full Text Available One 8 year female child had asymptomatic, anaesthetic, hypohidrotic, atrophic, yellowish, waxy plaque on the front of left thigh since 2 months. No nerve thickening was observed clinically or histopathologically. Hyperkeratosis, follicular keratosis, epidermal atrophy, degeneration of collagen, mononuclear granulomas and perivascular mononuclear infiltrate confirmed the clinical diagnosis of atypical necrobiosis lipoidica.

  13. Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

    Directory of Open Access Journals (Sweden)

    Derek To

    2014-01-01

    Full Text Available We present a patient with atypical pyoderma gangrenosum (APG, which involved the patient’s arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  14. Atypical pyoderma gangrenosum mimicking an infectious process.

    Science.gov (United States)

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  15. Atypical Alpha Asymmetry in Adults with ADHD

    Science.gov (United States)

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

    2009-01-01

    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  16. Atypical fractures on long term bisphosphonates therapy.

    LENUS (Irish Health Repository)

    Hussein, W

    2011-01-01

    Bisphosphonates reduce fractures risk in patients with osteoporosis. A new pattern of fractures is now being noted in patients on prolonged bisphosphonate therapy. We report a case of an atypical femoral fracture with preceding pain and highlight the characteristics of these fractures.

  17. Atypical visuomotor performance in children with PDD

    NARCIS (Netherlands)

    Schlooz, W.A.J.M.; Hulstijn, W.

    2012-01-01

    Children with autism spectrum disorders (ASD) frequently encounter difficulties in visuomotor tasks, which are possibly caused by atypical visuoperceptual processing. This was tested in children (aged 9–12 years) with pervasive developmental disorder (PDD; including PDD-NOS and Asperger syndrome), a

  18. Does the Presence of Scrapie Affect the Ability of Current Statutory Discriminatory Tests To Detect the Presence of Bovine Spongiform Encephalopathy?

    Science.gov (United States)

    Simmons, M M; Chaplin, M J; Vickery, C M; Simon, S; Davis, L; Denyer, M; Lockey, R; Stack, M J; O'Connor, M J; Bishop, K; Gough, K C; Maddison, B C; Thorne, L; Spiropoulos, J

    2015-08-01

    Current European Commission (EC) surveillance regulations require discriminatory testing of all transmissible spongiform encephalopathy (TSE)-positive small ruminant (SR) samples in order to classify them as bovine spongiform encephalopathy (BSE) or non-BSE. This requires a range of tests, including characterization by bioassay in mouse models. Since 2005, naturally occurring BSE has been identified in two goats. It has also been demonstrated that more than one distinct TSE strain can coinfect a single animal in natural field situations. This study assesses the ability of the statutory methods as listed in the regulation to identify BSE in a blinded series of brain samples, in which ovine BSE and distinct isolates of scrapie are mixed at various ratios ranging from 99% to 1%. Additionally, these current statutory tests were compared with a new in vitro discriminatory method, which uses serial protein misfolding cyclic amplification (sPMCA). Western blotting consistently detected 50% BSE within a mixture, but at higher dilutions it had variable success. The enzyme-linked immunosorbent assay (ELISA) method consistently detected BSE only when it was present as 99% of the mixture, with variable success at higher dilutions. Bioassay and sPMCA reported BSE in all samples where it was present, down to 1%. sPMCA also consistently detected the presence of BSE in mixtures at 0.1%. While bioassay is the only validated method that allows comprehensive phenotypic characterization of an unknown TSE isolate, the sPMCA assay appears to offer a fast and cost-effective alternative for the screening of unknown isolates when the purpose of the investigation was solely to determine the presence or absence of BSE.

  19. Psychiatric syndromes associated with atypical chest pain

    Directory of Open Access Journals (Sweden)

    Nikolić Gordana

    2010-01-01

    Full Text Available Background/Aim. Chest pain often indicates coronary disease, but in 25% of patients there is no evidence of ischemic heart disease using standard diagnostic tests. Beside that, cardiologic examinations are repeated several times for months. If other medical causes could not be found, there is a possibility that chest pain is a symptom of psychiatric disorder. The aim of this study was to determine the presence of psychiatric syndromes, increased somatization, anxiety, stress life events exposure and characteristic of chest pain expression in persons with atypical chest pain and coronary patients, as well as to define predictive parameters for atypical chest pain. Method. We compared 30 patients with atypical chest pain (E group to 30 coronary patients (K group, after cardiological and psychiatric evaluation. We have applied: Mini International Neuropsychiatric Interview (MINI, The Symptom Checklist 90-R (SCL-90 R, Beck Anxiety Inventory (BAI, Holms-Rahe Scale of stress life events (H-R, Questionnaire for pain expression Pain-O-Meter (POM. Significant differences between groups and predictive value of the parameters for atypical chest pain were determined. Results. The E group participants compared to the group K were younger (33.4 ± 5.4 : 48.3 ± 6,4 years, p < 0.001, had a moderate anxiety level (20.4 ± 11.9 : 9.6 ± 3.8, p < 0.001, panic and somatiform disorders were present in the half of the E group, as well as eleveted somatization score (SOM ≥ 63 -50% : 10%, p < 0.01 and a higher H-R score level (102.0 ± 52.2 : 46.5 ± 55.0, p < 0.001. Pain was mild, accompanied with panic. The half of the E group subjects had somatoform and panic disorders. Conclusion. Somatoform and panic disorders are associated with atypical chest pain. Pain expression is mild, accompained with panic. Predictive factors for atypical chest pain are: age under 40, anxiety level > 20, somatization ≥ 63, presence of panic and somatoform disorders, H-R score > 102

  20. The atypical calpains: evolutionary analyses and roles in Caenorhabditis elegans cellular degeneration.

    Directory of Open Access Journals (Sweden)

    Peter I Joyce

    Full Text Available The calpains are physiologically important Ca(2+-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca(2+](i. We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks. We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca(2+ dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover.

  1. The atypical calpains: evolutionary analyses and roles in Caenorhabditis elegans cellular degeneration.

    Science.gov (United States)

    Joyce, Peter I; Satija, Rahul; Chen, Maozi; Kuwabara, Patricia E

    2012-01-01

    The calpains are physiologically important Ca(2+)-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca(2+)](i). We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca(2+) dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover.

  2. Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrPSc accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype

    Science.gov (United States)

    Background Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. Findings This study reports the failure to detect PrPSc in nervous or lymphoid tis...

  3. Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrP(Sc) accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype.

    Science.gov (United States)

    Greenlee, Justin J; Smith, Jodi D; Hamir, Amir N

    2016-04-01

    Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. This study reports the failure to detect PrP(Sc) in nervous or lymphoid tissues of Suffolk sheep of the PRNP ARQ/ARR genotype after oral inoculation with a U.S. scrapie isolate. Lambs were inoculated within the first 24 h of birth with 1 ml of a 10% (wt./vol.) brain homogenate derived from a clinically affected ARQ/ARQ sheep. The inoculated sheep were observed daily throughout the experiment for clinical signs suggestive of scrapie until they were necropsied at 86 months post inoculation. Tissues were collected for examination by immunohistochemistry and enzyme immunoassay, but all failed to demonstrate evidence of scrapie infection. Neonatal sheep of the ARQ/ARQ genotype receiving the same inoculum developed scrapie within 24 months. Lambs of the ARQ/ARR genotype that received the same inoculum by intracranial inoculation develop scrapie with a prolonged incubation period and with abnormal prion present within the central nervous system, but not peripheral lymphoid tissues. Results of this study suggest that ARQ/ARR sheep are resistant to oral infection with the scrapie isolate used even during the neonatal period.

  4. Establishment of the Method of Immunohistochemistry Assay for the Detection of Scrapie in Chinese Short-Tailed Han Sheep by Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The method of immunohistochemistry assay for the detection of scrapie in Chinese Short-tailed Han sheep was established using monoclonal antibody. Genomic DNA was isolated from Chinese Short-tailed Han sheep blood. Using the polymerase chain reaction technique, PrP27-30 gene sequence was amplified from Chinese Short-tailed Han sheep genomic DNA. By recombinant DNA technology, the recombinant protein of Chinese Short-tailed Han sheep PrP27-30 was obtained. Then, using standard methodology of myeloma cell fusion, a panel of monoclonal antibodies was generated. With mAbs, scrapie in Chinese Short-tailed Han sheep was detected by immunohistochemistry assay. The recombinant protein of Chinese Short-tailed Han sheep PrP27-30 was obtained and a panel of six hybridoma cell lines secreting specific antibodies to Chinese Short-tailed Han sheep PrP27-30 related to scrapie was obtained with one fusion between myeloma Sp2/0 and spleen cells from mice immunized with the purified recombinant protein. Four hybridoma cell lines can be used in immunohistochemistry assay for the detection of scrapie in Chinese Short-tailed Han sheep. So that the special monoclonal antibody developed in author's institute can be used to detect PrPsc of scrapie in Chinese Short-tailed Han sheep by immunohistochemistry in China.

  5. Atypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria.

    LENUS (Irish Health Repository)

    Casey, Jillian

    2014-02-01

    We report on clinical and genetic studies in a non-consanguineous Irish sib-pair with infantile dilated cardiomyopathy and retinopathy. A diagnosis of Alström Syndrome (AS) was considered and diagnostic testing pursued. The Alströms gene (ALMS1) is very large (23 exons) and diagnostic testing of mutational hotspots (exon 6, 8 and 10) was negative. Furthermore the siblings were tall and did not have the typical phenotype of nystagmus, photophobia, obesity or hearing loss and so the AS diagnosis was removed. We then sought to identify the causative gene in this family using whole exome sequencing. Unexpectedly, the exome analysis identified novel compound heterozygous ALMS1 mutations in exon 5 (c.777delT:p.D260fs*26) and exon 20 (c.12145_12146insC:p.S4049fs*36) that segregated with the phenotype. Although the siblings show some clinical overlap with AS, their phenotype is not classical. It is plausible that their atypical presentation may be due to the location of the ALMS1 mutations outside the usual mutational hotspots. Our findings show how atypical cases of AS may be missed under the current diagnostic guidelines and support consideration of complete ALMS1 sequencing in children with two or more features, even if all of the core clinical features of AS are not present.

  6. An atypical presentation of antiphospholipid antibody syndrome.

    Science.gov (United States)

    D'souza, Deepti; Dandakeri, Sukumar; Bhat, M Ramesh; Srinath, M K

    2015-01-01

    Cutaneous manifestations in antiphospholipid antibody syndrome (APS) though common, are extremely diverse and it is important to know which dermatological finding should prompt consideration of antiphospholipid syndrome. The cutaneous manifestations of APS vary from livedo reticularis to cutaneous necrosis, and systemic involvement is invariably an accomplice in APS. Cutaneous ulcers with sharp margins can be seen in APS and they are usually seen on the legs. This case had an atypical presentation, as the initial presentation was painful necrotic ulcers over the legs, which resembled pyoderma gangrenosum and she had no systemic manifestations. There was no history of any arterial or venous thrombosis or any abortions. Antiphospholipid syndrome can be tricky to diagnose when cutaneous lesions are atypical. Nonetheless, it is very important to pin down this syndrome early due to its systemic complications.

  7. An atypical presentation of antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Deepti D′Souza

    2015-01-01

    Full Text Available Cutaneous manifestations in antiphospholipid antibody syndrome (APS though common, are extremely diverse and it is important to know which dermatological finding should prompt consideration of antiphospholipid syndrome. The cutaneous manifestations of APS vary from livedo reticularis to cutaneous necrosis, and systemic involvement is invariably an accomplice in APS. Cutaneous ulcers with sharp margins can be seen in APS and they are usually seen on the legs. This case had an atypical presentation, as the initial presentation was painful necrotic ulcers over the legs, which resembled pyoderma gangrenosum and she had no systemic manifestations. There was no history of any arterial or venous thrombosis or any abortions. Antiphospholipid syndrome can be tricky to diagnose when cutaneous lesions are atypical. Nonetheless, it is very important to pin down this syndrome early due to its systemic complications.

  8. Primary atypical sacral meningioma- not always benign

    Energy Technology Data Exchange (ETDEWEB)

    Bhadra, A.K.; Casey, A.T.H.; Saifuddin, A.; Briggs, T.W. [Royal National Orthopaedic Hospital, Stanmore, London (United Kingdom)

    2007-06-15

    We present a case of an atypical recurrent meningioma of the sacrum with pulmonary metastasis in a 31-year-old man. He presented with deep-seated buttock pain and urinary hesitancy for 3 months. MRI revealed a lesion occupying the central and left side of the sacral canal at the S1-S2 level. Surgical excision of the lesion via a posterior approach was undertaken, and the patient became symptom-free post-operatively. Histology confirmed atypical meningioma. Eight months later he re-presented with similar symptoms, and MRI confirmed local recurrence. The patient underwent left hemisacrectomy. Six months later he again presented with low back pain and MRI confirmed a second local recurrence. A CT scan of the chest showed multiple lung metastases. The patient died of a severe chest infection 18 months later. (orig.)

  9. Atypical reactive histiocytosis. A case report.

    Directory of Open Access Journals (Sweden)

    Jorge E. Barleta del Castillo

    2004-08-01

    Full Text Available This paper presents the case of a 50 year old chronic alcoholic and heavy smoker female that was assisted at the provincial university hospital ¨Dr. Gustavo Aldereguía Lima¨ in Cienfuegos city due to a severe adenic syndrome and who was diagnosed as a case of atypical reactive histiocytosis , problem which disappeared with the abstinence of toxic habits, improving her health.

  10. Bisphosphonate-induced atypical subtrochanteric femoral fracture

    OpenAIRE

    2013-01-01

    The use of bisphosphonates (BPs) is universally accepted in the management of osteoporosis. However, a small percentage of patients have been recognised to develop atypical subtrochanteric fractures of the femur with the prolonged use of BPs. We report a rare case of bilateral insufficiency lesions in the proximal femora, where a major subtrochanteric fracture developed with a minor fall. This was successfully treated with internal fixation using proximal femoral nail.

  11. An atypical case of segmental spinal dysgenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zana, Elodie; Chalard, Francois; Sebag, Guy [Hopital Robert Debre, Department of Paediatric Imaging, Paris (France); Mazda, Keyvan [Hopital Robert Debre, Department of Paediatric Orthopaedic Surgery, Paris (France)

    2005-09-01

    Spinal segmental dysgenesis is a complex closed dysraphism. The diagnostic criteria are: lumbar or thoracolumbar vertebral dysgenesis causing kyphosis, focal spinal cord narrowing without exiting roots, deformity of the lower limbs and paraplegia or paraparesis. We present a newborn who showed atypical features of bifocal spinal cord narrowing, without any vertebral abnormality at the proximal level. This seems to be a variant of this rare entity, whose early diagnosis is important, as surgical stabilisation of the spine is required. (orig.)

  12. Atypical presentations of methemoglobinemia from benzocaine spray.

    Science.gov (United States)

    Tantisattamo, Ekamol; Suwantarat, Nuntra; Vierra, Joseph R; Evans, Samuel J

    2011-06-01

    Widely used for local anesthesia, especially prior to endoscopic procedures, benzocaine spray is one of the most common causes of iatrogenic methemoglobinemia. The authors report an atypical case of methemoglobinemia in a woman presenting with pale skin and severe hypoxemia, after a delayed repeat exposure to benzocaine spray. Early recognition and prompt management of methemoglobinemia is needed in order to lessen morbidity and mortality from this entity.

  13. An atypical mycobacterial infection of the shoulder

    Directory of Open Access Journals (Sweden)

    Christopher L Talbot

    2012-01-01

    Full Text Available Mycobacterium malmoense is an acid-fast non-tuberculous organism that most commonly causes pulmonary infection. Extrapulmonary infection has also been reported. With an increased emphasis being placed on the clinical importance of this organism, especially within Europe, we report the first case of septic arthritis of the shoulder caused by this organism. We also highlight the importance of considering atypical mycobacterium infection in the differential diagnosis of shoulder infection and issues surrounding the management of this entity.

  14. Atypical manifestations of multiple myeloma: Radiological appearance

    Energy Technology Data Exchange (ETDEWEB)

    Hess, Thomas [Department of Radiology, St-Vincenz Hospital, Auf dem Schafsberg, D-65549 Limburg (Germany)]. E-mail: t.hess@st-vincenz.de; Egerer, Gerlinde [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kasper, Bernd [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Rasul, Kakil Ibrahim [Hamad Medical Center, Moha (Qatar); Goldschmidt, Hartmut [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kauffmann, G.W. [Department of Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany)

    2006-05-15

    Diagnostic procedures performed on patients with multiple myeloma typically reveal lytic bone lesions, osteopenia or osteoporosis, bone marrow infiltration by plasma cells as well as overproduction of immunoglobulin or light chains in the serum or urine. Skeletal manifestations are extremely variable and the unusual forms have been described extensively. Extramedullary plasma-cell tumours (plasmocytoma) are found in about 5% of newly diagnosed patients with multiple myelomas. In this paper we present eight patients with atypical forms of multiple myeloma.

  15. Atypical retroperitoneal extension of iliopsoas bursitis

    Energy Technology Data Exchange (ETDEWEB)

    Coulier, B.; Cloots, V. [Department of Diagnostic Imaging, Cliniques St. Luc, Rue St Luc 8, 5004, Bouge, Namur (Belgium)

    2003-05-01

    We report two rare cases of iliopsoas bursitis extending into the retroperitoneal space. The first lesion contained much gas, mimicking a retroperitoneal abscess, and the second was responsible for atypical inguinal pain. The diagnosis was made by contrast-enhanced CT in both cases and arthrography in the first case. Iliopsoas bursitis in these two patients, it is hypothesized, extended into the retroperitoneum, at least in part, by way of intraneural or perineural structures. (orig.)

  16. An endogenous retrovirus and exogenous scrapie in a mouse model of aging.

    Science.gov (United States)

    Carp, R I; Meeker, H C; Kozlowski, I; Sersen, E A

    2000-01-01

    As we enter the post-genomic era, there is an increasing need for accurate methods of identifying host and pathogen factors that contribute to bacterial, viral and fungal disease. In addition, there is a requirement for fast and precise techniques to evaluate potential therapies for the prevention of infectious diseases. The development of useful and cost-effective model systems will be crucial in advancing our knowledge of all aspects of microbial pathogenesis. In this series, we will learn of animal models used to investigate diseases caused by a wide variety of pathogens, including HIV, Vibrio cholerae and Pseudomonas aeruginosa. A description of a model system specifically designed to study intracellular pathogens will be presented, as will a variety of the techniques currently used to exploit other useful models of infection. Additionally, a description of the mathematical models used to analyse the population biology of human onchocerciasis will be discussed. The series begins with an intriguing look at the possible connections between an endogenous retrovirus, the infectious agent of scrapie and accelerated senescence in a mouse model of early aging.

  17. Primary transmission of chronic wasting disease versus scrapie prions from small ruminants to transgenic mice expressing ovine or cervid prion protein.

    Science.gov (United States)

    Madsen-Bouterse, Sally A; Schneider, David A; Zhuang, Dongyue; Dassanayake, Rohana P; Balachandran, Aru; Mitchell, Gordon B; O'Rourke, Katherine I

    2016-09-01

    Development of mice expressing either ovine (Tg338) or cervid (TgElk) prion protein (PrP) have aided in characterization of scrapie and chronic wasting disease (CWD), respectively. Experimental inoculation of sheep with CWD prions has demonstrated the potential for interspecies transmission but, infection with CWD versus classical scrapie prions may be difficult to differentiate using validated diagnostic platforms. In this study, mouse bioassay in Tg338 and TgElk was utilized to evaluate transmission of CWD versus scrapie prions from small ruminants. Mice (≥5 per homogenate) were inoculated with brain homogenates from clinically affected sheep or goats with naturally acquired classical scrapie, white-tailed deer with naturally acquired CWD (WTD-CWD) or sheep with experimentally acquired CWD derived from elk (sheep-passaged-CWD). Survival time (time to clinical disease) and attack rates (brain accumulation of protease resistant PrP, PrPres) were determined. Inoculation with classical scrapie prions resulted in clinical disease and 100 % attack rates in Tg338, but no clinical disease at endpoint (>300 days post-inoculation, p.i.) and low attack rates (6.8 %) in TgElk. Inoculation with WTD-CWD prions yielded no clinical disease or brain PrPres accumulation in Tg338 at endpoint (>500 days p.i.), but rapid onset of clinical disease (~121 days p.i.) and 100 % attack rate in TgElk. Sheep-passaged-CWD resulted in transmission to both mouse lines with 100 % attack rates at endpoint in Tg338 and an attack rate of ~73 % in TgElk with some culled due to clinical disease. These primary transmission observations demonstrate the potential of bioassay in Tg338 and TgElk to help differentiate possible infection with CWD versus classical scrapie prions in sheep and goats.

