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Sample records for sporadic error-increasing effects

  1. IMF effect on sporadic-E layers at two northern polar cap sites: Part II ? Electric field

    OpenAIRE

    Nygre?n, T.; Aikio, A. T.; Voiculescu, M.; Ruohoniemi, J. M.

    2006-01-01

    This paper is the second in a series on a study of the link between IMF and sporadic-E layers within the polar cap. In Paper I (Voiculescu et al., 2006), an analysis of the sporadic-E data from Thule and Longyearbyen was presented. Here we concentrate on the electric field mechanism of sporadic-E generation. By means of model calculations we show that the mechanism is effective even at Thule, where the direction of the geomagnetic field departs from vertical only by 4. The model calc...

  2. IMF effect on sporadic-E layers at two northern polar cap sites: Part II Electric field

    Science.gov (United States)

    Nygrén, T.; Aikio, A. T.; Voiculescu, M.; Ruohoniemi, J. M.

    2006-05-01

    This paper is the second in a series on a study of the link between IMF and sporadic-E layers within the polar cap. In Paper I (Voiculescu et al., 2006), an analysis of the sporadic-E data from Thule and Longyearbyen was presented. Here we concentrate on the electric field mechanism of sporadic-E generation. By means of model calculations we show that the mechanism is effective even at Thule, where the direction of the geomagnetic field departs from vertical only by 4. The model calculations also lead to a revision of the electric field theory. Previously, a thin layer was assumed to grow at a convergent null in the vertical ion velocity, which is formed when the electric field points in the NW sector. Our calculations indicate that in the dynamic process of vertical plasma compression, a layer is generated at altitudes of high vertical convergence rather than at a null. Consequently, the layer generation is less sensitive than previously assumed to fluctuations of the electric field direction within the NW sector. The observed diurnal variations of sporadic-E occurrence at Longyearbyen and Thule are compared with the diurnal variations of the electric field, calculated using a representative range of IMF values by means of the statistical APL model. The results indicate that the main features of Es occurrence can be explained by the convection pattern controlled by the IMF. Electric fields calculated from the IMF observations are also used for producing distributions of sporadic-E occurrence as a function of electric field direction at the two sites. A marked difference between the distributions at Thule and Longyearbyen is found. A model estimate of the occurrence probability as a function of electric field direction is developed and a reasonable agreement between the model and the experimental occurrence is found. The calculation explains the differences between the distributions at the two sites in terms of the polar cap convection pattern. The conclusion is that the electric field is the major cause for sporadic-E generation and, consequently, IMF has a clear control on the occurrence of sporadic E within the polar cap.

  3. IMF effect on sporadic-E layers at two northern polar cap sites: Part I Statistical study

    Science.gov (United States)

    Voiculescu, M.; Aikio, A. T.; Nygrén, T.; Ruohoniemi, J. M.

    2006-05-01

    In this paper we investigate the relationship between polar cap sporadic-E layers and the direction of the interplanetary magnetic field (IMF) using a 2-year database from Longyearbyen (75.2 CGM Lat, Svalbard) and Thule (85.4 CGM Lat, Greenland). It is found that the MLT distributions of sporadic-E occurrence are different at the two stations, but both are related to the IMF orientation. This relationship, however, changes from the centre of the polar cap to its border. Layers are more frequent during positive By at both stations. This effect is particularly strong in the central polar cap at Thule, where a weak effect associated with Bz is also observed, with positive Bz correlating with a higher occurrence of Es. Close to the polar cap boundary, at Longyearbyen, the By effect is weaker than at Thule. On the other hand, Bz plays there an equally important role as By, with negative Bz correlating with the Es occurrence. Since Es layers can be created by electric fields at high latitudes, a possible explanation for the observations is that the layers are produced by the polar cap electric field controlled by the IMF. Using electric field estimates calculated by means of the statistical APL convection model from IMF observations, we find that the diurnal distributions of sporadic-E occurrence can generally be explained in terms of the electric field mechanism. However, other factors must be considered to explain why more layers occur during positive than during negative By and why the Bz dependence of layer occurrence in the central polar cap is different from that at the polar cap boundary.

  4. IMF effect on sporadic-E layers at two northern polar cap sites: Part I – Statistical study

    Directory of Open Access Journals (Sweden)

    M. Voiculescu

    2006-05-01

    Full Text Available In this paper we investigate the relationship between polar cap sporadic-E layers and the direction of the interplanetary magnetic field (IMF using a 2-year database from Longyearbyen (75.2 CGM Lat, Svalbard and Thule (85.4 CGM Lat, Greenland. It is found that the MLT distributions of sporadic-E occurrence are different at the two stations, but both are related to the IMF orientation. This relationship, however, changes from the centre of the polar cap to its border. Layers are more frequent during positive By at both stations. This effect is particularly strong in the central polar cap at Thule, where a weak effect associated with Bz is also observed, with positive Bz correlating with a higher occurrence of Es. Close to the polar cap boundary, at Longyearbyen, the By effect is weaker than at Thule. On the other hand, Bz plays there an equally important role as By, with negative Bz correlating with the Es occurrence. Since Es layers can be created by electric fields at high latitudes, a possible explanation for the observations is that the layers are produced by the polar cap electric field controlled by the IMF. Using electric field estimates calculated by means of the statistical APL convection model from IMF observations, we find that the diurnal distributions of sporadic-E occurrence can generally be explained in terms of the electric field mechanism. However, other factors must be considered to explain why more layers occur during positive than during negative By and why the Bz dependence of layer occurrence in the central polar cap is different from that at the polar cap boundary.

  5. Evidence for planetary wave effects on midlatitude backscatter and sporadic E layer occurrence

    Science.gov (United States)

    Voiculescu, Mirela; Haldoupis, Christos; Schlegel, Kristian

    In this paper a large database of midlatitude E region coherent backscatter, obtained with a 50 MHz Doppler system, is used to investigate the long-term variability in echo occurrence. The backscatter is found to be dominated by pronounced quasi-periodic variations with periods in the range from about 2 to 9 days that persist for time intervals from about 10 to maybe more than 20 days and have no relation to geomagnetic activity. The most commonly observed periods appear in two preferential bands, that is, the 2 to 3 day and the 4 to 6 day band. Using concurrent ionosonde data we find the variations in backscatter to be exactly in-phase with similar periodicities in the occurrence of relatively strong sporadic E layers. The present findings support the possibility that planetary waves are responsible for the observed long-term periodicities which indicates also a close relation between planetary waves and the well known, but not well understood, seasonal Es dependence. We suggest, the planetary wave option constitutes a new component into the research of midlatitude sporadic E layer formation and occurrence that needs to be considered and closely investigated.

  6. Midlatitude sporadic-E layers

    Science.gov (United States)

    Miller, K. L.; Smith, L. G.

    1976-01-01

    The partially transparent echo from midlatitude sporadic E layers was recorded by ionosondes between the blanketing frequency and the maximum frequency. The theory that the midlatitude sporadic E layers are not uniform in the horizontal plane but contain localized regions of high electron density was evaluated using data obtained by incoherent scatter radar and found to provide a satisfactory explanation. The main features of midlatitude sporadic E layers are consistent with the convergence of metallic ions as described by the wind shear theory applied to gravity waves and tides. The interference of gravity waves with other gravity waves and tides can be recognized in the altitudes of occurrence and the structure of the layers. Small scale horizontal irregularities are attributed in some cases to critical level effects and in others to fluid instabilities. The convergence of a meteor trail can, under some circumstances, account for localized enhancement of the electron density in the layer.

  7. Midlatitude sporadic-E layers

    International Nuclear Information System (INIS)

    The partially transparent echo from midlatitude sporadic E layers was recorded by ionosondes between the blanketing frequency and the maximum frequency. The theory that the midlatitude sporadic E layers are not uniform in the horizontal plane but contain localized regions of high electron density was evaluated using data obtained by incoherent scatter radar and found to provide a satisfactory explanation. The main features of midlatitude sporadic E layers are consistent with the convergence of metallic ions as described by the wind shear theory applied to gravity waves and tides. The interference of gravity waves with other gravity waves and tides can be recognized in the altitudes of occurrence and the structure of the layers. Small scale horizontal irregularities are attributed in some cases to critical level effects and in others to fluid instabilities. The convergence of a meteor trail can, under some circumstances, account for localized enhancement of the electron density in the layer

  8. Introduction to Sporadic Groups

    CERN Document Server

    Boya, Luis J

    2011-01-01

    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 $\\mathbb M$, 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.

  9. IMF effect on sporadic-E layers at two northern polar cap sites: Part I – Statistical study

    OpenAIRE

    Voiculescu, M.; Aikio, A. T.; Nygre?n, T.; Ruohoniemi, J. M.

    2006-01-01

    In this paper we investigate the relationship between polar cap sporadic-E layers and the direction of the interplanetary magnetic field (IMF) using a 2-year database from Longyearbyen (75.2 CGM Lat, Svalbard) and Thule (85.4 CGM Lat, Greenland). It is found that the MLT distributions of sporadic-E occurrence are different at the two stations, but both are related to the IMF orientation. This relationship, however, changes from the centre of the polar cap to its border. Layers are more freque...

  10. Midlatitude sporadic-E layers

    International Nuclear Information System (INIS)

    The starting point of this investigation is the partially transparent echo from midlatitude sporadic-E layers as recorded by ionosondes; this is the range of frequencies between the blanketing frequency and the maximum frequency. One interpretation is that it is a partial reflection at the steep gradients of electron density which characterize the vertical profile of the layers as recorded in rocket flights. The theory of reflection at gradients is developed and evaluated in the case of five layers. It is found that this mechanism is not sufficient to explain the phenomenon. An alternative explanation is that the midlatitude sporadic-E layers are not uniform in the horizontal plane but contain localized regions of high electron density. This is investigated using data obtained by incoherent-scatter radar and is found to provide a satisfactory explanation. The main features of midlatitude sporadic-E layers are consistent with the convergence of metallic ions as described by the wind-shear theory applied to gravity waves and tides. The interference of gravity waves with other gravity waves and tides can be recognized in the altitudes of occurrence and the structure of the layers. The small-scale horizontal irregularities are attributed in some cases to critical level effects and in others to fluid instabilities. The convergence of a meteor trail can, under some circumstances, account for localized enhancement of the electron density in the layersity in the layer

  11. Disorganized vascular structures in sporadic venous malformations: a possible correlation with balancing effect between Tie2 and TGF-?

    OpenAIRE

    Chen, Gang; Ren, Jian-gang; Zhang, Wei; Sun, Yan-fang; Wang, Feng-qin; Li, Rui-fang; Zhang, Jian; Zhao, Yi-fang

    2014-01-01

    Venous malformations (VMs) are among the most common slow-flow vascular malformations characterized by irregular venous channels, luminal thrombi, and phleboliths. To systematically manifest the disorganized vascular structures in sporadic VMs, we initially evaluated histopathological characteristics, perivascular cell coverage, adhesion molecules expression and vascular ultrastructures. Then, the expression of Tie2 and TGF-? in VMs was detected. Meanwhile, the in vitro studies were performe...

  12. Vertex operators and sporadic groups

    CERN Document Server

    Duncan, John F

    2008-01-01

    In the 1980's, the work of Frenkel, Lepowsky and Meurman, along with that of Borcherds, culminated in the notion of vertex operator algebra, and an example whose full symmetry group is the largest sporadic simple group: the Monster. Thus it was shown that the vertex operators of mathematical physics play a role in finite group theory. In this article we describe an extension of this phenomenon by introducing the notion of enhanced vertex operator algebra, and constructing examples that realize other sporadic simple groups, including one that is not involved in the Monster.

  13. Effects of Chinese herbal medicine Yinsiwei compound on spatial learning and memory ability and the ultrastructure of hippocampal neurons in a rat model of sporadic Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Yong-chang Diwu

    2011-02-01

    Full Text Available Objective: To study the effects of Chinese herbal medicine Yinsiwei compound (YSW on spatial learning and memory ability in rats with sporadic Alzheimer disease (SAD and the ultrastructural basis of the hippocampal neurons. Methods: A rat model of SAD was established by intracerebroventricular injection of streptozotocin. The rats were divided into six groups: sham-operation group, model group, donepezil control group, and YSW low, medium and high dose groups. Drug interventions were started on the 21st day after modeling and each treatment group was given the corresponding drugs by gavage for two months. Meanwhile, the model group and the sham-operation group were given the same volume of distilled water by gavage once a day for two months. The Morris water maze was adopted to test spatial learning and memory ability of the rats. The place navigation test and the spatial probe test were conducted. The escape latency, total swimming distance and swimming time in the target quadrant of the rats were recorded. Also, the hippocampus tissues of rats were taken out and the ultrastructure of hippocampus neurons were observed by an electron microscope.Results: In the place navigation test, compared with the model group, the mean escape latency and the total swimming distance of the donepezil group and the YSW low, medium and high dose groups were significantly shortened (P<0.05 or P<0.01. In the space probe test, the swimming time of each treatment group in the target quadrant was significantly longer than that of the model group (P<0.05 or P<0.01. For most of the test period, the donepezil group had no significant change compared with the YSW low, medium and high dose groups, respectively. The ultrastructure of the hippocampus neurons under the electron microscope also confirmed the efficacy of the drug treatment.Conclusion: Chinese herbal medicine YSW compound can improve spatial learning and memory impairment of rats with SAD. The ultrastructural basis may be that it can protect the microtubule structures of hippocampal neurons and prevent nerve axons from being damaged.

  14. FUS mutations in sporadic amyotrophic lateral sclerosis

    Science.gov (United States)

    Lai, Shiao-Lin; Abramzon, Yevgeniya; Schymick, Jennifer C.; Stephan, Dietrich A.; Dunckley, Travis; Dillman, Allissa; Cookson, Mark; Calvo, Andrea; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; Spataro, Rossella; Monsurro, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Lombardo, Federica; Mora, Gabriele; Restagno, Gabriella; Chiò, Adriano; Traynor, Bryan J.

    2010-01-01

    Mutations in the FUS gene have recently been described as a cause of familial ALS, but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1,295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease. PMID:20138404

  15. The lunar tide in sporadic E

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    R. J. Stening

    Full Text Available It seems that the wind shear theory is accepted for the explanation of sporadic E at mid and low latitudes. Some examples from Arecibo are displayed to show this. The effect of lunar tides should then modify the wind-shear theory in a manner that yields the observed features of the lunar tide in the critical frequency foEs and the height h'Es of the sporadic E. This is shown to imply that the phase of the lunar tide in h'Es should be the same as the phase of the lunar tide in the eastward wind and that the phase of the lunar tide in foEs is three hours later. Hourly values of foEs, f bEs (the blanketing critical frequency and h'Es from several observatories are analysed for the lunar semidiurnal tide. It is found that the phase of the tide in foEs is often about 3 hours later than for h'Es in agreement with the theory. Seasonal variations in the tide are also examined with the statistically most significant results (largest amplitudes usually occurring in summer. After reviewing the many difficulties associated with determining the lunar tide in Es, both experimentally and theoretically, the analysed phase results are compared with what might be expected from Hagan's global scale wave model. Agreement is only fair (a success rate of 69% among the cases examined but probably as good as might be expected.

    Key words. Ionosphere (ionosphere – atmosphere interactions – ionospheric irregularities, Meteorology and atmosphere dynamics (waves and tides

  16. Polytopes derived from sporadic simple groups

    OpenAIRE

    Michael Ian Hartley; Alexander Hulpke

    2010-01-01

    In this article, certain of the sporadic simple groups are analysed, and the polytopes having these groups as automorphism groups are characterised. The sporadic groups considered include all with order less than 4030387201, that is, all up to and including the order of the Held group. Four of these simple groups yield no polytopes, and the highest ranked polytopes are four rank 5 polytopes each from the Higman-Sims group, and the Mathieu group $M_...

  17. / Sporadic oral angiomyolipoma: Case report

    Scientific Electronic Library Online (English)

    Carlos, Álvarez Alvarez; Jacinto, Fernández Sanromán; Manuel, Fernández Castilla; Iosu, Antón Badiola.

    2007-09-01

    Full Text Available SciELO Spain | Language: English Abstract in spanish El angiomiolipoma (AML) es un tumor benigno infrecuente compuesto por una proporción variable de lipocitos, músculo liso y vasos de paredes gruesas. Forma parte de la familia de tumores originados en las células epitelioides perivasculares (PEComas), y muchos casos se asocian a esclerosis tuberosa, [...] siendo el riñón la localización más frecuente. Presentamos un caso de AML esporádico en el paladar duro de un varón de 52 años, una localización extremadamente rara para este tumor. El diagnóstico diferencial con otras lesiones mesenquimales tanto benignas como malignas de la zona se basa en la identificación histológica de los 3 componentes, siendo de ayuda las tinciones inmunohistoquímicas. Los AMLs localizados en cabeza y cuello no expresan HMB-45, un anticuerpo que identifica melanosomas inmaduros, mientras que los renales y hepáticos sí lo hacen, lo que sugiere que existen diferencias entre ambos AMLs. El tratamiento de elección es la exéresis quirúrgica completa, ya que estos tumores suelen tener un comportamiento benigno. Abstract in english Angiomyolipoma (AML) is a rare, benign tumour composed of a variable proportion of lipocytes, smooth muscle and thick-walled blood vessels. AML is part of a family of tumours arising from perivascular epithelioid cells (PEComas), and many cases are associated with tuberous sclerosis, with the kidney [...] being the most frequent site involved. We report a case of sporadic AML in the hard palate of a 52-year-old male, an extremely unusual location for this tumour. Differentiation from other benign and malignant oral mesenchymal lesions depends on recognition of the three histologic components, and immunohistochemical techniques may be helpful. AML occurring in the head and neck do not express HMB-45, an antibody that identifies immature melanosomes, conversely to the usual immunopositivity shown in AMLs from kidney and liver, suggesting that there are differences among them. A wide surgical excision is considered curative, as this tumour usually behaves in a benign fashion.

  18. [Sporadic inclusion body myositis and amyloid].

    Science.gov (United States)

    Aoki, Masashi; Suzuki, Naoki

    2014-07-01

    Sporadic inclusion body myositis (sIBM) is an intractable and progressive skeletal muscle disease of unknown etiology and without effective treatment. While the etiology is still unknown, however, genetic factors, aging, life style, and environmental factors may be involved. Muscle biopsy typically reveals endomysial inflammation, invasion of mononuclear cells into non-necrotic fibers and rimmed vacuoles, suggesting inflammation and degeneration co-exist as part of the pathomechanism. Recent studies implicate amyloid beta accumulation, defects of proteolysis, and immune system abnormalities. The clinical course is slow with chronic worsening. Diagnosis of sIBM is usually made 5 years after onset. Muscle weakness and atrophy in the quadriceps, wrist flexor and finger flexors are the typical neurological findings of sIBM. Dysphagia and asymmetric weakness are often found. Serum creatine kinase is usually below 2,000 IU/L. sIBM is generally refractory to current therapy, such as steroids or immunosuppressants. Elucidation of the pathomechanism of sIBM is the most important to therapy. PMID:24998819

  19. Antigliadin antibody in sporadic adult ataxia

    Directory of Open Access Journals (Sweden)

    Mahdi Aloosh

    2012-09-01

    Full Text Available Background: The most common neurologic manifestationof gluten sensitivity is ataxia, which accounts for up to 40%of idiopathic sporadic ataxia. Timing of diagnosis of glutenataxia is vital as it is one of the very few treatable causes ofsporadic ataxia and causes irreversible loss of Purkinje cells.Antigliadin antibody (AGA of the IgG type is the bestmarker for neurological manifestations of gluten sensitivity.This study was conducted to measure the prevalence ofgluten ataxia in a group of Iranian patients with idiopathicataxia.Methods: For 30 patients with idiopathic cerebellar ataxia, aquestionnaire about clinical and demographic data wascompleted. Serum AGA (IgA and IgG and antiendomysialantibody (AEA were assessed. Gluten ataxic patientsunderwent duodenal biopsy. Magnetic resonanceimaging was done for all patients to see if cerebellaratrophy is present.Results: Only 2 patients had a positive IgG AGA (6.7%who both had a positive AEA while none of themshowed changes of celiac disease in their duodenalbiopsies. Only presence of gastrointestinal symptomsand pursuit eye movement disorders were higher inpatients with gluten ataxia.Conclusion: Prevalence of gluten ataxia in Iranianpatients with idiopathic ataxia seems to be lower thanmost of other regions. This could be explained by smallsample size, differences in genetics and nutritionalhabits and also effect of serologic tests in clinical versusresearch setting. Further researches with larger samplesize are recommended.

  20. Darwinian behavior in a cold, sporadically fed pool of ribonucleotides.

    Science.gov (United States)

    Yarus, Michael

    2012-09-01

    A testable, explicit origin for Darwinian behavior, feasible on a chaotic early Earth, would aid origins discussion. Here I show that a pool receiving unreliable supplies of unstable ribonucleotide precursors can recurrently fill this role. By using numerical integration, the differential equations governing a sporadically fed pool are solved, yielding quantitative constraints for the proliferation of molecules that also have a chemical phenotype. For example, templated triphosphate nucleotide joining is >10(4) too slow, suggesting that a group more reactive than pyrophosphate activated primordial nucleotides. However, measured literature rates are sufficient if the Initial Darwinian Ancestor (IDA) resembles a 5'-5' cofactor-like dinucleotide RNA, synthesized via activation with a phosphorimidazolide-like group. A sporadically fed pool offers unforeseen advantages; for example, the pool hosts a novel replicator which is predominantly unpaired, even though it replicates. Such free template is optimized for effective selection during its replication. Pool nucleotides are also subject to a broadly based selection that impels the population toward replication, effective selection, and Darwinian behavior. Such a primordial pool may have left detectable modern traces. A sporadically fed ribonucleotide pool also fits a recognizable early Earth environment, has recognizable modern descendants, and suits the early shape of the phylogenetic tree of Earthly life. Finally, analysis points to particular data now needed to refine the hypothesis. Accordingly, a kinetically explicit chemical hypothesis for a terran IDA can be justified, and informative experiments seem readily accessible. PMID:22946838

  1. Bilateral sporadic aniridia: review of management

    Directory of Open Access Journals (Sweden)

    Caroline O Adeoti

    2010-09-01

    Full Text Available Caroline O Adeoti1, Adeyinka A Afolabi2, Adebimpe O Ashaye3, Adenike O Adeoye41Department of Ophthalmology, 2Department of Paediatrics, Ladoke Akintola University of Technology (LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 3University College Hospital, Ibadan, Oyo State, Nigeria; 4Obafemi Awolowo University Teaching Hospital, Ile Ife, Osun, Osun State, NigeriaPurpose: To report a rare case of bilateral sporadic aniridia in an African child and review the management modalities.Presentation: We report a case of bilateral sporadic aniridia with horizontal nystagmus, axial cataract optic disc, and fovea hypoplasia in a 5-year-old female patient. She was managed conservatively. Various modalities of treatment are reviewed.Keywords: aniridia, sporadic, nystagmus, cataract, glaucoma, keratopathy, tattooing, syndrome, fovea hypoplasia and optic disc hypoplasia

  2. Moonshine for Rudvalis's sporadic group I

    CERN Document Server

    Duncan, J F

    2006-01-01

    We introduce the notion of vertex operator superalgebra with enhanced conformal structure, which is a refinement of the notion of vertex operator superalgebra. We exhibit several examples, including a particular one which is self-dual, and whose full symmetry group is a direct product of a cyclic group of order seven with the sporadic simple group of Rudvalis. We thus obtain an analogue of Monstrous Moonshine for a sporadic group not involved in the Monster. Two variable analogues of the usual McKay--Thompson series are naturally associated to the action of the Rudvalis group on this object, and we provide explicit expressions for all the series arising.

  3. Atmosphere gravity waves and sporadic-E

    International Nuclear Information System (INIS)

    Observations of atmospheric gravity waves have identified several occasions when a wave-group propagating upwards can be associated first with a sporadic-E layer whose total electron content varies periodically, and later with a disturbance in the F-region varying with the same period. This paper reports four examples of such behaviour. (author)

  4. Genetics of familial and sporadic Alzheimer's disease.

    Science.gov (United States)

    Piaceri, Irene; Nacmias, Benedetta; Sorbi, Sandro

    2013-01-01

    Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder. A majority of cases manifest as a late onset sporadic form but genetically the disease is divided into familial cases and sporadic cases. The familial form is due to mutations in three major genes (amyloid precursor protein (APP) gene, presenilin1 (PSEN1) gene and presenilin 2 (PSEN2) gene). In contrast, many genetic and environmental factors may contribute to determining the sporadic AD form. Despite many years of research and great progress in the knowledge of the molecular pathogenesis of AD, a full understanding of the etiology of the sporadic form is still not yet in reach. Genome-wide association studies (GWASs) revealed the genetic complexity of the disease and recent studies suggested that epigenetic mechanisms may play an essential role in disease development. This review provides an overview of all the milestones in AD genetic research, as well as the new and promising approach, in order to better understand the genetic profile for predicting the risk of AD. PMID:23276979

  5. Pointed Hopf algebras over the sporadic groups

    CERN Document Server

    Andruskiewitsch, N; Graña, M; Vendramin, L

    2010-01-01

    We show that every finite-dimensional complex pointed Hopf algebra with group of group-likes isomorphic to a sporadic group is a group algebra, except for the Fischer group Fi22, the Baby Monster and the Monster. For these three groups, we give a short list of irreducible Yetter-Drinfeld modules whose Nichols algebra is not known to be finite-dimensional.

  6. MET Expression in Sporadic Renal Cell Carcinomas

    OpenAIRE

    Choi, Jong Sun; Kim, Mi-kyung; Seo, Jin Won; Choi, Yoon-la; Kim, Dong Hoon; Chun, Yi Kyeong; Ko, Young Hyeh

    2006-01-01

    Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was ...

  7. An atypical case of sporadic fatal insomnia

    OpenAIRE

    Mauro, Alessandro; Mortara, Paolo; Priano, Lorenzo; Pradotto, Luca Guglielmo

    2009-01-01

    Fatal insomnia is a rare human prion disease characterised by sleep-wake disturbances, thalamic degeneration and deposition of type 2 disease-specific prion protein (PrP(Sc)). This report details a patient with sporadic fatal insomnia who exhibited cerebral deposition of type 1 PrP(Sc) and neuropathological changes largely in the basal ganglia. Previous damage of this brain region by a surgically removed colloid cyst and the insertion of two intracerebral shunts may have influenced the distri...

  8. Antigliadin antibody in sporadic adult ataxia

    OpenAIRE

    Mahdi Aloosh; Navid Namazi; Parvin Tajik; Masoud Majed; Nahid Beladi Moghadam; Soodeh Razeghi Jahromi; Shahab Dowlatshahi; Mansoureh Togha; Shahriar Nafisi; Yaser Hamidian

    2012-01-01

    Background: The most common neurologic manifestationof gluten sensitivity is ataxia, which accounts for up to 40%of idiopathic sporadic ataxia. Timing of diagnosis of glutenataxia is vital as it is one of the very few treatable causes ofsporadic ataxia and causes irreversible loss of Purkinje cells.Antigliadin antibody (AGA) of the IgG type is the bestmarker for neurological manifestations of gluten sensitivity.This study was conducted to measure the prevalence ofgluten ataxia in a group of I...

  9. The genetics of radiation-induced and sporadic osteosarcoma: a unifying theory?

    International Nuclear Information System (INIS)

    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. Incoherent scatter radar observations of irregular structure in mid-latitude sporadic E layers

    Science.gov (United States)

    Miller, K. L.; Smith, L. G.

    1978-01-01

    The basic experiments used phase-coded pulses to record electron density profiles with a resolution of 600 m in range and 300 m in horizontal extent, while scanning in azimuth. Data from incoherent scatter radar were compared with simultaneous ionosonde observations. Observations of sporadic E layers by incoherent scatter radar were discussed in terms of the effects of the neutral wind system acting on metallic ions. Several features were noted in the data, which support the wind shear mechanism of layer formation. The sporadic E layers often contained a pronounced small-scale structure, especially at times when partially transparent echoes were observed by the ionosonde. Under specific conditions, the ions in a meteor trail can be converged by a shear in the neutral wind into a relatively small irregularity at the center of a sporadic E layer.

  11. Sporadic Medullary Microcarcinoma in a Young Patient - A Rare Case

    Directory of Open Access Journals (Sweden)

    Vijayshankar S

    2010-10-01

    Full Text Available Sporadic medullary microcarcinoma of thyroid is a rare disease detected usually in 0.15% of all thyroid malignancy. We report a case of sporadic medullary microcarcinoma (MMC of thyroid in a 24 year old male presenting as solitary thyroid nodule. There was no family history of medullary carcinoma of thyroid. Although medullary carcinoma in a familial setting have been reported, sporadic MMC is rare especially in a young patient.

  12. MRI of sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    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.

  13. Moonshine for Rudvalis's sporadic group II

    CERN Document Server

    Duncan, J F

    2006-01-01

    In Part I we introduced the notion of enhanced vertex operator superalgebra, and constructed an example which is self-dual, has rank 28, and whose full symmetry group is a seven-fold cover of the sporadic simple group of Rudvalis. In this article we construct a second enhanced vertex operator superalgebra whose full automorphism group is a cyclic cover of the Rudvalis group. This new example is self-dual and has rank -28. As in Part I, we can compute all the McKay--Thompson series associated to the action of the Rudvalis group explicitly. We observe that these series, when considered together with those of Part I, satisfy a genus zero property.

  14. Dynamical sporadicity and anomalous diffusion in the Levy motion

    Science.gov (United States)

    Wang, X.-J.

    1992-06-01

    Continuous-time sporadic dynamics that are intermediate between regular and random behaviors are discussed. A characterization of such processes is provided by a scale-dependent entropic quantity, and is applied to a model of Levy motion introduced by Klafter et al. (1987). The study suggests that sporadicity can be a feature of some physical systems exhibiting anomalous diffusion.

  15. Complete genomic landscape of a recurring sporadic parathyroid carcinoma.

    Science.gov (United States)

    Kasaian, Katayoon; Wiseman, Sam M; Thiessen, Nina; Mungall, Karen L; Corbett, Richard D; Qian, Jenny Q; Nip, Ka Ming; He, Ann; Tse, Kane; Chuah, Eric; Varhol, Richard J; Pandoh, Pawan; McDonald, Helen; Zeng, Thomas; Tam, Angela; Schein, Jacquie; Birol, Inanc; Mungall, Andrew J; Moore, Richard A; Zhao, Yongjun; Hirst, Martin; Marra, Marco A; Walker, Blair A; Jones, Steven J M

    2013-07-01

    Parathyroid carcinoma is a rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level, and the deleterious effects of hypercalcaemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested potential roles for the tumour suppressor MEN1 and proto-oncogene RET in benign parathyroid tumourigenesis, while the tumour suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumour specimens were analysed using high-throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well-characterized cancer genes such as mTOR, MLL2, CDKN2C, and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumours revealed loss of PIK3CA activating mutation during the evolution of the tumour from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of the short arm of chromosome 1, along with somatic missense and truncating mutations in CDKN2C and THRAP3, respectively, provides new evidence for the potential role of these genes as tumour suppressors in parathyroid cancer. The key somatic mutations identified in this study can serve as novel diagnostic markers as well as therapeutic targets. PMID:23616356

  16. Sporadic Lateral Ventricular Hemangioblastoma presenting with Intraventricular and Subarachnoid Haemorrhage

    OpenAIRE

    Mahasen Al-Najar; Azmy Al-Hadidy; Alaa Saleh; Ahmad Al-Tamimi; Asaad Al-Darawish; Fatima Obeidat

    2013-01-01

    Intraventricular hemangioblastoma (HB) is very rare; few cases of intraventricular HB have been reported in the literature, either sporadically or in association with von Hippel-Lindau disease. Furthermore, the incidence of ventricular haemorrhage from HB seems to be uncommon. We report a unique case of sporadic HB of the right lateral ventricle presenting with intratumoural and intraventricular haemorrhage in addition to multifocal intracranial superficial siderosis, indicating the presence ...

  17. Sporadic STEC O157 infection: secondary household transmission in Wales.

    OpenAIRE

    Parry, S. M.; Salmon, R. L.

    1998-01-01

    We conducted a study to quantify and characterize household transmission of Shiga toxin (Vero cytotoxin)-producing Escherichia coli O157 (STEC O157) following sporadic infection in Wales. Through total population surveillance, we identified 83 index case-patients and their household contacts. We screened fecal samples submitted from household contacts for STEC O157 and calculated the household transmission rate for sporadic STEC O157 infection to be 4% to 15%. Household contacts in groups at ...

  18. HF-induced plasma waves in ionospheric sporadic E

    International Nuclear Information System (INIS)

    The 430 MHz backscatter radar at Arecibo, Puerto Rico is used to diagnose the interaction of a powerful HF radio wave in a sporadic-E plasma. Resonant enhancements in the plasma line spectrum are observed to peak at the purely growing mode, that is, at 430 MHz +- f/sub HF/, where f/sub HF/ is the HF frequency. Altitude profile measurements of the scattered radar signal reveal sporadic-E enhancements at the ion line as well as at the two plasma lines. On the few occasions when plasma line excitation is observed outside of sporadic E in the upper E region between 130 km and 140 km altitude, only decay mode enhancements are evident. The sporadic-E plasma line enhancements along with the accompanying ion line enhancements are attributed to an HF-induced oscillating two-stream instability, which is parametrically driven near minimum threshold. Possible saturation mechanisms are examined. The dominance of the oscillating two-stream instability in sporadic E is consistent with theoretical predictions for parametric excitation in a collisionally dominated plasma containing steep electron density gradients in the vertical direction. The development of the oscillating two-stream instability is, however, most simply understood if the sporadic-E plasma exhibits horizontal patchiness over spatial scales much less than 300 m

  19. Sporadic-E associated with the Leonid meteor shower event of November 1998 over low and equatorial latitudes

    Directory of Open Access Journals (Sweden)

    H. Chandra

    Full Text Available Rapid radio soundings were made over Ahmedabad, a low latitude station during the period 16–20 November 1998 to study the sporadic-E layer associated with the Leonid shower activity using the KEL Aerospace digital ionosonde. Hourly ionograms for the period 11 November to 24 November were also examined during the years from 1994 to 1998. A distinct increase in sporadic-E layer occurrence is noticed on 17, 18 and 19 November from 1996 to 1998. The diurnal variations 
    of  f0Es and fbEs also show significantly enhanced values for the morning hours of 18 and 19 November 1998. The ionograms clearly show strong sporadic-E reflections at times of peak shower activity with multiple traces in the altitude range of 100–140 km in few ionograms. Sporadic-E layers with multiple structures in altitude are also seen in some of the ionograms (quarter hourly at Thumba, situated near the magnetic equator. Few of ionograms recorded at Kodaikanal, another equatorial station, also show sporadic- E reflections in spite of the transmitter power being significantly lower. These new results highlighting the effect of intense meteor showers in the equatorial and low latitude E-region are presented.

    Key words. Ionosphere (equatorial ionosphere – Radio science (ionospheric physics

  20. Dynamical model for the toroidal sporadic meteors

    Science.gov (United States)

    Pokorný, P.; Vokrouhlický, D.; Nesvorný, D.; Campbell-Brown, M.; Brown, P.

    2014-07-01

    The sporadic meteoroid complex (SMC) represents a major part of the meteoroid population in near-Earth space. Studies conducted over the past decades have identified six apparent SMC sources on the sky: (i)~north/south apex source, (ii)~helion/anti-helion source, and (iii)~south/north toroidal source. Nesvorný et al. (2011a) presented a steady-state dynamical model for the north/south apex source with Oort-cloud comets being the main source of these dust particles. Similarly, Nesvorný et al. (2011b) modeled the helion/anti-helion source using a steady-state population of dust released from Jupiter-family comets. The parent population of the toroidal dust particles has not previously been identified. Here we overcome this problem and present a consistent dynamical steady-state model for the toroidal source of the SMC. In particular, we show that sub-mm to mm particles released from Halley-type comets (HTCs), are able to explain all observed properties of the background average of the toroidal component of the SMC, including their typically small eccentricities. Interestingly, the toroidal component of the SMC shows the largest yearly variations. We show that the major variations may be due to prolific activity of periodic sources such as comet 96P/Machholz. Our steady-state model includes the following parts: (i) dust particles with sizes in the 0.1--5 mm range released from a synthetic population of HTCs consistent with the Levison et al. (2006) model, (ii) dynamical evolution of these particles tracked by a numerical integrator taking into account gravitational and radiative forces, and at the same time allowing them to be dynamically swept out of the Solar System, thermally or collisionally destroyed, and (iii) evaluation of the collision probability with the Earth using our new code appropriate for impactors with high eccentricity and inclination orbits (Pokorný & Vokrouhlický 2013). Figure shows results from our model that are compared and calibrated to the observations of Canadian Meteor Orbit Radar (CMOR). We also perform additional consistency checks, such as the contribution of the HTC dust particles to the other SMC sources and their contribution to the IR flux of the zodiacal cloud observed by the IRAS spacecraft.

  1. Emission spectrum of a sporadic fireball afterglow

    Science.gov (United States)

    Madiedo, J.; Trigo-Rodríguez, J.

    2014-07-01

    A mag. -11 fireball was imaged over southern Spain on April 14, 2013 at 22:35:49.8 ± 0.1s UTC. Its emission spectrum was also obtained. This event was assigned the SPMN code 140413 after the recording date. By the end of its atmospheric path, it exhibited a very bright flare which resulted in a persistent train whose spectrum was recorded. Here we present a preliminary analysis of this event and focus special attention on the evolution of the main emission lines in the spectrum of the afterglow. An array of low-lux CCD video devices (models 902H and 902H Ultimate from Watec Co.) operating from our stations at Sevilla and El Arenosillo was employed to record the SPMN140413 fireball. The operation of these systems is explained in [1,2]. Some of these are configured as spectrographs by attaching holographic diffraction gratings (1000 lines/mm) to the objective lens [3]. To calculate the atmospheric trajectory, radiant, and orbit we have employed our AMALTHEA software, which follows the planes intersection method [4]. The spectrum was analyzed with our CHIMET application [5]. The parent meteoroid impacted the atmosphere with an initial velocity of 28.9 ± 0.3 km/s and the fireball began at a height of 104.4 ± 0.5 km. The event ended at 80.7 ± 0.5 km above the ground level, with the main flare taking place at 83 ± 0.5 km. The calculated radiant and orbital parameters confirm the sporadic nature of the bolide. The calibrated emission spectrum shows that the most important contributions correspond to the Na I-1 (588.9 nm) and Mg I-2 (517.2 nm) multiplets. In the ultraviolet, the contribution from the H and K lines from Ca was also identified. As usual in meteor spectra, most of the lines correspond to Fe I. The train spectrum was recorded during about 0.12 seconds. This provided the evolution with time of the intensity of the emission lines in this signal. The contributions from Mg I, Na I, Ca I, Fe I, Ca II, and O I were identified in the afterglow, with the Na I-1 (588.9 nm) and Mg I-2 (517.2 nm) lines being the most important ones. The brightness of these lines decreased exponentially with time. Additional analyses are currently being performed to establish the conditions in the meteor train.

  2. Association studies in late onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Goate, A.M.; Lendon, C.; Talbot, C. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  3. Exceptional Algebra and Sporadic Groups at c=12

    CERN Document Server

    Cheng, Miranda C N; Kachru, Shamit; Whalen, Daniel

    2015-01-01

    In earlier works, it was seen that a ${\\mathbb Z}/2$ orbifold of the theory of 24 free two-dimensional chiral fermions admits various sporadic finite simple groups as global symmetry groups when viewed as an ${\\cal N}=1$, ${\\cal N}=2$, or ${\\cal N}=4$ superconformal field theory. In this note, we show that viewing the same theory as an SCFT with extended ${\\cal N}=1$ symmetry -- where the extension is the same one which arises in string compactification on manifolds of exceptional Spin$(7)$ holonomy -- yields theories which have global symmetry given by the sporadic groups $M_{24}, Co_2$ or $Co_3$. The partition functions twined by these symmetries, when decomposed into characters of the Spin(7) algebra, give rise to two-component vector-valued mock modular forms encoding an infinite-dimensional module for the corresponding sporadic groups.

  4. Molecular profile and copy number analysis of sporadic colorectal cancer in Taiwan

    Directory of Open Access Journals (Sweden)

    Li Ling-Hui

    2011-06-01

    Full Text Available Abstract Background Colorectal cancer (CRC is a major health concern worldwide, and recently becomes the most common cancer in Asia. The case collection of this study is one of the largest sets of CRC in Asia, and serves as representative data for investigating genomic differences between ethnic populations. We took comprehensive and high-resolution approaches to compare the clinicopathologic and genomic profiles of microsatellite instability (MSI vs. microsatellite stability (MSS in Taiwanese sporadic CRCs. Methods 1,173 CRC tumors were collected from the Taiwan population, and sequencing-based microsatellite typing assay was used to determine MSI and MSS. Genome-wide SNP array was used to detect CN alterations in 16 MSI-H and 13 MSS CRCs and CN variations in 424 general controls. Gene expression array was used to evaluate the effects of CN alterations, and quantitative PCR methods were used to replicate the findings in independent clinical samples. Results These 1,173 CRC tumors can be classified into 75 high-frequency MSI (MSI-H (6.4%, 96 low-frequency MSI (8.2% and 1,002 MSS (85.4%. Of the 75 MSI-H tumors, 22 had a BRAF mutation and 51 showed MLH1 promoter hypermethylation. There were distinctive differences in the extent of CN alterations between CRC MSS and MSI-H subtypes (300 Mb vs. 42 Mb per genome, p-value Conclusions Sporadic CRCs with MSI-H displayed distinguishable clinicopathologic features, which differ from those of MSS. Genomic profiling of the two types of sporadic CRCs revealed significant differences in the extent and distribution of CN alterations in the cancer genome. More than half of expressed genes showing CN differences can directly contribute to their expressional diversities, and the biological functions of the genes associated with CN changes in sporadic CRCs warrant further investigation to establish their possible clinical implications.

  5. Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients.

    Science.gov (United States)

    Benitez-Buelga, C; Sanchez-Barroso, L; Gallardo, M; Apellániz-Ruiz, María; Inglada-Pérez, L; Yanowski, K; Carrillo, J; Garcia-Estevez, L; Calvo, I; Perona, R; Urioste, M; Osorio, A; Blasco, M A; Rodriguez-Antona, C; Benitez, J

    2015-01-01

    Recently, we observed that telomeres of BRCA1/2 mutation carriers were shorter than those of controls or sporadic breast cancer patients, suggesting that mutations in these genes might be responsible for this event. Given the contradictory results reported in the literature, we tested whether other parameters, such as chemotherapy, could be modifying telomere length (TL). We performed a cross-sectional study measuring leukocyte TL of 266 sporadic breasts cancer patients treated with first-line chemotherapy, with a median follow-up of 240 days. Additionally, we performed both cross-sectional and longitudinal studies in a series of 236 familial breast cancer patients that included affected and non-affected BRCA1/2 mutation carriers. We have measured in leukocytes from peripheral blood: the TL, percentage of short telomeres (<3 kb), telomerase activity levels and the annual telomere shortening speed. In sporadic cases we found that chemotherapy exerts a transient telomere shortening effect (around 2 years) that varies depending on the drug combination. In familial cases, only patients receiving treatment were associated with telomere shortening but they recovered normal TL after a period of 2 years. Chemotherapy affects TL and should be considered in the studies that correlate TL with disease susceptibility. PMID:25528024

  6. Molecular and Survival Differences between Familial and Sporadic Gastric Cancers

    OpenAIRE

    Wen-Liang Fang; Shih-Ching Chang; Yuan-Tzu Lan; Kuo-Hung Huang; Su-Shun Lo; Anna Fen-Yau Li; Chin-Wen Chi; Chew-Wun Wu; Shih-Hwa Chiou

    2013-01-01

    Mismatch repair (MMR) and germline E-cadherin (CDH1) mutations are two of the major pathways of carcinogenesis in familial gastric cancer (GC). A total of 260 sporadic and 66 familial GC patients were enrolled and molecular and survival differences were compared. Familial GC patients had earlier onset and were diagnosed at an earlier stage and had both a better 5-year overall survival rate and 3-year disease-free survival rate compared with sporadic GC patients. Only in diffuse type GC, the M...

  7. Integral group ring of the Suzuki sporadic simple group

    CERN Document Server

    Bovdi, V A; Marcos, E N

    2008-01-01

    Using the Luthar--Passi method, we investigate the classical Zassenhaus conjecture for the normalized unit group of the integral group ring of the Suzuki sporadic simple group Suz. As a consequence, for this group we confirm the Kimmerle's conjecture on prime graphs.

  8. Role of KCNJ5 in familial and sporadic primary aldosteronism.

    Science.gov (United States)

    Mulatero, Paolo; Monticone, Silvia; Rainey, William E; Veglio, Franco; Williams, Tracy Ann

    2013-02-01

    Primary aldosteronism is characterised by the dysregulation of aldosterone production and comprises both sporadic forms, caused by an aldosterone-producing adenoma or bilateral adrenal hyperplasia, and familial forms (familial hyperaldosteronism types I, II and III). The two principal physiological regulators of aldosterone synthesis are angiotensin II and serum K(+), which reverse the high resting K(+) conductance and hyperpolarized membrane potential of adrenal glomerulosa cells. The resulting membrane depolarization causes the opening of voltage-gated Ca(2+) channels and an increase in intracellular Ca(2+) that stimulates aldosterone biosynthesis. Point mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K(+) channel 4 (GIRK4), have been implicated in the pathogenesis of both sporadic and familial forms of primary aldosteronism. These mutations interfere with the selectivity filter of GIRK4 causing Na(+) entry, cell depolarization and Ca(2+) channel opening, resulting in constitutive aldosterone production. Seven families with familial hyperaldosteronism caused by KCNJ5 germline mutations have so far been described, and multicentre studies have reported KCNJ5 mutations in approximately 40% of sporadic aldosterone-producing adenomas. Herein, we review the role of GIRK4 in adrenal pathophysiology and provide an overview of the clinical and biochemical phenotypes resulting from KCNJ5 mutations in patients with sporadic and familial primary aldosteronism. PMID:23229280

  9. Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

    OpenAIRE

    Sun, M. H.

    2004-01-01

    Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma...

  10. Resveratrol prevents tumorigenesis in mouse model of Kras activated sporadic colorectal cancer by suppressing oncogenic Kras expression.

    Science.gov (United States)

    Saud, Shakir M; Li, Weidong; Morris, Nicole L; Matter, Matthias S; Colburn, Nancy H; Kim, Young S; Young, Matthew R

    2014-12-01

    Sporadic and non-hereditary mutations account for the majority of colorectal cancers (CRC). After the loss of adenomatous polyposis coli (APC) function and activation of the ?-catenin/LEF signaling pathway, activating mutations in Kras are major drivers of sporadic CRC. Preventing the outgrowth of cells that develop sporadic mutations will decrease CRC. Resveratrol, a naturally occurring polyphenolic compound has anti-inflammatory, anti-oxidant and anti-cancer activities. We used a genetically engineered mouse model for sporadic CRC where the APC locus is knocked out and Kras is activated specifically in the distal colon to determine the effects of resveratrol on preventing and treating CRC. Feeding mice a diet supplemented with 150 or 300 ppm resveratrol (105 and 210mg daily human equivalent dose, respectively) before tumors were visible by colonoscopy resulted in a 60% inhibition of tumor production. In the 40% of mice that did develop tumors Kras expression was lost in the tumors. In a therapeutic assay where tumors were allowed to develop prior to treatment, feeding tumor bearing mice with resveratrol resulted in a complete remission in 33% of the mice and a 97% decrease in tumor size in the remaining mice. Analysis of miRNA expression in non-tumoral and tumoral colonic tissue of resveratrol treated mice showed an increased expression of miR-96, a miRNA previously shown to regulate Kras translation. These data indicate that resveratrol can prevent the formation and growth of colorectal tumors by downregulating Kras expression. PMID:25280562

  11. A possible case of Sporadic Aurora in 1843 from Mexico

    Scientific Electronic Library Online (English)

    José Manuel, Vaquero; María Cruz, Gallego; Fernando, Domínguez-Castro.

    2013-03-01

    Full Text Available SciELO Mexico | Language: English Abstract in spanish Recientemente, algunos autores han mostrado que algunas auroras pueden ser observadas a latitudes relativamente bajas cuando la actividad geomagnética es baja o moderada. Este tipo tan especial de aurora recibe el nombre de "aurora esporádica". Presentamos y analizamos en este trabajo un posible cas [...] o de "aurora esporádica" observada desde México el 19 de abril de 1843. Además, estudiamos la actividad solar y auroral alrededor de este evento. Abstract in english In recent years, some authors have shown that some auroras can be observed at relatively low latitude when the geomagnetic activity is quiet or moderate. This very special type of aurora is called "sporadic aurora". We present and analyze in this work a possible case of "sporadic aurora" observed in [...] Mexico on the 19 April 1843. Moreover, we study the solar and auroral activity around this event.

  12. Seroepidemiology and risk factors for sporadic norovirus/Mexico strain.

    Science.gov (United States)

    Peasey, Anne E; Ruiz-Palacios, Guillermo M; Quigley, Maria; Newsholme, William; Martinez, Julia; Rosales, Gustavo; Jiang, Xi; Blumenthal, Ursula J

    2004-06-01

    Risk factors associated with transmission of sporadic norovirus (NV; formerly Norwalk-like virus)/Mexico strain were identified in a seroepidemiological study conducted in rural Mexico. Acquisition of Mexico strain IgA antibodies was age-related; 34% of 1-4-year-olds were seropositive, compared with 81% of adults (PPersonal and domestic hygiene measures, such as hand washing, general cleanliness of the mother's clothing, and the type of room assigned for cooking were significantly associated with odds of a seroresponse. For infants, having a dog in or near the home was a risk factor for seroresponse (P<.01), whereas, for older children, the mother's involvement in agricultural activities was a risk factor (P<.001). This study provides initial evidence of risk factors associated with sporadic NV infection. Data indicate some similarities to risk factors associated with outbreaks of NV infection. PMID:15143470

  13. Sporadic Lateral Ventricular Hemangioblastoma presenting with Intraventricular and Subarachnoid Haemorrhage.

    Science.gov (United States)

    Al-Najar, Mahasen; Al-Hadidy, Azmy; Saleh, Alaa; Al-Tamimi, Ahmad; Al-Darawish, Asaad; Obeidat, Fatima

    2013-11-01

    Intraventricular hemangioblastoma (HB) is very rare; few cases of intraventricular HB have been reported in the literature, either sporadically or in association with von Hippel-Lindau disease. Furthermore, the incidence of ventricular haemorrhage from HB seems to be uncommon. We report a unique case of sporadic HB of the right lateral ventricle presenting with intratumoural and intraventricular haemorrhage in addition to multifocal intracranial superficial siderosis, indicating the presence of a subarachnoid haemorrhage (SAH) as well. Such a combination has not been reported before. In the future, the detection of an intraventricular mass in association with ventricular haemorrhage, with or without SAH, should include HB as a differential diagnosis, particularly when the imaging appearances are not typical of the more common intraventricular tumours. PMID:24273675

  14. 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.

  15. Volumetric cortical loss in sporadic and familial amyotrophic lateral sclerosis.

    OpenAIRE

    Turner; Hammers, A.; Allsop, J.; Al-chalabi, A.; Shaw, CE; Brooks, Dj; Leigh, Pn; Andersen, Pm

    2007-01-01

    Patients homozygous for the D90A mutation of the SOD1 gene (homD90A) demonstrate markedly slower progression of disease than those patients with sporadic ALS (SALS). PET studies have demonstrated a different cortical vulnerability in the two groups, reflected also in neurophysiological studies showing reduced cortical excitability in homD90A. Voxel-based morphometric analysis of magnetic resonance images (MRIs) enables the detection of regional differences in grey matter volume, and can be us...

  16. The Monster Sporadic Group and a Theory Underlying Superstring Models

    OpenAIRE

    Chapline, George

    1996-01-01

    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 fre...

  17. Novel BRAF Alteration in a Sporadic Pilocytic Astrocytoma

    OpenAIRE

    Gutmann, David H.; Leonard, Jeffrey R.; Aparna Kaul; Jinsheng Yu; Sonika Dahiya

    2012-01-01

    Pilocytic astrocytoma (PA) is the most frequently encountered glial tumor (glioma or astrocytoma) in children. Recent studies have identified alterations in the BRAF serine/threonine kinase gene as the likely causative mutation in these childhood brain tumors. The majority of these genetic changes involve chromosome 7q34 tandem duplication, resulting in aberrant BRAF fusion transcripts. In this paper, we describe a novel KIAA1549:BRAF fusion transcript in a sporadic PA tumor associated with i...

  18. The Cybrid Model of Sporadic Parkinson’s Disease

    OpenAIRE

    Trimmer, Patricia A.; Bennett, James P.

    2009-01-01

    Parkinson’s disease (PD) is the eponym attached to the most prevalent neurodegenerative movement disorder of adults, derived from observations of an early nineteenth century physician and paleontologist, James Parkinson, and is now recognized to encompass much more than a movement disorder clinically or dopamine neuron death pathologically. Most PD (~90%) is sporadic (sPD), is associated with mitochondrial deficiencies and has been studied in cell and animal models arising from use of mitoc...

  19. Darwinian Behavior in a Cold, Sporadically Fed Pool of Ribonucleotides

    OpenAIRE

    Yarus, Michael

    2012-01-01

    A testable, explicit origin for Darwinian behavior, feasible on a chaotic early Earth, would aid origins discussion. Here I show that a pool receiving unreliable supplies of unstable ribonucleotide precursors can recurrently fill this role. By using numerical integration, the differential equations governing a sporadically fed pool are solved, yielding quantitative constraints for the proliferation of molecules that also have a chemical phenotype. For example, templated triphosphate nucleotid...

  20. Clinical Perspective of Oxidative Stress in Sporadic ALS

    OpenAIRE

    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 elevate...

  1. ?-Catenin Mutation Status and Outcomes in Sporadic Desmoid Tumors

    Science.gov (United States)

    DeLaney, Thomas F.; Rosenberg, Andrew E.; Le, Long; Iafrate, A. John; Kobayashi, Wendy; Szymonifka, Jackie; Yeap, Beow Y.; Chen, Yen-Lin; Harmon, David C.; Choy, Edwin; Yoon, Sam S.; Raskin, Kevin A.; Hornicek, Francis J.; Nielsen, Gunnlauger P.

    2013-01-01

    Background. Mutations in the gene-encoding ?-catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoid tumors and to determine whether CTNNB1 mutation status correlates with disease outcome. Methods. Single-base extension genotyping of the CTNNB1 gene was performed on 145 sporadic, paraffin-embedded desmoid tumor specimens. Correlation of mutation status with outcome was performed on a subset of 115 patients who underwent macroscopically complete surgical resection. Results. CTNNB1 mutations were detected in 106 of 145 (73%) tumor specimens and in 86 of 115 (75%) specimens from patients who underwent curative-intent surgical resection, including discrete mutations in the following codons of CTNNB1 exon 3: T41A (46%), S45F (25%), S45P (1.7%), and S45C (0.9%). Desmoid tumors of the superficial trunk were significantly less likely to harbor CTNNB1 mutations than tumors located elsewhere, but none of the other examined clinicopathologic factors were found to be associated with CTNNB1 mutation status. At a median follow-up of 31 months, 5-year recurrence-free survival was slightly, although not statistically significantly, worse for patients with ?-catenin-mutated tumors than for those with wild-type tumors (58% vs. 74%, respectively). The specific CTNNB1 codon mutation did not correlate with the risk for recurrence. Conclusion. CTNNB1 mutations are indeed common in sporadic desmoid tumors. However, our study did not detect a statistically significant difference in recurrence risk according to either the CTNNB1 mutation status or the specific CTNNB1 mutation. PMID:23960186

  2. Insulin Signaling in Sporadic Alzheimer's Disease

    Science.gov (United States)

    Francesca-Fang Liao (University of Tennessee Health Science Center; Department of Pharmacology REV)

    2009-06-09

    Excessive production of ?-amyloid (A?) peptides from proteolytic cleavage of amyloid precursor protein is believed to play a central role in the pathogenesis of Alzheimer’s disease (AD). In particular, accumulated intracellular A? is found in vulnerable neurons, and the soluble oligomers of A? peptides [also termed A?-derived diffusible ligands (ADDLs)] are highly toxic to neurons. Evidence shows that both extracellular and intracellular ADDLs can compromise insulin signaling. Extracellular ADDLs can bind to synapses and decrease membrane insulin receptors (IRs) through an insulin signaling–dependent mechanism. Intracellular A? inhibits IR signaling in neurons by interfering with the association between phosphoinositide-dependent kinase 1 and Akt1 to preclude Akt1 activation. Together, these findings suggest that agents that stimulate insulin signaling may have neuroprotective effects. Indeed, insulin and insulin sensitizers have been shown to improve cognitive and memory functions in animal models of AD, as well as in AD patients.

  3. Numerical modelling of a metallic ion sporadic-E layer

    International Nuclear Information System (INIS)

    A one-dimensional time-dependent model of the ionosphere has been developed and applied to the study of a metallic ion sporadic-E layer observed in the Aladdin 1 experiment carried out at Eglin AFB, Florida, 20 November 1970. The model develops the molecular ion background ionosphere using a dynamic photochemical calculation from noon to a time near model sunset. A representative metallic ion altitude profile is then introduced, the divergence terms included in the continuity equations, and the integration carried forward. Introducing an ad hoc constant electric field of 2 mv m-1 directed to the south, the model metallic ion sporadic-E layer forms at the proper altitude and reaches the measured peak density in about a half hour. Changing the initial metallic ion profile changes the time to reach peak density and the degree of asymmetry of the layer, but the layer altitude is determined asymptotically by the location of the convergent node of the vertical ion velocity profile. The background ionospheric density calculated with the model agrees within experimental error with the experimental profile. The calculations support the hypothesis that midlatitude sporadic-E layers are caused by neutral-wind-induced compression of metallic ions resulting from meteoric ablation in the lower E region. (auth)

  4. 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.

  5. Genetic and neuroanatomic associations in sporadic frontotemporal lobar degeneration.

    Science.gov (United States)

    McMillan, Corey T; Toledo, Jon B; Avants, Brian B; Cook, Philip A; Wood, Elisabeth M; Suh, Eunran; Irwin, David J; Powers, John; Olm, Christopher; Elman, Lauren; McCluskey, Leo; Schellenberg, Gerard D; Lee, Virginia M-Y; Trojanowski, John Q; Van Deerlin, Vivianna M; Grossman, Murray

    2014-06-01

    Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are sensitive for tau or TDP-43 pathology in frontotemporal lobar degeneration (FTLD). Neuroimaging analyses have revealed distinct distributions of disease in FTLD patients with genetic mutations. However, genetic influences on neuroanatomic structure in sporadic FTLD have not been assessed. In this report, we use novel multivariate tools, Eigenanatomy, and sparse canonical correlation analysis to identify associations between SNPs and neuroanatomic structure in sporadic FTLD. Magnetic resonance imaging analyses revealed that rs8070723 (MAPT) was associated with gray matter variance in the temporal cortex. Diffusion tensor imaging analyses revealed that rs1768208 (MOBP), rs646776 (near SORT1), and rs5848 (PGRN) were associated with white matter variance in the midbrain and superior longitudinal fasciculus. In an independent autopsy series, we observed that rs8070723 and rs1768208 conferred significant risk of tau pathology relative to TDP-43, and rs646776 conferred increased risk of TDP-43 pathology relative to tau. Identified brain regions and SNPs may help provide an in vivo screen for underlying pathology in FTLD and contribute to our understanding of sporadic FTLD. PMID:24373676

  6. Multiple filarial species microfilaraemia: a comparative study of areas with endemic and sporadic onchocerciasis

    Directory of Open Access Journals (Sweden)

    Emmanuel Uttah & Dominic C. Ibeh

    2011-12-01

    Full Text Available Background & objectives: The study was aimed at determining the pattern of co-occurrence of species ofmicrofilaraemia between onchocerciasis endemic and sporadic populations.Methods: From every consenting person of one year and above, 50 ?l of day and night blood samples werecollected and processed respectively with Haemotoxylin and Giemsa as vital stains. Two skin snips (one eachfrom the waist and the shoulder were also taken from these individuals and processed.Results: Results showed single species microfilaraemia (86.4 and 82.3%, double species microfilaraemia (12.2and 16.9% and triple species microfilaraemia (1.4 and 0.7% for endemic and sporadic populations respectively.All the species had single species microfilaraemia mostly, but Mansonella perstans and Loa loa showed greatestt endency towa rds doubl e and t r ipl e spe c i e s mi c rof i l a r a emi a . The pr eva l enc e of Wuche re r ia banc rof t imicrofilaraemia among those positive for Onchocerca volvulus was significantly lower than the overall prevalenceof Wuchereria bancrofti. Wuchereria bancrofti microfilaraemia was most common among those who had L. loamicrofilaraemia. Wuchereria bancrofti microfilarial intensity was higher among those with M. perstansmicrofilaraemia than among those positive for any of the other filarial species. Similarly, the intensity of M.perstans microfilaraemia among those positive for W. bancrofti exceeded the overall intensity of M. perstans.Conclusion: It is concluded that there was no definite pattern in mf densities discernible from co-occurrenceinfections either in the onchocerciasis endemic or sporadic population. There could be varied outcomes ofonchocerciasis infection attributable to positive or negative regulatory effects of other pathogens harbored bythe victims.

  7. Gene expression profiling: Canonical molecular changes and clinicopathological features in sporadic colorectal cancers

    Directory of Open Access Journals (Sweden)

    Jin Cheon Kim, Seon Young Kim, Seon Ae Roh, Dong-Hyung Cho, Dae Dong Kim, Jeong Hyun Kim, Yong Sung Kim

    2008-11-01

    Full Text Available AIM: To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment.METHODS: Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction (RT-PCR.RESULTS: The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair (MMR defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis (P < 0.001. Amongst 47 differentially expressed genes, seven (PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory.CONCLUSION: We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.

  8. INTUSSUSCEPTION IN A CHILD WITH SPORADIC BURKITT LYMPHOMA

    Directory of Open Access Journals (Sweden)

    D. Meucci

    2009-11-01

    Full Text Available Introduction. Burkitt Lymphoma is a high grade lymphoma and it represents 8-10 % of all tumors in children less than 15 years old. There are two forms of Burkitt Lymphoma (BL: endemic and sporadic, that are indistinguishable by histology, but they have got a different geographical distribution. The sporadic form more commonly has an abdominal presentation. About eighty percent of these patients has predominantly intussusceptions. Materials and methods. We report a 5 years old girl with spasmodic abdominal pain who was addimitted in our Clinic. We diagnosed an intussusception by clinical examination and abdominal ultrasound scan. We decided to perform an emergency operation and we found a single pedicle neoformation on the anti-mesenteric wall of ileum, that was the patologic lead point. We reduced the intussusception and we resected the neoformation and a small length of ileum (about 4 cm. We performed a single-layer end-to-end ileo-ileum anastomosis and the appendicectomy. The histopathological examination and the immunohistochemistry study revealed a Burkitt Lymphoma. Results. The patient was dismissed on eighth postoperative day and she was referred to Pediatric Oncology Center for chemotherapy. The child was graded second class (R2 because lymph-nodes sampling was not performed and LDH levels were lower 500 U/l. Conclusions. The mayority of sporadic Burkitt Lymphoma patients presents with abdominal disease that required a laparotomy. The presenting symptoms included: an abdominal mass, intestinal obstruction, intussusceptions as acute abdomen. The role of surgery is very controversial. However, it’s required to confirm the diagnosis in the presence of extensive intrabdominal disease and to relieve the common presenting symptoms in the presence of acute abdomen. Some Authors argue that Surgery is important in the management of the complications.

  9. Sporadic impact flashes on the Moon and their implications

    Science.gov (United States)

    Trigo-Rodriguez, J. M.; Ortiz, J. L.; Llorca, J.; Santos-Sanz, P.

    The systematic impact flash survey that we carried out between 2001 and 2004 resulted in the first unambiguous detection of lunar sporadic impact flashes (Ortiz et al., 2006) and already allowed us to estimate the impact rate of objects on Earth as a function of their incoming energy under the assumption of a certain range of luminous efficiencies of the impact processes. Some present unknown parameters can be constrained in the future by monitoring impact flashes associated with meteoroid streams exhibiting a wide range of impact angles and energies. Here we further investigate some implications of the sporadic impact flashes detected so far and in particular we focus on whether the SMART-1 impact flash can give additional constraints on the luminous efficiency applicable to sporadic impacts, in order to derive more accurate impact rates on Earth. We have compared our derived impact fluxes with those obtained by Ceplecha (2001) and Brown et al. (2002) and we conclude that the present flux in the observed energy range would be underestimated. Finally, we conclude that the large lunar surface coverage and increasing sensitivity of modern video cameras makes this a powerful method to estimate terrestrial impact rates of large bodies that are statistically difficult to be detected from more limited atmospheric coverages characteristic of terrestrial networks. REFERENCES Brown, P., Spalding, R. E., Revelle, D. O., Tagliaferri, E., Worden, S. P. 2002. The flux of small near-Earth objects colliding with the Earth. Nature 420, 294-296. Ceplecha Z. (2001) in Collisional processes in the solar system, eds. Mikhail Ya. Marov and Hans Rickman, Astrophysics and Space Science library, Vol. 261, Dordrecht, Kluwer Academic Publishers, 35 - 50. Ortiz J.L., F.J. Aceituno, J.A. Quesada, J. Aceituno, M. Fernández, P. Santos-Sanz, J.M. Trigo-Rodríguez, J. Llorca, F.J. Martín-Torres, P. Montañés-Rodríguez, E. Pallé (2006) Icarus, in press.

  10. "Familial" versus "sporadic" intellectual disability: contribution of subtelomeric rearrangements

    Directory of Open Access Journals (Sweden)

    Rafati Maryam

    2012-01-01

    Full Text Available Abstract Background Cryptic subtelomeric rearrangements have been proposed as a significant cause of sporadic intellectual disability (ID but the role of such aberrations in familial ID has not yet been studied. As positive family history of ID had been proposed as an important and significant predicting factor of subtelomeric rearrangements, it was assumed that the contribution of subtelomeric aberrations in familial ID would be much more than the sporadic ones. Three hundred and twenty two patients from 102 unrelated families with more than two ID patients in the first degree relatives have been investigated. Assessment of subtelomeric rearrangements were carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA technique. Detected aberrations were then confirmed by Fluorescence in Situ Hybridization (FISH method. Results Among the families studied, 27.4% had 4-12, 36.3% had 3 and 36.3% had 2 affected individuals in the first degree relatives. One unbalanced translocation and 4 polymorphic changes were detected. The prevalence of clinically significant subtelomeric rearrangements was 0.98%. Conclusion This is the first investigation of subtelomeric aberrations in a large sample set of familial ID patients. Our results show that the contribution of subtelomeric rearrangements to familial ID is not as much as what had been determined for sporadic ones in the literature. Moreover, this study shows that the positive family history by alone, cannot be the most important and determining indicator of subtelomeric aberrations while it would be a good predicting factor when associated with dysmorphism or congenital malformations. These findings propose that other cryptic chromosomal abnormalities or even single gene disorders may be the main cause of familial ID rather than subtelomeric aberrations.

