WorldWideScience

Sample records for sporadic cjd patients

  1. Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

    Directory of Open Access Journals (Sweden)

    Ironside James W

    2007-08-01

    Full Text Available Abstract Background Sub-clinical variant Creutzfeldt-Jakob disease (vCJD infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrPSc, although achieving required sensitivity is a challenge. Methods We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS, which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples. Results Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system. Conclusion ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems.

  2. Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

    Science.gov (United States)

    Fagge, Timothy J; Barclay, G Robin; Stove, G Colin; Stove, Gordon; Robinson, Michael J; Head, Mark W; Ironside, James W; Turner, Marc L

    2007-01-01

    Background Sub-clinical variant Creutzfeldt-Jakob disease (vCJD) infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrPSc), although achieving required sensitivity is a challenge. Methods We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS), which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples. Results Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system. Conclusion ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems. PMID:17760958

  3. Application of quantitative DTI metrics in sporadic CJD

    Directory of Open Access Journals (Sweden)

    E. Caverzasi

    2014-01-01

    Full Text Available Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob–Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1 to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM in sporadic Jakob–Creutzfeldt disease, 2 to study changes in mean diffusivity and atrophy over time and 3 to explore their relationship with clinical scales. Twenty-six sporadic Jakob–Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume, T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei, but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score and increasing mean diffusivity.

  4. Re-assessment of PrP(Sc distribution in sporadic and variant CJD.

    Directory of Open Access Journals (Sweden)

    Richard Rubenstein

    Full Text Available Human prion diseases are fatal neurodegenerative disorders associated with an accumulation of PrP(Sc in the central nervous system (CNS. Of the human prion diseases, sporadic Creutzfeldt-Jakob disease (sCJD, which has no known origin, is the most common form while variant CJD (vCJD is an acquired human prion disease reported to differ from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. Peripheral tissue involvement in prion disease, as judged by PrP(Sc accumulation in the tonsil, spleen, and lymph node has been reported in vCJD as well as several animal models of prion diseases. However, this distribution of PrP(Sc has not been consistently reported for sCJD. We reexamined CNS and non-CNS tissue distribution and levels of PrP(Sc in both sCJD and vCJD. Using a sensitive immunoassay, termed SOFIA, we also assessed PrP(Sc levels in human body fluids from sCJD as well as in vCJD-infected humanized transgenic mice (Tg666. Unexpectedly, the levels of PrP(Sc in non-CNS human tissues (spleens, lymph nodes, tonsils from both sCJD and vCJD did not differ significantly and, as expected, were several logs lower than in the brain. Using protein misfolding cyclic amplification (PMCA followed by SOFIA, PrP(Sc was detected in cerebrospinal fluid (CSF, but not in urine or blood, in sCJD patients. In addition, using PMCA and SOFIA, we demonstrated that blood from vCJD-infected Tg666 mice showing clinical disease contained prion disease-associated seeding activity although the data was not statistically significant likely due to the limited number of samples examined. These studies provide a comparison of PrP(Sc in sCJD vs. vCJD as well as analysis of body fluids. Further, these studies also provide circumstantial evidence that in human prion diseases, as in the animal prion diseases, a direct comparison and intraspecies correlation cannot be made between the levels of PrP(Sc and infectivity.

  5. Impact of the clinical context on the 14-3-3 test for the diagnosis of sporadic CJD

    Directory of Open Access Journals (Sweden)

    Sierra-Moros Maríajosé

    2006-07-01

    Full Text Available Abstract Background The 14-3-3 test appears to be a valuable aid for the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD in selected populations. However, its usefulness in routine practice has been challenged. In this study, the influence of the clinical context on the performance of the 14-3-3 test for the diagnosis of sCJD is investigated through the analysis of a large prospective clinical series. Methods Six hundred seventy-two Spanish patients with clinically suspected sCJD were analyzed. Clinical classification at sample reception according to the World Health Organization's (WHO criteria (excluding the 14-3-3 test result was used to explore the influence of the clinical context on the pre-test probabilities, and positive (PPV and negative (NPV predictive values of the 14-3-3 test. Results Predictive values of the test varied greatly according to the initial clinical classification: PPV of 98.8%, 96.5% and 45.0%, and NPV of 26.1%, 66.6% and 100% for probable sCJDi (n = 115, possible sCJDi (n = 73 and non-sCJDi (n = 484 cases, respectively. According to multivariate and Bayesian analyses, these values represent an improvement of diagnostic certainty compared to clinical data alone. Conclusion In three different contexts of sCJD suspicion, the 14-3-3 assay provides useful information complementary to clinical and electroencephalographic (EEG data. The test is most useful supporting a clinical impression, whilst it may show deceptive when it is not in agreement with clinical data.

  6. The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD

    Directory of Open Access Journals (Sweden)

    Jeong Byung-Hoon

    2011-08-01

    Full Text Available Abstract Background Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s modulating susceptibility to prion disease. Ribosomal protein SA (RPSA, also called 37 kDa laminin receptor precursor (LRP/67 kDa laminin receptor (LR, acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR. Methods To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP analysis. Results We observed four single nucleotide polymorphisms (SNPs, including -8T>C (rs1803893 in the 5'-untranslated region (UTR of exon 2, 134-32C>T (rs3772138 in the intron, 519G>A (rs2269350 in the intron and 793+58C>T (rs2723 in the intron on the RPSA. The 519G>A (at codon 173 is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. Conclusion These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.

  7. Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob disease in Germany.

    Science.gov (United States)

    Krasnianski, Anna; Bohling, Geeske T; Harden, Markus; Zerr, Inga

    2015-09-01

    Psychiatric symptoms in sporadic Creutzfeldt-Jakob disease (sCJD) are still not sufficiently evaluated. To describe psychiatric symptoms in sCJD with respect to molecular subtype. Patients in this retrospective study were classified according to established diagnostic criteria. 248 sCJD patients with known molecular subtype were recruited from January 1993 to December 2004 and investigated. Psychiatric symptoms were defined according to Möller and colleagues and the AMDP system (Study Group for Methods and Documentation in Psychiatry) and were collected by direct examination by study physicians or extracted from medical documentation. Our data were compared with published data on variant CJD (vCJD). Psychiatric symptoms were common in sCJD patients (90%) and mostly found already at the disease onset (agitation in 64% of the patients, hallucinations in 45%, anxiety in 50%, depression in 37%). All psychiatric symptoms but illusions were found early in the disease course. Psychiatric symptoms in sCJD were less frequent than in vCJD. We provide the first detailed analysis of psychiatric symptoms in a large group of patients with sCJD with respect to differences concerning frequency and time point of occurrence of psychiatric symptoms between molecular subtypes. These data suggest that psychiatric symptoms occurring early in the disease course are common not only in vCJD but also in other CJD types. © Copyright 2015 Physicians Postgraduate Press, Inc.

  8. The epidemiological, clinical, and laboratory features of sporadic Creutzfeldt-Jakob disease patients in China: surveillance data from 2006 to 2010.

    Directory of Open Access Journals (Sweden)

    Chen Gao

    Full Text Available BACKGROUND: Creutzfeldt-Jakob disease (CJD is a rare, rapidly progressive fatal central nervous system disorder, which consists of three main catalogues: sporadic, familial, and iatrogenic CJD. METHODOLOGY/PRINCIPAL FINDINGS: In China, the surveillance for CJD started in 2006, covering 12 provincial Centers for Disease Control and Prevention (CDCs and 15 hospitals. From 2006 to 2010, 624 suspected patients were referred to China CJD surveillance. The epidemiological, clinical and laboratory features of sporadic CJD (sCJD were analysed. Both groups of probable and possible sCJD showed highest incidences in the population of 60 to 69 year-olds. The most common presenting symptoms were progressive dementia and mental-related symptoms (neurological symptoms including sleeping turbulence, depression, anxiety and stress. Among the four main clinical manifestations, myoclonus was more frequently observed in the probable sCJD patients. About 2/3 of probable sCJD cases showed positive 14-3-3 in CSF and/or periodic sharp wave complexes (PSWC in electroencephalography (EEG. The presence of myoclonus was significantly closely related with the appearance of PSWC in EEG. Polymorphisms of codon 129 in PRNP of the notified cases revealed a highly predominant M129M genotype in Han Chinese. Among 23 genetic human prion diseases, ten were D178N/M129M Fatal familial insomnia (FFI and five were T188K genetic CJD (gCJD, possibly indicating a special distribution of gCJD-related mutations in Han Chinese. CONCLUSION: From the period of 2006 to 2010, 261 patients were diagnosed as sCJD and 23 patients were diagnosed as genetic human prion diseases in China. The epidemiological, clinical and laboratory analysis data were consistent with the characteristics of sporadic CJD, which provide insight into the features of CJD in China.

  9. Detection and Localization of PrPSc in the Skeletal Muscle of Patients with Variant, Iatrogenic, and Sporadic Forms of Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Peden, Alexander H.; Ritchie, Diane L.; Head, Mark W.; Ironside, James W.

    2006-01-01

    Variant Creutzfeldt-Jakob disease (vCJD) differs from other human prion diseases in that the pathogenic prion protein PrPSc can be detected to a greater extent at extraneuronal sites throughout the body, principally within lymphoid tissues. However, a recent study using a high-sensitivity Western blotting technique revealed low levels of PrPSc in skeletal muscle from a quarter of Swiss patients with sporadic CJD (sCJD). This posed the question of whether PrPSc in muscle could also be detected in vCJD, sCJD, and iatrogenic (iCJD) patients from other populations. Therefore, we have used the same high-sensitivity Western blotting technique, in combination with paraffin-embedded tissue blotting, to screen for PrPSc in muscle tissue specimens taken at autopsy from 49 CJD patients in the United Kingdom. These techniques identified muscle PrPSc in 8 of 17 vCJD, 7 of 26 sCJD, and 2 of 5 iCJD patients. Paraffin-embedded tissue blotting analysis showed PrPSc in skeletal muscle in localized anatomical structures that had the morphological and immunohistochemical characteristics of nerve fibers. The detection of PrPSc in muscle tissue from all forms of CJD indicates the possible presence of infectivity in these tissues, suggesting important implications for assessing the potential risk of iatrogenic spread via contaminated surgical instruments. PMID:16507908

  10. Neuropsychological Symptoms in Sporadic Creutzfeldt-Jakob Disease Patients in Germany.

    Science.gov (United States)

    Krasnianski, Anna; Bohling, Geeske T; Heinemann, Uta; Varges, Daniela; Meissner, Bettina; Schulz-Schaeffer, Walter J; Reif, Andreas; Zerr, Inga

    2017-01-01

    The polymorphism at codon 129 of the prion protein gene (PRNP) and the PrPSc types 1 and 2 belong to a molecular classification of sporadic Creutzfeldt-Jakob disease (sCJD) that correlates well with the clinical and neuropathological phenotype of sCJD. The aim of the study was to perform the first detailed evaluation of neuropsychological deficits in a large group of definite sCJD patients with known molecular subtype. We analyzed neuropsychological symptoms in a cohort of 248 sCJD patients with known M129 V polymorphism of PRNP and prion protein type. Neuropsychological symptoms were very frequent in our patients (96%) and occurred as early as in the first third of the disease course. Besides amnesia and impaired attention (89% each), frontal lobe syndrome (75%), aphasia (63%), and apraxia (57%) were the most common neuropsychological deficits. There was no statistically significant difference with regard to frequency of neuropsychological symptoms between the subtypes. In MV2 and VV2 patients, the onset of neuropsychological symptoms was significantly later than in all other subtypes. We provide the first detailed analysis of neuropsychological symptoms in a large group of sCJD patients with known M129 V genotype and prion protein type. We suggest that the rate of progression of neuropsychological symptoms is subtype-specific. These data may improve the diagnosis in atypical sCJD subtypes.

  11. Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients.

    Science.gov (United States)

    Schmitz, Matthias; Llorens, Franc; Pracht, Alexander; Thom, Tobias; Correia, Ângela; Zafar, Saima; Ferrer, Isidre; Zerr, Inga

    2016-11-14

    The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondrial malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrP Sc ) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly.

  12. Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients

    Science.gov (United States)

    Schmitz, Matthias; Llorens, Franc; Pracht, Alexander; Thom, Tobias; Correia, Ângela; Zafar, Saima; Ferrer, Isidre; Zerr, Inga

    2016-01-01

    The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondrial malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrPSc) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly. PMID:27852982

  13. Comparison Between Sporadic and Misdiagnosed Sporadic Creutzfeldt-Jakob Disease: A Report of Two Cases.

    Science.gov (United States)

    Zhao, Xiongfei; Yu, Yingxin; Zhao, Zhiru; Xu, Jiaping

    2015-06-01

    Definite accurate diagnosis for Creutzfeldt-Jakob disease (CJD) depends on neuropathologic examination of brain biopsy or autopsy. However, transmissible nature makes the invasive examination dangerous. This study was set to determine that the clinical features are for the diagnosis of CJD through a comparison study. We compared clinical features of two cases with initial diagnosis of sporadic CJD. One case was finally diagnosed as definite sporadic CJD. According to World Health Organization diagnosis criteria, the other one, which had been diagnosed as probable sporadic CJD, was confirmed as limbic encephalitis after long-term follow-up. Compared with the case of definite sporadic CJD, the misdiagnosed case did not present typical electroencephalogram (EEG) and diffusion-weighted in magnetic resonance images (DWI) of CJD. However, cerebrospinal fluid in the misdiagnosed patient showed 14-3-3 protein positivity. The patient conditions improved after treatment. Through this case comparison, we conclude that EEG and DWI are necessary for accurate diagnosis of sporadic CJD. Further, long-term follow-up is crucial to diagnosis and treatment of CJD.

  14. Magnetic resonance spectroscopic abnormalities in sporadic and variant Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Pandya, H.G.; Coley, S.C.; Wilkinson, I.D.; Griffiths, P.D.

    2003-01-01

    AIM: To study the proton MR spectroscopic findings in Creutzfeldt-Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153

  15. Magnetic resonance spectroscopic abnormalities in sporadic and variant Creutzfeldt-Jakob disease

    Energy Technology Data Exchange (ETDEWEB)

    Pandya, H.G.; Coley, S.C.; Wilkinson, I.D.; Griffiths, P.D

    2003-02-01

    AIM: To study the proton MR spectroscopic findings in Creutzfeldt-Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153.

  16. Comparative Study of Prions in Iatrogenic and Sporadic Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Xiao, Xiangzhu; Yuan, Jue; Qing, Liuting; Cali, Ignazio; Mikol, Jacqueline; Delisle, Marie-Bernadette; Uro-Coste, Emmanuelle; Zeng, Liang; Abouelsaad, Mai; Gazgalis, Dimitris; Martinez, Manuel Camacho; Wang, Gong-Xian; Brown, Paul; Ironside, James W.; Gambetti, Pierluigi; Kong, Qingzhong; Zou, Wen-Quan

    2014-01-01

    Differentiating iatrogenic Creutzfeldt-Jakob disease (iCJD) from sporadic CJD (sCJD) would be useful for the identification and prevention of human-to-human prion transmission. Currently, the diagnosis of iCJD depends on identification of a recognized source of contamination to which patients have been exposed, in addition to fulfilling basic requirements for the establishment of diagnosis of CJD. Attempts to identify differences in clinical manifestations, neuropathological changes and pathological prion protein (PrPSc) between iCJD and sCJD have been unsuccessful. In the present study, using a variety of more sophisticated methods including sucrose step gradient sedimentation, conformational stability immunoassay, protein misfolding cyclic amplification (PMCA), fragment-mapping, and transmission study, we show no significant differences in gel profiles, oligomeric state, conformational stability and infectivity of PrPSc between iCJD and sCJD. However, using PMCA, we find that convertibility and amplification efficiency of PrPSc is greater in iCJD than in sCJD in a polymorphism-dependent manner. Moreover, two protease-resistant PrP C-terminal fragments (termed PrP-CTF12/13) were detected in all 9 cases of sCJD but not in 6 of 8 cases of iCJD tested in this study. The use of fragment mapping- and PMCA-based assays thus provides a means to distinguish most cases of iCJD from sCJD. PMID:25419482

  17. Sporadic Creutzfeldt-Jakob disease in a native Puerto Rican patient.

    Science.gov (United States)

    Del Pilar-Morales, Esteban A; Cali, Ignazio; Chapas, Javier; Bertrán-Pasarell, Jorge; Puoti, Gianfranco; Gambetti, Pierluigi; Nobo, Ulises

    2015-03-01

    The diagnosis of Creutzfeldt-Jakob disease (CJD) is often a challenge for most physicians given its extremely low incidence and different clinico-pathological presentations. We report the case of a 56-year old patient native to Puerto Rico suspected of sporadic Creutzfeldt-Jakob disease (sCD). The symptoms at onset were notorious for bilateral cortical blindness followed by rapidly progressive cognitive decline, visual deficit, increased levels of CSF 14-3-3 and tau along with positive brain MRI and EEG, are highly indicative of CJD. The definite diagnosis was confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC), in Cleveland, Ohio, USA. Lack of genetic mutations in the prion protein (PrP) gene, widespread histopathological changes and the accumulation of scrapie PrP (PrPSc) in the brain confirmed the diagnosis of sCJD. The patient, admitted to our institution in 2011, represents the first detailed report of sCJD in a native Puerto Rican patient living in Puerto Rico.

  18. CT and MRI in iatrogenic and sporadic Creutzfeldt-Jakob disease: as far as imaging perseives

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Santos, J.M. [Servicio de Radiodiagnostico, HU Dr. Morales Meseguer, Murcia (Spain)]|[Section of Neuroradiology, HU Virgen de la Arrixaca, Murcia (Spain); Lopez Corbalan, J.A. [Section of Neuroradiology, HU Virgen de la Arrixaca, Murcia (Spain); Martinez-Lage, J.F. [Service of Neurosurgery, HU Virgen de la Arrixaca, Murcia (Spain); Sicilis Guillen, J. [Service of Neurology, HU Virgen de la Arrixaca, Murcia (Spain)

    1996-04-01

    Creutzfeldt-Jakob Disease (CJD), an invariably fatal dementing illness, affects patients in middle and old age (sporadic form). However, the association of CJD with certain treatments (iatrogenic form) has been described in younger patients. The clinical onset of the two forms seems to differ; in the iatrogenic form a high frequency of the ataxic CJD variant has been reported. Nowadays, a definitive diagnosis of CJD is exclusively histological. We present five cases of CJD, one sporadic and the others iatrogenic, following dura mater grafts and analyse their CT and MRI features. CT typically demonstrates brain atrophy, generally progressive, but in sporadic CJD midfield MRI also showed abnormal signal, with predominant deep grey matter involvement. The use of narrow windows with proton-density sequences may reveal subtle cortical signal abnormalities not clearly visible with conventional windows. The early demonstration of these changes, in the appropriate clinical context, may suggest CJD and this supports the use of mid- or high magnetic fields in the diagnosis of CJD and other forms of dementia. In our cases of iatrogenic CJD, low-field MRI did not reveal more than the progressive atrophy displayed by CT, and raises the question on the one hand of possible differences, based on imaging, from the sporadic form, and on the other of the lack of sensitivity of low-field magnets to signal changes in CJD. (orig.)

  19. CT and MRI in iatrogenic and sporadic Creutzfeldt-Jakob disease: as far as imaging perseives

    International Nuclear Information System (INIS)

    Garcia Santos, J.M.; Lopez Corbalan, J.A.; Martinez-Lage, J.F.; Sicilis Guillen, J.

    1996-01-01

    Creutzfeldt-Jakob Disease (CJD), an invariably fatal dementing illness, affects patients in middle and old age (sporadic form). However, the association of CJD with certain treatments (iatrogenic form) has been described in younger patients. The clinical onset of the two forms seems to differ; in the iatrogenic form a high frequency of the ataxic CJD variant has been reported. Nowadays, a definitive diagnosis of CJD is exclusively histological. We present five cases of CJD, one sporadic and the others iatrogenic, following dura mater grafts and analyse their CT and MRI features. CT typically demonstrates brain atrophy, generally progressive, but in sporadic CJD midfield MRI also showed abnormal signal, with predominant deep grey matter involvement. The use of narrow windows with proton-density sequences may reveal subtle cortical signal abnormalities not clearly visible with conventional windows. The early demonstration of these changes, in the appropriate clinical context, may suggest CJD and this supports the use of mid- or high magnetic fields in the diagnosis of CJD and other forms of dementia. In our cases of iatrogenic CJD, low-field MRI did not reveal more than the progressive atrophy displayed by CT, and raises the question on the one hand of possible differences, based on imaging, from the sporadic form, and on the other of the lack of sensitivity of low-field magnets to signal changes in CJD. (orig.)

  20. Association between the PRNP 1368 polymorphism and the occurrence of sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Bratosiewicz-Wąsik, Jolanta; Smoleń-Dzirba, Joanna; Rozemuller, Annemieke J.; Jansen, Casper; Spliet, Wim; Jansen, Gerard H.; Wąsik, Tomasz J.; Liberski, Paweł P.

    2012-01-01

    Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. The etiology of sporadic form of CJD remains unsolved. In addition to the codon 129 polymorphism, polymorphisms in the non-coding region of PRNP are considered as important factors in sCJD development. To assess a possible association between PRNP 1368 SNP and sCJD, we compared the genotype, allele and haplotype frequencies of the 1368 SNP among 46 sCJD patients of Dutch origin with the respective frequencies in healthy controls. We detected a significant association between sCJD and 1368T/T genotype. A significant difference was also observed in 1368 alleles’ distribution. In the haplotype analysis, haplotype 1368C-129G was associated with decreased risk of sCJD in Dutch population. Our findings support the hypothesis that genetic variations in the regulatory region of the PRNP gene may influence the pathogenesis of sCJD. PMID:22895088

  1. Factors influencing the survival period in Japanese patients with sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Iwasaki, Yasushi; Akagi, Akio; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2015-10-15

    Although Japanese cases of sporadic Creutzfeldt-Jakob disease (sCJD) generally involve longer survival periods compared to those from other countries, details regarding the factors influencing survival are unclear. To determine the influence of certain factors on survival, we retrospectively assessed 51 Japanese MM1-type sCJD patients with respect to background, clinical course, and disease management. No significant differences were found between men and women, tracheotomy and nontracheotomy patients, or patients treated in public and other types of hospitals. Although the survival period of tube-fed patients was significantly longer than that of patients who were not tube fed, survival of patients fed via a nasal tube did not differ significantly from that of gastrostomy-fed patients. The proportion of tube-fed patients was 68.6% (35/51). Disease duration was not significantly associated with age or year of onset. However, it was associated with time from onset to first recognition of myoclonus, first recognition of periodic sharp-wave complexes on electroencephalogram, and progression to the akinetic mutism state. Mechanical ventilation was not performed for any patient. Because the total disease duration increased in cases with a slowly progressive clinical course as a natural outcome, we concluded that the most crucial factor contributing to the prolonged survival of Japanese sCJD patients was tube feeding once the akinetic mutism state had been reached. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Subtype and regional regulation of prion biomarkers in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Llorens, Franc; Zafar, Saima; Ansoleaga, Belén; Shafiq, Mohsin; Blanco, Rosi; Carmona, Marga; Grau-Rivera, Oriol; Nos, Carlos; Gelpí, Ellen; Del Río, José Antonio; Zerr, Inga; Ferrer, Isidre

    2015-08-01

    Creutzfeldt-Jakob disease (CJD) is a rapid progressive neurological disease leading to dementia and death. Prion biomarkers are altered in the cerebrospinal fluid (CSF) of CJD patients, but the pathogenic mechanisms underlying these alterations are still unknown. The present study examined prion biomarker levels in the brain and CSF of sporadic CJD (sCJD) cases and their correlation with neuropathological lesion profiles. The expression levels of 14-3-3, Tau, phospho-Tau and α-synuclein were measured in the CSF and brain of sCJD cases in a subtype- and region-specific manner. In addition, the activity of prion biomarker kinases, the expression levels of CJD hallmarks and the most frequent neuropathological sCJD findings were analysed. Prion biomarkers levels were increased in the CSF of sCJD patients; however, correlations between mRNA, total protein and their phosphorylated forms in brain were different. The observed downregulation of the main Tau kinase, GSK3, in sCJD brain samples may help to explain the differential phospho-Tau/Tau ratios between sCJD and other dementias in the CSF. Importantly, CSF biomarkers levels do not necessarily correlate with sCJD neuropathological findings. Present findings indicate that prion biomarkers levels in sCJD tissues and their release into the CSF are differentially regulated following specific modulated responses, and suggest a functional role for these proteins in sCJD pathogenesis. © 2014 British Neuropathological Society.

  3. [Perioperative considerations for performing a brain biopsy on a patient with subtype VV2 sporadic Creutzfeldt-Jakob disease].

    Science.gov (United States)

    Guerrero-Domínguez, R; Rubio-Romero, R; González-González, G; Jiménez, I

    2015-04-01

    Creutzfeldt-Jakob disease (CJD) is the most common transmissible spongiform encephalopathy. It is an infectious, progressive, degenerative neurological disorder, with a presumably long incubation period, but a rapid fatal course. CJD is transmitted by a proteinaceous infectious agent, or «prion». Because the prions are difficult to eradicate and are resistant to the currently used sterilization methods, special precautions must be taken with all surgical instruments. It is recommended the single-use equipment, destruction of contaminated equipment, decontamination of reusable instruments, use of protective clothing, and storing and quarantining surgical instruments. The single-use equipment and some tissues and body fluids from the patient with CJD are highly infectious and must be incinerated. We report a case of a patient who had undergone brain biopsy for suspected of CJD, being confirmed to have sporadic CJD. Specific preventive measures were taken to reduce the risk of transmission to healthcare workers. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Progressive Stroke-Like Symptoms in a Patient with Sporadic Creutzfeldt-Jakob Disease

    Directory of Open Access Journals (Sweden)

    Jukka Lyytinen

    2010-03-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrPSc induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG. Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrPSc.

  5. Diffusion MR imaging in sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    Burcak Cakir Pekoz

    2014-08-01

    Full Text Available Creutzfeldt-Jakob disease (CJD is a rare dementing disease and is thought to caused by a prion. It is characterized by rapidly progressive dementia, ataxia, myoclonus, akinetic mutism and eventual death. Brain biopsy or autopsy is required for a definitive diagnosis of CJD. Diffusion-weighted imaging became an important tool for early diagnosis of CJD because of the high sensitivity. We present 59-year-old female patient diagnosed as sporadic CJD with typical MR imagings. [Cukurova Med J 2014; 39(4.000: 880-883

  6. Redefining periodic patterns on electroencephalograms of patients with sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Shin, Jung-Won; Yim, Byeongsoo; Oh, Seung Hun; Kim, Nam Keun; Lee, Sang Kun; Kim, Ok-Joon

    2017-05-01

    We aimed to redefine various periodic patterns (PPs) observed on electroencephalography (EEG) in patients with sporadic Creutzfeldt-Jakob disease (sCJD) using the American Clinical Neurophysiology Society's (ACNS) Criteria. We analyzed EEG data of 23 patients with sCJD were admitted to two university hospitals between August 2005 and September 2015. We classified PPs on EEG data into three types: irregular periodic discharges (PDs) with superimposed rhythmic activities, appearing at a median of 8weeks after onset (w.a.o.); rhythmic sharp-and-wave, at a median of 11w.a.o.; and PDs with biphasic or triphasic morphology, at a median of 17w.a.o. Of 16 patients presenting with PPs, 14 had widespread lesions in both cortical and subcortical areas with clinical stage III at admission, and shorter time intervals for admission to hospital from disease onset than patients without PPs (Patients with PP, 11.6±12.2weeks; without PP, 18.2±8.3weeks; p=0.033). PPs largely presented as three types at different stages of disease progression, and patients who had PPs had more wide spread lesions and rapid disease progression. Our redefinition of PPs demonstrated on EEG using the ACNS criteria may contribute to further understanding of the pathological mechanisms of sCJD, and PPs might be a predictive factor of a rapid sCJD progression. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  7. Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.

    Science.gov (United States)

    Kobayashi, Atsushi; Parchi, Piero; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

    2016-06-01

    As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases. © 2015 Japanese Society of Neuropathology.

  8. The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients.

    Science.gov (United States)

    Moore, Roger A; Head, Mark W; Ironside, James W; Ritchie, Diane L; Zanusso, Gianluigi; Choi, Young Pyo; Pyo Choi, Young; Priola, Suzette A

    2016-02-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc). By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrP(Sc). In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrP(C) allotype to PrP(Sc) in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrP(Sc) with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrP(C) containing an M or V at residue 129 having a similar propensity to misfold into PrP(Sc) thus causing sCJD. By contrast, PrP(Sc) with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrP(Sc) containing V at residue 129. In both types of CJD, the PrP(Sc) allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrP(Sc) allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD.

  9. The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients.

    Directory of Open Access Journals (Sweden)

    Roger A Moore

    2016-02-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc. The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C into infectious PrP(Sc. By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD in the United Kingdom (UK are associated with exposure to an exogenous source of PrP(Sc. In both forms of CJD, heterozygosity at residue 129 for methionine (M or valine (V in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrP(C allotype to PrP(Sc in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrP(Sc with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrP(C containing an M or V at residue 129 having a similar propensity to misfold into PrP(Sc thus causing sCJD. By contrast, PrP(Sc with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrP(Sc containing V at residue 129. In both types of CJD, the PrP(Sc allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrP(Sc allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD.

  10. The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients

    Science.gov (United States)

    Moore, Roger A.; Head, Mark W.; Ironside, James W.; Ritchie, Diane L.; Zanusso, Gianluigi; Pyo Choi, Young; Priola, Suzette A.

    2016-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrPSc). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrPC) into infectious PrPSc. By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrPSc. In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrPC allotype to PrPSc in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrPSc with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrPC containing an M or V at residue 129 having a similar propensity to misfold into PrPSc thus causing sCJD. By contrast, PrPSc with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrPSc containing V at residue 129. In both types of CJD, the PrPSc allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrPSc allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD. PMID:26840342

  11. The Clinical Stages of Sporadic Creutzfeldt-Jakob Disease with Met/Met Genotype in Korean Patients.

    Science.gov (United States)

    Park, So Young; Wang, Min Jeong; Jang, Jae-Won; Park, Young Ho; Lim, Jae-Sung; Youn, Young Chul; Kim, Jungeun; Kim, SangYun

    2016-01-01

    Clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is currently based on changes occurring in the late disease stages, which limits early-stage detection. Therefore, we investigated the disease course from the vague symptomatic to the terminal phase. We retrospectively reviewed 36 sCJD patient records, classifying the disease progression into 4 stages based on clinical manifestations: vague symptomatic, possible CJD, probable CJD and chronic vegetative state. We analyzed findings from diffusion-weighted imaging (DWI), electroencephalography (EEG) and cerebrospinal fluid (CSF) 14-3-3 protein testing performed at each stage. In stage 1, the most distinctive feature was DWI hyperintensities in the neocortex, even with negative CSF 14-3-3 protein and EEG results. In stage 2, DWI hyperintensities in the limbic cortex were more remarkable. CSF 14-3-3 protein testing yielded positive results in >80% of patients; EEG showed sensitivity in disease stage-dependent differences in clinical symptoms and laboratory test results will facilitate early and accurate diagnosis. © 2016 S. Karger AG, Basel.

  12. Serum uric acid and lipid profiles in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Chen, Shuai; He, Shuang; Shang, Jun-Kui; Ma, Ming-Ming; Xu, Chang-Shui; Shi, Xiao-Hong; Zhang, Jie-Wen

    2016-02-01

    Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system. Brain lipid homeostasis and oxidative stress seem to play an important role in the disease pathogenesis. But little was known whether serum lipids and uric acid (a natural antioxidant) levels changed in patients with prion disease. Here we retrospectively reviewed and compared the serum lipids and uric acid levels of 19 probable sporadic CJD patients and 26 healthy control subjects. We found that the serum uric acid levels in sporadic CJD patients were significantly lower than that in controls (P=0.01). Serum triglycerides, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and apolipoprotein A1 (ApoA1) were similar in sporadic CJD patients and controls. However, LDL/HDL ratio was lower in sporadic CJD patients (P=0.003). The low serum uric acid and LDL/HDL ratio levels in sporadic CJD indicate that dysfunction in the lipid homeostasis and oxidative stress is associated with sporadic prion disease. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. Imaging and clinical characteristics of sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    HAN Shun-chang

    2013-04-01

    Full Text Available Five patients with sporadic Creutzfeldt-Jakob disease (sCJD presented rapidly progressive dementia which were subacute onset from 1 to 4 months. Among these cases, periodic synchronous discharge (PSD of electroencephalography (EEG was seen in 2 patients. Besides, 4 patients obtained positive results in cerebrospinal fluid (CSF analysis for 14-3-3 protein. The cranial MRI examination showed symmetrical or asymmetrical colored-ribbon-shaped high signals in cerebral cortex or basal ganglia by diffusion weighted imaging (DWI, suggesting that DWI had high sensitivity and specificity for the diagnosis of sCJD as a preferred method in the clinical examination of sCJD.

  14. Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Appel, S; Chapman, J; Cohen, O S; Rosenmann, H; Nitsan, Z; Blatt, I

    2015-03-01

    Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown. To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings. In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003-2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG. Sixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death. Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009.

    Science.gov (United States)

    Peckeu, Laurene; Delasnerie-Lauprètre, Nicole; Brandel, Jean-Philippe; Salomon, Dominique; Sazdovitch, Véronique; Laplanche, Jean-Louis; Duyckaerts, Charles; Seilhean, Danielle; Haïk, Stéphane; Hauw, Jean-Jacques

    2017-10-01

    Diagnostic criteria of Creutzfeldt-Jakob disease (CJD), a rare and fatal transmissible nervous system disease with public health implications, are determined by clinical data, electroencephalogram (EEG), detection of 14-3-3 protein in cerebrospinal fluid (CSF), brain magnetic resonance imaging and prion protein gene examination. The specificity of protein 14-3-3 has been questioned. We reviewed data from 1,572 autopsied patients collected over an 18-year period (1992-2009) and assessed whether and how 14-3-3 detection impacted the diagnosis of sporadic CJD in France, and whether this led to the misdiagnosis of treatable disorders. 14-3-3 detection was introduced into diagnostic criteria for CJD in 1998. Diagnostic accuracy decreased from 92% for the 1992-1997 period to 85% for the 1998-2009 period. This was associated with positive detections of 14-3-3 in cases with negative EEG and alternative diagnosis at autopsy. Potentially treatable diseases were found in 163 patients (10.5%). This study confirms the usefulness of the recent modification of diagnosis criteria by the addition of the results of CSF real-time quaking-induced conversion, a method based on prion seed-induced misfolding and aggregation of recombinant prion protein substrate that has proven to be a highly specific test for diagnosis of sporadic CJD.

  16. Anesthetic management in patients suspected of Creutzfeldt-Jakob disease -A case report-.

    Science.gov (United States)

    In, Chi Bum; Choi, Young Sil; Park, Eun Young; Chang, Dong Jin; Lee, Soo Kyung; Choi, Hyun; Moon, Hyun Soo

    2011-09-01

    Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder in which accumulation of the pathogenic prion protein induces neuronal damage and results in distinct pathologic features. This abnormal prion is an infectious protein and resistant to methods of sterilization currently being used. Therefore, management of definite, or suspected CJD patients requires additional precautions. We report our experience of a patient who had undergone brain biopsy for suspected of CJD. The patient was confirmed to have sporadic CJD.

  17. Decreased CSF transferrin in sCJD: a potential pre-mortem diagnostic test for prion disorders.

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    2011-03-01

    Full Text Available Sporadic Creutzfeldt-Jakob-disease (sCJD is a fatal neurodegenerative condition that escapes detection until autopsy. Recently, brain iron dyshomeostasis accompanied by increased transferrin (Tf was reported in sCJD cases. The consequence of this abnormality on cerebrospinal-fluid (CSF levels of Tf is uncertain. We evaluated the accuracy of CSF Tf, a 'new' biomarker, as a pre-mortem diagnostic test for sCJD when used alone or in combination with the 'current' biomarker total-tau (T-tau. Levels of total-Tf (T-Tf, isoforms of Tf (Tf-1 and Tf-β2, and iron saturation of Tf were quantified in CSF collected 0.3-36 months before death (duration from 99 autopsy confirmed sCJD (CJD+ and 75 confirmed cases of dementia of non-CJD origin (CJD-. Diagnostic accuracy was estimated by non-parametric tests, logistic regression, and receiver operating characteristic (ROC analysis. Area under the ROC curve (AUC, sensitivity, specificity, positive and negative predictive values (PV, and likelihood ratios (LR of each biomarker and biomarker combination were calculated. We report that relative to CJD-, CJD+ cases had lower median CSF T-Tf (125,7093 vs. 217,7893 and higher T-tau (11530 vs. 1266 values. AUC was 0.90 (95% confidence interval (CI, 0.85-0.94 for T-Tf, and 0.93 (95% CI, 0.89-0.97 for T-Tf combined with T-tau. With cut-offs defined to achieve a sensitivity of ∼85%, T-Tf identified CJD+ cases with a specificity of 71.6% (95% CI, 59.1-81.7, positive LR of 3.0 (95% CI, 2.1-4.5, negative LR of 0.2 (95% CI, 0.1-0.3, and accuracy of 80.1%. The effect of patient age and duration was insignificant. T-Tf combined with T-tau identified CJD+ with improved specificity of 87.5% (95%CI, 76.3-94.1, positive LR of 6.8 (95% CI, 3.5-13.1, negative LR of 0.2 (95% CI, 0.1-0.3, positive-PV of 91.0%, negative-PV of 80.0%, and accuracy of 86.2%. Thus, CSF T-Tf, a new biomarker, when combined with the current biomarker T-tau, is a reliable pre-mortem diagnostic test for sCJD.

  18. MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H.; Solymosi, L. [Department of Neuroradiology, University of Wuerzburg (Germany); Klisch, J.; Brechtelsbauer, D. [Department of Neuroradiology, University of Bonn, Bonn (Germany); Wolf, H.K. [Department of Neuropathology, University of Bonn, Bonn (Germany); Gass, S. [Department of Neurology, University of Bonn, Bonn (Germany)

    1998-02-01

    To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.) With 5 figs., 2 tabs., 23 refs.

  19. MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

    International Nuclear Information System (INIS)

    Urbach, H.; Solymosi, L.; Klisch, J.; Brechtelsbauer, D.; Wolf, H.K.; Gass, S.

    1998-01-01

    To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.)

  20. Towards an age-dependent transmission model of acquired and sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    de Pedro-Cuesta, Jesús; Mahillo-Fernandez, Ignacio; Calero, Miguel; Rábano, Alberto; Cruz, Mabel; Siden, Åke; Martínez-Martín, Pablo; Laursen, Henning; Ruiz-Tovar, María; Mølbak, Kåre

    2014-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood. From Danish and Swedish national registries we identified 167 definite and probable sCJD cases with onset from 1987 through 2003, and 835 age-, sex- and residence-matched controls along with their surgical histories. Main, anatomically or etiologically classified surgical procedures followed by a ≥20-year lag were analyzed using logistic regression, and stratified by age at first-registered surgical discharge. The risk of having a diagnosis of CJD depended strongly on age at first surgery with odds ratio (OR) of 12.80 (95% CI 2.56-64.0) in patients <30 years, 3.04 (95% 1.26-7.33) in 30-39 years, and 1.75 (95% CI 0.89-3.45) in ≥40 years, for anatomically classified surgical procedures. Similar figures were obtained for etiologically classified surgical procedures. Risk of surgical-acquired sCJD depends on age at exposure; this pattern is similar to age-specific profiles reported for CJD accidentally transmitted by human pituitary-derived growth hormone and susceptibility curves for variant CJD estimated after adjustment for dietary exposure to bovine spongiform encephalopathy. There might be an age-at-exposure-related susceptibility to acquire all CJD forms, including sCJD from routine surgery.

  1. The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

    DEFF Research Database (Denmark)

    Bahl, J.M.; Heegaard, N.H.; Falkenhorst, G.

    2009-01-01

    Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF......) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE...

  2. The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

    DEFF Research Database (Denmark)

    Bahl, Justyna Maria Czarna; Heegaard, Niels Henrik Helweg; Falkenhorst, Gerhard

    2009-01-01

    ) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE......Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF...

  3. Sporadic Creutzfeldt-Jakob Disease MM1+2C and MM1 are Identical in Transmission Properties.

    Science.gov (United States)

    Kobayashi, Atsushi; Matsuura, Yuichi; Iwaki, Toru; Iwasaki, Yasushi; Yoshida, Mari; Takahashi, Hitoshi; Murayama, Shigeo; Takao, Masaki; Kato, Shinsuke; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

    2016-01-01

    The genotype (methionine, M or valine, V) at polymorphic codon 129 of the PRNP gene and the type (1 or 2) of abnormal prion protein in the brain are the major determinants of the clinicopathological features of sporadic Creutzfeldt-Jakob disease (CJD), thus providing molecular basis for classification of sporadic CJD, that is, MM1, MM2, MV1, MV2, VV1 or VV2. In addition to these "pure" cases, "mixed" cases presenting mixed neuropathological and biochemical features have also been recognized. The most frequently observed mixed form is the co-occurrence of MM1 and MM2, namely MM1+2. However, it has remained elusive whether MM1+2 could be a causative origin of dura mater graft-associated CJD (dCJD), one of the largest subgroups of iatrogenic CJD. To test this possibility, we performed transmission experiments of MM1+2 prions and a systematic neuropathological examination of dCJD patients in the present study. The transmission properties of the MM1+2 prions were identical to those of MM1 prions because MM2 prions lacked transmissibility. In addition, the neuropathological characteristics of MM2 were totally absent in dCJD patients examined. These results suggest that MM1+2 can be a causative origin of dCJD and causes neuropathological phenotype similar to that of MM1. © 2015 International Society of Neuropathology.

  4. Novel mutation of the PRNP gene of a clinical CJD case

    Directory of Open Access Journals (Sweden)

    Collinge John

    2006-11-01

    Full Text Available Abstract Background Transmissible spongiform encephalopathies (TSEs, a group of neurodegenerative diseases, are thought to be caused by an abnormal isoform of a naturally occurring protein known as cellular prion protein, PrPC. The abnormal form of prion protein, PrPSc accumulates in the brain of affected individuals. Both isoforms are encoded by the same prion protein gene (PRNP, and the structural changes occur post-translationally. Certain mutations in the PRNP gene result in genetic TSEs or increased susceptibility to TSEs. Case presentation A 70 year old woman was admitted to the hospital with severe confusion and inability to walk. Relatives recognized memory loss, gait and behavioral disturbances over a six month period prior to hospitalization. Neurological examination revealed Creutzfeldt-Jakob disease (CJD related symptoms such as incontinence, Babinski sign and myoclonus. EEG showed periodic sharp waves typical of sporadic CJD and cerebrospinal fluid analysis (CSF was positive for the presence of the 14-3-3-protein. As the disease progressed the patient developed akinetic mutism and died in the tenth month after onset of the disease symptoms. Unfortunately, no autopsy material was available. PRNP sequencing showed the occurrence of a point mutation on one allele at codon 193, which is altered from ACC, coding for a threonine, to ATC, encoding an isoleucine (T193I. Conclusion Here we report a novel mutation of the PRNP gene found in an elderly female patient resulting in heterozygosity for isoleucine and threonine at codon 193, in which normally homozygosity for threonine is expected (T193. The patient presented typical clinical symptoms of CJD. EEG findings and the presence of the 14-3-3 protein in the CSF, contributed to CJD diagnosis, allowing the classification of this case as a probable CJD according to the World Health Organization (WHO accepted criteria.

  5. Diagnosing Sporadic Creutzfeldt-Jakob Disease in a Patient with a Suspected Status Epilepticus in the Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Harm J. van der Horn

    2013-01-01

    Full Text Available Objective. Several tests are available in the diagnostics of sporadic Creutzfeldt-Jakob disease (sCJD; however, none of these is conclusive. We review the values of these tests, from an intensive care unit (ICU perspective. Methods. Case report and review of the literature. Results. A 53-year-old woman initially presenting with psychiatric symptoms developed myoclonus and was admitted 1 month later to the ICU with a suspected nonconvulsive status epilepticus and respiratory insufficiency, probably due to extensive antiepileptic drug therapy. Typical MRI and EEG findings and a positive 14-3-3 protein led to the diagnosis of sCJD. All treatments were terminated, and autopsy confirmed sCJD. Conclusions. Clinical signs combined with MRI, EEG, and 14-3-3 and/or tau protein determination might be sufficient to diagnose or exclude sCJD and may therefore prevent the application of unnecessary diagnostic tests.

  6. Sporadic Creutzfeldt-Jakob disease with focal findings: caveats to current diagnostic criteria

    Science.gov (United States)

    Mader, Edward C.; El-Abassi, Rima; Villemarette-Pittman, Nicole R.; Santana-Gould, Lenay; Olejniczak, Piotr W.; England, John D.

    2013-01-01

    The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroence-phalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient's focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures. PMID:23717780

  7. R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD)

    Energy Technology Data Exchange (ETDEWEB)

    Cervenakova, L.; Brown, P.; Nagle, J. [and others

    1994-09-01

    There are conflicting reports on the association of deletions in the PRNP gene on chromosome 20 with CJD, a rapidly progressive fatal spongiform encephalopathy. We accumulated data suggesting that a deletion of R3-R4 type (parts of the third and fourth repeats are deleted from the area of four repeating 24 bp sequences in the 5{prime} region of the gene) is causing CJD. Screening of 129 unaffected control individuals demonstrated presence of a deletion of R2 type in four (1.55% of the studied chromosomes), but none of them had the R3-R4 type. Of 181 screened patients with spongiform encephalopathies, two had a deletion of R3-R4 type with no other mutations in the coding sequence. Both patients had a classical rapidly progressive dementing disease and diffuse spongiform degeneration, and both cases were apparently sporadic. The same R3-R4 type of deletion was detected in three additional neuropathologically confirmed spongiform encephalopathy patients, of which two had other known pathogenic mutations in the PRNP gene: at codon 178 on the methionine allele exhibiting the phenotype of fatal familial insomnia, and codon 200 causing CJD with severe dementia; the third was a patient with iatrogenic CJD who developed the disease after treatment with growth hormone extracted from cadaveric human pituitary glands. In all cases the deletion coincided with a variant sequence at position 129 coding for methionine.

  8. High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions.

    Science.gov (United States)

    Franceschini, Alessia; Baiardi, Simone; Hughson, Andrew G; McKenzie, Neil; Moda, Fabio; Rossi, Marcello; Capellari, Sabina; Green, Alison; Giaccone, Giorgio; Caughey, Byron; Parchi, Piero

    2017-09-06

    An early and accurate in vivo diagnosis of rapidly progressive dementia remains challenging, despite its critical importance for the outcome of treatable forms, and the formulation of prognosis. Real-Time Quaking-Induced Conversion (RT-QuIC) is an in vitro assay that, for the first time, specifically discriminates patients with prion disease. Here, using cerebrospinal fluid (CSF) samples from 239 patients with definite or probable prion disease and 100 patients with a definite alternative diagnosis, we compared the performance of the first (PQ-CSF) and second generation (IQ-CSF) RT-QuIC assays, and investigated the diagnostic value of IQ-CSF across the broad spectrum of human prions. Our results confirm the high sensitivity of IQ-CSF for detecting human prions with a sub-optimal sensitivity for the sporadic CJD subtypes MM2C and MM2T, and a low sensitivity limited to variant CJD, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. While we found no difference in specificity between PQ-CSF and IQ-CSF, the latter showed a significant improvement in sensitivity, allowing prion detection in about 80% of PQ-CSF negative CJD samples. Our results strongly support the implementation of IQ-CSF in clinical practice. By rapidly confirming or excluding CJD with high accuracy the assay is expected to improve the outcome for patients and their enrollment in therapeutic trials.

  9. Two sequential Tc-99m ECD SPECT studies in a case of sporadic Creutzfeldt-Jakob disease confirmed at autopsy.

    Science.gov (United States)

    Paghera, Barbara; Caobelli, Federico; Nisa, Lutfun; Puta, Erinda; Borroni, Barbara; Premi, Enrico; Padovani, Alessandro; Giubbini, Raffaele

    2011-08-01

    Creutzfeldt-Jakob disease (CJD) is a subacute spongiform encephalopathy characterized by rapidly progressive dementia, hard to diagnose during life. We present a case of a patient with pathologically confirmed sporadic form of CJD in whom initial diagnostic tests were negative. Two sequential brain single-photon emission computed tomography with Tc-99m ethyl-cysteinate dimer were performed, the first one was performed few days after the admission into hospital and the second, 1 month later. Both studies revealed a decrease in regional cerebral blood flow indicative of neuronal dysfunction, more pronounced in the second study. Current radionuclide scintigraphy can be an useful tool for the investigation of CJD.

  10. Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999–2008

    Science.gov (United States)

    Hamaguchi, Tsuyoshi; Noguchi-Shinohara, Moeko; Nozaki, Ichiro; Nakamura, Yosikazu; Sato, Takeshi; Kitamoto, Tetsuyuki; Mizusawa, Hidehiro

    2009-01-01

    To elucidate the association between medical procedures and sporadic Creutzfeldt-Jakob disease (sCJD), we analyzed medical procedures (any surgical procedure, neurosurgery, ophthalmic surgery, and blood transfusion) for patients registered by the CJD Surveillance Committee in Japan during 1999–2008. We conducted an age-stratified case–control study with 753 sCJD patients and 210 controls and a study of patients who underwent neurosurgical or ophthalmic surgical procedures at the same hospital. Although the control group was relatively small, no evidence was found that prion disease was transmitted through the investigated medical procedures before onset of sCJD. After onset of sCJD, 4.5% of the sCJD patients underwent operations, including neurosurgical for 0.8% and ophthalmic for 1.9%; no special precautions against transmission of prion diseases were taken. Fortunately, we have not identified patients with prion disease attributed to these operations. Our findings indicate that surgical procedures or blood transfusion had little effect on the incidence of sCJD. PMID:19193271

  11. Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Bielewicz, Joanna; Szczepańska-Szerej, Anna; Ogórek, Magdalena; Dropko, Piotr; Wojtal, Katarzyna; Rejdak, Konrad

    2018-02-09

    We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14-3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.

  12. Alien hand and leg as the presenting feature of probable sporadic Creutzfeldt-Jakob disease: A rare presentation of a rare disease

    Directory of Open Access Journals (Sweden)

    Banshi Lal Kumawat

    2015-01-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD can have varied clinical presentation depending upon the genotype at codon 129. The common presenting clinical features of sCJD are rapid onset cognitive impairment, ataxia, psychosis and visual signs (field defects, distortion, cortical blindness. Alien limb sign was first described in patients with corpus callosal tumors and later with other neurodegenerative conditions like corticobasal degeneration. Alien hand complaints as the presenting feature of sCJD has been described in literature, but simultaneous alien hand and leg has been rarely described as presenting feature of sCJD. We describe here a case of a 55-year-old man who presented with progressive left alien hand and leg as the sole clinical manifestation of probable sCJD.

  13. CSF Neurofilament Proteins Levels are Elevated in Sporadic Creutzfeldt-Jakob Disease

    NARCIS (Netherlands)

    van Eijk, Jeroen J. J.; van Everbroeck, Bart; Abdo, W. Farid; Kremer, Berry P. H.; Verbeek, Marcel M.

    2010-01-01

    In this study we investigated the cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and heavy chain (NFHp35), total tau (t-tau), and glial fibrillary acidic protein (GFAP) to detect disease specific profiles in sporadic Creutzfeldt Jakob disease (sCJD) patients and Alzheimer's disease

  14. Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism.

    Science.gov (United States)

    Amitrano, Sara; Marozza, Annabella; Somma, Serena; Imperatore, Valentina; Hadjistilianou, Theodora; De Francesco, Sonia; Toti, Paolo; Galimberti, Daniela; Meloni, Ilaria; Cetta, Francesco; Piu, Pietro; Di Marco, Chiara; Dosa, Laura; Lo Rizzo, Caterina; Carignani, Giulia; Mencarelli, Maria Antonietta; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2015-11-01

    In about 50% of sporadic cases of retinoblastoma, no constitutive RB1 mutations are detected by conventional methods. However, recent research suggests that, at least in some of these cases, there is somatic mosaicism with respect to RB1 normal and mutant alleles. The increased availability of next generation sequencing improves our ability to detect the exact percentage of patients with mosaicism. Using this technology, we re-tested a series of 40 patients with sporadic retinoblastoma: 10 of them had been previously classified as constitutional heterozygotes, whereas in 30 no RB1 mutations had been found in lymphocytes. In 3 of these 30 patients, we have now identified low-level mosaic variants, varying in frequency between 8 and 24%. In 7 out of the 10 cases previously classified as heterozygous from testing blood cells, we were able to test additional tissues (ocular tissues, urine and/or oral mucosa): in three of them, next generation sequencing has revealed mosaicism. Present results thus confirm that a significant fraction (6/40; 15%) of sporadic retinoblastoma cases are due to postzygotic events and that deep sequencing is an efficient method to unambiguously distinguish mosaics. Re-testing of retinoblastoma patients through next generation sequencing can thus provide new information that may have important implications with respect to genetic counseling and family care.

  15. In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Day, Gregory S; Gordon, Brian A; Perrin, Richard J; Cairns, Nigel J; Beaumont, Helen; Schwetye, Katherine; Ferguson, Cole; Sinha, Namita; Bucelli, Robert; Musiek, Erik S; Ghoshal, Nupur; Ponisio, Maria R; Vincent, Benjamin; Mishra, Shruti; Jackson, Kelley; Morris, John C; Benzinger, Tammie L S; Ances, Beau M

    2018-03-06

    To determine whether specific patterns of [ 18 F]-AV-1451 tau-PET retention are observed in patients with autopsy-proven sporadic Creutzfeldt-Jakob disease (CJD). In vivo [ 18 F]-AV-1451 PET neuroimaging was performed in 5 patients with sporadic CJD (median age, 66 years [63-74]), and results were compared to cognitively normal (CN) persons (n = 44; median age, 68 years [63-74]) and to participants with very mild Alzheimer disease (AD) dementia (n = 8; median age, 77 years [63-90]). Autopsy was completed in all patients with CJD, confirming the clinical diagnosis and permitting characterization of AD neuropathologic change (ADNC). All patients with CJD presented with rapidly progressive dementia, typical magnetic resonance brain imaging changes, and elevated CSF total tau (median = 6,519; range = 1,528-13,240 pg/mL). Death occurred within 9 months of symptom onset, with a median 1 month (0.2-3.3) interval from [ 18 F]-AV-1451 PET to autopsy. No unique pattern of [ 18 F]-AV-1451 retention was observed on visual inspection. Summary standardized uptake value ratios in patients with CJD (1.17, 1.08-1.36) were indistinguishable from CN persons (1.14, 0.84-1.54; p = 0.6), and well below those of participants with AD (2.23, 1.60-3.04; p ≤ 0.01). [ 18 F]-AV-1451 retention in patients with CJD and CN persons was similar in brain areas frequently affected in AD and CJD. Neuropathologic analysis confirmed the clinical diagnosis in all patients with CJD. Four patients with CJD also had low-level ADNC (A1B1C0); one patient had intermediate-level ADNC (A2B2C1/2). Increased [ 18 F]-AV-1451 retention was not observed in patients with rapidly progressive dementia due to sporadic CJD. The [ 18 F]-AV-1451 PET tracer maintains good specificity for paired helical tau filaments associated with AD dementia. © 2018 American Academy of Neurology.

  16. Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga

    2015-05-01

    The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. SCREENING FOR GENETIC CHANGES AND CODON 129 POLYMORPHISM IN PRNP GENE IN HEALTHY SLOVENIAN POPULATION AND SPORADIC CASES OF CREUTZFELDT-JAKOB DISEASE

    Directory of Open Access Journals (Sweden)

    Sava Smerkolj

    2004-11-01

    Full Text Available Background. Prion protein has an important role in development of prion diseases, fatal neurodegenerative disorders. As the codon 129 genotype of the prion protein gene (PRNP is a known susceptibility factor for the diseases, we wanted to determine its distribution in healthy Slovenian population and also in cases of sporadic Creutzfeldt-Jakob disease (sCJD. Furthermore, we wanted to screen the whole gene in order to establish the presence of genetic changes.Methods. We screened 350 DNA samples of healthy blood donors and 12 DNA samples of patients deceased of sCJD. After the amplification and conformation analysis had been done, the gene was sequenced using an automatic sequencer.Results. Methionine homozygotes comprised 46.8% of healthy population, valine homozygotes 12.1% and heterozygotes 41.1%; out of 12 sCJD patients 10 were methionine homozygotes (83.3%, 1 was valine homozygote (8.3% and 1 was heterozygote (8.3%.Found SNPs were combination of codon 76 change (228C > T and codon 84 change (252T > C in a single sample of healthy population, combination of codon 68 change (204T > C and codon 76 change (228C > T in two samples of healthy population and codon 117 change (351A > G in a healthy population sample and in a valine homozygote patient.Conclusions. In comparison to the pooled Caucasian population is genotype M/M frequency slightly increased on account of decreased genotype M/V frequency in healthy Slovenian population, suggesting a little higher risk for acquiring a new variant of CJD (vCJD, because up to date all confirmed vCJD cases except one heterozygote were methionine homozygotes. Codon 129 genotype distribution in sCJD can be described as disease-specific. The absence of pathogenic mutations in sCJD patients confirms the non-familial, sporadic disease form.

  18. Case series of probable sporadic Creutzfeldt-Jakob disease from Eastern India

    Directory of Open Access Journals (Sweden)

    Atanu Biswas

    2013-01-01

    Full Text Available Background: Creutzfeldt-Jakob disease is a rapidly progressive, fatal, transmissible neurodegenerative disorder caused by prion protein. It is still considered rare in countries like India. This is probably due to nonavailability of autopsy studies in majority of the center. The recent European diagnostic criterion for sporadic CJD (sCJD is useful for making an early diagnosis. Objective: To report a series of patients of probable sCJD from a neurology institute of eastern India. Materials and Methods: Patients of rapidly developing dementia fulfilling the diagnostic criteria for sCJD were included. All were investigated in detail to find out any possible treatable cause including electroencephalography (EEG, magnetic resonance imaging (MRI of brain, and cerebrospinal fluid analysis. Results: A total 10 patients of probable sCJD diagnosed using the European diagnostic criterion between December 2011 and January 2013. The clinical features are consistent with other reported series. While 60% of patients had the classical EEG findings, 100% had typical MRI features. Eight patients died within a mean duration of 4.56 months from the disease onset. Conclusions: The clinical features are similar to other reported series. Our observation raises question about the prevalence of this disease in India which needs more elaborate studies.

  19. Sporadic Creutzfeldt-Jakob Disease (sCJD)

    Centers for Disease Control (CDC) Podcasts

    2009-02-03

    In this podcast, Dr. Lynne Sehulster discusses Creutzfeldt-Jakob disease, a rare neurodegenerative disease. This disease is caused by a pathological accumulation in the brain of an abnormal protein known as prions.  Created: 2/3/2009 by Emerging Infectious Diseases.   Date Released: 2/3/2009.

