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Sample records for atypical scrapie phenotype

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein

    OpenAIRE

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

    2013-01-01

    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...

  7. Epidemiological investigations on the potential transmissibility of a rare disease: the case of atypical scrapie in Great Britain.

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    Ortiz-Peláez, A; Arnold, M E; Vidal-Diez, A

    2016-07-01

    Multiple cases of atypical scrapie in the same holding and co-existence with classical scrapie have been reported in Great Britain. A two-stage simulation tool was developed by combining a sampling algorithm and a hierarchical Bayesian model to simulate the number of positive cases of atypical scrapie from: (i) random sampling and (ii) using the actual sampled population in Great Britain, being the output probability of detection of flocks with one and more cases. Cluster analysis was conducted to assess the level of geographical over- and under-sampling over the years. The probability of detecting at least two cases of atypical scrapie in the same holding is much lower in simulated random data than in simulated actual data for all scenarios. Sampling bias in the selection of sheep for testing led to multiple sampling from fewer but larger holdings, Scotland, and areas of Wales were under-sampled and the South-West and East of England oversampled. The pattern of atypical scrapie cases observed is unlikely to be explained by a multi-case event epidemiologically linked. The co-existence of classical and atypical scrapie is a rare event with 19 holdings detected in GB and does not suggest an epidemiological link between the two types of disease. PMID:26976340

  8. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    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...

  9. 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

  10. The prevalence of atypical scrapie in sheep from positive flocks is not higher than in the general sheep population in 11 European countries

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    Liam Barry

    2010-02-01

    Full Text Available Abstract Background During the last decade, active surveillance for transmissible spongiform encephalopathies in small ruminants has been intensive in Europe. In many countries this has led to the detection of cases of atypical scrapie which, unlike classical scrapie, might not be contagious. EU legislation requires, that following detection of a scrapie case, control measures including further testing take place in affected flocks, including the culling of genotype susceptible to classical scrapie. This might result in the detection of additional cases. The aim of this study was to investigate the occurrence of additional cases in flocks affected by atypical scrapie using surveillance data collected in Europe in order to ascertain whether atypical scrapie, is contagious. Results Questionnaires were used to collect, at national level, the results of active surveillance and testing associated with flock outbreaks in 12 European countries. The mean prevalence of atypical scrapie was 5.5 (5.0-6.0 cases per ten thousand in abattoir surveillance and 8.1 (7.3-9.0 cases per ten thousand in fallen stock. By using meta-analysis, on 11 out of the 12 countries, we found that the probability of detecting additional cases of atypical scrapie in positive flocks was similar to the probability observed in animals slaughtered for human consumption (odds ratio, OR = 1.07, CI95%: 0.70-1.63 or among fallen stock (OR = 0.78, CI95%: 0.51-1.2. In contrast, when comparing the two scrapie types, the probability of detecting additional cases in classical scrapie positive flocks was significantly higher than the probability of detecting additional cases in atypical scrapie positive flocks (OR = 32.4, CI95%: 20.7-50.7. Conclusions These results suggest that atypical scrapie is not contagious or has a very low transmissibility under natural conditions compared with classical scrapie. Furthermore this study stressed the importance of standardised data collection to make good

  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.

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    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. PMID:22495232

  12. 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.

  13. Genotyping and surveillance for scrapie in Finnish sheep

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    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.

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

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    Verhoeven WMA

    2012-04-01

    Full Text Available Willem MA Verhoeven1,2, Jos IM Egger1,3,4, Marjolein H Willemsen5, Gert JM de Leijer6, Tjitske Kleefstra51Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, 2Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, 3Donders Centre for Cognition, Radboud University Nijmegen, Nijmegen, 4Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, 5Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, 6Dichterbij, Institutes for Intellectual Disabilities, Gennep, The NetherlandsAbstract: 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

  15. Atypical Down syndrome phenotype in a girl with 21;21 translocation trisomy.

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    Tuysuz, B; Yavuz, A; Ozdil, M; Caferler, J; Ozon, H

    2010-01-01

    We describe a girl with microcephaly, short stature, coarse face, severe growth and developmental delay, seizures, hypertonia, bilateral flexion contractures of the knees, and a de novo 21;21 translocation trisomy 21 in peripheral blood lymphocytes. Fluorescence in situ hybridization (FISH) analysis confirmed the trisomy 21 translocation using whole chromosome painting probe 21 (WCP21). Chromosome analysis which was also performed on skin fibroblasts and revealed mosaicism for a translocation trisomy 21 cell line (22.3%) as well as a second cell line consisting of one normal chromosome 21 and a small ring chromosome 21 derived from the translocation 21q21q (61%) and a third line consisting of monosomy 21 (16.7%). FISH analyses by LS121 probe for the critical (21q22.2-22.3) region of Down syndrome (DS) on interphase blood cells resulted with 30% two signals and 70% three signals, skin fibroblasts showed 84% single signal, 9% two signals and 7% three signals. The size of ring chromosome 21 in skin fibroblasts was very small and probably there was a large, more proximally located deletion including chromosome 21q22 band. We consider that the atypical DS phenotype of the patient originated from the small ring chromosome 21 and the monosomy 21 in the skin fibroblasts and other tissues not available for analysis. Therefore, the clinical findings of the patient were most similar to monosomy 21 mosaicism syndrome. PMID:20420031

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

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    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.

  17. Minder BSE en scrapie

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    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.

  18. Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria.

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    Hale, Caitlin L; Niederriter, Adrienne N; Green, Glenn E; Martin, Donna M

    2016-02-01

    CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary anomalies, and Ear malformations, including deafness and vestibular disorders) is a genetic condition characterized by a specific and recognizable pattern of features. Heterozygous pathogenic variants in the chromodomain helicase DNA-binding protein 7 (CHD7) are the major cause of CHARGE syndrome, and have been identified in 70-90% of individuals fulfilling clinical diagnostic criteria. Since 2004, when CHD7 was discovered as the causative gene for CHARGE syndrome, the phenotypic spectrum associated with pathogenic CHD7 variants has expanded. Predicted pathogenic CHD7 variants have been identified in individuals with isolated features of CHARGE including autism and hypogonadotropic hypogonadism. Here, we present genotype and phenotype data from a cohort of 28 patients who were considered for a diagnosis of CHARGE syndrome, including one patient with atypical presentations and a pathogenic CHD7 variant. We also summarize published literature on pathogenic CHD7 variant positive individuals who have atypical clinical presentations. Lastly, we propose a revision to current clinical diagnostic criteria, including broadening of the major features associated with CHARGE syndrome and addition of pathogenic CHD7 variant status as a major criterion. PMID:26590800

  19. 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.

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

    NARCIS (Netherlands)

    W.M.A. Verhoeven (Wim); J.I.M. Egger (Jos); M.H. Willemsen; G.J.M. de Leijer (Gert); T. Kleefstra (Tjitske)

    2012-01-01

    textabstractThe 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 disturban

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

    NARCIS (Netherlands)

    Verhoeven, W.M.; Egger, J.I.; Willemsen, M.H.; Leijer, G.J. de; Kleefstra, T.

    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, communi

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

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    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.

  3. Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

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    Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

    2016-01-01

    The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases. PMID:27187038

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

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    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.

  5. 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. PMID:25783686

  6. 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

  7. Role of Plasminogen in Propagation of Scrapie

    OpenAIRE

    Salmona, Mario; Capobianco, Raffaella; Colombo, Laura; De Luigi, Ada; Rossi, Giacomina; Mangieri, Michela; Giaccone, Giorgio; Quaglio, Elena; Chiesa, Roberto; Donati, Maria Benedetta; Tagliavini, Fabrizio; Forloni, Gianluigi

    2005-01-01

    To investigate whether plasminogen may feature in scrapie infection, we inoculated plasminogen-deficient (Plg−/−), heterozygous plasminogen-deficient (Plg+/−), and wild-type (Plg+/+) mice by the intracerebral or intraperitoneal (i.p.) route with the RML scrapie strain and monitored the onset of neurological signs of disease, survival time, brain, and accumulation of scrapie disease-associated forms of the prion protein (PrPSc). Only after i.p. inoculation, a slight, although significant, diff...

  8. 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

  9. 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.

  10. Role of plasminogen in propagation of scrapie.

    Science.gov (United States)

    Salmona, Mario; Capobianco, Raffaella; Colombo, Laura; De Luigi, Ada; Rossi, Giacomina; Mangieri, Michela; Giaccone, Giorgio; Quaglio, Elena; Chiesa, Roberto; Donati, Maria Benedetta; Tagliavini, Fabrizio; Forloni, Gianluigi

    2005-09-01

    To investigate whether plasminogen may feature in scrapie infection, we inoculated plasminogen-deficient (Plg(-/-)), heterozygous plasminogen-deficient (Plg(+/-)), and wild-type (Plg(+/+)) mice by the intracerebral or intraperitoneal (i.p.) route with the RML scrapie strain and monitored the onset of neurological signs of disease, survival time, brain, and accumulation of scrapie disease-associated forms of the prion protein (PrP(Sc)). Only after i.p. inoculation, a slight, although significant, difference in survival (P follicular dendritic or lymphoid cells in Plg(-/-) mice. Once the disease progressed and mice began to die of infection, differences were no longer apparent in either brains or spleens. In conclusion, our data indicate that plasminogen has no major effect on the survival of scrapie agent-infected mice. PMID:16103174

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

    Science.gov (United States)

    Cocanougher, Benjamin; Aypar, Umut; McDonald, Amber; Hasadsri, Linda; Bennett, Michael J; Edward Highsmith, W; D׳Aco, Kristin

    2015-06-01

    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. PMID:26217714

  12. 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.

  13. 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

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

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    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.

  15. Atypical Depression

    Directory of Open Access Journals (Sweden)

    Erhan Ertekin

    2013-09-01

    Full Text Available Atypical depression is defined as a specifier of major depressive disorder. Columbia criteria for atypical depression are commonly used to make a diagnosis. Female sex, onset at early age, chronic course, and higher rate of comorbidity (especially anxiety disorder and bipolar disorder is noteworthy in atypical depression. Although, the atypical depression seems to support the familial genetic transition, there is not any specific study supporting these data. In the treatment of atypical depression, monoamine oxidase inhibitors are reported to be more effective than tricyclic antidepressants. In recent studies, selective serotonin reuptake inhibitors have also proven to be efficient.

  16. Selective breeding for scrapie resistance in sheep

    OpenAIRE

    Cristina Santos Sotomaior; Fernanda Trentini Lopes Ribeiro; Rüdiger Daniel Ollhoff

    2012-01-01

    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 incre...

  17. 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. PMID:25821095

  18. 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.

  19. 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

  20. Architecture of secondary lymphoid tissue in sheep experimentally challenged with scrapie.

    Science.gov (United States)

    Davies, Marie L; Hopkins, Lee J; Halliday, Sue; Houston, Fiona; Hunter, Nora; McConnell, Ian

    2004-02-01

    Scrapie is a transmissible spongiform encephalopathy in which there is an accumulation of the abnormal form of the prion protein, PrPsc, in the lymphoreticular system and nervous system. There is a particular accumulation of PrPsc on follicular dendritic cells within the germinal centre of B-cell follicles. Because accumulation of PrPsc in the nervous system leads to neuronal cell loss we have examined PrPsc accumulation in the prescapular and mesenteric lymph nodes in relation to lymph node architecture of scrapie-challenged sheep. We demonstrate that an accumulation of PrPsc in the lymph node fails to result in gross defects in the microanatomy and phenotype of T- and B-cell areas in the lymph nodes. PMID:15027909

  1. 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.

  2. 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.

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

    OpenAIRE

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

    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-effecti...

  4. Impaired spleen structure and chemokine expression in ME7 scrapie-infected mice.

    Science.gov (United States)

    Kim, Soochan; Han, Sinsuk; Lee, Hyung Soo; Kim, Yong-Sun; Choi, Eun-Kyoung; Kim, Mi-Yeon

    2016-08-01

    We have previously demonstrated that prion protein-deficient (Prnp(0/0)) Zürich I mice display impaired T zone structure resulting from decreased splenic expression of the T cell homing chemokines, CCL19 and CCL21. Prions are transported to, and colonise in, the secondary lymphoid tissues. Therefore, in order to investigate how scrapie infection affects the splenic white pulp structure, we infected C57BL/6 mice with the mouse-adapted scrapie strain ME7 and analysed end-stage prion disease. We found that the white pulp regions of ME7-infected spleens were smaller, and contained markedly diminished T zones, as compared to control spleens. Although lymphoid tissue inducer cells were not affected, the expression of both CCL19 and CCL21 was decreased. In addition, the networks of follicular dendritic cells, which are known to express high levels of the cellular prion protein (PrP(C)) and to accumulate PrP(Sc) following scrapie infection, were larger in ME7-infected spleens. Further, they were associated with increased numbers of B cells expressing high levels of IgM. These data indicate that ME7-infected spleens display phenotype characteristics different from those reported for Prnp(0/0) spleens mainly due to the gain of PrP(Sc) function and suggest that the PrP(C) is required, not only to form the splenic white pulp structure, but also to maintain the intact T zone structure. PMID:27021907

  5. 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...

  6. 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

  7. 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.

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

    OpenAIRE

    Benjamin Cocanougher; Umut Aypar; Amber McDonald; Linda Hasadsri; Bennett, Michael J; Edward Highsmith, W.; Kristin D׳Aco

    2015-01-01

    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 so...

  9. 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.

  10. 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...

  11. 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...

  12. 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

  13. Scrapie-specific pathology of sheep lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    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.

  14. Scrapie-specific pathology of sheep lymphoid tissues.

    Science.gov (United States)

    McGovern, Gillian; Jeffrey, Martin

    2007-01-01

    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. PMID:18074028

  15. 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.

  16. Resistance of Neonatal Mice to Scrapie Is Associated with Inefficient Infection of the Immature Spleen

    OpenAIRE

    Ierna, Michelle; Farquhar, Christine F.; Outram, George W.; Bruce, Moira E.

    2006-01-01

    Previous studies demonstrated that neonatal mice up to about a week old are less susceptible than adult mice to infection by intraperitoneal inoculation with mouse-passaged scrapie. In peripherally inoculated adult mice, scrapie replicates in lymphoid tissues such as the spleen before invading the central nervous system. Here, we investigated scrapie susceptibility in neonatal mice in more detail, concentrating on spleen involvement. First, we demonstrated that neonatal mice are about 10 time...

  17. Scrapie-Specific Pathology of Sheep Lymphoid Tissues

    OpenAIRE

    Gillian McGovern; Martin Jeffrey

    2007-01-01

    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 regress...

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

    OpenAIRE

    Engel Bas; Davidse Aart; Bossers Alex; Melchior Marielle B; Hagenaars Thomas J; van Zijderveld Fred G

    2010-01-01

    Abstract 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 active scrapie surveillance as well as certain control measures in affected flocks. Here we analyze the data on genotype frequencies and scrapie prevalence in the Dutch sheep population obt...

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

    Science.gov (United States)

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

    2016-03-01

    To assess scrapie infectivity associated with caprine-origin tissues, bioassay can be performed using kids, lambs or transgenic mice expressing caprine or ovine prion (PRNP) alleles, but the incubation periods are fairly long. Although several classical ovine scrapie prion permissive cell lines with the ability to detect brain-derived scrapie prion have been available, no classical caprine scrapie permissive cell line is currently available. Therefore, the aims of this study were to generate a rabbit kidney epithelial cell line (RK13) stably expressing caprine wild-type PRNP (cpRK13) and then to assess permissiveness of cpRK13 cells to classical caprine scrapie prion propagation. The cpRK13 and plasmid control RK13 (pcRK13) cells were incubated with brain-derived classical caprine scrapie inocula prepared from goats or ovinized transgenic mice (Tg338, express ovine VRQ allele) infected with caprine scrapie. Significant PrP(Sc) accumulation, which is indicative of scrapie prion propagation, was detected by TSE ELISA and immunohistochemistry in cpRK13 cells inoculated with classical caprine scrapie inocula. Western blot analysis revealed the typical proteinase K-resistant 3 PrP(res) isoforms in the caprine scrapie prion inoculated cpRK13 cell lysate. Importantly, PrP(Sc) accumulation was not detected in similarly inoculated pcRK13 cells, whether by TSE ELISA, immunohistochemistry, or western blot. These findings suggest that caprine scrapie prions can be propagated in cpRK13 cells, thus this cell line may be a useful tool for the assessment of classical caprine prions in the brain tissues of goats. PMID:27216989

  20. 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.

  1. Cholesterol Metabolism in Brain and Skin Fibroblasts from Sarda Breed Sheep With Scrapie-resistant and Scrapie-susceptible Genotypes

    Directory of Open Access Journals (Sweden)

    Alessandra Pani

    2007-01-01

    Full Text Available Scrapie is a fatal spongiform encephalopathy of sheep, a transmissible form of prion disease caused by neuronal accumulation of the aberrantly conformed prion protein (PrPsc. Currently, no ante-mortem diagnostic tests are available to detect this untreatable disease in the pre-clinical stage, thus making difficult to control its spread. Recent evidence suggests that the production of PrPsc can be modulated by the levels of membrane cholesterol in neuronal cells. Since cholesterol levels in cell membranes are dependent on cholesterol homeostasis in the whole organism, we studied cholesterol metabolism in brain tissues, plasma and skin fibroblasts of Sarda breed sheep with scrapie-resistant (ARR/ARR and scrapie-susceptible (ARQ/ARQ prion protein genotypes, both not infected (ARQ/ARQ- and infected (ARQ/ARQ+ with scrapie. We found that, the levels of cytoplasmic cholesterol esters (CE in brains and skin fibroblasts from sheep with the ARQ/ARQ genotype were consistently higher than those from sheep with the ARR/ARR genotype. Conversely, the levels of free cholesterol (FC were lower in ARQ/ARQ, as compared to ARR/ARR sheep, thus resulting in a sharp reduction of the FC/CE ratio. Moreover, both uninfected and infected ARQ/ARQ sheep showed abnormally low levels of high density lipoprotein-cholesterol (HDL-C in their plasma, as compared to ARR/ARR sheep. These data other than adding new strength to the notion that altered levels of intracellular cholesterol may indicate the presence of a lipid metabolic state that predisposes to infection with, and accumulation of, PrPsc in the brain, discriminate for the first time between two distinct but related cellular pools of cholesterol, namely membrane FC on one hand and cytoplasmic CE on the other.

  2. Investigation of a simple model for within-flock transmission of scrapie

    NARCIS (Netherlands)

    Hagenaars, T.J.; Windig, J.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

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

    International Nuclear Information System (INIS)

    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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Age, scrapie status, PrP genotype and follicular dendritic cells in ovine ileal Peyer's patches.

    Science.gov (United States)

    Marruchella, Giuseppe; Ligios, Ciriaco; Di Guardo, Giovanni

    2012-10-01

    Follicular dendritic cells (FDCs) residing within ileal Peyer's patches (PPs) are of crucial relevance for sheep scrapie early pathogenesis and subsequent scrapie prion neuroinvasion. In this study, ileal PP follicles were significantly more numerous in lambs than in adult Sarda breed sheep, with significant differences being also found in lymphoid follicle area, perimeter and FDC density. Furthermore, PrPd deposition within ileal PPs and host's PrP genotype did not significantly influence these parameters. We conclude that age significantly affects FDC density in ileal PPs from Sarda breed ovines, independently from host's scrapie status and PrP genotype. PMID:21962485

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

    Directory of Open Access Journals (Sweden)

    Engel Bas

    2010-05-01

    Full Text Available Abstract 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 active scrapie surveillance as well as certain control measures in affected flocks. Here we analyze the data on genotype frequencies and scrapie prevalence in the Dutch sheep population obtained from both surveillance and affected flocks, to identify temporal trends. We also estimate the genotype-specific relative risks to become a detected scrapie case. Results We find that the breeding programme has produced a steady increase in the level of genetic scrapie resistance in the Dutch sheep population. We also find that a significant decline in the prevalence of scrapie in tested animals has occurred a number of years after the start of the breeding programme. Most importantly, the estimated scrapie prevalence level per head of susceptible genotype is also declining significantly, indicating that selective breeding causes a population effect. Conclusions The Dutch scrapie control programme has produced a steady rise in genetic resistance levels in recent years. A recent decline in the scrapie prevalence per tested sheep of susceptible prion protein genotype indicates that selective breeding causes the desired population effect.

  10. Changed iron regulation in scrapie-infected neuroblastoma cells.

    Science.gov (United States)

    Fernaeus, Sandra; Hälldin, Jonas; Bedecs, Katarina; Land, Tiit

    2005-02-18

    Prion diseases are characterized by the conversion of the normal cellular prion protein PrP(C) into a pathogenic isoform, PrP(Sc). The mechanisms involved in neuronal cell death in prion diseases are largely unknown, but accumulating evidence has demonstrated oxidative impairment along with metal imbalances in scrapie-infected brains. In this study, we report changes in cellular iron metabolism in scrapie-infected mouse neuroblastoma N2a cells (ScN2a). We detected twofold lower total cellular iron and calcein-chelatable cytosolic labile iron pool (LIP) in ScN2a cells as compared to the N2a cells. We also measured in ScN2a cells significantly lower activities of iron regulatory proteins 1 and 2 (IRP1 and IRP2, respectively), regulators of cellular iron by sensing cytosolic free iron levels and controlling posttranscriptionally the expression of the major iron transport protein transferrin receptor 1 (TfR1) and the iron sequestration protein ferritin. IRP1 and IRP2 protein levels were decreased by 40% and 50%, respectively, in ScN2a cells. TfR1 protein levels were fourfold reduced and ferritin levels were threefold reduced in ScN2a cells. TfR1 and ferritin mRNA levels were significantly reduced in ScN2a cells. ScN2a cells responded normally to iron and iron chelator treatment with respect to the activities of IRP1 and IRP2, and biosynthesis of TfR1 and ferritin. However, the activities of IRP1 and IRP2, and protein levels of TfR1 and ferritin, were still significantly lower in iron-depleted ScN2a cells as compared to the N2a cells, suggesting lower need for iron in ScN2a cells. Our results demonstrate that scrapie infection leads to changes in cellular iron metabolism, affecting both total cellular and cytosolic free iron, and the activities and expression of major regulators of cellular iron homeostasis. PMID:15710243

  11. Resistance of neonatal mice to scrapie is associated with inefficient infection of the immature spleen.

    Science.gov (United States)

    Ierna, Michelle; Farquhar, Christine F; Outram, George W; Bruce, Moira E

    2006-01-01

    Previous studies demonstrated that neonatal mice up to about a week old are less susceptible than adult mice to infection by intraperitoneal inoculation with mouse-passaged scrapie. In peripherally inoculated adult mice, scrapie replicates in lymphoid tissues such as the spleen before invading the central nervous system. Here, we investigated scrapie susceptibility in neonatal mice in more detail, concentrating on spleen involvement. First, we demonstrated that neonatal mice are about 10 times less susceptible than adults to intraperitoneal scrapie inoculation. Then we injected mice intraperitoneally with a scrapie dose that produced disease in all mice inoculated at 10 days or older but in only about a third of neonatally inoculated mice. In this experiment, spleens collected 70 days after scrapie injection of mice 10 days old or older almost all contained pathological prion protein, PrPSc, and those that were bioassayed all contained high infectivity levels. In contrast, at this early stage, only two of six spleens from neonatally inoculated mice had detectable, low infectivity levels; no PrPSc was detected, even in the two spleens. Therefore, neonatal mice have an impaired ability to replicate scrapie in their spleens, suggesting that replication sites are absent or sparse at birth but mature within 10 days. The increase in susceptibility with age correlated with the first immunocytochemical detection of the normal cellular form of prion protein, PrPc, on maturing follicular dendritic cell networks. As lymphoid tissues are more mature at birth in sheep, cattle, and humans than in mice, our results suggest that in utero infection with scrapie-like agents is theoretically possible in these species. PMID:16352571

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

    OpenAIRE

    Emmanuel E Comoy; 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

    2015-01-01

    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 ...

  13. Immunohistochemical detection and distribution of prion protein in a goat with natural scrapie.

    Science.gov (United States)

    Valdez, Reginald A; Rock, Matthew J; Anderson, Anne K; O'Rourke, Katherine I

    2003-03-01

    Formalin-fixed, paraffin-embedded tissue sections from a 3-year-old female Angora goat suffering from clinical scrapie were immunostained after hydrated autoclaving using a monoclonal antibody (mAb, F99/97.6.1; IgG1) specific for a conserved epitope on the prion protein. Widespread and prominent deposition of the scrapie isoform of the prion protein (PrPSc) was observed in the brain, brainstem, spinal cord, retina, postganglionic neurons associated with parasympathetic ganglia of myenteric and submucosal plexuses, Peyer's patches, peripheral lymph nodes, and pharyngeal and palatine tonsils. The goat was homozygous for PrP alleles encoding 5 octapeptide repeat sequences in the N-terminal region of the prion protein and isoleucine at codon 142, a genotype associated with high susceptibility and short incubation times in goats. The results of this study indicate that mAb F99/97.6.1 is useful for detection of PrPSc deposition, and this is a specific and reliable immunohistochemical adjunct to histopathology for diagnosis of natural caprine scrapie, although precise determination of the diagnostic sensitivity and specificity of the assay as a diagnostic test for scrapie in goats will require examination of a sufficiently large sample size. As with ovine scrapie, prion protein is widely distributed in the central and peripheral nervous systems, gastrointestinal tract, and lymphoid tissues in natural caprine scrapie. PMID:12661726

  14. 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.

  15. 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

  16. 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...

  17. Scrapie pathogenesis: the role of complement C1q in scrapie agent uptake by conventional dendritic cells.

    Science.gov (United States)

    Flores-Langarica, Adriana; Sebti, Yasmine; Mitchell, Daniel A; Sim, Robert B; MacPherson, Gordon G

    2009-02-01

    Mice lacking complement components show delayed development of prion disease following peripheral inoculation. The delay could relate to reduced scrapie prion protein (PrP(Sc)) accumulation on follicular dendritic cells (DCs). However conventional DCs (cDCs) play a crucial role in the early pathogenesis of prion diseases and complement deficiency could result in decreased PrP(Sc) uptake by cDCs in the periphery. To explore this possibility, we cultured murine splenic or gut-associated lymph node cDCs with scrapie-infected whole brain homogenate in the presence or absence of complement. Uptake decreased significantly if the serum in the cultures was heat-inactivated. Because heat inactivation primarily denatures C1q, we used serum from C1q(-/-) mice and showed that PrP(Sc) uptake was markedly decreased. PrP(Sc) internalization was saturable and temperature-dependent, suggesting receptor-mediated uptake. Furthermore, uptake characteristics differed from fluid-phase endocytosis. Immunofluorescence showed colocalization of C1q and PrP(Sc), suggesting interaction between these molecules. We evaluated the expression of several complement receptors on cDCs and confirmed that cDCs that take up PrP(Sc) express one of the C1q receptors, calreticulin. Our results show that C1q participates in PrP(Sc) uptake by cDCs, revealing a critical role for cDCs in initial prion capture, an event that takes place before the PrP(Sc) accumulation within the follicular DC network. PMID:19155476

  18. 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.

  19. Detection of PrPSc in Formalin Fixed Paraffin Embedded Tissue by Western Blot Differentiates Classical Scrapie, Nor98 Scrapie, and BSE

    Science.gov (United States)

    Transmissible spongiform encephalopathies including bovine spongiform encephalopathy and scrapie are fatal neurodegenerative disorders associated with the presence of an infectious abnormal isoform of normal mammalian proteins called prions (PrP**Sc). Identification of PrP**Sc in the CNS is typicall...

  20. Classical scrapie prions are associated with peripheral blood monocytes and T-lymphocytes from naturally infected sheep

    Science.gov (United States)

    Classical scrapie is a transmissible spongiform encephalopathy that affects sheep and goats. As detected by enzyme-linked immunoassay, previous studies suggested scrapie prions in the blood of sheep might be associated with B lymphocytes but not with monocytes or T lymphocytes. The association of sc...

  1. 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

  2. Dengue fever: atypical manifestation

    Directory of Open Access Journals (Sweden)

    Nataraj Gangasiddaiah

    2014-08-01

    Full Text Available Dengue fever is affecting millions of population globally. For the past one decade, we have seen several outbreaks and even causing significant mortality of affected population. We witnessed numerous pattern and multisystem presentation of dengue in this period. The CNS manifestation like encephalitis, polyneuropathy (GB like syndrome and paresthesias were uncommonly reported priorly. Pancreatitis, polyserositis, carditis of varying severity and hepatic failure are the, some of atypical manifestations observed in recent out breaks. So dengue illness can presents with multi system involvement and can account to significant mortality. Here an attempt was done to present varying, uncommon and atypical manifestation of dengue illness. [Int J Res Med Sci 2014; 2(4.000: 1804-1806

  3. 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.

  4. 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.

  5. 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

  6. [Atypical presentation of preeclampsia].

    Science.gov (United States)

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

    2015-09-01

    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.

  7. 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

  8. 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.

  9. Oral scrapie infection modifies the homeostasis of Peyer's patches' dendritic cells.

    Science.gov (United States)

    Dorban, Gauthier; Defaweux, Valérie; Levavasseur, Etienne; Demonceau, Caroline; Thellin, Olivier; Flandroy, Sylvain; Piret, Joëlle; Falisse, Nandini; Heinen, Ernst; Antoine, Nadine

    2007-09-01

    In transmitted prion diseases the immune system supports the replication and the propagation of the pathogenic agent (PrPSc). DCs, which are mobile cells present in large numbers within lymph organs, are suspected to carry prions through the lymphoid system and to transfer them towards the peripheral nervous system. In this study, C57Bl/6 mice were orally inoculated with PrPSc (scrapie strain 139A) and sacrificed at the preclinical stages of the disease. Immunolabelled cryosections of Peyer's patches were analysed by confocal microscopy. Membrane prion protein expression was studied by flow cytometry. In Peyer's patches (PP), dissected at day one and day 105 after oral exposure to scrapie, we observed an increased population of DCs localised in the follicular-associated epithelium. On day 105, PrPSc was found in the follicles inside the PP of prion-infected mice. A subset of Peyer's patches DCs, which did not express cellular prion protein on their surface in non-infected mice conditions, was prion-positive in scrapie conditions. Within Peyer's patches oral scrapie exposure thus induced modifications of the homeostasis of DCs at the preclinical stages of the disease. These results give new arguments in favour of the implication of DCs in prion diseases. PMID:17622551

  10. Murine scrapie infection causes an abnormal germinal centre reaction in the spleen.

    Science.gov (United States)

    McGovern, G; Brown, K L; Bruce, M E; Jeffrey, M

    2004-01-01

    Follicular dendritic cells (FDCs) of the lymphoreticular system play a role in the peripheral replication of prion proteins in some transmissible spongiform encephalopathies (TSEs), including experimental murine scrapie models. Disease-specific PrP (PrPd) accumulation occurs in association with the plasmalemma and extracellular space around FDC dendrites, but no specific immunological response has yet been reported in animals affected by TSEs. In the present study, morphology (light microscopical and ultrastructural) of secondary lymphoid follicles of the spleen were examined in mice infected with the ME7 strain of scrapie and in uninfected control mice, with or without immunological stimulation with sheep red blood cells (SRBCs), at 70 days post-inoculation or at the terminal stage of disease (268 days). Scrapie infection was associated with hypertrophy of FDC dendrites, increased retention of electron-dense material at the FDC plasma membrane, and increased maturation and numbers of B lymphocytes within secondary follicles. FDC hypertrophy was particularly conspicuous in immune-stimulated ME7-infected mice. The electron-dense material was associated with PrP Napoli accumulation, as determined by immunogold labelling. We hypothesize that immune system changes are associated with increased immune complex trapping by hypertrophic FDCs expressing PrP Napoli molecules at the plasmalemma of dendrites, and that this process is exaggerated by immune system stimulation. Contrary to previous dogma, these results show that a pathological response within the immune system follows scrapie infection. PMID:15003476

  11. Dynamics of a scrapie outbreak in a flock of Romanov sheep-estimation of transmission parameters

    NARCIS (Netherlands)

    Hagenaars, T.H.J.; Donelly, C.A.; Ferguson, N.M.; Anderson, R.M.

    2003-01-01

    Knowledge of epidemiological mechanisms and parameters underlying scrapie transmission in sheep flocks remains very limited at present. Here we introduce a method for fitting stochastic transmission models to outbreak data to estimate bounds on key transmission parameters. We apply this method to da

  12. 9 CFR 54.9 - Waiver of requirements for scrapie control pilot projects.

    Science.gov (United States)

    2010-01-01

    ... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Waiver of requirements for scrapie control pilot projects. 54.9 Section 54.9 Animals and Animal Products ANIMAL AND PLANT HEALTH...

  13. 9 CFR 79.7 - Waiver of requirements for scrapie control pilot projects.

    Science.gov (United States)

    2010-01-01

    ... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Waiver of requirements for scrapie control pilot projects. 79.7 Section 79.7 Animals and Animal Products ANIMAL AND PLANT HEALTH...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  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. 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...

  18. Lymphomatoid papulosis with a natural killer-cell phenotype

    NARCIS (Netherlands)

    Bekkenk, MW; Kluin, PM; Jansen, PM; Meijer, CJLM; Willemze, R

    2001-01-01

    Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma. The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell phenotype. We report an unusual case of LyP, in which the atyp

  19. Biology of PrPsc accumulation in two natural scrapie-infected sheep flocks.

    Science.gov (United States)

    Caplazi, Patrick; O'Rourke, Katherine; Wolf, Cynthia; Shaw, Daniel; Baszler, Timothy V

    2004-11-01

    Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrPsc, in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrPsc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrPsc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrPsc deposition in various tissues using single- and dual-label immunohistochemistry. Scrapie, as defined by PrPsc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrPsc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrPsc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrPsc deposition in the brain but widespread PrPsc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrPsc accumulation preceding deposition in the brain. PrPsc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrPsc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrPsc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrPsc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171

  20. Dermatofibroma: Atypical presentations

    Directory of Open Access Journals (Sweden)

    Mousumi Roy Bandyopadhyay

    2016-01-01

    Full Text Available Dermatofibroma is a common benign fibrohistiocytic tumor and its diagnosis is easy when it presents classical clinicopathological features. However, a dermatofibroma may show a wide variety of clinicopathological variants and, therefore, the diagnosis may be difficult. The typical dermatofibroma generally occurs as a single or multiple firm reddish-brown nodules. We report here two atypical presentations of dermatofibroma - Atrophic dermatofibroma and keloidal presentation of dermatofibroma. Clinical dermal atrophy is a common phenomenon in dermatofibromas as demonstrated by the dimpling on lateral pressure. However, this feature is exaggerated in the atrophic variant of dermatofibroma. Atrophic dermatofibroma is defined by dermal atrophy of more than 50% of the lesion apart from the usual features of common dermatofibroma. The keloidal variant of dermatofibroma should not be overlooked as a simple keloid. The findings of keloidal change in dermatofibromas may support that trauma is a possible cause of dermatofibroma.

  1. Dermatofibroma: Atypical Presentations.

    Science.gov (United States)

    Bandyopadhyay, Mousumi Roy; Besra, Mrinal; Dutta, Somasree; Sarkar, Somnath

    2016-01-01

    Dermatofibroma is a common benign fibrohistiocytic tumor and its diagnosis is easy when it presents classical clinicopathological features. However, a dermatofibroma may show a wide variety of clinicopathological variants and, therefore, the diagnosis may be difficult. The typical dermatofibroma generally occurs as a single or multiple firm reddish-brown nodules. We report here two atypical presentations of dermatofibroma - Atrophic dermatofibroma and keloidal presentation of dermatofibroma. Clinical dermal atrophy is a common phenomenon in dermatofibromas as demonstrated by the dimpling on lateral pressure. However, this feature is exaggerated in the atrophic variant of dermatofibroma. Atrophic dermatofibroma is defined by dermal atrophy of more than 50% of the lesion apart from the usual features of common dermatofibroma. The keloidal variant of dermatofibroma should not be overlooked as a simple keloid. The findings of keloidal change in dermatofibromas may support that trauma is a possible cause of dermatofibroma. PMID:26955137

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

    Directory of Open Access Journals (Sweden)

    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.

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

    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.

  4. Active Surveillance for Scrapie by Third Eyelid Biopsy and Genetic Susceptibility Testing of Flocks of Sheep in Wyoming

    OpenAIRE

    O'Rourke, Katherine I.; Duncan, John V.; Logan, James R.; Anderson, Anne K.; Norden, Dianne K.; Williams, Elizabeth S.; Combs, Bret A.; Stobart, Robert H.; Moss, Gary E.; Sutton, Diane L

    2002-01-01

    Control of scrapie, an ovine transmissible spongiform encephalopathy or prion disorder, has been hampered by the lack of conventional antemortem diagnostic tests. Currently, scrapie is diagnosed by postmortem examination of the brain and lymphoid tissues for PrPSc, the protein marker for this group of disorders. For live, asymptomatic sheep, diagnosis using tonsil or third-eyelid lymphoid tissue biopsy and PrPSc assay has been described. To evaluate the feasibility and efficacy of third-eyeli...

  5. Insights into the role of “prion-like” genes and proteins on scrapie susceptibility and ram fertility

    OpenAIRE

    Pimenta, Jorge Manuel Botelho Garcia Andrade

    2013-01-01

    Tese de Douoramento em Ciências Veterinárias. Especialidade de Produção Animal The established association between polymorphisms of prnp prion gene and susceptibility to scrapie disease in sheep prompted the development of breeding programmes aimed at increasing the natural resistance to scrapie in the European Union. In order to study the possible undesirable consequences from the widespread selection for the prnp genotype on ovine genetic diversity and reproduction, we primarily focused ...