  18. Prophylactic Nailing of Incomplete Atypical Femoral Fractures

    Directory of Open Access Journals (Sweden)

    Chang-Wug Oh

    2013-01-01

    Full Text Available Introduction. Recent reports have described the occurrence of low-energy subtrochanteric and femoral shaft fractures associated with long-term bisphosphonate use. Although information regarding the surgical treatment of these atypical femoral fractures is increasing, it is unclear if the preventive operation is useful in incomplete fractures. This study examined the results of preventive intramedullary nailing for incomplete atypical femoral fractures. Material and Methods. A retrospective search was conducted for patients older than 50 years receiving bisphosphonate therapy, with incomplete, nondisplaced fractures in either the subtrochanteric or diaphyseal area of the femur. Seventeen patients with a total of 20 incomplete, non-displaced lesions were included. The mean duration of bisphosphonate use was 50.5 months. Eleven of the 17 (64.7% patients had complete or incomplete fractures on the contralateral femur. All were treated with prophylactic fixation of an intramedullary (IM nail. The minimum followup was 12 months. Results. All cases healed with a mean period of 14.3 weeks. Nineteen of the 20 cases healed with the dissolution of incomplete fractures of the lateral aspect. A complete fracture developed at the time of nailing in one patient, but it healed with callus bridging. Conclusion. IM nailing appears to be a reliable way of preventing the progress of incomplete atypical femoral fractures.

  19. EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals

    DEFF Research Database (Denmark)

    Hald, Tine; Baggesen, Dorte Lau

    impact of PrP genotype of the embryo and/or of the ram and donor ewe on this risk was also assessed. The new data made available over the last three years further reinforce the view that classical scrapie could be vertically transmitted in sheep. Since the possibility of such vertical transmission....... Under natural exposure conditions, animals that are heterozygous or homozygous A136R154R171 display respectively a low or negligible risk of being infected. The genetic control of the susceptibility to classical scrapie is also likely to impact on the risk of transmitting the disease via embryo transfer...

  20. Transpupillary thermotherapy for atypical central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Kawamura R

    2012-01-01

    Full Text Available Ryosuke Kawamura1,2, Hidenao Ideta1, Hideyuki Hori1, Kenya Yuki2, Tsuyoshi Uno1, Tatsurou Tanabe1, Kazuo Tsubota2, Tsutomu Kawasaki11Ideta Eye Hospital, Kumamoto, Japan; 2Keio University, School of Medicine, Department of Ophthalmology, Tokyo, JapanBackground: Central serous chorioretinopathy (CSC has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC.Methods: We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 µm, and exposure time of 13–60 seconds to minimize retinal damage.Results: In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30. Final BCVA

  1. Atypical juvenile neuronal ceroid lipofuscinosis: A report of three cases

    Directory of Open Access Journals (Sweden)

    Gururaj Setty

    2013-01-01

    Full Text Available The diagnosis of juvenile neuronal ceroid lipofuscinosis (JNCL is usually based on age of onset, initial clinical symptoms, clinical progression, and pathologic findings. Our cases manifested atypical clinical symptomatology and/or pathologic findings and therefore, represent variant forms of JNCL. Case 1 and 2 presented with slow developmental regression from the age of 4 years and became blind and wheelchair bound at around 8 years. Pathologic finding of lymphocytes showed fingerprint inclusion which was consistent with JNCL. Mutational analysis was positive for CLN5 which usually presents as variant late infantile NCL (LINCL and more common in Finnish population. Case 3 presented with progressive visual loss from the age of 8 years. Clinical symptomatology and age of onset were similar to that of JNCL but was found to have low palmitoyl protein thioesterase, granular inclusion body, and CLN1 mutation, thus representing milder form of INCL. These three cases demonstrated phenotypic-genotypic variations. Pertinent issues relating diagnostic difficulties, ophthalmologic, neuroradiological, and laboratory aspects are discussed.

  2. Transcriptome analysis of CNS immediately before and after the detection of PrP(Sc) in SSBP/1 sheep scrapie.

    Science.gov (United States)

    Gossner, Anton G; Hopkins, John

    2014-10-10

    Sheep scrapie is a transmissible spongiform encephalopathy (TSE), progressive and fatal neurodegenerative diseases of the central nervous system (CNS) linked to the accumulation of misfolded prion protein, PrP(Sc). New Zealand Cheviot sheep, homozygous for the VRQ genotype of the PRNP gene are most susceptible with an incubation period of 193 days with SSBP/1 scrapie. However, the earliest time point that PrP(Sc) can be detected in the CNS is 125 days (D125). The aim of this study was to quantify changes to the transcriptome of the thalamus and obex (medulla) at times immediately before (D75) and after (D125) PrP(Sc) was detected. Affymetrix gene arrays were used to quantify gene expression in the thalamus and Illumina DGE-tag profiling for obex. Ingenuity Pathway Analysis was used to help describe the biological processes of scrapie pathology. Neurological disease and Cancer were common Bio Functions in each tissue at D75; inflammation and cell death were major processes at D125. Several neurological receptors were significantly increased at D75 (e.g. CHRNA6, GRM1, HCN2), which might be clues to the molecular basis of psychiatric changes associated with TSEs. No genes were significantly differentially expressed at both D75 and D125 and there was no progression of events from earlier to later time points. This implies that there is no simple linear progression of pathological or molecular events. There seems to be a step-change between D75 and D125, correlating with the detection of PrP(Sc), resulting in the involvement of different pathological processes in later TSE disease.

  3. Characterization of the atypical lymphocytes in African swine fever

    Science.gov (United States)

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Karalyan, N. Yu; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  4. Characterization of the atypical lymphocytes in African swine fever

    Directory of Open Access Journals (Sweden)

    Z. A. Karalyan

    2016-07-01

    Full Text Available Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection.

  5. Atypical meningioma and extensive calvarium defects in neurofibromatosis type 1

    Energy Technology Data Exchange (ETDEWEB)

    Simsek, Enver [Department of Paediatrics, Duzce Medical Faculty, Abant Izzet Baysal University, Konuralp-Duzce (Turkey); Yavuz, Cevdet [Department of Neurosurgery, Duzce Medical Faculty, Abant Izzet Baysal University, Konuralp-Duzce (Turkey); Ustundag, Nil [Department of Pathology, Abant Izzet Baysal University School of Medicine, Konuralp-Duzce (Turkey)

    2003-08-01

    A 9-year-old girl with neurofibromatosis type 1 (NF1) presented with a massive atypical meningioma and calvarial defect. Skull radiographs and cranial CT showed an extensive lytic bone lesion at the vertex. MRI demonstrated a large mass invading the calvarium and sagittal sinus. The histopathological and immunohistochemical diagnosis of the resected mass was atypical meningioma. To our knowledge, this is the first case of NF1 associated with atypical meningioma and massive calvarial defect in a child. (orig.)

  6. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  7. Hematological Side Effects of Atypical Antipsychotic Drugs

    Directory of Open Access Journals (Sweden)

    Serap Erdogan

    2009-10-01

    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  8. Determination of sex and scrapie resistance genotype in preimplantation ovine embryos.

    Science.gov (United States)

    Guignot, Florence; Baril, Gerard; Dupont, Francis; Cognie, Yves; Folch, Jose; Alabart, Jose Luis; Poulin, Naty; Beckers, Jean-Francois; Bed'hom, Bertrand; Babilliot, Jean-Marc; Mermillod, Pascal

    2009-02-01

    The aim of this study was to test the accuracy of genotype diagnosis after pre-amplification of DNA extracted from biopsies obtained by microblade cutting of ovine embryos and to evaluate the viability of biopsied embryos after vitrification/warming and transfer to recipients. Sex and PrP genotypes were determined. Sex diagnosis was done by PCR amplification of ZFX/ZFY and SRY sequences after PEP-PCR while PrP genotype determination was performed after specific pre-amplification of specific target including codons 136, 154 and 171. Embryos were collected at Day 7 after oestrus. Blastocysts and expanded blastocysts were biopsied immediately after collection whereas compacted morulae were biopsied after 24 hr of in vitro culture. Eighty-nine biopsied embryos were frozen by vitrification. Fresh and vitrified whole embryos were kept as control. DNA of biopsies was extracted and pre-amplified. Sex diagnosis was efficient for 96.6% of biopsies and PrP genotyping was determined in 95.8% of codons. After embryo transfer, no significant difference was observed in lambing rate between biopsied, vitrified control and fresh embryos (54.5%, 60% and 66.6%, respectively). Embryo survival rate was not different between biopsied and whole vitrified embryos (P = 0.38). At birth, 96.7% of diagnosed sex and 95.4% of predetermined codons were correct. Lamb PrP profiles were in agreement with parental genotype. PEP-PCR coupled with sex diagnosis and nested PCR coupled with PrP genotype predetermination are very accurate techniques to genotype ovine embryo before transfer. These original results allow planning of selection of resistant genotype to scrapie and sex of offspring before transfer of cryopreserved embryo.

  9. Atypical And Severe Enlargement Of Right Atrium.

    Science.gov (United States)

    Siniscalchi, Carmine; Rossetti, Pietro; Rocci, Anna; Rubino, Pasquale; Basaglia, Manuela; Gaibazzi, Nicola; Quintavalla, Roberto

    2016-09-13

    A 76 year-old woman was admitted to the Emergency Department for recent-onset dyspnea and cough. The electrocardiogram was considered inconclusive. A thoracic X-ray showed global cardiac profile enlargement. Computed tomography, acutely performed in the clinical suspicion of atypical pneumonia/myocarditis or pericardial effusion, showed cardiac enlargement especially of the right chambers. In order to investigate Ebstein's anomaly, pericardial cysts, tumors or other conditions of the right heart a simple trans-thoracic echocardiogram was performed. Four chambers view showed a giant right atrium aneurysm with moderate tricuspid regurgitation without stenosis or typical Ebstein's echocardiographic pattern.

  10. Wilson’s disease: Atypical imaging features

    Directory of Open Access Journals (Sweden)

    Venugopalan Y Vishnu

    2016-10-01

    Full Text Available Wilson’s disease is a genetic movement disorder with characteristic clinical and imaging features. We report a 17- year-old boy who presented with sialorrhea, hypophonic speech, paraparesis with repeated falls and recurrent seizures along with cognitive decline. He had bilateral Kayser Flescher rings. Other than the typical features of Wilson’s disease in cranial MRI, there were extensive white matter signal abnormalities (T2 and FLAIR hyperintensities and gyriform contrast enhancement which are rare imaging features in Wilson's disease. A high index of suspicion is required to diagnose Wilson’s disease when atypical imaging features are present.

  11. Atypical outcome in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Schmidt, K; Freidson, S

    1990-07-01

    This report describes the course of psychiatric illness in two boys. Both presented with attention deficit hyperactivity disorder (ADHD) in midchildhood; after puberty, one boy developed a schizophrenic illness while the other boy developed a major affective illness. Although the major ADHD outcome studies have found no link between the childhood occurrence of ADHD and psychosis in adulthood, occasionally such a link may exist. The theoretical and practical implications of this finding are discussed. It should be noted, however, that such outcome is highly atypical and very rare.

  12. Atypical Log D profile of rifampicin

    Directory of Open Access Journals (Sweden)

    Mariappan T

    2007-01-01

    Full Text Available The distribution coefficient (log D values of rifampicin, an essential first-line antitubercular drug, at gastrointestinal pH conditions are not reported in literature. Hence determinations were made using n-octanol and buffers ranging between pH 1-7. Also, log D values were predicted using Prolog D. Both the determinations showed opposite behaviour. The atypical experimental log D profile of rifampicin could be attributed to its surface-active properties, which also explained the reported permeability behaviour of the drug in various gastrointestinal tract segments.

  13. Atypical giant chondroblastoma mimicking a chondrosarcoma.

    Science.gov (United States)

    Dhanda, Sunita; Menon, Santosh; Gulia, Ashish

    2015-01-01

    Chondroblastoma is a rare, benign tumor derived from chondroblasts, commonly presenting in the second decade of life. It is usually found in the epiphysis or apophysis of long bones; however, it may rarely affect flat bones like scapula. Occasionally a histologically typical chondroblastoma may exhibit an aggressive behavior that is not normally associated with benign tumors such as a large size, pulmonary metastases, joint and soft-tissue infiltration and local recurrence. We present a case report of a patient with chondroblastoma showing atypical radiological presentation and non-concordance with age.

  14. Bisphosphonates and Atypical Fractures of Femur

    Directory of Open Access Journals (Sweden)

    Tero Yli-Kyyny

    2011-01-01

    Full Text Available Bisphosphonates are the most widely prescribed medicines for the treatment of osteoporosis and have generally been regarded as well-tolerated and safe drugs. Since 2005, there have been numerous case reports about atypical fractures of the femur linked to long-term treatment of osteoporosis with bisphosphonates. Some attempts to characterize pathophysiology and epidemiology of these fractures have been published as well. However, as the American Society for Bone and Mineral Research (ASBMR concluded in their task force report, the subject warrants further studies.

  15. Atypical calcific tendinitis with cortical erosions

    Energy Technology Data Exchange (ETDEWEB)

    Kraemer, E.J. [College of Medicine, Univ. of Iowa, Iowa City, IA (United States); El-Khoury, G.Y. [Dept. of Radiology and Orthopaedics, Univ. of Iowa, Iowa City, IA (United States)

    2000-12-01

    Objective. To present and discuss six cases of calcific tendinitis in atypical locations (one at the insertion of the pectoralis major and five at the insertion of the gluteus maximus).Patients and results. All cases were associated with cortical erosions, and five had soft tissue calcifications. The initial presentation was confusing and the patients were suspected of having infection or neoplastic disease.Conclusion. Calcific tendinitis is a self-limiting condition. It is important to recognize the imaging features of this condition to avoid unnecessary investigation and surgery. (orig.)

  16. Gorlin’s syndrome: Atypical case report

    Directory of Open Access Journals (Sweden)

    Sanjay N. Agrawal

    2014-10-01

    Full Text Available Gorlin syndrome or basal cell nevus syndrome (BCNS is a rare autosomal dominant disorder. The condition appears to have complete penetrance and variable expressivity, which makes clinilcal presentation among families variable. All known BCNS carry mutations in PATCHED gene. A 65 years old male patient presented with complaints of characteristic skin lesions on his face, back, palms since early adulthood. The lesions were pigmented nodules with characteristic border. The histopathology showed characteristic features suggestive of Basal Cell Carcinoma (BCC. This case was atypical due to appearance of lesions quite later in life.

  17. Atypical presentation of childhood obsessive compulsive disorder

    Directory of Open Access Journals (Sweden)

    Satyakam Mohapatra

    2016-01-01

    Full Text Available Obsessive-compulsive disorder (OCD is one of the most prevalent psychiatric disorders in children and adolescents. The phenomenology of OCD in children and adolescent is strikingly similar to that of adults. But at times, the presentation of OCD may be so atypical or unusual in children and adolescents that may lead to misdiagnosis or delay in diagnosis. We report a case of 10-year-old child who was initially misdiagnosed with schizophrenia, and treated with antipsychotic for 2 months. But once the core symptoms were recognized as obsessions and compulsions and appropriately treated in the line of OCD, the symptoms resolved significantly.

  18. Discovery of a novel, monocationic, small-molecule inhibitor of scrapie prion accumulation in cultured sheep microglia and rov cells PLoS one

    Science.gov (United States)

    Prion diseases, including sheep scrapie are neurodegenerative diseases with the fundamental pathogenesis involving conversion of normal cellular prion protein (PrPC) to disease-associated prion protein (PrPSc). An aromatic monocationic furamidine analogue (DB772), which has previously demonstrated a...

  19. Sheep scrapie susceptibility-linked polymorphisms do not modulate the initial binding of cellular to disease-associated prion protein prior to conversion

    NARCIS (Netherlands)

    Rigter, A.; Bossers, A.

    2005-01-01

    Conversion of the host-encoded protease-sensitive cellular prion protein (PrPC) into the scrapie-associated protease-resistant isoform (PrPSc) of prion protein (PrP) is the central event in transmissible spongiform encephalopathies or prion diseases. Differences in transmissibility and susceptibilit

  20. Primary transmission of chronic wasting disease versus scrapie prions from small ruminants to transgenic mice expressing ovine and cervid prion protein

    Science.gov (United States)

    Identifying transmissible spongiform encephalopathy (TSE) reservoirs that could lead to disease re-emergence is imperative to U.S. scrapie eradication efforts. Transgenic mice expressing the cervid (TgElk) or ovine (Tg338) prion protein have aided characterization of chronic wasting disease (CWD) an...

  1. A lympho-follicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep.

    Directory of Open Access Journals (Sweden)

    Caterina Maestrale

    Full Text Available In sheep scrapie, pathological prion protein (PrP(Sc deposition occurs in the lymphoreticular and central nervous systems. We investigated PrP(Sc distribution in scrapie-affected sheep showing simultaneous evidence of chronic lymphofollicular, lymphoproliferative/non-lymphofollicular, and/or granulomatous inflammations in their mammary gland, lung, and ileum. To do this, PrP(Sc detection was carried out via immunohistochemistry and Western Blotting techniques, as well as through inflammatory cell immunophenotyping. Expression studies of gene coding for biological factors modulating the host's inflammatory response were also carried out. We demonstrated that ectopic PrP(Sc deposition occurs exclusively in the context of lymphofollicular inflammatory sites, inside newly formed and well-organized lymphoid follicles harboring follicular dendritic cells. On the contrary, no PrP(Sc deposition was detected in granulomas, even when they were closely located to newly formed lymphoid follicles. A significantly more consistent expression of lymphotoxin α and β mRNA was detected in lymphofollicular inflammation compared to the other two types, with lymphotoxin α and β signaling new lymphoid follicles' formation and, likely, the occurrence of ectopic PrP(Sc deposition inside them. Our findings suggest that, in sheep co-affected by scrapie and chronic inflammatory conditions, only newly formed lymphoid follicles provide a suitable micro-environment that supports the scrapie agent's replication in inflammatory sites, with an increased risk of prion shedding through body secretions/excretions.

  2. Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease

    Science.gov (United States)

    The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (I...

  3. Relationship of PrPSc molecular properties with incubation time in a natural prion disease host: a characterization of three isolates of U.S. sheep scrapie

    Science.gov (United States)

    Determination of aspects of tertiary and quaternary structure of PrPSc associated with differences in disease presentation in the host is a key area of interest in the prion field. Previously, we determined that a U.S. scrapie isolate (136-VDEP) with a short incubation time upon passage in sheep als...