  20. MRI manifestation for the diagnosis of sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Xue Yonggang; Qi Ji; Xia Shuang

    2007-01-01

    Objective: To study the MRI features of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Three patients with clinically diagnosed sCJD underwent MR study, including SE T 1 WI, FSE T 2 WI, and DWI sequences. The MR imaging features were analyzed. Results: The lesions were not definite either in SE T 1 WI or in FSE T 2 WI, but were prominent in DWI. Abnormal hyperintensive signal appeared in the cerebral cortex, with the frontal, parietal, and occipital lobes being the mostly involved region. The subcortical white matter was normal. The bilateral caudate nuclei and thalami could also be involved. The abnormal signal could be either symmetrical or asymmetrical. There was diffuse atrophy of the brain parenchyma in the late phase of disease, especially in the cortex. Conclusion: With the application of MR study, especially the DWI, combined with its characteristic clinical manifestation, the diagnosis of sCJD can be made definitely. (authors)

  1. Genotype and phenotype analysis of patients with sporadic periodic paralysis.

    Science.gov (United States)

    Sung, Chih-Chien; Cheng, Chih-Jen; Lo, Yi-Fen; Lin, Mei-Shan; Yang, Sung-Sen; Hsu, Yu-Chuan; Lin, Shih-Hua

    2012-04-01

    Sporadic periodic paralysis (SPP), the second leading cause of hypokalemic periodic paralysis (HPP) in Asia, has a presentation similar to that of familial periodic paralysis (FPP) and is caused by gene mutations in the calcium (Ca(2+)) (CACNA1S) and sodium (Na(+)) (SCN4A) channels of skeletal muscle. The authors determined whether SPP shares similar genotype and phenotype with FPP. Sixty SPP patients who did not have a family history of paralysis, abnormal thyroid function tests and other identifiable causes of HPP, and 8 FPP patients were enrolled. Genomic DNA was isolated from blood leukocytes of all SPP and FPP patients. Genetic analysis of whole S4 segment in CACNA1S and SCN4A was performed. Phenotypic analysis included clinical presentations, laboratory data and precipitating events. All FPP patients had mutations in either CACNA1S or SCN4A, but only 4 SPP patients had de novo mutations in CACNA1S (R1239H) and SCN4A (R669×2, R1135H). SPP patients with de novo mutations manifested a phenotype indistinguishable from that of FPP patients except a later age of onset. SPP patients without mutations also had a later age of onset, significantly fewer attacks of paralysis than FPP patients, and unidentifiable precipitating factors. A minority of SPP patients had de novo CACNA1S or SCN4A mutations and may have a variant of FPP. The majority of SPP patients, those without mutations in CACNA1S and SCN4A, represent a unique subgroup of HPP patients, and this form of SPP usually manifests at a later age, is associated with fewer attacks and lacks apparent triggering factors.

  2. Cerebrospinal Fluid Biomarkers in the Diagnosis of Creutzfeldt-Jakob Disease in Slovak Patients: over 10-Year Period Review.

    Science.gov (United States)

    Koscova, Silvia; Zakova Slivarichova, Dana; Tomeckova, Ivana; Melicherova, Katarina; Stelzer, Martin; Janakova, Alzbeta; Kosorinova, Dana; Belay, Girma; Mitrova, Eva

    2017-10-01

    Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder. Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is difficult; however, it can be facilitated by suitable biomarkers. Aim of the present study is to compare levels of cerebrospinal fluid biomarkers (total tau protein, phosphorylated-tau protein, protein 14-3-3 and amyloid beta) in Slovak population of CJD suspect cases, retrospectively in over a 10-year period. One thousand three hundred sixty-four CSF samples from patients with suspect CJD, forming a homogenous group in terms of geographical as well as of equal transport conditions, storage and laboratory processing, were analysed. Definite diagnosis of Creutzfeldt-Jakob disease was confirmed in 101 patients with genetic form, and 60 patients with its sporadic form of the disease. Specificity of protein 14-3-3 and total tau in both forms CJD was similar (87 % for P14-3-3/85 % for total tau), sensitivity to P 14-3-3 and total tau was higher in sporadic Creutzfeldt-Jakob disease (sCJD) (90/95 %) than in genetic Creutzfeldt-Jakob disease (gCJD) (89/74 %). As expected, the total tau levels were significantly higher in CJD patients than in controls, but there was also significant difference between gCJD and sCJD (levels in gCJD were lower; p = 0.003). There was no significant difference in p-tau and Aβ 1-42 levels neither between both CJD forms nor between CJD patients and control group.

  3. PRNP variation in UK sporadic and variant Creutzfeldt Jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism

    Directory of Open Access Journals (Sweden)

    Will Robert G

    2009-12-01

    Full Text Available Abstract Background Genetic analysis of the human prion protein gene (PRNP in suspect cases of Creutzfeldt-Jakob disease (CJD is necessary for accurate diagnosis and case classification. Previous publications on the genetic variation at the PRNP locus have highlighted the presence of numerous polymorphisms, in addition to the well recognised one at codon 129, with significant variability between geographically distinct populations. It is therefore of interest to consider their influence on susceptibility or the clinico-pathological disease phenotype. This study aimed to characterise the frequency and effect of PRNP open reading frame polymorphisms other than codon 129 in both disease and control samples sourced from the United Kingdom population. Methods DNA was extracted from blood samples and genetic data obtained by full sequence analysis of the prion protein gene or by restriction fragment length polymorphism analysis using restriction enzymes specific to the gene polymorphism under investigation. Results 147 of 166 confirmed cases of variant CJD (vCJD in the UK have had PRNP codon 129 genotyping and all are methionine homozygous at codon 129; 118 have had full PRNP gene sequencing. Of the latter, 5 cases have shown other polymorphic loci: at codon 219 (2, 1.69%, at codon 202 (2, 1.69%, and a 24 bp deletion in the octapeptide repeat region (1, 0.85%. E219K and D202D were not found in sporadic CJD (sCJD cases and therefore may represent genetic risk factors for vCJD. Genetic analysis of 309 confirmed UK sCJD patients showed codon 129 genotype frequencies of MM: 59.5% (n = 184, MV: 21.4% (n = 66, and VV: 19.1% (n = 59. Thirteen (4.2% had the A117A polymorphism, one of which also had the P68P polymorphism, four (1.3% had a 24 bp deletion, and a single patient had a novel missense variation at codon 167. As the phenotype of this latter case is similar to sCJD and in the absence of a family history of CJD, it is unknown whether this is a form of

  4. The sensitivity of auxiliary examinations in different stages of sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    Jiao-jiao JIANG

    2017-06-01

    Full Text Available Objective To analyze the sensitivity of auxiliary examinations in different periods of sporadic Creutzfeldt-Jakob disease (sCJD. Methods The clinical data of 53 sCJD patients were retrospectively analyzed including the different stages of skull diffusion-weighted magnetic resonance imaging (DWI, 24-hour ambulatory electroencephalogram (EEG, 18F-FDG PET/CT (PET-CT and cerebrospinal fluid 14-3-3 protein. When calculating the sensitivity of an auxiliary examination, the diagnostic criteria were defined by combining the specific clinical manifestations with two or more positive results of other auxiliary examinations. Results There were 24, 53 and 22 sCJD patients, respectively, met the criterion of early (E, middle (M and later (L stage of disease (some patients fit 2 or 3 stages. The sensitivity of DWI (E: 58.3%, M: 85.4%, L: 94.7%, EEG (E: 45.8%, M: 62.7%, L: 77.8%, 14-3-3 protein in cerebrospinal fluid (E: 11.1%, M: 52.9% and PET-CT (E: 80%, M: 100% increased gradually with disease progression. The sensitivity of PET-CT was higher than the other auxiliary examinations for E and M stages; no PET-CT was conducted in L stage. High signal regions mainly distributed in the cortex in E and M stages, but in L stage, no significant difference was found on the distribution of high signal regions between cortex and basal ganglia. Conclusions The sensitivities of the auxiliary examinations were different for sCJD patients in different stages. Reexaminations in different periods may improve the sensitivity for sCJD diagnosis. The sensitivity of PET-CT was high, and the combination of PET-CT and other auxiliary examinations may play a key role in the diagnosis of sCJD. DOI: 10.11855/j.issn.0577-7402.2017.05.15

  5. Racial and ethnic differences in individuals with sporadic Creutzfeldt-jakob disease in the United States of America.

    Directory of Open Access Journals (Sweden)

    Brian S Appleby

    Full Text Available BACKGROUND: Little is known about racial and ethnic differences in individuals with sporadic Creutzfeldt-Jakob disease (sCJD. The authors sought to examine potential clinical, diagnostic, genetic, and neuropathological differences in sCJD patients of different races/ethnicities. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study of 116 definite and probable sCJD cases from Johns Hopkins and the Department of Veterans Affairs Healthcare Systems was conducted that examined differences in demographic, clinical, diagnostic, genetic, and neuropathological characteristics among racial/ethnic groups. Age at disease onset differed among racial/ethnic groups. Non-Hispanic Whites had a significantly older age at disease onset compared to the other groups (65 vs. 60, p = 0.036. Non-Whites were accurately diagnosed more rapidly than Whites (p = 0.008 and non-Hispanic Whites were more likely to have normal appearing basal ganglia on brain magnetic resonance imaging (MRI compared to minorities (p = 0.02. Whites were also more likely to undergo post-mortem evaluation compared to non-Whites (p = 0.02. CONCLUSIONS/SIGNIFICANCE: Racial/ethnic groups affected by sCJD demonstrated differences in age at disease onset, time to correct diagnosis, clinical presentation, and diagnostic test results. Whites were more likely to undergo autopsy compared to non-Whites. These results have implications in regards to case ascertainment, diagnosis, and surveillance of sCJD and possibly other human prion diseases.

  6. Sporadic Creutzfeldt–Jakob disease with cerebellar ataxia at onset in the UK

    Science.gov (United States)

    Cooper, S A; Murray, K L; Heath, C A; Will, R G; Knight, R S G

    2006-01-01

    Objective To determine the frequency, in the UK, of sporadic Creutzfeldt–Jakob Disease (sCJD) with a cerebellar ataxic onset, and to describe the clinical features of the syndrome. Methods A retrospective review of autopsy‐proved cases of sCJD cases in the UK, 1990–2005, identifying those presenting with cerebellar features without early cognitive decline. Results 29 of 618 (5%) patients with sCJD had an isolated cerebellar onset. Mean illness duration was 9 months. Subsequently, 21 (72%) developed myoclonus and 23 (79%) developed pyramidal features. Magnetic resonance imaging showed high signal in the basal ganglia in 11 of 14 (79%) patients. 7 of 15 (47%) patients were valine homozygotic at prion protein gene (PRNP)‐129. Only 8 (28%) cases were referred to the surveillance unit after death. Conclusion A better definition of sCJD presenting with an isolated cerebellar syndrome might improve future case recognition and contribute to the determination of its cause. PMID:16835290

  7. Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Gmitterová, K; Heinemann, U; Krasnianski, A; Gawinecka, J; Zerr, I

    2016-06-01

    Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P disease duration and clinical stage influenced the test sensitivity in all proteins. Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known. © 2016 EAN.

  8. Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc.

    Science.gov (United States)

    Puoti, Gianfranco; Giaccone, Giorgio; Mangieri, Michela; Limido, Lucia; Fociani, Paolo; Zerbi, Pietro; Suardi, Silvia; Rossi, Giacomina; Iussich, Selina; Capobianco, Raffaella; Di Fede, Giuseppe; Marcon, Gabriella; Cotrufo, Roberto; Filippini, Graziella; Bugiani, Orso; Tagliavini, Fabrizio

    2005-10-01

    In prion-related encephalopathies, microglial activation occurs early and is dependent on accumulation of disease-specific forms of the prion protein (PrPSc) and may play a role in nerve cell death. Previously, we found that different types of PrPSc (i.e. type 1 and type 2) coexisted in approximately 25% of patients with sporadic Creutzfeldt-Jakob disease (CJD); and a close relationship was detected between PrPSc type, the pattern of PrP immunoreactivity, and extent of spongiform degeneration. To investigate whether microglial reaction is related to the biochemical type and deposition pattern of PrPSc, we carried out a neuropathologic and biochemical study on 26 patients with sporadic CJD, including all possible genotypes at codon 129 of the prion protein gene. By quantitative analysis, we demonstrated that strong microglial activation was associated with type 1 PrPSc and diffuse PrP immunoreactivity, whereas type 2 PrPSc and focal PrP deposits were accompanied by mild microglia reaction. These findings support the view that the phenotypic heterogeneity of sporadic CJD is largely determined by the physicochemical properties of distinct PrPSc conformers.

  9. Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries. METHODS: The data from 57 Chinese sCJD patients were retrospectively analyzed, including demographic data, clinical manifestations, laboratory examinations, electroencephalograms (EEGs, diffusion-weighted imaging (DWI scans, positron emission tomography (PET scans, and pathological results. RESULT: The disease was pathologically confirmed in 11 patients. 39 cases were diagnosed as probable sCJD, and 7 were possible. Of the total cases, 33 were male, and 24 were female. The onset age ranged from 36 to 75 years (mean: 55.5, median: 57. Disease onset before the age of 60 occurred in 57.9% of patients. The disease duration from onset to death ranged 5-22 months (mean: 11.6, median: 11, and 51.9% of patients died 7 to 12 months after disease onset. The majority of patients presented with sub-acute onset with progressive dementia. 3 of the 9 patients who took 14-3-3 protein analysis had positive results (33.3%. The sensitivity of EEG was 79.6% (43/54. For DWI and PET examinations, the sensitivities were 94% (47/50 and 94.1% (16/17, respectively. In seven patients who did not show typical hyper-intensities on the first DWI examination, abnormalities of hypo-metabolism in the cerebral cortex were clearly detected by PET. In 13 out of the 17 patients, PET detected extra abnormal regions in addition to the hyper-intense areas observed in DWI. CONCLUSION: This is the first study to indicate that Chinese sCJD patients have a much earlier onset age and a longer disease duration than other populations, which is most likely related to racial differences. The longer disease duration may also be a probable characteristic of Asian populations. PET had high sensitivity for the

  10. Health professions and risk of sporadic Creutzfeldt- Jakob disease, 1965 to 2010

    NARCIS (Netherlands)

    E. Alcalde-Cabero; J. Almazán-Isla; J-P. Brandel (Jean-Philippe); M. Breithaupt; J. Catarino; S.J. Collins (Steven); J. Haybäck; R. Höftberger (Romana); E. Kahana; G.G. Kovacs (Gabor); A. Ladogana (Anna); E. Mitrová (Eva); A. Molesworth; Y. Nakamura; M. Pocchiari (Maurizio); M. Popovic; M. Ruiz-Tovar; A. Taratuto; C. van Duin; M. Yamada; R.G. Will (Robert); I. Zerr (Inga); J. de Pedro-Cuesta (Jesús)

    2012-01-01

    textabstractIn 2009, a pathologist with sporadic Creutzfeldt- Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network

  11. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

    Directory of Open Access Journals (Sweden)

    Chae Kim

    2011-09-01

    Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

  12. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

    Science.gov (United States)

    Kim, Chae; Haldiman, Tracy; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Sy, Man-Sun; Cohen, Mark; Safar, Jiri G

    2011-09-01

    The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD), are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc)) using novel conformational methods derived from a conformation-dependent immunoassay (CDI). In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc), we identified an extensive array of PrP(Sc) structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc) correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc) structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc) suggests that these conformers play an important role in the pathogenesis of sCJD.

  13. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  14. Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter

    NARCIS (Netherlands)

    Berghout, A.; Wiersinga, W. M.; Smits, N. J.; Touber, J. L.

    1990-01-01

    To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed.

  15. Long-term preclinical magnetic resonance imaging alterations in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Zanusso, Gianluigi; Camporese, Giulia; Ferrari, Sergio; Santelli, Luca; Bongianni, Matilde; Fiorini, Michele; Monaco, Salvatore; Manara, Renzo; Cagnin, Annachiara

    2016-10-01

    An asymptomatic 74-year-old woman, on follow-up for a carotid body tumor, showed magnetic resonance imaging (MRI) focal restricted diffusion confined to the left temporal and occipital cortices. Thirteen months later, diffusion-weighted images revealed a bilateral cortical ribbon sign involving all lobes. After 1 month, the patient developed gait instability and cognitive decline rapidly evolving to severe dementia and death within 3 months. Prion protein gene sequence, molecular, and neuropathological studies confirmed the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI changes and prion spreading in preclinical sCJD MM1. Ann Neurol 2016;80:629-632. © 2016 American Neurological Association.

  16. CHCH10 mutations in an Italian cohort of familial and sporadic ALS patients

    Science.gov (United States)

    Chiò, Adriano; Mora, Gabriele; Sabatelli, Mario; Caponnetto, Claudia; Traynor, Bryan J.; Johnson, Janel O.; Nalls, Mike A.; Calvo, Andrea; Moglia, Cristina; Borghero, Giuseppe; Monsurrò, Maria Rosaria; La Bella, Vincenzo; Volanti, Paolo; Simone, Isabella; Salvi, Fabrizio; Logullo, Francesco O.; Nilo, Riva; Battistini, Stefania; Mandrioli, Jessica; Tanel, Raffaella; Murru, Maria Rita; Mandich, Paola; Zollino, Marcella; Conforti, Francesca L.; Brunetti, Maura; Barberis, Marco; Restagno, Gabriella; Penco, Silvana; Lunetta, Christian

    2015-01-01

    Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) co-morbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n = 64) and apparently sporadic ALS (n = 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in two unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ∼1% of Italian ALS patients and are a cause of disease in subject without dementia or other atypical clinical signs. PMID:25726362

  17. The Prion Protein Preference of Sporadic Creutzfeldt-Jakob Disease Subtypes*

    Science.gov (United States)

    Klemm, Helen M. J.; Welton, Jeremy M.; Masters, Colin L.; Klug, Genevieve M.; Boyd, Alison; Hill, Andrew F.; Collins, Steven J.; Lawson, Victoria A.

    2012-01-01

    Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans. The disease encompasses a spectrum of clinical phenotypes that have been correlated with molecular subtypes that are characterized by the molecular mass of the protease-resistant fragment of the disease-related conformation of the prion protein and a polymorphism at codon 129 of the gene encoding the prion protein. A cell-free assay of prion protein misfolding was used to investigate the ability of these sporadic CJD molecular subtypes to propagate using brain-derived sources of the cellular prion protein (PrPC). This study confirmed the presence of three distinct sporadic CJD molecular subtypes with PrPC substrate requirements that reflected their codon 129 associations in vivo. However, the ability of a sporadic CJD molecular subtype to use a specific PrPC substrate was not determined solely by codon 129 as the efficiency of prion propagation was also influenced by the composition of the brain tissue from which the PrPC substrate was sourced, thus indicating that nuances in PrPC or additional factors may determine sporadic CJD subtype. The results of this study will aid in the design of diagnostic assays that can detect prion disease across the diversity of sporadic CJD subtypes. PMID:22930754

  18. Diffusion-weighted imaging and magnetic resonance spectroscopy of sporadic Creutzfeldt-Jakob disease: correlation with clinical course

    International Nuclear Information System (INIS)

    Kim, Jae Hyoung; Choi, Byung Se; Jung, Cheolkyu; Chang, YoungHee; Kim, SangYun

    2011-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal disease with variable clinical courses. The presence or absence of basal ganglia (BG) involvement has been reported to be associated with clinical course. We investigated the association of clinical course of sCJD with diffusion-weighted imaging (DWI) and MR spectroscopy (MRS) as well as BG involvement at early stage. DWI and single voxel proton MRS were performed in 14 patients with sCJD during the initial diagnostic workup. Apparent diffusion coefficient (ADC) and metabolites were measured in medial occipitoparietal cortices where large hyperintense DWI lesions were found in all patients. The presence or absence of BG involvement, ADC, N-acetylaspartate (NAA)/creatine (Cr) ratios, and choline (Cho)/Cr ratios were correlated with disease duration (i.e., the time from the symptom onset to death). The disease duration ranged from 2 to 31 months (median, 16). Hyperintense DWI lesions were observed bilaterally in both cortices and basal ganglia in eight patients and in cortices alone in six patients. Patients with BG involvement had shorter disease duration (median, 6.8 versus 20.5; p = 0.039) than those without and lower NAA/Cr ratios (median, 1.41 versus 2.03; p = 0.001). ADC and Cho/Cr ratios were not significantly different between the patients with BG involvement and those without. By multiple regression analysis, NAA/Cr ratios had the greatest correlation with the disease duration (p = 0.029). The disease duration of sCJD was variable. NAA/Cr ratios of the affected brain at the early stage of sCJD can be used as a useful parameter in predicting the clinical course. (orig.)

  19. Diffusion-weighted imaging and magnetic resonance spectroscopy of sporadic Creutzfeldt-Jakob disease: correlation with clinical course

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Hyoung; Choi, Byung Se; Jung, Cheolkyu [Seoul National University Bundang Hospital, Department of Radiology, Seoul National University College of Medicine, Seongnam-si (Korea, Republic of); Chang, YoungHee; Kim, SangYun [Seoul National University Bundang Hospital, Department of Neurology, Seoul National University College of Medicine, Seongnam-si (Korea, Republic of)

    2011-12-15

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal disease with variable clinical courses. The presence or absence of basal ganglia (BG) involvement has been reported to be associated with clinical course. We investigated the association of clinical course of sCJD with diffusion-weighted imaging (DWI) and MR spectroscopy (MRS) as well as BG involvement at early stage. DWI and single voxel proton MRS were performed in 14 patients with sCJD during the initial diagnostic workup. Apparent diffusion coefficient (ADC) and metabolites were measured in medial occipitoparietal cortices where large hyperintense DWI lesions were found in all patients. The presence or absence of BG involvement, ADC, N-acetylaspartate (NAA)/creatine (Cr) ratios, and choline (Cho)/Cr ratios were correlated with disease duration (i.e., the time from the symptom onset to death). The disease duration ranged from 2 to 31 months (median, 16). Hyperintense DWI lesions were observed bilaterally in both cortices and basal ganglia in eight patients and in cortices alone in six patients. Patients with BG involvement had shorter disease duration (median, 6.8 versus 20.5; p = 0.039) than those without and lower NAA/Cr ratios (median, 1.41 versus 2.03; p = 0.001). ADC and Cho/Cr ratios were not significantly different between the patients with BG involvement and those without. By multiple regression analysis, NAA/Cr ratios had the greatest correlation with the disease duration (p = 0.029). The disease duration of sCJD was variable. NAA/Cr ratios of the affected brain at the early stage of sCJD can be used as a useful parameter in predicting the clinical course. (orig.)

  20. Isolated visual symptoms at onset in sporadic Creutzfeldt-Jakob disease: the clinical phenotype of the “Heidenhain variant”

    Science.gov (United States)

    Cooper, S A; Murray, K L; Heath, C A; Will, R G; Knight, R S G

    2005-01-01

    Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD) is commonly understood to represent cases with early, prominent visual complaints. The term is clarified to represent those who present with isolated visual symptoms. This group may pose diagnostic difficulties and often present to ophthalmologists where they may undergo needless invasive procedures. Method: A retrospective review of 594 pathologically proved sCJD cases referred to the UK National CJD Surveillance Unit over a 15 year period to identify Heidenhain cases. Results: 22 cases had isolated visual symptoms at onset with a mean illness duration of 4 months. The mean age at disease onset was 67 years. Most displayed myoclonus, pyramidal signs, and a delay in the onset of dementia for some weeks. 17 (77%) were referred initially to ophthalmology. Two underwent cataract extraction before diagnosis. All tested cases were homozygous for methionine at codon 129 of the prion protein gene. Conclusions: This rare, but clinically distinct, group of patients with sCJD may cause diagnostic difficulties. Because ocular intervention carries with it the risk of onward transmission awareness of this condition among ophthalmologists is important. PMID:16170128

  1. A genome-wide investigation of copy number variation in patients with sporadic brain arteriovenous malformation.

    Directory of Open Access Journals (Sweden)

    Nasrine Bendjilali

    Full Text Available Brain arteriovenous malformations (BAVM are clusters of abnormal blood vessels, with shunting of blood from the arterial to venous circulation and a high risk of rupture and intracranial hemorrhage. Most BAVMs are sporadic, but also occur in patients with Hereditary Hemorrhagic Telangiectasia, a Mendelian disorder caused by mutations in genes in the transforming growth factor beta (TGFβ signaling pathway.To investigate whether copy number variations (CNVs contribute to risk of sporadic BAVM, we performed a genome-wide association study in 371 sporadic BAVM cases and 563 healthy controls, all Caucasian. Cases and controls were genotyped using the Affymetrix 6.0 array. CNVs were called using the PennCNV and Birdsuite algorithms and analyzed via segment-based and gene-based approaches. Common and rare CNVs were evaluated for association with BAVM.A CNV region on 1p36.13, containing the neuroblastoma breakpoint family, member 1 gene (NBPF1, was significantly enriched with duplications in BAVM cases compared to controls (P = 2.2×10(-9; NBPF1 was also significantly associated with BAVM in gene-based analysis using both PennCNV and Birdsuite. We experimentally validated the 1p36.13 duplication; however, the association did not replicate in an independent cohort of 184 sporadic BAVM cases and 182 controls (OR = 0.81, P = 0.8. Rare CNV analysis did not identify genes significantly associated with BAVM.We did not identify common CNVs associated with sporadic BAVM that replicated in an independent cohort. Replication in larger cohorts is required to elucidate the possible role of common or rare CNVs in BAVM pathogenesis.

  2. Laminar Distribution of the Pathological Changes in Sporadic and Variant Creutzfeldt-Jakob Disease

    Directory of Open Access Journals (Sweden)

    R. A. Armstrong

    2011-01-01

    Full Text Available The laminar distributions of the pathological changes in the cerebral cortex were compared in the prion diseases sporadic Creutzfeldt-Jakob disease (sCJD and variant CJD (vCJD. First, in some cortical regions, the vacuolation (“spongiform change” was more generally distributed across the cortex in sCJD. Second, there was greater neuronal loss in the upper cortex in vCJD and in the lower cortex in sCJD. Third, the “diffuse” and “florid” prion protein (PrPsc deposits were more frequently distributed in the upper cortex in vCJD and the “synaptic” deposits in the lower cortex in sCJD. Fourth, there was a significant gliosis mainly affecting the lower cortex of both disorders. The data suggest that the pattern of cortical degeneration is different in sCJD and vCJD which may reflect differences in aetiology and the subsequent spread of prion pathology within the brain.

  3. Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    S Birla

    2016-01-01

    Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

  4. A Genome Wide Association Study Links Glutamate Receptor Pathway to Sporadic Creutzfeldt-Jakob Disease Risk

    Science.gov (United States)

    Sanchez-Juan, Pascual; Bishop, Matthew T.; Kovacs, Gabor G.; Calero, Miguel; Aulchenko, Yurii S.; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Ángel; van der Lee, Sven J.; Ströbel, Thomas; Rivadeneira, Fernando; Hofman, Albert; Haïk, Stéphane; Combarros, Onofre; Berciano, José; Uitterlinden, Andre G.; Collins, Steven J.; Budka, Herbert; Brandel, Jean-Philippe; Laplanche, Jean Louis; Pocchiari, Maurizio; Zerr, Inga; Knight, Richard S. G.; Will, Robert G.; van Duijn, Cornelia M.

    2015-01-01

    We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis. PMID:25918841

  5. Variant Creutzfeldt-Jakob Disease (vCJD)

    Science.gov (United States)

    ... Form Controls Cancel Submit Search the CDC Variant Creutzfeldt-Jakob Disease (vCJD) Note: Javascript is disabled or is not ... gov . Recommend on Facebook Tweet Share Compartir Variant Creutzfeldt-Jakob disease (vCJD) is a prion disease that was first ...

  6. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients

    Directory of Open Access Journals (Sweden)

    Hanae Takatsuki, PhD

    2016-10-01

    Full Text Available Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 106/g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 106/g SD50 did not exist the infectivity.

  7. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients.

    Science.gov (United States)

    Takatsuki, Hanae; Fuse, Takayuki; Nakagaki, Takehiro; Mori, Tsuyoshi; Mihara, Ban; Takao, Masaki; Iwasaki, Yasushi; Yoshida, Mari; Murayama, Shigeo; Atarashi, Ryuichiro; Nishida, Noriyuki; Satoh, Katsuya

    2016-10-01

    Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 10 6 /g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 10 6 /g SD50 did not exist the infectivity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Investigation of VSX1 sequence variants in South Indian patients with sporadic cases of keratoconus.

    Science.gov (United States)

    Verma, Anshuman; Das, Manoranjan; Srinivasan, Muthiah; Prajna, Namperumalsamy V; Sundaresan, Periasamy

    2013-03-18

    The involvement of VSX1 gene for the genetic basis of keratoconus is unclear and controversial. The genetic screening of VSX1 from different ethnic populations can enlighten this subject. The aim of the present study is to investigate the role of VSX1 gene in patients with sporadic cases of keratoconus from South India. The VSX1 gene coding regions, including exon-intron boundaries were screened by direct sequencing analysis in 117 sporadic cases of keratoconus. The identified variations were also analyzed in 108 ethnic matched healthy blood donors. In the VSX1 gene screening, no pathogenic mutation was identified, whereas we could find the presence of four reported single nucleotide polymorphisms; c.546A>G (rs12480307), c.627+23G>A (rs6138482), c.627+84T>A (rs56157240) and c.504-24C>T (IVS3-24C). These variations were observed in similar frequency between cases and controls. The lack of VSX1 pathogenic variations in a large number of unrelated sporadic keratoconus patients tend to omit its role, and corroborate the involvement of other genetic, environmental or behavioural factors in the development of this complex disorder.

  9. BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.

    Directory of Open Access Journals (Sweden)

    Ainur R. Akilzhanova

    2013-05-01

    Full Text Available Background: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women. Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer. Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing. Results: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05; higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations. Conclusions: Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation. 

  10. Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD)

    Energy Technology Data Exchange (ETDEWEB)

    Gabizon, R.; Rosenmann, H.; Meiner, Z.; Kahana, I. (Hadassah Univ., Jerusalem (Israel)); Kahana, E. (Barzilai Medical Center, Ashkelon (Israel)); Shugart, Y.; Ott, J. (Columbia Univ., New York, NY (United States)); Prusiner, S.B. (Univ. of California, San Francisco, CA (United States))

    1993-10-01

    The inherited prion diseases are neurodegenerative disorders which are not only genetic but also transmissible. More than a dozen mutations in the prion protein gene that result in nonconservative amino acid substitutions segregate with the inherited prion diseases including familial Creutzfeldt-Jakob disease (CJD). In Israel, the incidence of CJD is about 1 case/10[sup 4] Libyan Jews. A Lys[sub 200] substitution segregates with CJD and is reported here to be genetically linked to CJD with a lod score of >4.8. Some healthy elderly Lys[sub 200] carriers > age 65 years were identified, suggesting the possibility of incomplete penetrance. In contrast, no linkage was found between the development of familial CJD and a polymorphism encoding either Met[sub 129] or Val[sub 129]. All Libyan Jewish CJD patients with the Lys[sub 200] mutation encode a Met[sub 129] on the mutant allele. Homozygosity for Met[sub 129] did not correlate with age at disease onset or the duration of illness. The frequency of the Met[sub 129] allele was higher in the affected pedigrees than in a control population of Libyan Jews. The frequency of the Met[sub 129] and Val[sub 129] alleles in the control Libyan population was similar to that found in the general Caucasian population. The identification of three Libyan Jews homozygous for the Lys[sub 200] mutation suggests frequent intrafamilial marriages, a custom documented by genealogical investigations. 26 refs., 3 figs., 6 tabs.

  11. Prevalence of mitochondrial DNA mutations in sporadic patients with nonsyndromic sensorineural hearing loss.

    Science.gov (United States)

    Jiang, Hua; Chen, Jia; Li, Ying; Lin, Peng-Fang; He, Jian-Guo; Yang, Bei-Bei

    2016-01-01

    Several mitochondrial DNA mutations have been reported to be associated with nonsyndromic hearing loss in several families. However, little is known about the prevalence of these mutations in sporadic patients with nonsyndromic sensorineural hearing loss. The purpose of our study was to investigate the incidence of these mitochondrial DNA mutations in such population. A total of 178 sporadic patients with nonsyndromic sensorineural hearing loss were enrolled in this study. Genomic DNA was extracted from the peripheral blood sample. We employed the SNaPshot(®) sequencing method to detect five mitochondrial DNA mutations, including A1555G and A827G in 12S rRNA gene and A7445G, 7472insC, and T7511C in tRNA(Ser(UCN)) gene. Meanwhile, we used polymerase chain reaction and sequenced the products to screen GJB2 gene mutations in patients carrying mitochondrial DNA mutations. We failed to detect the presence of A1555G mutation in 12S rRNA gene, and of A7445G, 7472insC, T7511C mutations in tRNA(Ser(UCN)) gene in our population. However, we found that 6 patients (3.37%) were carriers of a homozygous A827G mutation and one of them also carried homozygous GJB2 235delC mutation. Our findings in the present study indicate that even in sporadic patients with nonsyndromic sensorineural hearing loss, mitochondrial DNA mutations might also contribute to the clinical phenotype. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  12. Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients.

    Science.gov (United States)

    Mitropoulos, Konstantinos; Merkouri Papadima, Eleni; Xiromerisiou, Georgia; Balasopoulou, Angeliki; Charalampidou, Kyriaki; Galani, Vasiliki; Zafeiri, Krystallia-Vassiliki; Dardiotis, Efthymios; Ralli, Styliani; Deretzi, Georgia; John, Anne; Kydonopoulou, Kyriaki; Papadopoulou, Elpida; di Pardo, Alba; Akcimen, Fulya; Loizedda, Annalisa; Dobričić, Valerija; Novaković, Ivana; Kostić, Vladimir S; Mizzi, Clint; Peters, Brock A; Basak, Nazli; Orrù, Sandro; Kiskinis, Evangelos; Cooper, David N; Gerou, Spyridon; Drmanac, Radoje; Bartsakoulia, Marina; Tsermpini, Evangelia-Eirini; Hadjigeorgiou, Georgios M; Ali, Bassam R; Katsila, Theodora; Patrinos, George P

    2017-12-08

    Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS). Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific disease-associated haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic variants in question. To our knowledge, this is the first study to present a possible association between FTO gene variants and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled with the two-step validation strategy described herein has the potential to be applied to other types of human complex genetic disorders in order to identify variants of clinical significance.

  13. High-resolution analysis of DNA copy number alterations in patients with isolated sporadic keratoconus.

    Science.gov (United States)

    Abu-Amero, Khaled K; Hellani, Ali M; Al Mansouri, Sameer M; Kalantan, Hatem; Al-Muammar, Abdulrahman M

    2011-03-30

    To determine whether patients with sporadic, non-familial keratoconus and no pathogenic mutations in the visual system homeobox 1 (VSX1) gene have evidence of chromosomal copy number alterations. Twenty Saudi Arabian patients with isolated keratoconus, no family history of the disease and no mutations in VSX1 were recruited. Additionally, 10 ethnically-matched healthy controls were also recruited for this study. We screened patients for chromosomal copy number aberrations using the Agilent Human Genome CGH 244A Oligo Microarray Chip. None of the keratoconus patients screened had evidence of chromosomal copy number alterations when compared to normal ethnically matched controls. Chromosomal deletions and/or duplications were not detected in any of the patients tested here. Other chromosomal imbalances such as translocations, inversions, and some ploidies cannot be detected by current array CGH technology and other nuclear genetic or epigenetic factors cannot be excluded as a possible contributing factor to keratoconus pathogenesis.

  14. Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Concha-Marambio, Luis; Pritzkow, Sandra; Moda, Fabio; Tagliavini, Fabrizio; Ironside, James W; Schulz, Paul E; Soto, Claudio

    2016-12-21

    Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrP Sc ) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. vCJD has already been transmitted from human to human by blood transfusion, and the number of asymptomatic carriers of vCJD in the U.K. alone is estimated to be 1 in 2000 people. We used the protein misfolding cyclic amplification (PMCA) technique to analyze blood samples from 14 cases of vCJD and 153 controls, including patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. Our results showed that PrP Sc could be detected with 100% sensitivity and specificity in blood samples from vCJD patients. Detection was possible in any of the blood fractions analyzed and could be done with as little as a few microliters of sample volume. The PrP Sc concentration in blood was estimated to be ~0.5 pg/ml. Our findings suggest that PMCA may be useful for premortem noninvasive diagnosis of vCJD and to identify prion contamination of the blood supply. Further studies are needed to fully validate the technology. Copyright © 2016, American Association for the Advancement of Science.

  15. Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Nakatani, E; Kanatani, Y; Kaneda, H; Nagai, Y; Teramukai, S; Nishimura, T; Zhou, B; Kojima, S; Kono, H; Fukushima, M; Kitamoto, T; Mizusawa, H

    2016-09-01

    Akinetic mutism is thought to be an appropriate therapeutic end-point in patients with sporadic Creutzfeldt-Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset. The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms. Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14-1.99, and HR 2.15, 95% CI1.61-2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance. The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease. © 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  16. Effects of different experimental conditions on the PrPSc core generated by protease digestion: implications for strain typing and molecular classification of CJD.

    Science.gov (United States)

    Notari, Silvio; Capellari, Sabina; Giese, Armin; Westner, Ingo; Baruzzi, Agostino; Ghetti, Bernardino; Gambetti, Pierluigi; Kretzschmar, Hans A; Parchi, Piero

    2004-04-16

    The discovery of molecular subtypes of the pathological prion protein PrPSc has provided the basis for a novel classification of human transmissible spongiform encephalopathies (TSEs) and a potentially powerful method for strain typing. However, there is still a significant disparity regarding the understanding and nomenclature of PrPSc types. In addition, it is still unknown whether a specific PrPSc type is associated with each TSE phenotypic variant. In sporadic Creutzfeldt-Jakob disease (sCJD), five disease phenotypes are known, but only two major types of PrPSc, types 1 and 2, have been consistently reproduced. We further analyzed PrPSc properties in sCJD and variant CJD using a high resolution gel electrophoresis system and varying experimental conditions. We found that pH varies among CJD brain homogenates in standard buffers, thereby influencing the characteristics of protease-treated PrPSc. We also show that PrPSc type 1 and type 2 are heterogeneous species which can be further distinguished into five molecular subtypes that fit the current histopathological classification of sCJD variants. Our results shed light on previous disparities in PrPSc typing, provide a refined classification of human PrPSc types, and support the notion that the pathological TSE phenotype is related to PrPSc structure.

  17. Carotid, aorta and renal arteries intima-media thickness in patients with sporadic idiopathic hypoparathyroidism

    Directory of Open Access Journals (Sweden)

    Deshraj Meena

    2015-01-01

    Full Text Available Background: Alteration in homeostasis of calcium, phosphate and parathyroid hormone (PTH predispose to vascular calcification that increases the risk of cardiovascular morbidity and mortality. The data on this aspect are scarce in patients with sporadic idiopathic hypoparathyroidism (SIH. Objective: The aim was to assess the effect of altered calcium, phosphate and PTH homeostasis in patients with SIH on intima media thickness (IMT, a surrogate marker of increased vascular risk. Methods: In this case-control study, we measured carotid IMT (CIMT, aortic IMT (AIMT and renal arteries IMT (RIMT in 30 consecutive patients with SIH, and compared with healthy subjects. IMT was measured by ultrasound by a single operator blinded to subject′s details. Results: CIMT, AIMT, RIMT values in patients with SIH were significantly more than healthy subjects (0.60 ± 0.08 mm vs. 0.52 ± 0.09 mm, P = 0.001; 0.73 ± 0.09 mm vs. 0.65 ± 0.10, P = 0.004; and 0.34 ± 0.04 mm vs. 0.30 ± 0.05, P = 0.003, respectively. Clinical or biochemical parameters did not correlate with CIMT, AIMT and RIMT in patients with SIH. Conclusion: The vascular risk is increased in patients with SIH as assessed by CIMT, AIMT, and RIMT.

  18. The survival of patients with Stage III Colon Cancer is improved in HNPCC compared with sporadic cases. A Danish registry based study

    DEFF Research Database (Denmark)

    Brixen, Line Merrild; Bernstein, Inge Thomsen; Bülow, Steffen

    2013-01-01

    AIM: Patients with hereditary non-polyposis colorectal cancer (HNPCC) seem to have a better prognosis than those with sporadic colon cancer (CC)s. The aim was to compare survival after stage III CC in patients with HNPCC with those having sporadic CC. METHOD: 230 patients with hereditary cancer...... history of cancer. Patient characteristics, geographic differences and survival data were analyzed. RESULTS: The overall survival (OS) was better in HNPCC patients compared to sporadic CC after stratification for sex and age (p=0.02; CI 1.04-1.7). The 5-year survival was 70% in HNPCC patients compared...... from The Danish HNPCC-Register and 3557 patients with sporadic CC from The Danish Colorectal Cancer Database, diagnosed during May 2001-December 2008 were included. HNPCC patients were classified according to Mismatch Repair mutation status and family pedigree. Sporadic cases had no known family...

  19. AIP mutations in Brazilian patients with sporadic pituitary adenomas: a single-center evaluation

    Directory of Open Access Journals (Sweden)

    Paula Bruna Araujo

    2017-11-01

    Full Text Available Aryl hydrocarbon receptor-interacting protein (AIP gene mutations (AIPmut are the most frequent germline mutations found in apparently sporadic pituitary adenomas (SPA. Our aim was to evaluate the frequency of AIPmut among young Brazilian patients with SPA. We performed an observational cohort study between 2013 and 2016 in a single referral center. AIPmut screening was carried out in 132 SPA patients with macroadenomas diagnosed up to 40 years or in adenomas of any size diagnosed until 18 years of age. Twelve tumor samples were also analyzed. Leukocyte DNA and tumor tissue DNA were sequenced for the entire AIP-coding region for evaluation of mutations. Eleven (8.3% of the 132 patients had AIPmut, comprising 9/74 (12% somatotropinomas, 1/38 (2.6% prolactinoma, 1/10 (10% corticotropinoma and no non-functioning adenomas. In pediatric patients (≤18 years, AIPmut frequency was 13.3% (2/15. Out of the 5 patients with gigantism, two had AIPmut, both truncating mutations. The Y268* mutation was described in Brazilian patients and the K273Rfs*30 mutation is a novel mutation in our patient. No somatic AIP mutations were found in the 12 tumor samples. A tumor sample from an acromegaly patient harboring the A299V AIPmut showed loss of heterozygosity. In conclusion, AIPmut frequency in SPA Brazilian patients is similar to other populations. Our study identified two mutations exclusively found in Brazilians and also shows, for the first time, loss of heterozygosity in tumor DNA from an acromegaly patient harboring the A299V AIPmut. Our findings corroborate previous observations that AIPmut screening should be performed in young patients with SPA.

  20. Evolution of Diffusion-Weighted Magnetic Resonance Imaging Signal Abnormality in Sporadic Creutzfeldt-Jakob Disease, With Histopathological Correlation.

    Science.gov (United States)

    Eisenmenger, Laura; Porter, Marie-Claire; Carswell, Christopher J; Thompson, Andrew; Mead, Simon; Rudge, Peter; Collinge, John; Brandner, Sebastian; Jäger, Hans R; Hyare, Harpreet

    2016-01-01

    Prion diseases represent the archetype of brain diseases caused by protein misfolding, with the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion-weighted imaging (DWI) has emerged as the most sensitive magnetic resonance imaging (MRI) sequence for the diagnosis of sCJD, but few studies have assessed the evolution of MRI signal as the disease progresses. To assess the natural history of the MRI signal abnormalities on DWI in sCJD to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation. Gray matter involvement on DWI was assessed among 37 patients with sCJD in 26 cortical and 5 subcortical subdivisions per hemisphere using a semiquantitative scoring system of 0 to 2 at baseline and follow-up. A total brain score was calculated as the summed scores in the individual regions. In 7 patients, serial mean diffusivity measurements were obtained. Age at baseline MRI, disease duration, atrophy, codon 129 methionine valine polymorphism, Medical Research Council Rating Scale score, and histopathological findings were documented. The study setting was the National Prion Clinic, London, England. All participants had a probable or definite diagnosis of sCJD and had at least 2 MRI studies performed during the course of their illness. The study dates were October 1, 2008 to April 1, 2012. The dates of our analysis were January 19 to April 20, 2012. Correlation of regional and total brain scores with disease duration. Among the 37 patients with sCJD in this study there was a significant increase in the number of regions demonstrating signal abnormality during the study period, with 59 of 62 regions showing increased signal intensity (SI) at follow-up, most substantially in the caudate and putamen (P disease duration (r = 0.47, P = .003 at baseline and r = 0.35, P = .03 at follow-up), and the left

  1. Patients with sporadic and familial amyotrophic lateral sclerosis found value in genetic testing.

    Science.gov (United States)

    Wagner, Karin N; Nagaraja, Haikady N; Allain, Dawn C; Quick, Adam; Kolb, Stephen J; Roggenbuck, Jennifer

    2017-12-20

    Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a genetic disease. There is no consensus, however, as to the role of genetic testing in the care of the ALS patient. We conducted a survey to study patient access, attitudes, and experience with ALS genetic testing among patients enrolled in a US ALS registry. Among 449 survey respondents, 156 (34.7%) were offered testing and 105 of 156 (67.3%) completed testing. The majority of respondents with familial ALS (fALS) (31/45, 68.9%) were offered testing, while a minority of respondents with sporadic ALS (sALS) (111/404, 27.5%) were offered testing (p = .00001). Comparison of mean test experience scores between groups revealed that respondents with fALS were no more likely to report a favorable experience with genetic testing than those with sALS (p = .51). Respondents who saw a genetic counselor did not have significantly different test experience scores, compared to those who did not (p = .14). In addition, no differences in test experience scores were observed between those who received positive or negative genetic test results (p = .98). These data indicate that patients with ALS found value in clinical genetic testing. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  2. Analysis of prion strains by PrPSc profiling in sporadic Creutzfeldt-Jakob disease.

    Directory of Open Access Journals (Sweden)

    Gaby Schoch

    2006-02-01

    Full Text Available BACKGROUND: Prion diseases are a group of invariably fatal neurodegenerative disorders affecting humans and a wide range of mammals. An essential part of the infectious agent, termed the prion, is composed of an abnormal isoform (PrPSc of a host-encoded normal cellular protein (PrPC. The conversion of PrPC to PrPSc is thought to play a crucial role in the development of prion diseases and leads to PrPSc deposition, mainly in the central nervous system. Sporadic Creutzfeldt-Jakob disease (sCJD, the most common form of human prion disease, presents with a marked clinical heterogeneity. This diversity is accompanied by a molecular signature which can be defined by histological, biochemical, and genetic means. The molecular classification of sCJD is an important tool to aid in the understanding of underlying disease mechanisms and the development of therapy protocols. Comparability of classifications is hampered by disparity of applied methods and inter-observer variability. METHODS AND FINDINGS: To overcome these difficulties, we developed a new quantification protocol for PrPSc by using internal standards on each Western blot, which allows for generation and direct comparison of individual PrPSc profiles. By studying PrPSc profiles and PrPSc type expression within nine defined central nervous system areas of 50 patients with sCJD, we were able to show distinct PrPSc distribution patterns in diverse subtypes of sCJD. Furthermore, we were able to demonstrate the co-existence of more than one PrPSc type in individuals with sCJD in about 20% of all patients and in more than 50% of patients heterozygous for a polymorphism on codon 129 of the gene encoding the prion protein (PRNP. CONCLUSION: PrPSc profiling represents a valuable tool for the molecular classification of human prion diseases and has important implications for their diagnosis by brain biopsy. Our results show that the co-existence of more than one PrPSc type might be influenced by genetic

  3. Analysis of prion strains by PrPSc profiling in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Schoch, Gaby; Seeger, Harald; Bogousslavsky, Julien; Tolnay, Markus; Janzer, Robert Charles; Aguzzi, Adriano; Glatzel, Markus

    2006-02-01

    Prion diseases are a group of invariably fatal neurodegenerative disorders affecting humans and a wide range of mammals. An essential part of the infectious agent, termed the prion, is composed of an abnormal isoform (PrPSc) of a host-encoded normal cellular protein (PrPC). The conversion of PrPC to PrPSc is thought to play a crucial role in the development of prion diseases and leads to PrPSc deposition, mainly in the central nervous system. Sporadic Creutzfeldt-Jakob disease (sCJD), the most common form of human prion disease, presents with a marked clinical heterogeneity. This diversity is accompanied by a molecular signature which can be defined by histological, biochemical, and genetic means. The molecular classification of sCJD is an important tool to aid in the understanding of underlying disease mechanisms and the development of therapy protocols. Comparability of classifications is hampered by disparity of applied methods and inter-observer variability. To overcome these difficulties, we developed a new quantification protocol for PrPSc by using internal standards on each Western blot, which allows for generation and direct comparison of individual PrPSc profiles. By studying PrPSc profiles and PrPSc type expression within nine defined central nervous system areas of 50 patients with sCJD, we were able to show distinct PrPSc distribution patterns in diverse subtypes of sCJD. Furthermore, we were able to demonstrate the co-existence of more than one PrPSc type in individuals with sCJD in about 20% of all patients and in more than 50% of patients heterozygous for a polymorphism on codon 129 of the gene encoding the prion protein (PRNP). PrPSc profiling represents a valuable tool for the molecular classification of human prion diseases and has important implications for their diagnosis by brain biopsy. Our results show that the co-existence of more than one PrPSc type might be influenced by genetic and brain region-specific determinants. These findings

  4. vCJD risk in the Republic of Ireland.

    LENUS (Irish Health Repository)

    Harney, Michael S

    2003-11-26

    BACKGROUND: The Republic of Ireland has the second highest incidence of BSE worldwide. Only a single case of vCJD has been identified to date. METHODS: We estimate the total future number of clinical cases of vCJD using an established mathematical model, and based on infectivity of bovine tissue calculated from UK data and on the relative exposure to BSE contaminated meat. RESULTS: We estimate 1 future clinical case (95% CI 0-15) of vCJD in the Republic of Ireland. Irish exposure is from BSE infected indigenous beef products and from imported UK beef products. Additionally, 2.5% of the Irish population was exposed to UK beef through residing in the UK during the \\'at-risk\\' period. The relative proportion of risk attributable to each of these three exposures individually is 2:2:1 respectively. CONCLUSIONS: The low numbers of future vCJD cases estimated in this study is reassuring for the Irish population and for other countries with a similar level of BSE exposure.

  5. LGI1 antibody encephalopathy overlapping with sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Kim, Boaz; Yoo, Patrick; Sutherland, Tom; Boyd, Alison; Stehmann, Christiane; McLean, Catriona

    2016-01-01

    Objective: To report a rare case of leucine-rich, glioma inactivated 1 (LGI1) antibody–mediated autoimmune encephalopathy clinically overlapping with pathologically confirmed sporadic Creutzfeldt-Jakob disease (CJD). Methods: The patient was investigated with repeated brain MRI, EEG, CSF examination, whole-body fluorodeoxy-glucose positron emission tomography, genetic analysis of the prion protein gene (PRNP), and extensive serologic screening for paraneoplastic and autoimmune encephalopathy markers. Written informed consent was obtained from the patient's next of kin for access to clinical files for research purposes and for publication. Results: The patient was a 77-year-old man who presented with faciobrachial dystonic seizures (FBDS) secondary to LGI1 antibody–mediated autoimmune encephalopathy, with suggestive MRI findings and a complete response to treatment with combinatorial immunosuppression. Stereotactic biopsy of a nonenhancing T1 hyperintense basal ganglia lesion during the initial FBDS phase, albeit following immunosuppression, did not disclose evidence of lymphocytic inflammation. Following full remission of the FBDS, the patient manifested a rapidly progressive dementia associated with gross motor decline confirmed to be CJD at autopsy (molecular subtype VV3), with no evidence of a pathogenic PRNP mutation. Conclusions: Our patient highlights that these rare diseases are not invariably mutually exclusive and underscores the benefits of comprehensive neuropathologic examination of the brain to achieve an accurate diagnosis, especially in complex cases when the clinical trajectory dramatically deviates and a concomitant disease may need to be conscientiously considered to best explain the new clinical course. PMID:27354985

  6. Epidemiological trends and clinicopathological features of cutaneous melanoma in sporadic and xeroderma pigmentosum Tunisian patients.

    Science.gov (United States)

    Naouali, Chokri; Jones, Meriem; Nabouli, Imen; Jerbi, Manel; Tounsi, Haifa; Ben Rekaya, Mariem; Ben Ahmed, Melika; Bouhaouala, Balkiss; Messaoud, Olfa; Khaled, Aida; Zghal, Mohamed; Abdelhak, Sonia; Boubaker, Samir; Yacoub-Youssef, Houda

    2017-01-01

    Epidemiological features and trends of cutaneous melanoma (CM) in North-African populations remain unclear. Those populations are of particular interest as they belong to a mosaic of various other origins (sub-Saharan, European Ancestry, and North-African Berbers). The aim of this study is to draw epidemiological profile and clinicopathological features of CM in the Tunisian population. Incidence analyses were based on data from regional cancer registries. Clinical data were collected from dermatological departments and xeroderma pigmentosum (XP) referral centers and provided CM clinicopathological characteristics and progression. Statistical analyses were achieved using R packages and SPSS 20.0. The incidence of CM in Tunisia is relatively low (0.5-0.7 per 100,000 inhabitants per year). Gender differences were observed regarding anatomical distribution (P = 0.004). Acral lentiginous melanoma (ALM) was the most frequent histological subtype (32.3%); however, nodular melanoma (NM) was the most aggressive and responsible for 54.8% of deaths. CM in XP patients develops at a median age that is 42 years earlier than sporadic cases, with preferential localization on the head and neck (P melanoma features in Tunisia are closer to those of non-Caucasians, even though gender differences that are similar to those observed in Caucasians were uncovered. This study also emphasizes the aggressiveness of NM and its effect on melanoma patient deaths. Xeroderma pigmentosum stands as the major predisposing host factor. © 2016 The International Society of Dermatology.

  7. CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result.

    Science.gov (United States)

    Leitão, M J; Baldeiras, I; Almeida, M R; Ribeiro, M H; Santos, A C; Ribeiro, M; Tomás, J; Rocha, S; Santana, I; Oliveira, C R

    2016-09-01

    Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases.

  8. Multiple primary cutaneous melanomas in patients with FAMMM syndrome and sporadic atypical mole syndrome (AMS): what's worse?

    Science.gov (United States)

    Tchernev, Georgi; Ananiev, Julian; Cardoso, José-Carlos; Chokoeva, Anastasiya Atanasova; Philipov, Stanislav; Penev, Plamen Kolev; Lotti, Torello; Wollina, Uwe

    2014-08-01

    Atypical Mole Syndrome is the most important phenotypic risk factor for cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Since early diagnosis of melanoma is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers (sporadic and familial) is essential, as well as the recommendation of preventative measures that must be undertaken by these patients.We report two rare cases concerning patients with multiple primary skin melanomas in the setting of a familial and a sporadic syndrome of dysplastic nevi: the first patient is a 67-year-old patient with a history of multiple superficial spreading melanomas localized on his back. The second patient presented with multiple primary melanomas in advanced stage in the context of the so-called sporadic form of the syndrome of dysplastic nevi-AMS (atypical mole syndrome). In the first case, excision of the melanomas was carried out with an uneventful post-operative period. In the second case, disseminated metastases were detected, involving the right fibula, the abdominal cavity as well as multiple lesions in the brain. The patient declined BRAF mutation tests as well as chemotherapy or targeted therapies, and suffered a rapid deterioration in his general condition leading to death. We classified the second case as a sporadic form of the atypical mole syndrome, associated with one nodular and two superficial spreading melanomas.There are no data in the literature to allow us to understand if, in patients with multiple primary melanomas, there is any difference in terms of prognosis between those with and without a family history of a similar phenotype. To answer this and other questions related to these rare cases, further studies with a significant number of patients should be carried out.

  9. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

    Science.gov (United States)

    Bishop, Matthew T.; Will, Robert G.; Manson, Jean C.

    2010-01-01

    The biological determinants of the phenotypic variation in sporadic Creutzfeldt-Jakob disease (sCJD) are unknown. To categorize sCJD cases, the prion protein (PrP) codon 129 genotype and the biochemical characteristics of the disease-associated form of PrP (PrPSc) can be combined to form six subgroups (MM1, MM2, MV1, MV2, VV1, and VV2). This classification largely correlates with the known variation in the clinical and pathological features of sCJD, with the MM1 and MV1 cases representing the “classic” phenotype of sCJD. To address how this classification relates to different strains of sCJD we have inoculated each subgroup of sCJD to a panel of mice expressing different forms of the human PRNP gene (129MM, 129VV, and 129MV). We have established that all subtypes are transmissible to at least one genotype of mouse, and both agent and host factors determine transmission efficiency and the form of PrPSc deposited in the brain. Moreover, we have identified four distinct strains of sCJD using our in vivo strain typing panel. PMID:20547859

  10. Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients.

    Science.gov (United States)

    Vymetalkova, Veronika Polakova; Slyskova, Jana; Korenkova, Vlasta; Bielik, Ludovit; Langerova, Lucie; Prochazka, Pavel; Rejhova, Alexandra; Schwarzova, Lucie; Pardini, Barbara; Naccarati, Alessio; Vodicka, Pavel

    2014-01-31

    Mismatch repair (MMR) genes are known to be frequently altered in colorectal cancer (CRC). Both genetics and epigenetics modifications seems to be relevant in this phenomenon, however it is still not clear how these two aspects are interconnected. The present study aimed at characterizing of epigenetic and gene expression profiles of MMR genes in sporadic CRC patients from the Czech Republic, a country with one of the highest incidences of this cancer all over Europe. Expression levels and CpG promoter methylation status of all MMR genes were evaluated in DNA from tumor and adjacent mucosal samples of 53 incident CRC patients. We have found significantly increased transcription levels in EXO1 gene in tumor tissues (P = 0.05) and significant over-expression of MSH3 gene in colon tumors when compared to adjacent mucosal tissues (P = 0.02). Interestingly, almost all MMR genes were differently expressed when localization of tumors was compared. In particular, colon tumors showed an up-regulation of EXO1, MSH2, MSH3, MSH6, and PMS2 genes in comparison to rectal tumors (P = 0.02). Expression levels of all MMR genes positively correlated between each other. The promoter methylation of MLH1 gene was observed in 9% of CRC tissues only. In our study, we have observed different pattern of MMR genes expression according to tumor localization. However, a lack of association between methylation in MMR genes and their corresponding expressions was noticed in this study, the relationship between these two aspects is worthy to be analyzed in larger population studies and in pre-malignant stages.

  11. Risk of transmission of sporadic Creutzfeldt-Jakob disease by surgical procedures: systematic reviews and quality of evidence.

    Science.gov (United States)

    López, Fernando J García; Ruiz-Tovar, María; Almazán-Isla, Javier; Alcalde-Cabero, Enrique; Calero, Miguel; de Pedro-Cuesta, Jesús

    2017-10-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is potentially transmissible to humans. This study aimed to summarise and rate the quality of the evidence of the association between surgery and sCJD. Firstly, we conducted systematic reviews and meta-analyses of case-control studies with major surgical procedures as exposures under study. To assess quality of evidence, we used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Secondly, we conducted a systematic review of sCJD case reports after sharing neurosurgical instruments. Thirteen case-control studies met the inclusion criteria for the systematic review of case-control studies. sCJD was positively associated with heart surgery, heart and vascular surgery and eye surgery, negatively associated with tonsillectomy and appendectomy, and not associated with neurosurgery or unspecified major surgery. The overall quality of evidence was rated as very low. A single case-control study with a low risk of bias found a strong association between surgery conducted more than 20 years before disease onset and sCJD. Seven cases were described as potentially transmitted by reused neurosurgical instruments. The association between surgery and sCJD remains uncertain. Measures currently recommended for preventing sCJD transmission should be strongly maintained. Future studies should focus on the potential association between sCJD and surgery undergone a long time previously.

  12. The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

    DEFF Research Database (Denmark)

    Bahl, J.M.; Heegaard, N.H.; Falkenhorst, G.

    2009-01-01

    ) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE...

  13. Data on inflammasome gene polymorphisms of patients with sporadic malignant melanoma in a Brazilian cohort

    Directory of Open Access Journals (Sweden)

    Wanessa Cardoso da Silva

    2017-02-01

    Full Text Available This article presents data related to our another article entitled, Genotyping and differential expression analysis of inflammasome genes in sporadic malignant melanoma reveal novel contribution of CARD8, IL1B and IL18 in melanoma susceptibility and progression (W.C. Silva, T.M. Oshiro, D.C. Sá, D.D.G.S. Franco, C. Festa Neto, A. Pontillo, 2016 [2]. Data presented here refers to the distribution of selected inflammasome SNPs in a Brazilian case/control cohort. We have identified 4 inflammasome related Single Nucleotide Polymorphisms (SNPs for CARD8 (rs6509365; IL1B (rs1143643 and IL18 (rs5744256 and rs1834481 related to melanoma susceptibility/protection. This data can serve as a potential prognostic marker in sporadic malignant melanoma.