  6. Features of follicular dendritic cells in ovine pharyngeal tonsil: An in vivo and in vitro study in the context of scrapie pathogenesis

    OpenAIRE

    Toppets, Vinciane; Defaweux, Valérie; Piret, Joëlle; Kirschvinkc, Nathalie; Grobet, Luc; Antoine, Nadine

    2011-01-01

    Although the alimentary tract has been suggested as the most likely portal of entry in natural scrapie, a growing amount of data indicates that the respiratory system and more specifically the pharyngeal tonsils serve as a natural portal of entry for scrapie. This study describes for the first time the broad cell populations in the lymphoid compartment of pharyngeal tonsils and more specifically inside the lymphoid follicles where the scrapie agent accumulates during the period...

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

    Directory of Open Access Journals (Sweden)

    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

  8. Atypical vertebral Paget's disease.

    Science.gov (United States)

    Beaudouin, Constance; Dohan, Anthony; Nasrallah, Toufic; Parlier, Caroline; Touraine, Sébastien; Ea, Korng; Kaci, Rachid; Laredo, Jean-Denis

    2014-07-01

    A 40-year-old Mauritanian man consulted for back pain. A computed tomography of the spine showed patchy sclerosis of the fifth and seventh thoracic vertebral bodies with normal neural arch of T5 and sclerosis and hypertrophy of the neural arch of T7, as well as diffuse sclerosis of the T11 vertebral body with a normal neural arch. At MRI, low signal-intensity on T1-weighted images and high signal-intensity on T2-weighted images involved the whole T5 and T7 vertebrae and the vertebral body of T11. Working diagnoses included metastatic disease and lymphoma, and a biopsy of T7 and then T11 was carried out. Both showed pathological findings very suggestive of Paget's disease. Since CT is usually the more specific radiological examination in vertebral Paget's disease, we thought it could be useful to report this atypical CT presentation (patchy sclerosis of the vertebral body without diffuse bone texture changes and isolated involvement of the vertebral body) of vertebral Paget's disease. PMID:24445956

  9. Thrombotic microangiopathy: focus on atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Sperati, C John; Moliterno, Alison R

    2015-06-01

    Thrombotic microangiopathies (TMA) such as atypical hemolytic uremic syndrome (aHUS) have evolved from rare, fulminant childhood afflictions to uncommon diseases with acute and chronic phases involving both children and adults. Breakthroughs in complement and coagulation regulation have allowed redefinition of specific entities despite substantial phenotypic mimicry. Reconciliation of phenotypes and delivery of life saving therapies require a multidisciplinary team of experts. The purpose of this review is to describe advances in the molecular pathophysiology of aHUS and to share the 2014 experience of the multidisciplinary Johns Hopkins TMA Registry in applying diagnostic assays, reporting disease associations, and genetic testing. PMID:26043391

  10. 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...... 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....

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    McGovern, Gillian; Mabbott, Neil; Jeffrey, Martin

    2009-01-01

    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. PMID:19997557

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Scrapie Affects the Maturation Cycle and Immune Complex Trapping by Follicular Dendritic Cells in Mice

    OpenAIRE

    Gillian McGovern; Neil Mabbott; Martin Jeffrey

    2009-01-01

    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...

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

    OpenAIRE

    Warner Richard; Heasman Lindsay; Dexter Glenda E; Ryder Stephen J; Moore S Jo

    2009-01-01

    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 ...

  16. 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. PMID:24828439

  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. 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.

  19. Detection and clinical evolution of scrapie in sheep by 3rd eyelid biopsy.

    Science.gov (United States)

    Vargas, Francisco; Luján, Lluís; Bolea, Rosa; Monleón, Eva; Martín-Burriel, Inmaculada; Fernández, Antonio; De Blas, Ignacio; Badiola, Juan José

    2006-01-01

    The goal of this article was to characterize the clinical evolution of scrapie in naturally affected sheep. Eighteen sheep with scrapie diagnosed by examination of 3rd eyelid biopsy and 12 control ewes were studied throughout the duration of their disease. Diagnosis was confirmed postmortem by histopathologic, immunohistochemical, and Western blot analysis of nervous tissue. Complete clinical examinations were performed every 2 weeks for each animal, of which 3 clinical examinations per animal are reported. Those clinical signs that showed a significant frequency within the corresponding clinical examination were considered representative of each stage of the disease (ie, early, middle, and late). The representative clinical signs for the early stage were hypoesthesia in the limbs, alteration of mental status, and a body condition score gait abnormalities, and teeth grinding. On the basis of these results, we propose the calculation of an objective clinical index that allows the differentiation among clinical stages and that could be useful for further studies. The usefulness of 3rd eyelid lymphoid tissue biopsies for sequential clinical studies in naturally scrapie-affected sheep is demonstrated. PMID:16496940

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and CH1641 scrapie.

    Science.gov (United States)

    Jacobs, J G; Sauer, M; van Keulen, L J M; Tang, Y; Bossers, A; Langeveld, J P M

    2011-01-01

    With increased awareness of the diversity of transmissible spongiform encephalopathy (TSE) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. Exposure to bovine spongiform encephalopathy (BSE) has been associated with the human TSE, variant Creutzfeldt-Jakob disease, emphasizing the necessity in distinguishing low-risk TSE types from BSE. TSE type discrimination in ruminants such as cattle, sheep, goats and deer, requires the application of several prion protein (PrP)-specific antibodies in parallel immunochemical tests on brain homogenates or tissue sections from infected animals. This study uses in a single incubation step, three PrP-specific antibodies and fluorescent Alexa dye-labelled anti-mouse Fabs on a Western blot. The usual amount of brain tissue needed is 0.5 mg. This multiplex application of antibodies directed towards three different PrP epitopes enabled differential diagnosis of all established main features of classical scrapie, BSE and Nor98-like scrapie in sheep and goats, as well as the currently known BSE types C, H and L in cattle. Moreover, due to an antibody-dependent dual PrP-banding pattern, for the first time CH1641 scrapie of sheep can be reliably discriminated from the other TSE isolate types in sheep. PMID:20943889

  2. Disease-associated PrP in the enteric nervous system of scrapie-affected Suffolk sheep.

    Science.gov (United States)

    Heggebø, Ragna; González, Lorenzo; Press, Charles McL; Gunnes, Gjermund; Espenes, Arild; Jeffrey, Martin

    2003-05-01

    Disease-associated prion protein (PrP(d)) in the enteric nervous system (ENS) of 20- to 24-month-old Suffolk sheep in the late subclinical and early clinical phase of scrapie was studied. Sites in the alimentary tract extending from the forestomachs and abomasum to the colon from scrapie-affected sheep (PrP(ARQ/ARQ)) and scrapie-resistant sheep (PrP(ARR/ARQ) and PrP(ARR/ARR)) were examined. PrP(d) was found only in scrapie-affected sheep and was most prominent in the ENS when abundant deposits of PrP(d) were also present in adjacent lymphoid nodules. Immunolabelling with the nerve fibre markers PgP 9.5 and neuron-specific enolase and the satellite cell marker glial fibrillary acidic protein revealed the extensive ganglionated networks of the myenteric and submucosal plexi. Fewer nerve fibres were present in the lamina propria, T-cell dominated interfollicular areas and dome regions of Peyer's patches. A substantial network of nerve fibres was detected in many lymphoid nodules of both the scrapie-affected and scrapie-resistant sheep. Nerve fibres were also detected within the capsule of lymphoid nodules. Electron microscopy revealed the presence of nerves in the lymphoid nodules, showing a close association with follicular dendritic cells, lymphocytes and tingible body macrophages. In demonstrating that lymphoid nodules in the Peyer's patches of scrapie-affected sheep possess a substantial network of nerve fibres, the present study shows that nodules provide close contact between nerve fibres and cell populations known to contain abundant PrP(d), including follicular dendritic cells and tingible body macrophages, and that gut-associated lymphoid nodules in sheep may represent an important site for neuroinvasion. PMID:12692300

  3. 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......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...

  4. 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

  5. Familial benign pemphigus atypical localization

    OpenAIRE

    Reyes, Maria Veronica; Halac, Sabina; Mainardi, Claudio; Kurpis, Maria; Ruiz Lascano, Alejandro

    2016-01-01

    We present an atypical case of familial benign pemphigus (Hailey-Hailey disease), which presented as crusted, annular plaques limited to the back without intertriginous involvement. We could not find in the literature another patient with plaques located solely on the back without a prior history of classical disease.

  6. 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.

  7. Recognition and diagnosis of atypical depression.

    Science.gov (United States)

    Thase, Michael E

    2007-01-01

    The term atypical depression dates to the first wave of reports describing differential response to monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In contrast to more TCA-responsive depressions, patients with so-called atypical symptoms (e.g., hypersomnia, interpersonal sensitivity, leaden paralysis, increased appetite and/or weight, and phobic anxiety) were observed to be more responsive to MAOIs. After several decades of controversy and debate, the phrase "with atypical features" was added as an episode specifier in the DSM-IV in 1994. The 1-year prevalence of the defined atypical depression subtype is approximately 1% to 4%; around 15% to 29% of patients with major depressive disorder have atypical depression. Hardly "atypical" in contemporary contexts, atypical depression also is common in dysthymic bipolar II disorders and is notable for its early age at onset, more chronic course, and high rates of comorbidity with social phobia and panic disorder with agoraphobia. The requirement of preserved mood reactivity is arguably the most controversial of the DSM-IV criteria for atypical depression. When compared with melancholia, the neurobiological profiles of patients with atypical depression are relatively normal. The utility of the atypical depression subtype for differential therapeutics diminished substantially when the TCAs were supplanted as first-line antidepressants by the selective serotonin reuptake inhibitors. Although introduction of safer MAOIs has fostered renewed interest in atypical depression, the validity and importance of the DSM-IV definition of atypical depression for the nosology of affective illness remains an open question. PMID:17640153

  8. Scrapie Agent (Strain 263K) Can Transmit Disease via the Oral Route after Persistence in Soil over Years

    Science.gov (United States)

    Groschup, Martin H.; Peters, Rainer; Beekes, Michael; Terytze, Konstantin

    2007-01-01

    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 PrPSc 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 PrPSc 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. PMID:17502917

  9. The Oral Secretion of Infectious Scrapie Prions Occurs in Preclinical Sheep with a Range of PRNP Genotypes

    OpenAIRE

    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 inv...

  10. Atypical manifestations of early syphilis

    Directory of Open Access Journals (Sweden)

    Koranne R

    1990-01-01

    Full Text Available A study of 36 untreated patients with early syphilis revealed atypical variations namely; long incubation period of 101 days in I patient, more than 3 chancres in 1, undermined margin of the chancre along with tenderness in 1 and moderate to severe tenderness of the ulcers in 2 cases. In 3 patients there was no indurations of the ulcers. Three patients with primary syphilis had unilateral lymphadenitis, and in I case the lymph nodes were not only tender but showed tendency towardsmatingawell. Insecondarysyphilis, 11 out of 16 patients having condylomata lata had no other muco-cutaneous lesions. Concomitant presence of other venereal disease to account for the atypical manifestations was discounted- by appropriate laboratory tests, response to therapeutic agents and follow up.

  11. Atypical fractures, a biased perspective.

    Science.gov (United States)

    Aspenberg, Per

    2016-01-01

    When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good. PMID:26768286

  12. Atypical eating disorders: a review

    OpenAIRE

    Garcia, Frederico

    2011-01-01

    Frederico Duarte Garcia1, Héloïse Délavenne2, Pierre Déchelotte11Nutrition and Digestive System Research Group (EA 4311) and Nutrition Unit, Rouen Institute of Medical Research and Innovation, Federative Institute for Peptide Research (IFRMP 23), Rouen University and University Hospital, Rouen, France; 2Department of Addictology of the Rouen University Hospital, Rouen University, Rouen, FranceIntroduction: Atypical eating disorders (AEDs), also known ...

  13. Fenotipo atípico de Vibrio ordalii, bacteria altamente patogénica aislada desde salmón del Atlántico cultivado en las costas marinas del sur de Chile Atypical phenotype of Vibrio ordalii, a highly pathogenic bacteria isolated from Atlantic salmon reared on the marine coast of southern Chile

    Directory of Open Access Journals (Sweden)

    H Bohle

    2007-01-01

    amplification and characterization of the 16s rRNA of the isolates using polymerase chain reaction (PCR, followed by comparison of the nucleotide sequence with previously submitted bacterial 16s rRNA sequences from a gene bank. According to the results of the analysis, the agents producing the disease were bacteria that belonged to the Vibrio ordalii group. However, the dissimilarities discovered by using the morphological, physiological, biochemical, enzymatic and antigenic assays did indicate important differences from the reference strains of V. ordalii. Forthis reason it is suggested that the Chilean field isolates of V. ordalii could be considered as an atypical biotype and/or phenotype of V. ordalii,although more comparative studies between the complete genomes of these bacteria are required.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. 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... hours; and (8) Will report all test results to State and Federal animal health officials within...

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

    Directory of Open Access Journals (Sweden)

    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

  20. Evolving A-Type Artificial Neural Networks

    CERN Document Server

    Orr, Ewan

    2011-01-01

    We investigate Turing's notion of an A-type artificial neural network. We study a refinement of Turing's original idea, motivated by work of Teuscher, Bull, Preen and Copeland. Our A-types can process binary data by accepting and outputting sequences of binary vectors; hence we can associate a function to an A-type, and we say the A-type {\\em represents} the function. There are two modes of data processing: clamped and sequential. We describe an evolutionary algorithm, involving graph-theoretic manipulations of A-types, which searches for A-types representing a given function. The algorithm uses both mutation and crossover operators. We implemented the algorithm and applied it to three benchmark tasks. We found that the algorithm performed much better than a random search. For two out of the three tasks, the algorithm with crossover performed better than a mutation-only version.

  1. Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphotoxin pathway dramatically reduces scrapie susceptibility.

    Science.gov (United States)

    Mabbott, Neil A; Young, Janice; McConnell, Irene; Bruce, Moira E

    2003-06-01

    Transmissible spongiform encephalopathies (TSEs) may be acquired peripherally, in which case infectivity usually accumulates in lymphoid tissues before dissemination to the nervous system. Studies of mouse scrapie models have shown that mature follicular dendritic cells (FDCs), expressing the host prion protein (PrP(c)), are critical for replication of infection in lymphoid tissues and subsequent neuroinvasion. Since FDCs require lymphotoxin signals from B lymphocytes to maintain their differentiated state, blockade of this stimulation with a lymphotoxin beta receptor-immunoglobulin fusion protein (LT beta R-Ig) leads to their temporary dedifferentiation. Here, a single treatment with LT beta R-Ig before intraperitoneal scrapie inoculation blocked the early accumulation of infectivity and disease-specific PrP (PrP(Sc)) within the spleen and substantially reduced disease susceptibility. These effects coincided with an absence of FDCs in the spleen for ca. 28 days after treatment. Although the period of FDC dedifferentiation was extended to at least 49 days by consecutive LT beta R-Ig treatments, this had little added protective benefit after injection with a moderate dose of scrapie. We also demonstrate that mature FDCs are critical for the transmission of scrapie from the gastrointestinal tract. Treatment with LT beta R-Ig before oral scrapie inoculation blocked PrP(Sc) accumulation in Peyer's patches and mesenteric lymph nodes and prevented neuroinvasion. However, treatment 14 days after oral inoculation did not affect survival time or susceptibility, suggesting that infectivity may have already spread to the peripheral nervous system. Although manipulation of FDCs may offer a potential approach for early intervention in peripherally acquired TSEs, these data suggest that the duration of the treatment window may vary widely depending on the route of exposure. PMID:12768004

  2. Atypical extragonadal germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mainak Deb

    2012-01-01

    Full Text Available Aim: To review the experience with the diagnosis and management of extragonadal germ cell tumors (GCT with a subset analysis of those with atypical features. Materials and Methods: A retrospective chart review of patients of extragonadal germ cell tumors between 2000 and 2010 was carried out. Results: Fifteen children aged 7 days to 15 years (median, 1.5 years were included. Three had an antenatal diagnosis (one sacrococcygeal, one retrobulbar, one retroperitoneal tumor and were operated in the neonatal period. The locations were distributed between the retrobulbar area (1, anterior neck-thyroid gland (1, mediastinum (4, abdominothoracic extending through the esophageal hiatus (1, retroperitoneal (4 and sacrococcygeal (4. On histological examination, five harbored immature elements while two were malignant; the latter children received postexcision adjuvant chemotherapy. There was no mortality. At a median follow-up of 4.5 years (6 months to 8 years, 14/15 have had an event-free survival. One immature mediastinal teratoma that recurred locally 7.5 years after the initial operation was excised and adjuvant chemotherapy instituted. Conclusions: Extragonadal GCTs in children are uncommon and occasionally present with atypical clinical, radiological and histological features resulting in diagnostic and therapeutic dilemmas.

  3. Atypical Manifestation of Vestibular Schwannoma

    Directory of Open Access Journals (Sweden)

    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.

  4. CJD and Scrapie Require Agent-Associated Nucleic Acids for Infection.

    Science.gov (United States)

    Botsios, Sotirios; Manuelidis, Laura

    2016-08-01

    Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain-specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where >85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU-CJD and 22L scrapie particles to potent nucleases. Both agent-strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure to nucleases that are active in sarkosyl, infectivity of both agents was reproducibly reduced by ≥99%. No gold-stained host proteins or any form of PrP were visibly altered by these nucleases. In contrast, co-purifying protected mitochondrial DNA and circular SPHINX DNAs were destroyed. These findings demonstrate that TSE agents require protected genetic material to infect their hosts, and should reopen investigation of essential agent nucleic acids. J. Cell. Biochem. 117: 1947-1958, 2016. © 2016 Wiley Periodicals, Inc. PMID:26773845

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Typical and atypical AIS. Pathogenesis.

    Science.gov (United States)

    Dudin, M; Pinchuk, D

    2012-01-01

    AIS hypothesis has the right to recognition, if it explains the transition of "healthy" vertebra column into status of "scoliotic" one. AIS is the most investigated disease in the history of orthopedics, but up the present time there is no clear explanation of some its phenomena: vertebra column mono-form deformation along with its poly etiology character, interrelation of its origin and development and child's growth process etc. The key for authors' view at AIS was scoliosis with non-standard (concave side) rotation. On the bases of its' multifunctional instrumental investigation results (Rtg, EMG, EEG, optical topography, hormonal and neuropeptides trials, thermo-vision methods and other) in comparison with typical AIS was worked out the new hypothesis, part of it is suggested for discussion. In the work under observation is the sequence of appearance of typical and atypical scoliosis symptomatology beginning from the preclinical stage. PMID:22744477

  11. [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. PMID:19930927

  12. The effects of selective breeding against scrapie susceptibility on the genetic variability of the Latxa Black-Faced sheep breed

    OpenAIRE

    Legarra Andrés; Parada Analia; Alfonso Leopoldo; Ugarte Eva; Arana Ana

    2006-01-01

    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 inform...

  13. Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility

    OpenAIRE

    Mabbott, Neil; Young, J.; McConnell, I.; Bruce, Moira

    2003-01-01

    Transmissible spongiform encephalopathies (TSEs) may be acquired peripherally, in which case infectivity usually accumulates in lymphoid tissues before dissemination to the nervous system. Studies of mouse scrapie models have shown that mature follicular dendritic cells (FDCs), expressing the host prion protein (PrP(c)), are critical for replication of infection in lymphoid tissues and subsequent neuroinvasion. Since FDCs require lymphotoxin signals from B lymphocytes to maintain their differ...

  14. Accumulation profiles of PrPSc in hemal nodes of naturally and experimentally scrapie-infected sheep

    OpenAIRE

    Dassanayake, Rohana P; Truscott, Thomas C; Özyiğit, M Özgür; Zhuang, Dongyue; Schneider, David A; O’Rourke, Katherine I.

    2013-01-01

    Background In classical scrapie, the disease-associated abnormal isoform (PrPSc) of normal prion protein accumulates principally in the nervous system and lymphoid tissues of small ruminants. Lymph nodes traffic leukocytes via lymphatic and blood vasculatures but hemal nodes lack lymphatic vessels and thus traffic leukocytes only via the blood. Although PrPSc accumulation profiles are well-characterized in ovine lymphoid tissues, there is limited information on such profiles in hemal nodes. T...

  15. Tumor Necrosis Factor Alpha-Deficient, but Not Interleukin-6-Deficient, Mice Resist Peripheral Infection with Scrapie

    OpenAIRE

    Mabbott, Neil; Williams, Alun; Farquhar, Christine; Pasparakis, Manolis; Kollias, Giorgos; Bruce, Moira

    2000-01-01

    In most peripheral infections of rodents and sheep with scrapie, infectivity is found first in lymphoid tissues and later in the central nervous system (CNS). Cells within the germinal centers (GCs) of the spleen and lymph nodes are important sites of extraneural replication, from which infection is likely to spread to the CNS along peripheral nerves. Here, using immunodeficient mice, we investigate the identity of the cells in the spleen that are important for disease propagation. Despite po...

  16. Temporary blockade of the tumor necrosis factor receptor signaling pathway impedes the spread of scrapie to the brain

    OpenAIRE

    Mabbott, Neil; McGovern, Gillian; Jeffrey, Martin; Bruce, Moira

    2002-01-01

    Although the transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases, their agents usually replicate and accumulate in lymphoid tissues long before infection spreads to the central nervous system (CNS). Studies of a mouse scrapie model have shown that mature follicular dendritic cells (FDCs), which express the host prion protein (PrP(c)), are critical for replication of infection in lymphoid tissues. In the absence of mature FDCs, the spread of infection to the CNS is ...

  17. Unusual cerebral vascular prion protein amyloid distribution in scrapie-infected transgenic mice expressing anchorless prion protein

    OpenAIRE

    Rangel, Alejandra; Race, Brent; Klingeborn, Mikael; Striebel, James; Chesebro, Bruce

    2013-01-01

    Background In some prion diseases, misfolded aggregated protease-resistant prion protein (PrPres) is found in brain as amyloid, which can cause cerebral amyloid angiopathy. Small diffusible precursors of PrPres amyloid might flow with brain interstitial fluid (ISF), possibly accounting for the perivascular and intravascular distribution of PrPres amyloid. We previously reported that PrPres amyloid in scrapie-infected transgenic mice appeared to delay clearance of microinjected brain ISF trace...

  18. Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions

    OpenAIRE

    González, Lorenzo; Martin, Stuart; Hawkins, Stephen A.C.; Goldmann, Wilfred; Jeffrey, Martin; Sisó, Sílvia

    2010-01-01

    After detection of a high prevalence of scrapie in a large dairy goat herd, 72 infected animals were examined by immunohistochemistry with prion protein (PrP) antibody Bar224 to study the pathogenesis of the infection. Tissues examined included the brain and thoracic spinal cord (TSC), a wide selection of lymphoreticular system (LRS) tissues, the distal ileum and its enteric nervous system (ENS), and other organs, including the mammary gland. The whole open reading frame of the PRNP gene was ...

  19. 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.

  20. 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. PMID:26653410

  1. 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 (<9%) of 171R PrP(res) were detected. Enhanced 171R(res) proteolytic susceptibility could be excluded. Thus, these data support a nearly zero contribution of 171R PrP in PrP(res) of 171R/Q field scrapie-infected animals. This is suggestive of a poor adaptation of classical scrapie to this resistance allele under these natural conditions.

  2. Atypical presentations of Wolframs syndrome

    Directory of Open Access Journals (Sweden)

    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.

  3. Surgical Options for Atypical Facial Pain Syndromes.

    Science.gov (United States)

    Rahimpour, Shervin; Lad, Shivanand P

    2016-07-01

    Atypical neuropathic facial pain is a syndrome of intractable and unremitting facial pain that is secondary to nociceptive signaling in the trigeminal system. These syndromes are often recalcitrant to pharmacotherapy and other common interventions, including microvascular decompression and percutaneous procedures. Herein, the authors present two other viable approaches (nucleus caudalis dorsal root entry zone lesioning and motor cortex stimulation), their indications, and finally a possible treatment algorithm to consider when assessing patients with atypical facial pain. PMID:27325003

  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. Prion replication in the hematopoietic compartment is not required for neuroinvasion in scrapie mouse model.

    Science.gov (United States)

    Loeuillet, Corinne; Lemaire-Vieille, Catherine; Naquet, Philippe; Cesbron-Delauw, Marie-France; Gagnon, Jean; Cesbron, Jean-Yves

    2010-01-01

    Fatal neurodegenerative prion diseases are caused by the transmissible PrP(Sc) prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. However, prion replication also occurs in lymphoid cells. To assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic C57/BL6J background, by bone marrow replacement with hematopoietic cells expressing different levels of PrP protein. Nine different types of chimeric mice were inoculated intraperitoneally either with the lymphotropic Rocky Mountain Laboratory (RML) strain or the non lymphotropic ME-7 scrapie strain, at different doses. Here, we clearly demonstrate that overexpression of PrP by the hematopoietic system, or the lack of PrP expression by the bone marrow derived cells, does not change the incubation time period of the disease, even when the mice are infected at limiting doses. We conclude that the hematopoietic compartment is more or less permissive to prion replication, both for RML and ME-7, but does not play a role in neuroinvasion. PMID:20957200

  6. Interaction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure.

    Science.gov (United States)

    Dorban, Gauthier; Defaweux, Valérie; Demonceau, Caroline; Flandroy, Sylvain; Van Lerberghe, Pierre-Bernard; Falisse-Poirrier, Nandini; Piret, Joëlle; Heinen, Ernst; Antoine, Nadine

    2007-12-01

    In transmissible spongiform encephalopathies (TSEs), the infectious agent, called PrPsc, an abnormal isoform of the cellular prion protein, accumulates and replicates in lymphoid organs before affecting the nervous system. To clarify the cellular requirements for the neuroinvasion of the scrapie agent from the lymphoid organs to the central nervous system, we have studied, by confocal microscopy, the innervations within Peyer's patches, mesenteric lymph nodes and the spleen of mice in physiological conditions and after oral exposure to prion. Contacts between nerve fibres and PrPsc-associated cells, dendritic cells (DCs) and follicular dendritic cells (FDCs), were evaluated in preclinical prion-infected mice. Using a double immunolabelling strategy, we demonstrated the lack of innervation of PrPsc-accumulating cells (FDCs). Contacts between nerve fibers and PrPsc-propagating cells (DCs) were detected in T-cell zones and cell-trafficking areas. This supports, for the first time, the possible implication of dendritic cells in the prion neuroinvasion process. PMID:17823814

  7. Role of gut macrophages in mice orally contaminated with scrapie or BSE.

    Science.gov (United States)

    Maignien, Thomas; Shakweh, Monjed; Calvo, Pilar; Marcé, Dominique; Salès, Nicole; Fattal, Elias; Deslys, Jean-Philippe; Couvreur, Patrick; Lasmezas, Corinne Ida

    2005-07-25

    While there is a growing consensus on the understanding of the propagation pathways after oral infection of transmissible spongiform encephalopathy (TSE) agents and even if the central role of follicular dendritic cells is identified, little is known about the key players in the first steps of the infection and about the site of the disease development. We investigated the role of gut macrophages, which are capable of capturing aggregates of the prion protein. PLGA particles containing clodronate were designed in order to be orally administered and to target Peyer's patches for inducing gut-associated macrophages suicide in mice. Mice were subsequently infected with scrapie or BSE by the oral route. It was found that the efficacy of macrophage suppression in the Peyer's patches correlated well with an earlier appearance of PrPres in these formations and with a higher amount of PrPres at a later stage of the infection. Thus, the capture of infectious particles that have crossed the epithelial gut barrier and their elimination by macrophages seems to be a key event to restrict the amount of agent initiating the infection. PMID:15964722

  8. Prion replication in the hematopoietic compartment is not required for neuroinvasion in scrapie mouse model.

    Directory of Open Access Journals (Sweden)

    Corinne Loeuillet

    Full Text Available Fatal neurodegenerative prion diseases are caused by the transmissible PrP(Sc prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. However, prion replication also occurs in lymphoid cells. To assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic C57/BL6J background, by bone marrow replacement with hematopoietic cells expressing different levels of PrP protein. Nine different types of chimeric mice were inoculated intraperitoneally either with the lymphotropic Rocky Mountain Laboratory (RML strain or the non lymphotropic ME-7 scrapie strain, at different doses. Here, we clearly demonstrate that overexpression of PrP by the hematopoietic system, or the lack of PrP expression by the bone marrow derived cells, does not change the incubation time period of the disease, even when the mice are infected at limiting doses. We conclude that the hematopoietic compartment is more or less permissive to prion replication, both for RML and ME-7, but does not play a role in neuroinvasion.

  9. 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

    . 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......The risk of transmission of classical scrapie via the transfer of in vivo derived embryo in ovines was assessed, taking into account the scientific information made available since the last EFSA opinion on this topic (2010) (see http://www.efsa.europa.eu/en/efsajournal/pub/1429.htm). The potential...... 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...

  10. Protective effect of the AT137RQ and ARQK176 PrP alleles against classical scrapie in Sarda breed sheep

    Science.gov (United States)

    Vaccari, Gabriele; Scavia, Gaia; Sala, Marcello; Cosseddu, Gianmario; Chiappini, Barbara; Conte, Michela; Esposito, Elena; Lorenzetti, Raniero; Perfetti, Gabriella; Marconi, Paola; Scholl, Francesco; Barbaro, Katia; Bella, Antonino; Nonno, Romolo; Agrimi, Umberto

    2009-01-01

    The susceptibility of sheep to scrapie is under the control of the host’s prion protein (PrP) gene and is also influenced by the strain of the agent. PrP polymorphisms at codons 136 (A/V), 154 (R/H) and 171 (Q/R/H) are the main determinants of susceptibility/resistance of sheep to classical scrapie. They are combined in four main variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programmes have been undertaken on this basis in the European Union and the USA to increase the frequency of the resistant ARR allele in sheep populations. Herein, we report the results of a multi-flock study showing the protective effect of polymorphisms other than those at codons 136, 154 and 171 in Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 378 negative ARQ/ARQ controls from four scrapie outbreaks were submitted to sequencing of the PrP gene. The distribution of variations other than those at the standard three codons, between scrapie cases and negative controls, was statistically different in all flocks. In particular, the AT137RQ and ARQK176 alleles showed a clear protective effect. This is the first study demonstrating a protective influence of alleles other than ARR under field conditions. If further investigations in other sheep breeds and with other scrapie sources confirm these findings, the availability of various protective alleles in breeding programmes of sheep for scrapie resistance could be useful in breeds with a low frequency of the ARR allele and would allow maintaining a wider variability of the PrP gene. PMID:19171116

  11. 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.

  12. 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.

  13. Strain specific resistance to murine scrapie associated with a naturally occurring human prion protein polymorphism at residue 171.

    Directory of Open Access Journals (Sweden)

    James F Striebel

    2011-09-01

    Full Text Available Transmissible spongiform encephalopathies (TSE or prion diseases are neurodegenerative disorders associated with conversion of normal host prion protein (PrP to a misfolded, protease-resistant form (PrPres. Genetic variations of prion protein in humans and animals can alter susceptibility to both familial and infectious prion diseases. The N171S PrP polymorphism is found mainly in humans of African descent, but its low incidence has precluded study of its possible influence on prion disease. Similar to previous experiments of others, for laboratory studies we created a transgenic model expressing the mouse PrP homolog, PrP-170S, of human PrP-171S. Since PrP polymorphisms can vary in their effects on different TSE diseases, we tested these mice with four different strains of mouse-adapted scrapie. Whereas 22L and ME7 scrapie strains induced typical clinical disease, neuropathology and accumulation of PrPres in all transgenic mice at 99-128 average days post-inoculation, strains RML and 79A produced clinical disease and PrPres formation in only a small subset of mice at very late times. When mice expressing both PrP-170S and PrP-170N were inoculated with RML scrapie, dominant-negative inhibition of disease did not occur, possibly because interaction of strain RML with PrP-170S was minimal. Surprisingly, in vitro PrP conversion using protein misfolding cyclic amplification (PMCA, did not reproduce the in vivo findings, suggesting that the resistance noted in live mice might be due to factors or conditions not present in vitro. These findings suggest that in vivo conversion of PrP-170S by RML and 79A scrapie strains was slow and inefficient. PrP-170S mice may be an example of the conformational selection model where the structure of some prion strains does not favor interactions with PrP molecules expressing certain polymorphisms.

  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. Genetics Home Reference: atypical hemolytic-uremic syndrome

    Science.gov (United States)

    ... the genes associated with atypical hemolytic-uremic syndrome C3 CD46 CFB CFH CFHR5 CFI THBD Related Information ... Manual Consumer Version: Thrombocytopenia Merck Manual Professional Version: Complement System Orphanet: Atypical hemolytic-uremic syndrome Patient Support ...

  16. 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...

  17. 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.

  18. Cohort study of atypical pressure ulcers development.

    Science.gov (United States)

    Jaul, Efraim

    2014-12-01

    Atypical pressure ulcers (APU) are distinguished from common pressure ulcers (PU) with both unusual location and different aetiology. The occurrence and attempts to characterise APU remain unrecognised. The purpose of this cohort study was to analyse the occurrence of atypical location and the circumstances of the causation, and draw attention to the prevention and treatment by a multidisciplinary team. The cohort study spanned three and a half years totalling 174 patients. The unit incorporates two weekly combined staff meetings. One concentrates on wound assessment with treatment decisions made by the physician and nurse, and the other, a multidisciplinary team reviewing all patients and coordinating treatment. The main finding of this study identified APU occurrence rate of 21% within acquired PU over a three and a half year period. Severe spasticity constituted the largest group in this study and the most difficult to cure wounds, located in medial aspects of knees, elbows and palms. Medical devices caused the second largest occurrence of atypical wounds, located in the nape of the neck, penis and nostrils. Bony deformities were the third recognisable atypical wound group located in shoulder blades and upper spine. These three categories are definable and time observable. APU are important to be recognisable, and can be healed as well as being prevented. The prominent role of the multidisciplinary team is primary in identification, prevention and treatment. PMID:23374746

  19. Observing Behavior and Atypically Restricted Stimulus Control

    Science.gov (United States)

    Dube, William V.; Dickson, Chata A.; Balsamo, Lyn M.; O'Donnell, Kristin Lombard; Tomanari, Gerson Y.; Farren, Kevin M.; Wheeler, Emily E.; McIlvane, William J.

    2010-01-01

    Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded…

  20. 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

  1. 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. PMID:25024856

  2. 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.

  3. Disentangling the Emerging Evidence around Atypical Fractures

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Clark, Emma M

    2012-01-01

    Atypical femur fractures are rare but a growing concern, as they are more common in patients who use bisphosphonates. The best radiology-based studies have had access to only short-term exposure data, while the studies using prescription databases with substantial long-term data did not have access...

  4. Infant Perception of Atypical Speech Signals

    Science.gov (United States)

    Vouloumanos, Athena; Gelfand, Hanna M.

    2013-01-01

    The ability to decode atypical and degraded speech signals as intelligible is a hallmark of speech perception. Human adults can perceive sounds as speech even when they are generated by a variety of nonhuman sources including computers and parrots. We examined how infants perceive the speech-like vocalizations of a parrot. Further, we examined how…

  5. 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.

  6. 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.

  7. IMPY, a potential β-amyloid imaging probe for detection of prion deposits in scrapie-infected mice

    International Nuclear Information System (INIS)

    Introduction: A potential single-photon emission computed tomography imaging agent for labeling of Aβ 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 [125I]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 [125I]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 [125I]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 123I, this ligand may be useful to quantitate prion deposit burdens in TSEs by in vivo imaging

  8. 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

  9. 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.

  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. 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...

  12. 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

  13. 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. PMID:23658779

  14. 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.

  15. Features of follicular dendritic cells in ovine pharyngeal tonsil: an in vivo and in vitro study in the context of scrapie pathogenesis.

    Science.gov (United States)

    Toppets, Vinciane; Defaweux, Valerie; Piret, Joelle; Kirschvink, Nathalie; Grobet, Luc; Antoine, Nadine

    2011-05-15

    Although the alimentary tract has been suggested as the most likely portal of entry in natural scrapie, a growing amount of data indicates that the respiratory system and more specifically the pharyngeal tonsils serve as a natural portal of entry for scrapie. This study describes for the first time the broad cell populations in the lymphoid compartment of pharyngeal tonsils and more specifically inside the lymphoid follicles where the scrapie agent accumulates during the period of latency. Follicular dendritic cells (FDCs), stromal cells located in the light zone of the germinal centre of lymphoid follicles, seem to be the principal causal factor in the accumulation of the infectious agent in transmissible spongiform encephalopathy (TSE) diseases. Knowing that efficient lymphoreticular prion propagation requires PrPc expression, we analysed the expression of PrPc with the mouse monoclonal antibody Pri 909 both in situ and on FDC-cluster-enriched cell suspensions. In situ, a positive staining was observed in the germinal centre of pharyngeal lymph follicles. The germinal centre labelling was due to the presence of a follicular dendritic network as revealed after immunogold staining of isolated FDC clusters. Our results suggest that the pharyngeal lymphoreticular system and more specifically PrPc expressing follicular dendritic cells could serve as a prion "reservoir" during the latency phase, thus playing a key role during the scrapie lymphoinvasion. PMID:21353313

  16. 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...

  17. 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...

  18. Myenteric neurons of the ileum that express somatostatin are a target of prion neuroinvasion in an alimentary model of sheep scrapie

    Science.gov (United States)

    Scrapie disease is an orally transmissible spongiform encephalopathy disease of sheep in which the causative agent, the prion, can disseminate to the brain via nerves innervating the gut. Nerve cells intrinsic to the ileum (enteric neurons) are the first part of the peripheral nervous system invaded...

  19. 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.

  20. BRAF Mutation Is Associated With a Specific Cell Type With Features Suggestive of Senescence in Ovarian Serous Borderline (Atypical Proliferative) Tumors

    DEFF Research Database (Denmark)

    Zeppernick, Felix; Ardighieri, Laura; Hannibal, Charlotte G;

    2014-01-01

    Serous borderline tumor also known as atypical proliferative serous tumor (APST) is the precursor of ovarian low-grade serous carcinoma (LGSC). In this study, we correlated the morphologic and immunohistochemical phenotypes of 71 APSTs and 18 LGSCs with the mutational status of KRAS and BRAF, the...

