WorldWideScience
1

Solar eclipse effects of 22 July 2009 on Sporadic-E  

OpenAIRE

The total solar eclipse of 22 July 2009, was visible from some regions of China and the intense sporadic-E (Es) that broke out during the solar eclipse period over the eastern China provided a unique chance to study solar eclipse effects on the Es-layer. The ground based high-frequency (HF) vertical-incidence and oblique-incidence backscatter radio systems in Wuhan and an HF oblique receivers located in Suzhou were operated to detect the Es-layer. The vertical, oblique and backscatter ionogra...

Chen, G.; Zhao, Z.; Zhou, C.; Yang, G.; Zhang, Y.

2010-01-01

2

Solar eclipse effects of 22 July 2009 on Sporadic-E  

Directory of Open Access Journals (Sweden)

Full Text Available The total solar eclipse of 22 July 2009, was visible from some regions of China and the intense sporadic-E (Es that broke out during the solar eclipse period over the eastern China provided a unique chance to study solar eclipse effects on the Es-layer. The ground based high-frequency (HF vertical-incidence and oblique-incidence backscatter radio systems in Wuhan and an HF oblique receivers located in Suzhou were operated to detect the Es-layer. The vertical, oblique and backscatter ionograms of 22 and 23 July were recorded, processed and analyzed. The analyzing results show that the critical frequency of Es, the hop number and power of the rays transmitted from Wuhan to Suzhou as well as the Doppler frequency shift of the one-hop oblique-incidence waves reflected by the Es-layer all increased during the solar eclipse period. These variations are displayed in the paper and explained to be induced by the wind-field, which is produced by the powerful meridional air flows from the sunshine region to the moon's shadow.

G. Chen

2010-02-01

3

Effect of BRCA1 immunohistochemical localizations on prognosis of patients with sporadic breast carcinomas.  

Science.gov (United States)

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p=0.019 and p=0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p=0.05), prolonging the RF survival of the patients (p=0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases. PMID:24947414

Mylona, Eleni; Melissaris, Savvas; Nomikos, Alexandros; Theohari, Irene; Giannopoulou, Ioanna; Tzelepis, Konstantinos; Nakopoulou, Lydia

2014-08-01

4

Effects of Active Constituents of Crocus sativus L., Crocin on Streptozocin-Induced Model of Sporadic Alzheimer's Disease in Male Rats  

OpenAIRE

Background: The involvement of water-soluble carotenoids, crocins, as the main and active components of Crocus sativus L. extract in learning and memory processes has been proposed. In the present study, the effect of crocins on sporadic Alzheimer's disease induced by intracerebroventricular (icv) streptozocin (STZ) in male rats was investigated. Methods: Male adult Wistar rats (n = 90 and 260-290 g) were divided into 1, control; 2 and 3, crocins (15 and 30 mg/kg); 4, STZ; 5 and 6, STZ + croc...

Khalili, Mohsen; Hamzeh, Faezeh

2010-01-01

5

Effects of common haplotypes of the ileal sodium dependent bile acid transporter gene on the development of sporadic and familial colorectal cancer: A case control study  

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Full Text Available Abstract Background The genetics of sporadic and non-syndromic familial colorectal cancer (CRC is not well defined. However, genetic factors that promote the development of precursor lesions, i.e. adenomas, might also predispose to CRC. Recently, an association of colorectal adenoma with two variants (c.507C>T;p.L169L and c.511G>T;p.A171S of the ileal sodium dependent bile acid transporter gene (SLC10A2 has been reported. Here, we reconstructed haplotypes of the SLC10A2 gene locus and tested for association with non-syndromic familial and sporadic CRC compared to 'hyper-normal' controls who displayed no colorectal polyps on screening colonoscopy. Methods We included 150 patients with sporadic CRC, 93 patients with familial CRC but exclusion of familial adenomatous polyposis and Lynch's syndrome, and 204 'hyper-normal' controls. Haplotype-tagging SLC10A2 gene variants were identified in the Hapmap database and genotyped using PCR-based 5' exonuclease assays with fluorescent dye-labelled probes. Haplotypes were reconstructed using the PHASE algorithm. Association testing was performed with both SNPs and reconstructed haplotypes. Results Minor allele frequencies of all SLC10A2 polymorphisms are within previously reported ranges, and no deviations from Hardy-Weinberg equilibrium are observed. However, we found no association with any of the SLC10A2 haplotypes with sporadic or familial CRC in our samples (all P values > 0.05. Conclusion Common variants of the SLC10A2 gene are not associated with sporadic or familial CRC. Hence, albeit this gene might be associated with early stages of colorectal neoplasia, it appears not to represent a major risk factor for progression to CRC.

Friedrichs Nicolaus

2008-07-01

6

Automorphism groups of sporadic groups  

CERN Document Server

Among the simplest invariants of the sporadic finite simple groups are their outer automorphism groups. For 12 of the 26 possible isomorphism types of a sporadic simple group G, the outer automorphism group Out(G) has order 2, and in the remaining 14 cases, Out(G) is trivial. Historically the suspicion of the existence of a sporadic group was followed in fairly short order by the calculation of a good upper bound on the size of its outer automorphism group. In a few cases establishing the existence of certain outer automorphisms, like the existence of the groups themselves, presented difficulties overcome only with the use of machine computation. In any case these calculations can be difficult to track down in the literature. This note, which contains nothing new, is only intended to bring together these calculations. It also answers a question of Bob Oliver about the automorphism groups of some of these groups, how they might be calculated, and specifically whether the Sylow 2-subgroups of a sporadic simple ...

Lyons, Richard

2011-01-01

7

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  

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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.

Yong-chang Diwu

2011-02-01

8

Sporadic hemiplegic migraine and CREST syndrome  

OpenAIRE

Hemiplegic migraines are characterised by attacks of migraine with aura accompanied by transient motor weakness. There are both familial and sporadic subtypes, which are now recognised as separate entities by the International Classification of Headache Disorders, edition II (ICHD-II). The sporadic subtype has been associated with other medical conditions, particularly rheumatological diseases. We report the case of a woman with sporadic hemiplegic migraine associated with CREST syndrome (cal...

Grecco, Martin Pablo; Pieroni, Miguel; Otero, Marcela; Ferreiro, Jorge Luis; Figuerola, Mari?a Lourdes

2010-01-01

9

Giant aneurysm formation in sporadic renal angiomyolipoma  

OpenAIRE

Angiomyolipomas are the most common mesenchymal renal neoplasms. Two types have been described: (i) sporadic angiomyolipoma and (ii) angiomyolipoma associated with tuberous sclerosis. Giant aneurysm formation is usually noted in angiomyolipomas associated with tuberous sclerosis and is rare in sporadic variety. Tumor diameter and aneurysm diameter have been used as predictors of rupture. We report a rare case of aneurysm formation in a sporadic angiomyolipoma.

Patil, Aruna R.; Chandra, Ranjan; Gupta, Ashwani; Thukral, Brij Bhushan

2010-01-01

10

Sporadic hemiplegic migraine and CREST syndrome.  

Science.gov (United States)

Hemiplegic migraines are characterised by attacks of migraine with aura accompanied by transient motor weakness. There are both familial and sporadic subtypes, which are now recognised as separate entities by the International Classification of Headache Disorders, edition II (ICHD-II). The sporadic subtype has been associated with other medical conditions, particularly rheumatological diseases. We report the case of a woman with sporadic hemiplegic migraine associated with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia). Since there is a close relationship between migraine and Raynaud's phenomenon, it could be speculated that the sporadic hemiplegic migraines in our patient might be secondary to CREST syndrome. PMID:20130953

Grecco, Martin Pablo; Pieroni, Miguel; Otero, Marcela; Ferreiro, Jorge Luis; Figuerola, María de Lourdes

2010-04-01

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Ongoing developments in sporadic inclusion body myositis.  

Science.gov (United States)

Sporadic inclusion body myositis (IBM) is an acquired muscle disorder associated with ageing, for which there is no effective treatment. Ongoing developments include: genetic studies that may provide insights regarding the pathogenesis of IBM, improved histopathological markers, the description of a new IBM autoantibody, scrutiny of the diagnostic utility of clinical features and biomarkers, the refinement of diagnostic criteria, the emerging use of MRI as a diagnostic and monitoring tool, and new pathogenic insights that have led to novel therapeutic approaches being trialled for IBM, including treatments with the objective of restoring protein homeostasis and myostatin blockers. The effect of exercise in IBM continues to be investigated. However, despite these ongoing developments, the aetiopathogenesis of IBM remains uncertain. A translational and multidisciplinary collaborative approach is critical to improve the diagnosis, treatment, and care of patients with IBM. PMID:25399751

Machado, Pedro M; Ahmed, Mhoriam; Brady, Stefen; Gang, Qiang; Healy, Estelle; Morrow, Jasper M; Wallace, Amanda C; Dewar, Liz; Ramdharry, Gita; Parton, Matthew; Holton, Janice L; Houlden, Henry; Greensmith, Linda; Hanna, Michael G

2014-12-01

12

Sporadic wind wave horse-shoe patterns  

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Full Text Available The work considers three-dimensional crescent-shaped patterns often seen on water surface in natural basins and observed in wave tank experiments. The most common of these 'horse-shoe-like' patterns appear to be sporadic, i.e., emerging and disappearing spontaneously even under steady wind conditions. The paper suggests a qualitative model of these structures aimed at explaining their sporadic nature, physical mechanisms of their selection and their specific asymmetric form. First, the phenomenon of sporadic horse-shoe patterns is studied numerically using the novel algorithm of water waves simulation recently developed by the authors (Annenkov and Shrira, 1999. The simulations show that a steep gravity wave embedded into widespectrum primordial noise and subjected to small nonconservative effects typically follows the simple evolution scenario: most of the time the system can be considered as consisting of a basic wave and a single pair of oblique satellites, although the choice of this pair tends to be different at different instants. Despite the effective low-dimensionality of the multimodal system dynamics at relatively sho ' rt time spans, the role of small satellites is important: in particular, they enlarge the maxima of the developed satellites. The presence of Benjamin-Feir satellites appears to be of no qualitative importance at the timescales under consideration. The selection mechanism has been linked to the quartic resonant interactions among the oblique satellites lying in the domain of five-wave (McLean's class II instability of the basic wave: the satellites tend to push each other out of the resonance zone due to the frequency shifts caused by the quartic interactions. Since the instability domain is narrow (of order of cube of the basic wave steepness, eventually in a generic situation only a single pair survives and attains considerable amplitude. The specific front asymmetry is found to result from the interplay of quartic and quintet interactions and non-conservative effects: the growing and grown satellites have a specific value of phase with respect to the basic wave that corresponds to downwind orientation of the convex sides of wave fronts. As soon as the phase relation is violated, the satellite's amplitude quickly decreases down to the noise level.

S. Yu. Annenkov

1999-01-01

13

The lunar tide in sporadic E  

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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

R. J. Stening

14

Vascular changes in sporadic ergotism  

International Nuclear Information System (INIS)

Whereas the epidemic form of ergotism has been rare in the 20th century, the sporadic form has a wide distribution as a consequence of therapy with ergot-derivative drugs. Favourable prognosis of the condition, with complete recovery from the ischemic peripheral circulatory disorders can be obtained by early diagnosis. Precise evaluation of the history, with recognition of treatment of migraine headache or postpartum hemorraghe with ergot alkaloids, can be determinative in diagnosis. The specific pattern of the angiographic findings, as we saw it in 6 cases within the last 4 years, decisively confirms the diagnosis. We could demonstrate thread-, thorn- and hour glass-like narrowing of the vessels, due to spasm. Total occlusion with the development of collaterals may occur, but we saw no thrombus formation. The stenotic arterial segments had smooth margins. The distribution of the involved arteries was more focal than generalized and more peripheral than central. In two cases spasm could be abolished immediately by a pharmaceutical (i.a. injection of tolazoline) or by anesthetic procedures (halothane). The phenomenologic data, together with the complete reversal of the circulatory ischemic disorders after therapy (particularly the absolute ban of ergots), is so specific that other diseases of ischemic nature (emboli, arteriosclerosis, Buerger's disease, fibromuscular hyperplasia) can be excluded. (orig.)

15

The Sporadic Meteoroid Complex and Spacecraft Risk  

Science.gov (United States)

The meteoroid population in near-Earth space is typically broken down into two components: shower meteoroids which orbit in collimated streams, and the older sporadic meteoroids which have been dispersed into a much broader uncollimated distribution of orbits. The sporadic meteors dominate the meteoroid flux at Earth in the size range of those particles of the most of the risk to spacecraft (approximately 100 microns to 1 cm). We describe the results of numerical simulations of the sporadic meteoroid complex by full physical modeling of meteoroids from ejection from their parent body through their perturbation by planets and radiation forces though the end of their lives through collision or ejection from the solar system. This model together with comparison with optical and radar measurements of meteoroid fluxes in near Earth space will allow improved assessment of the risk to spacecraft in near-Earth space from the sporadic complex.

Wiegert, Paul; Vaubaillon, Jeremie

2009-01-01

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Absolute Alcohol Embolization of Sporadic Angiomyolipoma  

OpenAIRE

Angiomyolipoma is a benign hamartoma. Seventy percent of angiomyolipomas occur sporadically in the general population and the remainder are associated with a syndrome. Of patients with tuberous sclerosis, 60 to 80% have an angiomyolipoma. Sporadic angiomyolipomas tend to be single and occur in an older age group. In tuberous sclerosis, the lesions are usually bilateral and multiple. Therapy is indicated when there are symptoms or when the lesion is greater than 4 cm. Criteria for further embo...

Cantwell, Colin P.; Taubman, Kevin E.; Scorza, Leslie B.

2008-01-01

17

/ Sporadic oral angiomyolipoma: Case report  

Scientific Electronic Library Online (English)

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.

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

2007-09-01

18

Antigliadin antibody in sporadic adult ataxia  

Directory of Open Access Journals (Sweden)

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.

Mahdi Aloosh

2012-09-01

19

[APC mutation analysis in sporadic colorectal cancer].  

Science.gov (United States)

APC gene, responsible for familial adenomatous polyposiscoli, is one of the tumor suppressor genes involved in tumorigenesis of sporadic colorectal cancer. Because the majority of APC mutations are located in the 5' end of exon 15 and 95% of them generate stop codon, a coupled in vitro transcription and translation system (IVSP) was used to detect somatic APC mutation of exon 15 in sporadic colorectal cancer. Forty-nine mutated sporadic cases containing 59 truncated bands (9 cases with 2 bands) were identified. The results of the study showed: 1. APC frameshift mutations were more frequent than point mutations (60% vs 40%). Most of the frameshift mutations (32/35) were deletion or insertion of 1-2 bp, whereas 16 of all 23 point mutations presented C-to-T transitions. Mutations (57/59) were mostly but unevenly distributed in segment 2 and 3 of exon 15, while in segment 3, 69% (45/59) of all the mutations were predominantly located in mutation cluster region (codon 1286-1531). In seven of the 9 cases with 2 mutations their close proximity with each other is suggestive of the possibility of mutations at 2 independent alleles. The similarities between APC somatic and germline mutations suggest that APC gene might well have some common functions during the tumorigenesis of sporadic and hereditary coloretal cancer. PMID:9387290

Huang, J; Zheng, S; Jin, S

1996-11-01

20

Efficacy and Cost-Effectiveness of Immediate Surgery versus a Wait-and-See Strategy for Sporadic Nonfunctioning T1 Pancreatic Endocrine Neoplasms.  

Science.gov (United States)

Background: Whether patients with small (65 years of age, the two strategies provided similar results but the wait-and-see strategy was more cost-effective. Conclusions: The wait-and-see strategy for NF-PETs <2 cm represents a reasonable approach only in patients over 65 years of age; otherwise, immediate surgery is preferable. © 2014 S. Karger AG, Basel. PMID:25228538

Cucchetti, Alessandro; Ricci, Claudio; Ercolani, Giorgio; Campana, Davide; Cescon, Matteo; D'Ambra, Marielda; Pinna, Antonio Daniele; Minni, Francesco; Casadei, Riccardo

2014-09-10

21

The Genomic Architecture of Sporadic Heart Failure  

OpenAIRE

Common or sporadic systolic heart failure (heart failure) is the clinical syndrome of insufficient forward cardiac output resulting from myocardial disease. Most heart failure is the consequence of ischemic or idiopathic cardiomyopathy. There is a clear familial predisposition to heart failure, with a genetic component estimated to confer between 20 and 30% of overall risk. The multifactorial etiology of this syndrome has complicated identification of its genetic underpinnings. Until recently...

Dorn, Gerald W.

2011-01-01

22

Most common 'sporadic' cancers have a significant germline genetic component.  

Science.gov (United States)

Common cancers have been demarcated into 'hereditary' or 'sporadic' ('non-hereditary') types historically. Such distinctions initially arose from work identifying rare, highly penetrant germline mutations causing 'hereditary' cancer. While rare mutations are important in particular families, most cases in the general population are 'sporadic'. Twin studies have suggested that many 'sporadic' cancers show little or no heritability. To quantify the role of germline mutations in cancer susceptibility, we applied a method for estimating the importance of common genetic variants (array heritability, h(2)g) to twelve cancer types. The following cancers showed a significant (P g = 0.19 (95% CI = 0.01-0.37) and Australian set h(2)g = 0.30 (0.10-0.50); pancreatic h(2)g = 0.18 (0.06-0.30); prostate h(2)g = 0.81 (0.32-1); kidney h(2)g = 0.18 (0.04-0.32); ovarian h(2)g = 0.30 (0.18-0.42); esophageal adenocarcinoma h(2)g = 0.24 (0.14-0.34); esophageal squamous cell carcinoma h(2)g = 0.19 (0.07-0.31); endometrial UK set h(2)g = 0.23 (0.01-0.45) and Australian set h(2)g = 0.39 (0.02-0.76). Three cancers showed a positive but non-significant effect: breast h(2) g = 0.13 (0-0.56); gastric h(2)g = 0.11 (0-0.27); lung h(2)g = 0.10 (0-0.24). One cancer showed a small effect: bladder h(2)g = 0.01 (0-0.11). Among these cancers, previous twin studies were only able to show heritability for prostate and breast cancer, but we can now make much stronger statements for several common cancers which emphasize the important role of genetic variants in cancer susceptibility. We have demonstrated that several 'sporadic' cancers have a significant inherited component. Larger genome-wide association studies in these cancers will continue to find more loci, which explain part of the remaining polygenic component. PMID:24943595

Lu, Yi; Ek, Weronica E; Whiteman, David; Vaughan, Thomas L; Spurdle, Amanda B; Easton, Douglas F; Pharoah, Paul D; Thompson, Deborah J; Dunning, Alison M; Hayward, Nicholas K; Chenevix-Trench, Georgia; Macgregor, Stuart

2014-11-15

23

[Effect of point substitutions in the MnSOD, GPX1, and GSTP1 genes on the risk of familial and sporadic breast cancers in residents of the Alta? region of the Russian Federation].  

Science.gov (United States)

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer. PMID:21434422

Ermolenko, N A; Boiarskikh, U A; Sushko, A G; Voronina, E N; Selezneva, I A; Sinkina, T V; Lazarev, A F; Petrova, V D; Filipenko, M L

2010-12-01

24

Sporadic variety of pallido-pyramidal syndrome  

OpenAIRE

A rare case of a 40-year-old lady with a sporadic variety of the pallido-pyramidal syndrome (PPS) is reported. She had marked parkinsonian features on the left side. Her single photon emission computed tomography showed left frontoparietal and basal ganglia hypoperfusion. CT scan and central motor conduction time were normal. She responded partially to a combination of trihexyphenydil and L dopa/C dopa therapy. In view of the diversity in the genetic, clinical and laboratory features, it is p...

Kalita J; Misra U; Das B

2003-01-01

25

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

Science.gov (United States)

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.

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

1978-01-01

26

Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations.  

OpenAIRE

Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. While missense mutations in the beta cardiac myosin heavy chain (MHC) gene account for approximately half of all cases of familial hypertrophic cardiomyopathy, the molecular causes of sporadic hypertrophic cardiomyopathy are unknown. To determine whether beta cardiac MHC mutations are also associated with sporadic disease, we screened this gene in seven individu...

Watkins, H.; Thierfelder, L.; Hwang, D. S.; Mckenna, W.; Seidman, J. G.; Seidman, C. E.

1992-01-01

27

Tumour suppressor genes in sporadic epithelial ovarian cancer  

DEFF Research Database (Denmark)

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

Liu, Ying; Ganesan, Trivadi S

2002-01-01

28

Modifications of sporadic E-layers caused by seismic activity  

OpenAIRE

Contents: 1 Introduction 2 Formation and destruction of sporadic E-layers 3 Temporal variations of parameters of sporadic E-layers during earthquake preparation 3.1 Temporal variations of fbEs with time-scales of a few hours 3.2 Study of fbEs variations with characteristic time-scales of 0.5-3 hours 3.3 Variations of the parameters of sporadic E-layers with characteristic time-scales of 15-45 minutes 3.4 Sporadic E-layer variations with characteristic time-...

Liperovsky, V. A.; Pochotelov, O. A.; Liperovskaya, E. V.; Parrot, M.; Meister, C. -v; Alimov, O. A.

1998-01-01

29

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.

30

Sporadic aurorae observed in East Asia  

Directory of Open Access Journals (Sweden)

Full Text Available All the accessible auroral observations recorded in Chinese and Japanese histories during the interval AD 1840–1911 are investigated in detail. Most of these auroral records have never been translated into a Western language before. The East Asian auroral reports provide information on the date and approximate location of each auroral observation, together with limited scientific information on the characteristics of the auroral luminosity such as colour, duration, extent, position in the sky and approximate time of occurrence. The full translations of the original Chinese and Japanese auroral records are presented in an appendix, which contains bibliographic details of the various historical sources. (There are no known reliable Korean observations during this interval. A second appendix discusses a few implausible "auroral" records, which have been rejected. The salient scientific properties of all exactly dated and reliable East Asian auroral observations in the interval AD 1840–1911 are summarised succinctly. By comparing the relevant scientific information on exactly dated auroral observations with the lists of great geomagnetic storms compiled by the Royal Greenwich Observatory, and also the tabulated values of the Ak (Helsinki and aa (Greenwich and Melbourne magnetic indices, it is found that 5 of the great geomagnetic storms (aa>150 or Ak>50 during either the second half of the nineteenth century or the first decade of the twentieth century are clearly identified by extensive auroral displays observed in China or Japan. Indeed, two of these great storms produced auroral displays observed in both countries on the same night. Conversely, at least 29 (69% of the 42 Chinese and Japanese auroral observations occurred at times of weak-to-moderate geomagnetic activity (aa or Ak?50. It is shown that these latter auroral displays are very similar to the more numerous (about 50 examples of sporadic aurorae observed in the United States during the interval AD 1880–1940. The localised nature and spatial structure of some sporadic aurorae observed in East Asia is indicated by the use of descriptive terms such as "lightning", "rainbow", "streak" and "grid".

D. M. Willis

2007-03-01

31

Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2, or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve inactivation of the NF2 locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling could distinguish familial multiple meningiomas from sporadic solitary and sporadic multiple meningiomas. Methods We compared 73 meningiomas presenting as sporadic solitary (64, sporadic multiple (5 and familial multiple (4 tumors using genomic profiling by array comparative genomic hybridization (array CGH. Results Sporadic solitary meningiomas revealed genomic rearrangements consistent with at least two mechanisms of tumor initiation, as unsupervised cluster analysis readily distinguished tumors with chromosome 22 deletion (associated with loss of the NF2 tumor suppressor from those without chromosome 22 deletion. Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer chromosomal imbalance events overall, tumors with chromosome 22 deletion further clustered into two major groups that largely, though not perfectly, matched with their benign (WHO Grade I or advanced (WHO Grades II and III histological grade, with the latter exhibiting a significantly greater degree of genomic imbalance (P Conclusion Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members.

Roy Jennifer

2009-07-01

32

The Meteoroid Environment: Shower and Sporadic Meteors  

Science.gov (United States)

Interplanetary particles larger than 10^{13} kg (3 microns) create significant light and ionization when colliding with the atmosphere of the Earth. This provides a way to study the higher mass component of the interplanetary dust complex, since the collecting area of the Earth's atmosphere is large and the meteors resulting from these impacts are easily recorded with optical cameras and radars. Particles in this size range have too low a flux relative to the size scale of in-situ dust detectors to be captured in dust detectors, and are difficult to detect remotely. Meteoroids are generally divided into two broad categories: shower meteors, which appear to come from narrow radiants as seen from the surface of the Earth and occur over a limited range of the Earth's orbit every year, and sporadic meteors, which are always active and come from diffuse radiants. Recent advances in observing technology, particularly in automated data analysis, have produced great advances in the understanding of meteoroid distribution at 1 AU.

Campbell-Brown, M.

2007-01-01

33

Sporadic and hereditary amyotrophic lateral sclerosis (ALS).  

Science.gov (United States)

Genetic discoveries in ALS have a significant impact on deciphering molecular mechanisms of motor neuron degeneration. The identification of SOD1 as the first genetic cause of ALS led to the engineering of the SOD1 mouse, the backbone of ALS research, and set the stage for future genetic breakthroughs. In addition, careful analysis of ALS pathology added valuable pieces to the ALS puzzle. From this joint effort, major pathogenic pathways emerged. Whereas the study of TDP43, FUS and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways. Despite all these efforts, the etiology of most cases of sporadic ALS remains elusive. Newly acquired genomic tools now allow the identification of genetic and epigenetic factors that can either increase ALS risk or modulate disease phenotype. These developments will certainly allow for better disease modeling to identify novel therapeutic targets for ALS. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. PMID:25193032

Ajroud-Driss, Senda; Siddique, Teepu

2014-09-01

34

Oxidative Stress Biomarkers in Sporadic ALS  

Science.gov (United States)

Objective To investigate oxidative stress biomarkers in a cross-sectional pilot study of 50 participants with sporadic ALS (sALS) compared to 46 control subjects. Methods We measured urinary 8-oxodeoxyguanosine (8-oxodG), urinary 15-F2t-isoprostane (IsoP), and plasma protein carbonyl by ELISA methods. We also determined if ELISA measurement of 8-oxodG could be validated against measures from high pressure liquid chromatography coupled with electrochemical detection, the current standard method. Results 8-oxodG and IsoP levels adjusted for creatinine were significantly elevated in sALS participants. These differences persisted after age and gender were controlled in regression analyses. These markers are highly and positively correlated with each other. 8-oxodG measured by the two techniques from the same urine sample were positively correlated (P < .0001). Protein carbonyl was not different between sALS participants and controls. Conclusion Using ELISA we confirmed that certain oxidative stress biomarkers were elevated in sALS participants. ELISA may be reliable and thus useful in epidemiology studies requiring large numbers of samples to determine the significance of increased oxidative stress markers in sALS. Further studies are required. PMID:18574762

Mitsumoto, Hiroshi; Santella, Regina M.; Liu, Xinhua; Bogdanov, Mikhail; Zipprich, Jennifer; Wu, Hui-Chen; Mahata, Julie; Kilty, Mary; Bednarz, Kate; Bell, Daniel; Gordon, Paul H.; Hornig, Mady; Mehrazin, Mahsa; Naini, Ali; Beal, M. Flint; Factor-Litvak, Pam

2015-01-01

35

NPHS2 Variation in Sporadic Focal Segmental Glomerulosclerosis  

OpenAIRE

Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial and sporadic steroid-resistant focal segmental glomerulosclerosis (FSGS) in the pediatric population, but have not been well-characterized in late-onset disease. To investigate the role of NPHS2 polymorphisms in sporadic cases of late-onset FSGS, we studied 377 biopsy-confirmed FSGS cases and 919 controls. We identified 18 single nucleotide polymorphisms (SNPs) by resequencing a subgroup of cases a...

Mckenzie, Louise M.; Hendrickson, Sher L.; Briggs, William A.; Dart, Richard A.; Korbet, Stephen M.; Mokrzycki, Michelle H.; Kimmel, Paul L.; Ahuja, Tejinder S.; Berns, Jeffrey S.; Simon, Eric E.; Smith, Michael C.; Trachtman, Howard; Michel, Donna M.; Schelling, Jeffrey R.; Cho, Monique

2007-01-01

36

INTUSSUSCEPTION IN A CHILD WITH SPORADIC BURKITT LYMPHOMA  

OpenAIRE

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 spasm...

Meucci, D.; Di Maggio, G.; Garzi, A.; Burgio, A.; Ferrara, F.; Angotti, R.

2009-01-01

37

Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas  

OpenAIRE

Abstract Background Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve inactivation of the NF2 locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling...

Roy Jennifer; Engler David A; Betensky Rebecca A; Plotkin Scott; Mohapatra Gayatry; James Marianne; Stemmer-Rachamimov Anat; Nunes Fabio; Shen Yiping; Ramesh Vijaya; Gusella James F

2009-01-01

38

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

39

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

Directory of Open Access Journals (Sweden)

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

H. Chandra

40

A somatic truncating mutation in BRCA2 in a sporadic breast tumor  

Energy Technology Data Exchange (ETDEWEB)

Recently, a second susceptibility gene for hereditary breast and ovarian cancer, BRCA2, was cloned. The subsequent identification of heterozygous germ-line mutations confirmed its role as a predisposing factor in a subset of familial breast and ovarian cancer families. The possible involvement of BRCA2 in the sporadic forms of breast and ovarian tumors was addressed in three recent reports analyzing the gene for somatic mutations in 212 primary breast cancers and SS ovarian cancers. Although several alterations were identified, all except two changes were shown to represent germ-line mutations. Moreover, the two somatic BRCA2 alterations were found to be missense mutations resulting in a Asp309S-Glu change in one case and in a His2415Asn change in the other. Given the questionable effect of missense mutations on protein function, the role of BRCA2 in the carcinogenesis of sporadic breast tumors remains unclear. 10 refs., 1 fig.

Weber, B.H.F.; Brohm, M.; Stec, I. [Universitaet Wuerzburg (Germany)] [and others

1996-10-01

41

Variation of sporadic meteor background and solar activity  

Science.gov (United States)

Observations of the sporadic background meteors in 1996-2007 by the Bologna-Lecce-Modra forward-scatter radio system operating along two baselines are analyzed and discussed. The activity curves of sporadic meteor echoes and their variations indicate a direct correlation with the solar activity represented by the sunspot relative number R , as well as with the solar coronal index CI . The mass distribution exponents and its variations in the period of the 23rd solar cycle indicate a relatively stable population of the sporadic background meteoroid population in the surroundings of the Earth's orbit. Investigation of meteor heights compiled from the IAU MDC catalogue of precise photographic orbits for a period of five solar cycles do not exhibit any pronounced variation consistent with the solar cycle activity.

Porub?an, V.; Zigo, P.; Bu?ek, M.; Cevolani, G.; Trivellone, G.

2011-05-01

42

Stream and sporadic meteoroids associated with Near Earth Objects  

CERN Document Server

NEOs come close to the Earth's orbit so that any dust ejected from them, might be seen as a meteor shower. Orbits evolve rapidly, so that a similarity of orbits at one given time is not suffcient to prove a relationship, orbital evolution over a long time interval also has to be similar. Sporadic meteoroids can not be associated with a single parent body, they can only be classified as cometary or asteroidal. However, by considering one parameter criteria, many sporadics are not classified properly therefore two parameter approach was proposed.

Jopek, Tadeusz J

2014-01-01

43

Sporadic acoustic neuroma in young patient: our experience  

OpenAIRE

Acoustic neuroma is very rare in children and could be sporadic or as part of NF2. Our series of 10 cases deals with the patients of sporadic (non NF2) acoustic neuromas in pediatrics and adolescent patients. The age of the youngest patient in our series was 12 years. A review of similar cases in both English and non-English literature was made. It showed 34 such cases of acoustic neuromas as pediatric age group. Unlike adults, children do not usually report hearing loss and are often id...

Poletti, Am; Dubey, Sp; Calabrese, V.; Colombo, G.; Zanoletti, E.; Malvezzi, L.; Mazzoni, A.

2009-01-01

44

Parkin mutations in familial and sporadic Parkinson's disease among Indians.  

Science.gov (United States)

We observed a mutation frequency of 8.5% in Parkin gene among Indian PD patients based on sequencing and gene dosage analysis of its exons. We identified nine point mutations of which seven are novel and hitherto unreported. These mutations accounted for 14.3% familial PD, 6.9% young onset and 5.9% late onset sporadic PD. Of the 20 PD patients with mutations only two had homozygous mutations and one was a compound heterozygote. Homozygous exonic deletions were absent but heterozygous exon rearrangements were observed in 9.2% of patients (19% familial PD and 4.5% young onset sporadic PD). PMID:16500134

Chaudhary, Shashi; Behari, Madhuri; Dihana, Maninder; Swaminath, Pazhayannur V; Govindappa, Shyla T; Jayaram, Sachi; Goyal, Vinay; Maitra, Arindam; Muthane, Uday B; Juyal, R C; Thelma, B K

2006-05-01

45

SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease.  

Science.gov (United States)

Mitochondrial quality control has an impact on many diseases, but intense research has focused on the action of 2 genes linked to heritable forms of Parkinson disease (PD), PINK1 and PARK2/parkin, which act in a common pathway to promote mitophagy. However, criticism has been raised that little evidence links this mechanism to sporadic PD. To gain a greater insight into the mechanisms of PINK1-PARK2 mediated mitophagy, we undertook a genome-wide RNAi screen in Drosophila and human cell models. Strikingly, we discovered several components of the lipogenesis pathway, including SREBF1, playing a conserved role in mitophagy. Our results suggest that lipids influence the stabilization of PINK1 during the initiation of mitophagy. Importantly, SREBF1 has previously been identified as a risk locus for sporadic PD, and thus implicates aberrant mitophagy as contributing to sporadic PD. Our findings suggest a role for lipid synthesis in PINK1-PARK2 mediated mitophagy, and propose a mechanistic link between familial and sporadic PD, supporting a common etiology. PMID:24991824

Ivatt, Rachael M; Whitworth, Alexander J

2014-08-01

46

MEN1 gene analysis in sporadic adrenocortical neoplasms.  

Science.gov (United States)

Adrenocortical tumors occur as sporadic tumors, as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome or as part of other hereditary disorders. We recently cloned the MEN1 gene, a tumor-suppressor gene located on chromosome 11q13. Subsequently, we showed that sequential somatic inactivation of both alleles of the MEN1 gene contributes to the development of some sporadic endocrine neoplasms (parathyroid, enteropancreatic neuroendocrine, bronchial carcinoid, and pituitary tumors). We now studied whether somatic inactivation of the MEN1 gene contributes to the pathogenesis of sporadic adrenocortical neoplasms. Seven adrenocortical carcinomas, 2 adrenocortical carcinoma cell lines, and 11 aldosterone-secreting, 8 cortisol-secreting, and 5 nonsecreting benign adrenocortical tumors were studied. Seven tumors (5 of 5 carcinomas, 2 of 21 nonsecreting benign adenomas; P tumors and cell lines were screened for mutation throughout the MEN1 open-reading frame and adjacent splice junctions. None exhibited a mutation within the MEN1-coding region. We conclude that somatic MEN1 mutation within the MEN1-coding region does not occur commonly in sporadic adrenocortical tumors, although the majority of adrenocortical carcinomas exhibit 11q13 loss of heterozygosity. PMID:9920087

Heppner, C; Reincke, M; Agarwal, S K; Mora, P; Allolio, B; Burns, A L; Spiegel, A M; Marx, S J

1999-01-01

47

Role of KCNJ5 in familial and sporadic primary aldosteronism.  

Science.gov (United States)

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

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

2013-02-01

48

Sporadic hemiplegic migraine: A rare presentation in children  

Directory of Open Access Journals (Sweden)

Full Text Available We report a 12 year old girl with a history of migraine presenting with recurrent episodes of hemiparesis preceded by headache, which fulfilled the diagnostic criteria for sporadic hemiplegic migraine in ICHD – 2 [international classification of headache disorders 2].

