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1

The relative effects of electric fields and neutral winds on the formation of the equatorial sporadic E layer  

International Nuclear Information System (INIS)

This paper deals with an extension of the theory of mid-latitude blanketing sporadic E layer formation to the same phenomenon observed close to the geomagnetic equator. Generally the effect of the equatorial electrojet alone is considered for studying the sporadic E layer at the equator. The mid-latitude blanketing sporadic E, on the other hand, has been explained by the neutral wind shear theory. In the present study, a theory is developed to take account of both the electric field and the neutral wind effects. Models of the relevant parameters, both empirical and observational, have been used to solve the coupled equations of continuity and motion for a series of dip angles, ranging from 0.50 to 200. The effects of the electric field and the neutral wind are comparable within the range +-10. However, for angles greater than 10 the neutral wind effects become dominant and the effect of the electric field falls off rapidly

2

Solar eclipse effects of 22 July 2009 on Sporadic-E  

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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

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

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Venous malformations (VMs) are among the most common slow-flow vascular malformations characterized by irregular venous channels, luminal thrombi, and phleboliths. To systematically manifest the disorganized vascular structures in sporadic VMs, we initially evaluated histopathological characteristics, perivascular cell coverage, adhesion molecules expression and vascular ultrastructures. Then, the expression of Tie2 and TGF-? in VMs was detected. Meanwhile, the in vitro studies were performed for mechanism investigation. Our data showed that the perivascular ?-SMA(+) cell coverage and expression of adhesion molecules in VMs were significantly decreased compared with those in the normal skin tissues. We also found that the expression and phosphorylation levels of Tie2 were upregulated, whereas TGF-? was downregulated in VMs, and they were negatively correlated. Moreover, the in vitro results also revealed a possible balancing effect between Tie2 and TGF-?, as demonstrated by the findings that Ang-1 (agonist of Tie2) treatment significantly downregulated TGF-? expression, and treatment with recombinant TGF-? could also suppress Tie2 expression and phosphorylation. This study provided strong evidence supporting the disorganized vascular structures and dysregulation of related molecules in sporadic VMs, and demonstrated a possible balancing effect between Tie2 and TGF-?, which might help to develop novel therapeutics for vascular disorganization-related disorders. PMID:24966004

Chen, Gang; Ren, Jian-Gang; Zhang, Wei; Sun, Yan-Fang; Wang, Feng-Qin; Li, Rui-Fang; Zhang, Jian; Zhao, Yi-Fang

2014-01-01

4

Introduction to Sporadic Groups  

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

Luis J. Boya

2011-01-01

5

Introduction to Sporadic Groups  

CERN Document Server

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

Boya, Luis J

2011-01-01

6

Sporadic Ataxia and Multiple System Atrophy (MSA)  

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What is sporadic ataxia? Sporadic ataxia is a term designating a group of diseases of the central nervous system that occur without evidence ... or ILOCD) What are the symptoms of sporadic ataxia? Difficulty with balance and incoordination of the legs ...

7

Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenase of rat brain in vitro: relevance to sporadic Alzheimer's disease?  

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Lead is known to be a potent inhibitor of many enzymes working in the brain, thus possibly inducing functional problems in the brain under pathophysiological conditions. Among such enzymes are those involved in glucose metabolism and energy production. We investigated the inhibitory effects of low-level lead on brain hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and pyruvate dehydrogenase complex (PDHc) with rat brain homogenate. PDHc was distinctively inhibited when low-dose lead acetate was added last of all (IC50 = 5 microM) to the reaction mixture. The other enzymes were completely resistant to 5 microM of lead acetate. When the homogenate was preincubated with lead acetate HK was dramatically inhibited by low-level lead acetate (1-5 microM), in a manner dependent on both preincubation time and lead concentration. However, the inhibitory effect was abolished by coincubation with its substrates, glucose or ATP. The results suggest that exposure to low levels of lead may increase the risk of cerebral hypometabolism caused by direct inhibition of specific glucose-utilizing enzymes. In this context, lead might be regarded as a risk factor in the abnormal glucose metabolism seen in some kinds of neurodegenerative disorders such as sporadic Alzheimer's disease. PMID:10821444

Yun, S W; Hoyer, S

2000-01-01

8

Vertex operators and sporadic groups  

CERN Document Server

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

Duncan, John F

2008-01-01

9

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

10

Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort  

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Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer. PMID:24587289

Wang, Zhen; Tan, Huilian; Kong, Xianghua; Shu, Yang; Zhang, Yuchao; Huang, Yun; Zhu, Yufei; Xu, Heng; Wang, Zhiqiang; Wang, Ping; Ning, Guang; Kong, Xiangyin; Hu, Guohong; Hu, Landian

2014-01-01

11

Dynamical Model for the Toroidal Sporadic Meteors  

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More than a decade of radar operations by the Canadian Meteor Orbit Radar have allowed both young and moderately old streams to be distinguished from the dispersed sporadic background component. The latter has been categorized according to broad radiant regions visible to Earth-based observers into three broad classes: the helion and anti-helion source, the north and south apex sources, and the north and south toroidal sources (and a related arc structure). The first two are populated mainly by dust released from Jupiter-family comets and new comets. Proper modeling of the toroidal sources has not to date been accomplished. Here, we develop a steady-state model for the toroidal source of the sporadic meteoroid complex, compare our model with the available radar measurements, and investigate a contribution of dust particles from our model to the whole population of sporadic meteoroids. We find that the long-term stable part of the toroidal particles is mainly fed by dust released by Halley type (long period) comets (HTCs). Our synthetic model reproduces most of the observed features of the toroidal particles, including the most troublesome low-eccentricity component, which is due to a combination of two effects: particles' ability to decouple from Jupiter and circularize by the Poynting-Robertson effect, and large collision probability for orbits similar to that of the Earth. Our calibrated model also allows us to estimate the total mass of the HTC-released dust in space and check the flux necessary to maintain the cloud in a steady state.

Pokorný, Petr; Vokrouhlický, David; Nesvorný, David; Campbell-Brown, Margaret; Brown, Peter

2014-07-01

12

Antigliadin antibody in sporadic adult ataxia  

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Background The most common neurologic manifestation of gluten sensitivity is ataxia, which accounts for up to 40% of idiopathic sporadic ataxia. Timing of diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia and causes irreversible loss of Purkinje cells. Antigliadin antibody (AGA) of the IgG type is the best marker for neurological manifestations of gluten sensitivity. This study was conducted to measure the prevalence of gluten ataxia in a group of Iranian patients with idiopathic ataxia. Methods For 30 patients with idiopathic cerebellar ataxia, a questionnaire about clinical and demographic data was completed. Serum AGA (IgA and IgG) and antiendomysial antibody (AEA) were assessed. Gluten ataxic patients underwent duodenal biopsy. Magnetic resonance imaging was done for all patients to see if cerebellar atrophy is present. Results Only 2 patients had a positive IgG AGA (6.7%) who both had a positive AEA while none of them showed changes of celiac disease in their duodenal biopsies. Only presence of gastrointestinal symptoms and pursuit eye movement disorders were higher in patients with gluten ataxia. Conclusion Prevalence of gluten ataxia in Iranian patients with idiopathic ataxia seems to be lower than most of other regions. This could be explained by small sample size, differences in genetics and nutritional habits and also effect of serologic tests in clinical versus research setting. Further researches with larger sample size are recommended. PMID:24250853

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

2012-01-01

13

Analysis of standing wave patterns in VLF transmitter signals: Effects of sporadic E layers and in situ measurements of low electron density  

International Nuclear Information System (INIS)

An analysis of standing waver patterns formed by the reflection of VLFtransmitter signals incident upon a sporadi E layer is presented. The patterns were detected by electric field sensors on a sounding rocket designed to study the upward propagation of lightning-induced electric fields. To model the measured standing wave patterns it was necessary to have an accurate electron density profile. However, it has always been difficult to make accurate measurements of the low electron densities in the nighttime D and E regions. They devise a unique method to determine the electron concentration from the measured vertical wavelength of the standing wave patterns. The data from this analysis are then used to calibrate Langmuir probe measurements which, in turn, give a reasonable (but not perfect) electron density profile to use for full-wave modeling of the transmitter signals. This analysis yields several interesting characteristics, including the possibility that some energy is trapped in the sporadic E layer. The amplitude-versus-frequency characteristics of upgoing electromagnetic waves are also modeled. It is discovered that a sporadic E layer can act as a half-wave window at appropriate frequencies. A method for using VLF signals to measure electron densities without the existence of a standing wave pattern is also derived. Such a method is ideally suited for measuring the low electron densities in the nighttime D and E regions

14

Tramadol Use in Premature Ejaculation: Daily Versus Sporadic Treatment  

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Aim: Premature ejaculation (PME) is defined as ejaculation with the minimal sexual stimulation before, on or shortly after penetration and or before a person wishes it. It is a function of the time between intra-vaginal penetration and intra-vaginal ejaculation. Tramadol has shown efficacy in PME when used as sporadic basis. In this study, we compared the use of 100 mg of tramadol as sporadic treatment (administered 6-8 h before coitus) versus continued treatment with the objective of evaluating the therapeutic results of both modalities. We assumed our alternative hypothesis that they have similar effects. Materials and Methods: A prospective study was carried out on 60 patients divided into two groups of 30 patients each. Intra-vaginal ejaculation latency time (IELT) and coital frequency were measured both prior to and after the treatment. Group A received tramadol 100 mg daily for 4 weeks and on request (sporadically) for 4 weeks more. Group B was given placebo in the same manner. Results were statistically analyzed using the Student t-test. Results: Mean IELT prior to treatment was 59.2 s in Group A and 58.7 s in Group B. Mean pre-treatment coital frequency was 2.44 times/week for Group A and 2.13 times/week for Group B. Mean IELT was 202.5 s after continued tramadol treatment and 238.2 s after sporadic treatment in Group A. Mean IELT with daily placebo was 94.8 s and with sporadic placebo was 96.6 s. Coital frequency increased to 4.32 times/week with daily tramadol treatment and 4.86 times with sporadic treatment. Coital frequency increased to 2.88 times/week with daily placebo treatment and 3.23 times with sporadic treatment. Conclusions: The results of PME treatment with tramadol are similar with both continued and sporadic administration. The sex life of patients improved and they reported greater satisfaction with the sporadic treatment. PMID:24249927

Khan, Amil H.; Rasaily, Deepa

2013-01-01

15

Midlatitude Sporadic E Layers: Physical mechanisms and observational characteristics  

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The sporadic E and its abbreviation Es refer to rather thin layers of metallic ions which form in the dynamo region of the Earth’s ionosphere, mostly between 100 and 130 km, where ion motion is controlled by collisions with the neutrals, making them move with the local winds, while electrons are strongly magnetized. The physics of sporadic E relies on the Windshear theory, in which vertical shears in the horizontal wind can form layers of long-lived metallic ions through the combined action of ion-neutral collisional coupling and geomagnetic Lorentz forcing. Once formed, the layers tend to gradually descend with time downwards below 100 km where they eventually disappear because of 3-body recombination that becomes increasingly effective in depleting them of their plasma. This is a comprehensive presentation on sporadic E, a topic which has been researched extensively over many decades. First, it reviews the basics of windshear theory and its plasma convergence mechanisms and then updates our physical understanding through a synthesis of key observational characteristics and findings. The emphasis is placed on the wind shear control of the diurnal and sub-diurnal variability and altitude descent of sporadic E layers and the key role behind this of atmospheric tides, which also drive the formation of upper E region descending intermediate layers (IDL). The evidence suggests that IDLs constitute an integral part within a broader sporadic E layer system. The presentation summarizes observations that establish a role also for the planetary waves which, through the modulation of tides, affect sporadic E layer occurrence and longer-term variability. In addition, findings are presented that provide a better physical insight in relation with the seasonal dependence and the global occurrence of sporadic E layers. The observational facts imply that sporadic E is controlled macroscopically mostly by tidal and planetary wind atmospheric dynamics, the Earth’s magnetic field and the mean meteoric deposition. Finally, traces of sporadic E in altitude and time may help evaluate and validate neutral wind model predictions in the lower thermosphere.

Haldoupis, Christos

16

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

17

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

18

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.)

19

/ 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.

20

Medullary thyroid carcinoma: Sporadic, hereditary  

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Full Text Available Medullary thyroid cancer (MTC is uncommon thyroid tumor with specific characteristics which undoubtedly divide this tumor from other thyroid malignances. Patients with sporadic or hereditary form of MTC differ in clinical presentation, recurrence of the disease and outcome. The aim of study was to establish surgical characteristics of MTC as well as clinical factors that influence surgical treatment. The study group consisted of 68 patients with MTC managed at the Center for Endocrine Surgery between 1987. and 1999. Retrospective analysis included clinical form of the disease, general data, histological and other tumor characteristics. Mean age of the patients were 47.3 years (female/male ratio: 1.5:1. Mean size of tumor was 80.5 cm3, 72.1% patients had tumor greater than 4 cm. in diameter or extrathyroid spread. The majority of patients were in II and III stadium of the disease. Primary operation (at least total thyroidectomy was performed in 57 (84% patients. 2(3% had postoperatively temporally nerve palsy and 7(10.29% temporally hypoparathyroidism. The overall survival was 46.8 + 9.9% after 9 years and 63.6 + 7.2% at 5 years. Postoperative calcitonin value is significant predictor of survival /Spearman's coefficient (R=0.7048/, worse prognosis is in correlation with high postoperative calcitonin values. The treatment of choice is at least total thyroidectomy and central lymph nodes resection if enlarged lymph nodes are found. Precise operative technique lowers the risk of postoperative complications. Complex approach to the patient with MTC includes all available methods in pre and postoperative evaluation as well as surgeon's knowledge and skill.

Boži? Vesna D.

2003-01-01

 
 
 
 
21

Genetics Home Reference: Sporadic hemiplegic migraine  

Science.gov (United States)

... weakness, often affecting one side of the body (hemiparesis). Additional features of an aura can include difficulty ... sporadic hemiplegic migraine, some experience migraine headaches without hemiparesis. A related condition, familial hemiplegic migraine, has signs ...

22

Antigliadin antibody in sporadic adult ataxia  

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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

23

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

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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 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

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Bilateral sporadic aniridia: review of management  

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

Caroline O Adeoti

2010-09-01

25

Pointed Hopf algebras over the sporadic groups  

CERN Document Server

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

Andruskiewitsch, N; Graña, M; Vendramin, L

2010-01-01

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Genomic aspects of sporadic neurodegenerative diseases.  

Science.gov (United States)

Sporadic neurodegenerative diseases are complex in nature, that is, they involve multiple genetic and environmental factors that may play roles at the molecular level. In contrast to diseases with Mendelian inheritance, the genomic signatures of common sporadic forms of neurodegenerative diseases largely remain unknown. Over the past decade, genome-wide association studies employing common single-nucleotide polymorphisms have been intensively conducted, in which the theoretical framework is based on the "common disease-common variants" hypothesis. Another paradigm is a sequence-based association study under the "common disease-multiple rare variants" hypothesis. Because current next-generation sequencing technologies enable us to obtain virtually all the variants in human genome irrespective of allele frequencies, it is anticipated that sequence-based association studies will become the mainstream approach. In this review, we present brief overviews of molecular genetic approaches to elucidate the molecular bases of sporadic forms of neurodegenerative diseases, including Alzheimer disease, Parkinson disease, and multiple system atrophy as examples. PMID:25078619

Mitsui, Jun; Tsuji, Shoji

2014-09-19

27

Loss of merlin expression in sporadic meningiomas, ependymomas and schwannomas.  

Science.gov (United States)

Neurofibromatosis 2 (NF2) is an inherited disorder in which affected individuals develop schwannomas and meningiomas. NF2 is mapped to chromosome 22q in a region where frequent loss of heterozygosity also occurs in sporadic meningiomas, ependymomas, and schwannomas. Using NF2 protein (merlin or schwannomin)-specific antibodies, 11 of 14 sporadic schwannomas, three of eight sporadic ependymomas, and 16 of 19 sporadic meningiomas demonstrated significantly reduced or absent merlin expression, suggesting that NF2 may be involved in the pathogenesis of these sporadic tumors. PMID:9222206

Gutmann, D H; Giordano, M J; Fishback, A S; Guha, A

1997-07-01

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Sporadic randomness, Maxwell's Demon and the Poincaré recurrence times  

CERN Document Server

In the case of fully chaotic systems the distribution of the Poincare'recurrence times is an exponential whose decay rate is the Kolmogorov-Sinai(KS) entropy.We address the discussion of the same problem, the connection between dynamics and thermodynamics,in the case of sporadic randomness,using the Manneville map as a prototype of this class of processes. We explore the possibility of relating the distribution of Poincare' recurrence times to `thermodynamics',in the sense of the KS entropy,also in the case of an inverse power law. This is the dynamic property that Zaslavsly [Phys.Today(8), 39(1999)] finds to be responsible for a striking deviation from ordinary statistical mechanics under the form of Maxwell's Demon effect. We show that this way of estabi- lishing a connection between thermodynamics and dynamics is valid only in the case of strong chaos. In the case of sporadic randomness, resulting at long times in the Levy diffusion processes,the sensitivity to initial conditions is initially an inverse po...

Aquino, G; Scafetta, N; Aquino, Gerardo; Grigolini, Paolo; Scafetta, Nicola

2000-01-01

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

International Nuclear Information System (INIS)

Cancer is a disease of the genome, with the neoplastic phenotype being passed from one cell generation to the other. Radiation-induced cancer has often been considered to represent a unique entity amongst neoplasia, with the energy deposition being held responsible for both direct (gene mutations) and indirect (bystander effects, induced instability etc) alterations to the cellular genome. However, radiogenic tumours in man and experimental animals appear to be physiologically and genetically indistinguishable from their sporadic counterparts, suggesting that the aetiologies of these two tumour types are in fact closely related. We have conducted a general screen of the genetic alterations in radiation-induced mouse osteosarcoma, a tumour that is histopathologically indistinguishable from human sporadic osteosarcoma. Comparison of the two tumour types indicates the existence of a common set of genetic changes, providing additional evidence to support the concept that the molecular pathology of radiation-induced malignancy is no different to that of sporadic cancers. (author)

30

Sporadic hyperekplexia presenting with an ataxic gait.  

Science.gov (United States)

We describe a 62-year-old man with a sporadic form of hyperekplexia who presented with an unsteady gait, present since the age of 47. His clinical examination revealed an insecure broad-based gait and difficulty with tandem walking but no other abnormalities. For nearly a decade the patient was misdiagnosed with an idiopathic ataxia. A video electroencephalogram combined with an electromyogram during sudden auditory stimulus demonstrated an excessive startle response. An extensive work-up ruled out all the known causes of symptomatic hyperekplexia including anti-glycine receptor antibodies. Treatment with clonazepam markedly reduced the threshold and intensity of the startle response, enabling him to recover independence. Hyperekplexia is frequently associated with an awkward and hesitating gait, but these gait abnormalities might be confused with other causes of gait disorders if one is not aware of this disease. We report this patient to highlight that a correct diagnosis of hyperekplexia is crucial, because its treatment may change quality of life. PMID:24054400

Rouco, Idoia; Bilbao, Iker; Losada, Jose; Maestro, Iratxe; Zarranz, Juan Jose

2014-02-01

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

Inhibitor of prostacyclin production in sporadic haemolytic uraemic syndrome.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma from 5 of 6 patients with the sporadic form of haemolytic uraemic syndrome but was normal in the presence of plasma from 7 patients with the epidemic form of haemolytic uraemic syndrome or from patients with other renal diseases. The reduced PGI2 production was caused by an unstable inhibitor, extractable into polar lipid solvents, in sporadic haemolytic uraemic plasma. These results suggest that th...

Levin, M.; Elkon, K. B.; Nokes, T. J.; Buckle, A. M.; Dillon, M. J.; Hardisty, R. M.; Barratt, T. M.

1983-01-01

33

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Cryptic subtelomeric rearrangements have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been studied. As positive family history of ID had been proposed as an important and significant predicting factor of subtelomeric rearrangements, it was assumed that the contribution of subtelomeric aberrations in familial ID would be much more than the sporadic ones. Three hundr...

Rafati Maryam; Ghadirzadeh Mohammad R; Heshmati Yaser; Adibi Homeira; Keihanidoust Zarrintaj; Eshraghian Mohammad R; Dastan Jila; Hoseini Azadeh; Purhoseini Marzieh; Ghaffari Saeed R

2012-01-01

34

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

Directory of Open Access Journals (Sweden)

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

Nozières Cécile

2011-10-01

35

Joint observations of sporadic sodium and sporadic E layers at middle and low latitude in China  

Science.gov (United States)

The sporadic sodium layers (SSL) phenomena were studied with sodium (Na) lidar at Beijing (40. 5°N?116. 0°E) and Haikou (19.5°N, 109.1°E) in China. The main parameters of SSL and Es events were statistically analyzed at both observing sites. SSL occurrence has maximum near 22:00 LT, and Es occurrence has maximum before midnight. Comparison reveals that all the average values of height and strength factor of SSL and Es at Beijing are higher than those at Haikou, as well as the average of foEs. The correlation of SSL with Es is stronger at Haikou, and the formation of SSL is obviously influenced by seasonally varied chemical and dynamical processes.

Yang, Guotao; Wang, Jihong; Du, Lifang; Yue, Chuan; Wang, Zelong; Jiao, MS. Jing

36

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

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BRCA1 promoter methylation status does not predict response to tamoxifen in sporadic breast cancer patients.  

Science.gov (United States)

The purpose of this study is to investigate whether BRCA1 promoter methylation is associated with poorer outcome in sporadic breast cancer cases treated with tamoxifen. BRCA1 promoter methylation was determined by bisulfite pyrosequencing in two groups of sporadic breast cancer patients, systemically untreated (N = 497) and treated with adjuvant tamoxifen (N = 497). Associations of BRCA1 promoter methylation with clinopathological characteristics and the effect of BRCA1 promoter methylation on time to first recurrence (TTR) and overall survival (OS) were examined. No significant differences were observed between BRCA1 promoter methylation and clinopathological characteristics in untreated and tamoxifen-treated groups. Cut point analysis did not find any promising cut point for BRCA1 promoter methylation that would differentially influence TTR and OS in untreated and tamoxifen-treated group. Using the median (2.53 %) and an arbitrary value of 10 % as a cut point for methylation, we still found no significant effect of BRCA1 promoter methylation on TTR and OS in untreated and tamoxifen-treated group. Despite data suggesting that BRCA1 levels impact estrogen receptor response to tamoxifen, our results indicate that BRCA1 promoter methylation is not associated with poorer outcome in sporadic breast cancer cases treated with tamoxifen. PMID:22706629

Cerne, Jasmina Z; Zong, Lin; Jelinek, Jaroslav; Hilsenbeck, Susan G; Wang, Tao; Oesterreich, Steffi; McGuire, Sean E

2012-08-01

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Clinical significance of mismatch repair gene expression in sporadic colorectal cancer  

Science.gov (United States)

Mismatch repair (MMR) genes play an important role in the occurrence and development of sporadic colorectal cancer; however, the effect of MMR genes on clinicopathological features and prognosis remains unclear. The aim of the present study was to observe the clinical significance of MMR gene expression in sporadic colorectal cancer. Clinicopathological data and postoperative samples from 404 patients with sporadic colorectal cancer were obtained from the Affiliated Tumor Hospital of Xinjiang Medical University. The immunohistochemistry PV-9000 two-step method was performed to measure the protein expression of human mutL homolog 1 (hMLH1), human mutS homolog (hMSH) 2, human postmeiotic segregation increased 2 (hPSM2) and hMSH6. Differences in clinicopathological features, family history and survival time subsequent to surgery between groups with normal and aberrant MMR protein (MMRP) expression were compared. A total of 27.23% of all patients showed aberrant nuclear staining of MMRP. Among the patients with aberrant MMRP expression, a higher proportion of patients showed aberrant expression of more than one type of MMRP than aberrant expression of only one type of MMRP. Aberrant expression of hMLH1/hPSM2 was most commonly observed (29/404). In addition, aberrant MMRP expression in colorectal cancer was indicated predominantly in the right hemicolon. Histological type primarily showed mucinous adenocarcinoma. In addition, with increasing body mass index (BMI), the MMRP deficiency rate was also shown to increase gradually. There was a close association between MMRP expression deficiency and family history of cancer (P0.05). In conclusion, the immunohistochemistry PV-9000 two-step method can be used to measure MMRP expression in colorectal cancer. Aberrant MMRP expression is closely correlated with tumor location, histological type, BMI and tumor family history in sporadic colorectal cancer. Aberrant MMRP expression may have an effect on the prognosis of stage III patients.

SUN, ZHENQIANG; YU, XIANBO; WANG, HAIJIANG; ZHANG, SHUO; ZHAO, ZELIANG; XU, RUIWEI

2014-01-01

39

Daytime equatorial VHF radiowave scintillations and sporadic-E layer  

Science.gov (United States)

Daytime VHF radiowave scintillations at Trivandrum are compared with the E-region irregularities at Kodaikanal. It is shown that daytime scintillations at Trivandrum are basically of two categories. One type of scintillations is associated with the q type of sporadic-E occurrence during normal electrojet condition and is weak with peak-to-peak fluctuations of 1-2 dB. The other type of scintillations is associated with blanketing type of sporadic-E occurrence during counter electrojet condition with magnitude greater than 5 dB.

Koparkar, P. V.; Rastogi, R. G.; Sastri, J. H.

1989-08-01

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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

 
 
 
 
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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

42

Pointed Hopf algebras over some sporadic simple groups  

CERN Document Server

Any finite-dimensional complex pointed Hopf algebra with group of group-likes isomorphic to a sporadic group G, where G is one of the groups M12, M22, M23, M24, J1, J2, J3, Suz, HS, Co2, Co3, Ru, ON or T, is a group algebra.

Andruskiewitsch, N; Graña, M; Vendramin, L

2009-01-01

43

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

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FANCD2 associated with sporadic breast cancer risk.  

Science.gov (United States)

Several components of the Fanconi anaemia (FA) family of proteins allow the formation of the DNA repair complex foci formed by proteins such as BRCA1/2 and RAD51. Because the genes that participate in the DNA repair pathway have been described as low-penetrance breast cancer susceptibility genes, we postulated that variants in FA genes could also be associated with sporadic breast cancer risk. We studied seven SNPs in FANCA, FANCL and FANCD2 in a total of 897 consecutive and non-related sporadic breast cancer cases and 1033 unaffected controls from the Spanish population. We observed a statistically significant association with sporadic breast cancer for the variant rs2272125 (L1366L) located on FANCD2 (OR per allele=1.35; 95% C.I. 1.09-1.67; P=0.005). Both haplotype and diplotype analyses confirmed this association, where one haplotype and pooled diplotypes carrying it were associated with more than 4-fold risk (P=0.007 and P=0.006, respectively). Screening for potential causal variants in FANCD2 was performed, detecting one in the putative promoter region, which is located in a phylogenetically conserved motif with consensus binding sites for some transcriptional factors, suggesting a functional implication. Our data indicate that a relationship between FANCD2 and sporadic breast cancer risk may exist. PMID:16679306

Barroso, E; Milne, R L; Fernández, L P; Zamora, P; Arias, J I; Benítez, J; Ribas, G

2006-09-01

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

Science.gov (United States)

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

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

2014-12-01

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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

47

Systematic comparison of sporadic and syndromic pancreatic islet cell tumors.  

Science.gov (United States)

Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower malignancy rate (PICTs compared to sporadic cases. VHL was prevalent in ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL. PMID:20660572

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

2010-12-01

48

Measurements of the ionization heights of sporadic radio-meteors  

International Nuclear Information System (INIS)

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

49

The Monster Sporadic Group and a Theory Underlying Superstring Models  

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The pattern of duality symmetries acting on the states of compactified superstring models reinforces an earlier suggestion that the Monster sporadic group is a hidden symmetry for superstring models. This in turn points to a supersymmetric theory of self-dual and anti-self-dual K3 manifolds joined by Dirac strings and evolving in a 13 dimensional spacetime as the fundamental theory. In addition to the usual graviton and dilaton this theory contains matter-like degrees of fre...

Chapline, George

1996-01-01

50

Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease.  

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BACKGROUND: In patients with sporadic Creutzfeldt-Jakob disease, pathologic disease-associated prion protein (PrPSc) has been identified only in the central nervous system and olfactory-nerve tissue. Understanding the distribution of PrPSc in Creutzfeldt-Jakob disease is important for classification and diagnosis and perhaps even for prevention. METHODS: We used a highly sensitive method of detection--involving the concentration of PrPSc by differential precipitation with sodium phosphotungst...

Glatzel, M.; Abela, E.; Maissen, M.; Aguzzi, A.

2003-01-01

51

The Origin of stream and sporadic meteors, comets or asteroids  

Science.gov (United States)

Asteroids and Comets that come close to the Earth's orbit are called Near Earth Objects (NEOs). Any dust ejected from them, meteoroid streams will formed a~meteoroid stream with orbits that are similar to that of the parent body. If the Earth passes through such a stream, the meteoroids will ablate and produce meteors that are as meteor showers. In this region, orbits evolve rapidly, hence, over time the orbits of stream meteoroids will progressively diverge both from each other and from the orbit of the parent body, so that instead of being observed as a meteor shower, these meteoroids become part of the sporadic background. When a meteor shower is observed, a similarity in the orbits should indicate the parent and several test for this are discussed. If the parent is active, then it is a comet, but if no activity is found then it could either be an asteroid or a dormant comet. In this case, the behaviour of the meteor in the atmosphere will indicate whether the parent body was likely to be an asteroid or a comet. For sporadic meteoroids the situation is more complicated as they can not be associated with a givenparent body. All that can be done is to classify the orbits as being of comet or asteroid origin. Several criteria have been proposed and applied to the present day orbits of sporadic meteors. Using a single criterion can introduce a serious bias into the results with the fraction of comet orbits understated by up to 29%. Two parameter criteria have been suggested to remove this bias. Using these criteria on a set of ~78000 sporadic meteoroids 66-67% have comet type orbits. This fraction can differ for meteors observed by different techniques, i.e. video, photographic and radar, in general it decreases with decreasing brightness of the observed meteors.

Williams, I. P.; Jopek, T. J.

2014-07-01

52

Numerical modelling of a metallic ion sporadic-E layer  

International Nuclear Information System (INIS)

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

53

Genetic & Neuronanatomic Associations in Sporadic Frontotemporal Lobar Degeneration  

Science.gov (United States)

Genome-wide association studies have identified 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 neuroanatomical structure in sporadic FTLD have not been assessed. In this report we use novel multivariate tools, eigenanatomy and sparse canonical correlation analysis (SCCAN), to identify associations between SNPs and neuroanatomical structure in sporadic FTLD. MRI analyses revealed that rs8070723 (MAPT) was associated with grey matter variance in the temporal cortex. DTI 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

2014-01-01

54

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

55

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

56

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

57

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.