  14. Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study.

    Science.gov (United States)

    Wadsworth, Jonathan D F; Dalmau-Mena, Inmaculada; Joiner, Susan; Linehan, Jacqueline M; O'Malley, Catherine; Powell, Caroline; Brandner, Sebastian; Asante, Emmanuel A; Ironside, James W; Hilton, David A; Collinge, John

    2011-03-01

    Anonymous screening of lymphoreticular tissues removed during routine surgery has been applied to estimate the UK population prevalence of asymptomatic vCJD prion infection. The retrospective study of Hilton et al (J Pathol 2004; 203: 733-739) found accumulation of abnormal prion protein in three formalin-fixed appendix specimens. This led to an estimated UK prevalence of vCJD infection of ∼1 in 4000, which remains the key evidence supporting current risk reduction measures to reduce iatrogenic transmission of vCJD prions in the UK. Confirmatory testing of these positives has been hampered by the inability to perform immunoblotting of formalin-fixed tissue. Animal transmission studies offer the potential for 'gold standard' confirmatory testing but are limited by both transmission barrier effects and known effects of fixation on scrapie prion titre in experimental models. Here we report the effects of fixation on brain and lymphoreticular human vCJD prions and comparative bioassay of two of the three prevalence study formalin-fixed, paraffin-embedded (FFPE) appendix specimens using transgenic mice expressing human prion protein (PrP). While transgenic mice expressing human PrP 129M readily reported vCJD prion infection after inoculation with frozen vCJD brain or appendix, and also FFPE vCJD brain, no infectivity was detected in FFPE vCJD spleen. No prion transmission was observed from either of the FFPE appendix specimens. The absence of detectable infectivity in fixed, known positive vCJD lymphoreticular tissue precludes interpreting negative transmissions from vCJD prevalence study appendix specimens. In this context, the Hilton et al study should continue to inform risk assessment pending the outcome of larger-scale studies on discarded surgical tissues and autopsy samples.

  15. Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study

    Directory of Open Access Journals (Sweden)

    Magaly M. Sales

    1999-03-01

    Full Text Available Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP vs. 10 normal individuals (P = 0.67. Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.Inúmeros estudos têm mostrado que fibroblastos de pacientes com adenomatose hereditária de cólon e reto, que inclui polipose adenomatosa familial (FAP e a síndrome de Gardner, apresentam uma freqüência aumentada de aberrações cromossômicas após exposição a agentes físicos ou químicos, quando comparados aos controles normais. Para determinar a sensibilidade de linfócitos de pacientes com FAP e também com pólipos adenomatosos esporádicos (AP usou-se o radiomimético bleomicina (BLM. Foram estudados citogeneticamente 10 indivíduos com AP, 10 com FAP e 20 controles normais, pareados por sexo e idade. Indivíduos que apresentaram valores médios de quebras cromatídicas por célula superiores a 0,80 foram considerados sensíveis à droga. Observou-se uma diferença significativa entre pacientes com FAP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados na fase G2. Entretanto, nenhuma diferença significativa foi observada entre pacientes com AP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados. Nenhum indivíduo do grupo controle foi sensível à BLM e, entre os 20 pacientes, três mostraram suscetibilidade à droga. Não foi encontrada diferença significativa quanto a resposta à bleomicina entre indivíduos do sexo masculino e

  16. Generation of an integration-free induced pluripotent stem cell line (CSC-43 from a patient with sporadic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ana Marote

    2018-03-01

    Full Text Available An induced pluripotent stem cell (iPSC line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD. Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43 exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.

  17. Generation of a human induced pluripotent stem cell line (CSC-42 from a patient with sporadic form of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ekaterina Savchenko

    2018-03-01

    Full Text Available Skin fibroblasts were collected from a 44-year-old patient with sporadic case of Parkinson's disease (PD. The non-integrating Sendai virus vector encoding OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced pluripotent stem cells (iPSCs. Generated iPSCs had normal karyotypes, expressed common stem cell markers, and were capable of differentiating into all three germ layers. Generated line could be used for PD modeling to understand the mechanisms that influence the disorder.

  18. Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study

    Science.gov (United States)

    2011-01-01

    Background To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD. Methods The study included 127 patients with autopsy-confirmed sCJD (prevalence = 12.7%) and 873 with probable non-CJD diagnoses. Standard statistical measures of diagnostic accuracy were employed, including sensitivity (Se), specificity (Sp), predictive values (PVs), likelihood ratios (LRs), and Receiver Operating Characteristic (ROC) analysis. Results At optimal cutoff thresholds (empirically selected for 14-3-3, assayed by immunoblot; 976 pg/mL for tau and 2.5 ng/mL for S100B, both assayed by ELISA), Se and Sp respectively were 0.88 (95% CI, 0.81-0.93) and 0.72 (0.69-0.75) for 14-3-3; 0.91 (0.84-0.95) and 0.88 (0.85-0.90) for tau; and 0.87 (0.80-0.92) and 0.87 (0.84-0.89) for S100B. The observed differences in Sp between 14-3-3 and either of the other 2 markers were statistically significant. Positive LRs were 3.1 (2.8-3.6) for 14-3-3; 7.4 (6.9-7.8) for tau; and 6.6 (6.1-7.1) for S100B. Negative LRs were 0.16 (0.10-0.26) for 14-3-3; 0.10 (0.06-0.20) for tau; and 0.15 (0.09-0.20) for S100B. Estimates of areas under ROC curves were 0.947 (0.931-0.961) for tau and 0.908 (0.888-0.926) for S100B. Use of interval LRs (iLRs) significantly enhanced accuracy for patient subsets [e.g., 41/120 (34.2%) of tested sCJD patients displayed tau levels > 10,000 pg/mL, with an iLR of 56.4 (22.8-140.0)], as did combining tau and S100B [e.g., for tau > 976 pg/mL and S100B > 2.5 ng/mL, positive LR = 18.0 (12.9-25.0) and negative LR = 0.02 (0.01-0.09)]. Conclusions CSF 14-3-3, tau and S100B proteins are useful diagnostic markers of sCJD even in a low

  19. Variants of PLCXD3 are not associated with variant or sporadic Creutzfeldt-Jakob disease in a large international study.

    Science.gov (United States)

    Balendra, Rubika; Uphill, James; Collinson, Claire; Druyeh, Ronald; Adamson, Gary; Hummerich, Holger; Zerr, Inga; Gambetti, Pierluigi; Collinge, John; Mead, Simon

    2016-04-07

    Human prion diseases are relentlessly progressive neurodegenerative disorders which include sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). Aside from variants of the prion protein gene (PRNP) replicated association at genome-wide levels of significance has proven elusive. A recent association study identified variants in or near to the PLCXD3 gene locus as strong disease risk factors in multiple human prion diseases. This study claimed the first non-PRNP locus to be highly significantly associated with prion disease in genomic studies. A sub-study of a genome-wide association study with imputation aiming to replicate the finding at PLCXD3 including 129 vCJD and 2500 sCJD samples. Whole exome sequencing to identify rare coding variants of PLCXD3. Imputation of relevant polymorphisms was accurate based on wet genotyping of a sample. We found no supportive evidence that PLCXD3 variants are associated with disease. The marked discordance in vCJD genotype frequencies between studies, despite extensive overlap in vCJD cases, and the finding of Hardy-Weinberg disequilibrium in the original study, suggests possible reasons for the discrepancies between studies.

  20. Validation of 14-3-3 Protein as a Marker in Sporadic Creutzfeldt-Jakob Disease Diagnostic.

    Science.gov (United States)

    Schmitz, Matthias; Ebert, Elisabeth; Stoeck, Katharina; Karch, André; Collins, Steven; Calero, Miguel; Sklaviadis, Theodor; Laplanche, Jean-Louis; Golanska, Ewa; Baldeiras, Ines; Satoh, Katsuya; Sanchez-Valle, Raquel; Ladogana, Anna; Skinningsrud, Anders; Hammarin, Anna-Lena; Mitrova, Eva; Llorens, Franc; Kim, Yong Sun; Green, Alison; Zerr, Inga

    2016-05-01

    At present, the testing of 14-3-3 protein in cerebrospinal fluid (CSF) is a standard biomarker test in suspected sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis. Increasing 14-3-3 test referrals in CJD reference laboratories in the last years have led to an urgent need to improve established 14-3-3 test methods. The main result of our study was the validation of a commercially available 14-3-3 ELISA next to the commonly used Western blot method as a high-throughput screening test. Hereby, 14-3-3 protein expression was quantitatively analyzed in CSF of 231 sCJD and 2035 control patients. We obtained excellent sensitivity/specificity values of 88 and 96% that are comparable to the established Western blot method. Since standard protocols and preanalytical sample handling have become more important in routine diagnostic, we investigated in a further step the reproducibility and stability of 14-3-3 as a biomarker for human prion diseases. Ring trial data from 2009 to 2013 revealed an increase of Fleiss' kappa from 0.51 to 0.68 indicating an improving reliability of 14-3-3 protein detection. The stability of 14-3-3 protein under short-term and long-term storage conditions at various temperatures and after repeated freezing/thawing cycles was confirmed. Contamination of CSF samples with blood appears likely to be an important factor at a concentration of more than 2500 erythrocytes/μL. Hemolysis of erythrocytes with significant release of 14-3-3 protein started after 2 days at room temperature. We first define clear standards for the sample handling, short- and long-term storage of CSF samples as well as the handling of blood- contaminated samples which may result in artificially elevated CSF levels of 14-3-3.

  1. Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients.

    Science.gov (United States)

    Türk, Matthias; Schröder, Rolf; Khuller, Katharina; Hofmann, Andreas; Berwanger, Carolin; Ludolph, Albert C; Dekomien, Gabriele; Müller, Kathrin; Weishaupt, Jochen H; Thiel, Christian T; Clemen, Christoph S

    2017-08-01

    Mutations of the human valosin-containing protein, p97 (VCP) and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex genes cause motor neuron and cognitive impairment disorders. Here, we analyzed a cohort of German patients with sporadic amyotrophic lateral sclerosis and frontotemporal lobar degeneration comorbidity (ALS/FTD) for VCP and WASH complex gene mutations. Next-generation panel sequencing of VCP, WASH1, FAM21C, CCDC53, SWIP, strumpellin, F-actin capping protein of muscle Z-line alfa 1 (CAPZA1), and CAPZB genes was performed in 43 sporadic ALS/FTD patients. Subsequent analyses included Sanger sequencing, in silico analyses, real-time PCR, and CCDC53 immunoblotting. We identified 1 patient with the heterozygous variant c.26C>T in CAPZA1, predicted to result in p.Ser9Leu, and a second with the heterozygous start codon variant c.2T>C in CCDC53. In silico analysis predicted structural changes in the N-terminus of CAPZα1, which may interfere with CAPZα:CAPZβ dimerization. Though the translation initiation codon of CCDC53 is mutated, real-time PCR and immunoblotting did neither reveal any evidence for a CCDC53 haploinsufficiency nor for aberrant CCDC53 protein species. Moreover, a disease-causing C9orf72 repeat expansion mutation was later on identified in this patient. Thus, with the exception of a putatively pathogenic heterozygous c.26C>T CAPZA1 variant, our genetic analysis did not reveal mutations in VCP and the remaining WASH complex subunits. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

    Science.gov (United States)

    Alves, Chrystian J.; Dariolli, Rafael; Jorge, Frederico M.; Monteiro, Matheus R.; Maximino, Jessica R.; Martins, Roberto S.; Strauss, Bryan E.; Krieger, José E.; Callegaro, Dagoberto; Chadi, Gerson

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form is not genetically inherited. Attempts to translate therapeutic strategies have failed because the described mechanisms of disease are based on animal models carrying specific gene mutations and thus do not address sporadic ALS. In order to achieve a better approach to study the human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus system and submitted to microarray analyses using a whole human genome platform. DAVID analyses of differentially expressed genes identified molecular function and biological process-related genes through Gene Ontology. REVIGO highlighted the related functions mRNA and DNA binding, GTP binding, transcription (co)-repressor activity, lipoprotein receptor binding, synapse organization, intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways associated with Parkinson's disease and oxidative phosphorylation, highlighting iron homeostasis, neurotrophic functions, endosomal trafficking and ERK signaling. The analysis of most dysregulated genes and those representative of the majority of categorized genes indicates a strong association between mitochondrial function and cellular processes possibly related to motor neuron degeneration. In conclusion, iPSC-derived motor neurons from motor nerve fibroblasts of sporadic ALS patients may recapitulate key mechanisms of neurodegeneration and may offer an opportunity for translational investigation of sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic ALS patients highlights mitochondrial participation in the establishment of autonomous mechanisms associated with sporadic ALS

  3. Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions

    DEFF Research Database (Denmark)

    de Pedro-Cuesta, Jesús; Mahillo-Fernández, Ignacio; Rábano, Alberto

    2011-01-01

    Evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case-control study, the authors applied a risk-based classification of surgical interventions to determine the association...

  4. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Silvia Vanni

    2018-01-01

    Full Text Available Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively and in different genetic forms of prion diseases (gPrD in comparison to Alzheimer's disease (AD subjects and age-matched controls.Methods: Total RNA was obtained from the frontal cortex of vCJD (n = 20, iCJD (n = 11, sCJD (n = 23, gPrD (n = 30, and AD (n = 14 patients and age-matched controls (n = 30. RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis.Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level.Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue—together with specific molecular and conformational features of the pathological agent of the disease—seem to dictate the peculiar

  5. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases.

    Science.gov (United States)

    Vanni, Silvia; Zattoni, Marco; Moda, Fabio; Giaccone, Giorgio; Tagliavini, Fabrizio; Haïk, Stéphane; Deslys, Jean-Philippe; Zanusso, Gianluigi; Ironside, James W; Carmona, Margarita; Ferrer, Isidre; Kovacs, Gabor G; Legname, Giuseppe

    2018-01-01

    Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD ( n = 20), iCJD ( n = 11), sCJD ( n = 23), gPrD ( n = 30), and AD ( n = 14) patients and age-matched controls ( n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin

  6. Long-term outcome of patients with elevated parathyroid hormone levels after successful parathyroidectomy for sporadic primary hyperparathyroidism.

    Science.gov (United States)

    Solorzano, Carmen C; Mendez, William; Lew, John I; Rodgers, Steven E; Montano, Raquel; Carneiro-Pla, Denise M; Irvin, George L

    2008-07-01

    Untreated long-term elevated parathyroid hormone (PTH) levels after successful parathyroidectomy may predict recurrent hyperparathyroidism (HPT). Although elevated PTH levels have been reported in eucalcemic patients after parathyroidectomy for sporadic primary HPT, the long-term clinical significance of this finding remains unclear. Retrospective case series. Tertiary referral center. Five hundred seventy-six consecutive patients with HPT. Parathyroidectomy guided by intraoperative monitoring of PTH levels. Overall incidence of elevated PTH levels (measurements of >or= 70 pg/mL at any time during follow-up) and recurrent HPT (hypercalcemia and elevated PTH levels more than 6 months after parathyroidectomy). Of the 505 patients who underwent successful parathyroidectomy in this series and were followed up for more than 6 months, 337 (66.7%) consistently had PTH levels within the reference range, and 168 (33.3%) had elevated PTH levels. Of the 168 patients with elevated PTH levels, only 8 (4.8%) developed recurrent disease. The earliest recurrence occurred 2 years postoperatively. Factors associated with elevated PTH levels included advanced age, higher preoperative PTH levels, and mild postoperative renal insufficiency. Although one-third of the patients had elevated PTH levels after successful parathyroidectomy, most of these patients with elevated PTH levels (95%) will achieve long-term eucalcemia.

  7. MRI of sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Kong, A.; Vliet, A. Van der.

    2008-01-01

    Full text: The key MRI findings in five cases of sporadic Creutzfeldt-Jakob disease (CJD) are illustrated with four 'definite' and one 'probable' according to World Health Organization criteria. Close attention to fluid-attenuation inversion recovery and diffusion-weighted imaging sequences are important for diagnosis, noting especially restricted diffusion in cortical and deep grey matter. Our study and those of others show predominant cortical, caudate and thalamic involvement. This pattern is highly sensitive and specific for the diagnosis. Fluid-attenuation inversion recovery and diffusion-weighted imaging signal abnormality becomes progressively more extensive and bilateral as disease progresses, but may become less pronounced in end-stage disease because of atrophy.

  8. Absence of activating mutations in ras and gsp oncogenes in a cohort of nine patients with sporadic pediatric thyroid tumors.

    Science.gov (United States)

    Pauws, E; Tummers, R F; Ris-Stalpers, C; de Vijlder, J J; Voûte, T

    2001-06-01

    Characterization of the genetic background of pediatric thyroid carcinomas could aid in distinguishing between differently staged tumors with respect to treatment and prognosis. Two known genetic factors associated with thyroid carcinoma, the proto-oncogenes gsp and ras were investigated. DNA was extracted from paraffin sections from both tumor and normal thyroid tissue of nine patients (ages 9-16 years). Of these patients, eight were diagnosed with papillary carcinoma and one with follicular adenoma. The coding exons of gsp and the three known ras genes (H, K, and N-ras) were screened for mutations using SSCP-analysis. There were no mutations present in the ras and gsp proto-oncogenes hot spots, however, LOH of H-ras (chromosome location 11p15.5) was found in tumor tissue from one patient and a homozygous mutation in exon 12 of gsp causing a Pro-->Ser conversion was present in the thyroid tumor tissue from another patient. Two silent polymorphisms were detected, H-ras exon1, 86T-->C and gsp exon 5, 81T-->C. Our results indicate that the ras/gsp mutations found are probably late events in the tumorigenesis representing general oncogenic stress. In conclusion, it seems that ras/gsp activation is not a factor in the mechanism causing sporadic thyroid carcinoma in children. Copyright 2001 Wiley-Liss, Inc.

  9. A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease.

    Directory of Open Access Journals (Sweden)

    Olga Calero

    Full Text Available The β site APP cleaving enzyme 1 (BACE1 is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer's disease (AD pathology. Recent evidence suggests that the prion protein (PrP interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer's and Creutzfeldt-Jakob (CJD diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405 with sporadic CJD (sCJD. Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players.

  10. Diagnostic profiles of patients with late-onset Creutzfeldt-Jakob disease differ from those of younger Creutzfeldt-Jakob patients: a historical cohort study using data from the German National Reference Center.

    Science.gov (United States)

    Karch, André; Raddatz, Lena Maria; Ponto, Claudia; Hermann, Peter; Summers, David; Zerr, Inga

    2014-05-01

    In contrast to other neurodegenerative diseases, sporadic Creutzfeldt-Jakob disease (sCJD) is rarely diagnosed in patients older than 75 years. Data describing the characteristics of sCJD in the very old are rare and inconclusive. Therefore, a historical cohort study was designed to evaluate clinical, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) features of this group. Patients older than 75 years identified via the German surveillance program from 2001 to 2012 (n = 73) were compared to a random subsample of sCJD patients younger than 75 (n = 73) from the same time period using an historical cohort design. Older patients showed a faster disease progression represented by an earlier point of diagnosis and a shorter survival time (p disease, older patients presented slightly more often with dementia (p = 0.127) or dysarthria (p = 0.238), whereas disorders of the extrapyramidal (p = 0.056) and visual system (p = 0.015) were more common in the younger group. Atypical MRI profiles such as MRI lesions restricted to one hemisphere (p Creutzfeldt-Jakob disease cases in patients older than 75 years seems likely due to atypical clinical and radiological presentation. This might contribute to lower sCJD incidence rates in this age group.

  11. Clinical Characteristics of Patients with Sporadic Colorectal Cancer and Primary Cancers of Other Organs

    Directory of Open Access Journals (Sweden)

    Jung-Yu Kan

    2006-11-01

    Full Text Available Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December 2004. Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%, either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years. The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2% and six breast cancers (35.2% were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer

  12. Agraphia of Kanji (Chinese characters): an early symptom of sporadic Creutzfeldt-Jakob disease in a Japanese patient: a case report.

    Science.gov (United States)

    Nakamura, Keiko; Sakai, Kenji; Samuraki, Miharu; Nozaki, Ichiro; Notoya, Masako; Yamada, Masahito

    2014-08-06

    Slowly progressive cognitive decline is the most frequent initial manifestation in MM2-cortical-type sporadic Creutzfeldt-Jakob disease. Agraphia has never been noted in patients with this type of sporadic Creutzfeldt-Jakob disease, however, we report the case of a Japanese patient with sporadic Creutzfeldt-Jakob disease in whom agraphia of Kanji was an initial cardinal symptom. A 59-year-old right-handed Japanese woman complained of agraphia of Kanji (Chinese characters) as an initial symptom. A neurological examination revealed mild word-finding difficulty, constructive disturbance, hyperreflexia in her jaw and lower limbs, and bilateral extensor plantar reflexes. An examination of her cerebrospinal fluid revealed increased levels of 14-3-3 and total tau proteins, and abnormal conformation of the proteinase K-resistant prion protein. Diffusion-weighted magnetic resonance imaging showed diffuse hyperintensity in bilateral cerebral cortices. Single-photon emission computed tomography scans revealed hypoperfusion in the left temporal lobe, bilateral parietal and occipital lobes. An analysis of the prion protein gene demonstrated no mutation with homozygous for methionine at the codon 129. We diagnosed our patient with sporadic Creutzfeldt-Jakob disease. Although a histological examination was not performed, it was assumed that our patient could be the MM2-cortical type according to the clinical findings and the elevated levels of 14-3-3 protein in her cerebrospinal fluid. The left posterior inferior temporal area, which was affected in our patient as a hypoperfusion area, is associated with selecting and recalling Kanji characters. Focal signs as an early symptom and hypoperfusion areas in sporadic Creutzfeldt-Jakob disease are critical to recognize initial brain lesions damaged by the proteinase K-resistant prion protein accumulation.

  13. Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis.

    LENUS (Irish Health Repository)

    Gbadegesin, Rasheed A

    2012-01-01

    Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage kidney disease. Recent advances in molecular genetics show that defects in the podocyte play a major role in its pathogenesis and mutations in inverted formin 2 (INF2) cause autosomal dominant FSGS. In order to delineate the role of INF2 mutations in familial and sporadic FSGS, we sought to identify variants in a large cohort of patients with FSGS. A secondary objective was to define an approach for genetic screening in families with autosomal dominant disease. A total of 248 individuals were identified with FSGS, of whom 31 had idiopathic disease. The remaining patients clustered into 64 families encompassing 15 from autosomal recessive and 49 from autosomal dominant kindreds. There were missense mutations in 8 of the 49 families with autosomal dominant disease. Three of the detected variants were novel and all mutations were confined to exon 4 of INF2, a regulatory region responsible for 90% of all changes reported in FSGS due to INF2 mutations. Thus, in our series, INF2 mutations were responsible for 16% of all cases of autosomal dominant FSGS, with these mutations clustered in exon 4. Hence, screening for these mutations may represent a rapid, non-invasive and cost-effective method for the diagnosis of autosomal dominant FSGS.

  14. Does Contrast-Enhanced Cervical Ultrasonography Improve Preoperative Localization Results in Patients With Sporadic Primary Hyperparathyroidism?

    Directory of Open Access Journals (Sweden)

    Elias Karakas

    2012-01-01

    Full Text Available Objective: Pre-operative localization studies are inevitable in patients with primary hyperparathyroidism (pHPT, who are eligible for focused or minimally invasive parathyroidectomy (MIP. High-resolution ultrasonography (US in combination with planar 99m Tc-Sestamibi-scintigraphy (MIBI and additional single-photon emission computed tomography (SPECT are the standard procedures to localize enlarged parathyroid glands. Our aim was to evaluate the practicability and significance of contrast-enhanced ultrasonography (CEUS in patients with pHPT. Materials and Methods: All investigations were performed at the University Hospital Marburg. Totally, 25 patients with biochemical proven pHPT underwent preoperative US, MIBI/SPECT, and CEUS. For CEUS, a suspension of phospholipid-stabilized sulfur-hexafluoride (SF6 microbubbles in combination with a special 12 MHz linear US probe was used. All patients were investigated by two sonographers, who did not get to view the findings noted by the other. Finally, surgery was performed and histopathological results were obtained from 24 patients. Results: In 17 (68% patients, US and MIBI/SPECT already raised suspicion of parathyroid lesions and all suspected lesions were reassessed by CEUS. However, no additional information was obtained using CEUS. Especially in eight patients with negative or inconsistent US and MIBI/SPECT results, CEUS did not provide additional information regarding the site of the suspected parathyroid adenoma. Overall, no side effects were observed using CEUS. Surgical cure was achieved in all patients. Conclusion: In this limited cohort of patients, no additional information could be obtained using the costly CEUS compared to results of US and MIBI/SPECT.

  15. Sporadic occurrence of cryptococcal meningitis in HIV-seronegative patients: Uncommon etiology?

    Science.gov (United States)

    Das, Shukla; Datt, Shyama; Roy, Priyamvada; Saha, Rumpa; Xess, Immaculata

    2017-01-01

    Cryptococcosis in HIV-seronegative patients is rarely reported from India. This prospective study was conducted to look for cryptococcal meningitis in HIV-seronegative individuals and compare their laboratory features to cryptococcal meningitis in HIV-seropositive patients. Cerebrospinal fluid was collected from 153 suspected cases of meningitis and subjected to India ink preparation, antigen detection, and culture. Nineteen samples tested positive for Cryptococcus neoformans infection. Seventeen and two patients were HIV reactive and nonreactive, respectively. In vitro susceptibility of C. neoformans isolates to fluconazole and amphotericin B was performed using standard broth microdilution method and E-test. Eighteen strains were susceptible to amphotericin B, while fluconazole was reported susceptible in 15 strains. Hence, index of suspicion of C. neoformans infection as possible cause of meningitis must be maintained even in HIV-negative patients. Use of amphotericin B for treating C. neoformans meningitis should be restricted to prevent any increase in resistance.

  16. Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease

    Science.gov (United States)

    Pérez, María J.; Ponce, Daniela P.; Osorio-Fuentealba, Cesar; Behrens, Maria I.; Quintanilla, Rodrigo A.

    2017-01-01

    The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients. PMID:29056898

  17. Epidemiological evidence of higher susceptibility to vCJD in the young

    Directory of Open Access Journals (Sweden)

    Valleron Alain-Jacques

    2004-08-01

    Full Text Available Abstract Background The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE epidemic may provide a simpler explanation. Methods Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD, we examine whether the age characteristics of vCJD cases may be reproduced. Results The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%. Conclusions This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases.

  18. Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis

    DEFF Research Database (Denmark)

    Hellemans, Jan; Debeer, Philippe; Wright, Michael

    2006-01-01

    To further explore the allelic heterogeneity within the group of LEMD3-related disorders, we have screened a larger series of patients including 5 probands with osteopoikilosis or Buschke-Ollendorff syndrome (BOS), 2 families with the co-occurrence of melorheostosis and BOS, and 12 unrelated pati...

  19. Comparison of the clinical course of Japanese MM1-type sporadic Creutzfeldt-Jakob disease between subacute spongiform encephalopathy and panencephalopathic-type.

    Science.gov (United States)

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2014-06-01

    Approximately half of Japanese sporadic Creutzfeldt-Jakob disease (sCJD) cases show panencephalopathic-type (PE-type) pathology, which is a rare subtype in North Americans and Europeans. Until now, the differences in the clinical course between subacute spongiform encephalopathy (SSE) cases and PE-type cases have been unclear. To investigate the clinical course of both subtypes, clinical findings from 42 Japanese MM1-type sCJD cases (20 SSE cases and 22 PE-type cases) were retrospectively evaluated by statistical analysis. No significant differences could be found regarding age at disease onset, the period between disease onset and first observation of myoclonus, the period between disease onset and the first observation of periodic sharp-wave complexes on electroencephalogram, or the period between disease onset and progression to the akinetic mutism state - whereas total disease duration and the period between the akinetic mutism state and death were significantly longer in PE-type cases. The prolonged disease duration was induced by the extended survival period in the akinetic mutism state. There was a statistically significant difference between the two series regarding performance of tube-feeding, but no statistically significant difference regarding performance of tracheotomy or gastrostomy. None of the cases received mechanical ventilation. We speculate that the most crucial factor of the prolonged survival period of Japanese sCJD cases, particularly in the PE-type, is that the introduction of tube-feeding in the akinetic mutism state leads to the stabilization of the patient's general condition. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. An autopsied case of MV2K + C-type sporadic Creutzfeldt-Jakob disease presenting with widespread cerebral cortical involvement and Kuru plaques.

    Science.gov (United States)

    Iwasaki, Yasushi; Saito, Yufuko; Aiba, Ikuko; Kobayashi, Atsushi; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2017-06-01

    MV2-type sporadic Creutzfeldt-Jakob disease (sCJD), which was previously called "Kuru-plaque variant", was gradually revealed to have a wide spectrum and has been classified into three pathological subtypes: MV2K, MV2C and MV2K + C. We herein describe the detailed clinical findings and neuropathologic observations from an autopsied MV2K + C-type Japanese sCJD case with widespread cerebral cortical pathology and Kuru plaques. In the early stages of the disease, the patient exhibited gait disturbance with ataxia and dysarthria as well as gradual appearance of cognitive dysfunction. Diffusion-weighted images (DWI) on MRI revealed extensive cerebral cortical hyperintensity. Pathologic investigation revealed extensive spongiform change in the cerebral cortex, particularly in the deeper layers. Vacuole size varied, and some were confluent. Prion protein (PrP) immunostaining revealed extensive PrP deposition in the cerebral cortex, basal ganglia, thalamus, cerebellum, brainstem and spinal cord. In the cerebral cortex, synaptic-type, Kuru plaque-like, and coarse plaque-type PrP depositions were mainly observed, along with some perivacuolar-type PrP depositions. Kuru plaques and coarse plaque-type PrP depositions also were observed in the cerebellar cortex. PrP gene analysis revealed no mutations, and polymorphic codon 129 exhibited Met/Val heterozygosity. Western blot analysis revealed a mixture of intermediate-type PrP Sc and type 2 PrP Sc . Based on previous reports regarding MV2-type sCJD and the clinicopathologic findings of the present case, we speculated that it may be possible to clinically distinguish each MV2 subtype. Clinical presentation of the MV2K + C subtype includes predominant cerebral cortical involvement signs with ataxia and DWI hyperintensity of the cerebral cortex on MRI. © 2016 Japanese Society of Neuropathology.

  1. Sporadic incidence of Fascioliasis detected during Hepatobiliary procedures: A study of 18 patients from Sulaimaniyah governorate

    Directory of Open Access Journals (Sweden)

    Hawramy Tahir Abdullah Hussein

    2012-12-01

    Full Text Available Abstract Background Fascioliasis is an often-neglected zoonotic disease and currently is an emerging infection in Iraq. Fascioliasis has two distinct phases, an acute phase, exhibiting the hepatic migratory stage of the fluke’s life cycle, and a chronic biliary phase manifested with the presence of the parasite in the bile ducts through hepatic tissue. The incidence of Fascioliasis in Sulaimaniyah governorate was unexpected observation. We believe that shedding light on this disease in our locality will increase our physician awareness and experience in early detection, treatment in order to avoid unnecessary surgeries. Findings We retrospectively evaluated this disease in terms of the demographic features, clinical presentations, and managements by reviewing the medical records of 18 patients, who were admitted to the Sulaimani Teaching Hospital and Kurdistan Centre for Gastroenterology and Hepatology. Patients were complained from hepatobiliary and/or upper gastrointestinal symptoms and diagnosed accidentally with Fascioliasis during hepatobiliary surgeries and ERCP by direct visualization of the flukes and stone analysis. Elevated liver enzymes, white blood cells count and eosinophilia were notable laboratory indices. The dilated CBD, gallstones, liver cysts and abscess were found common in radiological images. Fascioliasis diagnosed during conventional surgical CBD exploration and choledochodoudenostomy, open cholecystectomy, surgical drainage of liver abscess, ERCP and during gallstone analysis. Conclusion Fascioliasis is indeed an emerging disease in our locality, but it is often underestimated and ignored. We recommend the differential diagnosis of patients suffering from Rt. Hypochondrial pain, fever and eosinophilia. The watercress ingestion was a common factor in patient’s history.

  2. Complicated Sporadic Cardiac Myxomas: A Second Recurrence and Myxomatous Cerebral Aneurysms in One Patient

    Directory of Open Access Journals (Sweden)

    Mazen E. Iskandar

    2013-01-01

    Full Text Available A second recurrence of an excised nonfamilial cardiac myxoma is rare. Myxomatous cerebral aneurysms as a complication of cardiac myxomas are equally rare. A unique case of a patient with a total of 4 myxomas over a 20-year interval is presented. Her most recent presentation was a second recurrence of a left atrial myxoma, a de novo right atrial myxoma, and multiple cerebral myxomatous aneurysms. The challenging reconstruction of the normal anatomy was achieved with the use of porcine extracellular matrix patches. A diagnostic cerebral angiogram was later performed, and the aneurysms will be monitored for growth and possible intervention.

  3. Sporadic Carney complex without PRKAR1A mutation in a young patient with ischemic stroke.

    Science.gov (United States)

    Aguiar de Sousa, Diana; Gouveia, Ana Isabel; Wessling, Ana; Geraldes, Ruth; Canhão, Patrícia

    2015-03-01

    We describe a 29-year-old male, with a previous history of testicular tumor, who presented with a posterior circulation ischemic stroke associated to an atrial myxoma. Dermatologic observation disclosed spotty skin and mucosal pigmentation (lentigines), and a cutaneous myxoma was histopathologically confirmed. Although there was no family history of any of the Carney complex (CNC) features and no mutations in the PRKAR1A gene were found, these findings lead to the diagnosis of CNC. We emphasize the importance of recognizing this entity in young patients with stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  4. Adult onset sporadic ataxias: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Orlando Graziani Povoas Barsottini

    2014-03-01

    Full Text Available Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

  5. Codon 219 polymorphism of PRNP in healthy caucasians and Creutzfeldt-Jakob disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Petraroli, R.; Pocchiari, M. [Instituto Superiore di Sanita, Rome (Italy)

    1996-04-01

    A number of point and insert mutations of the PrP gene (PRNP) have been linked to familial Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker disease (GSS). Moreover, the methionine/valine homozygosity at the polymorphic codon 129 of PRNP may cause a predisposition to sporadic and iatrogenic CJD or may control the age at onset of familial cases carrying either the 144-bp insertion or codon 178, codon 198, and codon 210 pathogenic mutations in PRNP. In addition, the association of methionine or valine at codon 129 and the point mutation at codon 178 on the same allele seem to play an important role in determining either fatal familial insomnia or CJD. However, it is noteworthy that a relationship between codon 129 polymorphism and accelerated pathogenesis (early age at onset or shorter duration of the disease) has not been seen in familial CJD patients with codon 200 mutation or in GSS patients with codon 102 mutation, arguing that other, as yet unidentified, gene products or environmental factors, or both, may influence the clinical expression of these diseases. 17 refs.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  7. Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers.

    Science.gov (United States)

    Young, Eric D; Ingram, Davis; Metcalf-Doetsch, William; Khan, Dilshad; Al Sannaa, Ghadah; Le Loarer, Francois; Lazar, Alexander J F; Slopis, John; Torres, Keila E; Lev, Dina; Pollock, Raphael E; McCutcheon, Ian E

    2017-09-08

    OBJECTIVE While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS. METHODS Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121). RESULTS SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor-β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor-2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018). CONCLUSIONS Complete resection is curative for SPS. Left untreated, however, these

  8. Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Llorens, Franc; Thüne, Katrin; Sikorska, Beata; Schmitz, Matthias; Tahir, Waqas; Fernández-Borges, Natalia; Cramm, Maria; Gotzmann, Nadine; Carmona, Margarita; Streichenberger, Nathalie; Michel, Uwe; Zafar, Saima; Schuetz, Anna-Lena; Rajput, Ashish; Andréoletti, Olivier; Bonn, Stefan; Fischer, Andre; Liberski, Pawel P; Torres, Juan Maria; Ferrer, Isidre; Zerr, Inga

    2017-04-27

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP Sc ). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca 2+ ) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca 2+ responsive genes in sCJD brain tissue, accompanied by two Ca 2+ -dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrP Sc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca 2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention.

  9. Establishment of induced pluripotent stem cell (iPSC line from a 57-year old patient with sporadic Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Anna Ochalek

    2016-07-01

    Full Text Available Peripheral blood mononuclear cells (PBMCs were collected from a clinically characterised 57-year old woman with sporadic Alzheimer's disease. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies.

  10. Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma

    NARCIS (Netherlands)

    H. Dannenberg (Hilde); W.N.M. Dinjens (Winand); M. Abbou; H. van Urk (Hero); B.K. Pauw; D. Mouwen; W.J. Mooi (Wolter); R.R. de Krijger (Ronald)

    2002-01-01

    textabstractPURPOSE: Recently, familial paraganglioma (PGL) was shown to be caused bymutations in the gene encoding succinate dehydrogenase subunit D (SDHD). However, the prevalence of SDHD mutations in apparently sporadic PGL is unknown. We studied the frequency and spectrum of

  11. Genetic determinants for cadmium and arsenic resistance among Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis patients

    Science.gov (United States)

    In Listeria monocytogenes serotype 4b from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resi...

  12. Higher prevalence of autoimmune diseases and longer spells of vertigo in patients affected with familial Ménière's disease: A clinical comparison of familial and sporadic Ménière's disease.

    Science.gov (United States)

    Hietikko, Elina; Sorri, Martti; Männikkö, Minna; Kotimäki, Jouko

    2014-06-01

    PURPOSE This study compared clinical features, predisposing factors, and concomitant diseases between sporadic and familial Ménière's disease (MD). METHOD Retrospective chart review and postal questionnaire were used. Participants were 250 definite patients with MD (sporadic, n =149; familial, n = 101) who fulfilled the American Academy of Otorhinolaryngology-Head and Neck Surgery (1995) criteria. RESULTS On average, familial patients were affected 5.6 years earlier than sporadic patients, and they suffered from significantly longer spells of vertigo (p = .007). The prevalence of rheumatoid arthritis (p = .002) and other autoimmune diseases (p = .046) was higher among the familial patients, who also had more migraine (p = .036) and hearing impairment (p = .002) in their families. CONCLUSION The clinical features of familial and sporadic MD are very similar in general, but some differences do exist. Familial MD patients are affected earlier and suffer from longer spells of vertigo.

  13. Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrPSc deposits in the brain.

    Science.gov (United States)

    Piao, Yue-Shan; Kakita, Akiyoshi; Watanabe, Hiroyuki; Kitamoto, Tetsuyuki; Takahashi, Hitoshi

    2005-06-01

    We report a case of human prion disease of 29 months duration in a 74-year-old Japanese man. The disease started with progressive sleeplessness and dementia. MRI showed gradually progressive cerebral atrophy. Neuronal loss, spongiform change and gliosis were evident in the thalamus and cerebral cortex, as well as in the striatum and amygdaloid nucleus. In the cerebellar cortex, mild-to-moderate depletion of Pukinje cells and spongiform change were observed. Mild neuronal loss in the inferior olivary nucleus was also seen. Immunohistochemistry revealed widespread perivacuolar deposits of abnormal prion protein (PrPsc) in the cerebral cortex, thalamus, basal ganglia, and brainstem, and minimal plaque-like deposits of PrPSc in the cerebellar cortex. In the cerebellar plaque-like deposits, the presence of amyloid fibrils was confirmed ultrastructurally. The entire pathology appeared to lie halfway between those of CJD and fatal insomnia, and further demonstrated the relationship between spongiform degeneration and PrPSc deposits, especially in the diseased thalamus. By immunoblotting, the thalamus was shown to contain the lowest amount of PrPSc among the brain regions examined. The PrPSc of type 2, in which the ratio of the three glycoforms was compatible with that of sporadic fatal insomnia (MM2-thalamic variant) reported previously, was also demonstrated. Analysis of the prion protein gene (PRNP) showed no mutation, and homozygosity for methionine at codon 129. In conclusion, we considered that this patient had been suffering from sporadic, pathologically atypical fatal insomnia.

  14. Stereotypic Movements in Case of Sporadic Creutzfeldt-Jakob Disease: Possible Role of Anti-NMDA Receptor Antibodies

    Directory of Open Access Journals (Sweden)

    Michelle Molina

    2012-12-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD and anti-NMDA receptor antibody encephalitis (NMDAE can both produce a rapidly progressive dementia with resulting state of catatonia or akinetic mutism. Both are associated with movement disorders. In published case series, myoclonus appears to be the most frequent movement disorder in sCJD, while stereotypic, synchronized, one-cycle-per-second movements such as arm or leg elevation, jaw opening, grimacing, head turning, and eye deviation are seen in NMDAE. We report a case of a 59-year-old woman with rapidly worsening cognitive disturbance leading to a nearly catatonic state interrupted by stereotypic movements. sCJD was diagnosed via periodic sharp wave complexes on EEG as well as cerebrospinal fluid (CSF 14-3-3 and tau protein elevation. Characteristic movement disorder of NMDAE was present in absence of ovarian mass or CSF pleiocytosis. Given prior case reports of presence of anti-NMDA receptor antibodies in sCJD, we propose that the movement disorder in this case was caused by anti-NMDA receptor antibodies whose formation was secondary to neuronal damage from prion disease. It is important to consider sCJD even in cases that have some clinical features suggestive of NMDAE.

  15. Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas.

    Science.gov (United States)

    Kruyt, Ivo J; Verheul, Jeroen B; Hanssens, Patrick E J; Kunst, Henricus P M

    2018-01-01

    OBJECTIVE Neurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS. METHODS The authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes. RESULTS Actuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm 3 both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients

  16. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    International Nuclear Information System (INIS)

    Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

    2002-01-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  17. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

    2002-04-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  18. Brains with sporadic Creutzfeldt-Jakob disease and copathology showed a prolonged end-stage of disease.

    Science.gov (United States)

    Miguelez-Rodriguez, Aitzol; Santos-Juanes, Jorge; Vicente-Etxenausia, Ikerne; Perez de Heredia-Goñi, Katty; Garcia, Beatriz; Quiros, Luis M; Lorente-Gea, Laura; Guerra-Merino, Isabel; Aguirre, Jose J; Fernandez-Vega, Ivan

    2018-05-01

    To investigate the expression of major proteins related to primary neurodegenerative diseases and their prognostic significance in brains with Creutzfeldt-Jakob disease (CJD). Thirty consecutive cases of confirmed CJD during the period 2010-2015 at Basque Brain bank were retrospectively reviewed. Moreover, major neurodegenerative-associated proteins (phosphorylated Tau, 4R tau, 3R tau, alpha-synuclein, TDP43, amyloid beta) were tested. Clinical data were reviewed. Cases were divided according to the presence or absence of copathology. Survival curves were also determined. Copathology was significantly associated with survival in brains with CJD (4.2±1.2 vs 9.2±1.9; P=0.019) and in brains with MM1/MV1 CJD (2.1±1.0 vs 6.7±2.8; P=0.012). Besides, the presence of more than one major neurodegenerative-associated protein was significantly associated with survival (4.2±1.2 vs 10.7±2.6; P=0.017). Thus, univariate analyses further pointed out variables significantly associated with better survival: copathology in CJD (HR=0.430; P=0.033); more than one neurodegenerative-associated protein in CJD (HR=0.369; P=0.036) and copathology in MM1/MV1 CJD (HR=0.525; P=0.032). The existence of copathology significantly prolongs survival in patients with rapidly progressive dementia due to CJD. The study of major neurodegenerative-associated proteins in brains with CJD could allow us to further understand the molecular mechanisms behind prion diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Distribution and Quantitative Estimates of Variant Creutzfeldt-Jakob Disease Prions in Tissues of Clinical and Asymptomatic Patients.

    Science.gov (United States)

    Douet, Jean Y; Lacroux, Caroline; Aron, Naima; Head, Mark W; Lugan, Séverine; Tillier, Cécile; Huor, Alvina; Cassard, Hervé; Arnold, Mark; Beringue, Vincent; Ironside, James W; Andréoletti, Olivier

    2017-06-01

    In the United-Kingdom, ≈1 of 2,000 persons could be infected with variant Creutzfeldt-Jakob disease (vCJD). Therefore, risk of transmission of vCJD by medical procedures remains a major concern for public health authorities. In this study, we used in vitro amplification of prions by protein misfolding cyclic amplification (PMCA) to estimate distribution and level of the vCJD agent in 21 tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person with vCJD. PMCA identified major levels of vCJD prions in a range of tissues, including liver, salivary gland, kidney, lung, and bone marrow. Bioassays confirmed that the quantitative estimate of levels of vCJD prion accumulation provided by PMCA are indicative of vCJD infectivity levels in tissues. Findings provide critical data for the design of measures to minimize risk for iatrogenic transmission of vCJD.

  20. Introduction to Sporadic Groups

    Directory of Open Access Journals (Sweden)

    Luis J. Boya

    2011-01-01

    Full Text Available This is an introduction to finite simple groups, in particular sporadic groups, intended for physicists. After a short review of group theory, we enumerate the 1+1+16=18 families of finite simple groups, as an introduction to the sporadic groups. These are described next, in three levels of increasing complexity, plus the six isolated ''pariah'' groups. The (old five Mathieu groups make up the first, smallest order level. The seven groups related to the Leech lattice, including the three Conway groups, constitute the second level. The third and highest level contains the Monster group M, plus seven other related groups. Next a brief mention is made of the remaining six pariah groups, thus completing the 5+7+8+6=26 sporadic groups. The review ends up with a brief discussion of a few of physical applications of finite groups in physics, including a couple of recent examples which use sporadic groups.

  1. Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrPSc) deposition in sporadic Creutzfeldt-Jakob disease supports a pathogenic role for small PrPSc deposits common to the various molecular subtypes.

    Science.gov (United States)

    Faucheux, B A; Morain, E; Diouron, V; Brandel, J-P; Salomon, D; Sazdovitch, V; Privat, N; Laplanche, J-L; Hauw, J-J; Haïk, S

    2011-08-01

    Neuronal death is a major neuropathological hallmark in prion diseases. The association between the accumulation of the disease-related prion protein (PrP(Sc) ) and neuronal loss varies within the wide spectrum of prion diseases and their experimental models. In this study, we investigated the relationships between neuronal loss and PrP(Sc) deposition in the cerebellum from cases of the six subtypes of sporadic Creutzfeldt-Jakob disease (sCJD; n=100) that can be determined according to the M129V polymorphism of the human prion protein gene (PRNP) and PrP(Sc) molecular types. The numerical density of neurones was estimated with a computer-assisted image analysis system and the accumulation of PrP(Sc) deposits was scored. The scores of PrP(Sc) immunoreactive deposits of the punctate type (synaptic type) were correlated with neurone counts - the higher the score the higher the neuronal loss - in all sCJD subtypes. Large 5- to 50-µm-wide deposits (focal type) were found in sCJD-MV2 and sCJD-VV2 subtypes, and occasionally in a few cases of the other studied groups. By contrast, the highest scores for 5- to 50-µm-wide deposits observed in sCJD-MV2 subtype were not associated with higher neuronal loss. In addition, these scores were inversely correlated with neuronal counts in the sCJD-VV2 subtype. These results support a putative pathogenic role for small PrP(Sc) deposits common to the various sCJD subtypes. Furthermore, the observation of a lower loss of neurones associated with PrP(Sc) type-2 large deposits is consistent with a possible 'protective' role of aggregated deposits in both sCJD-MV2 and sCJD-VV2 subtypes. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

  2. Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients.

    Science.gov (United States)

    Vrabec, Katarina; Boštjančič, Emanuela; Koritnik, Blaž; Leonardis, Lea; Dolenc Grošelj, Leja; Zidar, Janez; Rogelj, Boris; Glavač, Damjan; Ravnik-Glavač, Metka

    2018-01-01

    Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS) through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential expression of 10 miRNAs, including miR-9, miR-338, miR-638, miR-663a, miR-124a, miR-143, miR-451a, miR-132, miR-206, and let-7b, for which some connection to ALS was shown previously in ALS culture cells, animal models or patients, and in three miRNA host genes, including C1orf61 (miR-9), AATK (miR-338), and DNM2 (miR-638), in leukocyte samples of 84 patients with sporadic ALS. We observed significant aberrant dysregulation across our patient cohort for miR-124a, miR-206, miR-9, let-7b, and miR-638. Since we did not use neurological controls we cannot rule out that the revealed differences in expression of investigated miRNAs are specific for ALS. Nevertheless, the group of these five miRNAs is worth of additional research in leukocytes of larger cohorts from different populations in order to verify their potential association to ALS disease. We also detected a significant up-regulation of the AAKT gene and down-regulation of the DNM2 gene, and thus, for the first time, we connected these with sporadic ALS cases. These findings open up new research toward miRNAs as diagnostic biomarkers and epigenetic processes involved in ALS. The detected significant deregulation of AAKT and DNM2 in sporadic ALS also represents an interesting finding. The DNM2 gene was previously found to be mutated in Charcot-Marie-Tooth neuropathy-type CMT2M and centronuclear myopathy (CNM). In addition, as recent studies connected AATK and frontotemporal dementia (FTD) and DNM2 and hereditary spastic paraplegia (HSP), these two genes together with our results genetically connect, at least in part, five diseases, including FTD, HSP, Charcot-Marie-Tooth (type CMT2M), CNM, and ALS

  3. The human prion diseases. A review with special emphasis on new variant CJD and comments on surveillance.

    LENUS (Irish Health Repository)

    Keohane, C

    2012-02-03

    The transmissible spongiform encephalopathies or prion diseases represent a new group of diseases with unique clinical and neuropathological features, the transmission of which is both genetic and infectious. The responsible agent is unconventional and appears to be largely composed of a glycoprotein, the prion protein PrP. This is normally present on different cells. In prion diseases, it becomes converted to the pathogenic form PrPres which is resistant to proteinase and accumulates within the brain and this process is accompanied by the development of spongiform change, gliosis and neuronal loss. The human prion diseases include Kuru a progressive cerebellar degeneration with late dementia affecting Fore tribes in New-Guinea, now almost extinct, regarded as being related to cannibalism. Creutzfeldt-Jakob disease is the more frequent human prion disease. Its incidence is approximately one case per million per year. Four variants are now recognized: sporadic, familial, iatrogenic and the new variant. The latter represents a distinct clinico-pathological entity. It is now widely accepted that it is due to the same agent responsible for Bovine Spongiform Encephalopathy in cattle. Gerstmann-Straussler-Scheinker disease is a very rare inherited disorder due to a number of different mutations in the PRP gene, characterized by abundant deposits of plaque PrPres in the cerebral grey matter. Fatal familial insomnia is another inherited disorder due to a mutation at codon 178 of the PRP gene associated with methionine on codon 129 of the mutant allele. The main neuropathological change is neuronal loss in the thalamus with little or no spongiosis and usually no PrPres deposition. Following the emergence of new variant CJD in 1996, surveillance of all forms of prion diseases has been now been actively introduced in many European nations in order to determine the true incidence and geographic distribution of these rare disorders in humans.

  4. Increased expression of interleukin-21 along colorectal adenoma-carcinoma sequence and its predicating significance in patients with sporadic colorectal cancer.

    Science.gov (United States)

    Cui, Guanglin; Yuan, Aping; Zhu, Li; Florholmen, Jon; Goll, Rasmus

    2017-10-01

    The role and significance of interleukin (IL)-21 in the development of sporadic CRC have not been well defined. The aim of this study is therefore to investigate the dynamics of the IL-21 along colorectal adenoma-carcinoma sequence and to evaluate the impact of IL-21 on clinicopathological parameters and CRC prognosis. The real-time PCR results showed that the level of IL-21 in adenomas (n=50) and sporadic CRC (n=50) were significantly higher than that in normal controls (n=18), which were predominately observed in the adenoma/CRC stroma. Analysis revealed that IL-21 level was correlated with the overall survival time in CRC patients. Double immunofluorescence observations confirmed that IL-21 positive cells were mostly natural killer cells and T lymphocytes in the tumor stroma. These results indicate that significant increased IL-21 expression present within the adenoma/CRC microenvironment might have a potential predicating significance for survival time in patients with CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. No evidence for mutations in exons 1, 8 and 18 of the patched gene in sporadic skin lesions of Brazilian patients

    Directory of Open Access Journals (Sweden)

    Granja F.

    2003-01-01

    Full Text Available There is strong evidence that the patched (PTCH gene is a gene for susceptibility to the nevoid basal cell carcinoma syndrome. PTCH has also been shown to mutate in both familial and sporadic basal cell carcinomas. However, mutations of the gene seem to be rare in squamous cell carcinomas. In order to characterize the role of the gene in the broader spectrum of sporadic skin malignant and pre-malignant lesions, we performed a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP analysis of genomic DNA extracted from 105 adult patients (46 females and 59 males. There were 66 patients with basal cell carcinomas, 30 with squamous cell carcinomas, 2 with malignant melanomas and 7 patients with precancerous lesions. Two tissue samples were collected from each patient, one from the central portion of the tumor and another from normal skin. Using primers that encompass the entire exon 1, exon 8 and exon 18, where most of the mutations have been detected, we were unable to demonstrate any band shift. Three samples suspected to present aberrant migrating bands were excised from the gel and sequenced directly. In addition, we sequenced 12 other cases, including tumors and corresponding normal samples. A wild-type sequence was found in all 15 cases. Although our results do not exclude the presence of clonal alterations of the PTCH gene in skin cancers or mutations in other exons that were not screened, the present data do not support the presence of frequent mutations reported for non-melanoma skin cancer of other populations.

  6. Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

    Science.gov (United States)

    Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

    2016-12-01

    Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Sporadic lymphoplasmacytic cholecystitis: a clinicopathologic entity.

    Science.gov (United States)

    Hammer, Suntrea T G; Appelman, Henry D

    2014-08-01

    To describe a sporadic form of lymphoplasmacytic cholecystitis (LPC), a condition known to occur in patients with chronic biliary tract disease. One year's worth of cholecystectomies was reviewed for sporadic cases of LPC. Histologic, radiologic, and clinical findings were reviewed and compared with noninflamed controls. Sporadic cases were also compared histologically with obstructive LPC cases. Sporadic LPC made up 7% of cholecystectomies, had a male predominance (54.2%), and more often presented with clinical signs of acute inflammation compared with controls. Radiologic findings identified gallstones in 71.4% of patients. The second most common finding was unexplained extrahepatic biliary dilation. There were no unique histologic findings to separate sporadic cases from those associated with pancreatobiliary disease. While obstructive LPC is traditionally described as acalculous, chronic cholecystitis, we show this inflammatory pattern occurs both in the presence of gallstones and outside of previously described disease categories. In addition, LPC occurs in a unique patient demographic (older men), often presenting similarly to acute cholecystitis. Copyright© by the American Society for Clinical Pathology.

  8. Sporadic Creutzfeldt-Jakob disease with unusual initial presentation as posterior reversible encephalopathy syndrome: a case report.

    Science.gov (United States)

    Dirzius, Edgaras; Balnyte, Renata; Steibliene, Vesta; Gleizniene, Rymante; Gudinaviciene, Inga; Radziunas, Andrius; Petrikonis, Kestutis

    2016-11-22

    Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative prion disease. MRI findings are included in diagnostic criteria for probable CJD, giving a sensitivity and specificity more than 90%, but the atypical radiological presentations in the early stage of the disease could cause the diagnostic difficulties. CJD can be definitively diagnosed by histopathological confirmation, brain biopsy or at autopsy. We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months. The clinical symptoms deteriorated progressively to myoclonus and akinetic mutism already on the 14th week. The series of diagnostic examinations were done to exclude the possible causes of dementia. Initial MRI evaluation as posterior reversible encephalopathy syndrome (PRES) on the 9th week after the onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the 18th week allowed us to diagnose the probable sCJD. The histopathological findings after brain biopsy on the 14th week demonstrated the presence of the abnormal prion protein deposits in the grey matter by immunohistochemistry with ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD. In this article we focus our attention on a rare association between radiological PRES syndrome and early clinical stage of sCJD. Although concurrent manifestation of these conditions can be accidental, but the immunogenic or neuropeptide mechanisms could explain such radiological MRI findings. A thorough knowledge of differential diagnostic of PRES may be especially useful in earlier diagnosis of sCJD.

  9. Patients with chronic headache tend to have more psychological symptoms than those with sporadic episodes of pain

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Junqueira Zampieri

    2014-08-01

    Full Text Available There are controversial associations between headaches and psychological symptoms. Objective To design a profile of neuroticism, a term that groups variables related to negative personality traits, in patients with chronic daily headache (CDH when compared to episodic migraine (EM patients, applying the Factorial Scale of Emotional Adjustment/Neuroticism (NFS. Method One hundred adult patients with CDH and forty with EM answered the NFS. Results Comorbidities of subtypes of neuroticism (p=0.006 were more common in chronic daily headache patients, with three or more disorders (p=0.0002: dependent personality disorder (p=0.0001, anxiety, reduced concentration and production (p=0.0008, depression (p<0.0001, suicidal ideation (p=0.0008 and hopelessness even without depression (p<0.0001. Conclusion Patients with CDH tend to have dependent personality disorder, low production and concentration, anxiety, depression, suicidal ideation and hopelessness, superimposing two or more psychological disorders. These factors should be pondered for a better resolution in the treatment of CDH.

  10. Detection of RNA in the Plasma of Patients with Sporadic Creutzfeldt–Jakob Disease, Gerstmann–Straüssler Syndrome and Other Non-Transmissible Spongiform Encephalopathy Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kazuo Tsukui

    2010-01-01

    Full Text Available The infectious agent of transmissible spongiform encephalopathy (TSE was assumed to be the aggregate of abnormal prion protein isoform (PrPsc. We observed that lowering the pH of 3% SDS-inoculated plasma or brain homogenate after PK digestion to 4.5 (acidic SDS condition enabled to precipitate proteinase K-resistant prion protein (PrPres in plasma as well as PrPres in the brain with synthetic poly-A RNA as affinity aggregate. Therefore, we determined if RNA molecules could be used for discriminating TSE patients from healthy individuals. We also examined the plasma of patients with classical Creutzfeldt–Jakob disease (CJD and other brain disorders who were not diagnosed with TSE. The results indicated that RNA approximately 1.5–2.0 kb in length was commonly observed in the plasma of patients with brain disorders but was not detected in the plasma of healthy volunteers. Enhanced expression of RNA and its protection from endogenous nucleases might occur in the former group of patients. Moreover, we speculate that the non-transmissible neuronal disorders overlap with prion diseases.

  11. New variant of Creutzfeldt-Jakob (vCJD disease and other human prion diseases under epidemiological surveillance in Brazil

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Gattás

    Full Text Available Abstract To increase the timeliness of detection of human cases of the new variant of Creutzfeldt-Jakob disease (vCJD and to reduce the risk of transmission, the Brazilian Ministry of Health has established and standardized rules and control measures. These include the definition of criteria for suspect cases, reporting, monitoring, and control measures for illness prevention and transmission. Guidelines to be used by the team of health care staff were published and distributed to health workers. A detailed proposal for a simplified system of surveillance for prion diseases was developed and mandatory reporting introduced. Additional effort is necessary to increase vCJD case detection, thus making it necessary to establish a partnership with health care services for best identification of suspected cases and dissemination of information to all involved in the service dealing with vCJD investigation.

