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Sample records for sporadic error-increasing effects

  1. Effects of sulindac on sporadic colorectal adenomatous polyps.

    OpenAIRE

    Matsuhashi, N; Nakajima, A; Fukushima, Y.; Yazaki, Y.; Oka, T.

    1997-01-01

    BACKGROUND: Although sulindac is known to cause regression of colorectal adenomatous polyps in familial adenomatous polyposis, less is known about the effect of sulindac on sporadic adenomas. The precise mechanisms of these effects also remain to be determined. AIMS: Sulindac was given to patients with sporadic colorectal adenomatous polyps to evaluate its effects on them, and histological analysis was performed to elucidate the mechanism of the polyp regression, as well the kind of adenomato...

  2. 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

  3. Solar eclipse effects of 22 July 2009 on Sporadic-E

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    G. Chen

    2010-02-01

    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.

  4. Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population.

    Science.gov (United States)

    Daraei, A; Salehi, R; Salehi, M; Emami, M H; Janghorbani, M; Jonghorbani, M; Mohamadhashem, F; Tavakoli, H

    2012-06-01

    Colorectal cancer (CRC) is among the major causes of cancer-related morbidity, mortality, and human health problem worldwide. Single-nucleotide polymorphisms (SNPs) in different genes are reported to be effective in increased risk of CRC in different ethnic population. We conducted a case-control study in patients diagnosed with sporadic colorectal cancer (n = 115) and healthy controls based on colonoscopy evidences (n = 120).In this replicative study, we aimed to investigate the association of two previously reported polymorphisms, rs6983267 and rs4444903, with sporadic colorectal cancer in a subset of Iranian patients. Genotyping was performed via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significant relation was found between rs6983267 variant in the 8q24 region and colorectal cancer. The distribution of G/G genotypes among sporadic CRC patients was more frequent than that in the control group (P value = 0.001). The frequency of the G allele in the colorectal cancer patient group was also higher than that in the control group (65% vs. 48%; P value = 0.001). Compared with GG genotype, individuals with G/T and T/T genotypes had lower risk to develop sporadic CRC (OR = 0.357, 95% CI = 0.201-0.635). For the rs4444903 SNP, no significant association (P value = 0.149) was found with colorectal cancer risk. In conclusion, our findings suggest that the 8q24 rs6983267 SNP may play a pivotal role in the development of sporadic CRC in Iranian population. Therefore, it may be included as a potential genetic susceptibility marker for sporadic CRC. PMID:21567271

  5. Effects of blood-flow-restricted resistance training on muscle function in a 74-year-old male with sporadic inclusion body myositis: a case report

    DEFF Research Database (Denmark)

    Jørgensen, A N; Aagaard, P; Nielsen, J L; Frandsen, U; Diederichsen, L P

    2016-01-01

    Sporadic inclusion body myositis (sIBM) is a systemic disease that is characterized by substantial skeletal muscle weakness and muscle inflammation, leading to impaired physical function. The objective was to investigate the effect of low-load resistance exercise with concurrent partial blood flow...

  6. A study of stratospheric GW fluctuations and sporadic E at midlatitudes with focus on possible orographic effect of Andes

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    Hocke, Klemens; Tsuda, Toshitaka; de la Torre, Alejandro

    2002-10-01

    Longitudinal dependences of stratospheric gravity wave (GW) fluctuations and lower ionospheric irregularities (sporadic E) at midlatitudes are studied by means of radio occultation data of the Global Positioning System/Meteorology Experiment (GPS/MET) satellite mission. The zonal average of temperature variance of GW fluctuations with vertical scales less than 7 km at northern midlatitudes is observed to be similar to that at southern midlatitudes, but there is a significant interhemispheric difference in the longitudinal dependence of GW fluctuations. The GPS/MET data at northern midlatitudes show a rapid change of the gravity wave distribution from 25 to 35 km height, resulting in a broad maximum of temperature variance located over the Atlantic and Eurasia. We only find in the wave distribution at h = 25 km some weak traces of possible orographic effects. On the other hand, the distribution of GW fluctuations at southern midlatitudes has a strong and sharp maximum over Andes, which is obviously due to orographic wave generation by the interaction of surface wind with the Andean mountain ridge. This observation of the new GPS radio occultation technique is in agreement with previous measurements of spaceborne microwave and infrared limb sounders. The amplitude of the average wave field increases with height over Andes, while the amplitude maximum moves westward, against the prevailing wind. The temperature fluctuations have an apparent, dominant vertical wavelength of around 6 km. In situ measurements by a balloon-borne rawinsonde at Ushuaia, Argentina (54.7°S, 68.1°W) are compared to a simultaneous GPS/MET temperature profile. The balloon observations of temperature and horizontal wind are interpreted by a large amplitude mountain wave propagating to the upper stratosphere. Wave characteristics and atmospheric background conditions are investigated in detail for this mountain wave observation. Finally, the GPS/MET experiment indicates enhanced sporadic E in the lower ionosphere over Southern Andes. We assume that these plasma irregularities are generated by enhanced, upward wave flux due to the possible orographic effect of Andes.

  7. Introduction to Sporadic Groups

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    Luis J. Boya

    2011-01-01

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

  8. Introduction to Sporadic Groups

    CERN Document Server

    Boya, Luis J

    2011-01-01

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

  9. Sporadic and Exceptional

    CERN Document Server

    He, Yang-Hui

    2015-01-01

    We study the web of correspondences linking the exceptional Lie algebras $E_{8,7,6}$ and the sporadic simple groups Monster, Baby and the largest Fischer group. This is done via the investigation of classical enumerative problems on del Pezzo surfaces in relation to the cusps of certain subgroups of $PSL(2,R)$ for the relevant McKay-Thompson series in Generalized Moonshine. We also study Conway's sporadic group, as well as its association with the Horrocks-Mumford bundle.

  10. Effects of blood-flow-restricted resistance training on muscle function in a 74-year-old male with sporadic inclusion body myositis: a case report

    DEFF Research Database (Denmark)

    Jørgensen, A N; Aagaard, P; Nielsen, J L; Frandsen, U; Diederichsen, L P

    2015-01-01

    Sporadic inclusion body myositis (sIBM) is a systemic disease that is characterized by substantial skeletal muscle weakness and muscle inflammation, leading to impaired physical function. The objective was to investigate the effect of low-load resistance exercise with concurrent partial blood flow restriction to the working muscles (blood-flow-restricted (BFR) training) in a patient with sIBM. The training consisted of 12 weeks of lower extremity BFR training with low training loads (~25-RM). Th...

  11. [Effect of the novel nootropic and neuroprotective dipeptide noopept on the streptozotocin-induced model of sporadic Alzheimer disease in rats].

    Science.gov (United States)

    Ostrovskaia, R U; Tsaplina, A P; Vakhitova, Iu V; Salimgareeva, M Kh; Iamidanov, R S

    2010-01-01

    Streptozotocin-intracerebroventricularly treated rats are proposed as an experimental model of sporadic Alzheimer disease (AD). Diabetogenic toxin streptozotocin (STZ) administered in both cerebral ventricles in a dose of 3 mg/kg decreases the expression of NGF and BDNF mainly in the hippocampus and increases the content of malonic dialdehyde (MDA)--a product of lipid peroxidation--in the brain tissues. These metabolic changes are accompanied by a pronounced cognitive deficiency, which is manifested by long-term memory deterioration in the passive avoidance test. These manifestations of pathology are not accompanied by hyperglycemia in the case of intraventricular STZ administration, in contrast to the systemic (in particular, intraperitoneal) route of introduction that causes a pronounced increase in the blood glucose level. These results are consistent with the existing notions that (i) STZ administered intraventricularly provokes a complex of changes imitating the sporadic AD and (ii) this disease can be considered as a manifestation of type-III diabetes. The new original cognition enhancing and neuroprotective dipeptide noopept decreases the aforementioned metabolic changes and the accompanying long-term deterioration of the memory. Previously, this systemically active dipeptide was shown to be capable of increasing expression of NGF and BDNF in the hippocampus, stimulating the antibody production to beta-amyloid, inhibiting the lipid peroxidation, activating the endogenous antioxidant systems, and decreasing the rate of glutamate release (cholinopositive effect). Taken together, these data indicate that noopept can be considered as a multipotent substance acting upon several important pathogenic chainsof the sporadic AD. PMID:20184279

  12. Sporadic Reinhardt polygons

    CERN Document Server

    Hare, Kevin G

    2012-01-01

    Let $n$ be a positive integer, not a power of two. A \\textit{Reinhardt polygon} is a convex $n$-gon that is optimal in three different geometric optimization problems: it has maximal perimeter relative to its diameter, maximal width relative to its diameter, and maximal width relative to its perimeter. For almost all $n$, there are many Reinhardt polygons with $n$ sides, and many of them exhibit a particular periodic structure. While these periodic polygons are well understood, for certain values of $n$, additional Reinhardt polygons exist that do not possess this structured form. We call these polygons \\textit{sporadic}. We completely characterize the integers $n$ for which sporadic Reinhardt polygons exist, showing that these polygons occur precisely when $n=pqr$ with $p$ and $q$ distinct odd primes and $r\\geq2$. We also prove that a positive proportion of the Reinhardt polygons with $n$ sides are sporadic for almost all integers $n$, and we investigate the precise number of sporadic Reinhardt polygons that...

  13. Thermal effects from groundwater flow - A case study from a subarctic fen within the sporadic permafrost zone of Tavvavuoma, Sweden

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    Sjöberg, Ylva; Lyon, Steve; Pannetier, Romain; Coon, Ethan; Harp, Dylan; Frampton, Andrew; Painter, Scott

    2015-04-01

    The ground thermal regime and associated heat fluxes are the determining factors for permafrost distributions. On a large scale, permafrost is thus controlled by climatic factors; however, at local scales, especially in marginal permafrost areas, factors such as ground thermal properties, hydrology, and snow cover are important. Groundwater can transport heat in both lateral and vertical directions but its influence on ground temperatures at local scales in permafrost environments is not well studied due to the complexity of processes involved and the remoteness of potential study sites. In this study we combine field observations from a subarctic fen located within the sporadic discontinuous permafrost zone with numerical simulations using the Arctic Terrestrial Simulator (ATS). At the Tavvavuoma study site in northern Sweden, ground temperature profiles and groundwater levels were observed in boreholes every 15 minutes over the summer of 2013. These observations were simulated using the ATS down to 2 m depth across a gradient of permafrost conditions both within and surrounding the fen. Two-dimensional scenarios representing the fen under various groundwater fluxes were developed to quantify the influence of groundwater flows on the ground temperature/heat flux. Our modeling results show that heat transported by groundwater from lakes surrounding the fen is on the same order of magnitude as the vertical heat flux from the ground surface. The results suggest that heat transported by groundwater flows has a significant impact on the ground temperature distributions in the fen. As sporadic permafrost environments often contain substantial portions of unfrozen ground with active groundwater flow paths (such as fens) this heat transport mechanism is important for permafrost dynamics in these environments.