  4. A lympho-follicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep.

    Science.gov (United States)

    Maestrale, Caterina; Di Guardo, Giovanni; Cancedda, Maria Giovanna; Marruchella, Giuseppe; Masia, Mariangela; Sechi, Stefania; Macciocu, Simonetta; Santucciu, Cinzia; Petruzzi, Mara; Ligios, Ciriaco

    2013-01-01

    In sheep scrapie, pathological prion protein (PrP(Sc)) deposition occurs in the lymphoreticular and central nervous systems. We investigated PrP(Sc) distribution in scrapie-affected sheep showing simultaneous evidence of chronic lymphofollicular, lymphoproliferative/non-lymphofollicular, and/or granulomatous inflammations in their mammary gland, lung, and ileum. To do this, PrP(Sc) detection was carried out via immunohistochemistry and Western Blotting techniques, as well as through inflammatory cell immunophenotyping. Expression studies of gene coding for biological factors modulating the host's inflammatory response were also carried out. We demonstrated that ectopic PrP(Sc) deposition occurs exclusively in the context of lymphofollicular inflammatory sites, inside newly formed and well-organized lymphoid follicles harboring follicular dendritic cells. On the contrary, no PrP(Sc) deposition was detected in granulomas, even when they were closely located to newly formed lymphoid follicles. A significantly more consistent expression of lymphotoxin α and β mRNA was detected in lymphofollicular inflammation compared to the other two types, with lymphotoxin α and β signaling new lymphoid follicles' formation and, likely, the occurrence of ectopic PrP(Sc) deposition inside them. Our findings suggest that, in sheep co-affected by scrapie and chronic inflammatory conditions, only newly formed lymphoid follicles provide a suitable micro-environment that supports the scrapie agent's replication in inflammatory sites, with an increased risk of prion shedding through body secretions/excretions.

  5. Postmortem diagnosis of preclinical and clinical scrapie in sheep by the detection of disease-associated PrP in their rectal mucosa.

    Science.gov (United States)

    González, L; Dagleish, M P; Bellworthy, S J; Sisó, S; Stack, M J; Chaplin, M J; Davis, L A; Hawkins, S A C; Hughes, J; Jeffrey, M

    2006-03-11

    Samples of tissue from the central nervous system (cns), the lymphoreticular system (lrs) and the rectal mucosa of a large number of scrapie-exposed sheep, with and without signs of clinical disease, were examined immunohistochemically for evidence of disease-associated prion protein (PrP(d)). The rectal mucosa has received almost no attention so far in scrapie diagnosis, despite its abundant rectoanal mucosa-associated lymphoid tissue, and its accessibility. The scrapie-confirmed cases included 244 with clinical disease, of which 237 (97.1 per cent) were positive in the rectal mucosa, and 121 apparently healthy sheep, of which 104 (86 per cent) were positive in the rectal mucosa. PrP(d) was detected in 86.4 to 91.5 per cent of the other lrs tissues of the healthy sheep examined and in 77.7 per cent of their cns tissues. The stage of infection, therefore, affected the probability of a positive result in the rectal mucosa, whereas the breed, PrP genotype, age and sex had little or no independent effect. Accumulations of PrP(d) were observed in the rectal mucosa and other lrs tissues of vrq/arr sheep with preclinical and clinical scrapie, albeit with a lower frequency and magnitude than in sheep of other PrP genotypes. Western immunoblotting analyses of samples of rectal mucosa gave the characteristic PrP glycoprofile, with a sensitivity similar to that of immunohistochemistry.

  6. Experimental transmission of transmissible spongiform encephalopathies (scrapie, chronic wasting disease, transmissible mink encephalopathy) to cattle and their differentiation from bovine spongiform encephalopathy

    Science.gov (United States)

    Experimental cross-species transmission of TSE agents provides valuable information for identification of potential host ranges of known TSEs. This report provides a synopsis of TSE (scrapie, CWD, TME) transmission studies that have been conducted in cattle and compares these findings to those seen ...

  7. Distinct spatial activation of intrinsic and extrinsic apoptosis pathways in natural scrapie: association with prion-related lesions

    Science.gov (United States)

    Serrano, Carmen; Lyahyai, Jaber; Bolea, Rosa; Varona, Luis; Monleón, Eva; Badiola, Juan J.; Zaragoza, Pilar; Martín-Burriel, Inmaculada

    2009-01-01

    Neurodegeneration and gliosis are the main neuropathological features of prion diseases. However, the molecular mechanisms involved in these processes remain unclear. Several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. Here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. Expression changes obtained by real-time RT-PCR were also compared with the extent of classical scrapie lesions, such as prion deposition, neuronal vacuolisation, spongiosis, and astrogliosis as well as with the activation of caspase-3, using a stepwise regression. The results suggest that the factors assessed participate in apoptotic or inflammatory functions, depending on the affected area. The mitochondrial apoptosis pathway was associated with prion deposition in the prefrontal cortex (the less affected area), and with activation of caspase-3-mediated cell death via over-expression of BAK. In addition to its known association with astroglial activation, the extrinsic apoptosis pathway was also related to cell death and neuronal vacuolisation. PMID:19401142

  8. IMPY, a potential {beta}-amyloid imaging probe for detection of prion deposits in scrapie-infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Song, P.-J. [INSERM, U619, F-37000 Tours (France); Universite Francois-Rabelais, F-37000 Tours (France); IFR135, F-37000 Tours (France); Bernard, Serge [IFR135, F-37000 Tours (France); INRA, UR1282, IASP, 37380 Nouzilly (France)], E-mail: bernard@tours.inra.fr; Sarradin, Pierre [INRA, UR1282, IASP, 37380 Nouzilly (France); Vergote, Jackie [INSERM, U619, F-37000 Tours (France); Universite Francois-Rabelais, F-37000 Tours (France); IFR135, F-37000 Tours (France); Barc, Celine [INRA, UR1282, IASP, 37380 Nouzilly (France); Chalon, Sylvie [INSERM, U619, F-37000 Tours (France); Universite Francois-Rabelais, F-37000 Tours (France); IFR135, F-37000 Tours (France); Kung, M.-P.; Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Guilloteau, Denis [INSERM, U619, F-37000 Tours (France); Universite Francois-Rabelais, F-37000 Tours (France); IFR135, F-37000 Tours (France)

    2008-02-15

    Introduction: A potential single-photon emission computed tomography imaging agent for labeling of A{beta} plaques of Alzheimer's disease, IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), would be effective in detection of prion amyloid deposits in transmissible spongiform encephalopathies (TSEs). Methods: In vitro autoradiographic studies were carried out with [{sup 125}I]IMPY on brain sections from scrapie-infected mice and age-matched controls. Competition study was performed to evaluate the prion deposit binding specificity with nonradioactive IMPY. Results: Binding of [{sup 125}I]IMPY was observed in infected brain sections, while on age-matched control brain sections, there was no or very low labeling. Prion deposit binding was confirmed by histoblots with prion protein-specific monoclonal antibody 2D6. In the presence of nonradioactive IMPY, the binding of [{sup 125}I]IMPY was significantly inhibited in all regions studied. Conclusions: These findings indicate that IMPY can detect the prion deposits in vitro in scrapie-infected mice. Labeled with {sup 123}I, this ligand may be useful to quantitate prion deposit burdens in TSEs by in vivo imaging.

  9. Prion protein genotype survey confirms low frequency of scrapie-resistant K222 allele in British goat herds.

    Science.gov (United States)

    Goldmann, W; Marier, E; Stewart, P; Konold, T; Street, S; Langeveld, J; Windl, O; Ortiz-Pelaez, A

    2016-02-13

    Scrapie in goats is a transmissible, fatal prion disease, which is endemic in the British goat population. The recent success in defining caprine PRNP gene variants that provide resistance to experimental and natural classical scrapie has prompted the authors to conduct a survey of PRNP genotypes in 10 goat breeds and 52 herds to find goats with the resistant K222 allele. They report here the frequencies in 1236 tested animals of the resistance-associated K222 and several other alleles by breed and herd. Eight animals were found to be heterozygous QK222 goats (0.64 per cent genotype frequency, 95 per cent CI 0.28 to 1.27 per cent) but no homozygous KK222 goats were detected. The K222 allele was found in Saanen, Toggenburg and Anglo-Nubian goats. The fact that only a few goats with the K222 allele have been identified does not preclude the possibility to design and implement successful breeding programmes at national level.

  10. Establishment of a Stable PrPSc Panel from Brain Tissues of Experimental Hamsters with Scrapie Strain 263K

    Institute of Scientific and Technical Information of China (English)

    BAO-YUN ZHANG; CHAN TIAN; JUN HAN; CHEN GAO; QI SHI; JIAN-MING CHEN; HUI-YING JIANG; WEI ZHOU; XIAO-Ping DONG

    2009-01-01

    Objective To establish a stable PrPSc panel from brain tissues of experimental hamsters infected with scrapie agent 263K for evaluating diagnostic techniques of human and animals' prion diseases. Methods Thirty brain tissue samples from hamsters intracerebrally infected with scrapie strain 263K and another 30 samples from normal hamsters were selected to prepare 10%, 1%, and 0.5% brain homogenates, which were aliquoted into stocks. PrPSc in each brain homogenate was determined by proteinase K digestions followed by Western blot assay and partially by immunohistochemistry. Stability and glycoforms of PrPSc were repeatedly detected by PrPSc-specific Western blots in half a year and 3 years later. Results PrPSc signals were observed in all 10% brain homogenates of infected hamsters. Twenty out of 30 stocks and 19 out of 30 stocks were PrPSc positive in 1% and 0.5% brain homogenatesof infected hamsters, respectively. Twenty-seven out of 30 stocks presented three positive bands in 10% brain homogenates, whereas none of 1% and 0.5% homogenates contained 3 bands. The detection of PrPSc-specific signals stored in half a year and 3 years later demonstrated that the ratio of PrPSc positive samples and glycoforms was almost unchanged. All normal hamsters' brain homogenates were PrPSc negative. Conclusion A PrPSc panel of prion disease can be established, which displays reliably stable PrPSc-specific signals and glycoforms.

  11. The effects of selective breeding against scrapie susceptibility on the genetic variability of the Latxa Black-Faced sheep breed

    Directory of Open Access Journals (Sweden)

    Legarra Andrés

    2006-09-01

    Full Text Available Abstract Breeding sheep populations for scrapie resistance could result in a loss of genetic variability. In this study, the effect on genetic variability of selection for increasing the ARR allele frequency was estimated in the Latxa breed. Two sources of information were used, pedigree and genetic polymorphisms (fifteen microsatellites. The results based on the genealogical information were conditioned by a low pedigree completeness level that revealed the interest of also using the information provided by the molecular markers. The overall results suggest that no great negative effect on genetic variability can be expected in the short time in the population analysed by selection of only ARR/ARR males. The estimated average relationship of ARR/ARR males with reproductive females was similar to that of all available males whatever its genotype: 0.010 vs. 0.012 for a genealogical relationship and 0.257 vs. 0.296 for molecular coancestry, respectively. However, selection of only ARR/ARR males implied important losses in founder animals (87 percent and low frequency alleles (30 percent in the ram population. The evaluation of mild selection strategies against scrapie susceptibility based on the use of some ARR heterozygous males was difficult because the genetic relationships estimated among animals differed when pedigree or molecular information was used, and the use of more molecular markers should be evaluated.

  12. Atypical Celiac Disease: From Recognizing to Managing

    Directory of Open Access Journals (Sweden)

    B. Admou

    2012-01-01

    Full Text Available The nonclassic clinical presentation of celiac disease (CD becomes increasingly common in physician’s daily practice, which requires an awareness of its many clinical faces with atypical, silent, and latent forms. Besides the common genetic background (HLA DQ2/DQ8 of the disease, other non-HLA genes are now notably reported with a probable association to atypical forms. The availability of high-sensitive and specific serologic tests such as antitissue transglutuminase, antiendomysium, and more recent antideamidated, gliadin peptide antibodies permits to efficiently uncover a large portion of the submerged CD iceberg, including individuals having conditions associated with a high risk of developing CD (type 1 diabetes, autoimmune diseases, Down syndrome, family history of CD, etc., biologic abnormalities (iron deficiency anemia, abnormal transaminase levels, etc., and extraintestinal symptoms (short stature, neuropsychiatric disorders, alopecia, dental enamel hypoplasia, recurrent aphtous stomatitis, etc.. Despite the therapeutic alternatives currently in developing, the strict adherence to a GFD remains the only effective and safe therapy for CD.

  13. Elevated manganese levels in blood and central nervous system occur before onset of clinical signs in scrapie and bovine spongiform encephalopathy.

    Science.gov (United States)

    Hesketh, S; Sassoon, J; Knight, R; Hopkins, J; Brown, D R

    2007-06-01

    Prion diseases, or transmissible spongiform encephalopathies, are neurodegenerative diseases that can only be accurately diagnosed by analysis of central nervous system tissue for the presence of an abnormal isoform of the prion protein known as PrP(Sc). Furthermore, these diseases have long incubation periods during which there are no clear symptoms but where the infectious agent could still be present in the tissues. Therefore, the development of diagnostic assays to detect a surrogate marker for the presence of prion disease is essential. Previous studies on mice experimentally infected with scrapie, an ovine spongiform encephalopathy, suggested that changes in the levels of Mn occur in the blood and brain before the onset of symptoms of the disease. To assess whether these findings have relevance to the animal diseases scrapie and bovine spongiform encephalopathy, tissues from bovine spongiform encephalopathy- and scrapie-infected cattle and sheep were analyzed for their metal content and compared with values for noninfected animals. In field cases and experimentally infected animals, elevated Mn was associated with prion infection. Although some central nervous system regions showed elevated Mn, other regions did not. The most consistent finding was an elevation of Mn in blood. This change was present in experimentally infected animals before the onset of symptoms. In scrapie-infected sheep, elevated Mn levels occurred regardless of the genotype of the sheep and were even detected in scrapie-resistant sheep in which no symptoms of disease were detected. These findings suggest that elevated blood Mn could be a potential diagnostic marker for prion infection even in the absence of apparent clinical disease.

  14. Atypical relapse of hemolytic uremic syndrome after transplantation.

    NARCIS (Netherlands)

    Olie, K.H.; Florquin, S.; Groothoff, J.W.; Verlaak, R.; Strain, L.; Goodship, T.H.; Weening, J.J.; Davin, J.C.

    2004-01-01

    Atypical hemolytic uremic syndrome (HUS) frequently leads to end-stage renal failure and can relapse after transplantation. A 12-year-old girl presenting with familial atypical HUS with a factor H mutation was successfully transplanted 6 years after a first transplant that had failed because of imme

  15. Imaging the neurobiological substrate of atypical depression by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Salmaso, Dario [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Nardo, Davide [University of Rome La Sapienza, Department of Psychology, Rome (Italy); Jonsson, Cathrine; Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Gardner, Ann [Karolinska University Hospital Huddinge, Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm (Sweden)

    2007-01-15

    Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in {sup 99m}Tc-HMPAO uptake between groups. Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders. (orig.)

  16. Genetic characterization of atypical Citrobacter freundii.

    Science.gov (United States)

    Delgado, Gabriela; Souza, Valeria; Morales, Rosario; Cerritos, René; González-González, Andrea; Méndez, José Luis; Vázquez, Virginia; Cravioto, Alejandro

    2013-01-01

    The ability of a bacterial population to survive in different niches, as well as in stressful and rapidly changing environmental conditions, depends greatly on its genetic content. To survive such fluctuating conditions, bacteria have evolved different mechanisms to modulate phenotypic variations and related strategies to produce high levels of genetic diversity. Laboratories working in microbiological diagnosis have shown that Citrobacter freundii is very versatile in its colony morphology, as well as in its biochemical, antigenic and pathogenic behaviours. This phenotypic versatility has made C. freundii difficult to identify and it is frequently confused with both Salmonella enterica and Escherichia coli. In order to determine the genomic events and to explain the mechanisms involved in this plasticity, six C. freundii isolates were selected from a phenotypic variation study. An I-CeuI genomic cleavage map was created and eight housekeeping genes, including 16S rRNA, were sequenced. In general, the results showed a range of both phenotypes and genotypes among the isolates with some revealing a greater similarity to C. freundii and some to S. enterica, while others were identified as phenotypic and genotypic intermediary states between the two species. The occurrence of these events in natural populations may have important implications for genomic diversification in bacterial evolution, especially when considering bacterial species boundaries. In addition, such events may have a profound impact on medical science in terms of treatment, course and outcomes of infectious diseases, evading the immune response, and understanding host-pathogen interactions.

  17. Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta.

    Science.gov (United States)

    Balasubramanian, Meena; Cartwright, Ashley; Smith, Kath; Arundel, Paul; Bishop, Nicholas J

    2016-02-01

    We report a sibling-pair and a 4-year old child from two families with an atypical presentation in Osteogenesis imperfecta (OI). In the sib-pair, the older sibling initially came to medical attention due to a fracture history (Patient 1) and she was shown to have a COL1A2 mutation. In addition, she also had developmental delay, facial dysmorphism, and a history of frequent infections which led to a search for an alternate diagnosis. ArrayCGH revealed a 4.3 Mb duplication on chromosome 19q13.42q13.43, which was confirmed by FISH analysis. On further familial analysis, the younger sibling who had no previous fracture history was also found to have the COL1A2 mutation and tested positive for the 19q13.42q13.43 duplication (Patient 2). The 19q13 duplication appears to be the cause of intellectual disability in these siblings but given that this is a chromosomal duplication, it is still possible that there is an as yet unidentified cause that may account for the combined phenotype in this family. Patient 3 was a 4-year old child presenting with a femoral fracture, blue sclerae, developmental delay, and joint hypermobility. Genetic analyses confirmed a COL1A2 mutation but also revealed an 8.8 Mb deletion of 11q24.2q25, confirmed by G-band chromosome analysis. We discuss the differing phenotypes in patients presenting with atypical OI and stress the need to consider ancillary investigations in individuals presenting with heterogeneous phenotypic symptoms, not entirely attributable to OI.

  18. Clinical grand rounds: atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Hodgkins, Kavita S; Bobrowski, Amy E; Lane, Jerome C; Langman, Craig B

    2012-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

  19. Atypical Cogan's syndrome associated with coronary disease

    Institute of Scientific and Technical Information of China (English)

    Ivanovic Branislava; Tadic Marijana; Damjanov Nemanja; Simic Dragan; Zlatanovic Maja

    2011-01-01

    Cogan's syndrome (CS) is a rare inflammatory disorder characterized by interstitial keratitis and vestibuloauditory abnormalities often associated with various systemic manifestations. Involvement of cardiovascular system resembling systemic vasculitis may lead to severe complications and death. The present report describes a case of a female patient with atypical Cogan's syndrome presented with systemic manifestations and severe coronary and femoral artery stenosis.Despite the clinical improvement after glucocorticoids and cyclophosphamide, the patient required double aortocoronal bypass grafting one year letter. During three years follow-up, she was in stable condition, without stenocardial symptoms and claudication and her inflammatory parameters remain normal. This case highlights the rare involvement of coronary arteries without associated large-vessel vasculitis of the aortic arch in CS.

  20. Brugada Syndrome with atypical characteristics: Case report

    Directory of Open Access Journals (Sweden)

    Hatem Ari

    2013-09-01

    Full Text Available The Brugada Syndrome (BrS is a heterogeneous genetic disease characterized by persistent or transient ST-segment elevation in the right precordial electrocardiography (ECG leads and a high incidence of sudden death and life-threatening ventricular tachyarrhythmias in patients with structurally normal hearts. The syndrome generally manifests in men during adulthood. The ECG manifestations can be overt or concealed. We report a case of BrS whose type 1 ECG pattern during febrile state converted to type 2 ECG after alleviation of fever with atypical characteristics (78-year-old woman with monomorphic ventricular tachycardia on holter monitoring, a history of the sudden infant death of her child, and without inducible ventricular arrhythmia by programed ventricular stimulation [PVS].

  1. Pulmonary Atypical Adenomatous Hyperplasia And Bronchioloalveolar Carcinoma

    Institute of Scientific and Technical Information of China (English)

    MeilinXu; XiaYang; ZhiyaoZhang

    2004-01-01

    OBJECTIVE To study the relationship between atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). METHODS Morphometric, immunohistochemical and ultrastructural analyses were performed in 4 patients with low grade AAH, 5 with high grade AAH and 7 with BAC. RESULTS The mean nuclear areas of high grade AAH and BAC were greater than those of low grade AAH (P<0.05); p53 protein expression was negative in 4 cases of low grade AAH,while the positive rates in high grade AAH and BAC were 40% (2/5) and 57% (4/7), respectively. CONCLUSION The development of BAC is stepwise. AAH appears to be a lesion closely related with BAC, probably as its genuine precursor.