Sangavi Santhan, Jehangir HM, Mugunthan

2014-04-01

49

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

50

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

International Nuclear Information System (INIS)

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.

51

Exome sequencing in undiagnosed inherited and sporadic ataxias.  

Science.gov (United States)

Inherited ataxias are clinically and genetically heterogeneous, and a molecular diagnosis is not possible in most patients. Having excluded common sporadic, inherited and metabolic causes, we used an unbiased whole exome sequencing approach in 35 affected individuals, from 22 randomly selected families of white European descent. We defined the likely molecular diagnosis in 14 of 22 families (64%). This revealed de novo dominant mutations, validated disease genes previously described in isolated families, and broadened the clinical phenotype of known disease genes. The diagnostic yield was the same in both young and older-onset patients, including sporadic cases. We have demonstrated the impact of exome sequencing in a group of patients notoriously difficult to diagnose genetically. This has important implications for genetic counselling and diagnostic service provision. PMID:25497598

Pyle, Angela; Smertenko, Tania; Bargiela, David; Griffin, Helen; Duff, Jennifer; Appleton, Marie; Douroudis, Konstantinos; Pfeffer, Gerald; Santibanez-Koref, Mauro; Eglon, Gail; Yu-Wai-Man, Patrick; Ramesh, Venkateswaran; Horvath, Rita; Chinnery, Patrick F

2015-02-01

52

A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias  

Directory of Open Access Journals (Sweden)

Full Text Available Twenty-four cases of sporadic olivo-ponto-cerebellar atrophy (OPCA of adult onset were studied over a period of two years. Results suggest that this disorder has its usual onset in the 5th and 6th decade of life with a male: female ratio of 2:1. It manifests clinically with gait ataxia in all, dysarthria, other cerebellar signs and autonomic involvement in vast majority. There were features of basal ganglia involvement in some. No known identifiable environmental cause was found and genetically they are quite distinct from the known autosomal dominant spinocerebellar ataxias though sporadic occurrence in recessive inheritance or a de novo mutation could not be ruled out completely, but it is unlikely.

Sinha K K

1999-01-01

53

A possible case of Sporadic Aurora in 1843 from Mexico  

Scientific Electronic Library Online (English)

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.

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

2013-03-01

54

Biological and genetic markers of sporadic Alzheimer's disease.  

OpenAIRE

With the development of new treatments, there is an increasing need for early diagnosis of sporadic Alzheimer's disease. Therefore, biological markers allowing positive diagnosis early in the course of the disease are highly desirable. Cerebrospinal fluid levels of protein tau were shown to be significantly increased in patients with Alzheimer's disease. Although sensitivity is high, poor specificity limits the diagnostic value of this marker. The same is true for the 42 amino acid isoform of...

Engelborghs S; Pp, Deyn

2001-01-01

55

Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma  

OpenAIRE

Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1 beta. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish casecontrol study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was sig...

Verma, Deepti; Bivik, Cecilia; Farahani, Ensieh; Synnerstad, Ingrid; Fredrikson, Mats; Enerba?ck, Charlotta; Rosdahl, Inger; So?derkvist, Peter

2012-01-01

56

Tocilizumab infusion therapy normalizes inflammation in sporadic ALS patients  

OpenAIRE

Patients with sporadic amyotrophic lateral sclerosis (sALS) show inflammation in the spinal cord and peripheral blood. The inflammation is driven by stimulation of macrophages by aggregated superoxide dismutase 1 (SOD1) through caspase1, interleukin 1 (IL1), IL6 and chemokine signaling. Inflammatory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab inhibits global interleukin-6 (IL6) signaling, a key mechanism in chronic rheumatoid ...

Fiala, Milan; Mizwicki, Mathew T.; Weitzman, Rachel; Magpantay, Larry; Nishimoto, Norihiro

2013-01-01

57

Application of quantitative DTI metrics in sporadic CJD?  

OpenAIRE

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 ...

Caverzasi, E.; Henry, R. G.; Vitali, P.; Lobach, I. V.; Kornak, J.; Bastianello, S.; Dearmond, S. J.; Miller, B. L.; Rosen, H. J.; Mandelli, M. L.; Geschwind, M. D.

2014-01-01

58

Sporadic case of warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis syndrome.  

Science.gov (United States)

The term WHIM syndrome (WHIMS) is an acronym describing a rare primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis, the unusual association of neutropenia with bone marrow myeloid hypercellularity. WHIMS was recently associated with mutations in the gene encoding the chemokine receptor CXCR4 and as such is the first disease ascribed to abnormalities of chemokine signaling. We report a sporadic case of WHIMS in a woman presenting with recurrent infections and human papilloma virus-related genital dysplasia. PMID:16275383

Tarzi, Michael D; Jenner, Michael; Hattotuwa, Keith; Faruqi, Asma Z; Diaz, George A; Longhurst, Hilary J

2005-11-01

59

Insulin Signaling in Sporadic Alzheimer's Disease  

Science.gov (United States)

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.

Francesca-Fang Liao (University of Tennessee Health Science Center;Department of Pharmacology REV); Huaxi Xu (Burnham Institute for Medical Research;Neurodegenerative Disease Research Program REV)

2009-06-09

60

Genetic and neuroanatomic associations in sporadic frontotemporal lobar degeneration.  

Science.gov (United States)

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

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

61

Lightning-induced intensification of the ionospheric sporadic E layer.  

Science.gov (United States)

A connection between thunderstorms and the ionosphere has been hypothesized since the mid-1920s. Several mechanisms have been proposed to explain this connection, and evidence from modelling as well as various types of measurements demonstrate that lightning can interact with the lower ionosphere. It has been proposed, on the basis of a few observed events, that the ionospheric 'sporadic E' layer--transient, localized patches of relatively high electron density in the mid-ionosphere E layer, which significantly affect radio-wave propagation--can be modulated by thunderstorms, but a more formal statistical analysis is still needed. Here we identify a statistically significant intensification and descent in altitude of the mid-latitude sporadic E layer directly above thunderstorms. Because no ionospheric response to low-pressure systems without lightning is detected, we conclude that this localized intensification of the sporadic E layer can be attributed to lightning. We suggest that the co-location of lightning and ionospheric enhancement can be explained by either vertically propagating gravity waves that transfer energy from the site of lightning into the ionosphere, or vertical electrical discharge, or by a combination of these two mechanisms. PMID:15944700

Davis, C J; Johnson, C G

2005-06-01

62

Screening of hypoxia-inducible genes in sporadic ALS.  

LENUS (Irish Health Repository)

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.

Cronin, Simon

2008-10-01

63

The Meteor Complex near the Earth's Orbit: Sporadic Background, Streams, and Associations. III. Sources of Stream and Sporadic Meteoric Bodies  

Science.gov (United States)

An analysis of elements and quasi-constant parameters of meteoroid orbits is performed to estimate the contribution of asteroids of the Apollo, Amor, and Aten groups (AAA asteroids), main-belt asteroids, and short-period (SP) and long-period (LP) comets to the complex of stream and sporadic meteoric bodies. Both formal criteria and the methods of multidimensional classification with training samples are used, i.e., the dis criminant analysis and classification based on the criterion of the likelihood ratio in the case of a known distri bution over the classes. Among stream meteoroids with masses greater than 105 g intercepting the sphere of radius 1 AU, 72% represent the product of disintegration of AAA asteroids; 3% have their origin from main-belt asteroids; and 19 and 6% respectively, represent the product of the disintegration of nuclei of SP and LP comets. The corresponding estimates for sporadic meteoroids give, respectively, 32, 4, 7, and 57%. Thus, 75% of stream meteoroids are of asteroidal origin (72% being AAA asteroids); among sporadic meteoroids, 37% (32% being AAA asteroids). For all four classes, the four-dimensional (a, e, q, i)-distributions of meteoroid orbital elements are given and the characteristic features of these distributions are discussed.

Voloshchuk, Yu. I.; Vorgul', A. V.; Kashcheev, B. L.

64

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

Directory of Open Access Journals (Sweden)

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.

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

2008-11-01

65

Sporadic Ca and Ca+ layers at mid-latitudes: Simultaneous observations and implications for their formation  

Directory of Open Access Journals (Sweden)

Full Text Available We report on the observations of 188 sporadic layers of either Ca atoms and/or Ca ions that we have observed during 112 nights of lidar soundings of Ca, and 58 nights of Ca+ soundings, at Kühlungsborn, Germany (54° N, 12° E. The Ca+ soundings have been performed simultaneously and in a common volume with the Ca soundings by two separate lidars. Correlations between sporadic neutral and ionized metal layers are demonstrated through four case studies. A systematic study of the variations of occurrence of sporadic Ca and Ca+ layers reveals that neutral and ionized Ca layers are not as closely correlated as expected earlier: (a The altitude distribution shows the simultaneous occurrence of both sporadic Ca and Ca+ layers to be most likely only in the narrow altitude range between 90 and 95 km. Above that region, in the lower thermosphere, the sporadic ion layers are much more frequent than atom layers. Below 90 km only very few sporadic layers have been observed; (b The seasonal variation of sporadic Ca layers exhibits a minimum of occurrence in summer, while sporadic Ca+ layers do not show a significant seasonal variation (only the dense Ca+ layers appear to have a maximum in summer. At mid-latitudes sporadic Ca layers are more frequent than sporadic layers of other atmospheric metals like Na or K. For the explanation of our observations new formation mechanisms are discussed.Key words. Ionosphere (ion chemistry and composition; ionosphere-atmosphere interactions; mid-latitude ionosphere

J. Höffner

66

Therapeutic Potential of the Poly(ADP-ribose) Polymerase Inhibitor Rucaparib for the Treatment of Sporadic Human Ovarian Cancer  

OpenAIRE

Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer. We studied the growth inhibitory effects of rucaparib in a panel of 39 ovarian cancer cell lines that were each characterized for mutation and methylation status of BRCA1/2, baseline gene expression signatures, copy number variations of selected genes, PTEN status, and sensitivity to platinum-based chemotherapy. To study int...

Ihnen, Maike; Zu Eulenburg, Christine; Kolarova, Teodora; Qi, Jing Wei; Manivong, Kanthinh; Chalukya, Meenal; Dering, Judy; Anderson, Lee; Ginther, Charles; Meuter, Alexandra; Winterhoff, Boris; Jones, Sia?n; Velculescu, Victor E.; Venkatesan, Natarajan; Rong, Hong-mei

2013-01-01

67

Trimetazidine Prevents Oxidative Changes Induced in a Rat Model of Sporadic Type of Alzheimer?s Disease.  

Science.gov (United States)

Oxidative stress plays a major role in the pathogenesis of Alzheimer's disease (AD) of sporadic origin. The expression of DHCR24 (Seladin-1), marker for neuronal oxidative stress and degeneration, has been reported to be altered in the brains of AD patients. In the present study, we investigated the effect of trimetazidine (TMZ) on the hippocampal oxidative parameters and the expression of DHCR24 (Seladin-1) in an animal model of sporadic AD. Male rats were pre-treated with TMZ (25 mg/kg) after which injected with intracerebroventricular-streptozotocin (ICV-STZ)/Saline. Following 2, 7 and 14 days, animals of different groups were sacrificed with their brain excised to detect the hippocampal lipid peroxidation, superoxide dismutase (SOD), catalase activity, DHCR24 (Seladin-1) expression and possible histopathological changes. ICV-STZ administration induced significant oxidative changes in the hippocampus. Meanwhile, TMZ pre-treatment showed to ameliorate the oxidative stress, which was demonstrated by a significant rise in the hippocampal SOD and catalase activity, as well as a significant decrease in the malondialdehyde (MDA) level. TMZ administration also increased the expression of DHCR24 (Seladin-1) gene in the hippocampus. In conclusion, our findings indicated a neuroprotective effect of TMZ possibly related to its antioxidant activity resulting in the up-regulation of DHCR24 (Seladin-1). Such TMZ effects may be beneficial in minimizing oxidative stress in sporadic Alzheimer?s disease and possible prevention of disease progression. PMID:25597600

Hassanzadeh, Gholamreza; Hosseini, Amir; Pasbakhsh, Parichehr; Akbari, Mohammad; Ghaffarpour, Massoud; Takzare, Nasrin; Zahmatkesh, Maryam

2015-01-01

68

Application of quantitative DTI metrics in sporadic CJD.  

Science.gov (United States)

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. PMID:24624328

Caverzasi, E; Henry, R G; Vitali, P; Lobach, I V; Kornak, J; Bastianello, S; Dearmond, S J; Miller, B L; Rosen, H J; Mandelli, M L; Geschwind, M D

2014-01-01

69

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

Science.gov (United States)

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

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

2014-05-22

70

Imaging and clinical characteristics of sporadic Creutzfeldt-Jakob disease  

Directory of Open Access Journals (Sweden)

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.

HAN Shun-chang

2013-04-01

71

Sporadic Cryptosporidiosis, North Cumbria, England, 1996–2000  

OpenAIRE

Risk factors for sporadic cryptosporidiosis were determined in 152 patients and 466 unmatched controls who resided in two local government districts in North Cumbria, North West England, from March 1, 1996, to February 29, 2000. Risk was associated with the usual daily volume of cold unboiled tap water drunk (odds ratio [OR] 1.40, 95% confidence intervals [CI] 1.14 to 1.71 per pint consumed per day [p = 0.001]) and short visits to farms (OR 2.02, 95% CI 1.04 to 3.90, p = 0.04). Fifty-six (84%...

Goh, Stella; Reacher, Mark; Casemore, David P.; Verlander, Neville Q.; Chalmers, Rachel; Knowles, Margaret; Williams, Joy; Osborn, Keith; Richards, Sarah

2004-01-01

72

Representing the Sporadic Archimedean Polyhedra as Abstract Polytopes  

CERN Document Server

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).

Hartley, Michael

2009-01-01

73

Diffusion MR imaging in sporadic Creutzfeldt-Jakob disease  

Directory of Open Access Journals (Sweden)

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

Burcak Cakir Pekoz

2014-08-01

74

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

OpenAIRE

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...

Jagtap, Sunil V.; Nikumbh, Dhiraj B.; Desai, Sushama R.; Kshirsagar, Ashok Y.; Jitendra Khedkar; Chavan, Swati H.

2011-01-01

75

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

OpenAIRE

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 pati...

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

2008-01-01

76

Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers.  

DEFF Research Database (Denmark)

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.

Halvarsson, Britta; Anderson, Harald

2008-01-01

77

On Permanent and Sporadic Oscillations of the Magnetosphere  

CERN Document Server

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...

Guglielmi, A V

2014-01-01

78

Sporadic Hemangioblastoma of the Kidney: a rare renal tumor  

Directory of Open Access Journals (Sweden)

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

Liu Yang

2012-05-01

79

Cognitive disorders after sporadic ecstasy use? A case report.  

Science.gov (United States)

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

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

2015-06-01

80

A specific superoxide dismutase mutation is on the same genetic background in sporadic and familial cases of amyotrophic lateral sclerosis  

Energy Technology Data Exchange (ETDEWEB)

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons, causing progressive muscular atrophy, weakness, and death from respiratory failure, often within 2-3 years. Although most cases are sporadic, some 5%-10% are inherited as autosomal dominants with age-dependent penetrance. An ALS locus has been mapped to chromosome 21q, and causative mutations identified in the Cu/Zn superoxide dismutase (SOD1) gene. A majority of SOD1 mutations have been found in cases with a clear family history of ALS. However, we and others have also described SOD1 mutations in patients where the disease appears to be sporadic. This is especially true for the missense mutation in codon 113 of the SOD1 gene, which substitutes threonine for isoleucine (I113T). One explanation for this finding is that this codon is a mutational hot spot with sporadic cases representing new mutations. Another is that the inherited nature of the cases is disguised by the reduced penetrance of this specific mutation. We have now shown that each of six unrelated cases of I113T mutation that we have collected in the Scottish population occurs on the same genetic background. Association analysis of multiple flanking loci on chromosome 21q supports the conclusion of a founder effect, with the original mutational event occurring {ge}10 generations ago. 12 refs., 1 fig., 1 tab.

Hayward, C.; Brock, D.J.H. [Univ. of Edinburgh (United Kingdom); Swingler, R.J. [Dundee Royal Infirmary (United Kingdom)] [and others

1996-11-01

81

El Nino Southern Oscillation as Sporadic Oscillations between Metastable States  

CERN Document Server

The main objective of this article is to establish a new mechanism of the El Nino Southern Oscillation (ENSO), as a self-organizing and self-excitation system, with two highly coupled processes. The first is the oscillation between the two metastable warm (El Nino phase) and cold events (La Nina phase), and the second is the spatiotemporal oscillation of the sea surface temperature (SST) field. The interplay between these two processes gives rises the climate variability associated with the ENSO, leads to both the random and deterministic features of the ENSO, and defines a new natural feedback mechanism, which drives the sporadic oscillation of the ENSO. The new mechanism is rigorously derived using a dynamic transition theory developed recently by the authors, which has also been successfully applied to a wide range of problems in nonlinear sciences.

Ma, Tian

2008-01-01

82

An unusual case of sporadic Creutzfeldt-Jakob disease (CJD).  

Science.gov (United States)

A 49-year-old healthy white British female, not previously known to psychiatric services, presented with an acute onset of florid psychotic symptoms. Her symptoms included visual, auditory and tactile hallucinations as well as persecutory delusions. She was started on antipsychotic medication; however, her psychotic symptoms did not improve significantly in the first 3 months. Her blood tests were normal. Lumbar puncture was performed which was positive for protein 14-3-3. A computed tomography scan of the brain showed generalised atrophic changes. The history of early visual hallucinations, rapid cognitive decline and positive 14-3-3 result was in keeping with the Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD). Despite a short life expectancy as reported in literature, our patient, who was diagnosed with sCJD more than two-and-a-half years ago, is still alive. We therefore believe this is an important finding to report. PMID:22753302

Javed, Qaiser; Alam, Faouzi; Krishna, Sowmya; Jaganathan, Geetha

2010-01-01

83

Genetics of familial and sporadic amyotrophic lateral sclerosis.  

Science.gov (United States)

Diseases affecting motor neurons, such as amyotrophic lateral sclerosis (Lou Gerhig's disease), hereditary spastic paraplegia and spinal bulbar muscular atrophy (Kennedy's disease) are a heterogeneous group of chronic progressive diseases and are among the most puzzling yet untreatable illnesses. Over the last decade, identification of mutations in genes predisposing to these disorders has provided the means to better understand their pathogenesis. The discovery 13 years ago of SOD1 mutations linked to ALS, which account for less than 2% of total cases, had a major impact in the field. However, despite intensive research effort, the pathways leading to the specific motor neurons degeneration in the presence of SOD1 mutations have not been fully identified. This review provides an overview of the genetics of both familial and sporadic forms of ALS. PMID:16503123

Gros-Louis, Francois; Gaspar, Claudia; Rouleau, Guy A

2006-01-01

84

Aging and renewal events in sporadically modulated systems  

International Nuclear Information System (INIS)

We describe a form of modulation, namely a dishomogeneous Poisson process whose event rate changes sporadically and randomly in time with a chosen prescription, so as to share many statistical properties with a corresponding non-Poisson renewal process. Using our prescription the correlation function and the waiting time distribution between events are the same. If we study a continuous-time random walk, where the walker has only two possible velocities, randomly established at the times of the events, we show that the two processes also share the same second moment. However, the modulated diffusion process undergoes a dynamical transition between superstatistics and a Levy walk process, sharing the scaling properties of the renewal process only asymptotically. The aging experiment - based on the evaluation of the waiting time for the next event, given a certain time distance between another previous event and the beginning of the observation - seems to be the key experiment to discriminate between the two processes

85

A sporadic third layer in the ionosphere of Mars.  

Science.gov (United States)

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

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

2005-11-01

86

Continuous upflows and sporadic downflows observed in active regions  

CERN Document Server

We present a study of the temporal evolution of coronal loops in active regions and its implications for the dynamics in coronal loops. We analyzed images of the Atmospheric Imaging Assembly (AIA) on the Solar Dynamics Observatory (SDO) at multiple temperatures to detect apparent motions in the coronal loops. Quasi-periodic brightness fluctuations propagate upwards from the loop footpoint in hot emission at 1MK, while sporadic downflows are seen in cool emission below 1MK. The upward motion in hot emission increases just after the cool downflows. The apparent propagating pattern suggests a hot upflow from the loop footpoints, and is considered to supply hot plasma into the coronal loop, but a wavelike phenomenon cannot be ruled out. Coronal condensation occasionally happens in the coronal loop, and the cool material flows down to the footpoint. Emission from cool plasma could have a significant contribution to hot AIA channels in the event of coronal condensation.

Kamio, S; Curdt, W; Solanki, S K

2011-01-01

87

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

Directory of Open Access Journals (Sweden)

Full Text Available 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 analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test. Results The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B vs. 70% in the HNPCC group (p = ns. The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p Conclusion Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.

Mete Lupe

2008-09-01

88

A Tangled Web - Tau and Sporadic Parkinson's Disease  

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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.

PatrickALewis

2010-12-01

89

Diagnosing Sporadic Creutzfeldt-Jakob Disease: Accuracy of CSF 14-3-3 Protein Test of the Spinal Fluid  

Science.gov (United States)

... Guideline for PATIENTS and their FAMILIES DIAGNOSING SPORADIC CREUTZFELDT-JAKOB DISEASE: ACCURACY OF THE 14-3-3 PROTEIN TEST ... protein test in diagnosing sporadic CJD. WHAT IS CJD? CJD is a rare, progressive brain disorder. In ...

90

ERKed by LRRK2: a cell biological perspective on hereditary and sporadic Parkinson's disease.  

Science.gov (United States)

The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson's disease (PD); mutations in LRRK2 account for up to 40% of PD cases in some populations. LRRK2 is a large protein with a kinase domain, a GTPase domain, and multiple potential protein interaction domains. As such, delineating the functional pathways for LRRK2 and mechanisms by which PD-linked variants contribute to age-related neurodegeneration could result in pharmaceutically tractable therapies. A growing number of recent studies implicate dysregulation of mitogen activated protein kinases 3 and 1 (also known as ERK1/2) as possible downstream mediators of mutant LRRK2 effects. As these master regulators of growth, differentiation, neuronal plasticity and cell survival have also been implicated in other PD models, a set of common cell biological pathways may contribute to neuronal susceptibility in PD. Here, we review the literature on several major cellular pathways impacted by LRRK2 mutations--autophagy, microtubule/cytoskeletal dynamics, and protein synthesis--in context of potential signaling crosstalk involving the ERK1/2 and Wnt signaling pathways. Emerging implications for calcium homeostasis, mitochondrial biology and synaptic dysregulation are discussed in relation to LRRK2 interactions with other PD gene products. It has been shown that substantia nigra neurons in human PD and Lewy body dementia patients exhibit cytoplasmic accumulations of ERK1/2 in mitochondria, autophagosomes and bundles of intracellular fibrils. Both experimental and human tissue data implicate pathogenic changes in ERK1/2 signaling in sporadic, toxin-based and mutant LRRK2 settings, suggesting engagement of common cell biological pathways by divergent PD etiologies. PMID:24225420

Verma, Manish; Steer, Erin K; Chu, Charleen T

2014-08-01

91

A comparative sporadic-E layer study between two mid-latitude ionospheric stations  

Science.gov (United States)

Hourly systematic measurements of the highest frequency reflected by the sporadic-E layer (foEs) recorded from January 1976 to June 2009 at the ionospheric stations of Rome (Italy, 41.8°N, 12.5°E) and Gibilmanna (Italy, 37.9°N, 14.0°E) were considered to carry out a comparative study between the sporadic E layer (Es) over Rome and Gibilmanna. Different statistical analysis were performed taking into account foEs observations near the periods of minimum and maximum solar activity. The results reveal that: (1) independently from the solar activity, Es develops concurrently over extended regions in space, instead of being a spatially limited layer which is transported horizontally by neutral winds over a larger area; especially during summer months, when an Es layer is present at Rome, there is a high probability that an Es layer is also present over Gibilmanna, and vice versa; (2) Es layer lifetimes of 1-5 h were found; in particular, Es layers with lifetimes of 5 h both over Gibilmanna and Rome are observed with highest percentages of occurrence in summer ranging between 80% and 90%, independently from the solar activity; (3) latitudinal effects on Es layer occurrence emerge mostly for low solar activity during winter, equinoctial, and summer months, when Es layers are detected more frequently over Gibilmanna rather than Rome; (4) when the presence of an Es layer over Rome and Gibilmanna is not simultaneous, Es layer appearance both over Rome and Gibilmanna confirms to be a locally confined event, because drifting phenomena from Rome to Gibilmanna or vice versa have not been emphasized.

Pietrella, M.; Pezzopane, M.; Bianchi, C.

2014-07-01

92

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)

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

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

93

Radiosurgical treatment of sporadic vestibular schwannomas: A prospective cohort study  

International Nuclear Information System (INIS)

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

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SuprimeCam Observation of Sporadic Meteors during Perseids 2004  

CERN Document Server

We report the serendipitous findings of 13 faint meteors and 44 artificial space objects by Subaru SuprimeCam imaging observations during 11-16 August 2004. The meteors, at about 100km altitude, and artificial satellites/debris in orbit, at 500km altitude or higher, were clearly discriminated by their apparent defocused image sizes. CCD photometry of the 13 meteors, including 1 Perseid, 1 Aquarid, and 11 sporadic meteors, was performed. We defined a peak video-rate magnitude by comparing the integrated photon counts from the brightest portion of the track traversed within 33ms to those from a 0-mag star during the same time duration. This definition gives magnitudes in the range 4.0< V_{vr} <6.4 and 4.1< I_{vr}<5.9 for these 13 meteors. The corresponding magnitude for virtual naked-eye observers could be somewhat fainter especially for the V-band observation, in which the [OI] 5577 line lasting about 1 sec as an afterglow could contribute to the integrated flux of the present 5-10 min CCD exposure...

Iye, M; Yanagisawa, M; Ebizuka, N; Ohnishi, K; Hirose, C; Asami, N; Komiyama, Yu; Furusawa, H

2007-01-01

95

Biological and genetic markers of sporadic Alzheimer's disease.  

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Full Text Available With the development of new treatments, there is an increasing need for early diagnosis of sporadic Alzheimer's disease. Therefore, biological markers allowing positive diagnosis early in the course of the disease are highly desirable. Cerebrospinal fluid levels of protein tau were shown to be significantly increased in patients with Alzheimer's disease. Although sensitivity is high, poor specificity limits the diagnostic value of this marker. The same is true for the 42 amino acid isoform of beta-amyloid protein that is significantly decreased in cerebrospinal fluid of Alzheimer's disease patients. However, combining both markers could improve specificity at least allowing differentiation between Alzheimer's disease, normal ageing and depressive pseudodementia. Other biological markers such as cerebrospinal fluid levels of neurotransmitters, cytokines or superoxide dismutase were shown to have even less diagnostic value. The apolipoprotein epsilon 4 allele is a risk factor for Alzheimer's disease but not a diagnostic marker as many individuals who inherit epsilon 4 do not develop the disease. Till now, a single diagnostic marker allowing discrimination between Alzheimer's disease and other dementias does not exist. Combined cerebrospinal fluid levels of beta-amyloid protein and tau protein might be used as a marker that helps discriminating Alzheimer's disease from normal ageing and depression.

Engelborghs S

2001-04-01

96

Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas  

International Nuclear Information System (INIS)

For the development of renal cell carcinomas, it has been suggested that a germ-line or somatic mutation occurs on one of the homologous chromosomes 3p, and subsequently the other 3p segment is lost. The authors have examined the karyotype and/or the allelic combination on chromosomes 3 and 5 by restriction fragment length polymorphism analysis in normal kidney and tumor samples from 28 renal cell carcinomas that developed in two patients with von Hippel-Lindau disease. They then compared the results to those of sporadic tumors. An unbalanced translocation between chromosome 3p and 5q or other chromosomes was found to be the most common aberration. They developed a model of nonhomologous chromatid exchange involving breakpoint clusters at chromosomes 3p13, 3p11.2, 5q22, and 8q11.2. Subsequent chromatid segregation may result in net loss of the 3p segment either (1) in one step or (2) after a nondisjunctional loss of the derivative chromosome carrying the 3p segment. This general mechanism could also be implicated to expalin genetic changes occurring in other types of solid tumors

97

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.

98

Temperate zone sporadic-E maps /f/0/E/s/ greater than 7 MHz/  

Science.gov (United States)

Three maps are presented of f(0) sporadic-E greater than 7 MHz for temperate zones. During map preparation it was assumed that: (1) the geographical area would be between plus and minus 60 deg geomagnetic latitude, excluding the equatorial zone, (2) the maps would be for f(0) sporadic-E greater than 7 MHz, (3) sunspot cycle variation would be ignored, (4) one map would represent the peak sporadic-E period with a discontinuity at the geographic equator, (5) one map would represent non-peak periods with a discontinuity at the geographic equator, (6) one map would represent all twelve months with no equatorial discontinuity, and (7) previously determined coefficients for median and upper decile f(0) sporadic-E would be extrapolated to 7 MHz.

Smith, E. K.

1978-01-01

99

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

OpenAIRE

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)...

Pfaff, R.; Tsunoda, R. T.; Fukao, S.; Yamamoto, M.; Hayakawa, H.

2005-01-01

100

Alternative surgical strategies in patients with sporadic medullary thyroid carcinoma: Long-term follow-up  

OpenAIRE

The extent of surgical resection in patients with sporadic medullary thyroid carcinoma (SMTC) remains controversial. The aim of the present study was to discuss the prognosis of sporadic medullary thyroid carcinoma with different surgical treatments. Of 73 patients with SMTC (mean age of 43.78 years at diagnosis), 70 patients were followed up for 12.0-169.0 months (median 90.0). Having given their informed consent, 12 patients underwent total thyroidectomy with bilateral central neck dissecti...

Ma, Shi Hong; Liu, Qin Jiang; Zhang, You Cheng; Yang, Rong

2011-01-01

101

BRCA1 as a Therapeutic Target in Sporadic Epithelial Ovarian Cancer  

OpenAIRE

In sporadic epithelial ovarian cancer (EOC), the inactivation of BRCA1 through various mechanisms is a relatively common event. BRCA1 protein dysfunction results in the breakdown of various critical pathways in the cell, notably, the DNA damage response and repair pathway. Tumors from patients with BRCA1 germline mutations have an increased sensitivity to DNA damaging chemotherapeutic agents, such as cisplatin, due to defective DNA repair. Thus, inhibiting BRCA1 in sporadic EOC using novel ta...

Weberpals, Johanne I.; Amp Brien, Anna M. O.; Clark-knowles, Katherine V.

2010-01-01

102

Genetic-clinical profile of subjects with apparently sporadic extra-adrenal paragangliomas  

OpenAIRE

Background: Mutations in the genes encoding B, C, and D subunits of the succinate dehydrogenase (SDH) are involved in the pathogenesis of familial paraganglioma (PGL) syndrome. Many subjects with apparently sporadic extra-adrenal paragangliomas are found to be carrier for SDH mutation. Objective: Here we describe four subjects with apparently sporadic extra-adrenal paragangliomas with newly identified mutations in the SDH subunit B and the related clinical phenotype. Methods: Gene sequencing ...

ValeriaRamundo; ToninoErcolino; AntongiulioFaggiano

2012-01-01

103

TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions  

OpenAIRE

TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies. We performed ubiquitin and TDP-43 immunohistochemistry on 193 cases of familial and sporadic FTLD with or without MND. On selected cases, immunoelectron microscopy and bioc...

Cairns, Nigel J.; Neumann, Manuela; Bigio, Eileen H.; Holm, Ida E.; Troost, Dirk; Hatanpaa, Kimmo J.; Foong, Chan; White, Charles L.; Schneider, Julie A.; Kretzschmar, Hans A.; Carter, Deborah; Taylor-reinwald, Lisa; Paulsmeyer, Katherine; Strider, Jeffrey; Gitcho, Michael

2007-01-01

104

Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia  

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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.

Fritzsche Markus

2002-12-01

105

Sporadic meningioangiomatosis: imaging findings with histopathologic correlations in seven patients  

Energy Technology Data Exchange (ETDEWEB)

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.)

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

106

LGI1 gene mutation screening in sporadic partial epilepsy with auditory features.  

Science.gov (United States)

Partial epilepsy with auditory features occasionally segregates in families as an autosomal dominant trait. In some families mutations in the leucine-rich glioma inactivated (LGI1) gene have been identified. Sporadic cases might harbour either denovo or low-penetrant LGI1 mutations, which will substantially alter the family risk for epilepsy. We selected sixteen sporadic patients with cryptogenic temporal lobe epilepsy and partial seizures with auditory features. We compared clinical features of these patients with those of published autosomal dominant family cases. We screened these patients for LGI1 mutations. Comparing the sporadic patients with the published familial cases no difference in either the primary auditory features or in the other associated epileptic manifestations was identified. Sequence analysis of the whole LGI1 gene coding regions in sporadic patients did not reveal changes in the LGI1 gene. The genetic analysis demonstrates that LGI1 is not a major gene for sporadic cases of partial epilepsy with auditory features at least in the Italian population. Screening of sporadic patients for LGI1 mutations appears not useful in genetic counselling of these patients. PMID:15654555

Flex, E; Pizzuti, A; Di Bonaventura, C; Douzgou, S; Egeo, G; Fattouch, J; Manfredi, M; Dallapiccola, B; Giallonardo, A T

2005-01-01

107

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

DEFF Research Database (Denmark)

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.

van Eimeren, Thilo; Binkofski, Ferdinand

2010-01-01

108

A case study of a sporadic sodium layer observed by the ALOMAR Weber Na lidar  

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Full Text Available Several possible mechanisms for the production of sporadic sodium layers have been discussed in the literature, but none of them seem to explain all the accumulated observations. The hypotheses range from direct meteoric input, to energetic electron bombardment on meteoric smoke particles, to ion neutralization, to temperature dependent chemistry. The varied instrumentation located on Andøya and near Tromsø in Norway gives us an opportunity to test the different theories applied to high latitude sporadic sodium layers. We use the ALOMAR Weber sodium lidar to monitor the appearance and characteristics of a sporadic sodium layer that was observed on 5 November 2005. We also monitor the temperature to test the hypotheses regarding a temperature dependent mechanism. The EISCAT Tromsø Dynasonde, the ALOMAR/UiO All-sky camera and the SKiYMET meteor radar on Andøya are used to test the suggested relationships of sporadic sodium layers and sporadic E-layers, electron precipitation, and meteor deposition during this event. We find that more than one candidate is eligible to explain our observation of the sporadic sodium layer.

H. Nesse

2008-05-01

109

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

Science.gov (United States)

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

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

2015-01-01

110

Study of the HFE gene common polymorphisms in French patients with sporadic amyotrophic lateral sclerosis.  

Science.gov (United States)

Our objective was to investigate whether the C282Y (p.Cys 282 Tyr) and H63D (p. His 63 Asp) HFE polymorphisms were associated with sporadic amyotrophic lateral sclerosis (SALS) in the French population. We searched for a relation of HFE polymorphisms with the clinical characteristics of the disease. The HFE polymorphisms were studied in 824 patients with SALS and 583 controls. We compared the frequency of the polymorphisms between SALS and controls groups by univariate and multivariate statistics, taking into account gender, site, age-at-onset and survival. We did not observe significant difference in the frequency of H63D polymorphism between SALS and control group. We observed a significant difference for C282Y between patients and controls with a low frequency of the Y allele in patients (3.2%) compared to our control group (5.9%). Disease duration, distribution of gender, site-of-onset, age-at-onset did not differ between groups taking into account genotypes of each polymorphism. Our results in this large cohort of ALS patients indicate that H63D polymorphism is not associated with SALS in the French population. This conclusion does not exclude a weak effect of the HFE gene polymorphisms in certain ALS populations, or an effect of other rare HFE gene variants. PMID:22425014

Praline, Julien; Blasco, Hélène; Vourc'h, Patrick; Rat, Valérian; Gendrot, Chantal; Camu, William; Andres, Christian R

2012-06-15

111

Plasma lipid peroxidation in sporadic Parkinson's disease. Role of the L-dopa.  