58

Risk factors for sporadic colorectal cancer in southern Chinese  

Directory of Open Access Journals (Sweden)

Full Text Available AIM: To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index (BMI in sporadic colorectal cancer in southern Chinese.METHODS: A hospital-based case-control study was conducted from July 2002 to December 2008. There were 706 cases and 723 controls with their sex and age (within 5 years matched. An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer.RESULTS: No positive association was observed between smoking status and sporadic colorectal cancer risk. Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer (CRC (adjusted OR = 8.61 and 95% CI = 6.15-12.05; adjusted OR = 2.30, 95% CI = 1.27-4.17. Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer (adjusted OR = 1.62, 95% CI = 1.12-3.34 and in those with their BMI ? 24.0 kg/m2 (adjusted OR = 1.39, 95% CI = 1.10-1.75. Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers (adjusted OR = 7.60 and 95% CI = 5.13-11.25; adjusted OR = 7.52 and 95% CI = 5.13-11.01 and in those with their BMI ? 24.0 kg/m2 (adjusted OR = 1.38 and 95% CI = 1.04-1.83; adjusted OR = 1.35 and 95% CI = 1.02-1.79. The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer (adjusted OR = 2.51 and 95% CI = 1.24-5.07; adjusted OR = 1.82 and 95% CI = 1.17-2.82.CONCLUSION: Alcohol drinking, high BMI (? 24.0 kg/m2 and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.

Yi-Sheng Wei, Jia-Chun Lu, Lei Wang, Ping Lan, Hong-Jun Zhao, Zhi-Zhong Pan, Jun Huang, Jian-Ping Wang

2009-05-01

59

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

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

Emmanuel Uttah & Dominic C. Ibeh

2011-12-01

60

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

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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

 
 
 
 
61

Mutations in the RET proto-oncogene in sporadic pheochromocytomas  

Energy Technology Data Exchange (ETDEWEB)

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

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

1994-09-01

62

Early-onset colorectal cancer: A sporadic or inherited disease?  

Science.gov (United States)

Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a “sporadic” subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the “sporadic” subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this “sporadic” early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies. PMID:25253942

Stigliano, Vittoria; Sanchez-Mete, Lupe; Martayan, Aline; Anti, Marcello

2014-01-01

63

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

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

Rafati Maryam

2012-01-01

64

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

65

INTUSSUSCEPTION IN A CHILD WITH SPORADIC BURKITT LYMPHOMA  

Directory of Open Access Journals (Sweden)

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

D. Meucci

2009-11-01

66

Sporadic Creutzfeldt-Jakob disease: Clinical, pathological and molecular study  

Directory of Open Access Journals (Sweden)

Full Text Available phalopathiesare neurodegenerative diseasescaused by abnormal accumulation of pathogenicisoform the prion protein, which induces theformation of conglomerates protein resistantto degradation. They are also responsible forsynaptic dysfunction, neuronal damage and theclassic symptoms of disease. This membraneprotein is encoded by exon 2 of the gene PRNP,located on the short arm of chromosome 20 andappears to be involved in synaptic transmission,signal transduction, the antioxidant activity ofthe superoxid dismutasa, neuroplasticity andcell survival. One polymorphism at codon 129is associated with differential susceptibility todisease sporadic Creutzfeldt-Jakob disease.Aim: Clinical, pathological and molecularreport on an 58 year-old woman with pathologicaldiagnosis of Creutzfeldt-Jakob sporadicdisease.Methods and results. The clinic courseappears with a behavior depressive disorder withprogressive dementia and symptoms. At theend of the disease, the scenario progressed to aneurological deficit focused on the visual area.The MRI showed nonspecific hyperintensity incortiço-subcortical nucleus in the striatum, theEEG showed patterns of recurrent generalizeddischarges and complex three-phase, the brainbiopsy post-morten showed severe loss of theneuronal population in all the layers, vacuolesin the neuropil, in the neuronal soma and theglial. The analysis of sequence of the gene PRNPidentified homozygotes for methionine atcodon 129. The patient died at 3 months of theonset of symptoms.Conclusions: Epidemiology, clinical courseand paraclinical examinations confirmed thediagnosis of Creutzfeldt-Jakob sporadic.The genotyping for polymorphisms of riskbecomes useful tool to complement throughmolecular diagnosis and to deepen the understandingof the pathophysiology of Creutzfeldt-Jakob disease, both for sporadic forms and forthe new variant.

Victoria Eugenia Villegas

2008-12-01

67

Sporadic ALS/MND: a global neurodegeneration with retroviral involvement?  

Science.gov (United States)

Sporadic amyotrophic lateral sclerosis may be an aetiologically heterogenous disease. We confirmed elevated circulating IgG immune complexes, and altered IgG seroreactivities against human retroviral antigens (HIV-2 and HTLV immunoblots) in overlapping subgroups of patients. Together with preliminary findings of a positive polymerase chain reactivity for human T-lymphotropic virus (HTLV.tax/rex) in blood leukocytes of 5 out of 14 sALS patients, we interpret this as evidence for a retroviral involvement in this relentlessly progressive, often asymmetrically spreading neurodegeneration. The possibility of a secondary phenomenon seems unlikely, yet cannot be completely ruled out. PMID:7595609

Westarp, M E; Ferrante, P; Perron, H; Bartmann, P; Kornhuber, H H

1995-05-01

68

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

69

A faster exact multiprocessor schedulability test for sporadic tasks  

CERN Document Server

Baker and Cirinei introduced an exact but naive algorithm, based on solving a state reachability problem in a finite automaton, to check whether sets of sporadic hard real-time tasks are schedulable on identical multiprocessor platforms. However, the algorithm suffered from poor performance due to the exponential size of the automaton relative to the size of the task set. In this paper, we successfully apply techniques developed by the formal verification community, specifically antichain algorithms, by defining and proving the correctness of a simulation relation on Baker and Cirinei's automaton. We show our improved algorithm yields dramatically improved performance for the schedulability test and opens for many further improvements.

Lindström, Markus; Goossens, Joël

2011-01-01

70

Feasibility Analysis of Sporadic Real-Time Multiprocessor Task Systems  

CERN Document Server

We give the first algorithm for testing the feasibility of a system of sporadic real-time tasks on a set of identical processors, solving one major open problem in the area of multiprocessor real-time scheduling [S.K. Baruah and K. Pruhs, Journal of Scheduling, 2009]. We also investigate the related notion of schedulability and a notion that we call online feasibility. Finally, we show that discrete-time schedules are as powerful as continuous-time schedules, which answers another open question in the above mentioned survey.

Bonifaci, Vincenzo

2010-01-01

71

Screening of the PFN1 gene in sporadic ALS and in FTD  

Science.gov (United States)

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

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

2012-01-01

72

Study of sporadic-E clouds by backscatter radar  

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Full Text Available It is shown that swept-frequency backscatter ionograms covering a range of azimuths can be used to study the dynamics of sporadic-E clouds. A simple technique based on analytic ray tracing can be used to simulate the observed narrow traces associated with Es patches. This enables the location and extent of the sporadic-E clouds to be determined. The motion of clouds can then be determined from a time sequence of records. In order to demonstrate the method, results are presented from an initial study of 5 days of backscatter ionograms from the Jindalee Stage B data base obtained during March-April 1990. Usually 2–3 clouds were observed each day, mainly during the evening and up to midnight. The clouds lasted from 1–4 h and extended between 30°–80° in azimuth and 150-800 km in range. The clouds were mostly stationary or drifted generally westward with velocities of up to 80 m s–1. Only one cloud was observed moving eastward.

Z. Houminer

73

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

74

CLINICAL ASPECTS AND THERAPY OF SPORADIC BURKITT LYMPHOMA  

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Full Text Available

Burkitt’s lymphoma is a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants, that share many morphologic and immunophenotypic features. It is characterized by a high proliferation rate and propensity for extranodal sites such as gastrointestinal tract and reproductive organs. Brief-duration, high-intensity chemotherapy regimens including aggressive central nervous system prophylaxis have had remarkable success in the treatment of this disease in the sporadic form, with very high complete remission rate and overall survival  in adults. Although Burkitt's lymphoma is extremely chemosensitive, biologically targeted therapies should be developed, because current treatment options are suboptimal for patients with poor prognostic features or with relapsed disease.

Luana Fianchi

2009-11-01

75

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

76

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

77

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

78

Sporadic observation of the Fleischmann-Pons heat effect  

International Nuclear Information System (INIS)

An examination has been made of the heat production at ten palladium electrodes, each prepared in a different way. Seven of these produced heat during D2 evolution in a D2-O2 electrolysis cell (no recombination attempted) which coincided precisely with the prediction of classical electrochemical theory, and thus eliminated the suspicion of heat through unintended D2-O2 recombination. Three electrodes clearly produced an excess heat of ? 2-5 watts-cm-3. The heat was observed for periods of 10-33 hrs. In one electrode the excess heat production ''shut-off'' (after 33 hrs) with no apparent cause: it did not return in five days of further electrolysis. (author)

79

Sporadic community-acquired Legionnaires' disease in France: a 2-year national matched case-control study  

Science.gov (United States)

SUMMARY Legionnaires' disease (LD) is an aetiology of community-acquired bacterial pneumonia in adults, with a high case-fatality ratio (CFR). We conducted a matched case-control study to identify risk factors for sporadic, community-acquired LD. Cases of sporadic, community-acquired and biologically confirmed LD, in metropolitan France from 1 September 2002 to 31 September 2004, were matched with a control subject according to age, sex, underlying illness and location of residence within 5 km. We performed a conditional logistic regression on various host-related factors and exposures. Analysis was done on 546 matched pairs. The CFR was 3·5%. Age ranged from 18–93 years (mean 57 years), with a 3·6 male:female sex ratio. Cases were more likely to have smoked with the documentation of a dose-effect relation, to have travelled with a stay in a hotel (OR 6·1, 95% CI 2·6–14·2), or to have used a wash-hand basin for personal hygiene (OR 3·5, 95% CI 1·6–7·7) than controls. Tobacco and travel have been previously described as risk factors for LD, but this is the first time that such a dose-effect for tobacco has been documented among sporadic cases. These findings will provide helpful knowledge about LD and help practitioners in identifying patients at high risk. PMID:18211725

CHE, D.; CAMPESE, C.; SANTA-OLALLA, P.; JACQUIER, G.; BITAR, D.; BERNILLON, P.; DESENCLOS, J.-C.

2008-01-01

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

Sporadic faults in regular growth of eutectic composites  

International Nuclear Information System (INIS)

Structural imperfection of Sn-Pb, Cd-Sn, Cd-Pb, Cd-Zn, Zn-Sn, Cd-Bi, Zn-Bi eutectic compositions are investigated. The method of local X-ray spectrum analysis has been used to determine compositions of normal Csub(eutec)sup(n.c.) colonies corresponding to equal development rates of conjugate phases. For many alloys a deviation from the diagram eutectic concentration Csub(eutec)sup(d) is found. It is shown that sporadic violations of the regular growth of eutectic compositions are caused by the alterations in the composition of a liquid at the front of a two-phase packet. Local violations of eutectic compositions are nodes of branching eutectic phases, which follows from the data of stereometric metallography. The dependence of imperfections density on the crystallization conditions is determined

82

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

Science.gov (United States)

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

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

1997-06-01

83

Sporadic onset Creutzfeldt-Jacob disease: Interesting MRI observations  

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

Praveen K

2006-01-01

84

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

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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

85

Cellular tau pathology and immunohistochemical study of tau isoforms in sporadic tauopathies.  

Science.gov (United States)

Pathological inclusions in neurons and glial cells containing fibrillary aggregates of abnormally hyperphosphorylated tau protein are characteristic features in sporadic tauopathies. In the first part of this paper we outline the morphological features of some major sporadic tauopathies. In the second part, to better define the tau isoform composition, we report on the immunohistochemistry of tau isoforms in autopsied brains, including two cases with AD, two with diffuse neurofibrillary tangles with calcification, four with Pick's disease with Pick bodies (PiD), seven with progressive supranuclear palsy (PSP), six with corticobasal degeneration (CBD) and seven cases with argyrophilic grain disease. We used two monoclonal antibodies, RD3 and RD4, and a polyclonal antibody for exon 10 that effectively distinguish between three-repeat (3R) tau and four-repeat (4R) tau. Neuronal neurofibrillary tangles (NFT) in AD and diffuse neurofibrillary tangles with calcification contained both 3R-tau and 4R-tau. The Pick bodies were immunopositive for 3R-tau in two cases; however, in two other cases they were mainly immunopositive for 4R-tau. Thus, Pick bodies demonstrated heterogeneity. 3R-tau PiD contained 3R-tau glial inclusions, and 4R-tau PiD contained mainly 4R-tau glial inclusions. Glial inclusions were more abundant in 4R-tau PiD cases. In progressive supranuclear palsy and CBD, both neuronal and glial tau accumulation forming NFF, pretangles, tuft-shaped astrocytes, astrocytic plaques, coiled bodies and threads demonstrated 4R-tau in the cerebral cortices, although in the basal ganglia and brainstem neuronal and glial inclusions were occasionally immunopositive for 3R-tau in addition to 4R-tau. Argyrophilic grains (AG) were immunopositive for 4R-tau, although pretangles were weakly stained for 4R-tau. Thus the immunoreactivity for 4R-tau was different between AG and pretangles. Therefore, the isoform composition on immunohistochemical study showed heterogeneity in PiD, and was not uniform in the basal ganglia and brain stem in PSP and CBD. It is suggested that the isoform composition of sporadic tauopathies may have a spectrum in individual cases, and cellular isoform composition may differ in various brain regions. PMID:17080726

Yoshida, Mari

2006-10-01

86

Nonlocal theory of long-wavelength plasma waves associated with sporadic E layers  

International Nuclear Information System (INIS)

In this paper we calculate the nonlocal growth rate of gradient drift plasma waves under conditions where the electron density gradient scale length changes with altitude. The results are compared with the local growth rate and discussed in the context of the kilometer-scale waves which have been observed in the vicinity of mid-latitude sporadic E layers. These large-scale waves drastically violate the local approximation, kL/sub m/>>1, where k is the irregularity wave number and L/sub m/ is the minimum gradient scale length on the edge of a layer. The first step in the analysis is to derive a general eigenmode equation, starting with the same assumptions usually used in the derivation of the local dispersion relation for long wavelength waves. Modeling a sporadic E layer as a slab, the nonlocal growth rate spectrum is found by solving the eigenmode equation for this profile. The solution is an algebraic dispersion relation with a growth rate spectrum which is roughly proportional to k, rather than the k2 dependence predicted by conventional local theory at long wavelengths. At short wavelengths the nonlocal growth rate determined with the slab is unbounded, in disagreement with local theory. The slab is an inadequate model for short wavelength waves and a bound on the growth rate is instead derived from a theory which can be applied to any realistic profile with nonzero L/sub m/. At short wavelengths this bound is identical to the local growth rate expression, while at long wavelengths the bound remains proportional to k and thus is consistent with the dispersion relation for a slab. Nonlocal effects alone do not explain the dominance of kilometer scales, but they do tend to favor the excitation of long wavelengths

87

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

88

The role of inflammation in sporadic and familial Parkinson's disease.  

Science.gov (United States)

The etiology of Parkinson's disease (PD) is complex and most likely involves numerous environmental and heritable risk factors. Interestingly, many genetic variants, which have been linked to familial forms of PD or identified as strong risk factors, also play a critical role in modulating inflammatory responses. There has been considerable debate in the field as to whether inflammation is a driving force in neurodegeneration or simply represents a response to neuronal death. One emerging hypothesis is that inflammation plays a critical role in the early phases of neurodegeneration. In this review, we will discuss emerging aspects of both innate and adaptive immunity in the context of the pathogenesis of PD. We will highlight recent data from genetic and functional studies that strongly support the theory that genetic susceptibility plays an important role in modulating immune pathways and inflammatory reactions, which may precede and initiate neuronal dysfunction and subsequent neurodegeneration. A detailed understanding of such cellular and molecular inflammatory pathways is crucial to uncover pathogenic mechanisms linking sporadic and hereditary PD and devise tailored neuroprotective interventions. PMID:23665870

Deleidi, Michela; Gasser, Thomas

2013-11-01

89

Facing and managing natural disasters in the Sporades Islands, Greece  

Directory of Open Access Journals (Sweden)

Full Text Available The region of the Sporades Islands located in central Greece is at the mercy of many natural phenomena, such as earthquakes, due to the marine volcano "Psathoura", and the rift of Anatolia, forest fires, floods, landslides, storms, hail, snowfall and frost. The present work aims at studying the perceptions and attitudes of the residents regarding how they face and manage natural disasters. A positive public response during a hazard crisis depends not only upon the availability and good management of a civil defence plan but also on the knowledge and perception of the possible hazards by the local population. It is important for the stakeholders to know what the citizens expect from each of the separate stakeholders so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked about their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly the immediate response of stakeholders and their involvement and responsibilities at different, subsequent intervals of time following the disaster. The residents were also asked about the most common disasters that happen in their region and about the preparation activities of the stakeholders.

P. Karanikola

2013-11-01

90

Biochemical characterization of sporadic/familial hemiplegic migraine mutations.  

Science.gov (United States)

Sporadic hemiplegic migraine type 2 (SHM2) and familial hemiplegic migraine type 2 (FHM2) are rare forms of hemiplegic migraine caused by mutations in the Na(+),K(+)-ATPase ?2 gene. Today, more than 70 different mutations have been linked to SHM2/FHM2, randomly dispersed over the gene. For many of these mutations, functional studies have not been performed. Here, we report the functional characterization of nine SHM2/FHM2 linked mutants that were produced in Spodoptera frugiperda (Sf)9 insect cells. We determined ouabain binding characteristics, apparent Na(+) and K(+) affinities, and maximum ATPase activity. Whereas membranes containing T345A, R834Q or R879W possessed ATPase activity significantly higher than control membranes, P796S, M829R, R834X, del 935-940 ins Ile, R937P and D999H membranes showed significant loss of ATPase activity compared to wild type enzyme. Further analysis revealed that T345A and R879W showed no changes for any of the parameters tested, whereas mutant R834Q possessed significantly decreased Na(+) and increased K(+) apparent affinities as well as decreased ATPase activity and ouabain binding. We hypothesize that the majority of the mutations studied here influence interdomain interactions by affecting formation of hydrogen bond networks or interference with the C-terminal ion pathway necessary for catalytic activity of Na(+),K(+)-ATPase, resulting in decreased functionality of astrocytes at the synaptic cleft expressing these mutants. PMID:24704353

Weigand, Karl M; Swarts, Herman G P; Russel, Frans G M; Koenderink, Jan B

2014-07-01

91

Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma.  

Science.gov (United States)

Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1?. 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 case-control 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 significantly more common in male patients than in controls (OR, 2.22; CI, 1.27-3.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.33-6.30), which intensified in male patients (OR 4.03, CI 1.40-11.59). The NLRP1 variant (rs12150220) was significantly more common in fair-skinned female patients (OR, 1.85; CI, 1.04-3.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.33-25). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations. PMID:22524199

Verma, Deepti; Bivik, Cecilia; Farahani, Ensieh; Synnerstad, Ingrid; Fredrikson, Mats; Enerbäck, Charlotta; Rosdahl, Inger; Söderkvist, Peter

2012-07-01

92

Biological and genetic markers of sporadic Alzheimer's disease.  

Directory of Open Access Journals (Sweden)

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

93

Facing and managing natural disasters in the Sporades islands, Greece  

Science.gov (United States)

The region of the Sporades islands located in central Greece is at the mercy of many natural phenomena, such as earthquakes due to the marine volcano Psathoura and the rift of Anatolia, forest fires, floods, landslides, storms, hail, snowfall and frost. The present work aims at studying the perceptions and attitudes of the residents regarding how they face and manage natural disasters. A positive public response during a hazard crisis depends not only upon the availability and good management of a civil defense plan but also on the knowledge and perception of the possible hazards by the local population. It is important for the stakeholders to know what the citizens expect so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly about the immediate response of stakeholders and their involvement and responsibilities at different, subsequent intervals of time following the disaster. The residents were also asked about the most common disasters that happen in their region and about the preparation activities of the stakeholders.

Karanikola, P.; Panagopoulos, T.; Tampakis, S.; Karantoni, M. I.; Tsantopoulos, G.

2014-04-01

94

Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features.  

Science.gov (United States)

Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal reflux disease and occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zurich, Switzerland, and Kiel, Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished from tumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1-associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1-associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1-associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas. PMID:17006979

Anlauf, Martin; Garbrecht, Nele; Henopp, Tobias; Schmitt, Anja; Schlenger, Regina; Raffel, Andreas; Krausch, Markus; Gimm, Oliver; Eisenberger, Claus F; Knoefel, Wolfram T; Dralle, Henning; Komminoth, Paul; Heitz, Philipp U; Perren, Aurel; Klöppel, Gunter

2006-09-14

95

Localizing a putative mutation as the major contributor to the development of sporadic Hirschsprung disease to the RET genomic sequence between the promoter region and exon 2.  

Science.gov (United States)

Hirschsprung disease (HSCR), a congenital disorder characterized by intestinal obstruction due to absence of enteric ganglia along variable lengths of the intestinal tract, occurs both in familial and sporadic cases. RET mutations have been found in approximately 50% of the families, but explains only a minority of sporadic cases. This study aims at investigating a possible role of RET in sporadic HSCR patients. Haplotypes of 13 DNA markers, within and flanking RET, have been determined for 117 sporadic HSCR patients and their parents. Strong association was observed for six markers in the 5' region of RET. The largest distortions in allele transmission were found at the same markers. One single haplotype composed of these six markers was present in 55.6% of patients versus 16.2% of controls. Odds ratios (ORs) revealed a highly increased risk of homozygotes for this haplotype to develop HSCR (OR>20). These results allowed us to conclude that RET plays a crucial role in HSCR even when no RET mutations are found. An unknown functional disease variant(s) with a dosage-dependent effect in HSCR is likely located between the promoter region and exon 2 of RET. PMID:15138456

Burzynski, Grzegorz M; Nolte, Ilja M; Osinga, Jan; Ceccherini, Isabella; Twigt, Bas; Maas, Saskia; Brooks, Alice; Verheij, Joke; Plaza Menacho, Ivan; Buys, Charles H C M; Hofstra, Robert M W

2004-08-01

96

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

Directory of Open Access Journals (Sweden)

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

B. P. Williams

2007-02-01

97

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

Science.gov (United States)

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

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

2007-02-01

98

Upregulation of presenilin 1 in brains of sporadic, late-onset Alzheimer's disease.  

Science.gov (United States)

The activity of the ?-secretase involved in the cleavage of amyloid-? (A?) is increased in sporadic late-onset Alzheimer's disease (AD). Whether the corresponding ?-secretase activity is altered is still uncertain. We evaluated mRNA expression and protein levels of presenilin 1 (PS1) and ?-secretase activity in the frontal cortex of 32 cases with late-onset sporadic AD and those of 29 control subjects. We found a significant increase in PS1 mRNA, protein levels and ?-secretase activity in AD cases. These findings suggest that upregulation of PS1 leads to A? overproduction and accumulation in sporadic AD. PMID:20847436

Borghi, Roberta; Piccini, Alessandra; Barini, Erica; Cirmena, Gabriella; Guglielmotto, Michela; Tamagno, Elena; Fornaro, Michele; Perry, George; Smith, Mark A; Garuti, Anna; Tabaton, Massimo

2010-01-01

99

Microsatellite instability is rare in sporadic ovarian cancer  

Energy Technology Data Exchange (ETDEWEB)

Microsatellite instability was first demonstrated to be a common underlying mechanism in hereditary nonpolyposis colorectal cancer (HNPCC) and has recently been implicated in the development of several other human cancers. Although numerous genetic changes have been documented in ovarian cancer, their molecular bases are poorly understood. In investigating the molecular genetics of ovarian cancer, we analyzed twelve short tandem repeats that were amplified by PCR from DNA of 48 tumors and their corresponding lymphocyte samples. All of the 48 cases studied have no noticeable family history and, of them, 42 are epithelial (benign/borderline, 5; grade I, 4; GII, 4; GIII, 29) and 6 are nonepithelial. A microsatellite instability has been shown to be inversely correlated with the occurrence of allelic losses, half of those cases chosen have a fractional allele loss of {le}15 (median = .18 of 50 tumors tested for 86 loci from every chromosomal arm). The loci examined included eight dinucleotide repeats (D2S123, D9S104, D10S197, D11S904, D16S408, D16S421, D17S250, and D17S579), two trinucleotide repeats (DM and AR) and two tetranucleotide repeats (DXS981 and VWF). Despite the fact that HNPCC phenotype includes ovarian cancer and that microsatellite instability has been shown in one ovarian cancer from an HNPCC family, the allele sizes of 12 loci were found to be identical in all paired tumor and normal samples we studied except for one tumor at a single locus. The band shift displayed on polyacrylamide gel representing an additional allele of VWF was only observed in one grade III tumor. Our results are thus a strong indication that the alteration of microsatellite repeats may not play a major role in the development of sporadic ovarian cancer.

Chen, S.S.; Han, H.; Schwartz, P.E. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

1994-09-01

100

Novel KRAS Gene Mutations in Sporadic Colorectal Cancer  

Science.gov (United States)

Introduction In this article, we report 7 novel KRAS gene mutations discovered while retrospectively studying the prevalence and pattern of KRAS mutations in cancerous tissue obtained from 56 Saudi sporadic colorectal cancer patients from the Eastern Province. Methods Genomic DNA was extracted from formalin-fixed, paraffin-embedded cancerous and noncancerous colorectal tissues. Successful and specific PCR products were then bi-directionally sequenced to detect exon 4 mutations while Mutector II Detection Kits were used for identifying mutations in codons 12, 13 and 61. The functional impact of the novel mutations was assessed using bioinformatics tools and molecular modeling. Results KRAS gene mutations were detected in the cancer tissue of 24 cases (42.85%). Of these, 11 had exon 4 mutations (19.64%). They harbored 8 different mutations all of which except two altered the KRAS protein amino acid sequence and all except one were novel as revealed by COSMIC database. The detected novel mutations were found to be somatic. One mutation is predicted to be benign. The remaining mutations are predicted to cause substantial changes in the protein structure. Of these, the Q150X nonsense mutation is the second truncating mutation to be reported in colorectal cancer in the literature. Conclusions Our discovery of novel exon 4 KRAS mutations that are, so far, unique to Saudi colorectal cancer patients may be attributed to environmental factors and/or racial/ethnic variations due to genetic differences. Alternatively, it may be related to paucity of clinical studies on mutations other than those in codons 12, 13, 61 and 146. Further KRAS testing on a large number of patients of various ethnicities, particularly beyond the most common hotspot alleles in exons 2 and 3 is needed to assess the prevalence and explore the exact prognostic and predictive significance of the discovered novel mutations as well as their possible role in colorectal carcinogenesis. PMID:25412182

Naser, Walid M.; Shawarby, Mohamed A.; Al-Tamimi, Dalal M.; Seth, Arun; Al-Quorain, Abdulaziz; Nemer, Areej M. Al; Albagha, Omar M. E.

2014-01-01

 
 
 
 
101

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

102

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.

103

Results of surgery for sporadic primary hyperparathyroidism in patients with preoperatively negative sestamibi scintigraphy and ultrasound  

DEFF Research Database (Denmark)

The purpose of this study is to investigate the results of first-time surgery for sporadic primary hyperparathyroidism (pHPT) in patients with preoperatively negative sestamibi scintigraphy and ultrasound.

Bergenfelz, Anders O J; Wallin, Göran

2011-01-01

104

BRCA1 as a Therapeutic Target in Sporadic Epithelial Ovarian Cancer  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

105

Characterization of T gene sequence variants and germline duplications in familial and sporadic chordoma.  

Science.gov (United States)

Chordoma is a rare bone cancer that is believed to originate from notochordal remnants. We previously identified germline T duplication as a major susceptibility mechanism in several chordoma families. Recently, a common genetic variant in T (rs2305089) was significantly associated with the risk of sporadic chordoma. We sequenced all T exons in 24 familial cases and 54 unaffected family members from eight chordoma families (three with T duplications), 103 sporadic cases, and 160 unrelated controls. We also measured T copy number variation in all sporadic cases. We confirmed the association between the previously reported variant rs2305089 and risk of familial [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 0.93, 7.25, P = 0.067] and sporadic chordoma (OR = 2.85, 95% CI = 1.89, 4.29, P chordoma in families (OR = 4.14, 95% CI = 1.43, 11.92, P = 0.0086). Among sporadic cases, another common variant (rs3816300) was significantly associated with risk when jointly analyzed with rs2305089. The association with rs3816300 was significantly stronger in cases with early age onset. In addition, we identified three rare variants that were only observed among sporadic chordoma cases, all of which have potential functional relevance based on in silico predictions. Finally, we did not observe T duplication in any sporadic chordoma case. Our findings further highlight the importance of the T gene in the pathogenesis of both familial and sporadic chordoma and suggest a complex susceptibility related to T. PMID:24990759

Kelley, Michael J; Shi, Jianxin; Ballew, Bari; Hyland, Paula L; Li, Wen-Qing; Rotunno, Melissa; Alcorta, David A; Liebsch, Norbert J; Mitchell, Jason; Bass, Sara; Roberson, David; Boland, Joseph; Cullen, Michael; He, Ji; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen J; Parry, Dilys M; Goldstein, Alisa M; Yang, Xiaohong R

2014-10-01

106

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

107

Estrogen receptor-alpha promoter methylation in sporadic basal-like breast cancer of Chinese women.  