  2. Indications of atypical antipsychotics in the elderly.

    Science.gov (United States)

    McKean, Andrew; Monasterio, Erik

    2015-01-01

    Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.

  3. Atypical parakeratosis: a marker of dysplasia?

    Science.gov (United States)

    Voytek, T M; Kannan, V; Kline, T S

    1996-11-01

    The Bethesda System categorizes atypical parakeratosis (APK) as "ASCUS or SIL depending on the degree of cellular abnormalities." APK, however, is not well-defined. We retrospectively reviewed 68 cervicovaginal specimens with follow-up material to identify specific criteria and clinical significance of APK. APK cells were small cells, 2-3 times the diameter of neutrophil, with dense, orangeophilic cytoplasm, high nuclear cytoplasmic ratio, dense, often uneven chromatin, and irregular nuclear contour. Of 62 cases with APK, 37 had accompanying dysplastic cells. Of 25 cases with APK alone, follow-up revealed 12 with squamous intraepithelial lesion (5 HSIL and 7 LSIL) and 13 with benign changes. A major diagnostic pitfall of APK was inflammation with degeneration. Abundant APK cells, minimal inflammation and degeneration, and previous history of dysplasia frequently were associated with follow-up SIL. The findings of this study identify APK as an important marker for dysplasia that warrants careful evaluation and follow-up.

  4. Atypical Radiological Manifestation of Pulmonary Metastatic Calcification

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Hae; Kim, Eun Sun; Kim, Chul Hwan; Ham, Soo Youn; Oh, Yu Whan [Korea University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Metastatic pulmonary calcification is a condition of calcium deposition in the normal pulmonary parenchyma, and this is secondary to abnormal calcium metabolism without any prior soft tissue damage. The predisposing factors for this condition include chronic renal failure, hypercalcemia and increased tissue alkalinity. The most common radiologic manifestation consists of poorly defined nodular opacities in the upper lung zone. These opacities reflect the deposition of calcium salts in the pulmonary interstitium. We present here a case of metastatic pulmonary calcification in a patient who recovered from pneumonia with sepsis and whose high-resolution CT (HRCT) images demonstrated localized parenchymal airspace calcification that was limited to the bilateral lower lobes. These lower lobes had been involved with pneumonic consolidation without calcification, as seen on the previous CT scan. In summary, we report here on an atypical presentation of metastatic pulmonary calcification that showed dense airspace consolidation localized to the bilateral lower lobes in a patient with primary hyperparathyroidism and pneumonia.

  5. Emphysematous Cystitis: Report of an Atypical Case

    Directory of Open Access Journals (Sweden)

    Karen De Baets

    2011-01-01

    Full Text Available We report the atypical case of a nondiabetic 66-year old male with severe abdominal pain and vomiting who was found to have emphysematous cystitis. Of all gas-forming infections of the urinary tract emphysematous cystitis is the most common and the least severe. The major risk factors are diabetes mellitus and urinary tract obstruction. Most frequent causative pathogens are Escherichia coli and Klebsiella pneumoniae. The clinical presentation is nonspecific and ranges from asymptomatic urinary tract infection to urosepsis and septic shock. The diagnosis is made by abdominal imaging. Treatment consists of broad-spectrum antibiotics, bladder drainage, and management of the risk factors. Surgery is reserved for severe cases. Overall mortality rate of emphysematous cystitis is 7%. Immediate diagnosis and treatment is necessary because of the rapid progression to bladder necrosis, emphysematous pyelonephritis, urosepsis, and possibly fatal evolution.

  6. Single cell dynamic phenotyping

    OpenAIRE

    Katherin Patsch; Chi-Li Chiu; Mark Engeln; Agus, David B.; Parag Mallick; Shannon M. Mumenthaler; Daniel Ruderman

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype track...

  7. A case of atypical progressive supranuclear palsy

    Directory of Open Access Journals (Sweden)

    Spaccavento S

    2013-12-01

    Full Text Available Simona Spaccavento, Marina Del Prete, Angela Craca, Anna Loverre IRCCS Salvatore Maugeri Foundation, Cassano Murge, Bari, Italy Background: Progressive supranuclear palsy (PSP is a neurodegenerative extrapyramidal syndrome. Studies have demonstrated that PSP can present clinically as an atypical dementing syndrome dominated by a progressive apraxia of speech (AOS and aphasia. Aim: We aimed to investigate the clinical presentation of PSP, using a comprehensive multidimensional evaluation, and the disease response to various pharmacological treatments. Methods: A 72-year-old right-handed male, with 17 years education, who first presented with aphasia, AOS, depression, apathy, and postural instability at 69 years; a complete neuropsychological evaluation, tapping the different cognitive domains, was performed. Results: Testing revealed a moderate global cognitive deficit (Mini-Mental State Examination test score =20, low memory test scores (story recall, Rey’s 15-word Immediate and Delayed Recall, and poor phonemic and semantic fluency. The patient’s language was characterized by AOS, with slow speech rate, prolonged intervals between syllables and words, decreased articulatory accuracy, sound distortions, and anomia. Behavioral changes, such as depression, anxiety, apathy, and irritability, were reported. The neurological examination revealed supranuclear vertical gaze palsy, poor face miming, and a mild balance deficit. Magnetic resonance imaging showed only widespread cortical atrophy. Single photon emission computed tomography demonstrated left > right frontotemporal cortical abnormalities. After 6 months, a further neuropsychological assessment showed a progression in cognitive deficits, with additional attention deficits. The patient reported frequent falls, but the neurological deficits remained unchanged. Neuroimaging tests showed the same brain involvement. Conclusion: Our case highlights the heterogeneity of the clinical features in

  8. Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment.

    Science.gov (United States)

    Ware, Tyson L; Earl, John; Salomons, Gajja S; Struys, Eduard A; Peters, Heidi L; Howell, Katherine B; Pitt, James J; Freeman, Jeremy L

    2014-05-01

    Pyridox(am)ine phosphate oxidase (PNPO) deficiency causes severe early infantile epileptic encephalopathy and has been characterized as responding to pyridoxal-5'-phosphate but not to pyridoxine. Two males with PNPO deficiency and novel PNPO mutations are reported and their clinical, metabolic, and video-electroencephalographic (EEG) findings described. The first child showed electro-clinical responses to pyridoxine and deterioration when pyridoxine was withheld. At last review, he has well-controlled epilepsy with pyridoxal-5'-phosphate monotherapy and an autism spectrum disorder. The second child had a perinatal middle cerebral artery infarct and a myoclonic encephalopathy. He failed to respond to pyridoxine but responded well to pyridoxal-5'-phosphate. At the age of 21 months he has global developmental delay and hemiparesis but is seizure-free with pyridoxal-5'-phosphate monotherapy. Plasma and cerebrospinal fluid pyridoxamine levels were increased in both children during treatment with pyridoxine or pyridoxal-5'-phosphate. These observations indicate that differential responses to pyridoxine and pyridoxal-5'-phosphate treatment cannot be relied upon to diagnose PNPO deficiency.

  9. Healthy sheep that differ in scrapie associated PRNP genotypes exhibit significant differences of expression pattern associated with immune response and cell-to-cell signalling in retropharyngeal lymph nodes.

    Science.gov (United States)

    Komolka, Katrin; Ponsuksili, Siriluck; Schwerin, Manfred

    2013-04-15

    The present study was conducted to test the hypothesis whether prion protein gene (PRNP) associated scrapie susceptibility is connected with physiological changes in tissue involved in pathogen uptake, migration and propagation. Jejunum, ileal Peyer's patches, retropharyngeal lymph nodes, brain stem and liver of healthy and non scrapie-infected sheep with PRNP genotypes representing the scrapie risk class R1 (scrapie-resistant) and R5 (scrapie-susceptible), respectively, were comparatively analysed by microarray technology and quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Significantly higher expression levels of genes involved in immune response and cell communication pathways in retropharyngeal lymph nodes of R1 sheep in comparison with R5 animals strongly suggest PRNP associated physiological processes with impact as an early barrier in pathogen defence. Equal expression patterns in brain stem suggest no physiological differences in brain of healthy R1 and R5 animals. In addition, similar expression pattern in liver indicates that there are no transcriptional differences in genes of the hepatic energy metabolism between animals of scrapie classes R1 and R5.

  10. Multiple primary cutaneous melanomas in patients with FAMMM syndrome and sporadic atypical mole syndrome (AMS): what's worse?

    Science.gov (United States)

    Tchernev, Georgi; Ananiev, Julian; Cardoso, José-Carlos; Chokoeva, Anastasiya Atanasova; Philipov, Stanislav; Penev, Plamen Kolev; Lotti, Torello; Wollina, Uwe

    2014-08-01

    Atypical Mole Syndrome is the most important phenotypic risk factor for cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Since early diagnosis of melanoma is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers (sporadic and familial) is essential, as well as the recommendation of preventative measures that must be undertaken by these patients.We report two rare cases concerning patients with multiple primary skin melanomas in the setting of a familial and a sporadic syndrome of dysplastic nevi: the first patient is a 67-year-old patient with a history of multiple superficial spreading melanomas localized on his back. The second patient presented with multiple primary melanomas in advanced stage in the context of the so-called sporadic form of the syndrome of dysplastic nevi-AMS (atypical mole syndrome). In the first case, excision of the melanomas was carried out with an uneventful post-operative period. In the second case, disseminated metastases were detected, involving the right fibula, the abdominal cavity as well as multiple lesions in the brain. The patient declined BRAF mutation tests as well as chemotherapy or targeted therapies, and suffered a rapid deterioration in his general condition leading to death. We classified the second case as a sporadic form of the atypical mole syndrome, associated with one nodular and two superficial spreading melanomas.There are no data in the literature to allow us to understand if, in patients with multiple primary melanomas, there is any difference in terms of prognosis between those with and without a family history of a similar phenotype. To answer this and other questions related to these rare cases, further studies with a significant number of patients should be carried out.

  11. Malignant atypical cell in urine cytology: a diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Kakkar Nandita

    2006-01-01

    Full Text Available Abstract Aims The aim of this study was to find out the characteristic morphology of malignant atypical cells which were missed on routine cytology of urine. Materials and methods In this retrospective study, we examined detailed cytomorphology of 18 cases of atypical urinary cytology which were missed on routine examination and were further proved on histopathology as transitional cell carcinoma (TCC of bladder. The cytological features of these cases were compared with 10 cases of benign urine samples. Results There were 11 cases of high grade TCC and 7 cases of low grade TCC on histopathology of the atypical urine samples. Necrosis in the background and necrosed papillae were mostly seen in malignant atypical cells. The comet cells and cells with India ink nuclei (single cells with deep black structure-less nuclei were only observed in malignant atypical cells. The most consistent features in malignant atypical cells were: i high nuclear and cytoplasmic (N/C ratio ii nuclear pleomorphism iii nuclear margin irregularity iv hyperchromasia and v chromatin abnormalities Conclusion The present study emphasizes that nuclear features such as high N/C ratio, hyperchromasia and chromatin abnormalities are particularly useful for assessing the malignant atypical cells. Other cytological features such as comet cells and cells with India ink nuclei are also helpful for diagnosis but have limited value because they are less frequently seen.

  12. Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes.

    Science.gov (United States)

    Mojtabai, Ramin; Lavelle, Janet; Gibson, P Joseph; Bromet, Evelyn J

    2003-01-01

    This study compares the effects of atypical and conventional antipsychotic medications on treatment continuation and outcomes in a first admission sample of patients with schizophrenia treated in usual practice settings. In a sample of 189 participants with a research diagnosis of DSM-IV schizophrenia drawn from the Suffolk County Mental Health Project, we compared the effects of atypical and conventional agents on change of medication, medication gaps, and rehospitalization. For these analyses we used the method of survival analysis for recurrent events, in which the episodes of treatment rather than individual subjects are the units of analysis. In addition, we compared improvement in positive and negative symptoms from intake to 24- or 48-month followups for subjects who stayed on one type of medication or changed to atypicals from conventional antipsychotics. Atypical agents were associated with lower risk of medication change, medication gaps, and rehospitalization. Both conventional and atypical agents were associated with improvement of positive symptoms at followup, but only subjects on atypical agents at followup experienced a significant improvement in negative symptoms. We conclude that in usual practice settings, as in randomized clinical trials, atypical agents are associated with improved treatment continuation and outcomes.

  13. RECTAL BIOPSY IN SHEEP AND GOATS FOR MONITORING AND ANTE-MORTEM DIAGNOSIS OF SCRAPIE: NUMBER OF LYMPHOID FOLLICLES IN TWO CONSECUTIVE COLLECTIONS

    Directory of Open Access Journals (Sweden)

    Helen Caroline Raksa

    2016-07-01

    O acúmulo da PrPSc em tecidos linfoides levou ao desenvolvimento de procedimentos de biopsia para o diagnóstico ante mortem da scrapie em ovinos, utilizando tecidos acessíveis como a tonsila(5 e terceira pálpebra(6, e a técnica de imuno-histoquímica (IHQ. Por outro lado, a grande área de folículos linfoides presente no reto de ovinos(7 tornou a biopsia retal uma possibilidade de diagnóstico ante mortem da scrapie. Amostras da mucosa retal têm sido colhidas e analisadas por meio de provas de IHQ para avaliar a presença de PrPSc no tecido linfoide associado à mucosa retoanal (RAMALT, do inglês Recto-Anal Mucosa Associated Lymphoid Tissue(8,9. No Brasil, o primeiro relato de scrapie foi em 1978, em um ovino Hampshire Down, importado da Inglaterra(10. Segundo a OIE, de 2008 a 2014 foram sacrificados 41 animais no país, em surtos de scrapie(11. Desde 2008, o diagnóstico de scrapie é realizado por meio da técnica de IHQ a partir de amostras do SNC e tecidos linfoides(12. Porém, no caso de tecidos linfoides associados à mucosa retal, pode haver necessidade de novas colheitas em curtos intervalos de tempo devido à escassez de tecido para o diagnóstico da doença que, segundo Leal et al.(13, deve ser de no mínimo três folículos linfoides (FL por amostra. Visando ao reconhecimento de boas técnicas para o monitoramento e o diagnóstico ante mortem da scrapie, o presente estudo teve por objetivo avaliar a quantidade de tecido linfoide associado à mucosa retal obtido pela técnica de biopsia retal e com vistas à avaliação imuno-histoquímica, bem como a possibilidade de se realizarem dois procedimentos de biopsia consecutivos, em diferentes intervalos de tempo, em ovinos e caprinos.

  14. Pathogenesis of scrapie in ARQ/ARQ sheep after subcutaneous infection: effect of lymphadenectomy and immune cell subset changes in relation to prion protein accumulation.

    Science.gov (United States)

    Chianini, F; Sisó, S; Ricci, E; Eaton, S L; Finlayson, J; Pang, Y; Hamilton, S; Steele, P; Reid, H W; Cantile, C; Sales, J; Jeffrey, M; Dagleish, M P; González, L

    2013-04-15

    It is well established that the infectious agent of scrapie can replicate in the lymphoreticular system (LRS). However, the effects of removal of LRS target tissues on the pathogenesis of the infection and the accumulation of disease-associated prion protein (PrP(d)) in LRS tissues on specific immune cell subsets are poorly understood aspects. To address these questions 16 ARQ/ARQ sheep were subcutaneously inoculated in the drainage area of the prefemoral lymph node with brain homogenate derived from Suffolk sheep naturally infected with scrapie. Fourteen sheep were then subjected to either early (14-17 days post-inoculation [dpi]) or late (175-201 dpi) lymphadenectomy and culled at preclinical or clinical stages of infection. Neither late nor even early lymphadenectomy prevented infection or had any effect on the accumulation of PrP(d) in the LRS or CNS suggesting a rapid organic dissemination of the infectious agent after inoculation. Lymph nodes from eight scrapie inoculated sheep selected on the basis of the amount of PrP(d) in their LRS tissues (negative, low or high) were examined for six different immune cell markers. The PrP(d) negative lymph nodes from two sheep with no evidence of scrapie infection showed lower numbers of cluster of determination (CD) 21 positive cells than PrP(d) positive nodes, irrespective of their location (hind leg or head). However, quantitative differences in the expression of this marker were not detected when comparing lymph nodes with low and high levels of PrP(d) accumulation, suggesting that proliferation of CD21 positive cells is related to scrapie infection, but not directly linked to the magnitude of PrP(d) accumulation. An additional observation of the study was that sheep that were methionin-threonine at codon 112 of the prion protein gene showed lower attack rates than methionine homozygotes (67% and 100%, respectively) and also generally lower levels of PrP(d) accumulation in the LRS and brain and increased survival

  15. Phenotype definition in epilepsy.

    Science.gov (United States)

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  16. Results of surgical treatment of atypical endometrial hyperplasia

    Directory of Open Access Journals (Sweden)

    O. A. Gornykh

    2014-01-01

    Full Text Available The results of surgical treatment in 132 patients with atypical endometrial hyperplasia have been studied. Post-operative diagnosis was: en- dometrial cancer – in 19 %, atypical hyperplasia – in 35 %, simple and complex hyperplasia – in 33 %, only atrophic endometrial changes – in 13 % of patients. The tumor was within the endometrium in 5 patients, the superficial invasion of the myometrium (1–2 mm were in 8 patients, invasion to half of the myometrium – in 9 patients, invasion of more than half of the myometrium – in 3 patients. The questions of tactics of treatment of atypical endometrial hyperplasia is under discussion.

  17. Intracranial Tuberculoma Presenting as Atypical Eclampsia: A Case Report

    Science.gov (United States)

    Murugesan, Sharmila; Pradeep, Sunitha; John, Lopamudra; Kolluru, Vasavi

    2016-01-01

    Occurrence of eclampsia before 20 weeks of pregnancy and after 48 hours of delivery in the absence of typical signs of hypertension and or proteinuria is termed as atypical eclampsia. Atypical or non-classic eclampsia will have some symptoms of eclampsia but without the usual proteinuria or hypertension. All patients with atypical onset should undergo neurological evaluation to rule out neurologic causes of seizures. Cerebral tuberculosis is a rare and serious form of disease secondary to haematogenous spread of Mycobacterium tuberculosis. Here we present a case of cerebral tuberculoma with seizures in late pregnancy mimicking eclampsia. PMID:27504359

  18. A novel phenotype of sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Giaccone, G; Di Fede, Giuseppe; Mangieri, Michela; Limido, Lucia; Capobianco, Raffaella; Suardi, Silvia; Grisoli, Marina; Binelli, Simona; Fociani, Paolo; Bugiani, Orso; Tagliavini, Fabrizio

    2009-01-01

    An atypical case of sporadic Creutzfeldt-Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrP(Sc)) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype.

  19. A novel phenotype of sporadic Creutzfeldt–Jakob disease

    Science.gov (United States)

    Giaccone, G; Di Fede, Giuseppe; Mangieri, Michela; Limido, Lucia; Capobianco, Raffaella; Suardi, Silvia; Grisoli, Marina; Binelli, Simona; Fociani, Paolo; Bugiani, Orso; Tagliavini, Fabrizio

    2009-01-01

    An atypical case of sporadic Creutzfeldt–Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrPSc) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype. PMID:21686549

  20. Emergence of a novel bovine spongiform encephalopathy (BSE) prion from an atypical H-type BSE.

    Science.gov (United States)

    Masujin, Kentaro; Okada, Hiroyuki; Miyazawa, Kohtaro; Matsuura, Yuichi; Imamura, Morikazu; Iwamaru, Yoshifumi; Murayama, Yuichi; Yokoyama, Takashi

    2016-03-07

    The H-type of atypical bovine spongiform encephalopathy (H-BSE) was serially passaged in bovinized transgenic (TgBoPrP) mice. At the fourth passage, most challenged mice showed a typical H-BSE phenotype with incubation periods of 223 ± 7.8 days. However, a different phenotype of BSE prion with shorter incubation periods of 109 ± 4 days emerged in a minor subset of the inoculated mice. The latter showed distinct clinical signs, brain pathology, and abnormal prion protein profiles as compared to H-BSE and other known BSE strains in mice. This novel prion was transmitted intracerebrally to cattle, with incubation periods of 14.8 ± 1.5 months, with phenotypes that differed from those of other bovine prion strains. These data suggest that intraspecies transmission of H-BSE in cattle allows the emergence of a novel BSE strain. Therefore, the continuation of feed ban programs may be necessary to exclude the recycling of H-BSE prions, which appear to arise spontaneously, in livestock. Such measures should help to reduce the risks from both novel and known strains of BSE.