Science.gov (United States)

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). There are several methods to measure oxidative stress, being lipid peroxidation (LPO) one of the most frequently used. Endogenous plasma LPO was determined by a spectrofluorimetric method in fifty two patients with sporadic PD and in forty controls. To know the maximum capacity of lipids to peroxidate, LPO was also measured after co-incubation with Fe2+/H2O2 (exogenous LPO). All PD patients were taken L-dopa and the effect of this treatment on LPO levels was additionally studied. Urine catecholamines and their main metabolites were also analyzed, and their possible correlation to LPO statistically studied. Endogenous plasma LPO levels were 33% higher in PD group than in control group (P<0.001). Exogenous plasma or oxidizability was also higher in PD patients compared to controls (20%, P<0.05). The intake of L-dopa was negatively dose-related to endogenous and exogenous plasma LPO. In conclusion, plasma of PD patients has elevated levels of LPO and also is more prone to peroxidation than that in the control group. The results also suggest an antioxidant effect of L-dopa. PMID:16219327

Agil, Ahmad; Durán, Raquel; Barrero, Francisco; Morales, Blas; Araúzo, Mariano; Alba, Francisco; Miranda, Ma Teresa; Prieto, Isabel; Ramírez, Manuel; Vives, Francisco

2006-01-15

112

Sporadic medullary thyroid carcinoma: clinical data from a university hospital  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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 dia [...] gnosed 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 observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6-15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were highly useful for diagnosing s-medullary thyroid carcinoma. The rate of complete patient recovery was low, and none of the parameters analyzed were useful predictors of the thyroid tumor size. Our findings support previous recommendations for routine serum calcitonin evaluation and immunostaining analysis involving single thyroid nodules.

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

2009-05-01

113

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

Science.gov (United States)

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

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

114

Type 3 diabetes is sporadic Alzheimer?s disease: Mini-review.  

Science.gov (United States)

Alzheimer?s disease (AD) is the most common cause of dementia in North America. Growing evidence supports the concept that AD is a metabolic disease mediated by impairments in brain insulin responsiveness, glucose utilization, and energy metabolism, which lead to increased oxidative stress, inflammation, and worsening of insulin resistance. In addition, metabolic derangements directly contribute to the structural, functional, molecular, and biochemical abnormalities that characterize AD, including neuronal loss, synaptic disconnection, tau hyperphosphorylation, and amyloid-beta accumulation. Because the fundamental abnormalities in AD represent effects of brain insulin resistance and deficiency, and the molecular and biochemical consequences overlap with Type 1 and Type 2 diabetes, we suggest the term "Type 3 diabetes" to account for the underlying abnormalities associated with AD-type neurodegeneration. In light of the rapid increases in sporadic AD prevalence rates and vastly expanded use of nitrites and nitrates in foods and agricultural products over the past 30-40 years, the potential role of nitrosamine exposures as mediators of Type 3 diabetes is discussed. PMID:25088942

de la Monte, Suzanne M

2014-12-01

115

EVALUATION OF NF2 GENE DELETION IN SPORADIC SCHWANNOMAS, MENINGIOMAS, AND EPENDYMOMAS BY CHROMOGENIC IN SITU HYBRIDIZATION  

OpenAIRE

Fluorescent in situ hybridization (FISH), loss of heterozygosity (LOH)-testing and comparative genomic hybridization (CGH) have been used to detect NF2 gene alterations in both sporadic and NF2-associated CNS tumors. In this study, we performed chromogenic in situ hybridization (CISH) and immunohistochemistry to evaluate for NF2 gene deletion in a group of sporadic meningiomas, schwannomas, and ependymomas. Twenty-two sporadic tumors, including 9 ependymomas, 10 meningiomas, and 3 schwannomas...

Begnami, Maria D.; Palau, Mauricio; Rushing, Elisabeth J.; Santi, Mariarita; Quezado, Martha

2007-01-01

116

Meat consumption and meat preparation in relation to colorectal adenomas among sporadic and HNPCC family patients in The Netherlands  

OpenAIRE

Meat consumption and meat preparation methods are thought to be associated with the risk of sporadic colorectal cancer, and possibly adenomas. As the same somatic mutations occur in sporadic adenomas and hereditary non-polyposis colorectal cancer (HNPCC)-related adenomas, similar exogenous factors may play a role in the development of both types of adenoma. In a case control study among 57 sporadic colorectal adenoma cases and 62 adenoma cases from HNPCC families (and 148 adenoma-free control...

Voskuil, D. W.; Kampman, E.; Grubben, M. J. A. L.; Kok, F. J.; Nagengast, F. M.; Vasen, H. F. A.; Veer, P.

2002-01-01

117

Selected case from the Arkadi M. Rywlin International Pathology Slide Seminar: Sporadic lymphangioleiomyomatosis.  

Science.gov (United States)

Lymphangioleiomyomatosis (LAM) is a systemic, progressive, and fatal condition affecting almost exclusively women in their reproductive years. LAM most often occurs as a sporadic disease, but also occurs in women with tuberous sclerosis complex (TSC) (syndromic LAM). There are no pathologic differences between sporadic and syndromic LAM. Sporadic LAM is a rare disease with prevalence of approximately 1 to 2 cases per million women in the United States and among populations of white descent, and is even rarer among Asian and African individuals. Syndromic LAM affects 4% to 5% of women with TSC. Sporadic LAM is often found also in association with renal angiomyolipoma, the most common sign of TSC, but LAM associated with angiomyolipoma does not define TSC. Although LAM is not diagnostic for TSC either in isolation or in association with angiomyolipoma, still it is considered by some researchers as an incomplete expression (forme fruste) of TSC. LAM may involve the lungs and the axial lymphatics and lymph nodes of the thorax and retroperitoneum. In sporadic LAM, thoracic, intraabdominal, and cervical lymph nodes can be involved with or without lung involvement. The diagnosis of LAM is often delayed. A case of LAM in a young lady, which was complicated with pleural and peritoneal chylous effusions, is presented. The diagnosis was first made on a retroperitoneal lymph node biopsy. The patient had a prolonged prior history of respiratory problems owing to lung involvement, and eventually died 2 years after diagnosis. Focus on the clinicopathologic diagnosis of TSC is also made. PMID:20966650

Bisceglia, Michele; D'Alessandro, Vito; Simeone, Annalisa; Ben-Dor, David; Pasquinelli, Gianandrea

2010-11-01

118

Ionospheric Scintillations Induced by Sporadic-E Irregularities Over Low Latitude (P31)  

Science.gov (United States)

kalpanaa20@rediffmail.com The observations of daytime ionospheric scintillation are attributed to E- region irregularities at high and equatorial latitudes. In this paper, VHF amplitude scintillations recorded during the daytime period from 1991 to 1993 at low latitude station Varanasi (geomag. lat. 140 55/ N, long. 1540 E) are analyzed to study the behavior of sporadic-E irregularities during the active solar and magnetic periods. The amplitude scintillations of 250 MHz signal transmitted from geostationary satellite FLEETSAT situated at 730E longitude is monitored using a VHF receiver and chart recorder. In addition to the normal chart recording, data were also recorded digitally at a sampling rate of 10Hz on a few days. The daytime digital scintillation data have been analyzed to study some important parameters of scintillation producing sporadic-E irregularities like auto-correlation function, power spectral densities, signal de-correlation time etc. We report the behavior of these parameters under weak and strong scintillation conditions. Results of these studies yield information about the sporadic-E irregularity structures, its shape and size. Derived spectral index ranges between 2 and 10 and the characteristics length of sporadic-E irregularities varies from 150m to 3000 m. The estimated characteristic of these irregularities depends on the velocity and hence we estimate the minimum and maximum range of scale length of sporadic-E irregularities, observed in the ionosphere of Varanasi. These results are also discussed in the light of recent works.

Patel, K.; Singh, A. K.; Patel, R. P.; Singh, R. P.

2006-11-01

119

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

2003-02-01

120

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.)

121

Sporadic Creutzfeldt-Jakob disease presenting as a stroke mimic590.  

Science.gov (United States)

Creutzfeldt-Jakob disease is a rare neurodegenerative disease in which there is an abnormal accumulation of prion protein. It occurs with an incidence of approximately 1 per million per year. Sporadic Creutzfeldt-Jakob disease occurs in approximately 85% of cases, with familial, variant and iatrogenic forms less common. Typically sporadic Creutzfeldt-Jakob disease presents with a rapidly progressive dementia, but sub-variants include the Heidenhain and Oppenheimer-Brownell variants. The former presents with visual disturbance and the latter with ataxia. This article describes a 75-year-old man with a Heidenhain variant of sporadic Creutzfeldt-Jakob disease who presented with a sudden onset of homonymous hemianopia mimicking a stroke. PMID:22041731

Hirst, Claire L

2011-10-01

122

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

123

Altered Cholesterol Intracellular Trafficking and the Development of Pathological Hallmarks of Sporadic AD  

Science.gov (United States)

Compared to the rare familial early onset Alzheimer’s disease (AD) that results from gene mutations in AbPP and presenilin-1, the pathogenesis of sporadic AD is much more complex and is believed to result from complex interactions between nutritional, environmental, epigenetic and genetic factors. Among those factors, the presence APOE4 is still the single strongest genetic risk factor for sporadic AD. However, the exact underlying mechanism whereby apoE4 contributes to the pathogenesis of sporadic AD remains unclear. Here, we discuss how altered cholesterol intracellular trafficking as a result of apoE4 might contribute to the development of pathological hallmarks of AD including brain deposition of amyloid beta (Ab), neurofibrillary tangles, and synaptic dysfunction.

Chen, Xuesong; Hui, Liang; Soliman, Mahmoud L; Geiger, Jonathan D.

2014-01-01

124

Simultaneous observation of sporadic E with a rapid-run ionosonde and VHF coherent backscatter radar  

Directory of Open Access Journals (Sweden)

Full Text Available During the SEEK 2 rocket campaign, ionograms were recorded every minute at the Yamagawa Radio Observatory at about 90km west of the region monitored by a VHF (very high frequency coherent backscatter radar. Sporadic E-layer parameters, which include the critical (foEs and blanketing (fbEs frequencies, the layer height (h'Es, and the width of the range spread of sporadic E-traces, were compared with RTI (range-time-intensity plots of VHF quasi-periodic (QP and continuous coherent backscatter echoes. A close relationship was found between the appearance of QP echoes in the RTI plots and the level of spatial inhomogeneity in sporadic E plasma, signified here by the difference between foEs and fbEs. During QP echo events, foEs increased while fbEs decreased, so that the difference foEs-fbEs was enhanced, indicating the development of strong spatial structuring in electron density within a sporadic E-layer. On the other hand, increases in sporadic E range spreading also correlated with the occurrence of QP echoes but the degree of correlation varied from event to event. Continuous radar echoes were observed in association with low altitude sporadic E-layers, located well below 100 km and at times as low as 90 km. During the continuous echo events, both foEs and fbEs were less variable, and the difference foEs-fbEs was small and not as dynamic as in the QP echoes. On the other hand, the Es-layer spread intensified during continuous echoes, which means that some patchiness or corrugation in those low altitude layers is also necessary for the continuous backscatter echoes to take place.

T. Maruyama

2006-03-01

125

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

Directory of Open Access Journals (Sweden)

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.

DarylABosco

2013-12-01

126

Frequent NF2 Gene Transcript Mutations in Sporadic Meningiomas and Vestibular Schwannomas  

OpenAIRE

The gene for the hereditary disorder neurofibromatosis type 2 (NF2), which predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has been isolated. Mutations in the NF2 gene were found in both sporadic meningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of these NF2-...

Deprez, Ronald H. Lekanne; Bianchi, Albert B.; Groen, Nicole A.; Seizinger, Bernd R.; Hagemeijer, Anne; Drunen, Ellen; Bootsma, Dirk; Koper, Jan W.; Avezaat, Cees J. J.; Kley, Nikolai; Zwarthoff, Ellen C.

1994-01-01

127

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2011-04-15

128

C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population  

OpenAIRE

It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (familial ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1,757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1,523 from mainland Italy. Sixty (3.7%) of 1,624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathog...

Sabatelli, Mario; Conforti, Francesca Luisa; Zollino, Marcella; Mora, Gabriele; Monsurro?, Maria Rosaria; Volanti, Paolo; Marinou, Kalliopi; Salvi, Fabrizio; Corbo, Massimo; Giannini, Fabio; Battistini, Stefania; Penco, Silvana; Lunetta, Christian; Quattrone, Aldo; Gambardella, Antonio

2012-01-01

129

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

Directory of Open Access Journals (Sweden)

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.

Chupin Louis-Dominique

2008-11-01

130

Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer.  

Science.gov (United States)

Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer. We studied the growth inhibitory effects of rucaparib in a panel of 39 ovarian cancer cell lines that were each characterized for mutation and methylation status of BRCA1/2, baseline gene expression signatures, copy number variations of selected genes, PTEN status, and sensitivity to platinum-based chemotherapy. To study interactions with chemotherapy, we used multiple drug effect analyses and assessed apoptosis, DNA fragmentation, and ?H2AX formation. Concentration-dependent antiproliferative effects of rucaparib were seen in 26 of 39 (67%) cell lines and were not restricted to cell lines with BRCA1/2 mutations. Low expression of other genes involved in homologous repair (e.g., BCCIP, BRCC3, ATM, RAD51L1), amplification of AURKA or EMSY, and response to platinum-based chemotherapy was associated with sensitivity to rucaparib. Drug interactions with rucaparib were synergistic for topotecan, synergistic, or additive for carboplatin, doxorubicin or paclitaxel, and additive for gemcitabine. Synergy was most pronounced when rucaparib was combined with topotecan, which resulted in enhanced apoptosis, DNA fragmentation, and ?H2AX formation. Importantly, rucaparib potentiated chemotherapy independent of its activity as a single agent. PARP inhibition may be a useful therapeutic strategy for a wider range of ovarian cancers bearing deficiencies in the homologous recombination pathway other than just BRCA1/2 mutations. These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer. PMID:23729402

Ihnen, Maike; zu Eulenburg, Christine; Kolarova, Teodora; Qi, Jing Wei; Manivong, Kanthinh; Chalukya, Meenal; Dering, Judy; Anderson, Lee; Ginther, Charles; Meuter, Alexandra; Winterhoff, Boris; Jones, Siân; Velculescu, Victor E; Venkatesan, Natarajan; Rong, Hong-Mei; Dandekar, Sugandha; Udar, Nitin; Jänicke, Fritz; Los, Gerrit; Slamon, Dennis J; Konecny, Gottfried E

2013-06-01

131

First results of mapping sporadic E with a passive observing network  

Science.gov (United States)

Sporadic E (Es) can have dramatic effects on communications in the HF and low VHF range, producing over-the-horizon propagation for signals normally restricted to line-of-sight, and sometimes blocking F region propagation of signals in the lower HF range. Measuring the E region winds believed to produce Es is difficult, and no practical means of predicting Es occurrence currently exists other than statistical models. We describe a low-cost observing network based on software-controlled receivers that continuously watches for Es in near-real time using oblique HF propagation from existing transmitters. Results from an 11-day pilot campaign in July 2008 demonstrated that even a limited number of receivers in the network can readily determine the presence and extent of Es patches. These observations indicate that Es often develops quickly over regions of several hundred kilometers rather than gradually drifting across an area. These widespread Es “blooms” have been observed near winter solstice and occasionally at other times of the year; their lifetime depends on the season but can be several hours during the summer. The current network allows the extent of Es in portions of North America to be evaluated: the geographical distribution of Es and bounds on the density of the layer are inferred from its effects on the ionospheric maximum usable frequency (MUF). This study demonstrates quantitatively that Es mapping can provide information about Es layer geographical growth and decay. The observed sudden widespread Es blooms are space weather events that can have significant impact on HF/lower VHF communications and propagation model predictions.

Rice, D. D.; Sojka, J. J.; Eccles, J. V.; Raitt, J. W.; Brady, J. J.; Hunsucker, R. D.

2011-12-01

132

Chyloperitoneum, chylothorax and lower extremity lymphedema in woman with sporadic lymphangioleiomyomatosis successfully treated with sirolimus: a case report.  

Science.gov (United States)

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by diffuse thin-walled cysts throughout the lungs on computed tomography and diffuse proliferation of abnormal smooth muscle-like cells (LAM cells) on lung biopsy. LAM affects women almost exclusively, predominantly in their reproductive age. The most typical presenting symptoms include dyspnea, spontaneous pneumothorax, cough and chylothorax. Abdominal findings represent less common initial manifestations of the disease and may pose diagnostic difficulties. The treatment of LAM has not been fully established. Recent studies report effectiveness of sirolimus in LAM patients. We report the case of a 45-year-old woman with sporadic LAM, successfully treated with sirolimus, in whom the first manifestation of the disease was chyloperitoneum and after three and nine years, respectively, lymphedema of the left lower extremity and right sided chylothorax occurred. PMID:23057149

Chachaj, A; Drozdz, K; Chabowski, M; Dziegiel, P; Grzegorek, I; Wojnar, A; Jazwiec, P; Szuba, A

2012-06-01

133

Variation of sporadic meteor activity during the 23. cycle of solar activity  

International Nuclear Information System (INIS)

Analyses of the influence of solar activity on sporadic meteor counts based on visual and radar meteor observations present rather contradictory results, indicating a possible variation of the sporadic meteor counts with a solar activity, with the maximum in observed meteor rates occurring from zero up to about five years after the solar activity maximum. With this perspective, in the present paper observations of the sporadic meteor background, obtained by a forward-scatter radio system for meteor observation operating along the Bologna (Italy)-Modra (Slovakia) baseline in 1996-2007, are analysed and discussed. The activity curves of all echoes and their variations indicate a correlation with solar activity in the 23. solar cycle represented by the solar relative number R (corr. coef. 0.71), as well as with the solar coronal index C1 (corr. coef. 0.73). The mass distribution exponent s and its variations (with corr. coef. against R and C1, 0.12 and 0.25, respectively) does not show a correlation consistent with solar activity and, from the viewpoint of s, suggest the existence of a relatively stable population of sporadic background meteoroids in the surroundings of the Earth's orbit during the investigated period.

134

The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion disease  

OpenAIRE

Objective: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene.

Cordery, R.; Alner, K.; Cipolotti, L.; Ron, M.; Kennedy, A.; Collinge, J.; Rossor, M.

2005-01-01

135

Sporadic Emergence of Klebsiella pneumoniae Strains Resistant to Cefepime and Cefpirome in Greek Hospitals  

OpenAIRE

The sporadic emergence of Klebsiella pneumoniae strains resistant to cefepime and cefpirome was observed in Greek hospitals during 1996. Examination of six epidemiologically distinct strains and clones selected in vitro provided indications that resistance is due to the cooperation of decreased outer membrane permeability and hydrolysis of the cephalosporins by SHV-5 ?-lactamase, which was produced in large amounts.

Tzouvelekis, L. S.; Tzelepi, E.; Prinarakis, E.; Gazouli, M.; Katrahoura, A.; Giakkoupi, P.; Paniara, O.; Legakis, N. J.

1998-01-01

136

Adult onset sporadic ataxias: a diagnostic challenge / Ataxias esporádicas de início no adulto: um desafio diagnóstico  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese Pacientes com ataxia progressiva que se inicia na idade adulta, e sem histórico familiar da doença, são classificados no grupo das ataxias esporádicas. Existem várias categorias de doenças que podem se manifestar com ataxia esporádica, tais como: causas tóxicas, ataxias imunomediadas, deficiência de [...] vitaminas, doenças infecciosas, doenças degenerativas e até mesmo condições genéticas. Considerando a heterogeneidade no espectro clínico das ataxias esporádicas, a definição da etiologia constitui um desafio diagnóstico. Neste artigo de revisão, realizamos uma discussão sobre as diferentes categorias de doenças que causam ataxia com início na idade adulta sem histórico familiar, com ênfase nas características clínicas, aspectos de imagem e critérios diagnósticos. Abstract in english Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic cond [...] itions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

Orlando Graziani Povoas, Barsottini; Marcus Vinicius Cristino de, Albuquerque; Pedro, Braga Neto; José Luiz, Pedroso.

2014-03-01

137

Cigarette smoking, von Hippel–Lindau gene mutations and sporadic renal cell carcinoma  

OpenAIRE

We investigated whether smoking is associated with mutations in the Von Hippel–Lindau (VHL) gene in 337 cases of sporadic renal cell carcinoma (RCC) among 120?852 people followed for 11.3 years; the findings suggest that smoking causes RCC independently of VHL gene mutations.

Dijk, B. A. C.; Schouten, L. J.; Oosterwijk, E.; Hulsbergen-van Kaa, C. A.; Kiemeney, L. A. L. M.; Goldbohm, R. A.; Schalken, J. A.; Den Brandt, P. A.

2006-01-01

138

Sporadic Visceral Myopathy: Full Thickness Rectal Biopsy to Clinch the Diagnosis  

OpenAIRE

Chronic intestinal pseudo-obstruction (CIPO) may result fromdysfunctional intestinal nerves or muscles. Primary causesare uncommon and include familial and sporadic visceralmyopathies. Visceral myopathy may be characterized by CIPO,ureterohydronephrosis, and hepatobiliary dilation. The diagnosis ismade by the clinical history and characteristic findings of fibrousreplacement of the muscularis externa, vacuolar degeneration, andcytoplasmic inclusions in myocytes on a full thickness specimen of...

Reddy, Swapna B.; Hamerski, Christopher M.; Gavankar, Sheetal S.; Singson, Zarema J.; Suvarna Deshmukh-Rane; Carmichael, Joseph C.; Mark Li-cheng Wu; Lawry, George V.; Lee, Robert H.; Albers, Gregory C.; Parekh, Nimisha K.

2012-01-01

139

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

Directory of Open Access Journals (Sweden)

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.

Mueller Christopher R

2003-10-01

140

The P413L chromogranin B variation in French patients with sporadic amyotrophic lateral sclerosis.  

Science.gov (United States)

Chromogranins interact with mutant forms of superoxide dismutase 1 (SOD1) responsible for a portion of familial amyotrophic lateral sclerosis (ALS). A particular variation (P413L) in the chromogranin B gene, CHGB, has been recently associated with an earlier age at onset in both familial and sporadic ALS. The aim of our study was to evaluate the P413L chromogranin variation in French patients with sporadic amyotrophic lateral sclerosis. We developed a High Resolution DNA Melting (HRM) protocol to analyse the P413L variation in the CHGB gene in 540 French patients with sporadic ALS and 504 controls. The clinical characteristics of patients were analysed in relation to their genotype. Results showed that our study on a large cohort of French-Caucasian patients with SALS and controls failed to confirm an increased frequency of the 413L variant in SALS patients. This frequency was 5.3% in the SALS population and 5.5% in the control group. Moreover, we did not observe a previous observation of a difference of age at onset between T-allele carriers and non-carriers (median age of onset 60.4 vs. 62.0 years of age, respectively). Thus, our findings do not support the 413L variant of rs742710 as a risk factor for sporadic ALS in the French population. PMID:20932227

Blasco, Hélène; Corcia, Philippe; Veyrat-Durebex, Charlotte; Coutadeur, Cathleen; Fournier, Clémentine; Camu, William; Gordon, Paul; Praline, Julien; Andres, Christian R; Vourc'h, Patrick

2011-05-01

141

Near-infrared spectroscopy of blood plasma for diagnosis of sporadic Alzheimer's disease.  

Science.gov (United States)

There are currently no accepted blood-based biomarkers of sporadic Alzheimer's disease (AD). Augmented oxidative stress has been implicated in both neural and peripheral AD tissues. In this study, we determined whether short-wavelength near-infrared (NIR) spectrophotometry of blood plasma differentiates mild sporadic AD from normal aging. NIR analysis was conducted on 75 microl plasma samples from 19 AD, 27 amnestic MCI, and 17 normal elderly control (NEC) persons using an optical fiber-coupled, holographic grating-based NIR spectrograph. Five spectral bands associated with heme, R-CH, R-OH, H2O, and R-NH functional groups were sensitive to oxidative modification in pre-clinical studies and were pre-selected to develop a logistic regression model for sample classification. This model differentiated AD from NEC samples with a sensitivity of 80% and specificity of 77%. Fifteen and twelve MCI patients were classified with the NEC and AD groups, respectively. The spectra were not influenced by age, gender, exposure to cholinesterase inhibitors or vitamin E, or sample storage time. The NIR data further implicate oxidative stress in the systemic pathophysiology of sporadic AD and differentiate mild (and possibly pre-clinical) AD from NEC individuals with moderate-high accuracy. The procedure is minimally-invasive, rapid, relatively-inexpensive, and may provide a useful biological marker of sporadic AD. PMID:19363272

Burns, David H; Rosendahl, Scott; Bandilla, Dirk; Maes, Olivier C; Chertkow, Howard M; Schipper, Hyman M

2009-01-01

142

Genetic-clinical profile of subjects with apparently sporadic extra-adrenal paragangliomas  

Directory of Open Access Journals (Sweden)

Conclusions: Extra-adrenal paragangliomas, localized in the sympathetic ganglia (in the posterior thorax or in the abdomen, are very often SDHB-inherited form rather than sporadic tumor. Our data confirm the importance of genetic screening in patients affected with paragangliomas and enlarge the list of mutations responsible for the presence of these tumors.

ValeriaRamundo

2012-05-01

143

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.)

144

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

LENUS (Irish Health Repository)

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.

Kimmich, Okka

2012-02-01

145

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

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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.

Kim Nora

2012-07-01

146

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1998-02-01

147

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.)

148

Sporadic sodium and E layers observed during the summer 2002 MaCWAVE/MIDAS rocket campaign  

Directory of Open Access Journals (Sweden)

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.

B. P. Williams

2006-07-01

149

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

Science.gov (United States)

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 (disease susceptibility. PMID:25528024

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

150

Sporadic Creutzfeldt-Jakob disease presenting as progressive nonfluent aphasia with speech apraxia.  

Science.gov (United States)

Progressive non-fluent aphasia (PNFA) is typically associated with pathological changes consistent with frontotemporal lobar degeneration. A 65-year-old male presented with effortful speech, markedly impaired naming and features of speech apraxia, consistent with PNFA. Perceptuospatial function, calculation and executive function were intact. Brain SPECT showed left perisylvian hypoperfusion. He deteriorated profoundly over the subsequent eight months, with appearances on diffusion-weighted magnetic resonance imaging typical of sporadic Creutzfeldt-Jakob disease, which was confirmed pathologically at postmortem examination. While the presence of PNFA with speech apraxia is thought to predict underlying tauopathy, sporadic Creutzfeldt-Jakob disease may mimic this presentation and present in a highly circumscribed form not previously described. PMID:22732678

Kobylecki, Christopher; Thompson, Jennifer C; Jones, Matthew; Mills, Samantha J; Shaunak, Sandip; Ironside, James W; Snowden, Julie S; Richardson, Anna M

2013-01-01

151

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

Science.gov (United States)

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

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

2014-10-16

152

Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability.  

Science.gov (United States)

Many lines of evidence suggest that the retinoblastoma protein interacting zinc finger gene RIZ is a strong candidate for the tumor suppressor locus on 1p36, a region commonly deleted in many human cancers with chromosomal instability. In addition, a role for RIZ in tumors of the microsatellite instability pathway is suggested by frequent frameshift mutations in hereditary non-polyposis colorectal carcinomas. Here we studied RIZ mutations in sporadic cancers with microsatellite instability. Frameshift mutations in the two coding polyadenosine tracks of RIZ were found in 19 (48%) of 40 gastric carcinomas, 6 (33%) of 18 endometrial carcinomas, 14 (26%) of 51 of colorectal carcinomas, and 7 (54%) of 13 cell lines. Eleven tumor tissues showed biallelic inactivation of RIZ. In contrast, no frameshift mutations were found in 70 microsatellite stable tumors. These results suggest an important role for RIZ in sporadic cancers with microsatellite instability. PMID:10987271

Piao, Z; Fang, W; Malkhosyan, S; Kim, H; Horii, A; Perucho, M; Huang, S

2000-09-01

153

Otofaciocervical syndrome: a sporadic patient supports splitting from the branchio-oto-renal syndrome  

OpenAIRE

A sporadic patient with OFC syndrome is described. Distinguishing features were a long face with narrow nose, high arched palate, prominent and dysmorphic ears, long neck, sloping shoulders and clavicles, winged, low, and laterally set scapulae, tetralogy of Fallot, and deafness secondary to cochlear malformation. Some features present in the original family, including lateral cervical fistulae, have suggested that OFC syndrome could be a variant of BOR syndrome. The absence of preauricular t...

Dallapiccola, Bruno; Mingarelli, Rita

1995-01-01

154

The MM2-cortical form of sporadic Creutzfeldt-Jakob disease presenting with visual disturbance.  

Science.gov (United States)

A subclass of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by onset with visual symptoms (Heidenhain variant) has been reported to belong to the MM1 or MV1 type according to Parchi's classification. The authors report a 65-year-old woman with MM2-cortical sCJD with slowly progressive visual disturbance as the initial symptom. Diffusion-weighted MRIs revealed hyperintensity in both occipital cortices at an early stage. PMID:16894125

Nozaki, I; Hamaguchi, T; Noguchi-Shinohara, M; Ono, K; Shirasaki, H; Komai, K; Kitamoto, T; Yamada, M

2006-08-01

155

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

OpenAIRE

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...

Lindberg, Daniel

2007-01-01

156

LRE-TL: An Optimal Multiprocessor Scheduling Algorithm for Sporadic Task Sets  

OpenAIRE

This paper introduces LRE-TL, a scheduling algorithm based on LLREF, and demonstrates its flexibility and improved running time. Unlike LLREF, LRE-TL is optimal for sporadic task sets. While most LLREF events take O(n) time to run, the corresponding LRETL events take O(log n) time. LRE-TL also reduces the number of task preemptions and migrations by a factor of n. Both identical and uniform multiprocessors are considered.

Funk, Shelby; Nanadur, Vijaykant

2009-01-01

157

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

OpenAIRE

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...

Ibeh, Emmanuel Uttah Dominic C.

2011-01-01

158

Prevalence and spectrum of GATA4 mutations associated with sporadic dilated cardiomyopathy.  

Science.gov (United States)

Dilated cardiomyopathy (DCM) is the most frequent type of primary myocardial disorder responsible for substantial morbidity and mortality. DCM is the third most common cause of heart failure and the most common reason for heart transplantation. A recent study has implicated GATA4 mutation in the pathogenesis of familial DCM. However, the prevalence and spectrum of GATA4 mutations associated with sporadic DCM remain unclear. In this study, the coding exons and exon-intron boundaries of the GATA4 gene, which encodes a cardiac transcription factor crucial for normal cardiogenesis, were sequenced in 220 unrelated patients with sporadic DCM. A total of 200 unrelated ethnically-matched healthy individuals used as controls were genotyped. The functional characteristics of the mutant GATA4 were assayed in contrast to its wild-type counterpart using a luciferase reporter assay system. As a result, 3 novel heterozygous GATA4 mutations, p.V39L, p.P226Q and p.T279S, were identified in 3 unrelated patients with sporadic DCM, with a mutational prevalence of approximately 1.36%. The missense mutations were absent in 400 control chromosomes and the altered amino acids were completely conserved evolutionarily across species. Functional analysis showed that the GATA4 mutants were consistently associated with significantly decreased transcriptional activity and markedly reduced the synergistic activation between GATA4 and NKX2-5. This study firstly links GATA4 mutations to increased susceptibility to sporadic DCM and provides novel insight into the molecular etiology underlying DCM, suggesting the potential implications for the early prophylaxis and allele-specific treatment of this common form of cardiomyopathy. PMID:25017055

Li, Jian; Liu, Wei-Dong; Yang, Zhang-Liang; Yuan, Fang; Xu, Lei; Li, Ruo-Gu; Yang, Yi-Qing

2014-09-15

159

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

OpenAIRE

Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average number of chromatid ...

Sales Magaly M.; Lucca Edmundo J. de; Yamashita Seizo; Saad Luis Henrique Cury

1999-01-01

160

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

OpenAIRE

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 specifi...

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

2010-01-01

161

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

OpenAIRE

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrPSc) induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary cons...

Lyytinen, Jukka; Sairanen, Tiina; Valanne, Leena; Salmi, Tapani; Paetau, Anders; Pekkonen, Eero

2010-01-01

162

Sporadic hemiplegic migraine: report of a case with clinical and radiological features  

OpenAIRE

A case of visual hallucination, headache and left hemiparesis is reported. The patient had a history of recurrent attacks of similar semiology for the previous 15 years. MRI brain revealed a cortical hyperintensity on T2W, FLAIR and diffusion weighted imaging (DWI) in the right cerebral hemisphere with a normal ADC (apparent diffusion coefficient) map and MR angiogram. Detailed workup for MELAS was negative. A diagnosis of sporadic hemiplegic migraine was made and he was managed conservative...

Bhatia, Rohit; Desai, Soaham; Tripathi, Manjari; Garg, Ajay; Padma, M. V.; Prasad, Kameshwar; Singh, Mamta B.

2008-01-01

163

Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer’s disease  

OpenAIRE

Alzheimer’s disease (AD) is characterized by amyloid ? (A?) accumulation in the brain and is classified as familial early-onset (FAD) or sporadic late-onset (SAD). Evidences suggest that deficits in the brain expression of insulin degrading enzyme (IDE) and neprilysin (NEP), both proteases involved in amyloid degradation, may promote A? deposition in SAD. We studied by immunohistochemistry IDE and NEP cortical expression in SAD and FAD samples carrying the E280A presenilin-1 missense mut...

Dorfman, Vero?nica Berta; Pasquini, Laura; Riudavets, Miguel; Lo?pez-costa, Juan Jose?; Villegas, Andre?s; Troncoso, Juan Carlos; Lopera, Francisco; Castan?o, Eduardo Miguel; Morelli, Laura

2010-01-01

164

A case study of a sporadic sodium layer observed by the ALOMAR Weber Na LIDAR  

OpenAIRE

Several possible mechanisms for the production of sporadic sodium layers have been discussed in the literature, but none of them seem to explain all the accumulated observations. The hypotheses range from direct meteoric input, to energetic electron bombardment on meteoric smoke particles, to ion neutralization, to temperature dependent chemistry. The varied instrumentation located on Andøya and near Tromsø in Norway gives us an opportunity to test the different theories applied to high lat...

Nesse, H.; Heinrich, D.; Williams, B.; -p Hoppe, U.; Stadsnes, J.; Rietveld, M.; Singer, W.; Blum, U.; Sandanger, M. I.; Trondsen, E.

2008-01-01

165

Distinct patterns of APP processing in the CNS in autosomal-dominant and sporadic Alzheimer disease  

OpenAIRE

Autosomal-dominant Alzheimer disease (ADAD) is a genetic disorder caused by mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes. Studies from families with ADAD have been critical to support the amyloid cascade hypothesis of Alzheimer disease (AD), the basis for the current development of amyloid-based disease-modifying therapies in sporadic AD (SAD). However, whether the pathological changes in APP processing in the CNS in ADAD are similar to those obser...

Pera, Marta; Alcolea, Daniel; Sa?nchez-valle, Raquel; Guardia-laguarta, Cristina; Colom-cadena, Marti?; Badiola, Nahuai; Sua?rez-calvet, Marc; Llado?, Albert; Barrera-ocampo, Alvaro A.; Sepulveda-falla, Diego; Blesa, Rafael; Molinuevo, Jose? L.; Clarimo?n, Jordi; Ferrer, Isidre; Gelpi, Ellen

2012-01-01

166

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis  

OpenAIRE

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts con...