  14. Effects of blood-flow-restricted resistance training on muscle function in a 74-year-old male with sporadic inclusion body myositis: a case report

    DEFF Research Database (Denmark)

    JØrgensen, A N; Aagaard, P

    2015-01-01

    Sporadic inclusion body myositis (sIBM) is a systemic disease that is characterized by substantial skeletal muscle weakness and muscle inflammation, leading to impaired physical function. The objective was to investigate the effect of low-load resistance exercise with concurrent partial blood flow restriction to the working muscles (blood-flow-restricted (BFR) training) in a patient with sIBM. The training consisted of 12 weeks of lower extremity BFR training with low training loads (~25-RM). The patient was tested for mechanical muscle function and functional capacity before and after 6 and 12 weeks of training. Maximal horizontal gait speed increased by 19%, which was accompanied by 38-92% improvements in mechanical muscle function (maximal isometric strength, rate of force development and muscle power). In conclusion, BFR training was well tolerated by the patient with sIBM and led to substantial improvements in mechanical muscle function and gait speed.

  15. Genetics Home Reference: Sporadic hemiplegic migraine

    Science.gov (United States)

    ... Research studies PubMed Recent literature Conditions > Sporadic hemiplegic migraine On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed February 2014 What is sporadic hemiplegic migraine? Sporadic hemiplegic migraine is a rare form of ...

  16. 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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    Friedrichs Nicolaus

    2008-07-01

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

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

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    Yong-chang Diwu

    2011-02-01

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

  18. Dynamical model for the toroidal sporadic meteors

    Energy Technology Data Exchange (ETDEWEB)

    Pokorný, Petr; Vokrouhlický, David [Institute of Astronomy, Charles University, V Holešovičkách 2, CZ-18000 Prague 8 (Czech Republic); Nesvorný, David [Department of Space Studies, Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Campbell-Brown, Margaret; Brown, Peter, E-mail: petr.pokorny@volny.cz, E-mail: vokrouhl@cesnet.cz, E-mail: davidn@boulder.swri.edu, E-mail: margaret.campbell@uwo.ca, E-mail: pbrown@uwo.ca [Department of Physics and Astronomy, University of Western Ontario, London, ON N6A 3K7 (Canada)

    2014-07-01

    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.

  19. Tramadol use in premature ejaculation: Daily versus sporadic treatment

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    Amil H Khan

    2013-01-01

    Full Text Available 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.

  20. Tramadol Use in Premature Ejaculation: Daily Versus Sporadic Treatment

    Science.gov (United States)

    Khan, Amil H.; Rasaily, Deepa

    2013-01-01

    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

  1. Adult onset sporadic ataxias: a diagnostic challenge

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    Orlando Graziani Povoas Barsottini

    2014-03-01

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

  2. 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.)

  3. Effects of long-term resistance exercise training on autophagy in rat skeletal muscle of chloroquine-induced sporadic inclusion body myositis

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    Kwon, Insu; Lee, Youngil; Cosio-Lima, Ludmila M.; Cho, Joon-Yong; Yeom, Dong-Chul

    2015-01-01

    Purpose We examined whether resistance exercise training restores impaired autophagy functions caused by Chloroquine (CQ)-induced Sporadic Inclusion Body Myositis (sIBM) in rat skeletal muscle. Methods Male wistar rats were randomly assigned into three groups: Sham (n = 6), CQ (n = 6), and CQ + Exercise (CE, n = 6). To create a rat model of sIBM, rats in the CQ and CE group were intraperitoneally injected with CQ 5 days a week for 16 weeks. Rats in the CE group performed resistance exercise training 3 times a week for 8 weeks in conjunction with CQ starting from week 9 to week 16. During the training period, maximal carrying load, body weight, muscle weight, and relative muscle weight were measured. Autophagy responses were examined by measuring specific markers. Results While maximal carrying capacity for resistance exercise training was dramatically increased in the CE group, no significant changes occurred in the skeletal muscle weight as well as in the relative muscle weight of CE compared to the other groups. CQ treatment caused significant increases in the levels of Beclin-1 and p62, and decreases in the levels of LAMP-2 proteins. Interestingly, no significant differences in the LC3-II/I ratio or the LC3-II protein levels were observed. Although CQ-treatment groups suppressed the levels of the potent autophagy inducer, BNIP3, p62 levels were decreased in only the CE group. Conclusion Our findings demonstrate that sIBM induced by CQ treatment results in muscle degeneration via impaired autophagy and that resistance exercise training improves movable loading activity. Finally, regular exercise training may provide protection against sIBM by enhancing the autophagy flux through p62 protein. PMID:26525066

  4. Treatment of Sporadic Acute Puerperal Mastitis

    OpenAIRE

    Hager, W. David; Barton, John R.

    1996-01-01

    Objective: The purposes of this study were to compare the efficacy of amoxicillin and cephradine for the treatment of sporadic acute puerperal mastitis (SAPM) and to evaluate the microbiology and clinical parameters of this infection.

  5. Effect of sporadic destratification, seasonal overturn and artificial mixing on CH4 emissions at the surface of a subtropical hydroelectric reservoir (Nam Theun 2 Reservoir, Lao PDR)

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    Guérin, F.; Deshmukh, C.; Labat, D.; Pighini, S.; Vongkhamsao, A.; Guédant, P.; Rode, W.; Godon, A.; Chanudet, V.; Descloux, S.; Serça, D.

    2015-07-01

    Inland waters in general and specifically freshwater reservoirs are recognized as source of CH4 to the atmosphere. Although the diffusion at the air-water interface is the most studied pathway, its spatial and temporal variations are poorly documented. We measured fortnightly CH4 concentrations and physico-chemical parameters at nine stations in a subtropical monomictic reservoir which was flooded in 2008 (Nam Theun 2 Reservoir, Lao PDR). Based on these results, we quantified CH4 storage in the water column and diffusive fluxes from June 2009 to December 2012. We also compared emissions with aerobic methane oxidation calculated from Deshmukh et al. (2015). In this monomictic reservoir, the seasonal variations of CH4 concentration and storage were highly dependant of the thermal stratification. Hypolimnic CH4 concentration and CH4 storage reached their maximum in the warm dry season (WD) when the reservoir was stratified. They decreased during the warm wet (WW) season and reached its minimum after the reservoir overturned in the cool dry season (CD). The sharp decreases of the CH4 storage were concomitant with sporadic extreme diffusive fluxes (up to 200 mmol m-2 d-1). These hot moments of emissions occurred mostly in the inflow region in the WW season and during the overturn in the CD season in the area of the reservoir that has the highest CH4 storage. Although they corresponded to less than 10 % of the observations, these CH4 extreme emissions (> 5 mmol m-2 d-1) contributed up to 50 % of total annual emissions by diffusion. Based on our fortnightly monitoring, we determined that accurate estimation of the emissions can be determined from measurements made at least at a monthly frequency. During the transition between the WD and WW seasons, a new hotspot of emissions was identified upstream of the water intake where diffusive fluxes peaked at 600 mmol m-2 d-1 in 2010 down to 200 mmol m-2 d-1 in 2012. In the CD season, diffusive fluxes from this area were the lowest observed at the reservoir surface. Emissions from this area contributed 15-25 % to total annual emissions although they occur on a surface area representative of less than 1 % of the total reservoir surface. We highly recommend measurements of diffusive fluxes around water intakes in order to evaluate if such results can be generalized.

  6. Effect of sporadic destratification, seasonal overturn and artificial mixing on CH4 emissions at the surface of a subtropical hydroelectric reservoir (Nam Theun 2 Reservoir, Lao PDR

    Directory of Open Access Journals (Sweden)

    F. Guérin

    2015-07-01

    Full Text Available Inland waters in general and specifically freshwater reservoirs are recognized as source of CH4 to the atmosphere. Although the diffusion at the air–water interface is the most studied pathway, its spatial and temporal variations are poorly documented. We measured fortnightly CH4 concentrations and physico-chemical parameters at nine stations in a subtropical monomictic reservoir which was flooded in 2008 (Nam Theun 2 Reservoir, Lao PDR. Based on these results, we quantified CH4 storage in the water column and diffusive fluxes from June 2009 to December 2012. We also compared emissions with aerobic methane oxidation calculated from Deshmukh et al. (2015. In this monomictic reservoir, the seasonal variations of CH4 concentration and storage were highly dependant of the thermal stratification. Hypolimnic CH4 concentration and CH4 storage reached their maximum in the warm dry season (WD when the reservoir was stratified. They decreased during the warm wet (WW season and reached its minimum after the reservoir overturned in the cool dry season (CD. The sharp decreases of the CH4 storage were concomitant with sporadic extreme diffusive fluxes (up to 200 mmol m?2 d?1. These hot moments of emissions occurred mostly in the inflow region in the WW season and during the overturn in the CD season in the area of the reservoir that has the highest CH4 storage. Although they corresponded to less than 10 % of the observations, these CH4 extreme emissions (> 5 mmol m?2 d?1 contributed up to 50 % of total annual emissions by diffusion. Based on our fortnightly monitoring, we determined that accurate estimation of the emissions can be determined from measurements made at least at a monthly frequency. During the transition between the WD and WW seasons, a new hotspot of emissions was identified upstream of the water intake where diffusive fluxes peaked at 600 mmol m?2 d?1 in 2010 down to 200 mmol m?2 d?1 in 2012. In the CD season, diffusive fluxes from this area were the lowest observed at the reservoir surface. Emissions from this area contributed 15–25 % to total annual emissions although they occur on a surface area representative of less than 1 % of the total reservoir surface. We highly recommend measurements of diffusive fluxes around water intakes in order to evaluate if such results can be generalized.