  1. Teaching strategies for atypical presentation of illness in older adults.

    Science.gov (United States)

    Gray-Miceli, Deanna; Aselage, Melissa; Mezey, Mathy

    2010-07-01

    Atypical presentation of illness is a phenomenon where "seeing is believing." Expert geriatric nurses and clinicians know all too well the early signs and symptoms of this phenomenon, which frequently masquerades bacterial infections, pain, acute myocardial infarction, heart failure, or other serious medical ailments in older adults. Students, however, as novices to clinical practice, require interactive learning approaches to reflect on the patient's illness presentations, help with developing the necessary skills to analyze and synthesize clinically relevant data, and witness resolution of an atypical presentation when found and treated. Use of a case study as an educational tool can facilitate critical thinking about a clinical problem, such as atypical presentation of illness, for students within a problem-based learning format. Furthermore, we highlight strategies for teaching students atypical presentation of illness with consideration of student learning preferences, which include visual, auditory, reading, and kinesthetic modes of learning.

  2. The ability of haemolysins expressed by atypical enteropathogenic Escherichia coli to bind to extracellular matrix components

    Directory of Open Access Journals (Sweden)

    Caroline A Magalhães

    2011-03-01

    Full Text Available Typical and atypical enteropathogenic Escherichia coli (EPEC are considered important bacterial causes of diarrhoea. Considering the repertoire of virulence genes, atypical EPEC (aEPEC is a heterogeneous group, harbouring genes that are found in other diarrheagenic E. coli pathotypes, such as those encoding haemolysins. Haemolysins are cytolytic toxins that lyse host cells disrupting the function of the plasma membrane. In addition, these cytolysins mediate a connection to vascular tissue and/or blood components, such as plasma and cellular fibronectin. Therefore, we investigated the haemolytic activity of 72 aEPEC isolates and determined the correlation of this phenotype with the presence of genes encoding enterohaemolysins (Ehly and cytolysin A (ClyA. In addition, the correlation between the expression of haemolysins and the ability of these secreted proteins to adhere to extracellular matrix (ECM components was also assessed in this study. Our findings demonstrate that a subset of aEPEC presents haemolytic activity due to the expression of Ehlys and/or ClyA and that this activity is closely related to the ability of these isolates to bind to ECM components.

  3. Atypical presentation of infantile-onset farber disease with novel ASAH1 mutations.

    Science.gov (United States)

    Kim, Soo Yeon; Choi, Sun Ah; Lee, Sangmoon; Lee, Jin Sook; Hong, Che Ry; Lim, Byung Chan; Kang, Hyoung Jin; Kim, Ki Joong; Park, Sung-Hye; Choi, Murim; Chae, Jong-Hee

    2016-11-01

    Farber disease is a very rare autosomal recessive disease caused by mutation of ASAH1 that results in the accumulation of ceramide in various tissues. Clinical symptoms of classic Farber disease comprise painful joint deformity, hoarseness of voice, and subcutaneous nodules. Here, we describe a patient with Farber disease with atypical presentation of early onset hypotonia, sacral mass, congenital heart disease, and dysmorphic face since birth. Severe cognitive disability, failure to gain motor skills, failure to thrive, and joint contractures developed. Using whole-exome sequencing, we identified the compound heterozygote missense mutations of ASAH1 (p.R333C and p.G235R). Because of the diagnostic delay, she underwent sacral mass excision, which revealed enlarged lysosomes and zebra bodies. We report an atypical presentation of Farber disease with her pathology and associated genetic defect. This case expands the phenotypic spectrum of Farber disease to include novel mutations of ASAH1, which pose a diagnostic challenge. We also discuss the clinical utility of whole-exome sequencing for diagnosis of ultra-rare diseases. © 2016 Wiley Periodicals, Inc.

  4. Atypical presentation of mucopolysaccharidosis type IVA.

    Science.gov (United States)

    Rush, Eric T

    2016-09-01

    A 14 year old patient with short stature, type I diabetes, and cataracts was referred for evaluation of avascular necrosis of the femoral head. Radiography was suggestive of spondyloepiphyseal dysplasia with decreased bone mineral density for age. Targeted molecular and biochemical testing were normal in this patient. Whole exome sequencing was performed and showed compound heterozygosity for previously reported pathogenic GALNS variants which were diagnostic of mucopolysaccharidosis, type IVA (Morquio A). While this case describes neither a novel condition nor a new mutation, it does illustrate three important points in the diagnosis of patients with atypical forms of MPS IVA. First, that in many instances urine glycosaminoglycan analysis is not sufficient to rule out MPS IVA as a potential diagnosis. Patients in whom biochemical screening is advised should have measurement of leukocyte enzymatic activity. Second, that in patients with radiographic evidence of spondyloepiphyseal dysplasia with additional features or with normal targeted testing, MPS IVA should remain in the differential diagnosis. Third, that whole exome sequencing represents a viable diagnostic platform for evaluation of patients with unknown skeletal or metabolic disease.

  5. Atypical clinical response patterns to ipilimumab.

    Science.gov (United States)

    Ledezma, Blanca; Binder, Sandra; Hamid, Omid

    2011-08-01

    Patients with advanced melanoma have few treatment options, and survival is poor. However, improved understanding of how the immune system interacts with cancer has led to the development of novel therapies. Ipilimumab is a monoclonal antibody that inhibits cytotoxic T-lymphocyte antigen-4 (CTLA-4), a key negative regulator of host T-cell responses. This article presents cases of patients receiving ipilimumab in clinical trials along with a discussion of their significance and relevance to nursing practice. The patients showed different response patterns to ipilimumab and also had various typical immune-related adverse events (irAEs), which were managed successfully. The atypical response patterns produced by ipilimumab likely reflect its mechanism of action, which requires time for the immune system to mount an effective antitumor response. Meanwhile, lesions may appear to enlarge as a consequence of enhanced T-cell infiltration, although this may not necessarily be true disease progression. Patients receiving ipilimumab may respond very differently compared to how they might react to chemotherapy. Responses can take weeks or months to develop; therefore, clinicians should not terminate treatment prematurely, providing the patient's condition allows for continuation. Early recognition of irAEs combined with prompt management will ensure that events are more likely to resolve without serious consequences.

  6. Atypical Takotsubo syndrome during anagrelide therapy.

    Science.gov (United States)

    Proietti, Riccardo; Rognoni, Andrea; Ardizzone, Fabio; Maccio, Sergio; Santagostino, Alberto; Rognoni, Giorgio

    2009-07-01

    Anagrelide is a phosphodiesterase III inhibitor utilized in the treatment of essential thrombocythemia. Anagrelide can be responsible for positive inotropic and chonotropic activity of the cardiovascular system. Moreover, it can induce vasospam directly on the epicardial coronary arteries. In the literature, it is well reported that this inhibitor can determine serious cardiovascular side effects, including congestive heart failure, arrhythmia and acute coronary syndrome. We describe the case of a 75-year-old woman who developed a mid-ventricular Takotsubo syndrome while on anagrelide therapy. Takotsubo cardiomyopathy, also known as left ventricular ballooning syndrome, is characterized by a reversible ventricular contractile dysfunction with akinesis and expansion of apical segments and hyperkinesis of the basal segments. Recently, atypical cases with akinesia and dilation of mid-ventricular segment and hypercontraction of the apical segments, also called mid-ventricular and inverted Takotsubo syndrome, have been described. Even though the pathogenesis of Takotsubo syndrome is poorly understood, several mechanisms have been proposed, including catecholamine-induced myocardial stunning, and ischemia-mediated stunning due to multivessel epicardial or microvascular spasm. We think that in our case, the adverse response of anagrelide therapy was determined, by accumulated dosage of the drug, through an intensive inotropic stimulation and a sympathetic hyperactivation in a vulnerable myocardium. To our knowledge, this is one of the first reports of an association between anagrelide therapy and Takotsubo cardiomyopathy.

  7. Atypical focal nodular hyperplasia of the liver

    Institute of Scientific and Technical Information of China (English)

    Muhammad Rizwan Khan; Taimur Saleem; Tanveer Ul Haq; Kanwal Aftab

    2011-01-01

    BACKGROUND: Focal nodular hyperplasia, a benign hepatic tumor, is usually asymptomatic. However, rarely the entity can cause symptoms, mandating intervention. METHOD: We present a case of focal nodular hyperplasia of the liver, which caused a considerable diagnostic dilemma due to its atypical presentation. RESULTS: A 29-year-old woman presented with a 15-year history of a progressively increasing mass in the right upper quadrant which was associated with pain and emesis. Examination showed a firm, mobile mass palpable below the right subcostal margin. A computed tomography scan of the abdomen showed an exophytic mass arising from hepatic segments III and IVb. Trucut biopsy of the hepatic mass was equivocal. Angiography showed a vascular tumor that was supplied by a tortuous branch of the proper hepatic artery. Surgical intervention for removal of the mass was undertaken. Intra-operatively, two large discrete tumors were found and completely resected. Histopathological examination showed features consistent with focal nodular hyperplasia. CONCLUSION: This description of an unusual case of focal nodular hyperplasia of the liver highlights the point that the diagnosis of otherwise benign hepatic tumors may be difficult despite extensive work-up in some cases.

  8. Atypical moral judgment following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Angelica Muresan

    2012-07-01

    Full Text Available Previous research has shown an association between emotions, particularly social emotions, and moral judgments. Some studies suggested an association between blunted emotion and the utilitarian moral judgments observed in patients with prefrontal lesions. In order to investigate how prefrontal brain damage affects moral judgment, we asked a sample of 29 TBI patients (12 females and 17 males and 41 healthy participants (16 females and 25 males to judge 22 hypothetical dilemmas split into three different categories (non-moral, impersonal and personal moral. The TBI group presented a higher proportion of affirmative (utilitarian responses for personal moral dilemmas when compared to controls, suggesting an atypical pattern of utilitarian judgements. We also found a negative association between the performance on recognition of social emotions and the proportion of affirmative responses on personal moral dilemmas. These results suggested that the preference for utilitarian responses in this type of dilemmas is accompanied by difficulties in social emotion recognition. Overall, our findings suggest that deontological moral judgments are associated with normal social emotion processing and that frontal lobe plays an important role in both emotion and moral judgment.

  9. Nocturnal manifestations of atypical parkinsonian disorders.

    Science.gov (United States)

    Bhidayasiri, Roongroj; Jitkritsadakul, Onanong; Colosimo, Carlo

    2014-01-01

    Although nocturnal disturbances are increasingly recognized as an integral part of the continuum of daytime manifestations of Parkinson's disease (PD), there is still little evidence in the medical literature to support the occurrence of these complex phenomena in patients with atypical parkinsonian disorders (APDs). Based on the anatomical substrates in APDs, which are considered to be more extensive outside the basal ganglia than in PD, we might expect that patients with APDs encounter the whole range of nocturnal disturbances, including motor, sleep disorders, autonomic dysfunctions, and neuropsychiatric manifestations at a similar, or even greater, frequency than in PD. This article is a review of the current literature on the problems at nighttime of patients with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. MEDLINE, life science journals and online books were searched by querying appropriate key words. Reports were included if the studies were related to nocturnal manifestations in APDs. Forty articles fulfilled the selection criteria. Differences between these symptoms in APDs and PD are highlighted, given the evidence available about each manifestation. This analysis of nocturnal manifestations of APDs suggests the need for future studies to address these issues to improve the quality of life not only of patients with APDs but the caregivers who encounter the challenges of supporting these patients on a daily basis.

  10. Persistent consequences of atypical early number concepts

    Directory of Open Access Journals (Sweden)

    Michèle M. M. Mazzocco

    2013-09-01

    Full Text Available How does symbolic number knowledge performance help identify young children at risk for poor mathematics achievement outcomes? In research and practice, classification of mathematics learning disability (MLD, or dyscalculia is typically based on composite scores from broad measures of mathematics achievement. These scores do predict later math achievement levels, but do not specify the nature of math difficulties likely to emerge among students at greatest risk for long-term mathematics failure. Here we report that gaps in 2nd and 3rd graders’ number knowledge predict specific types of errors made on math assessments at Grade 8. Specifically, we show that early whole number misconceptions predict slower and less accurate performance, and atypical computational errors, on Grade 8 arithmetic tests. We demonstrate that basic number misconceptions can be detected by idiosyncratic responses to number knowledge items, and that when such misconceptions are evident during primary school they persist throughout the school age years, with variable manifestation throughout development. We conclude that including specific qualitative assessments of symbolic number knowledge in primary school may provide greater specificity of the types of difficulties likely to emerge among students at risk for poor mathematics outcomes.

  11. Atypical mitochondrial inheritance patterns in eukaryotes.

    Science.gov (United States)

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  12. DENGUE WITH ATYPICAL MANIFESTATIONS AND WHO CLASSIFICATION

    Directory of Open Access Journals (Sweden)

    Jayant Mahadeorao

    2015-09-01

    Full Text Available Dengue fever and dengue haemorrhagic fever are important arboviral diseases. Dengue virus belongs to family Flaviviridae , has four serotypes that spread by the bite of infected Aedes mosquitoes . Dengue epidemics can have a significant economic and health t oll. Worldwide, an estimated 3.6 billion people are at risk of infection with about 50 - 100 million new cases each year Illness produced by any of the four dengue virus serotypes varies from mild asymptomatic illness to severe fatal dengue haemorrhagic fe ver/dengue shock syndrome (DHF/DSS. During the early febrile stage clinicians cannot predict which patients will progress to severe disease. Atypical manifestations were reported are associated with high risk of mortality. The existing WHO dengue classific ation scheme and case definitions have some drawbacks. A global strategy to reduce the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently un der development could also make an important contribution to dengue control in the future

  13. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    Science.gov (United States)

    Ryan, Aisling M; Bermingham, Niamh; Harrington, Hugh J; Keohane, Catherine

    2006-12-01

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  14. Atypical presentations among Medicare beneficiaries with unstable angina pectoris.

    Science.gov (United States)

    Canto, John G; Fincher, Contessa; Kiefe, Catarina I; Allison, Jeroan J; Li, Qing; Funkhouser, Ellen; Centor, Robert M; Selker, Harry P; Weissman, Norman W

    2002-08-01

    Chest pain is a hallmark symptom in patients with unstable angina pectoris (UAP). However, little is known regarding the prevalence of an atypical presentation among these patients and its relation to subsequent care. We examined the medical records of 4,167 randomly sampled Medicare patients hospitalized with unstable angina at 22 Alabama hospitals between 1993 and 1999. We defined typical presentation as (1) chest pain located substernally in the left or right chest, or (2) chest pain characterized as squeezing, tightness, aching, crushing, arm discomfort, dullness, fullness, heaviness, pressure, or pain aggravated by exercise or relieved with rest or nitroglycerin. Atypical presentation was defined as confirmed UAP without typical presentation. Among patients with confirmed UAP, 51.7% had atypical presentations. The most frequent symptoms associated with atypical presentation were dyspnea (69.4%), nausea (37.7%), diaphoresis (25.2%), syncope (10.6%), or pain in the arms (11.5%), epigastrium (8.1%), shoulder (7.4%), or neck (5.9%). Independent predictors of atypical presentation for patients with UAP were older age (odds ratio 1.09, 95% confidence interval 1.01 to 1.17/decade), history of dementia (odds ratio 1.49, 95% confidence interval 1.10 to 2.03), and absence of prior myocardial infarction, hypercholesterolemia, or family history of heart disease. Patients with atypical presentation received aspirin, heparin, and beta-blocker therapy less aggressively, but there was no difference in mortality. Thus, over half of Medicare patients with confirmed UAP had "atypical" presentations. National educational initiatives may need to redefine the classic presentation of UAP to include atypical presentations to ensure appropriate quality of care.

  15. Atypical meningococcal meningitis with rashless presentation:A case report

    Institute of Scientific and Technical Information of China (English)

    Sunita; Singh Manpreet; Kapoor Dheeraj

    2012-01-01

    Meningococcal disease is the major health problem in developing world. The clinical presentation is varied, ranging from transient fever and bacteraemia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. The classical clinical manifestations of meningococcal disease have been well described, but atypical presentations if unrecognized, may lead to a delay in treatment and fatal outcome. We here report a case presented with atypical presentation of meningococcal meningitis without classical rash, which was diagnosed and managed successfully.

  16. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    LENUS (Irish Health Repository)

    Ryan, Aisling M

    2012-02-03

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  17. An Atypical Case of Pityriasis Rosea Gigantea after Influenza Vaccination

    Directory of Open Access Journals (Sweden)

    Dimitrios Papakostas

    2014-04-01

    Full Text Available Pityriasis rosea is a common erythematosquamous eruption, typically presenting along the cleavage lines of the skin. A wide spectrum of atypical manifestations may challenge even the most experienced physician. Here we report a rare case of a suberythrodermic pityriasis rosea with gigantic plaques after an influenza vaccination, and we discuss the possible triggers of atypical manifestations of such a common dermatological disease in the setting of an altered immunity.

  18. Heterologous PrP molecules interfere with accumulation of protease-resistant PrP in scrapie-infected murine neuroblastoma cells.

    OpenAIRE

    Priola, S A; Caughey, B; Race, R E; Chesebro, B

    1994-01-01

    Mutations within a host cellular protein, PrP, have been associated with disease in the transmissible spongiform encephalopathies. Murine neuroblastoma cells persistently infected with mouse scrapie accumulate protease-resistant PrP (PrP-res), the abnormal form of PrP associated with disease in the transmissible spongiform encephalopathies. These cells provide a controlled system in which to study the molecular interactions which are important in the formation of PrP-res. We have expressed re...

  19. Scrapie infection in experimental rodents and SMB-S15 cells decreased the brain endogenous levels and activities of Sirt1.

    Science.gov (United States)

    Wang, Jing; Zhang, Jin; Shi, Qi; Zhang, Bao-Yun; Chen, Cao; Chen, Li-Na; Sun, Jing; Wang, Hui; Xiao, Kang; Dong, Xiao-Ping

    2015-04-01

    Prion diseases are composed of a group of fatal neurodegenerative disorders resulting from misfolding of cellular prion (PrP(C)) into scrapie prion (PrP(Sc)). Sirt1, a class III histone deacetylase, has been reported to protect neuronal cells against PrP (106-126)-induced cell death. To address the potential role of Sirt1 during prion infection, the levels and enzyme activities of Sirt1 in the brains of scrapie-infected rodents, including hamsters infected with strain 263K, mice infected with strains 139A and ME7, and in prion infected SMB-S15 cells, were analyzed. Western blots revealed that endogenous Sirt1 levels were significantly decreased in all tested scrapie-infected models. Dynamic assays of brain Sirt1 levels in 263K-infected hamsters during incubation period showed a time-dependent decrease. The acetylating forms of Sirt1 target proteins, P53, PGC-1, and STAT3, markedly increased both in the brains of scrapie-infected rodents and in SMB-S15 cells, representing decreased Sirt1 activity. Immunofluorescent assays illustrated that Sirt1 predominately localized in cytosol of SMB-S15 cells but clearly distributed in nucleus of its normal partner cell line, SMB-PS. Moreover, accompanying with increase of Sirt1 level and decrease of acetyl-P53 level, treatments with Sirt1 activators SRT1720 and resveratrol in SMB-S15 cells significantly reduced PrP(Sc); at the same time, the cellular distribution of PrP proteins became normal, and the cell proliferating state was slightly improved. These data indicate that prion infection notably attenuates the Sirt1 activity in host cells. Sensitivity of the PrP(Sc) to Sirt1 activators highlights a potential role of Sirt1 in prion therapeutics.