  11. 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.

  12. Sporadic medullary thyroid carcinoma: clinical data from a university hospital

    OpenAIRE

    Correia-deur, Joya Emilie M.; Toledo, Rodrigo A.; Imazawa, Alice T.; Lourenc?o Jr, Delmar M.; Ezabella, Marilza C. L.; Tavares, Marcos R.; Toledo, Sergio P. A.

    2009-01-01

    INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes obs...

  13. 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

  14. Deletion analysis of chromosome 8p in sporadic colorectal adenomas.

    OpenAIRE

    Cunningham, C.; Dunlop, M. G.; Bird, C. C.; Wyllie, A. H.

    1994-01-01

    In order to assess the stage of colorectal tumorigenesis at which chromosome 8p loss of heterozygosity (LOH) occurs, 56 sporadic adenomas were examined for LOH at four polymorphic loci which show frequent LOH in carcinomas. LOH was found in only 5 out of 51 (9.8%) informative adenomas, whereas studies with the same markers in 85 informative carcinomas showed a LOH of 45%. The adenomas showing LOH were all in the 'high-risk' clinicopathological category, being 10 mm or more in diameter and sho...

  15. The monster sporadic group and a theory underlying superstring models

    International Nuclear Information System (INIS)

    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

  16. The monster sporadic group and a theory underlying superstring models

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Super-moonshine for Conway's largest sporadic group

    CERN Document Server

    Duncan, J F

    2005-01-01

    We study a self-dual N=1 super vertex operator algebra and prove that the full symmetry group is Conway's largest sporadic simple group. We verify a uniqueness result which is analogous to that conjectured to characterize the Moonshine vertex operator algebra. The action of the automorphism group is sufficiently transparent that one can derive explicit expressions for all the McKay-Thompson series. A corollary of the construction is that the perfect double cover of the Conway group may be characterized as a point-stabilizer in a spin module for the Spin group associated to a 24 dimensional euclidean space.

  18. Representing the Sporadic Archimedean Polyhedra as Abstract Polytopes

    CERN Document Server

    Hartley, Michael

    2009-01-01

    We present the results of an investigation into the representations of Archimedean polyhedra (those polyhedra containing only one type of vertex figure) as quotients of regular abstract polytopes. Two methods of generating these presentations are discussed, one of which may be applied in a general setting, and another which makes use of a regular polytope with the same automorphism group as the desired quotient. Representations of the 14 sporadic Archimedean polyhedra (including the pseudorhombicuboctahedron) as quotients of regular abstract polyhedra are obtained, and summarised in a table. The information is used to characterise which of these polyhedra have acoptic Petrie schemes (that is, have well-defined Petrie duals).

  19. 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.

  20. Screening of the PFN1 gene in sporadic ALS and in FTD

    Science.gov (United States)

    Tiloca, Cinzia; Ticozzi, Nicola; Pensato, Viviana; Corrado, Lucia; Del Bo, Roberto; Bertolin, Cinzia; Fenoglio, Chiara; Gagliardi, Stella; Calini, Daniela; Lauria, Giuseppe; Castellotti, Barbara; Bagarotti, Alessandra; Corti, Stefania; Galimberti, Daniela; Cagnin, Annachiara; Gabelli, Carlo; Ranieri, Michela; Ceroni, Mauro; Siciliano, Gabriele; Mazzini, Letizia; Cereda, Cristina; Scarpini, Elio; Sorarù, Gianni; Comi, Giacomo P.; D'Alfonso, Sandra; Gellera, Cinzia; Ratti, Antonia; Landers, John E.; Silani, Vincenzo

    2012-01-01

    Mutations in the profilin 1 (PFN1) gene, encoding a protein regulating filamentous actin growth through its binding to monomeric G-actin, have been recently identified in familial amyotrophic lateral sclerosis (ALS). Functional studies performed on ALS-associated PFN1 mutants demonstrated aggregation propensity, alterations in growth cone and cytoskeletal dynamics. Previous screening of PFN1 gene in sporadic ALS (SALS) cases led to the identification of the p.E117G mutation, which is likely to represent a less pathogenic variant according to both frequency data in controls/cases and functional experiments. To determine the effective contribution of PFN1 mutations in SALS, we analyzed a large cohort of 1168 Italian SALS patients and also included 203 FTD (Frontotemporal Dementia) cases given the great overlap between these two neurodegenerative diseases. We detected the p.E117G variant in 1 SALS and the novel synonymous change p.G15G in another patient, but none in a panel of 1512 controls. Our results suggest that PFN1 mutations in sporadic ALS and in FTD are rare, at least in the Italian population. PMID:23063648

  1. Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations.

    Science.gov (United States)

    Gu, X; Guo, L; Ji, H; Sun, S; Chai, R; Wang, L; Li, H

    2014-05-22

    The genetic heterogeneity of non-syndromic hearing loss (NSHL) has hampered the identification of its pathogenic mutations. Several recent studies applied targeted genome enrichment (TGE) and massively parallel sequencing (MPS) to simultaneously screen a large set of known hearing loss (HL) genes. However, most of these studies were focused on familial cases. To evaluate the effectiveness of TGE and MPS on screening sporadic NSHL patients, we recruited 63 unrelated sporadic NSHL probands, who had various levels of HL and were excluded for mutations in GJB2, MT-RNR1, and SLC26A4 genes. TGE and MPS were performed on 131 known HL genes using the Human Deafness Panel oto-DA3 (Otogenetics Corporation., Norcross, GA). We identified 14 pathogenic variants in STRC, CATSPER2, USH2A, TRIOBP, MYO15A, GPR98, and TMPRSS3 genes in eight patients (diagnostic rate?=?12.7%). Among these variants, 10 were novel compound heterozygous mutations. The identification of pathogenic mutations could predict the progression of HL, and guide diagnosis and treatment of the disease. PMID:24853665

  2. Prenatal deletion detection in a sporadic case of Duchenne muscular dystrophy without genotype information from the affected individual.

    Science.gov (United States)

    Peinemann, F; Wagner, M; Franke, U; Kulle, M; Reiss, J

    1991-02-01

    We describe the application of deletion screening by amplification of deletion-prone exons via polymerase chain reaction (PCR) in a family with a sporadic case of Duchenne muscular dystrophy (DMD). No DNA was available from the affected patient who died 12 years beforehand at the age of 18 years. Material obtained prenatally from two male fetuses exhibited an identical deletion. These findings effectively transformed a sporadic case into a familial case and a numerical carrier risk was substituted by obligate carrier status. Additionally an indirect genotype analysis was replaced by the possibility of direct DNA analysis. Genetic counselling, formerly based upon incomplete data, can now be aided by precise risk assessment. PMID:1851486

  3. Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients

    OpenAIRE

    Mete Lupe; Mottolese Marcella; Giannarelli Diana; Palmirotta Raffaele; Cosimelli Maurizio; Assisi Daniela; Stigliano Vittoria; Mancini Raffaello; Casale Vincenzo

    2008-01-01

    Abstract Background Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients. Methods We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970–1993. In 15 HNPCC patients we performed mutational an...

  4. Familial and sporadic pancreatic cancer share the same molecular pathogenesis

    Science.gov (United States)

    Norris, Alexis L.; Roberts, Nicholas J.; Jones, Siân; Wheelan, Sarah J.; Papadopoulos, Nickolas; Vogelstein, Bert; Kinzler, Kenneth W.; Hruban, Ralph H.; Klein, Alison P.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is nearly uniformly lethal, with a median overall survival in 2014 of only 6 months. The genetic progression of sporadic PDAC (SPC) is well established, with common somatic alterations in KRAS, p16/CDKN2A, TP53, and SMAD4/DPC4. Up to 10 % of all PDAC cases occur in families with two or more affected first-degree relatives (familial pancreatic cancer, FPC), but these cases do not appear to present at an obviously earlier age of onset. This is unusual because most familial cancer syndrome patients present at a substantially younger age than that of corresponding sporadic cases. Here we collated the reported age of onset for FPC and SPC from the literature. We then used an integrated approach including whole exomic sequencing, whole genome sequencing, RNA sequencing, and high density SNP microarrays to study a cohort of FPC cell lines and corresponding germline samples. We show that the four major SPC driver genes are also consistently altered in FPC and that each of the four detection strategies was able to detect the mutations in these genes, with one exception. We conclude that FPC undergoes a similar somatic molecular pathogenesis as SPC, and that the same gene targets can be used for early detection and minimal residual disease testing in FPC patients. PMID:25240578

  5. Familial and sporadic pancreatic cancer share the same molecular pathogenesis.

    Science.gov (United States)

    Norris, Alexis L; Roberts, Nicholas J; Jones, Siân; Wheelan, Sarah J; Papadopoulos, Nickolas; Vogelstein, Bert; Kinzler, Kenneth W; Hruban, Ralph H; Klein, Alison P; Eshleman, James R

    2015-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is nearly uniformly lethal, with a median overall survival in 2014 of only 6 months. The genetic progression of sporadic PDAC (SPC) is well established, with common somatic alterations in KRAS, p16/CDKN2A, TP53, and SMAD4/DPC4. Up to 10 % of all PDAC cases occur in families with two or more affected first-degree relatives (familial pancreatic cancer, FPC), but these cases do not appear to present at an obviously earlier age of onset. This is unusual because most familial cancer syndrome patients present at a substantially younger age than that of corresponding sporadic cases. Here we collated the reported age of onset for FPC and SPC from the literature. We then used an integrated approach including whole exomic sequencing, whole genome sequencing, RNA sequencing, and high density SNP microarrays to study a cohort of FPC cell lines and corresponding germline samples. We show that the four major SPC driver genes are also consistently altered in FPC and that each of the four detection strategies was able to detect the mutations in these genes, with one exception. We conclude that FPC undergoes a similar somatic molecular pathogenesis as SPC, and that the same gene targets can be used for early detection and minimal residual disease testing in FPC patients. PMID:25240578

  6. Sporadic Hemangioblastoma of the Kidney: a rare renal tumor

    Directory of Open Access Journals (Sweden)

    Liu Yang

    2012-05-01

    Full Text Available Abstract Hemangioblastoma is a benign and morphologically distinctive tumor that can occur sporadically or in association with von Hippel-Lindau disease in approximately 25% of the cases, and which involves the central nervous system in the majority of the cases. Rare occurrences of hemangioblastoma in peripheral nerves and extraneural tissues have been reported. This report describes one case of sporadic renal hemangioblastoma happened in a 16-year-old Chinese female patient, presenting with hematuria, and low back pain. Histologically, the tumors were circumscribed, and composed of sheets of large polygonal cells traversed by arborizing thin-walled blood vessels. The diagnosis of hemangioblastoma was confirmed by negative immunostaining for cytokeratin, and positive staining for ?-inhibin, S100 and neuron-specific enolase (NSE. This benign neoplasm which can be mistaken for various malignancies such as renal cell carcinoma, epithelioid hemangiopericytoma and epithelioid angiomyolipoma, deserves wider recognition for its occurrence as a primary renal tumor. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5445834246942699

  7. Dyssynchronous secretory endometrial glands often show sporadically acquired progesterone nonresponsiveness.

    Science.gov (United States)

    Howitt, Brooke E; Monte, Nicolas M; Elvin, Julia; Mutter, George L

    2015-05-01

    Primary sporadic gene-inactivating events within the progesterone response cascade might explain the presence of individual dyssynchronous (outlier) glands commonly observed in a secretory background. We queried morphologically dyssynchronous glands in mid-secretory endometrium with a series of markers normally downregulated by progesterone. Seventy-nine mid-secretory endometrial biopsies were stained with hematoxylin and eosin, MIB-1, PAX2, estrogen and progesterone receptors, and PTEN. Aberrant staining of glands was independently scored for each marker. Outlier glands overlapping between stains were enumerated. A total of 63% of cases had hematoxylin and eosin stained outlier glands (average 9), which often demonstrated failed progesterone-mediated downregulation of PAX2 (43%), estrogen (40%), and/or progesterone receptors (28%). Aberrations of progesterone response was seen in 70% to 85% of cases overall, averaging 10 to 30 glands/affected case. The frequency and burden of affected glands was similar to that seen for primary inactivating events of the PAX2 and PTEN genes (35% and 41% of cases, respectively, averaging 32 and 38 glands per affected patient). Sporadic gene-inactivating events are common during endometrial regeneration, and may cause morphologic changes unmasked by the hormonal context. Some of these dyssynchronous "outlier" glands, whether evident on hematoxylin and eosin stain or not, have an interrupted progesterone response. PMID:25844547

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

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald

    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 were linked to MMR status based on immunostaining and BRAF mutation status.MMR defects were identified in 22.7% of the tumors, with 46 classified as sporadic. When the clinical parameters of age, sex, and proximal tumor location were combined with the morphologic features with the highest relative risks (RRs), eg, mucinous differentiation (RR, 9.0), tumor-infiltrating lymphocytes (RR, 7.5), absence of necrosis (RR, 7.5), and expanding growth pattern (RR, 5.0) into a 7-factor index, the presence of at least 4 features identified the MMR-defective tumors with 92.3% sensitivity and 75.3% specificity and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb

  9. On Permanent and Sporadic Oscillations of the Magnetosphere

    CERN Document Server

    Guglielmi, A V

    2014-01-01

    In this paper we investigate the impact of permanent oscillations Pc3 on the excitation of sporadic oscillations Pi2 ( their periods are 10-45 and 40-150 s, respectively ). The hypothesis is formulated that Pc3 oscillations originating in front of the magnetosphere penetrate into the geomagnetic tail, cause a local depression in the current in the neutral sheet, and under favorable conditions stimulate a tearing instability. This leads to reconnection of magnetic field lines and an explosive release of magnetic energy stored in the tail. As a result, a substorm breaks up, with sporadic pulsations Pi2 as an important element of this process. It is expected from theoretical estimates and kinematic considerations that the higher the Pc3 frequency, the earlier the Pi2 trains start. We test this prediction using observational data from satellite measurements of the interplanetary magnetic field and on-ground magnetic measurements. The results confirm the theoretical expectation. Additional routes are proposed to t...

  10. Cognitive disorders after sporadic ecstasy use? A case report.

    Science.gov (United States)

    Ruis, Carla; Postma, Albert; Bouvy, Willem; van der Ham, Ineke

    2015-06-01

    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 a 39-year-old man who used an ecstasy tablet in 2005. This resulted in severe confusion for a few days. The confusion was followed by persistent memory complaints and difficulties orientating in new surroundings. An extensive neuropsychological examination 7 years after the ecstasy use revealed a severe memory disorder. Furthermore, his performance on a virtual reality test of navigation showed serious problems navigating in new surroundings. In comparison with matched control subjects (Bayesian approach for single case studies) his scores were significantly impaired on several subtasks of the navigation test. On a magnetic resonance imaging (MRI) scan of the brain bilateral hippocampal atrophy and sclerosis were visible, comparable to previous MRI studies describing hippocampal damage following ecstasy ingestion. This case report describes persistent memory and navigation disorders after sporadic ecstasy use, supported by structural brain abnormalities seen on the MRI scan. These findings revive the debate on whether sporadic ecstasy use can cause persistent cognitive deficits. PMID:24606066

  11. Electric field measurements of DC and long wavelength structures associated with sporadic-E layers and QP radar echoes

    Science.gov (United States)

    Pfaff, R.; Freudenreich, H.; Yokoyama, T.; Yamamoto, M.; Fukao, S.; Mori, H.; Ohtsuki, S.; Iwagami, N.

    2005-10-01

    Electric field and plasma density data gathered on a sounding rocket launched from Uchinoura Space Center, Japan, reveal a complex electrodynamics associated with sporadic-E layers and simultaneous observations of quasi-periodic radar echoes. The electrodynamics are characterized by spatial and temporal variations that differed considerably between the rocket's upleg and downleg traversals of the lower ionosphere. Within the main sporadic-E layer (95 110 km) on the upleg, the electric fields were variable, with amplitudes of 2 4 mV/m that changed considerably within altitude intervals of 1 3 km. The identification of polarization electric fields coinciding with plasma density enhancements and/or depletions is not readily apparent. Within this region on the downleg, however, the direction of the electric field revealed a marked change that coincided precisely with the peak of a single, narrow sporadic-E plasma density layer near 102.5 km. This shear was presumably associated with the neutral wind shear responsible for the layer formation. The electric field data above the sporadic-E layer on the upleg, from 110 km to the rocket apogee of 152 km, revealed a continuous train of distinct, large scale, quasi-periodic structures with wavelengths of 10 15 km and wavevectors oriented between the NE-SW quadrants. The electric field structures had typical amplitudes of 3 5 mV/m with one excursion to 9 mV/m, and in a very general sense, were associated with perturbations in the plasma density. The electric field waveforms showed evidence for steepening and/or convergence effects and presumably had mapped upwards along the magnetic field from the sporadic-E region below. Candidate mechanisms to explain the origin of these structures include the Kelvin-Helmholtz instability and the Es-layer instability. In both cases, the same shear that formed the sporadic-E layer would provide the energy to generate the km-scale structures. Other possibilities include gravity waves or a combination of these processes. The data suggest that these structures were associated with the lower altitude density striations that were the seat of the QP radar echoes observed simultaneously. They also appear to have been associated with the mechanism responsible for a well-defined pattern of "whorls" in the neutral wind data that were revealed in a chemical trail released by a second sounding rocket launched 15min later. Short scale (<100 m) electric field irregularities were also observed and were strongest in the sporadic-E region below 110km. The irregularities were organized into 2 3 layers on the upleg, where the plasma density also displayed multiple layers, yet were confined to a single layer on the downleg where the plasma density showed a single, well-defined sporadic-E peak. The linear gradient drift instability involving the DC electric field and the vertical plasma gradient is shown to be incapable of driving the observed waves on the upleg, but may have contributed to the growth of short scale waves on the topside of the narrow unstable density gradient observed on the downleg. The data suggest that other sources of free energy may have been important factors for the growth of the short scale irregularities. Keywords. Ionosphere (Mid-latitude ionosphere; Electric fields and currents; Ionospheric irregularities)

  12. Electric field measurements of DC and long wavelength structures associated with sporadic-E layers and QP radar echoes

    Directory of Open Access Journals (Sweden)

    S. Ohtsuki

    2005-10-01

    Full Text Available Electric field and plasma density data gathered on a sounding rocket launched from Uchinoura Space Center, Japan, reveal a complex electrodynamics associated with sporadic-E layers and simultaneous observations of quasi-periodic radar echoes. The electrodynamics are characterized by spatial and temporal variations that differed considerably between the rocket's upleg and downleg traversals of the lower ionosphere. Within the main sporadic-E layer (95–110 km on the upleg, the electric fields were variable, with amplitudes of 2–4 mV/m that changed considerably within altitude intervals of 1–3 km. The identification of polarization electric fields coinciding with plasma density enhancements and/or depletions is not readily apparent. Within this region on the downleg, however, the direction of the electric field revealed a marked change that coincided precisely with the peak of a single, narrow sporadic-E plasma density layer near 102.5 km. This shear was presumably associated with the neutral wind shear responsible for the layer formation. The electric field data above the sporadic-E layer on the upleg, from 110 km to the rocket apogee of 152 km, revealed a continuous train of distinct, large scale, quasi-periodic structures with wavelengths of 10–15 km and wavevectors oriented between the NE-SW quadrants. The electric field structures had typical amplitudes of 3–5 mV/m with one excursion to 9 mV/m, and in a very general sense, were associated with perturbations in the plasma density. The electric field waveforms showed evidence for steepening and/or convergence effects and presumably had mapped upwards along the magnetic field from the sporadic-E region below. Candidate mechanisms to explain the origin of these structures include the Kelvin-Helmholtz instability and the Es-layer instability. In both cases, the same shear that formed the sporadic-E layer would provide the energy to generate the km-scale structures. Other possibilities include gravity waves or a combination of these processes. The data suggest that these structures were associated with the lower altitude density striations that were the seat of the QP radar echoes observed simultaneously. They also appear to have been associated with the mechanism responsible for a well-defined pattern of "whorls" in the neutral wind data that were revealed in a chemical trail released by a second sounding rocket launched 15min later. Short scale (<100 m electric field irregularities were also observed and were strongest in the sporadic-E region below 110km. The irregularities were organized into 2–3 layers on the upleg, where the plasma density also displayed multiple layers, yet were confined to a single layer on the downleg where the plasma density showed a single, well-defined sporadic-E peak. The linear gradient drift instability involving the DC electric field and the vertical plasma gradient is shown to be incapable of driving the observed waves on the upleg, but may have contributed to the growth of short scale waves on the topside of the narrow unstable density gradient observed on the downleg. The data suggest that other sources of free energy may have been important factors for the growth of the short scale irregularities. Keywords. Ionosphere (Mid-latitude ionosphere; Electric fields and currents; Ionospheric irregularities

  13. Sporadic onset Creutzfeldt-Jacob disease: Interesting MRI observations

    Directory of Open Access Journals (Sweden)

    Praveen K

    2006-01-01

    Full Text Available We describe a 60-year-old woman with "probable" sporadic Creutzfeldt-Jacob disease (CJD who manifested with two months history of rapidly progressive dementia and abnormal behavior, speech and gait abnormality, excessive sleepiness and myoclonic jerks. Scalp EEG showed diffuse slowing of background activity to delta range and triphasic sharp wave complexes occurring periodically twice in one-second interval. Magnetic resonance Imaging (MRI of brain revealed high signal intensity on T2 weighted image (T2WI and fluid attenuated inversion recovery sequences in the caudate and putamen bilaterally. Diffusion weighted images showed bilateral symmetric hyperintense signals in the caudate and putamen. The role of MRI in the diagnosis of CJD is discussed.

  14. [Virological and clinical features of patients with sporadic hepatitis C].

    Science.gov (United States)

    Tang, Z; Wang, Y; Yu, Z; Yang, D; Hao, L

    1997-06-01

    In this study, the transmission route in 16 sporadic hepatitis C (SHC) patients was investigated. Three of them were surgeons who had often had occupational needlestick accidents, another 3 had close household contact with their spouses who had been diagnosed as chronic posttransfusion viral hepatitis C (PTHC), and the remaining 5 had potential parenteral exposure such as tooth extraction, injection or inoculation and so on. Five patients with SHC didn't have such history, their transmission route was not determined. Our result showed a lower viremia level in patients with SHC when compared to PTHC patients (the serum dilutions for HCV RNA detection was 10-100 times in the former and 100-10000 times in the latter. PPTHC, the patients with SHC in our study had milder liver demage and lower ALT levels, and most of them (10/16) were symptomless. PMID:15619815

  15. A sporadic third layer in the ionosphere of Mars.

    Science.gov (United States)

    Pätzold, M; Tellmann, S; Häusler, B; Hinson, D; Schaa, R; Tyler, G L

    2005-11-01

    The daytime martian ionosphere has been observed as a two-layer structure with electron densities that peak at altitudes between about 110 and 130 kilometers. The Mars Express Orbiter Radio Science Experiment on the European Mars Express spacecraft observed, in 10 out of 120 electron density profiles, a third ionospheric layer at altitude ranges of 65 to 110 kilometers, where electron densities, on average, peaked at 0.8 x 10(10) per cubic meter. Such a layer has been predicted to be permanent and continuous. Its origin has been attributed to ablation of meteors and charge exchange of magnesium and iron. Our observations imply that this layer is present sporadically and locally. PMID:16272118

  16. A data-driven model of biomarker changes in sporadic Alzheimer's disease

    OpenAIRE

    Young, Alexandra L.; Oxtoby, Neil P.; Daga, Pankaj; Cash, David M.; Fox, Nick C.; Ourselin, Sebastien; Schott, Jonathan M.; Alexander, Daniel C.

    2014-01-01

    Young et al. reformulate an event-based model for the progression of Alzheimer's disease to make it applicable to a heterogeneous sporadic disease population. The enhanced model predicts the ordering of biomarker abnormality in sporadic Alzheimer's disease independently of clinical diagnoses or biomarker cut-points, and shows state-of-the-art diagnostic classification performance.

  17. A Tangled Web - Tau and Sporadic Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    PatrickALewis

    2010-12-01

    Full Text Available Parkinson's disease (PD represents a major challenge for health care systems around the world: it is the most common degenerative movement disorder of old age, affecting over 100,000 people in the UK alone. A great deal of progress has been made in understanding the molecular basis of PD by taking advantage of advances in genetics, initially by the identification of genes responsible for rare mendellian forms of PD (outlined in table one, and more recently by applying genome wide association studies (GWAS to the sporadic form of the disease. Several such GWAS have now been carried out, with a meta-analysis currently under way. Using over 6000 cases and 10000 controls, two of these studies have identified variation at a number of loci as being associated with an increased risk of disease. Three genes stand out as candidates from these studies – the SNCA gene, coding for ? -synuclein, the LRRK2 gene, coding for leucine rich repeat kinase 2, and MAPT, coding for the microtubule associated protein tau. Point mutations in ? -synuclein, along with gene multiplication events, result in autosomal dominant PD, often with a significant dementia component. In addition to this, ? -synuclein is the principle component of the main pathological hallmark of PD, the Lewy body. Mutations in LRRK2 are the most common genetic cause of PD, and so again were a likely candidate for a susceptibility locus for the sporadic form of disease. More surprising, perhaps, was the identification of tau as a susceptibility factor for Parkinson's. In this review we will outline the role of tau in neurodegeneration and in different forms of parkinsonism, and speculate as to what the functional basis of this association might be.

  18. Critical Frequency and Sporadic E Level Patterns Above Biak During Meteor Showers

    Science.gov (United States)

    Rusnadi, Iyus Edi; Ristani, Nancy; Djamaluddin, Thomas

    2000-10-01

    Change of critical frequency and height of E sporadic formed certain patterns. Solar activity, geomagnetic activity, and meteor showers influence this change. In order to get the pattern of critical frequency and height of E sporadic formed by meteoroid cluster the effect from solar and geomagnetic activity should be eliminated. June Lyrids, Shower 217, and Perseids meteor shower has the pattern of y = ax3 + bx2 + cx + d, with y is the quantity of meteor and x local time, with 0,0001 Biak (01 deg 11 min S, 135 deg 07 min E) as 1. y = -0,6763 x + 15,476 at 15 to 17 June 1993 in 18.00-24.00 2. y = -0,0961 x3 + 1,0023x2 - 2,9815x + 5,2362 at 4 to 6 August 1993 in 0 1.00-06.00 and y = -0,0638x3 + 4,1376x2 - 89,175x + 641,15 at 4 to 6 August 1993 in 18.00-24.00 3. y = -0,0517x + 3,1683 at 12 to 14 August 1993 in 01.00-06.00 and y = 0,0349x3 - 2,1x2 + 41,588x - 268,44 at 12 to 14 August 1993 in 18.00-24.00 with y is the frequency in MHz and x local time. The research also obtained the pattern height of E sporadic as follows: 1. y = -5,625x + 201,63 476 at 15 to 17 June 1993 in 18.00-24.00 2. y = 2,125x3 - 22,425x2 + 66757x + 62,705 at 4 to 6 August 1993 in 01.00-06.00 and y=0,4478x3 - 26,966x2 + 538,21x - 3458,4 at 4 to 6 August 1993 in 18.00-24.00 3. y = 3,058x + 113,08 at 12 to 14 August 1993 in 0 1.00-06.00 and y =0,3072x3 - 18,411x2 + 364,54x - 2280,1 at 12 to 14 August 1993 in 18.00-24.00 with y is the height in kilometers (km) and x local time.

  19. Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda.

    Science.gov (United States)

    Fontanellas, Antonio; Martínez-Fresno, María; Garrido-Astray, María Concepción; Perucho, Teresa; Morán-Jiménez, María-Josefa; García-Bravo, María; Méndez, Manuel; Poblete-Gutiérrez, Pamela; Frank, Jorge; Henriques-Gil, Nuno; de Salamanca, Rafael Enríquez

    2010-08-01

    Porphyria cutanea tarda (PCT) results from decreased activity of hepatic uroporphyrinogen decarboxylase (UROD). Both sporadic and familial forms are characterised by typical cutaneous lesions triggered by genetic/environmental factors. Studies in rodents showed that cytochrome P4501A2 (CYP1A2) plays a central role in the synthesis of a competitive inhibitor of hepatic UROD, but there is little evidence in humans. The impact of smoking and CYP1A2 g-163C > A allelic variant upon first appearance of clinical signs was investigated in 102 patients (80 sporadic-PCT) and 150 healthy donors from Spain. We found an increase in the frequency of CYP1A2 g-163A allele in patients with PCT when compared with controls, although the more inducible A/A genotype had no effect on the onset age. In sporadic-PCT, smoking leads to earlier onset of clinically overt disease in moderate-to-heavy smokers (>or=10 cigarettes/day). In conclusion, this study provides evidence that smoking hastens the onset of cutaneous symptoms in sporadic-PCT patients. PMID:20163457

  20. Activating mutations in the RAS/mitogen-activated protein kinase signaling pathway in sporadic trichoblastoma and syringocystadenoma papilliferum.

    Science.gov (United States)

    Shen, Anne-Sophie; Peterhof, Eva; Kind, Peter; Rütten, Arno; Zelger, Bernhard; Landthaler, Michael; Berneburg, Mark; Hafner, Christian; Groesser, Leopold

    2015-02-01

    Trichoblastoma (TB) and syringocystadenoma papilliferum (SCAP) are both rare adnexal skin lesions occurring either sporadically or as secondary neoplasms in sebaceous nevi. TB and SCAP associated with sebaceous nevi have been shown to carry the same HRAS mutation as the underlying nevus. However, the genetic background of sporadic TB and SCAP has remained unknown. Therefore, we screened 18 sporadic TBs and 23 sporadic syringocystadenoma papillifera from 41 patients for the presence of activating mutations in RAS genes and other oncogenes. Using a RAS SNaPshot assay, HRAS mutations were detected in 2 (11%) of 18 sporadic TB and 6 (26%) of 23 sporadic syringocystadenoma papillifera. A KRAS mutation was identified in 1 sporadic SCAP. High-throughput oncogene mutation profiling furthermore identified BRAF V600E mutations in sporadic syringocystadenoma papillifera, which could be validated in 12 (52%) of 23 lesions using a BRAF SNaPshot assay. BRAF and RAS mutations were mutually exclusive in sporadic syringocystadenoma papillifera. No BRAF mutation could be detected in 3 syringocystadenoma papillifera secondarily arisen from a sebaceous nevus as well as in sporadic TB. In 14 lesions carrying an oncogenic mutation, nonlesional control tissue from the epidermal margin revealed a wild-type sequence, thus proving the somatic character of the mutation. Our results indicate that activation of the RAS-mitogen-activated protein kinase pathway by BRAF and RAS mutations contributes significantly to the tumorigenesis of sporadic SCAP and, less frequently, of sporadic TB. PMID:25532942

  1. Facing and managing natural disasters in the Sporades Islands, Greece

    Directory of Open Access Journals (Sweden)

    P. Karanikola

    2013-11-01

    Full Text Available 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 defence 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 from each of the separate stakeholders so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked about their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly 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.

  2. 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.

  3. Novel genetic mutations in a sporadic port-wine stain.

    Science.gov (United States)

    Lian, Christine Guo; Sholl, Lynette M; Zakka, Labib R; O, Teresa M; Liu, Cynthia; Xu, Shuyun; Stanek, Ewelina; Garcia, Elizabeth; Jia, Yonghui; MacConaill, Laura E; Murphy, George F; Waner, Milton; Mihm, Martin C

    2014-12-01

    IMPORTANCE Port-wine stains (PWSs) are common congenital cutaneous capillary malformations. A somatic GNAQ mutation was recently identified in patients with sporadic PWSs and Sturge-Weber syndrome. However, subsequent studies to confirm or extend this observation are lacking.OBSERVATIONS We report a long-standing, unilateral facial PWS of a man in his early 70s confirmed by histopathological analysis. Staged surgical excision of the vascular malformation was performed, and genomic DNA was extracted from the vascular malformation specimen and normal skin. Targeted next-generation sequencing of the coding sequence of 275 known cancer genes including GNAQ was performed in both specimens. A single-nucleotide variant(c.548G>A, p.Arg183Gln) in GNAQ was identified in the PWS-affected tissue but not in the normal skin sample. In addition, this sequencing approach uncovered several additional novel somatic mutations in the genes SMARCA4, EPHA3, MYB, PDGFR-?, and PIK3CA.CONCLUSIONS AND RELEVANCE Our findings confirm the presence of somatic mutations inGNAQ in the affected skin of a patient with congenital PWS, as well as alterations in several other novel genes of possible importance in the pathogenesis of PWS that may also offer substantial therapeutic targets. PMID:25188413

  4. Genetic studies into inherited and sporadic hemolytic uremic syndrome.

    Science.gov (United States)

    Warwicker, P; Goodship, T H; Donne, R L; Pirson, Y; Nicholls, A; Ward, R M; Turnpenny, P; Goodship, J A

    1998-04-01

    Hemolytic uremic syndrome (HUS) in adults carries a high morbidity and mortality, and its cause remains unknown despite many theories. Although familial HUS is rare, it affords a unique opportunity to elucidate underlying mechanisms that may have relevance to acquired HUS. We have undertaken a genetic linkage study based on a candidate gene approach. A common area bounded by the markers D1S212 and D1S306, a distance of 26 cM located at 1q32 segregated with the disease (Z max 3.94). We demonstrate that the gene for factor H lies within the region. Subsequent mutation analysis of the factor H gene has revealed two mutations in patients with HUS. In an individual with the sporadic/relapsing form of the disease we have found a mutation comprising a deletion, subsequent frame shift and premature stop codon leading to half normal levels of serum factor H. In one of the three families there is a point mutation in exon 20 causing an arginine to glycine change, which is likely to alter structure and hence function of the factor H protein. Factor H is a major plasma protein that plays a critical regulatory role in the alternative pathway of complement activation. In light of these findings and previous reports of HUS in patients with factor H deficiency, we postulate that abnormalities of factor H may be involved in the etiology of HUS. PMID:9551389

  5. Cerebrospinal Fluid Markers in Sporadic Creutzfeldt-Jakob Disease

    Directory of Open Access Journals (Sweden)

    Andrea Galassi

    2011-09-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG, and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF. In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP, a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated181 tau, and amyloid beta (A? peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most sensitive indicators of sCJD, the highest sensitivity, specificity and positive predictive value were obtained when all the above markers were combined. The latter approach also allowed a reliable differential diagnosis with other neurodegenerative dementias.

  6. Coincident extremely large sporadic sodium and sporadic E layers observed in the lower thermosphere over Colorado and Utah

    Directory of Open Access Journals (Sweden)

    B. P. Williams

    2007-02-01

    Full Text Available On the night of 2 June 2002, the sodium lidar in Fort Collins, CO (40.6 N, 105 W measured an extremely strong sporadic sodium layer lasting from 03:30 to 05:00 UT with several weaker layers later in the night at 06:00 and 09:00 UT. There is a double layer structure with peaks at 101 and 104 km. The peak sodium density was 21 000 atoms/cm3 with a column abundance of up to twice that of the normal sodium layer. The peak density was 500 times greater than the typical density at that altitude. The sporadic layer abundance and strength factor were higher than any reported in the literature. The two lidar beams, separated by 70 km at this altitude, both measured 0.6 h periodicities in the abundance, but out of phase with each other by 0.3 h. There is also evidence for strong wave activity in the lidar temperatures and winds. The NOAA ionosonde in Boulder, CO (40.0 N, 105 W measured a critical frequency (foEs of 14.3 MHz at 03:00 UT on this night, the highest value anytime during 2002. The high values of total ion density inferred means that Na+ fraction must have been only a few percent to explain the neutral Na layer abundances. The Bear Lake, Utah (41.9 N, 111.4 W dynasonde also measured intense Es between 02:00 and 05:00 UT and again from 06:00 to 08:00 UT about 700 km west of the lidar, with most of the ionograms during these intervals measuring Es up to 12 MHz, the limit of the ionosonde sweep. Other ionosondes around North America on the NGDC database measured normal foEs values that night, so it was a localized event within North America. The peak of Es activity observed in Europe during the summer of 2002 occurred on 4 June. The observations are consistent with the current theories where a combination of wind shears and long period waves form and push downward a concentrated layer of ions, which then chemically react and form a narrow layer of sodium atoms.

  7. Coincident extremely large sporadic sodium and sporadic E layers observed in the lower thermosphere over Colorado and Utah

    Science.gov (United States)

    Williams, B. P.; Berkey, F. T.; Sherman, J.; She, C. Y.

    2007-02-01

    On the night of 2 June 2002, the sodium lidar in Fort Collins, CO (40.6 N, 105 W) measured an extremely strong sporadic sodium layer lasting from 03:30 to 05:00 UT with several weaker layers later in the night at 06:00 and 09:00 UT. There is a double layer structure with peaks at 101 and 104 km. The peak sodium density was 21 000 atoms/cm3 with a column abundance of up to twice that of the normal sodium layer. The peak density was 500 times greater than the typical density at that altitude. The sporadic layer abundance and strength factor were higher than any reported in the literature. The two lidar beams, separated by 70 km at this altitude, both measured 0.6 h periodicities in the abundance, but out of phase with each other by 0.3 h. There is also evidence for strong wave activity in the lidar temperatures and winds. The NOAA ionosonde in Boulder, CO (40.0 N, 105 W) measured a critical frequency (foEs) of 14.3 MHz at 03:00 UT on this night, the highest value anytime during 2002. The high values of total ion density inferred means that Na+ fraction must have been only a few percent to explain the neutral Na layer abundances. The Bear Lake, Utah (41.9 N, 111.4 W) dynasonde also measured intense Es between 02:00 and 05:00 UT and again from 06:00 to 08:00 UT about 700 km west of the lidar, with most of the ionograms during these intervals measuring Es up to 12 MHz, the limit of the ionosonde sweep. Other ionosondes around North America on the NGDC database measured normal foEs values that night, so it was a localized event within North America. The peak of Es activity observed in Europe during the summer of 2002 occurred on 4 June. The observations are consistent with the current theories where a combination of wind shears and long period waves form and push downward a concentrated layer of ions, which then chemically react and form a narrow layer of sodium atoms.

  8. A novel mutation in the senataxin gene identified in a Chinese patient with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Zhao, Zhen-hua; Chen, Wen-Zu; Wu, Zhi-ying; Wang, Ning; Zhao, Gui-xian; Chen, Wan-jin; Murong, Shen-xing

    2009-04-01

    Our objective was to investigate the association between senataxin mutations and sporadic amyotrophic lateral sclerosis (ALS) in Chinese patients. DNA from 45 sporadic ALS patients was screened for mutations in senataxin using polymerase chain reaction (PCR) and direct sequencing. A novel variation, Thr1118Ile, was identified in a 42-year-old individual with sporadic ALS. This variation was not detected in 200 unrelated control individuals. In conclusion, the presence of this variation in a patient with sporadic ALS, and its absence in 200 controls, supports an association between senataxin and sporadic ALS. This study has broadened the mutation spectrum of senataxin and expanded the clinical phenotypes of senataxin mutations. PMID:19058054

  9. Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer

    OpenAIRE

    Suijkerbuijk, K. P. M.; Fackler, M. J.; Sukumar, S.; Gils, C. H.; Laar, T.; Wall, E.; Vooijs, M.; Diest, P. J.

    2008-01-01

    Background: Promoter methylation is a common epigenetic mechanism to silence tumor suppressor genes during breast cancer development. We investigated whether BRCA1-associated breast tumors show cancer-predictive methylation patterns similar to those found in sporadic tumors.

  10. Double atmospheric gravity wave frequency oscillations of sporadic E formed in a horizontal shear flow

    International Nuclear Information System (INIS)

    The new theory of sporadic E density oscillation with double atmospheric gravity wave (AGW) frequency in two-dimensional case taking into account ions ambipolar diffusion is presented. It is found that densities of multi-layered sporadic E, formed under the influence of atmospheric vortical perturbation (with vertical wavelength ?z?0) evolving in the horizontal shear flow (shear wave), can oscillate with up to double Brunt-Vaeisaelae frequency under the action of short-period AGW, in which shear wave is transformed. The formation of multi-layered sporadic E (inside regions with vertical thickness about ?z/2) and its density changes in every half AGW period close to ions convergence region occur by combined action of ion-neutral collision and Lorentz forcing and can cause additional accumulation of ions responsible for sporadic E density oscillation with double AGW frequency.

  11. Genome-wide association reveals three SNPs associated with sporadic amyotrophic lateral sclerosis through a two-locus analysis

    Directory of Open Access Journals (Sweden)

    Schymick Jennifer C

    2009-09-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal, degenerative neuromuscular disease characterized by a progressive loss of voluntary motor activity. About 95% of ALS patients are in "sporadic form"-meaning their disease is not associated with a family history of the disease. To date, the genetic factors of the sporadic form of ALS are poorly understood. Methods We proposed a two-stage approach based on seventeen biological plausible models to search for two-locus combinations that have significant joint effects to the disease in a genome-wide association study (GWAS. We used a two-stage strategy to reduce the computational burden associated with performing an exhaustive two-locus search across the genome. In the first stage, all SNPs were screened using a single-marker test. In the second stage, all pairs made from the 1000 SNPs with the lowest p-values from the first stage were evaluated under each of the 17 two-locus models. Results we performed the two-stage approach on a GWAS data set of sporadic ALS from the SNP Database at the NINDS Human Genetics Resource Center DNA and Cell Line Repository http://ccr.coriell.org/ninds/. Our two-locus analysis showed that two two-locus combinations--rs4363506 (SNP1 and rs3733242 (SNP2, and rs4363506 and rs16984239 (SNP3 -- were significantly associated with sporadic ALS. After adjusting for multiple tests and multiple models, the combination of SNP1 and SNP2 had a p-value of 0.032 under the Dom?Dom epistatic model; SNP1 and SNP3 had a p-value of 0.042 under the Dom × Dom multiplicative model. Conclusion The proposed two-stage analytical method can be used to search for joint effects of genes in GWAS. The two-stage strategy decreased the computational time and the multiple testing burdens associated with GWAS. We have also observed that the loci identified by our two-stage strategy can not be detected by single-locus tests.

  12. Comparison of valporic acid efficacy in familial versus sporadic cases of juvenile myoclonic epilepsy

    OpenAIRE

    Motamedi Mahmoud; Mohammad Ali Sahraian; Rahmat Masoud

    2006-01-01

    Background: Juvenile myoclonic epilepsy is a heterogeneous syndrome, both in genetic and clinical aspects. Aims: This study was conducted to compare the efficacy of valproic acid in familial versus sporadic cases of this syndrome. Settings and Design: Seventy patients with JME were identified; 24 patients (34.3%) had positive history of JME in their first degree relatives (group I) and 46 patients (65.7%) were sporadic (group II). Materials and Methods: Valproic acid was ...

  13. Genetic and phenotypic heterogeneity in sporadic and familial forms of paroxysmal dyskinesia

    OpenAIRE

    Groffen, Alexander J. A.; Klapwijk, Thom; Rootselaar, Anne-fleur; Groen, Justus L.; Tijssen, Marina A. J.

    2012-01-01

    Paroxysmal dyskinesia (PxD) is a group of movement disorders characterized by recurrent episodes of involuntary movements. Familial paroxysmal kinesigenic dyskinesia (PKD) is caused by PRRT2 mutations, but a distinct etiology has been suggested for sporadic PKD. Here we describe a cohort of patients collected from our movement disorders outpatient clinic in the period 1996–2011. Fifteen patients with sporadic PxD and 23 subjects from three pedigrees with familial PKD were screened for mutat...

  14. Chromatographically purified immunoglobulin G of endemic and sporadic goiter patients stimulates FRTL5 cell growth in a mitotic arrest assay.

    Science.gov (United States)

    Wilders-Truschnig, M M; Drexhage, H A; Leb, G; Eber, O; Brezinschek, H P; Dohr, G; Lanzer, G; Krejs, G J

    1990-02-01

    A strain of differentiated rat thyroid cells (FRTL5) in continuous culture was used to study the presence of thyroid growth-promoting immunoglobulins (TGI) in the serum of patients with endemic and sporadic euthyroid goiters. To identify true in vitro cell proliferation a microscopic mitotic arrest assay was used. Immunoglobulins G (IgGs) were prepared with QAE-Sephadex A-50 or protein-A-Sepharose. A positive growth stimulation index was found in IgG preparations of 65 of 71 patients with endemic goiter and in 9 of 14 IgG preparations of patients with sporadic goiter. IgG preparations of 15 control subjects from an area where endemic goiter due to iodine deficiency does not occur and of 18 subjects without iodine deficiency and without thyroid enlargement living in the endemic area did not stimulate FRTL5 cell growth. FRTL5 cell growth stimulation with IgGs of these euthyroid goiter patients could only be detected when IgG was tested in combination with a small dose of TSH. Immunoprecipitation with polyclonal and monoclonal antihuman IgG was able to abolish the growth-promoting effects. In 32 blinded samples the Feulgen cytobiochemical assay, formerly used to detect TGI, was compared with the FRTL5 mitotic arrest assay. The two methods showed similar results. Our observations of chromatographically purified IgG promoting thyroid cell proliferation in vitro provide good evidence that IgG was responsible for thyroid cell growth in vitro and suggest that autoimmune growth mechanisms may be involved in the pathogenesis of both endemic and sporadic goiters. PMID:1688867

  15. 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.

  16. Sporadic meningioangiomatosis: imaging findings with histopathologic correlations in seven patients

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Tae Yeon; Kim, Ji Hye; Yoo, So-Young; Eo, Hong [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Suh, Yeon-Lim; Ahn, Soomin [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of)

    2013-12-15

    Meningioangiomatosis (MA) is a rare benign cerebral lesion. We aimed to evaluate the CT and MR features of sporadic MA, with a focus on the correlation between imaging and histopathologic findings. CT (n = 7) and MR (n = 8) images of eight patients (6 men and 2 women; mean age, 12.8 years; range, 4-22 years) with pathologically proven MA were retrospectively reviewed. After dividing the MA lesions according to their distribution into cortical and subcortical white matter components, the morphologic characteristics were analyzed and correlated with histopathologic findings in seven patients. CT and MR images showed cortical (n = 4, 50 %) and subcortical white matter (n = 7, 88 %) components of MA. All four cortical components revealed hyperattenuation on CT scan and T1 isointensity/T2 hypointensity on MR images, whereas subcortical white matter components showed hypoattenuation on CT scan and T1 hypointensity/T2 hyperintensity on MR images. Two cortical components (25 %) demonstrated enhancement and one subcortical white matter component demonstrated cystic change. Seven cases were available for imaging-histopathologic correlation. In all seven cases, the cortex was involved by MA and six patients (86 %) showed subcortical white matter involvement by MA. There were excellent correlations between the imaging and histopathologic findings in subcortical white matter components, and the accuracy was 100 % (seven of seven); whereas there were poor correlations in cortical components, and the accuracy was 43 % (three of seven). The cerebral cortex and subcortical white matter were concomitantly involved by MA. Subcortical white matter components of MA were more apparent than cortical components on CT and MR imaging. (orig.)

  17. 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.

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

    DEFF Research Database (Denmark)

    van Eimeren, Thilo; Binkofski, Ferdinand

    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, patients with Parkin-associated PD often show a stable long-term response to dopaminergic therapy without developing treatment-induced motor complications. Therefore, we reasoned that this difference in vulnerability to develop dyskinesias under long-term dopaminergic therapy may be associated with differences in movement-related activation patterns in Parkin-associated compared to sporadic PD. To test this hypothesis, medicated non-dyskinetic patients with either Parkin-associated or sporadic PD underwent functional magnetic resonance imaging (fMRI) while performing externally specified or internally 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 response in some patients with Parkin-associated PD may not be related to differences in cortical recruitment. In conclusion, our findings corroborate a substantial pathophysiologic overlap between Parkin-associated and sporadic PD and lend further support to the notion that Parkin-associated PD is a suitable genetic model for sporadic PD.

  19. Mendelian genes for Parkinson's disease contribute to the sporadic forms of the disease†.

    Science.gov (United States)

    Spataro, Nino; Calafell, Francesc; Cervera-Carles, Laura; Casals, Ferran; Pagonabarraga, Javier; Pascual-Sedano, Berta; Campolongo, Antònia; Kulisevsky, Jaime; Lleó, Alberto; Navarro, Arcadi; Clarimón, Jordi; Bosch, Elena

    2015-04-01

    Parkinson's disease (PD) can be divided into familial (Mendelian) and sporadic forms. A number of causal genes have been discovered for the Mendelian form, which constitutes 10-20% of the total cases. Genome-wide association studies have successfully uncovered a number of susceptibility loci for sporadic cases but those only explain a small fraction (6-7%) of PD heritability. It has been observed that some genes that confer susceptibility to PD through common risk variants also contain rare causing mutations for the Mendelian forms of the disease. These results suggest a possible functional link between Mendelian and sporadic PD and led us to investigate the role that rare and low-frequency variants could have on the sporadic form. Through a targeting approach, we have resequenced at 49× coverage the exons and regulatory regions of 38 genes (including Mendelian and susceptibility PD genes) in 249 sporadic PD patients and 145 unrelated controls of European origin. Unlike susceptibility genes, Mendelian genes show a clear general enrichment of rare functional variants in PD cases, observed directly as well as with Tajima's D statistic and several collapsing methods. Our findings suggest that rare variation on PD Mendelian genes may have a role in the sporadic forms of the disease. PMID:25504046

  20. Genetic mutations in sporadic pituitary adenomas--what to screen for?

    Science.gov (United States)

    Lecoq, Anne-Lise; Kamenický, Peter; Guiochon-Mantel, Anne; Chanson, Philippe

    2015-01-01

    Pituitary adenomas are benign intracranial neoplasms that can result in morbidity owing to local invasion and/or excessive or deficient hormone production. The prevalence of symptomatic pituitary adenomas is approximately 1:1,000 in the general population. The vast majority of these tumours occur sporadically and are not part of syndromic disorders. However, germline mutations in genes known to predispose individuals to familial pituitary adenomas are found in a few patients with sporadic pituitary adenomas. Mutations in AIP (encoding aryl-hydrocarbon receptor-interacting protein) are the most frequently observed germline mutations. The prevalence of these mutations in patients with sporadic pituitary adenomas is ?4%, but can increase to 8-20% in young adults with macroadenomas or gigantism, and also in children. Germline mutations in MEN1 (encoding menin) result in multiple endocrine neoplasia type 1 and are found in very young patients with isolated sporadic pituitary adenomas, which highlights the importance of the chromosome 11q13 locus in pituitary tumorigenesis. In this Review, we describe the clinical features of patients with sporadic pituitary adenomas that are associated with AIP or MEN1 mutations, and discuss the molecular mechanisms that might be involved in pituitary adenoma tumorigenesis. We also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations. PMID:25350067

  1. Aberrant methylation of ERBB pathway genes in sporadic colorectal cancer.

    Science.gov (United States)

    Szmida, Elzbieta; Karpi?ski, Pawel; Leszczynski, Przemyslaw; Sedziak, Tomasz; Kielan, Wojciech; Ostasiewicz, Pawe?; Sasiadek, Maria M

    2014-11-01

    The ErbB signalling network plays a crucial role in the growth and progression of several cancers, including colorectal cancer (CRC), and includes potentially drug-targetable genes. Oncogenic activation of the ErbB pathway by mutations and focal amplifications have emerged recently as an important predictive marker of the prognosis of CRC patients. However, in contrast to genetic events, little is known about epigenetic alternations of ErbB-associated genes and their impact on gene expression. Genome-wide methylation in sporadic CRCs (n?=?12) paired with adjacent normal tissues have been previously analysed by Illumina Infinium HumanMethylation27 (HM27) at 27,578 CpG sites. For confirmation of our initial genome-wide analysis, we used a published HM27 dataset (GSE25062). Subsequently, CpG island methylation of selected ErbB pathway-associated genes was assessed on 233 CRC samples using methylation-sensitive polymerase chain reaction (MS-PCR) and analysed along with various genetic factors associated with CRC [epigenotype, BRAF and KRAS mutations, microsatellite instability (MSI)]. Methylation and expression integration was performed using published datasets including 25 pairs of CRC and normal colon tissues (GSE25062 and GSE25070), and confirmed with real-time PCR. Our previous microarray-based genome-wide DNA methylation analysis of 12 CRCs revealed that four ErbB-associated genes (PIK3CD, PKC?, ERBB4, ) were differentially methylated in CRCs. This was further confirmed by statistical re-analysis of an HM27 dataset (GSE25062). Frequent methylation at these loci in tumours was subsequently confirmed by MS-PCR (63 %, 43 %, 43 % and 92 %, respectively). Hypermethylation of PKC? associated with KRAS mutation (p?=?0.04), whereas hypermethylation of ERBB4 associated with high-methylation epigenotypes (HME), BRAF mutation and MSI (p?=?0.001, 0.002 and 0.0002, respectively). One of the four analysed genes (PKC?) was significantly downregulated in CRC tissue, as revealed by real-time PCR and re-analysis of the GSE25062 and GSE25070 datasets. After careful re-analysis of published methylation and expression data, we conclude that methylation of ERBB4, PAK7 and PIK3CD has no functional role in CRC carcinogenesis. In contrast, methylation seems to have a potential impact on the biology of colorectal tumours by negatively modulating the expression of PKC?. Importantly, the relationship between DNA methylation of PKC? and gene expression may warrant further attention in the context of colon cancer chemoprevention and anti-cancer therapy. PMID:25366420

  2. 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 (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 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 (fCJD(V180I)) or from Thr to Ala at residue 183 (fCJD(T183A)). Here we report that fCJD(V180I), but not fCJD(T183A), exhibits a proteinase K (PK)-resistant PrP (PrP(res)) 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 PrP(res) species in both fCJD(V180I) and VPSPr is likewise attributable to the absence of PrP(res) glycosylated at the first N-linked glycosylation site at residue 181, as in fCJD(T183A). In contrast to fCJD(T183A), both VPSPr and fCJD(V180I) exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrP(V180I) with a typical glycoform profile from cultured cells generates detectable PrP(res) 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 CJD(V180I) share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrP(C) to PrP(Sc) is inhibited, probably by a dominant-negative effect, or by other co-factors. PMID:23527023

  3. Comparison of Arecibo E-region data and sporadic-E theory: a measurement of the diffusion coefficient

    International Nuclear Information System (INIS)

    Incoherent scatter measurements using multiple-pulse techniques were performed at Arecibo to study the E region with a height resolution of 2.4 km. These simultaneous measurements of ion temperature, ion-neutral collision frequency, and electron density, as well as horizontal and vertical components of ion drift velocity, have allowed comparison between theories of sporadic-E and experiment. Sporadic-E layers were consistently observed to descend along the curve where the vertical ion drift velocity (V/sub z) was zero and its gradient delta V/sub z//delta Z was negative, as predicted by redistribution theory. Assuming no diffusion, the calculated effective recombination coefficient at the layer peak is more than an order of magnitude too small for NO+ or O2+, and varies with height in a manner which is unacceptable for a recombination coefficient. This indicates that the layer is composed of long-lived ions (probably metallic), and that the peak layer density is controlled by diffusion rather than recombination. By ignoring recombination, the diffusion coefficient was estimated from the layer thickness and the vertical gradient in the vertical ion velocity. The results were co

  4. A novel p.E121G heterozygous missense mutation of SOD1 in an apparently sporadic ALS case with a 14-year course.

    Science.gov (United States)

    Canosa, Antonio; Calvo, Andrea; Moglia, Cristina; Barberis, Marco; Brunetti, Maura; Cammarosano, Stefania; Manera, Umberto; Ilardi, Antonio; Restagno, Gabriella; Chiò, Adriano

    2015-03-01

    The frequency of SOD1 mutations differs among populations: in Italy they account for 13.6% of familial ALS and 0.7% of sporadic cases. We describe an apparently sporadic Italian ALS patient, carrying a novel p.E121G heterozygous missense mutation of SOD1, with a 14-year disease course and a prevalent lower motor neuron phenotype, which are not uncommon among SOD1 mutations carriers. To our knowledge, no other mutation of codon 121 of SOD1 has ever been reported. Three in silico models suggest a deleterious effect of the p.E121G mutation. Nevertheless, further studies are necessary to confirm its pathogenic role and to evaluate eventual genotype-phenotype correlations. PMID:25299943

  5. Observation of Electron Biteout Regions Below Twin Sporadic E layers at Arctic Latitude

    Science.gov (United States)

    Lehmacher, G. A.; Larsen, M. F.; Croskey, C. L.

    2013-12-01

    In February 2009, four sounding rockets were launched from Poker Flat, Alaska to study the small scale dynamics of the turbopause region. A 10-km vertical wavelength long-period gravity wave dominantly modulated wind and temperature profiles. Here we focus on the effects of this wave on the electron density structure, specifically, two narrow Es layers near 94 and 102 km observed in situ and by incoherent scatter radar. The layers were visible in several radar beams and the lower one showed clear downward phase progression. They were located about 1 km above the maximum wind shear and at the zero zonal wind crossing. These data will allow the construction and evolution of the layers as modified by the background conditions. Below both layers, the in situ measurements indicated regions of electron biteout or depletion by an order of magnitude. The lower depletions coincide with the local temperature minima. The sodium lidar did not observe sporadic sodium layers during that time, and electron densities were below the threshold of the radar. We discuss the possibilities of neutral metal or dust layers that may have either caused real electron depletions or may have shifted the payload potential so that electron collection was less efficient. Temperature, electron density, and zonal wind speed from two consecutive rocket flights

  6. Late onset sporadic Parkinson's disease caused by PINK1 mutations: clinical and functional study.

    Science.gov (United States)

    Gelmetti, Vania; Ferraris, Alessandro; Brusa, Livia; Romano, Francesca; Lombardi, Federica; Barzaghi, Chiara; Stanzione, Paolo; Garavaglia, Barbara; Dallapiccola, Bruno; Valente, Enza Maria

    2008-04-30

    Homozygous or compound heterozygous mutations in the PINK1 gene represent the second most frequent cause of autosomal recessive parkinsonism after Parkin. The phenotype differs from idiopathic Parkinson's disease for earlier onset, slower disease progression, and better response to therapy. Indeed, the rare patients with onset above 50 years are usually relatives of early-onset probands. Here, we report the first occurrence of compound heterozygous PINK1 mutations in a sporadic patient with a phenotype indistinguishable from idiopathic Parkinson's disease (PD), with onset in the late seventh decade, rapid progression and good response to levodopa that waned with time. Both mutations (p.A244G and p.V317I) were found to abolish the protective effect of wild-type PINK1 against staurosporine-induced apoptosis. These findings further expand the clinical spectrum of PINK1-related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD. PMID:18307263

  7. Current status of molecular markers for early detection of sporadic pancreatic cancer.

    Science.gov (United States)

    Chakraborty, Subhankar; Baine, Michael J; Sasson, Aaron R; Batra, Surinder K

    2011-01-01

    Pancreatic cancer (PC) is a highly lethal malignancy with near 100% mortality. This is in part due to the fact that most patients present with metastatic or locally advanced disease at the time of diagnosis. Significantly, in nearly 95% of PC patients there is neither an associated family history of PC nor of diseases known to be associated with an increased risk of PC. These groups of patients who comprise the bulk of PC cases are termed as "sporadic PC" in contrast to the familial PC cases that comprise only about 5% of all PCs. Given the insidious onset of the malignancy and its extreme resistance to chemo and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of PC, specifically aiming at the sporadic PC cohort. However, while several studies have established that asymptomatic individuals with a positive family history of PC and those with certain heritable syndromes are candidates for PC screening, the role of screening in identifying sporadic PC is still an unsettled question. The present review attempts to assess this critical question by investigating the recent advances made in molecular markers with potential use in the early diagnosis of sporadic PC - the largest cohort of PC cases worldwide. It also outlines a novel yet simple risk factor based stratification system that could be potentially employed by clinicians to identify those individuals who are at an elevated risk for the development of sporadic PC and therefore candidates for screening. PMID:20888394

  8. Genetic and phenotypic heterogeneity in sporadic and familial forms of paroxysmal dyskinesia.

    Science.gov (United States)

    Groffen, Alexander J A; Klapwijk, Thom; van Rootselaar, Anne-Fleur; Groen, Justus L; Tijssen, Marina A J

    2013-01-01

    Paroxysmal dyskinesia (PxD) is a group of movement disorders characterized by recurrent episodes of involuntary movements. Familial paroxysmal kinesigenic dyskinesia (PKD) is caused by PRRT2 mutations, but a distinct etiology has been suggested for sporadic PKD. Here we describe a cohort of patients collected from our movement disorders outpatient clinic in the period 1996-2011. Fifteen patients with sporadic PxD and 23 subjects from three pedigrees with familial PKD were screened for mutations in candidate genes. PRRT2 mutations co-segregated with PKD in two families and occurred in two sporadic cases of PKD. No mutations were detected in patients with non-kinesigenic or exertion-induced dyskinesia, and none in other candidate genes including PNKD1 (MR-1) and SLC2A1 (GLUT1). Thus, PRRT2 mutations also cause sporadic PKD as might be expected given the variable expressivity and reduced penetrance observed in familial PKD. Further genetic heterogeneity is suggested by the absence of candidate gene mutations in both sporadic and familial PKD suggesting a contribution of other genes or non-coding regions. PMID:22752065

  9. Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM).

    Science.gov (United States)

    Muzumdar, Mandar Deepak; Luo, Liqun; Zong, Hui

    2007-03-13

    The initiation and progression of many human cancers involve either somatic activation of protooncogenes or inactivation of tumor-suppressor genes (TSGs) in sporadic cells. Although sporadic gain-of-function of protooncogenes has been successfully modeled in mice [e.g., Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D, Tuveson DA, Jacks T (2001) Nature 410:1111-1116], generating a similar degree of sparseness of TSG loss-of-function remains a challenge. Here, we use mosaic analysis with double markers (MADM) to achieve TSG inactivation and concurrent labeling in sporadic somatic cells of mice, closely mimicking loss of heterozygosity as occurs in human cancers. As proof of principle, we studied the consequence of sporadic loss of p27kip1, a cyclin-dependent kinase inhibitor. MADM-mediated loss of p27kip1 results in mutant cell expansion markedly greater than that observed in conventional p27kip1 knockouts. Moreover, the direct comparison of WT and mutant cells at single-cell resolution afforded by MADM reveals that p27kip1 regulates organ size in vivo by cell-autonomous control of cell cycle exit timing. These studies establish MADM as a high-resolution method for modeling sporadic loss of heterozygosity in mice, providing insights into TSG function. PMID:17360552

  10. Sporadic microsatellite instability-high colon cancers rarely display immunohistochemical evidence of wnt signaling activation.

    Science.gov (United States)

    Panarelli, Nicole C; Vaughn, Cecily P; Samowitz, Wade S; Yantiss, Rhonda K

    2015-03-01

    Most sporadic colonic adenocarcinomas are microsatellite stable (MSS) and arise from conventional adenomas by dysregulation of the APC/?-catenin/Wnt signaling pathway. Sporadic adenocarcinomas with a high degree of microsatellite instability (MSI) likely arise from sessile serrated polyps through the serrated neoplastic pathway. These polyps contain BRAF mutations and are prone to epigenetic methylation that ultimately silences MLH1, leading to MSI and heralding progression of dysplasia to invasive adenocarcinoma. Most investigators believe that these 2 models of cancer progression are mutually exclusive, although recent studies describe Wnt signaling activation in serrated polyps and propose that it plays a role in the development of sporadic colonic adenocarcinomas with MSI. We sought to test this hypothesis by evaluating ?-catenin immunoexpression in 44 sporadic microsatellite unstable adenocarcinomas and 44 MSS colon cancers. We defined sporadic MSI-high carcinomas as those with loss of MLH1 and PMS2 immunostaining and BRAF V600E mutations that occurred in patients 50 years of age or older without a family history of colonic adenocarcinoma or Lynch syndrome. Forty-one (93%) of these carcinomas displayed membranous ?-catenin staining only, compared with 28 (64%) site-matched MSS tumors with abnormal nuclear ?-catenin staining. PMID:25602793

  11. Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer's disease

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

    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

  13. 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.

  14. On the spectrum of mid-latitude sporadic-E irregularities

    Science.gov (United States)

    Kyzyurov, Yu. V.

    2000-10-01

    We discuss the creation of mid-latitude sporadic-E plasma irregularities (with length-scales smaller than sporadic layer thickness) by the neutral atmosphere turbulence. Using fluid equations, the relation between plasma density fluctuations and the velocity field of neutrals is derived. After a brief discussion of the relevant neutral turbulence, the analytical expression for the power spectrum of plasma irregularities is obtained. This expression allows a power-law type of experimental irregularity spectra (the spectral index depends on sporadic-E characteristics) and possible departures in detail of the irregularity spectra from the power-law form to be explained. In addition, it allows us to make estimates of length-scales at which such departures must occur.

  15. Unusual Large Sporadic Angiomyolipoma Co-existing with Huge Simple Renal Cyst

    Directory of Open Access Journals (Sweden)

    Sunil V Jagtap

    2011-07-01

    Full Text Available Renal Angiomyolipoma (AML is an unusual benign mesenchymal tumor with no malignant potential. It is composed of adipose tissue, smooth muscle and abnormal thick walled blood vessels. It can occur sporadically or may be associated with tuberous sclerosis. Sporadic angiomyolipoma (AML coexisting with simple renal cyst is extremely rare and only one case report is available in the literature. In our case, unique combination of sporadic AML along with simple renal cyst with huge size and weight was noted. To the best of our knowledge, ours is the second such case and first case from India. Due to its large size, complete nephrectomy was performed to avoid chances of rupture and retroperitoneal hemorrhage. Post-operative period was uneventful and the patient ahs been on regular follow-up.

  16. Linking ?-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD.

    Science.gov (United States)

    Field, Nicholas C; Metcalf, James S; Caller, Tracie A; Banack, Sandra A; Cox, Paul A; Stommel, Elijah W

    2013-08-01

    Most amyotrophic lateral sclerosis (ALS) cases occur sporadically. Some environmental triggers have been implicated, including beta-methylamino-L-alanine (BMAA), a cyanobacteria produced neurotoxin. This study aimed to identify environmental risk factors common to three sporadic ALS patients who lived in Annapolis, Maryland, USA and developed the disease within a relatively short time and within close proximity to each other. A questionnaire was used to identify potential risk factors for ALS among the cohort of patients. One common factor among the ALS patients was the frequent consumption of blue crab. Samples of blue crab from the patients' local fish market were tested for BMAA using LC-MS/MS. BMAA was identified in these Chesapeake Bay blue crabs. We conclude that the presence of BMAA in the Chesapeake Bay food web and the lifetime consumption of blue crab contaminated with BMAA may be a common risk factor for sporadic ALS in all three patients. PMID:23660330

  17. An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis

    Directory of Open Access Journals (Sweden)

    DarylABosco

    2013-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been linked to the inheritable, or familial, form of ALS, much less is known about the cause(s of sporadic ALS, which accounts for approximately 90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1 protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a “toxic conformation” that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS.