  1. Primary lateral sclerosis mimicking atypical parkinsonism

    DEFF Research Database (Denmark)

    Norlinah, Ibrahim M; Bhatia, Kailash P; Østergaard, Karen;

    2007-01-01

    the atypical parkinsonian syndromes. Here we describe five patients initially referred with a diagnosis of levodopa-unresponsive atypical parkinsonism (n = 4) or primary progressive multiple sclerosis (n = 1), but subsequently found to have features consistent with PLS instead. Onset age varied from......Primary lateral sclerosis (PLS), the upper motor neurone variant of motor neurone disease, is characterized by progressive spinal or bulbar spasticity with minimal motor weakness. Rarely, PLS may present with clinical features resembling parkinsonism resulting in occasional misdiagnosis as one of...... eventually seen in all patients. Anterior horn cell involvement developed in three cases. Early gait disturbances resulting in falls were seen in all patients and none of them responded to dopaminergic medications. Two patients underwent dopamine transporter (DaT) SPECT scanning with normal results. Other...

  2. 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.)

  3. 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.

  4. 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.)

  5. Atypical anti-glomerular basement membrane disease

    OpenAIRE

    Troxell, Megan L.; Donald C Houghton

    2015-01-01

    Background Anti-glomerular basement membrane (anti-GBM) disease classically presents with aggressive necrotizing and crescentic glomerulonephritis, often with pulmonary hemorrhage. The pathologic hallmark is linear staining of GBMs for deposited immunoglobulin G (IgG), usually accompanied by serum autoantibodies to the collagen IV alpha-3 constituents of GBMs. Methods Renal pathology files were searched for cases with linear anti-GBM to identify cases with atypical or indolent course. Histopa...

  6. Atypical burkitt's lymphoma transforming from follicular lymphoma

    OpenAIRE

    Chung Lap P; Loong Florence; Hwang Yu Y; Chim Chor S

    2011-01-01

    Amongst follicular lymphoma that transforms into a high-grade lymphoma, majority are diffuse large B cell lymphoma. Here we reported a rare atypical Burkitt's lymphoma transformation from an asymptomatic follicular lymphoma. Lymph node biopsy showed a composite lymphoma with infiltration of the inter-follicular areas by high grade small non-cleaved lymphoma cells amongst neoplastic follicles. Moreover, FISH and molecular genetic study confirmed concomitant MYC translocations and t(14;18) in t...

  7. 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.

  8. Aggressive papillary adenocarcinoma on atypical localization

    Science.gov (United States)

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  9. 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

  10. 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.; Yu, Karalyan N.; 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

  11. 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.)

  12. 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

  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. PMID:26458670

  14. Trisomy 18 with unilateral atypical ectrodactyly

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, R.C. [Greenwood Genetic Center, SC (United States)

    1994-01-01

    Becerra et al. recently reported on an infant with multiple congenital anomalies who had trisomy 18. This preterm infant presented with bilateral ectrodactyly of feet, small cleft palate, esophageal atresia with associated tracheoesophageal fistula, congenital heart disease and other anomalies. The authors referenced article by Castle and Bernstein, in which they reported a male with trisomy 18 and cleft foot as well as a review of the literature which showed 2 other infants with trisomy 18 and ectrodactyly of the feet. An additional case of trisomy 18 associated with multiple congenital anomalies, including unilaterial, atypical ectrodactyly of the left foot.

  15. 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

    2016-01-01

    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. PMID:27649002

  16. Atypical Teratoid/Rrhabdoid Tumour of Brain

    Directory of Open Access Journals (Sweden)

    Meena Sidhu,P.Sakhuja,V.Malhotra,R.Gondal S.Kumar

    2003-04-01

    Full Text Available Primitive neuroectodermal tumor (PNET / medulloblastoma (MB are the most commonmalignantcentral nervous tumors of the first decade of life. Atypical teratoid / rhabdoid tumor (ATT / RT isa tumor of infancy and childhood although occasional cases have also been described in adults.ATT/RT has a characteristic histopathological, immunocytochemical and ultrastructural features.ATT /RT is a rare tumor, incidence of which remains to be defined with only hundred publishedcases. The present report docurilents the clinical features, histological and immunohistochemicalfindings of a case ofATT / RT.

  17. 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.

  18. Atypical Trigeminal Neuralgia Secondary to Meningioma

    OpenAIRE

    Premeshwar Niwant; Mukta Motwani; Sushil Naik

    2015-01-01

    Trigeminal neuralgia is a disorder of the fifth cranial nerve that causes episodes of intense, stabbing, electric shock-like pain that lasts from few seconds to few minutes in the areas of the face where the branches of the nerve are distributed. More than one nerve branch can be affected by the disorder. We report an unusual case of trigeminal neuralgia affecting right side of face presenting atypical features of neuralgia and not responding to the usual course of treatment. The magnetic res...

  19. 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.

  20. Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels ▿

    OpenAIRE

    Tribouillard-Tanvier, Déborah; Striebel, James F; Peterson, Karin E.; Chesebro, Bruce

    2009-01-01

    Activation of microglia and astroglia is seen in many neurodegenerative diseases including prion diseases. Activated glial cells produce cytokines as a protective response against certain pathogens and as part of the host inflammatory response to brain damage. In addition, cytokines might also exacerbate tissue damage initiated by other processes. In the present work using multiplex assays to analyze protein levels of 24 cytokines in scrapie agent-infected C57BL/10 mouse brains, we observed e...

  1. 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

  2. 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.

  3. 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 scra

  4. Pontine Infarct Presenting with Atypical Dental Pain: A Case Report.

    Science.gov (United States)

    Goel, Rajat; Kumar, Sanjeev; Panwar, Ajay; Singh, Abhishek B

    2015-01-01

    Orofacial pain' most commonly occurs due to dental causes like caries, gingivitis or periodontitis. Other common causes of 'orofacial pain' are sinusitis, temporomandibular joint(TMJ) dysfunction, otitis externa, tension headache and migraine. In some patients, the etiology of 'orofacial pain' remains undetected despite optimal evaluation. A few patients in the practice of clinical dentistry presents with dental pain without any identifiable dental etiology. Such patients are classified under the category of 'atypical odontalgia'. 'Atypical odontalgia' is reported to be prevalent in 2.1% of the individuals. 'Atypical orofacial pain' and 'atypical odontalgia' can result from the neurological diseases like multiple sclerosis, trigeminal neuralgia and herpes infection. Trigeminal neuralgia has been frequently documented as a cause of 'atypical orofacial pain' and 'atypical odontalgia'. There are a few isolated case reports of acute pontine stroke resulting in 'atypical orofacial pain' and 'atypical odontalgia'. However, pontine stroke as a cause of atypical odontalgia is limited to only a few cases, hence prevalence is not established. This case is one, where a patient presented with acute onset atypical dental pain with no identifiable dental etiology, further diagnosed as an acute pontine infarct on neuroimaging. A 40 years old male presented with acute onset, diffuse teeth pain on right side. Dental examination was normal. Magnetic resonance imaging(MRI) of the brain had an acute infarct in right pons near the trigeminal root entry zone(REZ). Pontine infarct presenting with dental pain as a manifestation of trigeminal neuropathy, has rarely been reported previously. This stresses on the importance of neuroradiology in evaluation of atypical cases of dental pain. PMID:26464604

  5. 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.

  6. Keloidal Atypical Fibroxanthoma: Case and Review of the Literature

    Science.gov (United States)

    Tongdee, Emily; Touloei, Khasha; Shitabata, Paul K.; Shareef, Shahjahan; Maranda, Eric L.

    2016-01-01

    Keloidal atypical fibroxanthoma (KAF) has recently been categorized as a variant of atypical fibroxanthoma. This paper will emphasize the importance of including KAF in both clinical and histological differential diagnosis of benign and malignant lesions which exhibit keloidal collagen and will also review the current literature on epidemiology, pathogenesis, histology, immunochemistry and treatments. PMID:27462224

  7. [Atypical cerebellar neurocytoma resembling a hemangioblastoma. A case report].

    Science.gov (United States)

    Lista Martínez, Olalla; Rivas López, Luis Alfredo; Pombo Otero, Jorge Francisco; Amaro Cendón, Santiago; Bravo García, Christian; Villa Fernández, Juan Manuel

    2014-01-01

    Through August 2013, 105 cases of intracranial extraventricular neurocytoma (EVN) had been described; 6% were located in cerebellum and 22% were atypical EVN. A rare morphologic form of neurocytoma, atypical EVN has had only 24 cases reported to date. Its prognosis is poorer than the typical central neurocytoma. This case report describes an atypical cerebellar EVN, a form that has not been reported yet, hence the interest of this article. We emphasise its cystic nature and mural nodule, in an infrequent presentation. EVN are low-incidence tumours that we need to take into consideration when making the differential diagnosis of cystic cerebellar lesions with mural nodule. Given that the prognosis of atypical EVNs depends on the atypical nature and on the grade of resection, medical follow up has to be more constant, due to the greater degree of recurrence. PMID:24837842

  8. 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.)

  9. [Treatment of atypical and neurotic depression].

    Science.gov (United States)

    Leitner, P; Umann, E; Kulawik, H

    1986-10-01

    Hitherto it has not been usual to talk in the German language about the therapy-oriented concept of two forms of the progress of atypical depression (Type A and Type V). The characteristic symptom of Type A is angst, together with phobias, physical complaints, etc. In Type V there are vegetative symptoms, often towards evening (Hypersomnia, difficulty in getting to sleep, increased appetite, increased weight, increased libido), accompanied by hysterical extrovert personality traits, and of intermittent occurrence. These clinical pictures are amenable to psychopharmalogical therapy. In conformity with the assumption of "somatic accommodation" treatment with antidepressives is recommended in the case neurotic depression, too, at least in the initial stages of treatment. PMID:3809300

  10. [Atypical early posttraumatic syndromes (author's transl)].

    Science.gov (United States)

    Muller, G E

    1974-01-01

    In a consecutive series of 1,925 head injuries, 283 patients (14.7%), could not be classified, neither in the group of simple head injuries without cerebral symptoms, nor in the group of typical concussions characterized by immediate amnesia or observed coma. We have prefered the rather neutral term of atypical early posttraumatic syndromes. In this group, apart from neurovegetative manifestations, partial disturbances of consciousness and perception, we have also classified delayed disturbances of consciousness. Special attention has been given to migraineous phenomena and to a syndrome, characteristic for children, described by Mealey. This is an intermediate group important from a medico-legal point of view because certain transient cerebral manifestations risk to be mistaken for psychological reactions. On the other hand symptoms probably of psychic origin were discussed. PMID:4469864

  11. 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.

  12. Atypical subtrochanteric and diaphyseal femoral fractures

    DEFF Research Database (Denmark)

    Shane, Elizabeth; Burr, David; Abrahamsen, Bo;

    2014-01-01

    Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exp....... Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs. © 2014 American Society for Bone and Mineral Research....... associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may...

  13. Case Report: Atypical Cornelia de Lange Syndrome.

    Science.gov (United States)

    Leanza, Vito; Rubbino, Gabriella; Leanza, Gianluca

    2014-01-01

    Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation. We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy. PMID:26834972

  14. 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. PMID:26471105

  15. 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

  16. Microarray Analysis of 8p23.1 Deletion in New Patients with Atypical Phenotypical Traits.

    Science.gov (United States)

    Khelifa, Hela Ben; Kammoun, Molka; Hannachi, Hanene; Soyah, Najla; Hammami, Saber; Elghezal, Hatem; Sanlaville, Damien; Saad, Ali; Mougou-Zerelli, Soumaya

    2015-12-01

    We describe two patients carrying deletions of chromosome 8p23.1 with a commonly critical region identified by means of oligonucleotide array comparative genomic hybridization (array CGH). They didn't present congenital heart defects or behavioral problems. Only one patient presented with intellectual disability and carrying deletion of TNKS gene. We presumed the inclusion of TNKS gene in the mental impairment. PMID:27617130

  17. 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.

  18. 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.

  19. Atypical chemokine receptors in cancer: friends or foes?

    Science.gov (United States)

    Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

    2016-06-01

    The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. PMID:26908826

  20. Close interactions between sympathetic neural fibres and follicular dendritic cells network are not altered in Peyer's patches and spleen of C57BL/6 mice during the preclinical stage of 139A scrapie infection.

    Science.gov (United States)

    Demonceau, Caroline; Piret, Joelle; Zorzi, Danièle; Thellin, Olivier; Heinen, Ernst

    2014-07-15

    During preclinical stage of prion diseases, secondary lymphoid organs seem to play an important role in prion amplification prior the invasion of the associated peripheral nervous system. In mice, it was shown that the relative positioning of follicular dendritic cells (FDC) and sympathetic nervous system (SNS) affects the velocity of neuroinvasion following scrapie inoculation. In this study, we checked if scrapie infection, by oral or intraperitoneal route, could influence this neuroimmune interface between FDC and tyrosine hydroxylase (TH) positive neural fibres within Peyer's patches (PP) and spleen of the C57BL/6 mouse strain. We concluded that, in vivo, scrapie 139A and ME7 strains do not modify FDC-SNS neuroimmune interface. However, age seems to alter this neuroimmune interface and thus could influence the neuroinvasion in prion pathogenesis. PMID:24841625

  1. 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

  2. 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.

  3. [Apropos of atypical melancholia with Sustiva (efavirenz)].

    Science.gov (United States)

    Lang, J P; Halleguen, O; Picard, A; Lang, J M; Danion, J M

    2001-01-01

    The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV

  4. Creutzfeldt-Jakob disease a case report, with special attention to the electroencephalogram in this disorder and to its possible relationships to kuru, scrapie and «mad cow disease»

    OpenAIRE

    A.H. Chapman; Djalma Vieira e Silva

    1993-01-01

    A case of Creutzfeldt-Jakob disease in a 58-year-old Brazillian cattle rancher and businessman is presented. The EEG was normal, which is consistent with the fact that it was made during the first half of his illness; in a later stage suppression of normal rhythms by slow moderate voltage waves would be expected. The resemblances of kuru, scrapie and "mad cow disease» to C-J disease are discussed. In each of these 4 illnesses the patient or affected animal (scrapie and «mad cow disease") (a) ...

  5. 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.

  6. 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.

  7. Acute rhabdomyolysis associated with atypical Guillain-Barré syndrome.

    OpenAIRE

    Scott, A. J.; Duncan, R; Henderson, L.; Jamal, G A; Kennedy, P G

    1991-01-01

    We report a patient with atypical Guillain-Barré syndrome associated with acute rhabdomyolysis. Rhabdomyolysis may be the cause of elevation of creatine kinase sometimes seen in patients with Guillain-Barré syndrome.

  8. 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

    2016-01-01

    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 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. PMID:26948374

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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. PMID:27331011

  15. 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

  16. CD21-Positive Follicular Dendritic Cells: A Possible Source of PrPSc in Lymph Node Macrophages of Scrapie-Infected Sheep

    OpenAIRE

    Herrmann, Lynn M.; Cheevers, William P.; Davis, William C.; Knowles, Donald P.; O’Rourke, Katherine I.

    2003-01-01

    Natural sheep scrapie is a prion disease characterized by the accumulation of PrPSc in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrPSc. In this study, lymph nodes were analyzed for the presence of PrPSc and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However,...

  17. Orthostatic Hypotension in Patients with Parkinson's Disease and Atypical Parkinsonism

    OpenAIRE

    Seyed-Mohammad Fereshtehnejad; Johan Lökk

    2014-01-01

    Orthostatic hypotension (OH) is one of the commonly occurring nonmotor symptoms in patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonism (AP). We aimed to review current evidences on epidemiology, diagnosis, treatment, and prognosis of OH in patients with IPD and AP. Major electronic medical databases were assessed including PubMed/MEDLINE and Embase up to February 2013. English-written original or review articles with keywords such as “Parkinson’s disease,” “atypical p...

  18. Atypical fibroxanthoma: An unusual skin neoplasm in xeroderma pigmentosum

    Directory of Open Access Journals (Sweden)

    Ranjana Bandyopadhyay

    2012-01-01

    Full Text Available Xeroderma pigmentosum (XP is a rare autosomal recessive disorder related to defective deoxyribonucleic acid (DNA repair. Various cutaneous manifestations related to ultraviolet (UV damage characterize the clinical course. Primary malignant cutaneous neoplasms like squamous cell carcinoma, basal cell carcinoma and malignant melanoma have been reported. Atypical fibroxanthoma is a rare dermal neoplasm occurring in UV-damaged skin. We report an unusual case of atypical fibroxanthoma in a 20-year-old male with XP.

  19. Atypical Fibroxanthoma: An Unusual Skin Neoplasm in Xeroderma Pigmentosum

    OpenAIRE

    Ranjana Bandyopadhyay; Dipanwita Nag; Sanjay Bandyopadhyay; Swapan Kumar Sinha

    2012-01-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder related to defective deoxyribonucleic acid (DNA) repair. Various cutaneous manifestations related to ultraviolet (UV) damage characterize the clinical course. Primary malignant cutaneous neoplasms like squamous cell carcinoma, basal cell carcinoma and malignant melanoma have been reported. Atypical fibroxanthoma is a rare dermal neoplasm occurring in UV-damaged skin. We report an unusual case of atypical fibroxanthoma in a 20-y...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Atypical Toxoplasma gondii genotype in feral cats from the Fernando de Noronha Island, northeastern Brazil.

    Science.gov (United States)

    Melo, R P B; Almeida, J C; Lima, D C V; Pedrosa, C M; Magalhães, F J R; Alcântara, A M; Barros, L D; Vieira, R F C; Garcia, J L; Mota, R A

    2016-07-15

    Toxoplasma gondii isolates from Brazil have a different phenotypic and genotypic pattern, with predominance of virulent isolates and recombinant genotypes, compared to the North Hemisphere. Considering that a new T. gondii genotype, non-pathogenic to mice, was previously identified from free-range chickens from the Fernando de Noronha Island, Brazil, this study aimed to identify genotypes of this parasite in tissue samples of feral cats (Felis catus) from this Brazilian Island. Anti-T. gondii IgG antibodies were detected in 18/31 (58%) feral cats. Two non-virulent T. gondii isolates were obtained by mouse bioassay. Genotyping was performed by PCR-RFLP using 10 genetic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, PK1, L358 and Apico) and an atypical strain of T. gondii (ToxoDB #146) was identified. This is the first report of this genotype in feral cats. PMID:27270396

  5. 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.

  6. Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels.

    Science.gov (United States)

    Fineberg, Jeffrey D; Ritter, David M; Covarrubias, Manuel

    2012-11-01

    A-type voltage-gated K(+) (Kv) channels self-regulate their activity by inactivating directly from the open state (open-state inactivation [OSI]) or by inactivating before they open (closed-state inactivation [CSI]). To determine the inactivation pathways, it is often necessary to apply several pulse protocols, pore blockers, single-channel recording, and kinetic modeling. However, intrinsic hurdles may preclude the standardized application of these methods. Here, we implemented a simple method inspired by earlier studies of Na(+) channels to analyze macroscopic inactivation and conclusively deduce the pathways of inactivation of recombinant and native A-type Kv channels. We investigated two distinct A-type Kv channels expressed heterologously (Kv3.4 and Kv4.2 with accessory subunits) and their native counterparts in dorsal root ganglion and cerebellar granule neurons. This approach applies two conventional pulse protocols to examine inactivation induced by (a) a simple step (single-pulse inactivation) and (b) a conditioning step (double-pulse inactivation). Consistent with OSI, the rate of Kv3.4 inactivation (i.e., the negative first derivative of double-pulse inactivation) precisely superimposes on the profile of the Kv3.4 current evoked by a single pulse because the channels must open to inactivate. In contrast, the rate of Kv4.2 inactivation is asynchronous, already changing at earlier times relative to the profile of the Kv4.2 current evoked by a single pulse. Thus, Kv4.2 inactivation occurs uncoupled from channel opening, indicating CSI. Furthermore, the inactivation time constant versus voltage relation of Kv3.4 decreases monotonically with depolarization and levels off, whereas that of Kv4.2 exhibits a J-shape profile. We also manipulated the inactivation phenotype by changing the subunit composition and show how CSI and CSI combined with OSI might affect spiking properties in a full computational model of the hippocampal CA1 neuron. This work unambiguously

  7. Atypical femoral fractures and current management

    Directory of Open Access Journals (Sweden)

    Nianye Zheng

    2016-10-01

    Full Text Available With the rapid increase in patients receiving bisphosphonates (BPs for treating osteoporosis, one of the clinical complications associated with its long-term use is atypical femoral fractures (AFFs. Although the absolute risk for AFFs is low and it was a consensus that AFFs were acceptable compared with the amount of osteoporotic fractures BPs have prevented, epidemiological studies have proved that BPs had a strong association with AFFs and possibly more people were going to suffer from this adverse effect with wide prescriptions of this drug. In addition, AFFs seemed to have impaired ability to heal. Thus, to understand the mechanism(s behind AFFs is important and desirable for considering preventive measures. This article reviewed the clinical features of AFFs as well as potential underlining pathological characteristics, such as the decreased turnover rate caused by BPs that led to multiple-level alternations, e.g., changes not only at cellular and tissue levels, but also related to changes in bone micro- and macrostructure and organic/inorganic contents, leading to potentially compromised mechanical properties of cortical bone when exposed to prolonged BP therapy. Severely suppressed bone turnover may also be the underlying mechanism for impaired fracture healing in patients with AFFs. The rising concerns about the risk for AFFs in nonosteoporotic patients receiving high-dose BPs to treat cancers were also discussed. Detailed investigation will help develop potential targeted pharmacological treatments such as parathyroid hormone. In addition, potential innovative internal fixation implants were discussed with regard to dynamic and biological fixation for enhancing AFF repair.

  8. Detection of water-soluble disease-associated PrP species in blood and brain of scrapie-infected hamster.

    Science.gov (United States)

    Abdel-Haq, Hanin

    2015-09-01

    The high-speed supernatant (S(HS)) of scrapie-infected hamster brain homogenate contains a soluble infectivity similar to that of the plasma that escapes leukodepletion and can transmit prion infection. This recent finding highlights the fact that soluble prion infectivity could be relevant for prion disease propagation and progression. PrP(Sc) is essential in prion disease pathogenesis, but little to nothing is known about the PrP(Sc) species that may be associated with this form of prion infectivity. Scrapie-infected hamster plasma and S(HS) were subjected to biochemical analysis, and the results demonstrate for the first time that soluble infectivity is associated with a water-soluble PrP(Sc) species with substantially different properties from classical PrP(Sc), the concentration of which seems to correlate with the magnitude and efficiency of the soluble infectivity. Such characteristics suggest that this species might represent the soluble prion agent itself or its vehicle, highlighting the need to adequately revise the strategies involved in prion removal, diagnosis, and therapy. PMID:26105967

  9. In-situ spectroscopic investigation of transmissible spongiform encephalopathies: application of Fourier-transform infrared spectroscopy to a scrapie-hamster model

    Science.gov (United States)

    Kneipp, Janina; Lasch, Peter; Beekes, Michael; Naumann, Dieter

    2002-03-01

    Transmissible spongiform encephalopathies (TSE), such as BSE in cattle, scrapie in sheep and goats, and Creutzfeldt-Jakob disease in man are a group of fatal infectious diseases of the central nervous system that are far from being fully understood. Presuming the pathological changes to originate from small disease-specific compositional and structural modifications at the molecular level, Fourier-transform infrared (FTIR) spectroscopy can be used to achieve insight into biochemical parameters underlying pathogenesis. We have developed an FTIR microspectroscopy-based strategy which, as a combination of image reconstruction and multivariate pattern recognition methods, permitted the comparison of identical substructures in the cerebellum of healthy and TSE-infected Syrian hamsters in the terminal stage of the disease. Here we present FTIR data about the pathological changes of scrapie-infected and normal tissue of the gray matter structures stratum granulosum and stratum moleculare. IR spectroscopy was also applied to tissue pieces of the medulla oblongata of infected and control Syrian hamsters. Mapping data were analyzed with cluster analysis and imaging methods. We found variations in the spectra of the infected tissue, which are due to changes in carbohydrates, nucleic acids, phospholipids, and proteins.

  10. Investigating emotional impairments in adults with autism spectrum disorders and the broader autism phenotype

    OpenAIRE

    Berthoz, Sylvie; Lalanne, Christophe; Crane, Laura; Hill, Elisabeth L.

    2013-01-01

    There is an increasing interest in the socio-affective atypicalities observed in adults with autism spectrum disorder (ASD). The aim of this study was to further explore emotional responsiveness in adults with ASD using well-validated self-reports of alexithymia and extend these with consideration of anhedonia, and to determine whether these features are part of a broader autism phenotype. Thirty-eight adults with ASD, 87 parents of ASD individuals and 47 typical controls completed the Autism...

  11. Utilização de biópsias da terceira pálpebra e mucosa retal em ovinos para diagnóstico de scrapie em uma propriedade da região sul do Brasil

    Directory of Open Access Journals (Sweden)

    Juliano S. Leal

    2012-10-01

    Full Text Available Scrapie é uma encefalopatia espongiforme transmissível (EET que causa lesões cerebrais degenerativas em ovinos e caprinos. Caracteriza-se pelo acúmulo, no tecido encefálico e linforreticular, da forma anormal da proteína priônica (PrP Sc que provoca a morte maciça de neurônios e células gliais, além de vacuolização intensa no tecido afetado. Esse trabalho descreve a utilização da técnica de imuno-histoquímica (IHQ para proteína priônica em tecido linforreticular de biópsias de terceira pálpebra e mucosa retal, como método diagnóstico de scrapie em ovinos. Realizaram-se exames de IHQ para scrapie em amostras de uma propriedade de origem de um ovino com diagnóstico dessa enfermidade. Utilizaram-se anticorpos monoclonais antipríon para diagnóstico ante mortem pela técnica de IHQ. Nas 318 amostras de biópsias analisadas, encontrou-se 19 resultados positivos para PrP Sc nos folículos de terceira pálpebra e não foi obtida marcação no tecido linfático de mucosa retal em nenhuma das amostras coletadas. Realizaram-se 18 necropsias dos animais positivos anteriormente por biópsia e 21 necropsias de ovinos parentes dos positivos de scrapie. Confirmou-se o resultado de scrapie pela IHQ após a necropsia dos animais positivos nas biópsias de terceira pálpebra. Nesses animais, os órgãos com maior número de cortes positivos foram a terceira pálpebra (18/18 e a tonsila (8/18. Nos ovinos com parentesco com os positivos, nenhum resultado de scrapie ocorreu. A utilização de tecidos linfoides no diagnóstico de scrapie por IHQ através de biópsias mostrou-se um método viável e eficaz para o diagnóstico pré-clínico.

  12. Frontal cortex functioning in the infant broader autism phenotype.

    Science.gov (United States)

    Holmboe, Karla; Elsabbagh, Mayada; Volein, Agnes; Tucker, Leslie A; Baron-Cohen, Simon; Bolton, Patrick; Charman, Tony; Johnson, Mark H

    2010-12-01

    Atypical attention has been proposed as a marker of the broader autism phenotype. In the present study we investigated this and the related process of inhibitory control at the youngest possible age through the study of infant siblings of children with an autism spectrum disorder (Sibs-ASD). Both attention and inhibition have been related to the frontal cortex of the brain. Nine- to ten-month-old Sibs-ASD and low-risk control infants completed the Freeze-Frame task, in which infants are encouraged to inhibit looks to peripherally presented distractors whilst looking at a central animation. The attractiveness of the central stimulus is varied in order to investigate the selectivity of infants' responses. In line with previous studies, it was found that a subset of Sibs-ASD infants had difficulty disengaging attention from a central stimulus in order to orient to a peripheral stimulus. The Sibs-ASD group also showed less Selective Inhibition than controls. However, Sibs-ASD infants did demonstrate Selective Inhibitory Learning. These results provide preliminary evidence for atypical frontal cortex functioning in the infant broader autism phenotype. PMID:20609478

  13. Symptomatic atypical femoral fractures are related to underlying hip geometry.

    Science.gov (United States)

    Taormina, David P; Marcano, Alejandro I; Karia, Raj; Egol, Kenneth A; Tejwani, Nirmal C

    2014-06-01

    The benefits of bisphosphonates are well documented, but prolonged use has been associated with atypical femur fractures. Radiographic markers for fracture predisposition could potentially aid in safer medication use. In this case-control designed study, we compared hip radiographic parameters and the demographic characteristics of chronic bisphosphonate users who sustained an atypical femoral fracture with a group of chronic bisphosphonate users who did not sustain an atypical femur fracture and also a group who sustained an intertrochanteric hip fracture. Radiographic parameters included were neck-shaft angle (NSA), hip-axis length (HAL) and center-edge angle (CE). Multivariate regression was used to evaluate the relationship between radiographic measures and femur fracture. Receiver-operating characteristic analysis determined cut-off points for neck-shaft angle and risk of atypical femur fracture. Ultimately, pre-fracture radiographs of 53 bisphosphonate users who developed atypical fracture were compared with 43 asymptomatic chronic bisphosphonate users and 64 intertrochanteric fracture patients. Duration of bisphosphonate use did not statistically differ between users sustaining atypical fracture and those without fracture (7.9 [±3.5] vs. 7.7 [±3.3] years, p=0.7). Bisphosphonate users who fractured had acute/varus pre-fracture neck-shaft angles (p<0.001), shorter hip-axis length (p<0.01), and narrower center-edge angles (p<0.01). Regression analysis revealed associations between neck-shaft angle (OR=0.89 [95% CI=0.81-0.97; p=0.01), center edge angle (OR=0.89 [95% CI=0.80-0.99]; p=0.03), and BMI (OR=1.15 [95% CI=1.02-1.31; p=0.03) with fracture development. ROC curve analysis (AUC=0.67 [95% CI=0.56-0.79]) determined that a cut-off point for neck-shaft angle <128.3° yielded 69% sensitivity and 63% specificity for development of atypical femoral fracture. Ultimately, an acute/varus angle of the femoral neck, high BMI, and narrow center-edge angle were

  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. Aberrant ERK 1/2 complex activation and localization in scrapie-infected GT1-1 cells

    Directory of Open Access Journals (Sweden)

    Didonna Alessandro

    2010-08-01

    Full Text Available Abstract Background Fatal neurodegenerative disorders such as Creutzfeldt-Jakob and Gerstmann-Sträussler-Scheinker diseases in humans, scrapie and bovine spongiform encephalopathy in animals, are characterized by the accumulation in the brain of a pathological form of the prion protein (PrP denominated PrPSc. The latter derives from the host cellular form, PrPC, through a process whereby portions of its α-helical and coil structures are refolded into β-sheet structures. Results In this work, the widely known in vitro model of prion replication, hypothalamic GT1-1 cell line, was used to investigate cellular and molecular responses to prion infection. The MAP kinase cascade was dissected to assess the phosphorylation levels of src, MEK 1/2 and ERK 1/2 signaling molecules, both before and after prion infection. Our findings suggest that prion replication leads to a hyper-activation of this pathway. Biochemical analysis was complemented with immunofluorescence studies to map the localization of the ERK complex within the different cellular compartments. We showed how the ERK complex relocates in the cytosol upon prion infection. We correlated these findings with an impairment of cell growth in prion-infected GT1-1 cells as probed by MTT assay. Furthermore, given the persistent urgency in finding compounds able to cure prion infected cells, we tested the effects on the ERK cascade of two molecules known to block prion replication in vitro, quinacrine and Fab D18. We were able to show that while these two compounds possess similar effects in curing prion infection, they affect the MAP kinase cascade differently. Conclusions Taken together, our results help shed light on the molecular events involved in neurodegeneration and neuronal loss in prion infection and replication. In particular, the combination of chronic activation and aberrant localization of the ERK complex may lead to a lack of essential neuroprotective and survival factors

  16. Comparison Study on Clinical and Neuropathological Characteristics of Hamsters Inoculated With Scrapie Strain 263K in Different Challenging Pathways

    Institute of Scientific and Technical Information of China (English)

    JIN ZHANG; XIAO-BO ZHOU; GUI-PING MA; YONG LIU; CAI-MIN XU; XIAO-PING DONG; LAN CHEN; BAO-YUN ZHAN; JUN HAN; XIN-LI XIAO; HAI-YAN TIAN; BIN-LING LI; CHEN GAO; JIAN-MEI GAO

    2004-01-01

    Objective To understand the infectious characteristics of a hamster-adapted scrapie strain 263K with five different routes of infection including intracerebral (i.c.), intraperitoneal (i.p.),intragastrical (i.g.), intracardiac and intramuscular (i. m.) approaches. Methods Hamsters were infected with crude- or fine-prepared brain extracts. The neuropathological changes, PrPSc deposits,and patterns of PK-resistant PrP were analyzed by HE stain, immunohistochemistry (IHC) assay and Western blot. Reactive gliosis and neuron loss were evaluated by glial fibrillary acidic protein (GFAP)and neuron specific enolase (NSE) specific IHC. Results The animals inoculated in i.m. and i.p.ways with crude PrPSc extracts showed clinical signs at the average incubation of 69.2+-2.8 and 65.5±3.9 days. Inoculation in i.c. and intracardiac ways with fine PrPSc extracts (0.00035 g) caused similar,but relative long incubation of around 90 days. Only oneout of eight hamsters challenged ini.g way with low dosage (0.01 g) became ill after a much longer incubation (185 d), while all animals (4/4)with high dosage (0.04 g) developed clinical signs 105 days postinfection. The most remarkable spongiform degeneration and PrPsc deposits were found in brain stem among the five challenge groups generally. The number of GFAP-positive astrocytes increased distinctly in brain stems in all infection groups, while the number of NSE-positive cells decreased significantly in cerebrum, except i.c. group. The patterns of PK-resistant PrP in brains were basically identical among the five infection routes. Conclusion Typical TSE could be induced in hamsters by inoculating strain 263K in the five infection ways. The incubation periods in bioassays depend on infective dosage, administrating pathway and preparation of PrPSc. The neuropathological changes and PrPSc deposits seem to be related with regions and inoculating pathways.

  17. 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.

  18. EPR dosimetry with synthetic A-type carbonated apatite

    International Nuclear Information System (INIS)

    Synthetic A-type carbonated apatite prepared in reproducible conditions were irradiated at room temperature with 60 Co γ rays. The EPR spectrum is associated to axial CO2- and orthorhombic CO3- species. Radicals used as dose marker in biological apatite are long live paramagnetic species. The stability of the post-irradiation signal of A-type apatite was investigated for more than one year. Measurements showed variations in the spectra attributed to unstable CO3- species, which can be eliminated by thermal treatments at 100 deg C for 24 hours. The CO2- spectrum can be identified in samples irradiated up to 0.2 Gy. All results indicate the A-type apatite as an appropriate material for radiotherapy dosimetry. (author)

  19. Atypical pyoderma gangrenosum in a patient with osteomyelofibrosis

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    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.

  20. 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.

  1. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

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    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.

  2. 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...

  3. 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.

  4. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder

    OpenAIRE

    Brett Silverstein; Jules Angst

    2015-01-01

    Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetit...

  5. 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

  6. Folie a trois : Atypical presentation as shared transient psychotic episode

    Directory of Open Access Journals (Sweden)

    V K Aravind

    2014-01-01

    Full Text Available Shared psychotic disorder or induced delusional disorder can occur in different clinical settings and profile and is not uncommon. A case of Folie a trois with atypical clinical presentation as shared acute transient episode in a bereavement setting is reported. Suggestibility, close association and intimacy of the affected persons and major stress as psychological trigger act as psychopathological factors.

  7. 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.

  8. ATYPICAL BULLOUS PYODERMA GANGRENOSUM WITH EARLY LESIONS MIMICKING CHICKEN POX

    OpenAIRE

    Ramesh; Kavya Raju; Gopal; Sharath Kumar; Nandini

    2013-01-01

    ABSTRACT : Pyoderma Gangrenosum (PG) rare neutrophilic dermatoses (1/100,00 0), of which Bullous Pyoderma gangrenosum is an atypical form, which is very rare. Bullous PG is usually associated with haematological disorders like myeloproliferative disorders, haematological malignancies specially AML and several other haematological disorders. It presents as a superficial haemorrhagic bulla which ulcerates, ulcers increase in size and heal with scarring. Treatmen...

  9. 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.

  10. 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

  11. 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

  12. An Atypical Splenic B Cell Progenitor Population Supports Antibody Production during Plasmodium Infection in Mice.

    Science.gov (United States)

    Ghosh, Debopam; Wikenheiser, Daniel J; Kennedy, Brian; McGovern, Kathryn E; Stuart, Johnasha D; Wilson, Emma H; Stumhofer, Jason S

    2016-09-01

    Hematopoietic stem and progenitor cells (HSPCs) function to replenish the immune cell repertoire under steady-state conditions and in response to inflammation due to infection or stress. Whereas the bone marrow serves as the primary niche for hematopoiesis, extramedullary mobilization and differentiation of HSPCs occur in the spleen during acute Plasmodium infection, a critical step in the host immune response. In this study, we identified an atypical HSPC population in the spleen of C57BL/6 mice, with a lineage(-)Sca-1(+)c-Kit(-) (LSK(-)) phenotype that proliferates in response to infection with nonlethal Plasmodium yoelii 17X. Infection-derived LSK(-) cells upon transfer into naive congenic mice were found to differentiate predominantly into mature follicular B cells. However, when transferred into infection-matched hosts, infection-derived LSK(-) cells gave rise to B cells capable of entering into a germinal center reaction, and they developed into memory B cells and Ab-secreting cells that were capable of producing parasite-specific Abs. Differentiation of LSK(-) cells into B cells in vitro was enhanced in the presence of parasitized RBC lysate, suggesting that LSK(-) cells expand and differentiate in direct response to the parasite. However, the ability of LSK(-) cells to differentiate into B cells was not dependent on MyD88, as myd88(-/-) LSK(-) cell expansion and differentiation remained unaffected after Plasmodium infection. Collectively, these data identify a population of atypical lymphoid progenitors that differentiate into B lymphocytes in the spleen and are capable of contributing to the ongoing humoral immune response against Plasmodium infection. PMID:27448588

  13. Conformational change in hamster scrapie prion protein (PrP27-30) associated with proteinase K resistance and prion infectivity.