Science.gov (United States)

Basal-like breast cancer (BLBC) appears to be characterized by a relatively unfavorable prognosis and lack of a specific therapeutic target. Estrogen receptor-alpha (ER?) has been widely accepted as a prognostic marker and a predictor for endocrine therapy response of breast cancer. This study aimed to clarify the correlation of ER? methylation with the pathogenesis and clinicopathological significance of sporadic BLBC of Chinese women without a family history of the cancer. The methylation of ER? promoter was investigated in genomic DNA of 60 sporadic BLBC with 108 cases of non-BLBC as control by methylation-specific polymerase chain reaction. We also investigated the expression of p53, breast cancer gene (BRCA)-1, and BRCA-2 by immunohistochemistry and analyzed the correlation between ER? methylation and clinicopathological features of BLBC. ER? methylation was observed in 48 of 60 (80.0%) sporadic BLBC, which was significantly higher than in sporadic non-BLBC cancer (47/108, 43.5%; ?2=20.89, pBRCA-1 and BRCA-2 expression in sporadic BLBC. The ER? methylation status in basal-like breast cancer was significantly higher than in sporadic non-basal-like breast cancer. It was associated with the lymph node metastasis, tumor stage, p53 nuclear accumulation, and BRCA-1 and BRCA-2 expression in BLBC. It may play an important role in BLBC pathogenesis. PMID:21625942

Jing, Ming-xi; Mao, Xiao-yun; Li, Chao; Wei, Jing; Liu, Chong; Jin, Feng

2011-08-01

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

Observation of temporal variations in global sporadic E occurrence rates derived from GPS radio occultation measurements  

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The GPS radio occultation (RO) technique has been established as a powerful tool for ionospheric research. With approximately one million of globally distributed profiles per year provided by the FORMOSAT-3/COSMIC satellites, our data base allows for sporadic E (Es) layer observation with a high spatial resolution and global coverage. Sporadic E layers are thin regions of enhanced electron density in the lower ionospheric E region. They cause strong amplitude scintillations in GPS occultation signals. We use Signal-to-Noise Ratio (SNR) profiles of the GPS L1 signal in order to obtain information on the sporadic E occurrence. Sudden changes in the vertical electron density gradients, which indicate the presence of a sporadic E layer, appear as strong fluctuations in the SNR above 85 km altitude. The FORMOSAT-3/COSMIC data, together with measurements collected by the satellites CHAMP and GRACE which provided continuously RO data since 2001 and 2006, respectively, enables initial trend analysis of Es occurrence. In this study we focus on the variations of sporadic E occurrence rates on different time scales. We will present the diurnal, annual and interannual variability of sporadic E layers and show their connection to other geophysical parameters like solar tides.

Arras, Christina; Wickert, Jens; Jacobi, Christoph; Heise, Stefan

2014-05-01

110

Wilms' tumor suppressor gene mutations in girls with sporadic isolated steroid-resistant nephrotic syndrome.  

Science.gov (United States)

Mutations in the Wilms' tumor suppressor gene (WT1) can lead to syndromic forms of steroid-resistant nephrotic syndrome (SRNS) such as Denys-Drash or Frasier syndrome and can cause isolated SRNS. A mutation within WT1 is a frequent cause of sporadic isolated SRNS in girls. In a worldwide cohort of girls, the rate of occurrence was 10.8%. Previous reports have indicated that in Chinese girls, the detection rate of WT1 mutations is 16.7% for early onset isolated nephrotic syndrome. The detection rate of WT1 mutations in Chinese girls with sporadic isolated SRNS is unknown. We examined WT1 mutations in 14 Chinese girls with sporadic isolated SRNS using polymerase chain reaction and direct sequencing and studied a control group of 38 boys with sporadic isolated SRNS. We identified a WT1 mutation in 1 of 14 (7.1% detection rate) Chinese girls with sporadic isolated SRNS. No mutations occurred in WT1 in the remaining 13 girls or the control group. Our investigation supports the necessity of genetic examination for mutations in WT1 in girls with sporadic isolated SRNS. PMID:24338413

Yang, Y H; Zhao, F; Feng, D N; Wang, J J; Wang, C F; Huang, J; Nie, X J; Xia, G Z; Chen, G M; Yu, Z H

2013-01-01

111

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

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

Schymick Jennifer C

2009-09-01

112

Expression of base excision repair key factors and miR17 in familial and sporadic breast cancer.  

Science.gov (United States)

Understanding of BRCA1/2 interaction with the base excision repair (BER) pathway could improve therapy based on 'synthetic lethality', whose effectiveness is based on homologous recombination deficiency in cells lacking functional BRCA genes. However, poly (ADP-ribose) polymerase (PARP) inhibitors failed in some patients and for this reason we explored BER key enzyme expression. In this study, the expression of BER enzymes (redox factor 1/apurinic-apyrimidinic endonuclease 1 (REF1/APEX1), NTH endonuclease III-like 1 (NTHL1), 8-oxoguanine DNA glycosylase (OGG1), PARP1) and of the scaffold protein XRCC1 (X-ray repair complementing defective repair in Chinese hamster cells 1) were investigated in familial (BRCA-related and not) and sporadic breast cancer cases. Furthermore, miR17 expression was measured because of its role in the epigenetic regulation of BRCA1. Gene expression was evaluated in BRCA1-mutated cell lines, SUM149PT and SUM1315MO2, and in a BRCA1-proficient triple-negative MDA-MB-231 cell line. A cohort of 27 familial and 16 sporadic breast cancer patients was then examined to confirm results obtained from the cell line model. APEX1/REF1 was found to be upregulated in familial BRCA-wild-type and sporadic cases, indicating this enzyme as a potential therapeutic target. Furthermore, XRCC1 was overexpressed in BRCAX patients; consequently, we suggest to test the effectiveness of inhibitors targeting two different BER components in preclinical studies. XRCC1, which is also involved in the non-homologous end-joining pathway, was found to be downregulated in BRCA2-related patients concurrently with no change in PARP1 expression. Interestingly, no difference in PARP1 and miR17 expression was found in BRCA-related and sporadic breast cancer cases. PARP1 and miR17 could therefore be further investigated as molecular biomarkers of 'BRCAness' phenotype, indicating patients which could really benefit from PARP inhibitor therapies. PMID:24556691

De Summa, S; Pinto, R; Pilato, B; Sambiasi, D; Porcelli, L; Guida, G; Mattioli, E; Paradiso, A; Merla, G; Micale, L; De Nittis, P; Tommasi, S

2014-01-01

113

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital  

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INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes 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. PMID:19488601

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

2009-01-01

114

Sporadic medullary thyroid carcinoma: clinical data from a university hospital  

Directory of Open Access Journals (Sweden)

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

2009-05-01

115

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.

116

MicroRNAs discriminate familial from sporadic non-BRCA1/2 breast carcinoma arising in patients ?35 years.  

Science.gov (United States)

The influence of genetic factors may contribute to the poor prognosis of breast cancer (BC) at a very young age. However BRCA1/2 mutations could not explain the majority of cases arising in these patients. MicroRNAs (miRs) have been implicated in biological processes associated with BC. Therefore, we investigated differences in miRs expression between tumors from young patients (?35 years) with sporadic or familial history and non-carriers of BRCA1/2 mutations. Thirty-six young Brazilian patients were divided into 2 groups: sporadic (NF-BC) or familial breast cancer (F-BC). Most of the samples were classified as luminal A and B and the frequency of subtypes did not differ between familial or sporadic cases. Using real time qPCR and discriminant function analysis, we identified 9 miRs whose expression levels rather than miR identity can discriminate between both patient groups. Candidate predicted targets were determined by combining results from miRWalk algorithms with mRNA expression profiles (n?=?91 differently expressed genes). MiR/mRNA integrated analysis identified 91 candidate genes showing positive or negative correlation to at least 1 of the 9 miRs. Co-expression analysis of these genes with 9 miRs indicated that 49 differentially co-expressed miR-gene interactions changes in F-BC tumors as compared to those of NF-BC tumors. Out of 49, 17 (34.6%) of predicted miR-gene interactions showed an inverse correlation suggesting that miRs act as post-transcriptional regulators, whereas 14 (28.6%) miR-gene pairs tended to be co-expressed in the same direction indicating that the effects exerted by these miRs pointed to a complex level of target regulation. The remaining 18 pairs were not predicted by our criteria suggesting involvement of other regulators. MiR-mRNA co-expression analysis allowed us to identify changes in the miR-mRNA regulation that were able to distinguish tumors from familial and sporadic young BC patients non-carriers of BRCA mutations. PMID:25006670

Bastos, Elen Pereira; Brentani, Helena; Pasini, Fatima Solange; Silva, Aderbal Ruy T; Torres, Cesar Henrique; Puga, Renato David; Ribeiro Olivieri, Eloisa Helena; Piovezani, Amanda Rusiska; Pereira, Carlos Alberto de Bragança; Machado-Lima, Ariane; Carraro, Dirce Maria; Brentani, Maria Mitzi

2014-01-01

117

MicroRNAs Discriminate Familial from Sporadic Non-BRCA1/2 Breast Carcinoma Arising in Patients <=35 Years  

Science.gov (United States)

The influence of genetic factors may contribute to the poor prognosis of breast cancer (BC) at a very young age. However BRCA1/2 mutations could not explain the majority of cases arising in these patients. MicroRNAs (miRs) have been implicated in biological processes associated with BC. Therefore, we investigated differences in miRs expression between tumors from young patients (?35 years) with sporadic or familial history and non-carriers of BRCA1/2 mutations. Thirty-six young Brazilian patients were divided into 2 groups: sporadic (NF-BC) or familial breast cancer (F-BC). Most of the samples were classified as luminal A and B and the frequency of subtypes did not differ between familial or sporadic cases. Using real time qPCR and discriminant function analysis, we identified 9 miRs whose expression levels rather than miR identity can discriminate between both patient groups. Candidate predicted targets were determined by combining results from miRWalk algorithms with mRNA expression profiles (n?=?91 differently expressed genes). MiR/mRNA integrated analysis identified 91 candidate genes showing positive or negative correlation to at least 1 of the 9 miRs. Co-expression analysis of these genes with 9 miRs indicated that 49 differentially co-expressed miR-gene interactions changes in F-BC tumors as compared to those of NF-BC tumors. Out of 49, 17 (34.6%) of predicted miR-gene interactions showed an inverse correlation suggesting that miRs act as post-transcriptional regulators, whereas 14 (28.6%) miR-gene pairs tended to be co-expressed in the same direction indicating that the effects exerted by these miRs pointed to a complex level of target regulation. The remaining 18 pairs were not predicted by our criteria suggesting involvement of other regulators. MiR–mRNA co-expression analysis allowed us to identify changes in the miR-mRNA regulation that were able to distinguish tumors from familial and sporadic young BC patients non-carriers of BRCA mutations. PMID:25006670

Bastos, Elen Pereira; Brentani, Helena; Pasini, Fatima Solange; Silva, Aderbal Ruy T.; Torres, Cesar Henrique; Puga, Renato David; Olivieri, Eloisa Helena Ribeiro; Piovezani, Amanda Rusiska; Pereira, Carlos Alberto de Braganca; Machado-Lima, Ariane; Carraro, Dirce Maria; Brentani, Maria Mitzi

2014-01-01

118

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

119

Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas?  

Science.gov (United States)

PURPOSE To determine the prognostic significance of histologic type in radiation-associated soft tissue sarcomas (RASs) and determine whether RASs are associated with an inferior prognosis compared with sporadic soft tissue sarcomas (STSs). PATIENTS AND METHODS One hundred thirty primary RASs were identified from 7,649 STS patients from 1982 to 2007. Multivariate analysis of clinicopathologic factors for disease-specific survival (DSS) was performed for RASs, and a multivariate analysis of radiation exposure was also performed for RASs and sporadic sarcomas. A matched-cohort analysis was performed for radiation-associated and sporadic malignant fibrous histiocytoma (MFH). Results Most RASs were high grade (83%), deep (87%), and truncal (61.5%). The median interval between radiation therapy and RAS development was 10 years (range, 1.3 to 74 years), which varied significantly by histologic type (P = .003). The 5-year DSS was 58%, and independent predictors were size > 5 cm, margin positivity, and histologic type. Multivariate analysis of histologic types of primary, high-grade radiation-associated and sporadic STSs showed that RAS was associated with a worse DSS (hazard ratio, 1.7; range, 1.1 to 2.4; P = .007). For pleomorphic MFH-the most common RAS type-the 5-year DSS was 44% versus 66% in a matched cohort of sporadic MFH patients (P = .07). DSS was significantly worse in primary RAS malignant peripheral nerve sheath tumors (MPNSTs) compared with unmatched sporadic MPNSTs (P = .001). CONCLUSION Histologic type, margin status, and tumor size are the most important independent predictors of DSS in patients with RASs. DSS in patients with primary RAS is significantly worse compared with sporadic STS independent of sarcoma histologic type. PMID:20308666

Gladdy, Rebecca A; Qin, Li-Xuan; Moraco, Nicole; Edgar, Mark A; Antonescu, Cristina R; Alektiar, Kaled M; Brennan, Murray F; Singer, Samuel

2010-04-20

120

A Common BACE1 Polymorphism Is a Risk Factor for Sporadic Creutzfeldt-Jakob Disease  

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The ? site APP cleaving enzyme 1 (BACE1) is the rate-limiting ?-secretase enzyme in the amyloidogenic processing of APP and A? formation, and therefore it has a prominent role in Alzheimer’s disease (AD) pathology. Recent evidence suggests that the prion protein (PrP) interacts directly with BACE1 regulating its ?-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by A? oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer’s and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP) involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, A? oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players. PMID:22952813

Calero, Olga; Bullido, Maria J.; Clarimon, Jordi; Frank-Garcia, Ana; Martinez-Martin, Pablo; Lleo, Alberto; Rey, Maria Jesus; Sastre, Isabel; Rabano, Alberto; de Pedro-Cuesta, Jesus; Ferrer, Isidro; Calero, Miguel

2012-01-01

 
 
 
 
121

Analysis of the FoodNet case-control study of sporadic Salmonella serotype Enteritidis infections using persons infected with other Salmonella serotypes as the comparison group.  

Science.gov (United States)

Use of well persons as the comparison group for laboratory-confirmed cases of sporadic salmonellosis may introduce ascertainment bias into case-control studies. Data from the 1996-1997 FoodNet case-control study of laboratory-confirmed Salmonella serogroups B and D infection were used to estimate the effect of specific behaviours and foods on infection with Salmonella serotype Enteritidis (SE). Persons with laboratory-confirmed Salmonella of other serotypes acted as the comparison group. The analysis included 173 SE cases and 268 non-SE controls. SE was associated with international travel, consumption of chicken prepared outside the home, and consumption of undercooked eggs prepared outside the home in the 5 days prior to diarrhoea onset. SE phage type 4 was associated with international travel and consumption of undercooked eggs prepared outside the home. The use of ill controls can be a useful tool in identifying risk factors for sporadic cases of Salmonella. PMID:18611288

Voetsch, A C; Poole, C; Hedberg, C W; Hoekstra, R M; Ryder, R W; Weber, D J; Angulo, F J

2009-03-01

122

BRCA 1/2-mutation related and sporadic breast and ovarian cancers: More alike than different  

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

MelissaA.Burgess

2014-02-01

123

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

124

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

125

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

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

Sunil V Jagtap

2011-07-01

126

Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer.  

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Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1? (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers. PMID:24457463

Deb, Siddhartha; Johansson, Ida; Byrne, David; Nilsson, Cecilia; Investigators, kConFab; Constable, Leonie; Fjällskog, Marie-Louise; Dobrovic, Alexander; Hedenfalk, Ingrid; Fox, Stephen B

2014-09-01

127

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

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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

128

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

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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

129

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

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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 co...

Maruyama, T.; Saito, S.; Yamamoto, M.; Fukao, S.

2006-01-01

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

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.)

132

A transcriptome signature distinguished sporadic from post-radiotherapy radiation-induced sarcomas  

International Nuclear Information System (INIS)

Exposure to ionizing radiation is a known risk factor for cancer. However, up to now, rigorously defined scientific criteria that could establish case-by-case the radiation-induced (RI) origin of a tumour have been lacking. To identify genes that could constitute a RI signature, we compared the transcriptome of 12 sarcomas arising in the irradiation field of a primary tumour following radiotherapy with the transcriptome of 12 sporadic sarcomas. This learning/training set contained four leiomyosarcomas, four osteosarcomas and four angiosarcomas in each subgroup. We identified a signature of 135 genes discriminating RI from sporadic sarcomas. The robustness of this signature was tested by the blind case-by-case classification of an independent set of 36 sarcomas of various histologies. Thirty-one sarcomas were classified as RI or sporadic; it was not possible to propose an aetiology for the five others. After the code break, it was found that one sporadic sarcoma was mis-classified as RI. Thus, the signature is robust with a sensitivity of 96%, a positive and a negative predictive value of 96 and 100%, respectively and a specificity of 62%. The functions of the genes of the signature suggest that RI sarcomas were subject to chronic oxidative stress probably due to mitochondrial dysfunction. (authors)

133

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

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

Bernhardt, P. A.; Selcher, C. A.; Siefring, C.; Wilkens, M.; Compton, C.; Bust, G.; Yamamoto, M.; Fukao, S.; Takayuki, O.; Wakabayashi, M.; Mori, H.

2005-10-01

134

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

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

S. Fukao

2005-10-01

135

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

136

CT findings of sporadic cherubism in a 6 year old boy  

International Nuclear Information System (INIS)

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

137

Sporadic Human Cryptosporidiosis Caused by Cryptosporidium cuniculus, United Kingdom, 2007–2008  

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To investigate sporadic human cryptosporidiosis trends in the United Kingdom, we tested 3,030 Cryptosporidium spp.–positive fecal samples, submitted for routine typing in 2007–2008, for C. cuniculus. C. cuniculus prevalence was 1.2%; cases were mostly indigenous and occurred across all age groups. Most occurred during August–October and may be linked to exposure opportunities.

Chalmers, Rachel M.; Elwin, Kristin; Hadfield, Stephen J.; Robinson, Guy

2011-01-01

138

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

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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

139

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

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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

140

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.

 
 
 
 
141

Extensive genetic diversity identified among sporadic methicillin-resistant Staphylococcus aureus isolates recovered in Irish hospitals between 2000 and 2012.  

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Clonal replacement of predominant nosocomial methicillin-resistant Staphylococcus aureus (MRSA) strains has occurred several times in Ireland during the last 4 decades. However, little is known about sporadically occurring MRSA in Irish hospitals or in other countries. Eighty-eight representative pvl-negative sporadic MRSA isolates recovered in Irish hospitals between 2000 and 2012 were investigated. These yielded unusual pulsed-field gel electrophoresis and antibiogram-resistogram typing patterns distinct from those of the predominant nosocomial MRSA clone, ST22-MRSA-IV, during the study period. Isolates were characterized by spa typing and DNA microarray profiling for multilocus sequence type (MLST) clonal complex (CC) and/or sequence type (ST) and SCCmec type assignment, as well as for detection of virulence and antimicrobial resistance genes. Conventional PCR-based SCCmec subtyping was undertaken when necessary. Extensive diversity was detected, including 38 spa types, 13 MLST-CCs (including 18 STs among 62 isolates assigned to STs), and 25 SCCmec types (including 2 possible novel SCCmec elements and 7 possible novel SCCmec subtypes). Fifty-four MLST-spa-SCCmec type combinations were identified. Overall, 68.5% of isolates were assigned to nosocomial lineages, with ST8-t190-MRSA-IID/IIE±SCCM1 predominating (17.4%), followed by CC779/ST779-t878-MRSA-?SCCmec-SCC-SCCCRISPR (7.6%) and CC22/ST22-t032-MRSA-IVh (5.4%). Community-associated clones, including CC1-t127/t386/t2279-MRSA-IV, CC59-t216-MRSA-V, CC8-t008-MRSA-IVa, and CC5-t002/t242-MRSA-IV/V, and putative animal-associated clones, including CC130-t12399-MRSA-XI, ST8-t064-MRSA-IVa, ST398-t011-MRSA-IVa, and CC6-t701-MRSA-V, were also identified. In total, 53.3% and 47.8% of isolates harbored genes for resistance to two or more classes of antimicrobial agents and two or more mobile genetic element-encoded virulence-associated factors, respectively. Effective ongoing surveillance of sporadic nosocomial MRSA is warranted for early detection of emerging clones and reservoirs of virulence, resistance, and SCCmec genes. PMID:24395241

Kinnevey, Peter M; Shore, Anna C; Brennan, Grainne I; Sullivan, Derek J; Ehricht, Ralf; Monecke, Stefan; Coleman, David C

2014-01-01

142

Genetic Cross-Interaction between APOE and PRNP in Sporadic Alzheimer's and Creutzfeldt-Jakob Diseases  

Science.gov (United States)

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

Calero, Olga; Bullido, Maria J.; Clarimon, Jordi; Frank-Garcia, Ana; Martinez-Martin, Pablo; Lleo, Alberto; Rey, Maria Jesus; Rabano, Alberto; Blesa, Rafael; Gomez-Isla, Teresa; Valdivieso, Fernando; de Pedro-Cuesta, Jesus; Ferrer, Isidro; Calero, Miguel

2011-01-01

143

Observations and theory of irregularities of middle latitude sporadic E layers  

International Nuclear Information System (INIS)

An experimental and theoretical study is presented of irregularities of the order of 6 meters in wavelength which are revealed by radar observation to be present in the E-region of the middle latitude ionosphere. Systematic observations of the irregularities were carried out by the author at lioka (360N), Japan by using a 25 MHz radar and a multifrequency (4.64 MHz) radar during the years 1973-1977. The irregularities are observed to be field-aligned structures to within the observational errors. They are closely associated with sporadic-E (Es) layers and occur mostly in the lower E-region near 100 km. The occurrence of irregularities is predominantly in the nighttime with a maximum at pre-midnight (approx. 75% in summer). Seasonal occurrence of these irregularities shows a summer maximum, minima in equinoxes and a secondary peak in winter. The irregularities move predominantly in the westward direction with speeds of the order of 60 m/s. For the purpose of understanding the observed behavior of the irregularities, it is necessary, as a first step, to determine the characteristics of middle latitude Es-layers in which these irregularities are spawned. In the absence of observations, these characteristics had to be deduced by suitably generalizing the well-known linear windshear theory of Es-layer formation by including the effects of neutral air vertical motion and ionospheric electric fields. The next step is to develop the gradient-drift instability theorvelop the gradient-drift instability theory of the irregularities applicable to the middle latitude field geometry. Numerical calculations have been performed to illustrate the conclusions of both the Es-layer theory and the instability theory of the irregularities

144

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

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

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

1994-09-01

145

Comparison of sporadic sodium layer characteristics observed at different time resolutions  

Science.gov (United States)

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

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

2013-11-01

146

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

147

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

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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

148

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

International Nuclear Information System (INIS)

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

149

Electron temperature in nighttime sporadic E layer at mid-latitude  

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Full Text Available Electron temperature in the sporadic E layer was measured with a glass-sealed Langmuir probe at a mid-latitude station in Japan in the framework of the SEEK (Sporadic E Experiment over Kyushu-2 campaign which was conducted in August 2002. Important findings are two fold: (1 electron temperature and electron density vary in the opposite sense in the height range of 100–108 km, and electron temperature in the Es layer is lower than that of ambient plasma, (2 electron temperature in these height ranges is higher than the possible range of neutral temperature.

These findings strongly suggest that the heat source that elevates electron temperature much higher than possible neutral temperature exists at around 100 km, and/or that the physical parameter values, which are used in the present theory to calculate electron temperature, are not proper.

K.-I. Oyama

2008-03-01

150

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.)

151

Expression of myogenic regulatory factors and myo-endothelial remodeling in sporadic inclusion body myositis  

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Muscle repair relies on coordinated activation and differentiation of satellite cells, a process that is unable to counterbalance progressive degeneration in sporadic inclusion body myositis (s-IBM). To explore features of myo regeneration, the expression of myogenic regulatory factors Pax7, MyoD and Myogenin and markers of regenerating fibers was analyzed by immunohistochemistry in s-IBM muscle compared with polymyositis, dermatomyositis, muscular dystrophy and age-matched controls. In addit...

Wanschitz, Julia V.; Dubourg, Odile; Lacene, Emmanuelle; Fischer, Michael B.; Ho?ftberger, Romana; Budka, Herbert; Romero, Norma B.; Eymard, Bruno; Herson, Serge; Butler-browne, Gillian S.; Voit, Thomas; Benveniste, Olivier

2013-01-01

152

Absence of RET proto-oncogene abnormalities in sporadic parathyroid tumors  

Energy Technology Data Exchange (ETDEWEB)

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

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

1994-09-01

153

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

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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

154

Homozygous somatic Wt1 point mutations in sporadic unilateral Wilms tumor.  

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Wilms tumor may be caused by loss of function of genes at different loci. A Wilms tumor suppressor gene, WT1, at chromosome 11 band p13, has recently been cloned and characterized. WT1 has been implicated in the development of Wilms tumor by virtue of mutations in patients with genitourinary anomalies and susceptibility to Wilms tumor. Homozygous intragenic mutations have been reported in Wilms tumors, but usually not in sporadic unilateral Wilms tumors, which constitute the majority of Wilms...

Coppes, M. J.; Liefers, G. J.; Paul, P.; Yeger, H.; Williams, B. R.

1993-01-01

155

Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells.  

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Children with associated Wilms' tumor, aniridia, genitourinary malformations, and mental retardation (WAGR syndrome) frequently have a cytogenetically visible germ line deletion of chromosomal band 11p13. In accordance with the Knudson hypothesis of two-hit carcinogenesis, the absence of this chromosomal band suggests that loss of both alleles of a gene at 11p13 causes Wilms' tumor. Consistent with this model, chromosomes from sporadically occurring Wilms' tumor cells frequently show loss of ...

Reeve, A. E.; Sih, S. A.; Raizis, A. M.; Feinberg, A. P.

1989-01-01

156

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

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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

157

Earth's influx of different populations of sporadic meteoroids from photographic and television data  

International Nuclear Information System (INIS)

Precise photographic and television double- and multi-station data on 3624 sporadic meteors in the mass range from 2 x 10-5 grams to 2 x 107 grams form the basis of this paper. The applied classification criteria and procedures are defined and described. A survey of 7 different populations of sporadic meteoroids known so far is presented. The total numbers and masses of meteoroids as a function of mass are given for individual groups and for all sporadic meteors. The absolute calibration of the influx to the Earth was carried out by comparison with the results of Halliday et al. (1984). The comparison with the visual and cratering data revealed good agreement in the narrow ''visual'' interval of masses, and disagreement in the extrapolated parts of the visual and cratering flux curves. The slope of the cumulative number curve for the meteorite-dropping fireballs (type I) with masses larger than 1 kg was found as -0.69 in perfect agreement with the results of Halliday et al. (1984). The final mass scale derived in this paper is situated between the scale of McCrosky and the scale of Halliday. The relative significance of the different groups of meteoroids changes with the mass quite dramatically. The total influx of sporadic meteoroids in the mass interval of 12 orders from 2 x 107 to 2 x 10-5 grams resulted in 5 x 109 grams per year for the entire Earth's surface. Most of this mass comes in the form of larger meteoroids. Bulk densities and ablation coefficient are presented for the individual meteor groups depending on different ablation models of several authors and some extreme concepts of this problem are discussed. (author). 3 figs., 6 tabs., 38 refs

158

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

159

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

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Abstract Background Interstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been investigated. As the balanced chromosomal abnormalities commonly lead to the recurrent ID or multiple congenital anomalies, this study was designed to evaluate whether it was justified to investigate such aberrations in familial ID patients. Three hundre...

Rafati Maryam; Seyyedaboutorabi Elaheh; Ghadirzadeh Mohammad R; Heshmati Yaser; Adibi Homeira; Keihanidoust Zarrintaj; Eshraghian Mohammad R; Javadi Gholam; Dastan Jila; Mosavi-Jarrahi Alireza; Hoseini Azadeh; Purhoseini Marzieh; Ghaffari Saeed R

2012-01-01

160

Novel somatic MEN1 gene alterations in sporadic primary hyperparathyroidism and correlation with clinical characteristics.  

Science.gov (United States)

Primary hyperparathyroidism (pHPT) is a common endocrine disease that in more than 95% of cases is sporadic and only in some cases is caused by inherited disorders, isolated or as part of multiple endocrine neoplasia (MEN1 and 2). Somatic mutations of MEN1 gene have also been described in sporadic parathyroid tumors. In our study, we examined the presence of alterations in MEN1 gene in a series of 39 patients who had undergone surgery for sporadic pHPT (35 with parathyroid adenoma or hyperplasia, 4 with a carcinoma). A genotype-phenotype correlation was also analysed. After DNA extraction from paraffin-embedded tissues, we amplified by PCR and sequenced the exons 2-10 of the MEN1 gene. Somatic MEN1 mutations were detected in 6 of the 35 patients with a benign parathyroid lesion examined (17.1%), whereas no alterations were found in the carcinomas. Four novel MEN1 gene mutations were identified as follows: one frameshift mutation (222insT, exon 2), one frameshift deletion (912delTA, exon 5), one in-frame deletion (835del18, exon 4) and one missense mutation (P291A, exon 6). In addition, one missense mutation (L89R, exon 2) and one nonsense mutation (Q536X, exon 10) were previously reported. Moreover, two polymorphisms were also found: one allele carried a R171Q polymorphism (1/39 tumors), while a D418D polymorphism (GAC/GAT) was found in 15 and 8 tumors in hetero (CT) and homozygosity (TT), respectively. In no case (mutations and/or polymorphisms) did we find a genotype-phenotype correlation. In conclusion, our data demonstrate the presence of somatic alterations of the MEN1 tumor suppressor gene in about one fifth of benign sporadic parathyroid tumors. The absence of a genotype-phenotype correlation, however, suggests the involvement of other genetic/epigenetic factors for the full expression of the disease. PMID:15754732

Scarpelli, D; D'Aloiso, L; Arturi, F; Scillitani, A; Presta, I; Bisceglia, M; Cristofaro, C; Russo, D; Filetti, S

2004-12-01

 
 
 
 
161

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

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

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

1994-09-01

162

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

163

Genetic variants in sporadic Parkinson's disease: East vs West.  

Science.gov (United States)

A number of gene variants or single nucleotide polymorphisms (SNPs) have been shown to modulate the risk of Parkinson's disease (PD). These variants are identified from genetic association studies of familial PD and candidate genes, and from genome wide association studies (GWAS). These include REP1 dinucleotide repeat polymorphism within the promoter region of the SNCA gene, and SNPs within the vicinity of SNCA and LRRK2 genes. A number of exonic variants of LRRK2 (G2385R, R1628P, S1647T, M1646T, A419V, R1398H, N551K, Y2189C) have been shown to influence PD risk in various ethnic populations. Numerous GWAS linked loci including BST1 (bone marrow stromal cell antigen 1), PARK16 (parkinson disease 16 susceptibility), GAK (cyclin G associated kinase), and HLA (human leukocyte antigen) have also been identified. The genetic variants have differential effect on PD risk in Eastern and Western populations. Knowing the basis behind ethnic-specific variances would further our understanding of the pathophysiologic mechanisms and help planning of genetic testing programmes. PMID:22166457

Peeraully, Tasneem; Tan, E K

2012-01-01

164

Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B status  

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AIM: To evaluate joint effects of Methylentetrahydrofolate reductase (MTHFR) C677T genotypes, and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients.METHODS: We examined the associations between MTHFR C677T genotype, and promoter methylation of P16, hMLH1, and hMSH2 tumor-related genes among 151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-speci...