  18. Norovirus genotype diversity in community-based sporadic gastroenteritis incidents: A five-year study.

    Science.gov (United States)

    Bruggink, Leesa D; Dunbar, Natalie L; Marshall, John A

    2015-06-01

    Although norovirus is a known cause of sporadic gastroenteritis, the incidence and genotypes of norovirus associated with sporadic community-based gastroenteritis are poorly understood. The current study examined this issue by using material from alleged food poisoning incidents in the state of Victoria, Australia, for the period 2008-2012. Norovirus was identified, by either ORF (open reading frame) 1 or ORF 2 RT-PCR methodology, in 159 of 379 (42.0%) sporadic gastroenteritis incidents, thereby showing that norovirus was an important cause of sporadic gastroenteritis. The number of sporadic norovirus incidents did not vary significantly from year to year, indicating that the pool of circulating norovirus remained constant. Norovirus ORF 1 genotypes identified included GI.1, GI.2, GI.3, GI.4, GI.b, GI.d, GII.2, GII.4 (including variants 2006a, 2006b, 2007, and 2009), GII.16, GII.22, GII.b, GII.e, and GII.g. Norovirus ORF 2 genotypes identified included GI.1, GI.2, GI.3, GI.4, GI.6, GII.2, GII.3, GII.4 (variants 2006b, 2009, 2009-like, 2012, and "unknown"), GII.6, GII.7, GII.9, GII.12, and GII.13. Five ORF 1/ORF 2 norovirus recombinant forms were confirmed: GII.b/GII.3, GII.e/GII.4 (2012), GII.e/GII.4 (unknown), GII.g/GII.12 and GII.16/GII.2. Although the incidence of ORF 2 GI.3 was significantly higher in children than in adults, this was not the case for other major ORF 2 genotypes (GII.2, GII.4, and GII.6) which occurred equally in all age groups. The findings demonstrate the importance and diverse nature of norovirus in sporadic community-based gastroenteritis incidents and indicate that the development of successful vaccine strategies may be difficult. J. Med. Virol. 87:961-969, 2015. © 2015 Wiley Periodicals, Inc. PMID:25784155

  19. De Novo Truncating FUS Gene Mutation as a Cause of Sporadic Amyotrophic Lateral Sclerosis

    OpenAIRE

    Dejesus-hernandez, Mariely; Kocerha, Jannet; Finch, Nicole; Crook, Richard; Baker, Matt; Desaro, Pamela; Johnston, Amelia; Rutherford, Nicola; Wojtas, Aleksandra; Kennelly, Kathleen; Wszolek, Zbigniew K.; Graff-radford, Neill; Boylan, Kevin; Rademakers, Rosa

    2010-01-01

    Mutations in the gene encoding fused in sarcoma (FUS) were recently identified as a novel cause of amyotrophic lateral sclerosis (ALS), emphasizing the genetic heterogeneity of ALS. We sequenced the genes encoding superoxide dismutase (SOD1), TAR DNA-binding protein 43 (TARDBP) and FUS in 99 sporadic and 17 familial ALS patients ascertained at Mayo Clinic. We identified two novel mutations in FUS in two out of 99 (2.0%) sporadic ALS patients and established the de novo occurrence of one FUS m...

  20. Lidar observations of sporadic Na layers over Gadanki (13.5° N, 79.2° E)

    OpenAIRE

    Vishnu Prasanth, P.; Sridharan, S.; Bhavani Kumar, Y.; Narayana Rao, D.

    2007-01-01

    We studied the characteristics of sporadic sodium layers (SSLs) observed with the sodium (Na) resonance scattering lidar at Gadanki (13.5° N, 79.2° E). The SSLs were observed on a total of 63 occasions during 464 h of Na lidar observations from January 2005 to February 2006. The observations showed that one SSL event occurred, on average, every 7 h. The most prominent sporadic layer, which formed on 12 February 2005, exhibited a peak density of 60 722 Na atoms/cm³ around 92 km and it was n...

  1. Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study

    Directory of Open Access Journals (Sweden)

    Chupin Louis-Dominique

    2008-11-01

    Full Text Available Abstract Background Sporadic colorectal cancers (CRC are multifactorial diseases resulting from the combined effects of numerous genetic, environmental and behavioral risk factors. Genetic association studies have suggested low-penetrance alleles of extremely varied genes to be involved in susceptibility to CRC in Caucasian populations. Methods Through a large genetic association study based on 1023 patients with sporadic CRC and 1121 controls, we tested a panel of these low-penetrance alleles to find out whether they could determine "genotypic profiles" at risk for CRC among individuals of the French population. We examined 52 polymorphisms of 35 genes – drawn from inflammation, xenobiotic detoxification, one-carbon, insulin signaling, and DNA repair pathways – for their possible contribution to colorectal carcinogenesis. The risk of cancer associated with these polymorphisms was assessed by calculation of odds ratios (OR using multivariate analyses and logistic regression. Results Whereas all these polymorphisms had previously been found to be associated with CRC risk, especially in Caucasian populations, we were able to replicate the association for only five of them. Three SNPs were shown to increase CRC risk: PTGS1 c.639C>A (p.Gly213Gly, IL8 c.-352T>A, and MTHFR c.1286A>C (p.Ala429Glu. On the contrary, two other SNPs, PLA2G2A c.435+230C>T and PPARG c.1431C>T (p.His477His, were associated with a decrease in CRC risk. Further analyses highlighted genotypic combinations having a greater predisposing effect on CRC (OR 1.97, 95%CI 1.31–2.97, p = 0.0009 than the allelic variants that were examined separately. Conclusion The identification of CRC-predisposing combinations, composed of alleles PTGS1 c.639A, PLA2G2A c.435+230C, PPARG c.1431C, IL8 c.-352A, and MTHFR c.1286C, highlights the importance of inflammatory processes in susceptibility to sporadic CRC, as well as a possible crosstalk between inflammation and one-carbon pathways.

  2. Midnight variations of spreading of ionospheric sporadic E-layers before earthquakes

    Directory of Open Access Journals (Sweden)

    Dieter H.H. Hoffmann

    2012-04-01

    Full Text Available

    In the present study, ionospheric phenomena caused by earthquakes of magnitudes M >4.0 were investigated. Night-time observations of the spreading of sporadic E-layers (Es-spread performed every 15 min by the Dushanbe and Petropavlovsk-Kamchatsky (middle Asia vertical sounding stations were studied. The mean relative occurrence frequency of Esspread at different values of the blanketing frequency fbEs was considered, and the dependence of Es-spread on the season as well as on the year through an 11-yr solar activity cycle were studied. The fbEs characterizes the maximum plasma density of the Es-layer. The analysis shows that 1- 3 days before seismic shocks in the Earth crust at depths of h <80 km, the occurrence frequency of the Es-spread increases a few hours before midnight. This effect is characteristic of a strengthening of the turbulization of the E-layer plasma. On the basis that the radius of the earthquake preparation region (RD is estimated by the Dobrovolsky formula RD ? exp(M km, it was found that Es-spread is observed more often when the distance between the epicenter and the radar station is not greater than RD + 150 km. In cases of earthquakes at greater distances and depths, no midnight effect was found. The authors act on the assumption that the Es-spread might be caused by acoustic waves with periods of 20 s to 5 min. When such acoustic disturbances propagate from the Earth surface they will have maximum amplitudes if they move nearly vertically to greater altitudes.


  3. Somatic mutations of the PTEN tumor suppressor gene in sporadic follicular thyroid tumors.

    Science.gov (United States)

    Halachmi, N; Halachmi, S; Evron, E; Cairns, P; Okami, K; Saji, M; Westra, W H; Zeiger, M A; Jen, J; Sidransky, D

    1998-11-01

    The PTEN (MMAC1/TEP1) tumor suppressor gene was recently isolated and mapped to human chromosome band 10q23. Homozygous deletions and mutations of PTEN were observed in cell lines and sporadic cancers of the breast, kidney, and central nervous system. Germline mutations in PTEN were recently found in Cowden disease, an autosomal dominant inherited syndrome, previously mapped to chromosome bands 10q22-23. This disease is associated with a wide variety of malignancies and hamartomas of ectodermal, mesodermal, and endodermal origin. The most common neoplasms in Cowden disease patients arise in the breast, skin, and thyroid (follicular subtype). To determine the involvement of PTEN in sporadic follicular thyroid tumors, we first analyzed sporadic follicular adenomas and carcinomas for deletions of the PTEN gene. Loss of heterozygosity was found in 7/26 (27%) follicular carcinomas and 2/27 (7%) follicular adenomas, one of which was a small hemizygous deletion (approximately 3 cm). Sequence analysis of the entire PTEN coding region revealed two mutations in carcinomas with 10q loss. Our findings suggest that the PTEN tumor suppressor gene is occasionally inactivated in sporadic follicular thyroid tumors. PMID:9790504

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

    International Nuclear Information System (INIS)

    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.)

  5. The Study of DNA Methyltransferase-3B Promoter Variant Genotype among Iranian Sporadic Breast Cancer Patients

    OpenAIRE

    Eftekhar, Ebrahim; Rasti, Mozhgan; Nahgibalhossaini, Fakhraddin; Sadeghi, Yasaman

    2014-01-01

    Background: DNA methyltransferase-3B (DNMT3B) is an important enzyme responsible for maintaining the DNA methylation pattern in eukaryotic cells. In this study we have investigated the correlation between the 46359C?T polymorphism in the DNMT3B gene and the risk of breast cancer incidence among sporadic breast cancer patients in Fars Province, Southern Iran.

  6. CT findings of sporadic cherubism in a 6 year old boy

    International Nuclear Information System (INIS)

    Cherubism is a rare hereditary disease that affects the jaws in children. This condition shows distinctive computed tomography (CT) imaging features of multilocular, expansile, cystic lesions limited to the maxilla and mandible bilaterally, which can play a key role in the diagnosis of cherubism. We report here a case of sporadic cherubism with characteristic radiologic findings in a 6-year-old Korean boy.

  7. CT findings of sporadic cherubism in a 6 year old boy

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Beom Seok; Kim, Jinna; Shin, Na Young; KIm, Chang Hoon [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-01-15

    Cherubism is a rare hereditary disease that affects the jaws in children. This condition shows distinctive computed tomography (CT) imaging features of multilocular, expansile, cystic lesions limited to the maxilla and mandible bilaterally, which can play a key role in the diagnosis of cherubism. We report here a case of sporadic cherubism with characteristic radiologic findings in a 6-year-old Korean boy.

  8. The role of the breast cancer susceptibility gene 1 (BRCA1 in sporadic epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Mueller Christopher R

    2003-10-01

    Full Text Available Abstract Mutations within the BRCA1 tumor suppressor gene occur frequently in familial epithelial ovarian carcinomas but they are a rare event in the much more prevalent sporadic form of the disease. However, decreased BRCA1 expression occurs frequently in sporadic tumors, and the magnitude of this decrease has been correlated with increased disease progression. The near absence of somatic mutations consequently suggests that there are alternative mechanisms that may contribute to the observed loss of BRCA1 in sporadic tumors. Indeed, both allelic loss at the BRCA1 locus and epigenetic hypermethylation of the BRCA1 promoter play an important role in BRCA1 down-regulation; yet these mechanisms alone or in combination do not always account for the reduced BRCA1 expression. Alternatively, misregulation of specific upstream factors that control BRCA1 transcription may be a crucial means by which BRCA1 is lost. Therefore, determining how regulators of BRCA1 expression may be co-opted during sporadic ovarian tumorigenesis will lead to a better understanding of ovarian cancer etiology and it may help foster the future development of novel therapeutic strategies aimed at halting ovarian tumor progression.

  9. Germline and somatic SDHx alterations in apparently sporadic differentiated thyroid cancer.

    Science.gov (United States)

    Ni, Ying; Seballos, Spencer; Ganapathi, Shireen; Gurin, Danielle; Fletcher, Benjamin; Ngeow, Joanne; Nagy, Rebecca; Kloos, Richard T; Ringel, Matthew D; LaFramboise, Thomas; Eng, Charis

    2015-04-01

    Along with breast and endometrial cancers, thyroid cancer is a major component cancer in Cowden syndrome (CS). Germline variants in SDHB/C/D (SDHx) genes account for subsets of CS/CS-like cases, conferring a higher risk of breast and thyroid cancers over those with only germline PTEN mutations. To investigate whether SDHx alterations at both germline and somatic levels occur in apparently sporadic breast cancer and differentiated thyroid cancer (DTC), we analyzed SDHx genes in the following four groups: i) 48 individuals with sporadic invasive breast adenocarcinoma for germline mutation; ii) 48 (expanded to 241) DTC for germline mutation; iii) 37 pairs DTC tumor-normal tissues for germline and somatic mutation and mRNA expression levels; and iv) data from 476 patients in the Cancer Genome Atlas thyroid carcinoma dataset for validation. No germline SDHx variant was found in a pilot series of 48 breast cancer cases. As germline SDHx variants were found in our pilot of 48 thyroid cancer cases, we expanded to three series of DTC comprising a total 754 cases, and found 48 (6%) with germline SDHx variants (Pthyroid tumors showed consistent loss of SDHC/D gene expression (P<0.001), which is associated with earlier disease onset and higher pathological-TNM stage. Therefore, we conclude that both germline and somatic SDHx mutations/variants occur in sporadic DTC but are very rare in sporadic breast cancer, and overall loss of SDHx gene expression is a signature of DTC. PMID:25694510

  10. Radio tomographic imaging of sporadic-E layers during SEEK-2

    Directory of Open Access Journals (Sweden)

    S. Fukao

    2005-10-01

    Full Text Available During the SEEK-2 Rocket Campaign in August 2002, a Dual Band Beacon (DBB transmitting to Ground Receivers provided unique data on E-Region electron densities. Information from two rocket beacons and four ground receivers yielded multiple samples of E-region horizontal and vertical variations. The radio beacon measurements were made at four sites (Uchinoura, Tarumizu, Tanegashima, Takazaki in Japan for two rockets (S310-31 and S310-32 launched by the Institute of Space and Aeronautical Science (ISAS. Analysis was completed for four sets of beacon data to provide electron density images of sporadic-E layers. Signals from the two-frequency beacons on the SEEK-2 rockets were processed to yield total electron content (TEC data that was converted into electron density measurements. Wide variations in layer structures were detected. These included horizontal sporadic-E variations, vertical profiles of double, single, and weak layers. The radio beacon measurements were shown to be in agreement with the in-situ SEEK-2 sensors. The first tomographic image of a sporadic-E layer was produced from the data. The rocket beacon technique was shown to be an excellent tool to study sporadic-E layers because absolute TEC accuracy of 0.01 TEC Units can be easily obtained and, with proper receiver placement, electron density images can be produced using computerized ionospheric tomography with better than 1km horizontal and vertical resolution. Keywords. Ionospheric irregularities – Instruments and techniques – Mid-latitude ionosphere

  11. Genetic cross-interaction between APOE and PRNP in sporadic Alzheimer's and Creutzfeldt-Jakob diseases.

    Science.gov (United States)

    Calero, Olga; Bullido, María J; Clarimón, Jordi; Frank-García, Ana; Martínez-Martín, Pablo; Lleó, Alberto; Rey, María Jesús; Rábano, Alberto; Blesa, Rafael; Gómez-Isla, Teresa; Valdivieso, Fernando; de Pedro-Cuesta, Jesús; Ferrer, Isidro; Calero, Miguel

    2011-01-01

    Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) represent two distinct clinical entities belonging to a wider group, generically named as conformational disorders that share common pathophysiologic mechanisms. It is well-established that the APOE ?4 allele and homozygosity at polymorphic codon 129 in the PRNP gene are the major genetic risk factors for AD and human prion diseases, respectively. However, the roles of PRNP in AD, and APOE in CJD are controversial. In this work, we investigated for the first time, APOE and PRNP genotypes simultaneously in 474 AD and 175 sporadic CJD (sCJD) patients compared to a common control population of 335 subjects. Differences in genotype distribution between patients and control subjects were studied by logistic regression analysis using age and gender as covariates. The effect size of risk association and synergy factors were calculated using the logistic odds ratio estimates. Our data confirmed that the presence of APOE ?4 allele is associated with a higher risk of developing AD, while homozygosity at PRNP gene constitutes a risk for sCJD. Opposite, we found no association for PRNP with AD, nor for APOE with sCJD. Interestingly, when AD and sCJD patients were stratified according to their respective main risk genes (APOE for AD, and PRNP for sCJD), we found statistically significant associations for the other gene in those strata at higher previous risk. Synergy factor analysis showed a synergistic age-dependent interaction between APOE and PRNP in both AD (SF?=?3.59, p?=?0.027), and sCJD (SF?=?7.26, p?=?0.005). We propose that this statistical epistasis can partially explain divergent data from different association studies. Moreover, these results suggest that the genetic interaction between APOE and PRNP may have a biological correlate that is indicative of shared neurodegenerative pathways involved in AD and sCJD. PMID:21799773

  12. 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, P<0.001). Using immunohistochemistry, 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 (P<0.0001). One patient had a deleterious MSH2 mutation, and another had a variant of uncertain significance in MSH6. These 2 tumors could be easily distinguished from sporadic tumors using mismatch-repair protein immunohistochemistry. 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. PMID:24625416

  13. 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.

  14. Comparison of sporadic sodium layer characteristics observed at different time resolutions

    Science.gov (United States)

    Liu, Y. J.; Clemesha, B. R.; Wang, J. H.; Cheng, X. W.

    2013-11-01

    Sporadic sodium (Nas) layers, occurring in roughly the same height range as ionospheric sporadic-E layers, were first detected by lidar some 30 yr ago. Nas layers have a typical thickness of a few hundred meters to a few km, with peak atom concentrations several times that of the background layer. Despite a great deal of excellent work over the past decades, the source of Nas layers is still not altogether clear, partly as a result of our incomplete knowledge of Nas layer characteristics. In this paper we concentrate on some typical case studies chosen from the ~127 h of sporadic sodium layer observations made at a time resolution of 1.5 s at Yanqing (115.97° E, 40.47° N), Beijing, China. This is a much better time resolution than what has been employed in most earlier measurements. The results show that the Nas layer peak heights are dispersed at slightly different although adjacent heights. When averaged over several minutes, as has been the case with most earlier measurements, the height scatter results in an apparent layer thickness of a few km. We conclude, therefore, that these dispersed peaks at different but adjacent heights constitute the 5 min Nas layer. Similar to the observations of sporadic-E-ion (Es) layers and meteor rate, we observe quasi-periodic fluctuations on a timescale on the order of several minutes in the peak height and the peak density of sporadic layers, which is a universal feature but concealed by the lower temporal resolution previously adopted. Spatially localized multiple scatterers and multiple thin layers with similar apparent movement in Nas layers are also found. We discuss the possible formation mechanism by the direct deposition of large swarms of micrometeoroids and demonstrate a typical example of meteor trails evolving into a Nas layer, which suggests that this mechanism might indeed occur.

  15. Gene ontology analysis of pairwise genetic associations in two genome-wide studies of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Kim Nora

    2012-07-01

    Full Text Available Abstract Background It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO. Results We first estimated all pairwise additive and nonadditive genetic effects using the multifactor dimensionality reduction (MDR method that makes few assumptions about the underlying genetic model. Statistical significance was evaluated using permutation testing in two genome-wide association studies of ALS. The detection data consisted of 276 subjects with ALS and 271 healthy controls while the replication data consisted of 221 subjects with ALS and 211 healthy controls. Both studies included genotypes from approximately 550,000 single-nucleotide polymorphisms (SNPs. Each SNP was mapped to a gene if it was within 500?kb of the start or end. Each SNP was assigned a p-value based on its strongest joint effect with the other SNPs. We then used the Exploratory Visual Analysis (EVA method and software to assign a p-value to each gene based on the overabundance of significant SNPs at the ??=?0.05 level in the gene. We also used EVA to assign p-values to each GO group based on the overabundance of significant genes at the ??=?0.05 level. A GO category was determined to replicate if that category was significant at the ??=?0.05 level in both studies. We found two GO categories that replicated in both studies. The first, ‘Regulation of Cellular Component Organization and Biogenesis’, a GO Biological Process, had p-values of 0.010 and 0.014 in the detection and replication studies, respectively. The second, ‘Actin Cytoskeleton’, a GO Cellular Component, had p-values of 0.040 and 0.046 in the detection and replication studies, respectively. Conclusions Pathway analysis of pairwise genetic associations in two GWAS of sporadic ALS revealed a set of genes involved in cellular component organization and actin cytoskeleton, more specifically, that were not reported by prior GWAS. However, prior biological studies have implicated actin cytoskeleton in ALS and other motor neuron diseases. This study supports the idea that pathway-level analysis of GWAS data may discover important associations not revealed using conventional one-SNP-at-a-time approaches.

  16. Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Santama Niovi

    2007-01-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal disorder caused by the progressive degeneration of motoneurons in brain and spinal cord. Despite identification of disease-linked mutations, the diversity of processes involved and the ambiguity of their relative importance in ALS pathogenesis still represent a major impediment to disease models as a basis for effective therapies. Moreover, the human motor cortex, although critical to ALS pathology and physiologically altered in most forms of the disease, has not been screened systematically for therapeutic targets. Results By whole-genome expression profiling and stringent significance tests we identify genes and gene groups de-regulated in the motor cortex of patients with sporadic ALS, and interpret the role of individual candidate genes in a framework of differentially expressed pathways. Our findings emphasize the importance of defense responses and cytoskeletal, mitochondrial and proteasomal dysfunction, reflect reduced neuronal maintenance and vesicle trafficking, and implicate impaired ion homeostasis and glycolysis in ALS pathogenesis. Additionally, we compared our dataset with publicly available data for the SALS spinal cord, and show a high correlation of changes linked to the diseased state in the SALS motor cortex. In an analogous comparison with data for the Alzheimer's disease hippocampus we demonstrate a low correlation of global changes and a moderate correlation for changes specifically linked to the SALS diseased state. Conclusion Gene and sample numbers investigated allow pathway- and gene-based analyses by established error-correction methods, drawing a molecular portrait of the ALS motor cortex that faithfully represents many known disease features and uncovers several novel aspects of ALS pathology. Contrary to expectations for a tissue under oxidative stress, nuclear-encoded mitochondrial genes are uniformly down-regulated. Moreover, the down-regulation of mitochondrial and glycolytic genes implies a combined reduction of mitochondrial and cytoplasmic energy supply, with a possible role in the death of ALS motoneurons. Identifying candidate genes exclusively expressed in non-neuronal cells, we also highlight the importance of these cells in disease development in the motor cortex. Notably, some pathways and candidate genes identified by this study are direct or indirect targets of medication already applied to unrelated illnesses and point the way towards the rapid development of effective symptomatic ALS therapies.

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

    International Nuclear Information System (INIS)

    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.)

  18. Gravity wave modulation of gradient drift instabilities in mid-latitude sporadic E irregularities

    International Nuclear Information System (INIS)

    Recent E region VHF backscatter echoes observed by the MU radar at mid-latitudes show quasi-periodic striations with a fairly constant range vs. time tilt in a RTI display. These features are explained in terms of gravity waves with frequencies close to the Brunt-Vaisala frequency which modulate the shape of sporadic E layers. The conditions of instability, when the magnetic field has a significant dip angle, is revised. Differing from previous work, the authors argue that conditions of local gradient drift instability are not sufficient and one has to consider the integrated properties of each magnetic filed tube. Stratified sporadic E layers are stable using this new criteria, unless they are distorted to produce unstable integrated gradients. Gravity waves with phase fronts parallel to the magnetic dip angle are capable of producing such distortion, imposing its own temporal and spatial periodicity on the echoes

  19. 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.

  20. Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.

    Science.gov (United States)

    Sneddon, Sophie; Leon, Justine S; Dick, Ian M; Cadby, Gemma; Olsen, Nola; Brims, Fraser; Allcock, Richard J N; Moses, Eric K; Melton, Phillip E; de Klerk, Nicholas; Musk, A W Bill; Robinson, Bruce W S; Creaney, Jenette

    2015-05-25

    Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM. PMID:25796603

  1. VCP gene analyses in Japanese patients with sporadic amyotrophic lateral sclerosis identify a new mutation.

    Science.gov (United States)

    Hirano, Makito; Nakamura, Yusaku; Saigoh, Kazumasa; Sakamoto, Hikaru; Ueno, Shuichi; Isono, Chiharu; Mitsui, Yoshiyuki; Kusunoki, Susumu

    2015-03-01

    Accumulating evidence has proven that mutations in the VCP gene encoding valosin-containing protein (VCP) cause inclusion body myopathy with Paget disease of the bone and frontotemporal dementia. This gene was later found to be causative for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, occurring typically in elderly persons. We thus sequenced the VCP gene in 75 Japanese patients with sporadic ALS negative for mutations in other genes causative for ALS and found a novel mutation, p.Arg487His, in 1 patient. The newly identified mutant as well as known mutants rendered neuronal cells susceptible to oxidative stress. The presence of the mutation in the Japanese population extends the geographic region for involvement of the VCP gene in sporadic ALS to East Asia. PMID:25457024

  2. A RET mutation with decreased penetrance in the family of a patient with a "sporadic" pheochromocytoma.

    Science.gov (United States)

    Arum, Seth M; Dahia, Patricia L M; Schneider, Katherine; Braverman, Lewis E

    2005-11-01

    We present the case of a 38-yr-old man with a sporadic, multifocal pheochromocytoma and paraganglioma who was discovered to carry a Y791F germline mutation in exon 13 of the RET proto-oncogene. This mutation was found in his 65-yr-old mother and his 86-yr-old maternal grandmother. Neither of them had either biochemical evidence of pheochromocytoma or medullary thyroid carcinoma. The patient had a pro-phylactic thyroidectomy, which revealed mild C-cell hyperplasia. This case brings to discussion several issues: (1) the benefit of screening patients with apparently sporadic pheochromocytomas for genetic mutations; (2) the management of patients and families with "lower-risk" RET mutations; and (3) the possibility that lower-penetrance RET mutations may contribute to the list of causes of familial pheochromocytomas. PMID:16388093

  3. Trends in mortality from sporadic Creutzfeldt-Jakob disease in France 1992-7

    OpenAIRE

    D Aignaux, J.; Laplanche, J.; Delasnerie-laupre, N.; Brandel, J.; Peoc H, K.; Salomon, D.; Hauw, J.; Alperovitch, A.

    2000-01-01

    This study examined trends in mortality from sporadic Creutzfeldt-Jakob disease in France for 1992-7 by age, genotype at the codon 129 of the prion protein gene, and geographical area. Case ascertainment was based on notifications by neurologists, neuropathologists, and laboratories; 324 deaths from definite or probable Creutzfeldt-Jakob disease were registered during the study period. The yearly number of deaths increased significantly between 1992 and 1997. The rise was highe...

  4. Molecular Genetic Analysis of 103 Sporadic Colorectal Tumours in Czech Patients

    OpenAIRE

    Vasovcak, Peter; Pavlikova, Kristyna; Sedlacek, Zdenek; Skapa, Petr; Kouda, Martin; Hoch, Jiri; Krepelova, Anna

    2011-01-01

    The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in Europe. To evaluate whether sporadic CRCs in Czech patients have specific mutational profiles we analysed somatic genetic changes in known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH) at the APC locus, microsatellite instability (MSI), and methylation of the MLH1 promoter) in 103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9% of tumours), follow...

  5. The role of electric field and neutral wind in the generation of polar cap sporadic E

    OpenAIRE

    Nygre?n, T.; Voiculescu, M.; Aikio, A. T.

    2008-01-01

    This paper investigates the roles of electric field and neutral wind in the generation of sporadic-E layers within the polar cap. Two Es layers above Svalbard, observed by the EISCAT Svalbard Radar (ESR), were chosen for investigation. The radar experiment contains four beam directions, and this was used for determining the electric field. The neutral wind was obtained from the HWM93 model. Formation of Es layers was calculated by integrating the continuity equation under the action of drivin...

  6. Multiple filarial species microfilaraemia: a comparative study of areas with endemic and sporadic onchocerciasis

    OpenAIRE

    Ibeh, Emmanuel Uttah Dominic C.

    2011-01-01

    Background & objectives: The study was aimed at determining the pattern of co-occurrence of species ofmicrofilaraemia between onchocerciasis endemic and sporadic populations.Methods: From every consenting person of one year and above, 50 ?l of day and night blood samples werecollected and processed respectively with Haemotoxylin and Giemsa as vital stains. Two skin snips (one eachfrom the waist and the shoulder) were also taken from these individuals and processed.Results: Results showed sin...

  7. Re-Assessment of PrPSc Distribution in Sporadic and Variant CJD

    OpenAIRE

    Rubenstein, Richard; Chang, Binggong

    2013-01-01

    Human prion diseases are fatal neurodegenerative disorders associated with an accumulation of PrPSc 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 b...

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

    OpenAIRE

    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

    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 patho...

  9. Insulin-Resistant Brain State: the culprit in sporadic Alzheimer’s Disease?

    OpenAIRE

    Correia, So?nia 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 su...

  10. Molecular Genetic Studies of Sporadic and MEN1-Associated Endocrine Pancreatic Tumors

    OpenAIRE

    Lindberg, Daniel

    2007-01-01

    Pancreatic endocrine tumors (PETs) may cause typical syndromes of hormone excess, or appear clinically non-functioning without hormonal symptoms. PETs occur sporadically, in association with the multiple endocrine neoplasia type 1 (MEN1) syndrome, or rarely the von Hippel-Lindau syndrome. Molecular genetic investigations may reveal pathways important for tumor development, and be of clinical use. The aim of this thesis was to investigate regulation of different genes involved in cell prolifer...

  11. Maxillary sporadic Burkitt's lymphoma associated with neuro-orbital involvement in an Indian male

    OpenAIRE

    Manne, Rakesh Kumar; Madu, Chandra Sekhar; Talla, Harsh Vardhan

    2014-01-01

    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 non...

  12. Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells

    OpenAIRE

    Israel, Mason A.; Yuan, Shauna H.; Bardy, Cedric; Reyna, Sol M.; Mu, Yangling; Herrera, Cheryl; Hefferan, Michael P.; Gorp, Sebastiaan; Nazor, Kristopher L.; Boscolo, Francesca S.; Carson, Christian T.; Laurent, Louise C.; Marsala, Martin; Gage, Fred H.; Remes, Anne M.

    2012-01-01

    Our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer’s disease, both caused by a duplication of the amyloid-? precursor protein gene...

  13. Risk factors for sporadic Campylobacter infections: results of a case-control study in southeastern Norway.

    OpenAIRE

    Kapperud, G.; Skjerve, E.; Bean, N. H.; Ostroff, S. M.; Lassen, J.

    1992-01-01

    In 1989 and 1990, a case-control study designed to identify risk factors for sporadic infections with thermotolerant Campylobacter bacteria was conducted in three counties in southeastern Norway. The investigation was confined to infections which were acquired in Norway. A total of 52 bacteriologically confirmed cases and 103 controls matched by age, sex, and geographic region were interviewed. The following risk factors were found to be independently associated with illness in conditional lo...

  14. Terdiurnal signatures in sporadic E layers at midlatitudes

    OpenAIRE

    Fytterer, T.; Arras, C.; Jacobi, C.

    2013-01-01

    Global Positioning System radio occultation measurements by the FORMOsa SATellite mission-3/Constellation Observing System for Meteorology, Ionosphere and Climate satellites were used to analyse the behaviour of the signature of the terdiurnal tide in sporadic E (ES) layers at midlatitudes (43–63° N). According to theory, the occurrence of ES is expected when the vertical zonal wind shear, which is mainly owing to solar tides, is negative. 4 yr means, based on 3-monthl...

  15. Four new species of Dolichopoda Bolivar, 1880 from Southern Sporades and Western Turkey (Orthoptera, Rhaphidophoridae, Dolichopodainae)

    OpenAIRE

    Mauro Rampini; Claudio Di Russo; Mehmet Taylan; Arianna Gelosa; Marina Cobolli

    2012-01-01

    A description of four new species of Dolichopoda Bolivar, 1880 (Orthoptera, Rhaphidophoridae) from Eastern Aegean region (Southern Sporades), including Western Turkey, is reported. This brings to a total of 11 the number of Dolichopoda species recorded for caves of the Aegean area. Overall, these species show a high degree of morphological homogeneity and they are very close to Dolichopoda paraskevi Boudou-Saltet, 1973 from Crete and Dolichopoda naxia Boudou-Saltet, 1972 from Cyclades (Naxos ...

  16. Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma

    OpenAIRE

    Kim Vaiphei; Aruna Rangan; Rajinder Singh

    2012-01-01

    AIM: To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS: ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining...

  17. The prereversal enhancement in the vertical drift for Fortaleza and the sporadic E layer

    Science.gov (United States)

    Carrasco, A. J.; Batista, I. S.; Abdu, M. A.

    2005-11-01

    Using ionogram-recorded data for the location of Fortaleza (3.8S, 38.0W; magnetic latitude=-6), the relation between the evening prereversal enhancement in the vertical F region plasma drift (E×B) and the diurnal variation of the sporadic E layer (Es) is examined. The database examined corresponds to the period of June 2001. The F region vertical drifts obtained as dhF/dt for quiet days reveal that when the amplitudes of the evening prereversal enhancement (PRE) are higher, an interruption of an ongoing sporadic E layer is observed. A recent investigation by Abdu et al. [2003. Journal of Geophysical Research 108(A6), 1254. doi: 10.1029/2002JA009285.], showed that an upward electric field, intensified during the PRE, can be responsible for the inhibition of the sporadic E layer. In this work, we investigate the possible influence of a modified conductivity on the PRE development. The model developed by Batista et al. [1986. Journal of Geophysical Research 91(A11), 12055 12064.], based on the work of Heelis et al. [1974. Planetary and Space Science 22, 743 756.], was used to test the response of the PRE (its amplitude, time of occurrence and time of inversion) when the electrical conductivity of the E region is modified, specifically around sunset. The real cause of this modified conductivity is not investigated here, but the presence of a sporadic E layer could partially contribute to that. The causes of the agreement or disagreement between the computed and the observed value of vertical drift are discussed.

  18. Striatal Dopaminergic Functioning in Patients with Sporadic and Hereditary Spastic Paraplegias with Parkinsonism

    OpenAIRE

    Kim, Ji Seon; Kim, Jong Min; Kim, Yu Kyeong; Kim, Sang Eun; Yun, Ji Young; Jeon, Beom S.

    2013-01-01

    Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the cl...

  19. AP5Z1/SPG48 frequency in autosomal recessive and sporadic spastic paraplegia

    OpenAIRE

    Schlipf, Nina A.; Schu?le, Rebecca; Klimpe, Sven; Karle, Kathrin N.; Synofzik, Matthis; Wolf, Julia; Riess, Olaf; Scho?ls, Ludger; Bauer, Peter

    2014-01-01

    Hereditary spastic paraplegias (HSP) constitute a rare and highly heterogeneous group of neurodegenerative disorders, defined clinically by progressive lower limb spasticity and pyramidal weakness. Autosomal recessive HSP as well as sporadic cases present a significant diagnostic challenge. Mutations in AP5Z1, a gene playing a role in intracellular membrane trafficking, have been recently reported to be associated with spastic paraplegia type 48 (SPG48). Our objective was to determine the rel...

  20. Hereditary and Sporadic Forms of A?-Cerebrovascular Amyloidosis and Relevant Transgenic Mouse Models

    OpenAIRE

    Samir Kumar-Singh

    2009-01-01

    Cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-? (A?)-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer’s disease (AD) and Down’s syndrome. Moreover, A?-CAA is also associated with rare hereditary cerebrovascular amyloido...

  1. Novel Cryptosporidium Genotypes in Sporadic Cryptosporidiosis Cases: First Report of Human Infections with a Cervine Genotype

    OpenAIRE

    Ong, Corinne S. L.; Eisler, Diane L.; Alikhani, Alireza; Fung, Vicki W. K.; Tomblin, Joan; Bowie, William R.; Isaac-renton, Judith L.

    2002-01-01

    In this study, we genotyped parasites from the fecal specimens of sporadic cryptosporidiosis cases in British Columbia from 1995 to 1999. Genotyping was conducted by polymerase chain amplification of the internal transcribed spacer region, a hypervariable region in the 18S rRNA gene and the Cryptosporidium oocyst wall protein gene. Subsequent analysis was by restriction fragment length polymorphism and DNA sequencing. We identified two new Cryptosporidium genotypes in humans. One of these gen...

  2. Comparison of clinicopathologic features of young and older patients with sporadic colorectal adenocarcinoma

    OpenAIRE

    Emre Gönüllü; Emel Gönüllü; Ça?r? Tiryaki; Recai Çapo?lu; Murat Burç Yaz?c?o?lu; Mustafa Celalettin Haksal; Ahmet Alponat

    2014-01-01

    Aim. There is still considerable controversy and debate regarding the features of colorectal cancer in young and older patients. In the present study, the influence of age on clinicopathological characteristics of sporadic colorectal cancer is analyzed retrospectively. Method. A total of 170 cases of colectomy for adenocarcinoma in Kocaeli University Medical School, Turkey, Department of Surgery between January 2001 and September 2005 were studied. Results. Of the 170 pati...

  3. Familial genes in sporadic disease: Common variants of ?-Synuclein gene associate with Parkinson’s disease

    OpenAIRE

    Ross, Owen A.; Gosal, David; Stone, Jeremy T.; Lincoln, Sarah J.; Heckman, Michael G.; Irvine, Brent G.; Johnston, Janet A.; Gibson, J. Mark; Farrer, Matthew J.; Lynch, Timothy

    2007-01-01

    Genetic variation of the ?-synuclein gene (SNCA) is known to cause familial parkinsonism, however the role of SNCA variants in sporadic Parkinson’s disease (PD) remains elusive. The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish PD patients. There is evidence for association with alternate regions, of protection and risk which may act independently/synergistically, within the promoter region (Rep1; OR: 0.59, 95% CI: 0.3...

  4. Effects of grassland renovation on carbon concentrations and aggregate distribution in temperate grassland soils

    OpenAIRE

    Linsler, Deborah

    2013-01-01

    The effects of continuous tillage on the distribution of soil organic matter (SOM) and aggregates have been well studied for arable soils. However, less is known about the effects of sporadic tillage on SOM and aggregate dynamics in grassland soils. The objectives of the present thesis were (I) to study the longer-term effects of sporadic tillage of grassland on organic carbon (Corg) stocks and the distribution of aggregates and SOM, (II) to investigate the combined effects of sporadic tillag...

  5. Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

    Science.gov (United States)

    Stefanova, Natalia A.; Muraleva, Natalia A.; Korbolina, Elena E.; Kiseleva, Elena; Maksimova, Kseniya Yi.; Kolosova, Nataliya G.

    2015-01-01

    The amyloid cascade hypothesis posits that deposition of the amyloid ? (A?) peptide in the brain is a key event in the initiation of Alzheimer's disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of A? is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of A?1–42 and extracellular A? deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease. PMID:25595891

  6. Nuclear localization of SMN and FUS is not altered in fibroblasts from patients with sporadic ALS.

    Science.gov (United States)

    Kariya, Shingo; Sampson, Jacinda B; Northrop, Lesley E; Luccarelli, Christopher M; Naini, Ali B; Re, Diane B; Hirano, Michio; Mitsumoto, Hiroshi

    2014-12-01

    Abstract Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no established biological marker. Recent observation of a reduced number of gems (survival motor neuron protein (SMN)-positive nuclear bodies) in cells from patients with familial ALS and the mouse models suggests an involvement of SMN in ALS pathology. At a molecular level, fused in sarcoma (FUS), one of the familial ALS-linked proteins, has been demonstrated to directly interact with SMN, while impaired nuclear localization of mutated FUS causes defective gem formation. Our objective was to determine whether gems and/or nuclear FUS levels in skin derived fibroblasts from sporadic ALS patients are consistently reduced and thus could constitute a novel and readily available biomarker of the disease. Fibroblasts from 20 patients and 17 age-matched healthy controls were cultured and co-immunostained for SMN and FUS. Results showed that no difference was detected between the two groups in the number of gems and in expression pattern of FUS. The number of gems negatively correlated with the age at biopsy in both ALS and control subjects. In conclusion, the expression pattern of SMN and FUS in fibroblasts cannot serve as a biomarker for sporadic ALS. Donor age-dependent gem reduction is a novel observation that links SMN with cellular senescence. PMID:24809826

  7. C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population.

    Science.gov (United States)

    Sabatelli, Mario; Conforti, Francesca Luisa; Zollino, Marcella; Mora, Gabriele; Monsurrò, Maria Rosaria; Volanti, Paolo; Marinou, Kalliopi; Salvi, Fabrizio; Corbo, Massimo; Giannini, Fabio; Battistini, Stefania; Penco, Silvana; Lunetta, Christian; Quattrone, Aldo; Gambardella, Antonio; Logroscino, Giancarlo; Simone, Isabella; Bartolomei, Ilaria; Pisano, Fabrizio; Tedeschi, Gioacchino; Conte, Amelia; Spataro, Rossella; La Bella, Vincenzo; Caponnetto, Claudia; Mancardi, Gianluigi; Mandich, Paola; Sola, Patrizia; Mandrioli, Jessica; Renton, Alan E; Majounie, Elisa; Abramzon, Yevgeniya; Marrosu, Francesco; Marrosu, Maria Giovanna; Murru, Maria Rita; Sotgiu, Maria Alessandra; Pugliatti, Maura; Rodolico, Carmelo; Moglia, Cristina; Calvo, Andrea; Ossola, Irene; Brunetti, Maura; Traynor, Bryan J; Borghero, Giuseppe; Restagno, Gabriella; Chiò, Adriano

    2012-08-01

    It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1523 from mainland Italy. Sixty (3.7%) of 1624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally matched control samples (1238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived 1 year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucleotide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the most common mutation in Italy and the second most common in Sardinia. PMID:22418734

  8. Nuclear localization of SMN and FUS is not altered in fibroblasts from patients with sporadic ALS

    Science.gov (United States)

    Kariya, Shingo; Sampson, Jacinda B.; Northrop, Lesley E.; Luccarelli, Christopher M.; Naini, Ali B.; Re, Diane B.; Hirano, Michio; Mitsumoto, Hiroshi

    2015-01-01

    Background Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no established biological marker. Recent observation of a reduced number of gems (survival motor neuron protein (SMN)-positive nuclear bodies) in cells from patients with familial ALS and the mouse models suggests an involvement of SMN in ALS pathology. At a molecular level, fused in sarcoma (FUS), one of the familial ALS-linked proteins, has been demonstrated to directly interact with SMN, while impaired nuclear localization of mutated FUS causes defective gem formation. Objective To determine whether gems and/or nuclear FUS levels in skin derived-fibroblasts from sporadic ALS patients are consistently reduced and thus could constitute a novel and readily-available biomarker of the disease. Methods Fibroblasts from 20 patients and 17 age-matched healthy controls were cultured and co-immunostained for SMN and FUS. Results No difference was detected between two groups in the number of gems and in expression pattern of FUS. The number of gems negatively correlated with the age at biopsy in both ALS and control subjects. Conclusions The expression pattern of SMN and FUS in fibroblasts cannot serve as a biomarker for sporadic ALS. Donor age-dependent gem reduction is a novel observation that links SMN with cellular senescence. PMID:24809826

  9. Case-control study of presenilin-1 intronic polymorphism in sporadic early and late onset Alzheimer's disease

    OpenAIRE

    Yasuda, M.; Hirono, N.; Maeda, K.; Imamura, T.; Mori, E.; Tanaka, C.

    1999-01-01

    OBJECTIVE—Presenilin-1 is a major causative gene for early onset familial Alzheimer's disease, and the apolipoprotein E ?4 allele is a major genetic risk factor known to influence late onset and sporadic early onset Alzheimer's disease. The presenilin-1 1/1 genotype has recently been reported to be associated with sporadic Alzheimer's disease. The purpose of this study is to determine whether Alzheimer's disease is associated with presenilin-1 gene polymorphism and the...

  10. Sporadic Fundic Gland Polyps with Epithelial Dysplasia : Evidence for Preferential Targeting for Mutations in the Adenomatous Polyposis Coli Gene

    OpenAIRE

    Abraham, Susan C.; Park, Seun Ja; Mugartegui, Lilian; Hamilton, Stanley R.; Wu, Tsung-teh

    2002-01-01

    Gastric fundic gland polyps (FGPs) occur in two distinct clinicopathological scenarios: sporadic and familial adenomatous polyposis (FAP) associated. FAP-associated FGPs arise through somatic second hit alterations of the adenomatous polyposis coli (APC) gene and frequently demonstrate epithelial dysplasia (Am J Pathol 2000, 157:747–754). Sporadic FGPs, in contrast, tend to contain ?-catenin gene mutations and only infrequently show dysplasia (Am J Pathol 2001, 158:1005–1010). However, s...

  11. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome.

    OpenAIRE

    Wilkin, D. J.; Szabo, J. K.; Cameron, R.; Henderson, S.; Bellus, G. A.; Mack, M. L.; Kaitila, I.; Loughlin, J.; Munnich, A.; Sykes, B.; Bonaventure, J.; Francomano, C. A.

    1998-01-01

    More than 97% of achondroplasia cases are caused by one of two mutations (G1138A and G1138C) in the fibroblast growth factor receptor 3 (FGFR3) gene, which results in a specific amino acid substitution, G380R. Sporadic cases of achondroplasia have been associated with advanced paternal age, suggesting that these mutations occur preferentially during spermatogenesis. We have determined the parental origin of the achondroplasia mutation in 40 sporadic cases. Three distinct 1-bp polymorphisms we...

  12. The role of hypermethylation of the hMLH1 promoter region in HNPCC versus MSI+ sporadic colorectal cancers

    OpenAIRE

    Wheeler, J.; Loukola, A.; Aaltonen, L.; Mortensen, N.; Bodmer, W.

    2000-01-01

    INTRODUCTION—Hypermethylation of the promoter region of the hMLH1 gene is associated with absent expression of MLH1 protein in sporadic colorectal cancers with microsatellite instability (MSI+), and it has been proposed that methylation may be a mechanism of inactivation in Knudson's hypothesis. The incidence of hypermethylation of the hMLH1 promoter in hereditary non-polyposis colorectal cancer (HNPCC) versus MSI+ sporadic colorectal cancer was investigated and compared.?METHODS—DNA wa...

  13. Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

    OpenAIRE

    Kirzin, Sylvain; Marisa, Laetitia; Guimbaud, Rosine; Reynies, Aure?lien; Legrain, Miche?le; Laurent-puig, Pierre; Cordelier, Pierre; Prade?re, Bernard; Bonnet, Delphine; Meggetto, Fabienne; Portier, Guillaume; Brousset, Pierre; Selves, Janick

    2014-01-01

    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 ...

  14. Simultaneous and common-volume three-lidar observations of sporadic metal layers in the mesopause region

    Science.gov (United States)

    Yi, Fan; Zhang, Shaodong; Yu, Changming; Zhang, Yunpeng; He, Yujin; Liu, Fuchao; Huang, Kaiming; Huang, Chunming; Tan, Ying

    2013-09-01

    We report on the first simultaneous three-lidar observations of sporadic metal layers in the mesopause region. The case studies indicate that the sporadic layering events can be observed generally in three neutral metal atom species (Na, Fe and Ca) or two neutral atom and one ion species (Na, Fe and Ca+). The density enhancements of all the sporadic metal atom and ion species occurred in overlapping altitude range and moved following almost the same track, indicating that the sporadic metal layers are usually a mixture of multiple metal atom and ion species, meanwhile suggesting that all these metal species in a mixture are product of the same or similar source processes. Some strong multi-metal sporadic layering events were found to manifest a regular altitude relation that the Nas is highest, the Fes is a few to tens of hundreds of meters lower than the Nas, while the Cas is a few hundred meters lower than the Fes, and the Cas+ is lowest. This altitude sequence coincides well with the boiling-point dependent differential ablation in the thermal ablation theory. For those weak multi-metal sporadic events, the altitude relation becomes complicated. Profiles from two short sequences of a single night show that the formation/variation of the Cas+ layer features appeared to follow the related Nas and Fes layer features with a delayed period of ?5 min. At altitudes above 105 km, weak single-species Cas+ layers were occasionally observed. This appears to reflect a feature of the sputtering ablation. For the explanation of our observations the formation mechanism issues of sporadic metal layers are discussed in detail.

  15. Genetic analysis of the ATG7 gene promoter in sporadic Parkinson's disease.

    Science.gov (United States)

    Chen, Dongfeng; Pang, Shuchao; Feng, Xungang; Huang, Wenhui; Hawley, Robert G; Yan, Bo

    2013-02-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease. The majority of PD cases are sporadic, for which genetic causes and underlying molecular mechanisms remain largely unclear. Autophagy, a highly conserved cellular process that governs the breakdown of long-lived proteins and organelles, has been involved in the degradation of ?-synuclein (?-Syn), the main component of Lewy bodies. Accumulating evidence implicates deregulation of autophagy in the development and progression of sporadic PD. Altered autophagic gene expression has been observed in the brain tissues from PD patients and animal models. We hypothesized that changes in expression levels of autophagy-related genes (ATGs), rather than mutations associated with amino acid changes, may contribute to PD onset. In this study, the ATG7 gene promoter was sequenced bi-directionally in groups of sporadic PD patients and ethnic-matched healthy controls. As predicted, four novel heterozygous variants, 11313449G>A, 11313811T>C, 11313913G>A and 11314041G>A, were identified in five PD patients, but in none of the controls, which significantly decreased transcriptional activities of the ATG7 gene promoter. Two novel heterozygous variants, 11312947G>A and 11313006C>G, were only found in controls, which did not affect transcriptional activities of the ATG7 gene promoter. The other five novel variants were found in PD patients and controls with similar frequencies. Taken together, the sequence variants within the ATG7 gene promoter identified in PD patients may change ATG7 protein levels, which in turn would influence autophagic activity, contributing to PD onset as a risk factor. PMID:23295909

  16. TP53 Codon 72 Heterozygosity May Promote MicrosatelliteInstability in Sporadic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Mehdi Nikbahkt Dastjerdi

    2010-01-01

    Full Text Available Objective: The polymorphic variants at codon 72 of the p53 gene, encoding prolineor arginine at residue 72, produce marked changes in the p53 structure. From theevidence that the DNA mismatch repair system and p53 interact to maintain genomicintegrity, we hypothesized that codon 72 variations may influence the prevalence ofmicrosatellite instability (MSI, a feature of malignancies associated with mismatchrepair deficiency in sporadic colorectal cancer.Materials and Methods: We investigated the frequency of MSI in three P53 codon72 genotypes using genomic DNAs from 144 paraffin blocks of sporadic colorectaladenocarcinomas by testing the BAT-26 poly(A marker. We used PCR-SSCP analysisto detect tumor sample MSI for the nonisotopic detection of deletions in the BAT-26 poly (A mononucleotide repeat. Associations between qualitative variables wereevaluated using the ?2-test. Statistical significance level was set to p ? 0.05.Results: MSI analysis revealed that 24.3% of the tumors (n=35 were MSI-positiveand 75.7% (n=109 were MSI-negative. The frequency of microsatellite instability inthe arginine/arginine, arginine/proline and proline/proline genotypes were 11 (16.9%,22 (36.1% and 2 (11.1% respectively. A significant difference in distribution of MSIwas found for the arginine/proline genotype compared with the grouped arginine/arginineand proline/proline genotypes (p=0.05.Conclusion: Our findings suggested that colorectal adenocarcinomas arising in individualswith the p53 codon 72 arginine/proline heterozygosity are more prone tomicrosatellite instability than those with other p53 genotypes. In our study, MSI wasimportant in the carcinogenesis of sporadic colorectal cancer arising in pro/arg heterozygotes.

  17. Sporadic E tidal variabilities and characteristics observed with the Cyprus Digisonde

    Science.gov (United States)

    Oikonomou, Christina; Haralambous, Haris; Haldoupis, Christos; Meek, Chris

    2014-11-01

    In this study, ionogram observations made with the Cyprus digisonde (35°N; 33°E) are analyzed by applying an ionosonde height-time-intensity (HTI) methodology. The aim is to study dominant periodicities and diurnal patterns in occurrence and altitude transport of sporadic E (Es) and intermediate descending layers (IDL), which are impacted upon by solar thermospheric tides via the windshear layer formation mechanism in the E and lower F region ionosphere. The results show the diurnal occurrence and altitude descent of sporadic E to be dominated by a semidiurnal tide-like periodicity, which prevails, with some differences, in all seasons. It is characterized by a daytime layer starting near sunrise at ~125 km, followed by a nighttime layer appearing first in late afternoon at ~130 km; both layers descend in altitude with speeds between about 2 and 3 km/h, therefore reaching the 100 km level in ~10-12 h. Also, a terdiurnal tide-like periodicity is present in daily Es occurrence and altitude descent but only in summer solstice. In addition, the data show fast-descending layers to originate at F region altitudes near sunrise and sunset, which are subject to a semidiurnal periodicity. Although these layers are rarely seen by the digisonde below about 180 km for most times and never during the night, the data hint that they connect with sporadic E layers below, therefore, both IDLs and Es form an integral tidal ion layer system in the lower ionosphere. An exceptional result is the detection during daytime of strong intermediate descending layers in March equinox, starting at F region and descending downwards with speeds of ~10 km/h. Although an effort is made to interpret this equinoctial IDL signature, more work is needed for its understanding.

  18. Analysis of wave-like oscillations in parameters of sporadic E layer and neutral atmosphere.

    Czech Academy of Sciences Publication Activity Database

    Mošna, Zbyšek; Koucká Knížová, Petra

    90-91, SI (2012), s. 172-178. ISSN 1364-6826. [IAGA/ICMA/CAWSES-II TG4 Workshop on Vertical Coupling in the Atmosphere-Ionosphere System /4./. Prague, 14.02.2011-18.02.2011] R&D Projects: GA AV ?R IAA300420704 Institutional support: RVO:68378289 Keywords : Sporadic E * Planetary waves * Tidal waves * Mid-latitude ionosphere Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.417, year: 2012 http://www.sciencedirect.com/science/article/pii/S1364682612001186

  19. Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hirohide; Snow, B.J.; Bhatt, M.H.; Peppard, R.; Eisen, A.; Calne, D.B. (Univ. of British Columbia, Vancouver (Canada))

    1993-10-23

    Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology.

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

    OpenAIRE

    Bratosiewicz-wa?sik, Jolanta; Smolen?-dzirba, Joanna; Rozemuller, Annemieke J.; Jansen, Casper; Spliet, Wim; Jansen, Gerard H.; Wa?sik, Tomasz J.; Liberski, Pawe? 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 ...

  1. Sporadic Creutzfeldt-Jakob Disease Presenting with Visual Disturbance—A Case Report in China

    Directory of Open Access Journals (Sweden)

    Guohong Tian

    2013-07-01

    Full Text Available Creutzfeldt-Jakob disease (CJD is a rare but fatal neurodegenerative prion disease. Classic CJD comprises a clinical triad of rapidly progressive dementia, myoclonus, and EEG abnormality. At initial presentation, this classic triad is present only in a minority of cases. Visual impairment is one of the predominant manifestations in the course of CJD, especially in Heidenhain variant phenotype. We reported a case presenting with progressive blurred vision, along with other neurological symptoms, who diagnosed as sporadic CJD with cortical blindness in China.

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

    OpenAIRE

    Armstrong, R. A.

    2010-01-01

    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...

  3. Analysis of Prion Strains by PrPSc Profiling in Sporadic Creutzfeldt–Jakob Disease

    OpenAIRE

    Schoch, G.; Seeger, H.; Bogousslavsky, J.; Tolnay, M.; Janzer, R. C.; Aguzzi, A.; Glatzel, M.

    2005-01-01

    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 (sC...

  4. Acute Relapsing Pancreatitis with Pseudocyst Formation due to Sporadic Hypertriglyceridemic Pancreatitis: A Case Report

    OpenAIRE

    Monib, Sherif M.; El-barbary, Hany M.

    2012-01-01

    Acute pancreatitis is one of the common causes of the acute abdomen that should be included in any differential diagnosis for acute abdominal pain; it is also well known with its variant causes, of which most common is biliary tree stones, alcoholic pancreatitis, followed by a long list of other less common causes. We have reported a rare case of relapsing acute pancreatitis due to atypical sporadic hypertriglyceridemia (Frederickson’s type IV) in a young male patient who was seen in the ac...

  5. A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features

    Directory of Open Access Journals (Sweden)

    Fernandez Bridget A

    2012-08-01

    Full Text Available Abstract Background Idiopathic pulmonary fibrosis (IPF is an adult-onset Idiopathic Interstitial Pneumonia (IIP usually diagnosed between age 50 to 70?years. Individuals with Familial Pulmonary Fibrosis (FPF have at least one affected first or second-degree relative and account for 0.5-20% of cases. Methods We ascertained and collected DNA samples from a large population-based cohort of IPF patients from Newfoundland, Canada. For each proband, a family history was documented and medical records were reviewed. Each proband was classified as familial (28 patients or sporadic (50 patients and all 78 probands were screened for variants in four highly penetrant, adult-onset PF genes (SFTPC, SFTPA2, TERT,TERC. Results Seventy-eight IPF probands were enrolled of whom 28 (35.9% had a positive family history. These 28 familial patients led to the recruitment of an additional 49 affected relatives (total of 77 FPF patients. By age 60?years, 42% of the familial cohort had been diagnosed with PF compared with only 16% of the sporadic patient collection (?2?=?8.77, p?=?0.003. Mean age of diagnosis in the familial group was significantly younger than the sporadic group (61.4?years vs. 66.6?yrs, p?=?0.012 with a wider age range of diagnosis (19–92?years compared with 47–82?years. Thirty-three of 77 (42.8% FPF patients had a tissue diagnosis and all but five had usual interstitial pneumonia histology. Compared with other published case series, the familial IIP histologies were more homogeneous. Three of 28 familial probands (10.7% and none of the 50 sporadic probands had pathogenic variants in the four genes tested. All three familial probands had mutations in TERT. Other phenotypes associated with telomerase deficiency were present in these families including cirrhosis, bone marrow hypoplasia and premature graying. Telomere length assays were performed on mutation carriers from two families and confirmed telomere-related deficiency. Conclusion The proportion of familial cases in our cohort is higher than any previously reported estimate and we suggest that this is due to the fact that Newfoundland cohort is ethnically homogeneous and drawn from a founder population. In our patient collection, diagnosis with IPF prior to age 45?years predicted familial disease. In two of the three TERT mutation families, the pedigree appearance is consistent with genetic anticipation. In the other 25 FPF families negative for mutations in known PF genes, we did not identify other telomerase associated medical problems (bone marrow dysfunction, cirrhosis and we hypothesize that there are novel PF genes segregating in our population.

  6. Current Status of Molecular Markers for Early Detection of Sporadic Pancreatic Cancer

    OpenAIRE

    Chakraborty, Subhankar; Baine, Michael J.; Sasson, Aaron R.; Batra, Surinder K.

    2010-01-01

    Pancreatic cancer (PC) is a highly lethal malignancy with near 100% mortality. This is in part due to the fact that most patients present with metastatic or locally advanced disease at the time of diagnosis. Significantly, in nearly 95% of PC patients there is neither an associated family history of PC nor of diseases known to be associated with an increased risk of PC. These groups of patients who comprise the bulk of PC cases are termed as “sporadic PC” in contrast to the familial PC ca...

  7. BP1, an Isoform of DLX4 Homeoprotein, Negatively Regulates BRCA1 in Sporadic Breast Cancer

    OpenAIRE

    Brian J Kluk, Yebo Fu

    2010-01-01

    Introduction: Several lines of evidence point to an important role for BP1, an isoform of DLX4 homeobox gene, in breast carcinogenesis and progression. BRCA1 is a well-known player in the etiology of breast cancer. While familial breast cancer is often marked by BRCA1 mutation and subsequent loss of heterozygosity, sporadic breast cancers exhibit reduced expression of wild type BRCA1, and loss of BRCA1 expression may result in tumor development and progression.Methods: The Cister algorithm an...

  8. Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning

    International Nuclear Information System (INIS)

    Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology

  9. Psychiatric presentation of sporadic Creutzfeldt-Jakob disease: a challenge to current diagnostic criteria.

    Science.gov (United States)

    Ali, Rehiana; Baborie, Atik; Larner, Andrew J; White, Richard

    2013-01-01

    Pathological diagnosis remains the gold standard for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), but being able to differentiate between CJD and non-prion diseases clinically is important because many of the non-prion, rapidly progressive dementias are treatable. Diagnostic criteria need both high sensitivity and specificity while remaining applicable to clinical practice. Despite extensive updates to the clinical criteria for sCJD, there remains a heavy emphasis on neurological signs. We describe a psychiatric presentation of sCJD that did not fulfill the diagnostic criteria until very late in a prolonged disease course and required biopsy for diagnosis. PMID:24247860

  10. Glycoform-selective prion formation in sporadic and familial forms of prion disease

    OpenAIRE

    Xiao, X.; Yuan, J.; Hai?k, 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 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 ...

  11. Variable Somatic TIE2 Mutations in Half of Sporadic Venous Malformations

    OpenAIRE

    Soblet, J.; Limaye, N.; Uebelhoer, M.; Boon, L. M.; Vikkula, M.

    2013-01-01

    Venous malformations (VMs) are the most frequent vascular malformations referred to specialized vascular anomaly centers. A rare (1-2%) familial form, termed cutaneomucosal venous malformation (VMCM), is caused by gain-of-function mutations in TIE2. More recently, sporadic VMs, characterized by the presence of large unifocal lesions, were shown to be caused by somatic mutations in TIE2. These include a frequent L914F change, and a series of double mutations in cis. All of which cause ligand-i...

  12. Sporadic ALS is not associated with VAPB gene mutations in Southern Italy

    OpenAIRE

    Conforti, Francesca Luisa; Sprovieri, Teresa; Mazzei, Rosalucia; Ungaro, Carmine; Tessitore, Alessandro; Tedeschi, Gioacchino; Patitucci, Alessandra; Magariello, Angela; Gabriele, Annalia; Labella, Vincenzo; Simone, Isabella Laura; Majorana, Giovanni; Monsurro?, Maria Rosaria; Valentino, Paola; Muglia, Maria

    2006-01-01

    Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred t...

  13. The inhomogeneous structure of the midlatitude sporadic E-layer traces

    Science.gov (United States)

    Akchurin, Adel; Yusupov, Kamil

    Investigation of the inhomogeneities structure produced in the ionospheric E layer, and their relationship with the rest of the ionosphere have a long history. The main long source of information about irregularities in the E layer is vertical sounding (VS), where the main inhomogeneities seen as sporadic E layer or Es. The main feature of the Es-layer is the semitransparent at VS. To explain the transparence use three main models that are closely related to the inhomogeneities structural characteristics. This is cloud (large-scale inhomogeneities), blob or scattering (array of small-scale inhomogeneities) models and model of a thin layer with significant gradients of the electron density at the boundaries. If the semitransparency of the first two models based on the "gap" between the inhomogeneities, the third based on the effects of tunneling through a thin layer and appearance of transparent windows (with half the electron gyrofrequency size) in the presence of the characteristic modes intermode coupling of propagation in ionospheric magnetized plasma. Based on these models and frequent sounding with the high height resolution will be analyzed the contribution of each model in the reflected signal for about a two-year series. Focus will be on the model of a thin layer in the presence of the intermode coupling. According to the theory, intermode coupling is possible with longitudinal propagation in the polar regions, with high frequency of electron collisions, and the electron density steep gradient. Attempts to detect this coupling in conditions close to the longitudinal propagation were not very successful. Namely, it has not yet succeeded in the polar regions (as in [Jalonen, 1981]) to find beatings by type of coupling between two ordinary modes (o-z-o and o) as an interference pattern with a decreasing step between minima with increasing frequency, except individual cases. At middle latitudes this effect is weaker and may have a slightly different form, e.g., as a dip on AFC of Es-trace in the frequency range 3.5-4 MHz. We succeeded to detect such dips, which in contrast to the mode coupling in the polar regions have, at best, two interference maxima/peaks. We associate them with the appearance of the two modes interference o and o-z-o. The latter is the result of the mode coupling, and so when the steep gradient of the thin Es-layer certain the threshold value, the full interference pattern is present not on all traces. Therefore, this phenomenon may be a reliable indicator of the gradient value. Previously, we have established the characteristic frequency properties of interference o-x-modes (interference signature). Now we describe the characteristic frequency properties of the interference o- and o-z-o modes at Es-traces. This work was supported by RFBR grant 13-05-00967 A

  14. 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

    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 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 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 with 56% in sporadic CC (p

  15. 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.

  16. Amyloid deposits and inflammatory infiltrates in sporadic inclusion body myositis: the inflammatory egg comes before the degenerative chicken.

    Science.gov (United States)

    Benveniste, Olivier; Stenzel, Werner; Hilton-Jones, David; Sandri, Marco; Boyer, Olivier; van Engelen, Baziel G M

    2015-05-01

    Sporadic inclusion body myositis (sIBM) is the most frequently acquired myopathy in patients over 50 years of age. It is imperative that neurologists and rheumatologists recognize this disorder which may, through clinical and pathological similarities, mimic other myopathies, especially polymyositis. Whereas polymyositis responds to immunosuppressant drug therapy, sIBM responds poorly, if at all. Controversy reigns as to whether sIBM is primarily an inflammatory or a degenerative myopathy, the distinction being vitally important in terms of directing research for effective specific therapies. We review here the pros and the cons for the respective hypotheses. A possible scenario, which our experience leads us to favour, is that sIBM may start with inflammation within muscle. The rush of leukocytes attracted by chemokines and cytokines may induce fibre injury and HLA-I overexpression. If the protein degradation systems are overloaded (possibly due to genetic predisposition, particular HLA-I subtypes or ageing), amyloid and other protein deposits may appear within muscle fibres, reinforcing the myopathic process in a vicious circle. PMID:25579751

  17. Enhancement and HF Doppler observations of sporadic-E during the solar eclipse of 22 July 2009

    Science.gov (United States)

    Chen, Gang; Zhao, Zhengyu; Yang, Guobin; Zhou, Chen; Yao, Ming; Li, Ting; Huang, Shou; Li, Ning

    2010-09-01

    The sporadic E (Es) frequently emerging in midlatitude during summer is a very special layer in the ionosphere, and its formation mechanism is different to from that of other layers. The total solar eclipse of 22 July 2009 provided a very unique opportunity to study the relationship of Es and solar radiation. During the solar eclipse day and the days before and after, the vertical incidence ionosonde was located in Wuhan to record the ionograms for this event. Two oblique incidence high-frequency radio systems were used to record the waves from Wuhan to Suzhou and from Wuhan to Huaian. The enhancement of Es during the eclipse period was observed in the vertical and oblique incidence ionograms. The quasi-periodic fluctuations in the critical frequency and Doppler frequency shift curves indicated the possible existence of the gravity waves, which may be responsible for the Es enhancement. However, we find that the enhancement occurred earlier than the appearance of gravity waves and consider that there may be other mechanisms which contribute to the observed enhancement in the ionosphere. A hypothesis is put forward that the cooling effect of the lunar shadow induced powerful airflow from the northern and southern limits of the shadow toward its center, which accelerated the irregularities in Es to produce the large-scale Doppler shift in the reflected waves and form the meridional windshear. Both the windshear and the gravity waves may affect the Es layer and increase the electron concentration. Many observed phenomena are in accordance with this.