  12. Expression of NF-kB and COX-2 in Young Versus Older Patients with Sporadic Colorectal Cancer.

    NARCIS (Netherlands)

    Suharti, C.; Gorp, E. van; Dolmans, W.M.V.; Groen, J.; Hadisaputro, S.; Djokomoeljanto, R.J.; Dme, O.A.; Meer, J.W.M. van der

    2009-01-01

    Aim: to investigate which recent infection could have caused the present dengue-like symptoms, in adult patients clinically fulfilling the WHO criteria for dengue, in which serologically were not confirmed for dengue virus infections. Methods: prospective study. During an outbreak of dengue (between

  13. Tailored Beta-catenin mutational approach in extra-abdominal sporadic desmoid tumor patients without therapeutic intervention

    International Nuclear Information System (INIS)

    Broekhoven, Danique L.M. van; Grünhagenl, Dirk J.; Dalen, Thijs van; Coevorden, Frits van; Bonenkamp, Han J.; Been, Lukas B.; Bemelmans, Marc H.A.; Dijkstra, Sander D.S.; Colombo, Chiara; Gronchi, Alessandro; Verhoef, Cornelis

    2016-01-01

    The efficacy of the classical treatment modalities surgery and radiotherapy in the treatment of aggressive fibromatosis is presently disputed and there is a shift towards a more conservative approach. The aim of the present study is to objectify tumor growth in patients with extra-abdominal or abdominal wall aggressive fibromatosis, while adhering to a “watchful waiting” policy. Other objectives are to investigate quality of life and to identify factors associated with tumor growth, in particular the relation with the presence of a CTNNB1-gene mutation in the tumor. GRAFITI is a nationwide, multicenter, prospective registration trial. All patients with extra-abdominal or abdominal wall aggressive fibromatosis are eligible for inclusion in the study. Main exclusion criteria are: history of familiar adenomatous polyposis, severe pain, functional impairment, life/limb threating situations in case of progressive disease. Patients included in the study will be treated with a watchful waiting policy during a period of 5 years. Imaging studies with ultrasound and magnetic resonance imaging scan will be performed during follow-up to monitor possible growth: the first years every 3 months, the second year twice and the yearly. In addition patients will be asked to complete a quality of life questionnaire on specific follow-up moments. The primary endpoint is the rate of progression per year, defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Secondary endpoints are quality of life and the rate of influence on tumor progression for several factors, such as CTNNB1-mutations, age and localization. This study will provide insight in tumor behavior, the effect on quality of life and clinicopathological factors predictive of tumor progression. The GRAFITI trial is registered in the Netherlands National Trial Register (NTR), number: NTR4714

  14. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: Family studies indicate a mutation type-dependent sex ratio of mutation frequencies

    Energy Technology Data Exchange (ETDEWEB)

    Becker, J.; Schmidt, W.; Olek, K. [Univ. of Bonn (Germany)] [and others

    1996-04-01

    The clinical manifestation of hemophilia A is caused by a wide range of different mutations. In this study the factor VIII genes of 147 severe hemophilia A patients-all exclusively from sporadic families-were screened for mutations by use of the complete panel of modern DNA techniques. The pathogenous defect could be characterized in 126 patients (85.7%). Fifty-five patients (37.4%) showed a F8A-gene inversion, 47 (32.0%) a point mutation, 14 (9.5%) a small deletion, 8 (5.4%) a large deletion, and 2 (1.4%) a small insertion. Further, four (2.7%) mutations were localized but could not be sequenced yet. No mutation could be identified in 17 patients (11.6%). Sixteen (10.9%) of the P identified mutations occurred in the B domain. Four of these were located in an adenosine nucleotide stretch at codon 1192, indicating a mutation hotspot. Somatic mosaicisms were detected in 3 (3.9%) of 76 patients` mothers, comprising 3 of 16 de novo mutations in the patients` mothers. Investigation of family relatives allowed detection of a de novo mutation in 16 of 76 two-generation and 28 of 34 three-generation families. On the basis of these data, the male:female ratio of mutation frequencies (k) was estimated as k = 3.6. By use of the quotients of mutation origin in maternal grandfather to patient`s mother or to maternal grandmother, k was directly estimated as k = 15 and k = 7.5, respectively. Considering each mutation type separately, we revealed a mutation type-specific sex ratio of mutation frequencies. Point mutations showed a 5-to-10-fold-higher and inversions a >10-fold- higher mutation rate in male germ cells, whereas deletions showed a >5-fold-higher mutation rate in female germ cells. Consequently, and in accordance with the data of other diseases like Duchenne muscular dystrophy, our results indicate that at least for X-chromosomal disorders the male:female mutation rate of a disease is determined by its proportion of the different mutation types. 68 refs., 1 fig., 5 tabs.

  15. Ultra-high-resolution C-arm flat-detector CT angiography evaluation reveals 3-fold higher association rate for sporadic intracranial cavernous malformations and developmental venous anomalies: a retrospective study in consecutive 58 patients with 60 cavernous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Kocak, Burak [Aksaray State Hospital, Department of Radiology, Aksaray (Turkey); Kizilkilic, Osman; Kocer, Naci; Islak, Civan [Istanbul University, Department of Radiology, Cerrahpasa Medical Faculty, Istanbul (Turkey); Oz, Buge; Bakkaloglu, Dogu Vuralli [Istanbul University, Department of Pathology, Cerrahpasa Medical Faculty, Istanbul (Turkey); Isler, Cihan [Istanbul University, Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul (Turkey)

    2017-06-15

    The imaging and surgical literature has confusing association rates for the association between sporadic intracranial cavernous malformations (CMs) and developmental venous anomalies (DVAs). In this study, our purpose was to determine the association rate using ultra-high-resolution C-arm flat-detector CT angiography (FDCTA) and compare it with literature. Fifty-eight patients with 60 sporadic intracranial CMs that underwent an FDCTA study were included in our retrospective study. Re-evaluation of radiological data was performed based on the criteria defined by authors. Isotropic volumetric reconstructions with ultra-high resolution (voxel size of 102 μm{sup 3} for initial; 67 μm{sup 3} and 32 μm{sup 3} for further evaluation) were used for assessment. Sixteen patients underwent surgery for excision of their CMs. Fifty-one of all patients (87.9 %) were associated with a DVA. Undefined local venous structures (UD-LVSs) were observed in the remaining 7 patients (12.1 %). The strength of interobserver agreement was excellent [kappa(k) coefficient = 0.923]. Ultra-high-resolution FDCTA evaluation of CMs and DVAs reveals 3-fold higher association rate compared to the literature. FDCTA for patients with sporadic CMs could help identify the associated DVAs that remained undetected or unclear with other imaging modalities, which can be useful in decision-making processes, planning surgery, and during operation. (orig.)

  16. Corticobasal syndrome due to sporadic Creutzfeldt-Jakob disease: a review and neuropsychological case report.

    Science.gov (United States)

    González, David Andrés; Soble, Jason R

    2017-04-01

    Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease with neuropsychological sequelae. This study highlighted a rare presentation of CJD (e.g. corticobasal syndrome [CBS]), reviewed updated diagnostic criteria and procedures for CJD (e.g. diffusion weighted imaging [DWI], real-time quaking-induced conversion [RT-QuIC]), and discussed differential diagnoses. Case report methodology focused on a 68-year-old, Hispanic, right-handed man with 11 years of education. He presented with a 1-2-month history of gait and motor difficulties (e.g. rigidity, myoclonus). After evaluation, a 'cortical ribboning' pattern on DWI and positive RT-QuIC was integrated with performance on neurobehavioral exam (i.e. alien limb phenomenon, unilateral ideomotor apraxia) and neuropsychological testing (i.e. frontal-parietal dysfunction pattern) to reach a diagnosis of sCJD-CBS. The patient expired 3 months after onset of symptoms. This literature review and case report highlighted the importance of staying abreast of developments in neurological literature and the added value of neuropsychology, when integrated with newer procedures, for confirming and excluding diagnostic considerations.

  17. Comparison of the level, distribution and form of disease-associated prion protein in variant and sporadic Creutzfeldt-Jakob diseased brain using conformation-dependent immunoassay and Western blot.

    Science.gov (United States)

    Choi, Young Pyo; Gröner, Albrecht; Ironside, James W; Head, Mark W

    2011-03-01

    Disease-associated prion protein (PrP(Sc)) can be distinguished from the cellular isoform (PrP(C)) by conformation-dependent immunoassay (CDI). This technique exploits the presence of an epitope, accessible in PrP(C), but only unmasked by denaturation in PrP(Sc). In this study, we investigated PrP(Sc) in different brain regions in variant and sporadic Creutzfeldt-Jakob disease (CJD) by using CDI, and directly compared the results with those obtained using the more commonly employed protease digestion and Western blotting. In general, there was good agreement between the results, although there were certain discrepancies in relative abundance when the regional distribution in variant CJD cases was considered. The results largely confirmed the previously described targeting of different brain regions by variant and sporadic CJD. Additionally, the combination of protease digestion and CDI detection demonstrated, for the first time, the presence of PrP(Sc) in variant CJD brains that is susceptible to proteolysis under standard conditions.

  18. UK approach to assessing assays and filters designed to reduce the risk of transfusion-transmitted vCJD.

    Science.gov (United States)

    Thomas, S; Turner, M L; Williamson, L M

    2013-09-01

    Three cases of vCJD transmission by blood transfusion have been reported in the UK, and a fourth case discovered at post-mortem. Modelling has been conducted to predict the number of cases that may occur in the future through transfusion, based on estimates of prevalence, infectivity and susceptibility, and a number of steps have been taken to reduce the risk of transmission. These include deferral of previously transfused donors, leucocyte depletion of all components, importation of plasma for certain patient groups and for fractionation, and the collection of the majority of platelets from single donors (by apheresis). However, even with these interventions, some future cases are still predicted. The UK-wide Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) considers the evidence for clinical and cost-effectiveness of any proposed intervention, such as prion assays and filters, and makes recommendations to the governments of the UK. The development of prion assays is challenging as prions do not generate an immune response, do not have nucleic acid and are present in blood in very low concentrations against a high background of normal prion protein. It is critically important that prion assays show high levels of sensitivity and - especially -specificity for a healthy blood donor population. Assessment is impacted by the very short supply of positive human samples, necessitating the use of animal models. Filters that are capable of removing prions from blood components have been developed and CE marked, but it is again necessary to use animal models to study their efficacy. Guidelines have been produced for the assessment of the quality of red cells filtered through these devices, and a clinical safety study has recently been completed. In conclusion, the evaluation of screening assays and prion filters is challenging, time-consuming and costly, but these evaluations are critical to policy making. Copyright © 2013 Elsevier Masson SAS. All

  19. All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

    Science.gov (United States)

    de Wolf, Christopher; Tan, Boon Chin; Smith, Antony; Groschup, Martin H.; Hunter, Nora; Hornsey, Valerie S.; MacGregor, Ian R.; Prowse, Christopher V.; Turner, Marc; Manson, Jean C.

    2011-01-01

    Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion. PMID:21858015

  20. Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

    Science.gov (United States)

    Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

    2017-12-01

    We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

  1. Mad Cows and CJD A Physicist's View of Prion Brain Diseases

    CERN Document Server

    Morrison, Douglas Robert Ogston

    1997-01-01

    The research of Carleton Gajdusek on a stone-age tribe in Papua New Guinea, who suffered from a mysterious disease, kuru, spread by cannibalism, is described and short extracts from his films will be shown. Some deaths from kuru are still occuring after 45 years. This disease is believed to be caused by an entirely new mechanism, not a virus or bacteria, but by a small molecule known as a prion that occurs naturally in many living forms. The Prion Only hypothesis of Stan Prusiner is discussed critically. It has been calculated that 900,000 cows in Britain had the Mad Cow disease, BSE, but most were slaughtered before symptoms were recognised. This epidemic started with 10 cases in the first year, and finally 160,000 were officially classified as having BSE; it is now slowly dying out. The human epidemic, caused by a new version of Creutzfeldt-Jakob Disease, nvCJD, affects mainly young people, has just begun with 10 cases in the first year. The average incubation time may be about 14 years then death follows i...

  2. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Kallenberg, K.; Summers, D. M.; Romero, C.; Taratuto, A.; Heinemann, U.; Breithaupt, M.; Varges, D.; Meissner, B.; Ladogana, A.; Schuur, M.; Haik, S.; Collins, S. J.; Jansen, Gerard H.; Stokin, G. B.; Pimentel, J.; Hewer, E.; Collie, D.; Smith, P.; Roberts, H.; Brandel, J. P.; van Duijn, C.; Pocchiari, M.; Begue, C.; Cras, P.; Will, R. G.; Sanchez-Juan, P.

    2009-01-01

    Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic

  3. Lessons from the response to the threat of transfusion-transmitted vCJD in Ireland.

    Science.gov (United States)

    Murphy, W G

    2013-09-01

    By the time vCJD was first described in 1996, it was already far too late to offset further disaster from transmission of the disease by blood transfusion: almost all the humans who would be infected and infectious were already diseased. Nothing done by the blood transfusion services around that time, with the exception of excluding transfusion recipients as blood donors, would have made any useful contribution to containing the extent of the epidemic. The ability to spread emerging diseases before the problem is manifest or understood is a fixed and unavoidable feature of blood transfusion as it is practiced today. A second fixed property of blood transfusion is that the root cause of disaster is not within the control of the blood transfusion universe. Strategies that have emerged to cope with similar threat in other enterprises that also contain these properties comprise the components of robust design: surveillance, preparedness for action, engagement, herding together, evasion or avoidance, early adoption of potentially useful measures, engineered resilience, defence in depth, damage limitation including modularity and removal of feedback loops, and contingency, redundancy and failure management, and ultimately, individual escape. Early adoption of leucodepletion based on the possibility that it might work rather than any hard evidence was a good example of threat management. Exclusion of previously transfused donors is a robust mechanism for containing any future infection; optimal blood use structures that provide a national transfusion rate as low as possible also constitute an effective threat management strategy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata determined by an easy Z-score (eZIS) analysis of (99m)Tc-ECD-SPECT images in a case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Hayashi, Yuichi; Iwasaki, Yasushi; Yoshikura, Nobuaki; Asano, Takahiko; Hatano, Taku; Tatsumi, Shinsui; Satoh, Katsuya; Kimura, Akio; Kitamoto, Tetsuyuki; Yoshida, Mari; Inuzuka, Takashi

    2015-11-15

    We report a case of autopsy-verified MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD) in a 46-year-old patient with a 16-month history of abnormal behavior, progressive dementia, insomnia, and speech disturbances without family history. Neurological examination revealed progressive dementia, frontal signs, insomnia, speech disturbance, gait disturbance and bilaterally exaggerated tendon reflexes. Both brain MRI and cerebrospinal fluid examinations, including 14-3-3 protein, yielded normal results. An easy Z-score (eZIS) analysis for (99m)Tc-ethyl cysteinate dimer-single photon emission computed tomography ((99m)Tc-ECD-SPECT) revealed decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata. PRNP gene analysis revealed methionine homozygosity at codon 129 without mutation. Neuropathological examinations revealed severe neuronal loss, gliosis, and hypertrophic astrocytosis in the medial thalamus and inferior olivary nucleus. A slight depletion of Purkinje cells was observed. PrP immunostaining showed no obvious PrP deposits in the basal ganglia, thalamus, cerebellum, or brainstem; however, mild synaptic-type PrP deposits with some smaller plaque-like structures were only partially observed in the localized region of the frontal lobe with the spongiform change. Western blot analyses of protease-resistant PrP showed a type 2 pattern. In conclusion, eZIS analysis of (99m)Tc-ECD-SPECT images is useful for detecting both thalamic and medullary lesions. This is the first case of medullary lesions detected in a live patient with MM2-thalamic-type sCJD using SPECT. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Brain sonography in African infants with complicated sporadic ...

    African Journals Online (AJOL)

    Background: To determine the structural findings in brain sonography of African infants with complicated sporadic bacterial meningitis. Materials and Methods: Retrospective assessment of medical records of patients who underwent brain sonography on account of complicated bacterial meningitis. The brain sonography ...

  6. Interpretation of electrodiagnostic findings in sporadic progressive muscular atrophy

    NARCIS (Netherlands)

    Visser, J.; de Visser, M.; van den Berg-Vos, R. M.; van den Berg, L. H.; Wokke, J. H. J.; de Jong, J. M. B. V.; Franssen, H.

    2008-01-01

    Objective We present the electrophysiologic data at baseline of 37 patients who were included in our prospective study on sporadic adult-onset progressive muscular atrophy (PMA). The aim was to correlate electrophysiological. signs of lower motor neuron (LMN) loss with clinical signs of LMN loss,

  7. Legionnaires’ Disease: Clinicoradiological Comparison of Sporadic Versus Outbreak Cases

    Directory of Open Access Journals (Sweden)

    Hafiz Rizwan Talib Hashmi

    2017-06-01

    Full Text Available Background: In 2015, New York City experienced the worst outbreak of Legionnaires’ disease in the history of the city. We compare patients seen during the 2015 outbreak with sporadic cases of Legionella during the past 5 years. Methods: We conducted a retrospective chart review of 90 patients with Legionnaires’ disease, including sporadic cases of Legionella infection admitted from 2010 to 2015 (n = 55 and cases admitted during the 2015 outbreak (n = 35. Results: We saw no significant differences between the 2 groups regarding demographics, smoking habits, alcohol intake, underlying medical disease, or residence type. Univariate and multivariate analyses showed that patients with sporadic case of Legionella had a longer stay in the hospital and intensive care unit as well as an increased stay in mechanical ventilation. Short-term mortality, discharge disposition, and most clinical parameters did not differ significantly between the 2 groups. Conclusions: We found no specific clinicoradiological characteristics that could differentiate sporadic from epidemic cases of Legionella . Early recognition and high suspicion for Legionnaires’ disease are critical to provide appropriate treatment. Cluster of cases should increase suspicion for an outbreak.

  8. An autopsied case of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease presenting with hyperintensities on diffusion-weighted MRI before clinical onset.

    Science.gov (United States)

    Iwasaki, Yasushi; Mori, Keiko; Ito, Masumi; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2017-02-01

    + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD), which suggests a broader spectrum of sCJD clinicopathological findings. © 2016 Japanese Society of Neuropathology.

  9. Prospective comparison of {sup 68}Ga-DOTATATE and {sup 18}F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

    Energy Technology Data Exchange (ETDEWEB)

    Archier, Aurelien; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Inserm UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Marseille (France); Varoquaux, Arthur; Beschmout, Eva [Aix-Marseille University, Department of Medical Imaging, Conception Hospital, Marseille (France); Garrigue, Philippe; Guillet, Benjamin [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, Department of Radiopharmacy, La Timone and North University Hospital, Marseille (France); Montava, Marion; Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Gabriel, Sophie [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Morange, Isabelle; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Barlier, Anne [Aix-Marseille, University, Laboratory of Biochemistry and Molecular Biology, Conception Hospital, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, Marseille (France); Pacak, Karel [National Institutes of Health, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD (United States)

    2016-07-15

    Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of {sup 68}Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. {sup 68}Ga-DOTATATE, {sup 18}F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). {sup 68}Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than {sup 18}F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). {sup 68}Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on {sup 68}Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). {sup 68}Ga-DOTATATE PET/CT is the most sensitive tool in the

  10. MRI of Creutzfeldt-Jakob disease: Imaging features and recommended MRI protocol

    Energy Technology Data Exchange (ETDEWEB)

    Collie, D.A.; Sellar, R.J.; Zeidler, M.; Colchester, A.C.F.; Knight, R.; Will, R.G

    2001-09-01

    Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More recently, a new clinically distinct form of the disease affecting younger patients, known as variant CJD (vCJD), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle. Characteristic appearances on magnetic resonance imaging (MRI) have been identified in several forms of CJD; sCJD may be associated with high signal changes in the putamen and caudate head and vCJD is usually associated with hyperintensity of the pulvinar (posterior nuclei) of the thalamus. These appearances and other imaging features are described in this article. Using appropriate clinical and radiological criteria and tailored imaging protocols, MRI plays an important part in the in vivodiagnosis of this disease. Collie, D.A. et al. (2001)

  11. MRI of Creutzfeldt-Jakob disease: Imaging features and recommended MRI protocol

    International Nuclear Information System (INIS)

    Collie, D.A.; Sellar, R.J.; Zeidler, M.; Colchester, A.C.F.; Knight, R.; Will, R.G.

    2001-01-01

    Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More recently, a new clinically distinct form of the disease affecting younger patients, known as variant CJD (vCJD), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle. Characteristic appearances on magnetic resonance imaging (MRI) have been identified in several forms of CJD; sCJD may be associated with high signal changes in the putamen and caudate head and vCJD is usually associated with hyperintensity of the pulvinar (posterior nuclei) of the thalamus. These appearances and other imaging features are described in this article. Using appropriate clinical and radiological criteria and tailored imaging protocols, MRI plays an important part in the in vivodiagnosis of this disease. Collie, D.A. et al. (2001)

  12. Multiorgan detection and characterization of protease-resistant prion protein in a case of variant CJD examined in the United States.

    Directory of Open Access Journals (Sweden)

    Silvio Notari

    2010-01-01

    Full Text Available Variant Creutzfeldt-Jakob disease (vCJD is a prion disease thought to be acquired by the consumption of prion-contaminated beef products. To date, over 200 cases have been identified around the world, but mainly in the United Kingdom. Three cases have been identified in the United States; however, these subjects were likely exposed to prion infection elsewhere. Here we report on the first of these subjects.Neuropathological and genetic examinations were carried out using standard procedures. We assessed the presence and characteristics of protease-resistant prion protein (PrP(res in brain and 23 other organs and tissues using immunoblots performed directly on total homogenate or following sodium phosphotungstate precipitation to increase PrP(res detectability. The brain showed a lack of typical spongiform degeneration and had large plaques, likely stemming from the extensive neuronal loss caused by the long duration (32 months of the disease. The PrP(res found in the brain had the typical characteristics of the PrP(res present in vCJD. In addition to the brain and other organs known to be prion positive in vCJD, such as the lymphoreticular system, pituitary and adrenal glands, and gastrointestinal tract, PrP(res was also detected for the first time in the dura mater, liver, pancreas, kidney, ovary, uterus, and skin.Our results indicate that the number of organs affected in vCJD is greater than previously realized and further underscore the risk of iatrogenic transmission in vCJD.

  13. Systematic comparison of sporadic and syndromic pancreatic islet cell tumors.

    Science.gov (United States)

    Erlic, Zoran; Ploeckinger, Ursula; Cascon, Alberto; Hoffmann, Michael M; von Duecker, Laura; Winter, Aurelia; Kammel, Gerit; Bacher, Janina; Sullivan, Maren; Isermann, Berend; Fischer, Lars; Raffel, Andreas; Knoefel, Wolfram Trudo; Schott, Matthias; Baumann, Tobias; Schaefer, Oliver; Keck, Tobias; Baum, Richard P; Milos, Ioana; Muresan, Mihaela; Peczkowska, Mariola; Januszewicz, Andrzej; Cupisti, Kenko; Tönjes, Anke; Fasshauer, Mathias; Langrehr, Jan; von Wussow, Peter; Agaimy, Abbas; Schlimok, Günter; Lamberts, Regina; Wiech, Thorsten; Schmid, Kurt Werner; Weber, Alexander; Nunez, Mercedes; Robledo, Mercedes; Eng, Charis; Neumann, Hartmut P H

    2010-12-01

    Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower malignancy rate (PICTs compared to sporadic cases. VHL was prevalent in ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.

  14. Amyloid- and FDG-PET in sporadic Creutzfeldt-Jakob disease: Correlation with pathological prion protein in neuropathology.

    Science.gov (United States)

    Matías-Guiu, Jordi A; Guerrero-Márquez, Carmen; Cabrera-Martín, María Nieves; Gómez-Pinedo, Ulises; Romeral, María; Mayo, Diego; Porta-Etessam, Jesús; Moreno-Ramos, Teresa; Carreras, José Luis; Matías-Guiu, Jorge

    2017-05-04

    The role of positron emission tomography (PET) in Creutzfeldt-Jakob disease is less defined than in other neurodegenerative diseases. We studied the correlation between the uptake of 18 F-florbetaben and 18 F-fluorodeoxyglucose with pathological prion protein deposition in histopathology in a case. A patient with 80 y old with a rapid neurological deterioration with a confirmed diagnosis of CJD was studied. PET and MRI studies were performed between 13-20 d before the death. A region of interest analysis was performed using Statistical Parametric Mapping. MRI showed atrophy with no other alterations. FDG-PET showed extensive areas of hypometabolism including left frontoparietal lobes as well as bilateral thalamus. Correlation between uptake of 18 F-florbetaben and pathological prion protein deposition was r = 0.786 (p < 0.05). Otherwise, correlation between uptake of 18 F-FDG and pathological prion protein was r = 0.357 (p = 0.385). Immunohistochemistry with β-amyloid did not show amyloid deposition or neuritic plaques. Our study supports the use of FDG-PET in the assessment of CJD. FDG-PET may be especially useful in cases of suspected CJD and negative MRI. Furthermore, this case report provides more evidence about the behavioral of amyloid tracers, and the possibility of a low-affinity binding to other non-amyloid proteins, such as the pathological prion protein, is discussed.

  15. Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China

    Science.gov (United States)

    Gao, Yong; Tan, Aihua; Yang, Xiaobo; Zhang, Haiying; Hu, Yanling; Qin, Xue; Li, Shan; Zhang, Shijun; Mo, Linjian; Liang, Zhenjia; Shi, Deyi; Huang, Zhang; Guan, Yingyong; Zhou, Jicheng; Winkler, Cheryl; O'Brien, Stephen J.; Xu, Jianfeng; Mo, Zengnan; Peng, Tao

    2014-01-01

    Background Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. Methods and Findings Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). Conclusions We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China. PMID:24941225

  16. A differential autophagy-dependent response to DNA double-strand breaks in bone marrow mesenchymal stem cells from sporadic ALS patients.

    Science.gov (United States)

    Wald-Altman, Shane; Pichinuk, Edward; Kakhlon, Or; Weil, Miguel

    2017-05-01

    Amyotrophic lateral sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors that leads to neuromuscular degeneration and has pathophysiological implications in non-neural systems. Our previous work showed abnormal levels of mRNA expression for biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in the brain, spinal cord and muscle of the SOD1 G93A ALS mouse model. These observations support the idea that there is a pathophysiological relevance for the ALS biomarkers discovered in human mesenchymal stem cells (hMSCs) isolated from bone marrow samples of ALS patients (ALS-hMSCs). Here, we demonstrate that ALS-hMSCs are also a useful patient-based model to study intrinsic cell molecular mechanisms of the disease. We investigated the ALS-hMSC response to oxidative DNA damage exerted by neocarzinostatin (NCS)-induced DNA double-strand breaks (DSBs). We found that the ALS-hMSCs responded to this stress differently from cells taken from healthy controls (HC-hMSCs). Interestingly, we found that ALS-hMSC death in response to induction of DSBs was dependent on autophagy, which was initialized by an increase of phosphorylated (p)AMPK, and blocked by the class III phosphoinositide 3-kinase (PI3K) and autophagy inhibitor 3-methyladenine (3MeA). ALS-hMSC death in response to DSBs was not apoptotic as it was caspase independent. This unique ALS-hMSC-specific response to DNA damage emphasizes the possibility that an intrinsic abnormal regulatory mechanism controlling autophagy initiation exists in ALS-patient-derived hMSCs. This mechanism may also be relevant to the most-affected tissues in ALS. Hence, our approach might open avenues for new personalized therapies for ALS. © 2017. Published by The Company of Biologists Ltd.

  17. The evolving genetic risk for sporadic ALS.

    Science.gov (United States)

    Gibson, Summer B; Downie, Jonathan M; Tsetsou, Spyridoula; Feusier, Julie E; Figueroa, Karla P; Bromberg, Mark B; Jorde, Lynn B; Pulst, Stefan M

    2017-07-18

    To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALS-associated genes in patients with SALS vs 324 normal controls. Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates. © 2017 American Academy of Neurology.

  18. Clinical and neuroimaging characteristics of 14 patients with prionopathy: a descriptive study.

    Science.gov (United States)

    Ortega-Cubero, S; Pagola, I; Luquin, M R; Viteri, C; Pastor, P; Gállego Pérez-Larraya, J; de Castro, P; Domínguez, I; Irimia, P; Martínez-Vila, E; Arbizu, J; Riverol, M

    2015-04-01

    Prionopathy is the cause of 62% of the rapidly progressive dementias (RPD) in which a definitive diagnosis is reached. The variability of symptoms and signs exhibited by the patients, as well as its different presentation, sometimes makes an early diagnosis difficult. Patients withdiagnosis of definite or probable prionopathy during the period 1999-2012 at our hospital were retrospectively reviewed.The clinical features and the results of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic analysis) were evaluated in order to identify some factors that may enable an earlier diagnosis to be made. A total of 14 patients are described: 6 with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4 with fatal familial insomnia, and 1 with the new variant. The median age at diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was the most common feature, followed by instability and cognitive impairment. 14-3-3 protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI) studies suggested the diagnosis in 13 of the 14 patients included. Most patients presenting with RPD suffer from a prion disease. In our series the most useful complementary tests were MRI and FDG-PET, being positive in 13 of the 14 patients studied. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  19. White matter involvement in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Caverzasi, Eduardo; Mandelli, Maria Luisa; DeArmond, Stephen J; Hess, Christopher P; Vitali, Paolo; Papinutto, Nico; Oehler, Abby; Miller, Bruce L; Lobach, Irina V; Bastianello, Stefano; Geschwind, Michael D; Henry, Roland G

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (PCreutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean

  20. Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer.

    Directory of Open Access Journals (Sweden)

    Marica Garziera

    Full Text Available OBJECTIVE: To screen and characterize germline variants for E-cadherin (CDH1 in non-hereditary gastric cancer (GC patients and in subjects at risk of GC. METHODS: 59 GCs, 59 first degree relatives (FDRs of GC, 20 autoimmune metaplastic atrophic gastritis (AMAGs and 52 blood donors (BDs were analyzed for CDH1 by direct sequencing, structural modelling and bioinformatics. Functional impact on splicing was assessed for intronic mutations. E-cadherin/β-catenin immunohistochemical staining and E-cadherin mRNA quantification using RT-PCR were performed. RESULTS: In GCs, 4 missense variants (p.G274S; p.A298T; p.T470I; p.A592T, 1 mutation in the 5'UTR (-71C>G and 1 mutation in the intronic IVS12 (c.1937-13T>C region were found. First pathogenic effect of p.A298T mutation was predicted by protein 3D modelling. The novel p.G274S mutation showed a no clear functional significance. Moreover, first, intronic IVS12 (c.1937-13T>C mutation was demonstrated to lead to an aberrant CDH1 transcript with exon 11 deletion. This mutation was found in 2 GCs and in 1 BD. In FDRs, we identified 4 variants: the polymorphic (p.A592T and 3 mutations in untranslated regions with unidentified functional role except for the 5'UTR (-54G>C that had been found to decrease CDH1 transcription. In AMAGs, we detected 2 alterations: 1 missense (p.A592T and 1 novel variant (IVS1 (c.48+7C>T without effect on CDH1 splicing. Several silent and polymorphic substitutions were found in all the groups studied. CONCLUSIONS: Overall our study improves upon the current characterization of CDH1 mutations and their functional role in GC and in individuals at risk of GC. Mutations found in untranslated regions and data on splicing effects deserve a particular attention like associated with a reduced E-cadherin amount. The utility of CDH1 screening, in addition to the identification of other risk factors, could be useful for the early detection of GC in subjects at risk (i.e. FDRs and AMAGs, and

  1. Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection

    International Nuclear Information System (INIS)

    El-Mokadem, Ismail; Lim, Alison; Kidd, Thomas; Garret, Katherine; Pratt, Norman; Batty, David; Fleming, Stewart; Nabi, Ghulam

    2016-01-01

    Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on

  2. Characteristics of Korean patients with suspected Creutzfeldt-Jakob disease with 14-3-3 protein in cerebrospinal fluid: Preliminary study of the Korean Creutzfeldt-Jakob disease active surveillance program.

    Science.gov (United States)

    Lim, Jae-Sung; Kwon, Hyung-Min; Jang, Jae-Won; Ju, Young-Ran; Kim, SuYeon; Park, Young Ho; Park, So Young; Kim, SangYun

    2015-01-01

    Although Korea had a national surveillance system for Creutzfeldt-Jakob disease (CJD), it was mainly dependent on attending physician's reports. Thus, little prospective data about the epidemiology, characteristics, and final diagnoses of suspected patients were available. We have established a nationwide network for the active surveillance of patients with suspected CJD. When the requested cerebrospinal fluid (CSF) samples tested positive for 14-3-3 protein, we investigated the clinical characteristics of the corresponding patients and followed them until their final diagnoses were confirmed. A total of 218 samples were requested for CSF assays from May 2010 to August 2012, and 106 (48.6%) were positive for 14-3-3 protein. In 89 patients with complete clinical data, 38 (42.7%) were diagnosed with probable CJD and the estimated annual occurrence of CJD was 16.3 persons-per-year. The most common diagnoses of the remainder were central nervous system infection and any-cause encephalopathy. Non-CJD subjects showed worse initial consciousness levels than CJD patients. This preliminary study showed that the number of reported cases of CJD and the true positivity rates of CSF 14-3-3 protein assays were both low in Korea. An active surveillance system is urgently needed to provide the latest nationwide epidemiological data of CJD.

  3. Visual art therapy in sporadic Creutzfeldt-Jakob disease: a case study.

    Science.gov (United States)

    Shrestha, Rajeet; Trauger-Querry, Barbara; Loughrin, Athena; Appleby, Brian S

    2016-01-01

    This paper describes the diagnostic and treatment utility of visual art therapy in a case of sporadic Creutzfeldt-Jakob disease. Visual art therapy was compared longitudinally with clinical and neuroimaging data over five-month period in an autopsy-confirmed case of sporadic Creutzfeldt-Jakob disease of MM2-cortical subtype. Art therapy sessions and content were useful in ascertaining neuropsychiatric symptoms during the course of her illness. Art therapy offered a unique emotional and cognitive outlet as illness progressed. Patients and families affected by sporadic Creutzfeldt-Jakob disease may benefit from art therapy despite the rapidly progressive nature of the illness. Art therapy can also be useful for assessment of patients with sporadic Creutzfeldt-Jakob disease by healthcare professionals.

  4. MAJOR MOLECULAR GENETIC DRIVERS IN SPORADIC PRIMARY HYPERPARATHYROIDISM.

    Science.gov (United States)

    Arnold, Andrew

    2016-01-01

    Primary hyperparathyroidism is primarily due to a solitary parathyroid adenoma but multi-gland disease, parathyroid carcinoma, and ectopic parathyroid hormone production can occur. Although primary hyperparathyroidism mostly presents sporadically, strong familial predispositions also exist. Much is known about heritable genetic mutations responsible for these syndromes, including multiple endocrine neoplasia types 1 and 2A, hyperparathyroidism-jaw tumor syndrome, and familial hypocalciuric hypercalcemia. Acquired mutations in common sporadic hyperparathyroidism have also been discovered. Here we focus on the most common and well-established genetic drivers: 1) involvement of the oncogene cyclin D1 in human neoplasia was first established in parathyroid adenomas, followed by recognition of its importance in other tumor types including breast cancer and B-lymphoid malignancy; and 2) somatic mutation of the MEN1 gene, first identified as the source of pathogenic germline mutations in patients with familial endocrinopathies, is found in a substantial fraction of non-familial parathyroid adenomas.

  5. Sporadic Creutzfeldt-Jakob disease: a clinico-neuropathological analysis of nine definite cases Doença de Creutzfeldt-Jakob do tipo esporádico: análise clínico-neuropatológica de nove casos da forma definida

    Directory of Open Access Journals (Sweden)

    CARLOS M. DE CASTRO COSTA

    1998-09-01

    Full Text Available The authors have analyzed clinico-neuropathologically nine cases of the definite sporadic form of Creutzfeldt-Jakob disease (CJD. All cases were female, with mean age of 62.7 years. Eighty-nine percent of the patients exhibited prodromal and initial psychiatric symptoms; definite signs of dementia, and myoclonus were present in 100% of cases. The EEG was abnormal in all cases and pseudoperiodic paroxysms were present in 56% of the patients. Their evolution time ranged from 3 to 19 months. Neuropathologically, brain and cerebellar atrophy, spongiosis, astrocytosis and neuronal loss were present in 100% of the patients. In 5 (56% of these 9 cases, prion protein (PrP amyloid plaques were detected in the cerebellum, by optical- and electronmicroscopy. There was a positive correlation between the number of plaques and the evolution time. The authors outline the similarities of their cases in the elderly with the new variant of CJD described in young people.Os autores analisaram, do ponto de vista clínico e neuropatológico, nove casos da forma esporádica definida da doença de Creutzfeldt-Jakob (DCJ. Todos eles eram mulheres, com idade média de 62,7 anos. Oitenta e nove por cento dos pacientes exibiram sintomas psiquiátricos prodrômicos e iniciais; sinais típicos de demência e mioclonias estavam presentes em 100% deles. O EEG foi anormal em todos os casos e apresentou paroxismos pseudoperiódicos em 56% dos pacientes. O tempo de evolução da doença variou de 3 a 19 meses. Do ponto de vista neuropatológico, atrofia cerebral e cerebelar, espongiose, astrocitose e perda neuronal estavam presentes em 100% dos pacientes. Em 5 (56% dos 9 casos, foi evidenciada, por microscopia óptica e eletrônica, a presença de placas amilóides de proteína prion (PrP no cerebelo. Havia correlação positiva entre o número de placas e o tempo de evolução da doença. Os autores salientam as semelhanças desses seus casos de pacientes idosos com a nova

  6. Creutzfeldt-Jakob disease in Ireland: epidemiological aspects 1980-2002.

    LENUS (Irish Health Repository)

    Horan, Gail

    2012-02-03

    Surveillance for Creutzfeldt-Jakob disease (CJD) has been carried out in the Republic of Ireland since 1980. Initial surveillance was passive and based on consented autopsy confirmation of CJD in patients in whom there was a high index of clinical suspicion. Since 1999, an active surveillance programme involving formal notification of all suspect CJD cases has been in place. The annual mortality rate has increased from 0.34 cases\\/million in 1980 to 1.27 cases\\/million in 2001. In all, 29 cases have been pathologically confirmed: 1 had variant CJD (vCJD), 1 had iatrogenic human growth hormone-induced CJD and 1 had fatal insomnia. Sporadic CJD (sCJD) accounted for the remainder. This paper details the change in incidence over 22 years as the surveillance programme in Ireland got under way; the increased incidence is attributed to better case ascertainment, as has occurred in other countries where active surveillance programmes have been established.

  7. Screening of hypoxia-inducible genes in sporadic ALS.

    LENUS (Irish Health Repository)

    Cronin, Simon

    2008-10-01

    Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations in these genes may reduce the levels or functioning of their products. VEGF and ANG belong to a larger group of angiogenic genes that are up-regulated under hypoxic conditions. We hypothesized that common genetic variation across other members of this group may also predispose to sporadic ALS. To screen other hypoxia-inducible angiogenic genes for association with SALS, we selected 112 tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes. Screening for association was performed in 270 Irish individuals with typical SALS and 272 ethnically matched unrelated controls. SNPs showing association in the Irish phase were genotyped in a replication sample of 281 Swedish sporadic ALS patients and 286 Swedish controls. Seven markers showed association in the Irish. The one modest replication signal observed in the Swedish replication sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs. the Irish cohort. We failed to detect association of common variation across 24 candidate hypoxia-inducible angiogenic genes with SALS.

  8. MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

    Science.gov (United States)

    Moda, Fabio; Suardi, Silvia; Di Fede, Giuseppe; Indaco, Antonio; Limido, Lucia; Vimercati, Chiara; Ruggerone, Margherita; Campagnani, Ilaria; Langeveld, Jan; Terruzzi, Alessandro; Brambilla, Antonio; Zerbi, Pietro; Fociani, Paolo; Bishop, Matthew T; Will, Robert G; Manson, Jean C; Giaccone, Giorgio; Tagliavini, Fabrizio

    2012-09-01

    In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  9. Genetic instability in inherited and sporadic leukemias.

    Science.gov (United States)

    Popp, Henning D; Bohlander, Stefan K

    2010-12-01

    Genetic instability due to increased DNA damage and altered DNA repair is of central significance in the initiation and progression of inherited and sporadic human leukemias. Although very rare, some inherited DNA repair insufficiency syndromes (e.g., Fanconi anemia, Bloom's syndrome) have added substantially to our understanding of crucial mechanisms of leukemogenesis in recent years. Conversely, sporadic leukemias account for the main proportion of leukemias and here DNA damaging reactive oxygen species (ROS) play a central role. Although the exact mechanisms of increased ROS production remain largely unknown and no single pathway has been detected thus far, some oncogenic proteins (e.g., the activated tyrosine kinases BCR-ABL1 and FLT3-ITD) seem to play a key role in driving genetic instability by increased ROS generation which influences the disease course (e.g., blast crisis in chronic myeloid leukemia or relapse in FLT3-ITD positive acute myeloid leukemia). Of course other mechanisms, which promote genetic instability in leukemia also exist. A newly emerging mechanism is the genome-wide alteration of epigenetic marks (e.g., hypomethylation of histone H3K79), which promotes chromosomal instability. Taken together genetic instability plays a critical role both in inherited and sporadic leukemias and emerges as a common theme in both inherited and sporadic leukemias. Beyond its theoretical impact, the analysis of genetic instability may lead the way to the development of innovative therapy strategies. © 2010 Wiley-Liss, Inc.

  10. Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

    DEFF Research Database (Denmark)

    Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei

    2017-01-01

    BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are ...... provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.......BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas...... was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p

  11. Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease

    Science.gov (United States)

    Gargini, Ricardo; García, Esther; Perry, George

    2017-01-01

    Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients' fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging. PMID:29201274

  12. FDG-PET in Creutzfeldt-Jakob disease: Analysis of clinical-PET correlation.

    Science.gov (United States)

    Renard, Dimitri; Castelnovo, Giovanni; Collombier, Laurent; Thouvenot, Eric; Boudousq, Vincent

    2017-11-02

    To assess the relationship between clinical pattern and cerebral glucose metabolism on [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in Creutzfeldt-Jakob disease (CJD). Predefined clinical signs (ataxia, visual, pyramidal, myoclonus, limb apraxia, limb dystonia, sensory, parkinsonism, and corticobasal syndrome [CBS]) and FDG-PET data were assessed in consecutive CJD patients. Two types of statistical parametric mapping (SPM) analyses, using stringent level of significance p < 0.001 and extent threshold of 100 voxels, were performed: one comparing CJD patients presenting specific sign against CJD patients without this specific sign (inter-CJD analysis), and one comparing CJD patients with specific sign against 18 healthy controls (CJD-control analysis). Fifteen CJD patients (11 probable and two histologically proven sporadic and two genetic CJD) were analyzed. CJD-control analysis of the entire CJD group showed lateralized frontal and parietal hypometabolism. When analyzing clinical CJD subgroups, inter-CJD analyses showed hypometabolism in more restricted areas than on CJD-control analyses. For CJD patients presenting with ataxia, visual signs and CBS (and CBS-associated signs), additional hypometabolic areas probably related to the specific signs were identified: pons and middle cerebellar peduncles in patients with ataxia; occipital cortex in patients with visual signs; and prerolandic and lateral parietal cortex in patients with CBS. For pyramidal signs, sensory loss, and parkinsonism, no abnormalities in brain areas typically involved in these signs were observed. In addition to lateralized frontal and parietal hypometabolism previously reported in CJD and observed here, hypometabolism in brain areas related to some specific signs (i.e. ataxia, visual signs, and CBS) is also seen.

  13. Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study.

    Directory of Open Access Journals (Sweden)

    Sylvain Kirzin

    Full Text Available Sporadic early onset colorectal carcinoma (EOCRC which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45-60 years were excluded to help define "young" and "old" groups. Thirty-nine cases of sporadic EOCRC (patients ≤ 45 years with microsatellite stable tumors were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013. Genetic studies also showed the absence of BRAF mutations (p = 0.022 and the methylator phenotype (p = 0.005 in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01. This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the

  14. Mutations in the RET proto-oncogene in sporadic pheochromocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Thibodeau, S.N.; Lindor, N.M.; Honchel, R. [Mayo Clinic and Foundation, Rochester, MN (United States)] [and others

    1994-09-01

    Mutations in the RET proto-oncogene have recently been demonstrated in kindreds with Multiple Endocrine Neoplasia (MEN) types 2A and 2B. Both of these autosomal dominant disorders are characterized by the development of neoplasia in cell lines of neural crest origin, such as medullary throid carcinomas and pheochromocytomas. Individuals with MEN 2B have, in addition, ganglioneuromas of the lips, tongue and colon, a marfanoid habitus, and corneal nerve thickening. Approximately 90% of patients with MEN 2A have a germline mutation in exons 10 or 11, while 95% of patients with MEN 2B have a T{yields}C transition in codon 918 of exon 16. In this study, pheochromocytomas from 29 individuals who had no clinical evidence of MEN 2A or 2B (sporadic) were examined for the presence of either germline or somatic mutations in exons 10, 11, and 16 of the RET proto-oncogene. Of the 29 tumors examined, 3 (10%) were found to have a mutation in one of the three exons. One tumor had a G{yields}A transition in codon 609 (exon 10), another had a 6 bp deletion encompassing codons 632 & 633 (exon 11), and the final tumor had a T{yields}C transition in codon 918 (exon 16). These mutations were not found in the corresponding normal DNA from these individuals, indicating that the mutation were somatic in origin. Although we cannot exclude the possibility of mutations in other regions of the RET proto-oncogene, our data suggests that: (1) individuals presenting with apparently sporadic pheochromocytomas are not likely to have undiagnosed MEN 2A or 2B; and (2) somatic mutations in the RET proto-oncogene contribute to the process of tumorigenesis in a small percentage of sporadic pheochromocytomas.

  15. Antithyroideaantistof hos to patienter med subakut dementiel udvikling, ataksi og myoklonus

    DEFF Research Database (Denmark)

    Kondziella, Daniel; Hansen, Klaus; Gonzalez, Teresa

    2012-01-01

    Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both disorders can have a similar clinical presentation. Two women, 67 and 63 year-old, with subacute dementia, ataxia, myoclonus...... and positive antithyroid antibodies were given oral steroids. Whereas one progressively declined and had histopathologically proven CJD, the other made a complete recovery and was diagnosed with HE. Anti-thyroid antibodies can occur in CJD, but when present in a patient with subacute dementia, ataxia...

  16. The driver landscape of sporadic chordoma.

    Science.gov (United States)

    Tarpey, Patrick S; Behjati, Sam; Young, Matthew D; Martincorena, Inigo; Alexandrov, Ludmil B; Farndon, Sarah J; Guzzo, Charlotte; Hardy, Claire; Latimer, Calli; Butler, Adam P; Teague, Jon W; Shlien, Adam; Futreal, P Andrew; Shah, Sohrab; Bashashati, Ali; Jamshidi, Farzad; Nielsen, Torsten O; Huntsman, David; Baumhoer, Daniel; Brandner, Sebastian; Wunder, Jay; Dickson, Brendan; Cogswell, Patricia; Sommer, Josh; Phillips, Joanna J; Amary, M Fernanda; Tirabosco, Roberto; Pillay, Nischalan; Yip, Stephen; Stratton, Michael R; Flanagan, Adrienne M; Campbell, Peter J

    2017-10-12

    Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

  17. A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic nontoxic goiter

    NARCIS (Netherlands)

    Wesche, M. F.; Tiel-V Buul, M. M.; Lips, P.; Smits, N. J.; Wiersinga, W. M.

    2001-01-01

    A randomized clinical trial was performed in consecutive patients with sporadic nontoxic nodular goiter to compare efficacy and side effects of iodine-131 ((131)I) therapy with suppressive levothyroxine (L-thyroxine) treatment. Sixty-four patients were randomized after stratification for sex and

  18. Clinical characteristics of familial and sporadic age-related macular degeneration: differences and similarities

    NARCIS (Netherlands)

    Saksens, N.T.M.; Kersten, E.; Groenewoud, J.M.M.; Grinsven, M.J.J.P. van; Ven, J.P.H. van de; Sanchez, C.I.; Schick, T.; Fauser, S.; Hollander, A.I. den; Hoyng, C.B.; Boon, C.J.F.

    2014-01-01

    PURPOSE: We describe the differences and similarities in clinical characteristics and phenotype of familial and sporadic patients with age-related macular degeneration (AMD). METHODS: We evaluated data of 1828 AMD patients and 1715 controls enrolled in the European Genetic Database. All subjects

  19. KCNQ1OT1 hypomethylation: A Novel disguised genetic predisposition in sporadic pediatric adrenocortical tumors?

    NARCIS (Netherlands)

    Wijnen, Mark; Alders, Mariëlle; Zwaan, Christian M.; Wagner, Anja; van den Heuvel-Eibrink, Marry M.

    2012-01-01

    Pediatric adrenal tumors, other than neuroblastoma, are rare and can be associated with a genetic predisposition. In this report we describe two patients with an isolated and apparently sporadic adrenocortical tumor; one girl with a carcinoma, the other girl with an adenoma. In both patients genetic

  20. Imaging movement-related activity in medicated Parkin-associated and sporadic Parkinson's disease

    DEFF Research Database (Denmark)

    van Eimeren, Thilo; Binkofski, Ferdinand; Buhmann, Carsten

    2010-01-01

    Treatment-related motor complications such as dyskinesias are a major problem in the long-term management of Parkinson's disease (PD). In sporadic PD, a relatively early onset of the disease is known to be associated with an early development of dyskinesias. Although linked with early onset...... selected movements. Patients with Parkin-associated and sporadic PD showed no difference in movement-related activation patterns. Moreover, the covariates 'age' and 'disease duration' similarly influenced brain activation in both patient groups. The present finding suggests that a stable long-term motor...

  1. Polimorfismo da apolipoproteína e nos familiares em primeiro grau de pacientes com doença de Alzheimer familial ou esporádica Apolipoprotein e polymorphism in first-degree relatives of patients with familial or sporadic Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    João de Castilho Cação

    2007-06-01

    Full Text Available INTRODUÇÃO: A apolipoproteína E (apo E é reconhecida como fator de risco para doença de Alzheimer (DA. OBJETIVO: Analisar o polimorfismo da apo E nos familiares em primeiro grau de pacientes com DA familial ou esporádica do tipo tardio, comparando a famílias sem DA. MÉTODO: Foram estudados 40 pacientes com DA familial ou esporádica do tipo tardio, sendo os grupos classificados como provável, segundo critérios da NINCS-ADRDA. RESULTADO: O alelo épsilon3 foi o mais freqüente em todos os grupos. Observou-se freqüência mais elevada de épsilon4 comparando os familiares dos probandos aos do grupo controle (pINTRODUCTION: Apolipoproteín E (apo E has been recognized as a risk factor for Alzheimer disease (AD. OBJECTIVE: To analyze apo E polymorphism in first-degree relatives of patients with familial or sporadic late-onset AD comparing with families without AD. METHOD: Forty patients with familial or sporadic late-onset of AD, being both groups classified as probable, according of NINCS-ADRDA’s criteria. RESULTS: Allele epsilon3 was the most frequent in all of these groups. Higher frequency of epsilon4 when comparing the relatives of the probands with the relatives of the control group (p<0,0001 was observed. Allele epsilon2 showed significant difference only between relatives of familial AD and relatives of control group (p=0,026. CONCLUSION: Apo E polymorphism has not differentiated familial from sporadic AD. The study of families allows to amplify the alelles epsilon2 and epsilon4 representativity, revealing, their value as protecting factor and of risk for AD, respectively.

  2. Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Victoria Gonzalo

    Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant

  3. Prion disease. The characteristics and diagnostic points in Japan

    International Nuclear Information System (INIS)

    Sanjo, Nobuo; Mizusawa, Hidehiro

    2010-01-01

    Prion disease develops when normal prion proteins change into transmissible abnormal prion proteins and the converted proteins accumulate in the brain. The Japanese Creutzfeldt-Jakob Disease (CJD) Surveillance Committee has identified 1,320 patients with prion diseases in the 10 years since 1999 (classified into 3 types: sporadic, 77.2%; hereditary, 16.7%; and environmentally acquired, 6.1%). Compared with patients in other countries, a relatively larger number of Japanese patients characteristically have dura mater graft-associated CJD and hereditary prion diseases. All the environmentally acquired cases, except 1 case of variant CJD, were acquired from dura grafts. Although most patients were diagnosed with a classical subtype of sporadic CJD (sCJD), whose features include rapidly progressing dementia, myoclonus, hyperintensity in the cerebral cortex and basal ganglia in diffusion-weighted magnetic resonance imaging, and periodic synchronous discharge in electroencephalography, the number of cases with atypical symptoms, such as MM2 (0.8%), MV2 (0.2%), VV1 (0%), and VV2 (0.2%) subtypes of sCJD cases, was not negligible. Appropriate diagnosis should be made based on clinical features, neuroradiological findings, cerebrospinal fluid (CSF) findings (14-3-3 and total tau proteins), and genetic analysis of polymorphisms. Hereditary prion diseases are classified into 3 major phenotypes: familial CJD (fCJD); Gerstmann-Straeussler-Scheinker disease (GSS), which mainly presents as spinocerebellar ataxia; and fatal familial insomnia. Many mutations of the prion protein gene have been identified, but V1801 (fCJD), P102L (GSS), and E200K (fCJD) mutations were the most common among the fCJD cases in Japan. Without a family history, genetic testing is necessary to distinguish even seemingly ''sporadic'' CJD from fCJD. Accurate diagnosis is important for clarification of the pathological process, prevention of secondary infection, and also psychological support. (author)

  4. Physical function and muscle strength in sporadic inclusion body myositis

    DEFF Research Database (Denmark)

    Jørgensen, Anders N; Aagaard, Per; Nielsen, Jakob L

    2017-01-01

    INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s...... chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). RESULTS: TUG performance was the strongest predictor of self-reported physical function (r(2) = 0.56, P ... to sensitively predict self-perceived physical function in sIBM patients. Notably, between-limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve, 2017....

  5. Cathepsin D polymorphism in Italian sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Bagnoli, Silvia; Nacmias, Benedetta; Tedde, Andrea; Guarnieri, Bianca Maria; Cellini, Elena; Ciantelli, Monica; Petruzzi, Concetta; Bartoli, Antonella; Ortenzi, Luigi; Serio, Antonio; Sorbi, Sandro

    2002-08-16

    A recent study has shown that a genetic variation in the Cathepsin D (catD) gene is a major risk factor for the development of Alzheimer's disease (AD). CatD is an intracellular aspartyl protease involved in neurodegeneration. A C-->T (Ala-->Val) transition at position 224 has been associated with altered intracellular maturation. Recently, a significant overrepresentation of the T allele of the catD gene in AD patients compared with controls was reported. However, this finding has not yet been confirmed. We analyzed the distribution of catD and apolipoprotein E polymorphisms in Italian patients with sporadic and familial AD (FAD). Our studies revealed that the distribution of catD polymorphism did not differ in AD and FAD patients and controls. Thus, our data do not support a role for the catD gene as a genetic risk factor in the development of AD.

  6. Vision loss due to coincident ocular and central causes in a patient with Heidenhain variant Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Foundas, Maria; Donaldson, Mark D; McAllister, Ian L; Bridges, Leslie R

    2008-03-01

    Creutzfeldt-Jakob disease (CJD) is a degenerative disease of the brain associated with a rapidly progressive spongiform encephalopathy. Visual symptoms and neuro-ophthalmological signs are not infrequent, and presentation to an ophthalmologist may result. A case is reported of an 89-years-old gentleman who presented with a short history of isolated deterioration in vision. He underwent ocular intervention but subsequently developed progressive dementia, asterixis, myoclonus, cerebellar and extrapyramidal signs, and cortical blindness. An electroencephalogram was consistent with CJD. The patient progressively deteriorated and died 9 weeks after symptom onset. Limited post-mortem examination confirmed CJD.

  7. BRCAness profile of sporadic ovarian cancer predicts disease recurrence.

    Directory of Open Access Journals (Sweden)

    Weiya Z Wysham

    Full Text Available The consequences of defective homologous recombination (HR are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes.To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival.Protein microarray analysis of ovarian cancer tissue was used to determine protein expression levels for defined DNA repair proteins. Correlation with clinical and pathologic parameters in 186 patients with advanced stage III-IV and grade 3 ovarian cancer was analyzed using Chi square, Kaplan-Meier method, Cox proportional hazard model, and cumulative incidence function.High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04. Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03.Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance.

  8. An autopsy-verified case of FTLD-TDP type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Hayashi, Yuichi; Iwasaki, Yasushi; Takekoshi, Akira; Yoshikura, Nobuaki; Asano, Takahiko; Mimuro, Maya; Kimura, Akio; Satoh, Katsuya; Kitamoto, Tetsuyuki; Yoshida, Mari; Inuzuka, Takashi

    2016-11-01

    Here we report an autopsy-verified case of frontotemporal lobar degeneration (FTLD)-transactivation responsive region (TAR) DNA binding protein (TDP) type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD). A 69-year-old woman presented with an 11-month history of progressive dementia, irritability, insomnia, and gait disturbance without a family history of dementia or prion disease. Neurological examination revealed severe dementia, frontal signs, and exaggerated bilateral tendon reflexes. Periodic sharp-wave complexes were not observed on the electroencephalogram. Brain diffusion MRI did not reveal abnormal changes. An easy Z score (eZIS) analysis for 99m Tc-ECD-single photon emission computed tomography ( 99m Tc-ECD-SPECT) revealed a bilateral decrease in thalamic regional cerebral blood flow (rCBF). PRNP gene analysis demonstrated methionine homozygosity at codon 129 without mutation. Cerebrospinal fluid (CSF) analysis showed normal levels of both 14-3-3 and total tau proteins. Conversely, prion protein was slowly amplified in the CSF by a real-time quaking-induced conversion assay. Her symptoms deteriorated to a state of akinetic mutism, and she died of sudden cardiac arrest, one year after symptom onset.  Despite the SPECT results supporting a clinical diagnosis of MM2-thalamic-type sCJD, a postmortem assessment revealed that this was a case of FTLD-TDP type A, and excluded prion disease. Thus, this case indicates that whereas a bilateral decreasing thalamic rCBF detected by 99m Tc-ECD-SPECT can be useful for diagnosing MM2-thalamic-type sCJD, it is not sufficiently specific. Postmortem diagnosis remains the gold standard for the diagnosis of this condition.