Pooneh Mokarram, Fakhraddin Naghibalhossaini

2008-01-01

165

Association study of human MTH1 Ile45Thr polymorphism with sporadic Parkinson's disease.  

Science.gov (United States)

Human MTH1, an oxidized purine nucleoside triphosphatase, hydrolyzes 8-oxo-dGTP thereby preventing its misincorporation into DNA. The present study was designed to investigate a possible link between the MTH1 Ile45Thr polymorphism and the development of sporadic Parkinson disease (PD). This case-control study consisted of 106 PD patients and 135 unrelated controls. MTH1 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that Ile45/Thr45 heterozygote and Thr45 allele tended to be more frequent in sporadic PD, although statistically not significant (0.085 vs. 0.044, corrected p = 0.591 and 0.052 vs. 0.022, p = 0.080, respectively). Stratification analysis by gender showed that Ile45/Thr45 heterozygote tended to be more frequent in male PD patients than in male controls (0.113 vs. 0.038, corrected p = 0.480). The male PD patients exhibited a borderline statistically significant higher frequency of the Thr45 allele than the controls (0.073 vs. 0.019, corrected p = 0.050). These results suggested to us that the Thr45 allele of MTH1 might be associated with sporadic PD in the Chinese male population. PMID:17917452

Jiang, Gaofeng; Xu, Lei; Wang, Lin; Song, Shizhen; Zhu, Changcai

2008-01-01

166

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

167

AIP Mutations are not identified in patients with sporadic pituitary adenomas.  

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The pathogenesis of pituitary adenomas remains a subject of interest. Recently, mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were identified as germline events leading to pituitary tumor predisposition in Finnish and Italian families with familial growth hormone-secreting pituitary adenomas and acromegaly. We examined the frequency of AIP mutations in pituitary tumors and blood of Canadian patients with sporadic pituitary somatotroph adenomas and sporadic pituitary adenomas of other types. Genomic DNA was extracted from pituitary tumors and white blood cells obtained from peripheral blood. Three PCR reactions were carried out to amplify the sites of known mutation, and amplified products were sequenced. AIP mutations were not detected as germline events in blood or as somatic alterations in tumors of 66 patients with pituitary adenomas. These included 50 acromegalics and 16 patients with other types of pituitary tumor. No mutations were detected in the blood of 22 controls and 10 patients with other endocrinopathies. Our results indicate that mutations in AIP are not identified in sporadic pituitary adenomas of Canadian patients. This rare mechanism of pituitary tumorigenesis appears to be unique to the initial Finnish and Italian families described. PMID:17916996

DiGiovanni, Rebecca; Serra, Stefano; Ezzat, Shereen; Asa, Sylvia L

2007-01-01

168

[AIP mutations in familial and sporadic pituitary adenomas: local experience and review of the literature].  

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Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19- year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age. PMID:19883897

Fajardo-Montañana, Carmen; Daly, Adrian F; Riesgo-Suárez, Pedro; Gómez-Vela, José; Tichomirowa, María A; Camara-Gómez, Rosa; Beckers, Albert

2009-01-01

169

C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population  

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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; Monsurro, 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; Chio, Adriano

2012-01-01

170

A Unique Profile of Adenomatous Polyposis Coli Gene Mutations in Iranian Patients Suffering Sporadic Colorectal Cancer  

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Full Text Available Objective: Colorectal cancer (CRC is one of the most common and aggressive cancers worldwide. The majority of CRC cases are sporadic that caused by somatic mutations. The Adenomatous Polyposis Coli (APC; OMIM 611731 is a tumor suppressor gene of Wnt pathway and is frequently mutated in CRC cases. This study was designed to investigate the spectrum of APC gene mutations in Iranian patients with sporadic colorectal cancer. Materials and Methods: In this descriptive study, Tumor and normal tissue samples were obtained from thirty randomly selected and unrelated sporadic CRC patients. We examined the hotspot region of the APC gene in all patients. Our mutation detection method was direct DNA sequencing. Results: We found a total of 8 different APC mutations, including two nonsense mutations (c.4099C>T and c.4348C>T, two missense mutations (c.3236C>G and c.3527C>T and four frame shift mutations (c.2804dupA, c.4317delT, c.4464_4471delATTACATT and c.4468_4469dupCA. The c.3236C>G and c.4468_4469dupCA are novel mutations. The overall frequency of APC mutation was 26.7% (8 of 30 patients. Conclusion: This mutation rate is lower in comparison with previous studies from other countries. The findings of present study demonstrate a different APC mutation spectrum in CRC patients of Iranian origin compared with other populations.

Mojtaba Hasanpour

2014-03-01

171

Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia.  

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Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder caused by mutations in one of seven known genes (FANCA,C,D2,E,F,G and BRCA2). Mutations in the FANCA gene are the most prevalent, accounting for two-thirds of FA cases. Affected individuals have greatly increased risks of acute myeloid leukemia (AML). This raises the question as to whether inherited or acquired mutations in FA genes might be involved in the development of sporadic AML. Quantitative fluorescent PCR was used to screen archival DNA from sporadic AML cases for FANCA deletions, which account for 40% of FANCA mutations in FA homozygotes. Four heterozygous deletions were found in 101 samples screened, which is 35-fold higher than the expected population frequency for germline FANCA deletions (P<0.0001). Sequencing FANCA in the AML samples with FANCA deletions did not detect mutations in the second allele and there was no evidence of epigenetic silencing by hypermethylation. However, real-time quantitative PCR analysis in these samples showed reduced expression of FANCA compared to nondeleted AML samples and to controls. These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML. PMID:14749703

Tischkowitz, M D; Morgan, N V; Grimwade, D; Eddy, C; Ball, S; Vorechovsky, I; Langabeer, S; Stöger, R; Hodgson, S V; Mathew, C G

2004-03-01

172

Rocket/Radar Sporadic-E Experiment Conducted during the El Coqui 2 Campaign  

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In order to investigate the complex electrodynamics and neutral-plasma coupling inherent to sporadic-E layers in the earth's mid-latitude ionosphere, a series of rocket/radar experiments were planned as part of the NASA El Coqui H Campaign from Tortuguero Launch Range, Puerto Rico, in March-April, 1998. The rocket experiments consisted of two pairs of "mother-daughter" payloads with limited apogees so that the payloads "hovered" in the sporadic-E region (95-125 km). Each payload pair included vector DC and AC electric field detectors, a highly accurate flux-gate DC magnetometer, an ion mass spectrometer, an ionization gauge, and spaced-electric field receivers to measure the wavelength and phase velocity of the unstable plasma waves. Separate rockets were included to simultaneously carry aloft TMA trails to measure the neutral wind and its velocity shear, believed responsible for the sporadic-E layer formation. In addition to the rocket experiments, incoherent scatter radar measurements of plasma density and drift velocity were gathered almost every night during the 3 week campaign. Continuous VHF backscatter radar operations were carried out from a site near Salinas, Puerto Rico, where 3-m backscatter echoes were observed associated with sporadic-E and other types of low altitude ionospheric layers. Other radars that operated during the campaign included an HF backscatter system near Ponce, Puerto Rico, and a second VHF backscatter radar set up near Aguadila Puerto Rico. On 24 March 1998, one of the instrumented rockets was launched, attaining an apogee of 129 km. The payloads successfully pierced an intense sporadic-E layer observed by both the Arecibo radar and the in-situ density and ion mass spectrometer probes. In-situ DC electric fields revealed very low (about 1-2 mV/m) ambient fields with small amplitude structures of the same order. No high frequency (short scale) waves were observed, consistent with the VHF backscatter observations at the time of the launch. An overview of the observations will be presented.

Pfaff, R.F.; Acuna, M.; Bounds, S.; Freudenreich, H.; Clemmons, J.; Earle, G.; Heelis, R.; Kudeki, E.; Franke, S.; Larsen, M.

1999-01-01

173

HLA-DRB1 frequency in patients with familial and sporadic rheumatoid arthritis in north east of Iran.  

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Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints that has a strong correlation with HLA-DRB1. Family history is considered a known risk factor for RA. The aims of this study were to compare the frequency of HLA-DRB1 alleles between patients with sporadic and familial RA and also between healthy controls with RA patients (sporadic and familial) and clarify if familial RA is more severe than sporadic RA. This study included 129 consecutive patients with sporadic and 48 cases with familial (first-degree siblings) RA who visited a rheumatology unit. Demographic data, including extra-articular involvement, mean disease activity according to DAS28 (ESR) criteria, and main laboratory findings, were compared between patients with sporadic and familial RA. HLA-DRB1 typing was carried out using the PCR-SSP method, and the frequency of each allele was determined in all cases and compared with the results of HLA-DRB1 frequencies in 72 healthy controls who were previously reported by our group in northeast Iran. Patients with sporadic and familial RA were matched in age and sex, most of the cases in both groups were females. The mean age of patients was 45 years. Ocular involvement was the most frequent extra-articular manifestation of our patients. There was no significant difference between the two groups in visual analogue scale (VAS) index, number of inflamed or tender joints, extra-articular involvements, and main laboratory findings. HLA-DRB1* 01 (55 %), 04 (48 %), and 03 (43 %) alleles were the most frequent alleles in both sporadic and familial diseases. The frequency of HLA-DRB1*11 and HLA-DRB1*13 was significantly higher in normal participants compared with RA (p?=?0.001). There was no significant difference in the HLA-DRB1 allele's frequency between sporadic and familial RA. Therefore, familial aggregation was not associated with RA severity. PMID:24760193

Saghafi, Massoud; Nohesara, Najmeh; Rafatpanah, Houshang; Shariati, Jaleh; Shakeri, Mohamad Taghi

2014-10-01

174

Sporadic—but Not Variant—Creutzfeldt-Jakob Disease Is Associated with Polymorphisms Upstream of PRNP Exon 1  

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Human prion diseases have inherited, sporadic, and acquired etiologies. The appearance of the novel acquired prion disease, variant Creutzfeldt-Jakob disease (vCJD), and the demonstration that it is caused by the same prion strain as that causing bovine spongiform encephalopathy, has led to fears of a major human epidemic. The etiology of classical (sporadic) CJD, which has a worldwide incidence, remains obscure. A common human prion-protein-gene (PRNP) polymorphism (encoding either methionin...

Mead, S.; Mahal, Sp; Beck, J.; Campbell, T.; Farrall, M.; Fisher, E.; Collinge, J.

2001-01-01

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RARB and STMN2 polymorphisms are not associated with sporadic Creutzfeldt-Jakob disease (CJD) in the Korean population.  

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Polymorphisms in the prion protein gene (PRNP) can affect the susceptibility of humans to prion diseases. Recently, aside from PRNP, single nucleotide polymorphisms (SNPs) of two candidate genes for susceptibility to human prion diseases have been identified by human genome-wide association studies (GWAS) in the British population. One SNP of retinoic acid receptor beta (RARB), which is correlated with prion disease incubation time in mice, was associated with human prion diseases such as variant and iatrogenic CJD in the British population. The other SNP of the gene that encodes SCG10 (STMN2), which is related to clinical onset of sporadic CJD, was also associated with variant CJD and kuru. In order to investigate whether two polymorphisms located in upstream of RARB and STMN2 are associated with sporadic CJD in the Korean population, we compared genotype and allele frequencies of these polymorphisms in 217 sporadic CJD patients and 216 healthy Koreans. The genotype distribution and allele frequencies in upstream of the RARB and STMN2 polymorphisms were not significantly different between healthy controls and Korean sporadic CJD patients. This finding indicates that the two SNPs are not correlated with genetic susceptibility to sporadic CJD in the Korean population. This is the first genetic association study of RARB and STMN2 with sporadic CJD in an Asian population. PMID:24414001

Jeong, Byung-Hoon; Kim, Hae-Jung; Lee, Kyung-Hee; Carp, Richard I; Kim, Yong-Sun

2014-04-01

176

Ongoing Activity in Temporally Coherent Networks Predicts Intra-Subject Fluctuation of Response Time to Sporadic Executive Control Demands  

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Can ongoing fMRI BOLD signals predict fluctuations in swiftness of a person’s response to sporadic cognitive demands? This is an important issue because it clarifies whether intrinsic brain dynamics, for which spatio-temporal patterns are expressed as temporally coherent networks (TCNs), have effects not only on sensory or motor processes, but also on cognitive processes. Predictivity has been affirmed, although to a limited extent. Expecting a predictive effect on executive performance for a wider range of TCNs constituting the cingulo-opercular, fronto-parietal, and default mode networks, we conducted an fMRI study using a version of the color–word Stroop task that was specifically designed to put a higher load on executive control, with the aim of making its fluctuations more detectable. We explored the relationships between the fluctuations in ongoing pre-trial activity in TCNs and the task response time (RT). The results revealed the existence of TCNs in which fluctuations in activity several seconds before the onset of the trial predicted RT fluctuations for the subsequent trial. These TCNs were distributed in the cingulo-opercular and fronto-parietal networks, as well as in perceptual and motor networks. Our results suggest that intrinsic brain dynamics in these networks constitute “cognitive readiness,” which plays an active role especially in situations where information for anticipatory attention control is unavailable. Fluctuations in these networks lead to fluctuations in executive control performance. PMID:24901995

Nozawa, Takayuki; Sugiura, Motoaki; Yokoyama, Ryoichi; Ihara, Mizuki; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Kanno, Akitake; Kawashima, Ryuta

2014-01-01

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High-throughput mutation profiling improves diagnostic stratification of sporadic medullary thyroid carcinomas.  

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Sporadic medullary thyroid carcinoma (MTC) harbors RET gene somatic mutations in up to 50 % of cases, and RAS family gene mutations occur in about 10 %. A timely and comprehensive characterization of molecular alterations is needed to improve MTC diagnostic stratification and design-tailored therapeutic approaches. Twenty surgically resected sporadic MTCs, previously analyzed for RET mutations by Sanger sequencing using DNA from formalin-fixed paraffin-embedded samples, were investigated for intragenic mutations in 50 cancer-associated genes applying a multigene Ion AmpliSeq next-generation sequencing (NGS) technology. Thirteen (65 %) MTCs harbored a RET mutation; 10 were detected at both Sanger and NGS sequencing, while 3 undetected by Sanger were revealed by NGS. One of the 13 RET-mutated cases also showed an F354L germline mutation in STK11. Of the seven RET wild-type MTCs, four cases (57.1 %) harbored a RAS mutation: three in HRAS (all Q61R) and one in KRAS (G12R). The three remaining MTCs (15 %) resulted as wild-type for all the 50 cancer-related genes. Follow-up was available in all but one RET-mutated case. At the end of follow-up, 7 of 12 (58 %) RET-mutated patients had relapsed, while the 4 RAS-mutated MTC patients were disease-free. Two of the three patients with MTC wild-type for all 50 genes relapsed during the follow-up period. Detection of mutations by NGS has the potential to improve the diagnostic stratification of sporadic MTC. PMID:24828033

Simbolo, Michele; Mian, Caterina; Barollo, Susi; Fassan, Matteo; Mafficini, Andrea; Neves, Diogo; Scardoni, Maria; Pennelli, Gianmaria; Rugge, Massimo; Pelizzo, Maria Rosa; Cavedon, Elisabetta; Fugazzola, Laura; Scarpa, Aldo

2014-07-01

178

Sporadic E tidal variabilities and characteristics observed with the Cyprus Digisonde  

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

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

2014-11-01

179

Altered CpG methylation in sporadic Alzheimer's disease is associated with APP and MAPT dysregulation.  

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The hallmark of Alzheimer's disease (AD) pathology is an accumulation of amyloid ? (A?) and phosphorylated tau, which are encoded by the amyloid precursor protein (APP) and microtubule-associated protein tau (MAPT) genes, respectively. Less than 5% of all AD cases are familial in nature, i.e. caused by mutations in APP, PSEN1 or PSEN2. Almost all mutations found in them are related to an overproduction of A?1-42, which is prone to aggregation. While these genes are mutation free, their function, or those of related genes, could be compromised in sporadic AD as well. In this study, pyrosequencing analysis of post-mortem brains revealed aberrant CpG methylation in APP, MAPT and GSK3B genes of the AD brain. These changes were further evaluated by a newly developed in vitro-specific DNA methylation system, which in turn highlighted an enhanced expression of APP and MAPT. Cell nucleus sorting of post-mortem brains revealed that the methylation changes of APP and MAPT occurred in both neuronal and non-neuronal cells, whereas GSK3B was abnormally methylated in non-neuronal cells. Further analysis revealed an association between abnormal APP CpG methylation and apolipoprotein E ?4 allele (APOE ?4)-negative cases. The presence of a small number of highly methylated neurons among normal neurons contribute to the methylation difference in APP and MAPT CpGs, thus abnormally methylated cells could compromise the neural circuit and/or serve as 'seed cells' for abnormal protein propagation. Our results provide a link between familial AD genes and sporadic neuropathology, thus emphasizing an epigenetic pathomechanism for sporadic AD. PMID:24101602

Iwata, Atsushi; Nagata, Kenichi; Hatsuta, Hiroyuki; Takuma, Hiroshi; Bundo, Miki; Iwamoto, Kazuya; Tamaoka, Akira; Murayama, Shigeo; Saido, Takaomi; Tsuji, Shoji

2014-02-01

180

TP53 Codon 72 Heterozygosity May Promote MicrosatelliteInstability in Sporadic Colorectal Cancer  

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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

 
 
 
 
181

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

182

Sporadic bilateral adrenal medullary hyperplasia: apparent false positive MIBG scan and expected MRI findings  

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Adrenal medullary hyperplasia is a rare cause of clinical symptoms and biochemical findings identical to pheochromocytoma occurring mostly in multiple endocrine neoplasia patients. The scenario of positive MIBG scan, but no focal lesion found on CT and MRI led to diagnostic and management difficulties. Like pheochromocytoma, surgical excision can lead to clinical and biochemical recovery. We report this unusual case of sporadic bilateral adrenal medullary hyperplasia, with hypertension and biochemical abnormalities alleviated after surgical adrenalectomy. Based on T2 values reported in literature, high signal focal lesions may not appear on T2-weighted MRI images until development of frank pheochromocytoma. MIBG scan remains the most sensitive imaging modality for this condition

183

Sporadic bilateral adrenal medullary hyperplasia: apparent false positive MIBG scan and expected MRI findings  

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Adrenal medullary hyperplasia is a rare cause of clinical symptoms and biochemical findings identical to pheochromocytoma occurring mostly in multiple endocrine neoplasia patients. The scenario of positive MIBG scan, but no focal lesion found on CT and MRI led to diagnostic and management difficulties. Like pheochromocytoma, surgical excision can lead to clinical and biochemical recovery. We report this unusual case of sporadic bilateral adrenal medullary hyperplasia, with hypertension and biochemical abnormalities alleviated after surgical adrenalectomy. Based on T2 values reported in literature, high signal focal lesions may not appear on T2-weighted MRI images until development of frank pheochromocytoma. MIBG scan remains the most sensitive imaging modality for this condition.

Yung, Babington C.K.; Loke, Tony K.L.; Tse, T.W.; Tsang, M.W.; Chan, James C.S. E-mail: jcschan@ha.org.hk

2000-10-01

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Outcome after prenatal detection of a sporadic, unstable translocation t(5;21).  

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Amniotic fluid cultures from a 37 year old woman showed a sporadic 46,XX,t(5;21)(5qter----5p13 or p14::5pter----5p13 or p14::21p12----21qter) complement. In the majority of metaphases the 5p fragment was attached to the stalks of chromosome 21; however, in 9% of metaphases, the fragment was loosely attached by a 'thread' and in 6% it was completely detached. Silver staining and in situ hybridisation with a homologous ribosomal gene probe, which localises to stalk regions (nucleolar organisers...

1986-01-01

185

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

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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

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Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics  

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A major recent discovery was the identification of an expansion of a non-coding GGGGCC hexanucleotide repeat in the C9ORF72 gene in patients with frontotemporal dementia and amyotrophic lateral sclerosis. Mutations in two other genes are known to account for familial frontotemporal dementia: microtubule-associated protein tau and progranulin. Although imaging features have been previously reported in subjects with mutations in tau and progranulin, no imaging features have been published in C9ORF72. Furthermore, it remains unknown whether there are differences in atrophy patterns across these mutations, and whether regional differences could help differentiate C9ORF72 from the other two mutations at the single-subject level. We aimed to determine the regional pattern of brain atrophy associated with the C9ORF72 gene mutation, and to determine which regions best differentiate C9ORF72 from subjects with mutations in tau and progranulin, and from sporadic frontotemporal dementia. A total of 76 subjects, including 56 with a clinical diagnosis of behavioural variant frontotemporal dementia and a mutation in one of these genes (19 with C9ORF72 mutations, 25 with tau mutations and 12 with progranulin mutations) and 20 sporadic subjects with behavioural variant frontotemporal dementia (including 50% with amyotrophic lateral sclerosis), with magnetic resonance imaging were included in this study. Voxel-based morphometry was used to assess and compare patterns of grey matter atrophy. Atlas-based parcellation was performed utilizing the automated anatomical labelling atlas and Statistical Parametric Mapping software to compute volumes of 37 regions of interest. Hemispheric asymmetry was calculated. Penalized multinomial logistic regression was utilized to create a prediction model to discriminate among groups using regional volumes and asymmetry score. Principal component analysis assessed for variance within groups. C9ORF72 was associated with symmetric atrophy predominantly involving dorsolateral, medial and orbitofrontal lobes, with additional loss in anterior temporal lobes, parietal lobes, occipital lobes and cerebellum. In contrast, striking anteromedial temporal atrophy was associated with tau mutations and temporoparietal atrophy was associated with progranulin mutations. The sporadic group was associated with frontal and anterior temporal atrophy. A conservative penalized multinomial logistic regression model identified 14 variables that could accurately classify subjects, including frontal, temporal, parietal, occipital and cerebellum volume. The principal component analysis revealed similar degrees of heterogeneity within all disease groups. Patterns of atrophy therefore differed across subjects with C9ORF72, tau and progranulin mutations and sporadic frontotemporal dementia. Our analysis suggested that imaging has the potential to be useful to help differentiate C9ORF72 from these other groups at the single-subject level. PMID:22366795

Weigand, Stephen D.; Boeve, Bradley F.; Senjem, Matthew L.; Gunter, Jeffrey L.; DeJesus-Hernandez, Mariely; Rutherford, Nicola J.; Baker, Matthew; Knopman, David S.; Wszolek, Zbigniew K.; Parisi, Joseph E.; Dickson, Dennis W.; Petersen, Ronald C.; Rademakers, Rosa; Jack, Clifford R.; Josephs, Keith A.

2012-01-01

187

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

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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

188

Inter-decadal variability of Sporadic-E layer at Argentine Islands, Antarctica?  

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The diurnal variations of Sporadic-E layer (Es) occurrence and of various Es characteristics over Argentine Islands (65.3oS; 64.3oW) have been determined for autumn, winter, spring and summer during both low and high solar activity level for solar cycles 21, 22 and 23. Although identical equipments were used only for cycles 22 and 23, an attempt is made to identify possible inter-decadal variations, which seem to have been documented for other locations. There seems to be true inter-cycle dif...

Foppiano, A. J.; Flores, P. A.

2008-01-01

189

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

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BACKGROUND: Prion diseases are a group of invariably fatal neurodegenerative disorders affecting humans and a wide range of mammals. An essential part of the infectious agent, termed the prion, is composed of an abnormal isoform (PrPSc) of a host-encoded normal cellular protein (PrPC). The conversion of PrPC to PrPSc is thought to play a crucial role in the development of prion diseases and leads to PrPSc deposition, mainly in the central nervous system. Sporadic Creutzfeldt-Jakob disease (sC...

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

2006-01-01

190

Device for investigation of sporadic radiowave radiation of the Earth ionosphere  

International Nuclear Information System (INIS)

The first unit of experimental device to investigate sporadic radiowave radiation of the barth ionosphere has been developed. The radiowave radiation reception is performed using the zenith 16-element radiotelescope with the width of the main petal of radiation pattern of approximately 26 deg at the frequency of 38 MHz. Symmetric half-wave vibrators serve as the elements of radiotelescope. Scintillation muon telescopes are used for the purpose of simultaneous detection of cosmic ray muons on sea level. The coincidence-anticoincidence circuit is used for more strict selection of splashes of sporodic radiowave radiation and investigation of their fine structure

191

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

192

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

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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

193

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

194

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

195

Large airglow enhancements produced via wave-plasma interactions in sporadic E  

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In the past there has been great interest in monitoring enhanced 557.7 nm O(¹S) emissions from the thermosphere in connection with high-power, high-frequency (HF) radio wave modification of the F region ionosphere. These emissions are considered to be evidence that the HF-modified electron distribution function is non-Maxwellian because a significant flux of ˜5-6 eV electrons is required to produce the airglow. The suprathermal tail is believed to develop as a result of nonlinear plasma processes. Past F region observations of 557.7 nm airglow at Arecibo Observatory, Puerto Rico have yielded only a few Rayleighs of enhanced emissions. Recently, airglow enhancements were monitored in sporadic E above Arecibo. Surprisingly, these experiments yielded ˜55 Rayleighs of enhanced 557.7 nm airglow and the first observations of emissions from the N2 first positive molecular bands. The observations imply that a large flux of energetic (5-10 eV) electrons is generated as part of the wave-plasma interaction in sporadic E.

Djuth, F. T.; Bernhardt, P. A.; Tepley, C. A.; Gardner, J. A.; Kelley, M. C.; Broadfoot, A. L.; Kagan, L. M.; Sulzer, M. P.; Elder, J. H.; Selcher, C.; Isham, B.; Brown, C.; Carlson, H. C.

196

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

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

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

2013-08-01

197

Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases.  

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We quantified vascular changes in the frontal lobe and basal ganglia of four inherited small vessel diseases (SVDs) including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), hereditary multi-infarct dementia of Swedish type (Swedish hMID), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Vascular pathology was most severe in CADASIL, and varied with marginally greater severity in the basal ganglia compared to the frontal lobe. The overall sclerotic index values in frontal lobe were in the order CADASIL???HERNS?>?PADMAL?>?Swedish hMID?>?sporadic SVD, and in basal ganglia CADASIL?>?HERNS?>?Swedish hMID?>?PADMAL> sporadic SVD. The subcortical white matter was almost always more affected than any gray matter. We observed glucose transporter-1 (GLUT-1) protein immunoreactivities were most affected in the white matter indicating capillary degeneration whereas collagen IV (COL4) immunostaining was increased in PADMAL cases in all regions and tissue types. Overall, GLUT-1?:?COL4 ratios were higher in the basal ganglia indicating modifications in capillary density compared to the frontal lobe. Our study shows that the extent of microvascular degeneration varies in these genetic disorders exhibiting common end-stage pathologies but is the most aggressive in CADASIL. PMID:23387519

Craggs, Lucinda J L; Hagel, Christian; Kuhlenbaeumer, Gregor; Borjesson-Hanson, Anne; Andersen, Oluf; Viitanen, Matti; Kalimo, Hannu; McLean, Catriona A; Slade, Janet Y; Hall, Roslyn A; Oakley, Arthur E; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Rajesh N

2013-09-01

198

Magnesium Protects Cognitive Functions and Synaptic Plasticity in Streptozotocin-Induced Sporadic Alzheimer's Model  

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Alzheimer’s disease (AD) is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP), dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3? at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3? in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy. PMID:25268773

Bao, Jian; Wang, Zhi-Hao; Zeng, Juan; Liu, En-Jie; Li, Xiao-Guang; Huang, Rong-Xi; Gao, Di; Li, Meng-Zhu; Zhang, Yao; Liu, Gong-Ping; Wang, Jian-Zhi

2014-01-01

199

Genotyping of outbreak-related and sporadic isolates of Clostridium difficile belonging to serogroup C.  

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Serogroup C of Clostridium difficile is the serogroup most frequently related to outbreaks. Fifty-six toxigenic serogroup C isolates of C. difficile were genotyped by ribotyping PCR (ribo-PCR), random amplified polymorphic DNA (RAPD) assay, and pulsed-field gel electrophoresis (PFGE). Thirty-five of the 56 isolates were recovered from four unrelated outbreaks (Belgium, 1987, 1992, and 1995; France, 1992 to 1993) 7 derived from a spatiotemporal cluster in Cotonou, Benin (1992), and 14 were sporadic isolates. The serogroup C reference strain, also isolated during an outbreak (Belgium, 1983), was genotyped too. Ribo-PCR, the RAPD assay, and PFGE generated 2, 5, and 11 major genotypes, respectively. Combination of the three methods finally yielded 13 general types, although ribo-PCR did not play any role in enhancing resolution. Three general types were recovered from all the isolates from the five outbreaks and the cluster, with two types being predominant. The 14 sporadic serogroup C isolates were divided into 11 overall genotypes. These results indicate that genotyping methods, and more particularly the combination of the RAPD assay and PFGE, can resolve genetic diversity within toxigenic, serogroup C C. difficile strains. Also, this study suggests that outbreak-related serogroup C strains are limited to a few genetically stable and apparently very widely (internationally and intercontinentally) distributed genotypes. PMID:8940447

van Dijck, P; Avesani, V; Delmee, M

1996-01-01

200

Methicillin-resistant Staphylococcus aureus: phylogenetic relatedness between European epidemic clones and Swiss sporadic strains.  

Science.gov (United States)

We have compared the phylogenetic diversity of methicillin-resistant Staphylococcus aureus (MRSA) strains from Switzerland and their phylogenetic relationships with European epidemic clones, using multiprimer random amplification polymorphic DNA (RAPD). Strains included 24 European epidemic clones (59 strains), 66 sporadic strains isolated in Switzerland in 1996-1997, and 15 reference strains of five other Staphylococcus species. Similarity and clustering analysis with the Jaccard's coefficient showed that the maximum genetic distance between MRSA strains was 0.43, whereas the minimum genetic distance between the six Staphylococcus species was 0.97, indicating that the method permits phylogenetic hierarchization. The 24 MRSA clones reported to be epidemic in European countries during the 1990s were distributed into seven different genetic clusters with a maximum distance of 0.29 among them. This clustering pattern was confirmed by the analysis of a subset of MRSA strains by multilocus enzyme electrophoresis at 12 loci. Most of the sporadic Swiss strains were distributed into these seven different genetic clusters, together with the epidemic MRSA clones. This suggests that there is no phylogenetic cluster specific to epidemic clones of MRSA. PMID:11144423

Blanc, D S; Bañuls, A L; Hauser, P M; Moreillon, P; Francioli, P; Tibayrenc, M

2000-01-01

 
 
 
 
201

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

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

Rafati Maryam

2012-01-01

202

Protein tyrosine phosphatase receptor-like genes are frequently hypermethylated in sporadic colorectal cancer.  