  7. Synchrony in Metapopulations with Sporadic Dispersal

    Science.gov (United States)

    Jeter, Russell; Belykh, Igor

    2015-06-01

    We study synchronization in ecological networks under the realistic assumption that the coupling among the patches is sporadic/stochastic and due to rare and short-term meteorological conditions. Each patch is described by a tritrophic food chain model, representing the producer, consumer, and predator. If all three species can migrate, we rigorously prove that the network can synchronize as long as the migration occurs frequently, i.e. fast compared to the period of the ecological cycle, even though the network is disconnected most of the time. In the case where only the top trophic level (i.e. the predator) can migrate, we reveal an unexpected range of intermediate switching frequencies where synchronization becomes stable in a network which switches between two nonsynchronous dynamics. As spatial synchrony increases the danger of extinction, this counterintuitive effect of synchrony emerging from slower switching dispersal can be destructive for overall metapopulation persistence, presumably expected from switching between two dynamics which are unfavorable to extinction.

  8. Antigliadin antibody in sporadic adult ataxia

    Directory of Open Access Journals (Sweden)

    Mahdi Aloosh

    2012-09-01

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

  9. Predicting sporadic Grid data transfers

    International Nuclear Information System (INIS)

    The increasingly common practice of (1) replicating datasets and (2) using resources as distributed data stores in Grid environments has lead to the problem of determining which replica can be accessed most efficiently. Due to diverse performance characteristics and load variations of several components in the end-to-end path linking these various locations, selecting a replica location from among many requires accurate prediction information of end-to-end data transfer times between the sources and sinks. In this paper, we present a prediction system that is based on combining end-to-end application throughput observations and network load variations, drawing from their merits of capturing whole system performance and variations in load patterns respectively. We develop a set of regression models to derive predictions that characterize the effect of network load variations on file transfer times. We apply these techniques to the GridFTP data movement tool, part of the Globus Toolkit(sup TM), and observe performance gains of up to 10% in prediction accuracy when compared to approaches based on past system behavior in isolation

  10. Predicting sporadic Grid data transfers.

    Energy Technology Data Exchange (ETDEWEB)

    Vazhkudai, S.; Schopf, J. M.

    2002-04-30

    The increasingly common practice of (1) replicating datasets and (2) using resources as distributed data stores in Grid environments has lead to the problem of determining which replica can be accessed most efficiently. Due to diverse performance characteristics and load variations of several components in the end-to-end path linking these various locations, selecting a replica location from among many requires accurate prediction information of end-to-end data transfer times between the sources and sinks. In this paper, we present a prediction system that is based on combining end-to-end application throughput observations and network load variations, drawing from their merits of capturing whole system performance and variations in load patterns respectively. We develop a set of regression models to derive predictions that characterize the effect of network load variations on file transfer times. We apply these techniques to the GridFTP data movement tool, part of the Globus Toolkit{sup TM}, and observe performance gains of up to 10% in prediction accuracy when compared to approaches based on past system behavior in isolation.

  11. MET Expression in Sporadic Renal Cell Carcinomas

    OpenAIRE

    Choi, Jong Sun; Kim, Mi-Kyung; Seo, Jin Won; CHOI, YOON-LA; Kim, Dong Hoon; Chun, Yi Kyeong; Ko, Young Hyeh

    2006-01-01

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

  12. On the influence of sunspot activity on sporadic radio meteors

    International Nuclear Information System (INIS)

    The effect of sunspot activity on sporadic meteor rates has been investigated. The data of Christchurch (lat., 43deg37'S) for the periods Feb.1960-Jan. 1961 and 1963-65; of Ottawa (lat., 45deg N) for the period 1958-62 and of Waltair (lat., 17deg53'N) by forward scatter of radio waves from Dehra Dun (lat., 30deg30'N) for the period Dec.1974-Nov.1975 have been considered. The lowest recorded mean hourly meteor rate on any day in a month is considered to be typical of sporadic meteor activity for that month, and the corresponding value of sunspot number on that day is considered for this correlation study. In no case the correlation has been found to be significant at P = 0.01 level. The data for Ottawa for five years have been divided into four seasons each year and an analysis similar to the above is carried out in respect of all echoes or only long duration ones. In all the cases the correlation has been found to be insignificant. Finally, the plots of N (the normalized percentage deviation) against sunspot activity also reveal no preferential alignment for the scatter of the points. Hence it is concluded that there is no correlation between sunspot activity and aporadic meteor rates. (auth.)

  13. Census of the complex hyperbolic sporadic triangle groups

    OpenAIRE

    Deraux, Martin; Parker, John; Paupert, Julien

    2011-01-01

    The goal of this paper is to give a conjectural census of complex hyperbolic sporadic triangle groups. We prove that only finitely many of these sporadic groups are lattices. We also give a conjectural list of all lattices among sporadic groups, and for each group in the list we give a conjectural group presentation, as well as a list of cusps and generators for their stabilizers. We describe strong evidence for these conjectural statements, showing that their validity depends on the solution...

  14. 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)

  15. Sporadic aurorae observed in East Asia

    Directory of Open Access Journals (Sweden)

    D. M. Willis

    2007-03-01

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

  16. Sporadic aurorae observed in East Asia

    Science.gov (United States)

    Willis, D. M.; Stephenson, F. R.; Fang, Huiping

    2007-03-01

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

  17. Method for identifying patients with sporadic burkitt's lymphoma, identification method and use of compounds for the treatment of sporadic burkitt's lymphoma

    OpenAIRE

    Campanero, Miguel R.; Molina Privado, Irene

    2009-01-01

    The invention relates to a method for the effective diagnosis of patients with sporadic Burkitt's lymphoma, based on identifying protein E2F1 in biological samples from said patients, which can be performed by RT-PCR or western blot. In addition, E2F1 has been shown to play an etiopathogenic role in the aforementioned disease and, as such, E2F1-specific RNAi can be used to treat said patients.

  18. Sporadic Corticobasal Syndrome due to FTLD-TDP

    OpenAIRE

    Tartaglia, Maria Carmela; Sidhu, Manu; Laluz, Victor; Racine, Caroline; Rabinovici, Gil D.; Creighton, Kelly; Karydas, Anna; Rademakers, Rosa; Huang, Eric J.; Bruce L. Miller; DeArmond, Stephen J.; Seeley, William W.

    2009-01-01

    Sporadic corticobasal syndrome (CBS) has been associated with diverse pathological substrates, but frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP) has only been linked to CBS among progranulin mutation carriers. We report the clinical, neuropsychological, imaging, genetic, and neuropathological features of GS, a patient with sporadic corticobasal syndrome. Genetic testing revealed no mutations in the microtubule associated protein tau (MAPT) or progranulin (...

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

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina; Lindmark, Gudrun; Nilbert, Mef

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers were linked to MMR status based on immunostaining and BRAF mutation status.MMR defects were identified in 22.7% of the tumors, with 46 classified as sporadic. When the clinical parameters of age, sex, an...

  20. Sporadic hemangioblastomas are characterized by cryptic VHL inactivation

    OpenAIRE

    Shankar, Ganesh M.; Taylor-Weiner, Amaro; Lelic, Nina; Jones, Robert T.; Kim, James C.; Francis, Joshua M.; Abedalthagafi, Malak; Borges, Lawrence F; Coumans, Jean-Valery; Curry, William T.; Nahed, Brian V.; Shin, John H; Paek, Sun Ha; Park, Sung-Hye; Stewart, Chip

    2014-01-01

    Hemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangio...

  1. VPS35 Parkinson's disease phenotype resembles the sporadic disease.

    Science.gov (United States)

    Struhal, Walter; Presslauer, Stefan; Spielberger, Sabine; Zimprich, Alexander; Auff, Eduard; Bruecke, Thomas; Poewe, Werner; Ransmayr, Gerhard

    2014-07-01

    Recently a new autosomal dominant Parkinson's disease mutation (p.Asp620Asn) in the VPS35 gene was discovered. The clinical features of 14 PD patients with this mutation from three Austrian families were evaluated. Age at disease-onset appears lower and depression was more common in Austrian patients compared to sporadic PD patients. However, we were unable to identify a specific clinical maker of VPS35 patients, who otherwise resemble sporadic PD patients. PMID:24557499

  2. Stream and sporadic meteoroids associated with Near Earth Objects

    OpenAIRE

    Jopek, Tadeusz J.; Williams, Iwan P.

    2014-01-01

    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...

  3. Quantifying Location Privacy: The Case of Sporadic Location Exposure

    OpenAIRE

    Shokri, Reza; Theodorakopoulos, Georgios; Danezis, George; Hubaux, Jean-Pierre; Le Boudec, Jean-Yves

    2011-01-01

    Mobile users expose their location to potentially untrusted entities by using location-based services. Based on the frequency of location exposure in these applications, we divide them into two main types: Continuous and Sporadic. These two location exposure types lead to different threats. For example, in the continuous case, the adversary can track users over time and space, whereas in the sporadic case, his focus is more on localizing users at certain points in time. We propose a systemati...

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

    Science.gov (United States)

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

    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.

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

    Directory of Open Access Journals (Sweden)

    H. Chandra

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

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

  6. Trimetazidine prevents oxidative changes induced in a rat model of sporadic type of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Gholamreza Hassanzadeh

    2015-01-01

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

  7. Variation of sporadic meteor background and solar activity

    Science.gov (United States)

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

    2011-05-01

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

  8. Mandibular osteomas in sporadic colorectal carcinoma. A genetic marker

    DEFF Research Database (Denmark)

    Søndergaard, J O; Rasmussen, M S; Videbaek, H; Bernstein, Inge Thomsen; Myrhøj, T; Kristiansen, V B; Sommer, P; Bülow, Steffen

    1993-01-01

    Pantomography of the mandible was performed in 98 patients with sporadic colorectal adenocarcinoma. Twenty-eight patients (29%) had osteomas versus 5% in a control group (P < 0.001). Mandibular osteomas are found in most patients with the premalignant dominant syndrome familial adenomatous...... polyposis. Sporadic colorectal cancer examinations of married couples have shown that diet has only a moderate influence on the development of colorectal cancer, whereas pedigree studies indicate a genetic component. On this basis we conclude that mandibular osteomas are probably genetic markers of the...