Chio?, A.; Schymick, Jc; Restagno, G.; Scholz, Sw; Lombardo, F.; Lai, Sl; Mora, G.; Fung, Hc; Britton, A.; Arepalli, S.; Gibbs, Jr; Nalls, M.; Berger, S.; Kwee, Lc; Oddone, Ez

2009-01-01

167

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

OpenAIRE

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 his...

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

2013-01-01

168

Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed  

OpenAIRE

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression pro...

Tamburini, Beth A.; Trapp, Susan; Phang, Tzu Lip; Schappa, Jill T.; Hunter, Lawrence E.; Modiano, Jaime F.

2009-01-01

169

Microvascular pathology and morphometrics of sporadic and hereditary small vessel diseases of the brain.  

Science.gov (United States)

Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology. PMID:25323665

Craggs, Lucinda J L; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Raj N

2014-09-01

170

Enhanced sporadic E occurrence rates during the Geminid meteor showers 2006–2010  

OpenAIRE

Northern Hemisphere midlatitude sporadic E (Es) layer occurrence rates derived from FORMOSAT-3/COSMIC GPS radio occultation (RO) measurements during the Geminid meteor showers 2006–2010 are compared with meteor rates obtained with the Collm (51.3° N, 13.0° E) VHF meteor radar. In most years, Es rates increase after the shower, with a short delay of few days. This indicates a possible link between meteor influx and the production...

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

2013-01-01

171

Microsatellite-stable diploid carcinoma: a biologically distinct and aggressive subset of sporadic colorectal cancer.  

OpenAIRE

Chromosomal instability and microsatellite instability represent the major pathways for colorectal cancer (CRC) progression. However, a significant percentage of CRC shows neither pattern of instability, and thus represents a potentially distinctive form of the disease. Flow cytometry was used to determine the degree of DNA aneuploidy in 46 consecutive sporadic colorectal cancers. Microsatellite status was determined by PCR amplification using standard markers, while immunostaining was used t...

Hawkins, Nj; Tomlinson, I.; Meagher, A.; Ward, Rl

2001-01-01

172

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

OpenAIRE

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...

Correia, So?nia C.; Santos, Renato X.; Perry, George; Zhu, Xiongwei; Moreira, Paula I.; Smith, Mark A.

2011-01-01

173

Presenilin 1 intronic polymorphism is not associated with Alzheimer type neuropathological changes or sporadic Alzheimer's disease  

OpenAIRE

BACKGROUND—A genetic association between the presenilin 1 (PS-1) intronic polymorphism and sporadic Alzheimer's disease has been a matter of controversy. Recent findings have suggested that the PS-1 polymorphism is not associated with Alzheimer's disease or amyloid ?-protein (A?) deposition in brains from patients with Alzheimer's disease.?OBJECTIVES—To elucidate the influence of the PS-1 polymorphism on Alzheimer type neuropathological changes and the development...

Sodeyama, N.; Itoh, Y.; Suematsu, N.; Matsushita, M.; Otomo, E.; Mizusawa, H.; Yamada, M.

1998-01-01

174

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

OpenAIRE

The occurrence of sporadic E (Es) layer has been a hot scientific topic for a long time. Global Navigation Satellite System (GNSS) based Radio Occultation (RO) has been proven a powerful technique on 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. We first show some examples of multiple Es layers occurred in one RO event. Based on the evaluations ...

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

2014-01-01

175

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

OpenAIRE

Abstract 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...

Majorana Giovanni; Simone Isabella; Labella Vincenzo; Gabriele AnnaLia; Magariello Angela; Patitucci Alessandra; Tedeschi Gioacchino; Tessitore Alessandro; Ungaro Carmine; Mazzei Rosalucia; Sprovieri Teresa; Conforti Francesca; Monsurrò Maria; Valentino Paola; Muglia Maria

2006-01-01

176

Chromosome 2p, 3p, 5q and 18q status in sporadic gastric cancer.  

OpenAIRE

AIM: The genetic make-up of gastric cancers in low-risk population groups from South Africa is largely unknown. The purpose of this study was to ascertain the incidence of microsatellite instability and loss of heterozygosity in this population. METHODS: Thirty-seven gastrectomy specimens for sporadic gastric cancer were analysed for the following clinicopathological parameters: age, gender, race, histopathological type, size of tumour, lymph node status and the presence/absence of Helicobact...

Chetty, R.; Naidoo, R.; Tarin, M.; Sitti, C.

2002-01-01

177

Re-Assessment of PrPSc Distribution in Sporadic and Variant CJD  

OpenAIRE

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...

Rubenstein, Richard; Chang, Binggong

2013-01-01

178

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

OpenAIRE

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...

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

179

Tumor suppress genes screening analysis on 4q in sporadic colorectal carcinoma  

OpenAIRE

AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients.METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH sca...

Li-xin Jiang, Jie Xu

2008-01-01

180

Anti-superoxide dismutase antibodies are associated with survival in patients with sporadic amyotrophic lateral sclerosis  

OpenAIRE

Our objective was to test the hypothesis that aberrantly modified forms of superoxide dismutase (SOD1) influence the disease course for sporadic amyotrophic lateral sclerosis (SALS). We probed for anti-SOD1 antibodies (IgM and IgG) against both the normal and aberrantly oxidized-SOD1 (SODox) antigens in sera from patients with SALS, subjects diagnosed with other neurological disorders and healthy individuals, and correlated the levels of these antibodies to disease duration and/or severity. A...

Blitterswijk, Marka; Gulati, Sunita; Smoot, Elizabeth; Jaffa, Matthew; Maher, Nancy; Hyman, Bradley T.; Ivinson, Adrian J.; Scherzer, Clemens R.; Schoenfeld, David A.; Cudkowicz, Merit E.; Brown, Robert H.; Bosco, Daryl A.

2011-01-01

181

Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis  

DEFF Research Database (Denmark)

To further explore the allelic heterogeneity within the group of LEMD3-related disorders, we have screened a larger series of patients including 5 probands with osteopoikilosis or Buschke-Ollendorff syndrome (BOS), 2 families with the co-occurrence of melorheostosis and BOS, and 12 unrelated patients with isolated melorheostosis. Seven novel LEMD3 mutations were identified, all predicted to result in loss-of-function of the protein. We confirm that loss-of-function mutations in the LEMD3 gene can result in either osteopoikilosis or BOS. However, LEMD3 germline mutations were only found in two melorheostosis patients belonging to a different BOS family and one sporadic patient with melorheostosis. The additional presence of osteopoikilosis lesions in these patients seemed to distinguish them from the group of sporadic melorheostosis patients where no germline LEMD3 mutation was identified. Somatic mosaicism for a LEMD3 mutation in the latter group was also not observed, and therefore we must conclude that the genetic defect in the majority of sporadic and isolated melorheostosis remains unknown.

Hellemans, Jan; Debeer, Philippe

2006-01-01

182

Investigations on the plasma irregularities associated with midlatitude sporadic-E layers  

International Nuclear Information System (INIS)

The Cornell University Portable Radar Interferometer (CUPRI), a 50 MHz Doppler radar system, was operated during May and August/September, 1983 on the island of St. Croix (17.70N, 64.80W) to study the plasma instabilities associated with nighttime sporadic-E layers. The CURPI beam was directed over Arecibo, Puerto Rico, during these experiments, and on several nights concurrent F region plasma drifts and electron density profiles were measured by the Arecibo observatory's 430 MHz radar. CUPRI was stationed at Ft. Macon, North Carolina, in August 1984 for another collaborative experiment involving the launch of a sounding rocket from Wallops Island, Virginia. The usual E region linear plasma fluid theory is adequate to explain many features of the 3-m waves probed by the radar. Measurements at St. Croix determined that the 3-m sporadic-E irregularities are highly field-aligned (to within 0.30) as the theory predicts. Some of the radar spectra obtained from St. Croix are narrow, similar to equatorial type 1. Linear theory reveals that the type 1 3-m waves could be generated at midlatitudes with drift velocities well below the sound speed because of the very sharp gradients associated with metallic ion sporadic-E layers. Two events during the St. Croix campaign show evidence of large scale plasma waves, with horizontal wavelengths of 6-10 km and periods of 2-5 minutes

183

Genomic era diagnosis and management of hereditary and sporadic colon cancer.  

Science.gov (United States)

The morbidity and mortality attributable to heritable and sporadic carcinomas of the colon are substantial and affect children and adults alike. Despite current colonoscopy screening recommendations colorectal adenocarcinoma (CRC) still accounts for almost 140000 cancer cases yearly. Familial adenomatous polyposis (FAP) is a colon cancer predisposition due to alterations in the adenomatous polyposis coli gene, which is mutated in most CRC. Since the beginning of the genomic era next-generation sequencing analyses of CRC continue to improve our understanding of the genetics of tumorigenesis and promise to expand our ability to identify and treat this disease. Advances in genome sequence analysis have facilitated the molecular diagnosis of individuals with FAP, which enables initiation of appropriate monitoring and timely intervention. Genome sequencing also has potential clinical impact for individuals with sporadic forms of CRC, providing means for molecular diagnosis of CRC tumor type, data guiding selection of tumor targeted therapies, and pharmacogenomic profiles specifying patient specific drug tolerances. There is even a potential role for genomic sequencing in surveillance for recurrence, and early detection, of CRC. We review strategies for diagnostic assessment and management of FAP and sporadic CRC in the current genomic era, with emphasis on the current, and potential for future, impact of genome sequencing on the clinical care of these conditions. PMID:25493239

Esplin, Edward David; Snyder, Michael Paul

2014-12-10

184

C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population  

Science.gov (United States)

It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (familial ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1,757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1,523 from mainland Italy. Sixty (3.7%) of 1,624 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 (1,238 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 one year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucloetide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the commonest mutation in Italy and the second more common in Sardinia. PMID:22418734

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

2012-01-01

185

A statistical analysis on the relationship between thunderstorms and the sporadic E Layer over Rome  

Science.gov (United States)

Meteorological processes (cold fronts, mesoscale convective complexes, thunderstorms) in the troposphere can generate upward propagating waves in the neutral atmosphere affecting the behaviour of the ionosphere. One type of these waves are the internal atmospheric gravity waves (AGWs) which are often generated by thunderstorms. Davis & Johnson (2005) found in low pressure systems that a localized intensification of the sporadic E layer (Es) can be attributed to lightnings. To confirm this result, we have performed two different statistical analysis using the time series of the critical frequency (foEs), the virtual height of the sporadic E layer (h'Es), and meteorological observations (lightnings, Infrared maps) over the ionospheric station of Rome (41.9o N, 12.5o E). In the first statistical analysis, we separated the days of 2009 into two groups: stormy days and fair-weather days, then we studied the occurrence and the properties of the Es separately for the two different groups. No significant differences have been found. In the second case, a superposed epoch analysis (SEA) was used to study the behaviour of the critical frequency and virtual height 100 hours before and after the lightnings. The SEA shows a statistically significant decrease in the critical frequency after the time of the lightnings, which indicates a sudden decrease in the electron density of the sporadic E layer associated with lightnings.

Barta, V.; Scotto, C.; Pietrella, M.; Sgrigna, V.; Conti, L.; Sátori, G.

2013-11-01

186

Abnormalities of esophagal transit in patients with sporadic nontoxic goitre  

International Nuclear Information System (INIS)

Esophageal transit (E.T.) was investigated in 122 consecutive euthyroid patients with scintigraphically proven goitre, and compared to 26 control subjects. E.T. was quantified using the 81mKr transit time, a highly sensitive technique capable of detecting even minor E.T. disorders. Abnormal E.T. was observed in 39% of goitrous patients, while it was normal in all controls. Occurrence of delayed E.T. was not correlated with either goitre firmness, the presence of symptoms of neck discomfort, difficulties in swallowing, or nodularity. E.T. delay was more frequent and more severe with larger goitres. In addition, E.T. delay was significantly correlated with asymmetry and 'low lying' goitres. In summary, the present studies are the first demonstration of frequent E.T. anomalies in goitrous patients. The data suggest that E.T. impairment could be mediated by two mechanisms: a direct compression effect in patients with large, asymmetrical, partially retrosternal goitres; and an indirect functional esophageal anomaly in patients with small goitres. (orig.)

187

Abnormalities of esophagal transit in patients with sporadic nontoxic goitre  

Energy Technology Data Exchange (ETDEWEB)

Esophageal transit (E.T.) was investigated in 122 consecutive euthyroid patients with scintigraphically proven goitre, and compared to 26 control subjects. E.T. was quantified using the /sup 81m/Kr transit time, a highly sensitive technique capable of detecting even minor E.T. disorders. Abnormal E.T. was observed in 39% of goitrous patients, while it was normal in all controls. Occurrence of delayed E.T. was not correlated with either goitre firmness, the presence of symptoms of neck discomfort, difficulties in swallowing, or nodularity. E.T. delay was more frequent and more severe with larger goitres. In addition, E.T. delay was significantly correlated with asymmetry and 'low lying' goitres. In summary, the present studies are the first demonstration of frequent E.T. anomalies in goitrous patients. The data suggest that E.T. impairment could be mediated by two mechanisms: a direct compression effect in patients with large, asymmetrical, partially retrosternal goitres; and an indirect functional esophageal anomaly in patients with small goitres.

Glinoer, D.; Verelst, J.; Ham, H.R.

1987-08-01

188

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

Science.gov (United States)

Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45–60 years were excluded to help define “young” and “old” groups. Thirty-nine cases of sporadic EOCRC (patients?45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p?=?0.013). Genetic studies also showed the absence of BRAF mutations (p?=?0.022) and the methylator phenotype (p?=?0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p?=?0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the TNFR1 pathway have been identified as potential biomarkers for both the diagnosis and treatment of this disease. PMID:25083765

Kirzin, Sylvain; Marisa, Laetitia; Guimbaud, Rosine; De Reynies, Aurélien; Legrain, Michèle; Laurent-Puig, Pierre; Cordelier, Pierre; Pradère, Bernard; Bonnet, Delphine; Meggetto, Fabienne; Portier, Guillaume; Brousset, Pierre; Selves, Janick

2014-01-01

189

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

OpenAIRE

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...

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

190

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

OpenAIRE

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...

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

1999-01-01

191

Outcome of sporadic amyotrophic lateral sclerosis treated With non-invasive ventilation and riluzole Sobrevida en pacientes con esclerosis lateral amiotrófica esporádica tratados con ventilación no invasiva y riluzole  

OpenAIRE

Sporadic amyotrophic lateral sclerosis (sALS) is a progressive degenerative motor neuron disorder lacking specific treatment. Riluzole is the only drug able to modestly slow down the course of the disease. Respiratory insufficiency is the main cause of death; non invasive ventilation (NIV) has shown to improve survival. Our aim was to evaluate the effect of NIV and riluzole on survival. Ninety seven patients with a diagnosis of sALS were assessed and followed up for 60 months. Twenty nine pat...

Martín Sívori; Rodri?guez, Gabriel E.; Daniel Pascansky; César Séenz; Sica, Roberto E. P.

2007-01-01

192

Younger age at onset of sporadic Parkinson’s disease among subjects occupationally exposed to metals and pesticides  

Directory of Open Access Journals (Sweden)

Full Text Available An earlier age at onset of Parkinson’s disease (PD has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58. Independent samples Student t-test revealed that subjects with occupational exposure to metals and/or pesticides (n=36 were significantly (p=0.013 younger than unexposed controls (n=22. These subjects were then divided into three groups [high (n=18, low (n=18, and unexposed (n=22] to ascertain if duration of exposure further influenced age at onset of PD. One-way ANOVA revealed that subjects in the high exposure group were significantly (p=0.0121 younger (mean age: 50.33 years than unexposed subjects (mean age: 60.45 years. Subjects were also stratified by exposure type (metals vs. pesticides. These results suggest that chronic exposure to metals and pesticides is associated with a younger age at onset of PD among patients with no family history of the disease and that duration of exposure is a factor in the magnitude of this effect.

Ratner Marcia H.

2014-09-01

193

Seasonal variability and descent of mid-latitude sporadic E layers at Arecibo  

Directory of Open Access Journals (Sweden)

Full Text Available Sporadic E layers (Es follow regular daily patterns in variability and altitude descent, which are determined primarily by the vertical tidal wind shears in the lower thermosphere. In the present study a large set of sporadic E layer incoherent scatter radar (ISR measurements are analyzed. These were made at Arecibo (Geog. Lat. ~18° N; Magnetic Dip ~50° over many years with ISR runs lasting from several hours to several days, covering evenly all seasons. A new methodology is applied, in which both weak and strong layers are clearly traced by using the vertical electron density gradient as a function of altitude and time. Taking a time base equal to the 24-h local day, statistics were obtained on the seasonal behavior of the diurnal and semidiurnal tidal variability and altitude descent patterns of sporadic E at Arecibo. The diurnal tide, most likely the S(1,1 tide with a vertical wavelength around 25 km, controls fully the formation and descent of the metallic Es layers at low altitudes below 110 km. At higher altitudes, there are two prevailing layers formed presumably by vertical wind shears associated mainly with semidiurnal tides. These include: 1 a daytime layer starting at ~130 km around midday and descending down to 105 km by local midnight, and 2 a less frequent and weaker nighttime layer which starts prior to midnight at ~130 km, descending downwards at somewhat faster rate to reach 110 km by sunrise. The diurnal and semidiurnal-like pattern prevails, with some differences, in all seasons. The differences in occurrence, strength and descending speeds between the daytime and nighttime upper layers are not well understood from the present data alone and require further study.

N. Christakis

2009-03-01

194

TP53 Codon 72 Heterozygosity May Promote MicrosatelliteInstability in Sporadic Colorectal Cancer  

Directory of Open Access Journals (Sweden)

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.

Mehdi Nikbahkt Dastjerdi

2010-01-01

195

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

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Results Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31% and from 69.1 to 86.2% (average 76.6% respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%. This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial nitric oxide synthase 690 C/T and glu298asp; vitamin K-dependent coagulation factor seven arg353glu, glycoprotein Ia/IIa 873 G/A and E-selectin ser128arg. Conclusion This study provides an alternative and reliable method to approach complex diseases. Indeed, the application of a novel artificial intelligence-based method offers a new insight into genetic markers of sporadic ALS pointing out the existence of a strong genetic background.

Marocchi Alessandro

2008-05-01

196

Sporadic electromagnetic emissions in the AKR frequency range associated with electrostatic plasma turbulence  

International Nuclear Information System (INIS)

The authors present heretofore unreported Viking observations of sporadic AKR bursts occurring well above the electron gyrofrequency together with spiky electrostatic emissions recorded just above the lower hybrid frequency, which exhibit a high degree of correlation in time. Both types of waves show simultaneous large amplitude variations of the order of 30-40 dB on time scales of a few hundreds of ms. Possible interpretations which may account for the observed correlation are investigated. Arguments are given which suggest that such events could be the signature of small scale nonlinear structures in the plasma

197

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

Directory of Open Access Journals (Sweden)

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.

Guohong Tian

2013-07-01

198

Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases.  

OpenAIRE

Newly diagnosed, histologically proven, sporadic PETs observed from June 2004 to March 2007 in 24 Italian centers were included in a specific data set. RESULTS: Two hundred ninety-seven patients (mean age 58.6+/-14.7 years, females 51.2%, males 48.8%) were analyzed. In 73 cases (24.6%), the tumor was functioning (F) (53 insulinomas, 15 gastrinomas, 5 other syndromes) and in 232 (75.4%) it was non-functioning (NF); in 115 cases (38.7%), the diagnosis was incidental. The median tumor size w...

Dogliotti, Luigi

2010-01-01

199

Sporadic paroxysmal exercise induced dystonia : report of a case and review of the literature.  

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Full Text Available Sporadic paroxysmal exercise induced dystonia (PEID is a rare condition. So far only fifteen cases have been reported in the world literature. It is characterised by dystonic posture on prolonged exercise, which gets relieved with rest. In general, these are refractory to medical treatment. We report one such case, along with review of the literature. The lower limbs were spared and only right shoulder was tucked up with the head turning to right side. The duration of exercise necessary to bring out the dystonic posture gradually diminished with time, a feature not reported previously.

Bhattacharyya K

2000-10-01

200

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

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Full Text Available Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP vs. 10 normal individuals (P = 0.67. Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.

Sales Magaly M.

1999-01-01

201

A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy.  

Science.gov (United States)

Mutations in the Angiogenin gene (ANG) linked to 14q11.2 have been recently discovered to be associated with Amyotrophic Lateral Sclerosis (ALS) in Irish and Scottish populations. In our study we investigated the role of ANG gene in ALS patients from southern Italy. We found a novel mutation in the signal peptide of the ANG gene in a sporadic patient with ALS (SALS). The molecular analysis of the ANG gene also demonstrated an allelic association with the rs11701 single nucleotide polymorphism (SNP) in familial ALS (FALS) but not in SALS patients. Our finding supports the evidence that the ANG gene is involved in ALS. PMID:17703939

Conforti, F L; Sprovieri, T; Mazzei, R; Ungaro, C; La Bella, V; Tessitore, A; Patitucci, A; Magariello, A; Gabriele, A L; Tedeschi, G; Simone, I L; Majorana, G; Valentino, P; Condino, F; Bono, F; Monsurrò, M R; Muglia, M; Quattrone, A

2008-01-01

202

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

OpenAIRE

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 ...

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

203

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

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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.

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

1993-10-23

204

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

205

De Novo Copy Number Variants Identify New Genes and Loci in Isolated, Sporadic Tetralogy of Fallot  

OpenAIRE

Tetralogy of Fallot (TOF), the most common severe congenital heart malformation, occurs sporadically, without other anomaly, and from unknown cause in 70% of cases. A genome-wide survey of 114 TOF patients and their unaffected parents identified 11 de novo copy number variants (CNVs) that were absent or extremely rare (<0.1%) in 2,265 controls. A second, independent TOF cohort (n = 398) was then examined for additional CNVs at these loci. In 1% (5/512, p = 0.0002, OR = 22.3) of non-syndromic ...

Greenway, Steven C.; Pereira, Alexandre C.; Lin, Jennifer C.; Depalma, Steven R.; Israel, Samuel J.; Mesquita, Sonia M.; Ergul, Emel; Conta, Jessie R.; Korn, Joshua M.; Mccarroll, Steven A.; Gorham, Joshua M.; Gabriel, Stacey; Altshuler, David A.; Lourdes Quintanilla-dieck, Maria; Artunduaga, Maria Alexandra

2009-01-01

206

Isolated sporadic bilateral split hand malformation: a case report and review of the literature  

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Full Text Available Typical cleft hand is a rare disorder usually inherited in an autosomal-dominant manner. We report a case of bilateral typical cleft hand in a 6-year-old male. There was no positive family history of such presentation, and no systemic manifestations were associated with this entity. Preanesthetic evaluation revealed no systemic or airway challenges and parents were counseled for routine surgical and anesthetic risks. The hands underwent successful surgical reconstruction with no peri-operative complications. To the best of our knowledge, this is the first report of an operated case of an isolated, bilateral, and sporadic typical split hand malformation.

Manjit Singh

2014-12-01

207

FMR1 gene premutation is a frequent genetic cause of late-onset sporadic cerebellar ataxia  

OpenAIRE

In an Italian population of 275 unrelated men affected by adult-onset sporadic progressive cerebellar ataxia, the authors found six patients carrying an FMR1 gene premutation. Age at onset (range, 53 to 69 years) and clinical-neuropathologic findings were consistent with the fragile-X tremor ataxia syndrome (FXTAS), although tremor was not as common as previously described. FXTAS accounted for 4.2% of the cases diagnosed at >50 years, suggesting that it is a frequent genetic cause of late-ons...

Migone, Nicola; Brussino, Alessandro; Brusco, Alfredo; Saluto, Alessandro

2005-01-01

208

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

OpenAIRE

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...

Armstrong, R. A.

2010-01-01

209

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

OpenAIRE

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 ...

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

210

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)

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

Brixen, Line Merrild; Bernstein, Inge Thomsen

2013-01-01

211

Multi-layer structure of mid-latitude sporadic-E observed during the SEEK-2 campaign  

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Full Text Available In the mid-latitude ionospheric region, sporadic-E layers (Es layers have often been observed, revealing multiple layers. The Es layers observed during the SEEK-2 rocket campaign showed double electron density peaks; namely, there are stable lower peaks and relatively unstable upper peaks. We examined the effects of wind shear and the electric fields on the generation of the multiple layer structure, in comparison with the electron density profile, the neutral wind, and the DC electric field observed by the S310 rocket experiments. The results showed that the neutral wind shear is mainly responsible for the generation of the lower layer, while the DC electric field makes a significant contribution to the formation of the upper layer. The difference between the lower and upper layers was also explained by the enhanced AC electric field observed at about 103–105 km altitude. The external DC electric field intensity is expected to be ~5 mV/m, which is enough to contribute to generate the Es layers in the ionosphere. Keywords. Ionosphere (Electric fields; Ionospheric irregularities, Mid-latitude ionosphere

T. Ono

2005-10-01

212

Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis Cases in the United States from 2003 to 2008  

OpenAIRE

Listeria monocytogenes can cause severe food-borne disease (listeriosis). Numerous outbreaks have involved three serotype 4b epidemic clones (ECs): ECI, ECII, and ECIa. However, little is known about the population structure of L. monocytogenes serotype 4b from sporadic listeriosis in the United States, even though most cases of human listeriosis are in fact sporadic. Here we analyzed 136 serotype 4b isolates from sporadic cases in the United States, 2003 to 2008, utilizing multiple tools inc...

Lee, Sangmi; Ward, Todd J.; Graves, Lewis M.; Tarr, Cheryl L.; Siletzky, Robin M.; Kathariou, Sophia

2014-01-01

213

An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1  

OpenAIRE

Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either inheritable or nonheritable modifications. The presence of a misfolded WT SOD1 in patients with sporadic ALS, along with the recently reported evidence that reducing SOD1 levels in astrocytes derived from sporadic patients inhibits astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire toxic properties simila...

Guareschi, Stefania; Cova, Emanuela; Cereda, Cristina; Ceroni, Mauro; Donetti, Elena; Bosco, Daryl A.; Trotti, Davide; Pasinelli, Piera

2012-01-01

214

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

Science.gov (United States)

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.

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

2012-01-01

215

Conditional Inactivation of Pten with EGFR Overexpression in Schwann Cells Models Sporadic MPNST.  

Science.gov (United States)

The genetic mechanisms involved in the transformation from a benign neurofibroma to a malignant sarcoma in patients with neurofibromatosis-type-1- (NF1-)associated or sporadic malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. It is hypothesized that many genetic changes are involved in transformation. Recently, it has been shown that both phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) play important roles in the initiation of peripheral nerve sheath tumors (PNSTs). In human MPNSTs, PTEN expression is often reduced, while EGFR expression is often induced. We tested if these two genes cooperate in the evolution of PNSTs. Transgenic mice were generated carrying conditional floxed alleles of Pten, and EGFR was expressed under the control of the 2',3'-cyclic nucleotide 3'phosphodiesterase (Cnp) promoter and a desert hedgehog (Dhh) regulatory element driving Cre recombinase transgenic mice (Dhh-Cre). Complete loss of Pten and EGFR overexpression in Schwann cells led to the development of high-grade PNSTs. In vitro experiments using immortalized human Schwann cells demonstrated that loss of PTEN and overexpression of EGFR cooperate to increase cellular proliferation and anchorage-independent colony formation. This mouse model can rapidly recapitulate PNST onset and progression to high-grade PNSTs, as seen in sporadic MPNST patients. PMID:23319880

Keng, Vincent W; Watson, Adrienne L; Rahrmann, Eric P; Li, Hua; Tschida, Barbara R; Moriarity, Branden S; Choi, Kwangmin; Rizvi, Tilat A; Collins, Margaret H; Wallace, Margaret R; Ratner, Nancy; Largaespada, David A

2012-01-01

216

[Mutational analysis of the connexin26 gene in sporadic cases of moderate to profound deafness].  

Science.gov (United States)

Non-syndromic neurosensory recessive deafness (NSRD) is one of the most common human sensory disorders. Mutations in the connexin 26 gene have been established as a major cause of inherited and sporadic non-syndromic deafness in different populations. The CX26 gene encodes the gap junction protein connexin 26 (beta-2, GJB2), whose expression was shown in several tissues and in the cochlea. The 30delG mutation is the most frequent mutation in the CX26 gene. It represents a deletion of guanosine (G) in a sequence of six Gs extending from position 30 to 35 of the CX26 cDNA. The deletion creates a frameshift resulting in a premature stop codon and a non-functional intracellular domain in the protein. The 30delG mutation can be detected at the molecular level using PCR followed by BsiYI digestion. We screened 164 mainly German patients with non-syndromic sporadic deafness for this mutation to determine its distribution in the German population. The frequency of the mutation in our analyzed patients was lower than in other studies and therefore indicates its dependency on geographically distinct populations. PMID:11056855

Kupka, S; Mirghomizadeh, F; Haug, T; Braun, S; Leistenschneider, P; Schmitz-Salue, C; Arold, R; Blin, N; Zenner, H P; Pfister, M

2000-09-01

217

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

Science.gov (United States)

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

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

2014-05-01

218

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

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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.

Samir Kumar-Singh

2009-04-01

219

Auditory adaptation is differentially impaired in familial and sporadic Alzheimer's disease.  

Science.gov (United States)

Neurophysiologic measures are particularly sensitive to alterations in attention and arousal. The purpose of this study was to evaluate the auditory adaptation of normal and mildly demented elderly people. We compared the automatic behavior of an auditory evoked potential (N100) in three age-matched groups of elderly subjects, one with familial Alzheimer's disease (AD), one with sporadic AD and one healthy group. All AD subjects corresponded clinically and neuropsychologically with the early stage of dementia. The dynamic range of auditory adaptation is known to be related to age, and normal auditory adaptation for the age was observed in our healthy aged and sporadic AD subjects, whereas the familial AD subjects lacked normal adaptation. The familial AD subjects also showed statistically significantly smaller peak amplitudes and shorter latencies of the N100 throughout the habituation test. This persistent difference in automatic habituation of sensory responses supports the view that different subtypes of AD are differentially affected. The observed differences give an objective measure of the impaired involuntary adaptive functions of neuronal networks involved in auditory processing in subtypes of AD. Since habituation reflects the most primitive stage of learning and short-term memory, altered habituation may predict faster deterioration of clinical status in the familial group of AD subjects. PMID:11905509

Tarkka, I M; Lehtovirta, M; Soininen, H; Pääkkönen, A; Karhu, J; Partanen, J

2002-02-01

220

Sporadic Visceral Myopathy: Full Thickness Rectal Biopsy to Clinch the Diagnosis  

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Full Text Available Chronic intestinal pseudo-obstruction (CIPO may result fromdysfunctional intestinal nerves or muscles. Primary causesare uncommon and include familial and sporadic visceralmyopathies. Visceral myopathy may be characterized by CIPO,ureterohydronephrosis, and hepatobiliary dilation. The diagnosis ismade by the clinical history and characteristic findings of fibrousreplacement of the muscularis externa, vacuolar degeneration, andcytoplasmic inclusions in myocytes on a full thickness specimen ofaffected viscera. Few case reports highlight sporadic hollow visceralmyopathy (SHVM in an adult involving the entire GI, biliary, andurinary tract, We present a unique case of abrupt onset of CIPO,biliary and urinary tract dilation in a 35-year-old Mexican woman,initially presumed to have lupus enterocolitis, and after failure torespond to immune modulating therapy, diagnosed by full thicknessrectal biopsy with SHVM, Early full thickness biopsy of affectedviscera in patients presenting with CIPO with associated biliary andurinary tract dilation should be considered. Our case demonstratesthe safety and adequacy of a full thickness rectal biopsy in making adiagnosis of SHVM.

Swapna B Reddy

2012-09-01

221

HER2 Amplification Has no Prognostic Value in Sporadic and Hereditary Ovarian Tumours  

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Full Text Available Abstract Whereas HER2 amplification is a well-known phenomenon in breast tumours, its frequency and clinical importance in ovarian cancer have not been established. The aim of the study was to compare the frequency of HER2 amplification in hereditary (BRCA-positive and sporadic (BRCA-negative ovarian tumours and to estimate the association of this gene alteration on clinical outcome in ovarian cancer patients. We analysed HER2 amplification in 53 ovarian tumours: 20 from mutation carriers (18 in BRCA1 and 2 in BRCA2 gene and 33 from non-carriers. Fluorescence in situ hybridization for HER2 was performed on 'touch' slides from frozen tumour samples or formalin-fixed, paraffin-embedded tissue. Our results indicate that high amplification (HER2: centromere ratio>5 is an infrequent phenomenon in ovarian tumours (6/53 cases. It occurs in both hereditary (4/20 and sporadic (2/33 tumours and no difference in the frequency of HER2 amplification exists between these groups. There is no significant difference in the clinical outcome of patients with HER2 amplified and non-amplified tumours (p = 0.3. Our results suggest a different biological role of HER2 amplification in ovarian and breast cancer.

Bro?ek Izabela

2006-11-01

222

Role of VEGF-A and Its Receptors in Sporadic and MEN2-Associated Pheochromocytoma  

Science.gov (United States)

Pheochromocytoma (PHEO), a rare catecholamine producing tumor arising from the chromaffin cells, may occurs sporadically (76%–80%) or as part of inherited syndromes (20%–24%). Angiogenesis is a fundamental step in tumor proliferation and vascular endothelial growth factor (VEGF-A) is the most well-characterized angiogenic factor. The role of angiogenic markers in PHEO is not fully understood; investigations were therefore made to evaluate the expression of VEGF-A and its receptors in PHEO and correlate to clinical parameters. Twenty-nine samples of PHEO were evaluated for VEGF-A, VEGF receptor-1 (VEGFR-1) VEGFR-2 expression and microvessel density (MVD) by immunohistochemistry. Clinical data were reviewed in medical records. The mean age of patients was 38 ± 14 years, and 69% were woman. VEGF-A, VEGFR-1 and VEGFR-2 staining were detected in nearly all PHEO samples. No significant correlation was observed between VEGF-A, VEGFR-1, VEGFR-2 expression or MVD and age at diagnosis, tumor size or sporadic and hereditary PHEO. However, the levels of expression of these molecules were significantly higher in malignant PHEO samples (p = 0.027, p = 0.003 and p = 0.026, respectively).VEGF-A and its receptors were shown to be up-regulated in malignant PHEO, suggesting that these molecules might be considered as therapeutic targets for unresectable or metastatic tumors. PMID:24675699

Ferreira, Carla Vaz; Siqueira, Débora Rodrigues; Romitti, Mírian; Ceolin, Lucieli; Brasil, Beatriz Assis; Meurer, Luise; Capp, Clarissa; Maia, Ana Luiza

2014-01-01

223

Identification of novel FUS mutations in sporadic cases of amyotrophic lateral sclerosis.  

Science.gov (United States)

Mutations in the FUS gene have been recently associated with amyotrophic lateral sclerosis (ALS). While most of the variants have been identified in patients with a family history of the disease, a few mutations were also found in sporadic patients. Considering this, we wanted to evaluate the frequency of mutations in the coding region of the FUS gene in a sporadic ALS (SALS) cohort compared to a control population. We tested 475 SALS cases of European origin and 475 matched controls for coding variations in the 15 exons of the FUS gene. Rare novel variants were identified in a total of five SALS patients: one missense, one deletion, one frameshift, and one nonsense substitution. Two of the four variants are located in the carboxy terminal of the protein where the previously reported variants were mostly clustered. In conclusion, FUS gene mutations are rare in SALS, with four new FUS variants identified in five different SALS cases. These findings will help evaluate the proportion of FUS variations in the SALS population, and to better understand its contributing role to ALS pathology. PMID:21261515

Belzil, Veronique V; Daoud, Hussein; St-Onge, Judith; Desjarlais, Anne; Bouchard, Jean-Pierre; Dupre, Nicolas; Lacomblez, Lucette; Salachas, François; Pradat, Pierre-François; Meininger, Vincent; Camu, William; Dion, Patrick A; Rouleau, Guy A

2011-03-01

224

Source attribution of human salmonellosis and campylobacteriosos using a systematic review of studies of sporadic infections  

DEFF Research Database (Denmark)

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.

Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

225

Clinical characteristics and risk factors of sporadic Hepatitis E in central China  

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Full Text Available Abstract Background Epidemiological investigations, detections and vaccines of hepatitis E (HE have been paid a focus of attention in prior studies, while studies on clinical features and risk factors with a large number of sporadic HE patients are scarce. Results Sporadic HE can occur throughout the year, with the highest incidence rate in the first quarter of a year, in central of China. Of the 210 patients, 85.2% were male, and the most common clinical symptoms were jaundice (85.7%, fatigue (70.5% and anorexia (64.8%. Total bilirubin (TBil, blood urea nitrogen (BUN, and international normalized ratio (INR were found as major risk factors for death of HE patients. There was an overall mortality of 10%, and the mortality in the cirrhotic and non-cirrhotic group was 25% and 6.47%, respectively. Moreover, hepatitis E virus (HEV infected patients with liver cirrhosis had a higher mortality and incidence of complications. Conclusions TBil, BUN, and INR are major risk factors of mortality for HE. Liver cirrhosis can aggravate HE, and lead to a higher mortality. HEV infection can cause decompensation in patients with cirrhosis, as evidenced by a worsening Child-Pugh score.

Xia Ningshao

2011-04-01

226

Study of the generation mechanism for Sporadic Sodium Layers observed in the Brazilian low latitude sector  

Science.gov (United States)

Using data obtained from LIDARs installed at São José dos Campos (23.2°S, 45.9°W) and Wuhan (30.5°N, 114.4°E), we have observed the main characteristics of Sporadic Sodium Layers (Nas), including full width at half maximum, peak height, intensity, preferred time of occurrence and vertical motion. These characteristics, observed during the period from 1996 to 2008, were used to make a comparison of seasonal, annual and nocturnal variation, typical peak height, width and speed of descent between the two locations. The results show good agreement between the two locations, leading us to believe that the same mechanism is responsible for the formation of Nas observed in Brazil (low latitude) and China (medium latitude). Besides the study with LIDAR data, we analyzed meteor radar and ionosonde data from the Brazilian sector in order to investigate the possible contribution of ionospheric sporadic layers (Es) and wind shear in the formation of Nas. In the near future, all-sky images of the sodium airglow emission will also be used in an attempt to observe the horizontal dimensions and motion direction of Nas clouds. In this paper we show the results obtained so far and discuss the possible mechanisms for the generation of this phenomenon.

Amorim, D. C.; Clemesha, B. R.; Simonich, D. M.; Pimenta, A. A.; Yang, G.

2013-05-01

227

Influence of Poly(ethylene glycol) Degradation on Voiding Sporadically Occurring in Solder Joints with Electroplated Cu  

Science.gov (United States)

This paper presents a comprehensive study of the effect of poly(ethylene glycol) (PEG) degradation on the void formation known to take place sporadically at the interface between electroplated Cu and Pb-free solder. Thorough chemical analysis of our plating solution, carried out at different times of the deposition process by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, reveals a dramatic shift in the peaks to lower mass range with time. Scanning electron microscopy cross-sectional images of solder joints with Cu samples that have been plated at different times in the course of solution aging show a decrease in void formation. A decreasing magnitude of the deposition overpotential also seen during aging suggests that, breaking down to lower-molecular-weight fragments, PEG loses its suppression effect and likely has lower impact on the voiding propensity. This indirect correlation is confirmed further by the use of plating solutions containing PEG with preselected molecular weight. We also report on the effect of the surface area-to-solution volume ratio on PEG degradation studied by comparative experiments performed in a 50-mL bath with a rotating disc electrode and in a larger cell (Hull cell) with volume of 267 mL. The results show that, at fixed charge per unit volume, PEG degrades at a greatly accelerated rate in the Hull cell featuring higher electrode surface-to-solution volume ratio. Analysis of solder joints with accordingly grown Cu layers suggests that the voiding decreases faster with the accelerated rate of PEG degradation.

Wafula, F.; Yin, L.; Borgesen, P.; Andala, D.; Dimitrov, N.

2012-07-01

228

Common volume coherent and incoherent scatter radar observations of mid-latitude sporadic E-layers and QP echoes  

OpenAIRE

Common-volume observations of sporadic E-layers made on 14-15 June 2002 with the Arecibo incoherent scatter radar and a 30MHz coherent scatter radar imager located on St. Croix are described. Operating in dual-beam mode, the Arecibo radar detected a slowly descending sporadic E-layer accompanied by a series of dense E-region plasma clouds at a time when the coherent scatter radar was detecting quasi-periodic (QP) echoes. Using coherent radar imaging, we collocate the sources of the coherent s...

Hysell, D. L.; Larsen, M. F.; Zhou, Q. H.

2004-01-01

229

High frequency of the expanded C9ORF72 hexanucleotide repeat in familial and sporadic Greek ALS patients.  

OpenAIRE

An intronic expansion of a hexanucleotide GGGGCC repeat in the C9ORF72 gene has recently been shown to be an important cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in familial and sporadic cases. The frequency has only been defined in a small number of populations where the highest sporadic rate was identified in Finland (21.1%) and the lowest in mainland Italy (4.1%). We examined the C9ORF72 expansion in a series of 146 Greek ALS cases, 10.95% (n = 16) of ca...

Mok, K. Y.; Koutsis, G.; Schottlaender, L. V.; Polke, J.; Panas, M.; Houlden, H.

2012-01-01

230

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

DEFF Research Database (Denmark)

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 (

Jensen, Thomas DyrsØ; Li, Jian

2011-01-01

231

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

DEFF Research Database (Denmark)

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 (

Jensen, Thomas DyrsØ; Li, Jian

2011-01-01

232

A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A*  

OpenAIRE

The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled v...

Fishman-jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B. H.; Mandel, Silvia A.

2009-01-01

233

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

234

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

Science.gov (United States)

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.

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

1977-01-01

235

A Novel Partitioned Scheduling Algorithm of Constrained-deadline Sporadic Task Systems on Multiprocessors  

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Full Text Available In this paper, a novel efficient DBF (eDBFc partitioned scheduling algorithm of constrained-deadline sporadic task systems on multiprocessors is proposed. A criterion which tracks the demand bound function exactly as needed is used in the novel algorithm. The using of the new criterion in eDBFc avoids the incorrect judgment made by density algorithm and DBF* algorithm in determining whether a processor can accommodate an additional task. We give the pseudo code of the new algorithm on least-number processors and fixed-number processors respectively, and derive the sufficient and necessary conditions for success of our algorithm. The experimental results show the superiority of the proposed algorithm over density algorithm and DBF* algorithm.

Qi Li

2010-10-01

236

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

Science.gov (United States)

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

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

237

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

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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.

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

2008-01-01

238

Mutational analysis of podocyte genes in children with sporadic steroid-resistant nephrotic syndrome.  

Science.gov (United States)

Recent studies have demonstrated that mutations in 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1, are associated with the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). Systematic investigation of all 4 genes for sporadic SRNS in China has not been performed. We examined 10 Chinese children with sporadic SRNS who showed no response to immunosuppressive agents and 20 SRNS controls who exhibited a response to prolonged steroid or immunosuppressive treatment and achieved complete remission. We analyzed mutations in the 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1. Mutational analysis was performed using polymerase chain reaction and direct sequencing. Of the 10 SRNS children who showed no response to immunosuppressive agents, the compound heterozygous NPHS1 mutations 2677A>G (T893A) and *142T>C were identified in 1 patient, while a heterozygous mutation in WT1, 1180C>T (R394W), was found in another patient. Of the 20 SRNS children showing complete remission who responded to prolonged steroid therapy or immunosuppressive agents, 4 heterozygous NPHS1 mutations, 928G>A, IVS8+30C>T, IVS21+14G>A, and IVS25-23C>T, were identified in 4 patients and a heterozygous CD2AP mutation, IVS7-135G>A, was identified in 1 patient. Our results indicate the necessity of genetic examination for mutations in podocyte genes in Chinese SRNS children who show no response to immunosuppressive agents. PMID:25501161

Feng, D N; Yang, Y H; Wang, D J; Meng, D C; Fu, R; Wang, J J; Yu, Z H

2014-01-01

239

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

Science.gov (United States)

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.

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

2014-07-01

240

Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastases  

DEFF Research Database (Denmark)

Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2-compromised group. In stage IV tumors re-expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor.

Larsen, Nicolai Balle; Rasmussen, Merete

2009-01-01

241

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

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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.

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

242

Clinical features and outcome of sporadic serogroup W135 disease Taiwan  

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Full Text Available Abstract Background Few published reports have evaluated the clinical features and outcome of serogroup W135 meningococcal disease. In Taiwan, W135 is the second most prevalent meningococcal disease serogroup. Method A nationwide study was conducted to retrospectively analyze epidemiologic data from 115 patients with laboratory confirmed meningococcal disease that occurred from 2001 through 2003. Results Serogroup W135 accounted for 26% of all cases and most (76.7% were older than 20 years. There were no cases of serogroup W135 meningococcal disease associated with Hajj pilgrims, and all cases were sporadic. In 88 patients with complete case records, we compared the presenting symptoms, signs, laboratory data, and outcomes between W135 and non-W135 patients. There were no differences in presenting symptoms except for the higher prevalence of pneumonia found in W135 patients (23.8% vs. 1.5%; OR: 20.6; 95%CI: 2.3–189.0; p = 0.003. The distribution of inflammatory cells in CSF in patients with meningitis was also different between W135 and non-W135 patients. W135 patients had a trend toward more intubations and shock but it did not achieve statistical significance. In multivariate analysis of factors associated with death, three independent factors were found: bacteremia without meningitis, altered mental status, and petechiae or purpura on admission. Conclusion Sporadic serogroup W135 meningococcal disease is an important component of the meningococcal disease burden in Taiwan, but it is not directly associated with Hajj pilgrims. Compared with patients infected by other serogroups of meningococci, patients with serogroup W135 were older and more likely to have extrameningeal involvement such as pneumonia.

Lin Ching-Yuang

2006-01-01

243

Paleolithic and Mediterranean diet pattern scores and risk of incident, sporadic colorectal adenomas.  

Science.gov (United States)

The Western dietary pattern is associated with higher risk of colorectal neoplasms. Evolutionary discordance could explain this association. We investigated associations of scores for 2 proposed diet patterns, the "Paleolithic" and the Mediterranean, with incident, sporadic colorectal adenomas in a case-control study of colorectal polyps conducted in Minnesota (1991-1994). Persons with no prior history of colorectal neoplasms completed comprehensive questionnaires prior to elective, outpatient endoscopy; of these individuals, 564 were identified as cases and 1,202 as endoscopy-negative controls. An additional group of community controls frequency-matched on age and sex (n = 535) was also recruited. Both diet scores were calculated for each participant and categorized into quintiles, and associations were estimated using unconditional logistic regression. The multivariable-adjusted odds ratios comparing persons in the highest quintiles of the Paleolithic and Mediterranean diet scores relative to the lowest quintiles were, respectively, 0.71 (95% confidence interval (CI): 0.50, 1.02; Ptrend = 0.02) and 0.74 (95% CI: 0.54, 1.03; Ptrend = 0.05) when comparing cases with endoscopy-negative controls and 0.84 (95% CI: 0.56, 1.26; Ptrend = 0.14) and 0.77 (95% CI: 0.53, 1.11; Ptrend = 0.13) when comparing cases with community controls. These findings suggest that greater adherence to the Paleolithic diet pattern and greater adherence to the Mediterranean diet pattern may be similarly associated with lower risk of incident, sporadic colorectal adenomas. PMID:25326623

Whalen, Kristine A; McCullough, Marji; Flanders, W Dana; Hartman, Terryl J; Judd, Suzanne; Bostick, Roberd M

2014-12-01

244

Tumor suppress genes screening analysis on 4q in sporadic colorectal carcinoma  

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Full Text Available AIM: To search candidate tumor suppressor genes (TSGs on chromosome 4q through detecting high loss of heterozygosity (LOH regions in sporadic colorectal carcinoma in Chinese patients.METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by ?2 test.RESULTS: Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%. The D4S2915 locus showed highest LOH frequency (36.17%. Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1, another flanked by D4S407 and D4S2939 locus (4q25-31.1. None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018 locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%, P = 0.01. On D4S1534 locus, LOH was significantly associated with liver metastasis (80% vs 17.25%, P = 0.012. No relationship was detected on other locus compared with clinicopathological features.CONCLUSION: By high resolution deletion mapping, two high frequency regions of LOH (4q12-21.1 and 4q25-31.1 were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.

Li-Xin Jiang, Jie Xu, Zhao-Wen Wang, Da-Peng Li, Zhi-Hai Peng, Jian-Jun Gao, Lin He, Hai-Tao Zheng

2008-09-01

245

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)

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

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

246

On a homotopy relation between the 2-local geometry and the Bouc complex for the sporadic group Co3  

CERN Document Server

We study the homotopy relation between the standard 2-local geometry and the Bouc complex for the sporadic group Co3. We also give a result concerning the relative projectivity of the reduced Lefschetz module associated to the aformentioned 2-local geometry.

Maginnis, J; Maginnis, John; Onofrei, Silvia

2005-01-01

247

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

OpenAIRE

Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD) is commonly understood to represent cases with early, prominent visual complaints. The term is clarified to represent those who present with isolated visual symptoms. This group may pose diagnostic difficulties and often present to ophthalmologists where they may undergo needless invasive procedures.

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

2005-01-01

248

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

Science.gov (United States)

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

249

Genetic Diversity of Norovirus and Sapovirus in Hospitalized Infants with Sporadic Cases of Acute Gastroenteritis in Chiang Mai, Thailand  

Science.gov (United States)

Stool specimens from hospitalized infants with sporadic gastroenteritis in Chiang Mai, Thailand, between July 2000 and July 2001 were examined for norovirus and sapovirus by reverse transcription-PCR and sequence analysis. These viruses were identified in 13 of 105 (12%) specimens. One strain was found to be a recombinant norovirus. PMID:15004104

Hansman, Grant S.; Katayama, Kazuhiko; Maneekarn, Niwat; Peerakome, Supatra; Khamrin, Pattara; Tonusin, Supin; Okitsu, Shoko; Nishio, Osamu; Takeda, Naokazu; Ushijima, Hiroshi

2004-01-01

250

Genetic Diversity of Norovirus and Sapovirus in Hospitalized Infants with Sporadic Cases of Acute Gastroenteritis in Chiang Mai, Thailand  

OpenAIRE

Stool specimens from hospitalized infants with sporadic gastroenteritis in Chiang Mai, Thailand, between July 2000 and July 2001 were examined for norovirus and sapovirus by reverse transcription-PCR and sequence analysis. These viruses were identified in 13 of 105 (12%) specimens. One strain was found to be a recombinant norovirus.

Hansman, Grant S.; Katayama, Kazuhiko; Maneekarn, Niwat; Peerakome, Supatra; Khamrin, Pattara; Tonusin, Supin; Okitsu, Shoko; Nishio, Osamu; Takeda, Naokazu; Ushijima, Hiroshi

2004-01-01

251

High prevalence and genetic diversity of noroviruses among children with sporadic acute gastroenteritis in Nanning City, China, 2010-2011.  

Science.gov (United States)

A molecular epidemiological study of Norovirus (NoV) infections in children aged genetic diversity of NoVs in children with sporadic acute gastroenteritis in Nanning. Our study findings indicate the need for continual surveillance to monitor epidemiological changes and potential new variants of these viruses. J. Med. Virol. 87:498-503, 2015. © 2014 Wiley Periodicals, Inc. PMID:25604456

Tan, Dongmei; Deng, Lili; Wang, Mingliu; Li, Xiugui; Ma, Yuyan; Liu, Wei

2015-03-01

252

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

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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.

TakutoHideyama

2011-11-01

253

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

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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 investigating 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. PMID:24604426

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

2014-02-01

254

Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis.  

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Sporadic amyotrophic lateral sclerosis (SALS) is a motor neuron degenerative disease of unknown etiology. Current thinking on SALS is that multiple genetic and environmental factors contribute to disease liability. Since neuronal acetylcholine receptors (nAChRs) are part of the glutamatergic pathway, we searched for sequence variants in CHRNA3, CHRNA4 and CHRNB4 genes, encoding neuronal nicotinic AChR subunits, in 245 SALS patients and in 450 controls. We characterized missense variants by in vitro mutagenesis, cell transfection and electrophysiology. Sequencing the regions encoding the intracellular loop of AChRs subunits disclosed 15 missense variants (6.1%) in 14 patients compared with only six variants (1.3%) in controls (P = 0.001; OR 4.48, 95% CI 1.7-11.8). The frequency of variants in exons encoding extracellular and transmembrane domains and in intronic regions did not differ. NAChRs formed by mutant alpha3 and alpha4 and wild-type (WT) beta4 subunits exhibited altered affinity for nicotine (Nic), reduced use-dependent rundown of Nic-activated currents (I(Nic)) and reduced desensitization leading to sustained intracellular Ca(2+) concentration, in comparison with WT-nAChR. The cellular loop has a crucial importance for receptor trafficking and regulating ion channel properties. Missense variants in this domain are significantly over-represented in SALS patients and alter functional properties of nAChR in vitro, resulting in increased Ca(2+) entry into the cells. We suggest that these gain-of-function variants might contribute to disease liability in a subset of SALS because Ca(2+) signals mediate nAChR's neuromodulatory effects, including regulation of glutamate release and control of cell survival. PMID:19628475

Sabatelli, Mario; Eusebi, Fabrizio; Al-Chalabi, Ammar; Conte, Amelia; Madia, Francesca; Luigetti, Marco; Mancuso, Irene; Limatola, Cristina; Trettel, Flavia; Sobrero, Fabrizia; Di Angelantonio, Silvia; Grassi, Francesca; Di Castro, Amalia; Moriconi, Claudia; Fucile, Sergio; Lattante, Serena; Marangi, Giuseppe; Murdolo, Marina; Orteschi, Daniela; Del Grande, Alessandra; Tonali, Pietro; Neri, Giovanni; Zollino, Marcella

2009-10-15

255

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

Scientific Electronic Library Online (English)

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.

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

2014-03-01

256

A sporadic Parkinson disease model via silencing of the ubiquitin-proteasome/E3 ligase component SKP1A.  

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The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled vector. SKP1A silencing resulted in increased susceptibility to neuronal damages induced by the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium ion and serum starvation, in parallel with a decline in the expression of the dopaminergic markers, dopamine transporter and vesicular monoamine transporter-2. SKP1A-deficient cells presented a delay in completion of the cell cycle and the inability to arrest at the G(0)/G(1) phase when induced to differentiate. Instead, the cells progressed through S phase, developing rounded aggregates with characteristics of aggresomes including immunoreactivity for gamma-tubulin, alpha-synuclein, ubiquitin, tyrosine hydroxylase, Hsc-70 (70-kDa heat shock cognate protein), and proteasome subunit, and culminating in a lethal phenotype. Conversely, stably enforced expression of wild type SKP1A duplicated the survival index of naïve SN4741 cells under proteasomal inhibition injury, suggesting a new structural role of SKP1 in dopaminergic neuronal function, besides its E3 ligase activity. These results link, for the first time, SKP1 to dopamine neuronal function and survival, suggesting an essential role in sporadic PD. In summary, this new model has reproduced to a significant extent the molecular alterations described in sporadic PD at the cellular level, implicating Skp1 as a potential modifier in sporadic PD neurodegeneration. PMID:19748892

Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B H; Mandel, Silvia A

2009-11-20

257

A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A*  

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The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled vector. SKP1A silencing resulted in increased susceptibility to neuronal damages induced by the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium ion and serum starvation, in parallel with a decline in the expression of the dopaminergic markers, dopamine transporter and vesicular monoamine transporter-2. SKP1A-deficient cells presented a delay in completion of the cell cycle and the inability to arrest at the G0/G1 phase when induced to differentiate. Instead, the cells progressed through S phase, developing rounded aggregates with characteristics of aggresomes including immunoreactivity for ?-tubulin, ?-synuclein, ubiquitin, tyrosine hydroxylase, Hsc-70 (70-kDa heat shock cognate protein), and proteasome subunit, and culminating in a lethal phenotype. Conversely, stably enforced expression of wild type SKP1A duplicated the survival index of naïve SN4741 cells under proteasomal inhibition injury, suggesting a new structural role of SKP1 in dopaminergic neuronal function, besides its E3 ligase activity. These results link, for the first time, SKP1 to dopamine neuronal function and survival, suggesting an essential role in sporadic PD. In summary, this new model has reproduced to a significant extent the molecular alterations described in sporadic PD at the cellular level, implicating Skp1 as a potential modifier in sporadic PD neurodegeneration. PMID:19748892

Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B. H.; Mandel, Silvia A.

2009-01-01

258

Sporadic plasma sheet ion injections into the high-altitude auroral bulge: Satellite observations  

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We report on a new feature of auroral substorms, namely, the sporadic though recurrent injections of magnetospheric ions throughout the auroral bulge. These injections are interpreted as time of flight dispersed ion structures (TDIS). Our analysis builds on a combination of measurements from Interball-Auroral, from UV imagery onboard Polar, from ground magnetometers, and also from observations on Geotail and from geostationary spacecraft. Backward tracing of ion trajectories from Interball-Auroral orbit using realistic three-dimensional magnetic and electric field models indicates that the injection region can extend over a wide range of radial distances, from ~7-40RE in the nearly equatorial magnetosphere. Both hydrogen and oxygen ions are shown to be injected toward the Earth's upper ionosphere. At Interball altitudes we find that ion injections are associated with two types of low-frequency torsional oscillations of the magnetic field: (1) shear Alfvén waves with a period of a few minutes with the highest amplitude near the bulge front and decreasing amplitude at lower latitudes and (2) higher-frequency shear Alfvén waves of the P1B type, strictly restricted to the poleward boundary of the surge, with a characteristic period of ~40 s. The systematic observation of sporadic TDIS during the auroral bulge expansion leads us to conclude that the same physical process is at work throughout the midtail. We also show that ion injections are detected well inside the bulge, which suggests that the injection fronts propagate from the outer to the inner magnetosphere over large distances. This topic is more extensively studied by V. Sergeev et al. (Plasma sheet ion injections into the auroral bulge: Correlative study of spacecraft and ground observations, submitted to Journal of Geophysical Research, 1999). We also show that the poleward boundary of the surge is associated with a prominent outflow of ionospheric H+ and O+. These ions in the hundred of eV to the keV range are heated perpendicularly to the local magnetic field and subsequently transported into the magnetotail. The expanding auroral bulge thus forms a significant source of ionospheric ions for the midtail magnetosphere.

Sauvaud, J.-A.; Popescu, D.; Delcourt, D. C.; Parks, G. K.; Brittnacher, M.; Sergeev, V.; Kovrazhkin, R. A.; Mukai, T.; Kokubun, S.

259

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

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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.

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

2010-05-01

260

Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.  

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Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 × 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for ALS. PMID:22509407

Diekstra, Frank P; Saris, Christiaan G J; van Rheenen, Wouter; Franke, Lude; Jansen, Ritsert C; van Es, Michael A; van Vught, Paul W J; Blauw, Hylke M; Groen, Ewout J N; Horvath, Steve; Estrada, Karol; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G; Robberecht, Wim; Andersen, Peter M; Melki, Judith; Meininger, Vincent; Hardiman, Orla; Landers, John E; Brown, Robert H; Shatunov, Aleksey; Shaw, Christopher E; Leigh, P Nigel; Al-Chalabi, Ammar; Ophoff, Roel A; van den Berg, Leonard H; Veldink, Jan H

2012-01-01

261

Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer  

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AIM: To determine the prognostic significance of deficient mismatch repair (dMMR) and BRAF V600E in Thai sporadic colorectal cancer (CRC) patients. METHODS: We studied a total of 211 out of 405 specimens obtained from newly diagnosed CRC patients between October 1, 2006 and December 31, 2007 at Siriraj Hospital, Mahidol University. Formalin-fixed paraffin-embedded blocks of CRC tissue samples were analyzed for dMMR by detection of MMR protein expression loss by immunohistochemistry or microsatellite instability using polymerase chain reaction (PCR)-DHPLC. BRAF V600E mutational analysis was performed in DNA extracted from the same archival tissues by two-round allele-specific PCR and analyzed by high sensitivity DHPLC. Associations between patient characteristics, MMR and BRAF status with disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier survival plots and log-rank test together with Cox’s proportional hazard regression. RESULTS: dMMR and BRAF V600E mutations were identified in 31 of 208 (14.9%) and 23 of 211 (10.9%) tumors, respectively. dMMR was more commonly found in patients with primary colon tumors rather than rectal cancer (20.4% vs 7.6%, P =0.01), but there was no difference in MMR status between the right-sided and left-sided colon tumors (20.8% vs 34.6%, P = 0.24). dMMR was associated with early-stage rather than metastatic disease (17.3% vs 0%, P = 0.015). No clinicopathological features such primary site or tumor differentiation were associated with the BRAF mutation. Six of 31 (19.3%) samples with dMMR carried the BRAF mutation, while 17 of 177 (9.6%) with proficient MMR (pMMR) harbored the mutation (P = 0.11). Notably, patients with dMMR tumors had significantly superior DFS (HR = 0.30, 95%CI: 0.15-0.77; P = 0.01) and OS (HR = 0.29, 95%CI: 0.10-0.84; P = 0.02) compared with patients with pMMR tumors. By contrast, the BRAF V600E mutation had no prognostic impact on DFS and OS. CONCLUSION: The prevalence of dMMR and BRAF V600E in Thai sporadic CRC patients was 15% and 11%, respectively. The dMMR phenotype was associated with a favorable outcome. PMID:25624727

Korphaisarn, Krittiya; Pongpaibul, Ananya; Limwongse, Chanin; Roothumnong, Ekkapong; Klaisuban, Wipawi; Nimmannit, Akarin; Jinawath, Artit; Akewanlop, Charuwan

2015-01-01

262

SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis  

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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.

Bourdon Violaine

2011-01-01

263

Satellite X ray mappings of sporadic auroral zone electron precipitation events in the local dusk sector  

International Nuclear Information System (INIS)

Simultaneous mappings of bremsstrahlung X ray events from the atmosphere resulting from electron precipitation have been performed from a satellite with an array of collimated cadmium telluride spectrometers. The X ray intensities and energy spectra (> or approx. =21 keV) where measured over contiguous view directions. The satellite, P78-1, was launched into a sun-synchronous noon-midnight orbital at approx.600-km altitude on February 24, 1979, and through its spinning motion with a approx.5.5-s period provides continual scans of the X ray sources below. Data are presented from three sporadic events in which the X ray intensities varied strongly with time. Within each of these events, bursts of approx.(30--100) second duration were observed. Some of the bursts were recorded in three or four sensors, thus setting a lower limit to their spatial extent of several hundred kilometers. Other bursts appeared in only one sensor, thereby restricting the area over which they could have been generated. These bursts of X rays emanated primarily from the dusk sector, a local time region where few balloon X ray measurements have been reported. The X ray fluxes were asymmetric about local dusk, the intensities at earlier times being quite low. During one of the X ray bursts in which the precipitation was confined to a relatively small spatial region it is estimated that the total number of electrons (>21 keV) precipitating into the atmosphere was approx.1023 per seconde was approx.1023 per second

264

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

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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. PMID:12244034

Mølbak, Kåre; Neimann, Jakob

2002-10-01

265

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

DEFF Research Database (Denmark)

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.

MØlbak, Kåre; Neimann, Jacob

2002-01-01

266

Clinical and histological features of sporadic non-A, non-B hepatitis.  

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Full Text Available The incidence of hepatitis A (HA, hepatitis B (HB, and non-A, non-B hepatitis (NANBH was 27%, 30% and 43% among 73 patients with sporadic hepatitis. Epidemiological data (geographical distribution, seasonal variation, age, sex, and occupation were not distinguishing of the type of hepatitis. Neither intrafamilial infection nor previous contact with viral hepatitis patients could be demonstrated in the NANBH cases. Fever and jaundice were less frequent in NANBH than in HA. Maximum levels of SGPT, serum bilirubin, ZTT, and gamma-globulin were significantly lower in NANBH than in HA and HB. Ten of 29 NANBH patients (35% presented abnormal SGPT activities for more than 6 months, and four (14% more than 12 months. In the ten patients with prolonged courses, jaundice was more frequent and maximum levels of SGPT were higher than in patients with transient courses. Histopathologic findings were not markedly different from those of HA and HB. Bile duct damage, fatty deposition, and giant multi-nucleated cells were recognized in 6, 12, and 2 NANBH patients, respectively. There were no characteristic ultrastructural changes in NANBH.

Hyodo,Ichinosuke

1984-08-01

267

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

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Full Text Available 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.

T. Nygrén

2008-11-01

268

Doppler investigation of night sporadic Es-layer during Sunrise in conjugated ionosphere  

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Several papers have been written about the observed relationship between night ionosphere disturbances and magnetic conjugate point sunrise. We present the results of the experimental research of plasma motion and variations of night-time Es -layer of ionosphere by multifrequency Doppler sounding (and total electron content measurements) during the winter solstice. Doppler measurements in a mode of vertical sounding simultaneously on 4 frequencies were carried out by the IZMIRAN (Moscow region) ionospheric facility Bazis-M(provided signals reflection from Esand F- layers of an ionosphere). To have total electron content variations the data of GPS net are used. The data analysis has shown that in night-time (period from 03 LT to 06 LT) the Es signal amplitude increase about 10 - 15 dB and it is proportional to increase in plasma electron density. Doppler measurements have shown the horizontal drifts (more than 10 m/sec) and upward movements of sporadic plasma clouds. The TEC measurements have indicated a complex behavior of night ionosphere during sunrise in the opposite conjugate hemisphere. It is showed that being combined these data definitely supports the hypothesis on partially reflected down coming Alfvenic waves generated in magnetic conjugated ionosphere by supersonic terminator motion.

Ruzhin, Yuri; Shagimuratov, Irk; Kim, Valery; Panchenko, Valery; Polimatidi, Valery; Berchadskaya, Irina

269

Morphology of sporadic E layer retrieved from COSMIC GPS radio occultation measurements: Wind shear theory examination  

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the basis of the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC)-measured fluctuations in the signal-to-noise ratio and excess phase of the GPS signal piercing through ionospheric sporadic E (Es) layers, the general morphologies of these layers are presented for the period from July 2006 to May 2011. It is found that the latitudinal variation in the Es layer occurrence is substantially geomagnetically controlled, most frequent in the summer hemisphere within the geomagnetic latitude region between 10° and 70° and very rare in the geomagnetic equatorial zone. Model simulations show that the summer maximum (winter minimum) in the Es layer occurrence is very likely attributed to the convergence of the Fe+ concentration flux driven by the neutral wind. In addition to seasonal and spatial distributions, the height-time variations in the Es layer occurrence in the midlatitude (>30°) region in summer and spring are primarily dominated by the semidiurnal tides, which start to appear at local time around 6 and 18 h in the height range 110-120 km and gradually descend at a rate of about 0.9-1.6 km/h. In the low-latitude (<30°) region, the diurnal tide dominates. The Horizontal Wind Model (HWM07) indicates that the height-time distribution of Es layers at middle latitude (30°-60°) is highly coincident with the zonal neutral wind shear. However, Es layer occurrences in low-latitude and equatorial regions do not correlate well with the zonal wind shear.

Chu, Y. H.; Wang, C. Y.; Wu, K. H.; Chen, K. T.; Tzeng, K. J.; Su, C. L.; Feng, W.; Plane, J. M. C.

2014-03-01

270

No evidence of somatic aryl hydrocarbon receptor interacting protein mutations in sporadic endocrine neoplasia  

DEFF Research Database (Denmark)

Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were recently observed in patients with pituitary adenoma predisposition (PAP). Though AIP mutation-positive individuals with prolactin-, mixed growth hormone/prolactin-, and ACTH-producing pituitary adenomas as well as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age. Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas. Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations bydirect sequencing. No somatic mutations were identified. However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X) with a complete loss of the wild-type allele in the tumors. These results are in agreement with previous studies in that prolactin-producing adenomas are component tumors in PAP. The data also support the previous finding that somatic AIP mutations are not common in pituitary adenomas and suggest that such mutations are rare in other endocrine tumors as well.

Raitila, A; Georgitsi, M

2007-01-01

271

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

Science.gov (United States)

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.

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

2015-01-01

272

Radiation Therapy in Management of Sporadic and Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors  

Science.gov (United States)

Introduction: Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas in which complete surgical resection is the mainstay of therapy. However, the recurrence rate is high and few options remain for refractory or metastatic MPNST. This study examines the outcomes of adjuvant radiation therapy in MPNST in patients with and without neurofibromatosis type 1 (NF1) and reviews the literature on use of radiation for MPNST. Methods: A retrospective review of 33 MPNST patients between 1990 and 2012 evaluated at the NIH. All diagnoses were pathologically confirmed at the NCI. Clinical presentation, treatment, and survival were analyzed. Results: Thirty-three patients were included 18 NF1-associated, 15 sporadic tumors. Tumor location included extremity (58%), trunk (36%), and head/neck (6%). Histologic grade showed 25 high-grade tumors compared to 7 low-grade tumors. Twenty patients were treated with radiation therapy (median total dose of 58.5?Gy with 1.8?Gy/fraction). A median survival of all patients was 46.5?months and 43.7% overall 5-year survival. Prognostic factors include extent of resection, tumor location, and histology grade. Radiation was not found to be a prognostic factor for overall survival. Conclusion: This study is consistent with previous studies regarding the role of radiation in the management of MPNST. Prospective evaluation of adjuvant radiation will allow to more fully define the role of radiation in MPNST. PMID:25452937

Kahn, Jenna; Gillespie, Andy; Tsokos, Maria; Ondos, John; Dombi, Eva; Camphausen, Kevin; Widemann, Brigitte C.; Kaushal, Aradhana

2014-01-01

273

Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt-Jakob disease.  

Science.gov (United States)

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause a variety of chronic diseases in central nervous system (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt-Jakob disease (sCJD) has still been unknown. In this study, we comparatively analyzed complete mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in control by haplogroup and allele frequencies. We classified the mtDNAs into 40 sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups. Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one in control (PG, p.(=) in NADH dehydrogenase subunit 4 (ND4) and m.12372G>A, p.(=) in NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of controls. Our study, for the first time, screened the variations of mtDNA of Chinese sCJD patients and identified some potential disease-related mutations for further investigations. PMID:24667788

Zhang, Jin; Zhang, Zhi-Xia; Du, Peng-Chen; Zhou, Wei; Wu, Su-Dong; Wang, Qi-Ling; Chen, Cao; Shi, Qi; Chen, Chen; Gao, Chen; Tian, Chan; Dong, Xiao-Ping

2015-01-01

274

Neuron-specific mitochondrial DNA deletion levels in sporadic Alzheimer's disease.  

Science.gov (United States)

Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, including sporadic Alzheimer´s disease (AD). Mitochondrial DNA (mtDNA) deletions are markers of oxidative damage and increase with age. To unravel the impact of mtDNA damage on AD development, we analyzed mtDNA deletion levels in diverse neuronal cell types of four brain regions (hippocampal CA1 and CA2 regions, nucleus tractus spinalis nervi trigemini, and the cerebellum) that exhibit differing levels of vulnerability to AD related changes at progressive Braak stages compared with age-matched controls. Neurons from these four brain regions were collected using laser microdissection, and analyzed using quantitative polymerase chain reaction (qPCR). Although, no correlation between mtDNA deletion levels and AD progression were found, the data revealed regional and cell type specific selective vulnerability towards mtDNA deletion levels. In conclusion, unexpected results were obtained as granule cells from the cerebellum and neurons from the nucleus tractus spinalis nervi trigemini of the brain stem displayed significant higher mtDNA deletion levels than pyramidal cells from hippocampal CA1 and CA2 region in age and AD. PMID:24156256

Gerschütz, Anne; Heinsen, Helmut; Grünblatt, Edna; Wagner, Anne K; Bartl, Jasmin; Meissner, Christoph; Fallgatter, Andreas J; Al-Sarraj, Safa; Troakes, Claire; Ferrer, Isidro; Arzberger, Thomas; Deckert, Jürgen; Riederer, Peter; Fischer, Matthias; Tatschner, Thomas; Monoranu, Camelia M

2013-12-01

275

A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus.  