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The activity of phosphatases could be influenced by genetic, as well as epigenetic alterations. In our study, we have investigated the methylation status of four PTPRs: PTPRM, PTPRT, PTPRR and PTPRZ1, which were pre-selected using microarray techniques as being alternatively methylated in sporadic colorectal cancer (CRC). The analyses were carried out on 131 surgical specimens obtained from sporadic CRC patients. The methylation status of the four genes was examined using methyl specific PCR (MSP). The analysis of promoter methylation using an Illumina 27K microarray revealed four protein tyrosine phosphatases PTPRM, PTPRT, PTPRR and PTPRZ1 as being hypermethylated with ?-value ?0.2 and P?0.05. Subsequent analysis using MSP confirmed these observations-the frequency of promoter methylation was significantly higher in tumor cells compared with matched normal tissue for each of the analyzed genes. There was no association observed between the methylation status of PTPRs and either CIMP, K-ras (codon 12) and BRAF (exon 15, V600E) mutations or tumor localization (proximal/distal). The results of our study show a statistically significant difference between promoter methylation in cancerous and healthy tissue. This result supports the hypothesis that the PTPR family has an important role in the etiology of CRC. PMID:23096495

Laczmanska, Izabela; Karpinski, Pawel; Bebenek, Marek; Sedziak, Tomasz; Ramsey, David; Szmida, Elzbieta; Sasiadek, Maria M

2013-01-01

203

Histopathologic, immunohistochemical, and polymerase chain reaction assays in the study of cases with fatal sporadic myocarditis.  

Science.gov (United States)

Paraffin tissue blocks from 27 cases with sporadic myocarditis were collected during a 12-year period at a single medical examiner's office. Blocks were studied by using histopathology; immunohistochemistry for viruses (adenovirus, enterovirus, influenza A and B, and human herpes types 4 and 5), bacteria (Neisseria meningitidis, Ehrlichia sp, spotted fever group Rickettsia) and parasites (Toxoplasma gondii and Trypanosoma cruzi); and polymerase chain reaction (PCR)/RT-PCR for adenovirus and enterovirus. We identified enterovirus in 5 (18.5%) cases and Sarcocystis in a 36-year-old woman who had focal inflammation and myocyte necrosis. Immunohistochemical evidence of enteroviruses was found in the myocytes of 2 patients less than 6 months old who had diffuse mononuclear myocardial inflammation, interstitial pneumonitis; one also had encephalitis. In these 2 patients, the presence of enterovirus was confirmed by RT-PCR targeting the 5' nontranslated region and was serotyped as coxsackievirus B2 by sequencing the VP1 capsid region. In another 3 cases (ages 12, 47, and 54), enterovirus was detected by the 5' nontranslated region region; VP1 sequencing identified these as echoviruses 6, 13, and 7, respectively. Accurately identifying an infectious agent is the foundation for clinical and public health interventions. Despite using multiple diagnostic methods, an organism could only be detected in a small proportion of sporadic myocarditis cases. PMID:17602724

Guarner, Jeannette; Bhatnagar, Julu; Shieh, Wun-Ju; Nolte, Kurt B; Klein, Dennis; Gookin, Michelle S; Peñaranda, Silvia; Oberste, M Steven; Jones, Tara; Smith, Chalanda; Pallansch, Mark A; Zaki, Sherif R

2007-09-01

204

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

205

Altered basal ganglia echogenicity early in sporadic Creutzfeldt-Jakob disease.  

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Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease caused by conformational alteration of the ubiquitous prion protein. Sporadic CJD appears to progress faster if the basal ganglia are shown to be affected on magnetic resonance imaging. Transcranial B-mode sonography (TCS) enables visualization of differences in tissue echogenicity, which can be associated with changes in the cerebral metabolism of various metals. These metabolic changes are considered 1 of the potential mechanisms of the brain damage in CJD; TCS hyperechogenicity may reflect changes in metal homeostasis in CJD. We report a 63-year-old woman who presented with typical sporadic CJD. One month after she fell ill, a magnetic resonance imaging scan of her brain showed diffuse cortical but no obvious basal ganglia involvement. However, TCS revealed moderate hyperechogenicity of both lentiform nuclei. The patient's disease progressed quickly and she died 2 months later. TCS may show basal ganglia alteration early in the disease course of patients with quickly progressing CJD, thus aiding in premortem diagnosis. PMID:24674965

Veselinovic, Nikola; Pavlovic, Aleksandra M; Petrovic, Boris; Ristic, Aleksandar; Novakovic, Ivana; Svabic Medjedovic, Tamara; Pavlovic, Dragan; Sternic, Nada

2014-03-01

206

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

207

A Novel PHEX Gene Mutation in a Patient with Sporadic Hypophosphatemic Rickets.  

Science.gov (United States)

Phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) is a common cause of X-linked hypophosphatemic (XLH) rickets. Diverse PHEX gene mutations have been reported; however, gene mutations in sporadic rickets are less common than in XLH rickets. Herein, we describe a 50-year-old female patient with sporadic hypophosphatemic rickets harboring a novel splicing-site mutation in the PHEX gene (c.663+1G>A) at the exon 5-intron 5 boundary. The patient had recently suffered from right thigh pain and an aggravated waddling gait. She also presented with very short stature, generalized bone pain, and muscle weakness. Despite low serum phosphate levels, her phosphate reabsorption rate was lower than normal. Additionally, her 1,25-dihydroxyvitamin D3 concentration was lower than normal, although FGF23 level was normal. After treatment with alfacalcidol and elemental phosphate, her rachitic symptoms subsided, and callus formation was observed in the fracture site on the right femur. PMID:25031893

Kang, Yea Eun; Hong, Jun Hwa; Kim, Jimin; Joung, Kyong Hye; Kim, Hyun Jin; Ku, Bon Jeong; Kim, Koon Soon

2014-06-01

208

Association of sporadic breast cancer with PTEN/MMAC1/TEP1 promoter hypermethylation.  

Science.gov (United States)

PTEN/MMAC1/TEP1 encodes a tumor suppressor protein, which regulates cell cycle progression, translation, and apoptosis by blocking the activation of Akt/PKB. The loss of PTEN function increases cell survival and induces tumor invasion. In this study, PTEN promoter status and its correlation with genetic and pathologic parameters were analyzed in genomic DNA from Iranian patients with breast cancer. DNA methylation patterns in the CpG islands were determined by a methylation-specific PCR (MSP) assay. PTEN promoter methylation was found to be present in 37 of 53(70%) tumor tissues and none in 20 normal counterparts. Moreover, promoter methylation was found in patients with heterozygote mutation in the PTEN gene. The pathological history of cancerous tissue sections showed that PTEN gene could be inactivated at the stages III and IV in sporadic breast cancer. These findings suggested that promoter hypermethylation of PTEN might contribute to the progression of sporadic breast cancer in human. PMID:20237868

Sadeq, Vallian; Isar, Nassiri; Manoochehr, Tavassoli

2011-06-01

209

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

210

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

211

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

212

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

213

Screening for sporadic or familial medullary thyroid carcinoma. Scintiscan s and radio-immunotherapy  

International Nuclear Information System (INIS)

The screening for sporadic medullary thyroid carcinoma relies upon calcitoninemia level, basal or during pentagastrine stimulation test. MEN2 are associated with nearly the third of medullary thyroid carcinoma. In these cases, prognosis of thyroid carcinoma is mainly driven by the tumor status at the time of surgery. Up to date, diagnosis relies upon the genetic screening. Prophylactic thyroidectomy indication may take account of calcitoninemia. Most of the molecules that have been suggested for scintiscan lack of accuracy and large use cannot be recommended. Promising results have been obtained with monoclonal antibodies anti-CEA, particularly with dual targeting antiCEA antiDTPA. This last technique may also be used for radio-guided surgery. Its use for radio-immunotherapy is under investigation. (authors)

214

Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer disease.  

Science.gov (United States)

The Alzheimer amyloid protein precursor (APP) is subject to proteolysis by ADAM10 and ADAM17, precluding the formation of A?. Recently, coding variations in ADAM10 resulting in altered function have been reported in familial Alzheimer disease (AD). The authors carried out a large-scale (n = 576: Controls, 271; AD, 305) resequencing study of ADAM10 in sporadic AD. The results do not support a significant role for ADAM10 mutations in AD. The results also make it clear that the careful examination of ancestry required in any case-control comparison is especially true with rare variations, where even a very small number of variations might form the basis of scientific conclusions. PMID:20381196

Cai, Guiqing; Atzmon, Gil; Naj, Adam C; Beecham, Gary W; Barzilai, Nir; Haines, Jonathan L; Sano, Mary; Pericak-Vance, Margaret; Buxbaum, Joseph D

2012-02-01

215

Immunological reactivity against neuronal and non-neuronal antigens in sporadic adult-onset cerebellar ataxia.  

Science.gov (United States)

In recent years, the involvement of the immune system in acquired forms of cerebellar ataxia has been frequently demonstrated. In this study, we describe 6 out of 49 patients with subacute or chronic progressive cerebellar ataxia in whom antibodies against neuronal and non-neuronal antigens were identified. Two women had anti-Yo antibodies; two patients had anti-gliadin antibodies in the presence of celiac disease; one patient had a complex autoimmune disorder associated with anti-Ro-52/SS-A and anti-muscle-specific kinase antibodies, and a patient developed subacute cerebellar syndrome associated with the presence of a prostatic adenocarcinoma and atypical antibodies reacting both with cerebellar tissue and with the prostatic tumor. Our study confirms previous findings in paraneoplastic syndromes, and indicates that at least 10% of sporadic cerebellar ataxia may be related to immune-mediated mechanisms. PMID:19786780

Fancellu, Roberto; Pareyson, Davide; Corsini, Elena; Salsano, Ettore; Laurà, Matilde; Bernardi, Gaetano; Antozzi, Carlo; Andreetta, Francesca; Colecchia, Maurizio; Di Donato, Stefano; Mariotti, Caterina

2009-01-01

216

Brou\\'e's abelian defect group conjecture holds for the sporadic simple Conway group Co_3  

CERN Document Server

In the representation theory of finite groups, there is a well-known and important conjecture due to M. Brou\\'e. He conjectures that, for any prime p, if a p-block A of a finite group G has an abelian defect group P, then A and its Brauer corresponding block A_N of the normaliser N_G(P) of P in G are derived equivalent (Rickard equivalent). This conjecture is called Strong Version of Brou\\'e's Abelian Defect Group Conjecture. In this paper, we prove that the strong version of Brou\\'e's abelian defect group conjecture is true for the non-principal 2-block A with an elementary abelian defect group P of order 8 of the sporadic simple Conway group Co_3. This result completes the verification of the strong version of Brou\\'e's abelian defect group conjecture for all primes p and for all p-blocks of Co_3.

Koshitani, Shigeo; Noeske, Felix

2010-01-01

217

Travelling ionosphere disturbances and the sporadic F2 layer in the mean latitude ionosphere  

International Nuclear Information System (INIS)

The results of the investigation of relation between travelling ionospheric disturbances (TID) and the sporadic F2s layer in the day time in the mean latitudes are reported. It is shown that TID can lead to formation of the F2s layer. In winter, during the period of low solar activity when the F2 layer maximum is the lowest, TID leads to F2 layer formation mostly propagating in the meridional plane to the equator. In winter during the period of high solar activity registered in the Nsub(m)F2 layer medium scale TID are mostly propagated in the zonal direction and do not lead to F2s formation

218

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

219

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

220

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

 
 
 
 
221

Risk factors associated with sporadic salmonellosis in adults: a case-control study.  

Science.gov (United States)

In order to identify and assess recent risk factors for sporadic human infections with Salmonella enterica, we conducted a case-control study in Lower Saxony, Germany. The data collection was based on standardized telephone interviews with 1017 cases and 346 controls aged >14 years. Odds ratios were calculated in single-factor and multi-factor analyses for Salmonella cases and two different control groups, i.e. population controls and controls with rotavirus infection. Multi-factor analysis revealed associations between sporadic Salmonella infections for two exposures by both sets of controls: consumption of raw ground pork [adjusted odds ratio (aOR) 2·38, 95% confidence interval (CI) 1·27-4·44] and foreign travel (aOR 2·12, 95% CI 1·00-4·52). Other exposures included consumption of food items containing eggs (aOR 1·43, 95% CI 0·80-2·54), consumption of chicken meat (aOR 1·77, 95% CI 1·26-2·50), outdoor meals/barbecues (aOR 3·96, 95% CI 1·41-11·12) and taking gastric acidity inhibitors (aOR 2·42, 95% CI 1·19-4·92), all were significantly associated with respect to one of the two control groups. The impact of consuming food items containing eggs or chicken meat was lower than expected from the literature. This might be a consequence of Salmonella control programmes as well as increased public awareness of eggs and chicken products being a risk factor for salmonellosis. Efforts to reduce Salmonella infections due to raw pork products should be intensified. PMID:22717173

Ziehm, D; Dreesman, J; Campe, A; Kreienbrock, L; Pulz, M

2013-02-01

222

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

223

MicroRNA-137/181c regulates serine palmitoyltransferase and in turn amyloid ?, novel targets in sporadic Alzheimer's disease.  

Science.gov (United States)

The contribution of mutations in amyloid precursor protein (APP) and presenilin (PSEN) to familial Alzheimer's disease (AD) is well established. However, little is known about the molecular mechanisms leading to amyloid ? (A?) generation in sporadic AD. Increased brain ceramide levels have been associated with sporadic AD, and are a suggested risk factor. Serine palmitoyltransferase (SPT) is the first rate-limiting enzyme in the de novo ceramide synthesis. However, the regulation of SPT is not yet understood. Evidence suggests that it may be posttranscriptionally regulated. Therefore, we investigated the role of miRNAs in the regulation of SPT and amyloid ? (A?) generation. We show that SPT is upregulated in a subgroup of sporadic AD patient brains. This is further confirmed in mouse model studies of risk factors associated with AD. We identified that the loss of miR-137, -181c, -9, and 29a/b-1 increases SPT and in turn A? levels, and provides a mechanism for the elevated risk of AD associated with age, high-saturated-fat diet, and gender. Finally, these results suggest SPT and the respective miRNAs may be potential therapeutic targets for sporadic AD. PMID:21994399

Geekiyanage, Hirosha; Chan, Christina

2011-10-12

224

Global protein differential expression profiling of cerebrospinal fluid samples pooled from Chinese sporadic CJD and non-CJD patients.  

Science.gov (United States)

The shotgun proteomic based on the approach of tandem mass tag (TMT) labeling has received increasing attention for neuroproteomics analysis and becomes an effective tool for the identification and quantification of a large number of proteins for the purpose of revealing key proteins involved in the neuronal dysfunction and an inflammatory response associated with neurodegenerative disorders. To assess the potential expression difference of proteins in cerebrospinal fluids (CSF) between Creutzfeldt-Jakob disease (CJD) and non-CJD patients, the pooled CSF samples from 39 Chinese probable sporadic CJD (sCJD) patients and from 52 non-CJD cases were comparably analyzed with the methodology of TMT labeling and RP-RP-UPLC-MS/MS. Totally, 437 possible proteins were identified in the tested CSF specimen, among them, 49 proteins with 95 % confidence interval. Differential assays showed among those 49 CSF proteins, 12 were upregulated and 13 were downregulated significantly in the sCJD compared to non-CJD. The most affected pathway of the differential expression proteins in CSF of sCJD was complement and coagulation cascade. Western blots for six selected changed proteins in the pooled CSF samples revealed the similar altering profiles in the groups of sCJD and non-CJD as proteomics. Furthermore, CSF samples from 24 CJD patients and 24 non-CJD patients were randomly selected and subjected individually into the Western blots of an increased protein (phosphoglycerate mutase 1) and a decreased one (alpha-1-antichymotrysin), which also confirmed the altering tendency of these identified proteins. Those data indicate that proteomic assay of CSF is a powerful technique not only for selection of the potential biomarkers for the development of diagnostic tool of CJD but also for supplement of useful scientific clues for understanding the CSF homeostasis during the pathogenesis of prion diseases. PMID:23912784

Chen, Cao; Xiao, Di; Zhou, Wei; Shi, Qi; Zhang, Hui-Fang; Zhang, Jin; Tian, Chan; Zhang, Jian-Zhong; Dong, Xiao-Ping

2014-02-01

225

Characterization of human sporadic ALS biomarkers in the familial ALS transgenic mSOD1(G93A) mouse model.  

Science.gov (United States)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of motor neurons. Although most cases of ALS are sporadic (sALS) and of unknown etiology, there are also inherited familial ALS (fALS) cases that share a phenotype similar to sALS pathological and clinical phenotype. In this study, we have identified two new potential genetic ALS biomarkers in human bone marrow mesenchymal stem cells (hMSC) obtained from sALS patients, namely the TDP-43 (TAR DNA-binding protein 43) and SLPI (secretory leukocyte protease inhibitor). Together with the previously discovered ones-CyFIP2 and RbBP9, we investigated whether these four potential ALS biomarkers may be differentially expressed in tissues obtained from mutant SOD1(G93A) transgenic mice, a model that is relevant for at least 20% of the fALS cases. Quantitative real-time PCR analysis of brain, spinal cord and muscle tissues of the mSOD1(G93A) and controls at various time points during the progression of the neurological disease showed differential expression of the four identified biomarkers in correlation with (i) the tissue type, (ii) the stage of the disease and (iii) the gender of the animals, creating thus a novel spatiotemporal molecular signature of ALS. The biomarkers detected in the fALS animal model were homologous to those that were identified in hMSC of our sALS cases. These results support the possibility of a molecular link between sALS and fALS and may indicate common pathogenetic mechanisms involved in both types of ALS. Moreover, these results may pave the path for using the mSOD1(G93A) mouse model and these biomarkers as molecular beacons to evaluate the effects of novel drugs/treatments in ALS. PMID:23836781

Lilo, Eitan; Wald-Altman, Shane; Solmesky, Leonardo J; Ben Yaakov, Keren; Gershoni-Emek, Noga; Bulvik, Shlomo; Kassis, Ibrahim; Karussis, Dimitrios; Perlson, Eran; Weil, Miguel

2013-12-01

226

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

227

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

2015-02-15

228

Genome-wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic loss.  

Science.gov (United States)

Through the use of a candidate gene approach, several previous studies have identified loss of heterozygosity (LOH) at putative tumor-suppressor gene (TSG) loci in sporadic pituitary tumors. This study reports a genome-wide allelotyping by use of 122 microsatellite markers in a large cohort of tumors, consisting of somatotrophinomas and non-functioning adenomas. Samples were first subject to prior whole genome amplification by primer extension pre-amplification (PEP) to circumvent limitations imposed by insufficient DNA for whole-genome analysis with this number of microsatellite markers. The overall mean frequency of loss in invasive tumors was significantly higher than that in their non-invasive counterparts (7 vs. 3% somatotrophinomas; 6 vs. 3% non-functioning adenomas, respectively). Analysis of the mean frequency of LOH, across all markers to individual chromosomal arms, identified 13 chromosomal arms in somatotrophinomas and 10 in non-functioning tumors, with LOH greater than the 99% upper confidence interval calculated for the rate of overall random allelic loss. In the majority of cases, these losses were more frequent in invasive tumors than in their non-invasive counterparts, suggesting these to be markers of tumor progression. Other regions showed similar frequencies of LOH in both invasive and non-invasive tumors, implying these to be early changes in pituitary tumorigenesis. This genome-wide study also revealed chromosomal regions where losses were frequently associated with an individual marker, for example, chromosome arm 1q (LOH > 30%). In some cases, these losses were subtype-specific and were found at a higher frequency in invasive tumors than in their non-invasive counterparts. Identification of these regions of loss provides the first preliminary evidence for the location of novel putative TSGs involved in pituitary tumorigenesis that are, in some cases, subtype-specific. This investigation provides an unbiased estimate of global aberrations in sporadic pituitary tumors as assessed by LOH analysis. The identification of multiple "hotspots" throughout the genome may be a reflection of an unstable chromatin structure that is susceptible to a deletion or epigenetic-mediated gene-silencing events. PMID:12759921

Simpson, D J; Bicknell, E J; Buch, H N; Cutty, S J; Clayton, R N; Farrell, W E

2003-07-01

229

Amplitude morphology of GPS radio occultation data for sporadic-E layers  

Science.gov (United States)

Using the Global Positioning System radio occultation (GPSRO) technique, the observation of the global ionosphere becomes possible. The irregularity in the ionospheric sporadic-E (Es) layer, which is probably caused by wind shear, can be investigated by analyzing the signal-to-noise ratio (SNR) of RO signal. In this study, the relation between the amplitude of RO signals and the electron density profiles of the ionosphere is simulated, and RO data recorded in the time period from mid-2008 to mid-2011 are used for the analysis. Based on the simulation results, the multiple-layer-type (MLT) and the single-layer-type (SLT) Es layers which are defined by the shape of SNR, are used to analyze the global distribution of Es layer. The seasonal MLT Es layer is compared with the seasonal wind shear, which is obtained from the Horizontal Wind Model (HWM07). Furthermore, the seasonal MLT Es layer is compared with the SLT Es layer, and the global altitude distributions of MLT and SLT Es layers are similar while the magnitude distributions are different. Unlike the MLT Es layer, the global distribution of the SLT Es layer is similar to the distribution of E region peak electron density (NmE), which is related to the solar zenith angle.

Yeh, Wen-Hao; Huang, Cheng-Yung; Hsiao, Tung-Yuan; Chiu, Tsen-Chieh; Lin, Chien-Hung; Liou, Yuei-An

2012-11-01

230

Widespread RNA metabolism impairment in sporadic inclusion body myositis TDP43-proteinopathy.  

Science.gov (United States)

TDP43 protein mislocalization is a hallmark of the neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal dementia, and mutations in the gene encoding TDP43 cause both disorders, further highlighting its role in disease pathogenesis. TDP43 is a heterogenous ribonucleoprotein, therefore suggesting that alterations in RNA metabolism play a role in these disorders, although direct evidence in patients is lacking. Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy occurring in adults aged older than 50 years and abnormal cytoplasmic accumulations of TDP43 have been consistently described in sIBM myofibers. Here, we exploit high quality RNA from frozen sIBM muscle biopsies for transcriptomic studies on TDP43-proteinopathy patient tissue. Surprisingly, we found widespread sIBM-specific changes in the RNA metabolism pathways themselves. Consistent with this finding, we describe novel RNA binding proteins to mislocalize in the cytoplasm of sIBM myofibers and splicing changes in MAPT, a gene previously shown to play a role in sIBM. Our data indicate widespread alterations of RNA metabolism are a novel aspect of disease pathogenesis in sIBM. These findings also document an association, in TDP43-proteinopathy patients, between heterogenous ribonucleoprotein pathology and RNA metabolism alterations and carry importance for neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. PMID:24462217

Cortese, Andrea; Plagnol, Vincent; Brady, Stefen; Simone, Roberto; Lashley, Tammaryn; Acevedo-Arozena, Abraham; de Silva, Rohan; Greensmith, Linda; Holton, Janice; Hanna, Michael G; Fisher, Elizabeth M C; Fratta, Pietro

2014-06-01

231

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

232

[Association of mismatch repair gene polymorphism with susceptibility to sporadic colorectal cancer in Tianjin region].  

Science.gov (United States)

To investigate the possible association of mismatch repair gene single nucleotide polymorphisms (SNPs) with susceptibility to sporadic colorectal cancer (SCRC), the genotypes of hMLH1 394G/C, hMSH2 943-1G/A, hMSH2 1917T/G, and hMSH2 2783C/A were detected by PCR-denaturing high-performance liquid chromatography (DHPLC) in 600 SCRC patients and 600 healthy controls. The genotype distribution of hMSH2 2783C/A in SCRC patients (90%, 9%, and 1%) was significantly different from that in the controls (95%, 4.8%, and 0.23%; chi2 = 11.91, P reanges of 95% CI were 1.03-3.03 and 1.38-103.2). When combined analysis of three SNPs was performed, the haplotype distribution in SCRC patients was significantly different from that in controls (chi2 = 38.38, P < 0.01). In reference to 394G/943-1G /2783C haplotype, 394G/943-1G /2783A haplotype contributed significantly to SCRC (OR = 2.18, 95% CI: 1.40-3.40). These results indicate that hMSH2 2783C/A polymorphism has potential to be a susceptibility factor for SCRC and the 394G/943-1G /2783A haplotype might increase the risk of developing SCRC. PMID:21513149

Li, Hui-Chen; Feng, Hui-Yuan; Zhang, Xi-Peng; Liu, Rui; Ma, Dong-Wang; Qin, Hai; Zhou, Yi; Yu, Lin

2010-12-01

233

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

234

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.

235

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

Science.gov (United States)

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

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

2014-01-01

236

The G389R mutation in the MAPT gene presenting as sporadic corticobasal syndrome.  

Science.gov (United States)

A few patients with mutations in the microtubule-associated protein tau gene (MAPT), affected by frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T), may clinically present with a corticobasal syndrome (CBS). We report a case of apparently sporadic CBS bearing a mutation in the MAPT gene so far associated with frontotemporal dementia (FTD) phenotype. The patient is a 41-year-old man with progressive asymmetric signs of cortical and basal ganglia involvement consistent with CBS. Magnetic resonance imaging showed asymmetric cortical atrophy and unusual corticospinal tract hyperintensity in T2-weighted images. Genetic testing revealed a heterozygous G to C mutation at the first base of codon 389 of the MAPT gene, changing glycine to arginine (G389R), in the patient and his unaffected elderly father. In conclusion, the MAPT G389R mutation shows phenotypic variability resulting in both FTD and CBS. The mutation also demonstrates incomplete penetrance. Corticospinal tract degeneration is an exceptional finding. PMID:18307268

Rossi, Giacomina; Marelli, Cecilia; Farina, Laura; Laurà, Matilde; Maria Basile, Anna; Ciano, Claudia; Tagliavini, Fabrizio; Pareyson, Davide

2008-04-30

237

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.

2002-01-01

238

The relationship between meteor, wind shear, and sporadic-E layer  

Science.gov (United States)

The formation of sporadic-E (Es) layer is explained by several explanations, and wind shear theory and meteor ionized mechanism are mostly used to explain it. If only use each one of wind shear theory and meteor ionized mechanism, it cannot explain the formation of Es layer completely. Only meteor ionized mechanism cannot explain the difference of Es layer activity between north and south hemisphere, and only wind shear theory cannot explain the source of large amount of ionized particle in Es layer. In this study, the activity of Es layer is compared with the meteor information and the global vertical drift information of ionized particles. The global and local meteor information is obtained from International Meteor Organization (IMO) and Radio Meteor Observing Bulletin (RMOB), respectively. The global vertical drift information of ionized particles is calculated by using International Geomagnetic Reference Field (IGRF) model, Horizontal Wind Model (HWM07), and Mass Spectrometer-Incoherent Scatter (MSISE-90) model. The activity of Es layer is based on the value of irregular degree (ID) index, which is derived from the signal to noise ratio (SNR) of Global Positioning System (GPS) radio occultation (RO) data. With both wind shear theory and meteor ionized mechanism, the source of the ionized particles in Es layer and the difference of Es layer activity between north and south hemisphere can be explained completely.

Yeh, W.; Liu, J. G.; Huang, C.; Chen, S.

2013-12-01

239

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

240

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

 
 
 
 
241

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

242

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

Science.gov (United States)

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

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

2010-01-01

243

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, Jesus; Mahillo-Fernandez, Ignacio; Calero, Miguel; Rabano, Alberto; Cruz, Mabel; Siden, Ake; Martinez-Martin, Pablo; Laursen, Henning; Ruiz-Tovar, Maria; M?lbak, Kare

2014-01-01

244

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

245

Striatal dopaminergic functioning in patients with sporadic and hereditary spastic paraplegias with parkinsonism.  

Science.gov (United States)

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[(99)mTc]technetium ([(99)mTc]TRODAT-1). The [(99)mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder. PMID:24265532

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

2013-11-01

246

An orbifold theory of genus zero associated to the sporadic group M24  

International Nuclear Information System (INIS)

Let V?l be the self-dual (or holomorphic) bosonic conformal field theory associated with the spin lattice ?l of rank l divisible by 24. In earlier work of the authors we showed how it is possible to establish the existence and uniqueness of irreducible g-twisted sectors for V?l, for certain automorphisms g of V?l, and to establish the modular invariance of the space of partition functions Z (g,h,?) corresponding to commuting pairs g, h of elements in certain groups G of automorphisms of V?l. In the present work we show that if we take l=24 and G the sporadic simple group M24, then the corresponding orbifold has the genus zero property. That is, each Z (g,h,?) is either identically zero or a hauptmodul, i.e., it generates the field of functions on the subgroup of SL2(R) which fixes Z (g,h,?), which then necessarily has genus zero. (orig.)

247

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

248

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

249

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

Directory of Open Access Journals (Sweden)

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

250

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

251

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

252

Sporadic and Thermospheric Enhanced Sodium Layers Observed by a Lidar Chain over China  

Science.gov (United States)

We report the statistical features of sporadic sodium layers (SSLs) and the thermospheric enhanced sodium layers (TeSLs) observed by a lidar chain located at Beijing (40.2N,116.2E), Hefei (31.8N, 117.3E), Wuhan (30.5N, 114.4E), and Haikou (19.5N, 109.1E). The average SSL occurrence rate was approximately 46.0, 12.3, 13.8, and 15.0 hr per SSL at Beijing, Hefei, Wuhan, and Haikou, respectively. However, the TeSLs occurred relatively infrequently and were more likely to appear at low and high latitudinal sites. Both the SSLs and TeSLs at four lidar sites showed evident summer enhancements and correlated well with Es (foEs>4MHz). The co-observations of SSLs at three lidar site pairs, i.e., Hefei -- Beijing, Hefei -- Wuhan and Hefei -- Beijing, indicated that a large-scale SSL extended horizontally for at least a few hundred kilometers and exhibited a tidal-induced modulation. Moreover, the SSLs were better correlated for the Hefei -- Wuhan and Hefei -- Haikou pairs than the Hefei -- Beijing pair, which suggested a difference in the dynamical/chemical process in mesosphere and lower thermosphere (MLT) between the Beijing site and the other sites.

Xue, X.