  9. Stream and sporadic meteoroids associated with Near Earth Objects

    Science.gov (United States)

    Jopek, Tadeusz J.; Williams, Iwan P.

    2015-03-01

    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 sufficient 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.

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

    OpenAIRE

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

    2013-01-01

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

  11. Stream and sporadic meteoroids associated with Near Earth Objects

    CERN Document Server

    Jopek, Tadeusz J

    2014-01-01

    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.

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

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina; Lindmark, Gudrun; Nilbert, Mef

    2008-01-01

    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...

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

    OpenAIRE

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

    2013-01-01

    Mutations in the gene-encoding ?-catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations and to determine whether the CTNNB1 mutation status correlates with disease outcome.

  14. Studies in sporadic inclusion body myositis

    OpenAIRE

    Arnardóttir, Snjólaug

    2003-01-01

    Aims: The general aims of the present study were to increase the understanding of the disease process in s-lBM by analysing the cytoskeletal structure in muscle fibres and their regeneration potential; and also to evaluate sensory function in patients with s-IBM to test the hypothesis of an associated neurogenic component or a concomitant neuropathy in s-IBM; and to evaluate therapeutic options by analysing the effect of IVIg treatment on the muscle inflammation; and to e...

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

    Scientific Electronic Library Online (English)

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

    2013-03-01

    Full Text Available 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.

  16. On permanent and sporadic pulsations of the magnetosphere

    Science.gov (United States)

    Guglielmi, A. V.

    2015-05-01

    A question concerning the influence of permanent Pc3-band pulsations (periods from 10 to 45 s) on the excitation of sporadic Pi2-band pulsations (40 to 150 s) is raised. It is hypothesized that, being generated ahead of the front of the Earth's magnetosphere, the Pc3 penetrate into the geomagnetic tail where they cause local depression in the electric current in the neutral sheet and, under favorable conditions, initiate tearing instability. This leads to the reconnection of the magnetic field lines and explosion-like release of the magnetic energy stored in the tail. As a result, a substorm arises with the sporadic Pi2 pulsations being its important element. Ways are suggested to theoretically substantiate and experimentally validate this hypothesis.

  17. A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias

    Directory of Open Access Journals (Sweden)

    Sinha K K

    1999-01-01

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

  18. Distinct X-chromosome SNVs from some sporadic AD samples

    OpenAIRE

    A. Gómez-Ramos; P. Podlesniy; Soriano, E.; Avila, J.

    2015-01-01

    Sporadic Alzheimer disease (SAD) is the most prevalent neurodegenerative disorder. With the development of new generation DNA sequencing technologies, additional genetic risk factors have been described. Here we used various methods to process DNA sequencing data in order to gain further insight into this important disease. We have sequenced the exomes of brain samples from SAD patients and non-demented controls. Using either method, we found a higher number of single nucleotide variants (SNV...

  19. Clinical Perspective of Oxidative Stress in Sporadic ALS

    OpenAIRE

    D’Amico, Emanuele; FACTOR-LITVAK, PAM; Santella, Regina M.; MITSUMOTO, HIROSHI

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevate...

  20. Double localization of a unilateral sporadic vestibular schwannoma

    OpenAIRE

    Barbara, M.; Ronchetti, F.; Manni, V.; Monini, S.

    2008-01-01

    Vestibular schwannoma may present as a sporadic or genetically-based multi-localized benign neoplasm of the internal auditory canal and/or cerebello-pontine angle region. Multiple localization is generally regarded as genetic in origin and often affects the stato-acoustic bundle on both sides. A case of double vestibular schwannoma localized on the same stato-acoustic bundle is presented. After removal, slight histological differences were found between the two separate masses. From these fin...

  1. Application of dopplionograms to an understanding of sporadic E

    International Nuclear Information System (INIS)

    The dopplionogram can be used to infer the vertical motion of plasma contours under some circumstances. In a sporadic E sequence, motions downward from above, and upward from below, are observed as the layer peak plasma density increases: this is interpreted as consistent with plasma convergence resulting from an east-west wind shear. When divergent motions occur, the layer is observed to dissipate and recede rapidly

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

    LENUS (Irish Health Repository)

    Cronin, Simon

    2008-10-01

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

  3. Sporadic Desmoid Tumor. An Exceptional Cause of Cystic Pancreatic Lesion

    Directory of Open Access Journals (Sweden)

    Aurélien Amiot

    2016-05-01

    Full Text Available Context Desmoid tumors are rare, benign soft tissue tumors, characterized by the proliferation of fibroblasts in an abundant collagen extra-cellular matrix. Intraabdominal forms involve the mesentery and retroperitoneum and usually occur associated with familial adenomatous polyposis or Gardner?s syndrome. Sporadic cases are more uncommon. Although desmoid tumors do not metastasize, their evolution can be lifethreatening due to aggressive local invasion, such as mesentery involvement. Case report We herein report a very rare location of sporadic desmoid tumors involving the pancreatic tail, presenting as a cystic lesion. A 51-year-old woman presented with recurrent abdominal pain and weight loss. The diagnosis of mucinous cystadenocarcinoma was suspected preoperatively and the patient underwent a splenopancreatectomy with en-bloc resection of the left colonic flexure, duodenojejunal junction and part of the posterior gastric wall. Pathological analysis revealed fibroblastic proliferation arising in musculoaponeurotic structures consistent with a desmoid tumor. The diagnosis was confirmed by immunocytochemical analysis and the assessment of the beta-catenin gene mutation. Perioperative examination reported gastric and small-bowel invasion. No treatment was given postoperatively to prevent desmoid tumor recurrence. After a 1-year follow-up, no recurrence was observed. Conclusion Desmoid tumors are very rare in the pancreas and their diagnosis can be difficult, such as in our case where it presented as a cystic lesion. In contrast to intra-abdominal forms, sporadic pancreatic desmoid tumors are more frequent than those associated with familial adenomatous polyposis.

  4. Sporadic hemangioblastomas are characterized by cryptic VHL inactivation.

    Science.gov (United States)

    Shankar, Ganesh M; Taylor-Weiner, Amaro; Lelic, Nina; Jones, Robert T; Kim, James C; Francis, Joshua M; Abedalthagafi, Malak; Borges, Lawrence F; Coumans, Jean-Valery; Curry, William T; Nahed, Brian V; Shin, John H; Paek, Sun Ha; Park, Sung-Hye; Stewart, Chip; Lawrence, Michael S; Cibulskis, Kristian; Thorner, Aaron R; Van Hummelen, Paul; Stemmer-Rachamimov, Anat O; Batchelor, Tracy T; Carter, Scott L; Hoang, Mai P; Santagata, Sandro; Louis, David N; Barker, Fred G; Meyerson, Matthew; Getz, Gad; Brastianos, Priscilla K; Cahill, Daniel P

    2014-01-01

    Hemangioblastomas consist of 10-20% neoplastic "stromal" cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas. PMID:25589003

  5. Cervical dystonia: about familial and sporadic cases in 88 patients

    Directory of Open Access Journals (Sweden)

    Carlos Henrique F. Camargo

    2014-02-01

    Full Text Available Cervical dystonia (CD affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic. Eighty-eight patients with CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p<0.001. The severity of symptoms was higher in patients with sporadic dystonia than in familial patients (p<0.01. Generalized cases were more severe in patients with a family history (p<0.01. Sporadic patients had higher levels of pain than familial cases (p<0.05. We expect soon to present the results of genetic analyzes of these patients.

  6. Body site of cutaneous malignant melanoma--a study on patients with hereditary and multiple sporadic tumours.

    Science.gov (United States)

    Gillgren, P; Brattström, G; Frisell, J; Palmgren, J; Ringborg, U; Hansson, J

    2003-06-01

    Individuals with an increased risk of developing cutaneous malignant melanoma (CMM) include members of kindreds with hereditary cutaneous malignant melanoma (HCMM) and patients who have already been treated for a CMM. Some of these patients develop multiple primary cutaneous malignant melanomas (MCMMs). Ultraviolet radiation is the main instigator of CMM. There are indications that patients in these high-risk groups react differently to sunlight than patients who develop a single sporadic CMM. The objectives of this study were to analyse tumour site in patients with HCMM and sporadic MCMM. Data on 2517 patients with 2608 CMMs from a population-based regional cancer registry were used. The new computer program EssDoll was used for the analyses of primary tumour sites. This software is able to analyse any chosen body area(s) with reference to the number of tumours arising there. When the site of the first and second tumours in patients with sporadic MCMM were analysed in a skin 'field division', there was a significant concordance with respect to site (P < 0.0001). In patients with MCMM, the second primary tumour was significantly thinner than the first (P = 0.001). Primary tumour sites in patients with HCMM were compared with those in patients with a single sporadic CMM. In HCMM we found significantly fewer tumours in the head and neck area and more on the trunk. These differences remained significant in two different body area models, even when stratified for age (P < 0.05). In conclusion, a site-concordance was noted for sporadic MCMM. This may be the result of a 'field effect'. Our results indicate that intermittent ultraviolet exposure may be of relatively greater importance than chronic exposure in HCMM. PMID:12777983

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

    Directory of Open Access Journals (Sweden)

    Emmanuel Uttah & Dominic C. Ibeh

    2011-12-01

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

  8. Sporadic impact flashes on the Moon and their implications

    Science.gov (United States)

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

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

  9. Application of quantitative DTI metrics in sporadic CJD

    Directory of Open Access Journals (Sweden)

    E. Caverzasi

    2014-01-01

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

  10. Application of quantitative DTI metrics in sporadic CJD.

    Science.gov (United States)

    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

    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

  11. Application of quantitative DTI metrics in sporadic CJD?

    Science.gov (United States)

    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

    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

  12. INTUSSUSCEPTION IN A CHILD WITH SPORADIC BURKITT LYMPHOMA

    Directory of Open Access Journals (Sweden)