  9. Glycoform-Selective Prion Formation in Sporadic and Familial Forms of Prion Disease

    Science.gov (United States)

    Xiao, Xiangzhu; Yuan, Jue; Haïk, Stéphane; Cali, Ignazio; Zhan, Yian; Moudjou, Mohammed; Li, Baiya; Laplanche, Jean-Louis; Laude, Hubert; Langeveld, Jan; Gambetti, Pierluigi; Kitamoto, Tetsuyuki; Kong, Qingzhong; Brandel, Jean-Philippe; Cobb, Brian A.; Petersen, Robert B.; Zou, Wen-Quan

    2013-01-01

    The four glycoforms of the cellular prion protein (PrPC) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrPSc) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrPSc in the recently identified variably protease-sensitive prionopathy (VPSPr) is the absence of a diglycosylated form, also notable in familial Creutzfeldt-Jakob disease (fCJD), which is linked to mutations in PrP either from Val to Ile at residue 180 (fCJDV180I) or from Thr to Ala at residue 183 (fCJDT183A). Here we report that fCJDV180I, but not fCJDT183A, exhibits a proteinase K (PK)-resistant PrP (PrPres) that is markedly similar to that observed in VPSPr, which exhibits a five-step ladder-like electrophoretic profile, a molecular hallmark of VPSPr. Remarkably, the absence of the diglycosylated PrPres species in both fCJDV180I and VPSPr is likewise attributable to the absence of PrPres glycosylated at the first N-linked glycosylation site at residue 181, as in fCJDT183A. In contrast to fCJDT183A, both VPSPr and fCJDV180I exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrPV180I with a typical glycoform profile from cultured cells generates detectable PrPres that also contains the diglycosylated PrP in addition to mono- and unglycosylated forms upon PK-treatment. Taken together, our current in vivo and in vitro studies indicate that sporadic VPSPr and familial CJDV180I share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrPC to PrPSc is inhibited, probably by a dominant-negative effect, or by other co-factors. PMID:23527023

  10. Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

    Science.gov (United States)

    Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong; Wang, Wenju; Jiang, Lihong

    2018-03-05

    BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (PASD (PASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

  11. Mutation analysis for DJ-1 in sporadic and familial parkinsonism: screening strategy in parkinsonism.

    Science.gov (United States)

    Tomiyama, Hiroyuki; Li, Yuanzhe; Yoshino, Hiroyo; Mizuno, Yoshikuni; Kubo, Shin-Ichiro; Toda, Tatsushi; Hattori, Nobutaka

    2009-05-22

    DJ-1 mutations cause autosomal recessive parkinsonism (ARP). Although some reports of DJ-1 mutations have been published, there is lack of information on the prevalence of these mutations in large-scale studies of both familial and sporadic parkinsonism. In this genetic screening study, we analyzed the distribution and frequency of DJ-1 mutations by direct nucleotide sequencing of coding exons and exon-intron boundaries of DJ-1, in 386 parkin-negative parkinsonism patients (371 index cases: 67 probands of autosomal recessive parkinsonism families, 90 probands of autosomal dominant parkinsonism families, 201 patients with sporadic parkinsonism, and 13 with unknown family histories) from 12 countries (Japan 283, China 27, Taiwan 22, Korea 22, Israel 16, Turkey 5, Philippines 2, Bulgaria 2, Greece 2, Tunisia 1, USA 2, Ukraine 1, unknown 1). None had causative mutation in DJ-1, suggesting DJ-1 mutation is very rare among patients with familial and sporadic parkinsonism from Asian countries and those with other ethnic background. This is in contrast to the higher frequencies and worldwide distribution of parkin- and PINK1-related parkinsonism in ARP and sporadic parkinsonism. Thus, after obtaining clinical information, screening for mutations in (1) parkin, (2) PINK1, (3) DJ-1, (4) ATP13A2 should be conducted in that order, in ARP and sporadic parkinsonism, based on their reported frequencies. In addition, haplotype analysis should be employed to check for homozygosity of 1p36, which harbors a cluster of causative genes for ARP such as DJ-1, PINK1 and ATP13A2 in ARP and sporadic parkinsonism, especially in parkinsonism with consanguinity.

  12. Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature

    Directory of Open Access Journals (Sweden)

    Nozières Cécile

    2011-10-01

    Full Text Available Abstract Background Somatotropinoma, a pituitary adenoma characterised by excessive production of growth hormone (GH, is extremely rare in childhood. A genetic defect is evident in some cases; known genetic changes include: multiple endocrine neoplasia type 1 (MEN1; Carney complex; McCune-Albright syndrome; and, more recently identified, aryl hydrocarbon receptor-interacting protein (AIP. We describe seven children with somatotropinoma with a special focus on the differences between genetic and sporadic forms. Methods Seven children who presented in our regional network between 1992 and 2008 were included in this retrospective analysis. First-type therapy was somatostatin (SMS analogues or transsphenoidal surgery. Control was defined as when insulin-like growth factor-1 (IGF-1 levels were within the normal range for the patient's age at 6 months after therapy, associated with decreasing tumour volume. Results Patients were aged 5-17 years and the majority (n = 6 were male. Four patients had an identified genetic mutation (McCune-Albright syndrome: n = 1; MEN1: n = 1; AIP: n = 2; the remaining three cases were sporadic. Accelerated growth rate was reported as the first clinical sign in four patients. Five patients presented with macroadenoma; invasion was noted in four of them (sporadic: n = 1; genetic: n = 3. Six patients were treated with SMS analogues; normalisation of IGF-1 occurred in one patient who had a sporadic intrasellar macroadenoma. Multiple types of therapy were necessary in all patients with an identified genetic mutation (4 types: n = 1; 3 types: n = 2; 2 types: n = 1, whereas two of the three patients with sporadic somatotropinoma required only one type of therapy. Conclusions This is the first series that analyzes the therapeutic response of somatotropinoma in paediatric patients with identified genetic defects. We found that, in children, genetic somatotropinomas are more invasive than sporadic somatotropinomas. Furthermore

  13. Cortical restricted diffusion as the predominant MRI finding in sporadic Creutzfeldt-Jakob disease

    Energy Technology Data Exchange (ETDEWEB)

    Talbott, Sabrina D.; Sattenberg, Ronald J.; Heidenreich, Jens O. (Dept. of Radiology, Univ. of Louisville, Louisville (United States)), e-mail: sdtalb02@gwise.louisville.edu; Plato, Brian M (Dept. of Neurology, Univ. of Louisville, Louisville (United States)); Parker, John (Dept. of Pathology and Laboratory Medicine, Univ. of Louisville, Louisville (United States))

    2011-04-15

    Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder with MR findings predominantly limited to the grey matter of the cortex and the basal ganglia. Sporadic Creutzfeldt-Jakob disease can produce a spectrum of MR imaging findings of the brain, most notably on DWI and FLAIR sequences. Involvement of the basal ganglia and neocortex is the most common finding, but isolated involvement of the cortex can also be seen. We describe the clinical history and MRI findings of three patients with sporadic Creutzfeldt-Jakob disease confirmed by brain biopsy or autopsy and review the literature of imaging manifestations of this disease

  14. Cortical restricted diffusion as the predominant MRI finding in sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Talbott, Sabrina D.; Sattenberg, Ronald J.; Heidenreich, Jens O.; Plato, Brian M; Parker, John

    2011-01-01

    Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder with MR findings predominantly limited to the grey matter of the cortex and the basal ganglia. Sporadic Creutzfeldt-Jakob disease can produce a spectrum of MR imaging findings of the brain, most notably on DWI and FLAIR sequences. Involvement of the basal ganglia and neocortex is the most common finding, but isolated involvement of the cortex can also be seen. We describe the clinical history and MRI findings of three patients with sporadic Creutzfeldt-Jakob disease confirmed by brain biopsy or autopsy and review the literature of imaging manifestations of this disease

  15. Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Statland, Jeffrey M; Barohn, Richard J; McVey, April L; Katz, Jonathan S; Dimachkie, Mazen M

    2015-11-01

    When approaching a patient with suspected motor neuron disease (MND), the pattern of weakness on examination helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing. MNDs exist on a spectrum, from a pure lower motor neuron to mixed upper and lower motor neuron to a pure upper motor neuron variant. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic, which is invariably fatal. This article describes a pattern approach to identifying MND and clinical features of sporadic ALS. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Hospital Admissions, Biological Therapy, and Surgery in Familial and Sporadic Cases of Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Trier Moller, Frederik; Andersen, Vibeke; Andersson, Mikael

    2015-01-01

    BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial...... and sporadic cases of IBD. However, patients with familial CD had significantly higher risk of major surgery than sporadic CD cases after 2 years of disease duration (hazard ratio, 1.62; 95% confidence interval, 1.26-2.07). Also, sensitivity analysis suggested a slightly reduced time from diagnosis to first......-related hospitalization, biological treatment, and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886 IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16 years, totaling 164,979 person-years. We observed no difference in risk of hospital admissions between familial...

  17. BRCA 1/2-Mutation Related and Sporadic Breast and Ovarian Cancers: More Alike than Different

    Science.gov (United States)

    Burgess, Melissa; Puhalla, Shannon

    2014-01-01

    No longer is histology solely predictive of cancer treatment and outcome. There is an increasing influence of tumor genomic characteristics on therapeutic options. Both breast and ovarian cancers are at higher risk of development in patients with BRCA 1/2-germline mutations. Recent data from The Cancer Genome Atlas and others have shown a number of genomic similarities between triple negative breast cancers (TNBCs) and ovarian cancers. Recently, poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising activity in hereditary BRCA 1/2-mutated and sporadic breast and ovarian cancers. In this review, we will summarize the current literature regarding the genomic and phenotypic similarities between BRCA 1/2-mutation related cancers, sporadic TNBCs, and sporadic ovarian cancers. We will also review Phase I, II, and III data using PARP inhibitors for these malignancies and compare and contrast the results with respect to histology. PMID:24579064

  18. Risk factors for sporadic ovarian cancer

    Directory of Open Access Journals (Sweden)

    M. M. Vysotsky

    2010-01-01

    Full Text Available The review of the literature on the problems of sporadic ovarian cancer details the present views of its disputable risk factors, such as dietary habits, body weight, contraception, and labor, and age of commencing a sexual activity. It discusses the dietary and sexual behavior model that has changed since the Neolithic, as well as the number of menses and ovulations throughout the reproductive peri- od. The works by authors dealing with the impact of smoking and alcohol consumption on the risk of ovarian cancer are analyzed.

  19. Immunohistochemistry for annexin A10 can distinguish sporadic from Lynch syndrome-associated microsatellite-unstable colorectal carcinoma.

    Science.gov (United States)

    Pai, Reetesh K; Shadrach, Bonnie L; Carver, Paula; Heald, Brandie; Moline, Jessica; Church, James; Kalady, Matthew F; Burke, Carol A; Plesec, Thomas P; Lai, Keith K; Gonzalo, David H; Pai, Rish K

    2014-04-01

    Differentiating sporadic microsatellite-unstable colorectal carcinoma due to MLH1 promoter hypermethylation from Lynch syndrome (LS)-associated tumors due to mutations in mismatch-repair proteins is time consuming, cost intensive, and requires advanced laboratory testing. A mutation in BRAF has been shown to be highly specific for sporadic tumors; however, a significant proportion of sporadic microsatellite-unstable tumors lack BRAF mutations. MLH1 promoter methylation analysis is subsequently used to differentiate LS and sporadic tumors, but both tests require specialized laboratories and are costly. Through previous gene expression profiling of serrated polyps, we identified annexin A10 as a protein highly expressed in sessile serrated adenomas/polyps. As these polyps give rise to the majority of sporadic microsatellite-unstable tumors, we evaluated the ability of annexin A10 expression to discriminate between LS and sporadic tumors. A marked increase in annexin A10 mRNA was observed in sporadic microsatellite-unstable tumors compared with LS tumors (378-fold increase, Pimmunohistochemistry, annexin A10 was expressed in 23/53 (43%) BRAF-mutated and 9/22 (41%) BRAF wild-type sporadic tumors. In contrast, only 3/56 (5%) LS tumors were positive for annexin A10 (Pimmunohistochemistry. Only 1/28 (4%) LS tumors with loss of MLH1 was positive for annexin A10. This patient did not have a deleterious MLH1 mutation but rather germline promoter hypermethylation of MLH1. On the basis of these results, immunohistochemistry for annexin A10 may be a useful marker to distinguish sporadic from LS-associated microsatellite-unstable colon cancer.

  20. Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Es, M.A. van; Vught, P.W. van; Veldink, J.H.; Andersen, P.M.; Birve, A.; Lemmens, R.; Cronin, S.; Kooi, A.J. van der; Visser, M. de; Schelhaas, H.J.; Hardiman, O.; Ragoussis, I.; Lambrechts, D.; Robberecht, W.; Wokke, J.H.J.; Ophoff, R.A.; Berg, L.H. van den

    2009-01-01

    A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS,

  1. Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case-control study

    NARCIS (Netherlands)

    S.M. Rosso (Sonia); E.J. Landweer; M. Houterman; C.M. van Duijn (Cornelia); J.C. van Swieten (John); L. Donker Kaat (Laura)

    2003-01-01

    textabstractA retrospective case-control study was carried out on 80 patients with sporadic frontotemporal dementia and 124 age, sex, and surrogate informant matched controls with respect to various medical and environmental risk factors. Head trauma was associated with an odds ratio of 3.3 (95%

  2. ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Bueno, R C; Canevari, R A; Villacis, R A R

    2014-01-01

    BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p...

  3. Sporadic nocturnal frontal lobe epilepsy: A consecutive series of 8 cases

    Directory of Open Access Journals (Sweden)

    Shih-Bin Yeh

    2014-09-01

    Discussion: These cases confirm that sporadic NFLE closely resembles familial NFLE, and comprises a set of distinct clinical manifestations, with variable intensity, and variable scalp EEG epileptiform abnormalities across sleep and wakefulness, which have previously been identified in Caucasian patients from Europe and North America.

  4. S182 and STM2 gene missense mutations in sporadic alzheimer disease

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Susumu; Matsushita, Sachio; Hasegawa, Yoshio; Muramatsu, Taro [Kurihama National Hospital, Yokosuka (Japan)] [and others

    1996-07-26

    The linkage of genes S182 and STM2 to early-onset or late-onset sporadic Alzheimer disease (AD) was not found in a group of 97 clinically-diagnosed AD patients and 46 autopsy-confirmed AD cases, using PCR-RFLP methods. 7 refs.

  5. High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

    Science.gov (United States)

    Sarika, H L; Papathoma, A; Garofalaki, M; Vasileiou, V; Vlassopoulou, B; Anastasiou, E; Alevizaki, M

    2012-12-01

    Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece. © 2012 Blackwell Publishing Ltd.

  6. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

    2015-01-01

    Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

  7. The First Report of a Patient with Probable Variant Creutzfeldt-Jakob Disease in Turkey

    Directory of Open Access Journals (Sweden)

    Demet Özbabalık Adapınar

    2011-12-01

    Full Text Available Variant Creutzfeldt-Jakob disease (vCJD was first reported in the UK in 1996. Here, we report the first Turkish case of vCJD. A 47-year-old man, who has never lived outside of Turkey and had had no transfusion, was admitted to the University Hospital with speech disorder, cognitive decline and ataxia following depression, irritability, and personality change. The immunoassay of the 14-3-3 protein in the cerebrospinal fluid was negative. Brain magnetic resonance imaging revealed high-signal lesions involving the bilateral caudate and lentiform nucleus on T2- and diffusion-weighted imaging. The patient developed akinetic mutism 10 months after disease onset. The clinical presentation and neuroimaging findings were compatible with the vCJD cases reported since 1996 and met the World Health Organization’s case definition for probable vCJD.

  8. Antithyroideaantistof hos to patienter med subakut dementiel udvikling, ataksi og myoklonus

    DEFF Research Database (Denmark)

    Kondziella, Daniel; Hansen, Klaus; Gonzalez, Teresa

    2012-01-01

    Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both disorders can have a similar clinical presentation. Two women, 67 and 63 year-old, with subacute dementia, ataxia, myoclonus and posit......Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both disorders can have a similar clinical presentation. Two women, 67 and 63 year-old, with subacute dementia, ataxia, myoclonus...... and positive antithyroid antibodies were given oral steroids. Whereas one progressively declined and had histopathologically proven CJD, the other made a complete recovery and was diagnosed with HE. Anti-thyroid antibodies can occur in CJD, but when present in a patient with subacute dementia, ataxia...

  9. Tumour suppressor genes in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies in the western world, and sporadic epithelial ovarian cancer is its most predominant form. The aetiology of sporadic ovarian cancer remains unknown. Genetic studies have enabled a better understanding...... of the evolution of tumour progression. A major focus of research has been to identify tumour suppressor genes implicated in sporadic ovarian cancer over the past decade. Several tumour suppressor genes have been identified by strategies such as positional cloning and differential expression display. Further...... research is warranted to understand fully their contribution to the pathogenesis of sporadic ovarian cancer....

  10. Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

    LENUS (Irish Health Repository)

    Kimmich, Okka

    2012-02-01

    Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects <50 years of age; 22 subjects >50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige\\'s syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1\\/61 (2%) control subjects, 27\\/32 (84%) patients with adult-onset primary torsion dystonia and 32\\/73 (44%) unaffected relatives [siblings (20\\/36; 56%), offspring (11\\/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.

  11. SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

    Directory of Open Access Journals (Sweden)

    Christine S. Higham

    2017-01-01

    Full Text Available Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1- associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST has been reported. Methods. We evaluated the objective response (OR rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%. Results. 34 NF1 (median age 33 years and 14 sporadic (median age 40 years MPNST patients enrolled. Five of 28 (17.9% evaluable NF1 MPNST patients had a partial response (PR, as did 4 of 9 (44.4% patients with sporadic MPNST. Stable disease (SD was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

  12. Radiosurgical treatment of sporadic vestibular schwannomas: A prospective cohort study

    International Nuclear Information System (INIS)

    Martel V, Freddy; Iniguez S, Rodrigo; Venencia M, Daniel; Tagle M, Patricio; Besa D, Pelayo; Lorenzoni S, Jose

    2008-01-01

    Objective: To analyze the preliminary experience of radiosurgery for Vestibular Schwannomas at the Pontificia Universidad Catolica de Chile. Material and methods: The first 17 patients with sporadic Vestibular Schwannomas treated by radiosurgery at our institution are reported. The marginal dose used was 12 to 12.5 Gy. prescribed at the 70 or 80 isodose fine. Patients were controlled at 6, 12 and 24 months with magnetic resonance, audiometric study and clinical examination. Results: In all of the 17 patients treated a decrease tumor enhancement on MR was demonstrated. In 16 patients (94%) a pattern of central tumor necrosis was observed during the firs year Actuarial useful hearing was maintained in 62.5% at 2 year after treatment. Facial nerve function was maintained in all of the 15 patients with normal function at treatment (100%). Trigeminal function was maintained in ah of the 14 patients (100%) with previous normal trigeminal function. The mean time to return to work or normal activities was 11.5 days after treatment. Conclusions: These preliminary results are comparable with results published in the literature and reinforce the demonstrate role of radiosurgery in the management of vestibular schwannomas

  13. Creutzfeldt jakob disease

    International Nuclear Information System (INIS)

    Haider, E.; Raja, S.; Wali, W.; Tariq, M.

    2013-01-01

    A case of 50 years of age, male with sporadic Creutzfeldt Jakob Disease (sCJD) is reported. Patient had dementia, behavioural abnormalities, unsteady gait and myoclonic jerks. Magnetic resonance imaging (MRI) brain T2 weighted and Fluid Attenuated Inverse Recovery (FLAIR) images showed abnormally increased signal intensity in caudate nucleus and putamen. Scalp electroencephalogram (EEG) revealed periodic synchronous biphasic sharp wave complexes. On the basis of history, clinical findings, typical MRI brain and EEG changes, diagnosis of sporadic CJD was made. (author)

  14. Dietary factors and microsatellite instability in sporadic colon carcinomas

    NARCIS (Netherlands)

    Diergaarde, B.; Braam, H.; Muijen, van G.N.P.; Ligtenberg, M.J.L.; Kok, F.J.; Kampman, E.

    2003-01-01

    Microsatellite instability (MSI) occurs in 10-20% of the sporadic colon carcinomas and appears to be primarily due to alterations in hMLH1 and hMSH2. Little is known about the role of diet in MSI-related colon carcinogenesis. We used data from a Dutch population-based case-control study on sporadic

  15. Predictors of Preoperative Tinnitus in Unilateral Sporadic Vestibular Schwannoma

    Directory of Open Access Journals (Sweden)

    Georgios Naros

    2017-08-01

    Full Text Available ObjectiveNearly two-thirds of patients with vestibular schwannoma (VS are reporting a significantly impaired quality of life due to tinnitus. VS-associated tinnitus is attributed to an anatomical and physiological damage of the hearing nerve by displacing growth of the tumor. In contrast, the current pathophysiological concept of non-VS tinnitus hypothesizes a maladaptive neuroplasticity of the central nervous system to a (hidden hearing impairment resulting in a subjective misperception. However, it is unclear whether this concept fits to VS-associated tinnitus. This study aims to determine the clinical predictors of VS-associated tinnitus to ascertain the compatibility of both pathophysiological concepts.MethodsThis retrospective study includes a group of 478 neurosurgical patients with unilateral sporadic VS evaluated preoperatively regarding the occurrence of ipsilateral tinnitus depending on different clinical factors, i.e., age, gender, tumor side, tumor size (T1–T4 according to the Hannover classification, and hearing impairment (Gardner–Robertson classification, GR1–5, using a binary logistic regression.Results61.8% of patients complain about a preoperative tinnitus. The binary logistic regression analysis identified male gender [OR 1.90 (1.25–2.75; p = 0.002] and hearing impairment GR3 [OR 1.90 (1.08–3.35; p = 0.026] and GR4 [OR 8.21 (2.29–29.50; p = 0.001] as positive predictors. In contrast, patients with large T4 tumors [OR 0.33 (0.13–0.86; p = 0.024] and complete hearing loss GR5 [OR 0.36 (0.15–0.84; p = 0.017] were less likely to develop a tinnitus. Yet, 60% of the patients with good clinical hearing (GR1 and 25% of patients with complete hearing loss (GR5 suffered from tinnitus.ConclusionThese data are good accordance with literature about non-VS tinnitus indicating hearing impairment as main risk factor. In contrast, complete hearing loss appears a negative predictor for tinnitus. For the first

  16. Sporadic cases of adult measles: a research article.

    Science.gov (United States)

    Premaratna, Ranjan; Luke, Nathasha; Perera, Harsha; Gunathilake, Mahesh; Amarasena, Pubudu; Chandrasena, T G A Nilmini

    2017-01-10

    Measles caused by a paramyxovirus, characterized by fever, malaise, cough, coryza conjunctivitis, a maculopapular rash is known to result in pneumonia, encephalitis and death. Fatal cases of measles in Sri Lanka are rare after implementation of the National Immunization Programme in 1984. Thereafter 0.1% case fatality rate was observed during October 1999-June 2000 which is a very low figure compared to other regional countries. Immunization guidelines were further revised in 2001, 2011 and in 2012 when additional immunization was recommended to age group 4-21 years; who are likely to have inadequate immunization, in order to achieve elimination of Measles by 2020. However, in 2013-2014, 4690 cases were reported and the majority were children less than 1 year of age. The occurrence in adults is hard to retrieve in published epidemiological reports, however had been 38% (out of 1008 patients) in the 3rd quarter of 2013. During this outbreak 73/101 (72%) reported from the North Central Province of Sri Lanka had been more than 12 years of age with 50% being more than 29 years. 14 Sri lankan adult patients [median age 32 years (range 25-48)] who presented sporadically from June 2014 to March 2016, with confirmed measles infection were enrolled retrospectively after informed consent. Details with regards to their clinical presentation, immunization and other relevant areas were collected using an interviewer administered questionnaire or using patient management records. The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3-5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection. At least a 3-5

  17. The Heterogeneity Between Lynch-Associated and Sporadic MMR Deficiency in Colorectal Cancers.

    Science.gov (United States)

    Liu, Guo-Chen; Liu, Ran-Yi; Yan, Jun-Ping; An, Xin; Jiang, Wu; Ling, Yi-Hong; Chen, Jie-Wei; Bei, Jin-Xin; Zuo, Xiao-Yu; Cai, Mu-Yan; Liu, Ze-Xian; Zuo, Zhi-Xiang; Liu, Ji-Hong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2018-02-20

    Previous studies demonstrated that prognosis of germline deficiency in mismatch repair protein (dMMR) was different from that of sporadic dMMR. The underlying mechanism has not been studied. From a prospectively maintained database, we collected dMMR colorectal cancer (CRC) patients identified by postoperative immunohistochemistry screening. According to genetic test, patients were grouped as Lynch-associated or sporadic dMMR. We compared the clinical-pathological features, prognosis, and immunoreactive differences between the two groups. By whole-exome sequencing and neoantigen detection pipeline, mutational frequencies and neoantigen burdens were also compared. All statistical tests were two-sided. Sixty-seven sporadic dMMR and 85 Lynch-associated CRC patients were included in the study. Sporadic dMMR patients were older (P < .001) and their tumors were poorly differentiated (P = .03). The survival was better in the Lynch-associated group (P = .001). After adjustment, the difference still remained statistically significant (hazard ratio = 0.29, 95% confidence interval = 0.09 to 0.95, P = .04). The scores of Crohn's-like reaction (CRO; P < .001), immunoreactions in the invasive margin (IM; P = .01), tumor stroma (TS; P = .009), and cancer nest (CN; P = .02) of the Lynch-associated group were statistically significantly higher. The numbers of CD3+, CD8+, Foxp3+ tumor-infiltrating lymphocytes (TILs) in IM; CD3+, CD4+ TILs in TS; and CD3+, CD4+, CD8+ TILs in CN were statistically significantly higher in Lynch-associated dMMR patients. Based on the 16 patients who under went whole-exome sequencing, there were also more somatic mutations and neoantigen burdens in the Lynch-associated group compared with the sporadic dMMR group (439/pt vs 68/pt, P = .006; 628/pt vs 97/pt, P = .009). There are heterogeneities in dMMR CRCs. Lynch-associated dMMR patients present with more somatic mutations and neoantigens compared with sporadic dMMR, which probably results in stronger

  18. Immunoekspresja białka LAMP2 w ośrodkowym układzie nerwowym u osób chorych na sporadyczną postać choroby Creutzfeldta-Jakoba (sCJD

    Directory of Open Access Journals (Sweden)

    Piotr Gębski

    2010-09-01

    Full Text Available Wstęp: Sporadyczna postać choroby Creutzfeldta-Jakoba (sCJD to śmiertelna choroba neurologiczna z grupy pasażowalnych encefalopatii gąbczastych (TSE. Ze względu na obecność polimorfizmu w kodonie 129. genu PRNP oraz typ patologicznego białka PrPSc sCJD podzielono na 6 podtypów, różniących się obrazem histopatologicznym oraz spektrum objawów klinicznych. LAMP2 to białko błonowe będące składnikiem późnych endosomów i lizosomów, stanowiące waż- ny element systemu endosomalno-lizosomalnego odgrywającego kluczową rolę w procesach wewnątrzkomórkowej degradacji białek. Udowodniono, iż zaburzenia w systemach wewnątrzkomórkowej degradacji białek odgrywają istotną rolę w patogenezie chorób neurodegeneracyjnych. Celem pracy było określenie immunoekspresji białka LAMP2 w materiale pochodzącym od osób chorych na podtypy choroby sCJD. Materiał i metody: Materiałem do badań było 26 archiwalnych wycinków mózgów chorych na sCJD. Przy wykorzystaniu metod immunohistochemicznych oraz przy użyciu laserowego mikroskopu konfokalnego (Olympus FluoView 1000 oceniono immunoekspresję białek LAMP2 i PrPSc w zgromadzonym materiale. Grupę badaną podzielono na podgrupy ze względu na podtyp choroby sCJD. Wyniki półilościowej oceny siły reakcji immunohistochemicznych dla badanych białek poddano analizie statystycznej. Dokonano analizy korelacji pomiędzy średnimi wartościami siły reakcji immunohistochemicznych. Przy wykorzystaniu metody analizy wariancji oceniono różnice pomiędzy typami sCJD oraz pomiędzy grupami wiekowymi. Wyniki: W grupie badanej 7 przypadków stanowiły osoby z podtypem 1., 9 przypadków – osoby z podtypem 2., 2 przypadki – osoby z podtypem 3. i 1 przypadek – pacjent z podtypem 5. choroby sCJD. Wykazano istotne statystycznie korelacje pomiędzy siłą reakcji immunohistochemicznej dla białek LAMP2 i PrPSc. Znaleziono istotne statystycznie różnice pomiędzy podtypami sCJD ze wzgl

  19. [Lung transplantation in sporadic lymphangioleiomyomatosis: study of 7 cases].

    Science.gov (United States)

    Ansótegui Barrera, Emilio; Mancheño Franch, Nuria; Peñalver Cuesta, Juan Carlos; Vera-Sempere, Francisco; Padilla Alarcón, José

    2013-10-19

    Sporadic lymphangioleiomyomatosis (S-LAM) is a rare disease that affects only women. It is characterized by an abnormal proliferation of immature smooth muscle cells (LAM cells) that grow in an aberrant manner in the airway, parenchymal lung lymph and blood vessels, determining the onset of pulmonary cystic lesions. The disease has no treatment, progressing to respiratory failure, and lung transplantation (LT) may be a treatment option at this stage. Our goal was to study 7 patients undergoing LT for S-LAM. We studied a series of clinical and demographic characteristics, diagnostic modality and post-transplant outcomes. We performed a descriptive analysis of the series. The Kaplan-Meier method was used to estimate survival. The mean age of onset of symptoms was 35 years, the diagnosis of 37 years and that of LT 38 years. The most common symptom was dyspnea. Four patients had a history of pneumothorax and pleural effusion. The mean forced expiratory volume in one second was 32.7% and the diffusing capacity for carbon monoxide was 29%. All patients were subjected to LT and survival was 100, 85.7 and 57.1% at one, 3 and 5 years, respectively. Three died of bronchiolitis obliterans and 2 necropsies did not show evidence of disease recurrence. LT is a therapeutic option in patients with S-LAM with an advanced respiratory functional impairment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. BRCA promoter methylation in sporadic versus BRCA germline mutation-related breast cancers.

    Science.gov (United States)

    Vos, Shoko; Moelans, Cathy Beatrice; van Diest, Paul Joannes

    2017-05-31

    In breast cancer, BRCA promoter hypermethylation and BRCA germline mutations are said to occur together rarely, but this property has not yet been translated into a clinical test. Our aim in this study was to investigate the diagnostic value of BRCA1/2 methylation in distinguishing breast carcinomas of BRCA1 and BRCA2 germline mutation carriers from sporadic breast carcinomas using a recently developed BRCA methylation assay based on methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). MS-MLPAs were performed to assess BRCA1 and BRCA2 methylation in breast carcinoma tissues from 39 BRCA1 and 33 BRCA2 germline mutation carriers, 80 patients with sporadic breast cancer, and normal breast tissues from 5 BRCA1 and 4 BRCA2 mutation carriers and 5 nonmutation carriers. Methylation frequencies varied considerably between CpG sites across the BRCA1 and BRCA2 promoters. Some CpG sites were methylated more frequently in BRCA1/2-related than in sporadic carcinomas, whereas other CpG sites were methylated more frequently in sporadic carcinomas, with large variances in sensitivity and specificity as a consequence. The diagnostic value of BRCA promoter methylation analysis in distinguishing BRCA1/2-related from sporadic breast carcinomas seems to be considerably dependent on the targeted CpG sites. These findings are important for adequate use of BRCA methylation analysis as a prescreening tool for BRCA germline genetic testing or to identify BRCAness patients who may benefit from targeted therapies such as poly(adenosine diphosphate-ribose) polymerase inhibitors.

  1. Sporadic aurorae observed in East Asia

    Directory of Open Access Journals (Sweden)

    D. M. Willis

    2007-03-01

    Full Text Available All the accessible auroral observations recorded in Chinese and Japanese histories during the interval AD 1840–1911 are investigated in detail. Most of these auroral records have never been translated into a Western language before. The East Asian auroral reports provide information on the date and approximate location of each auroral observation, together with limited scientific information on the characteristics of the auroral luminosity such as colour, duration, extent, position in the sky and approximate time of occurrence. The full translations of the original Chinese and Japanese auroral records are presented in an appendix, which contains bibliographic details of the various historical sources. (There are no known reliable Korean observations during this interval. A second appendix discusses a few implausible "auroral" records, which have been rejected. The salient scientific properties of all exactly dated and reliable East Asian auroral observations in the interval AD 1840–1911 are summarised succinctly. By comparing the relevant scientific information on exactly dated auroral observations with the lists of great geomagnetic storms compiled by the Royal Greenwich Observatory, and also the tabulated values of the Ak (Helsinki and aa (Greenwich and Melbourne magnetic indices, it is found that 5 of the great geomagnetic storms (aa>150 or Ak>50 during either the second half of the nineteenth century or the first decade of the twentieth century are clearly identified by extensive auroral displays observed in China or Japan. Indeed, two of these great storms produced auroral displays observed in both countries on the same night. Conversely, at least 29 (69% of the 42 Chinese and Japanese auroral observations occurred at times of weak-to-moderate geomagnetic activity (aa or Ak≤50. It is shown that these latter auroral displays are very similar to the more numerous (about 50 examples of sporadic aurorae observed in the United States

  2. Sporadic aurorae observed in East Asia

    Directory of Open Access Journals (Sweden)

    D. M. Willis

    2007-03-01

    Full Text Available All the accessible auroral observations recorded in Chinese and Japanese histories during the interval AD 1840–1911 are investigated in detail. Most of these auroral records have never been translated into a Western language before. The East Asian auroral reports provide information on the date and approximate location of each auroral observation, together with limited scientific information on the characteristics of the auroral luminosity such as colour, duration, extent, position in the sky and approximate time of occurrence. The full translations of the original Chinese and Japanese auroral records are presented in an appendix, which contains bibliographic details of the various historical sources. (There are no known reliable Korean observations during this interval. A second appendix discusses a few implausible "auroral" records, which have been rejected. The salient scientific properties of all exactly dated and reliable East Asian auroral observations in the interval AD 1840–1911 are summarised succinctly. By comparing the relevant scientific information on exactly dated auroral observations with the lists of great geomagnetic storms compiled by the Royal Greenwich Observatory, and also the tabulated values of the Ak (Helsinki and aa (Greenwich and Melbourne magnetic indices, it is found that 5 of the great geomagnetic storms (aa>150 or Ak>50 during either the second half of the nineteenth century or the first decade of the twentieth century are clearly identified by extensive auroral displays observed in China or Japan. Indeed, two of these great storms produced auroral displays observed in both countries on the same night. Conversely, at least 29 (69% of the 42 Chinese and Japanese auroral observations occurred at times of weak-to-moderate geomagnetic activity (aa or Ak≤50. It is shown that these latter auroral displays are very similar to the more numerous (about 50 examples of sporadic

  3. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma.

    Science.gov (United States)

    Bayley, Jean-Pierre; Kunst, Henricus P M; Cascon, Alberto; Sampietro, Maria Lourdes; Gaal, José; Korpershoek, Esther; Hinojar-Gutierrez, Adolfo; Timmers, Henri J L M; Hoefsloot, Lies H; Hermsen, Mario A; Suárez, Carlos; Hussain, A Karim; Vriends, Annette H J T; Hes, Frederik J; Jansen, Jeroen C; Tops, Carli M; Corssmit, Eleonora P; de Knijff, Peter; Lenders, Jacques W M; Cremers, Cor W R J; Devilee, Peter; Dinjens, Winand N M; de Krijger, Ronald R; Robledo, Mercedes

    2010-04-01

    Paragangliomas and phaeochromocytomas are neuroendocrine tumours associated frequently with germline mutations of SDHD, SDHC, and SDHB. Previous studies have shown the imprinted SDHAF2 gene to be mutated in a large Dutch kindred with paragangliomas. We aimed to identify SDHAF2 mutation carriers, assess the clinical genetic significance of SDHAF2, and describe the associated clinical phenotype. We undertook a multicentre study in Spain and The Netherlands in 443 apparently sporadic patients with paragangliomas and phaeochromocytomas who did not have mutations in SDHD, SDHC, or SDHB. We analysed DNA of 315 patients for germline mutations of SDHAF2; a subset (n=200) was investigated for gross gene deletions. DNA from a group of 128 tumours was studied for somatic mutations. We also examined a Spanish family with head and neck paragangliomas with a young age of onset for the presence of SDHAF2 mutations, undertook haplotype analysis in this kindred, and assessed their clinical phenotype. We did not identify any germline or somatic mutations of SDHAF2, and no gross gene deletions were noted in the subset of apparently sporadic patients analysed. Investigation of the Spanish family identified a pathogenic germline DNA mutation of SDHAF2, 232G-->A (Gly78Arg), identical to the Dutch kindred. SDHAF2 mutations do not have an important role in phaeochromocytoma and are rare in head and neck paraganglioma. Identification of a second family with the Gly78Arg mutation suggests that this is a crucial residue for the function of SDHAF2. We conclude that SDHAF2 mutation analysis is justified in very young patients with isolated head and neck paraganglioma without mutations in SDHD, SDHC, or SDHB, and in individuals with familial antecedents who are negative for mutations in all other risk genes. Dutch Cancer Society, European Union 6th Framework Program, Fondo Investigaciones Sanitarias, Fundación Mutua Madrileña, and Red Temática de Investigación Cooperativa en Cáncer. 2010

  4. MTHFR polymorphisms as prognostic factors in sporadic colorectal cancer.

    Science.gov (United States)

    Osian, Gelu; Procopciuc, Lucia; Vlad, Liviu

    2007-09-01

    Theoretically, individuals having at least one mutant allele present a modified activity of the MTHFR enzyme and low methylation, DNA synthesis-repair respectively, which could imply a higher risk of colorectal cancer. The purpose of this study was to investigate the relations of these mutations with the clinico-pathological aspects of colorectal cancer. The study included 69 patients with sporadic colorectal cancer. The relative risk in homozygous patients with a normal allele and for mutations C667T and A1298C, in heterozygous patients with one normal and one mutant allele, and for homozygous patients for the mutant allele was calculated. C667T and A1298C mutations represent a risk factor for colorectal cancer with an OR (odds ratio) = 2.13 (CI (0.51-8.91)) and 3 (CI(0.3-29.58), respectively, in homozygous patients. These mutations are associated with a more frequent location of lesions at the colon level, OR=2.3 and 2.15 respectively. The incidence of the A1298C mutation was more frequent in stage N0 than N+ (p<0.05), pT2 vs. pT3 (p<0.05), as well as in Dukes stages B and D vs. A or C (p<0.05). The results obtained support the hypothesis of an increased colorectal cancer prevalence in patients with one of the MTHFR gene mutations. These patients develop colon cancer more frequently, they present lymph node invasion more rarely, and develop more often distant metastases.

  5. Mutation analysis of the RET gene in individuals with sporadic and familial pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Iyengar, S.; Sirugo, G.; Bale, A.E. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1994-09-01

    Pheochromocytoma is common to many familial cancer syndromes including multiple endocrine neoplasia type 2A (MEN2A), von Hippel-Lindau (VHL) and neurofibromatosis (NF). Although sporadic cases of pheochromocytoma have been examined for mutations in exons 10, 11 and 16 of the RET gene, only one case with a mutation in exon 16 has been reported thus far. We are performing systematic examination of exons of the RET gene, which has previously been associated with mutation in both MEN2 A and B, to determine the role RET may play in the etiology of pheochromocytoma. Seventeen cases of sporadic pheochromocytoma and 3 cases of sporadic medullary thyroid carcinoma were obtained from the pathology archives. Histopathology of all specimens was confirmed to be either pheochromocytoma or medullary thyroid carcinoma before DNA was extracted from 0.5{mu} thin sections of paraffin-embedded tissue. DNA from familial pheochromocytoma patients was also available for analysis. All sporadic and familial cases were amplified for exons 2, 6 and 16 of the RET gene. Single strand conformational polymorphism (SSCP) analysis was performed for exons 2 and 6. On finding a variation in the SSCP pattern in the pheochromocytoma kindred we sequenced all the samples for exon 2. A single base pair variation was found, which did not segregate with pheochromocytoma in the family. No variant SSCP patterns have been observed with the exon 6 PCR products thus far. Exon 16 PCR products were subjected to DNA restriction analysis with Fok I. This enzyme detects a single base pair change associated with MEN2 B. With the exception of one sample with sporadic medullary thyroid carcinoma, all samples showed the normal pattern on DNA restriction analysis. Thus we can exclude exons 2 and 6 of the RET gene in the pathogenesis of pheochromocytoma. SSCP analyses with other exons in the RET gene are underway.

  6. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

  7. Reducing Aircraft Down for Lack of Parts with Sporadic Demand

    National Research Council Canada - National Science Library

    Bachman, Tovey

    2004-01-01

    .... Because of their sporadic demand, it is difficult to decide when to buy these items and in what quantities. As systems become more reliable and failure rates decrease, the number of these infrequently demanded parts is likely to grow...

  8. Post-and prenatal testing for FSHD: Diagnostic approach for sporadic and familial cases

    Energy Technology Data Exchange (ETDEWEB)

    Bakker, E.; Wielen, M.J.R. van der; Losekoot, M. [Leiden Univ. (Netherlands)] [and others

    1994-09-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder. A major locus for FSHD was localized at the distal part of chromosome 4q. More recently, a disease associated DNA rearrangement was detected with the polymorphic probe p13E-11 (D4F104S1). In most FSHD patients, a shortened (< 28 kb instead of 50-300 kb) allele was detected. In sporadic patients a de novo deletion was found to be associated with the occurrence of FSHD. Diagnostically there were a number of problems to overcome. (1) About 5% of families show no linkage to chromosome 4q35. (2) Some 10% normal individuals show a shortened p13E11 allele, which is located at chromosome 10q. Our diagnostic strategy is as follows: If in sporadic patients a shortened p13E-11 allele is detected and neither parent shows this allele, then a de novo deletion has occurred and FSHD is proven. If no shortened allele is detected FSHD is less likely. In case one of the parents shows a shortened allele then clinical investigations and linkage studies are performed for both chromosome 4 and 10 markers. In familial cases both p13E-11 and polymorphic markers are tested. A shortened p13E-11 allele and/or chromosome 4 haplotype segregating with FSHD can be used for presymptomatic and prenatal diagnosis. Up to now, 45 sporadic cases and 21 families were referred for diagnosis. In 22 sporadic cases a shortened allele was detected, 13 were proven de novo. The first prenatal test was recently performed. The index patient was a de novo case with a shortened allele; the fetus had inherited this allele.

  9. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  10. Clinical Significance of Microsatellite Instability in Sporadic Epithelial Ovarian Tumors

    OpenAIRE

    Yoon, Bo-Sung; Kim, Young-Tae; Kim, Jae-Hoon; Kim, Sang-Wun; Nam, Eun-Ji; Cho, Nam-Hoon; Kim, Jae-Wook; Kim, Sunghoon

    2008-01-01

    Purpose We evaluated the expression of microsatellite instability (MSI) in sporadic ovarian tumors using 5 standard and 9 new MSI markers to determine the clinical significance of MSI in sporadic epithelial ovarian tumors. Materials and Methods MSI was examined in 21 borderline and 25 malignant ovarian tumors. Polymerase chain reaction (PCR) was performed using the 5 markers recommended by the National Cancer Institute (NCI) for colon cancer and 9 additional markers. MSI was determined using ...

  11. Sporadic isolated congenital asplenia with fulminant pneumococcal meningitis: a case report and updated literature review.

    Science.gov (United States)

    Iijima, Shigeo

    2017-12-18

    Isolated congenital asplenia (ICA) is a rare and life-threatening condition that predisposes patients to severe bacterial infections. Most of the reported cases are familial and the mode of inheritance is usually autosomal dominant. Here, we report a case of sporadic isolated asplenia and review the literature while focusing on sporadic cases. We report the case of an 11-month-old female infant who developed fulminant pneumococcal meningitis. The pneumococcal vaccine-unimmunized patient was hospitalized with fever, irritability, and purpura, and was diagnosed as having meningitis, septic shock, and disseminated intravascular coagulation. Streptococcus pneumoniae was isolated from both cerebrospinal fluid and blood. She was successfully treated with prompt antibiotic therapy. During hospitalization, abdominal ultrasonography and computed tomography findings, scintigraphy results, and Howell-Jolly body-containing red blood cells indicated the presence of asplenia without any visceroarterial anomalies. Moreover, the findings of peripheral blood smears and spleen ultrasonographic examinations of her parents were normal. Majority of sporadic ICA cases were detected only after the onset of overwhelming infection and had a high mortality. In cases of severe invasive pneumococcal disease, a systematic search for Howell-Jolly bodies on blood smears and the presence of asplenia on abdominal imaging are essential for detecting ICA even in the absence of any family history. After the diagnosis of ICA, patient and parent education, vaccinations, antibiotic prophylaxis, and prompt empiric treatment of febrile episode should be provided.

  12. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    Directory of Open Access Journals (Sweden)

    Adriana Handra-Luca

    2015-01-01

    Full Text Available Thyroid heterotopic bone formation (HBF in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years. The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.. Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.. The number and size of HBFs (total: 28 ranged between 1 and 23/thyroid gland (one bilateral and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular. The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp. without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm, and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated.

  13. Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

    Science.gov (United States)

    Moura, M M; Cavaco, B M; Pinto, A E; Domingues, R; Santos, J R; Cid, M O; Bugalho, M J; Leite, V

    2009-01-01

    Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10–16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P=0.0051) and number of lymph node metastases (P=0.0017), and presented more often multifocal tumours (P=0.037) and persistent disease at last control (P=0.0242) than group 2. Detectable serum calcitonin levels at last screening (P=0.0119) and stage IV disease (P=0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk. PMID:19401695

  14. High-risk population in sporadic pancreatic adenocarcinoma: guidelines for screening.

    Science.gov (United States)

    Bruenderman, Elizabeth H; Martin, Robert C G

    2015-03-01

    Pancreatic cancer (PC) is one of the most deadly forms of cancer in the United States, with an annual incidence to death ratio of 0.92 because of the late stage at diagnosis. Identification of high-risk individuals (HRIs) that would be ideal for screening is needed to identify precursor lesions and small early stage disease. Those with a genetic predisposition have largely been identified, but little is known about those at high-risk for sporadic PC. This study asserts that a high-risk population does exist in sporadic pancreatic adenocarcinoma and proposes simple guidelines for screening. A systematic review was conducted of the literature regarding identification of and screening in high-risk groups. Those with the highest genetic risk of developing PC include those with hereditary pancreatitis (87 times more likely at age 55), Peutz-Jehgers syndrome (132 times more likely at age 50), p16-Leiden mutations (48 times more likely), and familial pancreatic cancer (FPC) kindreds (32 times more likely). Those with the highest risk of developing sporadic PC include those with new-onset diabetes older than 50 y and smoking history. Given that sporadic PC is the single largest patient population effected with this devastating disease, some form of screening should be initiated. Currently, the medical community does nothing to attempt early detection of PC. However, sufficient evidence now exists to begin a screening protocol in a high-risk cohort, which would be patients with new-onset diabetes older than 50 y and a smoking history. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Absence of RET proto-oncogene abnormalities in sporadic parathyroid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pausova, Z.; Janicic, N.; Konrad, E. [McGill Univ. and Royal Victoria Hospital, Montreal (Canada)] [and others

    1994-09-01

    Parathyroid tumors can occur either sporadically or as a part of inherited cancer syndromes such as multiple endocrine neoplasia (MEN) type 2A. Recently, development of this syndrome has been shown to be related to specific mutations in the RET proto-oncogene, a putative receptor tyrosine kinase. Activation of this proto-oncogene has been demonstrated not only in tumors of the MEN 2A syndrome, but also in other neoplasia of neuroectoderm origin, namely papillary thyroid carcinoma where a rearrangement of the RET proto-oncogene has been found. In the present study, a role of the RET proto-oncogene in the development of sporadic parathyroid tumors was investigated by analyzing DNA samples obtained from 13 parathyroid adenomas and 6 parathyroid hyperplasias. Southern blot, using BamHI restricted DNA, did not reveal any gross alteration of the gene. Polymerase chain reaction (PCR) was then employed to amplify DNA fragments corresponding to exons 10 and 11 in which all MEN 2A mutations have been identified. Amplified DNA fragments were all of expected size (exon 10, 182 bp; exon 11, 233 bp). Since a single point mutation at codon 634 has been found to be associated in close to 90% of cases with development of parathyroid tumors in patients with the MEN 2A syndrome, exon 11, containing this codon, was further examined by direct sequence analysis. Sequences obtained from all tumors tested, however, did not differ from the wild type sequence. Therefore, the mutation of the RET proto-oncogene commonly associated with parathyroid neoplasias in MEN 2A is uncommon in sporadic parathyroid tumors. This suggests that the pathogenesis of parathyroid tumors occurring sporadically may be different from those occurring in patients with the MEN 2A syndrome.

  16. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations

    NARCIS (Netherlands)

    Lakhani, S. R.; Jacquemier, J.; Sloane, J. P.; Gusterson, B. A.; Anderson, T. J.; van de Vijver, M. J.; Farid, L. M.; Venter, D.; Antoniou, A.; Storfer-Isser, A.; Smyth, E.; Steel, C. M.; Haites, N.; Scott, R. J.; Goldgar, D.; Neuhausen, S.; Daly, P. A.; Ormiston, W.; McManus, R.; Scherneck, S.; Ponder, B. A.; Ford, D.; Peto, J.; Stoppa-Lyonnet, D.; Bignon, Y. J.; Struewing, J. P.; Spurr, N. K.; Bishop, D. T.; Klijn, J. G.; Devilee, P.; Cornelisse, C. J.; Lasset, C.; Lenoir, G.; Barkardottir, R. B.; Egilsson, V.; Hamann, U.; Chang-Claude, J.; Sobol, H.; Weber, B.; Stratton, M. R.; Easton, D. F.

    1998-01-01

    BACKGROUND: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic

  17. Down-regulation of BRCA1 in chronic pancreatitis and sporadic pancreatic adenocarcinoma.

    Science.gov (United States)

    Beger, Carmela; Ramadani, Marco; Meyer, Stephan; Leder, Gerd; Krüger, Martin; Welte, Karl; Gansauge, Frank; Beger, Hans G

    2004-06-01

    BRCA1 and BRCA2 are considered to be breast cancer susceptibility genes that may also contribute to pancreatic cancer development because family studies revealed mutation carriers to have an increased risk of developing pancreatic cancer. However, as demonstrated for breast and ovarian cancer, inactivation of BRCA in sporadic diseases is based on alteration in gene expression or functional alteration. To study a potential correlation of BRCA1 and BRCA2 to chronic pancreatitis and development of sporadic pancreatic adenocarcinoma, we have analyzed the expression of these genes by quantitative PCR and performed immunohistochemical analyses in normal pancreatic tissues, chronic pancreatitis, and pancreatic cancer specimens. BRCA1 expression was down-regulated in chronic alcoholic pancreatitis, in particular on the RNA level. Furthermore, our data indicate suppressed BRCA1 expression in pancreatic cancer on both the RNA and protein levels. Quantitative analysis of BRCA1 protein expression demonstrated regular staining in 50% of tumor specimens tested and reduced staining in 50% of tumor specimens tested. Correlation with the clinical outcome revealed a significantly better 1-year overall survival for patients with BRCA1-regular as compared with BRCA1-reduced or BRCA1-absent tumors. In contrast, no substantial differences in BRCA2 expression were found in chronic pancreatitis and pancreatic cancer samples. Our data demonstrate alteration of BRCA1 expression in chronic pancreatitis and sporadic pancreatic adenocarcinoma. We, for the first time, provide evidence for a role of BRCA1 in pancreatic carcinogenesis of noninherited tumors and for clinical outcome.

  18. Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia.

    Science.gov (United States)

    Giordano, Ilaria; Harmuth, Florian; Jacobi, Heike; Paap, Brigitte; Vielhaber, Stefan; Machts, Judith; Schöls, Ludger; Synofzik, Matthis; Sturm, Marc; Tallaksen, Chantal; Wedding, Iselin M; Boesch, Sylvia; Eigentler, Andreas; van de Warrenburg, Bart; van Gaalen, Judith; Kamm, Christoph; Dudesek, Ales; Kang, Jun-Suk; Timmann, Dagmar; Silvestri, Gabriella; Masciullo, Marcella; Klopstock, Thomas; Neuhofer, Christiane; Ganos, Christos; Filla, Alessandro; Bauer, Peter; Tezenas du Montcel, Sophie; Klockgether, Thomas

    2017-09-05

    To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations. The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing. The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94 ± 0.74, p 10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6 ± 6.0 vs 16.0 ± 5.8, p = 0.0200) and a slower annual SARA increase (1.1 ± 2.3 vs 3.3 ± 3.2, p = 0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made. Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort. NCT02701036. © 2017 American Academy of Neurology.

  19. Similar phenotype characteristics comparing familial and sporadic premature ovarian failure.

    Science.gov (United States)

    Janse, Femi; Knauff, Erik A H; Niermeijer, Martinus F; Eijkemans, Marinus J; Laven, Joop S E; Lambalk, Cornelius B; Fauser, Bart C J M; Goverde, Angelique J

    2010-07-01

    Premature ovarian failure (POF) is characterized by secondary amenorrhea before the age of 40 years, along with repeated increased follicle-stimulating hormone and low estrogen concentrations. POF is considered a complex genetic disease with a familial presentation in 12% to 50% of cases. POF may originate from different genes and various gene-environment interactions. The aim of this study was to identify possible differences in phenotype comparing women with familial and women with sporadic POF. A multicenter study was initiated in the Netherlands using standardized phenotyping. For each woman, medical history, menstrual cycle, and fertility and smoking status were assessed and a standardized examination was performed. Based on a detailed three-generation family history, women were identified as having either familial (defined as having at least one relative with POF) or sporadic POF. A total of 58 familial cases and 142 sporadic cases of POF were identified. Maternal age at menopause was significantly lower in the women with familial compared with the women with sporadic POF (41.0 +/- 7.5 and 49.7 +/- 2.6 y, respectively; P hormone-binding globulin concentration was significantly higher in the women with familial than in the women with sporadic POF (73.6 +/- 37.1 and 55.2 +/- 26.9 nmol/L, respectively; P = 0.002). All other characteristics, such as parity, bone mineral density, and serum follicle-stimulating hormone and lipid levels were similar, as was the incidence of autoimmunity and cytogenetic abnormalities. Familial and sporadic POF do not differ in phenotype except for maternal menopause age and sex hormone-binding globulin concentration. Future studies are needed to unravel the genotype-phenotype interactions in POF.

  20. Differential diagnosis of Jakob-Creutzfeldt disease

    OpenAIRE

    Paterson, RW; Torres-Chae, CC; Kuo, AL; Ando, T; Nguyen, EA; Wong, K; DeArmond, SJ; Haman, A; Garcia, P; Johnson, DY; Miller, BL; Geschwind, MD

    2012-01-01

    Objectives: To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Design: Retrospective medical record review. Setting: A specialty referral center of a tertiary academic medical center. Participants: One hundred sixty-three serial patients over a 5.5-y...

  1. Sporadic colorectal cancer: Studying ways to an end

    Science.gov (United States)

    Fidalgo, Paulo; Filipe, Bruno; Albuquerque, Cristina; Fonseca, Ricardo; Chaves, Paula; Pereira, António D

    2015-01-01

    Introduction Although colorectal cancer (CRC) has often been regarded as a single entity, different pathways may lead to macroscopically similar cancers. These pathways may evolve into a patchy colonic field defect that we aimed to study in consecutive CRC patients. Methods In a single-center, observational, prospective study, consecutive CRC patients were included if surgery and a perioperative colonoscopy were planned. Personal and familial history data were collected. Tumors were studied for microsatellite instability (MSI) status, DNA repair protein expression (DRPE) and presence of BRAF and/or APC mutations. Macroscopically normal mucosa samples were tested for APC mutations. Presence and location of synchronous and metachronous adenomas and patient follow-up were analyzed. The association of two categorical variables was tested through the Fisher’s exact test (SPSS 19). Results Twenty-four patients (12 male, mean age 69 years) were studied. High-grade MSI (MSI-H) was found in eight tumors—these were significantly more common in the right colon (p = 0.047) and more likely to have an altered DRPE (p = 0.007). BRAF mutation was found in two of six tested MSI-H tumors. APC gene mutations were found in nine of 16 non-MSI-H tumors and absent in normal mucosa samples. There was a nonsignificant co-localization of CRC and synchronous adenomas and a significant co-localization (p = 0.05) of synchronous and metachronous adenomas. Discussion Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non-MSI-H tumors, the expected APC gene mutations were not detected by the most commonly used techniques in a high number of cases. More studies are needed to fully characterize these tumors and to search for common early events in normal mucosa patches, which might explain the indirect evidence found here for a field defect in the colon. PMID:27087959

  2. Clinical Perspective of Oxidative Stress in Sporadic ALS

    Science.gov (United States)

    D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

  3. Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Yacoub Magdi H

    2006-01-01

    Full Text Available Abstract Background To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH. Methods Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test. Results We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P Conclusion Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.

  4. Identification of epigenetically altered genes in sporadic amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Claudia Figueroa-Romero

    Full Text Available Amyotrophic lateral sclerosis (ALS is a terminal disease involving the progressive degeneration of motor neurons within the motor cortex, brainstem and spinal cord. Most cases are sporadic (sALS with unknown causes suggesting that the etiology of sALS may not be limited to the genotype of patients, but may be influenced by exposure to environmental factors. Alterations in epigenetic modifications are likely to play a role in disease onset and progression in ALS, as aberrant epigenetic patterns may be acquired throughout life. The aim of this study was to identify epigenetic marks associated with sALS. We hypothesize that epigenetic modifications may alter the expression of pathogenesis-related genes leading to the onset and progression of sALS. Using ELISA assays, we observed alterations in global methylation (5 mC and hydroxymethylation (5 HmC in postmortem sALS spinal cord but not in whole blood. Loci-specific differentially methylated and expressed genes in sALS spinal cord were identified by genome-wide 5mC and expression profiling using high-throughput microarrays. Concordant direction, hyper- or hypo-5mC with parallel changes in gene expression (under- or over-expression, was observed in 112 genes highly associated with biological functions related to immune and inflammation response. Furthermore, literature-based analysis identified potential associations among the epigenes. Integration of methylomics and transcriptomics data successfully revealed methylation changes in sALS spinal cord. This study represents an initial identification of epigenetic regulatory mechanisms in sALS which may improve our understanding of sALS pathogenesis for the identification of biomarkers and new therapeutic targets.

  5. Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease

    Science.gov (United States)

    Green, A; Thompson, E; Stewart, G; Zeidler, M; McKenzie, J; MacLeod, M; Ironside, J; Will, R; Knight, R

    2001-01-01

    OBJECTIVES—The detection of the protein 14-3-3 in the CSF has been shown to be a reliable and sensitive marker for sporadic Creutzfeldt-Jakob disease (CJD). Other brain-specific proteins such as neuron specific enolase (NSE), S-100b, and tau protein have also been reported to be increased in the CSF of patients with sporadic CJD. In 1996a variant of CJD (vCJD) was described which is likely to be causally linked to the bovine spongiform encephalopathy agent. This study reports and compares the findings of CSF brain specific protein analysis in 45 patients with vCJD and in 34 control patients.
METHODS—The CSF from 45 patients with vCJD and 34 controls were investigated for the presence of 14-3-3 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting with chemiluminescent detection. Tau protein, S-100b, and NSE concentrations in CSF were measured using enzyme immunoassays.
RESULTS—Protein 14-3-3 was detected in the CSF of 22/45 patients with vCJD and in 3/34 controls. The mean concentrations of NSE, S-100b, and tau protein in CSF were significantly raised in patients with vCJD compared with controls. The positive predictive value of CSF 14-3-3 was 86% and the negative predictive value was 63%. These values are lower than those reported for sporadic CJD. An increased CSF tau had a positive predictive value of 93% and a negative predictive value of 81%. The combination of CSF 14-3-3 and/or increased CSF tau had a positive predictive value of 91% and a negative predictive value of 84%.
CONCLUSIONS—CSF protein 14-3-3 is not as useful a marker for vCJD as it is for sporadic CJD. Increased concentration of CSF tau was found to be a sensitive marker of vCJD but as concentrations may be increased in many forms of non-CJD dementia, this may limit its usefulness as a diagnostic test.

 PMID:11385008

  6. Neuroradiology of human prion diseases, diagnosis and differential diagnosis.

    Science.gov (United States)

    Gaudino, Simona; Gangemi, Emma; Colantonio, Raffaella; Botto, Annibale; Ruberto, Emanuela; Calandrelli, Rosalinda; Martucci, Matia; Vita, Maria Gabriella; Masullo, Carlo; Cerase, Alfonso; Colosimo, Cesare

    2017-05-01

    Human transmissible spongiform encephalopathies (TSEs), or prion diseases, are invariably fatal conditions associated with a range of clinical presentations. TSEs are classified as sporadic [e.g. sporadic Creutzfeldt-Jakob disease (sCJD), which is the most frequent form], genetic (e.g. Gerstmann-Straussler-Scheinker disease, fatal familial insomnia, and inherited CJD), and acquired or infectious (e.g. Kuru, iatrogenic CJD, and variant CJD). In the past, brain imaging played a supporting role in the diagnosis of TSEs, whereas nowadays magnetic resonance imaging (MRI) plays such a prominent role that MRI findings have been included in the diagnostic criteria for sCJD. Currently, MRI is required for all patients with a clinical suspicion of TSEs. Thus, MRI semeiotics of TSEs should become part of the cultural baggage of any radiologist. The purposes of this update on the neuroradiology of CJD are to (i) review the pathophysiology and clinical presentation of TSEs, (ii) describe both typical and atypical MRI findings of CJD, and (iii) illustrate diseases mimicking CJD, underlining the MRI key findings useful in the differential diagnosis.