  20. Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients.

    Directory of Open Access Journals (Sweden)

    Kirsten A Petrie

    Full Text Available Fibrodysplasia Ossificans Progressiva (FOP is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation.

  1. Atypical benign partial epilepsy of childhood with acquired neurocognitive, lexical semantic, and autistic spectrum disorder.

    Science.gov (United States)

    Allen, Nicholas M; Conroy, Judith; Deonna, Thierry; McCreary, Dara; McGettigan, Paul; Madigan, Cathy; Carter, Imogen; Ennis, Sean; Lynch, Sally A; Shahwan, Amre; King, Mary D

    2016-01-01

    Atypical benign partial epilepsy (ABPE) of childhood or pseudo-Lennox syndrome is a form of idiopathic focal epilepsy characterized by multiple seizure types, focal and/or generalized epileptiform discharges, continuous spike-wave during sleep (CSWS), and sometimes reversible neurocognitive deficits. There are few reported cases of ABPE describing detailed correlative longitudinal follow-up of the various associated neurocognitive, language, social communicative, or motor deficits, in parallel with the epilepsy. Furthermore, the molecular inheritance pattern for ABPE and the wider spectrum of epilepsy aphasia disorders have yet to be fully elucidated. We describe the phenotype-genotype study of a boy with ABPE with follow-up from ages 5 to 13 years showing acquired oromotor and, later, a specific lexical semantic and pervasive developmental disorder. Exome sequencing identified variants in SCN9A, CPA6, and SCNM1. A direct role of the epilepsy in the pathogenesis of the oromotor and neurocognitive deficits is apparent.

  2. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs.

    Science.gov (United States)

    Trollor, Julian N; Chen, Xiaohua; Sachdev, Perminder S

    2009-01-01

    Neuroleptic malignant syndrome (NMS) is a rare but potentially severe idiosyncratic adverse reaction usually seen in the context of treatment with antipsychotic drugs. Although NMS is historically associated with the classic or 'typical' antipsychotic drugs, it is also a potential adverse effect of atypical antipsychotic drugs. The widespread use of atypical antipsychotic drugs highlights the need to examine the data relating to the symptomatology, diagnosis, classification and management of NMS with these newer agents. We used MEDLINE and EMBASE to identify NMS case reports and systematic reviews published to June 2008 related to the atypical antipsychotic drugs clozapine, olanzapine, risperidone, paliperidone, aripiprazole, ziprasidone, amisulpride and quetiapine. Case reports and reviews were systematically examined. Our review suggests that, in general, NMS associated with atypical antipsychotic drugs manifests in a typical manner. One notable exception is clozapine-induced NMS, which appears less likely to manifest with extrapyramidal features, including rigidity and tremor. The available literature highlights the divergence of opinion relating to the core diagnostic features of NMS and its conceptualization as a categorical versus dimensional disorder. Both these issues have relevance for the identification of atypical or milder forms of NMS, which are sometimes seen with atypical antipsychotic drugs.

  3. Mitochondrial DNA sequence analysis of patients with 'atypical psychosis'.

    Science.gov (United States)

    Kazuno, An-A; Munakata, Kae; Mori, Kanako; Tanaka, Masashi; Nanko, Shinichiro; Kunugi, Hiroshi; Umekage, Tadashi; Tochigi, Mamoru; Kohda, Kazuhisa; Sasaki, Tsukasa; Akiyama, Tsuyoshi; Washizuka, Shinsuke; Kato, Nobumasa; Kato, Tadafumi

    2005-08-01

    Although classical psychopathological studies have shown the presence of an independent diagnostic category, 'atypical psychosis', most psychotic patients are currently classified into two major diagnostic categories, schizophrenia and bipolar disorder, by the Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria. 'Atypical psychosis' is characterized by acute confusion without systematic delusion, emotional instability, and psychomotor excitement or stupor. Such clinical features resemble those seen in organic mental syndrome, and differential diagnosis is often difficult. Because patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) sometimes show organic mental disorder, 'atypical psychosis' may be caused by mutations of mitochondrial DNA (mtDNA) in some patients. In the present study whole mtDNA was sequenced for seven patients with various psychotic disorders, who could be categorized as 'atypical psychosis'. None of them had known mtDNA mutations pathogenic for mitochondrial encephalopathy. Two of seven patients belonged to a subhaplogroup F1b1a with low frequency. These results did not support the hypothesis that clinical presentation of some patients with 'atypical psychosis' is a reflection of subclinical mitochondrial encephalopathy. However, the subhaplogroup F1b1a may be a good target for association study of 'atypical psychosis'.

  4. Atypical sonographic patterns of fibroadenoma of the breast : pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kook, Shin Ho; Kim, Myung Sook; Pae, Won Kil [Kangbuk Samsung Hospital, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-03-01

    To correlate the atypical sonographic patterns of fibroadenoma of the breast with the pathologic findings. Among 203 surgically proven 43 which were sonographically atypical fibroadenomas, were retrospectively reviewed. The diagnostic criteria for atypical variety, as seen on sonography, were an ill-defined margin, microlobulated or irregular shape, heterogeneous internal echo-pattern, posterior shadowing, microcalcification, and clefts. The atypical sonographic patterns of these 43 fibroadenomas were analysed and compared with the pathologic findings. Among 43 lesions, ill-defined margins or irregular shapes were seen in 15 cases, heterogeneous internal echo-patterns in 27, posterior attenuation in nine, and clefts in seven. Thirty-seven (86%) of the 43 were predominantly ductal or had a mixed ductal and stromal component. Eleven (73.3%) of fifteen ill-defined margin or irregular shaped lesions were caused by interdigitation of surrounding normal breast parenchyma and mass. Twenty two (81.5%) of 27 heterogeneous internal echo-pat-terns were related to dilated ducts, phyllodes features, collagen bundles, adenosis, microcalcification, or fat vacuoles. Eight (88.9%) of nine posterior attenuations were caused by collagen bundles, microcalcification, ductal proliferation or dilatation. All seven cases showing clefts revealed phyllodes features and dilated ducts. Most atypical fibroadenomas had a predominantly ductal or mixed component. Ill-defined margin or irregular shape was mainly due to interdigitation of normal surrounding parenchyma. Variable histologic features were related to the heterogeneous internal echo-pattern, posterior shadowing, and the clefts revealed by atypical sonographic findings.

  5. Treatment of Scrapie Pathogen 263K With Tetracycline Partially Abolishes Protease-resistant Activity in vitro and Reduces Infectivity in vivo

    Institute of Scientific and Technical Information of China (English)

    YAN-JUN GUO; DE-XIN WANG; XIAO-PING DONG; JUN HAN; HAI-LAN YAO; BAO-YUN ZHANG; JIAN-MEI GAO; JIN ZHANG; XIN-LI XIAO; XIAO-FAN WANG; WEI-QIN ZHAO

    2007-01-01

    Objective To study the possible effect of tetracycline on protease-resistant activity in vitro and infectivity in vivo of a scrapie strain 263K.Methods Scrapie pathogens were incubated with tetracycline at different concentrations for various periods of time and protease-resistant PrP signals were evaluated with proteinase K-treatment and Western blots.The preparations treated with tetracycline were intracerebrally inoculated into golden hamsters and typical TSE manifestations were noted.PrPSc in brain tissues of the infected animals was detected by PrP specific Western blot assays. Results Protease-resistant PrP was significantly reduced in or removed from the preparations treated with tetracycline in a dose-dependant manner.Compared with the control group after incubated for 53.75±0.50 days,the preparations treated with 5 mmol/L and 20 mmol/L tetracycline prolonged the incubation time of 61.5±1.73 and 59.5±0.58 days (P<0.05). Conclusion Treatment of scrapie pathogen 263K with tetracycline reduces or removes its protease-resistant activity in vitro.

  6. Pallister-Killian syndrome: A mild case diagnosed by fluorescence in situ hybridization. Review of the literature and expansion of the phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Bielanska, M.M.; Khalifa, M.M.; Duncan, A.M.V. [Queen`s Univ., Kingston, Ontario (Canada)

    1996-10-16

    Pallister-Killian syndrome (PKS) is a rare disorder characterized by a specific combination of anomalies, mental retardation and mosaic presence of a supernumerary isochromosome 12p which is tissue-limited. We report an atypical case of PKS with a mild phenotype. Fluorescence in situ hybridization (FISH) was used to demonstrate that the supernumerary marker chromosome identified in the patient`s fibroblasts was an isochromosome 12p. This study broadens the spectrum of PKS phenotype. It also illustrates the usefulness of fluorescence in situ hybridization in diagnosis of patients with chromosomal abnormalities and mild or atypical clinical findings. 40 refs., 2 figs., 1 tab.

  7. Cytosolic PrP can participate in prion-mediated toxicity.

    Science.gov (United States)

    Thackray, Alana M; Zhang, Chang; Arndt, Tina; Bujdoso, Raymond

    2014-07-01

    Prion diseases are characterized by a conformational change in the normal host protein PrPC. While the majority of mature PrPC is tethered to the plasma membrane by a glycosylphosphatidylinositol anchor, topological variants of this protein can arise during its biosynthesis. Here we have generated Drosophila transgenic for cytosolic ovine PrP in order to investigate its toxic potential in flies in the absence or presence of exogenous ovine prions. While cytosolic ovine PrP expressed in Drosophila was predominantly detergent insoluble and showed resistance to low concentrations of proteinase K, it was not overtly detrimental to the flies. However, Drosophila transgenic for cytosolic PrP expression exposed to classical or atypical scrapie prion inocula showed a faster decrease in locomotor activity than similar flies exposed to scrapie-free material. The susceptibility to classical scrapie inocula could be assessed in Drosophila transgenic for panneuronal expression of cytosolic PrP, whereas susceptibility to atypical scrapie required ubiquitous PrP expression. Significantly, the toxic phenotype induced by ovine scrapie in cytosolic PrP transgenic Drosophila was transmissible to recipient PrP transgenic flies. These data show that while cytosolic PrP expression does not adversely affect Drosophila, this topological PrP variant can participate in the generation of transmissible scrapie-induced toxicity. These observations also show that PrP transgenic Drosophila are susceptible to classical and atypical scrapie prion strains and highlight the utility of this invertebrate host as a model of mammalian prion disease. Importance: During prion diseases, the host protein PrPC converts into an abnormal conformer, PrPSc, a process coupled to the generation of transmissible prions and neurotoxicity. While PrPC is principally a glycosylphosphatidylinositol-anchored membrane protein, the role of topological variants, such as cytosolic PrP, in prion-mediated toxicity and prion

  8. Lipopolysaccharide heterogeneity in the atypical group of novel emerging Brucella species.

    Science.gov (United States)

    Zygmunt, Michel S; Jacques, Isabelle; Bernardet, Nelly; Cloeckaert, Axel

    2012-09-01

    Recently, novel Brucella strains with phenotypic characteristics that were atypical for strains belonging to the genus Brucella have been reported. Phenotypically many of these strains were initially misidentified as Ochrobactrum spp. Two novel species have been described so far for these strains, i.e., B. microti and B. inopinata, and other strains genetically related to B. inopinata may constitute other novel species as well. In this study, we analyzed the lipopolysaccharides (LPS) (smooth LPS [S-LPS] and rough LPS [R-LPS]) of these atypical strains using different methods and a panel of monoclonal antibodies (MAbs) directed against several epitopes of the Brucella O-polysaccharide (O-PS) and R-LPS. Among the most striking results, Brucella sp. strain BO2, isolated from a patient with chronic destructive pneumonia, showed a completely distinct S-LPS profile in silver stain gels that looked more similar to that of enterobacterial S-LPS. This strain also failed to react with MAbs against Brucella O-PS epitopes and showed weak reactivity with anti-R-LPS MAbs. B. inopinata reference strain BO1 displayed an M-dominant S-LPS type with some heterogeneity relative to the classical M-dominant Brucella S-LPS type. Australian wild rodent strains belonging also to the B. inopinata group showed a classical A-dominant S-LPS but lacked the O-PS common (C) epitopes, as previously reported for B. suis biovar 2 strains. Interestingly, some strains also failed to react with anti-R-LPS MAbs, such as the B. microti reference strain and B. inopinata BO1, suggesting modifications in the core-lipid A moieties of these strains. These results have several implications for serological typing and serological diagnosis and underline the need for novel tools for detection and correct identification of such novel emerging Brucella spp.

  9. Fluoroquinolone resistance in atypical pneumococci and oral streptococci: evidence of horizontal gene transfer of fluoroquinolone resistance determinants from Streptococcus pneumoniae.

    Science.gov (United States)

    Ip, Margaret; Chau, Shirley S L; Chi, Fang; Tang, Julian; Chan, Paul K

    2007-08-01

    Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of > or =4.0 microg/ml and unique sequence variations within the quinolone resistance-determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison with the Streptococcus pneumoniae R6 strain, were examined. These strains were reidentified using phenotypic methods, including detection of optochin susceptibility, bile solubility, and agglutination by serotype-specific antisera, and genotypic methods, including detection of pneumolysin and autolysin genes by PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis based on concatenated sequences of the six MLST loci distinguished the "atypical" strains from pneumococci, and these strains clustered closely with S. mitis. However, all these strains and five of nine strains from the viridans streptococcal group possessed one to three gyrA, gyrB, parC, and parE genes whose QRDR sequences clustered with those of S. pneumoniae, providing evidence of horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from pneumococci into viridans streptococci. These genes also conferred fluoroquinolone resistance to viridans streptococci. In addition, the fluoroquinolone resistance determinants of 32 well-characterized Streptococcus mitis and Streptococcus oralis strains from bacteremic patients were also compared. These strains have unique amino acid substitutions in GyrA and ParC that were distinguishable from those in fluoroquinolone-resistant pneumococci and the "atypical" isolates. Both recombinational events and de novo mutations play an important role in the development of fluoroquinolone resistance.

  10. First Japanese case of atypical progeroid syndrome/atypical Werner syndrome with heterozygous LMNA mutation.

    Science.gov (United States)

    Motegi, Sei-ichiro; Yokoyama, Yoko; Uchiyama, Akihiko; Ogino, Sachiko; Takeuchi, Yuko; Yamada, Kazuya; Hattori, Tomoyasu; Hashizume, Hiroaki; Ishikawa, Yuichi; Goto, Makoto; Ishikawa, Osamu

    2014-12-01

    Atypical progeroid syndrome (APS), including atypical Werner syndrome (AWS), is a progeroid syndrome involving heterozygous mutations in the LMNA gene encoding the nuclear protein lamin A/C. We report the first Japanese case of APS/AWS with a LMNA mutation (p.D300N). A 53-year-old Japanese man had a history of recurrent severe cardiovascular diseases as well as brain infarction and hemorrhages. Although our APS/AWS patient had overlapping features with Werner syndrome (WS), such as high-pitched voice, scleroderma, lipoatrophy and atherosclerosis, several cardinal features of WS, including short stature, premature graying/alopecia, cataract, bird-like face, flat feet, hyperkeratosis on the soles and diabetes mellitus, were absent. In immunofluorescence staining and electron microscopic analyses of the patient's cultured fibroblasts, abnormal nuclear morphology, an increase in small aggregation of heterochromatin and a decrease in interchromatin granules in nuclei of fibroblasts were observed, suggesting that abnormal nuclear morphology and chromatin disorganization may be associated with the pathogenesis of APS/AWS.

  11. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2007-08-01

    Full Text Available Abstract Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. Methods We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library, and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration. Results In five trials (2,206 patients participants presented with a depressive episode, and in 25 trials (6,174 patients the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12. With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22 in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10. In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials, somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics

  12. The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration.

    Science.gov (United States)

    Pellecchia, M T; Valente, E M; Cif, L; Salvi, S; Albanese, A; Scarano, V; Bonuccelli, U; Bentivoglio, A R; D'Amico, A; Marelli, C; Di Giorgio, A; Coubes, P; Barone, P; Dallapiccola, B

    2005-05-24

    Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal-recessive disorder caused by mutations in the PANK2 gene. The authors report clinical and genetic findings of 16 patients with PKAN. The authors identified 12 mutations in the PANK2 gene, five of which were new. Only nine patients could be classified as classic or atypical PKAN, and intermediate phenotypes are described. Two patients presented with motor tics and obsessive-compulsive behavior suggestive of Tourette syndrome.

  13. An atypical 0.8 Mb inherited duplication of 22q11.2 associated with psychomotor impairment.

    Science.gov (United States)

    Pebrel-Richard, Céline; Kemeny, Stéphan; Gouas, Laetitia; Eymard-Pierre, Eléonore; Blanc, Nathalie; Francannet, Christine; Tchirkov, Andreï; Goumy, Carole; Vago, Philippe

    2012-11-01

    Microduplications 22q11.2 have been recently characterized as a new genomic duplication syndrome showing an extremely variable phenotype ranging from normal or mild learning disability to multiple congenital defects and sharing some overlapping features with DiGeorge/velocardiofacial syndrome (DGS/VCFS), including heart defects, urogenital abnormalities and velopharyngeal insufficiency. We present an atypical and inherited 0.8-Mb duplication at 22q11.2, in the distal segment of the DGS/VCFS syndrome typically deleted region (TDR), in a 3-year-old boy with motor delay, language disorders and mild facial phenotype. This 22q11.2 microduplication was identified by MLPA, designed to detect recurrent microdeletions and microduplications of chromosomal regions frequently involved in mental retardation syndromes and was further characterized by aCGH. The duplicated region encompasses 14 genes, excluding TBX1 but including CRKL, ZNF74, PIK4CA, SNAP29 and PCQAP known to contribute to several aspects of the DGS/VCFS phenotype. To the best of our knowledge, only one case of an isolated duplication in the distal segment of the TDR between chromosome 22-specific low-copy repeats B (LCR22-B) and D (LCR22-D) has been published, but the present report is the first one with a detailed description of physical and developmental features in a patient carrying this kind of atypical 22q11.2 duplication. This case illustrates the importance of reporting unusual 22q11.2 duplications to further evaluate the incidence of these rearrangements in the general population and to improve genotype-phenotype correlations and genetic counseling.

  14. Ichthyosiform mycosis fungoides with alopecia and atypical membranous nephropathy

    Directory of Open Access Journals (Sweden)

    Qiang Zhou

    2011-01-01

    Full Text Available We describe here a rare case of variant of mycosis fungoides (MF: ichthyosiform MF with alopecia and atypical membranous nephropathy. The diagnosis was made based on the following findings: generalized ichthyosis-like eruption, alopecia, enlarged superficial lymph nodes, proteinuria, and hematuria, the histological features of the skin biopsy from both ichthyotic and alopecic lesions with immunohistochemical staining, and the renal biopsy examination with immunofluorescence. The histological examination of ichthyotic and alopecic lesions displayed a predominant infiltration of atypical lymphocytes in the upper dermis with the characteristics of epidermotropism and folliculotropism. Immunohistochemical studies demonstrated that most infiltrated atypical lymphocytes were CD3, CD4, and CD45RO positive, whereas negative for CD5, CD7, CD20, CD30, and CD56. A renal biopsy examination revealed atypical membranous nephropathy with deposition of immunoglobulin G (IgG, IgM, IgA, C1q, and C3. In this case atypical membranous nephropathy was involved, which is very uncommon and has never been presented in the literature to date. Although ichthyosiform MF usually features a relatively favorable course, diffuse alopecia and the renal involvement in this case might indicate aggressive disease and poor prognosis.