  18. CHANGES IN THE MOUSE ESTRUS CYCLE IN RESPONSE TO Brca1 INACTIVATION SUGGEST A POTENTIAL LINK BETWEEN RISK FACTORS FOR FAMILIAL AND SPORADIC OVARIAN CANCER

    OpenAIRE

    Hong, Hao; Yen, Hai-yun; Brockmeyer, Amy; Liu, Ying; Chodankar, Rajas; Pike, Malcolm C.; Stanczyk, Frank Z.; Maxson, Robert; Dubeau, Louis

    2009-01-01

    Menstrual cycle activity is the most important risk factor for sporadic serous ovarian carcinoma while a germline mutation in BRCA1 is the most important risk factor for the familial form. Given the rarity of BRCA1 mutations in sporadic ovarian cancers, we hypothesized that BRCA1 influences the menstrual cycle in a way that mimics the factors underlying sporadic ovarian cancer predisposition, making BRCA1 mutations redundant in such cancers. We compared the length of each phase of the estrus ...

  19. Comparison of Observations of Sporadic-E Layers in the Nighttime and Daytime Mid-Latitude Ionosphere

    Science.gov (United States)

    Pfaff, R.; Freudenreich, H.; Rowland, D.; Klenzing, J.; Clemmons, J.; Larsen, M.; Kudeki, E.; Franke, S.; Urbina, J.; Bullett, T.

    2012-01-01

    A comparison of numerous rocket experiments to investigate mid-latitude sporadic-E layers is presented. Electric field and plasma density data gathered on sounding rockets launched in the presence of sporadic-E layers and QP radar echoes reveal a complex electrodynamics including both DC parameters and plasma waves detected over a large range of scales. We show both DC and wave electric fields and discuss their relationship to intense sporadic-E layers in both nighttime and daytime conditions. Where available, neutral wind observations provide the complete electrodynamic picture revealing an essential source of free energy that both sets up the layers and drives them unstable. Electric field data from the nighttime experiments reveal the presence of km-scale waves as well as well-defined packets of broadband (10's of meters to meters) irregularities. What is surprising is that in both the nighttime and daytime experiments, neither the large scale nor short scale waves appear to be distinctly organized by the sporadic-E density layer itself. The observations are discussed in the context of current theories regarding sporadic-E layer generation and quasi-periodic echoes.

  20. Is PFAPA syndrome really a sporadic disorder or is it genetic?

    Science.gov (United States)

    Akelma, Ahmet Zulfikar; Cizmeci, Mehmet Nevzat; Kanburoglu, Mehmet Kenan; Mete, Emin; Bozkaya, Davut; Tufan, Naile; Catal, Ferhat

    2013-08-01

    Periodic fever syndromes are a group of disorders sharing similar symptoms, characterized primarily by regularly recurring fevers. PFAPA syndrome, one of the members of this group of disorders, is a clinical entity of unknown etiology which is frequently seen in the early childhood. Currently, the pathogenesis and the genetic basis of most of the disorders in the periodic fever spectrum are known, other than that of PFAPA syndrome. Although, classically PFAPA syndrome is known as a sporadic disease, we propose that it is not sporadic. We think that PFAPA syndrome may be an inherited disease and this hypothesis is supported by the clinical mimicry of PFAPA syndrome with other periodic fever syndromes with well-known genetic transmissions, frequent occurrence of the condition in members of the same family and emergence of common genetic mutations in the periodic fever syndrome spectrum. Moreover, our clinical observation that most of the patients diagnosed with PFAPA syndrome were of the same families strongly suggest a probable genetic transmission of this disorder. We have decided to discuss this hypothesis to contribute to the literature and assist our colleagues who are dealing with this commonly overlooked and often misdiagnosed disorder. PMID:23660131

  1. AP5Z1/SPG48 frequency in autosomal recessive and sporadic spastic paraplegia.

    Science.gov (United States)

    Schlipf, Nina A; Schüle, Rebecca; Klimpe, Sven; Karle, Kathrin N; Synofzik, Matthis; Wolf, Julia; Riess, Olaf; Schöls, Ludger; Bauer, Peter

    2014-09-01

    Hereditary spastic paraplegias (HSP) constitute a rare and highly heterogeneous group of neurodegenerative disorders, defined clinically by progressive lower limb spasticity and pyramidal weakness. Autosomal recessive HSP as well as sporadic cases present a significant diagnostic challenge. Mutations in AP5Z1, a gene playing a role in intracellular membrane trafficking, have been recently reported to be associated with spastic paraplegia type 48 (SPG48). Our objective was to determine the relative frequency and clinical relevance of AP5Z1 mutations in a large cohort of 127 HSP patients. We applied a targeted next-generation sequencing approach to analyze all coding exons of the AP5Z1 gene. With the output of high-quality reads and a mean coverage of 51-fold, we demonstrated a robust detection of variants. One 43-year-old female with sporadic complicated paraplegia showed two heterozygous nonsynonymous variants of unknown significance (VUS3; p.[R292W];[(T756I)]). Thus, AP5Z1 gene mutations are rare, at least in Europeans. Due to its low frequency, systematic genetic testing for AP5Z1 mutations is not recommended until larger studies are performed to add further evidence. Our findings demonstrate that amplicon-based deep sequencing is technically feasible and allows a compact molecular characterization of multiple HSP patients with high accuracy. PMID:25333062

  2. 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

    Salmonella spp. and Campylobacter spp. are widespread and important causes of human illness worldwide. Disease is most frequently associated with foodborne transmission, but other routes of exposure, such as direct contact with live animals and person-to-person transmission, are recognized. 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 risk factors for disease, and often use different methodologies and settings. Systematic reviews (SR) consist of a formal process for literature review focused on a specific research question, and include the identification of relevant literature, quality assessment of relevant studies, summarization 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 of cases and controls, and estimated odds ratios for investigated risk factors were recovered and analyzed with the purpose of assisting attribution of human disease. The most significant results were illustrated using forest plots.

  3. Temporal evolution of the HF-enhanced plasma line in sporadic E

    International Nuclear Information System (INIS)

    The high-power, high-frequency (HF) facility at Arecibo, Puerto Rico, has been used to study the excitation of Langmuir waves in mid-latitude sporadic E. Measurements of the temporal evolution of so-called HF-enhanced plasma line (HFPL) were made using the Arecibo 430-MHz radar. After HF turn-on in the plasma the HFPL exhibits a rapid growth phase followed by a quick overshoot. During periods of strong HFPL excitation the e-folding growth time of the HFPL power is typically approx-lt 20 ?s, and the total overshoot period is ?1 ms. On the basis of the current observations, mode conversion of the HF wave into Langmuir waves near HF reflection appears to be a promising mechanism for the production of Langmuir waves in sporadic E. Caviton formation at the critical layer is expected to accompany this process, and there is some evidence that the 430-MHz radar is probing the plasma in a region where density cavities of this nature form. While no specific explanation is offered for the HFPL overshoot, it appears that this phenomenon is fundamental to the Langmuir wave excitation process

  4. Nuclear expression of ?-catenin predicts the efficacy of meloxicam treatment for patients with sporadic desmoid tumors.

    Science.gov (United States)

    Hamada, Shunsuke; Urakawa, Hiroshi; Kozawa, Eiji; Futamura, Naohisa; Ikuta, Kunihiro; Shimoyama, Yoshie; Nakamura, Shigeo; Ishiguro, Naoki; Nishida, Yoshihiro

    2014-05-01

    This study aimed to determine the prevalence of ?-catenin nuclear positivity as a prognostic factor in patients with desmoid tumors (DTs) treated with meloxicam, a cyclooxygenase-2 (COX-2) selective inhibitor. Between 2003 and 2012, consecutive 31 patients with extraabdominal, sporadic DTs were prospectively treated with meloxicam as a systemic medical therapy. Immunohistochemistry was performed on formalin-fixed material to quantify the nuclear expression of ?-catenin and Ki-67, and cytoplasmic expression of COX-2. All clinicopathological characteristics including the intensity of immunohistochemical staining were analyzed with respect to their prognostic value for meloxicam treatment. Of the 31 patients with meloxicam treatment, there was 1 with complete remission (CR), 7 with partial remission (PR), 12 with stable disease (SD), and 11 with progressive disease (PD). Higher nuclear expression of ?-catenin was significantly associated with a poor response (PD/SD) (p?=?0.017). The positivity of COX-2 and Ki-67 and none of the other clinical variables were associated with prognosis. The nuclear expression of ?-catenin can predict the efficacy of meloxicam treatment for patients with sporadic DTs. PMID:24390670

  5. Observations of neutral winds, wind shears, and wave structure during a sporadic-E/QP event

    Directory of Open Access Journals (Sweden)

    R. T. Tsunoda

    2005-10-01

    Full Text Available The second Sporadic E Experiment over Kyushu (SEEK-2 was carried out on 3 August 2002, during an active sporadic-E event that also showed quasi-periodic (QP echoes. Two rockets were launched into the event from Kagoshima Space Center in southern Japan 15 min apart. Both carried a suite of instruments, but the second rocket also released a trimethyl aluminum (TMA trail to measure the neutral winds and turbulence structure. In a number of earlier measurements in similar conditions, large winds and shears that were either unstable or close to instability were observed in the altitude range where the ionization layer occurred. The SEEK-2 wind measurements showed similar vertical structure, but unlike earlier experiments, there was a significant difference between the up-leg and down-leg wind profiles. In addition, wave or billow-like fluctuations were evident in the up-leg portion of the trail, while the lower portion of the down-leg trail was found to have extremely strong turbulence that led to a rapid break-up of the trail. The large east-west gradient in the winds and the strong turbulence have not been observed before. The wind profiles and shears, as well as the qualitative characteristics of the strong turbulence are presented, along with a discussion of the implications of the dynamical features. Keywords. Ionosphere (Mid-latitude ionosphere; Ionospheric irregularities; Electric field and currents

  6. Hereditary and Sporadic Forms of A?-Cerebrovascular Amyloidosis and Relevant Transgenic Mouse Models

    Directory of Open Access Journals (Sweden)

    Samir Kumar-Singh

    2009-04-01

    Full Text Available Cerebral amyloid angiopathy (CAA refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-? (A?-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer’s disease (AD and Down’s syndrome. Moreover, A?-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the A? domain of the amyloid precursor protein (APP such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic A? variants or an unaltered A?42/A?40 ratio favor vascular A? deposition over parenchymal plaques, but higher than critical levels of A?40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels.

  7. Necroptosis drives motor neuron death in models of both sporadic and familial ALS

    Science.gov (United States)

    Re, Diane B.; Verche, Virginia Le; Yu, Changhao; Amoroso, Mackenzie W.; Politi, Kristin A.; Phani, Sudarshan; Ikiz, Burcin; Hoffmann, Lucas; Koolen, Martijn; Nagata, Tetsuya; Papadimitriou, Dimitra; Nagy, Peter; Mitsumoto, Hiroshi; Kariya, Shingo; Wichterle, Hynek; Henderson, Christopher E.; Przedborski, Serge

    2014-01-01

    SUMMARY Most cases of neurodegenerative disease are sporadic, hindering the use of genetic mouse models to analyze disease mechanisms. Focusing on the motor neuron (MN) disease amyotrophic lateral sclerosis (ALS) we therefore devised a fully humanized co-culture model composed of human adult primary sporadic ALS (sALS) astrocytes and human embryonic stem cell-derived MNs. The model reproduces the cardinal features of human ALS: sALS astrocytes, but not those from control patients, trigger selective death of MNs. The mechanisms underlying this non-cell-autonomous toxicity were investigated in both astrocytes and MNs. Although causal in familial ALS (fALS), SOD1 does not contribute to the toxicity of sALS astrocytes. Death of MNs triggered by either sALS or fALS astrocytes occurs through necroptosis, a form of programmed necrosis involving receptor-interacting protein 1 and the mixed lineage kinase domain-like protein. The necroptotic pathway therefore constitutes a novel potential therapeutic target for this incurable disease. PMID:24508385

  8. "Familial" versus "Sporadic" intellectual disability: contribution of common microdeletion and microduplication syndromes

    Directory of Open Access Journals (Sweden)

    Rafati Maryam

    2012-01-01

    Full Text Available Abstract Background Interstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID but the role of such aberrations in familial ID has not yet been investigated. As the balanced chromosomal abnormalities commonly lead to the recurrent ID or multiple congenital anomalies, this study was designed to evaluate whether it was justified to investigate such aberrations in familial ID patients. Three hundred and twenty eight patients from 101 unrelated Iranian families with more than two ID patients in the first-degree relatives, have been investigated. Assessment of a panel of 21 common Microdeletion and Microduplication syndromes (CMMS was carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA technique. Results Among the families studied, 27.7% had 4-12, 35.6% had 3 and 36.6% had 2 affected individuals in the first-degree relatives. An autosomal dominant inheritance of Williams-Beuren syndrome (WBS was detected in a family with no clinical suspicion of WBS. The prevalence of CMMS was therefore,0.99%. Conclusion This is the first investigation of a panel of CMMS in a large sample set of "familial ID patients". The findings of this study showed the low prevalence of CMMSs in "familial ID" patients in spite of the significant contribution of such aberrations in "sporadic ID" which has a very useful practical impact by avoiding unnecessary diagnostic tests in "familial ID" patients.

  9. Identification of chromosome aberrations in sporadic microsatellite stable and unstable colorectal cancers using array comparative genomic hybridization

    DEFF Research Database (Denmark)

    Jensen, Thomas DyrsØ; Li, Jian

    2011-01-01

    Colorectal cancer (CRC) is one of the most common cancers in Denmark and in the western world in general, and the prognosis is generally poor. According to the traditional molecular classification of sporadic colorectal cancer, microsatellite stable (MSS)/chromosome unstable (CIN) colorectal cancers constitute approximately 85% of sporadic cases, whereas microsatellite unstable (MSI) cases constitute the remaining 15%. In this study, we used array comparative genomic hybridization (aCGH) to identify genomic hotspot regions that harbor recurrent copy number changes. The study material comprised fresh samples from 40 MSS tumors and 20 MSI tumors obtained from 60 Danish CRC patients. We identified five small genomic regions (

  10. Expression and localization of BRCA1 protein by immunofluorescence technique in sporadic breast cancer

    International Nuclear Information System (INIS)

    Full text: Introduction. BRCA1 protein is a tumor suppressor subjected to a nuclear-cytoplasmic shuttle, involved in the tumorigenesis of breast cancer. Controversy exists regarding the meaning of the expression and subcellular localization in sporadic breast cancer, particularly the one with triple-negative phenotype. The purpose of this study was to evaluate the pattern of expression and subcellular localization of BRCA1 in a well- characterized breast tumors sporadic, and compared with adjacent normal breast. Methods. We analyzed, by immunofluorescence, the expression / localization of BRCA1 in cuts of tumor and adjacent normal tissue fixed in formaldehyde and embedded in paraffin, of 22 cases, majority being triple negative phenotype. 3 sections were studied tumor and normal tissue per patient (03.05 fields / section) using con focal microscopy and evaluated the percentage of cells with BRCA1 nuclear foci. For statistical analysis of differences in expression / BRCA1 localization between tumor and normal tissue was used Mann Whitney U test, and to determine the associations with the content and status of estrogen receptor (E R) and progesterone (P R), fraction of activated A kt and clinico pathologic characteristics test was used of Spea rman rank correlation was considered significant when p < 0.05. Results. We observed cytoplasmic and nuclear expression of BRCA1 in all sections of normal and tumor tissue analyzed, although the latter showed a significantly largegh the latter showed a significantly larger cell with BRCA1 nuclear foci (53%)compared with the corresponding adjacent normal tissue (33 %, p = 0.004, n = 12). Furthermore, a positive correlation was obtained between the percentage of cells with nuclear foci and content (p = 0.003)and status (p = 0.002)of R E in the total cases studied. No correlation was found between the percentage of cells with nuclear foci and the contents of R P (p = 0.996), activated Ak t fraction (p = 0.753), age (p = 0.695)and lymph node involvement (p = 0.730). Conclusions. BRCA1 is a cytoplasmic and nuclear protein in normal and tumor breast tissue, and the latter has a higher percentage of BRCA1 nuclear foci, possibly in response to increase genetic aberrations characteristic of malignant cells. the association found between the nuclear localization of BRCA1 and R E content level could be explained tumor up regulation by R E on DNA repair mediated by BRCA1. Considering these results, it seems useful to conduct a study with a larger population and elucidate the mechanisms involved in intracellular trafficking of BRCA1 in breast cancer esporádico.Expresión and location of the BRCA1 -1 protein by immunofluorescence technique in sporadic breast cancer

  11. BRCA1 Expression Is Epigenetically Repressed in Sporadic Ovarian Cancer Cells by Overexpression of C-Terminal Binding Protein 2

    Directory of Open Access Journals (Sweden)

    Taymaa May

    2013-06-01

    Full Text Available INTRODUCTION: Ovarian cancer is the leading cause of mortality from gynecological malignancy despite advancements in novel therapeutics. We have recently demonstrated that the transcriptional co-repressor C-terminal binding protein 2 (CtBP2 is overexpressed in epithelial ovarian carcinoma. MATERIALS AND METHODS: Reverse-transcribed cDNA from CtBP2 wild-type and knockdown ovarian cancer cell lines was hybridized to Affymetrix Gene 1.0 ST microarrays, and differentially expressed genes were studied. Immunohistochemical analysis of CtBP2 and BRCA1 staining of ovarian tissues was performed. Chromatin immunoprecipitation (ChIP and luciferase assays were carried out. The effect of the drugs 4-methylthio-2-oxobutyric acid (MTOB and poly(ADP-ribose polymerase (PARP inhibitor Olaparib on CtBP2 wild-type and knockdown cell lines was examined using methylthiazol tetrazolium assays and an xCELLigence System. RESULTS: Eighty-five genes involved in DNA repair, mitotic checkpoint, nucleosome assembly, and the BRCA1 network were differentially regulated by CtBP2 expression. ChIP and luciferase reporter assays using a BRCA1 promoter-regulated luciferase construct indicated that the CtBP2 complex binds the BRCA1 promoter and represses BRCA1 transcription. Immunohistochemistry illustrated a significant inverse CtBP2 and BRCA1 expression in a panel of malignant ovarian tumor tissues. The CtBP2 inhibitor MTOB suppressed ovarian cancer cell survival in a CtBP2-dependent manner. Ovarian cancer cells with CtBP2 knockdown did not display increased sensitivity to the PARP inhibitor Olaparib. CONCLUSION: CtBP2 is an ovarian cancer oncogene that may play a significant role in epigenetically silencing BRCA1 function in sporadic epithelial ovarian cancer. CtBP2-specific inhibitors, such as MTOB, may be effective adjunct therapies in the management of patients with CtBP2-positive ovarian carcinoma.

  12. Sporadic Creutzfeldt-Jakob disease: a clinico-neuropathological analysis of nine definite cases

    Directory of Open Access Journals (Sweden)

    COSTA CARLOS M. DE CASTRO

    1998-01-01

    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.

  13. Azathioprine does not reduce adenoma formation in a mouse model of sporadic intestinal tumorigenesis

    Science.gov (United States)

    Wielenga, Mattheus CB; van Lidth de Jeude, Jooske F; Rosekrans, Sanne L; Levin, Alon D; Schukking, Monique; D’Haens, Geert RAM; Heijmans, Jarom; Jansen, Marnix; Muncan, Vanesa; van den Brink, Gijs R

    2014-01-01

    AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis. METHODS: Azathioprine was administered via drinking water (estimated 6-20 mg/kg body weight per day) to ApcMin/+ and wildtype mice. Control animals received vehicle only (DMSO) dissolved in drinking water. At 15 wk of age all mice were sacrificed and intestines of ApcMin/+ were harvested for evaluation of polyp number. Azathioprine induced toxicity was investigated by immunohistochemical analysis on spleens. RESULTS: All azathioprine treated mice showed signs of drug-associated toxicity such as weight loss and development of splenic T-cell lymphomas. Although this suggests that the thiopurine concentration was clearly in the therapeutic range, it did not reduce tumor formation (48 ± 3.1 adenomas vs 59 ± 5.7 adenomas, P = 0.148). CONCLUSION: We conclude that in the absence of inflammation, azathioprine does not affect intestinal tumorigenesis. PMID:25469037

  14. Four new species of Dolichopoda Bolivar, 1880 from Southern Sporades and Western Turkey (Orthoptera, Rhaphidophoridae, Dolichopodainae).

    Science.gov (United States)

    Rampini, Mauro; Russo, Claudio Di; Taylan, Mehmet Sait; Gelosa, Arianna; Cobolli, Marina

    2012-01-01

    A description of four new species of Dolichopoda Bolivar, 1880 (Orthoptera, Rhaphidophoridae) from Eastern Aegean region (Southern Sporades), including Western Turkey, is reported. This brings to a total of 11 the number of Dolichopoda species recorded for caves of the Aegean area. Overall, these species show a high degree of morphological homogeneity and they are very close to Dolichopoda paraskevi Boudou-Saltet, 1973 from Crete and Dolichopoda naxia Boudou-Saltet, 1972 from Cyclades (Naxos Island). The Western Turkish species are morphologically not closely related to the other Anatolian species; this suggests an independent origin for the taxa occurring in the Southern Taurus and Black Sea regions. These new data help to better define the already high level of diversity of the Hellenic Dolichopoda and strengthen the hypothesis that the central area of dispersal for the genus would correspond to the ancient Aegean plate. PMID:22768003

  15. Four new species of Dolichopoda Bolivar, 1880 from Southern Sporades and Western Turkey (Orthoptera, Rhaphidophoridae, Dolichopodainae

    Directory of Open Access Journals (Sweden)

    Mauro Rampini

    2012-06-01

    Full Text Available A description of four new species of Dolichopoda Bolivar, 1880 (Orthoptera, Rhaphidophoridae from Eastern Aegean region (Southern Sporades, including Western Turkey, is reported. This brings to a total of 11 the number of Dolichopoda species recorded for caves of the Aegean area. Overall, these species show a high degree of morphological homogeneity and they are very close to D. paraskevi Boudou-Saltet, 1973 from Crete and D. naxia Boudou-Saltet, 1972 from Cyclades (Naxos Island. The Western Turkish species are morphologically not closely related to the other Anatolian species; this suggests an independent origin for the taxa occurring in the Southern Taurus and Black Sea regions. These new data help to better define the already high level of diversity of the Hellenic Dolichopoda and strengthen the hypothesis that the central area of dispersal for the genus would correspond to the ancient Aegean plate.

  16. Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer.

    Science.gov (United States)

    Humar, Bostjan; Graziano, Francesco; Cascinu, Stefano; Catalano, Vincenzo; Ruzzo, Anna M; Magnani, Mauro; Toro, Tumi; Burchill, Tudor; Futschik, Matthias E; Merriman, Tony; Guilford, Parry

    2002-11-21

    Truncating mutations in the gene for the cell to cell adhesion protein E-cadherin are the most consistent genetic alterations observed in sporadic and hereditary diffuse gastric cancer (DGC). In addition to these inactivating mutations, a CDH1 promoter polymorphism at position -160 has been reported to lead to transcriptional downregulation of the gene in vitro. We therefore performed a case-control study to investigate whether this variant is associated with an increased susceptibility to DGC. The frequency of the -160A allele was significantly higher (PC and the 2076C-->T variant) were genotyped and shown to be equally distributed among cases and controls. Haplotype analysis with the three polymorphisms confirmed an association with disease (P-160C-->A CDH1 promoter polymorphism may be in linkage disequilibrium with a distinct aetiological locus or acts in combination with other functional variants in or near the CDH1 region. PMID:12444556

  17. Horizontal structure of sporadic E layer observed with a rocket-borne magnesium ion imager

    Science.gov (United States)

    Kurihara, J.; Koizumi-Kurihara, Y.; Iwagami, N.; Suzuki, T.; Kumamoto, A.; Ono, T.; Nakamura, M.; Ishii, M.; Matsuoka, A.; Ishisaka, K.; Abe, T.; Nozawa, S.

    2010-12-01

    To study the spatial structure of midlatitude sporadic E (Es) layers, the ultraviolet resonant scattering by magnesium ions (Mg+) in an Es layer was observed during the evening twilight with the Magnesium Ion Imager (MII) on the sounding rocket launched from the Uchinoura Space Center in Kagoshima, Japan. The in situ electron density measured by an onboard impedance probe showed that the Es layer was located at an altitude of 100 km during both the ascent and descent of the flight. Simultaneous observation with a ground-based ionosonde at Yamagawa identified the signature of horizontally "patchy" structures in the Es layer. The MII successfully scanned the horizontal Mg+ density perturbations in the Es layer and found that they had patchy and frontal structures. The horizontal scale and alignment of the observed frontal structure is generally consistent with a proposed theory. To our knowledge, this is the first observation of the two-dimensional horizontal structure of Mg+ in an Es layer.

  18. GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations.

    Science.gov (United States)

    Green, Claire L; Tawana, Kiran; Hills, Robert K; Bödör, Csaba; Fitzgibbon, Jude; Inglott, Sarah; Ancliff, Phil; Burnett, Alan K; Linch, David C; Gale, Rosemary E

    2013-06-01

    GATA2 mutations have recently been reported in acute myeloid leukaemia (AML) patients with CEBPA-double mutations. To explore their impact on this favourable-risk disease, we determined GATA2 status in 153 sporadic AML patients and three members of a germ-line CEBPA-mutant family at AML presentation. Overall, 27% (15/55) CEBPA-double, 16% (7/43) CEBPA-single and 0% (0/55) normal karyotype/CEBPA-wild-type patients were GATA2-mutant. All familial AML patients acquired both a second CEBPA and a GATA2 mutation. CEBPA and GATA2 mutant levels indicated that both mutations were likely to be early events in leukaemogenesis. GATA2 status did not impact on the favourable outcome of CEBPA-double/FLT3-inernal tandem duplication-negative patients. PMID:23560626

  19. Mutational analysis of familial and sporadic amyotrophic lateral sclerosis with OPTN mutations in Japanese population.

    Science.gov (United States)

    Naruse, Hiroya; Takahashi, Yuji; Kihira, Tameko; Yoshida, Sohei; Kokubo, Yasumasa; Kuzuhara, Shigeki; Ishiura, Hiroyuki; Amagasa, Masaharu; Murayama, Shigeo; Tsuji, Shoji; Goto, Jun

    2012-10-01

    Our objective was to elucidate the genetic epidemiology of familial amyotrophic lateral sclerosis (FALS) and sporadic ALS (SALS) with OPTN mutations in the Japanese population. Mutational analysis of OPTN was conducted in 18 FALS pedigrees in whom mutations in other causative genes have been excluded and in 218 SALS patients by direct nucleotide sequence analysis. Novel non-synonymous variants identified in ALS patients were further screened in 271 controls. Results showed that although no mutations were identified in the FALS pedigrees, a novel heterozygous non-synonymous variant c.481G > A (p.V161M) was identified in one SALS patient, who originated from the southernmost part of the Kii Peninsula. The mutation was not present in 271 controls. As the clinical feature, the patient carrying V161M showed predominantly upper motor neuron signs with slow progression. This study suggests that mutations in OPTN are not the main cause of ALS in the Japanese population. PMID:22708870

  20. Metal ions and isotopes in sporadic E-layers during the Perseid meteor shower

    Science.gov (United States)

    Herrmann, U.; Eberhardt, P.; Hidalgo, M. A.; Kopp, E.; Smith, L. G.

    1977-01-01

    The electron density and positive-ion composition above Wallops Island were measured on August 12, 1976, about 12 hours after the maximum of the Perseid shower. At launch time, 4.5 MHz was recorded for fbEs, corresponding to an electron density of 2.4 x 10 to the 5th power per cu cm. Electron profile and ion composition measurements confirmed the presence of a sporadic E-layer with two maxima at 101.3 and 105.4 km. The electron density was measured with a pair of boom-mounted probes at fixed potential. The positive ion composition above 77 km was measured with a magnetic mass spectrometer employing a liquid He cryopump. Some of the salient results of the (still incomplete) analysis are discussed.

  1. Non-apolipoprotein E and apolipoprotein E genetics of sporadic Alzheimer's disease.

    Science.gov (United States)

    Seripa, Davide; Panza, Francesco; Franceschi, Marilisa; D'Onofrio, Grazia; Solfrizzi, Vincenzo; Dallapiccola, Bruno; Pilotto, Alberto

    2009-07-01

    The genetic epidemiology of sporadic Alzheimer's disease (SAD) remains a very active area of research,making it one of the most prolifically published areas in medicine and biology. Numerous putative candidate genes have been proposed. However, with the exception of apolipoprotein E (APOE), the only confirmed genetic risk factor for SAD, all the other data appear to be not consistent. Nevertheless, the genetic risk for SAD attributable to the APOE gene in the general population is 20-0%, providing a strong evidence for the existence of additional genetic risk factors. The first part of the present article was dedicated to non-APOE genetics of SAD, reviewing chromosomes-by-chromosomes the available data concerning the major candidate genes. The second part of this article focused on some recently discovered aspects of the APOE polymorphism and their implications for SAD. An attempt to identify the future directions for non-APOE genetic research in SAD was also discussed. PMID:19496238

  2. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

    Directory of Open Access Journals (Sweden)

    Hai-Tao Zheng, Li-Xin Jiang, Zhong-Chuan Lv, Da-Peng Li, Chong-Zhi Zhou, Jian-Jun Gao, Lin He, Zhi-Hai Peng

    2008-01-01

    Full Text Available AIM: 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.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed 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 ?2 test.RESULTS: 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 (< 30% by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively. On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030. No relationship was detected on other loci compared with clinicopathological features.CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (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.

  3. Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells

    Science.gov (United States)

    Israel, Mason A.; Yuan, Shauna H.; Bardy, Cedric; Reyna, Sol M.; Mu, Yangling; Herrera, Cheryl; Hefferan, Michael P.; Van Gorp, Sebastiaan; Nazor, Kristopher L.; Boscolo, Francesca S.; Carson, Christian T.; Laurent, Louise C.; Marsala, Martin; Gage, Fred H.; Remes, Anne M.; Koo, Edward H.; Goldstein, Lawrence S. B.

    2012-01-01

    Our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer’s disease, both caused by a duplication of the amyloid-? precursor protein gene1 (APP; termed APPDp), two with sporadic Alzheimer’s disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APPDp patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-?(1–40), phospho-tau(Thr 231) and active glycogen synthase kinase-3? (aGSK-3?). Neurons from APPDp and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with ?-secretase inhibitors, but not ?-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3? levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-?, in GSK-3? activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer’s disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer’s disease, even though it can take decades for overt disease to manifest in patients. PMID:22278060

  4. Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

    Science.gov (United States)

    Israel, Mason A; Yuan, Shauna H; Bardy, Cedric; Reyna, Sol M; Mu, Yangling; Herrera, Cheryl; Hefferan, Michael P; Van Gorp, Sebastiaan; Nazor, Kristopher L; Boscolo, Francesca S; Carson, Christian T; Laurent, Louise C; Marsala, Martin; Gage, Fred H; Remes, Anne M; Koo, Edward H; Goldstein, Lawrence S B

    2012-02-01

    Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-? precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-?(1-40), phospho-tau(Thr?231) and active glycogen synthase kinase-3? (aGSK-3?). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with ?-secretase inhibitors, but not ?-secretase inhibitors, caused significant reductions in phospho-Tau(Thr?231) and aGSK-3? levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-?, in GSK-3? activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients. PMID:22278060

  5. Sporadic fundic gland polyps: an immunohistochemical study of their antigenic profile.

    Science.gov (United States)

    Declich, P; Isimbaldi, G; Sironi, M; Galli, C; Ferrara, A; Caruso, S; Baldacci, M P; Stioui, S; Privitera, O; Boccazzi, G; Federici, S

    1996-08-01

    Fundic Gland Polyps (FGPs) are small sessile (2-5 mm), usually multiple polyps arising in the gastric, acid-secreting mucosa of disputed histogenesis. They have been described in a sporadic form, prevalently in middle aged females, or associated with familial adenomatosis coli-Gardner's syndrome. We performed an immunohistochemical study on 24 sporadic FGPs, using monoclonal antibodies (MAbs) against differentiation markers, class II MHC antigens (HLA-DR), oncofetal and proliferation antigens, aimed to characterize the antigenic profile of the polyps. A preliminary cytogenetic study on five polyps was also done, using an in situ culture method after collagenase treatment. Cytokeratins 8-18 (CAM 5.2 MAb) and 20 (IT-Ks 20.8 MAb), Epithelial Membrane Antigen (EMA) and Chromogranin A were normally expressed by FGPs. FGPs did not express HLA II DR. FGPs did not react with an anti-CEA MAb (F6), but they were frequently positive (22/24, 91.6%) with B72.3 MAb (reacting with the cancer-associated mucin epitope sialyl-Tn). The PC10 MAb (against PCNA or cyclin) showed enhanced expression in the deep glandular-cystic compartment of FGPs; the PCNA index of FGPs was significantly higher than in normal fundic mucosa. The cytogenetic study on the 5 cases analysed, revealed a normal karyotype. We have demonstrated that FGPs express in the paranuclear zone the sialyl-Tn epitope, a side-chain sugar normally masqued in adult gastric mucins, thus revealing an alteration in mucin synthesis; FGPs' higher proliferation index as compared with normal fundic mucosa supports the hypothesis of their hyperproliferative nature. PMID:8897516

  6. BRCA1 mutations in Algerian breast cancer patients: high frequency in young, sporadic cases

    Directory of Open Access Journals (Sweden)

    Nancy Uhrhammer, Amina Abdelouahab, Laurence Lafarge, Viviane Feillel, Ahmed Ben Dib, Yves-Jean Bignon

    2008-01-01

    Full Text Available Breast cancer rates and median age of onset differ between Western Europe and North Africa. In Western populations, 5 to 10 % of breast cancer cases can be attributed to major genetic factors such as BRCA1 and BRCA2, while this attribution is not yet well defined among Africans. To help determine the contribution of BRCA1 mutations to breast cancer in a North African population, we analysed genomic DNA from breast cancer cases ascertained in Algiers. Both familial cases (at least three breast cancers in the same familial branch, or two with one bilateral or diagnosed before age 40 and sporadic cases less than 38 years of age were studied. Complete sequencing plus quantitative analysis of the BRCA1 gene was performed. 9.8 % (5/51 of early-onset sporadic and 36.4 % (4/11 of familial cases were found to be associated with BRCA1 mutations. This is in contrast 10.3 % of French HBOC families exhibiting a BRCA1 mutation. One mutation, c.798_799delTT, was observed in two Algerian families and in two families from Tunisia, suggesting a North African founder allele. Algerian non-BRCA1 tumors were of significantly higher grade than French non-BRCA tumors, and the age at diagnosis for Algerian familial cases was much younger than that for French non-BRCA familial cases. In conclusion, we observed a much higher frequency of BRCA1 mutations among young breast cancer patients than observed in Europe, suggesting biological differences and that the inclusion criterea for analysis in Western Europe may not be applicable for the Northern African population.

  7. First report of sporadic Na layers at Qingdao (36° N, 120° E), China

    Science.gov (United States)

    Ma, Z.; Wang, X.; Chen, L.; Wu, J.

    2014-07-01

    This paper reports, for the first time, observational results of mesopause sporadic Na (Nas) layers by a ground-based lidar at Qingdao (36° N, 120° E), China. Based on ~ 430 h of observational data on 95 nights from December 2007 to June 2012, we have selected a total of 53 Nas layer events. It is found that characteristics of Nas layers over Qingdao have general similarity with those over nearby sites, Wuhan (30° N, 114° E) and Hefei (32° N, 117° E), but not those over the site Hachioji (35° N, 139° E) at nearly the same latitude as Qingdao. At the same time, parameters of sporadic E (Es) layers were recorded by an ionosonde. The fact that Es layer occurrence probabilities of 19, 22, and 18% in time intervals before, during, and after the Nas layers are very close to the average occurrence ratio of the nocturnal Es layer (21%), may reveal a general independence between Nas and Es layers over Qingdao. Only those strong Nas layers above the peak altitude of the main Na layer might have a significant correlation with Es layers. In addition, a total of 11 high-altitude (above 105 km) Nas layer events have been surveyed specially. It is found that these high-altitude Nas layers were usually weak. And they possessed long-duration (> 147 min) and broad-layer width (4.0 km) compared with Nas layers below 105 km (> 96 min and 2.4 km). These characteristics are in accord with observational results at Wuhan. It is suggested that there is little correlation between this kind of Nas layers and Es layers. Finally, the summer topside enhancement phenomenon of Na atoms observed at Qingdao is in accord with several earlier observational results at different sites (18, 30, and 54° N) in the Northern Hemisphere.

  8. Interpretation of Results From Sporadic and Continuous GPS Measurements In The Azores Region

    Science.gov (United States)

    Bastos, L.; Fernendes, R. M. S.; Ambrosius, B. A. C.

    With the goal to contribute for a better understanding of the mechanisms associated with the complex system of faults in the Azores Triple Junction region, the AOUP is carrying out geodetic observations (GPS and gravimetry) in the Azores Archipelago since 1988. In 1999, in collaboration with DEOS, a densification network has been established in the five islands of the Central Group (located in the Eurasia-Africa boundary deformation area). Furthermore, two permanent GPS stations were installed on the Faial and Terceira islands, in 2000 and 2001, respectively. A third GPS station, installed in Azores by the Portuguese Mapping Institute (IPCC), is available since 1999. This paper is focused on the results of the combination of sporadic campaign data and continuous measurements for these three stations, covering a time-span of valid observations of more than eight years. The relative motions are studied at two levels: analysing the baseline changes (independent of the reference frame definition) and investigating the horizontal and vertical components (in ITRF2000). Validation of the results obtained with sporadic campaigns by continuous measurements is done for the same stations. Due to the occurrence of a strong earthquake in Faial in July, 1998, data from this station is analysed in more detail. With respect to the vertical component, the GPS results are evaluated considering also the information obtained from absolute gravimetric observations made on that station. Its behaviour is analysed taking into account the geophysical framing. The impact of the different methodolo- gies used in data acquisition and the importance of an integrated approach for a better understanding of the geodynamic and geophysical processes occurring in this region are discussed.

  9. MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project.

    Science.gov (United States)

    Pasquali, Elena; García-Borrón, José C; Fargnoli, Maria Concetta; Gandini, Sara; Maisonneuve, Patrick; Bagnardi, Vincenzo; Specchia, Claudia; Liu, Fan; Kayser, Manfred; Nijsten, Tamar; Nagore, Eduardo; Kumar, Rajiv; Hansson, Johan; Kanetsky, Peter A; Ghiorzo, Paola; Debniak, Tadeusz; Branicki, Wojciech; Gruis, Nelleke A; Han, Jiali; Dwyer, Terry; Blizzard, Leigh; Landi, Maria Teresa; Palmieri, Giuseppe; Ribas, Gloria; Stratigos, Alexander; Council, M Laurin; Autier, Philippe; Little, Julian; Newton-Bishop, Julia; Sera, Francesco; Raimondi, Sara

    2015-02-01

    The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects. PMID:24917043

  10. Sporadic colorectal cancer and individual susceptibility: A review of the association studies investigating the role of DNA repair genetic polymorphisms.

    Czech Academy of Sciences Publication Activity Database

    Naccarati, Alessio; Pardini, B.; Hemminki, K.; Vodi?ka, Pavel

    2007-01-01

    Ro?. 635, 2-3(2007), s.118-145. ISSN 1383-5742 R&D Projects: GA MZd NR8563; GA ?R GA310/05/2626 Institutional research plan: CEZ:AV0Z50390512 Keywords : Sporadic colorectal cancer * Individual susceptibility * DNA repair Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.353, year: 2007

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

    Directory of Open Access Journals (Sweden)

    TakutoHideyama

    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.

  12. Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type.

    Science.gov (United States)

    Javed, H; Khan, M M; Ahmad, A; Vaibhav, K; Ahmad, M E; Khan, A; Ashafaq, M; Islam, F; Siddiqui, M S; Safhi, M M; Islam, F

    2012-05-17

    The objective of the present study was to assess the neuroprotective role of rutin (vitamin P) and delineate the mechanism of action. Recent evidence indicates that rutin exhibits antioxidant potential and protects the brain against various oxidative stressors. More precisely, the aim of the present study was to examine the modulating impacts of rutin against cognitive deficits and oxidative damage in intracerebroventricular-streptozotocin (ICV-STZ)-infused rats. Rats were injected bilaterally with ICV-STZ (3 mg/kg), whereas sham rats received the same volume of vehicle. After 2 weeks of streptozotocin (STZ) infusion, rats were tested for cognitive performance using Morris water maze tasks and thereafter euthanized for further biochemical, histopathological, and immunohistochemical studies. Rutin pretreatment (25 mg/kg, orally, once daily for 3 weeks) significantly attenuated thiobarbituric acid reactive substances (TBARS), activity of poly ADP-ribosyl polymerase, and nitrite level and decreased level of reduced glutathione (GSH) and activities of its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and catalase in the hippocampus of ICV-STZ rats. ICV-STZ rats showed significant cognitive deficits, which was improved significantly by rutin supplementation. The results indicate that rutin attenuates STZ-induced inflammation by reducing the expression of cyclooxygenase-2 (COX-2), glial fibrillary acidic protein (GFAP), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), nuclear factor-kB, and preventing the morphological changes in hippocampus. The study thereby suggests the effectiveness of rutin in preventing cognitive deficits and might be beneficial for the treatment of sporadic dementia of Alzheimer type (SDAT). PMID:22441036

  13. Mutations in the HFE gene and sporadic amyotrophic lateral sclerosis risk: a meta-analysis of observational studies

    Scientific Electronic Library Online (English)

    M., Li; L., Wang; W., Wang; X.L., Qi; Z.Y., Tang.

    2014-03-01

    Full Text Available SciELO Brazil | Language: English Abstract in english Iron homeostasis dysregulation has been regarded as an important mechanism in neurodegenerative diseases. The H63D and C282Y polymorphisms in the HFE gene may be involved in the development of sporadic amyotrophic lateral sclerosis (ALS) through the disruption of iron homeostasis. However, studies i [...] nvestigating the relationship between ALS and these two polymorphisms have yielded contradictory outcomes. We performed a meta-analysis to assess the roles of the H63D and C282Y polymorphisms of HFE in ALS susceptibility. PubMed, MEDLINE, EMBASE, and Cochrane Library databases were systematically searched to identify relevant studies. Strict selection criteria and exclusion criteria were applied. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A fixed- or random-effect model was selected, depending on the results of the heterogeneity test. Fourteen studies were included in the meta-analysis (six studies with 1692 cases and 8359 controls for C282Y; 14 studies with 5849 cases and 13,710 controls for H63D). For the C282Y polymorphism, significant associations were observed in the allele model (Y vs C: OR=0.76, 95%CI=0.62-0.92, P=0.005) and the dominant model (YY+CY vs CC: OR=0.75, 95%CI=0.61-0.92, P=0.006). No associations were found for any genetic model for the H63D polymorphism. The C282Y polymorphism in HFE could be a potential protective factor for ALS in Caucasians. However, the H63D polymorphism does not appear to be associated with ALS.

  14. Simulation of the sporadic E layer response to prereversal associated evening vertical electric field enhancement near dip equator

    Science.gov (United States)

    Carrasco, A. J.; Batista, I. S.; Abdu, M. A.

    2007-06-01

    The role of the molecular and metallic ions in the formation of sporadic E layers (Es layers) has been an active area of research for many years. Ionosonde data of the Es layer parameter, fbEs (the blanketing frequency of sporadic layer), and ftEs (the top frequency of Es trace), obtained over the Brazilian sites, Fortaleza, and São Luis, show that the diurnal variations of these parameters often present a disruption that is coincident with the evening prereversal electric field/vertical drift enhancement, to reappear after about 2 hours. In this work we have developed a model of the E region with the objective to describe all the phases of the life cycle of the sporadic layer and its relation to the evening vertical electric field enhancement that is associated with the development of the prereversal zonal electric field enhancement. The model calculates the densities of NO+, O2+, O+, N2+, and Fe+ in the height region 86-140 km by simultaneously solving the continuity and momentum equations for each of the species. For low latitudes this model shows that winds and electric fields each play distinct roles in the vertical transport of plasma leading to Es layer formation. The results of our numerical simulation confirm the dominant role of the vertical electric field as the cause of the inhibition/disruption of the sporadic layer in the evening. More specifically, the results reveal that an upward directed (positive) vertical electric field is capable of disrupting an ongoing sporadic layer, whereas a downward (negative) electric field favors its formation or even intensification, thus corroborating the conclusions of the recent study by Abdu et al. (2003).

  15. Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors.

    Science.gov (United States)

    Dahia, P L; Marsh, D J; Zheng, Z; Zedenius, J; Komminoth, P; Frisk, T; Wallin, G; Parsons, R; Longy, M; Larsson, C; Eng, C

    1997-11-01

    The majority of familial medullary thyroid neoplasms are associated with germ-line mutations of the RET proto-oncogene, yet very little is known about the mechanisms involved in the pathogenesis of familial and sporadic nonmedullary thyroid tumors. A subset of thyroid tumors have loss of heterozygosity of chromosome 10q22-23, a region harboring the gene responsible for Cowden disease, an autosomal dominant hamartoma syndrome associated with thyroid and breast tumors. PTEN/MMAC1/TEP1 codes for a dual-specificity phosphatase and is likely a tumor suppressor gene. We sought to determine the PTEN status in a series of epithelial thyroid neoplasms. We studied 95 sporadic thyroid tumors, of which 39 were papillary thyroid carcinomas (PTCs), 12 were follicular carcinomas, 9 were anaplastic carcinomas, 5 were Hürthle cell carcinomas, 21 were nonfunctioning follicular adenomas, and 9 were Hürthle cell adenomas. Direct sequencing of PCR-amplified products was performed for all nine exons of PTEN. Two polymorphic markers, one located in intron 8 and another, a dinucleotide repeat marker, AFMa086wg9, located within intron 2, were analyzed in paired blood-tumor DNA samples to assess hemizygous deletions of PTEN. We found a somatic frameshift mutation in one PTC, which was expected to generate a premature stop codon 2 amino acids downstream. Twenty-six % of informative benign tumors (four follicular adenomas and three Hürthle cell adenomas) and only 3 of 49 (6.1%) informative malignant tumors (one PTC, one follicular carcinoma, and one anaplastic carcinoma) showed evidence of hemizygous deletion of PTEN (P = 0.046). We conclude that a subset of thyroid tumors have somatic deletions of the PTEN gene, predominantly the benign forms, and that small intragenic mutations of PTEN are infrequent in thyroid tumors. We speculate that other mechanisms of PTEN inactivation, rather than small intragenic mutations, might occur in the hemizygously deleted samples and act as the "Knudson second hit." Alternatively, other tumor suppressor genes mapping to chromosome 10q22-23 could be the actual targets for such deletions and thus represent the various hits in the pathway of multistep carcinogenesis. PMID:9354427

  16. AMACR is associated with advanced pathologic risk factors in sporadic colorectal adenomas

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    Sotiris Lakis, Theodora Papamitsou, Constantina Panagiotopoulou, Rodoula Kotakidou, Vassiliki Kotoula

    2010-05-01

    Full Text Available AIM: To analyze ?-methylacyl CoA racemase (AMACR expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-five cases of sporadic colorectal adenomas were categorized according to the Vienna classification for Gastrointestinal Neoplasia. These corresponded to a total of 98 different intra-lesion microscopic fields that were further independently assigned a histological grade based on the old nomenclature (mild, moderate, severe dyplasia and carcinoma in situ. AMACR expression was evaluated by immunohistochemistry and statistical analysis was performed to investigate possible associations with various clinicopathologic parameters of adenomas i.e. gender, age, localization, grade of dysplasia, size and configuration.RESULTS: Patient age ranged from 41 to 84 years (mean 65 ± 13.2 years; 37 patients were males and 18 were females. Adenomas ranged in size between 0.5 and 30 cm (mean 2 ± 1.3 cm, including 18 tubular, 16 villous, 20 mixed or tubulovillous, and 1 giant sessile villous adenoma. AMACR expression was observed in 3 out of 16 (18.8% of low-grade vs 23 out of 35 (62.8% of high-grade lesions (P = 0.002. Most adenomas exhibiting high grade dysplasia with in situ carcinoma-like areas stained positive for AMACR (15/17 or 88.2% as compared to adenomas with high grade dysplasia which contained severe dysplasia-like foci (6/15 or 40%, (P = 0.005. In AMACR positive adenomas featuring severe dysplasia-like or in situ carcinoma-like areas, AMACR staining was not necessarily observed in the in situ component. Positivity in intra-lesion of mild, moderate or severe dysplasia-like foci was more often encountered in adenomas harboring in situ, intramucosal or infiltrative carcinoma [21/33 (63.6% vs 9/40 (22.5%, P 1 cm stained more frequently for AMACR than smaller ones [27/45 (60% vs 2/10 (20%, P = 0.02]. Overall, AMACR expression was associated with the grade of dysplasia, as well as with the size and configuration of adenomas, i.e. the consensus risk factors applied to colorectal adenoma patient surveillance.CONCLUSION: It may be worthy to further evaluate the possible use of AMACR as an additional risk factor for the assessment of colorectal adenoma patients.

  17. SEEK-2 (Sporadic-E Experiment over Kyushu 2 ? Project Outline, and Significance

    Directory of Open Access Journals (Sweden)

    R. Pfaff

    2005-10-01

    Full Text Available SEEK-2 (Sporadic-E Experiment over Kyushu 2 is an observation campaign to study the spatial structure of the field-aligned irregularity (FAI and sporadic-E(Es-layer by means of two sounding rockets and a ground-based observation network with radars and optical instruments. The experiment was successfully conducted on 3 August 2002, with successive launches of two sounding rockets from the Uchinoura Space Center (USC of the Japan Aerospace Exploration Agency (JAXA. The timing of the experiment was carefully selected, while intense quasi-periodic (QP echoes were observed with two radars in Tanegashima. The main Es-layer, with its double-layered structure, was observed at altitudes of 103–105 km, the presence of which was well accounted for by the ion accumulation due to neutral-wind shear. Several minor peaks were detected in the electron density profiles at altitudes of up to 130 km. The intensity of the electric field was 5–10 mV/m and showed intense fluctuations below 110 km. Wave-like variation of the electric field was seen above 110 km. From radar experiments, we found that QP echoes appeared around 105 km, which agreed well with the main Es-layer height. The QP echoes propagated to the west-northwest, with frontal structures elongated from north-northeast to south-southwest. Radar observations conduced throughout the SEEK-2 period, on the other hand, showed that frontal structures of the QP echoes were most frequently propagated to the southeast. This result was consistent with the direction of gravity-wave propagation observed with the OH imager during the same period. The rocket beacon experiment with the Es-layers revealed the spatial structure of the plasma densities. On the basis of these results and those from SEEK-1 in 1996, we examined the structures of the nighttime mid-latitude E-region. We concluded that the QP echoes reflect the horizontal structures of the main Es-layers. The source of the structures was not clearly determined from the experiments, but the candidates are gravity waves and the Kelvin-Helmholtz instability. The azimuth-dependent Es-instability may have contributed to enhance structures of the QP echoes, although this instability may not be a major source of the QP structure in SEEK-2. Polarization electric fields were induced from the Es-layer with QP echoes, mapped upward along the geomagnetic field, and played an important role in determining the structures of the whole ionospheric E-region. Keywords. Mid-latitude ionosphere – Ionospheric irregularities – Ionosphere-atmosphere interactions

  18. 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.

    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 was the least accurate with 79% sensitivity at 90% specificity. Many of the sCJD patients had extremely elevated t-tau values but normal values of the AD-marker p-tau. Protein 14-3-3 was very sensitive (95%) although the specificity was relatively low (75%). A combination of elevated t-tau concentration with the presence of 14-3-3 protein in CSF gave the best test specificity of 96% at 84% sensitivity. We conclude that the combination of more than one CSF marker for neurodegeneration can improve the diagnostic test accuracy for sCJD against neurological controls including patients with other dementias Udgivelsesdato: 2009/11

  19. The role of electric field and neutral wind in the generation of polar cap sporadic E

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    Nygrén, T.; Voiculescu, M.; Aikio, A. T.

    2008-11-01

    This paper investigates the roles of electric field and neutral wind in the generation of sporadic-E layers within the polar cap. Two Es layers above Svalbard, observed by the EISCAT Svalbard Radar (ESR), were chosen for investigation. The radar experiment contains four beam directions, and this was used for determining the electric field. The neutral wind was obtained from the HWM93 model. Formation of Es layers was calculated by integrating the continuity equation under the action of driving forces due to neutral wind and electric field. A flat height profile of metal ions was assumed in the beginning. The calculation gives the time variation of the layer, which can be compared with observations. In one case the electric field was shown to be the main driving agent in layer generation. In the other case the electric field was weak and the layer was produced mainly by the neutral wind, but the electric field had influence on the height of the layer. A fairly good agreement between the variations of the observed and calculated layer altitudes was obtained and some agreement between the intensity variations was also found.

  20. Temporal and regional variations in sporadic Creutzfeldt-Jakob disease in Japan, 2001-2010.

    Science.gov (United States)

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

    2015-04-01

    SUMMARY The objective of this study was to examine temporal and regional variations of sporadic Creutzfeldt-Jakob disease (sCJD) in a retrospective study using Japanese national surveillance data from 2001 to 2010. We calculated the incidence of sCJD by age and sex, derived the standardized incidence in each of the 47 prefectures, and performed spatial disease clustering analysis. The average annual incidence of sCJD was 1·026 per million in men (637 patients) and 1·132 per million in women (733 patients), a significant sex difference after adjustment for age (P = 0·001). The ratios of familial CJD to sCJD apparently increased between 2001-2005 and 2006-2010, possibly as a result of the nationwide introduction of genetic testing after 2006. Based on the data of 2006-2010, certain geographical clusters of sCJD were identified. The incidence of sCJD was higher in several specific prefectures compared to the national average. Thus, sCJD appears to have regional variations, suggesting the existence of genetic or region-specific factors affecting the incidence of the disease. PMID:25034354

  1. Subtype and Regional-Specific Neuroinflammation in Sporadic Creutzfeldt–Jakob Disease

    Science.gov (United States)

    Llorens, Franc; López-González, Irene; Thüne, Katrin; Carmona, Margarita; Zafar, Saima; Andréoletti, Olivier; Zerr, Inga; Ferrer, Isidre

    2014-01-01

    The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt–Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony stimulating factors, cathepsins, members of the complement system, and members of the integrin and CTL/CTLD family with particular regional and sCJD subtype patterns. Analysis of cytokines and mediators at protein level shows expression of selected molecules and receptors in neurons, in astrocytes, and/or in microglia, thus suggesting interactions between neurons and glial cells, mainly microglia, in the neuroinflammatory response in sCJD. Similar inflammatory responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive deregulation of inflammatory mediators with disease progression. Yet, inflammatory molecules involved are subjected to species differences in humans and mice. Moreover, inflammatory-related cell signaling pathways NF?B/IKK and JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD. Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD. PMID:25136317

  2. First symptom and initial diagnosis in sporadic CJD patients in Germany.

    Science.gov (United States)

    Krasnianski, Anna; Kaune, Judith; Jung, Klaus; Kretzschmar, Hans A; Zerr, Inga

    2014-09-01

    To describe the first symptom/sign and first diagnosis in patients with sporadic Creutzfeldt-Jakob disease (sCJD) in Germany with respect to M129V polymorphism of the prion protein gene and prion protein type. Data on the first symptom/sign and first diagnosis were studied in 492 sCJD patients with probable and definite sCJD and known M129V polymorphism. Unspecific prodromal symptoms such as headache, fatigue, sleep disturbances, "peculiar feeling in the head", photophobia or weight loss were found in about 10 % of the patients. No prodromal symptoms were found in MV2 and VV1 patients. Dementia was the most common first symptom (37 %) followed by cerebellar (34 %), visual (15 %), and psychiatric disturbances (14 %). The CJD diagnosis was the first diagnosis in only 35 % of the patients (in 42 % of MM, 28 % of MV, and 24.5 % of VV patients). We provide a detailed analysis on clinical presentation and first diagnosis in a large group of patients with sCJD with respect to M129V genotype and prion protein type. These data emphasize the importance of knowledge about CJD and especially rare CJD types among physicians of different specializations. Our findings may improve early recognition of atypical CJD forms. PMID:25022936

  3. 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

    Introduction 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. Methods 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. Results 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 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. PMID:25279832

  4. FUS mutations in sporadic amyotrophic lateral sclerosis: clinical and genetic analysis.

    Science.gov (United States)

    Sproviero, William; La Bella, Vincenzo; Mazzei, Rosalucia; Valentino, Paola; Rodolico, Carmelo; Simone, Isabella Laura; Logroscino, Giancarlo; Ungaro, Carmine; Magariello, Angela; Patitucci, Alessandra; Tedeschi, Gioacchino; Spataro, Rossella; Condino, Francesca; Bono, Francesco; Citrigno, Luigi; Monsurrò, Maria Rosaria; Muglia, Maria; Gambardella, Antonio; Quattrone, Aldo; Conforti, Francesca Luisa

    2012-04-01

    Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients with FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants (3'-untranslated region [UTR] variant, c.*41G>A; c.523+3ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from within our cohort. This study underlines the importance of population-based mutation screening of newly identified genes. PMID:22055719

  5. Maxillary sporadic Burkitt's lymphoma associated with neuro-orbital involvement in an Indian male.

    Science.gov (United States)

    Manne, Rakesh Kumar; Madu, Chandra Sekhar; Talla, Harsh Vardhan

    2014-04-01

    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. PMID:24963253

  6. Risk factors for sporadic Vibrio parahaemolyticus gastroenteritis in east China: a matched case-control study.

    Science.gov (United States)

    Yan, W X; Dai, Y; Zhou, Y J; Liu, H; Duan, S G; Han, H H; Chen, Y

    2015-04-01

    SUMMARY To determine risk factors for sporadic Vibrio parahaemolyticus gastroenteritis, we conducted a population-based case-control study in sentinel hospital surveillance areas of Shanghai and Jiangsu province, China. Seventy-one patients with diarrhoea and confirmed V. parahaemolyticus infections were enrolled, and they were matched with 142 controls for gender, age and residential area. From the multivariable analysis, V. parahaemolyticus infections were associated with antibiotics taken during the 4 weeks prior to illness [odds ratio (OR) 8·1, 95% confidence interval (CI) 1·2-56·4)], frequent eating out (OR 3·3, 95% CI 1·1-10·1), and shellfish consumption (OR 3·2, 95% CI 1·0-9·9), with population-attributable fractions of 0·09, 0·25, and 0·14, respectively. Protective factors included keeping the aquatic products refrigerated (OR 0·4, 95% CI 0·1-0·9) and pork consumption (OR 0·2, 95% CI 0·1-0·8). Further study of the association of V. parahaemolyticus gastroenteritis with prior antibiotic use and shellfish consumption is needed. PMID:24992005

  7. Risk factors for sporadic Campylobacter infections: results of a case-control study in southeastern Norway.

    Science.gov (United States)

    Kapperud, G; Skjerve, E; Bean, N H; Ostroff, S M; Lassen, J

    1992-12-01

    In 1989 and 1990, a case-control study designed to identify risk factors for sporadic infections with thermotolerant Campylobacter bacteria was conducted in three counties in southeastern Norway. The investigation was confined to infections which were acquired in Norway. A total of 52 bacteriologically confirmed cases and 103 controls matched by age, sex, and geographic region were interviewed. The following risk factors were found to be independently associated with illness in conditional logistic regression analysis: consumption of sausages at a barbecue (odds ratio [OR] = 7.64; P = 0.005), daily contact with a dog (OR = 4.26; P = 0.024), and eating of poultry which was brought into the house raw (frozen or refrigerated) (OR = 3.20; P = 0.024). The risk associated with consumption of sausages at a barbecue could not be attributed to cross-contamination from poultry products. By univariate analysis, consumption of poultry which was brought raw and frozen was associated with illness (OR = 2.42; P = 0.042), even though freezing substantially reduces the number of viable campylobacters. When poultry consumption was examined by country of origin, eating of poultry produced in Denmark or Sweden was strongly associated with illness (OR = 13.66; P = 0.014), whereas consumption of poultry produced in Norway was not (OR = 1.33; P = 0.41). PMID:1452694

  8. 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.

  9. Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.

    Science.gov (United States)

    Rabin, Stuart J; Kim, Jae Mun Hugo; Baughn, Michael; Libby, Ryan T; Kim, Young Joo; Fan, Yuxin; Libby, Randell T; La Spada, Albert; Stone, Brad; Ravits, John

    2010-01-15

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (P motor neuron degeneration. Data deposition: GeneChip raw data (CEL-files) have been deposited for public access in the Gene Expression Omnibus (GEO), www.ncbi.nlm.nih.gov/geo, accession number GSE18920. PMID:19864493

  10. 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

    2014-08-01

    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 (PrP(Sc)) 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 PrP(Sc) between iCJD and sCJD. However, using PMCA, we find that convertibility and amplification efficiency of PrP(Sc) 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

  11. Case study on complex sporadic E layers observed by GPS radio occultations

    Science.gov (United States)

    Yue, X.; Schreiner, W. S.; Zeng, Z.; Kuo, Y.-H.; Xue, X.

    2015-01-01

    The occurrence of sporadic E (Es) layers has been a hot scientific topic for a long time. The GNSS (global navigation satellite system)-based radio occultation (RO) has proven to be a powerful technique for detecting the global Es layers. In this paper, we focus on some cases of complex Es layers based on the RO data from multiple missions processed in UCAR/CDAAC (University Corporation for Atmospheric Research (UCAR) the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) Data Analysis and Archive Center (CDAAC)). We first show some examples of multiple Es layers occurred in one RO event. Based on the evaluations between colocated simultaneous RO events and between RO and lidar observations, it could be concluded that some of these do manifest the multiple Es layer structures. We then show a case of the occurrence of Es in a broad region during a certain time interval. The result is then validated by independent ionosondes observations. It is possible to explain these complex Es structures using the popular wind shear theory. We could map the global Es occurrence routinely in the near future, given that more RO data will be available. Further statistical studies will enhance our understanding of the Es mechanism. The understanding of Es should benefit both Es-based long-distance communication and accurate neutral RO retrievals.

  12. The Phox2B homeobox gene is mutated in sporadic neuroblastomas.

    Science.gov (United States)

    van Limpt, Vera; Schramm, Alexander; van Lakeman, Arjan; Sluis, Peter; Chan, Alvin; van Noesel, Max; Baas, Frank; Caron, Huib; Eggert, Angelika; Versteeg, Rogier

    2004-12-01

    Neuroblastomas are embryonal tumours of the sympatho-adrenal lineage with a clinical course ranging from spontaneous regression to fatal progression. The Phox2B homeobox transcription factor functions in the differentiation of the sympatho-adrenal lineage. Targets of Phox2B are, for example, genes of the (nor)adrenalin synthesis route, like Dopamine Beta Hydroxylase (DBH). Congenital Central Hypoventilation Syndrome was recently found to result from Phox2B mutations and two such patients in addition developed neuroblastoma. A germline mutation in Phox2B was identified in a family with hereditary neuroblastoma. Here, we report the first analysis of Phox2B in a series of 237 sporadic neuroblastomas and 22 cell lines. Six frameshift mutations were found in exons 2 and 3; including one in cell line SK-N-SH. Two patients showed de novo constitutional mutations. One of them was diagnosed with Haddad syndrome. All analysed cases expressed the mutated and wild-type Phox2B alleles. Ectopic expression of TrkA, the Nerve Growth Factor receptor, strongly downregulated Phox2B and DBH expression in cell line SH-SY5Y. However, TrkA and Phox2B showed a positive correlation in a panel of 66 neuroblastoma tumours. Although Phox2B mutations are infrequent (2.3%), they implicate a role for the Phox2B pathway in oncogenesis. PMID:15516980

  13. Sporadic amyotrophic lateral sclerosis with pallido-nigro-luysian degeneration: a TDP-43 immunohistochemical study.

    Science.gov (United States)

    Miki, Yasuo; Mori, Fumiaki; Nunomura, Jinichi; Ookawa, Keizou; Yajima, Nobuhisa; Yagihashi, Soroku; Wakabayashi, Koichi

    2010-04-01

    Recently, Nishihira et al. demonstrated the presence of two types of TDP-43 pathology in sporadic amyotrophic lateral sclerosis (ALS) (Acta Neuropathol 2008; 116: 169-182). Type 1 represents the TDP-43 distribution pattern observed in classic ALS, whereas type 2 shows the presence of TDP-43 inclusions in the frontotemporal cortex, hippocampal formation, neostriatum and substantia nigra and is significantly associated with dementia. However, ALS with pallido-nigro-luysian degeneration (PNLD) is very rare. We recently encountered a case of ALS with PNLD of 9 years duration, in which the patient received artificial respiratory support for 6 years. In our case, neuronal loss and TDP-43-positive neuronal cytoplasmic inclusions were found in the globus pallidus, substantia nigra and subthalamic nucleus. Neither neuronal loss nor TDP-43-immunoreactive inclusions were found in the frontotemporal cortex and hippocampus. These findings suggest that the pallido-nigro-luysian system is also involved in the disease process of ALS and that ALS with PNLD is different from ALS with dementia based on the distribution pattern of neuronal loss and TDP-43 accumulation. PMID:19703266

  14. Risk factors for sporadic infection with Salmonella Enteritidis, Denmark, 1997-1999

    DEFF Research Database (Denmark)

    MØlbak, Kåre; Neimann, Jacob

    2002-01-01

    In a prospective case-control study of sporadic Salmonella Enteritidis infection in Denmark (1997-1999), foreign travel was reported by 25% of 455 case patients and 8% of 507 controls (odds ratio (OR) = 3.7, 95% confidence interval (CI): 2.4, 5.5). Among nontravelers, 80% of 335 cases and 81% of 467 controls had consumed eggs or dishes containing raw or undercooked eggs during the week before disease onset or interview, while 35% of cases and 19% of controls had incurred this exposure the day before onset or interview (OR = 2.2, 95% CI: 1.5, 3.1). Specific exposures included consumption of buttermilk dessert (OR = 11.7), homemade ice cream (OR = 4.3), raw eggs (OR = 3.4), and eggs fried "sunny side up" (OR = 2.5). Among persons who had used eggs in the week before disease onset or interview, eggs from battery laying hens were associated with disease (white eggs: OR = 2.4, brown eggs: OR = 1.9), whereas consumption of pasteurized eggs tended to be protective (OR = 0.3). The study confirmed that eggs are the principal source of S. Enteritidis in Denmark. This conclusion was reached through the use of an exposure time window that corresponds to the most relevant incubation period rather than the maximum incubation period. The authors recommend this method in studies that have the objective of determining risk associated with common exposures.

  15. Sporadic E ionization layers observed with radar imaging and ionospheric modification

    Science.gov (United States)

    Hysell, D. L.; Munk, J.; McCarrick, M.

    2014-10-01

    Sporadic E ionization layers have been observed in the daytime subauroral ionospheric E layer by a 30 MHz radar in Alaska. The radar detects coherent backscatter from meter-scale field-aligned plasma density irregularities. The irregularities were generated by ionospheric modification—by the emission of strong HF electromagnetic waves directly beneath the layers—making the layers visible to the radar. Aperture-synthesis methods are used to generate imagery of the layers from the radar data. The layers are patchy, with patches organized along fronts spaced by tens of kilometers and propagating slowly toward the southwest. Similar, naturally occurring layers are commonly observed at middle latitudes at night in the absence of ionospheric modification. That the patchy layers can be found at high magnetic latitudes during the day argues that they are most likely produced through the interaction of the ionospheric layer with neutral atmospheric waves and instabilities. Attenuation of the radar echoes when the HF emission frequency exceeded the third harmonic of the electron gyrofrequency was observed and is discussed.