  7. Sporadic potassium layers and their connection to sporadic E layers in the mesopause region at Beijing, China

    Directory of Open Access Journals (Sweden)

    Jing Jiao

    2017-06-01

    Full Text Available A double-laser beam lidar to measure potassium (K layer at Beijing (40.5° N, 116.2° E was successfully developed in 2010. The parameters of sporadic Ks layers and their distributions were given. The seasonal distribution of Ks occurrence frequency was obtained, with two maxima in July and January. The seasonal distributions of sporadic Es layer occurrence frequency over Beijing differ from those of Ks. However, the good correlation between Es and Ks in the case-by-case studies supports the mechanism of neutralization of metal ions in a descending Es layer.

  8. Creutzfeldt-Jakob Disease

    Science.gov (United States)

    ... CJD: Sporadic CJD develops spontaneously for no known reason. It accounts for 85 percent of cases. On average, sporadic CJD first appears between ages 60 and 65. Familial CJD is caused by certain changes in the chromosome 20 gene coding the biological ...

  9. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    I. Zerr; K. Kallenberg; D.M. Summers; C. Romero; A. Taratuto; U. Heinemann; M. Breithaupt; D. Varges; B. Meissner; A. Ladogana (Anna); M. Schuur (Maaike); S. Haik; S.J. Collins (Steven); G.H. Jansen (Gerard); G.B. Stokin; J. Pimentel; E. Hewer; D. Collie; P. Smith; H. Roberts; J.P. Brandel; P. Tikka-Kleemola (Päivi); M. Pocchiari (Maurizio); C. Begue; P. Cras (Patrick); R.G. Will; P. Sanchez-Juan (Pascual)

    2009-01-01

    textabstractSeveral molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications

  10. Comparing Sporadic and Outbreak-associated Foodborne Illness

    Centers for Disease Control (CDC) Podcasts

    2016-11-04

    Dr. Eric Ebel, a veterinarian and risk analyst with USDA’s Food Safety and Inspection Service, discusses his article on sporadic and outbreak-associated cases of foodborne illness.  Created: 11/4/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/4/2016.

  11. Prevalence of Abnormal Cervical Smears from Sporadic Screening ...

    African Journals Online (AJOL)

    The aim of the study was to find the prevalence of abnormal smears in an unscreened population of sexually active women attending a gynaecological clinic. “Pap” smears were taken sporadically for cytological examination from sexually active women attending gynaecological clinics at the Federal Medical Centre Gombe.

  12. Cyclin D1 genotype and expression in sporadic hemangioblastomas.

    NARCIS (Netherlands)

    Gijtenbeek, J.M.M.; Sprenger, S.H.E.; Franke, B.; Wesseling, P.; Jeuken, J.W.M.

    2005-01-01

    Central nervous system (CNS) hemangioblastomas are highly-vascularized tumors occurring in sporadic form or as a manifestation of von Hippel-Lindau disease (VHL). The VHL protein (pVHL) regulates various target genes, one of which is the CCND1 gene, encoding cyclin D1, a protein that plays a

  13. Dyschromatosis symmetrica hereditaria: Report of a sporadic case ...

    African Journals Online (AJOL)

    ... hands and feet, with no family history of similar lesions. The diagnosis was confirmed by the typical histologic finding of basal hyperpigmentation with normal number of melanocytes and absence of melanin incontinence from a hyperpigmented lesion. Keywords: DyschromatosisSymmetricaHereditaria, Nigerian, Sporadic ...

  14. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  15. [The practice guideline 'Dermatomyositis, polymyositis and sporadic inclusion body myositis'

    NARCIS (Netherlands)

    Hoogendijk, J.E.; Bijlsma, J.W.J.; Engelen, B.G.M. van; Lindeman, E.J.M.; Royen-Kerkhof, A. van; Rie, M.A. de; Visser, M. de; Jennekens, F.G.I.

    2005-01-01

    This guideline presents recommendations for the diagnosis and treatment of dermatomyositis, polymyositis and sporadic inclusion body myositis (sIBM) according to the best available evidence. Characteristic skin abnormalities can be sufficient for the diagnosis of dermatomyositis. In case of doubt, a

  16. When does ALS start? ADAR2-GluA2 hypothesis for the etiology of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Takuto eHideyama

    2011-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most common adult-onset motor neuron disease. More than 90% of ALS cases are sporadic, and the majority of sporadic ALS patients do not carry mutations in genes causative of familial ALS; therefore, investigation specifically targeting sporadic ALS is needed to discover the pathogenesis. The motor neurons of sporadic ALS patients express unedited GluA2 mRNA at the Q/R site in a disease-specific and motor neuron-selective manner. GluA2 is a subunit of the AMPA receptor, and it has a regulatory role in the Ca2+-permeability of the AMPA receptor after the genomic Q codon is replaced with the R codon in mRNA by adenosine-inosine conversion, which is mediated by adenosine deaminase acting on RNA 2 (ADAR2. Therefore, ADAR2 activity may not be sufficient to edit all GluA2 mRNA expressed in the motor neurons of ALS patients. To investigate whether deficient ADAR2 activity plays pathogenic roles in sporadic ALS, we generated genetically modified mice (AR2 in which the ADAR2 gene was conditionally knocked out in the motor neurons. AR2 mice showed an ALS-like phenotype with the death of ADAR2-lacking motor neurons. Notably, the motor neurons deficient in ADAR2 survived when they expressed only edited GluA2 in AR2/GluR-BR/R (AR2res mice, in which the endogenous GluA2 alleles were replaced by the GluR-BR allele that encoded edited GluA2. In heterozygous AR2 mice with only one ADAR2 allele, approximately 20% of the spinal motor neurons expressed unedited GluA2 and underwent degeneration, indicating that half-normal ADAR2 activity is not sufficient to edit all GluA2 expressed in motor neurons. It is likely therefore that the expression of unedited GluA2 causes the death of motor neurons in sporadic ALS. We hypothesize that a progressive downregulation of ADAR2 activity plays a critical role in the pathogenesis of sporadic ALS and that the pathological process commences when motor neurons express unedited GluA2.

  17. [Sporadic juvenile forms of Huntington's chorea].

    Science.gov (United States)

    Zinchenko, A P; Goncharov, V D; Burtianskii, D L; Zakhar'ev, Iu M

    1980-01-01

    Six patients with Huntington's chorea in the age of 15-24 years old, suffered from diffusive choreic hyperkynesis with slowly progressive dementia. The development of this disease in childhood and adolescence was atypical, as nobody in the family and in kin sufferred from it and it was difficult to diagnose the disease. Recognition of the disease was promoted by pneumoencephalography, electromyography and memory investigation.

  18. Is sporadic Alzheimer's disease a developmental disorder?

    Science.gov (United States)

    Arendt, Thomas; Stieler, Jens; Ueberham, Uwe

    2017-11-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of higher age that specifically occurs in human. Its clinical phase, characterized by a decline in physiological, psychological, and social functioning, is preceded by a long clinically silent phase of at least several decades that might perhaps even start very early in life. Overall, key functional abilities in AD patients decline in reverse order of the development of these abilities during normal childhood and adolescence. Early symptoms of AD, thus, typically affect mental functions that have been acquired only during very recent hominid evolution and as such are specific to human. Neurofibrillar degeneration, a typical neuropathological lesion of the disease and one of the most robust pathological correlates of cognitive impairment, is rarely seen in non-primate mammals and even non-human primates hardly develop a pathology comparable to those seen in AD patients. Neurofibrillar degeneration is not randomly distributed throughout the AD brain. It preferentially affects brain areas that become increasingly predominant during the evolutionary process of encephalization. During progression of the disease, it affects cortical areas in a stereotypic sequence that inversely recapitulates ontogenetic brain development. The specific distribution of cortical pathology in AD, moreover, appears to be determined by the modular organization of the cerebral cortex which basically is a structural reflection of its ontogeny. Here, we summarize recent evidence that phylogenetic and ontogenetic dimensions of brain structure and function provide the key to our understanding of AD. More recent molecular biological studies of the potential pathogenetic role of a genomic mosaic in the brains of patients with AD might even provide arguments for a developmental origin of AD. This article is part of a series "Beyond Amyloid". © 2017 International Society for Neurochemistry.

  19. Transarterial ethanol ablation for sporadic and non-hemorrhaging angiomyolipoma in the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Takebayashi, Shigeo [Department of Radiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024 (Japan)], E-mail: take2922@urahp.yokohama-cu.ac.jp; Horikawa, Ayumi; Arai, Mito; Iso, Shinichiroh [Department of Radiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024 (Japan); Noguchi, Kazumi [Department of Urology, Yokohama City University Medical Center, Yokohama (Japan)

    2009-10-15

    Purpose: We evaluated the efficacy and side effects of transarterial ethanol ablation in sporadic and non-hemorrhaging angiomyolipomas (AMLs) in the kidney. Material and Methods: A total of 10 patients with solitary and sporadic AMLs underwent selective transarterial absolute ethanol ablation for prophylaxis against hemorrhage. We confirmed the ratio areas of tumor vessel on angiogram, those of infraction on post-ablation computed tomography (CT) and those of tumor reduction in a 3-, 6- and 12-month follow-up CT. Results: Once or twice a single infusion of 1 or 2 ml absolute ethanol achieved in a total occlusion of 22 feeding arteries which consisted of 7 proximal interlobar arteries, 12 distal interlobar arteries and 3 renal capsular arteries. Nontarget occlusion did not occur by ethanol reflux in any cases but occurred causing spasms provoked by repeated inflation and deflation of the balloon in one case. Total occlusion of tumor vessels was observed in 7 patients and 92-95% occlusion in 3. Ethanol ablation produced 1.8-22.5% (mean 8.4 {+-} 6.8%) areas of infarctions but the outcome was not serious in all cases. Mean percentage areas of tumor reduction were 29.4 {+-} 10.6% in a 3-month follow-up, 45.7 {+-} 11.9% in a 6-month and 59.3 {+-} 11.5% in a 12-month follow-up. Conclusions: Absolute ethanol ablation for sporadic and non-hemorrhaging AML is safe and effective in reducing majority of tumor area in a 1-year follow-up.

  20. Advanced atherosclerosis is associated with increased medial degeneration in sporadic ascending aortic aneurysms.

    Science.gov (United States)

    Albini, Paul T; Segura, Ana Maria; Liu, Guanghui; Minard, Charles G; Coselli, Joseph S; Milewicz, Dianna M; Shen, Ying H; LeMaire, Scott A

    2014-02-01

    The pathogenesis of non-familial, sporadic ascending aortic aneurysms (SAAA) is poorly understood, and the relationship between ascending aortic atherosclerosis and medial degeneration is unclear. We evaluated the prevalence and severity of aortic atherosclerosis and its association with medial degeneration in SAAA. Atherosclerosis was characterized in ascending aortic tissues collected from 68 SAAA patients (mean age, 62.9 ± 12.0 years) and 15 controls (mean age, 56.6 ± 11.4 years [P = 0.07]) by using a modified American Heart Association classification system. Upon histologic examination, 97% of SAAA patients and 73% of controls showed atherosclerotic changes. Most SAAA samples had intermediate (types 2 and 3, 35%) or advanced atherosclerosis (types ≥ 4; 40%), whereas most control samples showed minimal atherosclerosis (none or type 1, 80%; P atherosclerosis grade. Advanced atherosclerosis was associated with higher grades of smooth muscle cell depletion (P atherosclerosis than in patients with minimal (P = 0.04) or intermediate atherosclerosis (P = 0.04). Immunostaining showed marked CD3+ T-cell and CD68+ macrophage infiltration, MMP-2 and MMP-9 production, and cryopyrin expression in the medial layer adjacent to atherosclerotic plaque. SAAA tissues exhibited advanced atherosclerosis that was associated with severe medial degeneration and increased aortic diameter. Our findings suggest a role for atherosclerosis in the progression of sporadic ascending aortic aneurysms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. The RET protooncogene in sporadic pheochromocytomas: Frequent multiple endocrine neoplasias type 2 - like mutations and new molecular defects

    Energy Technology Data Exchange (ETDEWEB)

    Beldjord, C.; Desclaux-Arramond, F.; Raffin-Sanson, M. [Universitat Rene Descartes, Paris (France)] [and others

    1994-09-01

    To assess the pathophysiological role of the RET protooncogene in sporadic pheochromocytomas, we examined the two regions of the gene in which molecular defects are specifically associated with the Multiple Endocrine Neoplasias (MEN) type 2A (exons 8-11) and type 2B (exon 16). The sequences of both regions were amplified by RT-PCR or PCR from tumor RNA and/or constitutive DNA. The amplified products were analyzed by denaturing gradient gel electrophoresis using chemical clamps. In 28 patients with unilateral sporadic tumors six RET mutations were found: three in the MEN2A region, and three in the MEN2B region. Five patients had missense mutations: two in the MEN2A region (C634W and D631Y), and three in the MEN2B region (M918T). Analysis of leukocyte DNA in three of these patients confirmed that RET mutations were only present in tumor DNA. The sixth patient had lost exon 10 in the tumor cDNA due to the deletion of the dinucleotide AG at the 3{prime} splice acceptor site of intron 9; this molecular defect was only found in the tumor DNA. Thus RET mutations of the MEN 2A and MEN 2B regions are also found in ca. 20% of sporadic pheochromocytomas. We describe new types of molecular defects of the RET protooncogene in the MEN2A region which involve non-cysteine residues and the loss of exon 10. Further studies should be extended to analyze the entire RET gene. These findings have a profound clinical impact for the management of patients with supposedly sporadic pheochromocytomas.

  2. Does the survival motor neuron copy number variation play a role in the onset and severity of sporadic amyotrophic lateral sclerosis in Malians?

    Directory of Open Access Journals (Sweden)

    Modibo Sangare

    2016-06-01

    Conclusion: Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.

  3. The Role of Iron In Sporadic E Layers

    Science.gov (United States)

    Vondrak, T.; Woodcock, K. R. I.; Plane, J. M. C.

    Sporadic E layers in the lower thermosphere are mostly composed of metallic ions, of which Fe+ is the most abundant. Because dielectric recombination (Fe+ + elec- tron) is very slow, the lifetime of Fe+ above about 100 km is at least several days. However, below this height molecular ions such as FeO+, FeO2+ and FeN2+ form in- creasingly rapidly through reactions with O3, O2 and N2, respectively. These undergo rapid dissociative recombination with electrons, causing Fe+ to be neutralised increas- ingly rapidly as a sporadic E layer descends. Indeed, this is the most likely mechanism for the formation of the sporadic neutral Fe layers that are observed by lidar. However, atomic O plays a very important role in reducing these molecular ions back to Fe+, competing with dissociative recombination and thus slowing the rate at which Fe+ is neutralised and a sporadic E layer dissipates. This paper will discuss a laboratory and modelling study of the reactions of FeO+, FeO2+ and FeN2+ with atomic O. These reactions were studied (for the first time) in a fast flow tube, using the pulsed laser ablation of a rotating iron rod as the source of Fe+ ions in the upstream section of the tube. Reactants were then added to produce molecular ions, and atomic O further downstream through a movable injector. Fe+ and the molecular ions were detected at the downstream end of the tube using a two-stage quadrupole mass spectrometer. The spectroscopy of the FeO+ ion, observed by laser induced fluorescence, will also be discussed as a candidate for future ground-based lidar studies of the ion chemistry of the lower thermosphere.

  4. Measurements of the ionization heights of sporadic radio-meteors

    International Nuclear Information System (INIS)

    Baggaley, W.J.; Webb, T.H.

    1980-01-01

    The echo heights and echo point ionization densities of 4587 sporadic radio-meteors have been determined using a calibrated interferometric height-finding system. Over the height interval 92 to 96 km no association was found between height and ionization but, for radio-meteors ablating above and below this region, significant and opposite trends exist in the data. It is suggested that this could be evidence for the influx of two distinct meteoroid populations. (author)

  5. Stable and sporadic symbiotic communities of coral and algal holobionts

    Science.gov (United States)

    Hester, Eric R; Barott, Katie L; Nulton, Jim; Vermeij, Mark JA; Rohwer, Forest L

    2016-01-01

    Coral and algal holobionts are assemblages of macroorganisms and microorganisms, including viruses, Bacteria, Archaea, protists and fungi. Despite a decade of research, it remains unclear whether these associations are spatial–temporally stable or species-specific. We hypothesized that conflicting interpretations of the data arise from high noise associated with sporadic microbial symbionts overwhelming signatures of stable holobiont members. To test this hypothesis, the bacterial communities associated with three coral species (Acropora rosaria, Acropora hyacinthus and Porites lutea) and two algal guilds (crustose coralline algae and turf algae) from 131 samples were analyzed using a novel statistical approach termed the Abundance-Ubiquity (AU) test. The AU test determines whether a given bacterial species would be present given additional sampling effort (that is, stable) versus those species that are sporadically associated with a sample. Using the AU test, we show that coral and algal holobionts have a high-diversity group of stable symbionts. Stable symbionts are not exclusive to one species of coral or algae. No single bacterial species was ubiquitously associated with one host, showing that there is not strict heredity of the microbiome. In addition to the stable symbionts, there was a low-diversity community of sporadic symbionts whose abundance varied widely across individual holobionts of the same species. Identification of these two symbiont communities supports the holobiont model and calls into question the hologenome theory of evolution. PMID:26555246

  6. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Ulrike Esslinger

    Full Text Available Dilated cardiomyopathy (DCM is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS to assess the contribution of missense variants to sporadic DCM.116,855 single nucleotide variants (SNVs were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value<0.01. The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3. In silico fine mapping identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF<0.01 demonstrated significant association for TTN variants only (P = 0.0085. All candidate genes but one (SLC39A8 exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. We also investigated a panel of 48 known cardiomyopathy genes. Collectively, rare (n = 228, P = 0.0033 or common (n = 36, P = 0.019 variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here.We identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology.

  7. Prognostic impact of changes in base excision repair machinery in sporadic colorectal cancer.

    Science.gov (United States)

    Azambuja, Daniel B; Leguisamo, Natalia M; Gloria, Helena C; Kalil, Antonio Nocchi; Rhoden, Ernani; Saffi, Jenifer

    2018-01-01

    to evaluate the prognostic value of base excision repair proteins in sporadic colorectal cancer. Pre-treatment tumor samples from 72 patients with sporadic colorectal adenocarcinoma were assessed for APC, MPG, Polβ, XRCC1 and Fen1 expression by immunohistochemistry. The associations of molecular data were analyzed in relation to clinical features and TNM staging as a prognosis predictor and disease-free survival. Higher levels of MPG, Polβ and XRCC1, but not Fen1, were associated with unfavorable pathological outcomes, such as poor cellular differentiation, advanced TNM stages, presence of lymphatic and perineural invasions and metastatic lymph nodes. MPG and Polβ overexpression were associated with right-sided CRC. However, only MPG high expression is associated with shorter disease-free survival in CRC patients. Our results suggest that increased expression of MPG, Polβ and XRCC1 are more likely to evolve to poor pathological outcomes, but only the elevated expression of MPG protein predicts recurrence. The BER proteins appear to be suitable candidates to refine the TNM current staging of colorectal cancer. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Onset and spreading patterns of lower motor neuron involvements predict survival in sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Fujimura-Kiyono, Chieko; Kimura, Fumiharu; Ishida, Simon; Nakajima, Hideto; Hosokawa, Takafumi; Sugino, Masakazu; Hanafusa, Toshiaki

    2011-11-01

    To define patterns of spread through the order of lower motor neuron involvement (first, second or third order), relationships between interval or sites of affected areas from onset to involvement of a second region, and prognosis, including 5 year survival, normal preservation of motor function at onset of respiratory symptoms and cumulative occurrence of each region and direction of spread. 150 patients with sporadic amyotrophic lateral sclerosis (ALS) underwent follow-up at 3 month intervals until the appearance of respiratory symptoms. Symptom appearances were determined using the revised version of the ALS Functional Rating Scale. Median survival with combined type onset (two regions simultaneously) was shorter (18 months) than with bulbar onset (26 months, p=0.01). The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. 5 year survival rate was 21% for lower limb onset, 18% for upper limb onset and 16% for bulbar onset. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Early manifestations of bulbar symptoms within 1 year were associated with worse survival (pspread longitudinally to adjacent regions. Bulbar function remained preserved in 27%, lower limb function in 10% and upper limb function in 2.7%. The interval between onset and involvement of the second region is an important predictor of survival. The data support the contiguous anatomical propagation of lower motor neuron involvement in sporadic ALS.

  9. Angiotensin converting enzyme insertion/deletion polymorphism in sporadic and familial Alzheimer's disease and longevity.

    Science.gov (United States)

    Nacmias, Benedetta; Bagnoli, Silvia; Tedde, Andrea; Cellini, Elena; Bessi, Valentina; Guarnieri, Biancamaria; Ortensi, Luigi; Piacentini, Silvia; Bracco, Laura; Sorbi, Sandro

    2007-01-01

    A recent, large meta-analysis has reproposed the role of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a risk factor for Alzheimer's disease (AD). To further investigate the proposed association and to better clarify the role of ACE as a risk factor for AD, we analyzed the genotype and allele frequency distribution of ACE I/D and apolipoprotein E (APOE) gene polymorphisms in 235 Italian patients with sporadic AD, 153 with familial AD (FAD), 192 healthy controls and 111 centenarians. Patients with AD were consecutively gathered from among the outpatients from the Neurology Department at the University of Florence. All 691 subjects were genotyped for ACE and APOE polymorphisms. There were no significant differences in ACE genotypes or allele frequencies in all the studied groups, even after stratification for APOE epsilon4 carrier status. Centenarians show the highest allele D frequency, although the value is not significant, thus suggesting a possible implication of the D allele as an epistatic allele that has pleiotropic age-dependent effects. In conclusion, our data suggest that the ACE allelic variant is not a susceptibility factor in sporadic and familial AD (FAD), nor does it mitigate the effect of the APOE epsilon4 allele in the risk of developing AD. Moreover, our data do not suggest a possible involvement of the D allele in longevity.

  10. Creutzfeldt-Jacob Disease: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Aysu Şen

    2006-02-01

    Full Text Available Creutzfeldt-Jakob Disease (CJD is characterised by subacute progressive dementia, cerebellar ataxia, myoclonic jerks together with pyramidal and extrapyramidal signs. It is a rare prion disease and definitive diagnosis can only be made by biopsy. It becomes progressively worse and the death is the rule. We presented two CJD cases because of their demonstrative characteristics. A 43 year-old female and a 52 year-old male patient was suspected to be CJD due to presence of subacute severe cognitive deterioration, neuropsychiatric disturbances, myoclonic jerks, ataxia, pyramidal and extrapyramidal signs and also periodic spike and wave complexes in EEG. Patients were lost in a short period of time because of the complications of disease process. Medical autopsy were done in both cases for definitive diagnosis and autopsy results displayed characteristic pathologic findings of CJD. Patients were diagnosed as definitive sporadic CJD according to Master’s, French and European criterias. CJD should be considered in patients with rapidly progressive dementia, that starts with various neuropsychiatric symptoms. Although seen very rare, CJD is a untreatable, fatal disease. Therefore we emphasize that, preventive precaution should be taken when a CJD diagnosis is suspected

  11. Sporadic hemiplegic migraine with normal imaging as the initial manifestation of CADASIL.

    Science.gov (United States)

    Monteiro, Cecília; Barros, José; Taipa, Ricardo; Pereira-Monteiro, José

    2012-02-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be present with negative family history and, especially in younger patients, with normal brain magnetic resonance. For this reason, those CADASIL patients that present only with migraine may be misdiagnosed. In the case of migraine with motor aura, sporadic hemiplegic migraine (SHM) is one of the possible misdiagnoses. We present a case of a patient who, in the first years of her disease, met the clinical criteria for SHM. A diagnosis of CADASIL was considered only when her sister presented with headache and an unknown leukoencephalopathy. This case illustrates the need for a careful review of the clinical and family history during the follow-up of primary headaches.

  12. Four Sporadic Pediatric Cases of Yersinia enterocolitica O:8 Infection in a Rural Area of Japan.

    Science.gov (United States)

    Minami, Kisei; Yasuda, Ryu; Terakawa, Runa; Koike, Yumi; Takeuchi, Koichi; Higuchi, Tsukasa; Horiuchi, Ayaka; Kubota, Noriko; Hidaka, Eiko; Kawakami, Yoshiyuki

    2017-03-24

    In the spring of 2015, we experienced a cluster of 4 sporadic cases of yersiniosis in children in Nagano prefecture, a rural area of Japan. Two patients developed appendicitis-like episodes; one had acute gastroenteritis, and the other had bacteremia associated with liver abscess. The causative agent of these infections was Yersinia enterocolitica serogroup O:8. None of the patients had an underlying illness, and all have recovered completely. The patients were neither socially nor geographically related to each other. These 4 consecutive cases suggest that Y. enterocolitica O:8 has spread substantially in the middle part of Japan, and that this virulent strain might be more common than previously reported in our country.

  13. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

    Science.gov (United States)

    Penco, Silvana; Buscema, Massimo; Patrosso, Maria Cristina; Marocchi, Alessandro; Grossi, Enzo

    2008-05-30

    Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial

  14. The ‘Pokemon’ (ZBTB7) Gene: No Evidence of Association with Sporadic Breast Cancer

    Science.gov (United States)

    Salas, Antonio; Vega, Ana; Milne, Roger L.; García-Magariños, Manuel; Ruibal, Álvaro; Benítez, Javier; Carracedo, Ángel

    2008-01-01

    It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from North and Central Spanish patients. We genotyped 15 SNPs in ZBTB7, including the flanking regions, with an average coverage of 1 SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of allele, genotype and haplotype frequencies between cases and controls did not reveal associations using Pearson’s chi-square test and a permutation procedure to correct for multiple test. In this, the first study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association. PMID:21892298

  15. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

    Science.gov (United States)

    Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

    2008-01-07

    To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

  16. The 2-min walk test is sufficient for evaluating walking abilities in sporadic inclusion body myositis.

    Science.gov (United States)

    Alfano, L N; Lowes, L P; Dvorchik, I; Yin, H; Maus, E G; Flanigan, K M; Mendell, J R

    2014-03-01

    Sporadic inclusion body myositis causes progressive functional loss due to declining muscle strength. Although the underlying cause is unknown, clinical trials are underway to improve strength and function. Selection of appropriate outcome measures is critical for the success of these trials. The 6-min walk test has been the de facto standard for assessing function in neuromuscular disease; however, the optimal walking test has not been determined in this disease. In this study, 67 individuals with sporadic inclusion body myositis completed a battery of quantitative strength and functional tests including timed walking tests, patient-reported outcomes, and other tasks. The 2-min and 6-min walk tests are highly correlated to each other (r=0.97, pwalk test, but 7% of subjects were unable to walk the full 6-min of the 6-min walk test due to fatigue. The 2-min walk test demonstrates similar correlation to all outcomes compared to the 6-min walk test, is less fatiguing and better tolerated. Results suggest that the 2-min walk test is a better alternative to tests of longer duration. Further research is needed to determine longitudinal changes on this outcome. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. [Microsatellite alterations on chromosome 9p21-22 in sporadic colorectal cancer].

    Science.gov (United States)

    Zhang, Y; Lai, M

    1999-12-01

    To study whether alteration of p16 plays an important role in the development of colorectal carcinomas and the relationship between the molecular changes of 9p21-22 chromosome subregion in sporadic colorectal cancers. To detect microsatellite instability (MSI) and loss of heterozygosity (LOH) by PCR, denatured-polyacrylamide gel-electrophoresis and silver staining (microsatellite DNA-PCR-silver staining method) and to compare the results with the clinopathological parameters. Between MSI positive and negative cases and the clinopathological findings, some evidences found in the MSI positive group were as follows: (1) tendency towards younger patients (usually < 50 years in age, P < 0.05); (2) more frequently seen in mucoid carcinomas (P < 0.01). Microsatellite DNA-PCR-silver staining method is very sensitive in detecting even a tiny change of a single base. MSI occured in the selected microsatellite loci of different subregions and different chromosomes might be different in significance, therefore, a right choice of the suitable loci for studying the microsatellite changes is important. Since the frequency of loss of heterozygosity at 9p21-22 is low (merely 8.42%), it is considered that p16 is not closely associated with the development of sporadic colorectal cancer.

  18. Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Sala, Sergio Della; Abrahams, Sharon; Logie, Robert H; Méndez, Luis Guillermo; Lopera, Francisco

    2011-06-01

    Short-term memory binding of visual features which are processed across different dimensions (shape-colour) is impaired in sporadic Alzheimer's disease, familial Alzheimer's disease, and in asymptomatic carriers of familial Alzheimer's disease. This study investigated whether Alzheimer's disease also impacts on within-dimension binding processes. The study specifically explored whether visual short-term memory binding of features of the same type (colour-colour) is sensitive to Alzheimer's disease. We used a neuropsychological battery and a short-term memory binding task to assess patients with sporadic Alzheimer's disease (Experiment 1), familial Alzheimer's disease (Experiment 2) due to the mutation E280A of the Presenilin-1 gene and asymptomatic carriers of the mutation. The binding task assessed change detection within arrays of unicoloured objects (Colour Only) or bicoloured objects the colours of which had to be remembered separately (Unbound Colours) or together (Bound Colours). Performance on the Bound Colours condition (1) explained the largest proportion of variance between patients (sporadic and familial Alzheimer's disease), (2) combined more sensitivity and specificity for the disease than other more traditional neuropsychological tasks, (3) identified asymptomatic carriers of the mutation even when traditional neuropsychological measures and other measures of short-term memory did not and, (4) contrary to shape-colour binding, correlated with measures of hippocampal functions. Colour-colour binding and shape-colour binding both appear to be sensitive to AD even though they seem to rely on different brain mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Positive 14-3-3 and tau proteins in a sporadic Creutzfeldt-Jakob disease case and a brief perspective of prion diseases in Colombia.

    Science.gov (United States)

    Escandón-Vargas, Kevin; Zorrilla-Vaca, Andrés; Corral-Prado, Raúl Heli

    2016-02-24

    Prion diseases are rare neurodegenerative disorders occurring worldwide and affecting both humans and animals. Herein, we present the case of a patient diagnosed with definite sporadic Creutzfeldt-Jakob disease in Cali, Colombia. Besides neurological examination, 14-3-3 and tau proteins were valuable tools supporting the diagnosis. We also present a brief perspective of the prion diseases reported in Colombia to date. Although the incidence of prion diseases is unknown in Colombia, our literature review revealed that one case of scrapie in 1981 and 29 human sporadic cases of Creutzfeldt-Jakob disease have been documented and published in our country.

  20. Endplate Structure and Parameters of Neuromuscular Transmission in Sporadic Centronuclear Myopathy Associated with Myasthenia

    Science.gov (United States)

    Liewluck, Teerin; Shen, Xin-Ming; Milone, Margherita; Engel, Andrew G.

    2011-01-01

    Centronuclear myopathy is a pathologically diagnosed congenital myopathy. The disease genes encode proteins with membrane modulating properties (MTM1, DNM2, and BIN1) or alter excitation-contraction coupling (RYR1). Some patients also have myasthenic symptoms but electrodiagnostic and endplate studies in these are limited. A sporadic patient had fatigable weakness and a decremental EMG response. Analysis of centronuclear myopathy disease- and candidate- genes identified no mutations. Quantitative endplate structure and in vitro microelectrode studies revealed simplified postsynaptic regions, endplate remodeling with normal nerve terminal size, normal synaptic vesicle density, and mild acetylcholine receptor deficiency. The amplitude of the miniature endplate potential was decreased to 60% of normal. Quantal release by nerve impulse was reduced to 40% of normal due to a decreased number of releasable quanta. The safety margin of neuromuscular transmission is compromised by decreased quantal release by nerve impulse and by a reduced postsynaptic response to the released quanta. PMID:21482111

  1. No evidence of somatic aryl hydrocarbon receptor interacting protein mutations in sporadic endocrine neoplasia

    DEFF Research Database (Denmark)

    Raitila, A; Georgitsi, M; Karhu, A

    2007-01-01

    . Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations by direct sequencing. No somatic mutations were identified. However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X...... as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age. Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1...... (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas...

  2. The monster sporadic group and a theory underlying superstring models

    International Nuclear Information System (INIS)

    Chapline, G.

    1996-09-01

    The pattern of duality symmetries acting on the states of compactified superstring models reinforces an earlier suggestion that the Monster sporadic group is a hidden symmetry for superstring models. This in turn points to a supersymmetric theory of self-dual and anti-self-dual K3 manifolds joined by Dirac strings and evolving in a 13 dimensional spacetime as the fundamental theory. In addition to the usual graviton and dilaton this theory contains matter-like degrees of freedom resembling the massless states of the heterotic string, thus providing a completely geometric interpretation for ordinary matter. 25 refs

  3. Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.

    Directory of Open Access Journals (Sweden)

    Alexandra V Stavropoulou

    Full Text Available Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24. In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6% of familial cancer cases and in 27/592 (4.6% of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%. The majority of BRCA1 carriers (71.2% presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.

  4. Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

    NARCIS (Netherlands)

    Pinto, Mafalda; Wub, Ying; Mensink, Rob G. J.; Cirnes, Luis; Seruca, Raquel; Hofstra, Robert M. W.

    2008-01-01

    In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation,

  5. A specific superoxide dismutase mutation is on the same genetic background in sporadic and familial cases of amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Hayward, C.; Brock, D.J.H. [Univ. of Edinburgh (United Kingdom); Swingler, R.J. [Dundee Royal Infirmary (United Kingdom)] [and others

    1996-11-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons, causing progressive muscular atrophy, weakness, and death from respiratory failure, often within 2-3 years. Although most cases are sporadic, some 5%-10% are inherited as autosomal dominants with age-dependent penetrance. An ALS locus has been mapped to chromosome 21q, and causative mutations identified in the Cu/Zn superoxide dismutase (SOD1) gene. A majority of SOD1 mutations have been found in cases with a clear family history of ALS. However, we and others have also described SOD1 mutations in patients where the disease appears to be sporadic. This is especially true for the missense mutation in codon 113 of the SOD1 gene, which substitutes threonine for isoleucine (I113T). One explanation for this finding is that this codon is a mutational hot spot with sporadic cases representing new mutations. Another is that the inherited nature of the cases is disguised by the reduced penetrance of this specific mutation. We have now shown that each of six unrelated cases of I113T mutation that we have collected in the Scottish population occurs on the same genetic background. Association analysis of multiple flanking loci on chromosome 21q supports the conclusion of a founder effect, with the original mutational event occurring {ge}10 generations ago. 12 refs., 1 fig., 1 tab.

  6. Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

    Science.gov (United States)

    Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

    2017-04-01

    We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

  7. Rapid progressive visual decline and visual field defects in two patients with the Heidenhain variant of Creutzfeld-Jakob disease.

    Science.gov (United States)

    Lenk, Janine; Engellandt, Kay; Terai, Naim; Bottesi, Antonia; Matthé, Egbert

    2018-02-08

    Heidenhain variant of Creutzfeldt-Jakob (HvCJD) is a rare disease, patients presenting with loss of visual acuity and a decline in visual fields. Two patients with rapid loss of visual acuity and declining visual fields presented with homonymic hemianopsia over several weeks. Cranial MRI showed neither stroke nor other morphological changes explaining the severe visual field defects. Neurological examination revealed no pathologies. However, lumbar puncture showed an increase in total protein in cerebrospinal fluid (CSF). Visual field testing revealed further deterioration during follow-up. Several weeks later, patients' behaviour changed markedly, exhibiting aggression, declining memory function and physical degeneration. The suspected diagnosis was the Heidenhain variant of Creutzfeld-Jakob disease (HvCJD). CSF analysis showed evidence of PrP Sc and 14-3-3 protein. Both patients died within 8 weeks of the CJD diagnosis. Loss of visual acuity and a decline in visual fields without corresponding MRI findings and marked changes in behaviour should lead to a diagnosis of HvCJD. Corresponding diagnostic tests should be performed for confirmation. The prognosis for survival is poor and should be immediately communicated to affected patients and their relatives. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Cohen, O S; Kimiagar, I; Korczyn, A D; Nitsan, Z; Appel, S; Hoffmann, C; Rosenmann, H; Kahana, E; Chapman, J

    2016-05-01

    Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ± 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies. © 2016 EAN.

  9. Spread Direction and Prognostic Factors in Limb-Onset Sporadic Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Hu, Fangfang; Jin, Jiaoting; Jia, Rui; Xiang, Li; Qi, Huaguang; Chen, Xin; Dang, Jingxia

    2016-01-01

    To investigate the spread direction and prognostic factors in limb-onset sporadic amyotrophic lateral sclerosis (sALS). Medical records of 128 patients with sALS were reviewed. Variables studied were age at symptom onset, gender, region and lateralization of onset, onset to diagnosis interval (ODI), progression direction, bulbar-involved, time from onset to bulbar-involved, ALSFRS-r, upper motor neuron (UMN) signs and progression rate. First, the horizontal and vertical directions are major spreading directions in limb-onset sALS. Second, in crossed and interposed groups, while ODI is shorter, the progression rate is faster and UMN signs are more pronounced (p spread directions in limb-onset sALS. Except for ALSFRS-r and ODI, bulbar-involved is an adverse factor for ALS progression, and progression rate is related to the time from onset symptoms to bulbar-involved. © 2016 S. Karger AG, Basel.

  10. Loss of p27 expression and microsatellite instability in sporadic colorectal cancer.

    Science.gov (United States)

    Sarli, Leopoldo; Bottarelli, Lorena; Azzoni, Cinzia; Campanini, Nicoletta; Di Cola, Gabriella; Barilli, Angela Luciana; Marchesi, Federico; Mazzeo, Antonio; Salvemini, Carlo; Morari, Silvia; Di Mauro, Davide; Donadei, Enrico; Necchi, Fransesca; Roncoroni, Luigi; Bordi, Cesare

    2006-08-01

    The role of the loss of p27 protein expression in the oncogenesis of colorectal cancer is still in debate. In this study, we prospectively examined the immunohistochemical expression of p27 in 108 consecutive colorectal cancers, and we analysed the relationship with the results, the clinicopathological data, microsatellite instability (MSI) and other genetic alterations of tumours. Unselected patients (108) who underwent curative colorectal resection for sporadic colorectal cancer in a three-year period were evaluated for MSI using 6 microsatellite markers, and for the presence of p27, p53, Fhit, Mlh1 and Msh2 proteins by means of immunostaining. The relationships between these markers were analysed. p27 protein expression was examined for association with disease recurrences and survival. Lack of p27 expression was noted in 33 out of 108 (30.5%) colorectal cancer cases (Pcancers (Pcancers with MSI (Pcancers.

  11. Regional neuronal network failure and cognition in late-onset sporadic Alzheimer disease.

    Science.gov (United States)

    Carter, S F; Embleton, K V; Anton-Rodriguez, J M; Burns, A; Ralph, M A L; Herholz, K

    2014-06-01

    The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas. Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts. Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment. © 2014 by American

  12. Sporadic versus Radiation-Associated Angiosarcoma: A Comparative Clinicopathologic and Molecular Analysis of 48 Cases

    Directory of Open Access Journals (Sweden)

    Jennifer Hung

    2013-01-01

    Full Text Available Angiosarcomas are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy. We compared clinicopathologic and biologic features of sporadic angiosarcomas (SA and radiation-associated angiosarcomas (RAA. Methods. From a University of Michigan institutional database, 37 SA and 11 RAA were identified. Tissue microarrays were stained for p53, Ki-67, and hTERT. DNA was evaluated for TP53 and ATM mutations. Results. Mean latency between radiotherapy and diagnosis of RAA was 11.9 years: 6.7 years for breast RAA versus 20.9 years for nonbreast RAA (P=0.148. Survival after diagnosis did not significantly differ between SA and RAA (P=0.590. Patients with nonbreast RAA had shorter overall survival than patients with breast RAA (P=0.03. The majority of SA (86.5% and RAA (77.8% were classified as high-grade sarcomas (P=0.609. RAA were more likely to have well-defined vasoformative areas (55.6% versus 27%, P=0.127. Most breast SA were parenchymal in origin (80%, while most breast RAA were cutaneous in origin (80%. TMA analysis showed p53 overexpression in 25.7% of SA and 0% RAA, high Ki-67 in 35.3% of SA and 44.4% RAA, and hTERT expression in 100% of SA and RAA. TP53 mutations were detected in 13.5% of SA and 11.1% RAA. ATM mutations were not detected in either SA or RAA. Conclusions. SA and RAA are similar in histology, immunohistochemical markers, and DNA mutation profiles and share similar prognosis. Breast RAA have a shorter latency period compared to nonbreast RAA and a significantly longer survival.

  13. Rapidly aggravated Creutzfeldt-Jacob disease: autopsy-proven case

    International Nuclear Information System (INIS)

    Park, Seung Hyun; Kang, Hyun Koo; Yu, Hyeon; Lee, Sang Chun

    2005-01-01

    Creutzfeldt-Jakob disease (DJD) is one of the transmissible spongiform encephalopathies, which is mediated by what has been known as 'prion'. It is a rare and fatal progressive neurodegenerative disease that affects the middle and old aged. There are a number of subtypes of CJD, one of which is the sporadic type characterized by rapidly progressing clinical symptoms, including progressive dementia, myoclonic jerk, and pyramidal or extrapyramidal syndrome. Patients usually end up dying within 1 to 2 years of contacting the disease. We report an autopsy-proven case of sporadic CJD with clinical symptoms that progressed within several days, along with dramatic changes on diffusion weighted magnetic resonance images

  14. Distinct neuropsychological characteristics in Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Snowden, J S; Mann, D M A; Neary, D

    2002-12-01

    To characterise the nature of cognitive change in Creutzfeldt-Jakob disease (CJD). Case histories are reported of four patients with sporadic (sCJD) and two with familial CJD (fCJD), with postmortem pathological findings in four cases. The data derived from cognitive examination are examined with respect to the presence or absence of a variety of characteristics to elicit performance profiles across cognitive domains. Three patients with sCJD exhibited clear focal cortical deficits. One patient had visual impairment leading to cortical blindness, associated with posterior hemisphere abnormalities on single photon emission computed tomography (SPECT) imaging; two others had impairments in language, mirrored by left hemisphere SPECT abnormalities. The remaining three patients showed no specific cortical symptomatology. Despite these differences all six patients shared common qualitative characteristics: episodic unresponsiveness, interference effects, and profound verbal and motor perseveration. These common features are interpreted in terms of impaired activation and regulation of neocortex from subcortical structures. Findings from postmortem pathological examination and from the published literature provide converging evidence to implicate a critical role of the thalamus. These preliminary findings suggest that sCJD and fCJD may be associated with distinct neuropsychological characteristics.

  15. SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis

    Directory of Open Access Journals (Sweden)

    Bourdon Violaine

    2011-01-01

    Full Text Available Abstract Background Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the SMARCB1 (INI1 tumor suppressor gene were described in familial and sporadic schwannomatosis patients. Methods To delineate the SMARCB1 gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas. Results Nine variants scattered along the sequence of SMARCB1 were identified. Five of them were classified as deleterious. All five patients carrying a SMARCB1 mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age. Conclusions These results suggest that patients with schwannomas have a significant probability of carrying a SMARCB1 mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the SMARCB1 gene.

  16. SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis.

    Science.gov (United States)

    Rousseau, Guillaume; Noguchi, Tetsuro; Bourdon, Violaine; Sobol, Hagay; Olschwang, Sylviane

    2011-01-24

    Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the SMARCB1 (INI1) tumor suppressor gene were described in familial and sporadic schwannomatosis patients. To delineate the SMARCB1 gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas. Nine variants scattered along the sequence of SMARCB1 were identified. Five of them were classified as deleterious. All five patients carrying a SMARCB1 mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age. These results suggest that patients with schwannomas have a significant probability of carrying a SMARCB1 mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the SMARCB1 gene.

  17. Anesthetic Considerations of Sporadic Inclusion Body Myositis in an Elderly Man With Orthopedic Trauma.

    Science.gov (United States)

    Steck, Dominik T; Choi, Christine; Gollapudy, Suneeta; Pagel, Paul S

    2016-04-01

    Sporadic inclusion body myositis (IBM) is an inflammatory myopathy characterized by progressive asymmetric extremity weakness, oropharyngeal dysphagia, and the potential for exaggerated sensitivity to neuromuscular blockers and respiratory compromise. The authors describe their management of a patient with IBM undergoing urgent orthopedic surgery. An 81-year-old man with IBM suffered a left intertrochanteric femoral fracture after falling down stairs. His IBM caused progressive left proximal lower extremity, bilateral distal upper extremity weakness (left > right), and oropharyngeal dysphagia (solid food, pills). He denied dyspnea, exercise intolerance, and a history of aspiration. Because respiratory insufficiency resulting from diaphragmatic dysfunction and prolonged duration of action of neuromuscular blockers may occur in IBM, the authors avoided using a neuromuscular blocker. After applying cricoid pressure, anesthesia was induced using intravenous lidocaine, propofol, remifentanil followed by manual ventilation with inhaled sevoflurane in oxygen. Endotracheal intubation was accomplished without difficulty; anesthesia was then maintained using remifentanil and sevoflurane. The fracture was repaired with a trochanteric femoral nail. The patient was extubated without difficulty and made an uneventful recovery. In summary, there is a lack of consensus about the use of neuromuscular blockers in patients with IBM. The authors avoided these drugs and were able to easily secure the patient's airway and maintain adequate muscle relaxation using a balanced sevoflurane-remifentanil anesthetic. Clinical trials are necessary to define the pharmacology of neuromuscular blockers in patients with IBM and determine whether use of these drugs contributes to postoperative respiratory insufficiency in these vulnerable patients.

  18. A Unifying Hypothesis for Familial and Sporadic Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Carole J. Proctor

    2012-01-01

    Full Text Available Alzheimer's disease (AD is characterised by the aggregation of two quite different proteins, namely, amyloid-beta (Aβ, which forms extracellular plaques, and tau, the main component of cytoplasmic neurofibrillary tangles. The amyloid hypothesis proposes that Aβ plaques precede tangle formation but there is still much controversy concerning the order of events and the linkage between Aβ and tau alterations is still unknown. Mathematical modelling has become an essential tool for generating and evaluating hypotheses involving complex systems. We have therefore used this approach to discover the most probable pathway linking Aβ and tau. The model supports a complex pathway linking Aβ and tau via GSK3β, p53, and oxidative stress. Importantly, the pathway contains a cycle with multiple points of entry. It is this property of the pathway which enables the model to be consistent with both the amyloid hypothesis for familial AD and a more complex pathway for sporadic forms.

  19. Sporadic Insulinoma Presenting as Early Morning Night Terrors.

    Science.gov (United States)

    Beisang, Daniel; Forlenza, Gregory P; Luquette, Mark; Sarafoglou, Kyriakie

    2017-06-01

    A 16-year-old boy with a recent diagnosis of night terrors was evaluated for recurrent early morning hypoglycemia after an early morning seizure. Evaluation in clinic with critical laboratories identified hyperinsulinemic hypoglycemia. Additional investigation revealed a sporadic insulinoma as the etiology of his hypoglycemia and all symptoms were resolved after pancreaticoduodenectomy. The importance of obtaining critical laboratory samples is highlighted and appropriate radiologic, medical, and pathologic testing is discussed. We additionally review the medical and surgical management of hyperinsulinemic hypoglycemia. A discussion of multiple endocrine neoplasia type 1 associated insulinomas is included as well. This case highlights the importance of considering hypoglycemia in the evaluation of night terrors and new-onset seizures. Copyright © 2017 by the American Academy of Pediatrics.

  20. Creutzfeldt-Jakob disease versus anti-LGI1 limbic encephalitis in a patient with progressive cognitive dysfunction, psychiatric symptoms, involuntary facio-brachio-crural movement, and an abnormal electroencephalogram: a case report

    Directory of Open Access Journals (Sweden)

    Sun L

    2015-06-01

    Full Text Available Li Sun, Jie Cao, Chang Liu, Yudan LvDepartment of Neurology, The First Hospital of JiLin University, ChangChun, People’s Republic of ChinaAbstract: Diagnosis of Creutzfeldt-Jakob disease (CJD is often challenging in elderly individuals, not only because of its variable clinical features but also because of nonspecific changes on the electroencephalogram (EEG in the early stages of the disease. Here we report on a patient who presented with progressive cognitive dysfunction, psychiatric symptoms, involuntary facio-brachio-crural movement, and an abnormal EEG. We provide a detailed analysis and differential diagnosis between anti-leucine-rich glioma inactivated 1 (LGI1 limbic encephalitis versus CJD, in the hope of providing a new understanding of CJD. A 65-year-old Chinese man presented with slowly progressive cognitive decline with psychiatric symptoms. On admission, he presented with facial grimacing and brief left upper limb dystonic posturing lasting 1–2 seconds, with hyponatremia that was difficult to rectify. Neurological examination showed increased muscle tension in the left limb but without pathological reflexes. His early EEG showed focal periodic wave complexes. Diffusion-weighted magnetic resonance imaging showed a suspected “lace sign” in the occipital cortex. His cerebrospinal fluid was negative for LGI1 antibodies and positive for 14-3-3 brain protein. Therefore, we made a presumptive diagnosis of CJD. At the following visit, a second EEG showed paroxysmal sharp wave complexes, but the patient had a poor prognosis. Atypical facio-brachio-crural movement and nonspecific EEG changes may occasionally be found in patients with CJD or anti-LGI1 encephalitis. Clinicians should not be dissuaded from a diagnosis of CJD where the EEG does not show paroxysmal sharp wave complexes in the early stages but abnormal facio-brachio-crural movement is present.Keywords: abnormal facio-brachio-crural movement, hyponatremia, Creutzfeldt

  1. Burden of rare variants in ALS genes influences survival in familial and sporadic ALS.

    Science.gov (United States)

    Pang, Shirley Yin-Yu; Hsu, Jacob Shujui; Teo, Kay-Cheong; Li, Yan; Kung, Michelle H W; Cheah, Kathryn S E; Chan, Danny; Cheung, Kenneth M C; Li, Miaoxin; Sham, Pak-Chung; Ho, Shu-Leong

    2017-10-01

    Genetic variants are implicated in the development of amyotrophic lateral sclerosis (ALS), but it is unclear whether the burden of rare variants in ALS genes has an effect on survival. We performed whole genome sequencing on 8 familial ALS (FALS) patients with superoxide dismutase 1 (SOD1) mutation and whole exome sequencing on 46 sporadic ALS (SALS) patients living in Hong Kong and found that 67% had at least 1 rare variant in the exons of 40 ALS genes; 22% had 2 or more. Patients with 2 or more rare variants had lower probability of survival than patients with 0 or 1 variant (p = 0.001). After adjusting for other factors, each additional rare variant increased the risk of respiratory failure or death by 60% (p = 0.0098). The presence of the rare variant was associated with the risk of ALS (Odds ratio 1.91, 95% confidence interval 1.03-3.61, p = 0.03), and ALS patients had higher rare variant burden than controls (MB, p = 0.004). Our findings support an oligogenic basis with the burden of rare variants affecting the development and survival of ALS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. RET single nucleotide polymorphism in Indonesians with sporadic Hirschsprung’s disease

    Directory of Open Access Journals (Sweden)

    Saryono

    2010-08-01

    Full Text Available The tyrosine kinase receptor RET, which is the protein product of the RET gene, is involved in the development of the mammalian nervous system that causes Hirschsprung’s disease (HSCR. RETs are cell surface molecules that are expressed in cells derived from the neural crest. The purpose of this study was to investigate the polymorphism of the RET gene in HSCR in the Yogyakarta population. Genomic DNA was extracted from surgically removed bowel tissues of 54 unrelated HSCR patients. Exon 2 of the RET gene was amplified by polymerase chain reaction (PCR and analyzed by restriction fragment length polymorphism (RFLP. Molecular results were compared with clinical performance of Hirschsprung patients. RET polymorphism was detected in exon 2 in all of the 54 Indonesian HSCR patients. The allelic distribution of the c135GàA polymorphism in the RET exon 2 indicated that the A allele was more frequent in patients than in control individuals (chi-square test, p= 0.001. Thus the RET variant allele A is over-represented in patients affected with the HSCR phenotype. Polymorphism of exon 2 of the RET gene was found in sporadic Hirschsprung’s disease in the Yogyakarta population, which suggests that the RET gene plays important roles in the pathogenesis of HSCR.

  3. RET single nucleotide polymorphism in Indonesians with sporadic Hirschsprung’s disease

    Directory of Open Access Journals (Sweden)

    Saryono Saryono

    2016-02-01

    Full Text Available The tyrosine kinase receptor RET, which is the protein product of the RET gene, is involved in the development of the mammalian nervous system that causes Hirschsprung’s disease (HSCR. RETs are cell surface molecules that are expressed in cells derived from the neural crest. The purpose of this study was to investigate the polymorphism of the RET gene in HSCR in the Yogyakarta population. Genomic DNA was extracted from surgically removed bowel tissues of 54 unrelated HSCR patients. Exon 2 of the RET gene was amplified by polymerase chain reaction (PCR and analyzed by restriction fragment length polymorphism (RFLP. Molecular results were compared with clinical performance of Hirschsprung patients. RET polymorphism was detected in exon 2 in all of the 54 Indonesian HSCR patients. The allelic distribution of the c135GàA polymorphism in the RET exon 2 indicated that the A allele was more frequent in patients than in control individuals (chi-square test, p= 0.001. Thus the RET variant allele A is over-represented in patients affected with the HSCR phenotype. Polymorphism of exon 2 of the RET gene was found in sporadic Hirschsprung’s disease in the Yogyakarta population, which suggests that the RET gene plays important roles in the pathogenesis of HSCR.

  4. Whole-exome sequencing improves the diagnosis yield in sporadic infantile spasm syndrome.

    Science.gov (United States)

    Dimassi, S; Labalme, A; Ville, D; Calender, A; Mignot, C; Boutry-Kryza, N; de Bellescize, J; Rivier-Ringenbach, C; Bourel-Ponchel, E; Cheillan, D; Simonet, T; Maincent, K; Rossi, M; Till, M; Mougou-Zerelli, S; Edery, P; Saad, A; Heron, D; des Portes, V; Sanlaville, D; Lesca, G

    2016-02-01

    Infantile spasms syndrome (ISs) is characterized by clinical spasms with ictal electrodecrement, usually occurring before the age of 1 year and frequently associated with cognitive impairment. Etiology is widely heterogeneous, the cause remaining elusive in 40% of patients. We searched for de novo mutations in 10 probands with ISs and their parents using whole-exome sequencing (WES). Patients had neither consanguinity nor family history of epilepsy. Common causes of ISs were excluded by brain magnetic resonance imaging (MRI), metabolic screening, array-comparative genomic hybridization (CGH) and testing for mutations in CDKL5, STXBP1, and for ARX duplications. We found a probably pathogenic mutation in four patients. Missense mutations in SCN2A (p.Leu1342Pro) and KCNQ2 (p.Ala306Thr) were found in two patients with no history of epilepsy before the onset of ISs. The p.Asn107Ser missense mutation of ALG13 had been previously reported in four females with ISs. The fourth mutation was an in-frame deletion (p.Phe110del) in NR2F1, a gene whose mutations cause intellectual disability, epilepsy, and optic atrophy. In addition, we found a possibly pathogenic variant in KIF3C that encodes a kinesin expressed during neural development. Our results confirm that WES improves significantly the diagnosis yield in patients with sporadic ISs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Long-term survival following radiotherapy and cytarabine chemotherapy for sporadic primary central nervous system lymphoma

    International Nuclear Information System (INIS)

    Poettgen, C.; Stuschke, M.; Stueben, G.; Schmitz, A.; Grehl, S.; Schwechheimer, K.; Wacker, H.H.; Rauhut, F.; Kleuker, S.; Wilhelm, H.; Fehlings, T.

    2003-01-01

    Purpose: To analyze the long-term results following whole brain radiotherapy (WBRT) with sequential intrathecal (i.th.) cytosine arabinoside (Ara-C) ± intravenous (i.v.) Ara-C in patients with primary central nervous system lymphoma (PCNSL). Patients and Methods: 14 patients were treated between July 1987 and August 1995. All had sporadic PCNSL with proven histology of high-grade CNS lymphoma (twelve diffuse large-cell B-lymphomas, one lymphoblastic lymphoma, one large T-cell lymphoma). Patients were treated with two to four cycles of induction chemotherapy (40 mg/m 2 Ara-C i.th.), four patients received additional Ara-C i.v. (150 mg/m 2 , d1-4). WBRT was administered using 1.8-Gy fractions. Intrathecal chemotherapy was planned afterwards in 4-week intervals for 6 months. Posttreatment neurocognitive evaluations were performed in two long-term survivors. Results: Two of four patients who received i.v. and i.th. induction chemotherapy showed progressive disease, and irradiation was started immediately. Six of 14 patients received 50.4 Gy WBRT, four patients had WBRT up to 39.6 Gy followed by a 10.8-Gy boost. Five patients died early during therapy either due to a decline of the general medical condition or progressive disease. Median survival was 41 months (95% confidence interval: 6-79 months), survival at 3 and 5 years was 59% and 42%, respectively. Six patients survived for 3 years, two younger patients are still alive (> 12 years). They show only slightly impaired neurocognitive functions without clinical relevance. Conclusion: This WBRT-based protocol with i.th. meningeal prophylaxis using Ara-C ± i.v. Ara-C yields substantial long-term survival with moderate toxicity. The value of i.v. chemotherapy is currently being investigated in prospective studies. (orig.)

  6. Mendelian Genes and Risk of Intracerebral Hemorrhage and Small-Vessel Ischemic Stroke in Sporadic Cases.

    Science.gov (United States)

    Chong, Michael; O'Donnell, Martin; Thijs, Vincent; Dans, Antonio; López-Jaramillo, Patricio; Gómez-Arbeláez, Diego; Mondo, Charles; Czlonkowska, Anna; Skowronska, Marta; Oveisgharan, Shahram; Yusuf, Salim; Paré, Guillaume

    2017-08-01

    Mendelian strokes are rare genetic disorders characterized by early-onset small-vessel stroke. Although extensively studied among families with syndromic features, whether these genes affect risk among sporadic cases is unknown. We sequenced 8 genes responsible for Mendelian stroke in a case-control study of sporadic stroke cases (≤70 years). Participants included 1251 primary stroke cases of small-vessel pathology (637 intracerebral hemorrhage and 614 small-vessel ischemic stroke cases) and 1716 controls from the INTERSTROKE study (Study of the Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World). Overall, the prevalence of canonical disease-causing mutations was 0.56% in cases and 0.23% in controls (odds ratio=1.89; 95% confidence interval, 0.54-7.57; P =0.33). CADASIL (Cerebral Autosomal Dominant Arteriopathies with Subcortical Infarcts and Leukoencephalopathies) mutations were more frequent among cases (0.48%) than controls (0.23%) but were not significantly associated with stroke risk (odds ratio=2.03; 95% confidence interval, 0.58-8.02; P =0.27). Next, we included all rare nonsynonymous mutations to investigate whether other types of mutations may contribute to stroke risk. Overall, 13.5% of cases and 14.2% of controls were carriers of at least one rare nonsynonymous mutation among the 8 Mendelian stroke genes. Mutation carriers were not at elevated risk of stroke (odds ratio=0.93; 95% confidence interval, 0.75-1.16; P =0.55). In the absence of syndromic features and family history of stroke, screening for Mendelian mutations among small-vessel stroke patients is unlikely to have high diagnostic utility. © 2017 American Heart Association, Inc.