LENUS (Irish Health Repository)

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements.

Monecke, Stefan

2011-04-01

276

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

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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.

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

2009-02-01

277

Sequential sporadic-E layers at low latitudes in the Indian sector  

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Full Text Available A study of the formation and movement of sequential Sporadic-E layers observed during the night-time hours at two Indian low-latitude stations, SHAR (dip 10°N and Waltair (dip 20°N shows that the layer are formed around 19:00 h. IST at altitudes of ~180 km. They descend to the normal E-region altitude of about 100 km in three to four hours and becomes blanketing type of Es before they disappear. However, the absence of these descending layers at an equatorial station, Trivandrum (dip 2°N gives the experimental evidence for wind shear theory. The meridional neutral wind derived from the height variation of the F-layer showed significant poleward wind during the descent of these layers. Hence it is inferred that these layers are formed as a consequence of the convergence of plasma by the poleward wind and the equatorward propagating gravity waves (inferred from the height fluctuations of F-layer.

Key words. Ionosphere (active experiments; equatorial ionosphere · ionospheric irregularities

P. T. Jayachandran

278

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.  

Science.gov (United States)

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. PMID:24128326

Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

2014-01-01

279

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

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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.

K.-I. Oyama

2008-09-01

280

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

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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.

Cracco Laura

2011-10-01

281

Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia  

International Nuclear Information System (INIS)

Objective: To describe the chest computed tomographic (CT) findings of Legionella pneumophila pneumonia. Methods: CT scans obtained from 23 sporadic cases of L. pneumophila pneumonia were retrospectively reviewed. Chest CT findings were analyzed with regard to the patterns and distributions of pulmonary abnormalities. We also analyzed the histopathology of lungs from guinea pigs with experimentally induced L. pneumophila pneumonia. Results: Consolidation and ground-glass opacity (GGO) were the main findings of CT scans in L. pneumophila pneumonia. The distribution of opacities was categorized as non-segmental (n = 20) and segmental (n = 4). Non-segmental distribution may follow an onset of segmental distribution. Pleural effusion was observed in 14 (58.3%) patients, of which 13 were accompanied with non-segmental distribution. Abscess formation was observed in only one immunocompromised patient. In the animal pneumonia model, the lesions comprised of terminal bronchioles, alveolar spaces, and interstitia. Small bacilli were observed to be contained by many macrophages within the alveoli. Conclusion: Non-segmental distribution was significantly more frequent than segmental distribution in L. pneumophila pneumonia. It is possible that L. pneumophila infection initially results in segmental pneumonia, which progresses to typical non-segmental distribution.

282

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

Science.gov (United States)

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

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

2014-04-01

283

Sporadic Long-term Variability in Radio Activity from a Brown Dwarf  

CERN Document Server

Radio activity has been observed in a large variety of stellar objects, including in the last few years, ultra-cool dwarfs. To explore the extent of long-term radio activity in ultra-cool dwarfs, we use data taken over an extended period of 9 hr from the Very Large Array of the source 2MASS J05233822-1403022 in September 2006, plus data taken in 2004. The observation taken in September 2006 failed to detect any radio activity at 8.46 GHz. A closer inspection of earlier data reveals that the source varied from a null detection on 3 May 2004, to $\\approx$95 $\\mu$Jy on 17 May 2004, to 230 $\\mu$Jy on 18 June 2004. The lack of detection in September 2006 suggests at least a factor of ten flux variability at 8.46 GHz. Three short photometric runs did not reveal any optical variability. In addition to the observed pulsing nature of the radio flux from another ultra-cool source, the present observations suggests that ultra-cool dwarfs may not just be pulsing but can also display long-term sporadic variability in thei...

Antonova, A; Hallinan, G; Golden, A; Koen, C

2007-01-01

284

Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls  

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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.

van der Wall Elsken

2010-04-01

285

Molecular prenatal diagnosis of a sporadic alobar holoprosencephalic fetus: genotype-phenotype correlations  

Science.gov (United States)

Summary Objective holoprosencephaly is the most common forebrain malformation syndrome with a multifactorial etiology. Currently, mutations are identified in 5–10% of non syndromic, non-chromosomal cases in at least 12 genes. We report the molecular prenatal diagnosis of a fetus with alobar holoprosencephaly. Methods CTG band karyotyping and array CGH genome-wide cytogenetic screenings were done, in conjunction with DNA sequence analyses of the SHH, ZIC2, SIX3 and TGIF genes in search of a molecular etiology and with comparison of findings to prior cases. Results standard CTG band karyotyping and array CGH genome-wide screening failed to identify plausible chromosome imbalances or structural anomalies. However, extensive sequencing of the genomic DNA from the fetus and both parents on all exon and exon-intron boundaries of the four most commonly mutated genes: SHH, ZIC2, SIX3 and TGIF, identified codon 100 of the sonic hedgehog (SHH) gene having a hotspot for loss-of-function mutations in our case and others. Conclusion mutations in codon 100 of SHH were discovered in both sporadic and autosomal dominant inherited cases with evidence of variable expressivity and penetrance. Collectively, this study reinforces the complexity of genotype-phenotype correlations in the prenatal diagnosis of holoprosencephalic fetuses. PMID:23181171

Gekas, Jean; Sergi, Consolato; Kamnasaran, Deepak

2012-01-01

286

Allelic imbalance of HER2 variant in sporadic breast and ovarian cancer.  

Science.gov (United States)

Both breast and ovarian cancers are associated with HER2 receptor activation, which usually results from receptor overexpression and/or gene amplification. The HER-2 gene harbors a polymorphism at codon 655 (GTC/valine to ATC/isoleucine) in the transmembrane domain region, which has been associated with an elevated risk of breast cancer. The objective of this study was to determine whether the polymorphism is under a selection pressure during breast and ovarian carcinogenesis. The Ile/Val genotype was present in 41% (9/22) of the normal DNA of breast cancer patients. An allelic imbalance in the tumor tissue was found in three breast tumors, with overrepresentation of the Val allele. HER-2 was amplified and overexpressed in these tumors. Half of the eight ovarian tumor patients carried heterozygous Ile/Val genotypes. In contrast to breast tumors, all these ovarian cancer specimens showed the presence of the Ile allele. In our selected set of tumors, the Val allele was overrepresented in the subset of HER2-positive breast cancers and the Ile allele in serous ovarian cancer. Further analyses of tumors with known gene amplifications and overexpression may reveal novel associations between germline polymorphisms and development of sporadic tumors. PMID:16682283

Puputti, Marjut; Sihto, Harri; Isola, Jorma; Butzow, Ralf; Joensuu, Heikki; Nupponen, Nina N

2006-05-01

287

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

DEFF Research Database (Denmark)

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.

Schlehofer, B; Schlaefer, K

2007-01-01

288

Clinical and Genetic Aspects of Sporadic Non-Medullar Thyroid Cancer  

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Full Text Available The role of somatic mutations in sporadic thyroid cancer is unclear today. Probably they coming out as aetiological factors in carcinogenesis as well as, respectfully to many authors, can to participate in TC pathogenesis and to determine the clinical course and prognosis of the disease. For today as main oncogenes taking part in initiation of thyroid malignant tumors are considered: RET/PTC, TRK, PTEN, P53, RAS, MET, PPAR?. By means of genetic investigations scientists are trying to solve problems with thyroid cancer differentiated diagnostics (cytokeratin-19, cytokeratin-20, mesothelial cells antigen (Hector Battifora MEsotelial (cell or HBME-1, loss of heterozigitoty (LOH in short arm of 3 chromosome (gene VHL -von Hippel Lindau, 3?26. Recently in foreign literature appeared reports of activated mutations in gene BRAF which most frequently are occurred in melanoma and papillary TC. Prognosis of thyroid cancer may reflected by the LOH as a biological breakage as well as changes of tumor suppressive gene P53 which fraught with decrease of disease prognosis. Thus, both researchers and clinicians have many questions concerning the role of genome, particularly in order to precise of genetic abnormality influence on tumor growth and therefore for assessment of clinical prognosis and with aim to chose adequate treatment tactic in each case.

U Rumjanzeva

2006-03-01

289

Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia  

Energy Technology Data Exchange (ETDEWEB)

Objective: To describe the chest computed tomographic (CT) findings of Legionella pneumophila pneumonia. Methods: CT scans obtained from 23 sporadic cases of L. pneumophila pneumonia were retrospectively reviewed. Chest CT findings were analyzed with regard to the patterns and distributions of pulmonary abnormalities. We also analyzed the histopathology of lungs from guinea pigs with experimentally induced L. pneumophila pneumonia. Results: Consolidation and ground-glass opacity (GGO) were the main findings of CT scans in L. pneumophila pneumonia. The distribution of opacities was categorized as non-segmental (n = 20) and segmental (n = 4). Non-segmental distribution may follow an onset of segmental distribution. Pleural effusion was observed in 14 (58.3%) patients, of which 13 were accompanied with non-segmental distribution. Abscess formation was observed in only one immunocompromised patient. In the animal pneumonia model, the lesions comprised of terminal bronchioles, alveolar spaces, and interstitia. Small bacilli were observed to be contained by many macrophages within the alveoli. Conclusion: Non-segmental distribution was significantly more frequent than segmental distribution in L. pneumophila pneumonia. It is possible that L. pneumophila infection initially results in segmental pneumonia, which progresses to typical non-segmental distribution.

Yu Hui [Department of Respiratory Diseases, Shanghai Pneumology Hospital, Tongji University, Shanghai (China); Higa, Futoshi; Hibiya, Kenji; Furugen, Makoto [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Sato, Yoko [Tomishiro Chuo Hospital, Okinawa (Japan); Shinzato, Takashi [Nakagami General Hospital, Okinawa (Japan); Haranaga, Shusaku; Yara, Satomi; Tateyama, Masao [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Fujita, Jiro, E-mail: fujita@med.u-ryukyu.ac.j [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Li, Huiping [Department of Respiratory Diseases, Shanghai Pneumology Hospital, Tongji University, Shanghai (China)

2010-06-15

290

G1/S Cell Cycle Checkpoint Dysfunction in Lymphoblasts from Sporadic Parkinson's Disease Patients.  

Science.gov (United States)

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among aging individuals, affecting greatly the quality of their life. However, the pathogenesis of Parkinson's disease is still incompletely understood to date. Increasing experimental evidence suggests that cell cycle reentry of postmitotic neurons precedes many instances of neuronal death. Since cell cycle dysfunction is not restricted to neurons, we investigated this issue in peripheral cells from patients suffering from sporadic PD and age-matched control individuals. Here, we describe increased cell cycle activity in immortalized lymphocytes from PD patients that is associated to enhanced activity of the cyclin D3/CDK6 complex, resulting in higher phosphorylation of the pRb family protein and thus, in a G1/S regulatory failure. Decreased degradation of cyclin D3, together with increased p21 degradation, as well as elevated levels of CDK6 mRNA and protein were found in PD lymphoblasts. Inhibitors of cyclin D3/CDK6 activity like sodium butyrate, PD-332991, and rapamycin were able to restore the response of PD cells to serum stimulation. We conclude that lymphoblasts from PD patients are a suitable model to investigate cell biochemical aspects of this disease. It is suggested that cyclin D3/CDK6-associated kinase activity could be potentially a novel therapeutic target for the treatment of PD. PMID:25182869

Esteras, Noemí; Alquézar, Carolina; Bartolomé, Fernando; de la Encarnación, Ana; Bermejo-Pareja, Félix; Molina, José Antonio; Martín-Requero, Angeles

2014-09-01

291

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

Science.gov (United States)

The occurrence of sporadic E (Es) layer has been a hot scientific topic for a long time. Global Navigation Satellite System (GNSS) based Radio Occultation (RO) has been proven a powerful technique on 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. We first show some examples of multiple Es layers occurred in one RO event. Based on the evaluations between co-located simultaneous RO events and between RO and Lidar observations, it could be concluded that some of these do manifest the multiple Es layered 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 the independent ionosondes observations. These complex Es structures could be understood well by 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 on the Es mechanism. The specification on Es should benefit both the Es based long distance communication and accurate neutral RO retrievals.

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

2014-09-01

292

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

Directory of Open Access Journals (Sweden)

Full Text Available The occurrence of sporadic E (Es layer has been a hot scientific topic for a long time. Global Navigation Satellite System (GNSS based Radio Occultation (RO has been proven a powerful technique on 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. We first show some examples of multiple Es layers occurred in one RO event. Based on the evaluations between co-located simultaneous RO events and between RO and Lidar observations, it could be concluded that some of these do manifest the multiple Es layered 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 the independent ionosondes observations. These complex Es structures could be understood well by 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 on the Es mechanism. The specification on Es should benefit both the Es based long distance communication and accurate neutral RO retrievals.

X. Yue

2014-09-01

293

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

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Full Text Available Abstract 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 twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients. Direct sequencing of these PCR products revealed 3 nucleotide substitutions. Two of these were found within intron 3 of the gene, harbouring 4 variant DHPLC profiles. The third nucleotide variation (Asp130Glu was the only substitution present in the coding region of the VAPB gene, and it occurred within exon 4. It was found in three patients out of 125. The frequency of the detected exon variation in the VAPB gene was not significantly different between patients and controls. In conclusion, our study suggests that VAPB mutations are not a common cause of adult-onset SALS.

Majorana Giovanni

2006-05-01

294

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

Science.gov (United States)

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

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

2014-09-01

295

Towards an Age-Dependent Transmission Model of Acquired and Sporadic Creutzfeldt-Jakob Disease  

Science.gov (United States)

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

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

296

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

Science.gov (United States)

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

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

2014-06-24

297

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

Science.gov (United States)

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

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

298

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

Science.gov (United States)

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

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

2014-01-01

299

Seasonal correlation of sporadic schizophrenia to Ixodes ticks and Lyme borreliosis  

Directory of Open Access Journals (Sweden)

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.

Fritzsche Markus

2002-11-01

300

Clinical and pathological implications of GSTM1 and GSTT1 gene deletions in sporadic breast cancer  

Directory of Open Access Journals (Sweden)

Full Text Available There is a lack of consensus about the influence of GST M1/T1 gene deletions (DEL on sporadic breast cancer (SBC. To evaluate the occurrence of DEL in 177 SBC cases and in 169 controls, and compare clinical and biological characteristics. A lower frequency of GSTM1 DEL was observed in mulatto women, OR=0.48 (0.24–0.98. The risk of nuclear grade 3 tumors (GN3 was lower in patients with GSTT1 DEL, OR=0.37 (0.15–0.90. DEL of at least one gene (ALOG was associated with women who had not breastfed, OR=0.41 (0.19–0.88, and with negative hormone receptor, HR–, ORadj=2.25 (1.03–4.90. Both genes deleted (BGD was associated with non-classic invasive ductal carcinoma (NCDC, ORadj=12.09 (1.03–142.03. Mulatto women with SBC had a lower frequency of GSTM1 DEL, while tumors differentiated were related to GSTT1 DEL. HRtumors were related with DEL ALOG, and the BGD was associated with a greater risk of NCDC.

Maria Salete Costa Gurgel

2011-12-01

301

Chickens and Cattle as Sources of Sporadic Domestically Acquired Campylobacter jejuni Infections in Finland?  

Science.gov (United States)

A substantial sampling among domestic human campylobacter cases, chicken process lots, and cattle at slaughter was performed during the seasonal peak of human infections. Campylobacter jejuni isolates (n = 419) were subtyped using pulsed-field gel electrophoresis with SmaI, and isolates representing overlapping types (n = 212) were further subtyped using KpnI for restriction. The SmaI/KpnI profiles of 55.4% (97/175) of the human isolates were indistinguishable from those of the chicken or cattle isolates. The overlapping SmaI/KpnI subtypes accounted for 69.8% (30/43) and 15.9% (32/201) of the chicken and cattle isolates, respectively. The occurrence of identical SmaI/KpnI subtypes with human C. jejuni isolates was significantly associated with animal host species (P < 0.001). A temporal association of isolates from chickens and patients was possible in 31.4% (55/175) of the human infections. Besides chickens as sources of C. jejuni in the sporadic infections, the role of cattle appears notable. New approaches to restrict the occurrence of campylobacters in other farm animals may be needed in addition to hygienic measures in chicken production. However, only about half of the human infections were attributable to these sources. PMID:19542336

Hakkinen, Marjaana; Nakari, Ulla-Maija; Siitonen, Anja

2009-01-01

302

Integrating conservation and development at the National Marine Park of Alonissos, Northern Sporades, Greece: perception and practice.  

Science.gov (United States)

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. PMID:18626688

Oikonomou, Zoi-Sylvia; Dikou, Angela

2008-11-01

303

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.)

304

Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease.  

OpenAIRE

Alzheimer's disease (AD) is associated with deposition of amyloid beta (Abeta) in the brain, which is reflected by low concentration of the Abeta1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional Abeta peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of Abeta. Here, we test the hypothesis that AD is characterized by a specific CSF Abeta isoform pattern that is distinct when comparing sporadic AD (SAD) ...

Portelius, E.; Andreasson, U.; Ringman, J. M.; Buerger, K.; Daborg, J.; Buchhave, P.; Hansson, O.; Harmsen, A.; Gustavsson, M. K.; Hanse, E.; Galasko, D.; Hampel, H.; Blennow, K.; Zetterberg, H.

2010-01-01

305

Orbital sporadic Burkitt lymphoma in an adult diabetic African American female and a review of adult orbital cases  

OpenAIRE

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, pro...

Carmody J; Rp, Misra; Mp, Langford; Wa, Byrd; Ditta L; Vekovius B; Texada DE

2011-01-01

306

P14ARF deficiency and its correlation with overexpression of p53/MDM2 in sporadic vestibular schwannomas.  

Science.gov (United States)

Recent studies have shed considerable light into schwannomas. To date, only merlin has been identified as a hallmark or pathogenesis of both sporadic and NF2-related schwannomas. Here, we show, by immunoblot and immunohistochemical analyses of 58 sporadic vestibular schwannomas, that upregulation of p53 was observed in 90 % of tumors examined. No p53 mutations were found in 12 % tumors analyzed. Expression of p14ARF was negative in 95 % of tumors, while overexpression of MDM2 was found in all specimens. Aberrant DNA hypermethylation of the p14ARF promoter was observed in three of seven tumors examined (43 %), associated with remarkably decreased mRNA levels. The very high degree of concordance in the aberrations of the p14ARF/MDM2/p53 pathway in this tumor may be considered to be a new player in the pathogenesis of sporadic vestibular schwannomas. Moreover, expression of p21 (waf1) was negative in all tumors, suggesting that the aberration of this pathway is associated with greater attenuation of p21-mediated signals that are critical for growth inhibition. These data are in agreement with the model in RT-4 rat schwannoma cells: i.e., overexpression of ARF was associated with accumulation of p21 expression both at protein and mRNA levels. ShRNA knock-down of p53 expression attenuated p21-mediated increase in cellular arrest in the G1-phase, suggesting that p14ARF regulates p21 protein levels through a p53-dependent pathway. Thus, this study reveals a high degree of concordance in the aberrations of the p14ARF/MDM2/p53 pathway with the development of sporadic vestibular schwannomas. PMID:24964769

Chen, Ying; Wang, Zhao-Yan; Wu, Hao

2014-06-26

307

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

OpenAIRE

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 ...

Ck, Choi Bernard; Connolly Tim; Godal Deborah L; Olsen Elina; Jansen Gerard H; Coulthart Michael B; Wang Zheng; Cashman Neil R

2011-01-01

308

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

OpenAIRE

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 investigating 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 HF...

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

2014-01-01

309

Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance  

OpenAIRE

Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We then set out to determine the relative occurrence of sporadic and familial cases and to examine the likelihood of having seizures for individuals with the microdeletion in familial cases. The 15q13.3 mi...

Dibbens, Leanne M.; Mullen, Saul; Helbig, Ingo; Mefford, Heather C.; Bayly, Marta A.; Bellows, Susannah; Leu, Costin; Trucks, Holger; Obermeier, Tanja; Wittig, Michael; Franke, Andre; Caglayan, Hande; Yapici, Zuhal; Sander, Thomas; Eichler, Evan E.

2009-01-01

310

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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.

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

311

Normal in vivo skeletal muscle oxidative metabolism in sporadic inclusion body myositis assessed by 31P-magnetic resonance spectroscopy.  

OpenAIRE

Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy metabolism may be of pathogenic relevance. To test this hypothesis we used 31P magnetic resonance spectroscopy to assess in vivo skeletal muscle mitochondrial function in the calf muscles of 12 patie...

Lodi, R.; Taylor, Dj; Tabrizi, Sj; Hilton-jones, D.; Squier, Mv; Seller, A.; Styles, P.; Schapira, Ah

1998-01-01

312

E-region wind-driven electrical coupling of patchy sporadic-E and spread-F at midlatitude  

Directory of Open Access Journals (Sweden)

Full Text Available This paper investigates the role of neutral winds in the generation of relatively large polarization electric fields across patchy sporadic-E layers, which then map upward to the F region, to create conditions for medium-scale spread-F. The calculations are based on an analytical model that uses the current continuity equation and field-aligned current closures to the F region in order to describe quantitatively a Hall polarization process inside sporadic-E plasma patches during nighttime. In applying this model we use experimentally known values for E and F region, conductances, the ambient electric fields and prevailing neutral winds, in order to estimate the polarization fields that build up inside sporadic-E. It is found that the relatively strong west-southwest neutral winds during summer nighttime can provide the free energy for the generation of sizable polarization electric fields, which have comparable eastward and north-upward components and reach values of several mV/m. Given that the sporadic-E patches have sizes from a few to several tens of kilometers, the polarization fields can map easily to the F region bottomside where they impact ExB plasma uplifts and westward bulk motions, in line with key observational properties of medium-scale spread-F. However, the present simple model needs further development to also include wind forcing of the F region plasma and possible polarization processes inside spread-F. Keywords. Ionosphere (Electric fields and currents; Ionospheric irregularities; Mid-latitude ionosphere

C. Haldoupis

2005-09-01

313

Clinical features of sporadic Creutzfeldt-Jakob disease in China and its auxiliary examinations: A report of 55 cases  

OpenAIRE

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 clinica...

Yan, Bo; Zhang, Jia-tang; Zhao, Wei; Ma, Lin; Yin, Da-yi; Jia, Wei-quan; Huang, Xu-sheng; Lang, Sen-yang; Pu, Chuan-qiang; Yu, Sheng-yuan

2013-01-01

314

Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.  

OpenAIRE

Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein protein was identified in some autosomal-dominantly inherited familial PD pedigrees, and light microscopic studies demonstrated alpha-synuclein immunoreactivity in LBs of sporadic PD and DLB. To characterize alpha-synuclein in LBs, we raised monoclonal antibodi...

Baba, M.; Nakajo, S.; Tu, P. H.; Tomita, T.; Nakaya, K.; Lee, V. M.; Trojanowski, J. Q.; Iwatsubo, T.

1998-01-01

315

Evidence for an association of TP53 codon 72 polymorphism with sporadic colorectal cancer risk in Isfahan  

OpenAIRE

  • 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 ...

    Mehdi Nikbakht Dastjerdi; Mansoor Salehi; Mohammad Reza Mohajeri; Fereshteh Morsali; Hamid Mirohammad Sadeghi; Ebrahim Esfandiary

    2008-01-01

316

Autosomal Recessive and Sporadic Non Syndromic Hearing Loss and the Incidence of Cx26 Mutations in a Province of Iran  

OpenAIRE

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 pre...

Hashemzadeh Chaleshtori, M.; Montazer Zohour, M.; Hoghooghi Rad, L.; Pour-jafari, H.; Dd, Farhud; Dolati, M.; Safa Chaleshtori, K.; Sasanfar, R.; Hosseinipour, A.; Andonian, L.; Tolouei, A.; Ghadami, M.; Ma, Patton

2006-01-01

317

Conventional and molecular approaches to isolates of Salmonella hadar from sporadic and epidemic cases  

OpenAIRE

In September 1994 an outbreak of gastroenteritis occurred in 437 people who had consumed lunch in the canteen of a factory in Central Italy. Salmonella sp. was isolated from stools of 99 patients and in 73 of them Salmonella hadar was identified. This is the first outbreak caused by this serotype described in Italy. In order to examine the genotypic basis of the epidemic strains, molecular typing was applied to sporadic strains isolated before and after the outbreak episode. For...

Fantasia, Mirella; Paglietti, Bianca; Filetici, Emma; Anastasio, Maria Paola; Rubino, Salvatore

1997-01-01

318

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

Science.gov (United States)

Atypical Mole Syndrome is the most important phenotypic risk factor for cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Since early diagnosis of melanoma is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers (sporadic and familial) is essential, as well as the recommendation of preventative measures that must be undertaken by these patients.We report two rare cases concerning patients with multiple primary skin melanomas in the setting of a familial and a sporadic syndrome of dysplastic nevi: the first patient is a 67-year-old patient with a history of multiple superficial spreading melanomas localized on his back. The second patient presented with multiple primary melanomas in advanced stage in the context of the so-called sporadic form of the syndrome of dysplastic nevi-AMS (atypical mole syndrome). In the first case, excision of the melanomas was carried out with an uneventful post-operative period. In the second case, disseminated metastases were detected, involving the right fibula, the abdominal cavity as well as multiple lesions in the brain. The patient declined BRAF mutation tests as well as chemotherapy or targeted therapies, and suffered a rapid deterioration in his general condition leading to death. We classified the second case as a sporadic form of the atypical mole syndrome, associated with one nodular and two superficial spreading melanomas.There are no data in the literature to allow us to understand if, in patients with multiple primary melanomas, there is any difference in terms of prognosis between those with and without a family history of a similar phenotype. To answer this and other questions related to these rare cases, further studies with a significant number of patients should be carried out. PMID:25096163

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

2014-08-01

319

HER2 Amplification Has no Prognostic Value in Sporadic and Hereditary Ovarian Tumours  

OpenAIRE

Abstract Whereas HER2 amplification is a well-known phenomenon in breast tumours, its frequency and clinical importance in ovarian cancer have not been established. The aim of the study was to compare the frequency of HER2 amplification in hereditary (BRCA-positive) and sporadic (BRCA-negative) ovarian tumours and to estimate the association of this gene alteration on clinical outcome in ovarian cancer patients. We analysed HER2 amplifica...

Bro?ek Izabela; Karda? Iwona; Ochman Karolina; D?bniak Jaros?aw; Stukan Maciej; Ratajska Magdalena; Morzuch Lucyna; Emerich Janusz; Limon Janusz

2006-01-01

320

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

OpenAIRE

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...

Hashemzadeh Chaleshtori, M.; Dd, Farhud; Ma, Patton

2007-01-01

321

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

OpenAIRE

PURPOSE: Recently, familial paraganglioma (PGL) was shown to be caused bymutations in the gene encoding succinate dehydrogenase subunit D (SDHD). However, the prevalence of SDHD mutations in apparently sporadic PGL is unknown. We studied the frequency and spectrum of germ-line and somatic SDHD mutations in patients with parasympathetic PGL. EXPERIMENTAL DESIGH: We studied 57 unselected patients who developed parasympathetic PGLs (n = 105 t...

Dannenberg, H.; Dinjens, W. N. M.; Abbou, M.; Urk, H.; Pauw, B. K.; Mouwen, D.; Mooi, W. J.; Krijger, R. R.

2002-01-01

322

Clonal Multidrug-Resistant Shigella dysenteriae Type 1 Strains Associated with Epidemic and Sporadic Dysenteries in Eastern India  

OpenAIRE

Multidrug-resistant strains of Shigella dysenteriae type 1 were implicated in three outbreaks and sporadic cases of dysentery in eastern India in 2002 and 2003. After a hiatus of 14 years, this pathogen reemerged with an altered antibiotic resistance pattern. In addition to ampicillin, co-trimoxazole, tetracycline, chloramphenicol, and nalidixic acid, all the recent strains were resistant to norfloxacin, lomefloxacin, pefloxacin, and ofloxacin and showed reduced susceptibility to ciprofloxaci...

Pazhani, Gururaja Perumal; Sarkar, Bhaswati; Ramamurthy, Thandavarayan; Bhattacharya, S. K.; Takeda, Yoshifumi; Niyogi, S. K.

2004-01-01

323

Impaired Autophagy in Sporadic Inclusion-Body Myositis and in Endoplasmic Reticulum Stress-Provoked Cultured Human Muscle Fibers  

OpenAIRE

The hallmark pathologies of sporadic inclusion-body myositis (s-IBM) muscle fibers are autophagic vacuoles and accumulation of ubiquitin-positive multiprotein aggregates that contain amyloid-? or phosphorylated tau in a ?-pleated sheet amyloid configuration. Endoplasmic reticulum stress (ERS) and 26S proteasome inhibition, also associated with s-IBM, putatively aggrandize the accumulation of misfolded proteins. However, autophagosomal-lysosomal pathway formation and function, indicated by a...

Nogalska, Anna; D Agostino, Carla; Terracciano, Chiara; Engel, W. King; Askanas, Valerie

2010-01-01

324

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

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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.

Walsh Tom

2009-07-01

325

The role of NF2 gene mutations and pathogenesis-related proteins in sporadic vestibular schwannomas in young individuals.  

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Vestibular schwannomas (VSs) are benign tumors arising from eighth cranial nerve and most often occur sporadically in individuals of middle age group. Sporadic VSs are rarely reported in the young population. In this study, we evaluated clinical behaviors of 12 young sporadic VSs by the statistical comparison with a matched series of 145 adult cases. We found that young tumors were characterized by an earlier onset of initial symptom, shorter duration from the first symptom to diagnosis, and larger tumor size than adult ones. Standard sequencing demonstrated the presence of NF2 mutations in eight tumors. All NF2 mutations identified were truncating mutations (nonsense, frameshift, and splicing-site mutations). Earlier formation of VSs in young patients was evidenced by the high incidence of NF2 mutations (66.7%) far beyond our previous study in the adult case series (34.5%). Furthermore, young tumors exhibited deficient merlin or heightened phosphorylated merlin that was subsequently demonstrated to be well correlated with increased tumor size. Finally, we compared protein levels of four pathogenesis-related molecules between young and adult group but there was no significant difference. These results led us to suggest that high frequency of NF2 mutations may play a critical role in early tumorigenesis of young VSs. Moreover, merlin deficiency or phosphorylation status of merlin was involved in their earlier development. Further study remains to fully understand the mechanism for the rapid growth of young VSs. PMID:24619252

Chen, Hongsai; Zhang, Xiaoman; Zhang, Zhihua; Yang, Tao; Wang, Zhaoyan; Wu, Hao

2014-07-01

326

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

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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.

G. G. Didebulidze

2008-06-01

327

Currents and turbulence in and near mid-latitude sporadic E-layers caused by strong acoustic impulses  

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Full Text Available The generation of Hall and field-aligned currents in and in the vicinity of nighttime mid-latitude sporadic E-layers moving under the action of strong acoustic impulses of seismic, anthropogenic, or meteorological nature is considered in a model presented in this paper. The influence of the electrical polarization fields caused by charges at the horizontal edges of the sporadic layers and the finite conductivity of the external circuits are also taken into account. The theoretical model is applicable for ionospheric altitudes between 95 and 130 km. The estimates show that under certain conditions in a system with two sporadic E-layers, one of which is the current generator and the other is situated in the external circuit, the Farley-Buneman instability could be generated. On the other hand, observations show that Farley-Buneman waves are likely responsible for the infrequent echoes of mid-latitude 50-MHz backscatter with Doppler velocities near 300 m s–1. The possibility exists that the proposed current-generator model is at the origin of the observed mid-latitude Farley-Buneman waves.

K. Schlegel

328

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

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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.

Anna Kowalska

2009-12-01

329

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

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? 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.

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

2013-01-01

330

B7-H4 gene polymorphisms are associated with sporadic breast cancer in a Chinese Han population  

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Full Text Available Abstract Background B7-H4, a co-inhibitory molecule of the B7 family, can restrain T cell proliferation, cytokine secretion and the development of cytotoxicity. B7-H4 is expressed in tumor tissues at a higher level than in normal tissues, and has a potential effect to protect tumors from anti-tumor immune responses. This case-control study was carried out to determine the potential influences of B7-H4 gene polymorphisms on the susceptibility and progression of breast cancer in Han women of Northeast China. Methods We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414 and tagged all common haplotypes (frequency greater than or equal to 1% in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP technique was used to determine the genotypes. Results Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively. The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively. Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881, but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031. And the AAA and the GCG haplotypes also respectively have significant influences on tumor size and ER status. Conclusion These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.

Fu Zhenkun

2009-11-01

331

The occurrence of sporadic-E and noctilucent clouds, and correlations with meteor and auroral activities, May to August, 1977 - 1991.  

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An analysis of 15 years of sporadic-E and noctilucent cloud results is examined with especial regard to correlations with the occurrence of meteor and auroral activities. A complex pattern is revealed in which it seems probable major meteor shower maxima play an important role in providing input of metallic ions and solid dusty material. Possible broad-scale scenarios for the formation of sporadic-E and noctilucent clouds are suggested.

McBeath, A.

1993-08-01

332

Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.  

OpenAIRE

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 und...

Lonlay, P.; Fournet, J. C.; Rahier, Jacques; Gross-morand, M. S.; Poggi-travert, F.; Foussier, V.; Bonnefont, J. P.; Brusset, M. C.; Brunelle, F.; Robert, J. J.; Nihoul-fe?ke?te?, C.; Saudubray, J. M.; Junien, C.

1997-01-01

333

Evaluation of the role of AIP, CDKN1B, miR-107 and AHRR in the pathogenesis of sporadic and familial pituitary adenomas  

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Pituitary adenomas are common benign intracranial neoplasms, with the vast majority of such tumours being sporadic. The pathogenesis of sporadic pituitary adenomas remains unclear; however, abnormal microRNAs (miRNAs) expression profiles have been recently associated with these adenomas, suggesting that miRNAs can contribute to tumour formation. In about 5% of cases, pituitary adenomas occur in a familial setting, often as part of multiple endocrine tumours syndromes, such as multiple endocri...

Trivellin, Giampaolo

2011-01-01

334

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

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Full Text Available 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 and Genomatix program were used to identify potential BP1 binding sites in BRCA1 gene. Real-time PCR, Western blot and immunohistochemistry analysis were performed to verify the expression of BRCA1 and BP1 in cell lines and breast cancer tissues. Double-stranded siRNA transfection was carried out for silencing BP1 expression. ChIP and EMSA were used to confirm that BP1 specifically binds to BRCA1.Results: A putative BP1 binding site was identified in the first intron of BRCA1, which was confirmed by chromatin immunoprecipiation and electrophoresis mobility shift assay. BP1 and BRCA1 expression were inversely correlated in breast cancer cell lines and tissues, suggesting that BP1 may suppress BRCA1 transcription through consensus sequence binding.Conclusions: BP1 homeoprotein represses BRCA1 expression through direct binding to its first intron, which is consistent with a previous study which identified a novel transcriptional repressor element located more than 500 base pairs into the first intron of BRCA1, suggesting that the first intron plays an important role in the negative regulation of BRCA1. Although further functional studies are necessary to confirm its repressor activity towards BRCA1, the elucidation of the role of BP1 in breast tumorigenesis holds great promise in establishing BP1 as a novel target for drug therapy.