2013-12-01

253

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

DEFF Research Database (Denmark)

Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE was the least accurate with 79% sensitivity at 90% specificity. Many of the sCJD patients had extremely elevated t-tau values but normal values of the AD-marker p-tau. Protein 14-3-3 was very sensitive (95%) although the specificity was relatively low (75%). A combination of elevated t-tau concentration with the presence of 14-3-3 protein in CSF gave the best test specificity of 96% at 84% sensitivity. We conclude that the combination of more than one CSF marker for neurodegeneration can improve the diagnostic test accuracy for sCJD against neurological controls including patients with other dementias Udgivelsesdato: 2009/11

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

2009-01-01

254

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

Science.gov (United States)

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

255

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

256

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

Science.gov (United States)

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 this purpose phage type, resistance to antibiotics, DNA plasmid profile and sites of insertion of the mobile element of IS200 were determined. The epidemic strains were genetically distinct from the non-epidemic isolates; they were shown to be phage type 26, harbouring four small plasmids, were resistant to nalidixic acid and showed a unique characteristic IS200 fingerprint. The typing methods used in this study allowed the identification and discrimination of the outbreak strains from related isolates. They can thus be considered as a tool for epidemiological purposes. In addition we should point out the emerging resistance to nalidixic acid, largely used in veterinary medicine, in Salm. hadar. PMID:9134723

Fantasia, M; Paglietti, B; Filetici, E; Anastasio, M P; Rubino, S

1997-04-01

257

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

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

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

2014-09-01

258

Sporadic E ionization layers observed with radar imaging and ionospheric modification  

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

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

2014-10-01

259

Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal cancer patients.  

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MYH, OGG1 and MTH1 are members of base excision repair (BER) families, and MYH germline mutations were recently identified in patients with multiple adenomas or familial adenomatous polyposis (FAP). A total of 20 APC-negative Korean FAP patients were analyzed for OGG1, MYH and MTH1 germline mutations. A total of 19 hereditary nonpolyposis colorectal cancer (HNPCC), 86 suspected HNPCC, and 246 sporadic colorectal cancer cases were investigated for OGG1 and MYH mutations. A total of 14 R154H OGG1 polymorphisms were identified in hereditary, sporadic colorectal cancers, and normal controls. For the case-control analysis of OGG1 R154H, a total of 625 hereditary or sporadic colorectal cancer patients and 527 normal controls were screened. R154H was a rare polymorphism associated with sporadic colorectal cancer patents (OR: 3.586, P= 0.053). R154H does not segregate with cancer phenotypes. Upon examining the possibility of recessive inheritance of R154H, we could not identify any complementary mutations in OGG1, MYH or MTH1. Samples with R154H were further screened for mutations of K-ras, beta-catenin, APC, p53, BRAF and the microsatellite instability (MSI) status. Eight somatic mutations were identified in these genes and G:C to T:A transversion mutations were not dominant in samples harboring R154H. This result raises the possibility that OGG1 R154H may function as a low/moderate-penetrance modifier for colorectal cancer development. PMID:15449173

Kim, I-J; Ku, J-L; Kang, H C; Park, J-H; Yoon, K-A; Shin, Y; Park, H-W; Jang, S G; Lim, S-K; Han, S Y; Shin, Y-K; Lee, M R; Jeong, S-Y; Shin, H-R; Lee, J S; Kim, W-H; Park, J-G

2004-11-01

260

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.)

 
 
 
 
261

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

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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.

Oikonomou, Zoi-Sylvia; Dikou, Angela

2008-11-01

262

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

Scientific Electronic Library Online (English)

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

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

263

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.

264

The T/G mutation in exon 8 of HMSH2 gene in the sporadic colon cancer patients  

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Full Text Available The DNA mismatch repair (MMR system guards against genomic instability, therefore the mutations in the human MMR genes cause the majority of the hereditary nonpolyposis colorectal cancer (HNPCC and a small percentage of the sporadic colon cancer. hMSH2 is one of MMR genes involved in the correction of mispairing during replication and its mutations are associated with both - microsatellite instability and the hereditary and sporadic colon tumor genesis. The aim of this study was to analyze the T/G mutation (codon 458 in exon 8 of hMSH2 gene in the sporadic colon cancer cells. We also examined the relationship between the T/G mutation of hMSH2 gene, and the selected prognostic factors such as Dukes’ stage, histological grade and lymph node metastasis. We analyzed samples of tumor from 75 patients with sporadic colorectal cancers. The mutation in the hMSH2 gene ware determined by the RFLP-PCR. We found T/G mutation in exon 8 of hMSH2 gene in 5 patients (6,7%. There was no statistically significant difference between this mutation and selected clinical parameters. The results of our studies revealed that mutations of hMSH2 gene may lead to development of colorectal cancer. No dependence between the mutation of hMSH2 gene and clinical parameters, suggests that the mutation of hMSH2 gene may have a critical significance for the first steps of carcinogenesis in colon epithelial.

Dziki Adam

2006-01-01

265

Gene Amplification and Overexpression of CDK4 in Sporadic Breast Carcinomas Is Associated with High Tumor Cell Proliferation  

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Amplification of the cyclin-dependent kinase 4 (CDK4) gene, located at 12q13-q14, has been found as an alternative genetic alteration to CDKN2A inactivation in various human tumors including malignant gliomas and sarcomas. In the present study, we have evaluated the frequency of the CDK4 gene amplification in sporadic breast cancer by applying a nonradioactive quantitative differential polymerase chain reaction based on fluorescent DNA technology. Fluorescent-labeled polymerase chain reaction...

An, Han-xiang; Beckmann, Matthias W.; Reifenberger, Guido; Bender, Hans G.; Niederacher, Dieter

1999-01-01

266

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

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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

267

HNPCC versus sporadic microsatellite-unstable colon cancers follow different routes toward loss of HLA class I expression  

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Full Text Available Abstract Background Abnormalities in Human Leukocyte Antigen (HLA class I expression are common in colorectal cancer. Since HLA expression is required to activate tumor antigen-specific cytotoxic T-lymphocytes (CTL, HLA class I abnormalities represent a mechanism by which tumors circumvent immune surveillance. Tumors with high microsatellite instability (MSI-H are believed to face strong selective pressure to evade CTL activity since they produce large amounts of immunogenic peptides. Previous studies identified the prevalence of HLA class I alterations in MSI-H tumors. However, those reports did not compare the frequency of alterations between hereditary and sporadic MSI-H tumors neither the mechanisms that led to HLA class I alterations in each subgroup. Methods To characterize the HLA class I expression among sporadic MSI-H and microsatellite-stable (MSS tumors, and HNPCC tumors we compared immunohistochemically the expression of HLA class I, ?2-microglobulin (?2m, and Antigen Processing Machinery (APM components in 81 right-sided sporadic and 75 HNPCC tumors. Moreover, we investigated the genetic basis for these changes. Results HLA class I loss was seen more frequently in MSI-H tumors than in MSS tumors (p ?2m and APM components genes. Conclusion HLA class I aberrations are found at varying frequencies in different colorectal tumor types and are caused by distinct genetic mechanisms. Chiefly, sporadic and hereditary MSI-H tumors follow different routes toward HLA class I loss of expression supporting the idea that these tumors follow different evolutionary pathways in tumorigenesis. The resulting variation in immune escape mechanisms may have repercussions in tumor progression and behavior.

Fleuren Gert

2007-02-01

268

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

Scientific Electronic Library Online (English)

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

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

2001-07-01

269

Analysis of sporadic tuberous sclerosis patients with the TSC2 cDNA reveals several gene rearrangements and deletions  

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Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by hamartomas and hamartias in many organs including brain, skin, heart and kidneys. Two TSC genes have been localized through linkage analysis, TSC1 to 9q34 and TSC2 to 16p13.3. TSC2 was recently cloned. The distribution of sporadic TSC patients between TSC1 and TSC2 is at present unknown, but tests of genetic heterogeneity in families suggest that each is equally represented. Genetic heterogeneity may account for some of the variation in clinical expression; however, there is no evidence at present to support differences in clinical phenotypes between the 2 genetic loci. With the isolation of the TSC2 gene we have commenced mutation studies of our familial and sporadic TSC patients. Thus far six chromosome 16-linked families have been screened with the TSC2 cDNA and no detectable changes were observed using Southern analysis. In addition, 85 sporadic TSC patients were analyzed by Southern analysis. Using multiple restriction digests, nine patients revealed altered patterns, including three patients that appeared to have complete deletions. RT-PCR was performed on these patients confirming that the TSC2 gene was deleted. However, the remaining patients showed normal patterns, indicating that they either have TSC1 mutations or they possess more subtle small deletions or point mutations. At present we are designing an SSCP-based approach to determine the nature of the mutations in our 16 linked TSC families.

Wilson, P.J.; Short, M.P.; Bove, C. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1994-09-01

270

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

271

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

272

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

273

Genetic variability of the gene cluster CALHM 1-3 in sporadic Creutzfeldt-Jakob disease.  

Science.gov (United States)

Perturbations of calcium homeostasis have been associated with several neurodegenerative disorders. A common polymorphism (rs2986017) in the CALHM1 gene, coding for a regulator of calcium homeostasis, is a genetic risk factor for the development of Alzheimer disease (AD). Although some authors failed to confirm these results, a meta-analysis has shown that this polymorphism modulates the age at disease onset. Furthermore, a recent association study has explored the genetic variability of CALHM1 gene and two adjacent paralog genes (CALHM3 and CALHM2) in an Asian population. Since several lines of evidence suggest that AD and prion diseases share pathophysiologic mechanisms, we investigated for the first time the genetic variability of the gene cluster formed by CALHM1 and its paralogs in a series of 235 sporadic Creutzfeldt-Jakob disease (sCJD) patients, and compared the genotypic and allelic frequencies with those presented in 329 controls from the same ancestry. As such, this work also represents the first association analysis of CALHM genes in sCJD. Sequencing analysis of the complete coding regions of the genes demonstrated the presence of 10 single nucleotide polymorphisms (SNP) within the CALHM genes. We observed that rs4918016-rs2986017-rs2986018 and rs41287502-rs41287500 polymorphic sites at CALHM1 were in linkage disequilibrium. We found marginal associations for sCJD risk at CALHM1 polymorphic sites rs41287502 and rs41287500 [coding for two linked missense mutations (p.(Met323Ile); (Gly282Cys)], and rs2986017 [p.(Leu86Pro)]. Interestingly, a TGG haplotype defined by the rs4918016-rs2986017-rs2986018 block was associated with sCJD. These findings underscore the need of future multinational collaborative initiatives in order to corroborate these seminal data. PMID:22874670

Calero, Olga; Bullido, María J; Clarimón, Jordi; Hortigüela, Rafael; Frank-García, Ana; Martínez-Martín, Pablo; Lleó, Alberto; Rey, María Jesús; Sastre, Isabel; Rábano, Alberto; de Pedro-Cuesta, Jesús; Ferrer, Isidro; Calero, Miguel

2012-01-01

274

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

275

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

Science.gov (United States)

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. PMID:20877436

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

2010-01-01

276

SOD1 oxidation and formation of soluble aggregates in yeast: Relevance to sporadic ALS development  

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Misfolding and aggregation of copper–zinc superoxide dismutase (Sod1) are observed in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Mutations in Sod1 lead to familial ALS (FALS), which is a late-onset disease. Since oxidative damage to proteins increases with age, it had been proposed that oxidation of Sod1 mutants may trigger their misfolding and aggregation in FALS. However, over 90% of ALS cases are sporadic (SALS) with no obvious genetic component. We hypothesized that oxidation could also trigger the misfolding and aggregation of wild-type Sod1 and sought to confirm this in a cellular environment. Using quiescent, stationary-phase yeast cells as a model for non-dividing motor neurons, we probed for post-translational modification (PTM) and aggregation of wild-type Sod1 extracted from these cells. By size-exclusion chromatography (SEC), we isolated two populations of Sod1 from yeast: a low-molecular weight (LMW) fraction that is catalytically active and a catalytically inactive, high-molecular weight (HMW) fraction. High-resolution mass spectrometric analysis revealed that LMW Sod1 displays no PTMs but HMW Sod1 is oxidized at Cys146 and His71, two critical residues for the stability and folding of the enzyme. HMW Sod1 is also oxidized at His120, a copper ligand, which will promote loss of this catalytic metal cofactor essential for SOD activity. Monitoring the fluorescence of a Sod1-green-fluorescent-protein fusion (Sod1-GFP) extracted from yeast chromosomally expressing this fusion, we find that HMW Sod1-GFP levels increase up to 40-fold in old cells. Thus, we speculate that increased misfolding and inclusion into soluble aggregates is a consequence of elevated oxidative modifications of wild-type Sod1 as cells age. Our observations argue that oxidative damage to wild-type Sod1 initiates the protein misfolding mechanisms that give rise to SALS. PMID:24936435

Martins, Dorival; English, Ann M.

2014-01-01

277

Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis.  

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Previous histopathologic studies of sporadic inclusion body myositis (sIBM) identified sarcoplasmic aggregation and myonuclear depletion of the predominantly nuclear heterogeneous nuclear ribonucleoprotein (hnRNP) TDP-43 in sIBM myofibers. Here, we examined sIBM muscle for abnormalities in two other hnRNPs hnRNPA1 and hnRNPA2B1, mutations in which cause multisystem proteinopathy associated with rimmed-vacuolar myopathies. Muscle biopsy specimens from 13 patients with sIBM and 13 patients without sIBM (dermatomyositis N=3, polymyositis N=3, muscular dystrophy N=3, motor neuron disease N=2, non-neuromuscular disease N=2) underwent immunohistochemistry for hnRNPA1, hnRNPA2B1, and TDP-43. Muscle transcriptional microarray data from 27 patients with sIBM and 12 patients without neuromuscular disease was analyzed. Depletion of hnRNPA1 and hnRNPA2B1 was present in 15% and 7% of sIBM myonuclei, respectively, compared with 1% and 0% of myonuclei in non-sIBM muscle. Sarcoplasmic aggregates of hnRNPA1 and hnRNPA2B1 distinct from TDP-43 aggregates were also found in sIBM. hnRNPA1 and hnRNPA2B1, as well as other hnRNPs, gene expression was unaltered in sIBM compared to normal muscle. Along with TDP-43, other hnRNPs, including hnRNPA1 and hnRNPA2B1, are depleted from sIBM myonuclei at the protein but not transcript level. The depletion of multiple hnRNPs from sIBM myonuclei together with their sarcoplasmic aggregation suggests that one aspect of sIBM pathophysiology may involve abnormal RNA metabolism that includes hyperassembly of ribonucleoprotein granules mediated by prion-like domains in hnRNPs, evolving into pathological aggregates. PMID:24857366

Pinkus, Jack L; Amato, Anthony A; Taylor, J Paul; Greenberg, Steven A

2014-07-01

278

Immunohistochemical and molecular genetic analyses of multiple sporadic gastrointestinal stromal tumors  

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Full Text Available A 77-year-old Japanese male patient was admitted to our hospital complaining of general fatigue and melena. A gastroduodenal endoscopic examination revealed no definitive localized lesions. However, both a large amount of cruor and blood flow from the small intestine into the ascending colon was observed during the colonoscopic examination. At least three tumors, believed to originate from the small intestine, were detected by abdominal computed tomography. Based on these findings, multiple and hemorrhagic small intestinal tumors were diagnosed and surgical treatment of the tumors planned. During the celiotomy, twelve tumors were found in the small intestine. Intestinal wedge or partial resection was applied. All excised specimens demonstrated morphology of a submucosal tumor and the largest tumor had a delle with coagulation on the mucosal face. In the histological findings, hematoxylin and eosin staining showed spindle cell morphology. The immunohistochemical examination revealed that the tumor cells were diffusely positive for KIT and CD34. The myenteric plexus layer of the small intestine was focal-positive for KIT and showed no intestinal cells of Cajal hyperplasia. The tumor sequencing results revealed an identical missense mutation in codon 642 of c-kit exon 13 leading to the replacement of lysine by glutamic acid and a silent germ-line mutation in exon 12 of the PDGFRA gene concerning whole blood, normal mucosa and tumors. We concluded that the current subject was categorized as having multiple sporadic-type gastrointestinal stromal tumor with identical mutational types. Although the patient did not receive any adjuvant chemotherapy, there has been no sign of recurrence over the 3 years since the surgery.

Masatsugu Hiraki

2010-09-01

279

Influence of tides and planetary waves on E sporadic layer at mid latitudes  

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This paper describes the influence that tides and planetary waves have on the variability shown by the main characteristics of the E sporadic (Es) layer, that is the top frequency (ftEs) and the lowest virtual height (h’Es). The study is based on ionograms recorded during the summertime of 2013, a year falling in the maximum of solar activity of cycle 24, and precisely in June, July, August and September, by the Advanced Ionospheric Sounder by Istituto Nazionale di Geofisica e Vulcanologia (AIS-INGV) ionosondes installed at Rome (41.8°N, 12.5°E) and Gibilmanna (37.9°N, 14.0°E), Italy. We applied the height-time-intensity (HTI) methodology proposed by Haldoupis et al. (2006) to investigate how tides control the Es dynamics. As a whole, the HTI analysis showed that a well-defined semidiurnal periodicity characterizes the Es layer descent and occurrence for all the considered months, although in September some cases which showed a prevailing diurnal periodicity were recorded. Through the application of the wavelet analysis it was also found that the tidal oscillations shown by ftEs and h’Es are affected by a strong amplitude modulation with periods of several days but with important differences between the two parameters. This amplitude modulation is a proof that Es layers are indirectly affected by planetary waves through their nonlinear interaction with tides at lower altitudes; this nonlinear interaction produces the presence of secondary waves with frequencies that are the sum and difference of the primary waves frequencies involved in the interaction as proposed by Teitelbaum and Vial [1991]. This work adds to those that were already done by Haldoupis et al. (2004, 2006), and confirms that ionosonde data, especially those registered in summertime, can be used as a powerful tool for studying tidal and planetary waves properties, as well as their climatology, in the mesosphere-low-termosphere region.

Pezzopane, Michael; Pignalberi, Alessio; Zuccheretti, Enrico

280

Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas  

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Full Text Available AIM: To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis.METHODS: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN, n = 30; indefinite, n = 77], and 80 paired sporadic gastric carcinomas (SGC as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MSP and confirmed by denatured high performance liquid chromatography (DHPLC. Immunohistochemical staining was used to detect protein expression. The correlation between GATA-4 and GATA-5 methylation and clinicopathological characteristics of patients including Helicobacter pylori (H. pylori infection was analyzed.RESULTS: GATA-4 and GATA-5 methylation was frequently observed in SGCs (53.8% and 61.3%, respectively and their corresponding normal tissues (41.3% and 46.3% by MSP. The result of MSP was consistent with that of DHPLC. Loss of both GATA-4 and GATA-5 proteins was associated with their methylation in SGCs (P = 0.01. Moreover, a high frequency of GATA-4 and GATA-5 methylation was found in both gastric low-grade GIN (57.1% and 69.0% and indefinite for dysplasia (42.9% and 46.7%, respectively. However, GATA-4 and GATA-5 methylation was detected only in 4/32 (12.5% and 3/39 (7.7% of normal gastric biopsies. GATA-4 methylation in both normal gastric mucosa and low-grade GIN was also significantly associated with H. pylori infection (P = 0.023 and 0.027, two-sides.CONCLUSION: Epigenetic inactivation of GATA-4 (and GATA-5 by methylation of CpG islands is an early frequent event during gastric carcinogenesis and is significantly correlated with H. pylori infection.

Xian-Zi Wen, Yoshimitsu Akiyama, Kai-Feng Pan, Zhao-Jun Liu, Zhe-Ming Lu, Jing Zhou, Lian-Kun Gu, Cai-Xuan Dong, Bu-Dong Zhu, Jia-Fu Ji, Wei-Cheng You, Da-Jun Deng

2010-03-01

 
 
 
 
281

Developments in the surgical management of sporadic synchronous bilateral renal tumours  

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Objective To examine our experience with managing sporadic bilateral renal masses, focusing on trends in surgical management over time, because as loss of renal function is associated with adverse cardiovascular outcomes, nephron-sparing approaches are increasingly emphasized in the treatment of kidney tumours, creating new challenges for the treatment of bilateral tumours. Patients and Methods We identified all patients who underwent partial or radical nephrectomy (PN or RN) at Memorial Sloan-Kettering Cancer Center (MSKCC) during 1989-2008. We compared patients presenting with synchronous bilateral renal masses with those with unilateral tumour and evaluated trends in management using logistic regression. Results Of the 2777 patients studied, 73 (3%) presented with synchronous bilateral disease. The overall survival and clinical/pathologica features between groups were similar. Of those patients receiving bilateral operations for synchronous tumours, three had bilatera RN (all before 2003), 28 (38%) had an RN followed by a PN, 10 (14%) had a PN then an RN, and 32 (44%) had bilateral PN. Over time, the proportion of patients receiving bilateral PN increased (P < 0.001); 13 of 14 patients after 2005 had bilateral PN, compared with only 34% (16 of 45) between 1995 and 2004. Forty-five patients (62%) had the larger tumour removed during the first operation. The concordance rate between tumours in a specific histological subtype was 70% (51/73), and concordance for benign vs malignant disease was 90% (66/73). Conclusion The use of PN in the management of synchronous bilateral renal masses has increased over time. The contemporary treatment of synchronous bilateral renal masses at MSKCC involves staged PN when feasible, with the more involved kidney (often larger tumour) operated on first. PMID:19751262

Lowrance, William T.; Yee, David S.; Maschino, Alexandra C.; Cronin, Angel M.; Bernstein, Melanie; Thompson, R. Houston; Russo, Paul

2014-01-01

282

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

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

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

1994-09-01

283

Accumulation of altered aspartyl residues in erythrocyte membrane proteins from patients with sporadic amyotrophic lateral sclerosis.  

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Spontaneous protein deamidation of labile asparagines (Asn), generating abnormal l-isoaspartyl residues (IsoAsp), is associated with cell aging and enhanced by an oxidative microenvironment. The presence of isopeptide bonds impairs protein structure/function. To minimize the damage, IsoAsp can be "repaired" by the protein l-isoaspartyl/d-aspartyl O-methyltransferase (PIMT) and S-adenosylmethionine (AdoMet) is the methyl donor of this reaction. PIMT is a repair enzyme that initiates the conversion of l-isoAsp (or d-Asp) residues to l-Asp residues. Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease principally affecting motor neurons. The condition of oxidative stress reported in familial and sporadic forms of ALS prompted us to investigate Asn deamidation in ALS tissue. Erythrocytes (RBCs) were selected as a model system since they are unable to replace damaged proteins and protein methylesterification is virtually the only AdoMet-consuming reaction operating in these cells. Our data show that, in vitro assay, abnormal IsoAsp residues were significantly higher in ALS patients erythrocyte membrane proteins with an increased methyl accepting capability relative to controls (p<0.05). Moreover, we observed a reduction in AdoMet levels, while AdoHcy concentration was comparable to that detected in the control, resulting in a lower [AdoMet]/[AdoHcy] ratio. Then, the accumulation of altered aspartyl residues in ALS patients is probably related to a reduced efficiency of the S-adenosylmethionine (AdoMet)-dependent repair system causing increased protein instability at Asn sites. The increase of abnormal residues represents a new protein alteration that may be present not only in red blood cells but also in other cell types of patients suffering from ALS. PMID:24044898

D'Angelo, Stefania; Trojsi, Francesca; Salvatore, Anna; Daniele, Luca; Raimo, Marianna; Galletti, Patrizia; Monsurrò, Maria Rosaria

2013-11-01

284

Immunohistochemical and ultrastructural characterization of ubiquitinated eosinophilic fibrillary neuronal inclusions in sporadic amyotrophic lateral sclerosis.  

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We found eosinophilic fibrillary neuronal inclusions (EFNI) that were argyrophilic and immunoreactive for anti-ubiquitin in the cerebral cortex of a patient with sporadic amyotrophic lateral sclerosis (ALS) and mild personality changes. Both hematoxylin and eosin and Bodian's preparations revealed the EFNI to be rod-, flame-shaped, or spherical structures existing within the swollen neuronal perinuclear region in the third, fifth, and sixth layers of the fronto-parieto-temporal cortices including the primary motor cortex. On electron microscopy, filamentous profiles aggregated and formed a single bundle or globule in the neuronal perikaryon without any limiting membrane. Most EFNI had a characteristic multiple layer arrangement. The inner core consisted of randomly oriented granule-free tubules with a fuzzy outer contour, measuring 15-20 nm in diameter. The surrounding layer was made up of granule-associated filaments, electrondense free granules, and small vesicular profiles. Large autolysosome-like membrane-bound vesicular profiles were found scattered at the periphery. Neurofilaments were usually mingled with in the surrounding cytoplasm. Many EFNI were also found in dendrites, but only a few in axons. Both granule-free tubules and granule-associated filaments expressed ubiquitin protein epitopes. Aberrant phosphorylation of neurofilament protein and induction of alphaB-crystallin were shown to exist in EFNI-bearing swollen neurons. Despite having a variety of histological appearances, our observations revealed that EFNI all have common immunocytochemical and ultrastructural characteristics, and thus we assume that EFNI represent a series of cytological alterations in the motor and extra-motor cortices of ALS patients. PMID:9678516

Arima, K; Ogawa, M; Sunohara, N; Nishio, T; Shimomura, Y; Hirai, S; Eto, K

1998-07-01

285

Wave-associated sporadic neutral layers in the upper atmosphere / Camadas neutras esporádicas na alta atmosfera associadas com ondas atmosféricas  

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Full Text Available SciELO Brazil | Language: English Abstract in portuguese Camadas esporádicas neutras, com espessuras entre algumas centenas de metros e vários quilômetros, são observados por radar de laser na mesma faixa de altura que a E-esporádica ionosférica. Camadas Ns foram observadas pela primeira vez em sódio, 20 anos atrás, e mais recentemente foram observadas em [...] potássio, ferro e cálcio. Como no caso de Es existe uma ligação forte com ondas atmosféricas, e vários estudos mostraram uma possível conexão com oscilações de marés na baixa termosfera. Observações recentes em São José dos Campos mostraram que camadas de sódio esporádicas freqüentemente ocorrem nas alturas dos picos da concentração de sódio produzidos por uma onda atmosférica. Em alguns casos, onde o comprimento de onda vertical da oscilação é curto, pode-se identificar até 3 oscilações completas, sendo que e a camada esporádica sempre se forma no pico de altura maior. Nos casos de eventos de longa duração, observa-se uma propagação da camada Ns no sentido de alturas menores, acompanhando a propagação de fase da onda atmosférica. Baseado nestas observações propõe-se que a recombinação de íons de sódio seja responsável pela formação das camadas esporádicas. Abstract in english Sporadic neutral layers, with thicknesses between a few hundred meters and several kilometers, are observed by lidar in the same height range as ionospheric sporadic E. Ns layers were first observed in sodium, 20 years ago, and more recently have also been seen in potassium, iron and calcium. As in [...] the case of Es there is a strong link with atmospheric waves, and a number of studies have shown evidence for a possible connection with tidal oscillations in the lower thermosphere. Recent observations at São José dos Campos, Brazil, have shown that sporadic sodium layers are frequently observed to occur at the heights of peaks in sodium concentration corresponding to a propagating atmospheric wave. In cases where the vertical wavelength of the propagating wave is short, as many as three complete oscillations can sometimes be seen, and the sporadic layer always occurs at the highest wave maximum, typically in the range 95-100 km. In the case of long-lived events the Ns layer is observed to accompany the downward phase propagation of the atmospheric wave. On the basis of these observations a case is made for the recombination of sodium ions as the source of the observed sporadic layers.

B. R., Clemesha; P. P., Batista; D. M., Simonich.

286

Wave-associated sporadic neutral layers in the upper atmosphere / Camadas neutras esporádicas na alta atmosfera associadas com ondas atmosféricas  

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Full Text Available SciELO Brazil | Language: English Abstract in portuguese Camadas esporádicas neutras, com espessuras entre algumas centenas de metros e vários quilômetros, são observados por radar de laser na mesma faixa de altura que a E-esporádica ionosférica. Camadas Ns foram observadas pela primeira vez em sódio, 20 anos atrás, e mais recentemente foram observadas em [...] potássio, ferro e cálcio. Como no caso de Es existe uma ligação forte com ondas atmosféricas, e vários estudos mostraram uma possível conexão com oscilações de marés na baixa termosfera. Observações recentes em São José dos Campos mostraram que camadas de sódio esporádicas freqüentemente ocorrem nas alturas dos picos da concentração de sódio produzidos por uma onda atmosférica. Em alguns casos, onde o comprimento de onda vertical da oscilação é curto, pode-se identificar até 3 oscilações completas, sendo que e a camada esporádica sempre se forma no pico de altura maior. Nos casos de eventos de longa duração, observa-se uma propagação da camada Ns no sentido de alturas menores, acompanhando a propagação de fase da onda atmosférica. Baseado nestas observações propõe-se que a recombinação de íons de sódio seja responsável pela formação das camadas esporádicas. Abstract in english Sporadic neutral layers, with thicknesses between a few hundred meters and several kilometers, are observed by lidar in the same height range as ionospheric sporadic E. Ns layers were first observed in sodium, 20 years ago, and more recently have also been seen in potassium, iron and calcium. As in [...] the case of Es there is a strong link with atmospheric waves, and a number of studies have shown evidence for a possible connection with tidal oscillations in the lower thermosphere. Recent observations at São José dos Campos, Brazil, have shown that sporadic sodium layers are frequently observed to occur at the heights of peaks in sodium concentration corresponding to a propagating atmospheric wave. In cases where the vertical wavelength of the propagating wave is short, as many as three complete oscillations can sometimes be seen, and the sporadic layer always occurs at the highest wave maximum, typically in the range 95-100 km. In the case of long-lived events the Ns layer is observed to accompany the downward phase propagation of the atmospheric wave. On the basis of these observations a case is made for the recombination of sodium ions as the source of the observed sporadic layers.

B. R., Clemesha; P. P., Batista; D. M., Simonich.

1997-11-01

287

Population structure of Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis cases in the United States from 2003 to 2008.  