  7. Sporadic Ca and Ca+ layers at mid-latitudes: Simultaneous observations and implications for their formation

    Directory of Open Access Journals (Sweden)

    M. Gerding

    2001-01-01

    Full Text Available We report on the observations of 188 sporadic layers of either Ca atoms and/or Ca ions that we have observed during 112 nights of lidar soundings of Ca, and 58 nights of Ca+ soundings, at Kühlungsborn, Germany (54° N, 12° E. The Ca+ soundings have been performed simultaneously and in a common volume with the Ca soundings by two separate lidars. Correlations between sporadic neutral and ionized metal layers are demonstrated through four case studies. A systematic study of the variations of occurrence of sporadic Ca and Ca+ layers reveals that neutral and ionized Ca layers are not as closely correlated as expected earlier: (a The altitude distribution shows the simultaneous occurrence of both sporadic Ca and Ca+ layers to be most likely only in the narrow altitude range between 90 and 95 km. Above that region, in the lower thermosphere, the sporadic ion layers are much more frequent than atom layers. Below 90 km only very few sporadic layers have been observed; (b The seasonal variation of sporadic Ca layers exhibits a minimum of occurrence in summer, while sporadic Ca+ layers do not show a significant seasonal variation (only the dense Ca+ layers appear to have a maximum in summer. At mid-latitudes sporadic Ca layers are more frequent than sporadic layers of other atmospheric metals like Na or K. For the explanation of our observations new formation mechanisms are discussed.Key words. Ionosphere (ion chemistry and composition; ionosphere-atmosphere interactions; mid-latitude ionosphere

  8. Effects of common haplotypes of the ileal sodium dependent bile acid transporter gene on the development of sporadic and familial colorectal cancer: A case control study

    Directory of Open Access Journals (Sweden)

    Friedrichs Nicolaus

    2008-07-01

    Full Text Available Abstract Background The genetics of sporadic and non-syndromic familial colorectal cancer (CRC is not well defined. However, genetic factors that promote the development of precursor lesions, i.e. adenomas, might also predispose to CRC. Recently, an association of colorectal adenoma with two variants (c.507C>T;p.L169L and c.511G>T;p.A171S of the ileal sodium dependent bile acid transporter gene (SLC10A2 has been reported. Here, we reconstructed haplotypes of the SLC10A2 gene locus and tested for association with non-syndromic familial and sporadic CRC compared to 'hyper-normal' controls who displayed no colorectal polyps on screening colonoscopy. Methods We included 150 patients with sporadic CRC, 93 patients with familial CRC but exclusion of familial adenomatous polyposis and Lynch's syndrome, and 204 'hyper-normal' controls. Haplotype-tagging SLC10A2 gene variants were identified in the Hapmap database and genotyped using PCR-based 5' exonuclease assays with fluorescent dye-labelled probes. Haplotypes were reconstructed using the PHASE algorithm. Association testing was performed with both SNPs and reconstructed haplotypes. Results Minor allele frequencies of all SLC10A2 polymorphisms are within previously reported ranges, and no deviations from Hardy-Weinberg equilibrium are observed. However, we found no association with any of the SLC10A2 haplotypes with sporadic or familial CRC in our samples (all P values > 0.05. Conclusion Common variants of the SLC10A2 gene are not associated with sporadic or familial CRC. Hence, albeit this gene might be associated with early stages of colorectal neoplasia, it appears not to represent a major risk factor for progression to CRC.

  9. Somatic mutations of the ret Protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Romei, C.; Elisei, R.; Pinchera, A. [Univ. of Pisa (Italy)] [and others

    1996-04-01

    Germline point mutations in exons 10, 11, and 16 of the ret protooncogene have been identified as causative in multiple endocrine neoplasia type 2 and in familial medullary thyroid carcinoma (MTC). Somatic point mutations of the same gene, exclusively associated with codon 918 of exon 16, have also been reported in few cases of sporadic medullary thyroid carcinoma. We analyzed the blood and tumor DNA of 19 patients with sporadic MTC and 6 patients with primary parathyroid adenoma for point mutations at exons 10, 11, and 16 of the ret protooncogene by restriction analysis of the PCR-amplified product and by sequence analysis of exons 10 and 11. A Cys{sup 634}{r_arrow}Tyr mutation was found in both the tumoral and blood DNA of one patient, indicating that he was affected by an hereditary form of MTC, erroneously considered sporadic. In the other 18 patients with MTC, somatic point mutations of ret were found in 8 cases (44.4%). In 5 cases the mutation affected exon 16 (Met{sup 918}{r_arrow}Thr), and in 3 cases it affected exon 11 (Cys{sup 634}{r_arrow}Arg in 1 and Cys{sup 634}{r_arrow}Trp in 2); these 3 mutations were confirmed by sequence analysis. The remaining 10 patients had no mutation in exon 10 by either restriction analysis or sequence analysis. Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by {chi}{sup 2} analysis). No ret mutation was found in the tumoral DNA from parathyroid adenomas. Our findings indicate that the somatic ret point mutation frequently found in sporadic MTC may affect not only exon 16 but also exon 11 and is associated with less favorable clinical outcome. 14 refs., 2 figs., 3 tabs.

  10. Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Simon, Stéphanie; Lugan, Séverine; Bilheude, Jean-Marc; Perret-Liaudet, Armand; Ironside, James W.; Haik, Stéphane; Basset-Leobon, Christelle; Lacroux, Caroline; Peoch', Katell; Streichenberger, Nathalie; Langeveld, Jan; Head, Mark W.; Grassi, Jacques; Hauw, Jean-Jacques; Schelcher, Francois; Delisle, Marie Bernadette; Andréoletti, Olivier

    2008-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability. PMID:18389084

  11. Creutzfeldt-Jakob Disease Presenting as Expressive Aphasia and Nonconvulsive Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Hafiz B. Mahboob

    2018-01-01

    Full Text Available Creutzfeldt-Jakob disease (CJD, the most common form of human prion diseases, is a fatal condition with a mortality rate reaching 85% within one year of clinical presentation. CJD is characterized by rapidly progressive neurological deterioration in combination with typical electroencephalography (EEG and magnetic resonance imaging (MRI findings and positive cerebrospinal spinal fluid (CSF analysis for 14-3-3 proteins. Unfortunately, CJD can have atypical clinical and radiological presentation in approximately 10% of cases, thus making the diagnosis often challenging. We report a rare clinical presentation of sporadic CJD (sCJD with combination of both expressive aphasia and nonconvulsive status epilepticus. This patient presented with slurred speech, confusion, myoclonus, headaches, and vertigo and succumbed to his disease within ten weeks of initial onset of his symptoms. He had a normal initial diagnostic workup, but subsequent workup initiated due to persistent clinical deterioration revealed CJD with typical MRI, EEG, and CSF findings. Other causes of rapidly progressive dementia and encephalopathy were ruled out. Though a rare condition, we recommend consideration of CJD on patients with expressive aphasia, progressive unexplained neurocognitive decline, and refractory epileptiform activity seen on EEG. Frequent reimaging (MRI, video EEGs and CSF examination might help diagnose this fatal condition earlier.

  12. CAMS newly detected meteor showers and the sporadic background

    Science.gov (United States)

    Jenniskens, P.; Nénon, Q.; Gural, P. S.; Albers, J.; Haberman, B.; Johnson, B.; Morales, R.; Grigsby, B. J.; Samuels, D.; Johannink, C.

    2016-03-01

    The Cameras for Allsky Meteor Surveillance (CAMS) video-based meteoroid orbit survey adds 60 newly identified showers to the IAU Working List of Meteor Showers (numbers 427, 445-446, 506-507, and part of 643-750). 28 of these are also detected in the independent SonotaCo survey. In total, 230 meteor showers and shower components are identified in CAMS data, 177 of which are detected in at least two independent surveys. From the power-law size frequency distribution of detected showers, we extrapolate that 36% of all CAMS-observed meteors originated from ∼700 showers above the N = 1 per 110,000 shower limit. 71% of mass falling to Earth from streams arrives on Jupiter-family type orbits. The transient Geminids account for another 15%. All meteoroids not assigned to streams form a sporadic background with highest detected numbers from the apex source, but with 98% of mass falling in from the antihelion source. Even at large ∼7-mm sizes, a Poynting-Robertson drag evolved population is detected, which implies that the Grün et al. collisional lifetimes at these sizes are underestimated by about a factor of 10. While these large grains survive collisions, many fade on a 104-y timescale, possibly because they disintegrate into smaller particles by processes other than collisions, leaving a more resilient population to evolve.

  13. A review of drug therapy for sporadic fatal insomnia.

    Science.gov (United States)

    Tabaee Damavandi, Pardis; Dove, Martin T; Pickersgill, Richard W

    2017-09-03

    Sporadic fatal insomnia (sFI) is a rapid progressive neurodegenerative disease characterised by gradual to perpetual insomnia, followed by dysautonomia, coma and death. 1 The cause of sFI was recently mapped to a mutation in a protein, the prion, found in the human brain. It is the unfolding of the prion that leads to the generation of toxic oligomers that destroy brain tissue and function. Recent studies have confirmed that a methionine mutation at codon 129 of the human Prion is characteristic of sFI. Current treatment slows down the progression of the disease, but no cure has been found, yet. We used Molecular Docking and Molecular Dynamics simulation methods, to study the toxic Fatal-Insomnia-prion conformations at local unfolding. The idea was to determine these sites and to stabilise these regions against unfolding and miss-folding, using a small ligand, based on a phenothiazine "moiety". As a result we here discuss current fatal insomnia therapy and present seven novel possible compounds for in vitro and in vivo screening.

  14. Facing and managing natural disasters in the Sporades islands, Greece

    Science.gov (United States)

    Karanikola, P.; Panagopoulos, T.; Tampakis, S.; Karantoni, M. I.; Tsantopoulos, G.

    2014-04-01

    The region of the Sporades islands located in central Greece is at the mercy of many natural phenomena, such as earthquakes due to the marine volcano Psathoura and the rift of Anatolia, forest fires, floods, landslides, storms, hail, snowfall and frost. The present work aims at studying the perceptions and attitudes of the residents regarding how they face and manage natural disasters. A positive public response during a hazard crisis depends not only upon the availability and good management of a civil defense plan but also on the knowledge and perception of the possible hazards by the local population. It is important for the stakeholders to know what the citizens expect so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly about the immediate response of stakeholders and their involvement and responsibilities at different, subsequent intervals of time following the disaster. The residents were also asked about the most common disasters that happen in their region and about the preparation activities of the stakeholders.

  15. The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status

    International Nuclear Information System (INIS)

    Kruschewski, Martin; Mueller, Kathrin; Lipka, Sybille; Budczies, Jan; Noske, Aurelia; Buhr, Heinz Johannes; Elezkurtaj, Sefer

    2011-01-01

    The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21− combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21− carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status

  16. Sporadic Hirschsprung`s disease due to a novel nonsense mutation in the RET protooncogene

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, K.M.; Donis-Keller, H.; Langer, J.C. [and others

    1994-09-01

    Hirschsprung`s disease (HSCR, aganglionic megacolon) is characterized by a lack of ganglion cells along variable lengths of the hindgut. This is most likely due to a failure of the progenitor cells (that are destined to become the ganglion cells of the submucosal and myenteric plexuses) to complete their distal migration in the colon. Recently, mutations in the RET protoocogene have been reported in association with HSCR. We report a novel nonsense mutation resulting in a severely truncated protein. Germline DNA from a panel of 6 HSCR patients was analyzed by SSCP for 20 exons of RET. Eight exons were also directly sequenced. We identified a novel mutation within RET exon 2. The mutation (TAC{sub 36}{yields}TAG{sub 36}), which occurs at nucleotide position 108, involves the replacement of tyrosine with a stop codon and results in a truncated 35 amino acid protein. This mutation is the most 5{prime} nonsense mutation reported thus far. Interestingly, the patient has no prior family history of HSCR and was also diagnosed with multiple developmental anomalies including dysplastic kidney. Recent gene targeting studies with mouse models have shown that RET is essential for normal renal development. However, a parallel phenotype has not been seen in other reported HSCR patients with RET mutations. The observations reported here provide evidence that RET plays a role in human renal development. Ongoing studies will determine the extent of RET involvement in sporadic cases of HSCR.

  17. Risk factors and analysis of long-term headache in sporadic vestibular schwannoma: a multicenter cross-sectional study.

    Science.gov (United States)

    Carlson, Matthew L; Tveiten, Øystein Vesterli; Driscoll, Colin L; Boes, Christopher J; Sullan, Molly J; Goplen, Frederik K; Lund-Johansen, Morten; Link, Michael J

    2015-11-01

    The primary goals of this study were: 1) to examine the influence of disease and treatment on headache in patients with sporadic vestibular schwannoma (VS); and 2) to identify clinical predictors of long-term headache disability. This was a cross-sectional observational study with international multicenter enrollment. Patients included those with primary sporadic Headache Disability Inventory (HDI), the Hospital Anxiety and Depression Scale, and a VS symptom questionnaire. The main outcome measures were univariate and multivariable associations with HDI total score. The overall survey response rate was 79%. Data from 538 patients with VS were analyzed. The mean age at time of survey was 64 years, 56% of patients were female, and the average duration between treatment and survey was 7.7 years. Twenty-seven percent of patients received microsurgery, 46% stereotactic radiosurgery, and 28% observation. Patients with VS who were managed with observation were more than twice as likely to have severe headache disability compared with 103 control subjects without VS. When accounting for baseline differences, there was no statistically significant difference in HDI outcome between treatment modalities at time of survey. Similarly, among the microsurgery cohort, the long-term risk of severe headache disability was not different between surgical approaches. Multivariable regression demonstrated that younger age, greater anxiety and depression, and a preexisting diagnosis of headache were the primary predictors of severe long-term headache disability, while tumor size and treatment modality had little influence. At a mean of almost 8 years following treatment, approximately half of patients with VS experience headaches of varying frequency and severity. Patient-driven factors including age, sex, mental health, and preexisting headache syndrome are the strongest predictors of long-term severe headache disability. Tumor size and treatment modality have less impact. These data

  18. Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer.

    Science.gov (United States)

    Ghanipour, L; Jirström, K; Sundström, M; Glimelius, B; Birgisson, H

    2017-02-01

    Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases. Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46-12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant. No correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  19. A cohort study on 10-year survival of sporadic medullary thyroid carcinoma with somatic RET mutation

    Directory of Open Access Journals (Sweden)

    Li-Lun Chuang

    2016-11-01

    Full Text Available Somatic rearranged during transfection (RET mutations are reported in 40–50% of sporadic medullary thyroid carcinoma (sMTC patients with prognostic significance. As there is a lack of somatic RET mutations reported previously for the Taiwanese population, we tried to assess the presence of somatic RET mutations and evaluate the potential outcome predictors for our sMTC patients. We collected data from seven sMTC patients from the years 1997 to 2005 and analyzed their clinic-pathological features up to 2015. All patients were still alive to follow up for 11∼18 years. Tumor DNAs were extracted to assess exons 10–11 and 13–16, and the intron-exon boundaries of the RET gene. Six cases (86% were screened positive of somatic RET gene mutations in hotspot regions, one at M918T, one at C620R, and three at C634S, with another two rare mutations at L629Q and V642I. Comparing the current tumor, node, metastases staging system, the 10-year survival outcomes for our sMTC patients was not predicted by serum calcitonin and/or carcinoembryonic antigen, surgical extent, and presence of the somatic RET gene mutations. The small cohort demonstrated a relatively good outcome of sMTC patients to survive >10 years. In addition, intensive treatment with total thyroidectomy with extensive neck lymph node dissection seemed to be the critical determinant of better survival outcome for sMTC patients.

  20. Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis

    Science.gov (United States)

    2014-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to the death of affected individuals within years. The involvement of inflammation in the pathogenesis of neurodegenerative diseases, including ALS, is increasingly recognized but still not well understood. The aim of this study is to evaluate the levels of inflammation-related IL-1 family cytokines (IL-1β, IL-18, IL-33, IL-37) and their endogenous inhibitors (IL-1Ra, sIL-1R2, IL-18BP, sIL-1R4) in patients with sporadic ALS (sALS), Methods Sera were collected from 144 patients (125 patients were characterized by disease form, duration, and disability, using the revised ALS functional rating scale (ALSFRS-R) and from 40 matched controls. Cerebrospinal fluid (CSF) was collected from 54 patients with sALS and 65 patients with other non-infectious non-oncogenic diseases as controls. Cytokines and inhibitors were measured by commercial ELISA. Results Among the IL-1 family cytokines tested total IL-18, its endogenous inhibitor IL-18BP, and the active form of the cytokine (free IL-18) were significantly higher in the sALS sera than in controls. No correlation between these soluble mediators and different clinical forms of sALS or the clinical setting of the disease was found. IL-18BP was the only mediator detectable in the CSF of patients. Conclusions Among the IL-1 family cytokines, only IL-18 correlates with this disease and may therefore have a pathological role in sALS. The increase of total IL-18 suggests the activation of IL-18-cleaving inflammasome. Whether IL-18 upregulation in circulation of sALS patients is a consequence of inflammation or one of the causes of the pathology still needs to be addressed. PMID:24884937

  1. Normocalcemia and persistent elevated serum concentrations of 1-84 parathyroid hormone after operation for sporadic parathyroid adenoma

    DEFF Research Database (Denmark)

    Vestergaard, Henrik; ØStergaard Kristensen, Lars

    2002-01-01

    Elevated serum concentrations of 1-84 parathyroid hormone (PTH) after operation for sporadic parathyroid adenoma have been reported in previous studies, years after operation for primary hyperparathyroidism (pHPT). The cause and significance of this finding have not been elucidated. Primary...... hyperparathyroidism was diagnosed in 195 patients from January 1987 to December 1998. Operation for pHPT was performed in 124 patients. To evaluate long-term effects of elevated serum 1-84 PTH, biochemical variables and pre- and postoperative diseases were investigated from hospital case records. Of the 124 patients...... of diagnosis concerning clinical characteristics. More that 12 months after operation for pHPT, the patients in group B, with persistent elevated serum concentrations of 1-84 PTH, had a significantly (c2 = 11, p = 0.005, and power of test 0.66) higher frequency of cardiovascular diseases from ischemic heart...

  2. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Mitesh J Borad

    2014-02-01

    Full Text Available Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM. In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.

  3. Association between polymorphism of SMAD3 gene and risk of sporadic intracranial arterial aneurysms in the Chinese Han population.

    Science.gov (United States)

    Liao, Mao-Fan; Gong, Qiu-Wen; Liu, Liang; Xiong, Xiao-Yi; Zhang, Qin; Gong, Chang-Xiong; Yang, Qing-Wu

    2018-01-01

    Intracranial arterial aneurysms (IAAs) are locally abnormal dilations of the cerebral arteries and often result in subarachnoid hemorrhages (SAH). Genetic, molecular and cellular mechanisms of sporadic IAAs forms are poorly understood. In this study, we investigate the association between mothers against decapentaplegic homolog 3 (SMAD3) genotypes and the risk of sporadic intracranial arterial aneurysms among the Chinese Han population. A case-control study was conducted examining 330 IAA patients and 313 controls. There were eight single nucleotide polymorphisms of SMAD3 selected and genotyped using the polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Our results indicated that SMAD3 rs1065080 polymorphism was associated with a risk of IAAs in a codominant model (GA vs GG, OR=1.433; 95% CI 1.030-1.994; P=0.032). In summary, we observed that SMAD3 rs1065080 single nucleotide gene polymorphisms were significantly associated with patient susceptibility to IAAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Yu Hui [Department of Respiratory Diseases, Shanghai Pneumology Hospital, Tongji University, Shanghai (China); Higa, Futoshi; Hibiya, Kenji; Furugen, Makoto [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Sato, Yoko [Tomishiro Chuo Hospital, Okinawa (Japan); Shinzato, Takashi [Nakagami General Hospital, Okinawa (Japan); Haranaga, Shusaku; Yara, Satomi; Tateyama, Masao [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Fujita, Jiro, E-mail: fujita@med.u-ryukyu.ac.j [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Li, Huiping [Department of Respiratory Diseases, Shanghai Pneumology Hospital, Tongji University, Shanghai (China)

    2010-06-15

    Objective: To describe the chest computed tomographic (CT) findings of Legionella pneumophila pneumonia. Methods: CT scans obtained from 23 sporadic cases of L. pneumophila pneumonia were retrospectively reviewed. Chest CT findings were analyzed with regard to the patterns and distributions of pulmonary abnormalities. We also analyzed the histopathology of lungs from guinea pigs with experimentally induced L. pneumophila pneumonia. Results: Consolidation and ground-glass opacity (GGO) were the main findings of CT scans in L. pneumophila pneumonia. The distribution of opacities was categorized as non-segmental (n = 20) and segmental (n = 4). Non-segmental distribution may follow an onset of segmental distribution. Pleural effusion was observed in 14 (58.3%) patients, of which 13 were accompanied with non-segmental distribution. Abscess formation was observed in only one immunocompromised patient. In the animal pneumonia model, the lesions comprised of terminal bronchioles, alveolar spaces, and interstitia. Small bacilli were observed to be contained by many macrophages within the alveoli. Conclusion: Non-segmental distribution was significantly more frequent than segmental distribution in L. pneumophila pneumonia. It is possible that L. pneumophila infection initially results in segmental pneumonia, which progresses to typical non-segmental distribution.

  5. Maxillary sporadic Burkitt′s lymphoma associated with neuro-orbital involvement in an Indian male

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Manne

    2014-01-01

    Full Text Available Burkitt′s lymphoma (BL is the fastest growing malignancy of the lymphoreticular system to affect humans and has a potential ability to double in size every day. A case of maxillary sporadic BL (sBL associated with neuro-orbital involvement in an Indian male is presented. sBL initially presented as maxillary swelling with no obvious dental and periodontal changes. Histological specimen from incisional biopsy revealed a round cell malignant tumor and immunohistochemistry reactions favored nonHodgkin′s lymphoma consistent with BL. Four weeks later, patient presented with orbital involvement as diplopia, sixth cranial nerve palsy, and medial rectus palsy. Chemotherapy regimen according to LMB 89 protocol was started. During chemotherapy regimen patient showed bradycardia and Babinski response, suggestive of central nervous system involvement. sBL associated with orbital involvement is extremely rare and only seven cases have been reported. Our case showed unusual presentation; despite the aggressive tumor did not show any common clinical, radiological, and hematological findings. We also discussed the role of oral medicine specialist, importance of early diagnosis, and prompt referral in management of maxillary sBL.

  6. Chlamydia pecorum: fetal and placental lesions in sporadic caprine abortion.

    Science.gov (United States)

    Giannitti, Federico; Anderson, Mark; Miller, Myrna; Rowe, Joan; Sverlow, Karen; Vasquez, Marce; Cantón, Germán

    2016-03-01

    Chlamydial abortion in small ruminants is usually associated with Chlamydia abortus infection. Although Chlamydia pecorum has been detected in aborted ruminants and epidemiological data suggests that C. pecorum is abortigenic in these species, published descriptions of lesions in fetuses are lacking. This work describes fetoplacental lesions in a caprine abortion with C. pecorum infection, and further supports the abortigenic role of C. pecorum in ruminants. A 16-month-old Boer goat aborted twin fetuses at ~130 days of gestation. Both fetuses (A and B) and the placenta of fetus A were submitted for postmortem examination and diagnostic workup. At autopsy, the fetuses had moderate anasarca, intermuscular edema in the hindquarters (A), and brachygnathia and palatoschisis (B). In the placenta, the cotyledons were covered by yellow fibrinosuppurative exudate that extended into the adjacent intercotyledonary areas. Histologically, there was severe suppurative and necrotizing placentitis with vasculitis (arteriolitis) and thrombosis, multifocal lymphohistiocytic and neutrophilic hepatitis (A), and fibrinosuppurative enteritis in both fetuses. Chlamydia antigen was detected in the placenta by the direct fluorescent antibody test and in fetal intestines by immunohistochemistry. Nested polymerase chain reaction of DNA extracted from formalin-fixed, paraffin-embedded sections of placenta and intestine amplified 400 bp of the Chlamydia 16S rRNA gene that was sequenced and found to be 99% identical to C. pecorum by BLAST analysis. Other known abortigenic infectious agents were ruled out by specific testing. It is concluded that C. pecorum infection is associated with fetoplacental lesions and sporadic abortion in goats. © 2015 The Author(s).

  7. Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia

    Directory of Open Access Journals (Sweden)

    Fritzsche Markus

    2002-12-01

    Full Text Available Abstract Background Clusters by season and locality reveal a striking epidemiological overlap between sporadic schizophrenia and multiple sclerosis (MS. As the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodid ticks, a meta analysis has been performed between all neuropsychiatric birth excesses including MS and the epidemiology of spirochaetal infectious diseases. Results The prevalence of MS and schizophrenic birth excesses entirely spares the tropical belt where human treponematoses are endemic, whereas in more temperate climates infection rates of Borrelia garinii in ticks collected from seabirds match the global geographic distribution of MS. If the seasonal fluctuations of Lyme borreliosis in Europe are taken into account, the birth excesses of MS and those of schizophrenia are nine months apart, reflecting the activity of Ixodes ricinus at the time of embryonic implantation and birth. In America, this nine months' shift between MS and schizophrenic births is also reflected by the periodicity of Borrelia burgdorferi transmitting Ixodes pacificus ticks along the West Coast and the periodicity of Ixodes scapularis along the East Coast. With respect to Ixodid tick activity, amongst the neuropsychiatric birth excesses only amyotrophic lateral sclerosis (ALS shows a similar seasonal trend. Conclusion It cannot be excluded at present that maternal infection by Borrelia burgdorferi poses a risk to the unborn. The seasonal and geographical overlap between schizophrenia, MS and neuroborreliosis rather emphasises a causal relation that derives from exposure to a flagellar virulence factor at conception and delivery. It is hoped that the pathogenic correlation of spirochaetal virulence to temperature and heat shock proteins (HSP might encourage a new direction of research in molecular epidemiology.

  8. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

    Science.gov (United States)

    Diekstra, Frank P; Saris, Christiaan G J; van Rheenen, Wouter; Franke, Lude; Jansen, Ritsert C; van Es, Michael A; van Vught, Paul W J; Blauw, Hylke M; Groen, Ewout J N; Horvath, Steve; Estrada, Karol; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G; Robberecht, Wim; Andersen, Peter M; Melki, Judith; Meininger, Vincent; Hardiman, Orla; Landers, John E; Brown, Robert H; Shatunov, Aleksey; Shaw, Christopher E; Leigh, P Nigel; Al-Chalabi, Ammar; Ophoff, Roel A; van den Berg, Leonard H; Veldink, Jan H

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 × 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for

  9. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

    Directory of Open Access Journals (Sweden)

    Frank P Diekstra

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls. These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls. Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 × 10(-51 withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible

  10. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

    DEFF Research Database (Denmark)

    Ferrari, Raffaele; Wang, Yunpeng; Vandrovcova, Jana

    2017-01-01

    BACKGROUND: Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap betwee...

  11. Human herpesvirus 8 is not detectable in lesions of large plaque parapsoriasis, and in early-stage sporadic, familial, and juvenile cases of mycosis fungoides.

    Science.gov (United States)

    Amitay-Laish, Iris; Sarid, Ronit; Ben-Amitai, Dan; Kalt, Inna; Masa, Shiri Rivka; David, Michael; Feinmesser, Meora; Hodak, Emmilia

    2012-01-01

    Human herpesvirus (HHV) 8, an essential etiologic agent of Kaposi sarcoma, is also associated with several lymphoproliferative disorders. The involvement of HHV 8 in mycosis fungoides (MF) and large plaque parapsoriasis (LPP) is controversial, with contradictory reports from various countries worldwide. We sought to investigate the presence of the HHV 8 genome in skin lesions of LPP and early-stage sporadic, familial, and juvenile MF in patients in Israel. Archival paraffin-embedded and frozen samples from skin biopsies of untreated patients with LPP and early-stage MF performed in 1990 through 2006 were randomly collected from the department of dermatology of a tertiary medical center in central Israel. DNA was extracted, and a TaqMan-based real-time polymerase chain reaction assay specific for the K6 gene region was used to detect the HHV 8 genome. A total of 46 biopsies were sampled from 11 patients with LPP and 35 with early-stage MF (17 adults with sporadic MF, 10 children, and 8 patients with familial MF). In all, 44 samples were negative for HHV 8 DNA; two samples from adults with sporadic MF were positive. The presence of HHV 8 antibodies or virus sequences was not assessed in peripheral blood. The results of this study, conducted in a region relatively endemic for HHV 8, support most earlier studies showing a lack of association of HHV 8 infection with LPP and sporadic adult-type MF. To our knowledge, the lack of association of HHV 8 infection with juvenile and familial MF has not been previously reported. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  12. Disease: H00061 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available se (GSD); Gerstmann-Straussler-Scheinker disease (GSSD); Fatal familial insomnia (FFI) Prion diseases, also ...einker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to

  13. Sporadic-E and spread-F in high latitude region

    International Nuclear Information System (INIS)

    Tao, Kazuhiko

    1974-01-01

    The heretofore made morphological studies of sporadic-E and spread-F as the typical irregularities of electron density are reviewed. These phenomena have close correlation with other geophysical phenomena which occur in the atmosphere of superhigh altitude in high latitude region. Many of these phenomena occur from same causes. Although the quantitative data are insufficient, the sporadic-E and spread-F in high latitude region are supposed to be caused by the precipitating charged particles falling from magnetosphere. A system, which can observe such phenomena simultaneously using the measuring instruments carried by satellites in the atmosphere of high altitude over high latitude region, is desirable to solve such problems. In detail, the morphological study on sporadic-E obtained from the observation of vertically projected ionosphere and the morphological study on sporadic-E from the observation of forward scattering and slanting entrance are reviewed. The correlation of the occurrence frequency of sporadic-E with solar activity, geomagnetic activity and other phenomena was studied. The morphological study on spread-F occurrence is reviewed. The observation of the spread-F in high latitude region by the application of top side sounding is reviewed. The correlation of the sporadic-E and spread-F in high latitude region with other geophysical phenomena is discussed. Finally, the discrete phenomenon and the diffuse phenomenon are discussed too. (Iwakiri, K.)

  14. Summary and consensus in 7th International Conference on acoustic neuroma: An update for the management of sporadic acoustic neuromas

    Directory of Open Access Journals (Sweden)

    Hao Wu

    2016-12-01

    Full Text Available Sporadic vestibular schwannoma (acoustic neuroma is a benign tumor arising from cochleovestibular nerve. Nowadays, various specialties and medical centers are treating this disease, and the multidisciplinary collaboration is the trend. In an effort to promote a uniform standard for reporting clinical results, even for treatment indications, the mainly controversies were posed and discussed during the 7th International Conference on acoustic neuroma, and the agreement was summarized by the Committee of this conference. The main symptoms grading and tumor stage should note its name of classification for making them comparable. The goal of the modern managements for vestibular schwannoma is to improve the quality of life with lower mortality, lower morbidity and better neurological function preservation. The experience of surgical team and their preference might be a major factor for the outcome. Because of lacking of long-term follow-up large data after radiotherapy, and with the development of microsurgery, radiotherapy is now less recommended except for recurrent cases or elderly patients. Keywords: Sporadic acoustic neuroma, Vestibular schwannoma, Management, Symptoms grading, Tumor stage, Microsurgery, Radiotherapy

  15. Analysis of AP2S1, a calcium-sensing receptor regulator, in familial and sporadic isolated hypoparathyroidism.

    Science.gov (United States)

    Lambert, Anne-Sophie; Grybek, Virginie; Francou, Bruno; Esterle, Laure; Bertrand, Guylène; Bouligand, Jérôme; Guiochon-Mantel, Anne; Hieronimus, Sylvie; Voitel, Dorit; Soskin, Sylvie; Magdelaine, Corinne; Lienhardt, Anne; Silve, Caroline; Linglart, Agnès

    2014-03-01

    Except after neck surgery, hypoparathyroidism is a rare disease caused by defects in genes involved in parathyroid gland development (TBX1/22q11.2 del, GCMB, GATA3, TBCE) or function [calcium sensing receptor (CASR), GNA11, PTH], or the autoimmune polyglandular syndrome type 1 (AIRE). Approximately 90% of sporadic cases and 30% of familial cases of isolated hypoparathyroidism remain unexplained. Recurrent missense mutations in AP2S1, a calcium-sensing receptor regulator, have been recently identified in familial hyperparathyroidism. The aim of the study was to investigate AP2S1 as a putative hypoparathyroidism-causing gene. Sequencing analysis and quantitative genomic PCR of the AP2S1 gene in a large cohort of 10 index cases (from nine families) and 50 sporadic cases affected with isolated hypoparathyroidism were investigated. None of the 60 patients presented with nucleotidic changes or copy number variation in the AP2S1 gene, thereby excluding AP2S1 defects as a frequent cause of isolated hypoparathyroidism.

  16. Insulin-Resistant Brain State: the culprit in sporadic Alzheimer’s Disease?

    Science.gov (United States)

    Correia, Sónia C.; Santos, Renato X.; Perry, George; Zhu, Xiongwei; Moreira, Paula I.; Smith, Mark A.

    2011-01-01

    Severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer’s disease (sAD) pathology. Indeed, the “insulin-resistant brain state” has been hypothesized to form the core of the neurodegenerative events that occur in sAD. In this vein, intracerebroventricular administration of subdiabetogenic doses of streptozotocin (STZ) in rats can induce an insulin-resistant brain state, which is proposed as a suitable experimental model of sAD. This review highlights the involvement of disturbed brain insulin metabolism in sAD etiopathogenesis. Furthermore, current knowledge demonstrates that central STZ administration produces brain pathology and behavioral changes that resemble changes found in sAD patients. The STZ-intracerebroventricularly treated rat represents a promising experimental tool in this field by providing new insights concerning early brain alterations in sAD, which can be translated in novel etiopathogenic and therapeutic approaches in this disease. PMID:21262392

  17. [Sporadic case of non-progressive neurogenic muscular atrophy localized in both calf muscles].

    Science.gov (United States)

    Hara, Kenju; Tateyama, Maki; Suzuki, Naoki; Shibano, Ken; Tanaka, Keiko; Ishiguro, Hideaki

    2013-01-01

    A 60-year-old woman was admitted to our hospital because of difficulty in standing on her toes. Neurological examination showed muscle weakness in both calf muscles. Her serum creatine kinase (CK) level was slightly elevated. MRI revealed hyper-intense signals localized in both the gastrocnemius and soleus muscles. Histological examinations of biopsied muscle specimens showed a marked variation in fiber size, small angular fibers, and hypertrophic and splitting fibers, but no muscle fiber necrosis or regeneration or inflammatory cell infiltration. ATPase stained sections showed small grouped atrophy of type 1 fibers. NADH-TR stained sections showed target/targetoid fibers predominantly in type 1 fibers. Dysferlin immunoreactivity was normal. Follow-up clinical evaluation for one year showed no progression. This patient was diagnosed as having an unknown type of spinal muscular atrophy or benign calf amyotrophy. Sporadic cases characterized by elderly-onset, neurogenic muscular atrophy localized in both calf muscles, and non-progressive course are extremely rare in Japan.

  18. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

    Directory of Open Access Journals (Sweden)

    van der Wall Elsken

    2010-04-01

    Full Text Available Abstract Background Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like type that is known to have a low rate of lympho-vascular invasion (LVI, we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. Methods A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. Results LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78. Conclusion LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.

  19. Prokineticin 1 protein expression is a useful new prognostic factor for human sporadic colorectal cancer.

    Science.gov (United States)

    Nakazawa, Toshiyuki; Goi, Takanori; Hirono, Yasuo; Yamaguchi, Akio

    2015-05-01

    Hematogenous metastasis, regarded as closely related to angiogenic growth factors, is associated with colorectal cancer prognosis. The angiogenic growth factor prokineticin 1 (PROK1) has been cloned from endocrine cells. However, its protein expression in human malignant tumors has not been studied. The current study established the anti-PROK1 monoclonal antibody (mAb) and examined the relationship between the expression of PROK1 protein and human colorectal cancer. The expression of PROK1 protein was assessed in 620 resected sporadic colorectal cancer tissue samples by immunohistochemical staining with in-house-developed human PROK1 mAb to investigate the relationship of PROK1 expression to clinicopathologic factors, recurrence, and survival rate and to evaluate its prognostic significance. The expression of PROK1 protein was detected in 36 % (223/620) of human primary colorectal cancer lesions but no in the healthy mucosa adjacent to the colorectal cancer lesions. According to the clinicopathologic examinations, the frequency of positive PROK1 expression was significantly higher in cases with serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, liver metastasis, hematogenous metastasis, and higher stage disease. The recurrence rate and prognosis for patients with PROK1 expression-positive lesions were significantly worse. In the Cox proportional hazard model, PROK1 expression was an independent prognostic factor. The expression of PROK1 protein was identified for the first time as a new prognostic factor in colorectal cancer.

  20. CSF concentrations of cAMP and cGMP are lower in patients with Creutzfeldt-Jakob disease but not Parkinson's disease and amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Patrick Oeckl

    Full Text Available BACKGROUND: The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP and cyclic guanosine-3',5'-monophosphate (cGMP are important second messengers and are potential biomarkers for Parkinson's disease (PD, amyotrophic lateral sclerosis (ALS and Creutzfeldt-Jakob disease (CJD. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS the cerebrospinal fluid (CSF concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15 had lower cAMP (-70% and cGMP (-55% concentrations in CSF compared with controls (n = 11. There was no difference in PD, PD dementia (PDD and ALS cases. Receiver operating characteristic (ROC curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC of 0.86 (cAMP and 0.85 (cGMP. We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92 and to 93% and 100% for the ratio tau/cAMP (AUC 0.99. CONCLUSIONS/SIGNIFICANCE: We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.

  1. Investigation of DNA damage response and apoptotic gene methylation pattern in sporadic breast tumors using high throughput quantitative DNA methylation analysis technology

    Directory of Open Access Journals (Sweden)

    Prakash Neeraj

    2010-11-01

    Full Text Available Abstract Background- Sporadic breast cancer like many other cancers is proposed to be a manifestation of abnormal genetic and epigenetic changes. For the past decade our laboratory has identified genes involved in DNA damage response (DDR, apoptosis and immunesurvelliance pathways to influence sporadic breast cancer risk in north Indian population. Further to enhance our knowledge at the epigenetic level, we performed DNA methylation study involving 17 gene promoter regions belonging to DNA damage response (DDR and death receptor apoptotic pathway in 162 paired normal and cancerous breast tissues from 81 sporadic breast cancer patients, using a high throughput quantitative DNA methylation analysis technology. Results- The study identified five genes with statistically significant difference between normal and tumor tissues. Hypermethylation of DR5 (P = 0.001, DCR1 (P = 0.00001, DCR2 (P = 0.0000000005 and BRCA2 (P = 0.007 and hypomethylation of DR4 (P = 0.011 in sporadic breast tumor tissues suggested a weak/aberrant activation of the DDR/apoptotic pathway in breast tumorigenesis. Negative correlation was observed between methylation status and transcript expression levels for TRAIL, DR4, CASP8, ATM, CHEK2, BRCA1 and BRCA2 CpG sites. Categorization of the gene methylation with respect to the clinicopathological parameters showed an increase in aberrant methylation pattern in advanced tumors. These uncharacteristic methylation patterns corresponded with decreased death receptor apoptosis (P = 0.047 and DNA damage repair potential (P = 0.004 in advanced tumors. The observation of BRCA2 -26 G/A 5'UTR polymorphism concomitant with the presence of methylation in the promoter region was novel and emerged as a strong candidate for susceptibility to sporadic breast tumors. Conclusion- Our study indicates that methylation of DDR-apoptotic gene promoters in sporadic breast cancer is not a random phenomenon. Progressive epigenetic alterations in advancing

  2. Abnormal Fhit protein expression and high frequency of microsatellite instability in sporadic colorectal cancer.

    Science.gov (United States)

    Sarli, Leopoldo; Bottarelli, Lorena; Azzoni, Cinzia; Campanini, Nicoletta; Di Cola, Gabriella; Bader, Giovanni; Iusco, Domenico; Salvemini, Carlo; Caruso, Giuseppe; Donadei, Enrico; Pizzi, Silvia; D'Adda, Tiziana; Renato, Costi; Roncoroni, Luigi; Bordi, Cesare

    2004-07-01

    The role of Fhit protein in the oncogenesis of colorectal cancer is still in debate. Recent studies have revealed that reduced Fhit protein expression is associated with a deficiency of the mismatch repair protein. One hundred and twenty unselected patients who underwent curative resection for sporadic colorectal cancer in a three-year period were evaluated for microsatellite instability (MSI) using six microsatellite markers, and for the presence of Fhit and mismatch repair (MMR) proteins (Mlh1 and Msh2) by means of immunostaining. The relations between these markers were analysed. Reduced or absent Fhit expression was noted in 18 out of 118 patients. This altered expression was significantly higher in right-sided cancer (P = 0.005), mucinous tumours (P = 0.005) and in poorly differentiated histological types (P = 0.0001). MSI was found in 22 out of 109 patients, more so in right-sided cancer (P = 0.0001), poorly differentiated histology (P = 0.0001), and mucinous tumours (P = 0.0001). No association was found with TNM stage. MSI was present in 66.7% of tumours with altered Fhit expression and in only 10% of tumours with preserved or intermediate Fhit expression (P = 0.0001). Of the tumours with reduced or absent Fhit expression, 72.2% had loss of nuclear Mlh1 or Msh2 expression compared with only 14% of the preserved or intermediate Fhit expression tumours (P = 0.0001). These results support the hypothesis that deficiency in a MMR gene could be a cause of the high frequency of alterations in Fhit expression, and they permit the suggestion that FHIT gene alteration may be part of the genetic pathway involving MSI through which some colorectal cancers arise.

  3. Study on clinical features in general paresis of insane, HIV-associated dementia and Creutzfeldt-Jakob disease behaved as dementia

    Directory of Open Access Journals (Sweden)

    LIU Wen-yan

    2012-06-01

    Full Text Available Objective To investigate the clinical features of general paresis of insane (GPI, HIV-associated dementia (HAD and Creutzfeldt -Jakob disease (CJD. Methods The clinical features, laboratory examination, electroencephalography (EEG, magnetic resonance imaging (MRI, treatment and prognosis of 19 patients (GPI, n = 8; HAD, n = 6; CJD, n = 5 were analyzed retrospectively. Results The cases of three groups had cognitive impairment. At the same time, multiple systems (pyramidal system, extrapyramidal system and cerebellar and multiple cranial nerves were involved. In GPI patients, the results of rapid plasma regain circle card test (RPR and treponema pallidum particle agglutination assay (TPPA were all positive in 8 cases, venereal disease research laboratory tests (VDRL of CSF were positive in 4 cases, and Head MRI showed encephalatrophy in 6 cases. In HAD patients, serologic tests for HIV of all cases were positive, the average protein of CSF was increased significantly and Pandy's test was positive in 2 cases, Head MRI were characterized with multiple space occupying lesions or diffuse abnormal density image. In CJD patients, CSF 14-3-3 protein showed positive in 4 patients, EEG showed diffuse slow waves in 5 case, in which 1 case showed typical periodic triphasic wave, Head MRI in 3 sporadic CJD patients (sCJD showed swelling like changes in sulus of cortex area and 1 varaint CJD (vCJD patient showed hockey like change in thalamencephalon. Conclusion The clinical characteristics of dementia caused by GPI, HAD or CJD are varied, and the diagnosis mainly depends on clinical features, positive findings in serum, CSF, EEG and MRI detections.

  4. Human prion protein (PrP) 219K is converted to PrPSc but shows heterozygous inhibition in variant Creutzfeldt-Jakob disease infection.

    Science.gov (United States)

    Hizume, Masaki; Kobayashi, Atsushi; Teruya, Kenta; Ohashi, Hiroaki; Ironside, James W; Mohri, Shirou; Kitamoto, Tetsuyuki

    2009-02-06

    Prion protein gene (PRNP) E219K is a human polymorphism commonly occurring in Asian populations but is rarely found in patients with sporadic Creutzfeldt-Jakob disease (CJD). Thus the polymorphism E219K has been considered protective against sporadic CJD. The corresponding mouse prion protein (PrP) polymorphism variant (mouse PrP 218K) is not converted to the abnormal isoform (PrP(Sc)) and shows a dominant negative effect on wild-type PrP conversion. To define the conversion activity of this human molecule, we herein established knock-in mice with human PrP 219K and performed a series of transmission experiments with human prions. Surprisingly, the human PrP 219K molecule was converted to PrP(Sc) in variant CJD infection, and the conversion occurred more efficiently than PrP 219E molecule. Notably the knock-in mice with PRNP codon 219E/K showed the least efficient conversion compared with their hemizygotes with PRNP codon 219E/0 or codon 219K/0, or homozygotes with PRNP codon 219E/E or codon 219K/K. This phenomenon indicated heterozygous inhibition. This heterozygous inhibition was observed also in knock-in mice with PRNP codon 129M/V genotype. In addition to variant CJD infection, the human PrP 219K molecule is conversion-competent in transmission experiments with sporadic CJD prions. Therefore, the protective effect of PRNP E219K against sporadic CJD might be due to heterozygous inhibition.

  5. Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH: study protocol

    Directory of Open Access Journals (Sweden)

    Ennis Sarah

    2007-08-01

    Full Text Available Abstract Background Young women presenting with breast cancer are more likely to have a genetic predisposition to the disease than breast cancer patients in general. A genetic predisposition is known to increase the risk of new primary breast (and other cancers. It is unclear from the literature whether genetic status should be taken into consideration when planning adjuvant treatment in a young woman presenting with a first primary breast cancer. The primary aim of the POSH study is to establish whether genetic status influences the prognosis of primary breast cancer independently of known prognostic factors. Methods/design The study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1st June 2001 to 31st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period. Discussion Power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80% receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforward.

  6. Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH): study protocol

    International Nuclear Information System (INIS)

    Eccles, Diana; Gerty, Sue; Simmonds, Peter; Hammond, Victoria; Ennis, Sarah; Altman, Douglas G

    2007-01-01

    Young women presenting with breast cancer are more likely to have a genetic predisposition to the disease than breast cancer patients in general. A genetic predisposition is known to increase the risk of new primary breast (and other) cancers. It is unclear from the literature whether genetic status should be taken into consideration when planning adjuvant treatment in a young woman presenting with a first primary breast cancer. The primary aim of the POSH study is to establish whether genetic status influences the prognosis of primary breast cancer independently of known prognostic factors. The study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1 st June 2001 to 31 st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period. Power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80%) receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforward

  7. Greater Rupture Risk for Familial as Compared to Sporadic Unruptured Intracranial Aneurysms

    Science.gov (United States)

    Broderick, Joseph P.; Brown, Robert D.; Sauerbeck, Laura; Hornung, Richard; Huston, John; Woo, Daniel; Anderson, Craig; Rouleau, Guy; Kleindorfer, Dawn; Flaherty, Matthew L.; Meissner, Irene; Foroud, Tatiana; Moomaw, E. Charles J.; Connolly, E. Sander

    2009-01-01

    Background The risk of intracranial aneurysm (IA) rupture in asymptomatic members of families who have multiple affected individuals is not known. Methods First-degree unaffected relatives of those with a familial history of IA who had a history of smoking or hypertension but no known IA were offered cerebral magnetic resonance angiography (MRA) and followed yearly as part of an NINDS-funded study of familial IA (FIA Study). Results 2874 subjects from 542 FIA families were enrolled. After study enrollment, MRAs were performed in 548 FIA family members with no known history of IA. Of these 548 subjects, 113 subjects (20.6%) had 148 IAs by MRA of whom 5 subjects had IA >= 7 mm. Two subjects with an unruptured IA by MRA/CTA (3 mm and 4mm ACOM) subsequently had rupture of their IA. This represents an annual rate of 1.2 ruptures per 100 subjects (1.2% per year, 95% CI of 0.14% to 4.3% per year). None of the 435 subjects with a negative MRA have had a ruptured IA. Survival curves between the MRA positive and negative cohorts were significantly different (p = 0.004). This rupture rate of unruptured IA in the FIA cohort of 1.2% per year is approximately 17 times higher than the rupture rate for subjects with an unruptured IA in the International Study of Unruptured Aneurysm Study with a matched distribution of IA size and location - 0.069% per year. Conclusions Small unruptured IAs in patients from FIA families may have a higher risk of rupture than sporadic unruptured IAs of similar size, which should be considered in the management of these patients. PMID:19228834

  8. Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort

    Science.gov (United States)

    Wang, Zhen; Tan, Huilian; Kong, Xianghua; Shu, Yang; Zhang, Yuchao; Huang, Yun; Zhu, Yufei; Xu, Heng; Wang, Zhiqiang; Wang, Ping; Ning, Guang; Kong, Xiangyin; Hu, Guohong; Hu, Landian

    2014-01-01

    Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer. PMID:24587289

  9. The genetics of radiation-induced and sporadic osteosarcoma: a unifying theory?

    International Nuclear Information System (INIS)

    Rosemann, Michael; Kuosaite, Virginija; Nathrath, Michaela; Atkinson, Michael J.

    2002-01-01

    Cancer is a disease of the genome, with the neoplastic phenotype being passed from one cell generation to the other. Radiation-induced cancer has often been considered to represent a unique entity amongst neoplasia, with the energy deposition being held responsible for both direct (gene mutations) and indirect (bystander effects, induced instability etc) alterations to the cellular genome. However, radiogenic tumours in man and experimental animals appear to be physiologically and genetically indistinguishable from their sporadic counterparts, suggesting that the aetiologies of these two tumour types are in fact closely related. We have conducted a general screen of the genetic alterations in radiation-induced mouse osteosarcoma, a tumour that is histopathologically indistinguishable from human sporadic osteosarcoma. Comparison of the two tumour types indicates the existence of a common set of genetic changes, providing additional evidence to support the concept that the molecular pathology of radiation-induced malignancy is no different to that of sporadic cancers. (author)

  10. Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer's disease

    International Nuclear Information System (INIS)

    Lannfelt, L.; Lilius, L.; Viitanen, M.; Winblad, B.; Basun, H.; Houlden, H.; Rossor, M.; Hardy, J.

    1995-01-01

    Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer's disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer's disease families, as it is closely linked to the gene. Most cases of Alzheimer's disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer's disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.)

  11. Simultaneous observation of sporadic E with a rapid-run ionosonde and VHF coherent backscatter radar

    Directory of Open Access Journals (Sweden)

    T. Maruyama

    2006-03-01

    Full Text Available During the SEEK 2 rocket campaign, ionograms were recorded every minute at the Yamagawa Radio Observatory at about 90km west of the region monitored by a VHF (very high frequency coherent backscatter radar. Sporadic E-layer parameters, which include the critical (foEs and blanketing (fbEs frequencies, the layer height (h'Es, and the width of the range spread of sporadic E-traces, were compared with RTI (range-time-intensity plots of VHF quasi-periodic (QP and continuous coherent backscatter echoes. A close relationship was found between the appearance of QP echoes in the RTI plots and the level of spatial inhomogeneity in sporadic E plasma, signified here by the difference between foEs and fbEs. During QP echo events, foEs increased while fbEs decreased, so that the difference foEs-fbEs was enhanced, indicating the development of strong spatial structuring in electron density within a sporadic E-layer. On the other hand, increases in sporadic E range spreading also correlated with the occurrence of QP echoes but the degree of correlation varied from event to event. Continuous radar echoes were observed in association with low altitude sporadic E-layers, located well below 100 km and at times as low as 90 km. During the continuous echo events, both foEs and fbEs were less variable, and the difference foEs-fbEs was small and not as dynamic as in the QP echoes. On the other hand, the Es-layer spread intensified during continuous echoes, which means that some patchiness or corrugation in those low altitude layers is also necessary for the continuous backscatter echoes to take place.

  12. Simultaneous observation of sporadic E with a rapid-run ionosonde and VHF coherent backscatter radar

    Directory of Open Access Journals (Sweden)

    T. Maruyama

    2006-03-01

    Full Text Available During the SEEK 2 rocket campaign, ionograms were recorded every minute at the Yamagawa Radio Observatory at about 90km west of the region monitored by a VHF (very high frequency coherent backscatter radar. Sporadic E-layer parameters, which include the critical (foEs and blanketing (fbEs frequencies, the layer height (h'Es, and the width of the range spread of sporadic E-traces, were compared with RTI (range-time-intensity plots of VHF quasi-periodic (QP and continuous coherent backscatter echoes. A close relationship was found between the appearance of QP echoes in the RTI plots and the level of spatial inhomogeneity in sporadic E plasma, signified here by the difference between foEs and fbEs. During QP echo events, foEs increased while fbEs decreased, so that the difference foEs-fbEs was enhanced, indicating the development of strong spatial structuring in electron density within a sporadic E-layer. On the other hand, increases in sporadic E range spreading also correlated with the occurrence of QP echoes but the degree of correlation varied from event to event. Continuous radar echoes were observed in association with low altitude sporadic E-layers, located well below 100 km and at times as low as 90 km. During the continuous echo events, both foEs and fbEs were less variable, and the difference foEs-fbEs was small and not as dynamic as in the QP echoes. On the other hand, the Es-layer spread intensified during continuous echoes, which means that some patchiness or corrugation in those low altitude layers is also necessary for the continuous backscatter echoes to take place.

  13. Early pathology in sleep studies of patients with familial Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Givaty, Gili; Maggio, Nicola; Cohen, Oren S; Blatt, Ilan; Chapman, Joab

    2016-10-01

    In this study, we aimed to assess sleep function in patients with recent-onset familial Creutzfeldt-Jakob disease (fCJD). The largest cluster of fCJD patients is found in Jews of Libyan origin, linked to the prion protein gene (PRNP) E200K mutation. The high index of suspicion in these patients often leads to early diagnosis, with complaints of insomnia being a very common presenting symptom of the disease. The study included 10 fCJD patients diagnosed by clinical manifestations, magnetic resonance imaging (MRI) scan of the brain, elevated tau protein in the cerebrospinal fluid (CSF) and positive PRNP E200K mutation. Standard polysomnography was performed after a brief interview confirming the presence of sleep disturbances. All patients showed a pathological sleep pattern according to all scoring evaluation settings. The sleep stages were characterized by (i) disappearance of sleep spindles; (ii) outbursts of periodic sharp waves and shallowing of sleep consisting in increased Stage 2 and wake periods during the night, as well as decrease of slow-wave sleep and rapid eye movement (REM) sleep. Recordings of respiratory functions reported irregular breathing with central and obstructive apnea and hypopnea. The typical hypotonia occurring during the night and atonia during REM sleep were replaced by hyperactive sleep consisting of multiple jerks, movements and parasomnia (mainly talking) throughout the night. In conclusion, we report unique pathological sleep patterns in early fCJD associated with the E200K mutation. Specific respiratory disturbances and lack of atonia could possibly serve as new, early diagnostic tools in the disease. © 2016 European Sleep Research Society.

  14. Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis.

    Science.gov (United States)

    Azzoni, Cinzia; Bottarelli, Lorena; Campanini, Nicoletta; Di Cola, Gabriella; Bader, Giovanni; Mazzeo, Antonio; Salvemini, Carlo; Morari, Silvia; Di Mauro, Davide; Donadei, Enrico; Roncoroni, Luigi; Bordi, Cesare; Sarli, Leopoldo

    2007-02-01

    Colorectal cancer (CRC) ranks as the fourth most frequently diagnosed cancer worldwide. CRCs that arise proximally or distally to the splenic flexure show differences in epidemiologic incidence, morphology, and molecular alterations, suggesting the existence of two categories of CRC based on the site of origin. The aim of the present work is to investigate the histological and molecular differences between CRCs located proximally and distally to the splenic flexure, and their potential involvement in tumor prognosis and therapeutic strategies. We evaluated 120 patients affected by sporadic CRC for clinicopathologic features, microsatellite instability (MSI), loss of heterozygosity (LOH) of chromosomes 18q, 8p, and 4p; they were also investigated for hMlh1, hMsh2, Fhit, p27, and Cox-2 immunostaining. The mucinous histotype was more frequent in the proximal than in the distal CRCs (pcancer development between the proximal and the distal colon, with potential implications in the therapeutic approach.

  15. Genetics Home Reference: prion disease

    Science.gov (United States)

    ... which have overlapping signs and symptoms, include familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal ... Sc . Sporadic forms of prion disease include sporadic Creutzfeldt-Jakob disease (sCJD), sporadic fatal insomnia (sFI), and variably protease- ...

  16. Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation

    DEFF Research Database (Denmark)

    Ochalek, Anna; Mihalik, Balázs; Avci, Hasan X.

    2017-01-01

    , our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. Methods: We compared neurons derived from induced pluripotent stem cell (iPSC) lines of patients with early-onset familial Alzheimer's disease (fAD), all caused......, a physiological kinase of TAU, in neurons derived from AD iPSCs, as well as significant upregulation of amyloid precursor protein (APP) synthesis and APP carboxy-terminal fragment cleavage. Moreover, elevated sensitivity to oxidative stress, as induced by amyloid oligomers or peroxide, was detected in both f...

  17. Sporadic Endolymphatic Sac Tumor-A Very Rare Cause of Hearing Loss, Tinnitus, and Dizziness

    DEFF Research Database (Denmark)

    Schnack, Didde Trærup; Kiss, Katalin; Hansen, Søren

    2017-01-01

    Sporadic endolymphatic sac tumor is a very rare neoplasm. It is low malignant, locally destructive and expansive, but non-metastasizing. The tumor is very rare in the sporadic form, but more often associated with Von Hippel-Lindau disease. A 65-year old man with left sided tinnitus and hearing loss......-operative freeze-microscopy showed inflammation tissue, whereas subsequent microscopy showed papillary-cystic endolymphatic sac tumor. Endolymphatic sac tumor is a rare neoplasm. The tumor may present with asymmetrically sensory neural hearing loss with or without tinnitus, dizziness and facial nerve paresis...

  18. Reactive GTS Allocation Protocol for Sporadic Events Using the IEEE 802.15.4

    Directory of Open Access Journals (Sweden)

    Mukhtar Azeem

    2014-01-01

    by the IEEE 802.15.4 standard. The proposed control protocol ensures that a given offline sporadic schedule can be adapted online in a timely manner such that the static periodic schedule has not been disturbed and the IEEE 802.15.4 standard compliance remains intact. The proposed protocol is simulated in OPNET. The simulation results are analyzed and presented in this paper to prove the correctness of the proposed protocol regarding the efficient real-time sporadic event delivery along with the periodic event propagation.

  19. Human prion diseases in the Netherlands (1998-2009: clinical, genetic and molecular aspects.

    Directory of Open Access Journals (Sweden)

    Casper Jansen

    Full Text Available Prion diseases are rare and fatal neurodegenerative disorders that can be sporadic, inherited or acquired by infection. Based on a national surveillance program in the Netherlands we describe here the clinical, neuropathological, genetic and molecular characteristics of 162 patients with neuropathologically confirmed prion disease over a 12-year period (1998-2009. Since 1998, there has been a relatively stable mortality of Creutzfeldt-Jakob disease (CJD in the Netherlands, ranging from 0.63 to 1.53 per million inhabitants per annum. Genetic analysis of the codon 129 methionine/valine (M/V polymorphism in all patients with sporadic CJD (sCJD showed a trend for under-representation of VV cases (7.0%, compared with sCJD cohorts in other Western countries, whereas the MV genotype was relatively over-represented (22,4%. Combined PrP(Sc and histopathological typing identified all sCJD subtypes known to date, except for the VV1 subtype. In particular, a "pure" phenotype was demonstrated in 60.1% of patients, whereas a mixed phenotype was detected in 39.9% of all sCJD cases. The relative excess of MV cases was largely accounted for by a relatively high incidence of the MV 2K subtype. Genetic analysis of the prion protein gene (PRNP was performed in 161 patients and showed a mutation in 9 of them (5.6%, including one FFI and four GSS cases. Iatrogenic CJD was a rare phenomenon (3.1%, mainly associated with dura mater grafts. Three patients were diagnosed with new variant CJD (1.9% and one with variably protease-sensitive prionopathy (VPSPr. Post-mortem examination revealed an alternative diagnosis in 156 patients, most commonly Alzheimer's disease (21.2% or vascular causes of dementia (19.9%. The mortality rates of sCJD in the Netherlands are similar to those in other European countries, whereas iatrogenic and genetic cases are relatively rare. The unusual incidence of the VV2 sCJD subtype compared to that reported to date in other Western countries

  20. Inflammatory Gene Expression in Whole Peripheral Blood at Early Stages of Sporadic Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Pol Andrés-Benito

    2017-10-01

    Full Text Available ObjectiveCharacterization of altered expression of selected transcripts linked to inflammation in the peripheral blood of sporadic amyotrophic lateral sclerosis (sALS patients at early stage of disease to increase knowledge about peripheral inflammatory response in sALS.MethodsRNA expression levels of 45 genes were assessed by RT-qPCR in 22 sALS cases in parallel with 13 age-matched controls. Clinical and serum parameters were assessed at the same time.ResultsUpregulation of genes coding for factors involved in leukocyte extravasation (ITGB2, INPP5D, SELL, and ICAM1 and extracellular matrix remodeling (MMP9 and TIMP2, as well as downregulation of certain chemokines (CCL5 and CXC5R, anti-inflammatory cytokines (IL10, TGFB2, and IL10RA, pro-inflammatory cytokines (IL-6, and T-cell regulators (CD2 and TRBC1 was found in sALS cases independently of gender, clinical symptoms at onset (spinal, respiratory, or bulbar, progression, peripheral leukocyte number, and integrity of RNA. MMP9 levels positively correlated with age, whereas CCR5, CCL5, and TRBC1 negatively correlated with age in sALS but not in controls. Relatively higher TNFA expression levels correlate with higher creatinine kinase protein levels in plasma.ConclusionPresent findings show early inflammatory responses characterized by upregulation of factors enabling extravasation of leukocytes and extracellular matrix remodeling in blood in sALS cases, in addition to increased TNFA levels paralleling skeletal muscle damage.