Brian J. Kluk, Yebo Fu, Trina A. Formolo, Lei Zhang, Anne K. Hindle, Yan-gao Man, Robert S. Siegel, Patricia E. Berg, Chuxia Deng, Timothy A. McCaffrey, Sidney W. Fu

2010-01-01

335

Sporadic E layer at mid-latitudes: average properties and influence of atmospheric tides  

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This paper describes a study of the daily variability shown by the main characteristics of the sporadic E (Es) layer, that is the top frequency (ftEs) and the lowest virtual height (h'Es). The study is based on ionograms recorded by the Advanced Ionospheric Sounder by the Istituto Nazionale di Geofisica e Vulcanologia (AIS-INGV) ionosondes installed in the ionospheric stations at Rome (41.8° N, 12.5° E) and Gibilmanna (37.9° N, 14.0° E), Italy, during the summer (June, July, August and September) of 2013, a year falling in the ascending phase of solar cycle 24. The ftEs presents a diurnal variation characterized by two maxima, the first around noon is very well defined and the second in the evening/night is much less defined; the amplitude of both maxima decreases from June to September accompanied by a general decrease of the ftEs values which is more pronounced in the daytime than in the nighttime. h'Es also presents a diurnal variation characterized by two maxima but, unlike ftEs, these present the same amplitude which is independent from the considered month. Assuming that both ftEs and h'Es trends are influenced by the atmospheric tides, the height-time-intensity (HTI) technique was applied to deeply investigate how these waves control the Es dynamics. The HTI study, along with a fast Fourier transform analysis, show that a well-defined semidiurnal periodicity characterizes the Es layer dynamics most accurately in June and July, while in August and September the daytime semidiurnal periodicity becomes weaker and the role of the diurnal periodicity is consequently highlighted.

Pignalberi, A.; Pezzopane, M.; Zuccheretti, E.

2014-11-01

336

Up-regulation of hnRNP A1 gene in sporadic human colorectal cancers.  

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We have previously reported that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a major hnRNP, binds to G-rich repetitive sequences and quadruplex (G4') structures in DNA, including the 5'-TTAGGG-3' telomere repeat and 5'-GGCAG-3' short-tandem-repeat. DNA synthesis arrest at the (GGG) sites within these repeats in vitro was retrieved by the addition of the hnRNP A1 protein or its N-terminal proteolytic product, UP1, in a dose-dependent manner. Therefore, functional perturbation of hnRNP A1 may abrogate the genomic stability of telomere repeats and other G-rich sequences, independent of its major role in transcriptional and translational regulation. In the present study, we conducted genetic and expression analysis of the hnRNP A1 gene in sporadic human colorectal cancers to clarify its possible involvement in human carcinogenesis. Of 30 lesions, one harbored a mutation at the -11 position from the translation initiation site, but none in the coding region. A single nucleotide polymorphism, an A or G-allele, was found in the 5' upstream promoter region of the gene. Quantitative gene expression analysis revealed that 60% (18/30) of cases showed over-expression of hnRNP A1 in cancer tissues by 2-fold or greater, compared to their normal colon tissues, with values of 78, 64 and 40% for clinicopathological stages II, III and IV, respectively. Although the biological consequences of hnRNP A1 overexpression in colorectal cancers remain to be clarified, it could contribute to maintenance of telomere repeats in cancer cells with enhanced cell proliferation. Alternatively, since the variations in the stoichiometry of hnRNP family proteins are considered to affect cell-specific gene expression, quantitative alteration of hnRNP A1 could result in facilitation of transformation of colon epithelial cells as a consequence of transcriptional and translational perturbation. PMID:15703818

Ushigome, Mitsunori; Ubagai, Tsuneyuki; Fukuda, Hirokazu; Tsuchiya, Naoto; Sugimura, Takashi; Takatsuka, Jun; Nakagama, Hitoshi

2005-03-01

337

Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH: study protocol  

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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.

Ennis Sarah

2007-08-01

338

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

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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

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

2015-02-01

339

Outcome of triple negative breast cancer: comparison of sporadic and BRCA1-associated cancers.  

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The majority of breast cancers developing in BRCA1 mutation carriers are triple negative breast cancers (TNBC), an aggressive subtype that accounts for 15-20 % of sporadic breast cancer. We compare the clinical outcome and sites of relapse of TNBC in BRCA1 mutation carriers and non-carriers who received adjuvant chemotherapy. Women with stage I-III TNBC who had BRCA1 testing within 36 months of diagnosis and received adjuvant chemotherapy were identified from clinical databases at two academic institutions. Sites of relapse, freedom from distant metastasis (FFDM), and breast cancer-specific survival (BCSS) were determined. RCA1 carriers (n = 89) were significantly younger at diagnosis (P < 0.0001) than non-carriers (n = 175). FFDM at 5 years was 80.5 % for carriers and 76.9 % for non-carriers; with median follow-up of 55 months, hazard ratio (HR) was 0.90, P = 0.71. Sites of recurrence, including brain, did not differ significantly. BCSS at 5 years was 88.1 % for carriers and 81.4 % for non-carriers; HR 0.60; P = 0.15 at 55 months follow-up. BRCA1 carriers who underwent oophorectomy had a significantly lower rate of death from TNBC, with an adjusted HR of 0.30 (95 % CI 0.10-0.94). Adjusting for age, oophorectomy, and prophylactic mastectomy, BRCA1 mutation status was not an independent predictor of survival (HR 2.1; P = 0.13). BRCA1 mutation carriers with TNBC had similar survival rates and sites of recurrence to non-carriers after treatment with conventional chemotherapy. Carriers who underwent oophorectomy had a significantly lower rate of breast cancer-related death; this finding should be studied further in all women with TNBC. PMID:24839033

Tung, Nadine; Gaughan, Elizabeth; Hacker, Michele R; Lee, Larissa J; Alexander, Brian; Poles, Emily; Schnitt, Stuart J; Garber, Judy E

2014-07-01

340

Diagnostic value of diffusion-weighted imaging on sporadic Creutzfeldt-Jakob disease  

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Full Text Available Objective To explore the diagnostic value of diffusion-weighted imaging (DWI on sporadic Creutzfeldt-Jakob disease (sCJD.  Methods The MRI findings of 21 patients with clinically proved probable sCJD were analyzed retrospectively and the characteristics were summarized especially in DWI.  Results 1 All 21 cases of sCJD were shown abnormal in DWI, which appeared as linear hyperintensity signals in cerebral cortex and patchy hyperintensity in caudate nucleus and (or lenticular nucleus. 2 The abnormal signals were most commonly seen in cerebral cortex accompanied with the basal ganglia (16 cases, 76.19%. Besides, there were 3 cases of cortex involvement (14.29% and 2 cases of basal ganglia involvement (9.52% . Among the lesions in cerebral cortex, the frontal and parietal lobes were affected more commonly (15 cases, 78.95%; 13 cases, 68.42% than the temporal and occipital lobes (12 cases, 63.16%; 9 cases, 47.37%. 3 DWI was superior to T1WI, T2WI and FLAIR imaging sequences. The abnormal signals in DWI were accompanied by decreased apparent diffusion coefficient (ADC values. 4 During the follow-up in 5 patients, the range and intensity of high signal changed in DWI, and only one case presented reduced range of abnormal signal. Conclusions sCJD manifests characteristic changes on DWI, which should be suggested as an essential tool for diagnosing sCJD. doi: 10.3969/j.issn.1672-6731.2014.04.010

Yan-hui YANG

2014-04-01

341

Prion protein glycotype analysis in familial and sporadic Creutzfeldt-Jakob disease patients.  

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Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs) are characterised by the accumulation of a pathological conformer of PrP, named PrPsc. Molecular weight and glycosylation of the protease-resistant core of PrPsc (PrP27-30) are heterogeneous in different forms of TSEs. We analysed PrP27-30 glycotypes in a large number of TSE-affected patients: 50 sporadic CJD (sCJD), 1 iatrogenic CJD, 1 Gerstmann-Sträussler-Scheinker syndrome (GSS) with the Pro102Leu mutation of PrP, 3 familial CJD (fCJD) with the Glu200Lys mutation and, for the first time, 7 fCJD with the Val210ll3e mutation. All patients were screened for the polymorphic codon 129 of the PrP gene. PrP27-30 deglycosylation and PrPsc immunohistochemistry were performed in selected cases. We found that two PrP27-30 glycotypes (type 1A and type 2A) are produced in sCJD. Type 1A is more frequently associated with methionine than valine in position 129. Type 1A is also formed in Val210lle fCJD. In Glu200Lys fCJD and GSS patients, we found that PrP27-30 has the same mobility of type 1 but different glycosylation ratios (type 1B). Our findings indicate that the polymorphic residue 129 of PrP has a leading role in determining the proteinase degradation site of PrPsc while mutant residues 102 or 200 influence only the glycosylation pattern. PMID:10483920

Cardone, F; Liu, Q G; Petraroli, R; Ladogana, A; D'Alessandro, M; Arpino, C; Di Bari, M; Macchi, G; Pocchiari, M

1999-08-01

342

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

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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.

Edward C. Mader

2013-02-01

343

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

Science.gov (United States)

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

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

2013-02-11

344

Long-term survival following radiotherapy and cytarabine chemotherapy for sporadic primary central nervous system lymphoma  

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Purpose: To analyze the long-term results following whole brain radiotherapy (WBRT) with sequential intrathecal (i.th.) cytosine arabinoside (Ara-C) {+-} intravenous (i.v.) Ara-C in patients with primary central nervous system lymphoma (PCNSL). Patients and Methods: 14 patients were treated between July 1987 and August 1995. All had sporadic PCNSL with proven histology of high-grade CNS lymphoma (twelve diffuse large-cell B-lymphomas, one lymphoblastic lymphoma, one large T-cell lymphoma). Patients were treated with two to four cycles of induction chemotherapy (40 mg/m{sup 2} Ara-C i.th.), four patients received additional Ara-C i.v. (150 mg/m{sup 2}, d1-4). WBRT was administered using 1.8-Gy fractions. Intrathecal chemotherapy was planned afterwards in 4-week intervals for 6 months. Posttreatment neurocognitive evaluations were performed in two long-term survivors. Results: Two of four patients who received i.v. and i.th. induction chemotherapy showed progressive disease, and irradiation was started immediately. Six of 14 patients received 50.4 Gy WBRT, four patients had WBRT up to 39.6 Gy followed by a 10.8-Gy boost. Five patients died early during therapy either due to a decline of the general medical condition or progressive disease. Median survival was 41 months (95% confidence interval: 6-79 months), survival at 3 and 5 years was 59% and 42%, respectively. Six patients survived for 3 years, two younger patients are still alive (> 12 years). They show only slightly impaired neurocognitive functions without clinical relevance. Conclusion: This WBRT-based protocol with i.th. meningeal prophylaxis using Ara-C {+-} i.v. Ara-C yields substantial long-term survival with moderate toxicity. The value of i.v. chemotherapy is currently being investigated in prospective studies. (orig.)

Poettgen, C.; Stuschke, M.; Stueben, G.; Schmitz, A.; Grehl, S. [Dept. of Radiotherapy, Univ. Hospital Essen (Germany); Schwechheimer, K. [Dept. of Neuropathology, Univ. Hospital Essen (Germany); Wacker, H.H. [Lymph-Node Registry of the German Society of Pathology, Inst. of Hematopathology, Univ. of Kiel (Germany); Rauhut, F. [Dept. of Neurosurgery, Univ. Hospital Essen (Germany); Kleuker, S. [Dept. of Pediatrics, Univ. Hospital Essen (Germany); Wilhelm, H. [Dept. of Neurology, Univ. Hospital Essen (Germany); Fehlings, T. [Dept. of Diagnostic Radiology, Univ. Hospital Essen (Germany)

2003-09-01

345

Long-term survival following radiotherapy and cytarabine chemotherapy for sporadic primary central nervous system lymphoma  

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Purpose: To analyze the long-term results following whole brain radiotherapy (WBRT) with sequential intrathecal (i.th.) cytosine arabinoside (Ara-C) ± intravenous (i.v.) Ara-C in patients with primary central nervous system lymphoma (PCNSL). Patients and Methods: 14 patients were treated between July 1987 and August 1995. All had sporadic PCNSL with proven histology of high-grade CNS lymphoma (twelve diffuse large-cell B-lymphomas, one lymphoblastic lymphoma, one large T-cell lymphoma). Patients were treated with two to four cycles of induction chemotherapy (40 mg/m2 Ara-C i.th.), four patients received additional Ara-C i.v. (150 mg/m2, d1-4). WBRT was administered using 1.8-Gy fractions. Intrathecal chemotherapy was planned afterwards in 4-week intervals for 6 months. Posttreatment neurocognitive evaluations were performed in two long-term survivors. Results: Two of four patients who received i.v. and i.th. induction chemotherapy showed progressive disease, and irradiation was started immediately. Six of 14 patients received 50.4 Gy WBRT, four patients had WBRT up to 39.6 Gy followed by a 10.8-Gy boost. Five patients died early during therapy either due to a decline of the general medical condition or progressive disease. Median survival was 41 months (95% confidence interval: 6-79 months), survival at 3 and 5 years was 59% and 42%, respectively. Six patients survived for 3 years, two younger patients are still alive (> 12 years). They show onle still alive (> 12 years). They show only slightly impaired neurocognitive functions without clinical relevance. Conclusion: This WBRT-based protocol with i.th. meningeal prophylaxis using Ara-C ± i.v. Ara-C yields substantial long-term survival with moderate toxicity. The value of i.v. chemotherapy is currently being investigated in prospective studies. (orig.)

346

Epstein-Barr Virus (EBV)-positive Sporadic Burkitt Lymphoma: An Age-related Lymphoproliferative Disorder?  

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Epstein-Barr virus (EBV) is detected in 20% to 30% of sporadic Burkitt lymphoma (sBL). However, only a few studies of EBV-positive (EBV) sBL have been reported, and its characteristics still remain controversial. To highlight the features of EBV sBL, we compared the clinicopathologic characteristics of 33 cases of EBV and 117 cases of EBV-negative (EBV) sBL in Japan. EBV sBL showed significantly higher age distribution (median, 42 vs. 13 y; P<0.0001) and higher frequency of patients older than 50 years (48% vs. 16%, P<0.0001). We also revealed the difference of the involved sites. The EBV group showed significantly higher incidence of involvement of tonsil (P=0.027), adrenal gland (P=0.011), and cervical lymph node (P=0.040). In addition, the EBV group tended to have higher incidence of nodal involvement (P=0.078) and involvement of para-aorta lymph node (P=0.084) and heart (P=0.050). In contrast, the gastrointestinal tract was less frequently affected in EBV sBL (P=0.024). In addition, the less positivity for MUM1 (P=0.020) of EBV sBL was highlighted. These results indicate that biological behavior and pathogenesis of EBV sBL might be different from those of EBV sBL. Our results demonstrate that EBV sBL has an aspect of age-related disease and is a distinct clinicopathologic subtype, which should be distinguished from EBV sBL. PMID:25321330

Satou, Akira; Asano, Naoko; Nakazawa, Atsuko; Osumi, Tomoo; Tsurusawa, Masahito; Ishiguro, Atsushi; Elsayed, Ahmed Ali; Nakamura, Naoya; Ohshima, Koichi; Kinoshita, Tomohiro; Nakamura, Shigeo

2015-02-01

347

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

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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

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

2015-01-01

348

Prion proteins in subpopulations of white blood cells from patients with sporadic Creutzfeldt-Jakob disease.  

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Recent cases of prion transmission in humans following transfusions using blood donated by patients with asymptomatic variant Creutzfeldt-Jakob disease (CJD) implicate the presence of prion infectivity in peripheral blood. In this study, we examined the levels of the normal, cellular prion protein (PrPC), and the disease-causing isoform (PrPSc) in subpopulations of circulating white blood cells (WBCs) from patients with sporadic (s) CJD, age-matched neurological controls and healthy donors. Though widely distributed, the highest levels of PrPC were found in a subpopulation of T lymphocytes: approximately 12,000 PrPC molecules were found per CD4+CD45RA-CD62L- effector memory T helper cell. Although platelets expressed low levels of PrPC on their surface, their high abundance in circulation resulted in the majority of PrPC being platelet associated. Using quantitative fluorescence-activated cell sorting analysis, we found that neither WBC composition nor the amount of cell-surface PrPC molecules was altered in patients with sCJD. Eight different WBC fraction types from the peripheral blood of patients with sCJD were assessed for PrPSc. We were unable to find any evidence for PrPSc in purified granulocytes, monocytes, B cells, CD4+ T cells, CD8+ T cells, natural killer cells, nonclassical gamma delta T cells, or platelets. If human WBCs harbor prion infectivity in patients with sCJD, then the levels are likely to be low. PMID:19434060

Choi, Ed M; Geschwind, Michael D; Deering, Camille; Pomeroy, Kristen; Kuo, Amy; Miller, Bruce L; Safar, Jiri G; Prusiner, Stanley B

2009-06-01

349

SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis.  

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Mutations in the sequestosome 1 gene (SQSTM1) have recently been identified in patients with amyotrophic lateral sclerosis, accounting for 1.11%-4.92% of familial ALS and 2.42%-4.37% of sporadic amyotrophic lateral sclerosis (SALS). The mutation spectrum of SQSTM1 in Chinese patients with SALS remains unknown. Three hundred and six patients with SALS from the Department of Neurology, West China Hospital of Sichuan University were recruited for this study. From the same region, 350 healthy individuals were recruited as a control group. The encoding regions of SQSTM1 were screened by direct sequencing. Three novel nonsynonymous mutations- p. I99L, p. D337E, and p. L341V-were identified in 3 patients with SALS, none of which were found in healthy controls. The male patient carrying mutation p. I99L presented limb symptom at age of 34 and died in 34 months. Two late-onset patients carrying D337E and p. L341V mutations had bulbar and limb onset, respectively. Moreover, a c.1166-14_1166-11delTACT mutation in the intron 7 was found in a living male patient with limb onset at age of 62. None of the patients carrying SQSTM1 mutation showed clinical evidence of concomitant Paget disease of bone or mutation of the valosin-containing protein gene. The mutation frequency of SQSTM1 was 0.98% in Chinese patients with SALS, which was lower than those in other racial populations. PMID:24138988

Chen, Yongping; Zheng, Zhen-Zhen; Chen, Xueping; Huang, Rui; Yang, Yuan; Yuan, Lixing; Pan, Lei; Hadano, Shinji; Shang, Hui-Fang

2014-03-01

350

Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility  

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Full Text Available Abstract Background The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1 underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. Methods The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. Conclusion This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S to Phe (F changes a hydrophilic residue (S to a hydrophobic residue (F and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5' near gene, and rs746429 (synonymous (Ala (A to Ala (A, did not show significant associations with breast cancer incidence, yet were associated with lymph node metastasis in the previous study. This suggests that SIPA1 may be involved in different stages of breast carcinogenesis and since this study replicates a previous study of the associated SNP, it implicates variants of the SIPA1 gene as playing a potential role in breast cancer.

Lintell Nicholas A

2009-09-01

351

Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer  

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Full Text Available Abstract Background Cancers often arise within an area of cells (e.g. an epithelial patch that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations. Purpose To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1 are early steps in progression to colon cancer. Results Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls. In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million. Conclusions The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million crypts near cancers and TVAs suggests that the tumors arose in field defects that were deficient in DNA repair and that deficiencies in Pms2, Ercc1 and Xpf are early steps, often occurring together, in progression to colon cancer.

Facista Alexander

2012-04-01

352

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

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Full Text Available 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 intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson’s ?2 test and ? test for the ordinal data. P value < 0.05 was considered as significant. RESULTS: Age range was 40 to 86 years in males (mean = 43.36 and 45 to 70 years in females (mean = 56. HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32% had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression: (1 HACF - 40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2 DACF - strong in 25%, moderate in 37.5% and weak in 37.5%; and (3 carcinoma - negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05. Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036. Vegetarian diet intake and non-smokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05. Fhit protein had an inverse association with Ki67 expression. CONCLUSION: Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.

Kim Vaiphei

2012-01-01

353

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

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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.

Wu Yiqing

2010-03-01

354

Invasive behavior of ulcerative colitis-associated carcinoma is related to reduced expression of CD44 extracellular domain: comparison with sporadic colon carcinoma  

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Full Text Available Abstract Background To elucidate relations of invasion of ulcerative colitis (UC-associated carcinoma with its prognosis, the characteristics of invasive fronts were analyzed in comparison with sporadic colonic carcinomas. Methods Prognoses of 15 cases of UC-associated colonic carcinoma were compared with those of sporadic colon carcinoma cases, after which 75 cases of sporadic invasive adenocarcinoma were collected. Tumor budding was examined histologically at invasive fronts using immunohistochemistry (IHC of pancytokeratin. Expressions of beta-catenin with mutation analysis, CD44 extracellular domain, Zo-1, occludin, matrix matalloproteinase-7, laminin-5?2, and sialyl Lewis X (LeX were immunohistochemically evaluated. Results UC-associated carcinoma showed worse prognosis than sporadic colon carcinoma in all the cases, and exhibited a tendency to become more poorly differentiated when carcinoma invaded the submucosa or deeper layers than sporadic carcinoma. When the lesions were compared with sporadic carcinomas considering differentiation grade, reduced expression of CD44 extracellular domain in UC-associated carcinoma was apparent. Laminin-5?2 and sialyl-LeX expression showed a lower tendency in UC-associated carcinomas than in their sporadic counterparts. There were no differences in the numbers of tumor budding foci between the two lesion types, with no apparent relation to nuclear beta-catenin levels in IHC. Conclusions UC-associated carcinoma showed poorer differentiation when the carcinoma invaded submucosa or deeper parts, which may influence the poorer prognosis. The invasive behavior of UC-associated carcinoma is more associated with CD44 cleavage than with basement membrane disruption or sialyl-Lewis-antigen alteration.

Araki Kayo

2011-04-01

355

Observation of strong VHF-radar echoes from the E-region at 69°N and 54°N: Echo properties, relation to sporadic layers, and physical mechanisms  

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For more than ten years the Leibniz-Institute of Atmospheric Physics at Rostock University in Kühlungsborn has been operating two VHF-radars (53.5 MHz) at the Arctic location Andenes (69N, 16E) as well as the mid-latitude site Kühlungsborn (54.1N 11.8E). Both radars have primarily been used for the study of strong radar echoes from the summer mesopause region known as (polar) mesosphere summer echoes or (P)MSE. PMSE occur from mid May until mid August in an altitude range from 80 -90 km, i.e., at the time of year and in the altitude range where the atmosphere is supersaturated with respect to ice such that ice particles may form, modify the D-region plasma, and lead to spectacular radar echoes. The existence of echoes from above this altitude range has generally been deemed impossible since refractive index fluctuations arising from neutral dynamics such as turbulence are effectively destroyed at these altitudes owing to the exponential increase of viscosity with height. Also, plasma instabilities which occur between 90 -110 km height produce field aligned irregularities and should not lead to detectable echoes for vertically sounding radars at polar latitudes where the magnetic field lines are essentially perpendicular to the surface. It hence comes as a surprise that our recent observations in the altitude range from 90 -115 km reveals the presence of strong radar echoes both at 69N as well as 54N. These echoes have a typical duration of less than 1 hour and extend over less than 1 km in height. They occur in the entire altitude range from 90 to 115 km with a pronounced maximum at 100 km. The seasonal variation is marked by a pronounced maximum during the summer months. This paper describes the morphology and statistics of these echoes, discusses its relation to sporadic E-layers and sporadic metal layers, and closes with an initial attempt to identify a physical mechanism responsible for these structures.

Rapp, Markus; Leitert, Lasse; Latteck, Ralph; Zecha, Marius; Hoffmann, Peter; Höffner, Josef; Hoppe, Ulf-Peter; La Hoz, Cesar

356

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

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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.

Huang Yue

2012-01-01

357

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

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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.

M Hashemzadeh Chaleshtori

2007-05-01

358

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

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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.

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

359

Diurnal and seasonal variability of sporadic meteor flux: First observations of pre-sunrise secondary peak from Thumba  

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In this paper, we present diurnal variations of sporadic meteor flux rate based on radar observations made from Thumba (8.5oN, 77oE), located near the magnetic equator in the southern part of India. These observations are compared with the observations at Darwin, Buckland Park, and Davis, which are located at low, mid, and high latitudes, respectively, to examine the latitudinal differences in the sporadic meteor flux. The important observation is the occurrence of a secondary peak around 0300 LT at Thumba prior to the occurrence of the commonly observed morning peak around 0600 LT at all latitudes. This secondary peak has not been observed at Darwin, which is a low latitude station close to that of Thumba but in the southern hemisphere. Further, we find that this secondary peak has a clear seasonal variation. In summer (winter), the primary (secondary) peak is larger than the secondary (primary) peak while the primary and secondary peaks are comparable in equinoxes. Recent observations and models suggest that the main source seems to be earth’s apex with ~ 30% - 60 % contribution and the remaining are mostly originated from the helion and antihelion sources with a small contribution from south and north toroidal sources. However, the small scale features such as secondary peak in the diurnal meteor rate can be explained by the right combination of contribution from apex as well as helion and antihelion sources. Our observations are in good agreement with the results presented by the models of Janches et al. [2006], Fentzke and Janches [2008], and Fentzke et al. [2009].The observed diurnal rates also show seasonal and also latitudinal variabilities, which are interpreted in terms of observing geometry of the sporadic meteor sources in the local sky.

Phani Kumar, D. V.; Kwak, Y.; Patra, A. K.; Kim, K.; Yellaiah, G.; Kumar, K. K.; Reid, I. M.

2009-12-01

360

Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis  

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Mutations in the inverted formin 2 gene (INF2) have recently been identified as the most common cause of autosomal dominant focal and segmental glomerulosclerosis (FSGS). In order to quantify the contribution of various genes contributing to FSGS, we sequenced INF2 where all mutations have previously been described (exons 2 to 5) in a total of 215 probands and 281 sporadic individuals with FSGS, along with other known genes accounting for autosomal dominant FSGS (ACTN4, TRPC6 and CD2AP) in 21...

Barua, Moumita; Brown, Elizabeth J.; Charoonratana, Victoria T.; Genovese, Giulio; Sun, Hua; Pollak, Martin R.

2012-01-01

361

INVERTED FORMIN 2 MUTATIONS WITH VARIABLE EXPRESION IN PATIENTS WITH SPORADIC AND HEREDITARY FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS  

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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 ...

Gbadegesin, Rasheed; Lavin, Peter J.; Hall, Gentzon; Bartkowiak, B.; Homstad, A.; Jiang, R.; Wu, G.; Byrd, A.; Lynn, Kelvin; Wolfish, Norman; Ottati, Carolina; Stevens, Paul; Howell, David; Conlon, Peter; Winn, Michelle P.

2011-01-01

362

Phenotypic characteristics of colo-rectal cancer in I1307K APC germline mutation carriers compared with sporadic cases  

OpenAIRE

The I1307K APC germline mutation is associated with an increased risk to colo-rectal cancer (CRC). Whether and to what extent the phenotype of CRC in mutation carriers differs from sporadic cases, remains unknown. To gain insight into this issue, we analysed 307 unselected Israeli patients with CRC, who were treated in a single medical centre, for harbouring the I1307K mutation. Twenty-eight mutation carriers (9.1%) were detected. Two of 28 mutation carriers (7.1%) and 93/277 (33.6%) of non-c...

Figer, A.; Shtoyerman-chen, R.; Tamir, A.; Geva, R.; Irmin, L.; Flex, D.; Theodor, L.; Sulkes, A.; Sadetzki, S.; Bar-meir, S.; Friedman, E.

2001-01-01

363

Creutzfeldt-Jakob Disease (CJD) with a Mutation at Codon 148 of Prion Protein Gene : Relationship with Sporadic CJD  

OpenAIRE

Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrPC) converts into its pathogenic isoform (PrPSc). While PrPC conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrPSc...

Pastore, Manuela; Chin, Steven S.; Bell, Karen L.; Dong, Zhiqian; Yang, Qiwei; Yang, Lizhu; Yuan, Jue; Chen, Shu G.; Gambetti, Pierluigi; Zou, Wen-quan

2005-01-01

364

Sporadic and familial pheochromocytomas are associated with loss of at least two discrete intervals on chromosome 1p.  

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Pheochromocytomas are tumors of the adrenal medulla originating in the chromaffin cells derived from the neural crest. Ten % of these tumors are associated with the familial cancer syndromes multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and rarely, neurofibromatosis type 1, in which germ-line mutations have been identified in RET, VHL, and NF1, respectively. In both the sporadic and familial form of pheochromocytoma, allelic loss at 1p, 3p, 17p, and 22q has been reported, yet the molecular pathogenesis of these tumors is largely unknown. Allelic loss at chromosome 1p has also been reported in other endocrine tumors, such as medullary thyroid cancer and tumors of the parathyroid gland, as well as in tumors of neural crest origin including neuroblastoma and malignant melanoma. In this study, we performed fine structure mapping of deletions at chromosome 1p in familial and sporadic pheochromocytomas to identify discrete regions likely housing tumor suppressor genes involved in the development of these tumors. Ten microsatellite markers spanning a region of approximately 70 cM (1pter to 1p34.3) were used to screen 20 pheochromocytomas from 19 unrelated patients for loss of heterozygosity (LOH). LOH was detected at five or more loci in 8 of 13 (61%) sporadic samples and at five or more loci in four of five (80%) tumor samples from patients with multiple endocrine neoplasia type 2. No LOH at 1p was detected in pheochromocytomas from two VHL patients. Analysis of the combined sporadic and familial tumor data suggested three possible regions of common somatic loss, designated as PC1 (D1S243 to D1S244), PC2 (D1S228 to D1S507), and PC3 (D1S507 toward the centromere). We propose that chromosome 1p may be the site of at least three putative tumor suppressor loci involved in the tumorigenesis of pheochromocytomas. At least one of these loci, PC2 spanning an interval of <3.8 cM, is likely to have a broader role in the development of endocrine malignancies. PMID:11156410

Benn, D E; Dwight, T; Richardson, A L; Delbridge, L; Bambach, C P; Stowasser, M; Gordon, R D; Marsh, D J; Robinson, B G

2000-12-15

365

Gene expression profiling in peripheral blood mononuclear cells from patients with sporadic amyotrophic lateral sclerosis (sALS)  

OpenAIRE

The aim of this study was to identify gene expression profiles in peripheral blood mononuclear cells (PBMCs) from sporadic amyotrophic lateral sclerosis (sALS) patients to gain insights into the pathogenesis of ALS. We found that upregulation of LPS/TLR4-signaling associated genes was observed in the PMBCs from sALS patients after short-term cultivation, and that elevated levels of gene expression correlated with degree of peripheral blood monocyte activation and plasma LPS levels in sALS. Si...

Zhang, Rongzhen; Hadlock, Kenneth G.; Do, Hien; Yu, Stephanie; Honrada, Ronald; Champion, Stacey; Forshew, Dallas; Madison, Catherine; Katz, Jonathan; Miller, Robert G.; Mcgrath, Michael S.

2011-01-01

366

Transposons and integrons in colistin-resistant clones of Klebsiella pneumoniae and Acinetobacter baumannii with epidemic or sporadic behaviour.  

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Multiple transposons, integrons and carbapenemases were found in Klebsiella pneumoniae colistin-resistant isolates as well as a genomic resistance island of the AbaR type in Acinetobacter baumannii colistin-resistant isolates from different hospitals from Buenos Aires City. PFGE analysis showed a polyclonal dissemination of antimicrobial resistance mechanisms among K. pneumoniae isolates, while in A. baumannii isolates the epidemic clone 1 from South America was found. Resistance determinants associated with horizontal gene transfer are contributing to the evolution to pandrug resistance in both epidemic and sporadic clones. PMID:22723256

Arduino, Sonia M; Quiroga, María Paula; Ramírez, María Soledad; Merkier, Andrea Karina; Errecalde, Laura; Di Martino, Ana; Smayevsky, Jorgelina; Kaufman, Sara; Centrón, Daniela

2012-10-01

367

Risk factors associated with sporadic salmonellosis in children: a case-control study in Lower Saxony, Germany, 2008-2011.  

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SUMMARY We conducted a case-control study based on 884 laboratory-confirmed sporadic Salmonella cases reported to the German infectious disease notification system. For controls, we recruited 510 rotavirus cases via the same system. Univariable and multivariable logistic regression analyses were performed separately for children aged 0-3 years and 4-14 years. In both age groups, the highest odds ratios (OR) were found for raw ground pork consumption [0-3 years: OR 8·6, 95% confidence interval (CI) 2·4-30·8; 4-14 years: OR 4·5, 95% CI 1·1-19]. Further risk factors were exposure to animals (OR 1·6, 95% CI 1·1-2·1), consumption of poultry (OR 1·5, 95% CI 1·1-2·1), food items containing eggs (OR 1·5, 95% CI 1·1-2) and black pepper (OR 1·7, 95% CI 1·1-3·5) in children aged 0-3 years, and consumption of uncooked pork sausage (OR 3·6, 95% CI 1·4-9·3) in children aged 4-14 years. This study highlights the significance of raw pork products ('Mett' in German) as risk factors for sporadic salmonellosis in children in Germany. PMID:24886979

Ziehm, D; Rettenbacher-Riefler, S; Kreienbrock, L; Campe, A; Pulz, M; Dreesman, J

2014-06-01

368

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

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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.

Feng Qi-Sheng

2007-07-01

369

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

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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

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

2014-04-01

370

The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status  

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Full Text Available The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%. Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048. No differences were found in recurrence-free survival (p = 0.161. The p53+/p21? combination was seen in 68% (n = 49, the p53+/p21+ combination in 32% (n = 23. Patients with p53+/p21? carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003. Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status.

Sefer Elezkurtaj

2011-03-01

371

Germline mutations and genotype-phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea.  

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The aim of our study was to assess the frequency of germline mutations and develop the genetic testing strategy in patients with apparently sporadic pheochromocytoma/paraganglioma (PPGL) in Korea. We included 53 patients diagnosed with non-syndromic PPGL without a family history of PPGLs in three referral centers from 2004 to 2011. Succinate dehydrogenase complex B (SDHB), SDHD, Von Hippel-Lindau (VHL), and rearranged during transfection (RET) genes were examined by direct sequencing and multiple ligation-dependent probe amplification. The study patients were composed of 26 men and 27 women, and mean age was 50.1?±?13.5?years. The frequency of germline mutations was 13.2% (7/53): RET (n?=?2), VHL (n?=?1), SDHB (n?=?2), and SDHD (n?=?2). Six of seven mutation carriers were diagnosed before the age of 50. One of two patients harboring an SDHB mutation had malignant PPGLs. One patient with multifocal head and neck paraganglioma (PGL) and pheochromocytoma (PHEO) carried a SDHD mutation. The carriers of germline mutations in patients with apparently sporadic PPGL were 13.2% in our study. We recommend genetic testing in patients below 50?years and SDHD genetic testing in patients with multifocal PPGLs. In malignant PPGLs, SDHB genetic testing may be performed. PMID:24134185

Kim, J H; Seong, M-W; Lee, K E; Choi, H J; Ku, E J; Bae, J H; Park, S S; Choi, S H; Kim, S W; Shin, Cs; Kim, S Y

2014-11-01

372

Common volume coherent and incoherent scatter radar observations of mid-latitude sporadic E-layers and QP echoes  

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Full Text Available Common-volume observations of sporadic E-layers made on 14-15 June 2002 with the Arecibo incoherent scatter radar and a 30MHz coherent scatter radar imager located on St. Croix are described. Operating in dual-beam mode, the Arecibo radar detected a slowly descending sporadic E-layer accompanied by a series of dense E-region plasma clouds at a time when the coherent scatter radar was detecting quasi-periodic (QP echoes. Using coherent radar imaging, we collocate the sources of the coherent scatter with the plasma clouds observed by Arecibo. In addition to patchy, polarized scattering regions drifting through the radar illuminated volume, which have been observed in previous imaging experiments, the 30MHz radar also detected large-scale electrostatic waves in the E-region over Puerto Rico, with a wavelength of about 30km and a period of about 10min, propagating to the southwest. Both the intensity and the Doppler shifts of the coherent echoes were modulated by the wave.