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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 including multilocus genotyping, pulsed-field gel electrophoresis, and sequence analysis of the inlAB locus. ECI, ECII, and ECIa were frequently encountered (32, 17, and 7%, respectively). However, annually 30 to 68% of isolates were outside these ECs, and several novel clonal groups were identified. An estimated 33 and 17% of the isolates, mostly among the ECs, were resistant to cadmium and arsenic, respectively, but resistance to benzalkonium chloride was uncommon (3%) among the sporadic isolates. The frequency of clonal groups fluctuated within the 6-year study period, without consistent trends. However, on several occasions, temporal clusters of isolates with indistinguishable genotypes were detected, suggesting the possibility of hidden multistate outbreaks. Our analysis suggests a complex population structure of serotype 4b L. monocytogenes from sporadic disease, with important contributions by ECs and several novel clonal groups. Continuous monitoring will be needed to assess long-term trends in clonality patterns and population structure of L. monocytogenes from sporadic listeriosis. PMID:24705322

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

2014-06-01

288

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

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Full Text Available SciELO Brazil | Language: English Abstract in portuguese Inúmeros estudos têm mostrado que fibroblastos de pacientes com adenomatose hereditária de cólon e reto, que inclui polipose adenomatosa familial (FAP) e a síndrome de Gardner, apresentam uma freqüência aumentada de aberrações cromossômicas após exposição a agentes físicos ou químicos, quando compar [...] ados aos controles normais. Para determinar a sensibilidade de linfócitos de pacientes com FAP e também com pólipos adenomatosos esporádicos (AP) usou-se o radiomimético bleomicina (BLM). Foram estudados citogeneticamente 10 indivíduos com AP, 10 com FAP e 20 controles normais, pareados por sexo e idade. Indivíduos que apresentaram valores médios de quebras cromatídicas por célula superiores a 0,80 foram considerados sensíveis à droga. Observou-se uma diferença significativa entre pacientes com FAP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados na fase G2. Entretanto, nenhuma diferença significativa foi observada entre pacientes com AP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados. Nenhum indivíduo do grupo controle foi sensível à BLM e, entre os 20 pacientes, três mostraram suscetibilidade à droga. Não foi encontrada diferença significativa quanto a resposta à bleomicina entre indivíduos do sexo masculino e feminino. Entretanto, a distribuição de quebras induzidas por bleomicina em cada grupo cromossômico não foi similar nos pacientes do sexo feminino e controles normais. É possível que a sensibilidade cromossômica à BLM encontrada nos pacientes com FAP esteja relacionada a deficiência de reparo de DNA. Abstract in english 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 bleo [...] mycin 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.

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

289

Modeling of Sporadic Layers Meteoritic in Origin in the Mars' Ionosphere  

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Recent measurements of the Martian ionosphere has revealed the existence of low altitude layers at altitudes ranging from 70 and 90 km, well below the main photoionospheric peak. These peaks were detected by radio science experiments both Mars Global Surveyor (in 71 of 56000 profiles, [1]) and Mars Express (in 75 of 465 profiles, [2]). The presence of these layers was not limited to specific times of the day, longitude or latitude. Previous theoretical models [3,4] predicted the existence of a constant low altitude layer, with a maximum density of the same order of magnitude compared with the recent observations. Long-live metallic ions coming from meteoroid particles can increase the concentration of electrons. However, the models are not able to explain the huge variability of the observations. Similar layers have been observed in the Earth's atmosphere, especially during strong meteor shower and it is well known that they contain metallic ions coming from the ablation of extraterrestrial dust. Here we present a model of the vertical density profile of metallic species (magnesium and iron) between 60 and 120 km altitude. The model includes ablation of meteoroids, metal diffusion in the atmosphere, photoionization of neutrals by ultraviolet photons, and the chemistry of ions and neutrals including charge exchange between neutrals and ions. We have found that the presence of Mg and Fe reduces the concentration of the most abundant atmospheric ions and also increase the concentration of electrons below 90 km of altitude. Model results are compared with some selected electron density profiles observed by Mars Express in order to understand the existence of this sporadic layer. We obtain that in some conditions a low altitude layer can be formed which compared relatively well with the observations, even under steady state scenarios. However dynamic models or high meteoroid fluxes, i.e. meteor showers, are required to explain fully the observations. [1] Withers et al. (2008), J. Geophys. Res. 113, A12314. [2] Patzold et al. (2005), Science 310, 837-838. [3] Pesnell et al. (2000), J. Geophys. Res.105, 1695. [4] Molina-Cuberos et al. (2003), Planet. and Space Sci. 51, 239

Molina-Cuberos, G. J.; Peter, K.; Witasse, O. G.; Nuñez, M. J.; Paetzold, M.

2011-12-01

290

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

291

Analysis of Prion Strains by PrP(Sc Profiling in Sporadic Creutzfeldt-Jakob Disease.  

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

2005-12-01

292

Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer  

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Nutritional and genetic risk factors for intestinal tumors are additive on mouse tumor phenotype, establishing that diet and genetic factors impact risk by distinct combinatorial mechanisms. In a mouse model of dietary-induced sporadic small and large intestinal cancer in WT mice in which tumor etiology, lag, incidence, and frequency reflect >90% of intestinal cancer in Western societies, dietary-induced risk altered gene expression profiles predominantly in villus cells of the histologically normal mucosa, in contrast to targeting of crypt cells by inheritance of an Apc1638N allele or homozygous inactivation of p21Waf1/cip1, and profiles induced by each risk factor were distinct at the gene or functional group level. The dietary-induced changes in villus cells encompassed ectopic expression of Paneth cell markers (a lineage normally confined to the bottom of small intestinal crypts), elevated expression of the Wnt receptor Fzd5 and of EphB2 (genes necessary for Paneth cell differentiation and localization to the crypt bottom), and increased Wnt signaling in villus cells. Ectopic elevation of these markers was also present in the colon crypts, which are also sites of sporadic tumors in the nutritional model. Elevating dietary vitamin D3 and calcium, which prevents tumor development, abrogated these changes in the villus and colon cells. Thus, common intestinal cancer driven by diet involves mechanisms of tumor development distinct from those mechanisms that cause tumors induced by the rare inheritance of a mutant adenomatous polyposis coli (Apc) allele. This is fundamental for understanding how common sporadic tumors arise and in evaluating relative risk in the population. PMID:21652773

Wang, Donghai; Peregrina, Karina; Dhima, Elena; Lin, Elaine Y.; Mariadason, John M.; Augenlicht, Leonard H.

2011-01-01

293

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

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

Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

2012-01-01

294

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

295

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

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Full Text Available GPS (Global Positioning System Radio occultation (RO measurements from CHAMP, GRACE and FORMOSAT-3/COSMIC satellites at Northern Hemisphere midlatitides (50°–55° N are analysed to obtain the diurnal variation of sporadic E layer occurrence frequency in 2006 and 2007. Interconnections with zonal wind shears measured by meteor radar at Collm (51.3° N, 13° E, Germany, are investigated. According to theory, maximum Es occurrence is expected when the zonal wind shear, which is mainly produced by the semidiurnal tide in midlatitudes, is negative. This is confirmed by the present measurements and analysis.

C. Arras

2009-06-01

296

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

297

Involvement of ApoE E4 and H63D in sporadic Alzheimer's disease in a folate-supplemented Ontario population.  

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Dysregulation of iron homeostasis is implicated in Alzheimer's disease (AD). In this pilot study, common variants of the apolipoprotein E (APOE) and HFE genes resulting in the iron overload disorder of hereditary hemochromatosis (C282Y, H63D and S65C) were evaluated as factors in sporadic AD in an Ontario sample in which folic acid fortification has been mandatory since 1998. Laboratory studies also were done to search for genetic effects on blood markers of iron status, red cell folates and serum B12. Participants included 58 healthy volunteers (25 males, 33 females) and 54 patients with probable AD (20 males, 34 females). Statistical analyses were interpreted at the 95% confidence level. Contingency table and odds ratio analyses supported the hypothesis that in females of the given age range, E4 significantly predisposed to AD in the presence but not absence of H63D. In males, E4 significantly predisposed to AD in the absence of H63D, and H63D in the absence of E4 appeared protective against AD. Among E4+ AD patients, H63D was associated with significant lowering of red cell folate concentration, possibly as the result of excessive oxidative stress. However, folate levels in the lowest population quartile did not affect the risk of AD. A model is presented to explain the experimental findings. PMID:18525129

Percy, Maire; Moalem, Sharon; Garcia, Angeles; Somerville, Martin J; Hicks, Mark; Andrews, David; Azad, Azar; Schwarz, Peter; Beheshti Zavareh, Reza; Birkan, Rivka; Choo, Clara; Chow, Vinca; Dhaliwal, Sandeep; Duda, Victoria; Kupferschmidt, Anthony L; Lam, Kyla; Lightman, Deborah; Machalek, Karolina; Mar, Wanna; Nguyen, Frank; Rytwinski, Piotr J; Svara, Erin; Tran, Maithy; Wheeler, Kathleen; Yeung, Lisa; Zanibbi, Katherine; Zener, Rebecca; Ziraldo, Melissa; Freedman, Morris

2008-05-01

298

Finding genetic contributions to sporadic disease: A recessive locus at 12q24 commonly contributes to patent ductus arteriosus  

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The causes of many sporadic diseases are unexplained; the contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. We describe an approach to this problem by first searching for diseases with higher prevalence in populations with high rates of consanguinity, then determining whether disease cases are more commonly the product of consanguinous union than controls in such populations, followed by analysis of genetic linkage in consanguinous cases. We demonstrate the utility of this approach by investigation of congenital heart disease in Iran. We found that patent ductus arteriosus (PDA), a common congenital heart disease, accounts for a higher fraction of congenital heart disease in Iran (15%) than in the United States (2–7%). Moreover, Iranian PDA cases demonstrated a marked increase of parental consanguinity (63%), compared with the general Iranian population (25%) or control cases with tetralogy of Fallot (30%). The recurrence of PDA among siblings was 5%. A genomewide analysis of linkage in 21 unrelated consanguinous PDA cases demonstrated a multipoint logarithm of odds score of 6.27 in favor of linkage of PDA to a 3-centimorgan interval of chromosome 12q24, with 53% of kindreds linked. These findings together establish a recessive component to PDA and implicate a single locus, PDA1, in one third or more of all PDA cases in Iran; they further suggest a role for this locus in PDA worldwide. Finally, these results suggest a general approach to the identification of recessive contributions to sporadic diseases. PMID:12409608

Mani, Arya; Meraji, Seyed-Mahmoud; Houshyar, Roozbeh; Radhakrishnan, Jayaram; Mani, Alaleh; Ahangar, Mehrabeh; Rezaie, Tayebeh M.; Taghavinejad, Mohammad-Ali; Broumand, Behrooz; Zhao, Hongyu; Nelson-Williams, Carol; Lifton, Richard P.

2002-01-01

299

Role of topoisomerase I and thymidylate synthase expression in sporadic colorectal cancer: associations with clinicopathological and molecular features.  

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Topoisomerase I (Topo I) and thymidylate synthase (TS) are essential enzymes for the replication, transcription and repair of DNA, and are potential biomarkers in colorectal cancer (CRC). The aim of the study was to correlate the tissue expression of Topo I and TS in sporadic CRCs with relevant pathological and molecular features and patients' outcome. Topo I and TS expression was assessed by immunostaining in 112 consecutive primary CRCs. Increased expression of Topo I was found in 36% of tumors, preferentially rectal (50%) and with not otherwise specified (NOS) histology (44%). Topo I expression was associated with 18q allelic loss (LOH), (p=0.013), microsatellite stable phenotype (p=0.002) and normal expression of mismatch proteins hMLH1 and hMSH2 (p=0.0012 and p=0.02, respectively). High TS expression was found in 60% of tumors, more frequently in distal sites (62%) and with NOS histology (66%); no association with microsatellite instability was observed. Topo I seems to be involved in the chromosomal instability pathway of sporadic CRCs. Conversely, high TS expression is unlikely to affect the clinical behavior of microsatellite unstable CRCs. PMID:24332575

Azzoni, Cinzia; Bottarelli, Lorena; Cecchini, Stefano; Ziccarelli, Antonio; Campanini, Nicoletta; Bordi, Cesare; Sarli, Leopoldo; Silini, Enrico Maria

2014-02-01

300

Morphological evidence for lipid peroxidation and protein glycoxidation in spinal cords from sporadic amyotrophic lateral sclerosis patients.  

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For determining whether both the spinal cord motor neurons and glial cells are exposed to increased oxidative stress in amyotrophic lateral sclerosis (ALS), we performed an immunohistochemical investigation of end products of lipid peroxidation and protein glycoxidation in spinal cords from seven sporadic ALS patients and seven age-matched control individuals. In the ALS spinal cords, immunoreactivities for adducts of 4-hydroxy-2-nonenal-histidine and crotonaldehyde-lysine as markers of lipid peroxidation, N(epsilon)-(carboxymethyl)lysine as a marker of lipid peroxidation or protein glycoxidation, and pentosidine as a marker of protein glycoxidation were localized in the gray matter neuropil and almost all of the motor neurons, reactive astrocytes and microglia/macrophages, whereas none of the immunoreactivities for N(epsilon)-(carboxyethyl)lysine or argpyrimidine as markers of protein glycoxidation or enzymatic glycolysis, or pyrraline or imidazolone as markers of nonoxidative protein glycation were detectable. The control spinal cords displayed no significant immunoreactivities for any of these examined products. Our results indicate that in sporadic ALS, both lipid peroxidation and protein glycoxidation are enhanced in the spinal cord motor neurons and glial cells, and suggest that the formation of certain products in these abnormal reactions is implicated in motor neuron degeneration. PMID:11602233

Shibata, N; Nagai, R; Uchida, K; Horiuchi, S; Yamada, S; Hirano, A; Kawaguchi, M; Yamamoto, T; Sasaki, S; Kobayashi, M

2001-10-26

 
 
 
 
301

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

302

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

303

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

304

Novel approach to the molecular diagnosis of Marfan syndrome: application to sporadic cases and in prenatal diagnosis.  

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Marfan syndrome is an autosomal dominant disorder affecting the skeletal, ocular, and cardiovascular systems. Defects in the gene that encodes fibrillin-1 (FBN1), the main structural component of the elastin-associated microfibrils, are responsible for the disorder. Molecular diagnosis in families with Marfan syndrome can be undertaken by using intragenic FBN1 gene markers to identify and track the disease allele. However, in sporadic cases, which constitute up to 30% of the total, DNA-based diagnosis cannot be performed using linked markers but rather requires the identification of the specific FBN1 gene mutation. Due to the size and complexity of the FBN1 gene, identification of a causative Marfan syndrome mutation is not a trivial undertaking. Herein, we describe a comprehensive approach to the molecular diagnosis of Marfan syndrome that relies on the direct analysis of the FBN1 gene at the cDNA level and detects both coding sequence mutations and those leading to exon-skipping, which are often missed by analysis at the genomic DNA level. The ability to consistently determine the specific FBN1 gene mutation responsible for a particular case of Marfan syndrome allows both prenatal and pre-implantation diagnosis, even in sporadic instances of the disease. PMID:11251996

Toudjarska, I; Kilpatrick, M W; Lembessis, P; Carra, S; Harton, G L; Sisson, M E; Black, S H; Stern, H J; Gelman-Kohan, Z; Shohat, M; Tsipouras, P

2001-04-01

305

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

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

Junker Kerstin

2007-02-01

306

Common Variations in BMP4 Confer Genetic Susceptibility to Sporadic Congenital Heart Disease in a Han Chinese Population.  

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Congenital heart disease (CHD) is the most common birth defect in humans. The genetic causes of sporadic CHD remain largely unknown. Bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor-? (TGF-?) family, is required for normal heart development. Loss of BMP4 gene expression in mice is associated with septal defects, defective endocardial cushion remodeling, and abnormal semilunar valve formation. This study evaluated the contribution of single nucleotide polymorphisms (SNPs) in BMP4 to CHD susceptibility in a case-control study of 575 patients with CHD and 844 non-CHD control subjects in a Chinese population. The BMP4 SNP rs762642 was associated with CHD in an additive model (odds ratio [OR]add 1.22; 95 % confidence interval [CI] 1.04-1.43; P add = 0.02). Stratified analysis by CHD subtypes showed a significant association only between rs762642 and atrial septal defect (ORadd 1.33; 95 % CI 1.04-1.72; P add = 0.03) in the additive model. This study was the first to indicate that a common variant of BMP4 may contribute to susceptibility to sporadic CHD in a Chinese population. PMID:25022354

Qian, Bo; Mo, Ran; Da, Min; Peng, Wei; Hu, Yuanli; Mo, Xuming

2014-12-01

307

Rare copy number variants disrupt genes regulating vascular smooth muscle cell adhesion and contractility in sporadic thoracic aortic aneurysms and dissections.  

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Thoracic aortic aneurysms and dissections (TAAD) cause significant morbidity and mortality, but the genetic origins of TAAD remain largely unknown. In a genome-wide analysis of 418 sporadic TAAD cases, we identified 47 copy number variant (CNV) regions that were enriched in or unique to TAAD patients compared to population controls. Gene ontology, expression profiling, and network analysis showed that genes within TAAD CNVs regulate smooth muscle cell adhesion or contractility and interact with the smooth muscle-specific isoforms of ?-actin and ?-myosin, which are known to cause familial TAAD when altered. Enrichment of these gene functions in rare CNVs was replicated in independent cohorts with sporadic TAAD (STAAD, n = 387) and inherited TAAD (FTAAD, n = 88). The overall prevalence of rare CNVs (23%) was significantly increased in FTAAD compared with STAAD patients (Fisher's exact test, p = 0.03). Our findings suggest that rare CNVs disrupting smooth muscle adhesion or contraction contribute to both sporadic and familial disease. PMID:21092924

Prakash, Siddharth K; LeMaire, Scott A; Guo, Dong-Chuan; Russell, Ludivine; Regalado, Ellen S; Golabbakhsh, Hossein; Johnson, Ralph J; Safi, Hazim J; Estrera, Anthony L; Coselli, Joseph S; Bray, Molly S; Leal, Suzanne M; Milewicz, Dianna M; Belmont, John W

2010-12-10

308

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

309

Chromosome 5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutation carriers and sporadic breast tumors.  

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Comparative genomic hybridization (CGH) analysis has shown that chromosome 5q deletions are the most frequent aberration in breast tumors from BRCA1 mutation carriers. To map the location of putative 5q tumor suppressor gene(s), 26 microsatellite markers covering chromosome 5 were used in loss of heterozygosity (LOH) analysis of breast tumors from BRCA1 (n = 42) and BRCA2 mutation carriers (n = 67), as well as in sporadic cases (n = 65). High-density array CGH was also used to map chromosome 5 imbalance in 10 BRCA1 tumors. A high LOH frequency was found in BRCA1 tumors (range 19-82%), as compared to BRCA2 and sporadic tumors (ranges 11-44% and 7-43%, respectively). In all, 11 distinct chromosome 5 regions with LOH were observed, the most frequent being 5q35.3 (82%), 5q14.2 (71%) and 5q33.1 (69%) in BRCA1 tumors; 5q35.3 (44%), 5q31.3 (43%) and 5q13.3 (43%) in BRCA2 tumors and 5q31.3 (43%) in sporadic tumors. Array CGH analysis confirmed the very high frequency of 5q deletions, including candidate tumor suppressor genes such as XRCC4, RAD50, RASA1, APC and PPP2R2B. In addition, 2 distinct homozygous deletions were identified, spanning regions of 0.7-1.5 Mbp on 5q12.1 and 5q12.3-q13.1, respectively. These regions include only a few genes, most notably BRCC3/DEPDC1B (pleckstrin/G protein interacting and RhoGAP domains) and PIK3R1 (PI3 kinase P85 regulatory subunit). Significant association (p < or = 0.05) was found between LOH at certain 5q regions and factors of poor prognosis, including negative estrogen and progesterone receptor status, high grade, large tumor size and high portion of cells in S-phase. In conclusion, our results confirm a very high prevalence of chromosome 5q alterations in BRCA1 tumors, pinpointing new regions and genes that should be further investigated. PMID:16570289

Johannsdottir, Hrefna K; Jonsson, Goran; Johannesdottir, Gudrun; Agnarsson, Bjarni A; Eerola, Hannaleena; Arason, Adalgeir; Heikkila, Paivi; Egilsson, Valgardur; Olsson, Hakan; Johannsson, Oskar Th; Nevanlinna, Heli; Borg, Ake; Barkardottir, Rosa B

2006-09-01

310

Study of folate receptor genes in nonsyndromic familial and sporadic cleft lip with or without cleft palate cases.  

Science.gov (United States)

Folate receptor family members (FOLRs) mediate the delivery of 5-methyltetrahydrofolate to the interior of, out of within, or between cells in a process known as potocytosis. Three FOLRs and a pseudogene map to 11q13.4. The aim of this study was to verify whether FOLRs could be responsible for the onset of nonsyndromic cleft lip with or without cleft palate (CL/P). Linkage and linkage disequilibrium between genetic markers and disorder were analyzed. Patients and their mothers from 71 familial CL/P pedigrees and 75 sporadic cases from Italian population were investigated by PCR-SSCP analysis. Data from mutation scanning allowed us to find only a silent mutation in FOLR1 present in a mother and her child. Our findings do not support FOLR1 and FOLR2 genes in the onset of CL/P. PMID:15690375

Scapoli, Luca; Marchesini, Jlenia; Martinelli, Marcella; Pezzetti, Furio; Carinci, Francesco; Palmieri, Annalisa; Rullo, Rosario; Gombos, Fernando; Tognon, Mauro; Carinci, Paolo

2005-01-30

311

Late-onset sporadic ataxia, pontine lesion, and retroperitoneal fibrosis: a case of Erdheim-Chester disease.  

Science.gov (United States)

A 60-year-old man with progressive gait ataxia and mild pyramidal signs showed at MRI a pontine lesion with post-contrast enhancement in the left middle cerebellar peduncle. Diagnosis of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, was suggested, further supported by a previously diagnosed retroperitoneal fibrosis. X-ray films demonstrated characteristic bilateral and symmetric osteosclerosis of the long bones of the lower limbs, which at radionuclide studies exhibited a marked increase in technetium-99 uptake. A cerebral 18FDG-PET showed a relevant pontine uptake of the tracer. Re-evaluation of a past retroperitoneal biopsy showed an intense CD68+, CD1a-, and S100- infiltrate of histiocytes with foamy cytoplasm, thus confirming the diagnosis. ECD should be regarded as a rare cause of adult-onset sporadic ataxia, especially when pontine lesions and extraneurological manifestations are present. PMID:18810602

Salsano, E; Savoiardo, M; Nappini, S; Maderna, E; Pollo, B; Chinaglia, D; Guerra, U; Finocchiaro, G; Pareyson, D

2008-09-01

312

A sporadic case of benign myoclonus epilepsy of adult onset: its clinical aspects and electroencephalographic, polygraphic study.  

Science.gov (United States)

A sporadic case of myoclonus epilepsy of adult onset with a benign course is presented. Its clinical implications were discussed symptomatologically and nosologically. EEG findings consisted of the slowing of basic activity, characteristic polyspike and wave discharges or other paroxysmal patterns and photomyoclonic response (PMR). The PMR was well evoked by flashes of 6-21 Hz and of yellow or red color. Clinical similarities of this case to those of hereditary myoclonus epilepsy without progressive dementia and cerebellar ataxia, and pathognomonic characteristics of electrophysiological findings indicated that the myoclonic epilepsy syndrome might share basic properties, which are state-dependent, but independent of underlying neuropathology or heredity. During sleep, paroxysmal discharges with spike(s) significantly decreased in slow-wave sleep and almost recovered in REM sleep. This finding suggests that the brain stem may be responsible for the epileptogeneity in this case. PMID:3097366

Ishigooka, J; Wakatabe, H; Takahashi, A; Yoshida, Y; Murasaki, M

1986-06-01

313

MORA: an Energy-Aware Slack Reclamation Scheme for Scheduling Sporadic Real-Time Tasks upon Multiprocessor Platforms  

CERN Document Server

In this paper, we address the global and preemptive energy-aware scheduling problem of sporadic constrained-deadline tasks on DVFS-identical multiprocessor platforms. We propose an online slack reclamation scheme which profits from the discrepancy between the worst- and actual-case execution time of the tasks by slowing down the speed of the processors in order to save energy. Our algorithm called MORA takes into account the application-specific consumption profile of the tasks. We demonstrate that MORA does not jeopardize the system schedulability and we show by performing simulations that it can save up to 32% of energy (in average) compared to execution without using any energy-aware algorithm.

Nelis, Vincent

2009-01-01

314

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

315

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma  

Science.gov (United States)

Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50?350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50?8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations. PMID:24550739

Liang, Winnie S.; Fonseca, Rafael; Bryce, Alan H.; McCullough, Ann E.; Barrett, Michael T.; Hunt, Katherine; Patel, Maitray D.; Young, Scott W.; Collins, Joseph M.; Silva, Alvin C.; Condjella, Rachel M.; Block, Matthew; McWilliams, Robert R.; Lazaridis, Konstantinos N.; Klee, Eric W.; Bible, Keith C.; Harris, Pamela; Oliver, Gavin R.; Bhavsar, Jaysheel D.; Nair, Asha A.; Middha, Sumit; Asmann, Yan; Kocher, Jean-Pierre; Schahl, Kimberly; Kipp, Benjamin R.; Barr Fritcher, Emily G.; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Phillips, Lori; McDonald, Jackie; Adkins, Jonathan; Mastrian, Stephen D.; Placek, Pamela; Watanabe, Aprill T.; LoBello, Janine; Han, Haiyong; Von Hoff, Daniel; Craig, David W.; Stewart, A. Keith; Carpten, John D.

2014-01-01

316

Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma.  

Science.gov (United States)

Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50?350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50?8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations. PMID:24550739

Borad, Mitesh J; Champion, Mia D; Egan, Jan B; Liang, Winnie S; Fonseca, Rafael; Bryce, Alan H; McCullough, Ann E; Barrett, Michael T; Hunt, Katherine; Patel, Maitray D; Young, Scott W; Collins, Joseph M; Silva, Alvin C; Condjella, Rachel M; Block, Matthew; McWilliams, Robert R; Lazaridis, Konstantinos N; Klee, Eric W; Bible, Keith C; Harris, Pamela; Oliver, Gavin R; Bhavsar, Jaysheel D; Nair, Asha A; Middha, Sumit; Asmann, Yan; Kocher, Jean-Pierre; Schahl, Kimberly; Kipp, Benjamin R; Barr Fritcher, Emily G; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Phillips, Lori; McDonald, Jackie; Adkins, Jonathan; Mastrian, Stephen D; Placek, Pamela; Watanabe, Aprill T; Lobello, Janine; Han, Haiyong; Von Hoff, Daniel; Craig, David W; Stewart, A Keith; Carpten, John D

2014-02-01

317

Germline and somatic c-met mutations in multifocal/bilateral and sporadic papillary renal carcinomas of selected patients.  

Science.gov (United States)

Papillary renal carcinoma (PRC) comprises about 10% of all kidney epithelial tumors. Familiar/hereditary papillary renal carcinomas (HPRCs) have been described, but the majority of cases seem to be sporadic. HPRC is characterized by the predisposition to develop bilateral, multifocal renal tumors. Activating mutations in the tyrosine kinase domain (TK) of the hepatocyte growth factor (HGF) receptor, c-met, have been identified in both hereditary and sporadic PRC. The main aim of this study was to examine a family with no history of PRC in which the proband was a female patient affected by multiple and bilateral PRC at early onset. DNA mutation analysis has been performed by direct sequencing of exons 14-21 of c-met gene which include the TK domain. The proband displayed the germline c-met missense mutation g.3522G--> A in exon 16. Two other family members were found to carry the same mutation. The mutation analysis extended to 15 selected patients, allowed to identify the first case of an Italian patient affected by PRC displaying the somatic missense mutation g.3997 T-->C curved arrow C located in exon 19 of c-met. The mutation frequency of the selected-based population of PRC patients in this report was 12.5%. Furthermore, the phosphorylated c-met expression detected by immunohistochemistry in PRCs with germline/somatic or no c-met mutation, supports the concept that c-met activation may occur in PRC oncogenesis by c-met mutations and/or c-met over-expression. PMID:18636147

Salvi, Alessandro; Marchina, Eleonora; Benetti, Anna; Grigolato, Piergiovanni; De Petro, Giuseppina; Barlati, Sergio

2008-08-01

318

Regression of sporadic intra-abdominal desmoid tumour following administration of non-steroidal anti-inflammatory drug  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Desmoid tumours or fibromatoses are rare entities characterized by the benign proliferation of fibroblasts, which can be life-threatening due to their locally aggressive properties. Surgery is widely accepted as the first line of treatment for extra-abdominal desmoids; however, it is not recommended for intra-abdominal desmoids because of the high-risk of recurrence and difficulties with the operation. Here, we report on a patient with sporadic intra-abdominal desmoid tumours, who showed partial response following the intake of non-steroidal anti-inflammatory drugs. Case presentation A 73-year-old man presented with swelling and pain of the right leg. Computed tomography showed an abnormal multilocular soft-tissue mass (95 × 70 mm in the right pelvis, which was revealed by biopsy to be a desmoid tumour. Immunohistochemical analysis showed that the tumour cells expressed vimentin, but not smooth-muscle actin, CD34, or desmin. Very few Ki-67-positive cells were found. Non-cytotoxic treatment with etodolac (200 mg/day was chosen because of the patient's age, lack of bowel obstruction, and the likelihood of prostate cancer. Two years after the commencement of non-steroidal anti-inflammatory drug administration, computed tomography showed a decrease in tumour size (63 × 49 mm, and the disappearance of intratumoural septa. Conclusion Our case report suggests that non-steroidal anti-inflammatory drug treatment should be taken into consideration for use as first-line treatment in patients with sporadic intra-abdominal desmoid tumours.

Fujiwara Yoshinori

2008-02-01

319

Genetic abnormalities in sporadic parathyroid adenomas: Loss of heterozygosity for chromosome 3q markers flanking the calcium receptor locus  

Energy Technology Data Exchange (ETDEWEB)

Inactivating mutations of the parathyroid cell calcium receptor (CaR) gene cause one form of familial benign/hypocalciuric hypercalcemia, and in homozygous form, cause neonatal severe primary hyperparathyroidism with parathyroid hyperplasia. Thus, we postulated that partial or total loss of CaR function might contribute to calcium insensitivity or even stimulate cell proliferation in sporadic parathyroid adenomas (PAds). To examine this possibility, we sought loss of heterozygosity (LOH) for markers flanking the CaR locus (3cen-3q21) in 35 PAds. We used 16 highly-polymorphic PCR-based markers in paired normal and tumor DNA, extracted from archived surgical specimens. Nineteen to twenty-four of the DNA pairs were informative with at least one marker. In two informative pairs, we found LOH for markers D3S1303, D3S1267, or D3S1269, which are tightly-linked with and flank the CaR locus. In one tumor, deletion mapping confined the lost area between D3S1271 and D3S1238 (41.7 centimorgans, cM). In the other tumor, LOH spanned most of chromosome 3, ranging at least from D3S1307 to D3S1311 (271.4 cM). LOH was confirmed by repetition of the experiments and quantified by phosphorimaging. Thus, we found LOH encompassing the CaR locus in approximately 10% of sporadic PAds. These data are consistent with the hypothesis that loss of CaR function may occur in PAds, with functional consequences for calcium sensitivity and cell proliferation. 20 refs., 2 figs.