  16. HF Doppler radar observations of sporadic E at an Indian low latitude station, Visakhapatnam

    Directory of Open Access Journals (Sweden)

    M. S. S. R. K. N Sarma

    2009-02-01

    Full Text Available 5.5 MHz HF Doppler radar observations of Sporadic E over an Indian low latitude station, Visakhapatnam (17.7° N, 83.3° E and Dip 20° with 10 s resolution showed quasi-periodic variations of the echo strength and Doppler velocity variations with periods of a few minutes to a few tens of minutes. The echo strength and Doppler velocity variations with time in different range bins of the ES echo showed variations which are some times similar and some times significantly different in successive range bins at intervals of 7.5 km. The ES echo occurs with the height of maximum echo strength in the range of 100 km to 120 km and some times at 130 km. The altitude variation of the average Doppler velocity is highly variable and the height of maximum echo strength is not the same as the height of maximum Doppler velocity. Observations of ES echoes at different times of the day are presented to bring out the differences between the day and night time ES echoes. The relationship between Radar and ES parameters derived from Ionograms is poorer than that of mid latitudes which is quite consistent with the expectations based on gradient drift instability.

  17. Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report

    Directory of Open Access Journals (Sweden)

    Cracco Laura

    2011-10-01

    Full Text Available Abstract Background Sporadic fatal insomnia (sFI and fatal familial insomnia (FFI are rare human prion diseases. Case Presentation We report a case of a 33-year-old female who died of a prion disease for whom the diagnosis of sFI or FFI was not considered clinically. Following death of this patient, an interview with a close family member indicated the patient's illness included a major change in her sleep pattern, corroborating the reported autopsy diagnosis of sFI. Genetic tests identified no prion protein (PrP gene mutation, but neuropathological examination and molecular study showed protease-resistant PrP (PrPres in several brain regions and severe atrophy of the anterior-ventral and medial-dorsal thalamic nuclei similar to that described in FFI. Conclusions In patients with suspected prion disease, a characteristic change in sleep pattern can be an important clinical clue for identifying sFI or FFI; polysomnography (PSG, genetic analysis, and nuclear imaging may aid in diagnosis.

  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. MC1R gene variants and sporadic malignant melanoma susceptibility in the Canary Islands population.

    Science.gov (United States)

    Córdoba-Lanús, Elizabeth; Hernández-Jiménez, José G; Medina-Coello, Chaxiraxi; Espinoza-Jiménez, Adriana; González, Ana; Rodríguez-Pérez, María-Del-Cristo; Carretero-Hernández, Gregorio; Almeida, Pablo; Suárez-Hernández, José; Perera-Molinero, Antonio; Fernández-de-Misa, Ricardo

    2014-01-01

    Several MC1R variants are associated with increased risk of malignant melanoma (MM) in a variety of populations. We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands. Overall, 1,046 Caucasian individuals were included in the study. A thousand of them were genotyped for MC1R variants: 509 were sporadic MM patients and 491 were healthy control subjects from general population. The analysis was adjusted for age, sex, hair colour, eye colour, skin phototype and ancestry. We found that carriers of the R151C and R163Q variants were at an increased risk for melanoma OR 2.76 (1.59-4.78) and OR 5.62 (2.54-12.42), respectively. The risk of carrying RHC variants was 3.04 (1.90-4.86). Current study confirms the increased MM risk for R151C carriers. It also supports the association between R163Q variant and MM risk in the population on the Canary Islands, as opposed to reported on northern populations. These results highlight the importance of the sample population selection in this kind of studies. PMID:24170137

  20. Seasonal correlation of sporadic schizophrenia to Ixodes ticks and Lyme borreliosis

    Directory of Open Access Journals (Sweden)

    Fritzsche Markus

    2002-11-01

    Full Text Available Abstract Background Being born in winter and spring is considered one of the most robust epidemiological risk factors for schizophrenia. The aetiology and exact timing of this birth excess, however, has remained elusive so far. Since during phylogeny, Borrelia DNA has led to multiple germ-line mutations within the CB1 candidate gene for schizophrenia, a meta analysis has been performed of all papers on schizophrenic birth excesses with no less than 3000 cases each. All published numerical data were then plotted against the seasonal distributions of Ixodes ticks worldwide. Results In the United States, Europe and Japan the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodes ticks nine months earlier at the time of conception. South of the Wallace Line, which limits the spread of Ixodes ticks and Borrelia burgdorferi into Australia, seasonal trends are less significant, and in Singapore, being non-endemic for Ixodes ticks and Lyme disease, schizophrenic birth excesses are absent. Conclusion At present, it cannot be excluded that prenatal infection by B. burgdorferi is harmful to the implanting human blastocyst. The epidemiological clustering of sporadic schizophrenia by season and locality rather emphasises the risk to the unborn of developing a congenital, yet preventable brain disorder later in life.

  1. Environmental risk factors for sporadic acoustic neuroma (Interphone Study Group, Germany)

    DEFF Research Database (Denmark)

    Schlehofer, B; Schlaefer, K

    2007-01-01

    The only known risk factor for sporadic acoustic neuroma is high-dose ionising radiation. Environmental exposures, such as radiofrequency electromagnetic fields and noise are under discussion, as well as an association with allergic diseases. We performed a population-based case-control study in Germany investigating these risk factors in 97 cases with acoustic neuroma, aged 30 to 69 years, and in 194 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multiple logistic regression models. Increased risks were found for exposure to persistent noise (OR=2.31; 95% CI 1.15-4.66), and for hay fever (OR=2.20; 95% CI 1.09-4.45), but not for ionising radiation (OR=0.91; 95 % CI 0.51-1.61) or regular mobile phone use (OR=0.67; 95% CI 0.38-1.19). The study confirms results of recently published studies, although the pathogenetic mechanisms are still unknown.

  2. Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer.

    Science.gov (United States)

    Latimer, Jean J; Johnson, Jennifer M; Kelly, Crystal M; Miles, Tiffany D; Beaudry-Rodgers, Kelly A; Lalanne, Nancy A; Vogel, Victor G; Kanbour-Shakir, Amal; Kelley, Joseph L; Johnson, Ronald R; Grant, Stephen G

    2010-12-14

    The molecular etiology of breast cancer has proven to be remarkably complex. Most individual oncogenes are disregulated in only approximately 30% of breast tumors, indicating that either very few molecular alterations are common to the majority of breast cancers, or that they have not yet been identified. In striking contrast, we now show that 19 of 19 stage I breast tumors tested with the functional unscheduled DNA synthesis assay exhibited a significant deficiency of DNA nucleotide excision repair (NER) capacity relative to normal epithelial tissue from disease-free controls (n = 23). Loss of DNA repair capacity, including the complex, damage-comprehensive NER pathway, results in genomic instability, a hallmark of carcinogenesis. By microarray analysis, mRNA expression levels for 20 canonical NER genes were reduced in representative tumor samples versus normal. Significant reductions were observed in 19 of these genes analyzed by the more sensitive method of RNase protection. These results were confirmed at the protein level for five NER gene products. Taken together, these data suggest that NER deficiency may play an important role in the etiology of sporadic breast cancer, and that early-stage breast cancer may be intrinsically susceptible to genotoxic chemotherapeutic agents, such as cis-platinum, whose damage is remediated by NER. In addition, reduced NER capacity, or reduced expression of NER genes, could provide a basis for the development of biomarkers for the identification of tumorigenic breast epithelium. PMID:21118987

  3. Geographical variation of sporadic Legionnaires' disease analysed in a grid model

    DEFF Research Database (Denmark)

    Rudbeck, M.; Jepsen, Martin Rudbeck

    2010-01-01

    The aim was to analyse variation in incidence of sporadic Legionnaires' disease in a geographical information system in three time periods (1990-2005) by the application of a grid model and to assess the model's validity by analysing variation according to grid position. Coordinates of the addresses at time of disease of 606 confirmed cases with Legionnaires' disease were obtained. The incidence was calculated in cells of 10 x 10 km in 25 different grids superimposed on a map of Denmark. A 95% and 99% threshold was applied to identify cells with excess incidence representing potential clusters. Four cells had excess incidence in all three time periods. The analysis in 25 different grid positions indicated a low risk of overlooking cells with excess incidence in a random grid. The coefficient of variation ranged from 0.08 to 0.11 independent of the threshold. By application of a random grid model we demonstrated that it was possible to detect small areas with excess incidence that were not detected in the present surveillance system

  4. Energetics and structure of the lower E region associated with sporadic E layer

    Directory of Open Access Journals (Sweden)

    K.-I. Oyama

    2008-09-01

    Full Text Available The electron temperature (Te, electron density (Ne, and two components of the electric field were measured from the height of 90 km to 150 km by one of the sounding rockets launched during the SEEK-2 campaign. The rocket went through sporadic E layer (Es at the height of 102 km–109 km during ascent and 99 km–108 km during decent, respectively. The energy density of thermal electrons calculated from Ne and Te shows the broad maximum in the height range of 100–110 km, and it decreases towards the lower and higher altitudes, which implies that a heat source exists in the height region of 100 km–110 km. A 3-D picture of Es, that was drawn by using Te, Ne, and the electric field data, corresponded to the computer simulation; the main structure of Es is projected to a higher altitude along the magnetic line of force, thus producing irregular structures of Te, Ne and electric field in higher altitude.

  5. Construction of Fischer's sporadic group Fi'_{24} inside GL_{8671}(13)

    CERN Document Server

    Kim, Hyun Kyu

    2009-01-01

    In this article we construct an irreducible simple subgroup G = of GL_{8671}(13) from an irreducible subgroup T of GL_{11}(2) isomorphic to Mathieu's simple group M_{24} by means of Algorithm 2.5 of [13]. We also use the first author's similar construction of Fischer's sporadic simple group G_1 = Fi_{23} described in [11]. He starts from an irreducible subgroup T_1 of GL_{11}(2) contained in T which is isomorphic to M_{23}. In [7] J. Hall and L. S. Soicher published a nice presentation of Fischer's original 3-transposition group Fi_{24} [6]. It is used here to show that G is isomorphic to the simple commutator subgroup Fi'_{24} of Fi_{24}. We also determine a faithful permutation representation of G of degree 306936 with stabilizer G_1 = $\\cong$ Fi_{23}. It enabled MAGMA to calculate the character table of G automatically. Furthermore, we prove that G has two conjugacy classes of involutions z and u such that C_G(u) = $\\cong$ 2Aut(\\Fi_{22}). Moreover, we determine a presentation of H = C_G(z) and a faithfu...

  6. Sporadic pancreatic vasoactive intestinal peptide-producing tumor (VIPoma) in a 47-year-old male.

    Science.gov (United States)

    Abu-Zaid, Ahmed; Azzam, Ayman; Abudan, Zainab; Algouhi, Amani; Almana, Hadeel; Amin, Tarek

    2014-09-01

    VIPoma is an exceedingly unusual neuroendocrine neoplasm that autonomously secretes vasoactive intestinal polypeptide (VIP). Its reported incidence is approximately 1 per 10 million individuals per year. Herein, we report the case of sporadic pancreatic VIPoma in a 47-year-old male who presented with a six-month history of chronic, plentiful, watery diarrhea. On physical examination, the patient looked sick, lethargic and had signs of dehydration. Laboratory investigations revealed high VIP hormone level (989pg/mL), hypokalemia, hypercalcemia, hyperglycemia, high blood urea nitrogen, high creatinine, and metabolic acidosis on arterial blood gas. Contrast-enhanced computed tomography (CT) scan showed a 3.1×3.3×4.7cm, well-defined, enhancing lesion involving the pancreatic tail with a cystic component. Moreover, a 5.7×6.1×6.8cm metastatic hepatic lesion was identified. The patient underwent distal pancreatectomy with splenectomy, hepatic lesion resection, and lymph node dissection. Histopathological and immunohistochemical examination of the pancreatic and hepatic lesions revealed neuroendocrine tumor (VIPoma). Postoperatively, the patient received radiofrequency ablation for the hepatic lesion. A post-operative six-month follow-up showed significant symptomatic relief, reduced VIP hormone level (71pg/mL) and normalized electrolyte and acid-base profiles. However, a magnetic resonance imaging (MRI) scan showed a small residual metastatic liver lesion which was considered for hepatic artery embolization (HAE). The patient is still alive with a residual hepatic disease at 18months. We also present a brief literature review on VIPoma. PMID:24785507

  7. Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease

    Science.gov (United States)

    Haugarvoll, K.; Rademakers, R.; Kachergus, J.M.; Nuytemans, K.; Ross, O.A.; Gibson, J.M.; Tan, E.-K.; Gaig, C.; Tolosa, E.; Goldwurm, S.; Guidi, M.; Riboldazzi, G.; Brown, L.; Walter, U.; Benecke, R.; Berg, D.; Gasser, T.; Theuns, J.; Pals, P.; Cras, P.; De Deyn, P. Paul; Engelborghs, S.; Pickut, B.; Uitti, R.J.; Foroud, T.; Nichols, W.C.; Hagenah, J.; Klein, C.; Samii, A.; Zabetian, C.P.; Bonifati, V.; Van Broeckhoven, C.; Farrer, M.J.; Wszolek, Z.K.

    2014-01-01

    Objective Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p.R1441C. Methods We identified 33 affected and 15 unaffected LRRK2 c.4321C>T (p.R1441C) mutation carriers through an international consortium originating from three continents. The age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. Results The clinical presentation of Lrrk2 p.R1441C carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age at onset for parkinsonism was 60 years, range 30 –79 years; fewer than 20% of the patients had symptoms before the age 50 years, while by 75 years >90% of them had developed symptoms. Haplotype analysis suggests four independent founders for the p.R1441C mutation. Conclusions The distribution in age at onset and clinical features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S parkinsonism. Several independent founders of the p.R1441C substitution suggest this site is prone to recurrent mutagenesis. PMID:18337586

  8. Genetic polymorphisms of the E-cadherin promoter and risk of sporadic gastric carcinoma in Chinese populations.

    Science.gov (United States)

    Zhang, Baozhen; Pan, Kaifeng; Liu, Zhaojun; Zhou, Jing; Gu, Liankun; Ji, Jiafu; Ma, Junling; You, Wei-cheng; Deng, Dajun

    2008-09-01

    Frequent mutations and loss of expression of E-cadherin have been reported in a number of cancers. E-cadherin germ line mutations lead to a high risk of familial diffused gastric carcinoma. In the present study, to evaluate the effect of genetic polymorphisms in the E-cadherin promoter on the risk of sporadic gastric carcinoma (SGC), a comprehensive study was conducted in two populations with high and low risk of SGC in China, respectively. Five hundred seventy-two SGC cases and 625 controls from low-risk area and 589 individuals enrolled in a long-term follow-up survey in high-risk area were studied. Polymorphisms of E-cadherin around transcription start site (-437 to +314) were analyzed by sequencing. Five variations of -347del>A, -160C>A, -73A>C, +178T>C, and +234 13N ins>del were linked tightly. The -347del/del and its strongly linked +178T/T, +234 13N ins/ins genotypes increased male SGC risk in the high-risk area significantly [odds ratio (OR), 2.22; 95% confidence intervals (95% CI), 1.10-4.46] and correlated with the severity of gastric lesions. A synergetic effect was also observed between -347del/del genotype and Helicobacter pylori infection (OR, 4.93; 95% CI, 1.65-14.71). Compared with -347del-containing haplotypes, the -347A-containing haplotype [A((-347))-C((-160))-A((-73))-C((+178))-13N del((+234))] decreased the risk of SGC among male subjects (OR, 0.61; 95% CI, 0.37-1.01). Such correlation could not be observed among subjects from the low-risk area. The present data suggest that the -347del allele of E-cadherin strongly links with the +178T and +234 13N ins alleles. The -347del/del genotype may increase the susceptibility of SGC among males in the high-risk area of China. PMID:18768510

  9. Integrating Conservation and Development at the National Marine Park of Alonissos, Northern Sporades, Greece: Perception and Practice

    Science.gov (United States)

    Oikonomou, Zoi-Sylvia; Dikou, Angela

    2008-11-01

    Available information on the socioeconomic implications of marine protected areas (MPAs) for the socioculturally diverse Mediterranean region is scant. The National Marine Park of Alonissos, Northern Sporades (NMPANS), Greece was established in 1992 as a foundation for the conservation of the endangered Mediterranean monk seal Monachus monachus. The evolution of the degree of acceptance of and satisfaction from the NMPANS by involved stakeholder groups (fishermen, tourism operators, hoteliers and owners of rooms to let, governmental bodies, nongovernmental bodies, students, domestic and foreign tourists) were investigated 13 years after its establishment using written questionnaires delivered during personal interviews. The initial positive attitude of local professionals for the NMPANS has eroded due to the unsatisfactory fulfillment of expectations for socioeconomic development. Fishermen expressed dissatisfaction with, mistrust toward, and a reluctancy to communicate with the NMPANS’s management body. They believe that the fishery areas have decreased in actual geographic area because of the prohibitive measures; fish stocks are declining; compensation for damage to fishery equipment by the Mediterranean monk seal and for the prohibitive measures should be provided; and stricter enforcement of regulations should take place. On the other hand, tourism operators, who organize trips for tourists to the NMPANS, unanimously reported direct economic benefits. Furthermore, there was a disparity in the perception of socioeconomic benefits derived from the NMPANS between governmental bodies and local stakeholders. The governmental bodies and the nongovernmental organization MOm-Hellenic Society for the Study and Protection of the Monk Seal postulated that there had been considerable socioeconomic benefits for the local community of Alonissos due to the establishment of the NMPANS, whereas the local nongovernmental organization Ecological and Cultural Movement of Alonissos claimed benefits were scant. Tourists (domestic and foreign) believe that the NMPANS is not the main attraction to Alonissos Island but is part of a composite, including serenity, aesthetic beauty, and small-scale tourism development, which can turn Alonissos Island into an ideal eco-tourism destination; a common aspiration for both the tourists and the local community by general consensus. The aim of the NMPANS to integrate conservation and development lies in (1) the effectiveness of the NMPANS management body in formulating a strategic management plan that would accommodate stakeholders’ interests and aspirations and (2) a national policy of conservation and enhancement of natural resources with consistency and continuity. Quantitative assessment of the socioeconomic effectiveness of the Mediterranean MPAs using a common methodology would facilitate the identification of intraregional variation and better planning for the network of MPAs in the Mediterranean.

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

    International Nuclear Information System (INIS)

    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.)

  11. Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment

    OpenAIRE

    Hung, Kenneth E.; Maricevich, Marco A.; Richard, Larissa Georgeon; Chen, Wei Y.; Richardson, Michael P.; Kunin, Alexandra; Bronson, Roderick T.; Mahmood, Umar; Kucherlapati, Raju

    2010-01-01

    Most genetically engineered mouse (GEM) models for colon cancer are based on tissuewide or germline gene modification, resulting in tumors predominantly of the small intestine. Several of these models involve modification of the adenomatous polyposis coli (Apc) gene and are excellent models for familial cancer predisposition syndromes. We have developed a stochastic somatic mutation model for sporadic colon cancer that presents with isolated primary tumors in the distal colon and recapitulate...

  12. PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia: a case-control study in southwest China

    Scientific Electronic Library Online (English)

    Jing, WANG; Yuanzhi, XU; Jing, CHEN; Feiyu, WANG; Renhuan, HUANG; Songtao, WU; Linjing, SHU; Jingyi, QIU; Zhi, YANG; Junjie, XUE; Raorao, WANG; Jilin, ZHAO; Wenli, LAI.

    2013-06-01

    Full Text Available Our research aimed to look into the clinical traits and genetic mutations in sporadic non-syndromic anodontia and to gain insight into the role of mutations of PAX9, MSX1, AXIN2 and EDA in anodontia phenotypes, especially for the PAX9. Material and Methods The female proband and her fa [...] mily members from the ethnic Han families underwent complete oral examinations and received a retrospective review. Venous blood samples were obtained to screen variants in the PAX9, MSX1, AXIN2, and EDA genes. A case-control study was performed on 50 subjects with sporadic tooth agenesis (cases) and 100 healthy controls, which genotyped a PAX9 gene polymorphism (rs4904210). Results Intra-oral and panoramic radiographs revealed that the female proband had anodontia denoted by the complete absence of teeth in both the primary and secondary dentitions, while all her family members maintained normal dentitions. Detected in the female proband were variants of the PAX9 and AXIN2 including A240P (rs4904210) of the PAX9, c.148C>T (rs2240308), c.1365A>G (rs9915936) and c.1386C>T (rs1133683) of the AXIN2. The same variants were present in her unaffected younger brother. The PAX9 variations were in a different state in her parents. Mutations in the MSX1 and EDA genes were not identified. No significant diferences were found in the allele and genotype frequencies of the PAX9 polymorphism between the controls and the subjects with sporadic tooth agenesis. Conclusions These results suggest that the association of A240P with sporadic tooth agenesis still remains obscure, especially for different populations. The genotype/phenotype correlation in congenital anodontia should be verified.

  13. Lack of mutations of exon 2 of the MEN1 gene in endocrine and nonendocrine sporadic tumors

    Directory of Open Access Journals (Sweden)

    Costa S.C.

    2001-01-01

    Full Text Available In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1 syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue samples. We used 5 pairs of primers to encompass the complete coding sequence of exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP technique in 78 sporadic thyroid cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2 pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma and 24 breast cancers (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors. The PCR product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct sense and antisense sequencing did not identify mutations. These results suggest that the MEN1 gene is not important in breast, thyroid or adrenal sporadic tumorigenesis. Because the frequency of mutations varies significantly among tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid and adrenal cancers, another tumor suppressor gene residing in this region is likely to be involved in the tumorigenesis of these neoplasms.

  14. Lack of mutations of exon 2 of the MEN1 gene in endocrine and nonendocrine sporadic tumors

    Scientific Electronic Library Online (English)

    S.C., Costa; L.S., Nascimento; F.J., Ferreira; P.S., Mattos; L.H., Camara-Lopes; L.S., Ward.

    2001-07-01

    Full Text Available SciELO Brazil | Language: English Abstract in english In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most [...] of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue samples. We used 5 pairs of primers to encompass the complete coding sequence of exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) technique in 78 sporadic thyroid cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2 pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma) and 24 breast cancers (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors). The PCR product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct sense and antisense sequencing did not identify mutations. These results suggest that the MEN1 gene is not important in breast, thyroid or adrenal sporadic tumorigenesis. Because the frequency of mutations varies significantly among tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid and adrenal cancers, another tumor suppressor gene residing in this region is likely to be involved in the tumorigenesis of these neoplasms.

  15. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.

    OpenAIRE

    Leontiou, Ca; Gueorguiev, M.; Spuy, J.; Quinton, R.; Lolli, F.; Hassan, S.; Chahal, Hs; Igreja, Sc; Jordan, S.; Rowe, J.; Stolbrink, M.; Christian, Hc; Wray, J.; Bishop-bailey, D.; Berney, Dm

    2008-01-01

    CONTEXT: Mutations have been identified in the aryl hydrocarbon receptor-interacting protein (AIP) gene in familial isolated pituitary adenomas (FIPA). It is not clear, however, how this molecular chaperone is involved in tumorigenesis. OBJECTIVE: AIP sequence changes and expression were studied in FIPA and sporadic adenomas. The function of normal and mutated AIP molecules was studied on cell proliferation and protein-protein interaction. Cellular and ultrastructural AIP localization was det...

  16. Semidiurnal tidal signature in sporadic E occurrence rates derived from GPS radio occultation measurements at higher midlatitudes

    OpenAIRE

    Arras, C.; Jacobi, C.; Wickert, J.

    2009-01-01

    GPS (Global Positioning System) Radio occultation (RO) measurements from CHAMP, GRACE and FORMOSAT-3/COSMIC satellites at Northern Hemisphere midlatitides (50°–55° N) are analysed to obtain the diurnal variation of sporadic E layer occurrence frequency in 2006 and 2007. Interconnections with zonal wind shears measured by meteor radar at Collm (51.3° N, 13° E), Germany, are investigated. According to theory, maximum Es...

  17. Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt–Jakob disease: a case report

    OpenAIRE

    Rodríguez-Martínez Ana B; de Munain Adolfo; Ferrer Isidro; Zarranz Juan J; Atarés Begoña; Villagra Nuria T; Arteagoitia Jose M; Garrido Joseba M; Juste Ramón A

    2012-01-01

    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, fo...

  18. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome

    OpenAIRE

    Hsu, Amy P.; Sampaio, Elizabeth P.; Khan, Javed; Calvo, Katherine R.; Lemieux, Jacob E.; Patel, Smita Y.; Frucht, David M.; Vinh, Donald C.; Auth, Roger D.; Freeman, Alexandra F.; Olivier, Kenneth N.; Uzel, Gulbu; Zerbe, Christa S.; Spalding, Christine; Pittaluga, Stefania

    2011-01-01

    The syndrome of monocytopenia, B-cell and NK-cell lymphopenia, and mycobacterial, fungal, and viral infections is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis, and myeloid leukemias. Both autosomal dominant and sporadic cases occur. We identified 12 distinct mutations in GATA2 affecting 20 patients and relatives with this syndrome, including recurrent missense mutations affecting the zinc finger-2 domain (R398W and T354M), suggesting dominant inter...

  19. Sporadic Alzheimer’s Disease Begins as Episodes of Brain Ischemia and Ischemically Dysregulated Alzheimer’s Disease Genes

    OpenAIRE

    Pluta, Ryszard; Jab?on?ski, Miros?aw; U?amek-kozio?, Marzena; Kocki, Janusz; Brzozowska, Judyta; Januszewski, S?awomir; Furmaga-jab?on?ska, Wanda; Bogucka-kocka, Anna; Maciejewski, Ryszard; Czuczwar, Stanis?aw J.

    2013-01-01

    The study of sporadic Alzheimer’s disease etiology, now more than ever, needs an infusion of new concepts. Despite ongoing interest in Alzheimer’s disease, the basis of this entity is not yet clear. At present, the best-established and accepted “culprit” in Alzheimer’s disease pathology by most scientists is the amyloid, as the main molecular factor responsible for neurodegeneration in this disease. Abnormal upregulation of amyloid production or a disturbed clearance mechanism may l...

  20. Absence of RET proto-oncogene point mutations in sporadic hyperplastic and neoplastic lesions of the parathyroid gland.

    OpenAIRE

    Padberg, B. C.; Schro?der, S.; Jochum, W.; Kastendieck, H.; Roth, J.; Heitz, P. U.; Komminoth, P.

    1995-01-01

    We investigated the possible role of RET proto-oncogene mutations in the development of sporadic hyperplastic, benign, and malignant parathyroid lesions. DNA extracted from paraffin-embedded specimens of forty parathyroid lesions was screened for RET proto-oncogene point mutations in exons 10, 11, and 16 by nonisotopic polymerase chain reaction-based single-strand conformation polymorphism and heteroduplex gel electrophoresis. The nucleotide sequence of samples with aberrant band patterns was...

  1. Sporadic medullary thyroid carcinoma with a pedunculated intraluminal internal jugular vein recurrence: A case report and literature review

    OpenAIRE

    Patten, Darren K.; Flora, Rashpal; Tolley, Neil; Palazzo, Fausto

    2011-01-01

    Medullary thyroid carcinoma (MTC) is an uncommon usually slowly progressing neuroendocrine tumour that arises from calcitonin (CT) producing parafollicular C cells of the thyroid gland. It accounts for approximately 5% of all thyroid cancers. The majority of MTCs are sporadic (75%) whilst 25% are part of the MEN 2 hereditary syndrome (MEN 2A and MEN 2B and familial MTC). Mutations of the proto-oncogene, RET (Rearranged during Transfection), found on chromosome 10q11, are present in more than ...

  2. 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.

  3. The genetics of dementias, Part 3: A molecular basis for the multifactorial inheritance of sporadic Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Anna Kowalska

    2009-12-01

    Full Text Available The majority of Alzheimer’s disease cases, i.e. more than 85?0of the whole population of patients, can be referred to as the sporadic form of the disease, with a negative family history and complex inheritance. As the genetic background of sporadic Alzheimer’s disease is still largely unknown., strategies based on individual genetic risk profiling for either early prediction of the disease or its therapy and prevention are not possible. The APOE*4 allele of the gene for apolipoprotein E is still the only completely confirmed risk factor. Screening for new genetic risk factors with the use of genetic association analysis has many methodological difficulties and limitations. New combined approaches including genomics, proteogenomics, pharmacogenomics, epigenomics, and bioinformatics have to been applied in the future search for a molecular basis of AD. Genetic defects do not fully explain the complexity of the etiopathogenesis of this disease. It is rather certain that environmental factors (through epigenetic modifications in the patient’s epigenome also have impact on the initiation of neurodegeneration processes. The identification of new genetic and environmental risk factors would make it possible to understand epistatic processes, for example interactions between genes and between genes and environmental factors, responsible for the complex etiology and multifactorial inheritance of sporadic Alzheimer’s disease.

  4. Dysplastic nevi. Occurrence in first- and second-degree relatives of patients with 'sporadic' dysplastic nevus syndrome.

    Science.gov (United States)

    Crijns, M B; Vink, J; Van Hees, C L; Bergman, W; Vermeer, B J

    1991-09-01

    In this study a cross-sectional survey was undertaken among 156 living family members of 31 probands originally classified as having sporadic (histologically verified) dysplastic nevus syndrome (DNS). Seven (13.2%) of 53 parents had clinically recognizable DNS. Twenty-six (36.1%) of the 72 sibs showed dysplastic nevi. The diagnosis of DNS in family members was based on mainly clinical examination; in eight family members--those with only mild manifestation of DNS--a nevus was removed for histologic confirmation. After correction for pedigree size, we found that 60% of patients with "type A sporadic" DNS actually had one or more relatives with a DNS phenotype. Only 25% (8/30) of the probands were ultimately true sporadic cases without a DNS-affected first- or second-degree relative. In 15% (5/31) of the probands no conclusions concerning the type of DNS could be made because the pedigree size did not allow such a conclusion. We also found a higher prevalence of dysplastic nevi among the younger generation as compared with the older generation in our probands with DNS and their families as well as in a general population study of 400 individuals. This generation-dependent difference in expression of the DNS phenotype suggests that besides a genetic factor, other factors may play a role in the development of the characteristic phenotype. PMID:1892403

  5. The formation of sporadic E layers by a vortical perturbation excited in a horizontal wind shear flow

    Directory of Open Access Journals (Sweden)

    G. G. Didebulidze

    2008-06-01

    Full Text Available The formation of the mid-latitude sporadic E layers (Es layers by an atmospheric vortical perturbation excited in a horizontal shear flow (horizontal wind with a horizontal linear shear is investigated. A three-dimensional atmospheric vortical perturbation (atmospheric shear waves, whose velocity vector is in the horizontal plane and has a vertical wavenumber kz?0, can provide a vertical shear of the horizontal wind. The shear waves influence the vertical transport of heavy metallic ions and their convergence into thin and dense horizontal layers. The proposed mechanism takes into account the dynamical influence of the shear wave velocity in the horizontal wind on the vertical drift velocity of the ions. It also can explain the multi-layer structure of Es layers. The pattern of the multi-layer structure depends on the value of the shear-wave vertical wavelength, the ion-neutral collision frequency and the direction of the background horizontal wind. The modelling of formation of sporadic E layers with a single and a double peak is presented. Also, the importance of shear wave coupling with short-period atmospheric gravity waves (AGWs on the variations of sporadic E layer ion density is examined and discussed.

  6. Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas

    Directory of Open Access Journals (Sweden)

    Walsh Tom

    2009-07-01

    Full Text Available Abstract Background DNA repair genes critically regulate the cellular response to chemotherapy and epigenetic regulation of these genes may be influenced by chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115 sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms collected after chemotherapy. Additionally, we assessed whether promoter methylation of BRCA1, MLH1 or FANCF influenced response to chemotherapy or explained alterations in protein expression after chemotherapy exposure. Results Of 115 primary sporadic ovarian carcinomas, 39 (34% had low BRCA1 protein and 49 (42% had low BRCA2 expression. BRCA1 and BRCA2 protein expression were highly concordant (p Conclusion Low BRCA1 expression in primary sporadic ovarian carcinoma is associated with prolonged survival. Recurrent ovarian carcinomas commonly have increased BRCA1 and/or BRCA2 protein expression post chemotherapy exposure which could mediate resistance to platinum based therapies. However, alterations in expression of these proteins after chemotherapy are not commonly mediated by promoter methylation, and other regulatory mechanisms are likely to contribute to these alterations.

  7. [The genetics of dementias, Part 3: a molecular basis for the multifactorial inheritance of sporadic Alzheimer's disease].

    Science.gov (United States)

    Kowalska, Anna

    2009-01-01

    The majority of Alzheimer's disease cases, i.e. more than 85% of the whole population of patients, can be referred to as the sporadic form of the disease, with a negative family history and complex inheritance. As the genetic background of sporadic Alzheimer's disease is still largely unknown., strategies based on individual genetic risk profiling for either early prediction of the disease or its therapy and prevention are not possible. The APOE*4 allele of the gene for apolipoprotein E is still the only completely confirmed risk factor. Screening for new genetic risk factors with the use of genetic association analysis has many methodological difficulties and limitations. New combined approaches including genomics, proteogenomics, pharmacogenomics, epigenomics, and bioinformatics have to been applied in the future search for a molecular basis of AD. Genetic defects do not fully explain the complexity of the etiopathogenesis of this disease. It is rather certain that environmental factors (through epigenetic modifications in the patient' sepigenome) also have impact on the initiation of neurodegeneration processes. The identification of new genetic and environmental risk factors would make it possible to understand epistatic processes, for example interactions between genes and between genes and environmental factors, responsible for the complex etiology and multifactorial inheritance of sporadic Alzheimer's disease. PMID:20009121

  8. Deletion of Crry, the murine ortholog of the sporadic Alzheimer's disease risk gene CR1, impacts tau phosphorylation and brain CFH

    OpenAIRE

    Killick, R.; Hughes, T. R.; Morgan, B. P.; Lovestone, S.

    2013-01-01

    ? Crry is the murine ortholog of the sporadic Alzheimer's risk gene CR1. ? Deletion of Crry results in decreased tau phosphorylation. ? Deletion of Crry results in reduction in brain CFH – a biomarker of disease progression.

  9. Genetic association of urokinase-type plasminogen activator gene rs2227564 site polymorphism with sporadic Alzheimer's disease in the Han Chinese population?

    OpenAIRE

    Ji, Xuelian; Jia, Longfei; Jia, Jianping; Qi, Li

    2012-01-01

    A missense C/T polymorphism in exon 6 (the NCBI rsID is rs2227564) of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer's disease risk. The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer's disease by PCR-restriction fragment length polymorphism. Results showed that CC, CT and TT genotype distribution frequencies had significant differences between sporadic Alzheimer's disease patien...

  10. Investigation of DNA damage response and apoptotic gene methylation pattern in sporadic breast tumors using high throughput quantitative DNA methylation analysis technology

    OpenAIRE

    Prakash Neeraj; Gupta Pawan; Gochhait Sailesh; Chopra Rupali; Srivastava Niloo; Pal Ranjana; Agarwal Gaurav; Nk, Bamezai Rameshwar

    2010-01-01

    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 ...

  11. Mutation of the PAX6 gene in a sporadic patient with atypical aniridia

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, D.; Li, Y.; Traboulsi, E.I. [Wilmer Eye Institute, Baltimore, MD (United States)] [and others

    1994-09-01

    A 28 year-old man presented with poor vision since childhood and gradual further decline of several years duration. His visual acuity measures 20/200 OD with -11.50 + 0.50 x 150 and 20/100 OS with -12.25 + 0.25 x 35. He had a fine nystagmus. His visual fields were full. There was a circumferential pannus with areas of corneal stromal opacification. The iris was hypoplastic with atypical colobomatous defects. The lenses had scattered cortical opacities. The intraocular pressures were normal. The optic nerves had cup disk ratios of 0.6 OU. The family history was negative for similar defects. A diagnosis of aniridia was made and blood was drawn for analysis of the PAX6 gene. PCR amplification of exon 5 showed heterozygous fragments with one allele being larger than normal. Direct DNA sequencing of the individual heterozygous allele showed a 41 base pair insertion at nucleotide 483 in exon 5 of the paired domain. This frameshift mutation changed codon 71 to a stop codon. The diagnosis of aniridia was confirmed in this atypical patient, who will need to be monitored for his high risk of glaucoma. The risk of developing Wilms` tumor in patients with mutations within the aniridia gene is presumably negligible since the neighboring Wilms` tumor gene is unaffected. The identification of intragenic mutations of the PAX6 gene in patients with sporadic aniridia modifies the management of such patients because of recognition of the increased risk of glaucoma and by reducing the necessity for frequent monitoring for the presence of Wilms` tumor.

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

    Directory of Open Access Journals (Sweden)

    Edward C. Mader

    2013-02-01

    Full Text Available 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. Electroencephalography (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.

  13. De novo FUS mutations in 2 Korean patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kim, Young-Eun; Oh, Ki-Wook; Kwon, Min-Jung; Choi, Won-Jun; Oh, Seong-Il; Ki, Chang-Seok; Kim, Seung Hyun

    2015-03-01

    Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder. Approximately 5% of ALS patients are familial (fALS) cases, and the remaining 95% are apparently sporadic (sALS) cases. To date, a number of genes have been discovered as associated with ALS, but the genetic background of sALS is not yet fully understood. The occurrence of de novo mutations in ALS genes might be an explanation for sALS, but reduced penetrance could be an alternative theory. Previously, we screened mutations in 5 ALS genes including SOD1 and FUS in 9 fALS and 249 sALS patients and found a total of 15 patients with either SOD1 (7 fALS and 3 sALS) or FUS (1 fALS and 4 sALS) mutations. Interestingly, only 1 fALS patient had the FUS mutation, whereas 4 sALS patients had mutations in this gene. To determine if the FUS mutations in sALS were de novo, we performed genetic analysis on 2 sALS patients with living parents. Genetic analysis confirmed that 2 FUS mutations, including the c.1483C>T (p.Arg495*) and the c.1509_1510delAG (p.Gly504Trpfs*12) mutations, were found only in the patients and not in their parents, confirming the de novo occurrence of these mutations. These findings support the notion that de novo mutations are responsible for a certain proportion of sALS. PMID:25457557

  14. Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study

    Science.gov (United States)

    Davanipour, Zoreh; Sobel, Eugene; Ziogas, Argyrios; Smoak, Carey; Bohr, Thomas; Doram, Keith; Liwnicz, Boleslaw

    2014-01-01

    Aims This study’s primary purpose was to determine whether earlier findings suggesting an association between sporadic Creutzfeldt-Jakob disease (sCJD), a transmissible spongiform encephalopathy of humans and specific dietary components could be replicated. The a priori hypotheses were that consumption of (i) foods likely to contain organ tissue and (ii) raw/rare meat are associated with increased sCJD risk. Study Design Population-based case-control study. Place and Duration of Study Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 4 years. Methodology An 11-state case-control study of pathologically confirmed, definite sCJD cases, matched controls, and a sample of control-surrogates was conducted. Ninety-six percent (106/110) of the case data was obtained in 1991-1993, prior to variant CJD publicity. Results Using control self-responses, consumption of hot dogs, sausage, pepperoni, kielbasa, “other” canned meat, poultry liver, any stomach/intestine, beef stomach/intestine, any organ tissue, and beef organ tissue was individually associated with increased sCJD risk; odds ratios (OR) ranged from 2.4 to 7.2 (0.003 sausage, pepperoni and kielbasa was associated with significantly higher risk. The OR for gizzard consumption was 7.6, p<0.04. Bologna, salami, any liver, beef liver and pork stomach/intestine were marginally associated with sCJD: ORs ranged from 1.7 to 3.7; 0.05

  15. Hypermethylation-associated transcriptional silencing of E-cadherin in primary sporadic colorectal carcinomas.

    Science.gov (United States)

    Garinis, George A; Menounos, Panayiotis G; Spanakis, Nick E; Papadopoulos, Kostas; Karavitis, George; Parassi, Ismailou; Christeli, Evangelia; Patrinos, George P; Manolis, Evangelos N; Peros, George

    2002-12-01

    Loss of E (epithelial)-cadherin expression has been previously documented in sporadic colorectal carcinomas (SCRCs), but not as a consequence of mutations or allelic loss. In this study, the methylation status of the E-cadherin promoter was examined by utilizing the methylation-specific polymerase chain reaction (MSP) assay in 63 primary SCRCs and paired adjacent normal tissues. This was correlated with E-cadherin expression at both the RNA and the protein levels using multiplex reverse transcription (RT)-PCR and immunohistochemistry (IHC), respectively. Data were associated with the patients' clinicopathological features. Methylated alleles were present in 34/61 (56%) of the samples examined. Decreased E-cadherin mRNA expression was demonstrated in 29/61 carcinomas (47.5%) and was significantly associated with lymph node (LN) metastases (p = 0.03, Kruskal-Wallis) and tumour stages Astler-Coller B1 and B2 (p = 0.01, chi(2)). E-cadherin IHC expression was significantly associated with the absence of LN metastases (p = 0.01, chi(2)) and tumour stages Astler-Coller B1 and B2 (p = 0.002, Kruskal-Wallis) in 28/63 (44.4%) of the samples examined. Twenty-three out of 29 (79.3%) samples with decreased mRNA expression and 20/33 (60.6%) with detected protein expression revealed methylated (p = 0.03, Kruskal-Wallis) and unmethylated (p = 0.01, Kruskal-Wallis) alleles, respectively. In agreement with previous work demonstrating that somatic mutations and loss of heterozygosity of the E-cadherin gene are rare or absent in the majority of SCRCs studied so far, this study reports a consistent and uniform decrease or absence of E-cadherin expression, associated with aberrant methylation, in the majority of carcinomas examined, suggesting an epigenetically mediated loss of E-cadherin function in these carcinomas. PMID:12434413

  16. Sporadic amyotrophic lateral sclerosis of long duration is associated with relatively mild TDP-43 pathology.

    Science.gov (United States)

    Nishihira, Yasushi; Tan, Chun-Feng; Hoshi, Yasuhiro; Iwanaga, Keisuke; Yamada, Megumi; Kawachi, Izumi; Tsujihata, Mitsuhiro; Hozumi, Isao; Morita, Takashi; Onodera, Osamu; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2009-01-01

    Recently, sporadic amyotrophic lateral sclerosis (SALS), a fatal neurological disease, has been shown to be a multisystem proteinopathy of TDP-43 in which both neurons and glial cells in the central nervous system are widely affected. In general, the natural history of SALS is short (<5 years). However, it is also known that a few patients may survive for 10 years or more, even without artificial respiratory support (ARS). In the present study using TDP-43 immunohistochemistry, we examined various regions of the nervous system in six patients with SALS of long duration (10-20 years) without ARS, in whom lower motor-predominant disease with Bunina bodies and ubiquitinated inclusions (UIs) in the affected lower motor neurons was confirmed. One case also showed UIs in the hippocampal dentate granule cells (UDG). In all cases, except one with UDG, the occurrence of TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs) was confined to a few regions in the spinal cord and brainstem, including the anterior horns. In one case with UDG, TDP-43-ir NCIs were also detected in the substantia nigra, and some regions of the cerebrum, including the hippocampal dentate gyrus (granule cells). The number of neurons displaying NCIs in each region was very small (1-3 per region, except the dentate gyrus). On the other hand, the occurrence of TDP-43-ir glial cytoplasmic inclusions (GCIs) was more widespread in the central nervous system, including the cerebral white matter. Again, however, the number of glial cells displaying GCIs in each region was very small (1-3 per region). In conclusion, compared to the usual form of SALS, TDP-43 pathology shown in SALS of long duration was apparently mild in degree and limited in distribution, corresponding to the relatively benign clinical courses observed. It is now apparent that SALS of long duration is actually part of a TDP-43 proteinopathy spectrum. PMID:18923836

  17. Impact of sporadic reporting of poultry Salmonella serovars from selected developing countries.

    Science.gov (United States)

    Barbour, Elie K; Ayyash, Danielle B; Alturkistni, Wafa; Alyahiby, Areej; Yaghmoor, Soonham; Iyer, Archana; Yousef, Jehad; Kumosani, Taha; Harakeh, Steve

    2015-01-01

    This review documents the sporadic reporting of poultry Salmonella serovars in South Africa, Egypt, Indonesia, India, and Romania, five countries selected based on the importance of their distribution in different regions of the world and their cumulative significant population size of 1.6 billion. South Africa reported contamination of its poultry carcasses by S. Hadar, S. Blockley, S. Irumu, and S. Anatum. Results from Egypt showed that S. Enteritidis and S. Typhimurium were predominant in poultry along with other non-typhoid strains, namely S. Infantis, S. Kentucky, S. Tsevie, S. Chiredzi, and S. Heidelberg. In Indonesia, the isolation of Salmonella Typhi was the main focus, while other serovars included S. Kentucky, S. Typhimurium, and S. Paratyhi C. In India, S. Bareilly was predominant compared to S. Enteritidis, S. Typhimurium, S. Paratyphi B, S. Cerro, S. Mbandaka, S. Molade, S. Kottbus, and S. Gallinarum. Romania reported two Salmonella serovars in poultry that affect humans, namely S. Enteritidis and S. Typhimurium, and other non-typhoid strains including S. Infantis, S. Derby, S. Colindale, S. Rissen, S. Ruzizi, S. Virchow, S. Brandenburg, S. Bredeney, S. Muenchen, S. Kortrijk, and S. Calabar. The results showed the spread of different serovars of Salmonella in those five developing countries, which is alarming and emphasizes the urgent need for the World Health Organization Global Foodborne Infections Network (WHO-GFN) to expand its activities to include more strategic participation and partnership with most developing countries in order to protect poultry and humans from the serious health impact of salmonellosis. PMID:25596565

  18. Thymidylate synthase gene (TYMS polymorphisms in sporadic and hereditary breast cancer

    Directory of Open Access Journals (Sweden)

    Junior José da Silva Nogueira

    2012-12-01

    Full Text Available Abstract Background Breast cancer (BC is a genetic disorder characterized by growth and proliferation of breast cells in a disorderly. In Brazil, there are approximately 49.240 new cases of BC, every year. The BC etiology is still poorly understood. The BC can be sporadic (SBC or hereditary (HBC. Recent studies have correlated gene polymorphisms with the BC, such as alterations in thymidylate synthase gene (TYMS, which are used to improve diagnosis and prevention of the disease. Polymorphisms in the TYMS gene 5’-UTR region, usually present reps double (2R and/or triple (3R. Studies have shown that homozygous 3R/3R is overexpressed compared with 2R/2R genotype, and these polymorphic variations may contribute to individual susceptibility to the development of BC. In this context, the objective of this study was to evaluate the frequency of the TYMS 2R and 3R polymorphisms, comparing genotypic and allelic distribution with SBC and HBC patients. Methods In this study we included a total of 204 subjects, 70 with BC (33 with SBC, and 37 with HBC and 134 healthy subjects (controls. The Polymerase Chain Reaction was the method used. Results Results demonstrated a high frequency of the 3R allele at BC, SBC, and HBC groups. The frequency of genotype 2R/3R was significantly higher in BC group. This work showed association between the 2R/3R variants (OR = 4.14, CI95% = 1.77-9.71 in the development of SBC, and 2R/2R (OR = 0.233, CI95% = 1.63-7.65 and 2R/3R (OR = 3.53, CI95% = 0.06-0.81 for developing HBC. To BC, there was association with the genotype 2R/3R (OR: 3.79, CI95% = 2.03-7.08. Conclusion Our results show relation to the development of BC in association with the analyzed polymorphisms.

  19. 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.

  20. 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

    2013-02-11

    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

  1. Angiotensin-converting enzyme gene polymorphisms and risk for sporadic Alzheimer's disease: a meta-analysis.

    Science.gov (United States)

    Wang, Xue-Bin; Cui, Ning-Hua; Gao, Jia-Jia; Qiu, Xue-Ping; Yang, Na; Zheng, Fang

    2015-02-01

    Numerous studies have tested for associations between common polymorphisms of the angiotensin-converting enzyme gene and sporadic Alzheimer disease (SAD), but results have been inconclusive. Using meta-analysis, our study aimed to clarify the nature of the genetic risks contributed by the three polymorphisms (rs4291, rs4343, rs1800764) for developing SAD. Through searching of Pubmed, Embase, Alzgene and manually searching relevant references, a total of 14 articles with 26 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association studies. The heterogeneity across the studies was tested, as was publication bias. We observed significant association between SNP rs4291 and SAD using allelic comparison (OR = 1.08, 95% CI 1.03-1.14), homozygote comparison (OR = 1.16, 95% CI 1.04-1.30) and the recessive model (OR = 1.10, 95% CI 1.02-1.18). Association with SNP rs1800764 was revealed but it was not sufficiently robust to withstand the Benjamini-Hochberg method and stepdown Bonferroni correction. Significant association was not identified in the analysis for SNP rs4343. In subgroup analyses, the risk of SAD associated with SNP rs4291 appeared to be significant among Caucasians and in older cases (mean age ?75 years). Our results confirmed a significant but modest association between SNP rs4291 and SAD susceptibility. Further study of the pathogenetic characteristics of this polymorphism and independent confirmation of the association in larger studies are warranted. PMID:24851853

  2. Loss of heterozigosity in the short arm of human chromosome 3 in sporadic lung cancer

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    Lina Marcela Barrera

    2010-12-01

    Full Text Available Introduction: Loss of Heterozygocity (LOH in the short arm of human chromosome 3 (3p is a frequent event in different types of sporadic tumors, including lung cancer (LC.Aim: To determine 3p LOH in LC samples using 17 microsatellite markers.Methodology: In a pilot study on volunteers, thirteen LC biopsies (tumor tissue and 4 ml of blood (normal tissue from the same patient were collected. DNA extraction and Polymerase Chain Reaction (PCR were performed with 17 microsatellite markers to analyze LOH. Amplified fragments were run on 6% denaturalizing polyacrilamide gels and were visualized by using silver stain. Descriptive analysis was performed for each region on the 3p chromosome.Results: All tumors were informative for one or more of the analyzed markers. LOH was found in one or more loci in eleven samples (84.6%. The markers with major LOH were UBE1L (23.1%, D3S1317, D3S1300, D3S1284, D3S1274, D3S3049, and D3S1577 (15.4%. Three samples showed microsatellite instability (changes in the length of the microsatellite in different loci. The percentages of LOH for the regions of 3p were: 17.6 % for 3p24-25, 11.62% for 3p21-22, 20% for 3p13-14, and 18.42% for the 3p12 region.Conclusions: Chromosomal regions with allelic loss were identified where probably other GSTs involved in the development of the LC are localized. It should increases sample size and marker number in order to narrow a minimal region and to identify a unknown gene involved in LC.

  3. Genetic Association Between APP, ADAM10 Gene Polymorphism, and Sporadic Alzheimer's Disease in the Chinese Population.

    Science.gov (United States)

    Zeng, Fan; Shen, Cheng; Liu, Yu-Hui; Li, Jing; Zhu, Jie; Wang, Ye-Ran; Yan, Jia-Chuan; Gao, Chang-Yue; Zhou, Hua-Dong; Deng, Juan; Wang, Yan-Jiang

    2015-04-01

    Amyloid precursor protein (APP) is cleaved by ?-secretase and ?-secretase complex, and subsequently generates amyloid-? peptide (A?). The A? cascade is widely accepted as playing a role in the pathogenesis Alzheimer's disease (AD). Meanwhile, procession of APP by ?-secretase (mainly a disintegrin and metalloproteinase 10, ADAM10) precludes A? production, and produces soluble APP-? which is considered to be neuroprotective against AD. To explore the relationship between APP, ADAM10 gene polymorphism and sporadic AD (sAD), we conducted a case-control study in a Chinese Han cohort including 200 sAD patients and 243 control participants. Four target single nucleotide polymorphisms (SNPs) in or near the promoter of the APP gene and two in the promoter of the ADAM10 gene were selected and genotyped with a polymerase chain reaction-ligase detection reaction method. After adjustments for age, sex, and APOE ?4 status, only one target SNP, rs463946 was associated with the risk of sAD in the dominant (OR 1.52, 95 % CI 1.01-2.29, P = 0.045) and overdominant models (OR 1.59, 95 % CI 1.04-2.43, P = 0.031); the results also showed a borderline association of rs364048 (OR 1.53, 95 % CI 1.00-2.34, P = 0.048) and rs466433 (OR 1.53, 95 % CI 1.00-2.34, P = 0.048) with the risk of sAD in the overdominant model. However, these associations did not remain after multiple comparison correction. As for the ADAM10 gene, the two target SNPs (rs514049 and rs653765) were not associated with the risk of sAD either. No significant association was found between different haplotypes of the two genes and the risk of sAD. Conclusively, we did not find the association between APP, ADAM10 gene polymorphism, and the risk of sAD in our cohort of Chinese Han people. PMID:25631235

  4. Genetic and epigenetic silencing of the beclin 1 gene in sporadic breast tumors

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    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 beclin 1 in breast cancer.

  5. Sporadic Colorectal Cancer Development Shows Rejuvenescence Regarding Epithelial Proliferation and Apoptosis

    Science.gov (United States)

    Leiszter, Katalin; Galamb, Orsolya; Sipos, Ferenc; Krenács, Tibor; Veres, Gábor; Wichmann, Barnabás; Kalmár, Alexandra; Patai, Árpád V.; Tóth, Kinga; Valcz, Gábor; Molnár, Béla; Tulassay, Zsolt

    2013-01-01

    Background and Aims Sporadic colorectal cancer (CRC) development is a sequential process showing age-dependency, uncontrolled epithelial proliferation and decreased apoptosis. During juvenile growth cellular proliferation and apoptosis are well balanced, which may be perturbed upon aging. Our aim was to correlate proliferative and apoptotic activities in aging human colonic epithelium and colorectal cancer. We also tested the underlying molecular biology concerning the proliferation- and apoptosis-regulating gene expression alterations. Materials and Methods Colorectal biopsies from healthy children (n1?=?14), healthy adults (n2?=?10), adult adenomas (n3?=?10) and CRCs (n4?=?10) in adults were tested for Ki-67 immunohistochemistry and TUNEL apoptosis assay. Mitosis- and apoptosis-related gene expression was also studied in healthy children (n1?=?6), adult (n2?=?41) samples and in CRC (n3?=?34) in HGU133plus2.0 microarray platform. Measured alterations were confirmed with RT-PCR both on dependent and independent sample sets (n1?=?6, n2?=?6, n3?=?6). Results Mitotic index (MI) was significantly higher (p<0.05) in intact juvenile (MI?=?0.33±0.06) and CRC samples (MI?=?0.42±0.10) compared to healthy adult samples (MI?=?0.15±0.06). In contrast, apoptotic index (AI) was decreased in children (0.13±0.06) and significantly lower in cancer (0.06±0.03) compared to healthy adult samples (0.17±0.05). Eight proliferation- (e.g. MKI67, CCNE1) and 11 apoptosis-associated genes (e.g. TNFSF10, IFI6) had altered mRNA expression both in the course of normal aging and carcinogenesis, mainly inducing proliferation and reducing apoptosis compared to healthy adults. Eight proliferation-associated genes including CCND1, CDK1, CDK6 and 26 apoptosis-regulating genes (e.g. SOCS3) were differently expressed between juvenile and cancer groups mostly supporting the pronounced cell growth in CRC. Conclusion Colorectal samples from children and CRC patients can be characterized by similarly increased proliferative and decreased apoptotic activities compared to healthy colonic samples from adults. Therefore, cell kinetic alterations during colorectal cancer development show uncontrolled rejuvenescence as opposed to the controlled cell growth in juvenile colonic epithelium. PMID:24098334

  6. Macroautophagy in sporadic and the genetic form of Parkinson's disease with the A53T ?-synuclein mutation

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    Huang Yue

    2012-01-01

    Full Text Available Abstract Background The A53T mutation in the ?-synuclein gene causes autosomal-dominant Lewy body Parkinson's disease (PD. Cultured cell models have linked this mutation to increased cell macroautophagy, although evidence of enhanced macroautophagy in patients with this mutation has not been assessed. Objective To determine whether macroautophagy is increased by the A53T ?-synuclein gene mutation in PD patients and cell models. Methods Formalin-fixed paraffin-embedded 10 ?m-thick tissue sections from the substantia nigra and anterior cingulate cortex of two PD patients with the A53T ?-synuclein gene mutation were compared with four sporadic PD cases and four controls obtained from the Sydney Brain Bank. Lewy bodies were isolated from frontal cortex of a case with late stage PD (recruited from South Australian Brain Bank. Immunohistochemistry was performed for ?-synuclein and the macroautophagy markers autophagy-specific gene (ATG 5, ATG6/Beclin1 and ATG8/LC3. SH-SY5Y cells were transfected with wild type or A53T mutant ?-synuclein plasmids and observable changes in macroautophagy marker protein levels assessed using Western blotting. Results ?-Synuclein immunoreactive neurites and dots were more numerous in patients with A53T mutations compared with late stage sporadic PD patients, and perinuclear cytoplasmic ?-synuclein aggregates were observed in the ?-synuclein A53T gene transfected SH-SY5Y cells compared to wild type transfections. All PD patients (with or without A53T mutations had increased immunohistochemical evidence for macroautophagy compared with controls, and the levels of the ATG5 complex were equally increased in wild type and A53T ?-synuclein gene transfected cells compared to controls. Conclusion Despite increased ?-synuclein accumulation with A53T mutations, macroautophagy is not increased above that observed in sporadic patients with PD or in cells transfected with wild type ?-synuclein, suggesting that mutated ?-synuclein protein is not removed by macroautophagy.

  7. Congratulation to Margaret Chan Familial and Sporadic GJB2-Related Deafness in Iran: Review of Gene Mutations

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    M Hashemzadeh Chaleshtori

    2007-05-01

    Full Text Available Background: Mutations in the GJB2 gene encoding connexin 26 protein, are the main cause for autosomal recessive and sporadic non syndromic hearing loss in many populations. Here, we have taken together and reviewed results from our six previous publications, our unpublished data from ten Iranian provinces, as well as data from two previous mutation reports to provide a comprehensive collection of data for GJB2 mutations and deafness in Iran. Methods: In all, 1095 hearing impaired students and their deaf siblings from 890 families in 10 provinces of Iran were studied. The prevalence and type of the GJB2 gene mutations were investigated using nested PCR pre screening strategy and direct sequencing of the coding exon of the gene. Results: Altogether 31 different genetic variants were detected from which 17 GJB2 mutations were identified. GJB2 mutations were found in 14.6% of deaf families (18.29% of familial and 12.7% of sporadic cases. We found GJB2 mutations in both alleles in 78% of GJB2 mutations chromosomes. However, 35delG mutation was the most common GJB2 mutation accounting for 74.5% of the mutations in populations studied. Conclusion: Our data indicated that a specific combination of GJB2 mutations types and frequencies was presented in different populations of Iran. These results also highlight the importance of GJB2 mutations in development of hearing loss in familial and sporadic deaf families in different parts of the country and can be used as a basis of genetic counseling and clinical guideline in Iran.

  8. Source attribution of human campylobacteriosis using a meta-analysis of case-control studies of sporadic infections

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

    2012-01-01

    Campylobacter spp. is a widespread and important cause of human illness worldwide. Disease is frequently associated with foodborne transmission, but other routes of exposure, such as direct contact with live animals and person-to-person transmission, are also recognized. 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 campylobacteriosis have been published. These studies investigated a variety of potential risk factors for disease, often using different methodologies and settings. Systematic reviews (SRs) consist of a formal process for literature review focused on a specific research question, and include the identification of relevant literature, quality assessment of relevant studies, summarization or statistical analysis of data, and conclusions. With the objective of identifying the most important risk factors for human sporadic campylobacteriosis, we performed a SR of case-control studies of human sporadic cases and a meta-analysis of the obtained results. A combined SR focusing on Salmonella and Campylobacter studies was performed and the results analysed separately. From 1295 identified references, 131 passed the relevance screening, 73 passed the quality assessment stage, and data was extracted from 72 studies. Of these, 38 focused on campylobacteriosis. Information on exposures of cases and controls, and estimated odds ratios for investigated risk factors were collected and analysed. In the meta-analysis, heterogeneity between the studies and possible sources of bias were investigated, and pooled odds ratios for identified risk factors were estimated. Results suggest that travelling abroad, eating undercooked chicken, environmental sources, and direct contact with farm animals were significant risk factors for campylobacteriosis. Sub-analyses by geographical region, age group, and study period were performed, and differences were discussed.

  9. The role of electric fields in sporadic E layer formation over low latitudes under quiet and magnetic storm conditions

    Science.gov (United States)

    Abdu, M. A.; de Souza, J. R.; Batista, I. S.; Santos, A. M.; Sobral, J. H. A.; Rastogi, R. G.; Chandra, H.

    2014-08-01

    Sporadic E layers are formed dominantly by wind shear mechanism, but their formation and dynamics are driven also by ionospheric electric fields. Investigation of low latitude sporadic E layers under quiet conditions shows that Es layer formation during post sunset hours can be disrupted or enhanced depending upon the vertical structure of the vertical electric field arising from sunset electrodynamic processes. During magnetic storms the formation and disruption of these layers are also strongly controlled by vertical Hall electric field induced by the zonal magnetospheric electric fields that penetrates to equatorial/low latitude ionosphere. Observational results on storm time Es layer responses in the Brazilian and Indian-Asian longitudes are compared. An under-shielding prompt penetration electric field (PPEF) of westward polarity that dominate the night side ionosphere, or an over-shielding electric field also of westward polarity in the evening sector can cause formation of sporadic E layers near 100 km, while an eastward polarity electric field, (under-shielding/over-shielding depending upon local time) can lead to disruption of an Es layer in progress. Ionization convergence/divergence leading to the Es layer formation/disruption is driven by a vertical Hall electric field, induced by the primary zonal PPEF, in the presence of storm associated enhanced ratio of field line integrated Hall to Pedersen conductivity (?H)/(?P). A downward polarity of the Hall electric field leads to Es layer formation, while an upward polarity causes the Es layer disruption. An enhancement in the ?H/?P ratio can result from E layer conductivity enhancement due to energetic particle precipitation peculiar to the longitude of the South Atlantic Magnetic Anomaly (SAMA) and/or from a drastic reduction in integrated Pederson conductivity in the form of reduced foF2 that is observed in all longitudes.

  10. Transcription of Alu DNA elements in blood cells of sporadic Creutzfeldt-Jakob disease (sCJD)

    OpenAIRE

    Kiesel, Petra; Gibson, Toby J.; Ciesielczyk, Barbara; Bodemer, Monika; Kaup, Franz-josef; Bodemer, Walter; Zischler, Hans; Zerr, Inga

    2010-01-01

    Alu DNA elements were long considered to be of no biological significance and thus have been only poorly defined. However, in the past Alu DNA elements with well-defined nucleotide sequences have been suspected to contribute to disease, but the role of Alu DNA element transcripts has rarely been investigated. For the first time, we determined in a real-time approach Alu DNA element transcription in buffy coat cells isolated from the blood of humans suffering from sporadic Creutzfeldt-Jakob di...

  11. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma.

    OpenAIRE

    Pelicci, P. G.; Knowles, D. M.; Magrath, I.; Dalla-favera, R.

    1986-01-01

    We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines. This panel includes the two pathogenetic forms of BL: the endemic (African-type) BL (eBL) and sporadic (American-type) BL (sBL). In all cases tested, including fresh samples and cell lines, structural alterations of the 5' portion of the gene were detected...

  12. Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30.

    Science.gov (United States)

    Sofic, E; Salkovic-Petrisic, M; Tahirovic, I; Sapcanin, A; Mandel, S; Youdim, M; Riederer, P

    2015-04-01

    Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p sAD and indicate that multifunctional iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model. PMID:25252744

  13. miR-338-3p is over-expressed in blood, CFS, serum and spinal cord from sporadic amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    De Felice, Bruna; Annunziata, Anna; Fiorentino, Giuseppe; Borra, Marco; Biffali, Elio; Coppola, Cinzia; Cotrufo, Roberto; Brettschneider, Johannes; Giordana, Maria Luisa; Dalmay, Tamas; Wheeler, Guy; D'Alessandro, Raffaella

    2014-10-01

    Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Ninety percent of ALS patients are sporadic cases (sALS) with no clear genetic linkage. Accumulating evidence indicates that various microRNAs (miRNAs), expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, microRNA dysregulation contributes to some mental disorders and neurodegeneration diseases. In our research, the expression of one selected miRNA, miR-338-3p, which previously we have found over-expressed in blood leukocytes, was studied in several different tissues from sALS patients. For the first time, we detected a specific microRNA disease-related upregulation, miR-338-3p, in blood leukocytes as well in cerebrospinal fluid, serum, and spinal cord from sALS patients. Besides, staining of in situ hybridization showed that the signals of miR-338-3p were localized in the grey matter of spinal cord tissues from sALS autopsied patients. We propose that miRNA profiles found in tissue samples from sALS patients can be relevant to understand sALS pathogenesis and lead to set up effective biomarkers for sALS early diagnosis. PMID:25130371

  14. Mutation analysis of glial cell line-derived neurotrophic factor (GDNF), a ligand for the RET/GDNF receptor alpha complex, in sporadic phaeochromocytomas.

    Science.gov (United States)

    Dahia, P L; Toledo, S P; Mulligan, L M; Maher, E R; Grossman, A B; Eng, C

    1997-01-15

    Phaeochromocytomas usually occur sporadically but may also be a feature of three autosomal dominantly inherited cancer syndromes, multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and, very rarely, type 1 neurofibromatosis. Germ-line missense mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, cause multiple endocrine neoplasia type 2. In VHL, germ-line mutations in one of the three exons of the VHL tumor suppressor gene have been found in the majority of families. Whereas somatic mutations in the VHL gene have been common in sporadic renal cell carcinoma, a component cancer of VHL, somatic mutations in the RET and VHL genes together have been found in approximately 10% of sporadic phaeochromocytomas. Hence, other genes must also contribute to the pathogenesis of sporadic phaeochromocytomas. Recent data have suggested that glial cell line-derived neurotrophic factor (GDNF) is a ligand for RET and acts via a heterotetrameric receptor complex that includes GDNF receptor alpha, which provides ligand binding capabilities, and RET, which provides the signaling component. Thus, both GDNF and GDNFR-alpha are plausible candidate genes for involvement in the pathogenesis of phaeochromocytomas. To investigate the role of GDNF in sporadic phaeochromocytomas, we scanned a panel of 22 tumors. Among these samples, only a conservative sequence variant was detected in exon 2 of GDNF. No disease-associated somatic GDNF mutations or gross gene amplification were detected in these tumors, suggesting only a minor role for GDNF in the genesis of phaeochromocytomas. PMID:9000574

  15. Genomic mosaicism with increased amyloid precursor protein (APP) gene copy number in single neurons from sporadic Alzheimer's disease brains.