    R. Angotti

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

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

    2008-11-01

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

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

    Directory of Open Access Journals (Sweden)

    HAN Shun-chang

    2013-04-01

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

  15. Diffusion MR imaging in sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    Burcak Cakir Pekoz

    2014-08-01

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

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

    International Nuclear Information System (INIS)

    The pattern of duality symmetries acting on the states of compactified superstring models reinforces an earlier suggestion that the Monster sporadic group is a hidden symmetry for superstring models. This in turn points to a supersymmetric theory of self-dual and anti-self-dual K3 manifolds joined by Dirac strings and evolving in a 13 dimensional spacetime as the fundamental theory. In addition to the usual graviton and dilaton this theory contains matter-like degrees of freedom resembling the massless states of the heterotic string, thus providing a completely geometric interpretation for ordinary matter. 25 refs

  17. Emerging therapeutic options for sporadic inclusion body myositis

    Science.gov (United States)

    Alfano, Lindsay N; Lowes, Linda P

    2015-01-01

    Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. PMID:26445546

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

    Science.gov (United States)

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

    2015-03-01

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

  19. A Case Of Sporadic Mesenteric Fibromatosis Mimicking Pancreatic Mass

    Directory of Open Access Journals (Sweden)

    Halil ibrahim Tasci

    2015-03-01

    Full Text Available The term abdominal fibromatosis refers to sporadic, pelvic, and mesenteric lesions and to all the fibromatosis lesions seen in Gardner's syndrome. Sporadic fibromatosis, however, is very rarer and literature offers a limited number of cases. The 14-year-old female patient presented to our clinic with complaints of indefinite abdominal pain in the epigastric area for the last 2 months, dyspeptic problems, and vomiting after eating. Upon the patient's gastroscopy revealed a mass lesion pressuring the stomach, endoscopic ultrasonography was performed. A hyperechoic mass lesion of 9x5 cm thought to have originated from the pancreatic tail was detected. The mass was surgically excised. Although mesenteric fibromatosis shows the characteristics of a benign tumor pathologically, it is extremely aggressive clinically and has a very high rate of recurrence. These patients should be treated like they have malign tumors and surgeons should perform surgical resection as wide as possible. [Cukurova Med J 2015; 40(1.000: 138-142

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

    CERN Document Server

    Chapline, G

    1996-01-01

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

  1. On Permanent and Sporadic Oscillations of the Magnetosphere

    CERN Document Server

    Guglielmi, A V

    2014-01-01

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

  2. Sungrazing dust particles against the sporadic meteor background

    Science.gov (United States)

    Golubaev, A. V.

    2015-07-01

    From the results of the statistical study, the genetic relation between some meteors (from -5 m to +5 m ) of the sporadic background and the comets of the Kreutz, Marsden, and Kracht families has been revealed. The radiants of sporadic meteors are concentrated at the geocentric ecliptic latitudes 7°-10° northward and southward of the ecliptic. The radiants of the sungrazing meteoroids, that were detected on their heliocentric orbits "before" and "after" the perihelion passage, are concentrated in the elongation intervals of approximately 120°-165° and 20°-60° from the Sun, respectively. Each of the specified radiant regions, in its turn, breaks up into two groups. The group of radiants with elongations of about 30° and 155° from the Sun belongs to the Marsden and Kracht cometary families, while the group with 50° and 135°, to the Kreutz cometary family. In the distribution by perihelion distance, a sharp decrease of the number of observed dust particles with q chemical elements in meteoroids as a function of the perihelion distance).

  3. CLINICAL ASPECTS AND THERAPY OF SPORADIC BURKITT LYMPHOMA

    Directory of Open Access Journals (Sweden)

    Luana Fianchi

    2009-11-01

    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.

  4. De novo mutations from sporadic schizophrenia cases highlight important signaling genes in an independent sample.

    Science.gov (United States)

    Kranz, Thorsten M; Harroch, Sheila; Manor, Orly; Lichtenberg, Pesach; Friedlander, Yechiel; Seandel, Marco; Harkavy-Friedman, Jill; Walsh-Messinger, Julie; Dolgalev, Igor; Heguy, Adriana; Chao, Moses V; Malaspina, Dolores

    2015-08-01

    Schizophrenia is a debilitating syndrome with high heritability. Genomic studies reveal more than a hundred genetic variants, largely nonspecific and of small effect size, and not accounting for its high heritability. De novo mutations are one mechanism whereby disease related alleles may be introduced into the population, although these have not been leveraged to explore the disease in general samples. This paper describes a framework to find high impact genes for schizophrenia. This study consists of two different datasets. First, whole exome sequencing was conducted to identify disruptive de novo mutations in 14 complete parent-offspring trios with sporadic schizophrenia from Jerusalem, which identified 5 sporadic cases with de novo gene mutations in 5 different genes (PTPRG, TGM5, SLC39A13, BTK, CDKN3). Next, targeted exome capture of these genes was conducted in 48 well-characterized, unrelated, ethnically diverse schizophrenia cases, recruited and characterized by the same research team in New York (NY sample), which demonstrated extremely rare and potentially damaging variants in three of the five genes (MAFschizophrenia can illuminate risk genes that increase the propensity to develop schizophrenia across ethnicities. PMID:26091878

  5. The 'Pokemon' (ZBTB7) Gene: No Evidence of Association with Sporadic Breast Cancer.

    Science.gov (United States)

    Salas, Antonio; Vega, Ana; Milne, Roger L; García-Magariños, Manuel; Ruibal, Alvaro; Benítez, Javier; Carracedo, Angel

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Antonio Salas

    2008-01-01

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

  7. Sporadic observation of the Fleischmann-Pons heat effect

    Energy Technology Data Exchange (ETDEWEB)

    Kainthla, R.C.; Velev, O.; Kaba, L.; Lin, G.H.; Packham, N.J.C.; Szklarczyk, M.; Wass, J.; Bockris, J.O' M. (Texas A and M Univ., College Station, TX (USA). Dept. of Chemistry)

    1989-09-01

    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 D{sub 2} evolution in a D{sub 2}-O{sub 2} electrolysis cell (no recombination attempted) which coincided precisely with the prediction of classical electrochemical theory, and thus eliminated the suspicion of heat through unintended D{sub 2}-O{sub 2} recombination. Three electrodes clearly produced an excess heat of approx 2-5 watts-cm{sup -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).

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

    Science.gov (United States)

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

    2005-11-01

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

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

    Science.gov (United States)

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

    1997-06-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  11. El Nino Southern Oscillation as Sporadic Oscillations between Metastable States

    CERN Document Server

    Ma, Tian

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    S. Ohtsuki

    2005-10-01

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

  13. 29 CFR 553.30 - Occasional or sporadic employment-section 7(p)(2).

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Occasional or sporadic employment-section 7(p)(2). 553.30... Other Exemptions § 553.30 Occasional or sporadic employment-section 7(p)(2). (a) Section 7(p)(2) of the... basis to qualify for exemption under section 7(p)(2), the employee's decision to work in a...

  14. Spontaneous tumour shrinkage in 1261 observed patients with sporadic vestibular schwannoma

    DEFF Research Database (Denmark)

    Huang, Xiaoshan; Caye-Thomasen, P; Stangerup, S-E

    2013-01-01

    To determine the rate of spontaneous tumour shrinkage in a group of patients with sporadic vestibular schwannoma managed with a 'wait and scan' approach.......To determine the rate of spontaneous tumour shrinkage in a group of patients with sporadic vestibular schwannoma managed with a 'wait and scan' approach....

  15. The onset and extent of genomic instability in sporadic colorectal tumor progression

    Science.gov (United States)

    Stoler, Daniel L.; Chen, Neng; Basik, Mark; Kahlenberg, Morton S.; Rodriguez-Bigas, Miguel A.; Petrelli, Nicholas J.; Anderson, Garth R.

    1999-01-01

    Cancer cell genomes contain alterations beyond known etiologic events, but their total number has been unknown at even the order of magnitude level. By sampling colorectal premalignant polyp and carcinoma cell genomes through use of the technique inter-(simple sequence repeat) PCR, we have found genomic alterations to be considerably more abundant than expected, with the mean number of genomic events per carcinoma cell totaling approximately 11,000. Colonic polyps early in the tumor progression pathway showed similar numbers of events. These results indicate that, as with certain hereditary cancer syndromes, genomic destabilization is an early step in sporadic tumor development. Together these results support the model of genomic instability being a cause rather than an effect of malignancy, facilitating vastly accelerated somatic cell evolution, with the observed orderly steps of the colon cancer progression pathway reflecting the consequences of natural selection. PMID:10611348

  16. ERKed by LRRK2: A cell biological perspective on hereditary and sporadic Parkinson’s disease

    Science.gov (United States)

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

    2014-01-01

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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    P. Karanikola

    2013-11-01

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

  19. Facing and managing natural disasters in the Sporades islands, Greece

    Science.gov (United States)

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

    2014-04-01

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

  20. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    Science.gov (United States)

    Handra-Luca, Adriana; Dumuis-Gimenez, Marie-Laure; Bendib, Mouna; Anagnostis, Panagiotis

    2015-01-01

    Thyroid heterotopic bone formation (HBF) in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years). The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.). Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.). The number and size of HBFs (total: 28) ranged between 1 and 23/thyroid gland (one bilateral) and 1 and 10?mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular). The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp.) without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ?2?mm), and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated. PMID:26697239

  1. Clinicopathologic features of sporadic inclusion body myositis in China.

    Science.gov (United States)

    Li, Ke; Pu, Chuanqiang; Huang, Xusheng; Liu, Jiexiao; Mao, Yanling; Lu, Xianghui

    2015-01-01

    This study is to investigate the clinical and pathologic features of sporadic inclusion body myositis (sIBM) in China. We retrospectively evaluated the clinical and pathological features of consecutive patients in our department between January 1986 to May 2012. Total 28 cases of sIBM (20 males, 8 females, mean age was 56.93±8.79) were obtained by review of all 4099 muscle biopsy reports. The proportion of sIBM was 0.68% (28/4099) in China. Muscle weakness of quadriceps appeared 100% in 28 cases, while conspicuous atrophy of quadriceps appeared only in five cases (17.86%). Creatase values of 28 patients with sIBM were normal or mildly elevated. Muscle biopsies showed that atrophic fibers resembled more frequent in small angular and irregular shape (82.14%), less common in small round shape (17.86%). Rimmed vacuoles resembled crack (67.86%) and round (32.14%) shape. Mononuclear cell invasion into necrotic muscle fibers (35.71%) was more frequent than non-necrotic muscle fibers (7.14%). sIBM was still a rare disease in China compared to other countries. There were some certain specific pathological characteristics existed in Chinese sIBM patients. PMID:26188941

  2. 20 March 2015 solar eclipse influence on sporadic E layer

    Science.gov (United States)

    Pezzopane, M.; Pietrella, M.; Pignalberi, A.; Tozzi, R.