  15. Atypical periprosthetic acetabular fracture in long-term alendronate therapy

    Science.gov (United States)

    Marongiu, Giuseppe; Capone, Antonio

    2016-01-01

    Summary Bisphosphonates have been commonly used in the treatment of osteoporosis, demonstrating its efficacy in fracture risk reduction. However, even if are generally safe and well tolerated, concerns have emerged about atypical fractures related to its prolonged use. Although atypical femoral fracture are more common, case reports demonstrated that even other skeletal areas can be involved by unusual pattern of fracture. We report a atypical acetabular periprosthetic fracture in a 83-year-old female patient after prolonged alendronate treatment for osteoporosis and isolated acetabular revision surgery. The patient underwent to clinical, bioumoral and radiological evaluation and all the history cases were fully reported. We believe this periprosthetic fracture, according to the available data, may have similar underlying pathology to atypical femoral fractures. Awareness of symptoms, in addition to a regular radiographic survey may facilitate early diagnosis and possible prevention of spontaneous periprosthetic fractures, in patients receiving bisphosphonate therapy beyond 5 years. The treatment of this atypical periprosthetic fracture should include both surgical than pharmacological therapy to obtained bone healing. PMID:28228784

  16. An atypical 7q11.23 deletion in a normal IQ Williams–Beuren syndrome patient

    Science.gov (United States)

    Ferrero, Giovanni Battista; Howald, Cédric; Micale, Lucia; Biamino, Elisa; Augello, Bartolomeo; Fusco, Carmela; Turturo, Maria Giuseppina; Forzano, Serena; Reymond, Alexandre; Merla, Giuseppe

    2010-01-01

    Williams–Beuren syndrome (WBS; OMIM no. 194050) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion of 1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features. These insights for genotype–phenotype correlations came from the molecular and clinical analysis of patients with atypical deletions and mice models. Here we report a patient showing mild WBS physical phenotype and normal IQ, who carries a shorter 1 Mb atypical deletion. This rearrangement does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the hypothesis that hemizygosity of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms and in the specific motor and cognitive deficits observed in WBS patients. PMID:19568270

  17. An atypical 7q11.23 deletion in a normal IQ Williams-Beuren syndrome patient.

    Science.gov (United States)

    Ferrero, Giovanni Battista; Howald, Cédric; Micale, Lucia; Biamino, Elisa; Augello, Bartolomeo; Fusco, Carmela; Turturo, Maria Giuseppina; Forzano, Serena; Reymond, Alexandre; Merla, Giuseppe

    2010-01-01

    Williams-Beuren syndrome (WBS; OMIM no. 194050) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion of 1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features. These insights for genotype-phenotype correlations came from the molecular and clinical analysis of patients with atypical deletions and mice models. Here we report a patient showing mild WBS physical phenotype and normal IQ, who carries a shorter 1 Mb atypical deletion. This rearrangement does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the hypothesis that hemizygosity of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms and in the specific motor and cognitive deficits observed in WBS patients.

  18. Management of atypical lobular hyperplasia, atypical ductal hyperplasia, and lobular carcinoma in situ.

    Science.gov (United States)

    Clauser, Paola; Marino, Maria A; Baltzer, Pascal A T; Bazzocchi, Massimo; Zuiani, Chiara

    2016-01-01

    Atypical hyperplasia and lobular carcinoma in situ are rare proliferative breast lesions, growing inside ducts and terminal ducto-lobular units. They represent a marker of increased risk for breast cancer and a non-obligate precursor of malignancy. Evidence available on diagnosis and management is scarce. They are frequently found incidentally associated with other lesions, but can be visible through mammography, ultrasound or magnetic resonance. Due to the risk of underestimation, surgical excision is often performed. The analysis of imaging and histopathological characteristics could help identifying low-risk cases, for which surgery is not necessary. Chemopreventive agents can be used for risk reduction. Careful imaging follow up is mandatory; the role of breast MRI as screening modality is under discussion.

  19. Atypical cellular blue nevus or malignant blue nevus?*

    Science.gov (United States)

    Daltro, Luise Ribeiro; Yaegashi, Lygia Bertalha; Freitas, Rodrigo Abdalah; Fantini, Bruno de Carvalho; Souza, Cacilda da Silva

    2017-01-01

    Blue nevus is a benign melanocytic lesion whose most frequent variants are dendritic (common) blue nevus and cellular blue nevus. Atypical cellular blue nevus presents an intermediate histopathology between the typical and a rare variant of malignant blue nevus/melanoma arising in a cellular blue nevus. An 8-year-old child presented a pigmented lesion in the buttock since birth, but with progressive growth in the last two years. After surgical excision, histopathological examination revealed atypical cellular blue nevus. Presence of mitoses, ulceration, infiltration, cytological atypia or necrosis may occur in atypical cellular blue nevus, making it difficult to differentiate it from melanoma. The growth of blue nevus is unusual and considered of high-risk for malignancy, being an indicator for complete resection and periodic follow-up of these patients. PMID:28225968

  20. Gender-Atypical Mental Illness as Male Gender Threat.

    Science.gov (United States)

    Michniewicz, Kenneth S; Bosson, Jennifer K; Lenes, Joshua G; Chen, Jason I

    2016-07-01

    The present study examined whether men view gender-atypical (i.e., feminine) psychological disorders as threats to their gender status. Men and women (N = 355) rated their expectations of gender status loss, feelings of distress, and help-seeking intentions in response to 10 different stereotypically masculine and feminine psychological disorders. Men as compared to women expected greater gender status loss for, and reported more distress to, gender-atypical versus gender-typical disorders. Expectations of gender status loss partially mediated the link between participant gender and distress at the thought of gender-atypical disorders. These findings suggest that feminine disorders pose more powerful gender status threats for men than masculine disorders do and that men's expectations of gender status loss for feminine disorders drive their negative reactions to these mental illnesses. The discussion emphasizes the importance of considering the gender-typicality of disorders, and the implications of these findings for clinical interventions.

  1. Atypical pyoderma gangrenosum in a patient with osteomyelofibrosis

    Directory of Open Access Journals (Sweden)

    Živanović Dubravka

    2007-01-01

    Full Text Available Background. Atypical forms of pyoderma gangrenosum generally appear on the upper extremities; most frequently they are associated with myeloproliferative disorders, including osteomyelofibrosis. A response to systemic steroids is more pronounced than in classical form. Sometimes it may be the first sign of an underlying malignancy. Case report. We reported a patient with atypical pyoderma gangrenosum developed during the course of a myeloid malignancy - osteomyelofibrosis. The lesions occurred after a minor trauma. Painful blistering plaques, with an elevated, bluish-gray border were located on the dorsal aspect of hands. No skin malignancy was found. The lesions resolved rapidly to systemic steroids. Conclusion. Considering the unusual clinical presentation which makes the diagnosis difficult, as well as the fact that atypical forms of pyoderma gangrenosum can be the first sign of malignancies, especially myeloproliferative ones, recognizing this entity enables timely guiding future investigations toward their prompt detection.

  2. Rare Posterior Pharyngeal Mass: Atypical Marginal Zone Hyperplasia.

    Science.gov (United States)

    Eliçora, Sultan Şevik; Güven, Mehmet; Varli, Ali F; Yilmaz, Mahmut S; Alponat, Selin

    2016-03-01

    Cases of posterior pharyngeal masses are quite rare, and are typically derived from schwannoma or encephalocele, or are of vascular or infectious origin. They are clinically significant due to their tendency to cause airway obstruction. The aim of this study was to present a rare atypical marginal hyperplasia case of a posterior pharyngeal wall mass. A 10-year-old male was admitted to our clinic with dyspnea. A plane-surfaced 4 × 3 × 3 cm mass was observed on the posterior pharyngeal wall upon physical examination. The patient underwent magnetic resonance imaging and surgical treatment. Following excision of material from the patient's mass, a pathologic diagnosis of atypical marginal zone hyperplasia was made. Atypical marginal zone hyperplasia of the posterior pharyngeal wall has not yet been reported in the literature. Marginal zone hyperplasia associated with a lymphoproliferative disease should be considered when making differential diagnoses of posterior pharyngeal wall masses.

  3. Atypical femur fractures associated with bisphosphonates: from prodrome to resolution

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    Braulio Sastre-Jala

    2015-10-01

    Full Text Available Atypical fractures related to the prolonged use of bisphosphonates are caused by low energy mechanisms and are characterized by oblique and transverse lines and frequent bilateralism. We present a clinical case of a patient who we believe illustrates, both in clinical and radiological aspects, the new definition of atypical femur fracture related to treatment using bisphosphonates treated conservatively and successfully with discharge and teriparatide 20 mcg/80 mcl s.c./24h. The appearance of painful symptoms in the upper thigh, especially if bilateral, in patients treated with bisphosphonates for long periods of time, makes it necessary to dismiss bone lesions that might otherwise suggest atypical fracture. In those cases where the fracture is incomplete, restoring bone metabolism through the administration of teriparatide 20 mcg/80 mcl s.c./24h could prevent displaced fractures.

  4. Atypical Imaging Findings in Primary Central Nervous System Lymphoma

    Directory of Open Access Journals (Sweden)

    Zahra Afravi

    2010-05-01

    Full Text Available Background/Objective: The incidence of primary CNS lymphomas (PCNSL is increasing. Timely diagnosis of PCNSL can lead to proper therapeutic management. There are some atypical imaging findings that may easily be misdiagnosed as other pathologic processes such as infectious and demyelinative diseases. As a result, histopathologic diagnosis is necessary for all suspected lesions."nPatients and Methods: In this research we studied 120 cases of PCNSL over the past 16 years. Some of them had atypical imaging findings, suggesting many differential diagnoses. Having said that, stereotactic biopsy was performed for all cases and the diagnosis was proved."nResults: We selected some interesting cases with atypical imaging findings of PCNSL, which were unlikely to be diagnosed without histopathologic evaluation. "nConclusion: PCNSL must be kept in mind as a differential diagnosis for other brain lesions. Histopathologic diagnosis is necessary for prompt management.

  5. Fine-grained facial phenotype-genotype analysis in Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Hammond, Peter; Hannes, Femke; Suttie, Michael; Devriendt, Koen; Vermeesch, Joris Robert; Faravelli, Francesca; Forzano, Francesca; Parekh, Susan; Williams, Steve; McMullan, Dominic; South, Sarah T; Carey, John C; Quarrell, Oliver

    2012-01-01

    Wolf-Hirschhorn syndrome is caused by anomalies of the short arm of chromosome 4. About 55% of cases are due to de novo terminal deletions, 40% from unbalanced translocations and 5% from other abnormalities. The facial phenotype is characterized by hypertelorism, protruding eyes, prominent glabella, broad nasal bridge and short philtrum. We used dense surface modelling and pattern recognition techniques to delineate the milder facial phenotype of individuals with a small terminal deletion (breakpoint within 4p16.3) compared to those with a large deletion (breakpoint more proximal than 4p16.3). Further, fine-grained facial analysis of several individuals with an atypical genotype and/or phenotype suggests that multiple genes contiguously contribute to the characteristic Wolf-Hirschhorn syndrome facial phenotype.

  6. Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain.

    Science.gov (United States)

    Kong, Qingzhong; Zheng, Mengjie; Casalone, Cristina; Qing, Liuting; Huang, Shenghai; Chakraborty, Bikram; Wang, Ping; Chen, Fusong; Cali, Ignazio; Corona, Cristiano; Martucci, Francesca; Iulini, Barbara; Acutis, Pierluigi; Wang, Lan; Liang, Jingjing; Wang, Meiling; Li, Xinyi; Monaco, Salvatore; Zanusso, Gianluigi; Zou, Wen-Quan; Caramelli, Maria; Gambetti, Pierluigi

    2008-04-01

    Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to be caused by only one strain, BSE-C. BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE strains by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE strain-infected cattle. Sixty percent of the inoculated Tg mice became infected after 20 to 22 months of incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE strain-infected Tg mice, but none of the Tg mice infected with prions causing a sporadic human prion disease, showed the presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE strain-infected humanized Tg mouse brains are different from those from the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation times are observed for the BASE strain-infected Tg mice. These results suggest that in humans, the BASE strain is a more virulent BSE strain and likely lymphotropic.

  7. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  8. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  9. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-

  10. Atypical Pupillary Light Reflex in Individuals with Autism

    Science.gov (United States)

    2014-09-01

    AWARD NUMBER: W81XWH-10-1-0474 TITLE: Atypical Pupillary Light Reflex in Individuals with Autism ...30th/2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0474 Atypical Pupillary  Light  Reflex in Individuals with  Autism 5b. GRANT NUMBER...20,  p< .00005 in all instances].  15. SUBJECT TERMS Pupillary light reflex, autism , functional MRI 16. SECURITY CLASSIFICATION OF: 17

  11. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach.

  12. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    Directory of Open Access Journals (Sweden)

    Mishra Biswaranjan

    2007-10-01

    Full Text Available Neuroleptic malignant syndrome (NMS is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presentations of NMS have often varied, and we report another atypicality in presentation of NMS due to olanzapine use.

  13. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

    Directory of Open Access Journals (Sweden)

    Quevedo-Florez Leonardo

    2017-01-01

    Full Text Available The Neuroleptic Malignant Syndrome (NMS is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

  14. A child with myoclonus-dystonia (DYT11) misdiagnosed as atypical opsoclonus myoclonus syndrome

    DEFF Research Database (Denmark)

    Drivenes, Bergitte; Born, Alfred Peter; Ek, Jakob

    2015-01-01

    INTRODUCTION: DYT11 is an autosomal dominant inherited movement disorder characterized by myoclonus and dystonia. CLINICAL PRESENTATION: We present a case with atypical symptoms and with episodes of ataxia and myoclonus preceded by infections. Atypical presentation of opsoclonus myoclonus syndrome...

  15. Phenotypic Expansion of DGKE-Associated Diseases

    Science.gov (United States)

    Westland, Rik; Bodria, Monica; Carrea, Alba; Lata, Sneh; Scolari, Francesco; Fremeaux-Bacchi, Veronique; D’Agati, Vivette D.; Lifton, Richard P.; Gharavi, Ali G.; Ghiggeri, Gian Marco

    2014-01-01

    Atypical hemolytic uremic syndrome (aHUS) is usually characterized by uncontrolled complement activation. The recent discovery of loss-of-function mutations in DGKE in patients with aHUS and normal complement levels challenged this observation. DGKE, encoding diacylglycerol kinase-ε, has not been implicated in the complement cascade but hypothetically leads to a prothrombotic state. The discovery of this novel mechanism has potential implications for the treatment of infants with aHUS, who are increasingly treated with complement blocking agents. In this study, we used homozygosity mapping and whole-exome sequencing to identify a novel truncating mutation in DGKE (p.K101X) in a consanguineous family with patients affected by thrombotic microangiopathy characterized by significant serum complement activation and consumption of the complement fraction C3. Aggressive plasma infusion therapy controlled systemic symptoms and prevented renal failure, suggesting that this treatment can significantly affect the natural history of this aggressive disease. Our study expands the clinical phenotypes associated with mutations in DGKE and challenges the benefits of complement blockade treatment in such patients. Mechanistic studies of DGKE and aHUS are, therefore, essential to the design of appropriate therapeutic strategies in patients with DGKE mutations. PMID:24511134

  16. Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains

    Directory of Open Access Journals (Sweden)

    Di Bari Michele A

    2011-08-01

    Full Text Available Abstract Objective Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial. Methods To shed light on the matter, we analysed and compared cholesterol variations in ScN2a cells and in brains of Scrapie-infected C57Bl/6 mice, using two different methods: a fluorimetric-enzymatic cholesterol assay, and high performance liquid chromatography-mass spectroscopy (HPLC-MS. Results Compared to uninfected controls, similar cholesterol metabolism anomalies were observed in infected cells and brains by both methods; however, only HPLC-MS revealed statistically significant cholesterol variations, particularly in the cholesteryl esters (CE fraction. HPLC-MS analyses also revealed different fatty acid composition of the CE fraction in cells and brains. In N2a cells, their profile reflected that of serum, while in normal brains cholesteryl-linoleate only was found at detectable levels. Following prion infection, most CE species were increased in the CE pool of ScN2a cells, whereas a conspicuous amount of cholesteryl-arachidonate only was found to contribute to the cerebral increase of CE. Of interest, oral pravastatin administration to Scrapie-infected mice, was associated with a significant reduction of cerebral free cholesterol (FC along with a concomitant further increase of the CE pool, which included increased amounts of both cholesteryl-linoleate and cholesteryl-arachidonate. Conclusion Although mechanistic studies are needed to establish the pathophysiological relevance of changes in cerebral CE concentrations, to the best of our knowledge this is the first report to provide evidence of increased cholesterol esterification in brains of prion-infected mice, untreated and treated with pravastatin.

  17. Scientific and technical assistance on the provisional results of the study on genetic resistance to Classical scrapie in goats in Cyprus

    Directory of Open Access Journals (Sweden)

    European Food Safety Authority

    2012-11-01

    Full Text Available This EFSA Scientific Report reviews and discusses the provisional results of a study (EURL/Cypriot study on genetic resistance to Classical scrapie in goats in Cyprus. It is concluded that the provisional results obtained in the study further support the lower susceptibility to Classical scrapie in goats carrying the D146 and S146 alleles compared to wild type (N146N goats. The results from intracerebral challenge are not compatible with a level of resistance as high as the one observed in sheep carrying the ARR allele or in goats carrying the K222 allele. Final results from the oral challenge will be crucial in determining the level of resistance associated with the D146 and S146 alleles. Furthermore, it is concluded that the provisional results obtained in the study are compatible with the possibility to use the D146 and S146 alleles to build a genetic strategy to control and eradicate Classical scrapie in goats in Cyprus. However, the success of such a strategy will be determined by the level of resistance associated with the D146 and S146 alleles against infection with all the different TSE agents proved to be circulating in Cyprus, which at this stage of the EURL/Cypriot study remains to be definitively assessed. In addition, as compared to the results of the model developed in the study, it is concluded that the efficiency of the implementation in the field of a breeding strategy selecting for the D146 and S146 alleles may be lower due to potential practical constraints related to the management of genetic diversity, to the selection for production and health traits and to the need of moving animals for breeding purposes in Cyprus. Recommendations on aspects that may be considered when completing the study are formulated.

  18. Remarkable Activation of the Complement System and Aberrant Neuronal Localization of the Membrane Attack Complex in the Brain Tissues of Scrapie-Infected Rodents.

    Science.gov (United States)

    Lv, Yan; Chen, Cao; Zhang, Bao-Yun; Xiao, Kang; Wang, Jing; Chen, Li-Na; Sun, Jing; Gao, Chen; Shi, Qi; Dong, Xiao-Ping

    2015-12-01

    As an integral part of the innate immunity, the complement system has been reported to involve in the pathogenesis of prion diseases (PrD). However, the states of expression and activity of complement proteins in experimental models of scrapie infection are still not fully understood. Herein, the state of complement activation, the presence, and distribution as well as localization of C3 and membrane attack complex (MAC) in the brains of several scrapie-infected rodents were comparatively assessed through various methodologies. Our data illustrated a significant increase in the total complement activity (CH50, U/ml) in several scrapie-infected rodent brains at the terminal stage and a time-dependent upregulation of C1q in 263K-infected hamsters during the incubation period, intimating the sustained and progressive activation of the classical pathway during PrD progression. Confocal microscopy revealed robust activation of C3 and its localization to various central nervous system (CNS) cells with differential morphology in the brain tissues of both 263K-infected hamsters and 139A-infected C57BL/6 mice at disease end stages. Dynamic analyses of MAC in the brains of 263K-infected hamsters and 139A-infected C57BL/6 mice demonstrated remarkably time-dependent deposition during the incubation period, which may highlight a persistently activated terminal complement components. Moreover, immunofluorescent assays (IFAs) showed that MAC-specific signals appeared to overlap with morphologically abnormal neurons rather than proliferative astrocytes or activated microglia throughout the CNS of both 263K-infected hamsters and 139A-infected C57BL/6 mice. Overall, these results indicate that the activation of the complement system and the subsequent localization of the complement components to neurons may be a hallmark during prion infection, which ultimately contribute to the neurodegeneration in PrD.

  19. Prion disease detection, PMCA kinetics, and IgG in urine from sheep naturally/experimentally infected with scrapie and deer with preclinical/clinical chronic wasting disease.