    Science.gov (United States)

    Bushman, Diane M; Kaeser, Gwendolyn E; Siddoway, Benjamin; Westra, Jurgen W; Rivera, Richard R; Rehen, Stevens K; Yung, Yun C; Chun, Jerold

    2015-01-01

    Previous reports have shown that individual neurons of the brain can display somatic genomic mosaicism of unknown function. In this study, we report altered genomic mosaicism in single, sporadic Alzheimer's disease (AD) neurons characterized by increases in DNA content and amyloid precursor protein (APP) gene copy number. AD cortical nuclei displayed large variability with average DNA content increases of ~8% over non-diseased controls that were unrelated to trisomy 21. Two independent single-cell copy number analyses identified amplifications at the APP locus. The use of single-cell qPCR identified up to 12 copies of APP in sampled neurons. Peptide nucleic acid (PNA) probes targeting APP, combined with super-resolution microscopy detected primarily single fluorescent signals of variable intensity that paralleled single-cell qPCR analyses. These data identify somatic genomic changes in single neurons, affecting known and unknown loci, which are increased in sporadic AD, and further indicate functionality for genomic mosaicism in the CNS. PMID:25650802

  16. Sporadic renal cell carcinoma in young and elderly patients: are there different clinicopathological features and disease specific survival rates?

    Directory of Open Access Journals (Sweden)

    Junker Kerstin

    2007-02-01

    Full Text Available Abstract Background Sporadic renal cell carcinoma (RCC is rare in young adults. In the present retrospective study we reviewed clinicopathological features and disease specific survival rates in young patients (?45 years with RCC and compared them to old patients (?75 years with RCC. Methods Between 1992 and 2005 a total of 1042 patients were treated for RCC at our institution. We found 70 patients 45 years or younger (YP and 150 patients 75 years or older (OP at time of diagnosis. There were no differences in therapeutical approaches between both groups. Clinical and biologic parameters at diagnosis were compared and subjected to uni- and multivariate analysis to study cancer specific survival and progression rate. Mean postoperative follow-up in both groups was 50.1 months. Results Mean age was 39 years in YP and 80 years in OP, respectively. YP demonstrated significantly lower stage (pT1-pT2 N0 M0, p = 0.03, lower tumor grade (p = 0.01 and higher male-to-female ratio (p Conclusion Sporadic RCC in young patients have lower tumor stages and grades and a better outcome compared to elderly. Age?45 years was an independent prognostic factor for survival and progression.

  17. Diagnostic strategy for familial and sporadic cases of neuropathy associated with 17p11.2 deletion.

    Science.gov (United States)

    Infante, J; García, A; Combarros, O; Mateo, J I; Berciano, J; Sedano, M J; Gutiérrez-Rivas, E J; Palau, F

    2001-09-01

    Clinical, electrophysiologic and molecular studies were performed on at-risk members of 14 families with hereditary neuropathy with liability to pressure palsies (HNPP), in order to detect asymptomatic carriers of the 17p11.2 deletion. Sporadic cases due to de novo deletion accounted for 21% of the investigated HNPP families. Approximately one half of deletion carriers were asymptomatic and did not display significant signs on clinical examination. The electrophysiologic hallmark in both symptomatic and asymptomatic deletion carriers was the presence of a nonuniform sensorimotor demyelinating polyneuropathy with conduction abnormalities preferentially located at common entrapment sites and distal nerve segments. A perfect correlation was found between the molecular and electrophysiologic analyses. A reliable screening method to detect clinically unaffected carriers of the deletion in families with HNPP was the evaluation of motor conduction in at least two nerves across usual entrapment sites, especially the ulnar nerve at the elbow, and evaluation of sensory conduction in the sural nerve. In sporadic cases due to a de novo deletion, electrophysiologic studies were suggestive but not sufficient for the diagnosis, and molecular analysis represented the most sensitive diagnostic tool. PMID:11494267

  18. Haplotype of gene Nedd4 binding protein 2 associated with sporadic nasopharyngeal carcinoma in the Southern Chinese population

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    Feng Qi-Sheng

    2007-07-01

    Full Text Available Abstract Background Bcl-3 as an oncoprotein is overexpressed in nasopharyngeal carcinoma (NPC. Nedd4 binding protein 2 (N4BP2, which is located in the NPC susceptibility locus, is a Bcl-3 binding protein. This study is aimed to explore the association between N4BP2 genetic polymorphism and the risk of NPC. Methods We performed a hospital-based case-control study, including 531 sporadic NPC and 480 cancer-free control subjects from southern China. PCR-sequencing was carried out on Exons, promoter region and nearby introns of the N4BP2 gene. The expression pattern of N4BP2 and Bcl-3 was also analyzed. Results We observed a statistically significant difference in haplotype blocks ATTA and GTTG between cases and controls. In addition, three novel SNPs were identified, two of which were in exons (loc123-e3l-snp2, position 39868005, A/G, Met171Val; RS17511668-SNP2, position 39926432, G/A, Glu118Lys, and one was in the intron6 (RS794001-SNP1, position 39944127, T/G. Moreover, N4BP2 was at higher levels in a majority of tumor tissues examined, relative to paired normal tissues. Conclusion These data suggest that haplotype blocks ATTA and GTTG of N4BP2 is correlation with the risk of sporadic nasopharyngeal carcinoma in the Southern Chinese population and N4BP2 has a potential role in the development of NPC.

  19. Sporadic E layer Development and Disruption over Low Latitudes by Electric Fields during Quiet-times and Magnetic Storms

    Science.gov (United States)

    Abdu, M. A.; Souza, J. R.; Batista, I. S.; Fejer, B. G.; Sobral, J. H.

    2013-05-01

    Sporadic E layer formation over low- and equatorial latitudes is strongly controlled by electric fields with neutral winds/wind shears being their main drivers. The relative roles of the electric fields and winds vary from quiet to magnetically disturbed conditions. In the quiet time post sunset ionosphere these layers are disrupted or formed by the electric field structure of the plasma flow vortex. A recent investigation during magnetic storms revealed that the formation and disruption of Es layers are strongly controlled by the magnetospheric electric fields that penetrate to equatorial latitudes. A prompt penetration electric field (PPEF) of westward polarity that dominate the night side ionosphere can cause formation of sporadic E layers near 100 km, while a PPEF of eastward polarity that dominate the day- and evening sector can cause the disruption of an Es layer in progress. Generation of vertical Hall electric field, as induced by the primary zonal PPEF, in the presence of storm associated enhanced conductivity of the night E layer, is found to be responsible for vertical ion velocity convergence sufficient to influence the Es layer formation. A downward polarity of the Hall electric field leads to Es layer formation, while an upward polarity causes the Es layer disruption. An interplay of magnetic storm associated prompt penetration electric field and energetic particle precipitation is evident in the storm time Es layer response features observed in the region of the South Atlantic/American Magnetic Anomaly.

  20. Sporadic E layer development and disruption at low latitudes by prompt penetration electric fields during magnetic storms

    Science.gov (United States)

    Abdu, M. A.; Souza, J. R.; Batista, I. S.; Fejer, B. G.; Sobral, J. H. A.

    2013-05-01

    An investigation of low-latitude sporadic E layers during magnetic storms shows that the formation and disruption of these layers are strongly controlled by the magnetospheric electric fields that penetrate to equatorial ionosphere. It is observed that a prompt penetration electric field (PPEF) of westward polarity that dominates the nightside ionosphere can cause formation of sporadic E layers near 100 km, while a PPEF of eastward polarity that dominates the dayside and eveningside can lead to disruption of an Es layer in progress. It is shown that a vertical Hall electric field, induced by the primary zonal PPEF, in the presence of the storm-associated enhanced conductivity of the night E layer, can be responsible for vertical ion velocity convergence sufficient to influence the Es layer formation. A downward polarity of the Hall electric field leads to Es layer formation, while an upward polarity causes the Es layer disruption. An interplay of magnetic storm associated prompt penetration electric field and energetic particle precipitation is evident in the observed Es layer response features in the region of the South Atlantic/American magnetic anomaly reported here.

  1. Telomere shortening: a biological marker of sporadic colorectal cancer with normal expression of p53 and mismatch repair proteins.

    Science.gov (United States)

    Haghighi, Mahdi Montazer; Aghagolzadeh, Parisa; Zadeh, Saman Milani; Molaei, Mahsa; Zali, Mohammad Reza; Radpour, Ramin

    2014-04-01

    Uncontrolled growth of cells, a main criterion of cancer, is merged with pathologic telomere length alteration. Thereby, measurement of telomere length could provide important information on cell proliferation and senescence in cancer tissues. Telomere shortening and its potential correlation with clinicopathological predictive markers in sporadic colorectal cancer (CRC) with normal expression of mismatch repair (MMR) proteins (including Mlh1, Msh2, Pms2, and Msh6) and normal p53 expression was completely explored. Relative telomere length (RTL) was quantitatively measured in a cohort of 164 samples (68 patients with sporadic CRC and 96 healthy unrelated controls). Our results demonstrated a significant shortening of RTL in the tumor-derived tissue of patients compared with the control group (p<0.001). Interestingly, significant telomere shortening was observed in tumors from an ascending and sigmoid colon in comparison with tumors located in a descending colon. Additionally, the telomere length was significantly shorter in those with lymph node metastasis (p<0.05). The results suggest that pathological telomere shortening, leading to genome instability and lymphatic transformation, could serve as a potential sensitive detection and also as a classification marker for facilitating diagnosis and management of CRC. PMID:24495131

  2. Global phylogenomic analysis of nonencapsulated Streptococcus pneumoniae reveals a deep-branching classic lineage that is distinct from multiple sporadic lineages.

    Science.gov (United States)

    Hilty, Markus; Wüthrich, Daniel; Salter, Susannah J; Engel, Hansjürg; Campbell, Samuel; Sá-Leão, Raquel; de Lencastre, Hermínia; Hermans, Peter; Sadowy, Ewa; Turner, Paul; Chewapreecha, Claire; Diggle, Mathew; Pluschke, Gerd; McGee, Lesley; Köseo?lu Eser, Özgen; Low, Donald E; Smith-Vaughan, Heidi; Endimiani, Andrea; Küffer, Marianne; Dupasquier, Mélanie; Beaudoing, Emmanuel; Weber, Johann; Bruggmann, Rémy; Hanage, William P; Parkhill, Julian; Hathaway, Lucy J; Mühlemann, Kathrin; Bentley, Stephen D

    2014-12-01

    The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to ?-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent. PMID:25480686

  3. A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCA1

    OpenAIRE

    Godwin, Andrew K.; Vanderveer, Lisa; Schultz, David C.; Lynch, Henry T.; Altomare, Deborah A.; Buetow, Kenneth H.; Daly, Mary; Getts, Lori A.; Masny, Agnes; Rosenblum, Norman; Hogan, Michael; Ozols, Robert F.; Hamilton, Thomas C.

    1994-01-01

    Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17...

  4. Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer.

    Science.gov (United States)

    Cunningham, Julie M; Hebbring, Scott J; McDonnell, Shannon K; Cicek, Mine S; Christensen, G Bryce; Wang, Liang; Jacobsen, Steven J; Cerhan, James R; Blute, Michael L; Schaid, Daniel J; Thibodeau, Stephen N

    2007-05-01

    Previous studies suggest that enzymes involved in the androgen metabolic pathway are susceptibility factors for prostate cancer. Estrogen metabolites functioning as genotoxins have also been proposed as risk factors. In this study, we systematically tested the hypothesis that common genetic variations for those enzymes involved in the androgen and estrogen metabolic pathways increase risk for sporadic and familial prostate cancer. From these two pathways, 46 polymorphisms (34 single nucleotide polymorphisms, 10 short tandem repeat polymorphisms, and 2 null alleles) in 25 genes were tested for possible associations. Those genes tested included PRL, LHB, CYP11A1, HSD3B1, HSD3B2, HSD17B2, CYP17, SRD5A2, AKR1C3, UGT2B15, AR, SHBG, and KLK3 from the androgen pathway and CYP19, HSD17B1, CYP1A1, CYP1A2, CYP1B1, COMT, GSTP1, GSTT1, GSTM1, NQO1, ESR1, and ESR2 from the estrogen pathway. A case-control study design was used with two sets of cases: familial cases with a strong prostate cancer family history (n = 438 from 178 families) and sporadic cases with a negative prostate cancer family history (n = 499). The controls (n = 493) were derived from a population-based collection. Our results provide suggestive findings for an association with either familial or sporadic prostate cancer with polymorphisms in four genes: AKR1C3, HSD17B1, NQO1, and GSTT1. Additional suggestive findings for an association with clinical variables (disease stage, grade, and/or node status) were observed for single nucleotide polymorphisms in eight genes: HSD3B2, SRD5A2, SHBG, ESR1, CYP1A1, CYP1B1, GSTT1, and NQO1. However, none of the findings were statistically significant after appropriate corrections for multiple comparisons. Given that the point estimates for the odds ratio for each of these polymorphisms are <2.0, much larger sample sizes will be required for confirmation. PMID:17507624

  5. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome.

    Science.gov (United States)

    Hsu, Amy P; Sampaio, Elizabeth P; Khan, Javed; Calvo, Katherine R; Lemieux, Jacob E; Patel, Smita Y; Frucht, David M; Vinh, Donald C; Auth, Roger D; Freeman, Alexandra F; Olivier, Kenneth N; Uzel, Gulbu; Zerbe, Christa S; Spalding, Christine; Pittaluga, Stefania; Raffeld, Mark; Kuhns, Douglas B; Ding, Li; Paulson, Michelle L; Marciano, Beatriz E; Gea-Banacloche, Juan C; Orange, Jordan S; Cuellar-Rodriguez, Jennifer; Hickstein, Dennis D; Holland, Steven M

    2011-09-01

    The syndrome of monocytopenia, B-cell and NK-cell lymphopenia, and mycobacterial, fungal, and viral infections is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis, and myeloid leukemias. Both autosomal dominant and sporadic cases occur. We identified 12 distinct mutations in GATA2 affecting 20 patients and relatives with this syndrome, including recurrent missense mutations affecting the zinc finger-2 domain (R398W and T354M), suggesting dominant interference of gene function. Four discrete insertion/deletion mutations leading to frame shifts and premature termination implicate haploinsufficiency as a possible mechanism of action as well. These mutations were found in hematopoietic and somatic tissues, and several were identified in families, indicating germline transmission. Thus, GATA2 joins RUNX1 and CEBPA not only as a familial leukemia gene but also as a cause of a complex congenital immunodeficiency that evolves over decades and combines predisposition to infection and myeloid malignancy. PMID:21670465

  6. Retrospective analysis of sporadic and recurrent geomagnetic storms documented in 1859-1860 by the Russian network of observatories

    International Nuclear Information System (INIS)

    Complete text of publication follows. Based on an analysis of the available archived data from the Russian network of geomagnetic stations, we demonstrate that the famous Carrington event observed on the Sun in 1859 was responsible for the first and the greatest geomagnetic perturbation in the series of the recurrent geomagnetic storms, which reappeared later during several solar rotations in 1859-1860. Similar series were repeatedly observed in the subsequent years. These series are caused by the processes on the Sun and in the heliosphere related to the superposition of sporadic and corotating solar wind flows. Corresponding interplanetary magnetic fields can be retrospectively invoked from geomagnetic archives. Neither coronal holes nor active regions can separately explain observations. Active regions and coronal holes should be considered as unified complex for a proper explanation of the Bartels's M regions.

  7. Clinical and ultrastructural study of a sporadic case of hereditary sensory neuropathy. Morphological evidence for a slow rate fiber degeneration.

    Science.gov (United States)

    Ermel, A E; Devooght, H; Carton, H

    1979-01-01

    A sporadic case of hereditary sensory neuropathy, with a clinical course and severe trophic and sensory alterations typical for type II, is presented. There was a severe loss of myelin in the sural nerve biopsy taken from the ankle. The most impressive microscopic feature was the number of rudimentary onion bulbs with an empty core which contained nude axons in the peripheral schwann cell layers; they were interpreted as vestigial structures left by the former myelinated fibers. Electron microscopy also revealed a definite involvement of unmyelinated fibers with attempted regeneration, which was confirmed by the overrepresentation of small axons on their frequency distribution curve. The whole ultrastructural picture suggested the protracted nature of the fiber involvement. This may be considered as agreeing with the slow course proposed for a system degeneration. PMID:90133

  8. Source attribution of human salmonellosis using a meta-analysis of case-control studies of sporadic infections

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

    2012-01-01

    Salmonella is an important cause of human illness. Disease is frequently associated with foodborne transmission, but other routes of exposure are recognized. Identifying sources of disease is essential for prioritizing public health interventions. Numerous case-control studies of sporadic salmonellosis have been published, often using different methodologies and settings. Systematic reviews consist of a formal process for literature review focused on a research question. With the objective of identifying the most important risk factors for salmonellosis, we performed a systematic review of case-control studies and a meta-analysis of obtained results. Thirty-five Salmonella case-control studies were identified. In the meta-analysis, heterogeneity between studies and possible sources of bias were investigated, and pooled odds ratios estimated. Results suggested that travel, predisposing factors, eating raw eggs, and eating in restaurants were the most important risk factors for salmonellosis. Sub-analyses by serotype were performed when enough studies were available.

  9. Refined mapping of loss of heterozygosity on 1q31.1-32.1 in sporadic colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Zhou, Guo-Qiang Qiu, Jun-Wei Fan, Xiao-Liang Wang, Hua-Mei Tang, Li Huang, Yu-Hao Sun, Zhi-Hai Peng

    2008-03-01

    Full Text Available AIM: To explore precise deleted regions and screen the candidate tumor suppressor genes related to sporadic colorectal carcinoma.METHODS: Six markers on 1q31.1-32.1 were chosen. These polymorphic microsatellite markers in 83 colorectal cancer patients tumor and normal DNA were analyzed via PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for Loss of heterozygosity (LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors was performed by ?2 test.RESULTS: 1q31.1-32.1 exhibited higher LOH frequency in colorectal carcinoma. The average LOH frequency of 1q31.1-32.1 was 23.0%, with the highest frequency of 36.7% (18/49 at D1S2622, and the lowest of 16.4% (11/67 at D1S412, respectively. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622 (1q31.3-32.1. There was no significant association between LOH of each marker on 1q31.1-32.1 and the clinicopathological data (patient sex, age, tumor size, growth pattern or Dukes stage, which indicated that on 1q31.1-32.1, LOH was a common phenomenon in all kinds of sporadic colorectal carcinoma.CONCLUSION: Through our refined deletion mapping, the critical and precise deleted region was located within 2 cM chromosomal segment encompassing 2 loci (D1S413, D1S2622. No significant association was found between LOH and clinicopathologic features in 1q31.1-32.1.

  10. Immunoreactivity of valosin-containing protein in sporadic amyotrophic lateral sclerosis and in a case of its novel mutant.

    Science.gov (United States)

    Ayaki, Takashi; Ito, Hidefumi; Fukushima, Hiroko; Inoue, Takeshi; Kondo, Takayuki; Ikemoto, Akito; Asano, Takeshi; Shodai, Akemi; Fujita, Takuji; Fukui, Satoshi; Morino, Hiroyuki; Nakano, Satoshi; Kusaka, Hirofumi; Yamashita, Hirofumi; Ihara, Masafumi; Matsumoto, Riki; Kawamata, Jun; Urushitani, Makoto; Kawakami, Hideshi; Takahashi, Ryosuke

    2014-12-10

    BackgroundMutations in the valosin-containing protein (VCP) gene were first found to cause inclusion- body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD). Mutations in the VCP gene were later reported to occur in familial amyotrophic lateral sclerosis (ALS). But the role of VCP in the neurodegenerative processes that occur in ALS remains unknown. The purpose of the present study was to elucidate the role of VCP in the neurodegeneration seen in sporadic and VCP mutant ALS.ResultsImmunohistochemistry demonstrated that the frequency of distinct VCP-positive nuclei of spinal motor neurons of patients with sporadic ALS (SALS) and the ALS with VCP novel mutation (ALS-VCP, M158V) was increased, compared with that of the control cases. No VCP-positive inclusion bodies were observed in SALS patients, a ALS-VCP patient or in control subjects. Neuropathologic examination of the ALS-VCP case showed loss of motor neurons, the presence of Bunina bodies, and degeneration of the corticospinal tracts. Bunina bodies detected in this case were confirmed to show immunohistochemical and ultrastructural features similar to those previously described. Furthermore, neuronal intracytoplasmic inclusions immunopositive for TAR DNA-binding protein 43 kDa (TDP-43), phosphorylated TDP-43, ubiquitin (Ub), p62, and optineurin were identified in the spinal and medullary motoneurons, but not in the neocortex. Gene analysis of this ALS-VCP patient confirmed the de novo mutation of M158V, which was not found in control cases; and bioinformatics using several in silico analyses showed possible damage to the structure of VCP. Immunocytochemical study of cultured cells showed increased cytoplasmic translocation of TDP-43 in cells transfected with several mutant VCP including our patient¿s compared with wild-type VCP.ConclusionThese findings support the idea that VCP is associated with the pathomechanism of SALS and familial ALS with a VCP mutation, presumably acting through a dominant-negative mechanism. PMID:25492614

  11. Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

    Science.gov (United States)

    Liang, Winnie S.; Fonseca, Rafael; Bryce, Alan H.; McCullough, Ann E.; Barrett, Michael T.; Hunt, Katherine; Patel, Maitray D.; Young, Scott W.; Collins, Joseph M.; Silva, Alvin C.; Condjella, Rachel M.; Block, Matthew; McWilliams, Robert R.; Lazaridis, Konstantinos N.; Klee, Eric W.; Bible, Keith C.; Harris, Pamela; Oliver, Gavin R.; Bhavsar, Jaysheel D.; Nair, Asha A.; Middha, Sumit; Asmann, Yan; Kocher, Jean-Pierre; Schahl, Kimberly; Kipp, Benjamin R.; Barr Fritcher, Emily G.; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Phillips, Lori; McDonald, Jackie; Adkins, Jonathan; Mastrian, Stephen D.; Placek, Pamela; Watanabe, Aprill T.; LoBello, Janine; Han, Haiyong; Von Hoff, Daniel; Craig, David W.; Stewart, A. Keith; Carpten, John D.

    2014-01-01

    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. PMID:24550739

  12. A novel tumor suppressor gene RhoBTB2 (DBC2): frequent loss of expression in sporadic breast cancer.

    Science.gov (United States)

    Mao, Haiting; Qu, Xun; Yang, Yongmei; Zuo, Wenshu; Bi, Ye; Zhou, Chengjun; Yin, Haipeng; Deng, Biping; Sun, Jintang; Zhang, Lining

    2010-03-01

    RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cancer patients and normal controls and cell samples from cell lines were collected and reverse transcription (RT)-PCR was used to monitor the presence of RhoBTB2 mRNA. The protein expression of RhoBTB2 was detected by immunohistochemical staining. Cumulative survival time was assessed by the Kaplan-Meier method and Cox regression model. We discovered that RhoBTB2 expression was lacking in a breast ductal epithelial carcinoma cell line T-47D but was expressed in other types of tumor cell lines and normal tissues we tested. The results from tissue samples showed that RhoBTB2 was absent in 60% of breast cancers on both the mRNA and protein level. The results from RT-PCR were completely uniform with those from immunohistochemistry. We demonstrated that loss of RhoBTB2 more frequently occurred in postmenopausal patients of age >or=50 yr old and in patients with infiltrating ductal carcinoma of the breast. The prognostic value of RhoBTB2 in breast cancers also be assessed by a long-term follow-up investigation and we found that patients with RhoBTB2-negative breast cancer were linked to poor clinical prognosis. Therefore, the loss of RhoBTB2 expression is a common occurrence in breast cancers and it is an important factor in the development and prognosis of sporadic breast cancer. PMID:19937980

  13. Genetic abnormalities in sporadic parathyroid adenomas: Loss of heterozygosity for chromosome 3q markers flanking the calcium receptor locus

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, D.B.; Samowitz, W.S.; Davis, K. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)] [and others

    1995-10-01

    Inactivating mutations of the parathyroid cell calcium receptor (CaR) gene cause one form of familial benign/hypocalciuric hypercalcemia, and in homozygous form, cause neonatal severe primary hyperparathyroidism with parathyroid hyperplasia. Thus, we postulated that partial or total loss of CaR function might contribute to calcium insensitivity or even stimulate cell proliferation in sporadic parathyroid adenomas (PAds). To examine this possibility, we sought loss of heterozygosity (LOH) for markers flanking the CaR locus (3cen-3q21) in 35 PAds. We used 16 highly-polymorphic PCR-based markers in paired normal and tumor DNA, extracted from archived surgical specimens. Nineteen to twenty-four of the DNA pairs were informative with at least one marker. In two informative pairs, we found LOH for markers D3S1303, D3S1267, or D3S1269, which are tightly-linked with and flank the CaR locus. In one tumor, deletion mapping confined the lost area between D3S1271 and D3S1238 (41.7 centimorgans, cM). In the other tumor, LOH spanned most of chromosome 3, ranging at least from D3S1307 to D3S1311 (271.4 cM). LOH was confirmed by repetition of the experiments and quantified by phosphorimaging. Thus, we found LOH encompassing the CaR locus in approximately 10% of sporadic PAds. These data are consistent with the hypothesis that loss of CaR function may occur in PAds, with functional consequences for calcium sensitivity and cell proliferation. 20 refs., 2 figs.

  14. 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 importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.

  15. Epigenetic analysis of sporadic and Lynch-associated ovarian cancers reveals histology-specific patterns of DNA methylation.

    Science.gov (United States)

    Niskakoski, Anni; Kaur, Sippy; Staff, Synnöve; Renkonen-Sinisalo, Laura; Lassus, Heini; Järvinen, Heikki J; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

    2014-12-01

    Diagnosis and treatment of epithelial ovarian cancer is challenging due to the poor understanding of the pathogenesis of the disease. Our aim was to investigate epigenetic mechanisms in ovarian tumorigenesis and, especially, whether tumors with different histological subtypes or hereditary background (Lynch syndrome) exhibit differential susceptibility to epigenetic inactivation of growth regulatory genes. Gene candidates for epigenetic regulation were identified from the literature and by expression profiling of ovarian and endometrial cancer cell lines treated with demethylating agents. Thirteen genes were chosen for methylation-specific multiplex ligation-dependent probe amplification assays on 104 (85 sporadic and 19 Lynch syndrome-associated) ovarian carcinomas. Increased methylation (i.e., hypermethylation) of variable degree was characteristic of ovarian carcinomas relative to the corresponding normal tissues, and hypermethylation was consistently more prominent in non-serous than serous tumors for individual genes and gene sets investigated. Lynch syndrome-associated clear cell carcinomas showed the highest frequencies of hypermethylation. Among endometrioid ovarian carcinomas, lower levels of promoter methylation of RSK4, SPARC, and HOXA9 were significantly associated with higher tumor grade; thus, the methylation patterns showed a shift to the direction of high-grade serous tumors. In conclusion, we provide evidence of a frequent epigenetic inactivation of RSK4, SPARC, PROM1, HOXA10, HOXA9, WT1-AS, SFRP2, SFRP5, OPCML, and MIR34B in the development of non-serous ovarian carcinomas of Lynch and sporadic origin, as compared to serous tumors. Our findings shed light on the role of epigenetic mechanisms in ovarian tumorigenesis and identify potential targets for translational applications. PMID:25625843

  16. Analysis of RET proto-oncogene abnormalities in patients with MEN 2A, MEN 2B, familial or sporadic medullary thyroid carcinoma.

    Science.gov (United States)

    Chiefari, E; Russo, D; Giuffrida, D; Zampa, G A; Meringolo, D; Arturi, F; Chiodini, I; Bianchi, D; Attard, M; Trischitta, V; Bruno, R; Giannasio, P; Pontecorvi, A; Filetti, S

    1998-06-01

    Medullary thyroid carcinoma (MTC) may occur either as a sporadic or familial (FMTC) disease. Multiple endocrine neoplasia (MEN) type 2, inherited as an autosomal dominant disease, is characterized by coexistence of MTC with other endocrine neoplasia. Activating mutations of the RET proto-oncogene, involving the somatic or the germinal cell lineage, are found in both inherited and acquired forms. In this study, RET mutations were screened in 47 individuals either affected by MTC or belonging to families with hereditary MTC. Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by polymerase chain reaction and examined by DNA sequence and/or restriction enzyme analysis to detect mutations in purified amplicons. Six MEN 2A families with a germline mutation at codon 634, one FMTC family carrying a mutation at codon 618 and two MEN 2B families with a mutation at codon 918 were identified. In affected members of a MEN 2A family no known RET mutations were observed. Besides, we identified a germline mutation in a patient with apparently sporadic MTC and in two out of three sons, indicating the presence of a sporadic misclassified familial disease. In all of the families examined we were able to distinguish the affected vs unaffected (not at risk) members. A somatic mutation of codon 918 was detected in three out of ten patients with apparently sporadic MTC. PMID:9699127

  17. DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/?-catenin signaling pathway genes.

    Czech Academy of Sciences Publication Activity Database

    Farkas, S. A.; Vymetálková, Veronika; Vodi?ková, Ludmila; Vodi?ka, Pavel; Torbjörn, K. N.

    2014-01-01

    Ro?. 6, ?. 2 (2014), s. 179-191. ISSN 1750-1911 R&D Projects: GA ?R GPP304/11/P715; GA ?R(CZ) GAP304/12/1585; GA MZd NT14329 Institutional support: RVO:68378041 Keywords : CpG * DNA repair genes * sporadic colorectal cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.215, year: 2013

  18. Inference on germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area.

    Science.gov (United States)

    Betti, Marta; Casalone, Elisabetta; Ferrante, Daniela; Romanelli, Antonio; Grosso, Federica; Guarrera, Simonetta; Righi, Luisella; Vatrano, Simona; Pelosi, Giuseppe; Libener, Roberta; Mirabelli, Dario; Boldorini, Renzo; Casadio, Caterina; Papotti, Mauro; Matullo, Giuseppe; Magnani, Corrado; Dianzani, Irma

    2015-01-01

    Inherited loss-of-function mutations in the BAP1 oncosuppressor gene are responsible for an inherited syndrome with predisposition to malignant mesothelioma (MM), uveal and keratinocytic melanoma, and other malignancies. Germline mutations that were inherited in an autosomal dominant fashion were identified in nine families with multiplex MM cases and 25 families with multiple melanoma, renal cell carcinoma, and other tumors. Germline mutations were also identified in sporadic MM cases, suggesting that germline mutations in BAP1 occur frequently. In this article, we report the analysis of BAP1 in five multiplex MM families and in 103 sporadic cases of MM. One family carried a new truncating germline mutation. Using immunohistochemistry, we show that BAP1 is not expressed in tumor tissue, which is in accordance with Knudson's two hits hypothesis. Interestingly, whereas the three individuals who were possibly exposed to asbestos developed MM, the individual who was not exposed developed a different tumor type, that is, mucoepidermoid carcinoma. This finding suggests that the type of carcinogen exposure may be important for the cancer type that is developed by mutation carriers. On the contrary, the other families or the 103 sporadic patients did not show germline mutations in BAP1. Our data show that BAP1 mutations are very rare in patients with sporadic MM, and we report a new BAP1 mutation, extend the cancer types associated with these mutations, and suggest the existence of other yet unknown genes in the pathogenesis of familial MM. PMID:25231345

  19. Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation.

    Science.gov (United States)

    Gimm, O; Neuberg, D S; Marsh, D J; Dahia, P L; Hoang-Vu, C; Raue, F; Hinze, R; Dralle, H; Eng, C

    1999-02-11

    The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma. PMID:10022819

  20. Mutations in the RET proto-oncogene and the von Hippel-Lindau disease tumour suppressor gene in sporadic and syndromic phaeochromocytomas.

    Science.gov (United States)

    Eng, C; Crossey, P A; Mulligan, L M; Healey, C S; Houghton, C; Prowse, A; Chew, S L; Dahia, P L; O'Riordan, J L; Toledo, S P

    1995-12-01

    Phaeochromocytomas may occur sporadically, or as part of the inherited cancer syndromes multiple endocrine neoplasia (MEN) type 2, von Hippel-Lindau disease (VHL), and, rarely, in type 1 neurofibromatosis. In MEN 2, germline missense mutations have been found in one of eight codons within exons 10, 11, 13, 14, and 16 of the RET proto-oncogene. In VHL, germline mutations within one of the three exons are responsible for the majority of cases. To determine if somatic mutations similar to those seen in the germline in MEN 2 or VHL disease play a role in the pathogenesis of sporadic or familial phaeochromocytomas, we analysed 48 sporadic tumours and tumours from 17 MEN 2 and five VHL patients for mutations in RET exons 9, 10, 11, 13, 14, 15, and 16, and the entire coding sequence of VHL. Five of 48 sporadic phaeochromocytomas had RET mutations within exons 10, 11, and 16. Of these, one was proven to be germline and two were proven to be somatic mutations. Four of 48 had VHL mutations; these included both the bilateral cases in the series (one was proven to be a germline mutation) and two others, of which one was proven somatic. PMID:8825918

  1. Mutational Analysis of p27 (CDKN1 B and p18 (CDKN2C in Sporadic Pancreatic Endocrine Tumors Argues against Tumor-Suppressor Function

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    Daniel Lindberg

    2007-07-01

    Full Text Available Pancreatic endocrine tumors (PETs arise sporadically or are associated with multiple endocrine neoplasia type 1 (MENi syndrome or von Hippel-Lindau syndrome. About 90% of patients with familial MENi display detectable MEN1 gene (menin mutations. The cyclin-dependent kinase inhibitor p27 (CDKN1 B is a downstream target of menin and has been recently shown to be responsible for the multiple endocrine neoplasia-like syndrome in rats, where affected animals develop multiple tumors and hyperplasia in endocrine tissues, including the pancreatic islets of Langerhans. A germline nonsense truncation mutation of p27 has been recently described in a suspected MENi family without MENi mutation, raising the possibility that p27 mutation could be responsible for MENi phenotype. Somatic MENi mutations occur at low frequency in sporadic PETs; here, we subjected p27 to mutational analysis in 27 sporadic PETs. As an additional menin target, analysis of the p18(CDKN2C gene was included. In the p27 gene, one common polymorphism (V1 09G and one novel polymorphism (g/a in the noncoding part of exon 2 were identified. Three known polymorphisms were found in the p18 gene. These data suggest that p27 and p18 are unlikely to present classic tumor-suppressor genes in sporadic PETs.

  2. The molecular link between inefficient GluA2 Q/R site-RNA editing and TDP-43 pathology in motor neurons of sporadic amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Yamashita, Takenari; Kwak, Shin

    2014-10-10

    TAR DNA-binding protein (TDP-43) pathology and reduced expression of adenosine deaminase acting on RNA 2 (ADAR2), which is the RNA editing enzyme responsible for adenosine-to-inosine conversion at the GluA2 glutamine/arginine (Q/R) site, concomitantly occur in the same motor neurons of amyotrophic lateral sclerosis (ALS) patients; this finding suggests a link between these two ALS-specific molecular abnormalities. AMPA receptors containing Q/R site-unedited GluA2 in their subunit assembly are Ca(2+)-permeable, and motor neurons lacking ADAR2 undergo slow death in conditional ADAR2 knockout (AR2) mice, which is a mechanistic ALS model in which the ADAR2 gene is targeted in cholinergic neurons. Moreover, deficient ADAR2 induced mislocalization of TDP-43 similar to TDP-43 pathology seen in the sporadic ALS patients in the motor neurons of AR2 mice. The abnormal mislocalization of TDP-43 specifically resulted from activation of the Ca(2+)-dependent serine protease calpain that specifically cleaved TDP-43 at the C-terminal region, and generated aggregation-prone N-terminal fragments. Notably, the N-terminal fragments of TDP-43 lacking the C-terminus were demonstrated in the brains and spinal cords of ALS patients. Because normalization of either the Ca(2+)-permeability of AMPA receptors or the calpain activity in the motor neurons normalized the subcellular localization of TDP-43 in AR2 mice, it is likely that exaggerated calpain-dependent TDP-43 fragments played a role at least in the initiation of TDP-43 pathology. Elucidation of the molecular cascade of neuronal death induced by ADAR2 downregulation could provide a new specific therapy for sporadic ALS. In this review, we summarized the work from our group on the role of inefficient GluA2 Q/R site-RNA editing and TDP-43 pathology in sporadic ALS, and discussed possible effects of inefficient ADAR2-mediated RNA editing in general. PMID:24355598

  3. Características mamográficas do câncer de mama associadas aos polimorfismos GSTM1 e GSTT1 / Polymorphisms GSTM1 and GSTT1 and sporadic breast cancer mammographic features

    Scientific Electronic Library Online (English)

    Lívia Martins Tavares Scianni, Morais; Cássio, Cardoso Filho; Gustavo Jacob, Lourenço; Julia Yoriko, Shinzato; Luiz Carlos, Zeferino; Carmen Sílvia Passos, Lima; Maria Salete Costa, Gurgel.

    2008-02-01

    Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese INTRODUÇÃO: As enzimas do sistema da glutationa S-transferase (GST) modulam os efeitos da exposição a vários agentes citotóxicos e genotóxicos. Os genes GSTM1 e GSTT1 são polimórficos em humanos e suas deleções têm sido associadas ao aumento do risco de várias neoplasias, dentre elas o câncer de mam [...] a. OBJETIVO: Comparar a freqüência das deleções dos genes GSTM1 e GSTT1 em mulheres sadias e com câncer de mama e comparar as características mamográficas do câncer entre mulheres portadoras e não portadoras das referidas deleções. MÉTODOS: Foram determinadas as freqüências das referidas deleções por PCR em 100 pacientes portadoras de câncer de mama esporádico tratadas de setembro de 2004 a junho de 2005 e em 169 mulheres sadias doadoras de sangue no mesmo período e comparadas através do odds ratio (OR) com seus respectivos IC 95%. Foram revistos os prontuários e as mamografias das pacientes com câncer e avaliadas características mamográficas (padrão de distribuição do parênquima fibro-glandular, achados mamográficos ao diagnóstico e classificação BI-RADS), correlacionando-as às deleções gênicas através do cálculo da RP (razão de prevalência) com seus respectivos IC 95%. RESULTADOS: O GSTM1 esteve deletado em 40% dos cânceres e em 44,4% dos controles (OR=1,20; IC 95% 0,70-2,04; p=0,5659) enquanto o GSTT1 em 20% e 19,5%, respectivamente (OR=0,73; IC 0,37-1,44; p=0,4124). O padrão mamográfico denso esteve associado à deleção homozigótica do GSTM1 (RP= 2,43; IC 1,11-4,08). Não se observou associação entre as deleções do sistema GST e achados mamográficos ao diagnóstico e classificação BI-RADS. CONCLUSÃO: A deleção homozigótica do gene GSTM1 associou-se ao padrão mamográfico denso. Abstract in english INTRODUCTION: Enzymes of the Glutathione S-transferase system (GST) modulate the effects of exposure to several cytotoxic and genotoxic agents. The GSTM1 and GSTT1 genes are polymorphic in humans and their deletions have been associated to increased risk of many cancers, including breast cancer. OBJ [...] ECTIVE: To evaluate the occurrence of homozygous deletions of the GSTM1 and GSTT1 genes in women with sporadic breast cancer and in women without cancer and to compare breast cancer mammographic features between patients with and without these deletions. METHODS: The study evaluated 100 patients with sporadic breast cancer treated from September 2004 to June 2005 and 169 women without cancer, determining the frequency of the above-mentioned deletions by PCR and calculating the odds ratios and their 95% confidence intervals. Medical files and mammograms of 100 patients with breast cancer were evaluated and correlated with mammographic features such as density, mammographic findings and the BI-RADS classification. These findings were correlated with the genetic deletions by the PR (Prevalence-Ratio) with their respective 95% confidence intervals. RESULTS: The GSTM1 gene was deleted in 40% of the cancers and in 44.4% of controls (OR = 1.20; CI 95% 0.70 - 2.04; p=0.5659) while the GSTT1 gene was deleted in 20% and 19.5%, respectively (OR = 0.73; CI 95% 0.37-1.44; p=0.4124). High mammographic density had been associated with GSTM1 deletion (PR 2.43; CI 1.11 to 4.08). GST deletions were not associated with predominant mammographic findings and the BI-RADS classification. CONCLUSION: GSTM1 homozygous deletion was associated with high mammographic density.

  4. Epidemiological features and serological changes in sporadic acute hepatitis B among adults: an analysis of 202 cases

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    ZHENG Dongchun

    2014-01-01

    Full Text Available ObjectiveTo investigate the epidemiological features and serological changes in sporadic acute hepatitis B (AHB among adults. MethodsA total of 202 adult patients with AHB were selected as subjects. The epidemiological data of patients were collected, and follow-up was regularly performed for 48 weeks to monitor alanine aminotransferase (ALT, total bilirubin (TBil, hepatitis B virus (HBV DNA, and serological markers of HBV (HBV-Ms. Categorical data were analyzed by nonparametric rank sum test; comparison of continuous data between groups was made by independent-samples t test; correlation analysis was performed by Pearson test. ResultsAmong AHB patients, there were more males than females; the mean age was 42.99±7.31 years. Of all cases, 29.20% developed the disease by micro blood transmission, 17.33% by heterosexual transmission, and 48.02% by unknown route of transmission. Only 49.01% of the patients were positive for HBV DNA when visiting the hospital. The HBV DNA-positive group had a serum ALT level of 1973.2±445?3 U/L, and the HBV DNA-negative group had a serum ALT level of 1500.3±287.7 U/L, without significant difference between the two groups (t=1.852, P?0.05. The HBV DNA-positive group had a serum TBil level of 118.40±37.33 ?mol/L, and the HBV DNA-negative group had a serum TBil level of 81.06± 23.24 ?mol/L, with significant difference between the two groups (t=2.765, P?0?01. Eight patterns of HBV-Ms were found in the patients who first visited the hospital; in the most frequent pattern, which was seen in 39.11% of patients, HBsAg, HBeAg, anti-HBc, and anti-HBc IgM were detected, and in the second most frequent pattern, which was seen in 29.27% of patients, HBsAg, anti-HBe, anti-HBc, and anti-HBc IgM were detected. The monitoring of HBV-Ms in 99 AHB patients who had complete data showed that the negative conversion rate of HBsAg was 97.98%, and the average negative conversion time was 2.5 weeks; the cumulative positive conversion rate of anti-HBs was 83.84%; the negative conversion rate of HBeAg among HBeAg-positive patients was 100%, and all showed negative conversion within 4 weeks of onset; the positive conversion rate of anti-HBe was 80?81% in the 48-week follow-up; serum anti-HBc remained detectable. In the acute phase, the 202 patients had HBsAg levels below 200 ng/ml, and the HBsAg level was inversely proportional to the negative conversion time of HBsAg. ConclusionMicro blood transmission and sexual transmission have become the main routes of transmission for sporadic AHB among adults. Rapid HBV DNA clearance and rapid seroconversion of HBsAg and HBeAg are the characteristics of sporadic AHB among adults. The HBsAg level in acute phase is helpful for determining the outcome of AHB. In this study, 2 cases were finally converted into chronic HBV infection.

  5. Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas suggest a common pathway to tumorigenesis

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    Hogendoorn Pancras CW

    2009-05-01

    Full Text Available Abstract Background Paragangliomas of the head and neck are highly vascular and usually clinically benign tumors arising in the paraganglia of the autonomic nervous system. A significant number of cases (10–50% are proven to be familial. Multiple genes encoding subunits of the mitochondrial succinate-dehydrogenase (SDH complex are associated with hereditary paraganglioma: SDHB, SDHC and SDHD. Furthermore, a hereditary paraganglioma family has been identified with linkage to the PGL2 locus on 11q13. No SDH genes are known to be located in the 11q13 region, and the exact gene defect has not yet been identified in this family. Methods We have performed a RNA expression microarray study in sporadic, SDHD- and PGL2-linked head and neck paragangliomas in order to identify potential differences in gene expression leading to tumorigenesis in these genetically defined paraganglioma subgroups. We have focused our analysis on pathways and functional gene-groups that are known to be associated with SDH function and paraganglioma tumorigenesis, i.e. metabolism, hypoxia, and angiogenesis related pathways. We also evaluated gene clusters of interest on chromosome 11 (i.e. the PGL2 locus on 11q13 and the imprinted region 11p15. Results We found remarkable similarity in overall gene expression profiles of SDHD -linked, PGL2-linked and sporadic paraganglioma. The supervised analysis on pathways implicated in PGL tumor formation also did not reveal significant differences in gene expression between these paraganglioma subgroups. Moreover, we were not able to detect differences in gene-expression of chromosome 11 regions of interest (i.e. 11q23, 11q13, 11p15. Conclusion The similarity in gene-expression profiles suggests that PGL2, like SDHD, is involved in the functionality of the SDH complex, and that tumor formation in these subgroups involves the same pathways as in SDH linked paragangliomas. We were not able to clarify the exact identity of PGL2 on 11q13. The lack of differential gene-expression of chromosome 11 genes might indicate that chromosome 11 loss, as demonstrated in SDHD-linked paragangliomas, is an important feature in the formation of paragangliomas regardless of their genetic background.

  6. Analysis of the Jovian sporadic decameter emission features on the base of the new data obtained with the high frequency-time resolution waveform receiver.

    Science.gov (United States)

    Litvinenko, G. V.; Zakharenko, V. V.; Konovalenko, A. A.; Vinogradov, V. V.; Rucker, H. O.

    2009-04-01

    The Jovian sporadic decameter radiation (DAM) represents a phenomenon which is still fully unstudied. The dynamic spectrum has a very complex structure with many unclear properties. The details of how decameter radio bursts are generated in the magnetosphere of Jupiter are still a matter of debate. One of the possible way to understand the physical features of S-bursts as well as mechanism responsible for generation is to increase the temporal and frequency resolutions and look at the S-burst signal from macroscopic viewpoint to a microsecond timescale. Modern progress in electronics and computer technologies allows creating the super effective registration systems with high frequency and temporal resolutions (Digital Signal Processors (DSP) and the Waveform Receiver (WFR)). In the present time in the Ukraine was realized the combination of telescope (UTR-2) and equipment (WFR) with the possible best parameters for the Jovian decameter emission investigations: sensitiveness (antenna effective area is near 100 000 m2), frequency resolution (12 kHz), time resolution (less than 200 ns), dynamic range (70 dB). In November 2008 it was continuous registered 4 hours of Io-B S-burst strong storm with UTR-2 and waveform receiver. The obtained data of the Jovian S-burst radio emission were processed as with Fourier as well as with wavelet transform methods. The main goal of these investigations was to detect and analyze the "superfine" internal content of the individual S-burst as well as macroscopic properties of radiation. Fine structure was investigated on the base of two possible physical mechanisms: 1) the narrow-band random noise process; 2) the wide-band pulse process with frequency and time modulations. For the last case the "de-dispersion" methodology was successively used. The statistical examinations (including the correlation analysis) of the fine internal structures were carried out on a broad basis of the different simple and complex S-burst events. The features of modulation effects of macroscopic scales were also considered in details.

  7. Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis

    OpenAIRE

    Matsuzaki, K.

    2006-01-01

    Transforming growth factor-ß (TGF-ß) signaling occurring during human colorectal carcinogenesis involves a shift in TGF-ß function, reducing the cytokine’s antiproliferative effect, while increasing actions that promote invasion and metastasis. TGF-ß signaling involves phosphorylation of Smad3 at serine residues 208 and 213 in the linker region and serine residues 423 and 425 in the C-terminal region. Exogenous TGF-ß activates not only TGF-ß type I ...

  8. Autosomal Recessive and Sporadic Non Syndromic Hearing Loss and the Incidence of Cx26 Mutations in a Province of Iran

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    M Hashemzadeh Chaleshtori

    2006-05-01

    Full Text Available Despite the enormous heterogeneity of genetic hearing loss, mutations in the GJB2 (connexin 26 gene located on “DFNB1” locus (13q12 account for up to 50% of cases of autosomal recessive non-syndromic hearing loss (ARNSHL in some populations. This study describes the analysis of 100 autosomal recessive and sporadic nonsyndromic hearing loss individuals from 79 families each having at least one deaf child in Chehar Mahal va Bakhtiari province in west of Iran. We have investigated the prevalence of the connexin 26 gene mutations using nested PCR strategy to screen the predominant 35delG mutation and subsequent direct sequencing to detect other Cx26 mutations. Seven different genetic variants were detected from which one novel variant was including 363delC. The 35delG was the most common mutation found in 5 of 79 families (6.3%. Cx26 related deafness mutations (35delG, [V27I; E114G] and R127H were found in 12 of 158 chromosomes studied (7.8%. We conclude that the association of Cx26 mutations with deafness in Chehar Mahal va Bakhtiari province is low and looks like most other populations of Iran.

  9. The 2009-2010 MU radar head echo observation programme for sporadic and shower meteors: radiant densities and diurnal rates

    Science.gov (United States)

    Kero, J.; Szasz, C.; Nakamura, T.; Meisel, D. D.; Ueda, M.; Fujiwara, Y.; Terasawa, T.; Nishimura, K.; Watanabe, J.

    2012-09-01

    The aim of this paper is to give an overview of the monthly meteor head echo observations (528.8 h) conducted between 2009 June and 2010 December using the Shigaraki Middle and Upper atmosphere radar in Japan (34°.85 N, 136°.10 E). We present diurnal detection rates and radiant density plots from 18 separate observational campaigns, each lasting for at least one diurnal cycle. Our data comprise more than 106 000 meteors. All six recognized apparent sporadic meteor sources are discernable and their average orbital distributions are presented in terms of geocentric velocity, semimajor axis, inclination and eccentricity. The north and south apex have radiant densities an order of magnitude higher than other apparent source regions. The diurnal detection rates show clear seasonal dependence. The main cause of the seasonal variation is the tilt of the Earth's axis, causing the elevation of the Earth's apex above the local horizon to change as the Earth revolves around the Sun. Yet, the meteor rate variation is not symmetric with respect to the equinoxes. When comparing the radiant density at different times of the year, and thus at different solar longitudes along the Earth's orbit, we have found that the north and south apex source regions fluctuate in strength.

  10. Orbital sporadic Burkitt lymphoma in an adult diabetic African American female and a review of adult orbital cases

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    Carmody J

    2011-04-01

    Full Text Available John Carmody1, Raghunath P Misra1,2, Marlyn P Langford1, William A Byrd1, Lauren Ditta1, Bryan Vekovius1, Donald E Texada11Department of Ophthalmology, 2Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USAAbstract: A case of sporadic Burkitt lymphoma (sBL presenting with jaw and lid involvement in a diabetic adult African American female and a review of adult orbital Burkitt lymphoma cases are presented. Lid edema, visual loss, ophthalmoparesis, proptosis, and sinusitis progressed over 4 weeks despite antibiotic and steroid treatment. Upper lid biopsy histopathological evaluation and immunophenotyping revealed a homogenous mass of atypical CD10 and CD20-negative B-cells and tingible body macrophages yielding a "starry sky" appearance. Cytogenetic analysis detected a minor variant c-MYC translocation, but no Epstein–Barr virus RNA. Detection of multiple lesions prompted a diagnosis of stage IV disease that totally regressed following radiation and chemotherapy. Review results of the six adult orbital sBL cases support a poor prognosis and a heightened suspicion of variant CD10, CD20 and BCL6 positive sBL in adults presenting with jaw pain and rapidly progressive orbital symptoms, particularly in female, African American, and diabetic patients.Keywords: B-cells, Burkitt lymphoma, cancer, diabetes, eye, Epstein–Barr virus, orbit, tumor

  11. Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy.

    Science.gov (United States)

    Askanas, Valerie; Engel, W King; Nogalska, Anna

    2015-04-01

    Sporadic inclusion-body myositis (s-IBM) is the most common degenerative muscle disease in which aging appears to be a key risk factor. In this review we focus on several cellular molecular mechanisms responsible for multiprotein aggregation and accumulations within s-IBM muscle fibers, and their possible consequences. Those include mechanisms leading to: a) accumulation in the form of aggregates within the muscle fibers, of several proteins, including amyloid-?42 and its oligomers, and phosphorylated tau in the form of paired helical filaments, and we consider their putative detrimental influence; and b) protein misfolding and aggregation, including evidence of abnormal myoproteostasis, such as increased protein transcription, inadequate protein disposal, and abnormal posttranslational modifications of proteins. Pathogenic importance of our recently demonstrated abnormal mitophagy is also discussed. The intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson's disease patients, the two most common neurodegenerative diseases associated with aging, are also discussed. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. PMID:25241263

  12. Increased frequency of pathologic findings on transcranial B-mode parenchymal sonography in patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Pavlovic, Aleksandra M; Stevic, Zorica; Pekmezovic, Tatjana; Mijajlovic, Milija; Jovanovic, Zagorka; Lavrnic, Dragana

    2015-04-01

    Although amyotrophic lateral sclerosis (ALS) is characterized by involvement of motor neurons in the motor cortex, brainstem and spinal cord, there is accumulating evidence that it is a multisystem degenerative disease, with dysfunction of the striatonigral dopaminergic system as well. Transcranial B-mode sonography of the parenchyma enables depiction of the differing tissue echogenicity of midbrain and basal ganglia structures in various movement disorders. Transcranial B-mode sonography was performed in the standard manner in 101 patients with sporadic newly diagnosed ALS and 60 age- and gender-matched controls. Increased frequencies of pathologic substantia nigra hyper-echogenicity (p = 0.027), interrupted brainstem raphe (p = 0.003) and increased third ventricle diameter (p < 0.0001) were detected in ALS patients as compared with healthy controls. Only four ALS patients exhibited some features of parkinsonism. Pathologic findings on transcranial B-mode sonography of parenchyma did not correlate with clinical presentation, functional status or disease subtype. Our study provides additional evidence of multisystem involvement in ALS patients, particularly in subcortical areas. PMID:25701529

  13. Equatorial spread F and sporadic E-layer connections during the Brazilian Conjugate Point Equatorial Experiment (COPEX)

    Science.gov (United States)

    Batista, Inez S.; Abdu, M. A.; Carrasco, A. J.; Reinisch, B. W.; de Paula, E. R.; Schuch, N. J.; Bertoni, F.

    2008-06-01

    The Conjugate Point Equatorial Experiment (COPEX) was conducted in Brazil from October to December 2002. The observational instruments were placed at three sites nearly along a magnetic meridian, one at the magnetic equator and the other two at magnetically conjugate points. We analyzed the spread F (SF) occurrence and sporadic E (Es) layer characteristics in the simultaneous data to look for any possible relation between these two phenomena. The present study does not detect any significant correlation between the SF occurrence/generation at the magnetic equator and the presence of Es layers at the conjugate E regions along the same field line. The integrated field line conductivity is not significantly affected by the occurrence of Es at the conjugate E regions and its presence is not sufficient to inhibit the vertical drift and SF generation at the magnetic equator. Model results show that the presence of a vertical equatorial electric field (associated with the eastward electric field pre-reversal enhancement) is too week to affect the Es development at the conjugate stations.

  14. Recurrent RECQL4 Imbalance and Increased Gene Expression Levels Are Associated with Structural Chromosomal Instability in Sporadic Osteosarcoma

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    Georges Maire

    2009-03-01

    Full Text Available Osteosarcoma (OS is an aggressive bone tumor with complex abnormal karyotypes and a highly unstable genome, exhibiting both numerical- and structural-chromosomal instability (N- and S-CIN. Chromosomal rearrangements and genomic imbalances affecting 8q24 are frequent in OS. RECQL4 gene maps to this cytoband and encodes a putative helicase involved in the fidelity of DNA replication and repair. This protective genomic function of the protein is relevant because often patients with Rothmund-Thomson syndrome have constitutional mutations of RECQL4 and carry a very high risk of developing OS. To determine the relative level of expression of RECQL4 in OS, 18 sporadic tumors were studied by reverse transcription–polymerase chain reaction. All tumors overexpressed RECQL4 in comparison to control osteoblasts, and fluorescence in situ hybridization analysis of tumor DNA showed that expression levels were strongly copy number–dependent. Relative N- and S-CIN levels were determined by classifying copy number transitions within array comparative genomic hybridization profiles and by enumerating the frequency of break-apart fluorescence in situ hybridization within 8q24 using region-specific and control probes. Although there was no evidence that disruption of 8q24 in OS led to an elevated expression of RECQL4, there was a marked association between increased overall levels of S-CIN, determined by copy number transition frequency and higher levels of RECQL4.

  15. Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes.

    Science.gov (United States)

    Miloševi?, Milena; Stenovec, Matjaž; Kreft, Marko; Petruši?, Vladimir; Stevi?, Zorica; Trkov, Saša; Andjus, Pavle R; Zorec, Robert

    2013-07-01

    Astrocytes are considered essential in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). We have demonstrated previously that immunoglobulins G (IgG) isolated from patients with ALS enhance the mobility of acidic vesicles in cultured astrocytes in a Ca(2+)-dependent manner. Here we directly examined the impact of purified sporadic ALS IgG on cytosolic [Ca(2+)] ([Ca(2+)]i) in astrocytes. Confocal time-lapse images were acquired and fluorescence of a non-ratiometric Ca(2+) indicator was recorded before and after the application of IgG. ALS IgG (0.1 mg/ml) from 7 patients evoked transient increases in [Ca(2+)]i in ~50% of tested astrocytes. The probability of observing a response was independent of extracellular Ca(2+). The peak increase in [Ca(2+)]i developed ~3 times faster and the time integral of evoked transients was ~2-fold larger; the peak amplitude itself was not affected by extracellular Ca(2+). Application of pharmacological inhibitors revealed that activation of inositol-1,4,5-triphosphate receptors is necessary and sufficient to initiate transients in [Ca(2+)]i; the Ca(2+) influx through store-operated calcium entry prolongs the transient increase in [Ca(2+)]i. Thus, ALS IgG acutely affect [Ca(2+)]i by mobilizing both, intra- and extracellular Ca(2+) into the cytosol of cultured astrocytes. PMID:23623373

  16. Modeling sporadic alzheimer's disease: the insulin resistant brain state generates multiple long-term morphobiological abnormalities inclusive hyperphosphorylated tau protein and amyloid-beta. A Synthesis

    OpenAIRE

    Salkovic-petrisic, M.; Osmanovic, J.; Gru?nblatt, E.; Riederer, P.; Hoyer, S.

    2009-01-01

    Nosologically, Alzheimer's disease (AD) is not a single disorder. Missense gene mutations involved in increased formation of the amyloid-beta protein precursor derivatives amyloid-beta (Abeta)_{1-40} and Abeta_{1-42/43} lead to autosomal dominant familial AD, found in the minority of AD cases. However, millions of subjects suffer from sporadic AD (sAD) of late onset, for which no convincing evidence suggests Abeta as the primary disease-generating compound. Environmental factors operating dur...

  17. A expressão de genes reparadores do DNA nos tumores sincrônicos de câncer colorretal esporádico DNA repair gene expression in synchronic tumors of sporadic colorectal cancer

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    Igor Proscurshim

    2007-03-01

    Full Text Available RACIONAL: Um dos mecanismos genéticos presentes em aproximadamente 80% dos pacientes com síndrome hereditária não-polipóide do câncer colorretal (HNPCC são os defeitos nos genes reparadores de DNA, como o MSH2, MSH6 e MLH1, onde os tumores sincrônicos são relativamente freqüentes. Já no câncer colorretal esporádico as lesões sincrônicas são raras. OBJETIVO: Verificar se o mesmo mecanismo genético presente no HNPCC está presente no câncer colorretal esporádico que apresentam com lesões sincrônicas. MÉTODOS: Foram incluídos no estudo todos os pacientes com câncer colorretal sincrônico não HNPCC. Imunoistoquímica com anticorpos para MSH2,MSH6, e MLH1 foi realizada para cada tumor. RESULTADOS: Todos os pacientes apresentaram expressão normal de MSH2 e MLH1. O único gene com imunoexpressão alterada foi o MSH6. CONCLUSÃO: Possivelmente outro mecanismo genético seja responsável pelo surgimento de dois tumores sincrônicos no câncer colorretal esporádico.BACKGROUND: Mismatch repair genes (such as MSH2, MLH1 and MSH6 mutations are present in over 80% of hereditary non-polyposis colorectal cancer (HNPCC tumors, which frequently exhibit synchronous lesions. Sporadic colorectal cancer is rarely associated with synchronous lesions. AIM: To investigate the role of mismatch repair gene mutation in synchronous sporadic colorectal cancer. METHODS: Patients with sporadic synchronous colorectal adenocarcinomas were included in the study. Immunohistochemistry was performed using MSH2, MLH1 and MSH6 antibodies. RESULTS: All patients had two synchoronous lesions. None of them had altered MSH2 or MLH1 expression. One patient had altered MSH6 expression in both tumors. CONCLUSION: Possibly, other molecular mechanisms are involved in carcinogenesis of sporadic synchronous colorectal cancer.

  18. A expressão de genes reparadores do DNA nos tumores sincrônicos de câncer colorretal esporádico / DNA repair gene expression in synchronic tumors of sporadic colorectal cancer

    Scientific Electronic Library Online (English)

    Igor, Proscurshim; Rodrigo Oliva, Perez; Rosa Maria Nascimento, Santos; Edson Luiz, Zaparoli; Desidério Roberto, Kiss; Angelita, Habr-Gam.

    2007-03-01

    Full Text Available RACIONAL: Um dos mecanismos genéticos presentes em aproximadamente 80% dos pacientes com síndrome hereditária não-polipóide do câncer colorretal (HNPCC) são os defeitos nos genes reparadores de DNA, como o MSH2, MSH6 e MLH1, onde os tumores sincrônicos são relativamente freqüentes. Já no câncer colo [...] rretal esporádico as lesões sincrônicas são raras. OBJETIVO: Verificar se o mesmo mecanismo genético presente no HNPCC está presente no câncer colorretal esporádico que apresentam com lesões sincrônicas. MÉTODOS: Foram incluídos no estudo todos os pacientes com câncer colorretal sincrônico não HNPCC. Imunoistoquímica com anticorpos para MSH2,MSH6, e MLH1 foi realizada para cada tumor. RESULTADOS: Todos os pacientes apresentaram expressão normal de MSH2 e MLH1. O único gene com imunoexpressão alterada foi o MSH6. CONCLUSÃO: Possivelmente outro mecanismo genético seja responsável pelo surgimento de dois tumores sincrônicos no câncer colorretal esporádico. Abstract in english BACKGROUND: Mismatch repair genes (such as MSH2, MLH1 and MSH6) mutations are present in over 80% of hereditary non-polyposis colorectal cancer (HNPCC) tumors, which frequently exhibit synchronous lesions. Sporadic colorectal cancer is rarely associated with synchronous lesions. AIM: To investigate [...] the role of mismatch repair gene mutation in synchronous sporadic colorectal cancer. METHODS: Patients with sporadic synchronous colorectal adenocarcinomas were included in the study. Immunohistochemistry was performed using MSH2, MLH1 and MSH6 antibodies. RESULTS: All patients had two synchoronous lesions. None of them had altered MSH2 or MLH1 expression. One patient had altered MSH6 expression in both tumors. CONCLUSION: Possibly, other molecular mechanisms are involved in carcinogenesis of sporadic synchronous colorectal cancer.

  19. Proteasome Inhibition and Aggresome Formation in Sporadic Inclusion-Body Myositis and in Amyloid-? Precursor Protein-Overexpressing Cultured Human Muscle Fibers

    OpenAIRE

    Fratta, Pietro; Engel, W. King; Mcferrin, Janis; Davies, Kelvin J. A.; Lin, Sharon W.; Askanas, Valerie

    2005-01-01

    The 26S proteasome system is involved in eliminating various proteins, including ubiquitinated misfolded/unfolded proteins, and its inhibition results in cellular accumulation of protein aggregates. Intramuscle-fiber ubiquitinated multiprotein-aggregates are char-acteristic of sporadic inclusion-body myositis (s-IBM) muscle fibers. Two major types of aggregates exist, containing either amyloid-? (A?) or phosphorylated tau (p-tau). We have now asked whether abnormalities of the 26S proteasom...

  20. Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion-body myopathy.

    OpenAIRE

    Sarkozi, E.; Askanas, V.; Engel, W. K.

    1994-01-01

    Sporadic inclusion-body myositis is the most common progressive muscle disease of older patients. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired helical filaments and 6 to 10-nm fibrils, both resembling those of Alzheimer brain, and Congo-red positivity. Hereditary inclusion-body myopathy designates patients cytopathologically similar but without inflammation. In both muscle diseases, prion, and several proteins characteristic of Al...

  1. Refinements in the use of equivalent latitude for assimilating sporadic inhomogeneous stratospheric tracer observations, 1: Detecting transport of Pinatubo aerosol across a strong vortex edge

    OpenAIRE

    Good, P.; Pyle, J.

    2004-01-01

    The use of PV equivalent latitude for assimilating stratospheric tracer observations is discussed ? with particular regard to the errors in the equivalent latitude coordinate, and to the assimilation of sparse data. Some example measurements are assimilated: they sample the stratosphere sporadically and inhomogeneously. The aim was to obtain precise information about the isentropic tracer distribution and evolution as a function of equivalent latitude. Precision is important, if transport acr...

  2. Refinements in the use of equivalent latitude for assimilating sporadic inhomogeneous stratospheric tracer observations, 1: Detecting transport of Pinatubo aerosol across a strong vortex edge

    OpenAIRE

    Good, P.; Pyle, J.

    2004-01-01

    The use of PV equivalent latitude for assimilating stratospheric tracer observations is discussed - with particular regard to the errors in the equivalent latitude coordinate, and to the assimilation of sparse data. Some example measurements are assimilated: they sample the stratosphere sporadically and inhomogeneously. The aim was to obtain precise information about the isentropic tracer distribution and evolution as a function of equivalent latitude. Precision is important, if transport acr...

  3. Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt
    Jakob disease: a case report

    OpenAIRE

    Rodri?guez Marti?nez, Ana B.; Lo?pez Munain, Adolfo; Ferrer, Isidro; Zarranz, Juan J.; Atare?s, Begon?a; Villagra, Nuria T.; Arteagoitia, Jose? M.; Garrido, Joseba M.; Juste, Ramo?n A.

    2012-01-01

    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 CreutzfeldtJakob disease clinical phenotype with reactive depression, followed by ...

  4. Association of mutations in grlA and gyrA topoisomerase genes with resistance to ciprofloxacin in epidemic and sporadic isolates of methicillin-resistant Staphylococcus aureus.

    OpenAIRE

    Deplano, A.; Zekhnini, A.; Allali, N.; Couturier, M.; Struelens, M. J.

    1997-01-01

    The types of topoisomerase alterations in genomically diverse epidemic and sporadic strains of methicillin- and fluoroquinolone-resistant Staphylococcus aureus isolated from European hospitals between 1984 and 1994 were characterized. Convergent dual mutations in gyrA (codon 83, 84, or 88) and grlA (codon 79 and/or 80) were found in all strains exhibiting high-level resistance to ciprofloxacin (MIC, 16 to > or = 128 microg/ml). In some epidemic strains, the resistant phenotype and genotype ap...