    2015-11-01

    This paper shows how the solar eclipse occurred on 20 March 2015 influenced the sporadic E (Es) layer as recorded 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. In these locations, the solar eclipse was only partial, with the maximum area of the solar disk obscured by the Moon equal to ?54% at Rome and ?45% at Gibilmanna. Nevertheless, it is shown that the strong thermal gradients that usually accompany a solar eclipse, have significantly influenced the Es phenomenology. Specifically, the solar eclipse did not affect the Es layer in terms of its maximum intensity, which is comparable with that of the previous and next day, but rather in terms of its persistence. In fact, both at Rome and Gibilmanna, contrary to what typically happens in March, the Es layer around the solar eclipse time is always present. On the other hand, this persistence is also confirmed by the application of the height-time-intensity (HTI) technique. A detailed analysis of isoheight ionogram plots suggests that traveling ionospheric disturbances (TIDs) likely caused by gravity wave (GW) propagation have played a significant role in causing the persistence of the Es layer.

  3. Chlamydia pecorum: fetal and placental lesions in sporadic caprine abortion.

    Science.gov (United States)

    Giannitti, Federico; Anderson, Mark; Miller, Myrna; Rowe, Joan; Sverlow, Karen; Vasquez, Marce; Cantón, Germán

    2016-03-01

    Chlamydial abortion in small ruminants is usually associated with Chlamydia abortus infection. Although Chlamydia pecorum has been detected in aborted ruminants and epidemiological data suggests that C. pecorum is abortigenic in these species, published descriptions of lesions in fetuses are lacking. This work describes fetoplacental lesions in a caprine abortion with C. pecorum infection, and further supports the abortigenic role of C. pecorum in ruminants. A 16-month-old Boer goat aborted twin fetuses at ~130 days of gestation. Both fetuses (A and B) and the placenta of fetus A were submitted for postmortem examination and diagnostic workup. At autopsy, the fetuses had moderate anasarca, intermuscular edema in the hindquarters (A), and brachygnathia and palatoschisis (B). In the placenta, the cotyledons were covered by yellow fibrinosuppurative exudate that extended into the adjacent intercotyledonary areas. Histologically, there was severe suppurative and necrotizing placentitis with vasculitis (arteriolitis) and thrombosis, multifocal lymphohistiocytic and neutrophilic hepatitis (A), and fibrinosuppurative enteritis in both fetuses. Chlamydia antigen was detected in the placenta by the direct fluorescent antibody test and in fetal intestines by immunohistochemistry. Nested polymerase chain reaction of DNA extracted from formalin-fixed, paraffin-embedded sections of placenta and intestine amplified 400 bp of the Chlamydia 16S rRNA gene that was sequenced and found to be 99% identical to C. pecorum by BLAST analysis. Other known abortigenic infectious agents were ruled out by specific testing. It is concluded that C. pecorum infection is associated with fetoplacental lesions and sporadic abortion in goats. PMID:26965241

  4. Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia

    Directory of Open Access Journals (Sweden)

    Fritzsche Markus

    2002-12-01

    Full Text Available Abstract Background Clusters by season and locality reveal a striking epidemiological overlap between sporadic schizophrenia and multiple sclerosis (MS. As the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodid ticks, a meta analysis has been performed between all neuropsychiatric birth excesses including MS and the epidemiology of spirochaetal infectious diseases. Results The prevalence of MS and schizophrenic birth excesses entirely spares the tropical belt where human treponematoses are endemic, whereas in more temperate climates infection rates of Borrelia garinii in ticks collected from seabirds match the global geographic distribution of MS. If the seasonal fluctuations of Lyme borreliosis in Europe are taken into account, the birth excesses of MS and those of schizophrenia are nine months apart, reflecting the activity of Ixodes ricinus at the time of embryonic implantation and birth. In America, this nine months' shift between MS and schizophrenic births is also reflected by the periodicity of Borrelia burgdorferi transmitting Ixodes pacificus ticks along the West Coast and the periodicity of Ixodes scapularis along the East Coast. With respect to Ixodid tick activity, amongst the neuropsychiatric birth excesses only amyotrophic lateral sclerosis (ALS shows a similar seasonal trend. Conclusion It cannot be excluded at present that maternal infection by Borrelia burgdorferi poses a risk to the unborn. The seasonal and geographical overlap between schizophrenia, MS and neuroborreliosis rather emphasises a causal relation that derives from exposure to a flagellar virulence factor at conception and delivery. It is hoped that the pathogenic correlation of spirochaetal virulence to temperature and heat shock proteins (HSP might encourage a new direction of research in molecular epidemiology.

  5. RECQL4 helicase has oncogenic potential in sporadic breast cancers.

    Science.gov (United States)

    Arora, Arvind; Agarwal, Devika; Abdel-Fatah, Tarek Ma; Lu, Huiming; Croteau, Deborah L; Moseley, Paul; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Rakha, Emad A; Chan, Stephen Yt; Ellis, Ian O; Wang, Lisa L; Zhao, Yongliang; Balajee, Adayabalam S; Bohr, Vilhelm A; Madhusudan, Srinivasan

    2016-03-01

    RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund-Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a 'safe guardian of the genome', our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26690729

  6. MRI sequence findings in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Tian, Hui-jun; Zhang, Jia-tang; Lang, Sen-yang; Wang, Xiang-qing

    2010-11-01

    MRI has had an important role in the diagnosis of Creutzfeldt-Jakob disease (CJD). The aim of our study was to compare the efficacy of different MRI sequences among six biopsy-proven patients with sporadic CJD (sCJD) and seven patients with probable sCJD. These 13 patients with CJD aged from 36 years to 75 years (mean age: 55.5 years) were evaluated with T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) MRI and diffusion-weighted imaging (DWI). The characteristic MRI lesion pattern was found to be bilateral, symmetric and hyperintense signal changes in the basal ganglia and cortical regions. Two major lesion patterns were identified in all patients involving the cortex and basal ganglia. No signal abnormality was found in the thalamus. We found lesions in the cortex and basal ganglia in 7/13 patients (54%), isolated cortical involvement in 2/13 patients (15%), and isolated basal ganglia lesions in 4/13 patients (31%). The cortical involvement was widespread (in at least two regions) and usually included the frontal or occipital lobes (9/13, 69%) on DWI. Only one patient showed moderate high-signal intensity in the basal ganglia on T2-weighted MRI. T1-weighted MRI revealed no signal intensity abnormalities. We conclude that high signal changes in the basal ganglia and cerebral cortex on FLAIR and DWI are useful in the diagnosis of sCJD. Isolated cortical involvement on DWI and FLAIR should lead to a suspicion of CJD. DWI is the most sensitive MRI technique in the diagnosis of CJD, which supports an amendment to the clinical diagnostic criteria for sCJD to include findings from MRI. PMID:20727770

  7. Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Yacoub Magdi H

    2006-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

    This paper describes the diagnostic and treatment utility of visual art therapy in a case of sporadic Creutzfeldt-Jakob disease. Visual art therapy was compared longitudinally with clinical and neuroimaging data over five-month period in an autopsy-confirmed case of sporadic Creutzfeldt-Jakob disease of MM2-cortical subtype. Art therapy sessions and content were useful in ascertaining neuropsychiatric symptoms during the course of her illness. Art therapy offered a unique emotional and cognitive outlet as illness progressed. Patients and families affected by sporadic Creutzfeldt-Jakob disease may benefit from art therapy despite the rapidly progressive nature of the illness. Art therapy can also be useful for assessment of patients with sporadic Creutzfeldt-Jakob disease by healthcare professionals. PMID:26782687

  9. Regulation of BRCA1 expression and its relationship to sporadic breast cancer

    International Nuclear Information System (INIS)

    Germ-line mutations in the BRCA1 tumour suppressor gene contribute to familial breast tumour formation, but there is no evidence for direct mutation of the BRCA1 gene in the sporadic form of the disease. In contrast, decreased expression of the BRCA1 gene has been shown to be common in sporadic tumours, and the magnitude of the decrease correlates with disease progression. BRCA1 expression is also tightly regulated during normal breast development. Determining how these developmental regulators of BRCA1 expression are co-opted during breast tumourigenesis could lead to a better understanding of sporadic breast cancer aetiology and the generation of novel therapeutic strategies aimed at preventing sporadic breast tumour progression

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

    International Nuclear Information System (INIS)

    The new theory of sporadic E density oscillation with double atmospheric gravity wave (AGW) frequency in two-dimensional case taking into account ions ambipolar diffusion is presented. It is found that densities of multi-layered sporadic E, formed under the influence of atmospheric vortical perturbation (with vertical wavelength λz≠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 λz/2) and its density changes in every half AGW period close to ions convergence region occur by combined action of ion-neutral collision and Lorentz forcing and can cause additional accumulation of ions responsible for sporadic E density oscillation with double AGW frequency.

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

    DEFF Research Database (Denmark)

    Bergenfelz, Anders O J; Wallin, Göran; Jansson, Svante; Eriksson, Håkan; Mårtensson, Hans; Christiansen, Peer; Reihnér, Eva

    2011-01-01

    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.

  12. BRCA1 as a Therapeutic Target in Sporadic Epithelial Ovarian Cancer

    OpenAIRE

    Johanne I. Weberpals; Anna M. O'Brien; Clark-Knowles, Katherine V

    2010-01-01

    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...