Thompson, D.B.; Samowitz, W.S.; Davis, K. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)] [and others

1995-10-01

320

Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Inter-individual variation in DNA repair capacity is thought to modulate breast cancer risk. The phenotypic mutagen sensitivity assay (MSA measures DNA strand breaks in lymphocytes; women with familial and sporadic breast cancers have a higher mean number of breaks per cell (MBPC then women without breast cancer. Here, we explore the relationships between the MSA and the Rad51 gene, which encodes a DNA repair enzyme that interacts with BRCA1 and BRCA2, in BRCA1 mutation carriers and women with sporadic breast cancer. Methods Peripheral blood lymphoblasts from women with known BRCA1 mutations underwent the MSA (n = 138 among 20 families. BRCA1 and Rad51 genotyping and sequencing were performed to identify SNPs and haplotypes associated with the MSA. Positive associations from the study in high-risk families were subsequently examined in a population-based case-control study of breast cancer (n = 1170 cases and 2115 controls. Results Breast cancer diagnosis was significantly associated with the MSA among women from BRCA1 families (OR = 3.2 95%CI: 1.5-6.7; p = 0.004. The Rad51 5'UTR 135 C>G genotype (OR = 3.64; 95% CI: 1.38, 9.54; p = 0.02, one BRCA1 haplotype (p = 0.03 and in a polygenic model, the E1038G and Q356R BRCA1 SNPs were significantly associated with MBPC (p = 0.009 and 0.002, respectively. The Rad51 5'UTR 135C genotype was not associated with breast cancer risk in the population-based study. Conclusions Mutagen sensitivity might be a useful biomarker of penetrance among women with BRCA1 mutations because the MSA phenotype is partially explained by genetic variants in BRCA1 and Rad51.

Nie Jing

2011-06-01

 
 
 
 
321

Identification of microRNAs regulated by isothiocyanates and association of polymorphisms inside their target sites with risk of sporadic colorectal cancer.  

Science.gov (United States)

Sporadic colorectal cancer (CRC) is a typical multifactorial disease. Isothiocyanates (ITC) have been recently shown to inhibit development of CRC in many experimental models. MicroRNAs (miRNAs) are short noncoding RNAs that posttranscriptionally regulate gene expression through binding to 3' untranslated regions (3'UTR) of target mRNAs. MiRNAs are regulated by natural agents, ITCs included. In our study, using global expression profiling based on TaqMan Low-Density Arrays, we identified 3 common miRNAs (miR-155, miR-23b, miR-27b) regulated by ITCs (sulforaphane, iberin) in colonic epithelial cell lines NCM460 and NCM356. In silico predictions allowed us to find 9 relevant single nucleotide polymorphisms (SNPs) localized within the 3'UTRs of genes (AGTR1, TNFAIP2, PRKCB, HSPA9, RABGAP1, DICER1, ADAM19, VWA5A, and SIRT5) targeted by these ITC-related miRNAs. Finally, we observed that homozygous CC genotype of DICER1, rs1057035, was significantly associated with decreased risk of CRC (odds ratio = 0.49; 95% confidence interval: 0.25-0.95, P = 0.036) when compared to TT homozygote genotype; also, the C allele tended to have a protective effect (P = 0.072). This study showed that miRNAs could be involved in chemoprotective effects of natural agents; their function alteration through SNPs in their binding sites and flanking regions presents a new class of CRC risk factors. PMID:23441612

Slaby, Ondrej; Sachlova, Milana; Brezkova, Veronika; Hezova, Renata; Kovarikova, Alena; Bischofová, Svatava; Sevcikova, Sabina; Bienertova-Vasku, Julie; Vasku, Anna; Svoboda, Marek; Vyzula, Rostislav

2013-01-01

322

Simultaneous observations of solar sporadic radio emission by the radio telescopes UTR-2, URAN-2 and NDA within the frequency range 8-42 MHz  

Science.gov (United States)

From 25 June till 12 August 2011 sporadic solar radio emission was observed simultaneously by three separate radio telescopes: UTR-2 (Kharkov, Ukraine), URAN-2 (Poltava, Ukraine) and NDA (Nancay, France). During these observations some interesting phenomena were observed. Some of them are discussed in this paper.

Melnik, V.; Konovalenko, A.; Brazhenko, A.; Briand, C.; Dorovskyy, V.; Zarka, P.; Denis, L.; Bulatzen, V.; Frantzusenko, A.; Rucker, H.; Stanislavskyy, A.

2012-09-01

323

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. © 2014 Wiley Periodicals, Inc. 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

324

The molecular link between inefficient GluA2 Q/R site-RNA editing and TDP-43 pathology in motor neurons of sporadic amyotrophic lateral sclerosis patients.  

Science.gov (United States)

TAR DNA-binding protein (TDP-43) pathology and reduced expression of adenosine deaminase acting on RNA 2 (ADAR2), which is the RNA editing enzyme responsible for adenosine-to-inosine conversion at the GluA2 glutamine/arginine (Q/R) site, concomitantly occur in the same motor neurons of amyotrophic lateral sclerosis (ALS) patients; this finding suggests a link between these two ALS-specific molecular abnormalities. AMPA receptors containing Q/R site-unedited GluA2 in their subunit assembly are Ca(2+)-permeable, and motor neurons lacking ADAR2 undergo slow death in conditional ADAR2 knockout (AR2) mice, which is a mechanistic ALS model in which the ADAR2 gene is targeted in cholinergic neurons. Moreover, deficient ADAR2 induced mislocalization of TDP-43 similar to TDP-43 pathology seen in the sporadic ALS patients in the motor neurons of AR2 mice. The abnormal mislocalization of TDP-43 specifically resulted from activation of the Ca(2+)-dependent serine protease calpain that specifically cleaved TDP-43 at the C-terminal region, and generated aggregation-prone N-terminal fragments. Notably, the N-terminal fragments of TDP-43 lacking the C-terminus were demonstrated in the brains and spinal cords of ALS patients. Because normalization of either the Ca(2+)-permeability of AMPA receptors or the calpain activity in the motor neurons normalized the subcellular localization of TDP-43 in AR2 mice, it is likely that exaggerated calpain-dependent TDP-43 fragments played a role at least in the initiation of TDP-43 pathology. Elucidation of the molecular cascade of neuronal death induced by ADAR2 downregulation could provide a new specific therapy for sporadic ALS. In this review, we summarized the work from our group on the role of inefficient GluA2 Q/R site-RNA editing and TDP-43 pathology in sporadic ALS, and discussed possible effects of inefficient ADAR2-mediated RNA editing in general. This article is part of a Special Issue entitled RNA Metabolism 2013. PMID:24355598

Yamashita, Takenari; Kwak, Shin

2014-10-10

325

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

326

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.

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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

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

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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.

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

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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

330

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

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Full Text Available 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.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 developmental 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

2011-04-01

331

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

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It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from N...

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

2008-01-01

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Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas  

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The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and has in a previous study been correlated with a less favorable clinical outcome. In the present study, 46 MTCs were selected for investigation of the codon 918 mutation. The mutation was found in 29 tumors (63%), and was significantly correlated with a poor outcome, with regard to distant metastasis or tumor recurrence (p<10{sup 4}). Two tumors showed multifocal growth and C-cell hyperplasia, and these patients were therefore also investigated for germline mutations in exons 10, 11 and 16. The codon 918 mutation was found only in the tumors, thus of somatic origin. The RET codon 918 mutation may have prognostic impact, and therefore preoperative assessment may influence decision-making in the treatment of patients suffering from MTC. 13 refs., 1 fig., 1 tab.

Zedenius, J.; Svensson, A.; Baeckdahl, M.; Wallin, G. [Karolinska Hospital, Stockholm (Sweden)] [and others

1995-10-01

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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

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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

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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

336

Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS.  

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ALS is a terminal disease of motor neurons that is characterized by accumulation of proteinaceous deposits in affected cells. Pathological deposition of mutated Cu/Zn superoxide dismutase (SOD1) accounts for ?20% of the familial ALS (fALS) cases. However, understanding the molecular link between mutation and disease has been difficult, given that more than 140 different SOD1 mutants have been observed in fALS patients. In addition, the molecular origin of sporadic ALS (sALS) is unclear. By dissecting the amino acid sequence of SOD1, we identified four short segments with a high propensity for amyloid fibril formation. We find that fALS mutations in these segments do not reduce their propensity to form fibrils. The atomic structures of two fibril-forming segments from the C terminus, (101)DSVISLS(107) and (147)GVIGIAQ(153), reveal tightly packed ?-sheets with steric zipper interfaces characteristic of the amyloid state. Based on these structures, we conclude that both C-terminal segments are likely to form aggregates if available for interaction. Proline substitutions in (101)DSVISLS(107) and (147)GVIGIAQ(153) impaired nucleation and fibril growth of full-length protein, confirming that these segments participate in aggregate formation. Our hypothesis is that improper protein maturation and incompletely folded states that render these aggregation-prone segments available for interaction offer a common molecular pathway for sALS and fALS. PMID:24344300

Ivanova, Magdalena I; Sievers, Stuart A; Guenther, Elizabeth L; Johnson, Lisa M; Winkler, Duane D; Galaleldeen, Ahmad; Sawaya, Michael R; Hart, P John; Eisenberg, David S

2014-01-01

337

Explanation of the sporadic-E layer formation by comparing FORMOSAT-3/COSMIC data with meteor and wind shear information  

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formation of the sporadic E (Es) layer can be interpreted in several different ways, with wind shear theory and the meteor ionization mechanism being the most commonly used explanations. Nevertheless, neither the wind shear theory nor the meteor ionization mechanism alone can completely explain the formation of the Es layer. The meteor ionization mechanism cannot interpret the different activity in this layer between the Northern and Southern Hemispheres, while the wind shear theory cannot explain the source of the large amount of ionized particles in the Es layer. In this study, the activity in the Es layer is compared with information about meteors and the global vertical speed of ionized particles. The information about meteors is obtained from International Meteor Organization and Radio Meteor Observing Bulletin. The global vertical speed information for ionized particles is calculated using the International Geomagnetic Reference Field model, Horizontal Wind Model (HWM07), and Mass Spectrometer-Incoherent Scatter model. The activity in the Es layer is based on the value of the irregular degree index, which is derived from the signal-to-noise ratio obtained from Formosa Satellite Mission-3/Constellation Observing System for Meteorology, Ionosphere, and Climate (FORMOSAT-3/COSMIC) Global Positioning System radio occultation mission. Taking both wind shear theory and the meteor ionization mechanism together, the source of the ionized particles in the Es layer and the difference in the activity in the Es layer between Northern and Southern Hemispheres can thus be explained more completely.

Yeh, Wen-Hao; Liu, Jann-Yenq; Huang, Cheng-Yung; Chen, Shih-Ping

2014-04-01

338

Gain and loss of extracellular molecules in sporadic inclusion body myositis and polymyositis--a proteomics-based study.  

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Sporadic inclusion body myositis (sIBM) contains non-necrotic myofibers that are surrounded and/or invaded by inflammatory cells. In this study we aimed to identify selective molecules that are present at this site. Myofibers of four biopsies of sIBM that were surrounded and/or invaded by inflammatory cells were microdissected, pooled and profiled by proteomic studies using mass spectrometry. Normal skeletal muscle tissue served as control. Based on the table of proteins that were detected in sIBM only, we selected nine extracellular matrix molecules and validated the results performing immunofluorescence. Seven out of nine proteins that were detected in sIBM by mass spectrometry showed different immunohistochemical results in myositis and normal controls. Of these, the small leucine-rich repeat proteins proline arginine-rich end leucine-rich repeat protein (PRELP) and biglycan were deposited precisely at myofibers surrounded and/or invaded by inflammatory cells both in sIBM and polymyositis. The basement membrane (BM) molecules merosin, perlecan, nidogen-2 and collagen IV were variably destroyed or increased at these sites. P component, which ensheathed all myofibers in normal controls, was absent from invaded myofibers. Similar to BM remodeling, the specific deposition of PRELP and biglycan may represent a mechanism to defend against immune attack. Loss of P component may affect the anchorage of the myofiber in the endomysium. PMID:21672074

Doppler, Kathrin; Lindner, Alfred; Schütz, Wolfgang; Schütz, Monika; Bornemann, Antje

2012-01-01

339

Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS  

Science.gov (United States)

ALS is a terminal disease of motor neurons that is characterized by accumulation of proteinaceous deposits in affected cells. Pathological deposition of mutated Cu/Zn superoxide dismutase (SOD1) accounts for ?20% of the familial ALS (fALS) cases. However, understanding the molecular link between mutation and disease has been difficult, given that more than 140 different SOD1 mutants have been observed in fALS patients. In addition, the molecular origin of sporadic ALS (sALS) is unclear. By dissecting the amino acid sequence of SOD1, we identified four short segments with a high propensity for amyloid fibril formation. We find that fALS mutations in these segments do not reduce their propensity to form fibrils. The atomic structures of two fibril-forming segments from the C terminus, 101DSVISLS107 and 147GVIGIAQ153, reveal tightly packed ?-sheets with steric zipper interfaces characteristic of the amyloid state. Based on these structures, we conclude that both C-terminal segments are likely to form aggregates if available for interaction. Proline substitutions in 101DSVISLS107 and 147GVIGIAQ153 impaired nucleation and fibril growth of full-length protein, confirming that these segments participate in aggregate formation. Our hypothesis is that improper protein maturation and incompletely folded states that render these aggregation-prone segments available for interaction offer a common molecular pathway for sALS and fALS. PMID:24344300

Ivanova, Magdalena I.; Sievers, Stuart A.; Guenther, Elizabeth L.; Johnson, Lisa M.; Winkler, Duane D.; Galaleldeen, Ahmad; Sawaya, Michael R.; Hart, P. John; Eisenberg, David S.

2014-01-01

340

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

 
 
 
 
341

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

342

Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms?  

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Despite the large amount of information accumulated on the role played by ret activation in the oncogenesis of papillary thyroid carcinoma (PTC), the biological and clinical significance of such activation 'in vivo' remains controversial. The aim of this study was to address some of the existing controversies by comparing two groups of unselected PTCs, one with and the other without ret rearrangement, with regard to several clinicopathological and biological features. Thirty-three PTCs were selected at random. ret rearrangement was found in eight cases (24.2 per cent) using Southern blot analysis. The mean age of the patients with tumours displaying ret rearrangement (28 +/- 3.1 years) was significantly lower than that of the patients harbouring cases that did not present rearrangement (45 +/- 2.9 years). The large majority of the tumours with ret rearrangement displayed a papillary or mixed follicular-papillary pattern and very low proliferative activity. ret rearrangement correlated significantly with decreased cytoplasmic expression of E-cadherin. No significant differences were found regarding the gender of the patients, tumour size, multicentricity, extrathyroidal growth, vascular invasion, lymphocytic infiltration, lymph node involvement or the expression of E-cadherin (membrane), c-erb-B2, c-met, Bcl-2, and vimentin. It is proposed that sporadic PTCs harbouring a ret rearrangement occur frequently as slow growing, papillary, or predominantly papillary tumours that do not usually progress towards less differentiated neoplasms representing what might be described as a Bonsai phenotype. PMID:9713362

Soares, P; Fonseca, E; Wynford-Thomas, D; Sobrinho-Simões, M

1998-05-01

343

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.

2009-01-01

344

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

345

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

346

Sporadic desmoid-type fibromatosis: a stepwise approach to a non-metastasising neoplasm--a position paper from the Italian and the French Sarcoma Group.  

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Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (?85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/?-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis. PMID:24325833

Gronchi, A; Colombo, C; Le Péchoux, C; Dei Tos, A P; Le Cesne, A; Marrari, A; Penel, N; Grignani, G; Blay, J Y; Casali, P G; Stoeckle, E; Gherlinzoni, F; Meeus, P; Mussi, C; Gouin, F; Duffaud, F; Fiore, M; Bonvalot, S

2014-03-01

347

Subchronic infusion of the product of inflammation prostaglandin J2 models sporadic Parkinson's disease in mice  

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Full Text Available Abstract Background Chronic neuroinflammation is implicated in Parkinson's disease (PD. Inflammation involves the activation of microglia and astrocytes that release high levels of prostaglandins. There is a profound gap in our understanding of how cyclooxygenases and their prostaglandin products redirect cellular events to promote PD neurodegeneration. The major prostaglandin in the mammalian brain is prostaglandin D2, which readily undergoes spontaneous dehydration to generate the bioactive cyclopentenone prostaglandins of the J2 series. These J2 prostaglandins are highly reactive and neurotoxic products of inflammation shown in cellular models to impair the ubiquitin/proteasome pathway and cause the accumulation of ubiquitinated proteins. PD is a disorder that exhibits accumulation of ubiquitinated proteins in neuronal inclusions (Lewy bodies. The role of J2 prostaglandins in promoting PD neurodegeneration has not been investigated under in vivo conditions. Methods We addressed the neurodegenerative and behavioral effects of the administration of prostaglandin J2 (PGJ2 simultaneously into the substantia nigra/striatum of adult male FVB mice by subchronic microinjections. One group received unilateral injections of DMSO (vehicle, n = 6 and three groups received PGJ2 [3.4 ?g or 6.7 ?g (n = 6 per group or 16.7 ?g (n = 5] per injection. Immunohistochemical and behavioral analyses were applied to assess the effects of the subchronic PGJ2 microinfusions. Results Immunohistochemical analysis demonstrated a PGJ2 dose-dependent significant and selective loss of dopaminergic neurons in the substantia nigra while the GABAergic neurons were spared. PGJ2 also triggered formation of aggregates immunoreactive for ubiquitin and ?-synuclein in the spared dopaminergic neurons. Moreover, PGJ2 infusion caused a massive microglia and astrocyte activation that could initiate a deleterious cascade leading to self-sustained progressive neurodegeneration. The PGJ2-treated mice also exhibited locomotor and posture impairment. Conclusion Our studies establish the first model of inflammation in which administration of an endogenous highly reactive product of inflammation, PGJ2, recapitulates key aspects of PD. Our novel PGJ2-induced PD model strongly supports the view that localized and chronic production of highly reactive and neurotoxic prostaglandins, such as PGJ2, in the CNS could be an integral component of inflammation triggered by insults evoked by physical, chemical or microbial stimuli and thus establishes a link between neuroinflammation and PD neurodegeneration.

Figueiredo-Pereira Maria E

2009-07-01

348

A expressão de genes reparadores do DNA nos tumores sincrônicos de câncer colorretal esporádico DNA repair gene expression in synchronic tumors of sporadic colorectal cancer  

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Full Text Available RACIONAL: Um dos mecanismos genéticos presentes em aproximadamente 80% dos pacientes com síndrome hereditária não-polipóide do câncer colorretal (HNPCC são os defeitos nos genes reparadores de DNA, como o MSH2, MSH6 e MLH1, onde os tumores sincrônicos são relativamente freqüentes. Já no câncer colorretal esporádico as lesões sincrônicas são raras. OBJETIVO: Verificar se o mesmo mecanismo genético presente no HNPCC está presente no câncer colorretal esporádico que apresentam com lesões sincrônicas. MÉTODOS: Foram incluídos no estudo todos os pacientes com câncer colorretal sincrônico não HNPCC. Imunoistoquímica com anticorpos para MSH2,MSH6, e MLH1 foi realizada para cada tumor. RESULTADOS: Todos os pacientes apresentaram expressão normal de MSH2 e MLH1. O único gene com imunoexpressão alterada foi o MSH6. CONCLUSÃO: Possivelmente outro mecanismo genético seja responsável pelo surgimento de dois tumores sincrônicos no câncer colorretal esporádico.BACKGROUND: Mismatch repair genes (such as MSH2, MLH1 and MSH6 mutations are present in over 80% of hereditary non-polyposis colorectal cancer (HNPCC tumors, which frequently exhibit synchronous lesions. Sporadic colorectal cancer is rarely associated with synchronous lesions. AIM: To investigate the role of mismatch repair gene mutation in synchronous sporadic colorectal cancer. METHODS: Patients with sporadic synchronous colorectal adenocarcinomas were included in the study. Immunohistochemistry was performed using MSH2, MLH1 and MSH6 antibodies. RESULTS: All patients had two synchoronous lesions. None of them had altered MSH2 or MLH1 expression. One patient had altered MSH6 expression in both tumors. CONCLUSION: Possibly, other molecular mechanisms are involved in carcinogenesis of sporadic synchronous colorectal cancer.

Igor Proscurshim

2007-03-01

349

Somatic mutations of the ret Protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence  

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Germline point mutations in exons 10, 11, and 16 of the ret protooncogene have been identified as causative in multiple endocrine neoplasia type 2 and in familial medullary thyroid carcinoma (MTC). Somatic point mutations of the same gene, exclusively associated with codon 918 of exon 16, have also been reported in few cases of sporadic medullary thyroid carcinoma. We analyzed the blood and tumor DNA of 19 patients with sporadic MTC and 6 patients with primary parathyroid adenoma for point mutations at exons 10, 11, and 16 of the ret protooncogene by restriction analysis of the PCR-amplified product and by sequence analysis of exons 10 and 11. A Cys{sup 634}{r_arrow}Tyr mutation was found in both the tumoral and blood DNA of one patient, indicating that he was affected by an hereditary form of MTC, erroneously considered sporadic. In the other 18 patients with MTC, somatic point mutations of ret were found in 8 cases (44.4%). In 5 cases the mutation affected exon 16 (Met{sup 918}{r_arrow}Thr), and in 3 cases it affected exon 11 (Cys{sup 634}{r_arrow}Arg in 1 and Cys{sup 634}{r_arrow}Trp in 2); these 3 mutations were confirmed by sequence analysis. The remaining 10 patients had no mutation in exon 10 by either restriction analysis or sequence analysis. Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by {chi}{sup 2} analysis). No ret mutation was found in the tumoral DNA from parathyroid adenomas. Our findings indicate that the somatic ret point mutation frequently found in sporadic MTC may affect not only exon 16 but also exon 11 and is associated with less favorable clinical outcome. 14 refs., 2 figs., 3 tabs.

Romei, C.; Elisei, R.; Pinchera, A. [Univ. of Pisa (Italy)] [and others

1996-04-01

350

Increased BACE1 mRNA and noncoding BACE1-antisense transcript in sporadic inclusion body myositis muscle fibers – possibly caused by endoplasmic reticulum stress  

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Sporadic inclusion-body myositis (s-IBM) is the most common muscle disease of older persons. Its muscle-fiber phenotype shares several molecular similarities with Alzheimer-disease (AD) brain, including increased A?PP, accumulation of amyloid-? (A?), and increased BACE1 protein. A?42 is prominently increased in AD brain and within s-IBM fibers, and its oligomers are putatively toxic to both tissues -- accordingly, minimizing A?42 production can be a therapeutic objective in both tissues....

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

2010-01-01

351

Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer.  

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Germline mutations in LKB1 have been reported to underlie familial Peutz-Jeghers syndrome (PJS) with intestinal hamartomatous polyps and an elevated risk of various neoplasms. To investigate the prevalence of LKB1 germline mutations in PJS more generally, we studied samples from 33 unrelated PJS patients including eight non-familial sporadic patients, 20 familial patients and five patients with unknown family history. Nineteen germline mutations were identified, 12 (60%) in familial and four ...

Ylikorkala, A.; Avizienyte, E.; Tomlinson, Ip; Tiainen, M.; Roth, S.; Loukola, A.; Hemminki, A.; Johansson, M.; Sistonen, P.; Markie, D.; Neale, K.; Phillips, R.; Zauber, P.; Twama, T.; Sampson, J.

1999-01-01

352

Patterns of gene expression and copy-number alterations in VHL disease-associated and sporadic clear cell carcinoma of the kidney  

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Recent insights into the role of the VHL tumor suppressor gene in hereditary and sporadic clear cell carcinoma of the kidney (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic targets in ccRCC. We identified 14 regions of nonrandom copy-number change, including 7 regions of amplification (1q, 2q, 5q, 7q, 8q, 12p, and 20q) and 7 regions of deletion (1p, 3p, 4q, 6q, 8p, 9p, and 14q). An analysis aimed at identifying the relevant genes revealed VHL as one of 3 genes in the 3p deletion peak, CDKN2A and CDKN2B as the only genes in the 9p deletion peak, and MYC as the only gene in the 8q amplification peak. An integrated analysis to identify genes in amplification peaks that are consistently overexpressed among amplified samples confirmed MYC as a potential target of 8q amplification and identified candidate oncogenes in the other regions. A comparison of genomic profiles revealed that VHL disease-associated tumors are similar to a subgroup of sporadic tumors, and thus more homogeneous overall. Sporadic tumors without evidence of biallelic VHL inactivation fell into 2 groups: one group with genomic profiles highly dissimilar to the majority of ccRCC, and a second group with genomic profiles that are much more similar to tumors with biallelic inactivation of VHL. PMID:19470766

Beroukhim, Rameen; Brunet, Jean-Philippe; Di Napoli, Arianna; Mertz, Kirsten D.; Seeley, Apryle; Pires, Maira M.; Linhart, David; Worrell, Robert A.; Moch, Holger; Rubin, Mark A.; Sellers, William R.; Meyerson, Matthew; Linehan, W. Marston; Kaelin, William G.; Signoretti, Sabina

2009-01-01

353

A expressão de genes reparadores do DNA nos tumores sincrônicos de câncer colorretal esporádico / DNA repair gene expression in synchronic tumors of sporadic colorectal cancer  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese RACIONAL: Um dos mecanismos genéticos presentes em aproximadamente 80% dos pacientes com síndrome hereditária não-polipóide do câncer colorretal (HNPCC) são os defeitos nos genes reparadores de DNA, como o MSH2, MSH6 e MLH1, onde os tumores sincrônicos são relativamente freqüentes. Já no câncer colo [...] rretal esporádico as lesões sincrônicas são raras. OBJETIVO: Verificar se o mesmo mecanismo genético presente no HNPCC está presente no câncer colorretal esporádico que apresentam com lesões sincrônicas. MÉTODOS: Foram incluídos no estudo todos os pacientes com câncer colorretal sincrônico não HNPCC. Imunoistoquímica com anticorpos para MSH2,MSH6, e MLH1 foi realizada para cada tumor. RESULTADOS: Todos os pacientes apresentaram expressão normal de MSH2 e MLH1. O único gene com imunoexpressão alterada foi o MSH6. CONCLUSÃO: Possivelmente outro mecanismo genético seja responsável pelo surgimento de dois tumores sincrônicos no câncer colorretal esporádico. Abstract in english BACKGROUND: Mismatch repair genes (such as MSH2, MLH1 and MSH6) mutations are present in over 80% of hereditary non-polyposis colorectal cancer (HNPCC) tumors, which frequently exhibit synchronous lesions. Sporadic colorectal cancer is rarely associated with synchronous lesions. AIM: To investigate [...] the role of mismatch repair gene mutation in synchronous sporadic colorectal cancer. METHODS: Patients with sporadic synchronous colorectal adenocarcinomas were included in the study. Immunohistochemistry was performed using MSH2, MLH1 and MSH6 antibodies. RESULTS: All patients had two synchoronous lesions. None of them had altered MSH2 or MLH1 expression. One patient had altered MSH6 expression in both tumors. CONCLUSION: Possibly, other molecular mechanisms are involved in carcinogenesis of sporadic synchronous colorectal cancer.

Igor, Proscurshim; Rodrigo Oliva, Perez; Rosa Maria Nascimento, Santos; Edson Luiz, Zaparoli; Desidério Roberto, Kiss; Angelita, Habr-Gam.

2007-03-01

354

Rare Copy Number Variants Disrupt Genes Regulating Vascular Smooth Muscle Cell Adhesion and Contractility in Sporadic Thoracic Aortic Aneurysms and Dissections  

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Thoracic aortic aneurysms and dissections (TAAD) cause significant morbidity and mortality, but the genetic origins of TAAD remain largely unknown. In a genome-wide analysis of 418 sporadic TAAD cases, we identified 47 copy number variant (CNV) regions that were enriched in or unique to TAAD patients compared to population controls. Gene ontology, expression profiling, and network analysis showed that genes within TAAD CNVs regulate smooth muscle cell adhesion or contractility and interact wi...

Prakash, Siddharth K.; Lemaire, Scott A.; Guo, Dong-chuan; Russell, Ludivine; Regalado, Ellen S.; Golabbakhsh, Hossein; Johnson, Ralph J.; Safi, Hazim J.; Estrera, Anthony L.; Coselli, Joseph S.; Bray, Molly S.; Leal, Suzanne M.; Milewicz, Dianna M.; Belmont, John W.

2010-01-01

355

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

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

Jeong Byung-Hoon

2011-08-01

356

Intronic single nucleotide polymorphisms in the RET protooncogene are associated with a subset of apparently sporadic pheochromocytoma and may modulate age of onset.  

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Approximately 75% of pheochromocytomas are sporadic. Germline mutations in RET, VHL, SDHB, and SDHD have been shown to cause the 25% that are hereditary. Germline high penetrance gain-of-function RET mutations cause multiple endocrine neoplasia type 2, of which medullary thyroid carcinoma (MTC) and pheochromocytoma are components, whereas loss-of-function mutations cause Hirschprung disease (HSCR). A low-penetrance founder locus, in linkage disequilibrium with a RET ancestral haplotype comprising specific alleles at three intron (IVS) 1 single nucleotide polymorphisms (SNPs) (haplotype 0) and SNP A45A, predisposes to the majority of isolated HSCR. A different low-penetrance locus, in linkage disequilibrium with IVS 1 haplotype 2 and SNP S836S, was associated with a subset of sporadic MTC. We, therefore, sought to determine whether RET might also be a low-penetrance gene for apparently sporadic pheochromocytoma. We analyzed 104 pheochromocytoma cases without germline mutations in RET, VHL, SDHD, and SDHB for their status at A45, S836, three IVS 1 SNPs, and a novel upstream insertion/deletion variant. Pheochromocytoma cases were not associated with either A45A or S836S, but we found that cases were associated with haplotype 0 (P = 0.032). However, unlike HSCR, this pheochromocytoma-associated haplotype 0 was not associated with A45A. Taken together with the strengthening of association with the addition of the 5' insertion/deletion variant data (P = 0.016), our observations suggest the presence of a low-penetrance pheochromocytoma susceptibility locus in a region upstream of the putative loci for HSCR and apparently sporadic MTC. PMID:14557473

McWhinney, Sarah R; Boru, Getachew; Binkley, Philip K; Peczkowska, Mariola; Januszewicz, Andrzej A; Neumann, Hartmut P H; Eng, Charis

2003-10-01