    Science.gov (United States)

    Rubenstein, Richard; Chang, Binggong; Gray, Perry; Piltch, Martin; Bulgin, Marie S; Sorensen-Melson, Sharon; Miller, Michael W

    2011-09-01

    Prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. Low levels of infectious agent and limited, infrequent success of disease transmissibility and PrP(Sc) detection have been reported with urine from experimentally infected clinical cervids and rodents. We report the detection of prion disease-associated seeding activity (PASA) in urine from naturally and orally infected sheep with clinical scrapie agent and orally infected preclinical and infected white-tailed deer with clinical chronic wasting disease (CWD). This is the first report on PASA detection of PrP(Sc) from the urine of naturally or preclinical prion-diseased ovine or cervids. Detection was achieved by using the surround optical fiber immunoassay (SOFIA) to measure the products of limited serial protein misfolding cyclic amplification (sPMCA). Conversion of PrP(C) to PrP(Sc) was not influenced by the presence of poly(A) during sPMCA or by the homogeneity of the PrP genotypes between the PrP(C) source and urine donor animals. Analysis of the sPMCA-SOFIA data resembled a linear, rather than an exponential, course. Compared to uninfected animals, there was a 2- to 4-log increase of proteinase K-sensitive, light chain immunoglobulin G (IgG) fragments in scrapie-infected sheep but not in infected CWD-infected deer. The higher-than-normal range of IgG levels found in the naturally and experimentally infected clinical scrapie-infected sheep were independent of their genotypes. Although analysis of urine samples throughout the course of infection would be necessary to determine the usefulness of altered IgG levels as a disease biomarker, detection of PrP(Sc) from PASA in urine points to its potential value for antemortem diagnosis of prion diseases.

  20. Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome.

    Science.gov (United States)

    Wada, Taizo; Yasui, Masahiro; Toma, Tomoko; Nakayama, Yuko; Nishida, Mika; Shimizu, Masaki; Okajima, Michiko; Kasahara, Yoshihito; Koizumi, Shoichi; Inoue, Masami; Kawa, Keisei; Yachie, Akihiro

    2008-09-01

    X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (gammac) and usually characterized by the absence of T and natural killer (NK) cells. Here, we report an atypical case of XSCID presenting with autologous T and NK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G>A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual gammac expression and development of T and NK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.

  1. Impact of BCRP/MXR, MRP1 and MDR1/P-Glycoprotein on thermoresistant variants of atypical and classical multidrug resistant cancer cells

    DEFF Research Database (Denmark)

    Stein, Ulrike; Lage, Hermann; Jordan, Andreas;

    2002-01-01

    The impact of the ABC transporters breast cancer resistance protein/mitoxantrone resistance associated transporter (BCRP/MXR), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance gene-1/P-glycoprotein (MDR1/PGP) on the multidrug resistance (MDR) phenotype in chemoresistance...... and thermoresistance was investigated in the parental human gastric carcinoma cell line EPG85-257P, the atypical MDR subline EPG85-257RNOV, the classical MDR subline EPG85-257RDB and their thermoresistant counterparts EPG85-257P-TR, EPG85-257RNOV-TR and EPG85-257RDB-TR. Within the atypical MDR subline EPG85-257RNOV...... was increased relative to thermosensitive sublines. Although it could be shown that the overexpressed ABC transporters were functionally active, however, no decreased drug accumulations of doxorubicin, mitoxantrone and rhodamine 123 were observed. Thus, expression of BCRP/MXR, MRP1 and MDR1/PGP was found...

  2. Treatment of atypical trigeminal neuralgia with microvascular decompression

    Directory of Open Access Journals (Sweden)

    Hai Jian

    2006-01-01

    Full Text Available Aim: To explore the methods for achieving pain relief in patients with atypical trigeminal neuralgia (TN using microvascular decompression (MVD. Study Design and Settings: Retrospective study of 26 patients treated during the years 2000 to 2004. Materials and Methods: Twenty-six patients in whom vascular compression of the trigeminal nerve was identified by high definition magnetic resonance tomographic angiography (MRTA were treated with MVD for atypical TN in our department. Clinical presentations, surgical findings and clinical outcomes were analyzed retrospectively. Results: In this study, single trigeminal division was involved in only 2 patients (8% and two or three divisions in the other 24 patients (92%. Of prime importance is the fact that in 46.2% of the patients, several conflicting vessels were found in association. Location of the conflicts around the circumference of the trigeminal root was supero-medial to the root in 53.5%, supero-lateral in 30.8% and inferior in 15.7%. MVD for atypical TN resulted in complete pain relief in 50% of the patients with complete decompression, partial pain relief in 30.8% and poor pain relief or pain recurrence in 19.2% of the patients without complete decompression postoperatively. Conclusions: Complete decompression of the entire trigeminal root plays an important role in achieving pain relief in patients with atypical TN with MVD.

  3. Atypical pathogens in community acquired pneumonia of Egyptian children

    Institute of Scientific and Technical Information of China (English)

    Deraz TE; El Sahriggy SA; Shaheen MA; Motawea AA; Gomaa HE; Fawzy SH; Mohamed AA

    2009-01-01

    Objective:Diagnosis of atypical pathogens as an aetiology for community-acquired pneumonia (CAP)in chil-dren is a challenge world wide.The aim of this study was to detect the frequency of atypical pathogens as a cause of community-acquired pneumonia (CAP)in Egyptian children.Methods:From 50 children (with age ranged from 2 months to 1 2 years)hospitalized for community-acquired pneumonia;respiratory sputum samples were collected by induction or spontaneously.All samples were subjected to conventional cultures and Polymer-ase Chain Reaction(PCR)technique DNA extraction for identification of Mycoplasma,Chlamydia pneumoniae and Legionella pneumophila.Results:A definite pathogen was identified in 78% of the studied children;30%typical bacteria,8% candida albicans and atypical bacteria in 40% of the pneumonic children.Chlamydia pneumoniae was isolated from 26% of the children while Mycoplasma pneumoniae was isolated from 1 4%, whereas Legionella pneumophilla was not isolated at all.Conclusion:Atypical pathogens are evident as a po-tential aetiology for community-acquired pneumonia in (1 3.3%)of young and (80%)of older Egyptian chil-dren.

  4. Sonographic findings of typical and atypical scrotal trauma.

    Science.gov (United States)

    Sommers, Daniel N; Jensen, Jeff

    2015-06-01

    This review article illustrates sonographic findings in the setting of accidental and nonaccidental scrotal trauma. Although sonographic findings may be irrespective of the type of trauma, the goals of sonographic evaluation are similar in both atypical and typical mechanisms of scrotal injury. Familiarity with findings such as disruption of testicular integrity or vascularity facilitates prompt diagnosis and plays a critical role in clinical management.

  5. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

    NARCIS (Netherlands)

    Legendre, C.M.; Licht, C.; Muus, P.; Greenbaum, L.A.; Babu, S.; Bedrosian, C.; Bingham, C.; Cohen, D.J.; Delmas, Y.; Douglas, K.; Eitner, F.; Feldkamp, T.; Fouque, D.; Furman, R.R.; Gaber, O.; Herthelius, M.; Hourmant, M.; Karpman, D.; Lebranchu, Y.; Mariat, C.; Menne, J.; Moulin, B.; Nurnberger, J.; Ogawa, M.; Remuzzi, G.; Richard, T.; Sberro-Soussan, R.; Severino, B.; Sheerin, N.S.; Trivelli, A.; Zimmerhackl, L.B.; Goodship, T.; Loirat, C.

    2013-01-01

    BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We

  6. Transposition with atypical coronary pattern: the Aubert technique.

    Science.gov (United States)

    Pita-Fernández, Ana; González-López, María T; Gil-Jaurena, Juan M

    2017-03-06

    The arterial switch operation is currently the gold standard technique for repair of transposition of the great arteries. Some atypical coronary patterns such as intramural, interarterial, and a unique posterior button are associated with more complexity and surgical risk. We report a successful Aubert operation for transposition of the great arteries associated with a single and interarterial coronary artery arising from a posterior sinus.

  7. Late atypical atrial flutter after ablation of atrial fibrillation.

    Science.gov (United States)

    Ferreira, Raquel; Primo, João; Adão, Luís; Gonzaga, Anabela; Gonçalves, Helena; Santos, Rui; Fonseca, Paulo; Santos, José; Gama, Vasco

    2016-10-01

    Cardiac surgery for structural heart disease (often involving the left atrium) and radiofrequency catheter ablation of atrial fibrillation have led to an increased incidence of regular atrial tachycardias, often presenting as atypical flutters. This type of flutter is particularly common after pulmonary vein isolation, especially after extensive atrial ablation including linear lesions and/or defragmentation. The authors describe the case of a 51-year-old man, with no relevant medical history, referred for a cardiology consultation in 2009 for paroxysmal atrial fibrillation. After failure of antiarrhythmic therapy, he underwent catheter ablation, with criteria of acute success. Three years later he again suffered palpitations and atypical atrial flutter was documented. The electrophysiology study confirmed the diagnosis of atypical left flutter and reappearance of electrical activity in the right inferior pulmonary vein. This vein was again ablated successfully and there has been no arrhythmia recurrence to date. In an era of frequent catheter ablation it is essential to understand the mechanism of this arrhythmia and to recognize such atypical flutters.

  8. Exploring Atypical Verb+Noun Combinations in Learner Technical Writing

    Science.gov (United States)

    Luzon Marco, Maria Jose

    2011-01-01

    Professional and academic discourse is characterised by a specific phraseology, which usually poses problems for students. This paper investigates atypical verb+noun collocations in a corpus of English technical writing of Spanish students. I focus on the type of verbs that most frequently occurred in these awkward or questionable combinations and…

  9. Giant atypical ossifying fibromyxoid tumour of the calf

    Energy Technology Data Exchange (ETDEWEB)

    Harish, Srinivasan [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Cambridge (United Kingdom); Addenbrookes Hospital, Department of Radiology, Hills Road, Box 219, Cambridge (United Kingdom); Polson, Alexander; Griffiths, Meryl [Cambridge University Hospitals NHS Foundation Trust, Department of Histopathology, Cambridge (United Kingdom); Morris, Paul; Malata, Charles [Cambridge University Hospitals NHS Foundation Trust, Department of Plastic Surgery, Cambridge (United Kingdom); Bearcroft, Philip W.P. [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Cambridge (United Kingdom)

    2006-04-15

    We present a case of giant atypical ossifying fibromyxoid tumour (OFMT) of soft tissue, occurring in the calf, in a 77-year-old woman. The patient presented with a history of bleeding ulcer over a calf lump that had been present for over 4 years. Clinical presentation, radiological features and histopathologic findings are described, and the relevant literature is reviewed. (orig.)

  10. Stereological estimation of nuclear volume in benign and atypical meningiomas

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1993-01-01

    A stereological estimation of nuclear volume in benign and atypical meningiomas was made. The aim was to investigate whether this method could discriminate between these two meningeal neoplasms. The difference was significant and it was moreover seen that there was no overlap between the two grou...

  11. Atypical Presentation of Fibrolipomatous Hamartoma of Superficial Peroneal Nerve.

    Science.gov (United States)

    Dhinsa, Baljinder Singh; Lidder, Surjit; Abbasian, Ali

    2016-01-01

    Fibrolipomatous hamartoma is a rare presentation in the foot. An accurate diagnosis is key, with magnetic resonance imaging findings considered definitive. The management is dependent on the symptoms. We present an atypical presentation of fibrolipomatous hamartoma of the superficial peroneal nerve and discuss the current published data.

  12. The Cost-Effectiveness of Atypicals in the UK

    NARCIS (Netherlands)

    Heeg, Bart; Buskens, Erik; Botteman, Marc; Caleo, Sue; Ingham, Mike; Damen, Joep; de Charro, Frank; van Hout, Ben

    2008-01-01

    Background: In 2002, the National Institute for Health and Clinical Excellence (NICE), recommended atypical antipsychotics over conventional ones for first-line schizophrenia treatment, based on their lower risk of extrapyramidal symptoms. Objective: To estimate the incremental cost-effectiveness of

  13. Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction.

    Directory of Open Access Journals (Sweden)

    James F Graham

    Full Text Available Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C, to the disease-associated form, PrP(Sc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C and PrP(Sc isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C or to provide a scaffold ensuring correct alignment of PrP(C and PrP(Sc during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The α-chain of Na(+/K(+-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+/K(+-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C and Na(+/K(+-ATPase have previously been reported in astrocytes, our data highlight this molecule as

  14. Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC.

    Directory of Open Access Journals (Sweden)

    Sarah Vascellari

    Full Text Available Different transmissible spongiform encephalopathy (TSE-associated forms of prion protein (e.g. PrP(Sc can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrP(Sc propagation involves conversion from its normal isoform, PrP(C, by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrP(Sen as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI anchoring and the abundance of amyloid plaques and protease-resistant PrP(Sc (PrP(Res. Scrapie brain dilutions up to 10(-8 and 10(-13 were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrP(Res levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrP(C. Although the brains of 263K-affected mice had little immunoblot-detectable PrP(Res, RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrP(Res strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrP(Res levels. We also found that eQuIC, which incorporates a PrP(Sc immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML

  15. Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia.

    Science.gov (United States)

    Laas, Enora; Ballester, Marcos; Cortez, Annie; Gonin, Julie; Canlorbe, Geoffroy; Daraï, Emile; Graesslin, Olivier

    2015-04-01

    The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.

  16. Understanding A-type supergiants. I. Ultraviolet and visible spectral atlas of A-type supergiants

    CERN Document Server

    Verdugo, E; Gómez de Castro, A I

    1999-01-01

    This paper is the first of a series whose aim is to perform a systematic study of A-type supergiant atmospheres and winds. Here we present a spectral atlas of 41 A-supergiants observed by us in high and medium resolution in the visible and ultraviolet. The atlas consists of profiles of the H alpha , H beta , H gamma , H delta , H epsilon , Ca II (H and K), Na I (D1 and D2), Mg II/sub 4481/, Mg II uv1 and Fe II uv1, uv2, uv3, uv62, uv63, uv161 lines for 41 stars with spectral types ranging from B9 to A9 and luminosity classes Ia, Iab and Ib, and provides the basic data for a thoughtful study of these stars. The overall characteristics of the sample as well as the data reduction procedures are described. We also present some examples of spectral variability. Figures 1-3 are only available in electronic form at http://www.edpsciences.com. (27 refs).

  17. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

    Science.gov (United States)

    Wang, Kui-Rong; Jia, Yuan-Jing; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang; Feng, Zhi-Ying; Yao, Hong-Tian; Fan, Jun

    2016-01-01

    Abstract The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No

  18. Remarkable reductions of PAKs in the brain tissues of scrapie-infected rodent possibly linked closely with neuron loss.

    Science.gov (United States)

    Meng, Ge; Tian, Chan; Wang, Hui; Xu, Yin; Zhang, Bao-Yun; Shi, Qi; Gao, Chen; Chen, Cao; Fan, Xue-Yu; Wang, Jing; Xiao, Kang; Ren, Ke; Xue, Ming-Ming; Dong, Xiao-Ping

    2014-10-01

    Prion diseases are irreversible progressive neurodegenerative diseases characterized in the brain by PrP(Sc) deposits, neuronal degeneration, gliosis and by cognitive, behavioral and physical impairments, leading to severe incapacity and inevitable death. Proteins of the p21-activated kinase (PAK) family are noted for roles in gene transcription, cytoskeletal dynamics, cell cycle progression and survival signaling. In the present study, we aimed to identify the potential roles of PAKs during prion infection, utilizing the brains of scrapie agent-infected hamsters. Western blots and immunohistochemical assays showed that brain levels of PAK3 and PAK1, as well as their upstream activator Rac/cdc42 and downstream substrate Raf1, were remarkably reduced at terminal stage. Double-stained immunofluorescent assay demonstrated that PAK3 was expressed mainly in neurons. Dynamic analyses of the brain samples collected at the different time points during the incubation period illustrated successive decreases of PAK3, PAK1 and Raf1, especially phosphor Raf1, which correlated well with neuron loss. Rac/cdc42 in the brain tissues increased at early stage and reached to the top at mid-late stage, but diminished at final stage. Unlike the alteration of PAKs in vivo, PAK3 and PAK1, as well as Rac/cdc42 and Raf1 in the prion-infected cell line SMB-S15 remained unchanged compared with those of its normal cell line SMB-PS. Our data here indicate that the functions of PAKs and their associated signaling pathways are seriously affected in the brains of prion disease, which appear to associate closely with the extensive neuron loss.

  19. Infectious titres of sheep scrapie and bovine spongiform encephalopathy agents cannot be accurately predicted from quantitative laboratory test results.

    Science.gov (United States)

    González, Lorenzo; Thorne, Leigh; Jeffrey, Martin; Martin, Stuart; Spiropoulos, John; Beck, Katy E; Lockey, Richard W; Vickery, Christopher M; Holder, Thomas; Terry, Linda

    2012-11-01

    It is widely accepted that abnormal forms of the prion protein (PrP) are the best surrogate marker for the infectious agent of prion diseases and, in practice, the detection of such disease-associated (PrP(d)) and/or protease-resistant (PrP(res)) forms of PrP is the cornerstone of diagnosis and surveillance of the transmissible spongiform encephalopathies (TSEs). Nevertheless, some studies question the consistent association between infectivity and abnormal PrP detection. To address this discrepancy, 11 brain samples of sheep affected with natural scrapie or experimental bovine spongiform encephalopathy were selected on the basis of the magnitude and predominant types of PrP(d) accumulation, as shown by immunohistochemical (IHC) examination; contra-lateral hemi-brain samples were inoculated at three different dilutions into transgenic mice overexpressing ovine PrP and were also subjected to quantitative analysis by three biochemical tests (BCTs). Six samples gave 'low' infectious titres (10⁶·⁵ to 10⁶·⁷ LD₅₀ g⁻¹) and five gave 'high titres' (10⁸·¹ to ≥ 10⁸·⁷ LD₅₀ g⁻¹) and, with the exception of the Western blot analysis, those two groups tended to correspond with samples with lower PrP(d)/PrP(res) results by IHC/BCTs. However, no statistical association could be confirmed due to high individual sample variability. It is concluded that although detection of abnormal forms of PrP by laboratory methods remains useful to confirm TSE infection, infectivity titres cannot be predicted from quantitative test results, at least for the TSE sources and host PRNP genotypes used in this study. Furthermore, the near inverse correlation between infectious titres and Western blot results (high protease pre-treatment) argues for a dissociation between infectivity and PrP(res).

  20. Phenotypic and genotypic characterization of oral yeasts from Finland and the United States.

    Science.gov (United States)

    Hannula, J; Saarela, M; Alaluusua, S; Slots, J; Asikainen, S

    1997-12-01

    A total of 4-22 isolates of oral yeasts per subjects from 48 yeast-positive Finnish and American subjects (25 females and 23 males) were phenotyped and genotyped to determine the frequency of simultaneous oral carriage of multiple yeast taxa. An oral sample from either periodontal pockets, oral mucosa or saliva was obtained. All subjects yielded Candida albicans and 3 subjects an additional yeast species (Candida krusei, Candida glabrata or Saccharomyces cerevisiae). The API 20C Aux kit distinguished 9 different carbohydrate assimilation profiles among the C. albicans isolates. Thirty-eight of 46 C. albicans biotype I isolates were categorized in a single numerical profile. PCR analysis, using a random primer OPA-03 and a repetitive primer (GACA)4, detected 2 major genotypic groups among the C. albicans isolates; 44 subjects showing isolates with a "typical" PCR-profile and 4 subjects isolates with an "atypical" PCR-profile. The "atypical" PCR-profile was similar to that of Candida dubliniensis. All C. albicans isolates assimilated xylose, except 5, including the 4 with an "atypical" PCR-profile. No difference was found in distribution of oral yeast species, and of C. albicans phenotypes and genotypes between Finnish and American subjects. The present PCR method may offer a rapid and easy means of distinguishing oral Candida species.