  13. Heterogeneous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppression

    OpenAIRE

    Giglio, Sabrina; Provenzano, Aldesia; Mazzinghi, Benedetta; Becherucci, Francesca; Giunti, Laura; Sansavini, Giulia; Ravaglia, Fiammetta; Roperto, Rosa Maria; Farsetti, Silvia; Benetti, Elisa; Rotondi, Mario; Murer, Luisa; Lazzeri, Elena; Lasagni, Laura; Materassi, Marco

    2014-01-01

    In children, sporadic nephrotic syndrome can be related to a genetic cause, but to what extent genetic alterations associate with resistance to immunosuppression is unknown. In this study, we designed a custom array for next-generation sequencing analysis of 19 target genes, reported as possible causes of nephrotic syndrome, in a cohort of 31 children affected by sporadic steroid-resistant nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive clinical phenotype. Pat...

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

    OpenAIRE

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

    2012-01-01

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

  15. Discovering interactions among BRCA1 and other candidate genes associated with sporadic breast cancer.

    Science.gov (United States)

    Lo, Shaw-Hwa; Chernoff, Herman; Cong, Lei; Ding, Yuejing; Zheng, Tian

    2008-08-26

    Analysis of a subset of case-control sporadic breast cancer data, [from the National Cancer Institute's Cancer Genetic Markers of Susceptibility (CGEMS) initiative], focusing on 18 breast cancer-related genes with 304 SNPs, indicates that there are many interesting interactions that form two- and three-way networks in which BRCA1 plays a dominant and central role. The apparent interactions of BRCA1 with many other genes suggests the conjecture that BRCA1 serves as a protective gene and that some mutations in it or in related genes may prevent it from carrying out this protective function even if the patients are not carriers of known cancer-predisposing BRCA1 mutations. The method of analysis features the evaluation of the effect of a gene by averaging the effects of the SNPs covered by that gene. Marginal methods that test one gene at a time fail to show any effect. That may be related to the fact that each of these 18 genes adds very little to the risk of cancer. Analysis that relates the ratio of interactions to the maximum of the first-order effects discovers significant gene pairs and triplets. PMID:18711133

  16. Expression of proteins involved in DNA damage response in familial and sporadic breast cancer patients.

    Science.gov (United States)

    Partipilo, Giulia; Simone, Giovanni; Scattone, Anna; Scarpi, Emanuela; Azzariti, Amalia; Mangia, Anita

    2016-01-01

    Understanding the expression of proteins involved in DNA damage response could improve knowledge of the pathways that contribute to familial and sporadic breast cancer (BC). We aimed to assess the different roles of BRCA1, poly(ADP-ribose) polymerase-1 (PARP1), BRCT-repeat inhibitor of hTERT expression (BRIT1) and novel SWItch 5 (SWI5) expression in 130 sporadic and 73 familial BC samples, by immunohistochemistry. In the sporadic group, negative nuclear BRCA1 (nBRCA1) expression was associated with positive PgR (p?=?0.037). Negative association was found between nBRCA1 expression and HER2 (p?=?0.001). In the familial group, nBRCA1 expression was associated with ER (p?=?0.002). Reduced nBRCA1 expression was associated with higher histological grade and positive Ki67 both in sporadic (p?=?0.0010, p?=?0.047) and familial groups (p?factor associated with a high risk of sporadic tumor (OR 2.96, p?=?0.017). Our findings indicate that nPARP1 expression is an independent factor for sporadic BCs and PARP1 inhibitors could be a promising therapy for different phenotypes. PMID:26205471

  17. CSF analysis in patients with sporadic CJD and other transmissible spongiform encephalopathies.

    Science.gov (United States)

    Green, A; Sanchez-Juan, P; Ladogana, A; Cuadrado-Corrales, N; Sánchez-Valle, R; Mitrová, E; Stoeck, K; Sklaviadis, T; Kulczycki, J; Heinemann, U; Hess, K; Slivarichová, D; Saiz, A; Calero, M; Mellina, V; Knight, R; van Duijn, C M; Zerr, I

    2007-02-01

    Patients with suspected Creutzfeldt-Jakob disease (CJD) often have routine cerebrospinal fluid (CSF) analysis performed to exclude treatable inflammatory conditions; however, little information is available about the range of results obtained for CSF tests in patients with sporadic CJD and other transmissible spongiform encephalopathies (TSE). Data from 450 patients with sporadic CJD and 47 patients with other TSEs were collected as part of an EC-supported multinational study. Raised white cell counts of >5 cells/microl were found in three of 298 patients with sporadic CJD, with two cell counts of 7 cells/microl and one of 20 cells/microl. Total protein concentrations of >0.9 g/l were found in five of 438 patients with sporadic CJD, although none had a concentration of >1 g/l. CSF oligoclonal IgG was detected in eight of 182 sporadic CJD patients. Of the patients with other TSEs, six had elevated cell counts ranging from 6 to 14 cells/microl but none had total protein concentrations of >0.9 g/l and one patient had detectable oligoclonal IgG. None of the patients with sporadic CJD or other TSEs had abnormalities in all three tests. PMID:17250717

  18. PARK16 polymorphisms, interaction with smoking, and sporadic Parkinson's disease in Japan.

    Science.gov (United States)

    Miyake, Yoshihiro; Tanaka, Keiko; Fukushima, Wakaba; Kiyohara, Chikako; Sasaki, Satoshi; Tsuboi, Yoshio; Oeda, Tomoko; Shimada, Hiroyuki; Kawamura, Nobutoshi; Sakae, Nobutaka; Fukuyama, Hidenao; Hirota, Yoshio; Nagai, Masaki; Nakamura, Yoshikazu

    2016-03-15

    Epidemiological evidence on the relationships between PARK16 single nucleotide polymorphisms (SNPs) and Parkinson's disease (PD) is inconsistent. We examined this issue in Japan. Included were 229 cases within six years of PD onset. Controls were 356 patients without neurodegenerative disease. Compared with subjects with the AA genotype of SNP rs823128, those with the AG genotype, but not the GG genotype, had a significantly reduced risk of sporadic PD. Compared with the AA genotype of SNP rs947211, both the AG genotype and the GG genotype were significantly related to an increased risk of sporadic PD. Using subjects with the AA genotype of SNP rs823156 as a reference group, there were significant inverse relationships under the additive and dominant models. No significant relationships were found between SNPs rs16856139 or rs11240572 and sporadic PD. The CAAAC, the TGAGA, and the CAGAC haplotypes were significantly related to sporadic PD. The additive interaction between SNP rs823128 and smoking affecting sporadic PD was significant, although the multiplicative interaction was not significant. The PARK16 SNPs rs823128, rs947211, and rs823156 and the CAAAC, TGAGA, and CAGAC haplotypes may be significantly associated with sporadic PD in Japan. New evidence of an additive interaction between SNP rs823156 and smoking is suggested. PMID:26944116

  19. Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

    Science.gov (United States)

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

    2009-01-01

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

  20. Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Gabriel E. Rodríguez

    2012-01-01

    Full Text Available OBJECTIVES: Mitochondrial dysfunction has been reported in the central nervous system, hepatocytes and peripheral blood lymphocytes from patients with sporadic amyotrophic lateral sclerosis (SALS. However, the status of skin mitochondria has not been reported, in spite of the fact that SALS patients present skin abnormalities. The objective of the present study was to compare mitochondrial ultrastructural parameters in keratinocytes from patients with SALS and healthy controls. METHODS: Our study was based on the analysis of 112 skin mitochondria from 5 SALS patients and 99 organelles from 4 control subjects by electron microscopy. RESULTS: Computerized image analysis showed that mitochondrial major axis length, area and perimeter of the organelle were significantly smaller in SALS respect of healthy control subjects. Morphologically, SALS mitochondria presented cristolysis and breakage of the outer membrane. CONCLUSIONS: Mitochondrial dysfunction in the skin may possibly reflect changes occurring in mitochondria of the central nervous system. The analysis of mitochondrial morphology in this tissue may be of value to follow disease progression and, eventually, the effectiveness of current therapies for SALS.

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

    Directory of Open Access Journals (Sweden)

    Deshraj Meena

    2015-01-01

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

  2. Sporadic congenital transmission of avian leukosis virus in hens discharging the virus into the oviducts.

    Science.gov (United States)

    Tsukamoto, K; Hasebe, M; Kakita, S; Taniguchi, Y; Hihara, H; Kono, Y

    1992-02-01

    The efficacy of the albumen test for infectious avian leukosis virus (ALV) was examined in detecting congenitally transmitting hens. Seventy-three White Leghorn non-viremic hens with antibody to ALV were used. Eleven of the hens shed infectious ALV into their egg albumen, whereas only 7 of the 11 ALV-positive hens shed ALV antigens. The egg albumen test for infectious ALV was shown to be more effective in detecting the congenitally transmitting hens than that for ALV antigens. Then, twenty of the 62 hens which shed no infectious ALV into the albumen were studied for transmission of ALV to their embryos and for discharging ALV into the oviduct and vagina. Six of the 50 embryos from 4 hens were found to be infected with ALV but all of the 227 embryos from remaining 16 hens were free from the infection. Discharge of the virus into the oviduct and vagina was found both in the 4 transmitting hens and in 6 of the 16 non-transmitting hens. These results suggest that the hens discharging ALV into the oviduct, even though they do not shed ALV into egg albumen, may transmit the virus sporadically to their embryos. PMID:1313708

  3. Endoscopic mucosal resection and endoscopic submucosal dissection in the treatment of sporadic nonampullary duodenal adenomatous polyps.