  5. I-123 -FP-CIT and Tc-99m -HMPAO single photon emission computed tomography in a new sporadic case of rapid-onset dystonia-parkinsonism

    International Nuclear Information System (INIS)

    Rapid-onset dystonia-parkinsonism (RDP) is a rare, autosomal-dominantly inherited syndrome characterized by abrupt onset, over hours to days, of dystonic and parkinsonian symptoms. To date, RDP has been described in a small number of families, and in only four sporadic cases. Methods: We here report a new sporadic case of RDP who has a novel de novo mutation in the ATP1A3 gene. Striatal dopamine transporters have been assessed quantitatively using [123I]-FP-CIT SPECT. A volume of interest (VOI) was drawn within the occipital cortex to obtain non-specific activity and specific to nonspecific binding ratios (BR) were calculated. A single template of predefined VOI 3D-drawn on right and left caudate nucleus and putamen was applied to the spatially normalized BR images. BR values were compared to those obtained from an age-matched control group and from a group of patients suffering from Parkinson's disease (Hoehn and Yahr score 2 or 3). A [99mTc]-HMPAO cerebral blood flow study was also performed. Results: In the control group, BR values (mean Standard Deviation) were 3.5 ± 0.4 for the left striatum and 3.3 ± 0.3 for the right one. RDP patient's values were 3 and 2.7, respectively. In the Parkinson group, values were 1.6 ± 0.3 and 1.7 ± 0.4, respectively. [99mTc]-HMPAO scan showed homogeneous cortical and sub-cortical perfusion. Conclusion: Quantification of striatal [123I]-FP-CIT uptake in a new Sporadic case of RDP with ae in a new Sporadic case of RDP with a novel mutation in the ATP1A3 gene showed values just within the range of normality. [99mTc]-HMPAO scan was normal. (authors)

  6. Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson's disease and neurotoxin-induced parkinsonism.

    OpenAIRE

    Asanuma M; Miyazaki I; Fj, Diaz-corrales; Ogawa N

    2004-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ub...

  7. 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.

  8. High-Resolution Melting (HRM) Analysis of the Cu/Zn Superoxide Dismutase (SOD1) Gene in Japanese Sporadic Amyotrophic Lateral Sclerosis (SALS) Patients

    OpenAIRE

    Akimoto, Chizuru; Morita, Mitsuya; Atsuta, Naoki; Sobue, Gen; Nakano, Imaharu

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and the majority of ALS are sporadic (SALS). Recently, several causative genes for familial ALS (FALS) were identified, but the cause of the SALS is still unknown. This time, we aimed to identify the genetic background of SALS. First, we applied the new sensitive screening methods: high-resolution melting (HRM) analysis. HRM analysis detected 18 out of 19 known SOD1 gene mutations (94.7% sensitivity). Next, we sc...

  9. Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney.

    Science.gov (United States)

    Beroukhim, Rameen; Brunet, Jean-Philippe; Di Napoli, Arianna; Mertz, Kirsten D; Seeley, Apryle; Pires, Maira M; Linhart, David; Worrell, Robert A; Moch, Holger; Rubin, Mark A; Sellers, William R; Meyerson, Matthew; Linehan, W Marston; Kaelin, William G; Signoretti, Sabina

    2009-06-01

    Recent insights into the role of the von-Hippel Lindau (VHL) tumor suppressor gene in hereditary and sporadic clear-cell renal cell carcinoma (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic targets in ccRCC. We identified 14 regions of nonrandom copy-number change, including 7 regions of amplification (1q, 2q, 5q, 7q, 8q, 12p, and 20q) and 7 regions of deletion (1p, 3p, 4q, 6q, 8p, 9p, and 14q). An analysis aimed at identifying the relevant genes revealed VHL as one of three genes in the 3p deletion peak, CDKN2A and CDKN2B as the only genes in the 9p deletion peak, and MYC as the only gene in the 8q amplification peak. An integrated analysis to identify genes in amplification peaks that are consistently overexpressed among amplified samples confirmed MYC as a potential target of 8q amplification and identified candidate oncogenes in the other regions. A comparison of genomic profiles revealed that VHL disease-associated tumors are similar to a subgroup of sporadic tumors and thus more homogeneous overall. Sporadic tumors without evidence of biallelic VHL inactivation fell into two groups: one group with genomic profiles highly dissimilar to the majority of ccRCC and a second group with genomic profiles that are much more similar to tumors with biallelic inactivation of VHL. PMID:19470766

  10. WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer

    OpenAIRE

    Serafino, Annalucia; Moroni, Noemi; Zonfrillo, Manuela; Andreola, Federica; Mercuri, Luana; Nicotera, Giuseppe; Nunziata, Joseph; Ricci, Riccardo; Antinori, Armando; Rasi, Guido; Pierimarchi, Pasquale

    2014-01-01

    The key role of the Wnt/?-catenin signaling in colorectal cancer (CRC) insurgence and progression is now recognized and several therapeutic strategies targeting this pathway are currently in developing. Wnt/?-catenin signaling not only dominates the early stages of sporadic colorectal cancer (SCC), but could also represent the connection between inflammatory bowel diseases (IBD) and increased risk of developing SCC. The knowledge on the sequential molecular events of Wnt-signaling cascade i...

  11. LAMINAR DISTRIBUTION OF THE PATHOLOGICAL CHANGES IN SPORADIC FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP-43 PROTEINOPATHY: A QUANTITATIVE STUDY USING POLYNOMIAL CURVE FITTING

    Science.gov (United States)

    Armstrong, Richard A.; Hamilton, Ronald L.; Mackenzie, Ian R. A.; Hedreen, John; Cairns, Nigel J.

    2012-01-01

    Aims Previous data suggest heterogeneity in laminar distribution of the pathology in the molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP). To study this heterogeneity, we quantified the changes in density across the cortical laminae of neuronal cytoplasmic inclusions (NCI), glial inclusions (GI), neuronal intranuclear inclusions (NII), dystrophic neurites (DN), surviving neurons, abnormally enlarged neurons (EN), and vacuoles in regions of the frontal and temporal lobe. Methods Changes in density of histological features across cortical gyri were studied in ten sporadic cases of FTLD-TDP using quantitative methods and polynomial curve-fitting. Results Our data suggest that laminar neuropathology in sporadic FTLD-TDP is highly variable. Most commonly, NCI, DN, and vacuolation were abundant in the upper laminae and GI, NII, EN, and glial cell nuclei in the lower laminae. TDP-43-immunoreactive inclusions affected more of the cortical profile in longer duration cases, their distribution varied with disease subtype, but was unrelated to Braak tangle score. Different TDP-43-immunoreactive inclusions were not spatially correlated. Conclusions Laminar distribution of pathological features in ten sporadic cases of FTLD-TDL is heterogeneous and may be accounted for, in part, by disease subtype and disease duration. In addition, the feed-forward and feed-back cortico-cortical connections may be compromised in FTLD-TDP. PMID:22804696

  12. Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.

    Science.gov (United States)

    de Lonlay, P; Fournet, J C; Rahier, J; Gross-Morand, M S; Poggi-Travert, F; Foussier, V; Bonnefont, J P; Brusset, M C; Brunelle, F; Robert, J J; Nihoul-Fékété, C; Saudubray, J M; Junien, C

    1997-08-15

    Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia. PMID:9259578

  13. The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts.

    Science.gov (United States)

    Cudalbu, Cristina; McLin, Valérie A; Lei, Hongxia; Duarte, Joao M N; Rougemont, Anne-Laure; Oldani, Graziano; Terraz, Sylvain; Toso, Christian; Gruetter, Rolf

    2013-01-01

    C57BL/6 mice are the most widely used strain of laboratory mice. Using in vivo proton Magnetic Resonance Spectroscopy ((1)H MRS), we have repeatedly observed an abnormal neurochemical profile in the brains of both wild-type and genetically modified mice derived from the C57BL/6J strain, consisting of a several fold increase in cerebral glutamine and two fold decrease in myo-inositol. This strikingly abnormal neurochemical "phenotype" resembles that observed in chronic liver disease or portosystemic shunting and appeared to be independent of transgene, origin or chow and was not associated with liver failure. As many as 25% of animals displayed the abnormal neurochemical profile, questioning the reliability of this model for neurobiology. We conducted an independent study to determine if this neurochemical profile was associated with portosystemic shunting. Our results showed that 100% of the mice with high brain glutamine displayed portosystemic shunting by concomitant portal angiography while all mice with normal brain glutamine did not. Since portosystemic shunting is known to cause alterations in gene expression in many organs including the brain, we conclude that portosystemic shunting may be the most significant problem associated with C57BL/6J inbreeding both for its effect on the central nervous system and for its systemic repercussions. PMID:23936100

  14. Methionine adenosyltransferase activity in erythrocytes and spinal cord of patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ekegren, T; Askmark, H; Aquilonius, S M; Gomes-Trolin, C

    1999-08-01

    The role of transmethylation mechanisms in the etiology of amyotrophic lateral sclerosis (ALS) is hitherto unexplored. The activity of L-methionine S-adenosyltransferase (MAT), a regulatory enzyme of S-adenosylmethionine biosynthesis, was investigated in erythrocytes of 21 patients with ALS, spinal cord specimens of 7 ALS patients, and matched controls. In ALS patients the activity of MAT in erythrocytes was sex-dependent. In comparison with controls, the male group presented a 33% higher V(max) (P < 0.05) and a 41% decrease in the affinity of MAT for methionine (K(m), P < 0.05). The type of ALS onset (limb or bulbar), age, or duration of the disease did not influence erythrocyte MAT activity. In the spinal cord, the activity of MAT was homogeneously distributed through dorsal horn, ventral horn, and white matter. Comparisons between data from controls and ALS patients and analysis of sex effect showed no significant differences. The kinetic difference of erythrocyte MAT in the male group of ALS patients might be interesting to explore since it is well known that there is a male predominance of 1.5 to 2. 5:1 in ALS. PMID:10415148

  15. A case-control study of risk factors for sporadic campylobacter infections in Denmark

    DEFF Research Database (Denmark)

    Neimann, J.; Engberg, J.

    2003-01-01

    A case control study comprising 282 cases and 319 matched controls was conducted in Denmark during 1996-7. Two estimates of the odds ratio (OR) were determined for each risk factor with and without 'protective factors' fitted into the final model. Consumption of undercooked poultry (OR 4(.)5; 8(.)2), consumption of red meat at a barbecue (OR 2(.)3; 4(.)1), consumption of grapes (OR 1(.)6; 2(.)8) and drinking unpasteurized milk (OR 2(.)3; 11(.)8) were identified as risk factors in both models. Frequent consumption of pork chops (OR 4(.)4) and daily contact with domestic animals and pets were identified as risk factors in one of the two models only. Finally, foreign travel was found to be a significant risk factor (OR 2(.)5). Seasonal and regional interaction was observed for several risk factors and the time elapsed from interviewing of cases to interviewing of controls seemed to influence the effect of certain seasonal dependent risk factors.

  16. Intermittent thermal plasma acceleration linked to sporadic motions of the magnetopause, first Cluster results

    Directory of Open Access Journals (Sweden)

    J.-A. Sauvaud

    Full Text Available This paper presents the first observations with Cluster of a very dense population of thermal ionospheric ions (H+, He+, O+ locally "accelerated" perpendicularly to the local magnetic field in a region adjacent to the magnetopause and on its magnetospheric side. The observation periods follow a long period of very weak magnetic activity. Recurrent motions of the magnetopause are, in the presented cases, unexpectedly associated with the appearance inside closed field lines of recurrent energy structures of ionospheric ions with energies in the 5 eV to  ~1000 eV range. The heaviest ions were detected with the highest energies. Here, the ion behaviour is interpreted as resulting from local electric field enhancements/decreases which adiabatically enhance/lower the bulk energy of a local dense thermal ion population. This drift effect, which is directly linked to magnetopause motions caused by pressure changes, allows for the thermal ions to overcome the satellite potential and be detected by the suprathermal CIS Cluster experiment. When fast flowing, i.e. when detectable, the density (~ 1 cm-3 of these ions from a terrestrial origin is (in the cases presented here largely higher than the local density of ions from magnetospheric/plasma sheet origin which poses again the question of the relative importance of solar and ionospheric sources for the magnetospheric plasma even during very quiet magnetic conditions.

    Key words. Ionosphere (planetary ionosphere; plasma convection Magnetospheric physics (magnetopause, cusp and boundary layers

  17. 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 genetic CJD, or simply a neutral polymorphism. Conclusions This analysis of PRNP genetic variation in UK CJD patients is the first to show a comprehensive comparison with healthy individuals (n = 970 from the same population, who were genotyped for the three most common variations (codon 129, codon 117, and 24 bp deletion. These latter two genetic variations were equally frequent in UK sCJD or vCJD cases and a normal (healthy blood donor UK population.

  18. Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B status

    Directory of Open Access Journals (Sweden)

    Pooneh Mokarram, Fakhraddin Naghibalhossaini, Mehdi Saberi Firoozi, Seyed Vahid Hosseini, Ahmad Izadpanah, Heshmetalah Salahi, Seyed Ali Malek-Hosseini, Abdoulrasool Talei, Mehra Mojallal

    2008-06-01

    Full Text Available AIM: To evaluate joint effects of Methylentetrahydrofolate reductase (MTHFR C677T genotypes, and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients.METHODS: We examined the associations between MTHFR C677T genotype, and promoter methylation of P16, hMLH1, and hMSH2 tumor-related genes among 151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit.RESULTS: We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison, we did not find a significant association between methylation in tumors and any single genotype. However, in comparison to controls with the CC genotype, an increased risk of tumor methylation was associated with the CT genotype (OR = 2.5; 95% CI, 1.1-5.6. In case-case comparisons, folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high (above median versus low (below median serum folate/vitamin B12 levels were 4.9 (95% CI, 1.4-17.7, and 3.9 (95% CI, 1.1-13.9, respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group, especially in those with MTHFR CT (P = 0.01, and CT/TT (P = 0.002 genotypes, but not in those with the CC genotype (P = 1.0.CONCLUSION: We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes.

  19. CADASIL: Una forma de demencia vascular hereditaria: Presentación de un caso clínico aparentemente esporádico CADASIL: Hereditary vascular dementia: Description of an apparently sporadic clinical case

    Directory of Open Access Journals (Sweden)

    David Sáez

    2003-01-01

    Full Text Available Presentamos un caso de CADASIL (acrónimo inglés de arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía, que corresponde al primero de una serie de 4 casos diagnosticados en nuestro servicio desde 1998, con correlato clínico, imageno-lógico y de ultrapatología muscular (microscopia electrónica. Se trata de una paciente mujer con historia de dos crisis isquémicas cerebrales transitorias a los 29 años, sin factores de riesgo tradicionales para patología cerebrovascular, que luego de 7 años desarrolló síntomas de tipo depresivos, asociados a un cuadro de retraimiento sicomotor y parkinsonismo de carácter progresivo y sin respuesta a terapia farmacológica convencional. En su estudio, la resonancia nuclear magnética de cerebro mostró extensas alteraciones en sustancia blanca a nivel fronto-occipital, bilaterales, hiperintensas en T2 e hipointensas en T1, cuya señal no se reforzó con gadolinio, sin efecto de masa, asociadas a leucoaraiosis, compatibles con el diagnóstico de CADASIL. El estudio de una biopsia muscular mediante microscopia electrónica, confirmó una arteriopatia con depósito de material granular osmiofílico en los vasos sanguíneos, tipo CADASIL. No encontramos antecedentes de cuadros demenciales ni cerebrovasculares sintomáticos en otros parientes de la paciente, madre, padre, tíos, abuelos, por lo que es probable que se trate de un cuadro esporádico. No realizamos estudio genético ni biopsico de los parientes asintomáticos. Las características de la paciente ilustran cuando sospechar el diagnóstico de CADASIL, aún frente a un caso aparentemente esporádicoWe describe a patient with CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, the first of four patients diagnosed in our service since 1998, correlating clinical, imaging, and muscular pathology (on electronic microscopy data. The patient is a woman with no risk factors for cerebrovascular pathology who suffered two transient ischemic attacks at the age of 29. Seven years later, she developed symptoms of depression manifested as psychomotor withdrawal and progressive Parkinsonism that did not respond to pharmacological treatment. An MRI brain scan showed extensive bilateral alterations in the white matter in the frontal and occipital regions, hyperintense in T2 and hypointense in T1-weighted images, without gadolinium enhancement. They had no mass effect, were associated with leukoaraiosis, and were compatible with the diagnosis of CADASIL. Muscle biopsy showed an arteriopathy with CADASIL-type osmiophilic granular deposits in the blood vessels. No history of symptomatic dementia or cerebrovascular disorders were found among the patient’s mother, father, aunts, uncles, or grandparents. This is most likely a sporadic case. No genetic studies or biopsies were done in asymptomatic relatives

  20. Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer.

    Science.gov (United States)

    Cui, Guanglin; Qi, Haili; Gundersen, Mona D; Yang, Hang; Christiansen, Ingrid; Sørbye, Sveinung W; Goll, Rasmus; Florholmen, Jon

    2015-02-01

    Most sporadic colorectal cancers (CRCs) develop from preformed adenomas. Cytokines are involved in the transition from adenoma to CRC. Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family and involved in the development of chronic inflammation and cancer. The aim of this study was to evaluate the dynamics of the IL-33/ST2 axis during the sequence of progression from normal colorectum to adenoma to carcinoma and to investigate the association of IL-33 and ST2 expression with clinicopathological parameters and prognosis. The results demonstrated that the levels of IL-33 and ST2 in adenomas (n = 50), determined by real-time PCR, were significantly higher than those of normal controls (n = 30); the levels of both IL-33/ST mRNA in CRCs (n = 50) were higher than in normal controls but lower than in adenomas. Further analysis revealed that the expression level of ST2 in CRCs was associated with tumor/node/metastasis (TNM) stage. The log-rank test showed that neither the IL-33 nor the ST2 expression level was correlated with overall survival in patients with CRC. The increased expression of IL-33/ST2 in adenomas and CRC tissues was confirmed by immunohistochemistry and was observed in both the tumor stromal cells and adenomatous/cancerous cells. Notably, increased densities of IL-33-positive and ST2-positive microvessels were found in the stroma of adenomas and CRCs. In conclusion, increased expression of the IL-33/ST2 axis along the colorectal adenoma-carcinoma sequence might be involved in the neoplastic transformation via the participation of this axis in the regulation of angiogenesis. PMID:25324197

  1. Functional analysis of human Na+/K+-ATPase familial or sporadic hemiplegic migraine mutations expressed in Xenopus oocytes

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    Spiller, Susan; Friedrich, Thomas

    2014-01-01

    AIM: Functional characterization of ATP1A2 mutations that are related to familial or sporadic hemiplegic migraine (FHM2, SHM). METHODS: cRNA of human Na+/K+-ATPase ?2- and ?1-subunits were injected in Xenopus laevis oocytes. FHM2 or SHM mutations of residues located in putative ?/? interaction sites or in the ?2-subunit’s C-terminal region were investigated. Mutants were analyzed by the two-electrode voltage-clamp (TEVC) technique on Xenopus oocytes. Stationary K+-induced Na+/K+ pump currents were measured, and the voltage dependence of apparent K+ affinity was investigated. Transient currents were recorded as ouabain-sensitive currents in Na+ buffers to analyze kinetics and voltage-dependent pre-steady state charge translocations. The expression of constructs was verified by preparation of plasma membrane and total membrane fractions of cRNA-injected oocytes. RESULTS: Compared to the wild-type enzyme, the mutants G900R and E902K showed no significant differences in the voltage dependence of K+-induced currents, and analysis of the transient currents indicated that the extracellular Na+ affinity was not affected. Mutant G855R showed no pump activity detectable by TEVC. Also for L994del and Y1009X, pump currents could not be recorded. Analysis of the plasma and total membrane fractions showed that the expressed proteins were not or only minimally targeted to the plasma membrane. Whereas the mutation K1003E had no impact on K+ interaction, D999H affected the voltage dependence of K+-induced currents. Furthermore, kinetics of the transient currents was altered compared to the wild-type enzyme, and the apparent affinity for extracellular Na+ was reduced. CONCLUSION: The investigated FHM2/SHM mutations influence protein function differently depending on the structural impact of the mutated residue. PMID:24921013

  2. Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids

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    Ogata Hiroyuki

    2011-09-01

    Full Text Available Abstract Background The Mre11/Rad50 complex and the homologous SbcD/SbcC complex in bacteria play crucial roles in the metabolism of DNA double-strand breaks, including DNA repair, genome replication, homologous recombination and non-homologous end-joining in cellular life forms and viruses. Here we investigated the amino acid sequence of the Mimivirus R555 gene product, originally annotated as a Rad50 homolog, and later shown to have close homologs in marine microbial metagenomes. Results Our bioinformatics analysis revealed that R555 protein sequence is constituted from the fusion of an N-terminal Mre11-like domain with a C-terminal Rad50-like domain. A systematic database search revealed twelve additional cases of Mre11/Rad50 (or SbcD/SbcC fusions in a wide variety of unrelated organisms including unicellular and multicellular eukaryotes, the megaplasmid of a bacterium associated to deep-sea hydrothermal vents (Deferribacter desulfuricans and the plasmid of Clostridium kluyveri. We also showed that R555 homologs are abundant in the metagenomes from different aquatic environments and that they most likely belong to aquatic viruses. The observed phyletic distribution of these fusion proteins suggests their recurrent creation and lateral gene transfers across organisms. Conclusions The existence of the fused version of protein sequences is consistent with known functional interactions between Mre11 and Rad50, and the gene fusion probably enhanced the opportunity for lateral transfer. The abundance of the Mre11/Rad50 fusion genes in viral metagenomes and their sporadic phyletic distribution in cellular organisms suggest that viruses, plasmids and transposons played a crucial role in the formation of the fusion proteins and their propagation into cellular genomes.

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

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    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.

  4. Genetic polymorphisms of inflammatory response gene TNF-? and its influence on sporadic pancreatic neuroendocrine tumors predisposition risk.

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    Karakaxas, Dimitrios; Gazouli, Maria; Coker, Ahmet; Agalianos, Christos; Papanikolaou, Ioannis S; Patapis, Pavlos; Liakakos, Theodoros; Dervenis, Christos

    2014-10-01

    The diagnosed incidence of pancreatic neuroendocrine tumors (pNETs) is increasing; however, their etiology remains poorly understood. PNETs are a rare, heterogeneous group of tumors arising from the endocrine cells of the pancreas, and genetic risk factors for sporadic pNETs are inadequately understood. It is known that pNETs secrete biogenic amines, hormones and growth factors, tumor necrosis factor-a (TNF-?) being one of them. Furthermore, cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. The aim of our study was to analyze TNF-? promoter gene polymorphisms as risk factors for pNETs using germline DNA collected in a population-based case-control study of pancreatic cancer [42 pNET cases, 78 pancreatic ductal adenocarcinoma (PDAC) cases, 17 intraductal papillary mucinous neoplasm (IPMN) and 98 healthy controls] conducted in the Athens, Greece and Izmir, Turkey areas. For subsequent analysis, we excluded cases and controls with known genetic syndromes. The CC genotype at the -1031 position was more frequent in pNET and IPMN patients (p=0.0002 and p=0.009, respectively), suggesting its possible role in pNET development. Furthermore, the AA genotype at the -308 position was overrepresented in IPMN cases (p=0.03), and AA genotype at the -238 position was more frequent in PDAC cases (p=0.03) compared to healthy individuals. With regard to tumor characteristics, no statistically significant association was detected. Our findings suggest the putative role of TNF-? -1031 polymorphism in the development of pNET and IPMN, whereas the -308 polymorphism seems to be overrepresented among IPMN cases and -238 polymorphism among PDAC cases. PMID:25213764

  5. Electron density and plasma waves in mid-latitude sporadic-E layer observed during the SEEK-2 campaign

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    H. Mori

    2005-10-01

    Full Text Available The SEEK-2 campaign was carried out over Kyushu Island in Japan on 3 August 2002, by using the two sounding rockets of S310-31 and S310-32. This campaign was planned to elucidate generation mechanisms of Quasi-Periodic Echoes (QPEs associated with mid-latitude sporadic-E (Es layers. Electron number densities were successfully measured in the Es layers by using the impedance probe on board two rockets. The plasma waves in the VLF and ELF ranges were also observed on board the S310-32 rocket. Results of electron density measurement showed that there were one or two major peaks in the Es layers along the rockets' trajectories near the altitude of about 10km. There were some smaller peaks associated with the main Es layers in the altitude range from 90 to 120 km. These density peaks were distributed in a very large extent during the SEEK-2 campaign. The Es layer structure is also measured by using the Fixed Bias Probe (FBP, which has a high spatial resolution of several meters (the impedance probe has an altitude resolution of about 400 m. The comparison with the total electron content (TEC measured by the Dual Band Beacon revealed that the Es layer was also modulated in the horizontal direction with the scale size of 30–40 km. It was shown that the QP echoes observed by the ground-based coherent radar come from the major density peak of the Es layer. The plasma wave instrument detected the enhancement of VLF and ELF plasma waves associated with the operation of the TMA release, and also with the passage of the Es layers. Keywords. Ionosphere (Ionospheric irregularities; Midlatitude ionosphere; Plasma temeperature and density

  6. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

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    Cobbs Gary A

    2007-05-01

    Full Text Available Abstract Background N-acetyltransferase 1 (NAT1 and 2 (NAT2 are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD consist of Crohn's disease (CD and ulcerative colitis (UC, both are associated with increased colorectal cancer (CRC risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD. Methods A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes. Results No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs. Conclusion This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.

  7. Clinicopathological Significance of ATM-Chk2 Expression in Sporadic Breast Cancers: a Comprehensive Analysis in Large Cohorts1

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    Abdel-Fatah, Tarek M.A.; Arora, Arvind; Alsubhi, Nouf; Agarwal, Devika; Moseley, Paul M.; Perry, Christina; Doherty, Rachel; Chan, Stephen Y.T.; Green, Andrew R.; Rakha, Emad; Ball, Graham; Ellis, Ian O.; Madhusudan, Srinivasan

    2014-01-01

    ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1950). Low nuclear ATM protein level was significantly associated with aggressive breast cancer including larger tumors, higher tumor grade, higher mitotic index, pleomorphism, tumor type, lymphovascular invasion, estrogen receptor (ER)?, PR ?, AR ?, triple-negative, and basal-like phenotypes (Ps MIB1, p53 mutants, low MDM2, low Bcl-2, low p21, low Bax, high CDK1, and low Chk2 were also more frequent in tumors with low nuclear ATM level (Ps < .05). Low ATM protein level was significantly associated with poor survival including in patients with ER-negative tumors who received adjuvant anthracycline or cyclophosphamide, methotrexate, and 5-fluorouracil–based adjuvant chemotherapy (Ps < .05). Low nuclear Chk2 protein was likely in ER ?/PR ?/AR ?; HER-2 positive; breast cancer 1, early onset negative; low XRCC1; low SMUG1; low APE1; low pol?; low DNA-PKcs; low ATM; low Bcl-2; and low TOPO2A tumors (P < .05). In patients with ER + tumors who received endocrine therapy or ER-negative tumors who received chemotherapy, nuclear Chk2 levels did not significantly influence survival. In p53 mutant tumors, low ATM (P < .000001) or high Chk2 (P < .01) was associated with poor survival. When investigated together, low-ATM/high-Chk2 tumors have the worst survival (P = .0033). Our data suggest that ATM-Chk2 levels in sporadic breast cancer may have prognostic and predictive significance. PMID:25425972

  8. Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts.

    Science.gov (United States)

    Abdel-Fatah, Tarek M A; Arora, Arvind; Alsubhi, Nouf; Agarwal, Devika; Moseley, Paul M; Perry, Christina; Doherty, Rachel; Chan, Stephen Y T; Green, Andrew R; Rakha, Emad; Ball, Graham; Ellis, Ian O; Madhusudan, Srinivasan

    2014-11-01

    ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1950). Low nuclear ATM protein level was significantly associated with aggressive breast cancer including larger tumors, higher tumor grade, higher mitotic index, pleomorphism, tumor type, lymphovascular invasion, estrogen receptor (ER)-, PR -, AR -, triple-negative, and basal-like phenotypes (Ps MIB1, p53 mutants, low MDM2, low Bcl-2, low p21, low Bax, high CDK1, and low Chk2 were also more frequent in tumors with low nuclear ATM level (Ps < .05). Low ATM protein level was significantly associated with poor survival including in patients with ER-negative tumors who received adjuvant anthracycline or cyclophosphamide, methotrexate, and 5-fluorouracil-based adjuvant chemotherapy (Ps < .05). Low nuclear Chk2 protein was likely in ER -/PR -/AR -; HER-2 positive; breast cancer 1, early onset negative; low XRCC1; low SMUG1; low APE1; low pol?; low DNA-PKcs; low ATM; low Bcl-2; and low TOPO2A tumors (P < .05). In patients with ER + tumors who received endocrine therapy or ER-negative tumors who received chemotherapy, nuclear Chk2 levels did not significantly influence survival. In p53 mutant tumors, low ATM (P < .000001) or high Chk2 (P < .01) was associated with poor survival. When investigated together, low-ATM/high-Chk2 tumors have the worst survival (P = .0033). Our data suggest that ATM-Chk2 levels in sporadic breast cancer may have prognostic and predictive significance. PMID:25425972

  9. 53BP1 Expression In Sporadic And Inherited Ovarian Carcinoma: Relationship To Genetic Status And Clinical Outcomes

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    Pennington, Kathryn P; Wickramanayake, Anneka; Norquist, Barbara M; Pennil, Christopher C; Garcia, Rochelle L; Agnew, Kathy J; Taniguchi, Toshiyasu; Welcsh, Piri; Swisher, Elizabeth M

    2013-01-01

    Objectives 53BP1, a critical mediator of the DNA damage response, functions by regulating the balance between homologous recombination (HR) and the more error-prone non-homologous endjoining (NHEJ). Deletion of 53BP1 in brca1 (but not brca2) null cells partially restores HR and reverses sensitivity to poly-ADP-ribose polymerase inhibitors (PARPi). We characterized 53BP1 and BRCA1 expression and their association with clinical outcomes in sporadic and inherited ovarian carcinomas. Methods We evaluated 53BP1 and BRCA1 protein expression using immunohistochemistry in 248 ovarian carcinomas and mRNA expression in 89 cases with quantitative reverse transcriptase PCR. All subjects were comprehensively characterized for germline mutations in BRCA1 and BRCA2. Results BRCA1-mutated (but not BRCA2-mutated) ovarian carcinomas had significantly higher 53BP1 protein expression than wildtype carcinomas. 53BP1 message levels were significantly associated with BRCA1 message levels in wildtype and BRCA1-mutated but not BRCA2-mutated carcinomas. In wildtype carcinomas, lower 53BP1 message predicted improved survival (p=0.02, median survival 74 vs. 41 months, HR 0.49, 95% CI 0.27–0.88). Survival was not impacted by BRCA1 message level. 53BP1 expression was not associated with primary platinum resistance. In 54 paired primary and recurrent cases, 53BP1 protein expression was equally likely to decrease or increase, and there was no association between decreased 53BP1 at recurrence and the development of platinum resistance. Conclusions BRCA1-mutated ovarian carcinomas have higher 53BP1 protein expression than wildtype or BRCA2-mutated carcinomas, in opposition to previous findings in breast carcinomas. Higher 53BP1 protein, which promotes NHEJ, could explain the frequent chromosomal aberrations that are characteristic of BRCA1-mutated ovarian carcinomas. In wildtype ovarian carcinomas, decreased 53BP1 message predicts improved survival, but message and protein expression were not associated. PMID:23246380

  10. Sporadic meningioangiomatosis-associated atypical meningioma mimicking parenchymal invasion of brain: a case report and review of the literature

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    Luo Bo-ning

    2010-06-01

    Full Text Available Abstract Meningioangiomatosis is a rare hamartomatous lesion or meningiovascular malformation in brain. In extremely rare condition, meningioma may occur together with meningioangiomatosis, and only 19 cases have been described in English literature until now. We now report a case of meningioangiomatosis-associated meningioma with atypical and clear cell variant. A 34-year-old man presented a 3-month history of progressive numbness and weakness of his left lower extremity. He had no stigmata of neurofibromatosis type 2. Magnetic resonance imaging (MRI revealed multifocal lesions in the right frontoparietal lobe. The lesions were totally removed. Microscopically, parts of lesions were atypical and clear cell meningioma corresponding to WHO grade II. The adjacent brain parenchyma showed the histological features of meningioangiomatosis. Neoplastic cells in atypical meningioma area were immunoreactive to epithelial membrane antigen (EMA with high MIB-1 index of up to 20%. However, the spindle cells in meningioangiomatosis area were negative for EMA with low MIB-1 index of up to 1%. The diagnosis of atypical meningioma associated with sporadic meningioangiomatosis was made. To our knowledge, this is the first case of a meningioangiomatosis-associated meningioma with atypical and clear cell variant component to be described. The patient had been followed-up for 11 months without adjuvant radiotherapy or chemotherapy. No tumor recurrence was found during this period. Meningioangiomatosis-associated meningioma is more likely to occur in younger patients and histologically to mimic parenchymal invasion of brain. We suggest that postoperative radiotherapy or chemotherapy should be given careful consideration to avoid over-treatment due to erroneously interpret as malignant meningioma.

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

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    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.)

  12. Evidence for an association of TP53 codon 72 polymorphism with sporadic colorectal cancer risk in Isfahan

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    Mehdi Nikbakht Dastjerdi

    2008-12-01

    Full Text Available

    • BACKGROUND: A common polymorphism at codon 72 of TP53 gene has been associated with increased risk for many human cancers. We studied this TP53 polymorphism in colorectal adenocarcinomas in small population selected from Isfahan city.
    • METHODS: Samples: We undertook a case-control study on 180 controls and 180 paraffin block specimens of sporadic colorectal adenocarcinomas. PCR amplification of TP53 codon 72 polymorphism: TP53 codon 72 genotypes were detected by PCR using specific primer pairs for amplifying the Proline or the Arginine alleles.
    • STATISTICAL ANALYSES: The 42-test was used to assess the significance of any difference in the prevalence of TP53 codon 72 polymorphism between colorectal cancer patients and controls.
    • RESULTS: In control samples, the genotype distribution for TP53 polymorphism showed 28.3%, 48.9% and 22.8% for the Arginine/Arginine, Arginine/Proline and Proline/Proline genotypes, respectively. In the cancer group 40% of the cases were Arginine/Arginine, 42.2% were Arginine/Proline and 17.8% were Proline/Proline. A significant difference between cases and controls was found for the Arginine/Arginine genotype compared with (grouped Arginine/Proline and Proline/Proline genotypes (Odds Ratio = 1.686 (1.085-2.620, P = 0.02.
    • CONCLUSIONS: TP53 codon 72 polymorphism may be a genetic predisposing factor for colorectal adenocarcinomas in Isfahan city.
    • KEYWORDS: Colorectal adenocarcinoma, TP53, Arginine, Proline, Polymorphism.

  13. Sporadic urban leptospirosis

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    Elena Forouhar; Dimitra Mitsani

    2011-01-01

    Severe leptospirosis (Weil Syndrome) was diagnosed in an otherwise healthy environmental worker in Baltimore alleys in late November 2010. He developed multiple organ failure but responded to antibiotic therapy and experienced a full recovery within 4 weeks. His diagnosis was confirmed by a rise in indirect hemagglutinin titer (acute 0, convalescent 400). The subject had close contact with Baltimore alley rats; a similar epidemiologic exposure and location reported in an outbreak 15 years ago.

  14. A polymorphism in the regulatory region of PRNP is associated with increased risk of sporadic Creutzfeldt-Jakob disease

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    Will Robert G

    2011-05-01

    Full Text Available Abstract Background Creutzfeldt-Jakob disease (CJD is a rare transmissible neurodegenerative disorder. An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP, but there are also other coding and non-coding polymorphisms inside this gene. Methods We tested whether three non-coding polymorphism located inside the PRNP regulatory region (C-101G, G310C and T385C were associated with risk of CJD and with age at onset in a United Kingdom population-based sample of 131 sporadic CJD (sCJD patients and 194 controls. Results We found no disease association for either PRNP C-101G or PRNP T385C. Although the crude analysis did not show a significant association between PRNP G310C and sCJD (OR: 1.5; 95%CI = 0.7 to 2.9, after adjusting by PRNP M129V genotype, it resulted that being a C allele carrier at PRNP G310C was significantly (p = 0.03 associated with a 2.4 fold increased risk of developing sCJD (95%CI = 1.1 to 5.4. Additionally, haplotypes carrying PRNP 310C coupled with PRNP 129M were significantly overrepresented in patients (p = 0.02 compared to controls. Cases of sCJD carrying a PRNP 310C allele presented at a younger age (on average 8.9 years younger than those without this allele, which was of statistical significance (p = 0.05. As expected, methionine and valine homozygosity at PRNP M129V increased significantly the risk of sCJD, alone and adjusted by PRNP G310C (OR MM/MV = 7.3; 95%CI 3.9 to 13.5 and OR VV/MV = 4.0; 95%CI 1.7 to 9.3. Conclusions Our findings support the hypothesis that genetic variations in the PRNP promoter may have a role in the pathogenesis of sCJD.

  15. Serological profile of sporadic acute viral hepatitis in an area of hyper-endemic hepatitis B virus infection

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    Ayoola Ayobanji

    2001-01-01

    Full Text Available Background: Located in the south western part of Saudi Arabia, the Gizan region is largely a rural community in which hepatitis B and chronic liver disease including hepatocellular carcinoma are highly prevalent. Aim of study: To determine the relative frequencies of acute hepatitis A, B, C and E in acute viral hepatitis in an area of hyperendemic hepatitis B infection. Methods and materials: In a prospective study 246 consecutive patients (179 males and 67 females diagnosed in a 2-year period were tested for markers of Hepatitis A virus (HAV, hepatitis B virus (HBV, hepatitis C (HCV and hepatitis E virus (HEV. Results: Of the patients tested, 131 (53.3% were children (< 10 years, and 42 (17% were 11 - 20 years in age. Ig M anti -HAV, IgM anti-HBV, anti- HCV and IgM anti-HEV were positive in 37%, 19.1%, 3.7% and 13.7% respectively. Markers of these viruses were absent in 24.4%. Among 131 children (< 10 years the commonest cause of AVH was HAV occurring in 57.3% of the cases. In adults (> 21 years HBV was found in 35.6% and IgM anti -HAV was detected in only 6.8%. In contrast to the age- related decline in the frequency of acute HA, the proportion of acute HE were similar in all age groups (13.7% in children, 16.7% in adolescents and 11.0% in adults. Conclusion: The study indicated that HAV is still a common cause of AVH particularly among children in Gizan. Acute 1-113 had a low occurrence among the children, evidently as a consequence of the integration of HB vaccine into the Saudi Arabian national EPI, 10 years ago. With the availability of combined HB and HA vaccines, It should be possible to graft the vaccination against HAV on to the existing program in Saudi Arabia. Affecting 13.4% of the group studied, sporadic HEV constitute a significant cause of AVH in this population. Until HEV vaccine becomes widely available, its prevention would be mainly by the improvement of socio - economic and hygienic standards of the population.

  16. Clinical features of sporadic Creutzfeldt-Jakob disease in China and its auxiliary examinations: A report of 55 cases

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    Bo YAN

    2013-11-01

    Full Text Available Objectives?To analyze the clinical features of sporadic Creutzfeldt-Jakob disease (sCJD in China, and the sensitivity and specificity of auxiliary examinations to improve the early diagnostic rate of sCJD. Methods?Clinical manifestations, 14-3-3 protein test, electroencephalography (EEG, neuroimaging and neuropathology of 55 patients with sCJD were retrospectively analyzed. Results?Among 55 patients with sCJD, 10 were neuropathologically confirmed, 38 clinically probable and 7 clinically possible. The average age was 55.8 years old (ranging from 36-75 years and the interval between onset of symptoms and death ranged 5 to 22 months (average 11.4 months. The majority of patients showed subacute onset and the most frequent initial symptom was progressive dementia. Nine patients received 14-3-3 protein detection and 3 out of them had positive results (33.3%. Fifty-three patients underwent EEG examinations, 40 out of them showed typical periodic sharp wave complexes (PSWC, 75.5%. Abnormal hyperintense lesions on diffusion-weighted images (DWI were observed in 47/50 (94% patients. Of 16 patients who underwent 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT scan, 15 (93.8% showed hypometabolism, especially 13 patients showed abnormal high-intensity zone on PET/CT in addition to the hyper-intense areas observed in DWI. Conclusions?Chinese sCJD patients have a much earlier onset age and longer disease duration than those reported in the foreign literatures. The majority of patients have subacute onset, and the most frequent initial symptom is progressive dementia. For patients suspected of sCJD, typical EEG and brain DWI changes could provide important reference for clinical diagnosis of sCJD. PET/CT is of great value in early diagnosis and differential diagnosis of sCJD. DOI: 10.11855/j.issn.0577-7402.2013.10.016

  17. A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

    Science.gov (United States)

    Fogh, Isabella; Ratti, Antonia; Gellera, Cinzia; Lin, Kuang; Tiloca, Cinzia; Moskvina, Valentina; Corrado, Lucia; Sorarù, Gianni; Cereda, Cristina; Corti, Stefania; Gentilini, Davide; Calini, Daniela; Castellotti, Barbara; Mazzini, Letizia; Querin, Giorgia; Gagliardi, Stella; Del Bo, Roberto; Conforti, Francesca L.; Siciliano, Gabriele; Inghilleri, Maurizio; Saccà, Francesco; Bongioanni, Paolo; Penco, Silvana; Corbo, Massimo; Sorbi, Sandro; Filosto, Massimiliano; Ferlini, Alessandra; Di Blasio, Anna M.; Signorini, Stefano; Shatunov, Aleksey; Jones, Ashley; Shaw, Pamela J.; Morrison, Karen E.; Farmer, Anne E.; Van Damme, Philip; Robberecht, Wim; Chiò, Adriano; Traynor, Bryan J.; Sendtner, Michael; Melki, Judith; Meininger, Vincent; Hardiman, Orla; Andersen, Peter M.; Leigh, Nigel P.; Glass, Jonathan D.; Overste, Daniel; Diekstra, Frank P.; Veldink, Jan H.; van Es, Michael A.; Shaw, Christopher E.; Weale, Michael E.; Lewis, Cathryn M.; Williams, Julie; Brown, Robert H.; Landers, John E.; Ticozzi, Nicola; Ceroni, Mauro; Pegoraro, Elena; Comi, Giacomo P.; D'Alfonso, Sandra; van den Berg, Leonard H.; Taroni, Franco; Al-Chalabi, Ammar; Powell, John; Silani, Vincenzo; Brescia Morra, Vincenzo; Filla, Alessandro; Massimo, Filosto; Marsili, Angela; Viviana, Pensato; Puorro, Giorgia; La Bella, Vincenzo; Logroscino, Giancarlo; Monsurrò, Maria Rosaria; Quattrone, Aldo; Simone, Isabella Laura; Ahmeti, Kreshnik B.; Ajroud-Driss, Senda; Armstrong, Jennifer; Birve, Anne; Blauw, Hylke M.; Bruijn, Lucie; Chen, Wenjie; Comeau, Mary C.; Cronin, Simon; Soraya, Gkazi Athina; Grab, Josh D.; Groen, Ewout J.; Haines, Jonathan L.; Heller, Scott; Huang, Jie; Hung, Wu-Yen; Jaworski, James M.; Khan, Humaira; Langefeld, Carl D.; Marion, Miranda C.; McLaughlin, Russell L.; Miller, Jack W.; Mora, Gabriele; Pericak-Vance, Margaret A.; Rampersaud, Evadnie; Siddique, Nailah; Siddique, Teepu; Smith, Bradley N.; Sufit, Robert; Topp, Simon; Vance, Caroline; van Vught, Paul; Yang, Yi; Zheng, J.G.

    2014-01-01

    Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (?90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10?8; OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10?9; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10?9; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ?12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci. PMID:24256812

  18. Limited family structure and triple-negative breast cancer (TNBC) subtype as predictors of BRCA mutations in a genetic counseling cohort of early-onset sporadic breast cancers.

    Science.gov (United States)

    Zugazagoitia, Jon; Pérez-Segura, Pedro; Manzano, Arancha; Blanco, Ignacio; Vega, Ana; Custodio, Ana; Teulé, Alex; Fachal, Laura; Martínez, Beatriz; González-Sarmiento, Rogelio; Cruz-Hernández, Juan Jesús; Chirivella, Isabel; Garcés, Vicente; Garre, Pilar; Romero, Atocha; Caldés, Trinidad; Díaz-Rubio, Eduardo; de la Hoya, Miguel

    2014-11-01

    Early-onset diagnosis is an eligibility criterion for BRCA1 and BRCA2 (BRCA) testing in sporadic breast cancer patients. Limited family structure has been proposed as a predictor of BRCA mutation status in this group of patients. An overwhelming amount of data supports a strong association between BRCA1 mutations and triple-negative breast cancer (TNBC). Here, we analyze the feasibility of using limited family structure and TNBC as predictors of BRCA mutation status in early-onset breast cancer patients attending genetic counseling units. We have conducted the study in a cohort of sporadic early-onset (?35 years) breast cancer patients (N = 341) previously selected for BRCA genetic testing in Academic Hereditary Cancer Clinics from Spain. A retrospective review of medical records available at the time of risk assessment allowed us classifying patients according to family structure and TNBC. In addition, BRCAPRO score was calculated for all patients. Association between categorical variables was investigated using the Fisher's exact test. Binary Logistic Regression Analysis was used for multivariate analysis. Limited family structure (OR 3.61, p = 0.013) and TNBC (OR 3.14, p = 0.013) were independent predictors of BRCA mutation status. Mutation prevalence in the subgroup of patients with at least one positive predictor was 14%, whereas it dropped to 3% in non-TNBCs with adequate family history (OR 5.31, 95% CI 1.38-23.89, p = 0.006). BRCAPRO correctly discerned between limited and adequate family structures. Limited family structure and TNBC are feasible predictors of BRCA mutation status in sporadic early-onset (?35 years) breast cancer patients attending genetic counseling units. The low prevalence of mutations observed in non-TNBCs with adequate family structure suggests that this subgroup of patients might be excluded from genetic testing. PMID:25342642

  19. Genetic investigation of DNA-repair pathway genes PMS2, MLH1, MSH2, MSH6, MUTYH, OGG1 and MTH1 in sporadic colon cancer.

    Science.gov (United States)

    Schafmayer, Clemens; Buch, Stephan; Egberts, Jan Hendrik; Franke, Andre; Brosch, Mario; El Sharawy, Abdou; Conring, Mareike; Koschnick, Maralde; Schwiedernoch, Sven; Katalinic, Alexander; Kremer, Bernd; Fölsch, Ulrich R; Krawczak, Michael; Fändrich, Fred; Schreiber, Stefan; Tepel, Jürgen; Hampe, Jochen

    2007-08-01

    Mutations in DNA repair genes have previously been identified as causative factors for hereditary nonpolyposis colon cancer (HNPCC). Recent evidence also supports an association between DNA sequence variation in these genes and sporadic colorectal carcinoma (CRC). Genetic investigation of DNA repair genes PMS2, MLH1, MSH2, MSH6, MUTYH, OGG1 and MTH1, as possible susceptibility factors for sporadic CRC, was done using both a haplotype tagging and a candidate (i.e. coding) single nucleotide polymorphism (SNP) approach. Some 1,068 patients with operated CRC (median age at diagnosis: 59 years) were compared to 738 sex-matched control individuals (median age: 67 years). Haplotype tagging SNPs, previously reported risk variants and all known coding SNPs with a minor allele frequency >0.005 were genotyped in PMS2 (N = 10), MLH1 (N = 11), MSH2 (N = 18), MSH6 (N = 15), MUTYH (N = 7), OGG1 (N = 11) and MTH1 (N = 3). No evidence for an association between CRC and any of the 7 genes was detected, neither with the tagging or coding SNPs nor in a sliding window haplotype analysis (all nominal p-values >0.05). The previously reported risk variants D132H in MLH1 and R154H in OGG1 were not even observed in the German population. Genetic CRC risk factors so far identified in DNA repair genes seem to be rare and population-specific. Their association with the disease could not be replicated in German CRC samples. It remains to be elucidated by more systematic, large-scale experiments whether common variants in the same genes, but present across populations, represent risk factors for sporadic CRC. PMID:17417778

  20. I-123 -FP-CIT and Tc-99m -HMPAO single photon emission computed tomography in a new sporadic case of rapid-onset dystonia-parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, P.; Ravasi, L. [CEA, DSV, I2BM, SHF, LMNRB, F-91401 Orsay (France); Vidailhet, M.; Roze, E. [Hop La Pitie Salpetriere, Serv Neurol, Paris (France); Vidailhet, M. [Univ Paris 06, INSERM, U679, Paris (France); Kas, A. [URA CNRS CEA 2210, Orsay (France); Kas, A. [Hop La Pitie Salpetriere, Nucl Med Serv, Paris (France); Ozelius, L.J. [Mt Sinai Sch Med, Dept Genet and Genome Sci, New York, NY (United States); Clot, F. [INSERM, UMR Neurol et Therapeut Expt S679, Paris (France); Clot, F. [Univ Paris 06, UPMC, UMR S679, Paris (France); Clot, F. [Hop La Pitie Salpetriere, Inst Federat Neurosci IFR70, Paris (France); Clot, F. [Hop La Pitie Salpetriere, AP-HP, Dept Genet et Cytogenet, Paris (France); Hindie, E. [Hop St Louis, Nucl Med Serv, Paris (France); Hindie, E. [Univ Paris 07, Imagerie Mol Diagnost et Ciblage Therapeut, Ecole Doctorale B2T, IUH, Paris (France); Devaux, J.Y. [Hop St Antoine, Nucl Med Serv, F-75571 Paris (France); Roze, E. [Univ Paris 06, CNRS, UMR 7102, Paris (France)

    2008-07-01

    Rapid-onset dystonia-parkinsonism (RDP) is a rare, autosomal-dominantly inherited syndrome characterized by abrupt onset, over hours to days, of dystonic and parkinsonian symptoms. To date, RDP has been described in a small number of families, and in only four sporadic cases. Methods: We here report a new sporadic case of RDP who has a novel de novo mutation in the ATP1A3 gene. Striatal dopamine transporters have been assessed quantitatively using [{sup 123}I]-FP-CIT SPECT. A volume of interest (VOI) was drawn within the occipital cortex to obtain non-specific activity and specific to nonspecific binding ratios (BR) were calculated. A single template of predefined VOI 3D-drawn on right and left caudate nucleus and putamen was applied to the spatially normalized BR images. BR values were compared to those obtained from an age-matched control group and from a group of patients suffering from Parkinson's disease (Hoehn and Yahr score 2 or 3). A [{sup 99m}Tc]-HMPAO cerebral blood flow study was also performed. Results: In the control group, BR values (mean Standard Deviation) were 3.5 {+-} 0.4 for the left striatum and 3.3 {+-} 0.3 for the right one. RDP patient's values were 3 and 2.7, respectively. In the Parkinson group, values were 1.6 {+-} 0.3 and 1.7 {+-} 0.4, respectively. [{sup 99m}Tc]-HMPAO scan showed homogeneous cortical and sub-cortical perfusion. Conclusion: Quantification of striatal [{sup 123}I]-FP-CIT uptake in a new Sporadic case of RDP with a novel mutation in the ATP1A3 gene showed values just within the range of normality. [{sup 99m}Tc]-HMPAO scan was normal. (authors)

  1. The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual's susceptibility to sporadic colorectal cancer.

    Science.gov (United States)

    Gil, Justyna; Ramsey, Dave; Stembalska, Agnieszka; Karpinski, Pawel; Pesz, Karolina A; Laczmanska, Izabela; Leszczynski, Przemyslaw; Grzebieniak, Zygmunt; Sasiadek, Maria Malgorzata

    2012-01-01

    Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of "minor impact genes" such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors. We focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (-4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911C (Lys751Gln), XPF Arg415Gln, XPG Asp1104His, ERCC1 C118T]; homologous recombination repair [NBS1 Glu185Gln, Rad51 135G/C, XRCC3 C18067 (Thr241Met)]. The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher's exact test with a Bonferroni correction for multiple testing was used. We found that: (i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391, 3.7782) P=0.038], (ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR=0.4497, (95% CI 0.2215, 0.9131) P=0.031] for an individual with at least one A allele at this locus. (1) The XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer. (2) The NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC. PMID:21559836

  2. A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Fogh, Isabella; Ratti, Antonia; Gellera, Cinzia; Lin, Kuang; Tiloca, Cinzia; Moskvina, Valentina; Corrado, Lucia; Sorarù, Gianni; Cereda, Cristina; Corti, Stefania; Gentilini, Davide; Calini, Daniela; Castellotti, Barbara; Mazzini, Letizia; Querin, Giorgia; Gagliardi, Stella; Del Bo, Roberto; Conforti, Francesca L; Siciliano, Gabriele; Inghilleri, Maurizio; Saccà, Francesco; Bongioanni, Paolo; Penco, Silvana; Corbo, Massimo; Sorbi, Sandro; Filosto, Massimiliano; Ferlini, Alessandra; Di Blasio, Anna M; Signorini, Stefano; Shatunov, Aleksey; Jones, Ashley; Shaw, Pamela J; Morrison, Karen E; Farmer, Anne E; Van Damme, Philip; Robberecht, Wim; Chiò, Adriano; Traynor, Bryan J; Sendtner, Michael; Melki, Judith; Meininger, Vincent; Hardiman, Orla; Andersen, Peter M; Leigh, Nigel P; Glass, Jonathan D; Overste, Daniel; Diekstra, Frank P; Veldink, Jan H; van Es, Michael A; Shaw, Christopher E; Weale, Michael E; Lewis, Cathryn M; Williams, Julie; Brown, Robert H; Landers, John E; Ticozzi, Nicola; Ceroni, Mauro; Pegoraro, Elena; Comi, Giacomo P; D'Alfonso, Sandra; van den Berg, Leonard H; Taroni, Franco; Al-Chalabi, Ammar; Powell, John; Silani, Vincenzo

    2014-04-15

    Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (?90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10(-8); OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10(-9); OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10(-9); OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ?12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci. PMID:24256812

  3. 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 familial pheochromocytoma-paraganglioma.

  4. Mutations in APC, CTNNBI en K-ras genes and expression of hMLHI in sporadic colorectal carcinomas from the Netherlands Cohort Study

    OpenAIRE

    Luchtenborg, M.; Weijenberg, M. P.; Wark, P. A.; Merdan Saritas, M.

    2005-01-01

    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, ...

  5. Comparative peptidome analyses of the profiles of the peptides ranging from 1–10 KD in CSF samples pooled from probable sporadic CJD and non-CJD patients

    OpenAIRE

    Chen, Cao; Xiao, Di; Zhou, Wei; Zhang, Yong-chan; Shi, Qi; Tian, Chan; Zhang, Jin; Zhou, Chun-xi; Zhang, Jian-zhong; Dong, Xiao-ping

    2012-01-01

    The shotgun strategy applying tandem mass spectrometry has been widely used to identify the proteins that are differentially distributed among diseases for its high reliability and efficiency. To find out the potential difference of protein profiles in cerebrospinal fluids (CSF) between Creutzfeldt-Jakob disease (CJD) and non-CJD patients, especially in the fraction ranging from 1–10 KD, the CSF samples of 40 probable sporadic CJD (sCJD) patients, 32 non-CJD cases with dementia and 17 non-C...

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

    OpenAIRE

    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...

  7. Novel Antibody-Lectin Enzyme-Linked Immunosorbent Assay That Distinguishes Prion Proteins in Sporadic and Variant Cases of Creutzfeldt-Jakob Disease

    OpenAIRE

    Pan, Tao; Li, Ruliang; Wong, Boon-seng; Kang, Shin-chung; Ironside, James; Sy, Man-sun

    2005-01-01

    We used different anti-prion protein (anti-PrP) monoclonal antibodies to capture either full-length or truncated PrP species and then used biotinylated lectin to compare the nature of the glycans on bound PrP species present in control, sporadic Creutzfeldt-Jakob disease (sCJD), or variant CJD (vCJD) brains. When full-length PrP species in these three groups were compared, no significant difference in the binding of concanavalin A or Aleuria aurantia lectin was detected. However, the binding ...

  8. Negative Regulation of BRCA1 Gene Expression by HMGA1 Proteins Accounts for the Reduced BRCA1 Protein Levels in Sporadic Breast Carcinoma

    OpenAIRE

    Baldassarre, Gustavo; Battista, Sabrina; Belletti, Barbara; Thakur, Sanjay; Pentimalli, Francesca; Trapasso, Francesco; Fedele, Monica; Pierantoni, Giovanna; Croce, Carlo M.; Fusco, Alfredo

    2003-01-01

    A drastic reduction in BRCA1 gene expression is a characteristic feature of aggressive sporadic breast carcinoma. However, the mechanisms underlying BRCA1 downregulation in breast cancer are not well understood. Here we report that both in vitro and in vivo HMGA1b protein binds to and inhibits the activity of both human and mouse BRCA1 promoters. Consistently, murine embryonic stem (ES) cells with the Hmga1 gene deleted display higher Brca1 mRNA and protein levels than do wild-type ES cells. ...

  9. Isolation of the novel agent from human stool samples that is associated with sporadic non-A, non-B hepatitis.

    OpenAIRE

    Deka, N.; Sharma, M. D.; Mukerjee, R.

    1994-01-01

    The agent(s) responsible for sporadic non-A, non-B hepatitis in humans was serially transmitted in rhesus monkeys by intravenous inoculation of the stool extract from a patient. A novel agent called HFV (hepatitis French [origin] virus) was present as 27- to 37-nm particles in the infectious stool extract. Hepatopathic lesions were noticed in infected monkeys during the acute phase of illness. The purified viral 27- to 37-nm particles consist of a double-stranded DNA of approximately 20 kb an...

  10. The STK11/LKB1 Peutz-Jegher gene is not involved in the pathogenesis of sporadic sex cord-stromal tumors, although loss of heterozygosity at 19p13.3 indicates other gene alteration in these tumors.

    Science.gov (United States)

    Kato, Noriko; Romero, Marisa; Catasus, Lluis; Prat, Jaime

    2004-09-01

    Germ line mutations in the STK11/LKB1 tumor-suppressor gene (chromosome 19p13.3) are responsible for the Peutz-Jeghers syndrome (PJS). PJS patients frequently develop neoplasms of various organs. Ovarian sex cord-stromal tumor (SCST) with annular tubules, which shows a characteristic morphology intermediate between granulosa cell and Sertoli cell tumors, is distinctively associated with PJS. Although somatic mutations of STK11 are reportedly rare in sporadic forms of common cancers linked to PJS, there are no available studies assessing STK11 alterations in larger series of sporadic ovarian tumors with granulosa, Sertoli or combined differentiation. We examined 29 sporadic SCSTs for loss of heterozygosity (LOH) at 19p13.3, mutation, and promoter methylation of STK11. LOH at 19p13.3 was detected in 12 of 29 (41%) SCSTs, with the highest frequency at chromosome marker D19S894, which localizes approximately 3 mb centromeric to STK11, and it was more frequent in granulosa/Sertoli-stromal cell tumors (10 of 19; 52%) than in thecoma-fibroma tumors (2 of 10; 20%). The 2 fibrothecomas harboring LOH contained sex cord elements. None of the LOH-positive SCSTs demonstrated mutations or promoter methylation of STK11. Our results indicate that LOH at 19p13.3 in sporadic SCSTs targets a gene different from STK11, and may play a role in the pathogenesis of sporadic SCSTs, especially in tumors containing sex cord derivatives. PMID:15343512

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

    Directory of Open Access Journals (Sweden)

    Choi Bernard CK

    2011-10-01

    Full Text Available Abstract 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-prevalence clinical population. CSF tau showed better overall diagnostic accuracy than 14-3-3 or S100B. Reporting of quantitative assay results and combining tau with S100B could enhance case definitions used in diagnosis and surveillance of sCJD.

  12. Clinical and epidemiological evaluation of patients with sporadic colorectal cancer / Avaliação clínica e epidemiológica de pacientes com câncer colorretal esporádico

    Scientific Electronic Library Online (English)

    Glaucia Maria de Mendonça, Fernandes; Cássia Veridiana Dourado, Leme; Mariângela Torreglosa, Ruiz-Cintra; Érika Cristina, Pavarino; João Gomes, Netinho; Eny Maria, Goloni-Bertollo.

    2014-12-01

    Full Text Available Experiência: O presente estudo tem como objetivo realizar um levantamento de dados clínicos e fatores sociodemográficos e de risco de pacientes com câncer colorretal esporádico (CCRE) tratados entre 2004 e 2008 no Serviço de Coloproctologia de um hospital-escola na região Noroeste de São Paulo. M [...] étodos: Foram analisados 749 prontuários clínicos. Destes, 460 foram de pacientes com câncer de cólon e de 289 de pacientes com câncer retal. A maioria dos indivíduos era da raça branca, com mais de 62 anos de idade. As variáveis analisadas foram gênero, idade, cor da pele, ocupação profissional, consumo de álcool e tabagismo, história familiar de câncer e co-morbidades. A identificação do perfil clínico-sociodemográfico e dos fatores de risco em uma população com CCRE na região noroeste de São Paulo foi realizada para colaborar com as estratégias de prevenção. Resultados: A ocorrência de CCRE não diferiu muito entre gêneros. As ocupacões profissionais mais prevalentes foram as relacionadas aos afazeres domésticos, atividades agrícolas e comerciais. Entre as comorbidades, hipertensão e colelitíase foram as mais representativas. O método de diagnóstico e de tratamento mais comum para a maioria dos pacientes foi colonoscopia e cirurgia, respectivamente. Em média, o tempo de progressão da doença foi de oito meses. O número mediano de linfonodos extirpados variou entre 11 e 14. A metástase mais comum foi a hepática. Conclusão: A ocorrência de câncer colorretal é mais frequente em homens de pele branca com idade superior a 62 anos. A ocupação profissional parece ser mais importante para as pessoas expostas a agentes cancerígenos. Este tipo de tumor afeta principalmente as regiões distais do cólon e do reto, com a ocorrência de metástases no fígado. Geralmente, os indivíduos afetados exibem baixa sobrevida, devido à alta agressividade dessa neoplasia. Abstract in english Background: This study aims to perform a survey on clinical data, sociodemographic and risk factors from patients with sporadic colorectal cancer (SCRC) treated between 2004 and 2008 in the Coloproctology Service of a teaching hospital in the North-western region of São Paulo. Methods: We analyze [...] d 749 medical records. Of these, 460 were from colon cancer patients and 289 from rectal cancer patients. Most of the individuals had white skin and were aged over 62 years. The variables that were analyzed included gender, age, skin color, professional occupation, alcohol drinking and cigarette smoking, family history of cancer, and comorbidities. The identification of the clinical-sociodemographic profile and risk factors in a population with the SCRC the northwest region of São Paulo was performed to collaborate with prevention strategies. Results: The occurrence of SCRC did not differ much between genders. The most prevalent professional occupations were those related to household chores, agricultural and commercial activities. Among the comorbidities, hypertension and cholelithiasis were the most representative. The most common diagnosis method and treatment for the majority of patients were coloscopy and surgery, respectively. On average, the time of the disease progression was eight months. The median number of lymph nodes excised ranged between 11 and 14. The most common metastasis was hepatic. Conclusion: The occurrence of colorectal cancer is more frequent in men's white skin with aged over 62 years. Professional occupation seems to be more important for those exposed to carcinogenic agents. This type of tumor mostly affects the distal regions of the colon and rectum with the occurrence of liver metastasis. The affected individuals usually have low survival due to its high aggressiveness.

  13. -160C/A polymorphism in the E-cadherin gene promoter and risk of hereditary, familial and sporadic prostate cancer.

    Science.gov (United States)

    Jonsson, Björn-Anders; Adami, Hans-Olov; Hägglund, Maria; Bergh, Anders; Göransson, Ingela; Stattin, Pär; Wiklund, Fredrik; Grönberg, Henrik

    2004-04-10

    The E-cadherin (CDH1) gene has been associated with prostate carcinogenesis. The C/A polymorphism--160 base pairs relative to the transcription start site has been shown to decrease gene transcription. We analyzed the association between this polymorphism and the risk of sporadic, familial (2 close relatives) and hereditary (3 or more close relatives) prostate cancer. We combined data from 3 population-based epidemiologic studies in Sweden encompassing altogether 1,036 prostate cancer cases and 669 controls that were genotyped for the short nucleotide polymorphism. Odds ratios with 95% confidence intervals were estimated through unconditional logistic regression. We found no significant association between the A-allele and sporadic (OR = 1.0; 95% CI = 0.8-1.2) or familial (OR = 1.4; 95% CI = 0.9-2.2) prostate cancer. In contrast, risk of hereditary cancer was increased among heterozygote CA carriers (OR = 1.7; 95% CI = 1.0-2.7) and particularly among homozygote AA carriers (OR = 2.6; 95% CI = 1.4-4.9). Our data indicate that the -160 single nucleotide polymorphism in CDH1 is a low-penetrant prostate cancer susceptibility gene that might explain a proportion of familial and notably hereditary prostate cancer. PMID:14961571

  14. Association of IL-8-inducing strains of diffusely adherent Escherichia coli with sporadic diarrheal patients with less than 5 years of age

    Directory of Open Access Journals (Sweden)

    Ismail Mustafa Meraz

    2007-02-01

    Full Text Available The role of diffusely adherent Escherichia coli (DAEC in diarrheal disease has been controversial. However, DAEC strains were recently implicated in diarrheal disease in developing countries. To clarify whether DAEC are prevalent among sporadic cases of diarrheal illness in Osaka City, Japan, E. coli strains isolated between July 1997 and March 2000 during diarrheagenic E. coli (DEC investigation were retrospectively examined. DAEC strains were recognized among 41 (4.4% of 924 patients and formed the biggest subgroup of DEC. Previously, we reported that some DAEC strains caused epithelial cells to secrete as much IL-8 as enteroaggregative E. coli strains did. In this study, we attempted to evaluate epidemiologically whether the ability of DAEC to induce IL-8 was involved in the pathogenesis. Relationship among patient age, symptoms, Afa adhesins, season and IL-8 induction were examined. The subgroup of DAEC that possessed Afa genes and/or induced a high level of IL-8 was significantly prevalent among patients age 1 to 4 years; however total DAEC was not significantly high among the children compared to other age group. IL-8 inducing DAEC seems to play a role in causing sporadic diarrheal illnesses, particularly in pediatric fields. Investigations highlighting the relationship between IL-8 induction and enteropathogenicity are clearly necessary to confirm the role of DAEC in infectious enteritis.

  15. Association of IL-8-inducing strains of diffusely adherent Escherichia coli with sporadic diarrheal patients with less than 5 years of age

    Scientific Electronic Library Online (English)

    Ismail Mustafa, Meraz; Kentaro, Arikawa; Hiromi, Nakamura; Jun, Ogasawara; Atsushi, Hase; Yoshikazu, Nishikawa.

    2007-02-01

    Full Text Available SciELO Brazil | Language: English Abstract in english The role of diffusely adherent Escherichia coli (DAEC) in diarrheal disease has been controversial. However, DAEC strains were recently implicated in diarrheal disease in developing countries. To clarify whether DAEC are prevalent among sporadic cases of diarrheal illness in Osaka City, Japan, E. co [...] li strains isolated between July 1997 and March 2000 during diarrheagenic E. coli (DEC) investigation were retrospectively examined. DAEC strains were recognized among 41 (4.4%) of 924 patients and formed the biggest subgroup of DEC. Previously, we reported that some DAEC strains caused epithelial cells to secrete as much IL-8 as enteroaggregative E. coli strains did. In this study, we attempted to evaluate epidemiologically whether the ability of DAEC to induce IL-8 was involved in the pathogenesis. Relationship among patient age, symptoms, Afa adhesins, season and IL-8 induction were examined. The subgroup of DAEC that possessed Afa genes and/or induced a high level of IL-8 was significantly prevalent among patients age 1 to 4 years; however total DAEC was not significantly high among the children compared to other age group. IL-8 inducing DAEC seems to play a role in causing sporadic diarrheal illnesses, particularly in pediatric fields. Investigations highlighting the relationship between IL-8 induction and enteropathogenicity are clearly necessary to confirm the role of DAEC in infectious enteritis.