  1. Differential overexpression of SERPINA3 in human prion diseases.

    Science.gov (United States)

    Vanni, S; Moda, F; Zattoni, M; Bistaffa, E; De Cecco, E; Rossi, M; Giaccone, G; Tagliavini, F; Haïk, S; Deslys, J P; Zanusso, G; Ironside, J W; Ferrer, I; Kovacs, G G; Legname, G

    2017-11-15

    Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.

  2. Frequency of 22q11.2 microdeletion in sporadic non-syndromic tetralogy of Fallot cases.

    Science.gov (United States)

    Gioli-Pereira, L; Pereira, A C; Bergara, D; Mesquita, S; Lopes, A A; Krieger, J E

    2008-06-06

    Tetralogy of Fallot (TOF) is a congenital conotruncal heart defect commonly found in DiGeorge (DGS) and velocardiofacial (VCFS) syndromes. The deletion of chromosome 22q11 has also been demonstrated in sporadic or familial cases of TOF. The aim of the present study was to investigate the frequency of del22q11 in patients with non-syndromic TOF seen at a tertiary Pediatric Cardiology care center. One hundred and twenty three non-syndromic TOF patients were selected and evaluated by history, physical examination and review of medical records. Venous blood was drawn for genomic DNA extraction after informed consent 22q11 microdeletion diagnosis was conducted through a standardized SNP genotyping assay and consecutive homozygosity mapping. Phenotype-genotype correlations regarding cardiac anatomy were conducted. We evaluated 123 non-syndromic TOF patients for a 22q11 deletion. 105 (85.4%) patients presented pulmonary stenosis and 18 (14.6%) had pulmonary atresia. Eight patients (6.5%) were found to have a deletion. Of the deleted patients, three (37.5%) presented pulmonary atresia. We have verified a tendency towards a higher prevalence of pulmonary atresia when comparing TOF patients with and without 22q11 microdeletion. 22q11.2 deletion in non-syndromic TOF patients is present in approximately 6% of patients. We suggest a tendency towards a higher prevalence of pulmonary atresia in non-syndromic TOF patients with 22q11 microdeletion. Molecular genetic screening of non-syndromic TOF patient may be important for the correct care of these patients and a more specific genetic diagnostic and counseling.

  3. Differential response of idiopathic sporadic tumoral calcinosis to bisphosphonates

    Directory of Open Access Journals (Sweden)

    Karthik Balachandran

    2014-01-01

    Full Text Available Context: Tumoral calcinosis is a disorder of phosphate metabolism characterized by ectopic calcification around major joints. Surgery is the current treatment of choice, but a suboptimal choice in recurrent and multicentric lesions. Aims: To evaluate the efficacy of bisphosphonates for the management of tumoral calcinosis on optimized medical treatment. Settings and Design: The study was done in the endocrine department of a tertiary care hospital in South India. We prospectively studied two patients with recurrent tumoral calcinosis who had failed therapy with phosphate lowering measures. Materials and Methods: After informed consent, we treated both patients with standard age adjusted doses of bisphosphonates for 18 months. The response was assessed by X ray and whole body 99mTc-methylene diphosphonate bone scan at the beginning of therapy and at the end of 1 year. We also estimated serum phosphate levels and urinary phosphate to document serial changes. Results: Two patients (aged 19 and 5 years with recurrent idiopathic hyperphosphatemic tumoral calcinosis, following surgery were studied. Both patients had failed therapy with conventional medical management − low phosphate diet and phosphate binders. They had restriction of joint mobility. Both were given standard doses of oral alendronate and parenteral pamidronate respectively for more than a year, along with phosphate lowering measures. At the end of 1 year, one of the patients had more than 95% and 90% reduction in the size of the lesions in right and left shoulder joints respectively with total improvement in range of motion. In contrast, the other patient (5-year-old had shown no improvement, despite continuing to maintain normophosphatemia following treatment. Conclusions: Bisphosphonate therapy in tumoral calcinosis is associated with lesion resolution and may be used as a viable alternative to surgery, especially in cases with multicentric recurrence or treatment failure to other

  4. Sporadic hypokalemic paralysis caused by osmotic diuresis in diabetes mellitus.

    Science.gov (United States)

    Vishnu, Venugopalan Y; Kattadimmal, Anoop; Rao, Suparna A; Kadhiravan, Tamilarasu

    2014-07-01

    A wide variety of neurological manifestations are known in patients with diabetes mellitus. We describe a 40-year-old man who presented with hypokalemic paralysis. On evaluation, we found that the cause of the hypokalemia was osmotic diuresis induced by marked hyperglycemia due to undiagnosed diabetes mellitus. The patient had an uneventful recovery with potassium replacement, followed by glycemic control with insulin. Barring a few instances of symptomatic hypokalemia in the setting of diabetic emergencies, to our knowledge uncomplicated hyperglycemia has not been reported to result in hypokalemic paralysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Apolipoprotein E gene and sporadic frontal lobe dementia.

    NARCIS (Netherlands)

    M. Stevens (Martijn); C.M. van Duijn (Cornelia); P. de Knijff (Peter); B.A. Oostra (Ben); M.F. Niermeijer (Martinus); J.C. van Swieten (John); P. Heutink (Peter); C. van Broeckhoven (Christine)

    1997-01-01

    textabstractThe apolipoprotein E gene has been associated with various types of dementia. We studied the connection between the APOE gene and the risk and onset of disease in 34 patients with clinically diagnosed frontal lobe dementia (FLD) derived from a population-based study in the Netherlands. A

  6. Cognitive disorders after sporadic ecstasy use? A case report

    NARCIS (Netherlands)

    Ruis, Carla; Postma, Albert; Bouvy, Willem; van der Ham, Ineke

    2015-01-01

    Memory problems and changes in hippocampal structures after chronic ecstasy use are well described in the literature. Cognitive problems after incidental ecstasy use are rare, and the few patients described in case reports returned to their normal cognitive level after a relative short period. FV is

  7. A rare case of sporadic multiple trichoepitheliomas | Sanaa | Pan ...

    African Journals Online (AJOL)

    No other contributory medical history or similar cases in the family were reported by the patient. With the above features a clinical differential diagnosis of multiple basal cell carcinoma (BCC), multiples trichoepitheliomas or Bourneville's tuberous sclerosis was considered. Histopathological examination of the lesions was in ...

  8. Papillary thyroid cancer: sporadic or inherited? | Mogili | Journal of ...

    African Journals Online (AJOL)

    Background: Papillary thyroid cancer (PTC) is one of the most common thyroid malignancies, with an increase in incidence rates over the past few decades. Although the exact cause of thyroid cancer in most patients is still unclear, the possibility of genetic predisposition to PTC cannot be overlooked. Here, we report a case ...

  9. Higher cytoplasmic and nuclear poly(ADP-ribose) polymerase expression in familial than in sporadic breast cancer

    NARCIS (Netherlands)

    Klauke, M.L.; Hoogerbrugge-van der Linden, N.; Budczies, J.; Bult, P.; Prinzler, J.; Radke, C.; van Krieken, J.H.; Dietel, M.; Denkert, C.; Muller, B.M.

    2012-01-01

    Poly(ADP-ribose) polymerase 1 (PARP) is a key element of the single-base excision pathway for repair of DNA single-strand breaks. To compare the cytoplasmic and nuclear poly(ADP-ribose) expression between familial (BRCA1, BRCA2, or non BRCA1/2) and sporadic breast cancer, we investigated 39 sporadic

  10. Detection of infectivity in blood of persons with variant and sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Douet, Jean Yves; Zafar, Saima; Perret-Liaudet, Armand; Lacroux, Caroline; Lugan, Séverine; Aron, Naima; Cassard, Herve; Ponto, Claudia; Corbière, Fabien; Torres, Juan Maria; Zerr, Inga; Andreoletti, Olivier

    2014-01-01

    We report the presence of infectivity in erythrocytes, leukocytes, and plasma of 1 person with variant Creutzfeldt-Jakob disease and in the plasma of 2 in 4 persons whose tests were positive for sporadic Creutzfeldt-Jakob disease. The measured infectivity levels were comparable to those reported in various animals with transmissible spongiform encephalopathies.

  11. Diet-gene interactions in sporadic and hereditary colorectal carcinogenesis : epidemiological perspectives

    NARCIS (Netherlands)

    Voskuil, D.

    1999-01-01

    Colorectal cancer is known to develop by accumulation of alterations in regulatory genes. Both familial and environmental factors play a role in the etiology of colorectal cancer and its adenomatous precursor lesions. This thesis examines diet-gene interactions in sporadic and hereditary

  12. A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

    NARCIS (Netherlands)

    Wills, A-M.; Cronin, S.; Slowik, A.; Kasperaviciute, D.; Van Es, M. A.; Morahan, J. M.; Valdmanis, P. N.; Meininger, V.; Melki, J.; Shaw, C. E.; Rouleau, G. A.; Fisher, E. M. C.; Shaw, P. J.; Morrison, K. E.; Pamphlett, R.; Van den Berg, L. H.; Figlewicz, D. A.; Andersen, P. M.; Al-Chalabi, A.; Hardiman, O.; Purcell, S.; Landers, J. E.; Brown, R. H.

    2009-01-01

    Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. Methods: We

  13. Mechanism for the formation of sporadic-E layers in the high-latitude ionosphere

    Energy Technology Data Exchange (ETDEWEB)

    Vlasov, M.N.; Mishin, E.V.; Telegin, V.A.

    1980-09-01

    A model of the collective interaction of precipitating electrons and the ionospheric plasma is used to explain the formation of short-duration sporadic-E layers in the high-latitude ionosphere. The changes produced in electron density by this collective interaction mechanism are considered.

  14. Sporadic minute medullary thyroid carcinoma with a double RET mutation: A case report.

    Science.gov (United States)

    Yamamoto, Hiroyuki; Ishii, Jun; Chiba, Tomohiro; Nakazato, Yoko; Hirano, Kouichi; Kamma, Hiroshi

    2017-11-01

    We describe a 74-year-old man with a nodular goiter accompanied by an incidental sporadic minute medullary thyroid carcinoma (MTC). Histopathologically, the MTC was a well-defined 1.7 mm tumor in the upper one-third right lobe, with solid cell nests (SCNs) adjacent to the MTC. C-cells were scattered mainly around the SCNs, but C-cell hyperplasia was not evident in the background thyroid. The MTC cell phenotype was immunohistochemically identical to background C-cells, but was completely different from the SCN main cells. Direct DNA analyses of isolated MTC paraffin-embedded specimens revealed two RET proto-oncogene missense point mutations in exon 11 (i.e., C630R and C634W). The non-tumor thyroid tissue did not reveal any mutations. This study reports the smallest case of sporadic MTC with a double RET somatic mutation, substantiating that RET mutations can occur during a very early stage of carcinogenesis. The combined presence of C630R and C634W represent a novel somatic mutation in sporadic MTC. The present case indicates that the sporadic MTC originated from the surrounding C-cells of the SCNs without C-cell hyperplasia and that the SCN main cells may not be able to develop into an MTC. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  15. Glycoform-selective prion formation in sporadic and familial forms of prion disease

    NARCIS (Netherlands)

    Xiao, X.; Yuan, J.; Haïk, S.; Cali, I.; Zhan, Y.; Moudjou, M.; Li, B.; Laplanche, J.L.; Laude, H.; Langeveld, J.P.M.; Gambetti, P.

    2013-01-01

    The four glycoforms of the cellular prion protein (PrP(C)) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrP(Sc)) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrP(Sc) in the recently identified

  16. The clinical phenotype of hereditary versus sporadic prostate cancer: HPC definition revisited

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Aben, K.K.H.; Oort, I.M. van; Sedelaar, J.P.M.; Vasen, H.F.A.; Vermeulen, S.H.; Kiemeney, L.A.L.M.

    2016-01-01

    BACKGROUND: The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form

  17. Variation of sporadic meteor activity during the 23. cycle of solar activity

    International Nuclear Information System (INIS)

    Porubcan, V.; Zigo, P.; Cevolani, G.; Rozboril, J.; Pupillo, G.

    2009-01-01

    Analyses of the influence of solar activity on sporadic meteor counts based on visual and radar meteor observations present rather contradictory results, indicating a possible variation of the sporadic meteor counts with a solar activity, with the maximum in observed meteor rates occurring from zero up to about five years after the solar activity maximum. With this perspective, in the present paper observations of the sporadic meteor background, obtained by a forward-scatter radio system for meteor observation operating along the Bologna (Italy)-Modra (Slovakia) baseline in 1996-2007, are analysed and discussed. The activity curves of all echoes and their variations indicate a correlation with solar activity in the 23. solar cycle represented by the solar relative number R (corr. coef. 0.71), as well as with the solar coronal index C1 (corr. coef. 0.73). The mass distribution exponent s and its variations (with corr. coef. against R and C1, 0.12 and 0.25, respectively) does not show a correlation consistent with solar activity and, from the viewpoint of s, suggest the existence of a relatively stable population of sporadic background meteoroids in the surroundings of the Earth's orbit during the investigated period.

  18. Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT.

    Science.gov (United States)

    Voermans, Nicol C; Benveniste, Olivier; Minnema, Monique C; Lokhorst, Henk; Lammens, Martin; Meersseman, Wouter; Delforge, Michel; Kuntzer, Thierry; Novy, Jan; Pabst, Thomas; Bouhour, Françoise; Romero, Norma; Leblond, Veronique; Bergh, Peter van den; Vekemans, Marie-Christiane; van Engelen, Baziel G; Eymard, Bruno

    2014-12-02

    Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement. © 2014 American Academy of Neurology.

  19. EEG–EMG polygraphic study of dystonia and myoclonus in a case of Creutzfeldt–Jakob disease

    Directory of Open Access Journals (Sweden)

    Takao Hashimoto

    2015-01-01

    Full Text Available We report on a patient with sporadic Creutzfeldt–Jakob disease (CJD who showed dystonia, periodic myoclonus, and periodic sharp wave complexes (PSWCs on EEG. The EEG–EMG polygraphic study revealed that dystonia appeared without relation to periodic myoclonus and PSWCs and that dystonia EMGs were strongly suppressed after periodic myoclonus EMGs. These findings suggest that dystonia has a pathogenesis different from that of periodic myoclonus and PSWCs, but dystonia and periodic myoclonus may be generated through the sensorimotor cortex in CJD.

  20. [Correlation anslysis of sporadic breast cancer and BRCA1 gene plymorphisms in the Han Nationality and the Mongol Nationality of Inner Mongolia Region].

    Science.gov (United States)

    Ma, Jinzhu; Liu, Ming; Zhang, Xinlai; BuRi, Gude

    2015-12-08

    To study the correlationship between the BRCA1 gene polymorphisms, especially in 2731 loci (rs799917), and sporadic breast cancer in the Han nationality and the Mongol nationality of the Inner Mongolia region. Using the prospective study method, 103 cases of patients with sporadic breast cancer (case group) and 103 cases of normal physical examination people (control group) were enrolled. PCR and direct sequencing method were used for analyzing the correlationship of 2731 loci polymorphisms of BRCA1 and sporadic breast cancer in our zone. In the case group, the age stratification, pathologic stage, immunohistochemistry and the distribution of lymph node metastasis had no significant difference in two ethnic group (P> 0.05). The age stratification of control group also had no significant difference in two ethnic group (P>0. 05). There was no statistically significant difference in age stratification of the case group and the control group (P>0.05). In the Inner Mongolia region, BRCA1 gene 2731 loci genotypes check out three genotypes: namely TT, CT and CC. The frequencies of genotype TT, CT, CC in the case group were 13.1%, 26.2%, 60.7% ( the Han nationality) and 16.7%, 28.6%, 54.7% (the Mongol nationality), respectively. Meanwhile the frequencies of allele T and allele C were 71.8% and 28.2%. In the control group, the frequencies of genotype TT, CT, CC were 18.0%, 31.1%, 50.9% ( the Han nationality) and 23.8%, 38.1%, 38.1% ( the Mongol nationality), respectively, and the frequencies of allele T and allele C were 62.9% and 37.1%. BRCA1 gene 2 731 loci gene polymorphism had no significant difference in two groups (χ(2)=3.438, P=0.752), but T allele frequency distribution in the case group was significantly increased (χ(2)=4.185, P=0.041). There is no obvious correlation between the BRCA1 gene 2731 loci and sporadic breast cancer in the Han nationality and the Mongol nationality of the Inner Mongolia region. C allele of BRCA1 gene 2731 loci may be one of the

  1. Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt–Jakob disease: a case report

    Directory of Open Access Journals (Sweden)

    Rodríguez-Martínez Ana B

    2012-10-01

    Full Text Available Abstract Introduction The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. Case presentation A 74-year-old Caucasian woman showed a sporadic Creutzfeldt–Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77. Neuropathological findings showed: spongiform change in the patient’s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. Conclusion Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt–Jakob disease. This highlights the

  2. A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.

    Science.gov (United States)

    Hadiji-Abbes, N; Trifa, F; Choura, M; Khabir, A; Sellami-Boudawara, T; Frikha, M; Daoud, J; Mokdad-Gargouri, R

    2015-09-01

    Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer. Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP. We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain. A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Trismus Pseudocamptodactyly Syndrome: A Sporadic Cause of Trismus

    OpenAIRE

    Sreenivasan, Prathima; Peedikayil, Faizal C.; Raj, Sumal V.; Meundi, Manasa Anand

    2013-01-01

    Trismus pseudocamptodactyly syndrome is a very rare autosomal dominant inherited disorder characterized by the inability to completely open the mouth (trismus) and the presence of abnormally short tendon units causing the fingers to curve (camptodactyly). Early diagnosis and management of this condition is important to prevent facial deformities in the patient. Reporting such a case is important as case reports are one of the sources of data for calculating the prevalence of rare diseases. He...

  4. [A sporadic case of episodic ataxia with nystagmus (EA-2)].

    Science.gov (United States)

    Namekawa, M; Takiyama, Y; Ueno, N; Nishizawa, M

    1998-05-01

    A 39-year-old man with episodic ataxia with nystagmus (EA-2) was reported. He showed intermittent cerebellar dysfunction, i.e., ataxia, nystagmus, dysarthria and vertigo, since he was 10 years old. Although this attack lasted for several hours, he was normal with exception of interictal nystagmus. His parents and sister showed no episodic ataxia. We ruled out the diseases, which may cause episodic ataxia, such as multiple sclerosis, vascular disorders, metabolic disorders and congenital anomalies. He was released from the attack by treatment with acetazolamide. EA-2 has been associated with mutations in the alpha 1A-voltage dependent calcium channel gene (CACNL1A4), which is also affected in familial hemiplegic migraine (FMH) and spinocerebellar ataxia type 6 (SCA6). In EA-2, frame-shift mutation leading to premature stop and splice-site mutation leading to truncated, non-functional channel protein have been reported. However, our patient did not have the mutations in the CACNL1A4 gene that were previously reported. In addition, our patient did not have an expanded CAG allele in the CACNL1A4 gene which is responsible for SCA6. Further examination is required to address whether a new mutation exists in the CACNL1A4 gene in our patient.

  5. Characteristics of epidemic and sporadic strains of Acinetobacter baumannii isolated in Abu Dhabi hospitals.

    Science.gov (United States)

    Sonnevend, Agnes; Ghazawi, Akela; Al Munthari, Noura; Pitout, Martin; Hamadeh, Mohammad Baraa; Hashmey, Rayhan; Girgis, Safinaz Khaleel; Sheikh, Farrukh Amin; Al Haj, Mohamed; Nagelkerke, Nico; Pál, Tibor

    2013-04-01

    We compared the antibiotic susceptibility, clonal lineages and resistance genes of singleton Acinetobacter baumannii strains to those of isolates representing repeatedly encountered molecular types in five Abu Dhabi hospitals. One hundred and ten clinically relevant, non-repeat strains were typed by blaOXA-51-like allele sequencing and by PFGE, and selected isolates also by MLST. Resistance was assessed by MIC determinations and by disc diffusion. Genotyping was carried out by PCR, targeting 28 genes. The 80 epidemic strains belonged to worldwide lineages 1, 2 and 7, representing 11 pulsotypes and 9 genotypes, while the 30 sporadic isolates exhibited a high level of genetic variability and, with the exception of a small subgroup, were not associated with any recognized epidemic lineages. All epidemic subtypes carried the ISAba1-linked blaOXA-23 gene, and harboured the int, the blaPER and the armA genes significantly more frequently than their sporadic counterparts. They were all multi-drug resistant, including non-susceptibility to carbepenems, and were often extensively drug resistant, a phenomenon rarely seen among sporadic strains. Epidemic strains represented 78.8 % of intensive care unit isolates, causing more respiratory infections, while sporadic strains were more frequently isolated from wound and soft tissue infections. The study showed that among strains collected at the same time and from the same region, the very heterogeneous, sensitive sporadic strains, with the exception of a few non-susceptible singleton isolates, clearly differed from the highly resistant epidemic ones, which belonged to multiple pulsotypes and genotypes clustered into three worldwide clonal lineages carrying blaOXA-64, blaOXA-66 and blaOXA-69, respectively.

  6. Trismus Pseudocamptodactyly Syndrome: A Sporadic Cause of Trismus

    Directory of Open Access Journals (Sweden)

    Prathima Sreenivasan

    2013-01-01

    Full Text Available Trismus pseudocamptodactyly syndrome is a very rare autosomal dominant inherited disorder characterized by the inability to completely open the mouth (trismus and the presence of abnormally short tendon units causing the fingers to curve (camptodactyly. Early diagnosis and management of this condition is important to prevent facial deformities in the patient. Reporting such a case is important as case reports are one of the sources of data for calculating the prevalence of rare diseases. Here, we report a case of trismus pseudocamptodactyly syndrome in an eight-year-old boy with a brief review of the literature.

  7. Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Wong Nora

    2006-01-01

    Full Text Available Abstract Background Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle and the mitochondrial respiratory chain (succinate:ubiquinone oxidoreductase or complex II. Methods Using conformation sensitive gel electrophoresis (CSGE and direct DNA sequencing to analyse genomic DNA from peripheral blood lymphocytes, here we describe the mutation analysis of the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family history head and neck paraganglioma and five pheochromocytoma and/or paraganglioma families. Results Two sporadic patients were found to have a SDHB splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys missense mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif that constitutes the quinone-binding site of the succinate: ubiquinone oxidoreductase (SQR complex in E. coli. Together with our previous results, we found 27 germline mutations of SDH genes in 95 cases (28% of sporadic head and neck paraganglioma. In addition all index patients of five families showing hereditary pheochromocytoma-paraganglioma were found to carry germline mutations of SDHB: four of which were novel, c.343C>T (p.Arg115X, c.141G>A (p.Trp47X, c.281G>A (p.Arg94Lys, and c.653G>C (p.Trp218Ser, and one reported previously, c.136C>T, p.Arg46X. Conclusion In conclusion, these data indicate that germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma and further underline the importance of germline SDHB mutations in cases of

  8. Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer

    Science.gov (United States)

    2012-01-01

    Background Cancers often arise within an area of cells (e.g. an epithelial patch) that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations. Purpose To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1) are early steps in progression to colon cancer. Results Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls). In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs) removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections) from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million. Conclusions The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million

  9. HAS-1 genetic polymorphism in sporadic abdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Alberto Balbarini

    2009-04-01

    Full Text Available The hyaluronan synthase 1 (HAS-1 gene encodes a plasma membrane protein that synthesizes hyaluronan (HA, an extracellular matrix molecule. Accumulating evidence emphasizes the relevance of HA metabolism in an increasing number of processes of clinical interest, including abdominal aortic aneurysm (AAA. The existence of aberrant splicing variants of the HAS-1 gene could partly explain the altered extracellular matrix architecture and influence various biological functions, resulting in progressive arterial wall failure in the development of AAA. In the present study, we assessed the hypothesis that HAS-1 genetic 833A/G polymorphism could be associated with the risk of AAA by performing a case-control association study, involving AAA patients and healthy matched donors.

  10. Caregiver burden in atypical dementias: comparing frontotemporal dementia, Creutzfeldt-Jakob disease, and Alzheimer's disease.

    Science.gov (United States)

    Uflacker, Alice; Edmondson, Mary C; Onyike, Chiadi U; Appleby, Brian S

    2016-02-01

    Caregiver burden is a significant issue in the treatment of dementia and a known contributor to institutionalization of patients with dementia. Published data have documented increased caregiver burden in behavioral variant frontotemporal dementia (bvFTD) compared to Alzheimer's disease (AD). Another atypical dementia with high-perceived caregiver burden is sporadic Creutzfeldt-Jakob disease (sCJD), but no formal studies have assessed this perception. The aim of this study was to compare caregiver burden across atypical dementia etiologies. 76 adults with atypical dementia (young-onset AD [YOAD], bvFTD, language variant FTD [lvFTD], and sCJD) were administered an abbreviated version of the Zarit Burden Interview (ZBI), Neuropsychiatric Inventory (NPI-Q), and other assessment instruments during a five-year time period at Johns Hopkins Hospital (JHH). A Cox regression model examined differences between disease categories that impact mean ZBI scores. Mean ZBI scores were significantly different between dementia etiologies, with bvFTD and sCJD having the highest caregiver burden (p = 0.026). Mean NPI-Q caregiver distress scores were highest in bvFTD and sCJD (p = 0.002), with sCJD and bvFTD also having the highest number of endorsed symptom domains (p = 0.012). On regression analyses, an interactive variable combining final diagnosis category and NPI-Q total severity score demonstrated statistically significant differences in mean ZBI scores for sCJD and bvFTD. This study demonstrates that bvFTD and sCJD have increased levels of caregiver burden, NPI-Q caregiver distress, total severity scores, and number of endorsed symptom domains. These results suggest that higher caregiver burden in bvFTD and sCJD are disease specific and possibly related to neuropsychiatric symptoms.

  11. Can the TLR-4-Mediated Signaling Pathway Be “A Key Inflammatory Promoter for Sporadic TAA”?

    Directory of Open Access Journals (Sweden)

    Giovanni Ruvolo

    2014-01-01

    Full Text Available Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR and medial degeneration (MD occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR- 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR=14.4, P=0.0008 and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

  12. Differential diagnosis of Jakob-Creutzfeldt disease.

    Science.gov (United States)

    Paterson, Ross W; Torres-Chae, Charles C; Kuo, Amy L; Ando, Tim; Nguyen, Elizabeth A; Wong, Katherine; DeArmond, Stephen J; Haman, Aissa; Garcia, Paul; Johnson, David Y; Miller, Bruce L; Geschwind, Michael D

    2012-12-01

    To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Retrospective medical record review. A specialty referral center of a tertiary academic medical center. One hundred sixty-three serial patients over a 5.5-year period who ultimately had pathologically proven sCJD. The study used the subset of 97 patients for whom we had adequate medical records. Other diagnoses considered in the differential diagnosis and types of medical specialties assessing patients with sCJD. Ninety-seven subjects' records were used in the final analysis. The most common disease categories of misdiagnosis were neurodegenerative, autoimmune/paraneoplastic, infectious, and toxic/metabolic disorders. The most common individual misdiagnoses were viral encephalitis, paraneoplastic disorder, depression, vertigo, Alzheimer disease, stroke, unspecified dementia, central nervous system vasculitis, peripheral neuropathy, and Hashimoto encephalopathy. The physicians who most commonly made these misdiagnoses were primary care physicians and neurologists; in the 18% of patients who were diagnosed correctly at their first assessment, the diagnosis was almost always by a neurologist. The mean time from onset to diagnosis was 7.9 months, an average of two-thirds of the way through their disease course. Diagnosis of sCJD is quite delayed. When evaluating patients with rapidly progressive dementia with suspected neurodegenerative, autoimmune, infectious, or toxic/metabolic etiology, sCJD should also be included in the differential diagnosis, and appropriate diagnostic tests, such as diffusion brain magnetic resonance imaging, should be considered. Primary care physicians and neurologists need improved training in sCJD diagnosis.

  13. Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms?

    Science.gov (United States)

    Soares, P; Fonseca, E; Wynford-Thomas, D; Sobrinho-Simões, M

    1998-05-01

    Despite the large amount of information accumulated on the role played by ret activation in the oncogenesis of papillary thyroid carcinoma (PTC), the biological and clinical significance of such activation 'in vivo' remains controversial. The aim of this study was to address some of the existing controversies by comparing two groups of unselected PTCs, one with and the other without ret rearrangement, with regard to several clinicopathological and biological features. Thirty-three PTCs were selected at random. ret rearrangement was found in eight cases (24.2 per cent) using Southern blot analysis. The mean age of the patients with tumours displaying ret rearrangement (28 +/- 3.1 years) was significantly lower than that of the patients harbouring cases that did not present rearrangement (45 +/- 2.9 years). The large majority of the tumours with ret rearrangement displayed a papillary or mixed follicular-papillary pattern and very low proliferative activity. ret rearrangement correlated significantly with decreased cytoplasmic expression of E-cadherin. No significant differences were found regarding the gender of the patients, tumour size, multicentricity, extrathyroidal growth, vascular invasion, lymphocytic infiltration, lymph node involvement or the expression of E-cadherin (membrane), c-erb-B2, c-met, Bcl-2, and vimentin. It is proposed that sporadic PTCs harbouring a ret rearrangement occur frequently as slow growing, papillary, or predominantly papillary tumours that do not usually progress towards less differentiated neoplasms representing what might be described as a Bonsai phenotype.

  14. Sporadic insulinomas on volume perfusion CT: dynamic enhancement patterns and timing of optimal tumour-parenchyma contrast

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Liang; Xue, Hua-dan; Liu, Wei; Wang, Xuan; Sun, Hao; Li, Ping; Jin, Zheng-yu [Peking Union Medical College Hospital, Department of Radiology, Beijing (China); Wu, Wen-ming; Zhao, Yu-pei [Peking Union Medical College Hospital, Department of General Surgery, Beijing (China)

    2017-08-15

    To assess enhancement patterns of sporadic insulinomas on volume perfusion CT (VPCT), and to identify timing of optimal tumour-parenchyma contrast. Consecutive patients who underwent VPCT for clinically suspected insulinomas were retrospectively identified. Patients with insulinomas confirmed by surgery were included, and patients with familial syndromes were excluded. Two radiologists evaluated VPCT images in consensus. Tumour-parenchyma contrast at each time point was measured, and timing of optimal contrast was determined. Time duration of hyperenhancement (tumour-parenchyma contrast >20 Hounsfield units, HU) was recorded. Perfusion parameters were evaluated. Three dynamic enhancement patterns were observed in 63 tumours: persistent hyperenhancement (hyperenhancement time window ≥10 s) in 39 (61.9%), transient hyperenhancement (hyperenhancement <10 s) in 19 (30.2%) and non-hyperenhancement in 5 (7.9%). Timing of optimal contrast was 9 s after abdominal aorta threshold (AAT) of 200 HU, with tumour-parenchyma contrast of 77.6 ± 57.2 HU. At 9 s after AAT, 14 (22.2%) tumours were non-hyperenhancing, nine of which had missed transient hyperenhancement. Insulinomas with transient and persistent hyperenhancement patterns had significantly increased perfusion. Insulinomas have variable enhancement patterns. Tumour-parenchyma contrast is time-dependent. Optimal timing of enhancement is 9 s after AAT. VPCT enables tumour detection even if the hyperenhancement is transient. (orig.)

  15. Sporadic insulinomas on volume perfusion CT: dynamic enhancement patterns and timing of optimal tumour-parenchyma contrast.

    Science.gov (United States)

    Zhu, Liang; Wu, Wen-Ming; Xue, Hua-Dan; Liu, Wei; Wang, Xuan; Sun, Hao; Li, Ping; Zhao, Yu-Pei; Jin, Zheng-Yu

    2017-08-01

    To assess enhancement patterns of sporadic insulinomas on volume perfusion CT (VPCT), and to identify timing of optimal tumour-parenchyma contrast. Consecutive patients who underwent VPCT for clinically suspected insulinomas were retrospectively identified. Patients with insulinomas confirmed by surgery were included, and patients with familial syndromes were excluded. Two radiologists evaluated VPCT images in consensus. Tumour-parenchyma contrast at each time point was measured, and timing of optimal contrast was determined. Time duration of hyperenhancement (tumour-parenchyma contrast >20 Hounsfield units, HU) was recorded. Perfusion parameters were evaluated. Three dynamic enhancement patterns were observed in 63 tumours: persistent hyperenhancement (hyperenhancement time window ≥10 s) in 39 (61.9%), transient hyperenhancement (hyperenhancement perfusion. Insulinomas have variable enhancement patterns. Tumour-parenchyma contrast is time-dependent. Optimal timing of enhancement is 9 s after AAT. VPCT enables tumour detection even if the hyperenhancement is transient. • Enhancement patterns of insulinomas are variable and tumour-parenchyma contrast is time-dependent. • An optimized single-phase scan found 77.8% tumours to be hyperenhancing. • Hyperenhancing tumours increase to 84.1% and 87.3% with biphasic/triphasic scan. • Volume perfusion CT enables detection of insulinomas with missed transient hyperenhancement.

  16. Hypersensitivity pneumonitis due to metal working fluids: Sporadic or under reported?

    Science.gov (United States)

    Gupta, Amit; Rosenman, Kenneth D

    2006-06-01

    Occupational exposure to metal working fluids (MWF) is common with over 1.2 million workers in the United States involved in machine finishing, machine tooling, and other metalworking operations. MWF is a known cause of hypersensitivity pneumonitis (HP). Recent reports of outbreaks of hypersensitivity HP secondary to exposure to MWF are reported. Cases were identified through the Occupational Disease surveillance system in the State of Michigan and from referrals for evaluation to the Division of Occupational and Environmental Medicine at Michigan State University (MSU). Each patient underwent a clinical examination including an occupational history, lung function studies, radiographic imaging, and in some cases lung biopsies. Following the diagnosis of definite HP, an industrial hygiene investigation was carried out, which included a plant walk-through, and review of the "Injury and Illness" log. Air monitoring and microbial sampling results were reviewed. As part of Michigan's mandatory surveillance system for occupational illnesses, seven cases of suspected HP were identified in 2003-2004 from three facilities manufacturing automobile parts in Michigan. Each plant used semi-synthetic MWFs, and conducted a MWF management program including biocide additions. Two facilities had recently changed the MWF before the cases arose. Growth of mycobacteria was found in these two MWFs. Breathing zone samples for particulates of two employees in plant A (two cases) ranged from 0.48 to 0.56 mg/m3. In plant B (four cases), two employees' sampling results ranged from 0.10 to 0.14 mg/m3. No air sampling data were available from plant C. Hypersensitivity pneumonitis due to exposure to MWFs is under-recognized by health care providers, and current surveillance systems are inadequate to provide a true estimate of its occurrence. HP arose from environments with exposures well below the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for MWF, and

  17. Genetic and epigenetic silencing of the beclin 1 gene in sporadic breast tumors

    Directory of Open Access Journals (Sweden)

    Wu Yiqing

    2010-03-01

    Full Text Available Abstract Background Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors. Methods 20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs were collected. The mRNA expression of beclin 1 was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island. Results Decreased beclin 1 mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of beclin 1 mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the beclin 1 gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression. Conclusions These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of

  18. Genetic and epigenetic silencing of the beclin 1 gene in sporadic breast tumors

    International Nuclear Information System (INIS)

    Li, Zidong; Chen, Bo; Wu, Yiqing; Jin, Feng; Xia, Yongjing; Liu, Xiangjun

    2010-01-01

    Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors. 20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs) were collected. The mRNA expression of beclin 1 was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH) was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island. Decreased beclin 1 mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of beclin 1 mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the beclin 1 gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression. These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of beclin 1 in breast cancer

  19. Source attribution of human salmonellosis and campylobacteriosos using a systematic review of studies of sporadic infections

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro; Hald, Tine

    . Identifying the most important sources of human disease is essential for prioritizing food safety interventions and setting public health goals. Numerous case-control studies of sporadic infections of salmonellosis and campylobacteriosis have been published. These studies investigate a variety of potential...... or statistical analysis of data, and conclusions. With the objective of identifying the most important risk factors for human sporadic salmonellosis and campylobacteriosis, we performed a SR of case-control studies and meta-analysis of the obtained results. From 1,295 identified references, 132 passed...... the relevance screening, 73 passed the quality assessment stage, and data was extracted from 72. Of these studies, 34 investigated risk factors for human salmonellosis and 37 focused on campylobacteriosis. Heterogeneity between the studies and possible sources of bias were assessed. Information on exposures...

  20. Sporadic sodium and E layers observed during the summer 2002 MaCWAVE/MIDAS rocket campaign

    Directory of Open Access Journals (Sweden)

    B. P. Williams

    2006-07-01

    Full Text Available On 5 July 2002, a MaCWAVE (Mountain and Convective Waves Ascending VErtically payload launched from Andøya Rocket Range, Norway, observed narrow enhanced layers of electron density that were nearly coincident with sporadic sodium layers measured by the Weber sodium lidar at the nearby ALOMAR Observatory. We investigate the formation mechanism of these layers using the neutral wind and temperature profiles measured directly by the lidar and the vertical motion deduced from the sodium mixing ratio. Through comparisons of the lidar data to the sporadic E in situ data, we find support for the concentration and downward motion of ions to an altitude where chemical models predict the rapid conversion of sodium ions to neutral sodium.

  1. Earth's influx of different populations of sporadic meteoroids from photographic and television data

    International Nuclear Information System (INIS)

    Ceplecha, Z.

    1988-01-01

    Precise photographic and television double- and multi-station data on 3624 sporadic meteors in the mass range from 2 x 10 -5 grams to 2 x 10 7 grams form the basis of this paper. The applied classification criteria and procedures are defined and described. A survey of 7 different populations of sporadic meteoroids known so far is presented. The total numbers and masses of meteoroids as a function of mass are given for individual groups and for all sporadic meteors. The absolute calibration of the influx to the Earth was carried out by comparison with the results of Halliday et al. (1984). The comparison with the visual and cratering data revealed good agreement in the narrow ''visual'' interval of masses, and disagreement in the extrapolated parts of the visual and cratering flux curves. The slope of the cumulative number curve for the meteorite-dropping fireballs (type I) with masses larger than 1 kg was found as -0.69 in perfect agreement with the results of Halliday et al. (1984). The final mass scale derived in this paper is situated between the scale of McCrosky and the scale of Halliday. The relative significance of the different groups of meteoroids changes with the mass quite dramatically. The total influx of sporadic meteoroids in the mass interval of 12 orders from 2 x 10 7 to 2 x 10 -5 grams resulted in 5 x 10 9 grams per year for the entire Earth's surface. Most of this mass comes in the form of larger meteoroids. Bulk densities and ablation coefficient are presented for the individual meteor groups depending on different ablation models of several authors and some extreme concepts of this problem are discussed. (author). 3 figs., 6 tabs., 38 refs

  2. Height and critical frequency variations of the sporadic-E layer at midlatitudes

    Czech Academy of Sciences Publication Activity Database

    Šauli, Petra; Bourdillon, A.

    2008-01-01

    Roč. 70, č. 15 (2008), s. 1904-1910 ISSN 1364-6826 R&D Projects: GA AV ČR IAA300420704 Grant - others:European Union(XE) COST 296 Institutional research plan: CEZ:AV0Z30420517 Keywords : Sporadic E * Planetary waves * Tidal waves * Mid-latitude ionosphere * Wavelet transform Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.667, year: 2008

  3. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    Directory of Open Access Journals (Sweden)

    de Bruïne Adriaan P

    2005-12-01

    Full Text Available Abstract Background The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1 and Ras (K-ras pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. Methods In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Results Mutations at the phosphorylation sites (codons 31, 33, 37, and 45 in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656 and 36% (235/656, respectively. Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656. Nine percent of all tumours (58/656 lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. Conclusion CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.

  4. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    International Nuclear Information System (INIS)

    Lüchtenborg, Margreet; Weijenberg, Matty P; Wark, Petra A; Saritas, A Merdan; Roemen, Guido MJM; Muijen, Goos NP van; Bruïne, Adriaan P de; Brandt, Piet A van den; Goeij, Anton FPM de

    2005-01-01

    The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Mutations at the phosphorylation sites (codons 31, 33, 37, and 45) in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656) and 36% (235/656), respectively). Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656). Nine percent of all tumours (58/656) lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency

  5. Laparoscopic cryoablation of angiomyolipomas in adolescents and young adults: A report of four cases associated with tuberous sclerosis and 1 case of sporadic origin.

    Science.gov (United States)

    Trelborg, Karina; Nielsen, Tommy Kjærgaard; Østraat, Ernst Øyvind; Olsen, Lars Henning

    2016-12-01

    Renal angiomyolipomas (AMLs) can be of sporadic origin or associated with tuberous sclerosis (TS). TS-associated AMLs often present in childhood, tend to be bilateral and multiple, and often exhibit a faster growth rate with an increased risk of hemorrhage. Renal cryoablation is well described in adults, whereas experiences with adolescents and young adults are limited. We present here for the first time a series of renal AMLs within adolescents and young adults treated with laparoscopic assisted cryoablation (LCA). The aim was to evaluate whether LCA of AMLs in adolescents and young adults is a safe and feasible treatment modality. From October 2009 to September 2013 a total of five patients at our institution were diagnosed with AMLs requiring treatment. Four patients had TS and one had AML of sporadic origin, all five patients underwent LCA. Data were retrospectively collected by a systematic review of patient material and reassessment of renal imaging. The median age was 16 years (range 13-27 years). Eight AMLs with a median size of 3.9 cm (range 2.1-7.7 cm) were treated in five patients because of tumor size and rapid growth. Follow-up was a median 37 months (range 20-62 months), and all tumors showed a reduction in tumor size, and no regrowth was recognized (see summary table). The procedure was well tolerated, with only few perioperative complications and no postoperative complications. When considering the indication for treating AMLs, the origin (sporadic or TS associated) and size of the tumor are the decisive factors. To preserve renal function and prevent spontaneous hemorrhage caution should be intensified when tumors reach 4 cm, particularly if TS is present. After the diagnosis is established, patients should be monitored with renal imaging at regular intervals to identify rapid-growing tumors. As an alternative to current treatment modalities such as partial nephrectomy and super selective angioembolization, cryoablation is an emerging approach

  6. Measuring sporadic gastrointestinal illness associated with drinking water - an overview of methodologies.

    Science.gov (United States)

    Bylund, John; Toljander, Jonas; Lysén, Maria; Rasti, Niloofar; Engqvist, Jannes; Simonsson, Magnus

    2017-06-01

    There is an increasing awareness that drinking water contributes to sporadic gastrointestinal illness (GI) in high income countries of the northern hemisphere. A literature search was conducted in order to review: (1) methods used for investigating the effects of public drinking water on GI; (2) evidence of possible dose-response relationship between sporadic GI and drinking water consumption; and (3) association between sporadic GI and factors affecting drinking water quality. Seventy-four articles were selected, key findings and information gaps were identified. In-home intervention studies have only been conducted in areas using surface water sources and intervention studies in communities supplied by ground water are therefore needed. Community-wide intervention studies may constitute a cost-effective alternative to in-home intervention studies. Proxy data that correlate with GI in the community can be used for detecting changes in the incidence of GI. Proxy data can, however, not be used for measuring the prevalence of illness. Local conditions affecting water safety may vary greatly, making direct comparisons between studies difficult unless sufficient knowledge about these conditions is acquired. Drinking water in high-income countries contributes to endemic levels of GI and there are public health benefits for further improvements of drinking water safety.

  7. Sporadic nesting reveals long distance colonisation in the philopatric loggerhead sea turtle (Caretta caretta).

    Science.gov (United States)

    Carreras, Carlos; Pascual, Marta; Tomás, Jesús; Marco, Adolfo; Hochscheid, Sandra; Castillo, Juan José; Gozalbes, Patricia; Parga, Mariluz; Piovano, Susanna; Cardona, Luis

    2018-01-23

    The colonisation of new suitable habitats is crucial for species survival at evolutionary scale under changing environmental conditions. However, colonisation potential may be limited by philopatry that facilitates exploiting successful habitats across generations. We examine the mechanisms of long distance dispersal of the philopatric loggerhead sea turtle (Caretta caretta) by analysing 40 sporadic nesting events in the western Mediterranean. The analysis of a fragment of the mitochondrial DNA and 7 microsatellites of 121 samples from 18 of these nesting events revealed that these nests were colonising events associated with juveniles from distant populations feeding in nearby foraging grounds. Considering the temperature-dependent sex determination of the species, we simulated the effect of the incubation temperature and propagule pressure on a potential colonisation scenario. Our results indicated that colonisation will succeed if warm temperature conditions, already existing in some of the beaches in the area, extend to the whole western Mediterranean. We hypothesize that the sporadic nesting events in developmental foraging grounds may be a mechanism to overcome philopatry limitations thus increasing the dispersal capabilities of the species and the adaptability to changing environments. Sporadic nesting in the western Mediterranean can be viewed as potential new populations in a scenario of rising temperatures.

  8. Fruit and vegetable intake during pregnancy and risk for development of sporadic retinoblastoma.

    Science.gov (United States)

    Orjuela, Manuela A; Titievsky, Lina; Liu, Xinhua; Ramirez-Ortiz, Marco; Ponce-Castaneda, Veronica; Lecona, Evelia; Molina, Evelyn; Beaverson, Katherine; Abramson, David H; Mueller, Nancy E

    2005-06-01

    Little is known about the causes of sporadic (noninherited) retinoblastoma. Rates seem to be somewhat higher among poorer populations in Mexico. Fruits and vegetables are important sources of carotenoids and folate. We examined whether decreased gestational maternal intake of fruits and vegetables may contribute to development of sporadic retinoblastoma. At the Instituto Nacional de Pediatria in Mexico City, we conducted a hospital-based case-control study to evaluate prenatal maternal diet. We examined dietary intake of fruits and vegetables of mothers of 101 children with retinoblastoma and 172 control children using a dietary recall questionnaire and published food nutrient content tables. The reported number of mean daily servings of fruits and vegetables was lower among case mothers when compared with control mothers [vegetables: 2.28 in controls, 1.75 in cases (P vegetables and fruits was higher in controls (103 microg) than in cases (48 microg; P vegetables [odds ratios (OR), 3.4; 95% confidence interval (95% CI), 2.0-6.0] or with a low intake of folate (OR, 3.9; 95% CI, 2.1, 7.3), or lutein/zeaxanthin (OR, 2.6; 95% CI, 1.5-4.6) derived from fruits and vegetables. Decreased intake of vegetables and fruits during pregnancy and the consequent decreased intake of nutrients such as folate and lutein/zeaxanthin, necessary for DNA methylation, synthesis, and retinal function, may increase risk for having a child with sporadic retinoblastoma.

  9. Expression of the Circadian Clock Genes Pert, Per2 in Sporadic, Familial Breast Tumors

    Directory of Open Access Journals (Sweden)

    Sherry L. Winter

    2007-10-01

    Full Text Available There is a growing body of evidence implicating aberrant circadian clock expression in the development of cancer. Based on our initial experiments identifying a putative interaction between BRCA1, the clock proteins Per1, Per2, as well as the reported involvement of the circadian clock in the development of cancer, we have performed an expression analysis of the circadian clock genes Per1, Per2 in both sporadic, familial primary breast tumors, normal breast tissues using real-time polymerase chain reaction. Significantly decreased levels of Per1 were observed between sporadic tumors, normal samples (P < .00001, as well as a further significant decrease between familial, sporadic breast tumors for both Per1 (P < .00001, Per2 (P < .00001. Decreased Per1 was also associated with estrogen receptor negativity (53% vs 15%, P = .04. These results suggest a role for both Perl, Per2 in normal breast function, show for the first time that deregulation of the circadian clock may be an important factor in the development of familial breast cancer. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle, on the ability of cells to undergo apoptosis, potentially promoting carcinogenesis.

  10. Occurrence of the blanketing sporadic E layer during the recovery phase of the October 2003 superstorm

    Science.gov (United States)

    Denardini, Clezio Marcos; Resende, Laysa Cristina Araújo; Moro, Juliano; Chen, Sony Su

    2016-05-01

    We have routinely monitored the total frequency ( ftEs) and the blanketing frequency ( fbEs) of sporadic E layers with the digital sounder under the magnetic equator in the Brazilian sector. Sporadic layers appear in the equatorial region (Esq) at heights between 90 and 130 km, mainly due to irregularities in the equatorial electrojet current. However, during the recovery phase of the October 2003 superstorm, an anomalous intensification of the ionospheric density that exceeded the normal ambient background values for local time and location was observed. The parameter fbEs rose to almost 7.5 MHz during this event, due to a type "c" blanketing sporadic layer (Esc), which is driven by wind shear. This result is discussed in terms of the atmosphere dynamics based on magnetic signature of the equatorial electrojet current using magnetometer data. Also, using data measured by sensors onboard the Geostationary Operational Environmental Satellite (GOES) 10 we analyze the possible influence of the solar flare-associated X-ray flux as an additional source of ionization.

  11. Performance of D-Parameters in Isolating Meteor Showers from the Sporadic Background

    Science.gov (United States)

    Moorhead, Althea

    2016-01-01

    It is often necessary to draw a division between meteor showers and the sporadic meteor complex in order to study these components of the meteoroid environment. Meteor showers persist for less than a season and are composed of members with a greater-than-average degree of orbital similarity. The level of orbital similarity is often quantified using so-called D-parameters; a D-parameter cutoff may be employed to define or extract a shower. Depending on the study, this cutoff value may be chosen based on the size of the data-set, the percentage of sporadic meteors within the data-set, or the inclination of the shower in question. We argue that the cutoff value should also reject the strength of the shower compared to the local sporadic background. We therefore present a method for determining, on a per-shower basis, the D-parameter cutoff that limits the false-positive rate to an acceptable percentage. If the false-positive rate exceeds this percentage regardless of cutoff value, we deem the shower to be undetectable in our data. We apply this method to optical meteor observations from the NASA All-Sky and Southern Ontario Meteor Networks and present the detectable meteor showers and their characteristics.

  12. Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation: indicators of tumor staging and metastasis in adenocarcinomatous sporadic colorectal cancer in Indian population.

    Directory of Open Access Journals (Sweden)

    Rupal Sinha

    Full Text Available Colorectal cancer (CRC development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease.One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed.Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12 and MGMT methylation (p-value <0.049. Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044 and methylated RASSF1A (p-values 0.034, 0.044, FHIT (p-values 0.001, 0.047 and MGMT (p-values 0.018, 0.044 genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025. Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes.Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.

  13. N-acetyl transferase 2/environmental factors and their association as a modulating risk factor for sporadic colon and rectal cancer.

    Science.gov (United States)

    Procopciuc, Lucia M; Osian, Gelu; Iancu, Mihaela

    2017-09-01

    The aim of this study was to evaluate the association between environmental factors and colon or rectal cancer after adjusting for N-acetyl transferase 2 (NAT2) phenotypes. Ninety-six patients with sporadic colon cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP analysis. The risk for colon cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, and NAT2*5A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*7B-G857A, and NAT2*5A-C481T. High fried red meat intake associated with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39 (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001), respectively, for colon cancer, whereas in the case of rectal cancer, the risk increased to 7.55 (Pcolon cancer, whereas the risk for rectal cancer is 9.72 (Pcolon cancer. Fried red meat, alcohol, and smoking increase the risk of sporadic CRC, especially of colon cancer, in the case of rapid acetylators for the NAT2 variants. © 2016 Wiley Periodicals, Inc.

  14. Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Zedenius, J.; Svensson, A.; Baeckdahl, M.; Wallin, G. [Karolinska Hospital, Stockholm (Sweden)] [and others

    1995-10-01

    The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and has in a previous study been correlated with a less favorable clinical outcome. In the present study, 46 MTCs were selected for investigation of the codon 918 mutation. The mutation was found in 29 tumors (63%), and was significantly correlated with a poor outcome, with regard to distant metastasis or tumor recurrence (p<10{sup 4}). Two tumors showed multifocal growth and C-cell hyperplasia, and these patients were therefore also investigated for germline mutations in exons 10, 11 and 16. The codon 918 mutation was found only in the tumors, thus of somatic origin. The RET codon 918 mutation may have prognostic impact, and therefore preoperative assessment may influence decision-making in the treatment of patients suffering from MTC. 13 refs., 1 fig., 1 tab.

  15. Association of CD40 gene polymorphisms with sporadic breast cancer in Chinese Han women of Northeast China.

    Directory of Open Access Journals (Sweden)

    Chen Shuang

    Full Text Available BACKGROUND: Breast cancer is a polygenetic disorder with a complex inheritance pattern. Single nucleotide polymorphisms (SNPs, the most common genetic variations, influence not only phenotypic traits, but also interindividual predisposition to disease, treatment outcomes with drugs and disease prognosis. The co-stimulatory molecule CD40 plays a prominent role in immune regulation and homeostasis. Accumulating evidence suggests that CD40 contributes to the pathogenesis of cancer. Here, we set out to test the association between polymorphisms in the CD40 gene and breast carcinogenesis and tumor pathology. METHODOLOGY AND PRINCIPAL FINDINGS: Four SNPs (rs1800686, rs1883832, rs4810485 and rs3765459 were genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP method in a case-control study including 591 breast cancer patients and 600 age-matched healthy controls. Differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed by the Chi-square test for trends. Our preliminary data showed a statistically significant association between the four CD40 gene SNPs and sporadic breast cancer risk (additive P = 0.0223, 0.0012, 0.0013 and 0.0279, respectively. A strong association was also found using the dominant, recessive and homozygote comparison genetic models. In the clinical features analysis, significant associations were observed between CD40 SNPs and lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2, estrogen receptor (ER, progesterone receptor (PR and tumor protein 53 (P53 statuses. In addition, our haplotype analysis indicated that the haplotype C(rs1883832G(rs4810485, which was located within the only linkage disequilibrium (LD block identified, was a protective haplotype for breast cancer, whereas T(rs1883832T(rs4810485 increased the risk in the studied population, even after correcting the P value for multiple testing (P = 0.0337 and

  16. Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudia Maletzki

    Full Text Available BACKGROUND: Colorectal cancer (CRC represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113 along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113 were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total. Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt, B-raf(mut, HROC87: K-ras(wt, B-raf(mut, whereas the HROC113 cell line (K-ras(mut, B-raf(wt was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+ tumor cells, showing surface tumor marker expression (CEACAM(+. MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the

  17. Genomic Alterations Observed in Colitis-Associated Cancers Are Distinct From Those Found in Sporadic Colorectal Cancers and Vary by Type of Inflammatory Bowel Disease.

    Science.gov (United States)

    Yaeger, Rona; Shah, Manish A; Miller, Vincent A; Kelsen, Judith R; Wang, Kai; Heins, Zachary J; Ross, Jeffrey S; He, Yuting; Sanford, Eric; Yantiss, Rhonda K; Balasubramanian, Sohail; Stephens, Philip J; Schultz, Nikolaus; Oren, Moshe; Tang, Laura; Kelsen, David

    2016-08-01

    Patients with inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), are at increased risk for small bowel or colorectal cancers (colitis-associated cancers [CACs]). We compared the spectrum of genomic alterations in CACs with those of sporadic colorectal cancers (CRCs) and investigated differences between CACs from patients with CD vs UC. We studied tumor tissues from patients with CACs treated at Memorial Sloan Kettering Cancer Center or Weill Cornell Medical College from 2003 through 2015. We performed hybrid capture-based next-generation sequencing analysis of >300 cancer-related genes to comprehensively characterize genomic alterations. We performed genomic analyses of 47 CACs (from 29 patients with UC and 18 with CD; 43 primary tumors and 4 metastases). Primary tumors developed in the ileum (n = 2), right colon (n = 18), left colon (n = 6), and rectosigmoid or rectum (n = 21). We found genomic alterations in TP53, IDH1, and MYC to be significantly more frequent, and mutations in APC to be significantly less frequent, than those reported in sporadic CRCs by The Cancer Genome Atlas or Foundation Medicine. We identified genomic alterations that might be targeted by a therapeutic agent in 17 of 47 (36%) CACs. These included the mutation encoding IDH1 R132; amplification of FGFR1, FGFR2, and ERBB2; and mutations encoding BRAF V600E and an EML4-ALK fusion protein. Alterations in IDH1 and APC were significantly more common in CACs from patients with CD than UC. In an analysis of CACs from 47 patients, we found significant differences in the spectrum of genomic alterations in CACs compared with sporadic CRCs. We observed a high frequency of IDH1 R132 mutations in patients with CD but not UC, as well as a high frequency of MYC amplification in CACs. Many genetic alterations observed in CACs could serve as therapeutic targets. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Role of the biomarkers for the diagnosis of Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Dulamea, A; Solomon, E

    2016-01-01

    Sporadic Creutzfeldt-Jakob disease (CJD) is a human prion disease, rapidly progressive and fatal, characterized by spongiform encephalopathy. The characteristic triad of signs - rapidly progressive dementia, myoclonus and periodic sharp wave complexes (PSWC) on electroencephalography (EEG) - usually appear in the late stages of the disease. The clinical diagnosis of CJD ante-mortem involves the exclusion of the rapidly progressive non-prionic dementias, the definitive diagnosis requiring brain tissue confirmation. Authors evaluated the methods of clinical diagnosis for sporadic CJD. This study retrospectively reviewed the medical records of patients diagnosed with probable sporadic CJD, based on brain magnetic resonance imaging (MRI), EEG, cerebrospinal fluid (CSF) analysis and extensive laboratory work-up. Four patients with a mean age of 67 years were included in our study. The mean duration from diagnosis until death was of 3.2 weeks. The clinical features of the disease at onset were atypical. In the final stage of the disease, all patients presented rapidly progressive dementia and myoclonus. High levels of 14-3-3 protein and tau protein and normal levels of amyloid β1-42 were found at CSF analysis, in all patients. PSWC on EEG were present in 3 out of 4 patients at different moments of the disease. MRI showed hyperintense lesions in brain cortex, caudate nucleus, and putamen on T2, FLAIR, and DWI. CJD may present various clinical features and, since brain biopsy is usually difficult to perform, a combination of biomarkers is useful in order to establish the diagnosis in the early phase of the disease.

  19. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Directory of Open Access Journals (Sweden)

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  20. Outcome of sporadic amyotrophic lateral sclerosis treated With non-invasive ventilation and riluzole Sobrevida en pacientes con esclerosis lateral amiotrófica esporádica tratados con ventilación no invasiva y riluzole