    Science.gov (United States)

    Suzuki, Sachiko Y; Takata, Masuhiro; Teruya, Kenta; Shinagawa, Morikazu; Mohri, Shirou; Yokoyama, Takashi

    2008-02-01

    The scrapie prion protein (PrP27-30) is a crucial component of the prion and is responsible for its transmissibility. Structural information on this protein is limited because it is insoluble and shows aggregated properties. In this study, PrP27-30 was effectively dispersed using sonication under the weak alkaline condition. Subsequently, the small PrP27-30 aggregates were subjected to different pH, heat, and denaturing conditions. The loss of proteinase K (PK) resistance of PrP27-30 and prion infectivity were monitored along with spectroscopic changes. Prion inactivation could not be achieved by the loss of PK resistance alone; a significant loss of the PrP27-30 amyloid structure, which was represented by a decrease in thioflavin T fluorescence, was required for the loss of transmissibility.

  14. Trends in Scientific Literature on Atypical Antipsychotics in South Korea: A Bibliometric Study

    OpenAIRE

    López-Muñoz, Francisco; Shen, Winston W.; Pae, Chi-un; Moreno, Raquel; Rubio, Gabriel; Molina, Juan D.; Noriega, Concha; Pérez-Nieto, Miguel A.; Huelves, Lorena; Álamo, Cecilio

    2013-01-01

    Objective We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. Methods With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine...

  15. Decontamination of surgical instruments from prions. II. In vivo findings with a model system for testing the removal of scrapie infectivity from steel surfaces.

    Science.gov (United States)

    Lemmer, Karin; Mielke, Martin; Kratzel, Christine; Joncic, Marion; Oezel, Muhsin; Pauli, Georg; Beekes, Michael

    2008-01-01

    The unusual resistance of agents causing transmissible spongiform encephalopathies (TSEs) to chemical or thermal inactivation requires special decontamination procedures in order to prevent accidental transmission of these pathogens by surgical instruments. In the search for effective, instrument-compatible and routinely applicable decontamination procedures, a previous study [Lemmer, K., Mielke, M., Pauli, G. & Beekes, M. (2004). J Gen Virol 85, 3805-3816] identified promising reagents in an in vitro carrier assay using steel wires contaminated with the disease-associated prion protein, PrP(Sc). In the follow-up study presented here, these reagents were validated for their decontamination potential in vivo. Steel wires initially loaded with >or=3 x 10(5) LD(50) of 263K scrapie infectivity were implanted into the brains of hamsters after treatment for decontamination and subsequently monitored for their potential to trigger clinical disease or subclinical cerebral PrP(Sc) deposition within an observation period of 500 days. It was found that routinely usable reagents such as a commercially available alkaline cleaner (pH 12.2) applied for 1 h at 23 degrees C or for 10 min at 55 degrees C and a mixture of 0.2 % SDS and 0.3 % NaOH (pH 12.8) applied for 5 or 10 min at 23 degrees C achieved removal of 263K scrapie infectivity below the threshold of detection (titre reduction of >or=5.5 log(10) units). The increasing use during the past few years of similar model systems by different research groups will facilitate comparison and integration of findings on the decontamination of steel surfaces from prions. Methods identified as highly effective in the 263K steel wire model need to be validated for human TSE agents on different types of instrument surfaces. PMID:18089760

  16. Selection of ovine housekeeping genes for normalisation by real-time RT-PCR; analysis of PrP gene expression and genetic susceptibility to scrapie

    Directory of Open Access Journals (Sweden)

    Hurtado Ana

    2005-09-01

    Full Text Available Abstract Background Cellular prion protein expression is essential for the development of transmissible spongiform encephalopathies (TSEs, and in sheep, genetic susceptibility to scrapie has been associated to PrP gene polymorphisms. To test the hypothetical linkage between PrP gene expression and genetic susceptibility, PrP mRNA levels were measured by real-time RT-PCR in six ovine tissues of animals with different genotypes. Results Previous to the PrP gene expression analysis the stability of several housekeeping (HK genes was assessed in order to select the best ones for relative quantification. The normalisation of gene expression was carried out using a minimum of three HK genes in order to detect small expression differences more accurately than using a single control gene. The expression stability analysis of six HK genes showed a large tissue-associated variation reflecting the existence of tissue-specific factors. Thereby, a specific set of HK genes was required for an accurate normalisation of the PrP gene expression within each tissue. Statistical differences in the normalised PrP mRNA levels were found among the tissues, obtaining the highest expression level in obex, followed by ileum, lymph node, spleen, cerebellum and cerebrum. A tendency towards increased PrP mRNA levels and genetic susceptibility was observed in central nervous system. However, the results did not support the hypothesis that PrP mRNA levels vary between genotypes. Conclusion The results on PrP gene expression presented here provide valuable baseline data for future studies on scrapie pathogenesis. On the other hand, the results on stability data of several HK genes reported in this study could prove very useful in other gene expression studies carried out in these relevant ovine tissues.

  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. Atypical depression in the structure of organic mental disorders (literature review

    Directory of Open Access Journals (Sweden)

    Leonov S.F.

    2014-09-01

    Full Text Available The review of literature presents current data on cli¬nical picture and diagnostics of atypical depression. Rubric “atypical depression” includes a variety of depressive states characterized by reactively caused changes of mood, sensitivity to interpersonal contacts, inverted vegetative and somatic symptoms such as increased appetite and hypersomnia. The article considers the place of atypical depression in the structure of organic mental disorders. Positions of foreign authors that produce atypical depression as a clinical entity in the structure of Bipolar affective disorder II type are represented, the views of other authors on the structure of atypical depression are considered. The analysis of national concept of non-circular depression is carried out. Questions of atypical affective conditions acquire special significance due to preparation of International Classification of Diseases of the 11th revision, because inclusion in it of Bipolar affective disorder II type, a manifestation of which is considered to be atypical depressions, is under discussion.

  19. Diversity of Melissococcus plutonius from honeybee larvae in Japan and experimental reproduction of European foulbrood with cultured atypical isolates.

    Directory of Open Access Journals (Sweden)

    Rie Arai

    Full Text Available European foulbrood (EFB is an important infectious disease of honeybee larvae, but its pathogenic mechanisms are still poorly understood. The causative agent, Melissococcus plutonius, is a fastidious organism, and microaerophilic to anaerobic conditions and the addition of potassium phosphate to culture media are required for growth. Although M. plutonius is believed to be remarkably homologous, in addition to M. plutonius isolates with typical cultural characteristics, M. plutonius-like organisms, with characteristics seemingly different from those of typical M. plutonius, have often been isolated from diseased larvae with clinical signs of EFB in Japan. Cultural and biochemical characterization of 14 M. plutonius and 19 M. plutonius-like strain/isolates revealed that, unlike typical M. plutonius strain/isolates, M. plutonius-like isolates were not fastidious, and the addition of potassium phosphate was not required for normal growth. Moreover, only M. plutonius-like isolates, but not typical M. plutonius strain/isolates, grew anaerobically on sodium phosphate-supplemented medium and aerobically on some potassium salt-supplemented media, were positive for β-glucosidase activity, hydrolyzed esculin, and produced acid from L-arabinose, D-cellobiose, and salicin. Despite the phenotypic differences, 16S rRNA gene sequence analysis and DNA-DNA hybridization demonstrated that M. plutonius-like organisms were taxonomically identical to M. plutonius. However, by pulsed-field gel electrophoresis analysis, these typical and atypical (M. plutonius-like isolates were separately grouped into two genetically distinct clusters. Although M. plutonius is known to lose virulence quickly when cultured artificially, experimental infection of representative isolates showed that atypical M. plutonius maintained the ability to cause EFB in honeybee larvae even after cultured in vitro in laboratory media. Because the rapid decrease of virulence in cultured M

  20. Diversity of Melissococcus plutonius from honeybee larvae in Japan and experimental reproduction of European foulbrood with cultured atypical isolates.

    Science.gov (United States)

    Arai, Rie; Tominaga, Kiyoshi; Wu, Meihua; Okura, Masatoshi; Ito, Kazutomo; Okamura, Naomi; Onishi, Hidetaka; Osaki, Makoto; Sugimura, Yuya; Yoshiyama, Mikio; Takamatsu, Daisuke

    2012-01-01

    European foulbrood (EFB) is an important infectious disease of honeybee larvae, but its pathogenic mechanisms are still poorly understood. The causative agent, Melissococcus plutonius, is a fastidious organism, and microaerophilic to anaerobic conditions and the addition of potassium phosphate to culture media are required for growth. Although M. plutonius is believed to be remarkably homologous, in addition to M. plutonius isolates with typical cultural characteristics, M. plutonius-like organisms, with characteristics seemingly different from those of typical M. plutonius, have often been isolated from diseased larvae with clinical signs of EFB in Japan. Cultural and biochemical characterization of 14 M. plutonius and 19 M. plutonius-like strain/isolates revealed that, unlike typical M. plutonius strain/isolates, M. plutonius-like isolates were not fastidious, and the addition of potassium phosphate was not required for normal growth. Moreover, only M. plutonius-like isolates, but not typical M. plutonius strain/isolates, grew anaerobically on sodium phosphate-supplemented medium and aerobically on some potassium salt-supplemented media, were positive for β-glucosidase activity, hydrolyzed esculin, and produced acid from L-arabinose, D-cellobiose, and salicin. Despite the phenotypic differences, 16S rRNA gene sequence analysis and DNA-DNA hybridization demonstrated that M. plutonius-like organisms were taxonomically identical to M. plutonius. However, by pulsed-field gel electrophoresis analysis, these typical and atypical (M. plutonius-like) isolates were separately grouped into two genetically distinct clusters. Although M. plutonius is known to lose virulence quickly when cultured artificially, experimental infection of representative isolates showed that atypical M. plutonius maintained the ability to cause EFB in honeybee larvae even after cultured in vitro in laboratory media. Because the rapid decrease of virulence in cultured M. plutonius was a major

  1. Early Cytokine Elevation, PrPres Deposition, and Gliosis in Mouse Scrapie: No Effect on Disease by Deletion of Cytokine Genes IL-12p40 and IL-12p35

    OpenAIRE

    Tribouillard-Tanvier, Déborah; Race, Brent; Striebel, James F.; Carroll, James A.; Phillips, Katie; Chesebro, Bruce

    2012-01-01

    Neurodegenerative diseases are typically associated with an activation of glia and an increased level of cytokines. In our previous studies of prion disease, the cytokine response in the brains of clinically sick scrapie-infected mice was restricted to a small group of cytokines, of which IL-12p40, CCL2, and CXCL10 were present at the highest levels. The goal of our current research was to determine the relationship between cytokine responses, gliosis, and neuropathology during prion disease....

  2. Atypical form of cat scratch disease in immunocompetent patient

    Directory of Open Access Journals (Sweden)

    Kojić Miroslav

    2013-01-01

    Full Text Available Introduction. Cat scratch disease (CSD is an acute infectious disease with benign course caused by the bacteria Bartonella henselae. Clinically, it is usually manifested as regional lymphadenopathy and mild infective syndrome. Rare forms of the disease which usually occur in immunocompromised presons are: encephalitis, transverse myelitis, neuroretinitis, granulomatosus conjunctivitis, arthritis, hepatitis etc. Case report. We presented an atypical form of cat scratch disease in a young immunocompetent female person. The disease was manifested with prolonged fever, rash, purulent lymphadenitis and hepatitis. The diagnosis was based on characteristic patohystological finding and exclusion of the other causes of lymphadenopathy. The patient was treated by antibiotics for a few weeks, with surgical incision and drainage of the purulent lymphadenitis. Conclusion. Atypical forms of CSD could be an important differential-diagnostic problem, especially if there is no opportunity for serological confirmation of the disease.

  3. Multiplicity of A-type and related stars

    CERN Document Server

    North, Pierre L

    2013-01-01

    The origin of chemically peculiar stars remains enigmatic, especially regarding their frequency among their "normal" peers. In addition to magnetic fields and rotation, multiplicity may shed light on the question. We mention the main surveys of the three kinds performed so far of intermediate mass stars, either normal or chemically peculiar, magnetic or not: imaging, spectroscopic, and photometric. We also consider the mulitiplicity of red giant stars, since many of them are descendants of A-type stars, through Mermilliod's radial velocity monitoring of open cluster members. We briefly review the orbital properties of binary systems hosting chemically peculiar stars. Some specific objects of special interest are mentioned as deserving further study. Finally, we recall that some binary systems composed of A-type stars are progenitors of Type Ia supernovae, and evoke the potentialities of future surveys like Gaia.

  4. Combined Papillated Bowen Disease and Clear Cell Atypical Fibroxanthoma

    Directory of Open Access Journals (Sweden)

    Dimas Suárez-Vilela

    2010-05-01

    Full Text Available We describe a case of papillated Bowen disease (PBD, associated with a clear cell atypical fibroxanthoma (CCAFXA. The epidermal lesion showed a bowenoid papillomatous growth pattern with histologic features suggestive of infection by human papilloma virus (HPV. In the dermis a neoplasm made up by spindled or polygonal cells with wide clear cytoplasm and moderate nuclear pleomorphism was found. Immunohistochemical characteristics of these two lesions were clearly different. The atypical cells of the intraepidermal proliferation were positive for AE1-AE3 anticytokeratin antibody, EMA, p16, p53 and p63. The dermal tumor was positive for vimentin, CD10, CD68, CD99, alpha-1-antitrypsin and c-kit. Histological features and immunohistochemical profile of the dermal tumor corresponded to a CCAFXA, a very uncommon neoplasm of which only 10 cases have been reported. In situ hybridization for numerous types of HPVs was negative in both lesions.

  5. HOSPITAL OUTBREAK OF POST CAESAREAN WOUND INFECTION WITH ATYPICAL MYCOBACTERIA

    Directory of Open Access Journals (Sweden)

    Battu

    2016-06-01

    Full Text Available Study of 18 cases of post-operative CS wound infection due to Atypical Mycobacterium (M. chelonae were found in a single hospital over a six-month period. Though the contaminating source could not be identified, remedial control measures taken includes changing all the operative equipment, autoclave machine, air conditioners, exhaust fans of OT, linen and mattresses and solutions like betadine, savlon, spirit and also suture material replaced with new ones. Antibiotic protocols are changed and daily cleaning of OT with cetrimide solution and daily fumigation for one month. No further Atypical MB infective episode have occurred in the one and a half year since the study. Awareness of this ubiquitous opportunistic organism that is not easily eradicated from the hospital environment and strong suspicion of chronic post-operative wound infection, careful surveillance, detailed attention to disinfectant methods of medical devices and appropriate control measures are essential to prevent potential outbreaks.

  6. Magnetic field in atypical prominence structures: Bubble, tornado and eruption

    CERN Document Server

    Levens, P J; Ariste, A López; Labrosse, N; Dalmasse, K; Gelly, B

    2016-01-01

    Spectropolarimetric observations of prominences have been obtained with the THEMIS telescope during four years of coordinated campaigns. Our aim is now to understand the conditions of the cool plasma and magnetism in `atypical' prominences, namely when the measured inclination of the magnetic field departs, to some extent, from the predominantly horizontal field found in `typical' prominences. What is the role of the magnetic field in these prominence types? Are plasma dynamics more important in these cases than the magnetic support? We focus our study on three types of `atypical' prominences (tornadoes, bubbles and jet-like prominence eruptions) that have all been observed by THEMIS in the He I D_3 line, from which the Stokes parameters can be derived. The magnetic field strength, inclination and azimuth in each pixel are obtained by using the Principal Component Analysis inversion method on a model of single scattering in the presence of the Hanle effect. The magnetic field in tornadoes is found to be more ...

  7. Acute Zonal Occult Outer Retinopathy with Atypical Findings

    Directory of Open Access Journals (Sweden)

    Dimitrios Karagiannis

    2014-01-01

    Full Text Available Background. To report a case of acute zonal occult outer retinopathy (AZOOR with atypical electrophysiology findings. Case Presentation. A 23-year-old-female presented with visual acuity deterioration in her right eye accompanied by photopsia bilaterally. Corrected distance visual acuity at presentation was 20/50 in the right eye and 20/20 in the left eye. Fundus examination was unremarkable. Visual field (VF testing revealed a large scotoma. Pattern and full-field electroretinograms (PERG and ERG revealed macular involvement associated with generalized retinal dysfunction. Electrooculogram (EOG light rise and the Arden ratio were within normal limits bilaterally. The patient was diagnosed with AZOOR due to clinical findings, visual field defect, and ERG findings. Conclusion. This is a case of AZOOR with characteristic VF defects and clinical symptoms presenting with atypical EOG findings.

  8. Atypical feminized male’s agonistic behavior relative to males and females of Nile tilapia (Oreochromis niloticus L.

    Directory of Open Access Journals (Sweden)

    Felipe Becerril-Morales

    2015-11-01

    Full Text Available Early maturity during tilapia culture is a recurring problem. To avoid this, a series of techniques have been developed, including the production of YY-males. This technique involves the use of hormones to produce phenotypic females (XY genotype. However, incomplete transformations are frequently observed and the produced atypical feminized males (AFM could display an ambiguity in the phenotypic expression of behavioral patterns. The aim of this study was to measure the frequency and intensity of aggressive behavior as well as the role that initial residence plays when involving three phenotypes (males, females and AFM. The experiment consisted of three stages. Resident fish were AFM in the first stage, males in the second and females in the third. In each stage the resident fish confronted males, females and AFM acting as intruders. Aggressive behavior was exercised more frequently by resident fish. Intersexual confrontations showed higher levels of aggression compared to intrasexual confrontations. The frequency of confrontations was not significantly different in confrontations involving AFM, however, differences were observed in intensity of aggression. It is possible that an incomplete transformation at physiological level could be responsible for an inaccurate decoding of signal during confrontations.

  9. POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome

    Directory of Open Access Journals (Sweden)

    Cheldi Antonella

    2013-01-01

    Full Text Available Abstract Background POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. Case presentation We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. Conclusion The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.

  10. Atypical Papular Purpuric Eruption Induced by Parvovirus B19 Infection

    OpenAIRE

    Şeyma Kayalı; Nilden Tuygun; Halise Akça; Can Demir Karacan

    2016-01-01

    Parvovirus B19 infection’s most common dermatological manifestation is erythema infectiosum as also known the fifth disease. Rare clinical presentations of parvovirus B 19 like papulopurpuric gloves and socks syndrome and acropetechial syndrome has also been described re­cently. This study presents report of a case with atypical feature and distribution of rash due to parvovirus B19 in­fection. We want to emphasize that pediatricians should consider parvovirus B19 infection of any patient who...

  11. Childhood atypical meningioma with perineural spread: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Feng-Yu.; Wong, Alex Mun-Ching; Wong, Ho-Fai; Ng, Shu-Hang [Chang Gung Memorial Hospital, Department of Diagnostic Radiology, Kwei-Shan, Tao-Yuan (Taiwan); Wu, Chieh-Tsai [Chang Gung Memorial Hospital, Department of Neurosurgery, Kwei-Shan, Tao-Yuan (Taiwan); Lin, Kuang-Lin [Chang Gung Memorial Hospital, Division of Pediatric Neurology, Kwei-Shan, Tao-Yuan (Taiwan)

    2005-09-01

    Meningiomas are uncommon in children. When they occur, they are frequently associated with neurofibromatosis type 2. Childhood meningiomas are generally large and commonly associated with cyst formation and an unusual location. Perineural tumor spread, occasionally associated with head and neck malignancies, is very rare in meningiomas. We present the MR findings of an atypical meningioma with perineural spread in a 4.5-year-old girl. (orig.)

  12. Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Guo-yu Hu; Chao-hui Yuan; Kui Tan; Zhen-zhen Chen

    2011-01-01

    ATYPICAL chronic myeloid leukaemia (aCML),which shows both myeloproliferative and myeIodysplastic features,is a type of myeloproliferative/myelodysplastic disease as defined by the World Health Organisation (WHO) classification of the myeloid neoplasms.1 Because of the presence of neutrophilic leukocytosis,aCML may resemble chronic myeIogenous leukemia (CML).However,in contrast with CML,aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

  13. Epithelioid Schwannomas: An Analysis of 58 Cases Including Atypical Variants.

    Science.gov (United States)

    Hart, Jesse; Gardner, Jerad M; Edgar, Mark; Weiss, Sharon W

    2016-05-01

    The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y). Two patients had schwannomatosis 1. Tumors developed in the dermis/subcutis (n=56) or muscle (n=2) of the upper extremity (34.5%), lower extremity (34.5%), thorax/abdomen/back (18%), and less common anatomic locations including the scalp, neck, lip, and breast. They ranged in size from 0.25 to 4.5 cm (median, 2.0 cm). Typically circumscribed and surrounded by a perineurium, they comprised single or small groups of epithelioid schwann cells with a moderate amphophilic cytoplasm and occasional nuclear pseudoinclusions. Stroma varied from myxoid to hyalinized, often with thick-walled vessels (55 cases). Mitotic rate ranged from 0 to 9 mitoses/10 high-power field (HPF) (2.37 mm) in the most active areas (mean, 2 to 3 mitoses/10 HPFs). Thirteen cases (22%) were "atypical," defined by a high mitotic rate (≥3 mitoses per 10 HPFs) and nuclear size variation (≥3:1). All (56/56) expressed S100 protein; type IV collagen invested groups or individual cells (16/17). Melanoma markers were negative, except for melan A (1 case). Follow-up in 39 patients (median, 78 mo; range, 6 to 174 mo) indicated that 31 (79%) were alive without disease (including 9/13 atypical cases; median, 78 mo), 7 (18%) were alive with unknown status, and 1 patient had died of unrelated causes. One tumor recurred, but none metastasized. Epithelioid schwannomas, even those with atypical features, are benign and do not constitute a histologic continuum with epithelioid malignant peripheral nerve sheath tumors, which typically occur in deep soft tissues and have more anaplastic features. PMID:26752543

  14. Ureterolithiasis: classical and atypical findings on unenhanced helical computed tomography.

    Science.gov (United States)

    Vaswani, Kuldeep K; El-Dieb, Adam; Vitellas, Kenneth M; Bennett, William F; Bova, James G

    2002-03-01

    Evaluation of patients with acute flank pain using helical computed tomography (CT) is a well-accepted, rapid, and safe procedure in the emergency setting. Various primary and secondary signs are described in the literature for evaluation of these patients. Our purpose is to demonstrate both the classical findings associated with ureteral calculi on unenhanced helical CT and atypical findings and potential pitfalls. We also provide readers with a systematic approach to interpreting unenhanced helical CT scans performed for acute flank pain.

  15. Off-label indications for atypical antipsychotics: A systematic review

    OpenAIRE

    Fountoulakis, Konstantinos N; Nimatoudis, Ioannis; Iacovides, Apostolos; Kaprinis, George

    2004-01-01

    Introduction With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. Material and method MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory d...

  16. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    OpenAIRE

    Mishra Biswaranjan; Mishra Baikunthanath; Sahoo Saddichha; Arora Manu; Khess C.R.J

    2007-01-01

    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 presen...

  17. Atypical Attentional Networks and the Emergence of Autism

    OpenAIRE

    Keehn, Brandon; Müller, Ralph-Axel; Townsend, Jeanne

    2012-01-01

    The sociocommunicative impairments that define autism spectrum disorder (ASD) are not present at birth but emerge gradually over the first two years of life. In typical development, basic attentional processes may provide a critical foundation for sociocommunicative abilities. Therefore early attentional dysfunction in ASD may result in atypical development of social communication. Prior research has demonstrated that persons with ASD exhibit early and lifelong impairments in attention. The p...

  18. Magnetic field in atypical prominence structures: Bubble, tornado and eruption

    OpenAIRE

    Levens, P. J.; Schmieder, B.; Ariste, A. López; Labrosse, N.; Dalmasse, K.; Gelly, B.

    2016-01-01

    Spectropolarimetric observations of prominences have been obtained with the THEMIS telescope during four years of coordinated campaigns. Our aim is now to understand the conditions of the cool plasma and magnetism in `atypical' prominences, namely when the measured inclination of the magnetic field departs, to some extent, from the predominantly horizontal field found in `typical' prominences. What is the role of the magnetic field in these prominence types? Are plasma dynamics more important...

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

    OpenAIRE

    Mila eVulchanova; David eSaldaña; Sobh eChahboun; Valentin eVulchanov

    2015-01-01

    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 la...

  20. Long-term Deformation Measurements of Atypical Roof Timber Structures

    Directory of Open Access Journals (Sweden)

    Jiří Bureš

    2014-06-01

    Full Text Available The paper includes conclusions from evaluation of results obtained from long-termmeasuring of innovative atypical roof timber structures. Based on the results ofmeasurements of vertical and horizontal deformation components it is possible to analyzethe real behavior of structures in given conditions. By assessing deformations in variousstages, including particularly external and internal environment temperatures, relative airhumidity and moisture content of wood, decisive parameters for real structure behaviorcan be established. The data are processed from period 2001 – 2013.

  1. Atypical demyelinating lesions in patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Yetkin, Z. [Dept. of Radiology, Medical Coll. of Wisconsin, Milwaukee, WI (United States); Haughton, V.M. [Dept. of Radiology, Medical Coll. of Wisconsin, Milwaukee, WI (United States)]|[Dept. of Radiology, Medical Coll. of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee, WI (United States)

    1995-05-01

    We describe an atypical MRI appearance of multiple sclerosis (MS). Lesions characterized on T2-weighted images by a well-defined rim of increased signal intensity and a concentric region of higher signal intensity were seen in 6 of 132 patients with MS. On T1-weighted images these lesions were evident as regions of low signal intensity, often with a rim of contrast enhancement or increased signal intensity. These appearances tended to be shown by new, evolving lesions. (orig.)

  2. Identification of an emergent and atypical Pseudomonas viridiflava lineage causing bacteriosis in plants of agronomic importance in a Spanish region.

    Science.gov (United States)

    González, Ana J; Rodicio, M Rosario; Mendoza, M Carmen

    2003-05-01

    Pseudomonas strains with an atypical LOPAT profile (where LOPAT is a series of determinative tests: L, levan production; O, oxidase production; P, pectinolitic activity; A, arginine dihydrolase production; and T, tobacco hypersensibility) can be regarded as emergent pathogens in the Principality of Asturias (Spain), where they have been causing, since 1999, severe damage in at least three taxonomically unrelated orchard plants of agronomic importance: common bean (Phaseolus vulgaris), kiwifruit (Actinidia deliciosa), and lettuce (Lactuca sativa). These strains are mainly differentiated by production of yellowish mucoid material in hypersucrose medium, used for the levan test, and by a variable pectinolytic activity on different potato varieties. The atypical organisms were identified as Pseudomonas viridiflava based on their 16S rRNA sequences. Among them a certain intraspecies genetic heterogeneity was detected by randomly amplified polymorphic DNA (RAPD) typing. To differentiate between isolates of P. viridiflava and Pseudomonas syringae pathovars, a 16S ribosomal DNA restriction fragment length polymorphism method employing the restriction endonucleases SacI and HinfI was developed. This could be used as a means of reliable species determination after the usual phenotypical characterization, which includes the LOPAT tests. PMID:12732569

  3. Phenotypic transition of microglia into astrocyte-like cells associated with disease onset in a model of inherited ALS

    OpenAIRE

    Emiliano eTrias; Pablo eDíaz-Amarilla; Silvia eOlivera-Bravo; Eugenia eIsasi; Drechsel, Derek A.; Nathan eLopez; Charles Samuel Bradford; Kyle Edward Ireton; Beckman, Joseph S; Luis Hector Barbeito

    2013-01-01

    Microglia and reactive astrocytes accumulate in the spinal cord of rats expressing the Amyotrophic lateral sclerosis (ALS)-linked SOD1 G93A mutation. We previously reported that the rapid progression of paralysis in ALS rats is associated with the appearance of proliferative astrocyte-like cells that surround motor neurons. These cells, designated as Aberrant Astrocytes (AbA cells) because of their atypical astrocytic phenotype, exhibit high toxicity to motor neurons. However, the cellular or...

  4. Unusual phenotype of glucose transport protein type 1 deficiency syndrome: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Annio Posar

    2014-01-01

    Full Text Available The glucose transport protein type 1 (GLUT1 deficit causes a chronic brain energy failure. The classic phenotype of GLUT1 deficiency syndrome is characterized by: Mild to severe motor delay and mental retardation; infantile-onset epilepsy; head growth deceleration; movement disorders (ataxia, dystonia, spasticity; and non-epileptic paroxysmal events (intermittent ataxia, periodic confusion, recurrent headaches. During last years the classic phenotype of this syndrome, as originally reported, has expanded. We report the atypical phenotype of a boy with GLUT1 deficiency syndrome, characterized by mild mental retardation and drug-resistant absence seizures with onset at the age of 6 years, without movement disorders nor decrease of head circumference. A prompt diagnosis of this disorder is mandatory since the ketogenic diet might represent an effective treatment.

  5. Atypical Findings of Guillain-Barré Syndrome in Children

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2012-10-01

    Full Text Available ObjectiveGuillain-Barre syndrome (GBS is an immune-mediated polyneuropathy that occurs mostly after prior infection. The diagnosis of this syndrome is dependent heavily on the history and examination, although cerebrospinal fluid analysis and electrodiagnostic testing usually confirm the diagnosis. This is a retrospective study which was performed to investigate the atypical features of GBS.Materials & MethodsThirty three patients (21/63.6% males and 12/36.4% females with GBS were retrospectively studied and prospectively evaluated at the Child Neurology institute of Mofid Children Hospital of Shahid Beheshti University of Medical Sciences between May 2011 and September 2012.ResultsThe mean age was 5.4 years (range, 1.5-10.5.Twenty one patients (87.9 % had previous history of infections. Eight patients (24.2% admitted with atypical symptoms like upper limb weakness (3%, ptosis (3%, neck stiffness (3%, inability to stand (proximal weakness (9.1%, headache (3% and dysphagia (3%.According to disease process, weakness was ascending in 26 (78.8%, descending in 5 (15.2% and static in 2 (6.1% patients. Cranial nerve involvement was found in 8(24.3% children, most commonly as facial palsy in 3 (9.1%.ConclusionIn this study, 24.3% of our patients presented with atypical symptoms of GBS as upper limb weakness, ptosis, neck stiffness, inability to stand (proximal weakness, headache and dysphagia

  6. Elevated rates of atypical handedness in paedophilia: Theory and implications

    Science.gov (United States)

    Fazio, Rachel L.; Lykins, Amy D.; Cantor, James M.

    2014-01-01

    Multiple factors determine handedness including genetics, prenatal stress and post-natal environmental conditions. Atypical handedness, whether manifest as increased sinistrality or decreased strength of lateral preference, has been noted in a wide variety of populations with neuropathology. Those with atypical sexual preferences, specifically paedophilia, also manifest reduced rates of right-handedness. This paper uses the largest sample of phallometrically assessed men to date to establish the pattern of atypical handedness in paedophilia. Specifically, whereas prior research has largely characterized participants dichotomously as right-handed or non-right-handed and/or used self-report of writing hand, this paper expands upon such reports by using the Edinburgh Handedness Inventory's laterality quotient. Participants' handedness and phallometrically assessed sexual preference were analyzed both as continuous and categorical variables, and the responses of those scoring in the range of ambiguous-handedness were evaluated to ascertain whether they were ambiguously handed or more accurately described as mixed-handed. Results indicated those producing scores in the range of ambiguous-handedness demonstrated response patterns consistent with ambiguous-handedness, rather than mixed-handedness. Paedophiles demonstrated high rates of non-right-handedness primarily manifested as sinistrality, whereas those who had a sexual preference for pubescent children evidenced increased ambiguous-handedness. Results support a view of ambiguous-handedness as less pathological than previously hypothesized, and of a neurodevelopmental origin of paraphilic sexual preferences. PMID:24666135

  7. Atypical features of nanophthalmic macula- a spectral domain OCT study

    Directory of Open Access Journals (Sweden)

    Rao Aparna

    2012-06-01

    Full Text Available Abstract Background To report atypical features on Spectral domain optical coherence tomography (SD-OCT in a case of non-familial pure adult nanophthalmos. Case presentation A 39 year old male hyperope was found to have biometric and fundus findings typical of nanophthalmos. The additional atypical features included serous pigment epithelial detachment (PED in right eye and a cuff of subretinal fluid with underlying yellow deposits along superotemporal arcade in the left eye. Fundus flourescein angiogram showed hyperfluorescence due to window defect, dye pooling due to serous PED in right eye and leak superior to disc in right eye and superotemporally in left eye. Cirrus-SD OCT horizontal line scan passing through the fovea showed extensive inner limiting membrane corrugations causing distorted foveal contour in both eyes. A large juxtafoveal serous PED and a small extrafoval PED were seen with folds in the retinal pigment epithelium (RPE-choriocapillary layer in the right eye. Conclusion Structural disruptions in the RPE-choriocapillary complex in the form of folds or juxtafoveal serous PED and RPE folds can be atypical features of nanophthalmic macula better discerned on high resolution OCT.

  8. Paranoid personality masking an atypical case of frontotemporal dementia.

    Science.gov (United States)

    Iroka, Nneka; Jehangir, Waqas; Ii, Jay Littlefield; Pattan, Vishwanath; Yousif, Abdalla; Mishra, Arunesh K

    2015-05-01

    Frontotemporal dementia (FTD) is a debilitating disease that is well described in the "Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5)", and typically presents with memory impairment, progressive decline in cortical functioning, and behavioral changes. Age of onset is generally in the late fifties, and usually the first presentation involves a change in behavior and emotional blunting. Treatment of FTD involves management of any neurobehavioral symptoms while trials of atypical antipsychotics are ongoing but suggest some efficacy. We present a case of a patient who first presented with severe paranoid personality traits and frank persecutory delusions. This atypical presentation of our patient first led to her incorrect diagnosis of a psychotic disorder and paranoid personality disorder. As a result of this diagnosis, she was treated unsuccessfully. A subsequent magnetic resonance imaging (MRI) then showed atrophy of frontal and temporal lobes bilaterally (left more prominent than right) which confirmed the diagnosis of FTD. The importance of this case involves the atypical presentation of paranoia and delusions, and our patient's incorrect diagnosis based on her clinical presentation led to a trial of unsuccessful treatment. Only after performing an MRI, which showed atrophy, was the patient appropriately treated and deemed medically stable. This case report illustrates the importance of considering a rare presentation of frontotemporal lobe dementia with patients who are in the typical age range and present with paranoia and delusions.

  9. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Brett Silverstein

    2015-01-01

    Full Text Available Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1 The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2 Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3 Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4 Most probands who report atypical depression meet criteria for “somatic depression,” defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as “reactive” appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

  10. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder.

    Science.gov (United States)

    Silverstein, Brett; Angst, Jules

    2015-01-01

    Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression. PMID:26258131

  11. Atypical acute urticaria in children and its relationship with urticarial vasculitis

    OpenAIRE

    ARSLAN, Zafer; ÖZMEN, Serap; SÜRMELİ, Sara; ARDA, Nilüfer

    2011-01-01

    In childhood, urticarial lesions are sometimes associated with purpura. This form might be identified as atypical, and may also be related to urticarial vasculitis (UV). The aim of this study was to assess the clinicopathologic characteristics of UV in children with atypical urticaria. Materials and methods: Fifteen children with atypical urticaria were evaluated with medical history, physical examination, and laboratory and skin punch biopsy findings. Results: Infections were detected as...

  12. Solitary Atypical Adenomatous Hyperplasia in a 12-Year-Old Girl.

    Science.gov (United States)

    Jin, Moran; Lee, Yang-Haeng; Kim, Bomi; Yoon, Young Chul; Wi, Jin Hong

    2016-04-01

    Atypical adenomatous hyperplasia is a premalignant lesion reflecting a focal proliferation of atypical cells. These lesions are usually observed as incidental findings in lungs that have been resected due to other conditions, such as lung cancer. We report the youngest case of atypical adenomatous hyperplasia on record in a 12-year-old girl. In this patient, the lesion was found in association with pneumothorax.

  13. Healthcare Costs of Atypical Antipsychotic Use for Patients with Bipolar Disorder in a Medicaid Programme

    OpenAIRE

    Ying Qiu; Fu, Alex Z; Gordon G. Liu; Christensen, Dale B.

    2010-01-01

    Background: A large body of clinical studies have demonstrated the efficacy of atypical antipsychotic use in the treatment of bipolar disorder. Facing increasing budget pressure, third-party payers, such as state Medicaid programmes in the US, are demanding better understanding of the medical costs beyond atypical antipsychotic drug costs alone in treating bipolar disorder. Objective: To examine healthcare costs associated with the atypical antipsychotic treatments for bipolar disorder from a...

  14. Genetic Characterization of Atypical Mansonella (Mansonella) ozzardi Microfilariae in Human Blood Samples from Northeastern Peru

    OpenAIRE

    Marcos, Luis A.; Arrospide, Nancy; Recuenco, Sergio; Cabezas, Cesar; Gary J Weil; Fischer, Peter U.

    2012-01-01

    DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical microfilariae were clustered into the Mansonella...

  15. Atypical depression in the structure of organic mental disorders (literature review)

    OpenAIRE

    Leonov S.F.; Shusterman T.Y.; Rokutov S.V.; Shornikov A.V.

    2014-01-01

    The review of literature presents current data on cli¬nical picture and diagnostics of atypical depression. Rubric “atypical depression” includes a variety of depressive states characterized by reactively caused changes of mood, sensitivity to interpersonal contacts, inverted vegetative and somatic symptoms such as increased appetite and hypersomnia. The article considers the place of atypical depression in the structure of organic mental disorders. Positions of foreign authors that produce a...

  16. Atypical depression in the structure of organic mental disorders (literature review).

    OpenAIRE

    Spirina, I. D.; Leonov, S. F.; Shusterman, T. Y.; Rokutov, S. V.; Shornikov, A. V.