  16. Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson's disease and neurotoxin-induced parkinsonism.

    Directory of Open Access Journals (Sweden)

    Asanuma M

    2004-10-01

    Full Text Available Parkinson's disease (PD is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.

  17. Identification of sporadic mutations in the helix initiation motif of keratin 6 in two pachyonychia congenita patients: further evidence for a mutational hot spot.

    Science.gov (United States)

    Lin, M T; Levy, M L; Bowden, P E; Magro, C; Baden, L; Baden, H P; Roop, D R

    1999-04-01

    Pachyonychia congenita (PC) is a rare, autosomal dominant, ectodermal dysplasia characterized most distinctly by the presence of symmetric nail hypertrophy. In the Jadassohn-Lewandowsky form, or PC-1, additional cutaneous manifestations may include palmoplantar hyperkeratosis, hyperhidrosis, follicular keratoses, and oral leukokeratosis. Mutations have previously been identified in the 1A helix initiation motif of either keratin 6 or keratin 16 in patients with PC-1. In the current study, we have identified 2 sporadic, heterozygous mutations in the 1A helix region of the K6 isoform (K6a). The first mutation identified was a 3 base pair deletion (K6adelta N171). The second mutation was a C-to-A transversion resulting in an amino acid substitution (K6a N171K). These data, in combination with previous reports, provide further evidence that this location is a mutational hot spot. PMID:10232401

  18. Rydberg Matter clusters of alkali metal atoms: the link between meteoritic matter, polar mesosphere summer echoes (PMSE), sporadic sodium layers, polar mesospheric clouds (PMCs, NLCs), and ion chemistry

    CERN Document Server

    Olofson, Frans; Holmlid, Leif

    2010-01-01

    A material exists which links together the influx of meteoritic matter from interplanetary space, the polar mesosphere summer echoes (PMSE), the sporadic sodium layers, the polar mesospheric clouds (PMCs, NLCs), and the observed ion chemistry in the mesosphere. The evidence in these research fields is here analyzed and found to agree well with the properties of Rydberg Matter (RM). This material has been studied with numerous methods in the laboratory. Alkali atoms, mainly Na, reach the mesosphere in the form of interplanetary (meteoritic, cometary) dust. The planar RM clusters NaN usually contain N = 19, 37 or 61 atoms, and have the density of air at 90 km altitude where they float. The diameters of the clusters are 10-100 nm from laboratory high precision radio frequency spectroscopic studies. Such experiments show that RM clusters interact strongly with radar frequencies: this explains the radio frequency heating and reflection studies of PMSE layers. The clusters give the low temperature in the mesosphere...

  19. The response of sporadic E-layer to the total solar eclipse of July 22, 2009 over the equatorial ionization anomaly region of the Indian zone

    Science.gov (United States)

    Yadav, Sneha; Das, Rupesh M.; Dabas, R. S.; Gwal, A. K.

    2013-06-01

    The digital ionosonde located in Bhopal (23.2°N, 77.2°E), India has been used to investigate the responses of the Es layer in the equatorial ionization anomaly (EIA) crest to the total solar eclipse (TSE) of July 22, 2009. Results show the presence of intense Es layer during and after the eclipse period. The gravity waves induced by the solar eclipse propagated upward in the Es layer and produced the periodic disturbance. The results of the wavelet analysis display the presence of dominant oscillation of about 24-32, 16-20 and 8 min. The appearance of intense sporadic-E concomitantly with the signatures of gravity wave suggests that the wind shear introduced by the solar eclipse induced gravity wave might be the plausible mechanism behind the intensification of Es-layer ionization.

  20. Perfil da fluência: análise comparativa entre gagueira desenvolvimental persistente familial e isolada / Speech fluency profile: comparative analysis between the sporadic and familial persistent developmental stuttering

    Scientific Electronic Library Online (English)

    Cristiane Moço Canhetti de, Oliveira; Michele, Fiorin; Paula Roberta, Nogueira; Cecília Piccin, Laroza.

    1627-16-01

    Full Text Available OBJETIVO: avaliar e comparar a fluência de indivíduos com Gagueira Desenvolvimental Persistente Familial e de indivíduos com Gagueira Desenvolvimental Persistente Isolada, caracterizando a tipologia das disfluências, a porcentagem de disfluências, a taxa de elocução e a gravidade da gagueira. MÉTODO [...] : participaram 40 indivíduos, entre 6 e 42 anos de idade, divididos em dois grupos de 20 participantes cada um: Gagueira Desenvolvimental Persistente Familial e Gagueira Desenvolvimental Persistente Isolada. Os procedimentos utilizados nos grupos foram: histórias clínica e familial, avaliação da fluência e Instrumento de Gravidade da Gagueira. RESULTADOS: não houve diferenças estatisticamente significantes entre os grupos quanto à porcentagem de disfluências gagas, ao fluxo de sílabas e palavras por minuto, e a gravidade da gagueira. Nota-se uma tendência do grupo de pessoa com gagueira familial apresentar uma maior variabilidade da gravidade da gagueira, que foi de leve a muito grave, enquanto que, no grupo de pessoas com gagueira isolada, a gravidade variou de leve a grave. CONCLUSÃO: este estudo representa um primeiro esforço para a caracterização do perfil da fluência de subgrupos de pessoas que gaguejam, a saber, gagueira desenvolvimental persistente familial e gagueira desenvolvimental persistente isolada. Pode-se concluir que o perfil da fluência de pessoas com gagueira, independente do histórico familial, é semelhante. Vale ressaltar que a ocorrência de algumas tipologias gagas, repetição de palavra monossilábica, bloqueio e intrusão foram distintas entre os grupos. Abstract in english PURPOSE: to evaluate and compare the fluency between the familial and the sporadic persistent developmental stuttering, characterizing the typology and the frequency of the disfluencies, the speech rate and the severity of the stuttering. METHOD: 40 participants aged from 6 to 42 years old, divided [...] in two groups with twenty participants in each one: Familial Persistent Developmental Stuttering and Sporadic Persistent Developmental Stuttering. The procedures used were: clinical and familial history, assessment of fluency and Stuttering Severity Instrument. RESULTS: there were no statistically significant differences between the groups regarding the frequency of stuttering like disfluencies, the flow of syllables and words per minute and the severity of stuttering. It was noted a tendency of the group with familial stuttering to show a bigger variability of the severity of stuttering, going from mild to very severe, whereas in the group with sporadic stuttering, the severity varied from mild to severe. CONCLUSION: this study represents the first effort to the characterization of the speech fluency profile of the subgroups of people who stutter, namely familial persistent developmental stuttering and sporadic persistent developmental stuttering. It is possible to conclude that the speech fluency profile of people who stutter, independently of the familial history, is similar. It is noteworthy that the occurrence of some stuttering-like disfluencies, monosyllabic word repetition, block and intrusion were different between groups.

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

    Science.gov (United States)

    Kumawat, Banshi Lal; Sharma, Chandra Mohan; Nath, Kunal; Acharya, Mihir; Khandelwal, Dinesh; Jain, Deepak

    2015-01-01

    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. PMID:25745324

  2. 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.

  3. Comparative Genomic Analysis of Two Novel Sporadic Shiga Toxin-Producing Escherichia coli O104:H4 Strains Isolated 2011 in Germany

    Science.gov (United States)

    Tietze, Erhard; Dabrowski, Piotr Wojciech; Prager, Rita; Radonic, Aleksandar; Fruth, Angelika; Auraß, Philipp; Nitsche, Andreas; Mielke, Martin; Flieger, Antje

    2015-01-01

    A large outbreak of gastrointestinal disease occurred in 2011 in Germany which resulted in almost 4000 patients with acute gastroenteritis or hemorrhagic colitis, 855 cases of a hemolytic uremic syndrome and 53 deaths. The pathogen was an uncommon, multiresistant Escherichia coli strain of serotype O104:H4 which expressed a Shiga toxin characteristic of enterohemorrhagic E. coli and in addition virulence factors common to enteroaggregative E. coli. During post-epidemic surveillance of Shiga toxin-producing E. coli (STEC) all but two of O104:H4 isolates were indistinguishable from the epidemic strain. Here we describe two novel STEC O104:H4 strains isolated in close spatiotemporal proximity to the outbreak which show a virulence gene panel, a Shiga toxin-mediated cytotoxicity towards Vero cells and aggregative adherence to Hep-2 cells comparable to the outbreak strain. They differ however both from the epidemic strain and from each other, by their antibiotic resistance phenotypes and some other features as determined by routine epidemiological subtyping methods. Whole genome sequencing of these two strains, of ten outbreak strain isolates originating from different time points of the outbreak and of one historical sporadic EHEC O104:H4 isolate was performed. Sequence analysis revealed a clear phylogenetic distance between the two variant strains and the outbreak strain finally identifying them as epidemiologically unrelated isolates from sporadic cases. These findings add to the knowledge about this emerging pathogen, illustrating a certain diversity within the bacterial core genome as well as loss and gain of accessory elements. Our results do also support the view that distinct new variants of STEC O104:H4 repeatedly might originate from yet unknown reservoirs, rather than that there would be a continuous diversification of a single epidemic strain established and circulating in Germany after the large outbreak in 2011. PMID:25836671

  4. Immunohistochemical detection of ARID1A in colorectal carcinoma: loss of staining is associated with sporadic microsatellite unstable tumors with medullary histology and high TNM stage.

    Science.gov (United States)

    Ye, Jiqing; Zhou, Yi; Weiser, Martin R; Gönen, Mithat; Zhang, Liying; Samdani, Tushar; Bacares, Ruben; DeLair, Deborah; Ivelja, Sinisa; Vakiani, Efsevia; Klimstra, David S; Soslow, Robert A; Shia, Jinru

    2014-12-01

    AT-rich interactive domain-containing protein 1A (ARID1A), a chromatin remodeling gene recently discovered to be a tumor suppressor in ovarian cancers, has been found to be mutated at low frequencies in many other tumors including colorectal carcinoma (CRC). An association between ARID1A alteration and DNA mismatch repair (MMR) deficiency has been implicated; understanding this association may facilitate the understanding of the role of ARID1A in the various tumors. In this pilot study, we analyzed the immunohistochemical expression of ARID1A in a consecutive series of 257 CRCs that fulfilled a set of relaxed criteria for Lynch syndrome screening; 59 (23%) were MMR deficient by immunohistochemistry (44 MLH1/PMS2 deficient, 9 MSH2/MSH6 deficient, 4 MSH6 deficient, and 2 PMS2 deficient). ARID1A loss was observed in 9% (22/257) of the cohort: 24% of MMR-deficient tumors (14/59, 13 of the 14 being MLH1/PMS2 deficient) and 4% of MMR-normal tumors (8/198) (P < .05). MLH1 (mutL homolog 1) promoter hypermethylation was observed in 10 of the 13 MLH1/PMS2-deficient/ARID1A-loss tumors, indicating an association between ARID1A loss and sporadic microsatellite unstable CRCs. Among the MMR-deficient cases, ARID1A loss correlated with old age (P = .04), poor tumor differentiation (P < .01), medullary histology (P < .01), and an increased rate of nodal and distant metastasis (P = .03); these patients also trended toward a worse 5-year overall survival. Among MMR-normal tumors, no differences in clinicopathological features were detected between the groups stratified by ARID1A. In conclusion, our results suggest that ARID1A loss may be linked to a specific subset of sporadic microsatellite unstable CRCs that may be medullary but is more likely to present with metastatic disease, warranting further investigation. PMID:25311944

  5. Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients

    Directory of Open Access Journals (Sweden)

    Gemela Orsolya

    2007-03-01

    Full Text Available Abstract Background Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD is a typical example as patients with longstanding IBD are at an increased risk for developing colorectal cancer (CRC and mutations of the NOD2/CARD15 gene increase the risk for Crohn's disease (CD. Recently, NOD2/CARD15 has been associated with a risk for CRC in some studies, which stemmed from ethnically diverse populations. Our aim was to identify common NOD2/CARD15 mutations in Hungarian patients with sporadic CRC. Methods A total of 194 sporadic CRC patients (m/f: 108/86, age at diagnosis of CRC: 63.2 ± 9.1 years old and 200 healthy subjects were included. DNA was screened for SNP8, SNP12 and SNP13 NOD2/CARD15 mutations by denaturing-HPLC and confirmed by direct sequencing. Results NOD2/CARD15 mutations were found in 28 patients (14.4% and in 23 controls (11.5%, p = NS. Allele frequencies for SNP8/R702W (1.8% vs. 1.5% SNP12/G908R (1.8% vs. 1.8% and SNP13/3020insC (3.6% vs. 2.5% were also not statistically different between patients and controls. The clinicopathologic characteristics of CRC patients with or without NOD2/CARD15 mutations were not significantly different. Conclusion Our results suggest that common NOD2/CARD15 mutations alone do not contribute to CRC risk in the Hungarian population.

  6. Enhanced enteric virus detection in sporadic gastroenteritis using a multi-target real-time PCR panel: a one-year study.

    Science.gov (United States)

    Pang, Xiaoli L; Preiksaitis, Jutta K; Lee, Bonita E

    2014-09-01

    Viral gastroenteritis causes significant mortality and morbidity worldwide. Identifying the etiology of viral gastroenteritis is a challenge as most enteric viruses (EVs) are non-culturable. This study is to develop an EV testing panel using real-time PCR (EVPrtPCR) to simultaneously detect rotavirus, norovirus, sapovirus, astrovirus, and enteric adenovirus in stool samples. EVPrtPCR using universal amplification conditions was run in a single instrument run. EVPrtPCR was used to test 2,486 sporadic gastroenteritis samples submitted for EV testing using electron microscopy (EM) between July 2008 and July 2009. Retesting spiked negative stool samples and Salmon DNA as internal control were used to evaluate inhibition. EVPrtPCR detected viruses in significantly more samples: 748 (34%) as compared to 94 (3.8%) by EM. EM did not detect any norovirus, sapovirus, and mixed infection, and detected only 39% of rotavirus and 38.2% of enteric adenovirus positive samples. Four samples that tested positive for rotavirus and two for adenovirus and for small-round-structured viruses by EM were negative by EVPrtPCR. Norovirus was the most common virus detected (17.6%) with 92.4% as genogroup II, followed by rotavirus (6.8%), sapovirus (4.2%), astrovirus (2.0%), and enteric adenovirus (1.4%) with 9% samples positive for mixed infection. Overall, EV identification followed a U-shaped age distribution; positive samples were more common in children ?5 years old and adults >60 years old. Norovirus, sapovirus and astrovirus showed winter predominance and rotavirus peaked in the spring. No inhibition was observed. Molecular technology significantly enhanced the identification of EV causing sporadic gastroenteritis in Alberta. PMID:24242161

  7. Rearrangements at the 11p15 locus and overexpression of insulin-like growth factor-II gene in sporadic adrenocortical tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gicquel, C.; Schneid, H.; Le Bouc, Y. [Hopital Trousseau, Paris (France); Bertagna, X.; Francillard-Leblond, M.; Luton, J.P.; Girard, F. [Hopital Cochin, Paris (France)

    1994-06-01

    Little is known about the pathophysiology of sporadic adrenocortical tumors in adults. Because loss of heterozygosity at the 11p15 locus has been described in childhood tumors, particularly in adrenocortical tumors associated with the Beckwith-Wiedemann syndrome, and because insulin-like growth factor-II (IGF-II) is a crucial regulator of fetal adrenal growth, the authors looked for structural analysis at the 11p15 locus and IGF-II gene expression in 23 sporadic adrenocortical adult tumors: 6 carcinomas (5 with Cushing`s syndrome and 1 nonsecreting) and 17 benign adenomas (13 with Cushing`s syndrome, 1 pure androgen secreting, and 3 nonsecreting). Twenty-one patients were informative at the 11p15 locus, and six (four carcinomas and two adenomas) of them (28.5%) exhibited 11p15 structural abnormalities in tumor DNA (five, a uniparental disomy and one, a mosaicism). In a single case that could be further studied, a paternal isodisomy was observed. Very high IGF-II mRNA contents were detected in seven tumors (30%; 5 of the 6 carcinomas and 2 of the 17 adenomas). They were particularly found in tumors with uniparental disomy at the 11p15 locus. Overall, a strong correlation existed between IGF-II mRNA contents and DNA demethylation at the IGF-II locus. These data show that genetic alterations involving the 11p15 locus were highly frequent in malignant tumors, but found only in rare adenomas. These results in combination with evidence for overexpression of IGF-II from the 11p15.5 locus suggest that abnormalities in structure and/or expression of the IGF-II gene play a role as a late event of a multistep process of tumorigenesis. 58 refs., 6 figs., 4 tabs.

  8. Communicating a marine protected area through the local press: the case of the National Marine Park of Alonissos, Northern Sporades, Greece.

    Science.gov (United States)

    Dikou, Angela; Dionysopoulou, Niki

    2011-05-01

    Local distrust for Marine Protected Area (MPA) managers is emerging as an important factor obstructing the fulfillment of MPA objectives, and, thus, there is a need to develop a means of enhancing relationship building between MPA managers and local people. We used the National Marine Park of Alonissos, Northern Sporades (NMPANS), Greece, as a relevant case-study to investigate whether the local print media's framing of the marine park and its management affected locals' attitudes. We conducted a longitudinal review of local newspaper articles pertaining to the NMPANS during 1980-2008, and we conducted telephone interviews with local people. We found that salience of the NMPANS in the local print media remained limited and sporadic, the main stakeholder remained the centralized public sector, and the regional print media was rather detached, moderate, and largely supportive of the NMPANS throughout 1980-2008. The progression of the management periods of the NMPANS, however, was accompanied by increased importance of the NMPANS, increased deviance from conservation as the chief objective of the NMPANS's establishment, a shift from presenting facts to presenting reactions, and a shift from a positive to a mixed image of the NMPANS. Locals who relied on newspapers for local news were better informed about the NMPANS, more likely to accept the NMPANS, and more likely to participate in meetings regarding the NMPANS regardless of gender, age, and occupation than those who did not rely on newspapers. The local print media may be utilized as a free-choice learning vehicle to enhance the value of an MPA among local people and to enhance the development of trust between park managers and locals through a proactive, empowering, and cognitive media strategy. PMID:21424571

  9. Enfermedad de Creutzfeldt-Jakob esporádica: dos casos en medicina intensiva Sporadic Creutzfeldt-Jakob disease: two cases in intensive care

    Directory of Open Access Journals (Sweden)

    P. Cardinal

    2011-02-01

    Full Text Available Las enfermedades priónicas o encefalopatías espongiformes son una familia de raras patologías neurodegenerativas caracterizadas por periodos de incubación prolongados asociados a una lenta, irreversible e invariablemente mortal evolución. En humanos se las clasifica en esporádica, adquirida y hereditaria o genética. Realizar el diagnóstico de «enfermedad de Creutzfeldt-Jakob» es un verdadero desafío para el médico intensivista dada la variabilidad en la presentación clínica y su baja incidencia. Se presentan 2 pacientes admitidos en la UCI en los que, tras descartar varias patologías, se diagnosticó con un nivel de «probabilidad», de acuerdo a la clasificación de la OMS, enfermedad de Creutzfeldt-Jakob esporádica. Se analizan aspectos diagnósticos clínicos y analíticos de la enfermedad resaltando la utilidad de la identificación de la proteína 14-3-3 en el líquido cefalorraquídeo.Prion diseases or spongiform encephalopathies are a family of rare neurodegenerative diseases characterized by long incubation periods associated with slow, irreversible and invariably fatal evolution. In humans, they are classified as sporadic, acquired and hereditary or genetic. Diagnosing sporadic "Creutzfeldt-Jakob Disease" (sCJD is a real challenge for the intensive care physician, given the variability in its clinical presentation and its low incidence. The cases of two patients admitted to the Intensive Care Unit are presented. After ruling out other diseases, they were diagnosed with sCJD with a likelihood level according to the World Health Organization Classification. Clinical and laboratory diagnostic aspects of the disease were analyzed, highlighting the utility of 14-3-3 protein identification in the cerebrospinal fluid.

  10. Role for germline mutations and a rare coding single nucleotide polymorphism within the KCNJ5 potassium channel in a large cohort of sporadic cases of primary aldosteronism.

    Science.gov (United States)

    Murthy, Meena; Xu, Shengxin; Massimo, Gianmichele; Wolley, Martin; Gordon, Richard D; Stowasser, Michael; O'Shaughnessy, Kevin M

    2014-04-01

    Primary aldosteronism (autonomous aldosterone production with suppressed renin) plays an important pathophysiological role in what has been previously labeled as essential hypertension. Besides the recently described germline mutations in the KCNJ5 potassium channel associated with familial primary aldosteronism, somatic mutations in the same channel have been identified within aldosterone-producing adenomas. In this study, we have resequenced the flanking and coding region of KCNJ5 in peripheral blood DNA from 251 white subjects with primary aldosteronism to look for rare variants that might be important for the pathophysiology of sporadic primary aldosteronism. We have identified 3 heterozygous missense mutations (R52H, E246K, and G247R) in the cohort and found that 12 (5% of the cohort) were carriers for the rare nonsynonymous single nucleotide polymorphism rs7102584 causing E282Q substitution of KCNJ5. By expressing the channels in Xenopus oocytes and human adrenal H295R cells, we have shown that the R52H, E246K, and E282Q substitutions are functional, but the G247R mutation is indistinguishable from wild type. Although the functional substitutions are remote from the selectivity filter, they affect the inward-rectification, the ability of the KCNJ5 channels to conduct Na(+) currents and ATII-induced aldosterone release from the H295R cell line. Together these data suggest that germline variation in the KCNJ5 gene has a role to play in the common sporadic form as well as the much rarer syndromic forms of primary aldosteronism. PMID:24420545

  11. Subtype Analysis of Cryptosporidium Specimens from Sporadic Cases in Colorado, Idaho, New Mexico, and Iowa in 2007: Widespread Occurrence of One Cryptosporidium hominis Subtype and Case History of an Infection with the Cryptosporidium Horse Genotype?

    OpenAIRE

    Xiao, Lihua; Hlavsa, Michele C.; Yoder, Jonathan; Ewers, Christina; Dearen, Theresa; Yang, Wenli; Nett, Randall; Harris, Stephanie; Brend, Sarah M.; Harris, Meghan; Onischuk, Lisa; Valderrama, Amy L.; Cosgrove, Shaun; Xavier, Karen; Hall, Nancy

    2009-01-01

    Subtyping was conducted in late 2007 on 57 Cryptosporidium specimens from sporadic cases in Colorado, Idaho, New Mexico, and Iowa. One previously rare Cryptosporidium hominis subtype was indentified in 40 cases (70%) from all four states, and the Cryptosporidium horse genotype was identified in a pet shop employee with severe clinical symptoms.

  12. Subtype analysis of Cryptosporidium specimens from sporadic cases in Colorado, Idaho, New Mexico, and Iowa in 2007: widespread occurrence of one Cryptosporidium hominis subtype and case history of an infection with the Cryptosporidium horse genotype.

    Science.gov (United States)

    Xiao, Lihua; Hlavsa, Michele C; Yoder, Jonathan; Ewers, Christina; Dearen, Theresa; Yang, Wenli; Nett, Randall; Harris, Stephanie; Brend, Sarah M; Harris, Meghan; Onischuk, Lisa; Valderrama, Amy L; Cosgrove, Shaun; Xavier, Karen; Hall, Nancy; Romero, Sylvia; Young, Stephen; Johnston, Stephanie P; Arrowood, Michael; Roy, Sharon; Beach, Michael J

    2009-09-01

    Subtyping was conducted in late 2007 on 57 Cryptosporidium specimens from sporadic cases in Colorado, Idaho, New Mexico, and Iowa. One previously rare Cryptosporidium hominis subtype was identified in 40 cases (70%) from all four states, and the Cryptosporidium horse genotype was identified in a pet shop employee with severe clinical symptoms. PMID:19587303

  13. Nearby Supernova Factory Observations of SN 2006D: On Sporadic Carbon Signatures in Early Type Ia Supernova Spectra

    CERN Document Server

    Factory, T N S; Aldering, G; Antilogus, P; Aragon, C; Bailey, S; Baltay, C; Baron, E; Bauer, A; Buton, C; Bongard, S; Copin, Y; Gangler, E; Gilles, S; Kessler, R; Loken, S; Nugent, P; Pain, R; Parrent, J; Pécontal, E; Pereira, R; Perlmutter, S; Rabinowitz, D; Rigaudier, G; Runge, K; Scalzo, R; Smadja, G; Wang, L; Weaver, B A; Factory, The Nearby Supernova

    2006-01-01

    We present four spectra of the Type Ia supernova (SN Ia) 2006D extending from -7 to +13 days with respect to B-band maximum. The spectra include the strongest signature of unburned material at photospheric velocities observed in a SN Ia to date. The earliest spectrum exhibits C II absorption features below 14,000 km/s, including a distinctive C II \\lambda 6580 absorption feature. The carbon signatures dissipate as the SN approaches peak brightness. In addition to discussing implications of photospheric-velocity carbon for white dwarf explosion models, we outline some factors that may influence the frequency of its detection before and around peak brightness. Two effects are explored in this regard, including depopulation of the C II optical levels by non-LTE effects, and line-of-sight effects resulting from a clumpy distribution of unburned material with low volume-filling factor.

  14. Factores de riesgo de casos esporádicos de gastroenteritis por Campylobacter en niños / Risk factors for sporadic cases of Campylobacter infection in children

    Scientific Electronic Library Online (English)

    Marta, Fajó-Pascual; Pere Godoy, García; Jesús, Aramburu Arnuelos; Antoni, Nogués Biau.

    2009-08-01

    Full Text Available SciELO Public Health | Language: Spanish Abstract in spanish Objetivos: Identificar factores de riesgo en casos esporádicos de gastroenteritis por Campylobacter en niños [...] obacter. Se recogió información telefónicamente mediante cuestionario estructurado sobre predisposición individual, exposiciones alimentarias y no alimentarias. Mediante multivariado de regresión logística condicional se estimó la odds ratio ajustada (ORa) y el intervalo de confianza del 95% (IC95%). Resultados: Se incluyeron 45 casos y 45 controles. La edad mediana de los casos fue de 1,6 años. El consumo de fiambre >2 veces (ORa:4,2; IC95%:1,2-14,7), pollo >3 veces (ORa:3,6; IC95%:1,1-11,1) y toma previa de antibióticos (ORa:4,7; IC95%:1,1-19,6) se asociaron independientemente con la enfermedad. Conclusiones Se identificó la carne de pollo como factor de riesgo de campilobacteriosis, bien por consumo o por manipulación inadecuada que podría ocasionar contaminación cruzada de otros alimentos «listos para comer», como los fiambres. Abstract in english Objectives: To identify risk factors for sporadic cases of Campylobacter infection in children aged [...] cter. Information was gathered by telephone using a structured questionnaire on individual susceptibility and food and non-food exposures. A multivariate conditional logistic regression model was used to estimate adjusted odds ratios (ORa) and their 95% confidence intervals (95%CI). Results: Forty-five cases and 45 controls were included in the analysis. The median age of cases was 1.6 years. Factors independently associated with disease were consumption of cooked deli meat >2 times (ORa:4.2, 95%CI:1.2-14.7), chicken >3 times (ORa:3.6, 95%CI:1.1-11.1) in the week before symptom onset, and previous antibiotic intake (ORa:4.7, 95%CI:1.1-19.6). Conclusions: Chicken meat was a risk factor for sporadic cases of campylobacteriosis in children, whether through consumption or through cross-contamination with other «ready-to-eat» foods such as cooked deli meat.

  15. Factores de riesgo de casos esporádicos de gastroenteritis por Campylobacter en niños / Risk factors for sporadic cases of Campylobacter infection in children

    Scientific Electronic Library Online (English)

    Marta, Fajó-Pascual; Pere, Godoy García; Jesús, Aramburu Arnuelos; Antoni, Nogués Biau.

    2009-08-01

    Full Text Available SciELO Spain | Language: Spanish Abstract in spanish Objetivos: Identificar factores de riesgo en casos esporádicos de gastroenteritis por Campylobacter en niños [...] obacter. Se recogió información telefónicamente mediante cuestionario estructurado sobre predisposición individual, exposiciones alimentarias y no alimentarias. Mediante multivariado de regresión logística condicional se estimó la odds ratio ajustada (ORa) y el intervalo de confianza del 95% (IC95%). Resultados: Se incluyeron 45 casos y 45 controles. La edad mediana de los casos fue de 1,6 años. El consumo de fiambre >2 veces (ORa:4,2; IC95%:1,2-14,7), pollo >3 veces (ORa:3,6; IC95%:1,1-11,1) y toma previa de antibióticos (ORa:4,7; IC95%:1,1-19,6) se asociaron independientemente con la enfermedad. Conclusiones Se identificó la carne de pollo como factor de riesgo de campilobacteriosis, bien por consumo o por manipulación inadecuada que podría ocasionar contaminación cruzada de otros alimentos «listos para comer», como los fiambres. Abstract in english Objectives: To identify risk factors for sporadic cases of Campylobacter infection in children aged [...] cter. Information was gathered by telephone using a structured questionnaire on individual susceptibility and food and non-food exposures. A multivariate conditional logistic regression model was used to estimate adjusted odds ratios (ORa) and their 95% confidence intervals (95%CI). Results: Forty-five cases and 45 controls were included in the analysis. The median age of cases was 1.6 years. Factors independently associated with disease were consumption of cooked deli meat >2 times (ORa:4.2, 95%CI:1.2-14.7), chicken >3 times (ORa:3.6, 95%CI:1.1-11.1) in the week before symptom onset, and previous antibiotic intake (ORa:4.7, 95%CI:1.1-19.6). Conclusions: Chicken meat was a risk factor for sporadic cases of campylobacteriosis in children, whether through consumption or through cross-contamination with other «ready-to-eat» foods such as cooked deli meat.

  16. Quantitative expression analysis of APP pathway and tau phosphorylation-related genes in the ICV STZ-induced non-human primate model of sporadic Alzheimer's disease.

    Science.gov (United States)

    Park, Sang-Je; Kim, Young-Hyun; Nam, Gyu-Hwi; Choe, Se-Hee; Lee, Sang-Rae; Kim, Sun-Uk; Kim, Ji-Su; Sim, Bo-Woong; Song, Bong-Seok; Jeong, Kang-Jin; Lee, Youngjeon; Park, Young Il; Lee, Kyoung-Min; Huh, Jae-Won; Chang, Kyu-Tae

    2015-01-01

    The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-? (A?) and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer's disease (AD). Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD) research using intracerebroventricular administration of streptozotocin (icv STZ). To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP) pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than ?-secretase (BACE1) and cyclin-dependent kinase 5 (CDK5), all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased ?- and ?-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex. PMID:25622254

  17. Association of prion protein genotype and scrapie prion protein type with cellular prion protein charge isoform profiles in cerebrospinal fluid of humans with sporadic or familial prion diseases.

    Science.gov (United States)

    Schmitz, Matthias; Lüllmann, Katharina; Zafar, Saima; Ebert, Elisabeth; Wohlhage, Marie; Oikonomou, Panteleimon; Schlomm, Markus; Mitrova, Eva; Beekes, Michael; Zerr, Inga

    2014-05-01

    The present study investigates whether posttranslational modifications of cellular prion protein (PrP(C)) in the cerebrospinal fluid (CSF) of humans with prion diseases are associated with methionine (M) and/or valine (V) polymorphism at codon 129 of the prion protein gene (PRNP), scrapie prion protein (PrP(Sc)) type in sporadic Creutzfeldt-Jakob disease (sCJD), or PRNP mutations in familial Creutzfeldt-Jakob disease (fCJD/E200K), and fatal familial insomnia (FFI). We performed comparative 2-dimensional immunoblotting of PrP(C) charge isoforms in CSF samples from cohorts of diseased and control donors. Mean levels of total PrP(C) were significantly lower in the CSF from fCJD patients than from those with sCJD or FFI. Of the 12 most abundant PrP(C) isoforms in the examined CSF, one (IF12) was relatively decreased in (1) sCJD with VV (vs. MM or MV) at PRNP codon 129; (2) in sCJD with PrP(Sc) type 2 (vs. PrP(Sc) type 1); and (3) in FFI versus sCJD or fCJD. Furthermore, truncated PrP(C) species were detected in sCJD and control samples without discernible differences. Finally, serine 43 of PrP(C) in the CSF and brain tissue from CJD patients showed more pronounced phosphorylation than in control donors. PMID:24360565

  18. Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease.

    Science.gov (United States)

    Osmanovic Barilar, J; Knezovic, A; Grünblatt, E; Riederer, P; Salkovic-Petrisic, M

    2015-04-01

    Sporadic Alzheimer disease (sAD) is associated with impairment of insulin receptor (IR) signalling in the brain. Rats used to model sAD develop insulin-resistant brain state following intracerebroventricular treatment with a betacytotoxic drug streptozotocin (STZ-icv). Brain IR signalling has been explored usually at only one time point in periods ?3 months after the STZ-icv administration. We have investigated insulin signalling in the rat hippocampus at five time points in periods ?9 months after STZ-icv treatment. Male Wistar rats were given vehicle (control)- or STZ (3 mg/kg)-icv injection and killed 0.5, 1, 3, 6 and 9 months afterwards. Insulin-1 (Ins-1), IR, phospho- and total (p/t)-glycogen synthase kinase 3-? (GSK-3?), p/t-tau and insulin degrading enzyme (IDE) mRNA and/or protein were measured. Acute upregulation of tau and IR mRNA (p sAD research. PMID:25503661

  19. Observation of three-dimensional structures of quasi-periodic echoes associated with mid-latitude sporadic-E layers by MU radar ultra-multi-channel system

    Science.gov (United States)

    Saito, S.; Yamamoto, M.; Hashiguchi, H.; Maegawa, A.

    2006-07-01

    Quasi-periodic (QP) backscatter observed by VHF radars associated with the mid-latitude Sporadic-E (Es) layers is characterized by distinct striations on range-time-intensity (RTI) plots. Two competing models claim to explain the structure of unstable regions that scatter the radar waves: horizontally drifting patches at an almost constant altitude and unstable regions elongated in altitude along the geomagnetic field line. We have conducted interferometric imaging observations of QP radar echoes to investigate spatial structures of QP echoes, precisely. Kyoto University's newly developed ultra-multi-channel receiving system of middle and upper atmosphere (MU) radar was used. We used 19 independent channels for the radar imaging, and determined the three-dimensional structure and the motion of the QP echoes. During the observation from 30 May to 02 June 2005, well-defined QP echoes were observed on the nights of 31 May, 01 June, and 02 June 2005. Some of QP echoes were found at altitudes higher than 120 km and appeared to descend in altitude as they approached the radar. This result suggests that backscatter regions are developed along the geomagnetic field line from Es layer altitudes to as high as 130 km and that the fluctuations in plasma density and electric field observed by Pfaff et al. (2005) using in-situ measurements form a part of QP echoes.

  20. First results from the 2009-2010 MU radar head echo observation programme for sporadic and shower meteors: the Orionids 2009

    Science.gov (United States)

    Kero, J.; Szasz, C.; Nakamura, T.; Meisel, D. D.; Ueda, M.; Fujiwara, Y.; Terasawa, T.; Miyamoto, H.; Nishimura, K.

    2011-10-01

    The aim of this paper is to demonstrate the capabilities of a new automated analysis scheme developed for meteor head echo observations by the Shigaraki middle and upper atmosphere (MU) radar in Japan (?N, ?E). Our analysis procedure computes meteoroid range, velocity and deceleration as functions of time with unprecedented accuracy and precision. This is crucial for estimations of meteoroid mass and orbital parameters, as well as investigations into meteoroid-atmosphere interaction processes. We collected an extensive set of data (>500 h) between 2009 June and 2010 December. Here, we present initial results from data taken in 2009 October 19-21. More than 600 of about 10 000 head echoes recorded during 33 h were associated with the 1P/Halley dust of the Orionid meteor shower. These meteors constitute a very clear enhancement of meteor radiants centred around right ascension ?=? and declination ?=?. Their estimated atmospheric entry velocity of 66.9 km s-1 is in good agreement with 1P/Halley dust ejected in the year 1266 BC, which, according to simulations, crossed Earth's orbit at the time of our observation. The Orionid activity within the MU radar beam reached about 50 h-1 during radiant culmination. The flux of sporadic meteors in the MU radar data, coming primarily from the direction of the Earth's apex, peaked at about 700 h-1 during the same observations.

  1. Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity.

    Science.gov (United States)

    Fu, Yong-Juan; Nishihira, Yasushi; Kuroda, Shigetoshi; Toyoshima, Yasuko; Ishihara, Tomohiko; Shinozaki, Makoto; Miyashita, Akinori; Piao, Yue-Shan; Tan, Chun-Feng; Tani, Takashi; Koike, Ryoko; Iwanaga, Keisuke; Tsujihata, Mitsuhiro; Onodera, Osamu; Kuwano, Ryozo; Nishizawa, Masatoyo; Kakita, Akiyoshi; Ikeuchi, Takeshi; Takahashi, Hitoshi

    2010-07-01

    Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD. PMID:20140439

  2. Tissue classification for the epidemiological assessment of surgical transmission of sporadic Creutzfeldt-Jakob disease. A proposal on hypothetical risk levels

    Directory of Open Access Journals (Sweden)

    Calero Miguel

    2005-01-01

    Full Text Available Abstract Background Epidemiological studies on the potential role of surgery in Creutzfeldt-Jakob Disease transmission have disclosed associations with history of specific surgical interventions or reported negative results. Methods Within the context of a case-control study designed to address surgical risk of sporadic Creutzfeldt-Jakob Disease in Nordic European countries (EUROSURGYCJD Project, a strategy was adopted to categorise reported surgical procedures in terms of potential risk of Creutzfeldt-Jakob Disease acquisition. We took into account elements of biological plausibility, either clinically or experimentally demonstrated, such as tissue infectivity, PrP expression content or successful route of infection. Results We propose a classification of exposed tissues and anatomic structures, drawn up on the basis of their specific putative role as entry site for prion transmission through contact with surgical instruments that are not fully decontaminated. Conclusions This classification can serve as a reference, both in our study and in further epidemiological research, for categorisation of surgical procedures in terms of risk level of Creutzfeldt-Jakob Disease acquisition.

  3. CaMKII-dependent dendrite ramification and spine generation promote spatial training-induced memory improvement in a rat model of sporadic Alzheimer's disease.

    Science.gov (United States)

    Jiang, Xia; Chai, Gao-Shang; Wang, Zhi-Hao; Hu, Yu; Li, Xiao-Guang; Ma, Zhi-Wei; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2015-02-01

    Participation in cognitively stimulating activities can preserve memory capacities in patients with Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we used a rat model with hyperhomocysteinemia, an independent risk factor of AD, to study whether spatial training could remodel the synaptic and/or dendritic plasticity and the key molecular target(s) involved. We found that spatial training in water maze remarkably improved the subsequent short-term and long-term memory performance in contextual fear conditioning and Barnes maze. The trained rats showed an enhanced dendrite ramification, spine generation and plasticity in dentate gyrus (DG) neurons, and stimulation of long-term potentiation between perforant path and DG circuit. Spatial training also increased the levels of postsynaptic GluA1, GluN2A, GluN2B, and PSD93 with selective activation of calcium/calmodulin-dependent protein kinase II (CaMKII), although inhibition of CaMKII by stereotaxic injection of KN93 into hippocampal DG, abolished the training-induced cognitive improvement, dendrite ramification, and spine generation. We conclude that spatial training can preserve the cognitive function by CaMKII-dependent remodeling of dendritic plasticity in hyperhomocysteinemia-induced sporadic AD-like rats. PMID:25457025

  4. Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

    Science.gov (United States)

    Sen, Partha; Yang, Yaping; Navarro, Colby; Silva, Iris; Szafranski, Przemyslaw; Kolodziejska, Katarzyna E; Dharmadhikari, Avinash V; Mostafa, Hasnaa; Kozakewich, Harry; Kearney, Debra; Cahill, John B; Whitt, Merrissa; Bilic, Masha; Margraf, Linda; Charles, Adrian; Goldblatt, Jack; Gibson, Kathleen; Lantz, Patrick E; Garvin, A Julian; Petty, John; Kiblawi, Zeina; Zuppan, Craig; McConkie-Rosell, Allyn; McDonald, Marie T; Peterson-Carmichael, Stacey L; Gaede, Jane T; Shivanna, Binoy; Schady, Deborah; Friedlich, Philippe S; Hays, Stephen R; Palafoll, Irene Valenzuela; Siebers-Renelt, Ulrike; Bohring, Axel; Finn, Laura S; Siebert, Joseph R; Galambos, Csaba; Nguyen, Lananh; Riley, Melissa; Chassaing, Nicolas; Vigouroux, Adeline; Rocha, Gustavo; Fernandes, Susana; Brumbaugh, Jane; Roberts, Kari; Ho-Ming, Luk; Lo, Ivan F M; Lam, Stephen; Gerychova, Romana; Jezova, Marta; Valaskova, Iveta; Fellmann, Florence; Afshar, Katayoun; Giannoni, Eric; Muhlethaler, Vincent; Liang, Jinlong; Beckmann, Jacques S; Lioy, Janet; Deshmukh, Hitesh; Srinivasan, Lakshmi; Swarr, Daniel T; Sloman, Melissa; Shaw-Smith, Charles; van Loon, Rosa Laura; Hagman, Cecilia; Sznajer, Yves; Barrea, Catherine; Galant, Christine; Detaille, Thierry; Wambach, Jennifer A; Cole, F Sessions; Hamvas, Aaron; Prince, Lawrence S; Diderich, Karin E M; Brooks, Alice S; Verdijk, Robert M; Ravindranathan, Hari; Sugo, Ella; Mowat, David; Baker, Michael L; Langston, Claire; Welty, Stephen; Stankiewicz, Pawel

    2013-06-01

    Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis. PMID:23505205

  5. Toxic risk associated with sporadic occurrences of Microcystis aeruginosa blooms from tidal rivers in marine and estuarine ecosystems and its impact on Artemia franciscana nauplii populations.

    Science.gov (United States)

    D'ors, A; Bartolomé, M C; Sánchez-Fortún, S

    2013-02-01

    Microcystis aeruginosa is a species of freshwater cyanobacteria which can form harmful algal blooms in freshwater water bodies worldwide. However, in spite its sporadic occurrences for short periods of time in estuarine waters, their influence on zooplankton populations present in these ecosystems has not been extensively studied. In this work, Artemia franciscana was used as test organism model, studying mortality against several strains of M. aeruginosa with different degrees of toxigenicity, measuring whole-live cells and homogenate extracts. Results were compared with microcystin-LR equivalent content, measured by immunoassay. The results show that there were no significant differences between both exposure models (whole cells and extracts), and there are significant differences respect to the toxigenicity of cyanobacterial blooms depending of the M. aerugionosa strain involved in the process. Analysis of microcystin-LR equivalent concentration test immediately below the lowest significant concentration in all M. aerugionosa strains was used to determine the potential risk associated with the cell densities during a bloom. Comparison among the selected M. aerugionsa strains show that these factors have influence in the results obtained, and thus, several differences have been evidenced depending of the microcystin-LR equivalent production and the strain type involved. PMID:23246722

  6. RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Bignone, P A; Lee, K Y

    2007-01-01

    We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.

  7. Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis / Alteraciones morfológicas en las mitocondrias en la piel de enfermos con esclerosis lateral amiotrófica esporádica

    Scientific Electronic Library Online (English)

    Gabriel E., Rodríguez; Deniselle M. Claudia, González; Gisella M. Gargiulo, Monachelli; Juan J. López, Costa; Alejandro F. de, Nicola; Roberto E. P., Sica.

    2012-01-01

    Full Text Available SciELO Brazil | Language: English Abstract in spanish OBJETIVOS: Existen alteraciones en la función mitocondrial en el sistema nervioso central, en hepatocitos y en linfocitos de sangre periférica en SALS. Aunque, no se ha estudiado si existen cambios estructurales en las mitocondrias de la piel. Nuestro objetivo fue comparar la ultraestructura de mito [...] condrias en queratinocitos de enfermos con SALS con la de controles sanos. MÉTODO: Fueron analizadas en el microscopio electrónico 112 mitocondrias dérmicas de 5 pacientes y 99 provenientes de 4 controles. RESULTADOS: EL análisis computarizado mostró que el eje mayor mitocondrial, el área y el perímetro de las organelas fueran significativamente menor que en controles. Morfológicamente, las mitocondrias de SALS presentaron cristólisis y ruptura de la membrana externa. CONCLUSIÓN: La alteración mitocondrial en la piel posiblemente refleje cambios que también ocurran en las mitocondrias neuronales. Este análisis morfológico de las mitocondrias podría tener valor en el seguimiento de la enfermedad y eventualmente en la evaluación de la efectividad de futuras terapias. Abstract in english OBJECTIVES: Mitochondrial dysfunction has been reported in the central nervous system, hepatocytes and peripheral blood lymphocytes from patients with sporadic amyotrophic lateral sclerosis (SALS). However, the status of skin mitochondria has not been reported, in spite of the fact that SALS patient [...] s present skin abnormalities. The objective of the present study was to compare mitochondrial ultrastructural parameters in keratinocytes from patients with SALS and healthy controls. METHODS: Our study was based on the analysis of 112 skin mitochondria from 5 SALS patients and 99 organelles from 4 control subjects by electron microscopy. RESULTS: Computerized image analysis showed that mitochondrial major axis length, area and perimeter of the organelle were significantly smaller in SALS respect of healthy control subjects. Morphologically, SALS mitochondria presented cristolysis and breakage of the outer membrane. CONCLUSIONS: Mitochondrial dysfunction in the skin may possibly reflect changes occurring in mitochondria of the central nervous system. The analysis of mitochondrial morphology in this tissue may be of value to follow disease progression and, eventually, the effectiveness of current therapies for SALS.

  8. Enfermedad de Creutzfeldt-Jakob esporádica: dos casos en medicina intensiva / Sporadic Creutzfeldt-Jakob disease: two cases in intensive care

    Scientific Electronic Library Online (English)

    P., Cardinal; I., Pedemonte; J., Castelli; E., Zitto; A., Cacciatore; N., Zefferino.

    2011-02-01

    Full Text Available SciELO Spain | Language: Spanish Abstract in spanish Las enfermedades priónicas o encefalopatías espongiformes son una familia de raras patologías neurodegenerativas caracterizadas por periodos de incubación prolongados asociados a una lenta, irreversible e invariablemente mortal evolución. En humanos se las clasifica en esporádica, adquirida y heredi [...] taria o genética. Realizar el diagnóstico de «enfermedad de Creutzfeldt-Jakob» es un verdadero desafío para el médico intensivista dada la variabilidad en la presentación clínica y su baja incidencia. Se presentan 2 pacientes admitidos en la UCI en los que, tras descartar varias patologías, se diagnosticó con un nivel de «probabilidad», de acuerdo a la clasificación de la OMS, enfermedad de Creutzfeldt-Jakob esporádica. Se analizan aspectos diagnósticos clínicos y analíticos de la enfermedad resaltando la utilidad de la identificación de la proteína 14-3-3 en el líquido cefalorraquídeo. Abstract in english Prion diseases or spongiform encephalopathies are a family of rare neurodegenerative diseases characterized by long incubation periods associated with slow, irreversible and invariably fatal evolution. In humans, they are classified as sporadic, acquired and hereditary or genetic. Diagnosing sporadi [...] c "Creutzfeldt-Jakob Disease" (sCJD) is a real challenge for the intensive care physician, given the variability in its clinical presentation and its low incidence. The cases of two patients admitted to the Intensive Care Unit are presented. After ruling out other diseases, they were diagnosed with sCJD with a likelihood level according to the World Health Organization Classification. Clinical and laboratory diagnostic aspects of the disease were analyzed, highlighting the utility of 14-3-3 protein identification in the cerebrospinal fluid.

  9. New Variations in the Promoter Regions of Human DOCK4 and RAP1A Genes, and Coding Regions of RAP1A in Sporadic Breast Tumors

    Science.gov (United States)

    Jalali, Akram; Ebrahimi, Hassan; Ohadi, Mina; Karimloo, Masood; Shemirani, Atena Irani; Mohajer, Behrokh; Khorshid, Hamid Reza Khorram

    2009-01-01

    Breast cancer is the most common cancer among women in developed countries. The prevalence of the disease is increasing in the world. Its annual incidence among Iranian women is about 7000 cases. RAP1A, a tumor suppressor gene, is located at 1p13.3 and plays an important role in the cellular adhesion pathway and is involved in the pathogenesis of breast cancer. The DOCK4 gene, which is located at 7q31.1, specifically activates RAP1A gene. In the present study, DNA samples from 64 cases of sporadic breast tumors (referred to Mehrad Hospital in Tehran) were screened using PCR-SSCP method and the number of observed variations compared with the control group (100 normal women). Mutation detection for coding exons of RAP1A gene and the 500 bp upstream of transcription initiation site as promoters of both DOCK4 and RAP1A were carried out and compared with the control group. The promoter region of DOCK4 showed a heterozygous mutation with G>A transition at nucleotide ?303 in a fibroadenoma case. With regard to RAP1A we found a heterozygous mutation, G>A transition in an adenoid cystic carcinoma case, and another heterozygous mutation, G>T transversion in an intraductal papilloma case both at nucleotide +45. A homozygous variation, T>A transversion was also found at nucleotide +29 of a fibroadenoma case. The differences in the frequency of variations mentioned above were not statistically significant. However Fisher's exact showed significant difference for T>A transversion. Although, the higher frequency of these mutations and variations may be related to the disease, a larger sample size is needed for the confirmation of our findings. PMID:23407849

  10. Refinements in the use of equivalent latitude for assimilating sporadic inhomogeneous stratospheric tracer observations, 1: Detecting transport of Pinatubo aerosol across a strong vortex edge

    Directory of Open Access Journals (Sweden)

    P. Good

    2004-01-01

    Full Text Available The use of PV equivalent latitude for assimilating stratospheric tracer observations is discussed - with particular regard to the errors in the equivalent latitude coordinate, and to the assimilation of sparse data. Some example measurements are assimilated: they sample the stratosphere sporadically and inhomogeneously. The aim was to obtain precise information about the isentropic tracer distribution and evolution as a function of equivalent latitude. Precision is important, if transport across barriers like the vortex edge are to be detected directly. The main challenges addressed are the errors in modelled equivalent latitude, and the non-ideal observational sampling. The methods presented allow first some assessment of equivalent latitude errors and a picture of how good or poor the observational coverage is. This information determines choices in the approach for estimating as precisely as possible the true equivalent latitude distribution of the tracer, in periods of good and poor observational coverage. This is in practice an optimisation process, since better understanding of the equivalent latitude distribution of the tracer feeds back into a clearer picture of the errors in the modelled equivalent latitude coordinate. Error estimates constrain the reliability of using equivalent latitude to make statements like 'this observation samples air poleward of the vortex edge' or that of more general model-measurement comparisons. The approach is demonstrated for ground-based lidar soundings of the Mount Pinatubo aerosol cloud, focusing on the 1991-92 arctic vortex edge between 475-520K. Equivalent latitude is estimated at the observation times and locations from Eulerian model tracers initialised with PV and forced by UK Meteorological Office analyses. With the model formulation chosen, it is shown that tracer transport of a few days resulted in an error distribution that was much closer to Gaussian form, although the mean error was not significantly affected. The analysis of the observations revealed a small amount of irreversible transport of aerosol across the vortex edge during late January 1992, coincident with a strongly disturbed vortex.

  11. Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions.

    Science.gov (United States)

    Nishihira, Yasushi; Tan, Chun-Feng; Onodera, Osamu; Toyoshima, Yasuko; Yamada, Mitsunori; Morita, Takashi; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2008-08-01

    A nuclear protein, 43-kDa TAR DNA-binding protein (TDP-43), was recently identified as a component of the ubiquitinated inclusions (UIs) in frontotemporal lobar degeneration (FTLD-U) and sporadic amyotrophic lateral sclerosis (SALS). In the present study using immunohistochemistry, we examined various regions of the nervous system in a series of 35 SALS cases using a polyclonal antibody against TDP-43. Seven of the 35 cases had disease durations of more than 10 years with artificial respiratory support (ARS; duration: 69-156 months). In all cases, TDP-43-immunoreactive (ir) neuronal and glial cytoplasmic inclusions (NCIs and GCIs) were found together in many regions, including the histologically affected lower motor neuron nuclei. Cluster analysis of the distribution pattern of TDP-43-ir NCIs for cases without ARS (n = 28) identified two types (type 1, n = 16; type 2, n = 12). Type 2 was distinguished from type 1 by the presence of TDP-43-ir NCIs in the frontotemporal cortex, hippocampal formation, neostriatum and substantia nigra, and was significantly associated with dementia. Eleven of the 28 cases showed UIs in the hippocampal dentate granule cells, all of which had type-2 distribution pattern. Cases with ARS (n = 7) were also classified into the same types (type 1, n = 5; type 2, n = 2). Cases having type-1 distribution pattern (n = 21) showed no evident neuronal loss in most of the non-motor neuron nuclei where TDP-43-ir NCIs were present, whereas cases having type-2 distribution pattern (n = 14) often showed evident neuronal loss in the frontotemporal cortices, amygdaloid nuclei and substantia nigra. These findings indicate that SALS is a multisystem degenerative disease widely affecting both neurons and glial cells with a heterogeneous pattern of TDP-43-ir NCI distribution (SALS showing type-2 distribution pattern being closely linked to FTLD-U), and that long-term survival supported by a respirator has no apparent influence on the TDP-43 neuronal distribution pattern. PMID:18481073

  12. Sporadic amyotrophic lateral sclerosis: Widespread multisystem degeneration with TDP-43 pathology in a patient after long-term survival on a respirator.

    Science.gov (United States)

    Nishihira, Yasushi; Tan, Chun-Feng; Toyoshima, Yasuko; Yonemochi, Yosuke; Kondo, Hiroshi; Nakajima, Takashi; Takahashi, Hitoshi

    2009-12-01

    It has been reported that widespread multisystem degeneration can occur in patients with sporadic amyotrophic lateral sclerosis (SALS) who have survived for long periods with artificial respiratory support (ARS). We report a case of SALS of 8 years and 8 months duration in a 71-year-old woman, who received ARS for 7 years and 8 months. In this patient, the symptoms at the early stage were those of typical ALS, and a totally locked-in state with frontal lobe atrophy appeared a few years after the start of ARS. At autopsy, marked atrophy of the frontal lobe and brainstem tegmentum was evident. Microscopically, widespread multisystem degeneration with obvious neuronal loss was a feature. Bunina bodies and ubiquitinated inclusions were observed in the remaining lower motor neurons. Of interest was that Lewy body-like hyaline inclusions (LBHIs), which were later shown to be immunnoreactive (ir) for 43-kDa TAR DNA-binding protein (TDP-43) and ubiquitin, were also detected in neurons in various regions of the nervous system, including the lower and upper motor neuron nuclei. The distributions of neurons with TDP-43-ir and ubiquitin-ir cytoplasmic inclusions were also widespread in the nervous system, and in each region, the numbers of these neurons were apparently larger than those of neurons with LBHIs. Importantly, double-labeling immunofluorescence revealed that the widespread TDP-43-ir inclusions were often ubiqutinated. In conclusion, the entire pathological picture appeared to correspond well to the patient's long-standing, progressive disease, including the TDP-43 pathology with ubiquitination. These findings further strengthen the idea that TDP-43 abnormality is closely associated with the pathogenesis of SALS. PMID:19170893

  13. New Variations in the Promoter Regions of Human DOCK4 and RAP1A Genes, and Coding Regions of RAP1A in Sporadic Breast Tumors.

    Science.gov (United States)

    Jalali, Akram; Ebrahimi, Hassan; Ohadi, Mina; Karimloo, Masood; Shemirani, Atena Irani; Mohajer, Behrokh; Khorshid, Hamid Reza Khorram

    2009-07-01

    Breast cancer is the most common cancer among women in developed countries. The prevalence of the disease is increasing in the world. Its annual incidence among Iranian women is about 7000 cases. RAP1A, a tumor suppressor gene, is located at 1p13.3 and plays an important role in the cellular adhesion pathway and is involved in the pathogenesis of breast cancer. The DOCK4 gene, which is located at 7q31.1, specifically activates RAP1A gene. In the present study, DNA samples from 64 cases of sporadic breast tumors (referred to Mehrad Hospital in Tehran) were screened using PCR-SSCP method and the number of observed variations compared with the control group (100 normal women). Mutation detection for coding exons of RAP1A gene and the 500 bp upstream of transcription initiation site as promoters of both DOCK4 and RAP1A were carried out and compared with the control group. The promoter region of DOCK4 showed a heterozygous mutation with G>A transition at nucleotide -303 in a fibroadenoma case. With regard to RAP1A we found a heterozygous mutation, G>A transition in an adenoid cystic carcinoma case, and another heterozygous mutation, G>T transversion in an intraductal papilloma case both at nucleotide +45. A homozygous variation, T>A transversion was also found at nucleotide +29 of a fibroadenoma case. The differences in the frequency of variations mentioned above were not statistically significant. However Fisher's exact showed significant difference for T>A transversion. Although, the higher frequency of these mutations and variations may be related to the disease, a larger sample size is needed for the confirmation of our findings. PMID:23407849

  14. Multiple ?-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer’s disease subjects

    Directory of Open Access Journals (Sweden)

    Hata Saori

    2012-04-01

    Full Text Available Abstract Background Alcadein? (Alc? is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-? precursor protein (APP. Successive cleavage of APP by ?- and ?-secretases generates the aggregatable amyloid-? peptide (A?, while cleavage of APP or Alc? by ?- and ?-secretases generates non-aggregatable p3 or p3-Alc? peptides. A? and p3-Alc? can be recovered from human cerebrospinal fluid (CSF. We have previously reported alternative processing of APP and Alc? in the CSF of some patients with sporadic mild cognitive impairment (MCI and AD (SAD. Results Using the sandwich enzyme-linked immunosorbent assay (ELISA system that detects total p3-Alc?, we determined levels of total p3-Alc? in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease derived from three independent cohorts. Levels of A?40 correlated with levels of total p3-Alc? in all cohorts. Conclusions We confirm that A?40 is the most abundant A? species, and we propose a model in which CSF p3-Alc? can serve as a either (1 a nonaggregatable surrogate marker for ?-secretase activity; (2 as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism; or (3 both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alc? and A?40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of ?-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in A? metabolism

  15. Human Noroviruses and Sporadic Gastroenteritis

    Centers for Disease Control (CDC) Podcasts

    2008-08-05

    In this podcast, Dan Rutz speaks with Dr. Manish Patel, a medical officer with the Division of Viral Diseases at CDC, about an article in August 2008 issue of Emerging Infectious Diseases reporting on nororviruses. Dr. Patel reviewed 235 studies and identified 31 original studies about noroviruses. Norovirus is the leading cause of epidemic gastroenteritis.  Created: 8/5/2008 by Emerging Infectious Diseases.   Date Released: 7/30/2008.

  16. A spectral study of the mid-latitude sporadic E layer characteristic oscillations comparable to those of the tidal and the planetary waves

    Science.gov (United States)

    Pignalberi, A.; Pezzopane, M.; Zuccheretti, E.

    2015-01-01

    In this paper different spectral analyses are employed to investigate the tidal and planetary wave periodicities imprinted in the following two main characteristics of the sporadic E (Es) layer: the top frequency (ftEs) and the lowest virtual height (h?Es). The study is based on ionograms recorded during the summertime of 2013, and precisely in June, July, August and September, by the Advanced Ionospheric Sounder by Istituto Nazionale di Geofisica e Vulcanologia (AIS-INGV) ionosondes installed at Rome (41.8°N, 12.5°E) and Gibilmanna (37.9°N, 14.0°E), Italy. It was confirmed that the diurnal and semidiurnal atmospheric tides play a fundamental role in the formation of the mid-latitude Es layers, acting through their vertical wind-shear forcing of the long-living metallic ions in the lower thermosphere, and at the same time it was found that the planetary atmospheric waves might affect the Es layers acting through their horizontal wind-shear forcing with periods close to the normal Rossby modes, that is 2, 5, 10 and 16 days. The wavelet analysis shows also that the ftEs and h?Es tidal oscillations undergo a strong amplitude modulation with periods of several days and with important differences between the two parameters. This amplitude modulation, characterizing markedly the first thirty days of the ftEs spectrogram, suggests that Es layers are affected indirectly by planetary waves through their nonlinear interaction with the atmospheric tides at lower altitudes. This study wants to be a continuation of the Haldoupis et al. (2004) work in order to verify their results for the foEs characteristic and on the other hand to extend the study also to the h?Es characteristic not yet shown so far. Anyhow, the study confirms that ionosonde data, especially those registered in summertime, represent a powerful tool for studying tidal and planetary waves properties and their climatology in the mesosphere-low-thermosphere region.

  17. Refinements in the use of equivalent latitude for assimilating sporadic inhomogeneous stratospheric tracer observations, 1: Detecting transport of Pinatubo aerosol across a strong vortex edge

    Directory of Open Access Journals (Sweden)

    P. Good

    2004-01-01

    Full Text Available The use of PV equivalent latitude for assimilating stratospheric tracer observations is discussed – with particular regard to the errors in the equivalent latitude coordinate, and to the assimilation of sparse data. Some example measurements are assimilated: they sample the stratosphere sporadically and inhomogeneously. The aim was to obtain precise information about the isentropic tracer distribution and evolution as a function of equivalent latitude. Precision is important, if transport across barriers like the vortex edge are to be detected directly. The main challenges addressed are the errors in modelled equivalent latitude, and the non-ideal observational sampling. The methods presented allow first some assessment of equivalent latitude errors and a picture of how good or poor the observational coverage is. This information determines choices in the approach for estimating as precisely as possible the true equivalent latitude distribution of the tracer, in periods of good and poor observational coverage. This is in practice an optimisation process, since better understanding of the equivalent latitude distribution of the tracer feeds back into a clearer picture of the errors in the modelled equivalent latitude coordinate. Error estimates constrain the reliability of using equivalent latitude to make statements like "this observation samples air poleward of the vortex edge'" or that of more general model-measurement comparisons. The approach is demonstrated for ground-based lidar soundings of the Mount Pinatubo aerosol cloud, focusing on the 1991–1992 arctic vortex edge between 475–520 K. Equivalent latitude is estimated at the observation times and locations from Eulerian model tracers initialised with PV and forced by UK Meteorological Office analyses. With the model formulation chosen, it is shown that tracer transport of a few days resulted in an error distribution that was much closer to Gaussian form, although the mean error was not significantly affected. The analysis of the observations revealed a small amount of irreversible transport of aerosol across the vortex edge during late January 1992, coincident with a strongly disturbed vortex.

  18. Tratamiento de schwanomas vestibulares esporádicos mediante radiocirugía: Estudio prospectivo de cohorte / Radiosurgical treatment of sporadic vestibular schwannomas: A prospective cohort study

    Scientific Electronic Library Online (English)

    Freddy, Martel V; Rodrigo, Iñiguez S; Daniel, Venencia M; Patricio, Tagle M; Pelayo, Besa D; José, Lorenzoni S.

    2008-12-01

    Full Text Available SciELO Chile | Language: Spanish Abstract in spanish Objetivo: Analizar los resultados iniciales de un estudio prospectivo en pacientes con schwanomas vestibulares tratados con radiocirugía en la Pontificia Universidad Católica de Chile. Material y método: Se presentan 17 pacientes portadores de schwanomas vestibulares esporádicos tratados con radioci [...] rugía y seguidos entre 6 y 26 meses. El tratamiento fue realizado con acelerador lineal Varían clinac21 EX, con equipamiento Varían-Zmed. La dosis marginal administrada al tumor fue de 12 a 12,5 Gray El seguimiento a 6, 12 y 24 meses consta de resonancia magnética, audiometríay evaluación clínica. Resultados: La dosis marginal de irradiación usada fue entre 12y 12,5 Gray normalizada a la isodosis 70% u 80%. En todos los pacientes se documentó disminución de la captación de contraste del tumor y en 16 (94%) se observaron áreas de necrosis centro tumoral. No hubo mortalidad, la preservación de audición útil fue 62,5% actuaría! a 2 años. No ha existido deterioro de la función de los nervios facial ni trigémino. Todos los pacientes que previamente estaban trabajando retornaron a sus labores en promedio 11,5 días luego del tratamiento. Conclusiones: Los resultados iniciales de esta serieison comparables a los resultados publicados en la literatura y refuerzan el demostrado rol de la radiocirugía en el tratamiento de los schwanomas vestibulares. Abstract in english Objective: To analyze the preliminary experience of radiosurgery for Vestibular Schwannomas at the Pontificia Universidad Católica de Chile. Material and methods: Thefirst 17 patients with sporadic Vestibular Schwannomas treated by radiosurgery at our institution are reponed. The marginal dose used [...] was 12 to 12.5 Gy. prescribed at the 70 or 80 isodose Une. 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 firsyear Actuaría! 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%). Trigémina! function was maintained in all 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 demónstrate role oí radiosurgery in the management oí vestibular schwannomas.

  19. 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.

  20. Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within the NF2 locus

    Directory of Open Access Journals (Sweden)

    Jarbo Caroline

    2007-01-01

    Full Text Available Abstract Background Meningiomas are the most common intracranial neoplasias, representing a clinically and histopathologically heterogeneous group of tumors. The neurofibromatosis type 2 (NF2 tumor suppressor is the only gene known to be frequently involved in early development of meningiomas. The objective of this study was to identify genetic and/or epigenetic factors contributing to the development of these tumors. A large set of sporadic meningiomas were analyzed for presence of 22q macro-mutations using array-CGH in order to identify tumors carrying gene dosage aberrations not encompassing NF2. The NF2 locus was also comprehensively studied for point mutations within coding and conserved non-coding sequences. Furthermore, CpG methylation within the NF2 promoter region was thoroughly analyzed. Results Monosomy 22 was the predominant finding, detected in 47% of meningiomas. Thirteen percent of the tumors contained interstitial/terminal deletions and gains, present singly or in combinations. We defined at least two minimal overlapping regions outside the NF2 locus that are small enough (~550 kb and ~250 kb to allow analysis of a limited number of candidate genes. Bialleinactivationo the NF2 gne was detected in 36% of meningiomas. Among the monosomy 22 cases, no additional NF2 mutations could be identified in 35% (17 out of 49 of tumors. Furthermore, the majority of tumors (9 out of 12 with interstitial/terminal deletions did not have any detectable NF2 mutations. Methylation within the NF2 promoter region was only identified at a single CpG site in one tumor sample. Conclusion We confirmed previous findings of pronounced differences in mutation frequency between different histopathological subtypes. There is a higher frequency of biallelic NF2 inactivation in fibroblastic (52% compared to meningothelial (18% tumors. The presence of macro-mutations on 22q also shows marked differences between fibroblastic (86% and meningothelial (39% subtypes. Thus, inactivation of NF2, often combined with the presence of macro-mutation on 22q, is likely not as important for the development of the meningothelial subtype, as opposed to the fibroblastic form. Analysis of 40 CpG sites distributed within 750 bp of the promoter region suggests that NF2 promoter methylation does not play a major role in meningioma development.