D. L. Hysell

2004-09-01

373

Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis.  

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Cerebral cavernous malformations (CCMs) are vascular lesions affecting the central nervous system. CCM occurs either sporadically or in an inherited, autosomal dominant manner. Constitutional (germline) mutations in any of three genes, KRIT1, CCM2 and PDCD10, can cause the inherited form. Analysis of CCM lesions from inherited cases revealed biallelic somatic mutations, indicating that CCM follows a Knudsonian two-hit mutation mechanism. It is still unknown, however, if the sporadic cases of CCM also follow this genetic mechanism. We extracted DNA from 11 surgically excised lesions from sporadic CCM patients, and sequenced the three CCM genes in each specimen using a next-generation sequencing approach. Four sporadic CCM lesion samples (36%) were found to contain novel somatic mutations. Three of the lesions contained a single somatic mutation, and one lesion contained two biallelic somatic mutations. Herein, we also describe evidence of somatic mosaicism in a patient presenting with over 130 CCM lesions localized to one hemisphere of the brain. Finally, in a lesion regrowth sample, we found that the regrown CCM lesion contained the same somatic mutation as the original lesion. Together, these data bolster the idea that all forms of CCM have a genetic underpinning of the two-hit mutation mechanism in the known CCM genes. Recent studies have found aberrant Rho kinase activation in inherited CCM pathogenesis, and we present evidence that this pathway is activated in sporadic CCM patients. These results suggest that all CCM patients, including those with the more common sporadic form, are potentially amenable to the same therapy. PMID:24698976

McDonald, David A; Shi, Changbin; Shenkar, Robert; Gallione, Carol J; Akers, Amy L; Li, Stephanie; De Castro, Nicholas; Berg, Michel J; Corcoran, David L; Awad, Issam A; Marchuk, Douglas A

2014-08-15

374

The human homologue of unc-93 maps to chromosome 6q27 - characterisation and analysis in sporadic epithelial ovarian cancer  

DEFF Research Database (Denmark)

In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To identify the putative tumour suppressor gene, we established a physical map initially with YACs and subsequently with PACs/BACs from D6S264 to D6S149. To accelerate the identification of genes, we sequenced the entire contig of approximately 1.1 Mb. Seven genes were identified within the region of allele loss between D6S264 and D6S149.

Liu, Ying; Dodds, Phillippa

2002-01-01

375

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

DEFF Research Database (Denmark)

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.

Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

2012-01-01

376

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

Science.gov (United States)

Creutzfeldt-Jakob disease (CJD) is the most common transmissible spongiform encephalopathy. It is an infectious, progressive, degenerative neurological disorder, with a presumably long incubation period, but a rapid fatal course. CJD is transmitted by a proteinaceous infectious agent, or «prion». Because the prions are difficult to eradicate and are resistant to the currently used sterilization methods, special precautions must be taken with all surgical instruments. It is recommended the single-use equipment, destruction of contaminated equipment, decontamination of reusable instruments, use of protective clothing, and storing and quarantining surgical instruments. The single-use equipment and some tissues and body fluids from the patient with CJD are highly infectious and must be incinerated. We report a case of a patient who had undergone brain biopsy for suspected of CJD, being confirmed to have sporadic CJD. Specific preventive measures were taken to reduce the risk of transmission to healthcare workers. PMID:25146772

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

2014-08-18

377

Epigenetic analysis of sporadic and Lynch-associated ovarian cancers reveals histology-specific patterns of DNA methylation.  

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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

Niskakoski, Anni; Kaur, Sippy; Staff, Synnöve; Renkonen-Sinisalo, Laura; Lassus, Heini; Järvinen, Heikki J; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

2014-12-01

378

Clinicopathologic and immunohistochemical correlation in sporadic pancreatic endocrine tumors: possible roles of utrophin and cyclin D1 in malignant progression.  

Science.gov (United States)

Pancreatic endocrine tumors (PETs), both functioning and nonfunctioning, are usually well differentiated and progress slowly. The 2004 World Health Organization (WHO) criteria classify PETs according to clinicopathologic features and Ki-67 proliferative index. A tumor associated with poorer prognostic features may be considered "uncertain" in behavior, but the malignant classifications are reserved for tumors showing clear signs of aggressive behavior. It remains difficult to predict malignant progression in any individual PET. The cytoskeletal protein utrophin is encoded on chromosome 6q, a region frequently lost in malignant PETs. Cyclin D1 is a highly regulated mediator of the cell cycle and is frequently overexpressed in sporadic PETs. Sporadic PETs resected or biopsied from 40 patients were identified and classified using WHO criteria (19 benign/uncertain, 21 malignant). Distinctive patterns of biologic activity in unequivocally malignant PETs were demonstrated by immunohistochemistry for utrophin and cyclin D1. Utrophin localized to cell membranes (76% in malignant versus 21% in benign/uncertain PETs, P < .0006) and cyclin D1 staining showed nuclear positivity (67% in malignant versus 17% in benign/uncertain PETs, P < .003). Membranous utrophin localization was associated with significantly reduced patient survival (P = .045). Both membranous utrophin and nuclear cyclin D1 staining were also associated with higher Ki-67 proliferative indices. In our series, neither utrophin nor cyclin D1 was predictive of malignant progression in uncertain (WHO 1.2) PETs. Further studies are warranted to elucidate the role of utrophin and cyclin D1 in the malignant progression of PETs. PMID:17306326

Chang, Martin C; Xiao, Sheng; Nosé, Vânia

2007-05-01

379

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

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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.

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

380

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

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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.

Rodríguez-Martínez Ana B

2012-10-01

381

Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds.  

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Patients with autosomal dominant (AD), sporadic and X-linked severe congenital neutropenia (SCN) may have mutations in the elastase 2 (ELA2) or Wiskott-Aldrich syndrome (WAS) genes. Homozygous mutations in the HAX1 gene have recently been reported in autosomal recessive (AR) cases of primarily Middle-Eastern descent and the original Kostmann family. We screened 109 predominantly Caucasian SCN kindreds for mutations in these genes; 33 (30%) had 24 different ELA2 mutations, five of them novel, two kindreds (2%) had WAS mutations and four kindreds (4%) had three different HAX1 mutations, two of them novel. One HAX1 mutation (p.Ser43LeufsX11) was found in an AR Ashkenazi Jewish kindred, the other (p.Glu31LysfsX54) in two unrelated British patients with sporadic disease. Microsatellite analysis of the HAX1 locus revealed a common haplotype (maximum distance 4.1 Megabases) for the p.Glu31LysfsX54 patients, suggesting a possible ancestral founder. In functional assays, the level of spontaneous and staurosporine-induced apoptosis was increased in neutrophils from both p.Ser43LeufsX11 patients but not a p.Glu31LysfsX54 patient, suggesting the possible presence of modifying factors. The low incidence of HAX1 mutations in our study suggests that the frequency may vary between racial groups but suggests that irrespective of inheritance or racial origin, SCN patients should be screened for HAX1 mutations. PMID:19036076

Smith, Bradley N; Ancliff, Phil J; Pizzey, Arnold; Khwaja, Asim; Linch, David C; Gale, Rosemary E

2009-03-01

382

Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma: results from the Netherlands cohort study  

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Full Text Available Abstract Background Biallelic von Hippel-Lindau (VHL gene defects, a rate-limiting event in the carcinogenesis, occur in approximately 75% of sporadic clear-cell Renal Cell Carcinoma (RCC. We studied the VHL mutation status in a large population-based case group. Methods Cases were identified within the Netherlands cohort study on diet and cancer, which includes 120,852 men and women. After 11.3 years of follow-up, 337 incident cases with histologically confirmed epithelial cancers were identified. DNA was isolated from paraffin material collected from 51 pathology laboratories and revised by one pathologist, leaving material from 235 cases. VHL mutational status was assessed by SSCP followed by direct sequencing, after testing SSCP as a screening tool in a subsample. Results The number of mutations was significantly higher for clear-cell RCC compared to other histological types. We observed 131 mutations in 114 out of 187 patients (61% with clear-cell RCC. The majority of mutations were truncating mutations (47%. The mean tumor size was 72.7 mm for mutated tumors compared to 65.3 mm for wildtype tumors (p = 0.06. No statistically significant differences were observed for nuclear grade, TNM distribution or stage. In other histological types, we observed 8 mutations in 7 out of 48 patients (15%, 1 mutation in 1 of 6 oncocytoma, 3 mutations in 2 of 7 chromophobe RCC, 2 mutations in 2 of 30 papillary RCC, no mutations in 1 collecting duct carcinoma and 2 mutations in 2 of 4 unclassified RCC. Conclusion VHL mutations were detected in 61% of sporadic clear-cell RCC. VHL mutated and wildtype clear-cell RCC did not differ with respect to most parameters.

Schalken Jack A

2005-06-01

383

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

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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

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

384

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)

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

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

385

KRAS mutation detection in Tunisian sporadic coloractal cancer patients with direct sequencing, high resolution melting and denaturating high performance liquid chromatography.  

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The Kirsten Rat Sarcoma (KRAS) oncogene has been introduced recently as a genetic biomarker for metastatic sporadic colorectal cancer prior to anti-EGFR treatment. Identifying patients with KRAS mutations that not respond to EGFR targeted therapies require sensitive, rapid and efficacious routine technique. We have attempted to evaluate the efficiency of three conventional methods: direct sequencing, HRM and DHPLC, to detect mutations in codon 12 and 13 of the KRAS exon2 gene. For this first Tunisian study on KRAS, we detected 45.83% of altered KRAS gene among 48 formalin-fixed paraffin-embedded sporadic colorectal adenocarcinoma patients. The use of HRM-sequencing allowed as enlarging the detected KRAS exon 2 mutations (22/48) in comparison with direct sequencing (17/48). DHPLC was used to confirm results when consensus was not observed between HRM and direct sequencing. This study brings an interesting data concerning an inter-method validation between sequencing and HRM in the investigation of sporadic colorectal cancer biomarker. It also shows that KRAS mutations occur at similar frequencies in Tunisian patients as in other populations; and suggests that the same genes are at play in sporadic CRC cancer, despite ethnic, geographical and environmental differences between countries. PMID:22072121

Karim, Bougatef; Florence, Coulet; Kamel, Rouissi; Nadia, Kourda; Ines, Omrane; Raja, Marrakchi; Sarra, Ben Jileni; Florent, Soubrier; Amel, Ben Ammar-Elgaaied

386

Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer  

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Genetic defects in breast cancer (BC) susceptibility genes, most importantly BRCA1 and BRCA2, account for ?40% of hereditary BC and ovarian cancer (OC). Little is known about the contribution of constitutive (soma-wide) epimutations to the remaining cases. We developed bisulfite pyrosequencing assays to screen >600 affected BRCA1/BRCA2 mutation-negative patients from the German Consortium for Hereditary Breast and Ovarian Cancer for constitutive hypermethylation of ATM, BRCA1, BRCA2, RAD51C, PTEN and TP53 in blood cells. In a second step, patients with ?6% promoter methylation were analyzed by bisulfite plasmid sequencing to demonstrate the presence of hypermethylated alleles (epimutations), indicative of epigenetic gene silencing. Altogether we identified nine (1.4%) patients with constitutive BRCA1 and three (0.5%) with RAD51C hypermethylation. Epimutations were found in both sporadic cases, in particular in 2 (5.5%) of 37 patients with early-onset BC, and familial cases, in particular 4 (10%) of 39 patients with OC. Hypermethylation was always confined to one of the two parental alleles in a subset (12–40%) of the analyzed cells. Because epimutations occurred in cell types from different embryonal layers, they most likely originated in single cells during early somatic development. We propose that analogous to germline genetic mutations constitutive epimutations may serve as the first hit of tumor development. Because the role of constitutive epimutations in cancer development is likely to be largely underestimated, future strategies for effective testing of susceptibility to BC and OC should include an epimutation screen. PMID:22843497

Hansmann, Tamara; Pliushch, Galyna; Leubner, Monika; Kroll, Patricia; Endt, Daniela; Gehrig, Andrea; Preisler-Adams, Sabine; Wieacker, Peter; Haaf, Thomas

2012-01-01

387

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)

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.

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

388

High resolution observations of sporadic-E layers within the polar cap ionosphere using a new incoherent scatter radar experiment  

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Full Text Available High resolution observations of sporadic-E layers using a new experiment with the EISCAT (European Incoherent SCATter Svalbard radar (ESR are presented. The observations were made by means of a new type of hardware, which was connected in parallel with the standard receiver. The radar beam was aligned with the geomagnetic field. The experiment applies a new modulation principle. Two phase codes, one with 22 bits and the other with 5 bits, were transmitted at separate frequencies. Each bit was further modulated by a 5-bit Barker code. The basic bit length of both transmissions was 6 µs. Instead of storing the lagged products of the ionospheric echoes in the traditional way, samples of both the transmitted pulses and the ionospheric echoes were taken at intervals of 1 µs and stored on hard disk. The lagged products were calculated later in an off-line analysis. In the analysis a sidelobe-free Barker decoding technique was used. The experiment produces range ambiguities, which were removed by mathematical inversion. Sporadic-E layers were observed at 105–115 km altitudes, and they are displayed with a 150-m range resolution and a 10-s time resolution. The layers show sometimes complex shapes, including triple peaked structures. The thickness of these sublayers is of the order of 1–2 km and they may be separated by 5 km in range. While drifting downwards, the sublayers merge together to form a single layer. The plasma inside a layer is found to have a longer correlation length than that of the surrounding plasma. This may be an indication of heavy ions inside the layer. The field-aligned ion velocity is also calculated. It reveals shears in the meridional wind, which suggests that shears probably also exist in the zonal wind. Hence the wind shear mechanism is a possible generation mechanism of the layer. However, observations from the coherent SuperDARN radar indicate the presence of an ionospheric electric field pointing in the sector between west and north. Thus, the layer could also be produced by the electric field mechanism. This means that both mechanisms may be active simultaneously. Their relative importance could not be determined in this study.

Key words. Ionosphere; polar ionosphere, instruments and techniques

B. Damtie

389

Fatores de risco na gagueira desenvolvimental familial e isolada / Risk factors in the familial and sporadic developmental stuttering  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese OBJETIVO: investigar e comparar os achados dos fatores de risco para a cronicidade da gagueira em crianças com gagueira desenvolvimental familial e isolada. MÉTODOS: participaram 60 crianças de ambos os gêneros, divididas em dois grupos: GI - 30 crianças com gagueira desenvolvimental familial; GII - [...] 30 crianças com gagueira desenvolvimental isolada. A coleta de dados foi realizada por meio do Protocolo de Risco para a Gagueira do Desenvolvimento - PRGD (Andrade, 2006), que considera os seguintes fatores de risco: idade, gênero, tipo de surgimento e tempo de duração das disfluências, tipologia das disfluências, fatores comunicativos e qualitativos associados, histórico mórbido pré, peri e pós natal, fatores estressantes que ocorreram próximo ao surgimento do distúrbio, histórico familial, reação pessoal, familiar e social e atitudes familiares. RESULTADOS: quando o grupo I (GI) foi comparado com o grupo II (GII), a única diferença estatisticamente significante foi com relação aos fatores estressantes que ocorreram próximo ao surgimento do distúrbio. CONCLUSÃO: os resultados confirmam a natureza complexa da gagueira, bem como a necessidade de se investigar os vários fatores considerados como de risco para o distúrbio, com intuito de melhorar a compreensão de suas possíveis etiologias. Abstract in english PURPOSE: to investigate and compare the risk factors for stuttering between children with familial developmental stuttering and children with sporadic developmental stuttering. METHODS: 60 children of both genders with stuttering took part, divided in two groups: GI - 30 children with familial devel [...] opmental stuttering; GII - 30 children with sporadic developmental stuttering. Data were gathered through the Protocol of Risk for the Developmental Stuttering - PRGD (Andrade, 2006), which considers the following factors: age; gender; manner of onset and time of duration for the disfluencies; typology of the disfluencies; associated communicative and qualitative factors; physical and emotional stress; family history concerning stuttering; personal, familiar and social reaction, and familiar attitudes. RESULTS: when Group I (GI) was compared to Group II (GII), the only statically difference was related to emotional stress that occurred near the onset of the disorder. CONCLUSION: the results confirm the complexity of stuttering, as well as the need for investigating the risk factors for this disorder in order to improve the understanding of its possible etiologies.

Cristiane Moço Canhetti de, Oliveira; Heloisa Aparecida de, Souza; Ana Claudia dos, Santos; Denise, Cunha; Célia Maria, Giacheti.

2011-04-01

390

Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas suggest a common pathway to tumorigenesis  

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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.

Hogendoorn Pancras CW

2009-05-01

391

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

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Full Text Available Abstract Background- Sporadic breast cancer like many other cancers is proposed to be a manifestation of abnormal genetic and epigenetic changes. For the past decade our laboratory has identified genes involved in DNA damage response (DDR, apoptosis and immunesurvelliance pathways to influence sporadic breast cancer risk in north Indian population. Further to enhance our knowledge at the epigenetic level, we performed DNA methylation study involving 17 gene promoter regions belonging to DNA damage response (DDR and death receptor apoptotic pathway in 162 paired normal and cancerous breast tissues from 81 sporadic breast cancer patients, using a high throughput quantitative DNA methylation analysis technology. Results- The study identified five genes with statistically significant difference between normal and tumor tissues. Hypermethylation of DR5 (P = 0.001, DCR1 (P = 0.00001, DCR2 (P = 0.0000000005 and BRCA2 (P = 0.007 and hypomethylation of DR4 (P = 0.011 in sporadic breast tumor tissues suggested a weak/aberrant activation of the DDR/apoptotic pathway in breast tumorigenesis. Negative correlation was observed between methylation status and transcript expression levels for TRAIL, DR4, CASP8, ATM, CHEK2, BRCA1 and BRCA2 CpG sites. Categorization of the gene methylation with respect to the clinicopathological parameters showed an increase in aberrant methylation pattern in advanced tumors. These uncharacteristic methylation patterns corresponded with decreased death receptor apoptosis (P = 0.047 and DNA damage repair potential (P = 0.004 in advanced tumors. The observation of BRCA2 -26 G/A 5'UTR polymorphism concomitant with the presence of methylation in the promoter region was novel and emerged as a strong candidate for susceptibility to sporadic breast tumors. Conclusion- Our study indicates that methylation of DDR-apoptotic gene promoters in sporadic breast cancer is not a random phenomenon. Progressive epigenetic alterations in advancing tumors result in aberrant DDR-apoptotic pathway thereby promoting tumor development. We propose, since pathological epigenetic changes of the DDR-apoptotic genes are reversible modifications, these could further be targeted for therapeutic interventions.

Prakash Neeraj

2010-11-01

392

Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis  

OpenAIRE

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 ...

Matsuzaki, K.

2006-01-01

393

Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy.  

Science.gov (United States)

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

Askanas, Valerie; Engel, W King; Nogalska, Anna

2015-04-01

394

Orbital sporadic Burkitt lymphoma in an adult diabetic African American female and a review of adult orbital cases  

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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

Carmody J

2011-04-01

395

Is the mean blood leukocyte telomere length a predictor for sporadic thoracic aortic aneurysm? Data from a preliminary study.  

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Telomeres have been postulated as a universal clock that shortens in parallel with cellular aging. They are specialized DNA-protein structures at the ends of chromosome with remarkable functions--preventing their recognition as double-stranded DNA breaks, protecting their recombination and degradation, and avoiding a DNA damage cellular response. Telomere shortening is currently considered the best aging marker, but is also a predictor for age-related diseases, including cardiovascular diseases. Biological age clearly seems to be a better predictor of vascular risk rather than chronological age. This concept is supported by key assumptions that peripheral blood leukocyte telomere content accurately reflects that of the vascular wall and its decrease is associated with premature vascular disease. Thus, we are analyzing whether the mean of blood leukocyte telomere length might also be a predictor for sporadic thoracic aortic aneurysm (S-TAA). The preliminary results seem to be promising. Shorter telomeres were detected in patients than in controls. Thus, mean of blood leukocyte telomere length could contribute to identify individuals at S-TAA risk. PMID:22533425

Balistreri, Carmela Rita; Pisano, Calogera; Merlo, Daniele; Fattouch, Khalil; Caruso, Marco; Incalcaterra, Egle; Colonna-Romano, Giuseppina; Candore, Giuseppina

2012-04-01

396

Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease.  

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Peptidylarginine deiminases (PADs)-mediated post-translational citrullination processes play key roles in protein functions and structural stability through the conversion of arginine to citrulline in the presence of excessive calcium concentrations. In brain, PAD2 is abundantly expressed and can be involved in citrullination in disease. Recently, we have reported pathological characterization of PAD2 and citrullinated proteins in scrapie-infected mice, but the implication of protein citrullination in the pathophysiology in human prion disease is not clear. In the present study, we explored the molecular and biological involvement of PAD2 and the pathogenesis of citrullinated proteins in frontal cortex of patients with sporadic Creutzfeldt-Jakob disease (sCJD). We found increased expression of PAD2 in reactive astrocytes that also contained increased levels of citrullinated proteins. In addition, PAD activity was significantly elevated in patients with sCJD compared to controls. From two-dimensional gel electrophoresis and MALDI-TOF mass analysis, we found various citrullinated candidates, including cytoskeletal and energy metabolism-associated proteins such as vimentin, glial fibrillary acidic protein, enolase, and phosphoglycerate kinase. Based on these findings, our investigations suggest that PAD2 activation and aberrant citrullinated proteins could play a role in pathogenesis and have value as a marker for the postmortem classification of neurodegenerative diseases. PMID:20013286

Jang, Byungki; Jin, Jae-Kwang; Jeon, Yong-Chul; Cho, Han Jeong; Ishigami, Akihito; Choi, Kyung-Chan; Carp, Richard I; Maruyama, Naoki; Kim, Yong-Sun; Choi, Eun-Kyoung

2010-02-01

397

Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance.  

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Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We then set out to determine the relative occurrence of sporadic and familial cases and to examine the likelihood of having seizures for individuals with the microdeletion in familial cases. The 15q13.3 microdeletion was identified in 7 of 539 (1.3%) unrelated cases of IGE using quantitative PCR or SNP arrays and confirmed by array comparative genomic hybridization analysis using probes specific to the 15q13.3 region. The inheritance of this lesion was tracked using family studies. Of the seven microdeletions identified in probands, three were de novo, two were transmitted from an unaffected parent and in two cases the parents were unavailable. Non-penetrance of the microdeletion was identified in 4/7 pedigrees and three pedigrees included other family members with IGE who lacked the 15q13.3 deletion. The odds ratio is 68 (95% confidence interval 29-181), indicating a pathogenic lesion predisposing to epilepsy with complex inheritance and incomplete penetrance for the IGE component of the phenotype in multiplex families. PMID:19592580

Dibbens, Leanne M; Mullen, Saul; Helbig, Ingo; Mefford, Heather C; Bayly, Marta A; Bellows, Susannah; Leu, Costin; Trucks, Holger; Obermeier, Tanja; Wittig, Michael; Franke, Andre; Caglayan, Hande; Yapici, Zuhal; Sander, Thomas; Eichler, Evan E; Scheffer, Ingrid E; Mulley, John C; Berkovic, Samuel F

2009-10-01

398

Autosomal Recessive and Sporadic Non Syndromic Hearing Loss and the Incidence of Cx26 Mutations in a Province of Iran  

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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.

M Hashemzadeh Chaleshtori

2006-05-01

399

Molecular determination of infection source of a sporadic Legionella pneumonia case associated with a hot spring bath.  

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To determine the infection source of a sporadic Legionella pneumonia case associated with a hot spring bath, we used five molecular methods, including repetitive element polymerase chain reaction (rep-PCR), arbitrarily primed PCR (AP-PCR), ribotyping, restriction endonuclease analysis (REA), and macrorestriction endonuclease analysis (MREA) by pulsed-field gel electrophoresis. L. pneumophila serogroup (SG) 3 strain EY 3702, isolated from an intratracheal specimen of a 71-year-old Japanese female who developed pneumonia after nearly drowning in a hot spring spa bath, produced rep-PCR and AP-PCR fingerprints identical to those of L. pneumophila SG 3 strains EY 3768 and EY 3769 isolated from the bath water. Four epidemiologically unrelated L. pneumophila SG 3 strains showed different rep-PCR or AP-PCR fingerprints from those of the three EY strains (EY 3702, 3768, and 3769). The three EY strains were also genotypically indistinguishable by ribotyping with EcoRI and PstI, by REA with EcoRI or HindIII, and by MREA with NotI. Based on these results, we identified the bath water of the hot spring spa as the source of infection of this patient, even though the viable number of the organisms in the bath water was low (3 CFU/100 ml) when determined 27 days after her nearly drowning. PMID:9130230

Miyamoto, H; Jitsurong, S; Shiota, R; Maruta, K; Yoshida, S; Yabuuchi, E

1997-01-01

400

The association of single nucleotide polymorphism of the Fyn gene with sporadic Alzheimer's disease in the Chinese Han population.  

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Recent studies suggested genetic factors contribute to the pathogenesis of sporadic Alzheimer's disease (sAD). Fibroblast Yes related novel (Fyn), a tau kinase, has been reported to be associated with aberrant phosphorylated tau and neurofibrillary tangles formation. Fyn gene may be a potential candidate gene for AD. To investigate the association of the polymorphisms in Fyn gene with the susceptibility to sAD, we conducted a case-control study in a Chinese Han cohort including 200 sAD patients and 243 control participants. Four single nucleotide polymorphisms (SNPs) (rs111787668, rs1057979, rs6916861 and rs12910) within the promoter region of Fyn gene and one (rs7768046) in intron were selected and genotyped with a polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Logistic regression under four genetic models was used to analyze the association between target SNPs and the risk of sAD. After adjusting for age, sex and APOE ?4 status, no association was revealed between these SNPs or the haplotypes containing four SNPs and the risk of sAD (P>0.05). The SNPs in the selected regions of the Fyn gene are unlikely to confer the susceptibility of sAD in the Chinese Han population. Further studies with a larger sample size and different ethnic populations are needed to reveal the role of Fyn gene in the pathogenesis of sAD. PMID:24852829

Li, Jing; Zhou, Hua-Dong; Deng, Juan; Zhu, Jie; Li, Lin; Zhang, Meng; Zeng, Fan; Wang, Yan-Jiang

2014-07-11

401

Clinical and biological changes under treatment with lithium carbonate and valproic acid in sporadic amyotrophic lateral sclerosis.  

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The aim of this study was to evaluate the ability of lithium carbonate and valproate cotreatment to modify the survival rate and functional score of patients with definite sporadic amyotrophic lateral sclerosis (ALS). The clinical response of 18 enrolled patients was compared to the evolution of 31 ALS out-patients, carefully paired by age, gender, evolution rate and time of the disease, who never received treatment with lithium and/or valproate. The ALS functional rating scale, revised version (ALSFRS-R), was applied at baseline, 1 month, and every 4 months until the outcome (death or an adverse event). Biochemical markers, such as Cu/Zn superoxide dismutase and glutathione peroxidase activity, and reduced glutathione were assayed in plasma samples obtained at the baseline visit and after 5 and 9 months of treatment. Our results showed that lithium and valproate cotreatment significantly increased survival (p=0.016), and this treatment also exerted neuroprotection in our patients because all three markers reached levels that were not significantly different from the matched samples of healthy donors. The trial stopped after 21 months, when the sample was reduced to under two-thirds, due to the late adverse events of the treatment. The results call for large randomized clinical trials with the dual association, but at low doses to avoid adverse events. PMID:24667005

Boll, Marie-Catherine; Bayliss, Leo; Vargas-Cañas, Steven; Burgos, Jorge; Montes, Sergio; Peñaloza-Solano, Guillermo; Rios, Camilo; Alcaraz-Zubeldia, Mireya

2014-05-15

402

Sporadic haemangioblastoma of the kidney with rhabdoid features and focal CD10 expression: report of a case and literature review  

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Full Text Available Abstract We present here an intriguing case of sporadic renal haemangioblastoma occurring in a 61-year-old male. The tumor consisted of nests of polygonal cells and abundant capillary networks. The neoplastic cells generally showed abundant eosinophilic cytoplasm and prominent eccentric nuclei, resembling the rhabdoid cells. Pronounced intranuclear cytoplasmic pseudoinclusions were another significant feature seen. NSE, a-inhibin and S100 were positive in tumor cells and particularly, focal CD10 expressions were observed. This is possibly the first reported case of a haemangioblastoma showing a rhabdoid phenotype and CD10 immunopositivity. Malignant rhabdoid tumor and renal cell carcinoma with rhabdoid features were probably the most challenging mimics need to be differentiated. The result of focal CD10 staining in our case may further lead to confusion with renal cell carcinoma. To avoid misdiagnosis, more considerations should be attached to the rare neoplasm. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1068858553657049

Yin Wei-hua

2012-04-01

403

The Doppler observations of the night sporadic E- layer during the sunrise passage at the magnetic conjugated atmosphere.  

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There are some new evidences of the observed relationship between the night ionosphere disturbances and sunrise at the conjugate point. Here we present the results of the experimental research of the plasma motion and variations of the night-time ionospheric Es layer by the Doppler sounding (along with the total electron content measurements) during the winter solstice at northern ionosphere. Doppler measurements in a mode of vertical sounding simultaneously on the four frequencies were carried out by the IZMIRAN (Moscow, the latitude of 55°N) ionospheric facility "Bazis-M". To have the total electron content variations (TEC) the data of GPS net were used. The data analysis has shown that during the night-time (from 03 to 06 LT) the Es signal amplitude increase was about 10 - 15 dB and it was proportional to the growth of the plasma electron density. The Doppler measurements have shown the horizontal drifts (more than 10 m/sec) and upward movements of the sporadic plasma clouds. The TEC measurements have indicated a complex behavior of the night ionosphere during the sunrise passage in the opposite hemisphere. Being combined these data definitely support the hypothesis (Abramchuk @ Ruzhin, 1987) about partially reflected downward propogating Alfven waves that were generated in the magnetic conjugated ionosphere by the turbulence of the supersonic terminator motion.

Ruzhin, Y. Ya.; Kim, V. Yu.; Panchenko, V. A.; Polimatidi, V. P.; Bershadskaya, I. N.; Shagimuratov, I. I.; Shpakovsky, V. V.

2009-04-01

404

Global distribution of the migrating terdiurnal tide seen in sporadic E occurrence frequencies obtained from GPS radio occultations  

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Global Positioning System radio occultation measurements by FORMOsa SATellite mission-3/Constellation Observing System for Meteorology, Ionosphere and Climate satellites were used to analyse the characteristics of the 8-h oscillation in sporadic E (ES) layers. Six-year averages based on the 3-monthly mean zonal means from December 2006 to November 2012 were constructed for the amplitude of the terdiurnal oscillation in the occurrence frequency of ES. A global distribution from 60° S to 60° N is given, revealing two peaks above 100 km during solstice with one maximum at low and midlatitudes (approximately 10° to 40°) in each hemisphere. During equinox, the global distribution is marked by two dominant peaks centred at midlatitudes, while an additional weak maximum is located at very low southern latitudes. The seasonal characteristics around 110 km reveal large values during equinox at low and midlatitudes (40° S and in July near 30° S. The pattern around 90 km is dominated by a broad peak between 20° and 30° S from March to September. Comparisons with the terdiurnal oscillation in the neutral atmosphere derived from zonal wind and vertical zonal wind shear simulated with a circulation model of the middle atmosphere, as well as with satellite observations of the terdiurnal tide in temperature, fit quite well for the results above 100 km, but do not show agreement for lower altitudes.

Fytterer, Tilo; Arras, Christina; Hoffmann, Peter; Jacobi, Christoph

2014-12-01

405

Vascular changes in sporadic ergotism. Epidemiology, pathogenesis, clinical practice, and diagnosis with special regard to angiographic documentation  

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Whereas the epidemic form of ergotism has been rare in the 20th century, the sporadic form has a wide distribution as a consequence of therapy with ergot-derivative drugs. Favourable prognosis of the condition, with complete recovery from the ischemic peripheral circulatory disorders can be obtained by early diagnosis. Precise evaluation of the history, with recognition of treatment of migraine headache or postpartum hemorraghe with ergot alkaloids, can be determinative in diagnosis. The specific pattern of the angiographic findings, as we saw it in 6 cases within the last 4 years, decisively confirms the diagnosis. We could demonstrate thread-, thorn- and hour glass-like narrowing of the vessels, due to spasm. Total occlusion with the development of collaterals may occur, but we saw no thrombus formation. The stenotic arterial segments had smooth margins. The distribution of the involved arteries was more focal than generalized and more peripheral than central. In two cases spasm could be abolished immediately by a pharmaceutical (i.a. injection of tolazoline) or by anesthetic procedures (halothane). The phenomenologic data, together with the complete reversal of the circulatory ischemic disorders after therapy (particularly the absolute ban of ergots), is so specific that other diseases of ischemic nature (emboli, arteriosclerosis, Buerger's disease, fibromuscular hyperplasia) can be excluded.

Hagen, B.

1986-08-01

406

Sporadic distribution and distinctive variations of cylindrospermopsin genes in cyanobacterial strains and environmental samples from chinese freshwater bodies.  

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Increasing reports of cylindrospermopsins (CYNs) in freshwater ecosystems have promoted the demand for identifying all of the potential CYN-producing cyanobacterial species. The present study explored the phylogenetic distribution and evolution of cyr genes in cyanobacterial strains and water samples from China. Four Cylindrospermopsis strains and two Raphidiopsis strains were confirmed to produce CYNs. Mutant cyrI and cyrK genes were observed in these strains. Cloned cyr gene sequences from eight water bodies were clustered with cyr genes from Cylindrospermopsis and Raphidiopsis (C/R group) in the phylogenetic trees with high similarities (99%). Four cyrI sequence types and three cyrJ sequence types were observed to have different sequence insertions and repeats. Phylogenetic analysis of the rpoC1 sequences of the C/R group revealed four conserved clades, namely, clade I, clade II, clade III, and clade V. High sequence similarities (>97%) in each clade and a divergent clade IV were observed. Therefore, CYN producers were sporadically distributed in congeneric and paraphyletic C/R group species in Chinese freshwater ecosystems. In the evolution of cyr genes, intragenomic translocations and intergenomic transfer between local Cylindrospermopsis and Raphidiopsis were emphasized and probably mediated by transposases. This research confirms the existence of CYN-producing Cylindrospermopsis in China and reveals the distinctive variations of cyr genes. PMID:24928879

Jiang, Yongguang; Xiao, Peng; Yu, Gongliang; Shao, Jihai; Liu, Deming; Azevedo, Sandra M F O; Li, Renhui

2014-09-01

407

Genotyping of outbreak-associated and sporadic Yersinia pseudotuberculosis strains by novel multilocus variable-number tandem repeat analysis (MLVA).  

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Yersinia pseudotuberculosis human infections caused by serotype O:1 and O:3 isolates have been common in Finland and have also caused outbreaks. Epidemiological studies on the outbreaks have been limited by the lack of accurate typing methods. During the recent years, multilocus variable-number tandem repeat analysis (MLVA) has been successfully applied for molecular typing of several bacterial pathogens. We designed an MLVA scheme based on seven loci for Y. pseudotuberculosis. The method was able to discriminate clinical isolates of serotypes O:1 and O:3 into several MLVA types. The MLVA profiles were based on the number of 6 to 9 bp long tandem repeats in each locus. The number of repeats varied from 1 to 23 depending on the locus. The loci were all located in the bacterial chromosome for stability of the markers. The MLVA method developed was serotype-specific and will be a new additional tool for the epidemiological investigations of isolates associated with disease outbreaks and for comparison of sporadic isolates. PMID:24050949

Halkilahti, Jani; Haukka, Kaisa; Siitonen, Anja

2013-11-01

408