    2014-01-01

    The review of literature presents current data on cli­nical picture and diagnostics of atypical depression. Rubric “atypical depression” includes a variety of depressive states characterized by reactively caused changes of mood, sensitivity to interpersonal contacts, inverted vegetative and somatic symptoms such as increased appetite and hypersomnia. The article considers the place of atypical depression in the structure of organic mental disorders. Positions of foreign authors that produce a...

  17. Modeling and Estimation Techniques for Wide-Area Network Traffic with Atypical Components

    OpenAIRE

    Minton, Carl Edward

    2002-01-01

    A critical first step to improving existing and designing future wide-area networks is an understanding of the load placed on these networks. Efforts to model traffic are often confounded by atypical traffic - traffic particular to the observation site not ubiquitously applicable. The causes and characteristics of atypical traffic are explored in this thesis. Atypical traffic is found to interfere with parsimonious analytic traffic models. A detection and modeling tech...

  18. Atypical presentation of a cervical breast-cancer metastasis mimicking a dumbbell-shaped neurinoma

    Directory of Open Access Journals (Sweden)

    Christoph Kolja Boese

    2014-01-01

    CONCLUSION: The present case report and the reviewed literature point towards a growing clinical relevance of symptomatic LM in cancer patients and their possible atypical presentations and locations.

  19. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M;

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection...

  20. The Broad Autism Phenotype Questionnaire

    Science.gov (United States)

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  1. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  2. Atypical lymphocytes in malaria mimicking dengue infection in Thailand

    Directory of Open Access Journals (Sweden)

    Polrat Wilairatana

    2010-09-01

    Full Text Available Polrat Wilairatana1, Noppadon Tangpukdee1, Sant Muangnoicharoen1, Srivicha Krudsood2, Shigeyuki Kano31Department of Clinical Tropical Medicine, 2Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 3Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, JapanAbstract: Patients with uncomplicated falciparum or vivax malaria usually present with acute febrile illness and thrombocytopenia similar to dengue infection. We retrospectively studied atypical lymphocytes (AL and atypical lymphocytosis (ALO, defined as AL > 5% of total white blood cells in 1310 uncomplicated malaria patients. In 718 falciparum malaria patients, AL and ALO on day 0 were found in 53.2% and 5.7% of the patients, respectively, with median AL on admission of 1% (range 0%–10%, whereas in 592 vivax malaria patients, AL and ALO on day 0 were found in 55.4% and 9.5% of the patients, respectively, with median AL on admission of 1% (range 0%–14%. After antimalarial treatment, AL and ALO declined in both falciparum and vivax malaria. However, AL and ALO remained in falciparum malaria on days 7, 14, and 21, whereas AL and ALO remained in vivax malaria on days 7, 14, 21, and 28. In both falciparum and vivax malaria patients, there was a positive correlation between AL and total lymphocytes, but a negative correlation between AL and highest fever on admission, white blood cells, and neutrophils, eosinophils, and platelets (P < 0.05. In conclusion, AL or ALO may be found in uncomplicated falciparum and vivax malaria mimicking dengue infection. In tropical countries where both dengue and malaria are endemic, presence of AL or ALO in any acute febrile patients with thrombocytopenia (similar to the findings in dengue malaria could not be excluded. Particularly if the patients have risk of malaria infection, confirmative microscopic examination for malaria should be carried out

  3. Macrokinetics of Ethylene Epoxidation over A-type Silver Catalyst

    Institute of Scientific and Technical Information of China (English)

    Liang Rujun; Li Jianwei

    2015-01-01

    By taking the surface chemical reactions as the rate-controlling step, a possible reaction mechanism for ethylene epoxidation to synthesize ethylene oxide over the A-type silver catalyst was developed, while it was assumed that the ep-oxidation reaction would take place between ethylene and the un-dissociated adsorbed oxygen O2a on the solo active sites, while the deep oxidation would occur between ethylene and the dissociated adsorbed oxygen Oa on the adjacent multi-active sites. In order to describe the effect of 1,2-C2H4Cl2 (EDC) inhibitor on the ethylene epoxidation process, the reversible reac-tions between EDC and vinyl chloride (VC) on the active sites of silver catalyst was introduced. According to the assumed mechanism, the hyperbolic macro-kinetic model of ethylene epoxidation over the A-type silver catalyst was established, and the macrokinetic experiments were carried out in an internal-recycle gradientless reactor operating at a pressure of 2.1 MPa and a temperature in the range of 217.8—249.0℃, with the gas composition (molar fraction) consisting of 15.82%—34.65%C2H4, 2.55%—7.80%O2, 0.88%—6.15%CO2, 0.15—2.61μmol/mol of 1,2-C2H4Cl2 and 0.14—1.28μmol/mol of C2H3Cl. By means of the Simplex Optimal Method, the parameters of the macrokinetic models were estimated. Statistical test showed that the macrokinetic models developed for the A-type silver catalyst agree well with the experimental results.

  4. CD21-positive follicular dendritic cells: A possible source of PrPSc in lymph node macrophages of scrapie-infected sheep.

    Science.gov (United States)

    Herrmann, Lynn M; Cheevers, William P; Davis, William C; Knowles, Donald P; O'Rourke, Katherine I

    2003-04-01

    Natural sheep scrapie is a prion disease characterized by the accumulation of PrP(Sc) in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrP(Sc). In this study, lymph nodes were analyzed for the presence of PrP(Sc) and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However, a PrP N-terminus-specific mAb reacted with CD21+ FDC processes but not CD172a+ macrophages in secondary follicles. Neither the PrP N-terminus nor C-terminus-specific mAb reacted with CD172a+ macrophages in the medulla. These results indicate that lymph node follicular macrophages acquire PrP(Sc) by phagocytosis of CD21+ FDC processes. The results also suggest that follicular macrophages have proteases that process full-length PrP(Sc) to N-terminally truncated PrP(Sc). PMID:12651600

  5. Pressure-assisted dissociation and degradation of "proteinase K-resistant" fibrils prepared by seeding with scrapie-infected hamster prion protein.

    Science.gov (United States)

    Akasaka, Kazuyuki; Maeno, Akihiro; Murayama, Taichi; Tachibana, Hideki; Fujita, Yuzo; Yamanaka, Hitoki; Nishida, Noriyuki; Atarashi, Ryuichiro

    2014-01-01

    The crucial step for the fatal neurodegenerative prion diseases involves the conversion of a normal cellular protein, PrP(C), into a fibrous pathogenic form, PrP(Sc), which has an unusual stability against heat and resistance against proteinase K digestion. A successful challenge to reverse the reaction from PrP(Sc) into PrP(C) is considered valuable, as it would give a key to dissolving the complex molecular events into thermodynamic and kinetic analyses and may also provide a means to prevent the formation of PrP(Sc) from PrP(C) eventually in vivo. Here we show that, by applying pressures at kbar range, the "proteinase K-resistant" fibrils (rHaPrP(res)) prepared from hamster prion protein (rHaPrP [23-231]) by seeding with brain homogenate of scrapie-infected hamster, becomes easily digestible. The result is consistent with the notion that rHaPrP(res) fibrils are dissociated into rHaPrP monomers under pressure and that the formation of PrP(Sc) from PrP(C) is thermodynamically controlled. Moreover, the efficient degradation of prion fibrils under pressure provides a novel means of eliminating infectious PrP(Sc) from various systems of pathogenic concern.

  6. Atypical Papular Purpuric Eruption Induced by Parvovirus B19 Infection

    Directory of Open Access Journals (Sweden)

    Şeyma Kayalı

    2016-03-01

    Full Text Available Parvovirus B19 infection’s most common dermatological manifestation is erythema infectiosum as also known the fifth disease. Rare clinical presentations of parvovirus B 19 like papulopurpuric gloves and socks syndrome and acropetechial syndrome has also been described re­cently. This study presents report of a case with atypical feature and distribution of rash due to parvovirus B19 in­fection. We want to emphasize that pediatricians should consider parvovirus B19 infection of any patient who has leukopenia presenting with petechial/purpuric eruption of an unclear origin.

  7. Dengue Fever Presenting Atypically with Viral Conjunctivitis and Subacute Thyroiditis.

    Science.gov (United States)

    Sheraz, Faizan; Tahir, Hassan; Saqi, Jannavi; Daruwalla, Vistasp

    2016-06-01

    The majority of dengue viral infections are asymptomatic, though symptoms may range from self-limiting febrile illness to life threatening hemorrhagic manifestations. As the burden of disease is dramatically rising in recent years, more patients with atypical presentations and rare complications are increasingly reported. Dengue virus may rarely involve different organ systems including CNS, liver, and heart. However, involvement of eye and thyroid is extremely rare. We present a case of 32-year old patient who presented with conjunctivitis and subacute thyroiditis and was found to have dengue viral infection as the cause of these conditions. PMID:27376214

  8. Atypical presentation of sporotrichosis: report of three cases

    Directory of Open Access Journals (Sweden)

    Melissa Orzechowski Xavier

    2013-01-01

    Full Text Available Sporotrichosis occurs after fungal implantation of Sporothrix spp. in the skin, and is the main subcutaneous mycosis in Latin America. Here we describe three atypical cases of the disease. The first case report an extra-cutaneous occurrence of the disease with joint infection; the second one describes a patient with bilateral lymphocutaneous form of sporotrichosis; and the third shows a zoonotic cutaneous case with the development of an erythema nodosum as a hypersensitivity reaction. These cases show the disease importance on the region and the necessity of fungal culture to the diagnosis confirmation.

  9. Quantitative methods for somatosensory evaluation in atypical odontalgia

    DEFF Research Database (Denmark)

    Porporatti, André Luís; Costa, Yuri Martins; Stuginski-Barbosa, Juliana;

    2015-01-01

    A systematic review was conducted to identify reliable somatosensory evaluation methods for atypical odontalgia (AO) patients. The computerized search included the main databases (MEDLINE, EMBASE, and Cochrane Library). The studies included used the following quantitative sensory testing (QST......) methods: mechanical detection threshold (MDT), mechanical pain threshold (MPT) (pinprick), pressure pain threshold (PPT), dynamic mechanical allodynia with a cotton swab (DMA1) or a brush (DMA2), warm detection threshold (WDT), cold detection threshold (CDT), heat pain threshold (HPT), cold pain detection...... compared with healthy subjects. In clinical settings, the most reliable evaluation method for AO in patients with persistent idiopathic facial pain would be intraindividual assessments using HPT or mechanical allodynia tests....

  10. AMELANOTIC MELANOMA WITH ATYPICAL CLINICAL PRESENTATION AND MULTIPLE METASTASIS

    Directory of Open Access Journals (Sweden)

    Revathy

    2014-11-01

    Full Text Available A 52 year old woman presented with a history of asymptomatic skin lesions over left leg for the past 4 months. On examination she had multiple skin coloured papules and plaques over left leg. Oedema was also seen over left leg. Histopathology and immunohistochemistry proved the diagnosis of malignant melanoma. Radiological investigation showed metastasis to lung, liver and brain. The patient was asymptomatic at the time of admission but she developed rapid metastasis within a very short span of time. This case is reported for the rare atypical presentation of malignant melanoma.

  11. A family of congenital hepatic fibrosis and atypical retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Sunil Pawar

    2015-11-01

    Full Text Available Congenital hepatic fibrosis is a rare cause of portal hypertension and esophageal varices in children. We report cases of siblings with biopsy proven congenital hepatic fibrosis and with atypical retinitis pigmentosa. They presented with repeated episodes of jaundice along with progressive decrease of vision in night. They had hepatosplenomegaly and portal hypertension with esophageal varices. One of the siblings had a large regenerating nodule replacing the entire right lobe of the liver and other one developed repeated hematemesis. This constellation of diagnosis belongs to the ciliopathy group of disorders. The spectrum of ciliopathy disorders has been evolving, and it varies from mild to severe manifestations.

  12. Emerging molecular phenotypes of asthma.

    Science.gov (United States)

    Ray, Anuradha; Oriss, Timothy B; Wenzel, Sally E

    2015-01-15

    Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease. PMID:25326577

  13. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15

    Directory of Open Access Journals (Sweden)

    Sigman Marian

    2008-01-01

    Full Text Available Abstract Background Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15] that has been called inverted duplication 15 or isodicentric 15 [idic(15], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15 chromosomes arise through BP3:BP3 or BP4:BP5 recombination events. Results Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15, we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15 and the normal homologues. Conclusion Involvement of atypical BP in the generation of idic(15 chromosomes can lead to considerable structural heterogeneity.

  14. Fungal rhinosinusitis with atypical presentation - a report of two cases

    Institute of Scientific and Technical Information of China (English)

    Rafael da Costa Monsanto; Rodrigo Silva Orem; Fernanda Resende e Silva; Fabio Hiroshi Okuyama; Fabio Tadeu Moura Lorenzetti

    2015-01-01

    Rhinosinusitis affects approximately 20% of the population, and the chronic rhinosinusitis represents over 90% of all cases of rhinosinusitis. The correct diagnosis is important for proper treatment and to predict its evolution. This study presents two cases of atypical frontal sinus disease, which the follow-up revealed a diagnosis of fungal rhinosinusitis. The present study aims to describe the cases of two patients with atypical lesions on the left frontal sinus; the treatment options, surgical approach, results, diagnosis and follow-up are further discussed. A significant increase in the reported cases of fungal rhinosinusitis has been seen in the last two decades, justified by the use of broad-spectrum antibiotics and steroids, as well as the increased number of immunocompromised individuals. This study reports the cases of two patients with a type of fungal rhinosinusitis named "fungal ball", characterized by a tangle of hyphae in the sinuses without tissue invasion. The treatment included surgical removal of the fungal infectious process with aeration of the affected sinus, and the procedure was successfully performed in our patients.

  15. Atypical oculopalatal tremor as the presentation of vertebral artery dolichoectasia

    Science.gov (United States)

    Vanikieti, Kavin; Cheecharoen, Piyaphon; Jindahra, Panitha; Lueangaram, Sirin; Padungkiatsagul, Tanyatuth

    2016-01-01

    Vertebrobasilar dolichoectasia (VBD) is a rare dilative arteriopathy defined as elongation or widening of the intracranial vertebral and/or basilar arteries. The prevalence ranges from 0.06% to 5.8%. The majority of VBDs are asymptomatic. Downbeat nystagmus has been reported as a component of an infrequent ocular movement disorder in VBD. Nevertheless, oculopalatal tremor (OPT), delayed sequelae of a brainstem lesion, has never been demonstrated in VBD cases. Synchronized rhythmic involuntary contractions of the soft palate with an ocular pendular nystagmus, predominantly vertical pendular nystagmus, are the hallmark presentation. Our case demonstrated a 50-year-old female who presented with 3-month history of oscillopsia. Examination showed binocular conjugate torsional jerk nystagmus simultaneous with a contraction of the soft palate, defined as an atypical OPT, resulting from dolichoectatic left vertebral artery compressing on medulla, demonstrated by magnetic resonance imaging. Bilateral conjugate torsional jerk nystagmus simultaneous with palatal tremor, considering as an atypical OPT, should be included as one of the symptomatic presentations of vertebral artery dolichoectasia in spite of its rarity. PMID:27660495

  16. Atypical dermatophilosis of sheep in Kenya : clinical communication

    Directory of Open Access Journals (Sweden)

    J.K. Wabacha

    2007-06-01

    Full Text Available An outbreak of an atypical form of ovine dermatophilosis affecting the lips and muzzle with a very high morbidity in weaners and hoggets in Kenya is reported. Clinical diagnosis of ovine dermatophilosis was made and confirmed by direct microscopic examination as well as isolation and identification of Dermatophilus congolensis from scab material from the affected sheep. The morbidity rate within the flock was 31.8 % (237 / 745 with 98.3 % (233 / 237 of the affected sheep being weaners and hoggets. No fatalities were recorded. The lesions, confined in the lips and the muzzle, were swelling of both the upper and lower lips, circumscribed lumps in the skin of both the upper and lower lips, oedema of the head and the submandibular area and scabs and crusts on the lips and muzzle. Within 1 week following treatment with long acting oxytetracycline (20 % at a rate of 20 mg/kg body weight, intramuscularly and a topical application of oxytetracycline spray, lumps regressed in size and were covered by dark-brown scabs. Removal of the dark-brown scabs revealed erythematous areas covered with purulent material and horny erythematous projections (papillae projecting from the surfaces. Within the 2nd week, the horny erythematous projections formed greyish scabs, which later peeled off leaving alopaecic areas around the lips. The paper highlights atypical dermatophilosis of sheep and we believe that this is the first published report of an outbreak of ovine dermatophilosis in Kenya.

  17. Atypical streptococcal infection of gingiva associated with chronic mouth breathing.

    Science.gov (United States)

    Haytac, M Cenk; Oz, I Attila

    2007-01-01

    Streptococcal infections of oral tissues are mainly seen in young children who experience a variety of upper respiratory tract infections. The disease is characterized by fever, lymphadenopathy, and ulcers on the gingiva, lips, and tonsils. This case report presents an atypical streptococcal infection of the gingiva in an 18-year-old man. The patient was referred to the periodontology department complaining of a 2-month history of gingival enlargement. He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. Based on the otolaryngologic consultation and the hematologic, immunologic, and microbiologic tests, the final diagnosis was an atypical streptococcal gingivitis with chronic adenoid-related mouth breathing and oral hygiene neglect as contributing factors. Treatment consisted of a broad-spectrum antibiotic regimen, supragingival and subgingival debridement, adenoidectomy, and scaling and root planing. A good response to nonsurgical therapy was achieved despite poor patient compliance, and no recurrence of gingival enlargement was observed after 1 year. Streptococcal gingivitis should be included in the differential diagnosis of suppurative gingival enlargements. Furthermore, chronic mouth breathing may initiate and/or contribute to this disease.

  18. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

    Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

  19. Breast Metastases from Extramammary Malignancies: Typical and Atypical Ultrasound Features

    Energy Technology Data Exchange (ETDEWEB)

    Mun, Sung Hee [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Department of Radiology, Catholic University of Daegu College of Medicine, Daegu 712-702 (Korea, Republic of); Ko, Eun Young; Han, Boo-Kyung; Shin, Jung Hee [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Kim, Suk Jung [Department of Radiology, Inje University College of Medicine, Busan Paik Hospital, Busan 614-735 (Korea, Republic of); Cho, Eun Yoon [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)

    2014-07-01

    Breast metastases from extramammary malignancies are uncommon. The most common sources are lymphomas/leukemias and melanomas. Some of the less common sources include carcinomas of the lung, ovary, and stomach, and infrequently, carcinoid tumors, hypernephromas, carcinomas of the liver, tonsil, pleura, pancreas, cervix, perineum, endometrium and bladder. Breast metastases from extramammary malignancies have both hematogenous and lymphatic routes. According to their routes, there are common radiological features of metastatic diseases of the breast, but the features are not specific for metastases. Typical ultrasound (US) features of hematogenous metastases include single or multiple, round to oval shaped, well-circumscribed hypoechoic masses without spiculations, calcifications, or architectural distortion; these masses are commonly located superficially in subcutaneous tissue or immediately adjacent to the breast parenchyma that is relatively rich in blood supply. Typical US features of lymphatic breast metastases include diffusely and heterogeneously increased echogenicities in subcutaneous fat and glandular tissue and a thick trabecular pattern with secondary skin thickening, lymphedema, and lymph node enlargement. However, lesions show variable US features in some cases, and differentiation of these lesions from primary breast cancer or from benign lesions is difficult. In this review, we demonstrate various US appearances of breast metastases from extramammary malignancies as typical and atypical features, based on the results of US and other imaging studies performed at our institution. Awareness of the typical and atypical imaging features of these lesions may be helpful to diagnose metastatic lesions of the breast.

  20. Breast Metastases from Extramammary Malignancies: Typical and Atypical Ultrasound Features

    International Nuclear Information System (INIS)

    Breast metastases from extramammary malignancies are uncommon. The most common sources are lymphomas/leukemias and melanomas. Some of the less common sources include carcinomas of the lung, ovary, and stomach, and infrequently, carcinoid tumors, hypernephromas, carcinomas of the liver, tonsil, pleura, pancreas, cervix, perineum, endometrium and bladder. Breast metastases from extramammary malignancies have both hematogenous and lymphatic routes. According to their routes, there are common radiological features of metastatic diseases of the breast, but the features are not specific for metastases. Typical ultrasound (US) features of hematogenous metastases include single or multiple, round to oval shaped, well-circumscribed hypoechoic masses without spiculations, calcifications, or architectural distortion; these masses are commonly located superficially in subcutaneous tissue or immediately adjacent to the breast parenchyma that is relatively rich in blood supply. Typical US features of lymphatic breast metastases include diffusely and heterogeneously increased echogenicities in subcutaneous fat and glandular tissue and a thick trabecular pattern with secondary skin thickening, lymphedema, and lymph node enlargement. However, lesions show variable US features in some cases, and differentiation of these lesions from primary breast cancer or from benign lesions is difficult. In this review, we demonstrate various US appearances of breast metastases from extramammary malignancies as typical and atypical features, based on the results of US and other imaging studies performed at our institution. Awareness of the typical and atypical imaging features of these lesions may be helpful to diagnose metastatic lesions of the breast

  1. Differentiation of regions with atypical oligonucleotide composition in bacterial genomes

    Directory of Open Access Journals (Sweden)

    Reva Oleg N

    2005-10-01

    Full Text Available Abstract Background Complete sequencing of bacterial genomes has become a common technique of present day microbiology. Thereafter, data mining in the complete sequence is an essential step. New in silico methods are needed that rapidly identify the major features of genome organization and facilitate the prediction of the functional class of ORFs. We tested the usefulness of local oligonucleotide usage (OU patterns to recognize and differentiate types of atypical oligonucleotide composition in DNA sequences of bacterial genomes. Results A total of 163 bacterial genomes of eubacteria and archaea published in the NCBI database were analyzed. Local OU patterns exhibit substantial intrachromosomal variation in bacteria. Loci with alternative OU patterns were parts of horizontally acquired gene islands or ancient regions such as genes for ribosomal proteins and RNAs. OU statistical parameters, such as local pattern deviation (D, pattern skew (PS and OU variance (OUV enabled the detection and visualization of gene islands of different functional classes. Conclusion A set of approaches has been designed for the statistical analysis of nucleotide sequences of bacterial genomes. These methods are useful for the visualization and differentiation of regions with atypical oligonucleotide composition prior to or accompanying gene annotation.

  2. Atypical Face Perception in Autism: A Point of View?

    Science.gov (United States)

    Morin, Karine; Guy, Jacalyn; Habak, Claudine; Wilson, Hugh R; Pagani, Linda; Mottron, Laurent; Bertone, Armando

    2015-10-01

    Face perception is the most commonly used visual metric of social perception in autism. However, when found to be atypical, the origin of face perception differences in autism is contentious. One hypothesis proposes that a locally oriented visual analysis, characteristic of individuals with autism, ultimately affects performance on face tasks where a global analysis is optimal. The objective of this study was to evaluate this hypothesis by assessing face identity discrimination with synthetic faces presented with and without changes in viewpoint, with the former condition minimizing access to local face attributes used for identity discrimination. Twenty-eight individuals with autism and 30 neurotypical participants performed a face identity discrimination task. Stimuli were synthetic faces extracted from traditional face photographs in both front and 20° side viewpoints, digitized from 37 points to provide a continuous measure of facial geometry. Face identity discrimination thresholds were obtained using a two-alternative, temporal forced choice match-to-sample paradigm. Analyses revealed an interaction between group and condition, with group differences found only for the viewpoint change condition, where performance in the autism group was decreased compared to that of neurotypical participants. The selective decrease in performance for the viewpoint change condition suggests that face identity discrimination in autism is more difficult when access to local cues is minimized, and/or when dependence on integrative analysis is increased. These results lend support to a perceptual contribution of atypical face perception in autism. PMID:25683613

  3. Current status of atypical antipsychotics for the treatment of fibromyalgia.

    Science.gov (United States)

    Rico-Villademoros, F; Calandre, E P; Slim, M

    2014-06-01

    The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

  4. Benign occipital lobe seizures: Natural progression and atypical evolution

    Directory of Open Access Journals (Sweden)

    Prithika Chary

    2013-01-01

    Full Text Available Benign occipital seizure syndromes are benign childhood epilepsy syndromes and are mainly of two types, Panayiotopoulos syndrome, an autonomic epilepsy and idiopathic childhood occipital epilepsy of Gastaut (ICOE-G including the idiopathic photosensitive occipital lobe epilepsy. Although both these types are categorized as occipital seizures, they are distinct in presentation and management. They can also be tricky to diagnose as visual symptoms may not always be the presenting feature and it is also not very easy to elicit visual hallucinations during history taking. These seizures have a good response to treatment; however, there could be atypical evolution and refractoriness to treatment especially with ICOE-G. We describe three children who presented with visual and non-visual symptoms and the electroencephalography (EEG in all the three cases showed occipital paroxysms. We have emphasized the clues in the clinical history and EEG leading to the diagnosis of these distinct epilepsy syndromes. We have also discussed the natural course of these epilepsy syndromes with some atypical evolution, which clinicians need to be aware of during treatment of these children.

  5. Dual mechanism of action of the atypical tetracycline chelocardin.

    Science.gov (United States)

    Stepanek, Jennifer J; Lukežič, Tadeja; Teichert, Ines; Petković, Hrvoje; Bandow, Julia E

    2016-06-01

    Classical tetracyclines targeting the protein biosynthesis machinery are commonly applied in human and veterinary medicine. The development and spread of resistance seriously compromise the successful treatment of bacterial infections. The atypical tetracycline chelocardin holds promise as it retains activity against tetracycline-resistant strains. It has been suggested that chelocardin targets the bacterial membrane, thus differing in mode of action from that of classical tetracyclines. We investigated the mechanism of action of chelocardin using global proteome analysis. The proteome profiles after sublethal chelocardin stress were compared to a reference compendium containing antibiotic response profiles of Bacillus subtilis. This approach revealed a concentration-dependent dual mechanism of action. At low concentrations, like classical tetracyclines, chelocardin induces the proteomic signature for peptidyl transferase inhibition demonstrating that protein biosynthesis inhibition is the dominant physiological challenge. At higher concentrations B. subtilis mainly responds to membrane stress indicating that at clinically relevant concentrations the membrane is the main antibiotic target of chelocardin. Studying the effects on the membrane in more detail, we found that chelocardin causes membrane depolarization but does not lead to formation of large pores. We conclude that at growth inhibiting doses chelocardin not only targets protein biosynthesis but also corrupts the integrity of the bacterial membrane. This dual mechanism of action might prove beneficial in slowing the development of new resistance mechanisms against this atypical tetracycline. PMID:26969785

  6. Creutzfeldt-Jakob disease a case report, with special attention to the electroencephalogram in this disorder and to its possible relationships to kuru, scrapie and «mad cow disease»

    Directory of Open Access Journals (Sweden)

    A.H. Chapman

    1993-06-01

    Full Text Available A case of Creutzfeldt-Jakob disease in a 58-year-old Brazillian cattle rancher and businessman is presented. The EEG was normal, which is consistent with the fact that it was made during the first half of his illness; in a later stage suppression of normal rhythms by slow moderate voltage waves would be expected. The resemblances of kuru, scrapie and "mad cow disease» to C-J disease are discussed. In each of these 4 illnesses the patient or affected animal (scrapie and «mad cow disease" (a has a widespread spongiform encephalopathy and consequent dementia, myoclonic epilepsy and cerebellar and corticospinal symptoms, (b Each illness is caused by a virus (or virus-like organism called a PrP or prion which is unusually resistant to heat and entirely resistant to ultraviolet light and x-rays, (c This causative agent can be transmitted to other mammals by intracerebral injection or, in the proved cases of 3 of them, by the oral route. Unresolved questions about C-J disease include the following: Are C-J disease, kuru, scrapie and "mad cow disease" essentially similar illnesses caused by the same virus or by subtle variants of it? What is the incubation period of C-J disease, and does its virus exist for long periods of time in some asymptomatic persons, some of whom may never become neurologically ill? How does this virus enter the bodies of most persons with C-J disease, and why does the clinical disease characteristically occur only in middle age?

  7. Effects of Physical Atypicality on Children's Social Identities and Intergroup Attitudes

    Science.gov (United States)

    Patterson, Meagan M.; Bigler, Rebecca S.

    2007-01-01

    Individuals vary in the degree to which they are representative, or typical, of their social groups. To investigate the effects of atypicality on intergroup attitudes, elementary-school-age children (N = 97) attending a summer school program were assigned to novel color groups that included typical (blue or green) and atypical (light blue or light…

  8. The involvement of limbic structures in typical and atypical absence epilepsy

    NARCIS (Netherlands)

    Onat, F.Y.; Luijtelaar, E.L.J.M. van; Nehlig, A.; Snead, O.C.

    2013-01-01

    Typical and atypical seizures of absence epilepsy are thought to be generated by a rhythmogenic interplay between the cortex and the thalamus. However, the question remains as to which other subcortical and extrathalamic structures are involved in the pathophysiology of typical and atypical absence

  9. Atypical speech and language development : a consensus study on clinical signs in the Netherlands

    NARCIS (Netherlands)

    Visser-Bochane, Margot I; Gerrits, Ellen; van der Schans, Cees P; Reijneveld, Sijmen A; Luinge, Margreet R

    2016-01-01

    BACKGROUND: Atypical speech and language development is one of the most common developmental difficulties in young children. However, which clinical signs characterize atypical speech-language development at what age is not clear. AIM: To achieve a national and valid consensus on clinical signs and

  10. Automated flagging influences the inconsistency and bias of band cell and atypical lymphocyte morphological differentials.

    NARCIS (Netherlands)

    Meer, W. van der; Scott, C.S.; Keijzer, M.H. de

    2004-01-01

    This study evaluated inter- and intra-observer variabilities of band cell and atypical lymphocyte differentials and the influence of instrument flagging information on resulting microscopic differentials. Five stained slides with a range of band cell counts and five with variable numbers of atypical

  11. Traditional and Atypical Presentations of Anxiety in Youth with Autism Spectrum Disorder

    Science.gov (United States)

    Kerns, Connor Morrow; Kendall, Philip C.; Berry, Leandra; Souders, Margaret C.; Franklin, Martin E.; Schultz, Robert T.; Miller, Judith; Herrington, John

    2014-01-01

    We assessed anxiety consistent (i.e., "traditional") and inconsistent (i.e., "atypical") with diagnostic and statistical manual (DSM) definitions in autism spectrum disorder (ASD). Differential relationships between traditional anxiety, atypical anxiety, child characteristics, anxiety predictors and ASD-symptomology were…

  12. The relationship between atypical visual processing and social skills in young children with autism

    NARCIS (Netherlands)

    Hellendoorn, A.; Langstraat, I.; Wijnroks, L.; Buitelaar, J.; Daalen, E. van; Leseman, P.P.

    2014-01-01

    The present study examined whether atypical visual processing is related to the level of social skills in children with autism spectrum disorder (ASD). Thirty-eight young children with ASD (29 boys, 9 girls) were included. Atypical visual processing was assessed by coding the number of lateral glanc

  13. Next-generation phenotypic screening.

    Science.gov (United States)

    Warchal, Scott J; Unciti-Broceta, Asier; Carragher, Neil O

    2016-07-01

    Phenotypic drug discovery (PDD) strategies are defined by screening and selection of hit or lead compounds based on quantifiable phenotypic endpoints without prior knowledge of the drug target. We outline the challenges associated with traditional phenotypic screening strategies and propose solutions and new opportunities to be gained by adopting modern PDD technologies. We highlight both historical and recent examples of approved drugs and new drug candidates discovered by modern phenotypic screening. Finally, we offer a prospective view of a new era of PDD underpinned by a wealth of technology advances in the areas of in vitro model development, high-content imaging and image informatics, mechanism-of-action profiling and target deconvolution. PMID:27357617

  14. Epigenetics in heart failure phenotypes.

    Science.gov (United States)

    Berezin, Alexander

    2016-12-01

    Chronic heart failure (HF) is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF. PMID:27335803

  15. Capturing phenotypes for precision medicine.

    Science.gov (United States)

    Robinson, Peter N; Mungall, Christopher J; Haendel, Melissa

    2015-10-01

    Deep phenotyping followed by integrated computational analysis of genotype and phenotype is becoming ever more important for many areas of genomic diagnostics and translational research. The overwhelming majority of clinical descriptions in the medical literature are available only as natural language text, meaning that searching, analysis, and integration of medically relevant information in databases such as PubMed is challenging. The new journal Cold Spring Harbor Molecular Case Studies will require authors to select Human Phenotype Ontology terms for research papers that will be displayed alongside the manuscript, thereby providing a foundation for ontology-based indexing and searching of articles that contain descriptions of phenotypic abnormalities-an important step toward improving the ability of researchers and clinicians to get biomedical information that is critical for clinical care or translational research. PMID:27148566

  16. Finding our way through phenotypes.

    Directory of Open Access Journals (Sweden)

    Andrew R Deans

    2015-01-01

    Full Text Available Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  17. The expanding phenotypic spectra of kidney diseases: insights from genetic studies.

    Science.gov (United States)

    Stokman, Marijn F; Renkema, Kirsten Y; Giles, Rachel H; Schaefer, Franz; Knoers, Nine V A M; van Eerde, Albertien M

    2016-08-01

    Next-generation sequencing (NGS) has led to the identification of previously unrecognized phenotypes associated with classic kidney disease genes. In addition to improving diagnostics for genetically heterogeneous diseases and enabling a faster rate of gene discovery, NGS has enabled an expansion and redefinition of nephrogenetic disease categories. Findings from these studies raise the question of whether disease diagnoses should be made on clinical grounds, on genetic evidence or a combination thereof. Here, we discuss the major kidney disease-associated genes and gene categories for which NGS has expanded the phenotypic spectrum. For example, COL4A3-5 genes, which are classically associated with Alport syndrome, are now understood to also be involved in the aetiology of focal segmental glomerulosclerosis. DGKE, which is associated with nephrotic syndrome, is also mutated in patients with atypical haemolytic uraemic syndrome. We examine how a shared genetic background between diverse clinical phenotypes can provide insight into the function of genes and novel links with essential pathophysiological mechanisms. In addition, we consider genetic and epigenetic factors that contribute to the observed phenotypic heterogeneity of kidney diseases and discuss the challenges in the interpretation of genetic data. Finally, we discuss the implications of the expanding phenotypic spectra associated with kidney disease genes for clinical practice, genetic counselling and personalized care, and present our recommendations for the use of NGS-based tests in routine nephrology practice. PMID:27374918

  18. Gender Atypicality and Anxiety Response to Social Interaction Stress in Homosexual and Heterosexual Men.

    Science.gov (United States)

    Jacobson, Roi; Cohen, Hagit; Diamond, Gary M

    2016-04-01

    Gender non-conforming behavior and a homosexual sexual orientation have both been linked to higher levels of anxiety. This study examined the independent and interactive effects of gender atypicality and sexual orientation on levels of state anxiety immediately following a stressful social interaction task among a sample of homosexual and heterosexual Israeli men (n = 36). Gender atypicality was measured via both self-report and observer ratings. State anxiety was measured via both self-report immediately subsequent to the stressful social interaction task and pre- to post task changes in salivary cortisol. Results showed that self-reported gender atypicality and heterosexual sexual orientation predicted higher levels of self-reported social interaction anxiety, but not changes in cortisol. There were no sexual orientation by gender behavior interactions and there were no significant effects for observer rated gender atypicality. These findings suggest that gender atypicality, not homosexuality, place individuals at risk for increased anxiety. PMID:25946903

  19. $\\mathcal{N}=2$ supersymmetric field theories on 3-manifolds with A-type boundaries

    CERN Document Server

    Aprile, Francesco

    2016-01-01

    General half-BPS A-type boundary conditions are formulated for N=2 supersymmetric field theories on compact 3-manifolds with boundary. We observe that under suitable conditions manifolds of the real A-type admitting two complex supersymmetries (related by charge conjugation) possess, besides a contact structure, a natural integrable toric foliation. A boundary, or a general co-dimension-1 defect, can be inserted along any leaf of this preferred foliation to produce manifolds with boundary that have the topology of a solid torus. We show that supersymmetric field theories on such manifolds can be endowed with half-BPS A-type boundary conditions. We specify the natural curved space generalization of the A-type projection of bulk supersymmetries and analyze the resulting A-type boundary conditions in generic 3d non-linear sigma models and YM/CS-matter theories.

  20. Gender Atypicality and Anxiety Response to Social Interaction Stress in Homosexual and Heterosexual Men.

    Science.gov (United States)

    Jacobson, Roi; Cohen, Hagit; Diamond, Gary M

    2016-04-01

    Gender non-conforming behavior and a homosexual sexual orientation have both been linked to higher levels of anxiety. This study examined the independent and interactive effects of gender atypicality and sexual orientation on levels of state anxiety immediately following a stressful social interaction task among a sample of homosexual and heterosexual Israeli men (n = 36). Gender atypicality was measured via both self-report and observer ratings. State anxiety was measured via both self-report immediately subsequent to the stressful social interaction task and pre- to post task changes in salivary cortisol. Results showed that self-reported gender atypicality and heterosexual sexual orientation predicted higher levels of self-reported social interaction anxiety, but not changes in cortisol. There were no sexual orientation by gender behavior interactions and there were no significant effects for observer rated gender atypicality. These findings suggest that gender atypicality, not homosexuality, place individuals at risk for increased anxiety.

  1. Guiding atypical facial growth back to normal. Part 1: Understanding facial growth.

    Science.gov (United States)

    Galella, Steve; Chow, Daniel; Jones, Earl; Enlow, Donald; Masters, Ari

    2011-01-01

    Many practitioners find the complexity of facial growth overwhelming and thus merely observe and accept the clinical features of atypical growth and do not comprehend the long-term consequences. Facial growth and development is a strictly controlled biological process. Normal growth involves ongoing bone remodeling and positional displacement. Atypical growth begins when this biological balance is disturbed With the understanding of these processes, clinicians can adequately assess patients and determine the causes of these atypical facial growth patterns and design effective treatment plans. This is the first of a series of articles which addresses normal facial growth, atypical facial growth, patient assessment, causes of atypical facial growth, and guiding facial growth back to normal.

  2. The genome of Chelonid herpesvirus 5 harbors atypical genes

    Science.gov (United States)

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within the alphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of "atypical" DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis.

  3. Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing

    DEFF Research Database (Denmark)

    Rohlin, Anna; Rambech, Eva; Kvist, Anders;

    2016-01-01

    sixteen pathogenic or likely pathogenic variants and 30 variants of unknown clinical significance. Four of the pathogenic or likely pathogenic variants were found in BMPR1A in patients with unexplained familial adenomatous polyposis or atypical adenomatous polyposis, which extends the genotype......-phenotype spectrum for this gene. Nine patients had more than one variant remaining after the filtration, including three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional individual harbored a 24.2 kb duplication......Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel...

  4. Genetic testing in familial AD and FTD: mutation and phenotype spectrum in a Danish cohort

    DEFF Research Database (Denmark)

    Lindquist, S G; Schwartz, M; Batbayli, M;

    2009-01-01

    chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) techniques. Seven presumed pathogenic mutations (two PSEN1, one PSEN2, one APP, one MAPT, and two PGRN) were identified, including a novel PSEN2 mutation (V393M). No dosage aberrations were identified....... on chromosome 17, the MAPT and the PGRN genes, are associated with autosomal dominant inherited FTD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in families with inherited dementia. The identification of novel mutations and/or atypical genotype......-phenotype correlations contributes to further characterizing the disorders. DNA-samples from the 90 index cases from a Danish referral-based cohort representing families with presumed autosomal dominant inherited AD or FTD were screened for mutations in the known genes with sequencing, denaturing high-performance liquid...

  5. Risk factors for atypical endometrial hyperplasia in infertile women:possible association with polycystic ovarv syndrome

    Institute of Scientific and Technical Information of China (English)

    Lu Qun; Shen Huan; Tian Li; Zhu Sainan; Chen Xi

    2008-01-01

    Objective:Endometrial hyperplasia is considered as a precursor of endometrial carcinoma,in which oncogenic potential is low in hyperplasia without atypia,but high in a-typical hyperplasia.The objective of this study was to identify the risk factors for atypical endo-metrial hyperplasia in infertile women.Methods:Fifty four infertile women with endometrial hy-perplasia,which were selected from a large cohort of 2 098 women who desired for the future childbearing in our center,were diagnosed by hysteroscopy with directed biopsies or dilation and curettage(D&C),including 44 with hyperplasia without atypia,10 with atypical hyperplasia.Clinical characteristics were recorded in terms of age,body mass index(BMI),parity,insulin resistance,polycystic ovary syndrome(PCOS).Statistical comparison was made between women with hyperplasia without atypia and atypical hyperplasia.Logistic regression analysis Was em-ployed to assess the contribution of PCOS,obesity and insulin resistance to atypical hyperplasia.Results:The incidence of endometrial hyperplasia in infertile women Was 2.57%(54/2098),which included 1 0 women(0.48%)were diagnosed as atypical hyperplasia.PCOS in women with atypical hyperplasia(70%,7/10)was significantly higher than those of hyperplasia with-out atypia(27.27%,12/44).Stepwise regression analysis showed that PCOS contributed maximally to atypical endometrial hyperplasia in infertile women.Conclusion:PCOS is an independent risk factor for atypical endometrial hyperplasia in women with infertility.The infertile women with PCOS are at an increased risk for atypical endometrial hyperplasia and endometrial cancer.

  6. Assessing proteinase K resistance of fish prion proteins in a scrapie-infected mouse neuroblastoma cell line.

    Science.gov (United States)

    Salta, Evgenia; Kanata, Eirini; Ouzounis, Christos A; Gilch, Sabine; Schätzl, Hermann; Sklaviadis, Theodoros

    2014-11-13

    The key event in prion pathogenesis is the structural conversion of the normal cellular protein, PrP(C), into an aberrant and partially proteinase K resistant isoform, PrP(Sc). Since the minimum requirement for a prion disease phenotype is the expression of endogenous PrP in the host, species carrying orthologue prion genes, such as fish, could in theory support prion pathogenesis. Our previous work has demonstrated the development of abnormal protein deposition in sea bream brain, following oral challenge of the fish with natural prion infectious material. In this study, we used a prion-infected mouse neuroblastoma cell line for the expression of three different mature fish PrP proteins and the evaluation of the resistance of the exogenously expressed proteins to proteinase K treatment (PK), as an indicator of a possible prion conversion. No evidence of resistance to PK was detected for any of the studied recombinant proteins. Although not indicative of an absolute inability of the fish PrPs to structurally convert to pathogenic isoforms, the absence of PK-resistance may be due to supramolecular and conformational differences between the mammalian and piscine PrPs.

  7. Disease isolates of Streptococcus pseudopneumoniae and non-typeable S. pneumoniae presumptively identified as atypical S. pneumoniae in Spain.

    Directory of Open Access Journals (Sweden)

    Dora Rolo

    Full Text Available We aimed to obtain insights on the nature of a collection of isolates presumptively identified as atypical Streptococcus pneumoniae recovered from invasive and non-invasive infections in Spain. One-hundred and thirty-two isolates were characterized by: optochin susceptibility in ambient and CO(2-enriched atmosphere; bile solubility; PCR-based assays targeting pneumococcal genes lytA, ply, pspA, cpsA, Spn9802, aliB-like ORF2, and a specific 16S rRNA region; multilocus sequence analysis; and antimicrobial susceptibility. By multilocus sequence analysis, 61 isolates were S. pseudopneumoniae, 34 were pneumococci, 13 were S. mitis, and 24 remained unclassified as non-pneumococci. Among S. pseudopneumoniae isolates, 51 (83.6% were collected from respiratory tract samples; eight isolates were obtained from sterile sources. High frequency of non-susceptibility to penicillin (60.7% and erythromycin (42.6% was found. Only 50.8% of the S. pseudopneumoniae isolates displayed the typical optochin phenotype originally described for this species. None harbored the cpsA gene or the pneumococcal typical lytA restriction fragment length polymorphism. The Spn9802 and the specific 16S rRNA regions were detected among the majority of the S. pseudopneumoniae isolates (n = 59 and n = 49, respectively. The ply and pspA genes were rarely found. A high genetic diversity was found and 59 profiles were identified. Among the S. pneumoniae, 23 were capsulated and 11 were non-typeable. Three non-typeable isolates, associated to international non-capsulated lineages, were recovered from invasive disease sources. In conclusion, half of the atypical pneumococcal clinical isolates were, in fact, S. pseudopneumoniae and one-fourth were other streptococci. We identified S. pseudopneumoniae and non-typeable pneumococci as cause of disease in Spain including invasive disease.

  8. Atypical myopathy in grazing horses: a first exploratory data analysis.

    Science.gov (United States)

    Votion, Dominique-M; Linden, Annick; Delguste, Catherine; Amory, Hélène; Thiry, Etienne; Engels, Patrick; van Galen, Gaby; Navet, Rachel; Sluse, Francis; Serteyn, Didier; Saegerman, Claude

    2009-04-01

    Over the last decade, atypical myopathy (AM) in grazing horses has emerged in several European countries. An exploratory analysis was conducted to determine horse- and pasture-level indicators or factors associated with AM in Belgium. Belgian cases of AM confirmed by histology (n=57) were compared to their healthy co-grazing horses (n=77) and to pastured horses not involved with AM as controls (n=386). The pastures where confirmed cases were grazing (42 pastures; 38 sites; 44 incidences of AM) were compared with those of the controls (216 pastures; 96 sites; no incidence of AM). Statistically significant (Phorses (young age, inactivity, body condition poor to normal), management practices (permanent pasturing, spreading of manure) and pasture characteristics (humid, sloping pastures, accumulated dead leaves, presence of waterway) may increase the risk of AM. Specific interventions based on these factors might help to reduce the incidence of AM.

  9. Atypical diabetes in children: ketosis-prone type 2 diabetes.

    Science.gov (United States)

    Vaibhav, Atul; Mathai, Mathew; Gorman, Shaun

    2013-01-08

    Ketosis-prone type 2 diabetes mellitus also known as atypical or flatbush diabetes is being increasingly recognised worldwide. These patients are typically obese, middle-aged men with a strong family history of type 2 diabetes. The aetiology and pathophysiological mechanism is still unclear but some initial research suggests that patients with ketosis-prone type 2 diabetes have a unique predisposition to glucose desensitisation. These patients have negative autoantibodies typically associated with type 1 diabetes but have shown to have human leucocyte antigen (HLA) positivity. At initial presentation, there is an impairment of both insulin secretion and action. β Cell function and insulin sensitivity can be markedly improved by initiating aggressive diabetes management to allow for discontinuation of insulin therapy within a few months of treatment. These patients can be maintained on oral hypoglycaemic agents and insulin therapy can be safely discontinued after few months depending on their β cell function.

  10. An atypical presentation of cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Joshi Deepak

    2008-06-01

    Full Text Available Abstract Introduction The presentation of cystic fibrosis is dependant upon which organs are affected. Common presentations include chronic respiratory infections and malabsorption. Patients with atypical disease tend to present late in childhood or as adults. Eye manifestations of cystic fibrosis are less well known. Case presentation A 14-year-old Caucasian boy presented with tiredness and difficulty seeing at night, over a period of 6 months. Good vision was only described in bright conditions. There was no history of jaundice, steatorrhea or diarrhoea. Conclusion This is the first reported case of newly diagnosed cystic fibrosis-related liver disease in a teenage boy, whose presenting symptom was night blindness secondary to vitamin A deficiency.

  11. Atypical measles syndrome: unusual hepatic, pulmonary, and immunologic aspects.

    Science.gov (United States)

    Frey, H M; Krugman, S

    1981-01-01

    The atypical measles syndrome is a relatively new disease that was first recognized 15 years ago. Initially, it occurred in children who were exposed to wild measles virus several years after they were immunized with killed measles vaccine. It was characterized by a two- to three-day prodrome of high fever, cough, headache, and myalgia followed by a rash that resembled Rocky Mountain spotted fever, scarlet fever, or varicella and associated with roentgenographic evidence of pneumonia with or without pleural effusion. This report highlights three unusual manifestations of this syndrome: 1) transient hepatitis, 2) persistence of pulmonary lesions for several years, and 3) occurrence of excessively high measles hemagglutination-inhibition antibody titers. Today, this syndrome occurs predominantly in adolescents and young adults.

  12. Chikungunya fever: Atypical and lethal cases in the Western hemisphere

    Science.gov (United States)

    Torres, Jaime R.; Leopoldo Códova G.; Castro, Julio S.; Rodríguez, Libsen; Saravia, Víctor; Arvelaez, Joanne; Ríos-Fabra, Antonio; Longhi, María A.; Marcano, Melania

    2014-01-01

    A large epidemic of Chikungunya fever currently affects the Caribbean, Central and South America. Despite a high number of reported cases, little is known on the occurrence of severe clinical complications. We describe four Venezuelan patients with a severe and/or lethal course who exhibit unusual manifestations of the disease. Case 1 describes a 75 year-old man with rapid onset of septic shock and multi-organ failure. Cases 2 and 3 describe two patients with rapid aggressive clinical course who developed shock, severe purpuric lesions and a distinct area large of necrosis in the nasal region. Case 4 depicts a splenectomized woman with shock, generalized purpuric lesions, bullous dermatosis and acronecrosis of an upper limb. Chikungunya fever in the Western hemisphere may also associate with atypical and severe manifestations. Some patients experience a life-threatening, aggressive clinical course, with rapid deterioration and death due to multisystem failure. PMID:26793440

  13. Epidermoid cyst of the testis: An atypical sonographic appearance.

    Science.gov (United States)

    Chen, Shu-Ting; Chiou, Hong-Jen; Pan, Chin-Chen; Shen, Shu-Huei; Chou, Yi-Hong; Tiu, Chui-Mei; Wang, Hsin-Kai; Lai, Yi-Chen; Lin, Yung-Hui; Wang, Jane; Chang, Cheng-Yen

    2016-09-01

    Epidermoid cysts are rare. They represent the most common benign tumor of the testis. The sonographic appearances of testicular epidermoid cysts usually include avascular, mostly lamellated, heterogeneous internal echotexture, with hypoechoic and hyperechoic concentric rings, accounting for the typical onion-ring appearance. On MRI, epidermoid cysts show a low-signal-intensity center, with internal concentric rings of alternating high- and low-signal intensity on T2-weighted images, which correlates with the onion-ring appearance. We report a patient with testicular epidermoid cyst with atypical ultrasound and MRI appearances that led to the erroneous initial diagnosis of "burned-out" tumor. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:448-451, 2016. PMID:27028726

  14. Atypical teratoid/rhabdoid tumor: an unusual presentation

    Energy Technology Data Exchange (ETDEWEB)

    Gandhi, Chirag D. [Mount Sinai School of Medicine, Department of Neurosurgery, One Gustave L. Levy Place, Box 1136, Annenberg 8-06, New York, NY (United States); Krieger, Mark D.; McComb, J. Gordon [Children' s Hospital of Los Angeles, Division of Neurosurgery, Los Angeles, CA (United States)

    2004-10-01

    Atypical teratoid/ rhabdoid tumor (AT/RT) of the central nervous system is a rare, highly aggressive malignancy of infancy. Although it is reported infrequently in the literature, it has often been histologically confused with a primitive neuroectodermal tumor (PNET)/medulloblastoma (MB) but has a much worse prognosis. We present an infant with two AT/RT tumors, one suprasellar in location and the other within the vermis without evidence of tumor elsewhere. What makes this case unusual is that there were two separate lesions in different cranial compartments, with no evidence of subarachnoid seeding. In addition, the lesions had different magnetic resonance imaging (MRI) characteristics even though they were histologically the same. (orig.)

  15. Atypical post-finasteride syndrome: A pharmacological riddle

    Directory of Open Access Journals (Sweden)

    Anita K Gupta

    2016-01-01

    Full Text Available Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II. The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH as well as androgenic alopecia (AGA while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well. Although the postfinasteride syndrome (PFS is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting.

  16. Atypical post-finasteride syndrome: A pharmacological riddle.

    Science.gov (United States)

    Gupta, Anita K; Sharma, Neetu; Shukla, Prashant

    2016-01-01

    Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II. The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH) as well as androgenic alopecia (AGA) while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well. Although the postfinasteride syndrome (PFS) is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting. PMID:27298504

  17. Gaze Perception Develops Atypically in Children with Autism

    Directory of Open Access Journals (Sweden)

    Simon Webster

    2011-01-01

    Full Text Available The Mindblindness model is the main model of social cognitive development in autism. This model assumes that eye direction detection and eye contact detection develop typically in autism (Baron-Cohen, 1995. The model's assumption of maturational development implies that when these skills are abnormal, they must either be absent or developmentally delayed. In contrast, the atypical modularisation hypothesis predicts that these skills can develop deviantly—successfully but atypically—in children with autism. Two computer-based tasks were used to assess eye direction detection and eye contact detection in children with autism and in typically developing children. These skills were developmentally deviant in children with autism. The findings support a model of social cognition in autism that accounts for developmental processes.

  18. Cholesterol granuloma of the orbit: An atypical presentation

    Directory of Open Access Journals (Sweden)

    Syed A R Rizvi

    2014-01-01

    Full Text Available Cholesterol granuloma is a rare, well-defined lesion of the orbit. In the orbit, diploe of the frontal bone is involved almost exclusively. We report an atypical case of cholesterol granuloma involving superomedial quadrant of orbit. A 42-year-old male presented with progressive, painless, proptosis with infero-temporal displacement of left eye. A large mass was felt beneath the bony orbital margin in the superomedial quadrant of the left orbit. Computerized tomography (CT scan revealed an extraconal superomedial, heterogeneous enhancing mass which was isodense with brain and pushing the globe inferolaterally and anteriorly. Excision biopsy of the tumor revealed the typical features of a cholesterol granuloma without any epithelial elements. Cholesterol granuloma of the orbit is a rare entity, but it can be diagnosed and differentiated from other lesions of the superior orbit by its characteristic clinical, radiological and histopathological features. An appropriate intervention in time carries a good prognosis with almost no recurrence.

  19. Angiolymphoid hyperplasia with eosinophilia: Atypical appeareance in an older patient

    Directory of Open Access Journals (Sweden)

    Karabudak Ozlem

    2008-01-01

    Full Text Available We describe a 76-year-old man presenting with a chronic, non-healing ulcer of six-year duration on his left zygomatic area. The skin biopsy specimen taken from the lesion, showed increased vascular proliferation, edematous endothelial cells in the dermal blood vessels and perivascular eosinophilic/lymphocytic infiltration. The routine and specific blood tests were unremarkable. On the basis of these features, the patient was diagnosed as having angiolymphoid hyperplasia with eosinophilia (ALHE. We present the case because of its rarity in older people, atypical clinical appearance; and stress the consideration of ALHE in the differential diagnosis of chronic non-healing superficial ulcers confined to face and neck.

  20. Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Ziereisen, France; Damry, Nash; Christophe, Catherine [Queen Fabiola Children' s University Hospital, Department of Radiology, Brussels (Belgium); Dan, Bernard [Queen Fabiola Children' s University Hospital, Department of Neurology, Brussels (Belgium); Azzi, Nadira; Ferster, Alina [Queen Fabiola Children' s University Hospital, Department of Paediatrics, Brussels (Belgium)

    2006-03-15

    Unusual acute symptomatic and reversible early-delayed leukoencephalopathy has been reported to be induced by methotrexate (MTX). We aimed to identify the occurrence of such atypical MTX neurotoxicity in children and document its MR presentation. We retrospectively reviewed the clinical findings and brain MRI obtained in 90 children treated with MTX for acute lymphoblastic leukaemia or non-B malignant non-Hodgkin lymphoma. All 90 patients had normal brain imaging before treatment. In these patients, brain imaging was performed after treatment completion and/or relapse and/or occurrence of neurological symptoms. Of the 90 patients, 15 (16.7%) showed signs of MTX neurotoxicity on brain MRI, 9 (10%) were asymptomatic, and 6 (6.7%) showed signs of acute leukoencephalopathy. On the routine brain MRI performed at the end of treatment, all asymptomatic patients had classical MR findings of reversible MTX neurotoxicity, such as abnormal high-intensity areas localized in the deep periventricular white matter on T2-weighted images. In contrast, the six symptomatic patients had atypical brain MRI characterized by T2 high-intensity areas in the supratentorial cortex and subcortical white matter (n=6), cerebellar cortex and white matter (n=4), deep periventricular white matter (n=2) and thalamus (n=1). MR normalization occurred later than clinical recovery in these six patients. In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX. (orig.)

  1. Skin biopsies in the evaluation of atypical optic neuropathies.

    Science.gov (United States)

    Bielory, L; Kupersmith, M; Warren, F; Bystryn, J; Frohman, L

    1993-01-01

    Patients with atypical clinical presentations of common optic neuropathies such as optic neuritis (ON), anterior ischemic optic neuropathy (AION), or optic neuropathy of unknown etiology (UON) are difficult to distinguish from inflammatory autoimmune optic neuropathy (AON) which is typically associated with a poor visual prognosis, unless treated with high doses of corticosteroids and/or immunosuppressive agents. The authors retrospectively evaluated 34 patients [AON (n = 12); AION (n = 5); ON (n = 9); UON (n = 8)] with visual loss which deteriorated over weeks to months or followed an atypical course, for the presence of immunological markers suggestive of AON. These markers included serological testing for antiphospholipid (APA) and antinuclear (ANA) antibodies, and evaluation of histopathologic and immunofluorescent staining of skin biopsies. All patients underwent a skin biopsy. Four of the 12 patients with AON had urticarial cutaneous lesions which revealed leukocytoclastic and/or lymphohistiocytic vasculitis. Seven of the remaining eight AON patients had skin biopsies of non-lesional skin which revealed immunoreactant deposition. Seven of the 21 skin biopsies obtained from the non-AON patients had findings of vacuolization or mild perivascular infiltration of lymphocytes (n = 5) and immunofluorescent deposits (n = 2). Abnormal skin biopsies (92%;p = 0.0009) and circulating APA (82%; p = 0.013) were common in AON patients while ANA was not statistically increased in AON patients (p = 0.06) when compared to the remaining patients as a whole. AON patients typically demonstrate evidence of systemic autoimmune involvement, as manifested by cutaneous abnormalities such as urticarial vasculitis and/or immunoreactant deposition and circulating APA. These may serve as markers for identifying AON patients who may be treated with immunomodulatory agents. PMID:22822778

  2. Atypical integration of motion signals in Autism Spectrum Conditions.

    Directory of Open Access Journals (Sweden)

    Caroline E Robertson

    Full Text Available Vision in Autism Spectrum Conditions (ASC is characterized by enhanced perception of local elements, but impaired perception of global percepts. Deficits in coherent motion perception seem to support this characterization, but the roots and robustness of such deficits remain unclear. We aimed to investigate the dynamics of the perceptual decision-making network known to support coherent motion perception. In a series of forced-choice coherent motion perception tests, we parametrically varied a single stimulus dimension, viewing duration, to test whether the rate at which evidence is accumulated towards a global decision is atypical in ASC. 40 adult participants (20 ASC performed a classic motion discrimination task, manually indicating the global direction of motion in a random-dot kinematogram across a range of coherence levels (2-75% and stimulus-viewing durations (200-1500 ms. We report a deficit in global motion perception at short viewing durations in ASC. Critically, however, we found that increasing the amount of time over which motion signals could be integrated reduced the magnitude of the deficit, such that at the longest duration there was no difference between the ASC and control groups. Further, the deficit in motion integration at the shortest duration was significantly associated with the severity of autistic symptoms in our clinical population, and was independent from measures of intelligence. These results point to atypical integration of motion signals during the construction of a global percept in ASC. Based on the neural correlates of decision-making in global motion perception our findings suggest the global motion deficit observed in ASC could reflect a slower or more variable response from the primary motion area of the brain or longer accumulation of evidence towards a decision-bound in parietal areas.

  3. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  4. Atypical teratoid/rhabdoid tumor of the central nervous system in children: an atypical series and review

    Energy Technology Data Exchange (ETDEWEB)

    Fenton, Laura Z. [Department of Radiology, Children' s Hospital, 1056 East 19th Avenue B125, CO 80218, Denver (United States); Foreman, Nicholas K. [Department of Neuro-Oncology, Children' s Hospital, 1056 East 19th Avenue B125, CO 80218, Denver (United States)

    2003-08-01

    Primary atypical teratoid/rhabdoid tumor (AT/RhT) of the central nervous system is a recently described, highly malignant neoplasm in infants and young children. This tumor is an unusual combination of mixed cellular elements, similar but not typical of teratomas, and rhabdoid cells. This tumor is most common in the posterior fossa in children less than 2 years, and is radiologically similar to medulloblastoma. No pathognomonic imaging features are present. The two tumors can be separated on histologic, molecular, and cytogenetic grounds. Separation of these two tumor types is crucial because the prognosis for AT/RhT is grim even with current multimodality treatment. We present four consecutive cases of AT/RhT, three in locations other than the cerebellum, seen at our institution in a 14-month period, indicating that this tumor may be more common than previously thought. (orig.)

  5. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

    Science.gov (United States)

    Jansen, M.; Mohapatra, G.; Betensky, R.A.; Keohane, C.; Louis, D.N.

    2013-01-01

    Aims Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Postoperative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. PMID:21988727

  6. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

    LENUS (Irish Health Repository)

    2012-02-01

    Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

  7. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    Science.gov (United States)

    Boonlue, Tuanthon; Subongkot, Suphat; Dilokthornsakul, Piyameth; Kongsakon, Ronnachai; Pattanaprateep, Oraluck; Suanchang, Orabhorn; Chaiyakunapruk, Nathorn

    2016-01-01

    Background Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual atypical antipsychotics therapy. Outcomes were schizophrenia-related hospitalization and total health care cost. Logistic and Poisson regression were used to evaluate the risk of hospitalization, and generalized linear model with gamma distribution was used to determine the health care cost. All analyses were adjusted by employing propensity score and multivariable analyses. All cost estimates were adjusted according to 2013 consumer price index and converted to US$ at an exchange rate of 32.85 Thai bahts/US$. Results A total of 2,354 patients were included. Of them, 166 (7.1%) patients switched to typical antipsychotics. The adjusted odds ratio for schizophrenia-related hospitalization in atypical antipsychotic switching group was 1.87 (95% confidence interval [CI] 1.23–2.83). The adjusted incidence rate ratio was 2.44 (95% CI 1.57–3.79) for schizophrenia-related hospitalizations. The average total health care cost was lower in patients with antipsychotic switching (−$64; 95% CI −$459 to $332). Conclusion Switching from atypical to typical antipsychotics is associated with an increased risk of schizophrenia-related hospitalization

  8. Genetic characterization of atypical Mansonella (Mansonella) ozzardi microfilariae in human blood samples from northeastern Peru.

    Science.gov (United States)

    Marcos, Luis A; Arrospide, Nancy; Recuenco, Sergio; Cabezas, Cesar; Weil, Gary J; Fischer, Peter U

    2012-09-01

    DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical microfilariae were clustered into the Mansonella group and indistinguishable from M. ozzardi based on these DNA markers. PMID:22826497

  9. Comprehension of atypical literary text and scholastic achievement

    Directory of Open Access Journals (Sweden)

    Božin Aurel A.

    2009-01-01

    Full Text Available With the aim of gaining insight into literary text comprehension and the linkage between that comprehension and scholastic achievement during the first years of schooling, a research was conducted on the sample of 152 third and fourth grade pupils from one urban and one rural school. After having read silently a selected atypical excerpt from one literary text, interviewed pupils filled out the questionnaire constructed for the purposes of this research starting from the 11 categories of text comprehension singled out based on the theory of comprehension and interpretation of literary text and the current curriculum. In the first part of the research we applied the Children's orientation scale by Malka Margalit, and school marks were used as a measurement of scholastic achievement. Research results point out that, among other things, inferring on the basis of what has been read poses the greatest difficulty for third and fourth graders, that is, that almost three quarters of them are not capable of determining the meaning of some representative sentences from that text. In the positive sense, it was established that almost three quarters of them perceive beautiful poetic expressions and about 80% of them can at least to a certain extent recognize character descriptions, emotional situations and moods, that is, discover significant facts. Answers to the questions regarding the majority of categories of text comprehension are significantly correlated with scholastic achievement. As expected, the highest correlations between the measures on text comprehension categories are with the marks in native (Serbian language. Partial correlations between the measures on certain categories of text comprehension and measurements of scholastic achievement (excluding the influence of feeling of coherence are not significantly different from bivariate. Based on the obtained data, authors conclude that the utilized system of categories can be a useful tool for

  10. Detection of atypical seismic events on a regional scale

    Science.gov (United States)

    Solano-Hernandez, E. A.; Hjorleifsdottir, V.; Perez-Campos, X.; Iglesias, A.

    2013-12-01

    We propose an event-detection algorithm to locate seismic events on a regional scale. Our goal is to identify non-impulsive or 'atypical' events which are not detected by regional or global networks, due to their low P-wave amplitude. Ekstrom (2006) has developed and implemented a method to detect and locate sources of long-period seismic surface waves on a global scale. Atypical events are generated by, for example, rapid glacial movements (Ekstrom, et al., 2003; Ekstrom, et al., 2006), volcanic events (Schuler and Ekstrom, 2009) and landslides (Ekstrom and Stark, 2013). Furthermore, non-impulsive earthquakes have been located on oceanic transform faults (Abercrombie and Ekstrom, 2001). The current method (Ekstrom, 2006), that is applied on the scale of the globe, routinely detects events with magnitudes around Mw 5 and larger. In this work we wish to lower the detection threshold by using shorter period records registered by regional networks. The difficulty lies in that the shorter period records are strongly influenced by the heterogeneous crust and upper mantle, which need to be accounted for in the modeling process. Our proposed method involves first computing full waveforms, Green's functions or moment tensor responses, between a grid of test locations and existing seismic stations in a 3D medium. We then effectively back propagate observed data through cross correlation with the responses, obtaining a function that localizes in time and space at the source. Our method is a variant of the timereversal method presented by, for example, McMechan (1982), Tromp et al. (2005), Larmat et al. (2006), Gajewski and Tessmer (2005) and Kim et al. (2010). To calibrate the various parameters used by the detection method, we use the aftershocks sequence of the March 20, 2012 Ometepec, Guerrero, Mexico earthquake, recorded by the SSN (Mexican National Network). The lively aftershock sequence provided us with many events of different magnitudes, all occurring approximately

  11. The genome of Chelonid herpesvirus 5 harbors atypical genes

    Science.gov (United States)

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within thealphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of “atypical” DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis

  12. Integrating molecular, phenotypic and environmental data to elucidate patterns of crocodile hybridization in Belize.

    Science.gov (United States)

    Hekkala, Evon R; Platt, Steven G; Thorbjarnarson, John B; Rainwater, Thomas R; Tessler, Michael; Cunningham, Seth W; Twomey, Christopher; Amato, George

    2015-09-01

    The genus Crocodylus comprises 12 currently recognized species, many of which can be difficult to differentiate phenotypically. Interspecific hybridization among crocodiles is known to occur in captivity and has been documented between some species in the wild. The identification of hybrid individuals is of importance for management and monitoring of crocodilians, many of which are Convention on International Trade in Endangered Species (CITES) listed. In this study, both mitochondrial and nuclear DNA markers were evaluated for their use in confirming a suspected hybrid zone between American crocodile (Crocodylus acutus) and Morelet's crocodile (Crocodylus moreletii) populations in southern Belize where individuals and nests exhibiting atypical phenotypic features had previously been observed. Patterns observed in both phenotypic and molecular data indicate possible behavioural and ecological characteristics associated with hybridization events. The results of the combined analyses found that the majority of suspected hybrid samples represent crosses between female C. acutus and male C. moreletii. Phenotypic data could statistically identify hybrids, although morphological overlap between hybrids and C. moreletii reduced reliability of identification based solely on field characters. Ecologically, C. acutus was exclusively found in saline waters, whereas hybrids and C. moreletii were largely absent in these conditions. A hypothesized correlation between unidirectional hybridization and destruction of C. acutus breeding habitats warrants additional research. PMID:26473062

  13. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P;

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...

  14. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape cha

  15. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona;

    2016-01-01

    OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analy...

  16. Decreased Diagnostic Accuracy of Multislice Coronary Computed Tomographic Angiography in Women with Atypical Angina Symptoms

    Directory of Open Access Journals (Sweden)

    Wen-Ying Jin

    2016-01-01

    Conclusions: Although MSCT is a reliable diagnostic modality for the exclusion of significant coronary artery stenoses in all patients, gender and atypical symptoms might have some influence on its diagnostic accuracy.

  17. Evaluation of Atypical Lymphocyte Warnings of Sysmex XE-4000 in Outpatient Children

    Institute of Scientific and Technical Information of China (English)

    Xueling GUO; Tingbo ZHANG; Maofan WANG

    2014-01-01

    This study aimed to evaluate the atypical lymphocyte warnings of Sysmex XE-4000 in outpatient children. [Method] Randomly 280 specimens of outpatient children were selected to analyze atypical lymphocytes with Sysmex XE-4000 and artificial smear microscopy simultaneously. [Result] With artificial smear microscopy as the gold standard, the atypical lymphocyte warnings of Sysmex XE-4000 in outpatient children exhibited a sensitivity of 97.4%, specificity of 69.3%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 98.5%. [Conclusion] Sysmex XE-4000 shows a high sensitivity in atypical lymphocyte warnings, which can reduce the number of blood smears, improve the specificity of microscopy, and decline the labor intensity of inspection personnel. However, there are stil certain false positives to be confirmed by artificial microscopy.

  18. Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid-based cervical cytology.

    LENUS (Irish Health Repository)

    Chummun, K

    2012-12-01

    In 2008, the management of women in Ireland with atypical glandular cells changed to immediate referral to colposcopy. The optimal management of these women is unclear. A balance between the detection of occult disease and overtreatment is required.

  19. Research on the significance of TSPOT.TB test in diagnosing the atypical pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Jin Li; Qi-Huang Chen; Yan-Yu Pan; Wei-Zheng Chen; Wen-Feng Lin; Sai-Li Zeng

    2015-01-01

    Objective:To investigate the sensitivity and specificity of the TSPOT.TB test in diagnosing the atypical pulmonary tuberculosis.Methods:A total of 100 patients with suspected pulmonary tuberculosis were diagnosed by TSPOT.TB test and TST, and the difference between the two detection methods was compared.Results:The positive detection rate in the atypical pulmonary tuberculosis was significantly higher than that in the pulmonary tuberculosis group. The sensitivity (94.21), specificity (94.50), PPV (74.20), NPV (94.17), and LR+ (6.14) in the atypical pulmonary tuberculosis group by TSPOT.TB test were significantly higher than those by TST, while LR-(0.13) was significantly lower than that by TST.Conclusions:When compared with TST, TSPOT. TB test has a higher clinical application value, possesses advantages of rapidness and sensitivity, and plays a vital role in diagnosing atypical pulmonary tuberculosis.

  20. Bronchiectasis Exacerbations: The Role of Atypical Bacteria and Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Eugenios I Metaxas

    2015-01-01

    Full Text Available BACKGROUND: Aside from the known role of common bacteria, there is a paucity of data regarding the possible role of atypical bacteria and viruses in exacerbations of non-cystic fibrosis bronchiectasis.

  1. Patients with atypical hyperplasia of the endometrium should be treated in oncological centers

    DEFF Research Database (Denmark)

    Antonsen, Sofie Leisby; Ulrich, Lian; Høgdall, Claus

    2011-01-01

    OBJECTIVES: To examine the prevalence of undiagnosed endometrial carcinoma (EC) among women with a preoperative diagnosis of atypical endometrial hyperplasia (AEH) in correlation to age, BMI and menopause. METHODS: Data extracted from the Danish Gynecological Cancer Database (DGCD) covering women...

  2. Relations between A-type granites and copper mineralization as exemplified by the Machangqing Cu deposit

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper deals with the relations between the Machangqing rockbody which corresponds to the A-type granites and porphyry copper mineralization in terms of petrochemistry,trace element geochemistry,fluid inclusion geochemistry and isotope geochemistry.The results show that the Machangqing porphyry copper deposit was formed from the fluid predominated by magmatic fluid.This kind of ore-forming fluid was just differentiated from the magma responsible for the A-type granites.Therefore,as viewed from whether they contain water or not,the A-type granites can,at least,be divided into two types:water-bearing and water-free.The water-bearing A-type granites can serve as the host of porphyry copper deposits under certain geological conditions.

  3. Relations between A-type granites and copper mineralization as exemplified by the Machangqing Cu deposit

    Institute of Scientific and Technical Information of China (English)

    毕献武; 胡瑞忠; 叶造军; 邵树勋

    2000-01-01

    This paper deals with the relations between the Machangqing rockbody which corresponds to the A-type granites and porphyry copper mineralization in terms of petrochemistry, trace element geochemistry, fluid inclusion geochemistry and isotope geochemistry. The results show that the Machangqing porphyry copper deposit was formed from the fluid predominated by mag-matic fluid. This kind of ore-forming fluid was just differentiated from the magma responsible for the A-type granites. Therefore, as viewed from whether they contain water or not, the A-type granites can, at least, be divided into two types: water-bearing and water-free. The water-bearing A-type granites can serve as the host of porphyry copper deposits under certain geological conditions.

  4. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Nielsen, Lars P; Schiotz, Peter Oluf

    2006-01-01

    BACKGROUND: Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. METHODS: Seventy-five children were followed...

  5. Multiphasic strain differentiation of atypical mycobacteria from elephant trunk wash

    OpenAIRE

    Chan, Kok-Gan; Loke, Mun Fai; Ong, Bee Lee; Wong, Yan Ling; Hong, Kar Wai; Tan, Kian Hin; Kaur, Sargit; Ng, Hien Fuh; Abdul Razak, MFA; Ngeow, Yun Fong

    2015-01-01

    Background. Two non-tuberculous mycobacterial strains, UM_3 and UM_11, were isolated from the trunk wash of captive elephants in Malaysia. As they appeared to be identical phenotypes, they were investigated further by conventional and whole genome sequence-based methods of strain differentiation. Methods. Multiphasic investigations on the isolates included species identification with hsp65 PCR-sequencing, conventional biochemical tests, rapid biochemical profiling using API strips and the Bio...

  6. Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Susumu Imoto; Taisuke Nakajima; Kenji Ando; Keiji Mita; Katsumi Fukuda; Ryo Nishikawa; Yu-ichiro Koma; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2009-01-01

    We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

  7. Atypical Cutaneous Manifestations in Adult Onset Still’s Disease

    Directory of Open Access Journals (Sweden)

    Champa Nataraja

    2016-01-01

    Full Text Available Adult Onset Still’s Disease (AOSD, an adult variant of systemic onset juvenile idiopathic arthritis, is a rare systemic inflammatory disorder of unknown aetiology. The rarity of this disease is associated with low index of suspicion and delayed diagnosis in patients suffering from it and in the presence of atypical features the diagnosis can be further challenging. This is a case report on a 24-year-old woman, who was a diagnostic dilemma for 2 years due to the nonspecific symptoms of recurrent fever, generalized maculopapular persistent pruritic and tender rash, and polyarthralgia. She was initially diagnosed as leukocytoclastic vasculitis on a skin biopsy and was managed by a dermatologist with various medications including NSAIDs, hydroxychloroquine, dapsone, colchicine, cyclosporine, and high doses of oral steroids with minimal response. Subsequently, she has had multiple admissions with similar symptoms with raised inflammatory markers and negative septic workup. On one occasion, her iron study revealed hyperferritinaemia which led to the suspicion of AOSD. Once the rheumatic fever and infectious, malignant, autoimmune, and lymphoproliferative disorders were excluded, she was diagnosed as probable AOSD and managed successfully with IL-1 (interleukin-1 receptor antagonist, Anakinra, with remarkable and lasting response both clinically and biochemically.

  8. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins

    Directory of Open Access Journals (Sweden)

    Elisa E. Figueroa-Angulo

    2015-11-01

    Full Text Available Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs that interact with an iron responsive element (IRE located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis.

  9. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins.

    Science.gov (United States)

    Figueroa-Angulo, Elisa E; Calla-Choque, Jaeson S; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-11-26

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis.

  10. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Rose M. Ayoob

    2016-01-01

    Full Text Available The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males, mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  11. Atypical Time Course of Object Recognition in Autism Spectrum Disorder

    Science.gov (United States)

    Caplette, Laurent; Wicker, Bruno; Gosselin, Frédéric

    2016-01-01

    In neurotypical observers, it is widely believed that the visual system samples the world in a coarse-to-fine fashion. Past studies on Autism Spectrum Disorder (ASD) have identified atypical responses to fine visual information but did not investigate the time course of the sampling of information at different levels of granularity (i.e. Spatial Frequencies, SF). Here, we examined this question during an object recognition task in ASD and neurotypical observers using a novel experimental paradigm. Our results confirm and characterize with unprecedented precision a coarse-to-fine sampling of SF information in neurotypical observers. In ASD observers, we discovered a different pattern of SF sampling across time: in the first 80 ms, high SFs lead ASD observers to a higher accuracy than neurotypical observers, and these SFs are sampled differently across time in the two subject groups. Our results might be related to the absence of a mandatory precedence of global information, and to top-down processing abnormalities in ASD. PMID:27752088

  12. An Atypical Presentation of Allergic Myocardial İnfarction

    Directory of Open Access Journals (Sweden)

    Veysel Oktay

    2014-09-01

    Full Text Available Acute coronary syndromes secondary to hypersensitivity reactions related with allergic factors are defined as Kounis syndrome. Doxycycline is an antibiotic commonly used in clinical practice. In this report, we described an atypical presentation of Kounis syndrome in a patient who was admitted to the emergency service complaining of chest pain, generalized rash and fever. She was taking doxycycline for 3 days because of urinary tract infection. Non specific ST-T changes were seen on electrocardiography, positive troponin levels were detected and global left ventricular wall motion abnormalities were defined by echocardiography. The patient had no conventional risk factor for acute coronary syndrome. Normal coronary angiography results, improved left ventricular functions and symptoms by antihistaminic and steroid treatments were consistent with Kounis syndrome. All patients admitted with the concurrence of chest pain and allergic symptoms should be asked about exposure to allergens. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 202-4

  13. Atypical Enteropathogenic Escherichia coli Secretes Plasmid Encoded Toxin

    Directory of Open Access Journals (Sweden)

    Rita C. Ruiz

    2014-01-01

    Full Text Available Plasmid encoded toxin (Pet is a serine protease originally described in enteroaggregative Escherichia coli (EAEC prototype strain 042 whose entire characterization was essentially obtained from studies performed with the purified toxin. Here we show that Pet is not exclusive to EAEC. Atypical enteropathogenic Escherichia coli (aEPEC strains, isolated from diarrhea cases, express Pet and its detection in supernatants of infected HEp-2 cells coincides with the appearance of cell damage, which, in turn, were similar to those described with purified Pet. Pet secretion and the cytotoxic effects are time and culture medium dependent. In presence of DMEM supplemented with tryptone cell rounding and detachment were observed after just 5 h of incubation with the bacteria. In the absence of tryptone, the cytotoxic effects were detected only after 24 h of infection. We also show that, in addition to the prototype EAEC, other pet+ EAEC strains, also isolated from diarrhea cases, induce cellular damage in the same degree as the aEPEC. The cytotoxic effects of EAEC and aEPEC strains were significantly reduced in the presence of a serine protease inhibitor or anti-Pet IgG serum. Our results show a common aspect between the aEPEC and EAEC and provide the first evidence pointing to a role of Pet in aEPEC pathogenesis.

  14. ATYPICAL BULLOUS PYODERMA GANGRENOSUM WITH EARLY LESIONS MIMICKING CHICKEN POX

    Directory of Open Access Journals (Sweden)

    Ramesh

    2013-10-01

    Full Text Available ABSTRACT : Pyoderma Gangrenosum (PG rare neutrophilic dermatoses (1/100,00 0, of which Bullous Pyoderma gangrenosum is an atypical form, which is very rare. Bullous PG is usually associated with haematological disorders like myeloproliferative disorders, haematological malignancies specially AML and several other haematological disorders. It presents as a superficial haemorrhagic bulla which ulcerates, ulcers increase in size and heal with scarring. Treatment is mainly to identify and treat the cause. Pyoderma Gangrenosum shows rapid response to oral corticosteroid therapy. 1 , 3 . Clinical presentation: A 32yr old female presented with fever, multiple vesicles on face, upper limb, lower limb and trunk, and these early lesions looked like chicken pox lesions. Lesions increased in size to form haemorrhagic bullas which eroded to form ulcers, ulcers rapidly increased in size with necrotic base and erythematous to violaceous border. Investigation: Haemoglobin: 5.7gm%, Peripheral smear: normocytic and normochromic anaemia. Skin Biopsy: Sub corneal blisters with dermal and perifollicular n eutrophilic infiltrate. A diagnosis of Bullous Pyoderma gangrenosum was made. Patient’s anaemia was treated; oral prednisolone and topical steroids were started. Patient showed marked improvement to treatment.

  15. EVOLUTION OF ROTATIONAL VELOCITIES OF A-TYPE STARS

    International Nuclear Information System (INIS)

    The equatorial velocity of A-type stars undergoes an acceleration in the first third of the main sequence (MS) stage, but the velocity decreases as if the stars were not undergoing any redistribution of angular momentum in the external layers in the last stage of the MS phase. Our calculations show that the acceleration and the decrease of the equatorial velocity can be reproduced by the evolution of the differential rotation zero-age MS model with the angular momentum transport caused by hydrodynamic instabilities during the MS stage. The acceleration results from the fact that the angular momentum stored in the interiors of the stars is transported outward. In the last stage, the core and the radiative envelope are uncoupling, and the rotation of the envelope is a quasi-solid rotation; the uncoupling and the expansion of the envelope indicate that the decrease of the equatorial velocity approximately follows the slope for the change in the equatorial velocity of the model without any redistribution of angular momentum. When the fractional age 0.3 ∼MS ∼< 0.5, the equatorial velocity remains almost constant for stars whose central density increases with age in the early stage of the MS phase, while the velocity decreases with age for stars whose central density decreases with age in the early stage of the MS phase.

  16. Rest mutant zebrafish swim erratically and display atypical spatial preferences.

    Science.gov (United States)

    Moravec, Cara E; Li, Edward; Maaswinkel, Hans; Kritzer, Mary F; Weng, Wei; Sirotkin, Howard I

    2015-05-01

    The Rest/Nrsf transcriptional repressor modulates expression of a large set of neural specific genes. Many of these target genes have well characterized roles in nervous system processes including development, plasticity and synaptogenesis. However, the impact of Rest-mediated transcriptional regulation on behavior has been understudied due in part to the embryonic lethality of the mouse knockout. To investigate the requirement for Rest in behavior, we employed the zebrafish rest mutant to explore a range of behaviors in adults and larva. Adult rest mutants of both sexes showed abnormal behaviors in a novel environment including increased vertical swimming, erratic swimming patterns and a proclivity for the tank walls. Adult males also had diminished reproductive success. At 6 days post fertilization (dpf), rest mutant larva were hypoactive, but displayed normal evoked responses to light and sound stimuli. Overall, these results provide evidence that rest dysfunction produces atypical swimming patterns and preferences in adults, and reduced locomotor activity in larvae. This study provides the first behavioral analysis of rest mutants and reveals specific behaviors that are modulated by Rest.

  17. Transoral robotic surgery for atypical carcinoid tumor of the larynx.

    Science.gov (United States)

    Muderris, Togay; Bercin, Sami; Sevil, Ergun; Acar, Baran; Kiris, Muzaffer

    2013-11-01

    In recent years, transoral robotic surgery has been introduced as an efficient and a reliable method for excision of selected oral cavity, tongue base, and supraglottic tumors in otolaryngology. In this case report, a 39-year-old woman with a history of hoarseness and dysphagia for approximately 6 months is presented. The patient was diagnosed with atypical carcinoid tumor on the laryngeal aspect of the epiglottis, and excision of the tumor was performed through transoral robotic surgery using the robotic da Vinci surgical system, a 0-degree three-dimensional endoscope, 5-mm microinstruments compatible with the da Vinci robot, and a Feyh-Kastenbauer/Weinstein-O'Malley retractor. The mass was removed completely, and no complications occurred. The patient recovered without a need for tracheotomy. Findings of the 1-year clinical follow-up revealed no locoregional recurrence or distant metastasis. This case shows, once again, that transoral robotic surgery could be used safely and effectively regardless of pathologic diagnosis in the supraglottic region tumors. PMID:24220389

  18. Contraction stimulates muscle glucose uptake independent of atypical PKC.

    Science.gov (United States)

    Yu, Haiyan; Fujii, Nobuharu L; Toyoda, Taro; An, Ding; Farese, Robert V; Leitges, Michael; Hirshman, Michael F; Mul, Joram D; Goodyear, Laurie J

    2015-11-01

    Exercise increases skeletal muscle glucose uptake, but the underlying mechanisms are only partially understood. The atypical protein kinase C (PKC) isoforms λ and ζ (PKC-λ/ζ) have been shown to be necessary for insulin-, AICAR-, and metformin-stimulated glucose uptake in skeletal muscle, but not for treadmill exercise-stimulated muscle glucose uptake. To investigate if PKC-λ/ζ activity is required for contraction-stimulated muscle glucose uptake, we used mice with tibialis anterior muscle-specific overexpression of an empty vector (WT), wild-type PKC-ζ (PKC-ζ(WT)), or an enzymatically inactive T410A-PKC-ζ mutant (PKC-ζ(T410A)). We also studied skeletal muscle-specific PKC-λ knockout (MλKO) mice. Basal glucose uptake was similar between WT, PKC-ζ(WT), and PKC-ζ(T410A) tibialis anterior muscles. In contrast, in situ contraction-stimulated glucose uptake was increased in PKC-ζ(T410A) tibialis anterior muscles compared to WT or PKC-ζ(WT) tibialis anterior muscles. Furthermore, in vitro contraction-stimulated glucose uptake was greater in soleus muscles of MλKO mice than WT controls. Thus, loss of PKC-λ/ζ activity increases contraction-stimulated muscle glucose uptake. These data clearly demonstrate that PKC-λζ activity is not necessary for contraction-stimulated glucose uptake.

  19. Atypical Hemolytic Uremic Syndrome Recurrence after Renal Transplantation

    Science.gov (United States)

    Bouatou, Yassine; Bacchi, Véronique Frémeaux; Villard, Jean; Moll, Solange; Martin, Pierre-Yves; Hadaya, Karine

    2015-01-01

    Abstract Risk for atypical hemolytic uremic syndrome (aHUS) recurrence after renal transplantation is low with an isolated membrane cofactor protein mutation (MCP). We report the case of a 32-year-old woman with a MCP who underwent kidney transplantation with a good evolution at 12 months. At 15 and 35 months, 2 episodes of thrombotic microangiopathy (TMA), after a miscarriage and a preeclampsia, were misinterpreted as triggered by tacrolimus. After each episode however serum creatinine returned to baseline. Five years after transplantation, she had a self-limited rhinosinusitis followed 3 weeks later by an oliguric renal failure. Her complement profile was normal. Graft biopsy showed C3 glomerulonephritis with no “humps” on electron microscopy. No significant renal function improvement followed methylprednisolone pulsing. A second biopsy showed severe acute TMA lesions with C3 glomerular deposits. Despite weekly eculizumab for 1 month, dialysis was resumed. A new workup identified the “at-risk” complement factor H haplotype. Thus, aHUS recurrence should be ruled out in aHUS patients considered at low recurrence risk when a TMA is found in graft biopsy. Prompt eculizumab therapy should be considered to avoid graft loss as aHUS recurrence can first present as a C3 glomerulonephritis. PMID:27500215

  20. Rest Mutant zebrafish swim erratically and display atypical spatial preferences

    Science.gov (United States)

    Moravec, Cara E.; Li, Edward; Maaswinkel, Hans; Kritzer, Mary F.; Weng, Wei; Sirotkin, Howard I.

    2015-01-01

    The Rest/Nrsf transcriptional repressor modulates expression of a large set of neural specific genes. Many of these target genes have well characterized roles in nervous system processes including development, plasticity and synaptogenesis. However, the impact of Rest-mediated transcriptional regulation on behavior has been understudied due in part to the embryonic lethality of the mouse knockout. To investigate the requirement for Rest in behavior, we employed the zebrafish rest mutant to explore a range of behaviors in adults and larva. Adult rest mutants of both sexes showed abnormal behaviors in a novel environment including increased vertical swimming, erratic swimming patterns and a proclivity for the tank walls. Adult males also had diminished reproductive success. At 6 days post fertilization (dpf), rest mutant larva were hypoactive, but displayed normal evoked responses to light and sound stimuli. Overall, these results provide evidence that rest dysfunction produces atypical swimming patterns and preferences in adults, and reduced locomotor activity in larvae. This study provides the first behavioral analysis of rest mutants and reveals specific behaviors that are modulated by Rest. PMID:25712696

  1. MRI features of atypical teratoid/rhabdoid tumors in children

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Biao [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Shanghai Jiaotong University School of Medicine, Department of Radiology, XinHua Hospital (Chongming Branch), Shanghai (China); Feng, Xiao Yuan [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China)

    2013-08-15

    Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, highly malignant tumors of the central nervous system, usually occurring in young children. To investigate the MRI features of AT/RT, with special emphasis on diffusion-weighted imaging (DWI) and MR spectroscopy (MRS). MRI findings of 11 children with AT/RT were reviewed retrospectively, including DWI in 9 AT/RT children and MRS in 6 children. The neoplasms were infratentorial in 4 children and supratentorial in 5 children, both infra- and supratentorial in 1 child and multifocal in 1 child. AT/RT produced heterogeneous signal intensity from peripheral cysts in 7/11 (63%) and hemorrhage in 7/11 (63%). All lesions showed contrast enhancement of varying degrees. Seven (63%) had peritumoral edema. Nine (82%) were hyperintense on DWI with a mean {+-} SD ADC of 0.60 {+-} 0.13 x 10{sup -3} mm{sup 2} s{sup -1}. Six lesions (55%) exhibited elevated levels of choline and decreased NAA, and three had lipid peaks. A childhood intracranial tumor with off-midline location, peripheral cystic components, hemorrhage, low ADC, and lipid peaks on MRS suggests AT/RT to be considered a differential diagnosis. (orig.)

  2. Assesment, treatment and prevention of atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    Azar Nickavar

    2013-01-01

    Full Text Available Hemolytic uremic syndrome (HUS is a heterogeneous group of hemolytic disorders. Different terminologies have been described in HUS, which are as follows: (1 D+ HUS: Presentation with a preceding diarrhea; (2 typical HUS: D+ HUS with a single and self-limited episode; (3 atypical HUS (aHUS: Indicated those with complement dysregulation; (4 recurrent HUS: Recurrent episodes of thrombocytopenia and/or microangiopathic hemolytic anemia (MAHA after improvement of hematologic abnormalities; and (5 familial HUS: Necessary to distinct synchronous outbreaks of D+ HUS in family members and asynchronous disease with an inherited risk factor. aHUS is one of the potential causes of end-stage renal disease (ESRD in children. It has a high recurrence after renal transplantation in some genetic forms. Therefore, recognition of the responsible mechanism and proper prophylactic treatment are recommended to prevent or delay the occurrence of ESRD and prolong the length of survival of the transplanted kidney. A computerized search of MEDLINE and other databases was carried out to find the latest results in pathogenesis, treatment, and prevention of aHUS.

  3. Rotation and surface abundance peculiarities in A-type stars

    CERN Document Server

    Takeda, Yoichi; Kang, Dong-Il; Lee, Byeong-Cheol; Kim, Kang-Min

    2008-01-01

    In an attempt of clarifying the connection between the photospheric abundance anomalies and the stellar rotation as well as of exploring the nature of "normal A" stars, the abundances of seven elements (C, O, Si, Ca, Ti, Fe, and Ba) and the projected rotational velocity for 46 A-type field stars were determined by applying the spectrum-fitting method to the high-dispersion spectral data obtained with BOES at BOAO. We found that the peculiarities (underabundances of C, O, and Ca; an overabundance of Ba) seen in slow rotators efficiently decrease with an increase of rotation, which almost disappear at v_e sin i > 100 km s^-1. This further suggests that stars with sufficiently large rotational velocity may retain the original composition at the surface without being altered. Considering the subsolar tendency (by several tenths dex below) exhibited by the elemental abundances of such rapidly-rotating (supposedly normal) A stars, we suspect that the gas metallicity may have decreased since our Sun was born, contra...

  4. Using atypical symptoms and red flags to identify non-demyelinating disease.

    LENUS (Irish Health Repository)

    Kelly, Siobhan B

    2012-01-01

    Red flags and atypical symptoms have been described as being useful in suggesting alternative diagnoses to multiple sclerosis (MS) and clinically isolated syndrome (CIS); however, their diagnostic utility has not been assessed. The aim of this study was to establish the predictive value of red flags and the typicality\\/atypicality of symptoms at presentation in relation to the final diagnosis of patients referred with suspected MS.

  5. Atypical ultrasound features of parathyroid tumours may bear a relationship to their clinical and biochemical presentation

    OpenAIRE

    Chandramohan, Anuradha; Sathyakumar, Kirthi; John, Reetu Amrita; Manipadam, Marie Therese; Abraham, Deepak; Thomas V Paul; Thomas, Nihal; Paul, M. J.

    2013-01-01

    Objectives To describe atypical ultrasound features of parathyroid lesions and correlate them with clinical presentation and histopathology. Materials and methods Retrospective review of 264 patients with primary hyperparathyroidism who underwent ultrasound imaging prior to parathyroidectomy was performed. Patients with atypical ultrasound findings (n = 26) were identified; imaging findings were correlated with clinical presentation and histopathology. Results Twenty-one (80 %) lesions were a...

  6. CHALLENGE WITH ATYPICAL ANTIPSYCHOTIC DRUGS IN RISPERIDONE INDUCED NEUROLEPTIC MALIGNANT SYNDROME: A CASE REPORT

    OpenAIRE

    Mendhekar, D.N.; Jiloha, R.C.; M M Mehndiratta; War, L.

    2002-01-01

    There are several reports available on neuroleptic malignant syndrome (NMS) associated with risperidone but when a more stringent criterion is applied there are only a few. Report on challenge and rechallenge with various atypical antipsychotic drugs in re-emergence of post NMS psychosis is scanty. Our aim of presenting this is to highlight the differential response of various atypical antipsychotic drugs in the treatment of post NMS psychosis. This paper reports a young male with mild mental...

  7. Atypical depression: useful concept, but it's time to revise the DSM-IV criteria.

    Science.gov (United States)

    Thase, Michael E

    2009-12-01

    Stewart et al (2009) have outlined the evidence in support of the validity of the DSM-IV definition of the 'With Atypical Features' episode specifier. Although recognizing the historical significance and clinical utility of the concept of atypical depression, this article takes issue with the DSM-IV criteria. It is concluded that mood reactivity, the A or obligative criterion, is neither significantly associated with the other symptomatic criteria nor useful to diagnose atypical depression, and thus should be eliminated. Problems with operationalization, specification, and reliability of ratings of the diagnostic criteria further limit validity. Despite these limitations in classification, many of the features associated with atypical depression are linked to an early onset of affective illness, including trait-like interpersonal sensitivity, comorbid social anxiety and agoraphobia, a history of childhood physical or sexual trauma, and indicators of the 'soft' side of the bipolar spectrum. Neurophysiologic studies also suggest that chronic, early-onset atypical depressions differ from both melancholia and normality. Re-analyses of the Columbia group's seminal studies suggest that preferential response to phenelzine vs imipramine--arguably the strongest validator of atypical depression--similarly appears to be limited to patients with chronic, early-onset syndromes. The criteria for atypical depression need to be revised in DSM-V, including sharpening the operational definitions for the specific symptoms. The importance of age of onset and comorbid anxiety warrant further study. Research examining the validity of a subform of atypical depression characterized by trait-like interpersonal sensitivity and a chronic, early-onset course may further enhance the clinical utility of the DSM-V classification. PMID:19741592

  8. Good and bad at numbers: typical and atypical development of number processing and arithmetic

    OpenAIRE

    Iuculano, T.

    2012-01-01

    This thesis elucidates the heterogeneous nature of mathematical skills by examining numerical and arithmetical abilities in typical, atypical and exceptional populations. Moreover, it looks at the benefits of intervention for remediating and improving mathematical skills. First, we establish the nature of the ‘number sense’ and assess its contribution to typical and atypical arithmetical development. We confirmed that representing and manipulating numerosities approximately is fundamentally d...

  9. Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi.

    Science.gov (United States)

    Husain, Ehab A; Mein, Charles; Pozo, Lucia; Blanes, Alfredo; Diaz-Cano, Salvador J

    2011-04-01

    Atypical (dysplastic) melanocytic nevi are clinically heterogeneous malignant melanoma precursors, for which no topographic analysis of cell kinetic, cell cycle regulators and microsatellite profile is available. We selected low-grade atypical melanocytic nevi (92), high-grade atypical melanocytic nevi (41), melanocytic nevi (18 junctional, 25 compound) and malignant melanomas (16 radial growth phase and 27 vertical growth phase). TP53, CDKN2A, CDKN1A, and CDKN1B microsatellite patterns were topographically studied after microdissection; Ki-67, TP53, CDKN2A, CDKN1A, and CDKN1B expressions and DNA fragmentation by in situ end labeling for apoptosis were topographically scored. Results were statistically analyzed. A decreasing junctional-dermal marker expression gradient was observed, directly correlating with atypical melanocytic nevus grading. High-grade atypical melanocytic nevi revealed coexistent TP53-CDKN2A-CDKN1B microsatellite abnormalities, and significantly higher junctional Ki67-TP53 expression (inversely correlated with CDKN1A-CDKN1B expression and in situ end labeling). Malignant melanomas showed coexistent microsatellite abnormalities (CDKN2A-CDKN1B), no topographic gradient, and significantly decreased expression. Melanocytic nevi and low-grade atypical melanocytic nevi revealed sporadic junctional CDKN2A microsatellite abnormalities and no significant topographic kinetic differences. High-grade atypical melanocytic nevi accumulate junctional TP53-CDKN1A-CDKN1B microsatellite abnormalities, being progression TP53-independent and better assessed in the dermis. Melanocytic nevi and low-grade atypical melanocytic nevi show low incidence of microsatellite abnormalities, and kinetic features that make progression unlikely.

  10. Clonal Relationship among Atypical Enteropathogenic Escherichia coli Strains Isolated from Different Animal Species and Humans▿

    OpenAIRE

    Moura, Rodrigo A.; Sircili, Marcelo P.; Leomil, Luciana; Matté, Maria Helena; Trabulsi, Luiz R.; Elias, Waldir P.; Irino, Kinue; Antonio F. Pestana de Castro

    2009-01-01

    Forty-nine typical and atypical enteropathogenic Escherichia coli (EPEC) strains belonging to different serotypes and isolated from humans, pets (cats and dogs), farm animals (bovines, sheep, and rabbits), and wild animals (monkeys) were investigated for virulence markers and clonal similarity by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The virulence markers analyzed revealed that atypical EPEC strains isolated from animals have the potential to cause dia...

  11. Atypical Findings of Guillain-Barré Syndrome in Children

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2013-01-01

    Full Text Available How to cite this article: Karimzadeh P, Bakhshandeh Bali MK, Nasehi MM, Taheri Otaghsara SM, Ghofrani M. Atypical Findings of Guillain-Barré Syndrome in Children. Iran J Child Neurol Autumn 2012;6(4:17-22. AbstractObjectiveGuillain-Barre syndrome (GBS is an immune-mediated polyneuropathy that occurs mostly after  prior infection. The diagnosis of this syndrome is dependent heavily on the history and examination, although cerebrospinal fluid analysis and electrodiagnostic testing usually confirm the diagnosis. This is a retrospective study which was performed to investigate the atypical features of GBS.Materials & MethodsThirty three patients (21/63.6% males and 12/36.4% females with GBS were retrospectively studied and prospectively evaluated at the Child Neurology institute of Mofid Children Hospital of Shahid Beheshti University of Medical Sciences between May 2011 and September 2012.ResultsThe mean age was 5.4 years (range, 1.5-10.5.Twenty one patients (87.9 % had previous history of infections. Eight patients (24.2% admitted with atypical symptoms like upper limb weakness (3%, ptosis (3%, neck stiffness (3%, inability to stand (proximal weakness (9.1%, headache (3% and dysphagia (3%.According to disease process, weakness was ascending in 26 (78.8%, descending in 5 (15.2% and static in 2 (6.1% patients. Cranial nerve involvement was found in 8(24.3% children, most commonly as facial palsy in 3 (9.1%.ConclusionIn this study, 24.3% of our patients presented with atypical symptoms of GBS as upper limb weakness, ptosis, neck stiffness, inability to stand (proximal weakness, headache and dysphagia References:Hughes RA, Cornblath DR. Guillain-Barré syndrome. Lancet. 2005 Nov 5;366(9497:1653-66.McGillicuddy DC, Walker O, Shapiro NI, Edlow JA. Guillain-Barré syndrome in the emergency department. Ann Emerg Med. 2006 Apr;47(4:390-3.Cosi V, Versino M. Guillain-Barré syndrome. Neurol Sci. 2006;27(Suppl 1:S47-51.Hughes RA, Cornblath DR. Guillain

  12. Atypical Mole (Atypical Nevus)

    Science.gov (United States)

    ... melanoma). Remember the ABCDEs of melanoma lesions: A - Asymmetry: One half of the lesion does not mirror ... York: Mosby, 2003. Last Updated: 22 Dec 2008 Information for other ages: Child Teen Table of Contents: ...

  13. How do we choose between atypical antipsychotics? The advantages of amisulpride.

    Science.gov (United States)

    Mortimer, Ann M

    2004-03-01

    Clinician choice of an atypical antipsychotic may depend on a number of factors such as perceived efficacy, tolerability and cost. It is also important that the choice of treatment takes into consideration the previous response to treatment, experience of side-effects and personal clinical characteristics. The receptor-affinity profiles of the atypical antipsychotics differ; with the exception of amisulpride, a selective D2/D3 antagonist, all the atypical antipsychotics exhibit a greater affinity for the serotonin-2A receptors than dopamine receptors. However, there is no evidence that the variation in receptor affinities is relevant to efficacy. Indeed, the crucial factor may be fast dissociation from low affinity for the D2 receptor. Tolerability also varies between the atypical antipsychotics and the side-effect profile may be related to the receptor-affinity profile of the individual drugs. Extrapyramidal side-effects are generally less of a problem with most atypical drugs than with conventional drugs, but weight gain, loss of glycaemic control, sedation and hyperprolactinaemia remain problematic in some patients. Amisulpride is effective for the treatment of both positive and negative symptoms, and is well tolerated with regard to weight gain, glucose tolerance and sedation. In two clinical trials, the AMIRIS and SOLIANOL studies, amisulpride demonstrated clear advantages over some other atypical antipsychotics with respect to negative symptoms, depressive symptoms and weight gain.

  14. Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors.

    Science.gov (United States)

    Masiá, M; Gutiérrez, F; Padilla, S; Soldán, B; Mirete, C; Shum, C; Hernández, I; Royo, G; Martin-Hidalgo, A

    2007-02-01

    The aim of this study was to characterise community-acquired pneumonia (CAP) caused by atypical pathogens by combining distinctive clinical and epidemiological features and novel biological markers. A population-based prospective study of consecutive patients with CAP included investigation of biomarkers of bacterial infection, e.g., procalcitonin, C-reactive protein and lipopolysaccharide-binding protein (LBP) levels. Clinical, radiological and laboratory data for patients with CAP caused by atypical pathogens were compared by univariate and multivariate analysis with data for patients with typical pathogens and patients from whom no organisms were identified. Two predictive scoring models were developed with the most discriminatory variables from multivariate analysis. Of 493 patients, 94 had CAP caused by atypical pathogens. According to multivariate analysis, patients with atypical pneumonia were more likely to have normal white blood cell counts, have repetitive air-conditioning exposure, be aged <65 years, have elevated aspartate aminotransferase levels, have been exposed to birds, and have lower serum levels of LBP. Two different scoring systems were developed that predicted atypical pathogens with sensitivities of 35.2% and 48.8%, and specificities of 93% and 91%, respectively. The combination of selected patient characteristics and laboratory data identified up to half of the cases of atypical pneumonia with high specificity, which should help clinicians to optimise initial empirical therapy for CAP.

  15. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, Suppurative Hidradenitis (PA-PASH) Syndrome: An Atypical Presentation of a Rare Syndrome.

    Science.gov (United States)

    Ursani, Mohammad A; Appleyard, Joan; Whiteru, Onome

    2016-01-01

    BACKGROUND Pyogenic arthritis, pyoderma gangrenosum (PG), acne, and suppurative hidradenitis (PA-PASH) syndrome has been linked to an auto-inflammatory pathway. We report a case that is an atypical presentation of a rare syndrome, which supports literature suggesting that different phenotypes of PG-related syndromes may be a variation of the same pathogenic spectrum. Interestingly, our patient displayed a positive proteinase-3 antibody (PR-3). The clinical relevance of this is unclear. In recent literature, antineutrophil cytoplasmic autoantibodies (ANCA) positivity has been reported in various inflammatory conditions other than ANCA-associated vasculitis (AAV). CASE REPORT A 44-year-old African American male with history of pyogenic arthritis, acne, suppurative hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers located on the bilateral lower extremities, bilateral proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious etiologies for the ulcers were ruled out. Biopsy of an ulcer revealed PG. Colonoscopy revealed inflammation and ulceration with biopsy consistent with ulcerative colitis (UC). After treatment with prednisone, the ulcers healed within 4 weeks, and the chronic diarrhea resolved. CONCLUSIONS Our patient displayed a variation of PA-PASH syndrome and UC. Previously reported cases of similar phenotypes of PG-related syndromes have not presented in this fashion. Furthermore, the literature does not report cases of PG-related syndromes with an elevation in PR-3 antibody. Elevation in PR-3 has been reported in various inflammatory disorders aside from AAV. The relevance of this is currently unclear. It may be possible that the milieus of these various auto-inflammatory disorders may share pathogenic commonalities. PMID:27530224

  16. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, Suppurative Hidradenitis (PA-PASH) Syndrome: An Atypical Presentation of a Rare Syndrome

    Science.gov (United States)

    Ursani, Mohammad A.; Appleyard, Joan; Whiteru, Onome

    2016-01-01

    Patient: Male, 44 Final Diagnosis: PAPASH syndrome Symptoms: Recurrent skin ulcers • diarrhea • inflammatory arthritis Medication: Prednisone • anti-tumor necrosis factor Clinical Procedure: N/A Specialty: Rheumatology Objective: Rare disease Background: Pyogenic arthritis, pyoderma gangrenosum (PG), acne, and suppurative hidradenitis (PA-PASH) syndrome has been linked to an auto-inflammatory pathway. We report a case that is an atypical presentation of a rare syndrome, which supports literature suggesting that different phenotypes of PG-related syndromes may be a variation of the same pathogenic spectrum. Interestingly, our patient displayed a positive proteinase-3 antibody (PR-3). The clinical relevance of this is unclear. In recent literature, antineutrophil cytoplasmic autoantibodies (ANCA) positivity has been reported in various inflammatory conditions other than ANCA-associated vasculitis (AAV). Case Report: A 44-year-old African American male with history of pyogenic arthritis, acne, suppurative hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers located on the bilateral lower extremities, bilateral proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious etiologies for the ulcers were ruled out. Biopsy of an ulcer revealed PG. Colonoscopy revealed inflammation and ulceration with biopsy consistent with ulcerative colitis (UC). After treatment with prednisone, the ulcers healed within 4 weeks, and the chronic diarrhea resolved. Conclusions: Our patient displayed a variation of PA-PASH syndrome and UC. Previously reported cases of similar phenotypes of PG-related syndromes have not presented in this fashion. Furthermore, the literature does not report cases of PG-related syndromes with an elevation in PR-3 antibody. Elevation in PR-3 has been reported in various inflammatory disorders aside from AAV. The relevance of this is currently unclear. It may be possible that the milieus of these various

  17. Autistic adolescents show atypical activation of the brain's mentalizing system even without a prior history of mentalizing problems.

    Science.gov (United States)

    White, Sarah J; Frith, Uta; Rellecke, Julian; Al-Noor, Zainab; Gilbert, Sam J

    2014-04-01

    Some autistic children pass classic Theory of Mind (ToM) tasks that others fail, but the significance of this finding is at present unclear. We identified two such groups of primary school age (labelled ToM+ and ToM-) and a matched comparison group of typically developing children (TD). Five years later we tested these participants again on a ToM test battery appropriate for adolescents and conducted an fMRI study with a story based ToM task. We also assessed autistic core symptoms at these two time points. At both times the ToM- group showed more severe social communication impairments than the ToM+ group, and while showing an improvement in mentalizing performance, they continued to show a significant impairment compared to the NT group. Two independent ROI analyses of the BOLD signal showed activation of the mentalizing network including medial prefrontal cortex, posterior cingulate and lateral temporal cortices. Strikingly, both ToM+ and ToM- groups showed very similar patterns of heightened activation in comparison with the NT group. No differences in other brain regions were apparent. Thus, autistic adolescents who do not have a history of mentalizing problems according to our ToM battery showed the same atypical neurophysiological response during mentalizing as children who did have such a history. This finding indicates that heterogeneity at the behavioural level may nevertheless map onto a similar phenotype at the neuro-cognitive level.

  18. The Alternative Pathway of Complement and the Evolving Clinical-Pathophysiological Spectrum of Atypical Hemolytic Uremic Syndrome.

    Science.gov (United States)

    Berger, Bruce E

    2016-08-01

    Complement-mediated atypical hemolytic uremic syndrome (aHUS) comprises approximately 90% of cases of aHUS, and results from dysregulation of endothelial-anchored complement activation with resultant endothelial damage. The discovery of biomarker ADAMTS13 has enabled a more accurate diagnosis of thrombotic thrombocytopenic purpura (TTP) and an appreciation of overlapping clinical features of TTP and aHUS. Given our present understanding of the pathogenic pathways involved in aHUS, it is unlikely that a specific test will be developed. Rather the use of biomarker data, complement functional analyses, genomic analyses and clinical presentation will be required to diagnose aHUS. This approach would serve to clarify whether a thrombotic microangiopathy present in a complement-amplifying condition arises from the unmasking of a genetically driven aHUS versus a time-limited complement storm-mediated aHUS due to direct endothelial damage in which no genetic predisposition is present. Although both scenarios result in the phenotypic expression of aHUS and involve the alternate pathway of complement activation, long-term management would differ. PMID:27524217

  19. An atypical case of neuronal ceroid lipofuscinosis with co-inheritance of a variably penetrant POLG1 mutation

    Directory of Open Access Journals (Sweden)

    Staropoli John F

    2012-06-01

    Full Text Available Abstract Background The neuronal ceroid lipofuscinoses (NCLs, or Batten disease comprise the most common Mendelian form of childhood-onset neurodegeneration, but the functions of the known underlying gene products remain poorly understood. The clinical heterogeneity of these disorders may shed light on genetic interactors that modify disease onset and progression. Case presentation We describe a proband with congenital hypotonia and an atypical form of infantile-onset, biopsy-proven NCL. Pathologic and molecular work-up of this patient identified CLN5 mutations as well as a mutation―previously described as incompletely penetrant or a variant of unknown significance―in POLG1, a nuclear gene essential for maintenance of mitochondrial DNA (mtDNA copy number. The congenital presentation of this patient is far earlier than that described for either CLN5 patients or affected carriers of the POLG1 variant (c.1550 G > T, p.Gly517Val. Assessment of relative mtDNA copy number and mitochondrial membrane potential in the proband and control subjects suggested a pathogenic effect of the POLG1 change as well as a possible functional interaction with CLN5 mutations. Conclusions These findings suggest that an incompletely penetrant variant in POLG1 may modify the clinical phenotype in a case of CLN5 and are consistent with emerging evidence of interactions between NCL-related genes and mitochondrial physiology.

  20. Deciphering the Galaxy Guppy phenotype

    Directory of Open Access Journals (Sweden)

    Philip Shaddock

    2011-01-01

    Full Text Available Animal breeding hobbyists have been useful to science because they identify and isolate colorcoat mutations that geneticists can in turn use in their studies of the development and differentiation ofcolor cells. This paper discusses a very interesting color mutant, the Japanese Galaxy, tracing its creationfrom back to a self-educated genetics hobbyist, Hoskiki Tsutsui. The paper discusses a constituent genepreviously studied by Dr. Violet Phang, the snakeskin gene (the linked body and fin genes Ssb and Sst.And it discusses a gene previously unknown to science, the Schimmelpfennig Platinum gene (Sc.Through crossing experiments, the author determines that the combination of these two genes producesan intermediate phenotype, the Medusa. Incorporating the Grass (Gr, another gene unknown to sciencegene into the Medusa through a crossover produces the Galaxy phenotype. Microscope studies of thesnakeskin pattern in Galaxies and snakeskins reveals some parallels with similar studies made of theZebrafish Danio.

  1. Phenotypic expression in mucopolysaccharidosis VII.

    OpenAIRE

    Bernsen, P L; Wevers, R. A.; Gabreëls, F J; Lamers, K J; Sonnen, A E; Stekhoven, J H

    1987-01-01

    beta-glucuronidase deficiency is an extremely rare disorder which is known to have a considerable phenotypic variation. A survey of the clinical findings in 19 previously reported patients with mucopolysaccharidosis VII is presented together with the results of clinical and biochemical studies in two further patients. Because a similar clinical picture is present in a heterozygotic sister it is doubted whether all signs and symptoms can be attributed to the beta-glucuronidase deficiency. The ...

  2. Statistical models for trisomic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Lamb, N.E.; Sherman, S.L.; Feingold, E. [Emory Univ., Atlanta, GA (United States)

    1996-01-01

    Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on the trisomic chromosome. As with all aneuploid syndromes, however, a considerable degree of variation exists within each phenotype so that any given trait is present only among a subset of the trisomic population. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for such traits. The mapping strategy does not depend on the simple model but works in theory under any model that predicts that affected individuals have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by investigating what kinds of models give an expected increase in disomic homozygosity. We describe a number of basic statistical models for trisomic phenotypes. Some of these are logical extensions of standard models for disomic phenotypes, and some are more specific to trisomy. Where possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait. Finally, we determine the sample sizes required to identify the increased disomic homozygosity under each model. Most of the models we explore yield detectable increases in disomic homozygosity for some reasonable range of parameter values, usually corresponding to smaller trait frequencies. It therefore appears that our mapping method should be effective for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known. 21 refs., 8 figs., 1 tab.

  3. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  4. [Plasticity of the cellular phenotype].

    Science.gov (United States)

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours. PMID:21501574

  5. Genetic background of phenotypic variation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A noteworthy feature of the living world is its bewildering variability. A key issue in several biological disciplines is the achievement of an understanding of the hereditary basis of this variability. Two opposing, but not necessarily irreconcilable conceptions attempt to explain the underlying mechanism. The gene function paradigm postulates that phenotypic variance is generated by the polymorphism in the coding sequences of genes. However, comparisons of a great number of homologous gene and protein sequences have revealed that they predominantly remained functionally conserved even across distantly related phylogenic taxa. Alternatively, the gene regulation paradigm assumes that differences in the cis-regulatory region of genes do account for phenotype variation within species. An extension of this latter concept is that phenotypic variability is generated by the polyrnorphism in the overall gene expression profiles of gene networks.In other words, the activity of a particular gene is a system property determined both by the cis-regulatory sequences of the given genes and by the other genes of a gene network, whose expressions vary among individuals, too. Novel proponents of gene function paradigm claim that functional genetic variance within the coding sequences of regulatory genes is critical for the generation of morphological polymorphism. Note, however, that these developmental genes play direct regulatory roles in the control of gene expression.

  6. Adaptive evolution of molecular phenotypes

    Science.gov (United States)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-09-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak.

  7. Bile salts induce expression of the afimbrial LDA adhesin of atypical enteropathogenic Escherichia coli.

    Science.gov (United States)

    Torres, Alfredo G; Tutt, Christopher B; Duval, Lisabeth; Popov, Vsevolod; Nasr, Abdelhakim Ben; Michalski, Jane; Scaletsky, Isabel C A

    2007-04-01

    Atypical enteropathogenic Escherichia coli (aEPEC) strains are frequently implicated in infant diarrhoea in developing countries. Not much is known about the adherence properties of aEPEC; however, it has been shown that these strains can adhere to tissue-cultured cells. A chromosomal region designated the locus for diffuse adherence (LDA) confers aEPEC strain 22 the ability to adhere to culture cells. LDA is an afimbrial adhesin that contains a major subunit, LdaG, whose expression is induced on MacConkey agar at 37 degrees C. We hypothesized that the bile salts found in this culture media induce the expression of LdaG. Strain 22 and the LdaG mutant were grown in Luria-Bertani (LB) media in the presence or absence of bile salts and heat-extracted surface-expressed proteins were separated by SDS-PAGE to determine whether expression of the 25 kDa LdaG protein was induced. Western blot analysis with anti-LdaG confirmed that bile salts enhance LdaG expression at 37 degrees C. Adhesion assays on HeLa cells revealed that adhesion in a diffuse pattern of strain 22 increased in the presence of bile salts. We also confirmed that expression of the localized adherence pattern observed in the ldaG mutant required the presence of a large cryptic plasmid found in strain 22 and that this phenotype was not induced by bile salts. At the transcriptional level, the ldaG-lacZ promoter fusion displayed maximum beta-galactosidase activity when the parent strain was grown in LB supplemented with bile salts. Fluorescence Activated Cell Sorting analysis, immunogold labelling electron microscopy and immunofluorescence using anti-LdaG sera confirmed that LDA is a bile salts-inducible surface-expressed afimbrial adhesin. Finally, LdaG expression was induced in presence of individual bile salts but not by other detergents. We concluded that bile salts increase expression of LDA, conferring a diffuse adherence pattern and having an impact on the adhesion properties of this aEPEC strain.

  8. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

    Science.gov (United States)

    Cai, H L; Tan, Q Y; Jiang, P; Dang, R L; Xue, Y; Tang, M M; Xu, P; Deng, Y; Li, H D; Yao, J K

    2015-10-20

    Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.

  9. Atypical Endometriosis: a Clinicopathologic Study of 163 Cases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate the clinicopathologic features of atypical endometriosis (AEM), and to discuss the relations between AEMs and tumors.METHODS A retrospective analysis was performed on 163 cases of AEMs. The changes in the glandular epithelium, stroma, and their background and the relationship with coexisting tumors were observed.RESULTS The AEMs account of for 4.4% (163/3,724) of the endometriosis (EM) cases. Of 172 AEM foci of 163 patients, 168 were in the ovary, and the other 4 were in the fallopian tube, cervix and uterine serosa. Of the cases of ovarian EM, 6.8% were AEM. All of the 27 cases (15.7%) of the AEMs associated with a tumor were found in the ovaries, of which 15 were malignant,9 borderline, and 3 benign. Of the ovary AEMs, 14.9% were associated with a borderline or malignant tumor. The AEM epithelia were mainly arranged in the form of surface epithelia, with only a few glands. Present were characteristic features of moderate to marked pleomorphism, epithelial tufting, bud or firework-like structures on microscopy. Epithelial metaplastic changes were observed in 86 cases (50%) of the 172 AEM foci. Epithelium, endometrioid stroma, and fibrotic-collagen formed a three-layer structure in the wall of the AEM cysts. The endometrioid stroma were usually thin compared to the fibro-collagen tissue. The transformation from an AEM to a tumor was found in most of the malignant tumors.CONCLUSION AEM lesions have some features which are similar and also differ from both of the tumor and EM. AEMs have a relative higher potential for tumorigenesis and canceration, especially for ovarian cancer.The process of damage, repair, and scarring in EM foci over a long period may play a role in the development of EM into AEM and eventally into tumor formation.

  10. Atypical sulcal anatomy in young children with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    G. Auzias

    2014-01-01

    Full Text Available Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory

  11. Integrating binary traits with quantitative phenotypes for association mapping of multivariate phenotypes.

    Science.gov (United States)

    Mukhopadhyay, Indranil; Saha, Sujayam; Ghosh, Saurabh

    2011-01-01

    Clinical binary end-point traits are often governed by quantitative precursors. Hence it may be a prudent strategy to analyze a clinical end-point trait by considering a multivariate phenotype vector, possibly including both quantitative and qualitative phenotypes. A major statistical challenge lies in integrating the constituent phenotypes into a reduced univariate phenotype for association analyses. We assess the performances of certain reduced phenotypes using analysis of variance and a model-free quantile-based approach. We find that analysis of variance is more powerful than the quantile-based approach in detecting association, particularly for rare variants. We also find that using a principal component of the quantitative phenotypes and the residual of a logistic regression of the binary phenotype on the quantitative phenotypes may be an optimal method for integrating a binary phenotype with quantitative phenotypes to define a reduced univariate phenotype. PMID:22373144

  12. Multivariate Analysis of Genotype-Phenotype Association.

    Science.gov (United States)

    Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

    2016-04-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map

  13. Atypical leg symptoms: does routine measurement of the ankle brachial pressure index (ABPI) in primary care benefit patients?

    OpenAIRE

    Oesterling, Christine; Kalia, Amun; Chetcuti, Thomas; Walker, Steven

    2015-01-01

    Abstract Background : Managing patients with atypical leg symptoms in primary care can be problematic. Determining the ankle brachial pressure index (ABPI) may be readily performed to help diagnose peripheral arterial disease, but is often omitted where signs and symptoms are unclear. Question : Does routine measurement of ABPI in patients with atypical leg symptoms aid management increase satisfaction and safely reduce hospital referral? Methodology : Patients with atypical leg symptoms but ...

  14. Multiphasic strain differentiation of atypical mycobacteria from elephant trunk wash.

    Science.gov (United States)

    Chan, Kok-Gan; Loke, Mun Fai; Ong, Bee Lee; Wong, Yan Ling; Hong, Kar Wai; Tan, Kian Hin; Kaur, Sargit; Ng, Hien Fuh; Abdul Razak, Mfa; Ngeow, Yun Fong

    2015-01-01

    Background. Two non-tuberculous mycobacterial strains, UM_3 and UM_11, were isolated from the trunk wash of captive elephants in Malaysia. As they appeared to be identical phenotypes, they were investigated further by conventional and whole genome sequence-based methods of strain differentiation. Methods. Multiphasic investigations on the isolates included species identification with hsp65 PCR-sequencing, conventional biochemical tests, rapid biochemical profiling using API strips and the Biolog Phenotype Microarray analysis, protein profiling with liquid chromatography-mass spectrometry, repetitive sequence-based PCR typing and whole genome sequencing followed by phylogenomic analyses. Results. The isolates were shown to be possibly novel slow-growing schotochromogens with highly similar biological and genotypic characteristics. Both strains have a genome size of 5.2 Mbp, G+C content of 68.8%, one rRNA operon and 52 tRNAs each. They qualified for classification into the same species with their average nucleotide identity of 99.98% and tetranucleotide correlation coefficient of 0.99999. At the subspecies level, both strains showed 98.8% band similarity in the Diversilab automated repetitive sequence-based PCR typing system, 96.2% similarity in protein profiles obtained by liquid chromatography mass spectrometry, and a genomic distance that is close to zero in the phylogenomic tree constructed with conserved orthologs. Detailed epidemiological tracking revealed that the elephants shared a common habitat eight years apart, thus, strengthening the possibility of a clonal relationship between the two strains. PMID:26587340

  15. Comparison of two automated immunohistochemical procedures for the diagnosis of scrapie in domestic sheep and chronic wasting disease in North American white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus).

    Science.gov (United States)

    Baszler, T V; Kiupel, M; Williams, E S; Thomsen, B V; Gidlewski, T; Montgomery, D L; O'Rourke, K I; Hall, S M

    2006-03-01

    Two commercially available automated immunohistochemistry platforms, Ventana NexES and DakoCytomation Autostainer Universal Staining System, were compared for diagnosing sheep scrapie and cervid chronic wasting disease. Both automated platforms used the same antiprion protein monoclonal primary antibodies, but different platform-specific linker and amplification reagents and procedures. Duplicate sections of brainstem (at the level of the obex) and lymphoid tissue (retropharyngeal lymph node or tonsil) from the same tissue block were immunostained for the comparison. Examination of 1,020 tissues from 796 sheep revealed 100% concordance of results between the Ventana NexES and DakoCytomation platforms for diagnosing sheep scrapie from lymphoid tissue (103/103 positive; 405/405 negative) and brainstem (120/120 positive; 392/392 negative). Similarly, examination of 1,008 tissues from 504 white-tailed deer revealed 100% concordance between the Ventana NexES and DakoCytomation platforms for diagnosing chronic wasting disease from lymphoid tissue (104/104 positive; 400/400 negative) and brainstem (104/104 positive; 400/400 negative). Examination of 1,152 tissues from 482 mule deer revealed a concordance of 98.6% in lymphoid tissue and 99.9% in brainstem between the Ventana NexES and DakoCytomation platforms for diagnosing chronic wasting disease. The results indicate equivalence or near equivalence between the DakoCytomation and Ventana NexES autostainer platforms for identification of the disease-associated prion protein (PrPd)-positive and PrPd-negative brain and lymphoid tissues in sheep, white-tailed deer, and mule deer.

  16. Activation of Plant Immune Responses by a Gain-of-Function Mutation in an Atypical Receptor-Like Kinase1[C][W][OA

    Science.gov (United States)

    Bi, Dongling; Cheng, Yu Ti; Li, Xin; Zhang, Yuelin

    2010-01-01

    Arabidopsis (Arabidopsis thaliana) suppressor of npr1-1, constitutive1 (snc1) contains a gain-of-function mutation in a Toll/interleukin receptor-nucleotide binding site-leucine-rich repeat Resistance (R) protein and it has been a useful tool for dissecting R-protein-mediated immunity. Here we report the identification and characterization of snc4-1D, a semidominant mutant with snc1-like phenotypes. snc4-1D constitutively expresses defense marker genes PR1, PR2, and PDF1.2, and displays enhanced pathogen resistance. Map-based cloning of SNC4 revealed that it encodes an atypical receptor-like kinase with two predicted extracellular glycerophosphoryl diester phosphodiesterase domains. The snc4-1D mutation changes an alanine to threonine in the predicted cytoplasmic kinase domain. Wild-type plants transformed with the mutant snc4-1D gene displayed similar phenotypes as snc4-1D, suggesting that the mutation is a gain-of-function mutation. Epistasis analysis showed that NON-RACE-SPECIFIC DISEASE RESISTANCE1 is required for the snc4-1D mutant phenotypes. In addition, the snc4-1D mutant phenotypes are partially suppressed by knocking out MAP KINASE SUBSTRATE1, a positive defense regulator associated with MAP KINASE4. Furthermore, both the morphology and constitutive pathogen resistance of snc4-1D are partially suppressed by blocking jasmonic acid synthesis, suggesting that jasmonic acid plays an important role in snc4-1D-mediated resistance. Identification of snc4-1D provides us a unique genetic system for analyzing the signal transduction pathways downstream of receptor-like kinases. PMID:20508139

  17. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  18. Evolution of acetylcholinesterase and butyrylcholinesterase in the vertebrates: an atypical butyrylcholinesterase from the Medaka Oryzias latipes.

    Directory of Open Access Journals (Sweden)

    Leo Pezzementi

    Full Text Available Acetylcholinesterase (AChE and butyrylcholinesterase (BChE are thought to be the result of a gene duplication event early in vertebrate evolution. To learn more about the evolution of these enzymes, we expressed in vitro, characterized, and modeled a recombinant cholinesterase (ChE from a teleost, the medaka Oryzias latipes. In addition to AChE, O. latipes has a ChE that is different from either vertebrate AChE or BChE, which we are classifying as an atypical BChE, and which may resemble a transitional form between the two. Of the fourteen aromatic amino acids in the catalytic gorge of vertebrate AChE, ten are conserved in the atypical BChE of O. latipes; by contrast, only eight are conserved in vertebrate BChE. Notably, the atypical BChE has one phenylalanine in its acyl pocket, while AChE has two and BChE none. These substitutions could account for the intermediate nature of this atypical BChE. Molecular modeling supports this proposal. The atypical BChE hydrolyzes acetylthiocholine (ATCh and propionylthiocholine (PTCh preferentially but butyrylthiocholine (BTCh to a considerable extent, which is different from the substrate specificity of AChE or BChE. The enzyme shows substrate inhibition with the two smaller substrates but not with the larger substrate BTCh. In comparison, AChE exhibits substrate inhibition, while BChE does not, but may instead show substrate activation. The atypical BChE from O. latipes also shows a mixed pattern of inhibition. It is effectively inhibited by physostigmine, typical of all ChEs. However, although the atypical BChE is efficiently inhibited by the BChE-specific inhibitor ethopropazine, it is not by another BChE inhibitor, iso-OMPA, nor by the AChE-specific inhibitor BW284c51. The atypical BChE is found as a glycophosphatidylinositol-anchored (GPI-anchored amphiphilic dimer (G(2 (a, which is unusual for any BChE. We classify the enzyme as an atypical BChE and discuss its implications for the evolution of ACh

  19. A further case of a Prader-Willi syndrome phenotype in a patient with Angelman syndrome molecular defect

    Directory of Open Access Journals (Sweden)

    De Molfetta Greice Andreotti

    2002-01-01

    Full Text Available Angelman syndrome (AS and Prader-Willi syndrome (PWS are distinct human neurogenetic disorders; however, a clinical overlap between AS and PWS has been identified. We report on a further case of a patient showing the PWS phenotype with the AS molecular defect. Despite the PWS phenotype, the DNA methylation analysis of SNRPN revealed an AS pattern. Cytogenetic and FISH analysis showed normal chromosomes 15 and microsatellite analysis showed heterozygous loci inside and outside the 15q11-13 region. The presence of these atypical cases could be more frequent than previously expected and we reinforce that the DNA methylation analysis is important for the correct diagnosis of severe mental deficiency, congenital hypotonia and obesity.

  20. Analysis of Pena Shokeir phenotype.

    Science.gov (United States)

    Hall, J G

    1986-09-01

    At this point in time, we recognize that "Pena Shokeir" is not a diagnosis or a specific syndrome but rather a description of a phenotype produced by fetal akinesia or decreased in utero movement. In its "full blown" form, it is characterized by polyhydramnios, intrauterine growth retardation, pulmonary hypoplasia, craniofacial and limb anomalies, congenital contractures, short umbilical cord, and lethality. From the cases thus far reported, we would anticipate that the phenotype is present in a very heterogeneous group of disorders--heterogeneous both with regard to the specific anomalies present and with regard to the causes (which must include many environmental agents and multiple genetic forms). One challenge for the future is to better describe and delineate specific entities. In the meantime, we would do well to use the terms "Pena Shokeir phenotype" or "fetal akinesia/hypokinesia sequence," which do not imply a single entity. There are many practical aspects of recognizing this phenotype. The presence of any one of the cardinal signs of the fetal akinesia/hypokinesia sequence should alert the physician to look for the other associated anomalies, since specific treatment may be indicated, and catch-up or compensatory growth may occur, if given a chance. The ability to provide prenatal diagnosis and perhaps prenatal treatment in the future may allow us to alter dramatically the natural history of some cases. In others, we need to establish when treatment is possible and when it gives no benefit. Perhaps the most important insight gained from the study of the fetal akinesia sequence is the reaffirmation of the concept that function is an integral part of normal development. Specific structures do not develop in isolation but are part of a carefully timed and integrated system. The "use" of a structure in utero is necessary for its continuing and normal development. The old adage "use it or lose it" seems to apply just as appropriately to prenatal normal

  1. Hemogoblin phenotypes in Murgese horse

    OpenAIRE

    Carmela Bottiglieri; Rosario Rullo; Aldo Di Luccia; Elisa Pieragostini

    2010-01-01

    In this note we describe two new equine hemoglobin phenotypes found during a survey of the Murgese horse, a rare  Apulian native breed, among whose ancestors the Arabian surely plays an important role. To date we have analysed about  300 individual hemolysates by different chromatographic analyses (PAGIF, IPG, CMC). The results pointed out two unusu-  al patterns where the ratio of the α24Phe60Gln band to the α24Phe60Lys band was 93:7 and 70:30 rather than 60:40&nbs...

  2. Effect of Anterior Cervical Discectomy and Fusion on Patients with Atypical Symptoms Related to Cervical Spondylosis.

    Science.gov (United States)

    Muheremu, Aikeremujiang; Sun, Yuqing; Yan, Kai; Yu, Jie; Zheng, Shan; Tian, Wei

    2016-09-01

    Background A considerable number of patients with cervical spondylosis complain about one or multiple atypical symptoms such as vertigo, palpitations, headache, blurred vision, hypomnesia, and/or nausea. It remains unclear whether surgical intervention for cervical spondylosis can also effectively alleviate those symptoms. The current study was performed to see if anterior cervical diskectomy and fusion (ACDF) offers such an extra benefit for patients with cervical spondylosis. Objective To investigate if patients who received ACDF for the treatment of cervical spondylotic myelopathy and/or radiculopathy can also achieve alleviation of certain atypical symptoms associated with cervical spondylosis after the surgery in the long run. Methods Sixty-seven patients who underwent ACDF for the treatment of cervical spondylotic myelopathy and/or radiculopathy were involved in this study. All these patients also complained about various associated atypical symptoms. They were followed up for 26 to 145 months after the surgery. Severity and frequency scores of the atypical symptoms before the surgery and at last follow-up were compared by paired t tests. Results Most patients reported significantly alleviated symptoms at the last follow-up compared with before the surgery. The severity of vertigo, headache, nausea, and palpitations were significantly alleviated at the last follow-up (with p values of p cervical spondylotic myelopathy and/or radiculopathy, but it is not effective in alleviating symptoms such as tinnitus, blurred vision, and hypomnesia. It can be considered for alleviating atypical symptoms when other treatment options prove ineffective. PMID:27168319

  3. Lichen sclerosus: a potpourri of misdiagnosed cases based on atypical clinical presentations

    Directory of Open Access Journals (Sweden)

    Ventolini G

    2015-05-01

    Full Text Available Gary Ventolini, Ravi Patel, Robert Vasquez Texas Tech University Health Sciences Center Permian Basin, Odessa, TX, USA Objective: Lichen sclerosus (LS is a chronic progressive inflammatory autoimmune-induced disease that primarily affects the epidermis and dermis of the external genital-anal region. Intense and recalcitrant pruritus is the hallmark of LS. Physical exam reveals thinning, hyperkeratosis, and parchment-like appearance. However, the classic symptom and signs of LS may not always be present and patients may be asymptomatic for pruritus. Hence, we describe 15 misdiagnosed cases with atypical clinical presentations. We believe that the absence of pruritus contributed to their initial misdiagnosis. The purpose of this paper is to increase awareness of atypical presentations of LS. Methods: Data base review of de-identified clinical case pictures was performed. All patients had histopathology-confirmed diagnoses of LS. The data base file contains 800 cases of vulvovaginal disorders. The Institutional Review Board (IRB considered that searching a de-identified data base of pictures did not require IRB approval. Results: We identified 15 different atypical clinical cases. Patient ages were 18–75 years old. These patients were asymptomatic for pruritus and were misdiagnosed before they presented to the vulvovaginal specialized clinic. Conclusion: Fifteen patients asymptomatic for pruritus with histopathology-confirmed diagnosis of LS were identified. They illustrate atypical clinical presentations that LS may have. Keywords: vulvovaginal, vulvar, atypical, lichen sclerosus, asymptomatic

  4. Typical Versus Atypical Anorexia Nervosa Among Adolescents: Clinical Characteristics and Implications for ICD-11.

    Science.gov (United States)

    Silén, Yasmina; Raevuori, Anu; Jüriloo, Elisabeth; Tainio, Veli-Matti; Marttunen, Mauri; Keski-Rahkonen, Anna

    2015-09-01

    There is scant research on the clinical utility of differentiating International Classification of Diseases (ICD) 10 diagnoses F50.0 anorexia nervosa (typical AN) and F50.1 atypical anorexia. We reviewed systematically records of 47 adolescents who fulfilled criteria for ICD-10 F50.0 (n = 34) or F50.1 (n = 13), assessing the impact of diagnostic subtype, comorbidity, background factors and treatment choices on recovery. Atypical AN patients were significantly older (p = 0.03), heavier (minimum body mass index 16.7 vs 15.1 kg/m(2) , p = 0.003) and less prone to comorbidities (38% vs 71%, p = 0.04) and had shorter, less intensive and less costly treatments than typical AN patients. The diagnosis of typical versus atypical AN was the sole significant predictor of treatment success: recovery from atypical AN was 4.3 times (95% confidence interval [1.1, 17.5]) as likely as recovery from typical AN. Overall, our findings indicate that a broader definition of AN may dilute the prognostic value of the diagnosis, and therefore, ICD-11 should retain its distinction between typical and atypical AN. PMID:26010207

  5. Typical Versus Atypical Anorexia Nervosa Among Adolescents: Clinical Characteristics and Implications for ICD-11.

    Science.gov (United States)

    Silén, Yasmina; Raevuori, Anu; Jüriloo, Elisabeth; Tainio, Veli-Matti; Marttunen, Mauri; Keski-Rahkonen, Anna

    2015-09-01

    There is scant research on the clinical utility of differentiating International Classification of Diseases (ICD) 10 diagnoses F50.0 anorexia nervosa (typical AN) and F50.1 atypical anorexia. We reviewed systematically records of 47 adolescents who fulfilled criteria for ICD-10 F50.0 (n = 34) or F50.1 (n = 13), assessing the impact of diagnostic subtype, comorbidity, background factors and treatment choices on recovery. Atypical AN patients were significantly older (p = 0.03), heavier (minimum body mass index 16.7 vs 15.1 kg/m(2) , p = 0.003) and less prone to comorbidities (38% vs 71%, p = 0.04) and had shorter, less intensive and less costly treatments than typical AN patients. The diagnosis of typical versus atypical AN was the sole significant predictor of treatment success: recovery from atypical AN was 4.3 times (95% confidence interval [1.1, 17.5]) as likely as recovery from typical AN. Overall, our findings indicate that a broader definition of AN may dilute the prognostic value of the diagnosis, and therefore, ICD-11 should retain its distinction between typical and atypical AN.

  6. Exploring atypical verb+noun combinations in learner technical writing

    Directory of Open Access Journals (Sweden)

    María José Luzón Marco

    2011-12-01

    Full Text Available 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 attempt to explore the reasons why the learners deviate from NS's norms. The analysis indicates that these learners tend to have problems with a set of sub-technical and high-frequency verbs. Deviant combinations involving these verbs are frequently the result of a deficient knowledge of the phraseology of academic and technical discourse. The unawareness of collocations that are typical of this discourse often leads students to create V+N combinations by relying on the “Open Choice Principle” (Sinclair, 1991 or by using patterns from their mother tongue.El discurso profesional y académico se caracteriza por una fraseología específica, que suele plantear problemas a los estudiantes. Este artículo investiga colocaciones de verbo+nombre atípicas en un corpus de textos técnicos en inglés escritos por estudiantes españoles. El estudio se centra en los verbos que más frecuentemente aparecen en estas combinaciones atípicas y explora las razones por las que los estudiantes se desvían de la norma. El análisis indica que estos estudiantes suelen tener problemas con un grupo de verbos sub-técnicos y verbos de alta frecuencia. Las combinaciones atípicas en las que estos verbos aparecen son frecuentemente el resultado de un conocimiento deficiente de la fraseología del discurso académico y técnico. El desconocimiento de colocaciones que son típicas de este discurso a menudo lleva a los estudiantes a crear combinaciones basándose en el “principio de opción abierta” (Sinclair, 1991 o a usar colocaciones prestadas de su lengua materna.

  7. The phenotype and neural correlates of language in autism: an integrative review.

    Science.gov (United States)

    Groen, Wouter B; Zwiers, Marcel P; van der Gaag, Rutger-Jan; Buitelaar, Jan K

    2008-10-01

    Although impaired communication is one of the defining criteria in autism, linguistic functioning is highly variable among people with this disorder. Accumulating evidence shows that language impairments in autism are more extensive than commonly assumed and described by formal diagnostic criteria and are apparent at various levels. Phenotypically, most people with autism have semantic, syntactic and pragmatic deficits, a smaller number are known to have phonological deficits. Neurophysiologically, abnormal processing of low-level linguistic information points to perceptual difficulties. Also, abnormal high-level linguistic processing of the frontal and temporal language association cortices indicates more self-reliant and less connected neural subsystems. Early sensory impairments and subsequent atypical neural connectivity are likely to play a part in abnormal language acquisition in autism. This paper aims to review the available data on the phenotype of language in autism as well as a number of structural, electrophysiological and functional brain-imaging studies to provide a more integrated view of the linguistic phenotype and its underlying neural deficits, and to provide new directions for research and therapeutic and experimental applications. PMID:18562003

  8. Modelling neuroinflammatory phenotypes in vivo

    Directory of Open Access Journals (Sweden)

    Wyss-Coray Tony

    2004-07-01

    Full Text Available Abstract Inflammation of the central nervous system is an important but poorly understood part of neurological disease. After acute brain injury or infection there is a complex inflammatory response that involves activation of microglia and astrocytes and increased production of cytokines, chemokines, acute phase proteins, and complement factors. Antibodies and T lymphocytes may be involved in the response as well. In neurodegenerative disease, where injury is more subtle but consistent, the inflammatory response is continuous. The purpose of this prolonged response is unclear, but it is likely that some of its components are beneficial and others are harmful. Animal models of neurological disease can be used to dissect the specific role of individual mediators of the inflammatory response and assess their potential benefit. To illustrate this approach, we discuss how mutant mice expressing different levels of the cytokine transforming growth factor β-1 (TGF-β1, a major modulator of inflammation, produce important neuroinflammatory phenotypes. We then demonstrate how crosses of TGF-β1 mutant mice with mouse models of Alzheimer's disease (AD produced important new information on the role of inflammation in AD and on the expression of different neuropathological phenotypes that characterize this disease.

  9. Phenotypic plasticity in bacterial plasmids.

    Science.gov (United States)

    Turner, Paul E

    2004-01-01

    Plasmid pB15 was previously shown to evolve increased horizontal (infectious) transfer at the expense of reduced vertical (intergenerational) transfer and vice versa, a key trade-off assumed in theories of parasite virulence. Whereas the models predict that susceptible host abundance should determine which mode of transfer is selectively favored, host density failed to mediate the trade-off in pB15. One possibility is that the plasmid's transfer deviates from the assumption that horizontal spread (conjugation) occurs in direct proportion to cell density. I tested this hypothesis using Escherichia coli/pB15 associations in laboratory serial culture. Contrary to most models of plasmid transfer kinetics, my data show that pB15 invades static (nonshaking) bacterial cultures only at intermediate densities. The results can be explained by phenotypic plasticity in traits governing plasmid transfer. As cells become more numerous, the plasmid's conjugative transfer unexpectedly declines, while the trade-off between transmission routes causes vertical transfer to increase. Thus, at intermediate densities the plasmid's horizontal transfer can offset selection against plasmid-bearing cells, but at high densities pB15 conjugates so poorly that it cannot invade. I discuss adaptive vs. nonadaptive causes for the phenotypic plasticity, as well as potential mechanisms that may lead to complex transfer dynamics of plasmids in liquid environments. PMID:15166133

  10. Atypical femoral fracture due to chronic use of bisphosphonates: case report☆

    Science.gov (United States)

    Temponi, Eduardo Frois; de Carvalho Junior, Lúcio Honório; Costa, Lincoln Paiva

    2015-01-01

    The causal relationship between chronic use of bisphosphonates and occurrences of atypical femoral fractures has not yet been established. Nonetheless, it is known that their chronic use is more related to fractures with a pattern differing from that of classical osteoporotic fractures. Atypical fractures are still rare events and the benefit from using bisphosphonates remains greater for prevention and treatment of osteoporosis. There are few studies guiding the diagnosis and management of these fractures, thus making it difficult to achieve better results. In this report, we present the case of an elderly patient with an atypical femoral fracture that was managed in accordance with guidance from the American Society for Bone and Mineral Research. PMID:26401508

  11. Atypical p-ANCA in PSC and AIH: a hint toward a "leaky gut"?

    Science.gov (United States)

    Terjung, Birgit; Spengler, Ulrich

    2009-02-01

    Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are enigmatic chronic inflammatory diseases of the liver, which are frequently associated with chronic inflammatory bowel diseases. Both types of liver disease share various distinct autoantibodies such as atypical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), and thus are considered autoimmune disorders with atypical features. The discovery that atypical p-ANCA recognize both tubulin beta isoform 5 in human neutrophils and the bacterial cell division protein FtsZ has renewed the discussion on the potential role of microorganisms in the pathogenesis of both diseases. In this paper, we review the evidence for microbial infection in PSC and AIH and discuss new concepts how cross-recognition between microbial antigens in the gut and host components by the immune system along with stimulation of pattern recognition receptors might give rise to chronic hepatic inflammatory disorders with features of autoimmunity.

  12. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients.

    Science.gov (United States)

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-08-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image. PMID:27483175

  13. Effectiveness of an Inpatient Movement Disorders Program for Patients with Atypical Parkinsonism

    Directory of Open Access Journals (Sweden)

    Anna D. Hohler

    2012-01-01

    Full Text Available This paper investigated the effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism, who typically respond poorly to pharmacologic intervention and are challenging to rehabilitate as outpatients. Ninety-one patients with atypical parkinsonism participated in an inpatient movement disorders program. Patients received physical, occupational, and speech therapy for 3 hours/day, 5 to 7 days/week, and pharmacologic adjustments based on daily observation and data. Differences between admission and discharge scores were analyzed for the functional independence measure (FIM, timed up and go test (TUG, two-minute walk test (TMW, Berg balance scale (BBS and finger tapping test (FT, and all showed significant improvement on discharge (>.001. Clinically significant improvements in total FIM score were evident in 74% of the patients. Results were similar for ten patients whose medications were not adjusted. Patients with atypical parkinsonism benefit from an inpatient interdisciplinary movement disorders program to improve functional status.

  14. [Atypical angiographic appearances of aneurisms of the abdominal aorta (author's transl)].

    Science.gov (United States)

    Chermet, J; Kieffer, E; Taboury, J; Monnier, J P; Chalut, J

    1976-10-01

    On the basis of 72 radio-surgical cases of abdominal aortic aneurism, the authors stress the value of atypical angiographic findings, which are ten in number. The presence of clot within the aneurism itself may explain a disparity between radiological and surgical findings. Failure to recognize these atypical signs is very serious, when the diagnosis of aneurism is not suspected clinically. Antero-posterior and, above all, lateral abdominal aortography is essential in the angiographic study of aneurisms of the abdominal aorta. Careful search for these 10 atypical signs should make it possible to avoid missing latent aneurisms. Lateral abdominal aortography is essential in order to determine the state of the abdominal collaterals of the aorta and, in particular, the superior mesenteric artery. PMID:1003379

  15. Diagnosis of Infectious Mononucleosis by Combined Detection of Atypical Lymphocytes and Transaminase

    Institute of Scientific and Technical Information of China (English)

    HU Lihua; YANG Juhong; CUI Tianpen; XING Hui; CAI Pengcheng

    2006-01-01

    In order to explore the value of combined detection of atypical lymphocytes (ATL) and transaminase (alanine aminotransferase, ALT; asparate aminotransferase, AST) in the diagnosis of infectious mononucleosis (IM), The data of blood routine and liver function were collected from 54 IM patients, 34 acute hepatitis (AH) patients, 44 upper respiratory infection (URI) patients in Union Hospital during March 2002 to March 2005. Same data were also collected from 40 healthy children as normal control. These data were analyzed retrospectively. Both proportion of atypical lymphocytes and enzyme activity of transaminase were elevated simultaneously (ALT>40 IU/L,AST>45 IU/L) in 57.4% (31/54) IM patients. There was significant difference (P<0.01) between IM group and the other groups. Combined detection of atypical lymphocytes and transaminase can be regarded as a diagnostic marker of infectious mononucleosis.

  16. Atypical Antipsychotics and Other Therapeutic Options for Treatment of Resistant Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Allan H. Young

    2010-12-01

    Full Text Available Antidepressant therapies, such as selective serotonin reuptake inhibitors (SSRIs, are current first-line treatments for Major Depressive Disorder. However, over 50% of treated patients show an inadequate response to initial antidepressant therapy. If the therapeutic outcomes from two antidepressant therapies are suboptimal, potentially resulting in Treatment Resistant Depression, subsequent strategies include switching to another antidepressant or augmenting treatment by combining with other agents. When combined with SSRIs, atypical antipsychotics have supplementary action on dopaminergic and noradrenergic systems. Studies on combined treatment with atypical antipsychotics have shown significantly increased remission rates, shortened response times, and favorable side effects. Augmentation of antidepressants with atypical antipsychotics is now an acceptable treatment strategy which leads to increased remission rates and better outcomes for patients.

  17. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients

    Directory of Open Access Journals (Sweden)

    Aleksandra Aracki-Trenkić

    2016-06-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image.

  18. Flares on A-type stars: Evidence for heating of solar corona by nanoflares?

    CERN Document Server

    Svanda, M

    2016-01-01

    We analyzed the occurrence rates of flares on stars of spectral types K, G, F, and A, observed by Kepler. We found that the histogram of occurrence frequencies of stellar flares is systematically shifted towards a high-energy tail for A-type stars compared to stars of cooler spectral types. We extrapolated the fitted power laws towards flares with smaller energies (nanoflares) and made estimates for total energy flux to stellar atmospheres by flares. We found that for A-type stars the total energy flux density was at least 4-times smaller than for G-stars. We speculate that this deficit in energy supply may explain the lack of hot coronae on A-type stars. Our results indicate an importance of nanoflares for heating and formation of the solar corona.

  19. Flares on A-type Stars: Evidence for Heating of Solar Corona by Nanoflares?

    Science.gov (United States)

    Švanda, Michal; Karlický, Marian

    2016-11-01

    We analyzed the occurrence rates of flares on stars of spectral types K, G, F, and A, observed by Kepler. We found that the histogram of occurrence frequencies of stellar flares is systematically shifted toward a high-energy tail for A-type stars compared to stars of cooler spectral types. We extrapolated the fitted power laws toward flares with smaller energies (nanoflares) and made estimates for total energy flux to stellar atmospheres by flares. We found that, for A-type stars, the total energy flux density was at least four-times smaller than for G stars. We speculate that this deficit in energy supply may explain the lack of hot coronae on A-type stars. Our results indicate the importance of nanoflares for heating and formation of the solar corona.

  20. Total Hip Arthroplasty for Implant Rupture after Surgery for Atypical Subtrochanteric Femoral Fracture

    Directory of Open Access Journals (Sweden)

    Yu Ozaki

    2016-01-01

    Full Text Available Treatment methods for delayed union and nonunion of atypical femoral fracture are still controversial. Moreover, no treatment method has been established for implant rupture caused by delayed union and nonunion. We encountered a 74-year-old female in whom nonunion-induced implant rupture occurred after treatment of atypical subtrochanteric femoral fracture with internal fixation using a long femoral nail. It was unlikely that sufficient fixation could be obtained by repeating osteosynthesis alone. Moreover, the patient was elderly and early weight-bearing activity was essential for early recovery of ADL. Based on these reasons, we selected one-stage surgery with total hip arthroplasty and osteosynthesis with inverted condylar locking plate as salvage procedures. Bone union was achieved at 6 months after surgery. This case illustrated that osteosynthesis-combined one-staged total hip arthroplasty could be considered as one of the options for nonunion-induced implant rupture of atypical femoral subtrochanteric fracture.