    Science.gov (United States)

    Marques, Joana; Baldaque-Silva, Francisco; Pereira, Pedro; Arnelo, Urban; Yahagi, Naohisa; Macedo, Guilherme

    2015-06-25

    Although uncommon, sporadic nonampullary duodenal adenomas have a growing detection due to the widespread of endoscopy. Endoscopic therapy is being increasingly used for these lesions, since surgery, considered the standard treatment, carries significant morbidity and mortality. However, the knowledge about its risks and benefits is limited, which contributes to the current absence of standardized recommendations. This review aims to discuss the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in the treatment of these lesions. A literature review was performed, using the Pubmed database with the query: "(duodenum or duodenal) (endoscopy or endoscopic) adenoma resection", in the human species and in English. Of the 189 retrieved articles, and after reading their abstracts, 19 were selected due to their scientific interest. The analysis of their references, led to the inclusion of 23 more articles for their relevance in this subject. The increased use of EMR in the duodenum has shown good results with complete resection rates exceeding 80% and low complication risk (delayed bleeding in less than 12% of the procedures). Although rarely used in the duodenum, ESD achieves close to 100% complete resection rates, but is associated with perforation and bleeding risk in up to one third of the cases. Even though literature is insufficient to draw definitive conclusions, studies suggest that EMR and ESD are valid options for the treatment of nonampullary adenomas. Thus, strategies to improve these techniques, and consequently increase the effectiveness and safety of the resection of these lesions, should be developed. PMID:26140099

  4. Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH.

    Science.gov (United States)

    Jarbo, Caroline; Buckley, Patrick G; Piotrowski, Arkadiusz; Mantripragada, Kiran K; Benetkiewicz, Magdalena; Diaz de Ståhl, Teresita; Langford, Cordelia F; Gregory, Simon G; Dralle, Henning; Gimm, Oliver; Bäckdahl, Martin; Geli, Janos; Larsson, Catharina; Westin, Gunnar; Akerström, Göran; Dumanski, Jan P

    2006-03-01

    Pheochromocytoma is a predominantly sporadic neuroendocrine tumor derived from the adrenal medulla. Previous low resolution LOH and metaphase-CGH studies reported the loss of chromosomes 1p, 3q, 17p and 22q at various frequencies. However, the molecular mechanism(s) behind development of sporadic pheochromocytoma remains largely unknown. We have applied high-resolution tiling-path microarray-CGH with the primary aim to characterize copy number imbalances affecting chromosome 22 in 66 sporadic pheochromocytomas. We detected copy number alterations on 22q at a frequency of 44%. The predominant finding was monosomy 22 (30%), followed by terminal deletions in 8 samples (12%) and a single interstitial deletion. We further applied a chromosome 1 tiling-path array in 7 tumors with terminal deletions of 22q and found deletions of 1p in all cases. Our overall results suggest that at least 2 distinct regions on both 22q and 1p are important in the tumorigenesis of sporadic pheochromocytoma. A large proportion of pheochromocytomas also displayed indications of cellular heterogeneity. Our study is to our knowledge the first array-CGH study of sporadic pheochromocytoma. Future analysis of this tumor type should preferably be performed in the context of the entire human genome using genome-wide array-CGH, which is a superior methodological approach. Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html. PMID:16161042

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

    Science.gov (United States)

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

    2013-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Sunil V Jagtap

    2011-07-01

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

  7. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-02-01

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

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

    DEFF Research Database (Denmark)

    van Eimeren, Thilo; Binkofski, Ferdinand; Buhmann, Carsten; Hagenah, Johann; Strafella, Antonio P; Pramstaller, Peter P; Siebner, Hartwig R; Klein, Christine

    2010-01-01

    , 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...

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

    International Nuclear Information System (INIS)

    Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer's disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer's disease families, as it is closely linked to the gene. Most cases of Alzheimer's disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer's disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.)

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

    Directory of Open Access Journals (Sweden)

    T. Maruyama

    2006-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Daryl A Bosco

    2013-12-01

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

  13. Norovirus genotype diversity in community-based sporadic gastroenteritis incidents: a five-year study.

    Science.gov (United States)

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

    2015-06-01

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

  14. Immunoquantitative PCR for prion protein detection in sporadic Creutzfeldt-Jakob disease.

    OpenAIRE

    Gofflot, Stéphanie; Deprez, Manuel; Elmoualij, Benaïssa; Osman, Awad; Thonnart, Jean-François; Hougrand, Olivier; Heinen, Ernst; Zorzi, Willy

    2005-01-01

    BACKGROUND: The most common human prion disorder is Creutzfeldt-Jakob disease (CJD); it includes sporadic, familial, iatrogenic, and variant subtypes. Diagnostic tests aim at detection with the highest specificity of very small deposits of abnormal prion protein (PrP). METHODS: We used immunoquantitative PCR (iqPCR) to detect proteinase K-resistant PrP (PrPRes) in tissue from the middle frontal gyrus of 7 patients with sporadic CJD and 7 non-CJD cases. We compared iqPCR with routine optimized...

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

    Science.gov (United States)

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

    2015-11-01

    When approaching a patient with suspected motor neuron disease (MND), the pattern of weakness on examination helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing. MNDs exist on a spectrum, from a pure lower motor neuron to mixed upper and lower motor neuron to a pure upper motor neuron variant. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic, which is invariably fatal. This article describes a pattern approach to identifying MND and clinical features of sporadic ALS. PMID:26515618

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

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen; Børme, K K; Søndergaard, J O; Højgaard-Olsen, K; Bernstein, Inge Thomsen

    1995-01-01

    manifestations in familial adenomatous polyposis. None of the patients showed any sign of CHRPE. It is concluded that although genetic factors are presumably of importance in the development of sporadic colorectal cancer, CHRPE cannot be used as a marker for future risk of colorectal carcinoma except in...... polyposis families.......In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-15

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

  18. Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer.

    Science.gov (United States)

    Pikoulis, Emmanouil; Margonis, Georgios A; Angelou, Anastasios; Zografos, George C; Antoniou, Efstathios

    2016-03-01

    Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans. PMID:25768976

  19. P2X7 gene polymorphisms do not appear to be a susceptibility gene locus in sporadic cases of systemic lupus erythematosus.

    Science.gov (United States)

    Forchap, S L; Anandacoomarasamy, A; Wicks, J; Di Virgilio, F; Baricordi, O R; Rubbini, M; Trotta, F; Wiley, J; Manolios, N

    2008-11-01

    The P2X(7) receptor is a ligand-gated cation-selective channel that mediates ATP-induced apoptosis of cells of the immune system. A loss-of-function single nucleotide polymorphism (SNP) at position 1513 (1513 A-->C) of the P2X(7) gene has recently been identified in both healthy and chronic lymphocytic leukemia (CLL) B-cells, translating into a loss of P2X(7)-mediated apoptosis in these cells. This antiapoptotic effect results in increased B-cell numbers, thereby potentially contributing to the survival of B-CLL clones. It was hypothesized that prolonged cell survival may also predispose to induction of autoimmunity. The objective of this study is to analyze the role of the P2X(7) receptor and its loss-of-function 1513 A-->C polymorphism (SNP) in the development of systemic lupus erythematosus (SLE). DNA samples obtained from patients with sporadic SLE were analyzed for the presence of the 1513 A-->C polymorphism using polymerase chain reaction (PCR) amplification and then direct sequencing. No significant difference in allele frequencies (1513 A-->C polymorphism) between sporadic cases of SLE and controls was found. A loss-of-function SNP at position 1513 (1513 A-->C) of the P2X(7) gene does not appear to be a susceptibility gene locus for the development of sporadic SLE. PMID:18937793

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

    Directory of Open Access Journals (Sweden)

    Chupin Louis-Dominique

    2008-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Mueller Christopher R

    2003-10-01

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

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

    Scientific Electronic Library Online (English)

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

    2014-03-01

    Full Text Available 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.

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

    DEFF Research Database (Denmark)

    Raitila, A; Georgitsi, M; Karhu, A; Tuppurainen, K; Mäkinen, M J; Birkenkamp-Demtröder, K; Salmenkivi, K; Orntoft, T F; Arola, J; Launonen, V; Vahteristo, P; Aaltonen, L A

    2007-01-01

    (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas...

  4. Gluten ataxia of sporadic and hereditary cerebellar ataxia in patients from mainland China

    Directory of Open Access Journals (Sweden)

    Wen-Juan Guan

    2013-01-01

    Full Text Available Background: Gluten sensitivity (GS is a spectrum of disorders with diverse manifestations. Recent evidence suggests that ataxia may be the only manifestation of GS and that it may be one of the causes of sporadic ataxia. Aim: To investigate the prevalence of gluten ataxia among patients with ataxia in China. Materials and Methods: Serum levels of anti-gliadin, anti-transglutaminase 2 (TG2, and anti-transglutaminase 6 (TG6 antibodies measured in 125 patients with ataxia (100 patients with sporadic ataxia and 25 patients with hereditary ataxia and 51 healthy controls by enzyme-linked immunosorbent assay (ELISA. Results: The serum concentrations of anti-gliadin, anti-TG2 IgG, IgA, and TG6-IgG antibodies were elevated in ataxia patients, but the increase was not statistically significant. However, TG6-IgA serum levels were significantly higher in sporadic ataxia as compared to those in healthy controls (P < 0.05. Conclusions: These results provide evidence that sporadic ataxia in a subgroup of patients may be due to gluten ataxia in mainland China. Measurement of serum anti-TG6 antibodies along with anti-TG2 and anti-gliadin antibodies may be useful for diagnosing gluten ataxia.

  5. 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)

  6. 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.)

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

    Directory of Open Access Journals (Sweden)

    S. Fukao

    2005-10-01

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

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

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen; Børme, K K; Søndergaard, J O; Højgaard-Olsen, K; Bernstein, Inge Thomsen

    1995-01-01

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

  9. 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.

  10. Observation of electron biteout regions below sporadic E layers at polar latitudes

    Science.gov (United States)

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

    2015-03-01

    The descent of a narrow sporadic E layer near 95 km altitude over Poker Flat Research Range in Alaska was observed with electron probes on two consecutive sounding rockets and with incoherent scatter radar during a 2 h period near magnetic midnight. A series of four trimethyl aluminum chemical releases demonstrated that the Es layer remained just slightly above the zonal wind node, which was slowly descending due to propagating long-period gravity waves. The location of the layer is consistent with the equilibrium position due to combined action of the wind shear and electric fields. Although the horizontal electric field could not be measured directly, we estimate that it was ~ 2 mV m-1 southward, consistent with modeling the vertical ion drift, and compatible with extremely quiet conditions. Both electron probes observed deep biteout regions just below the Es enhancements, which also descended with the sporadic layers. We discuss several possibilities for the cause of these depletions; one possibility is the presence of negatively charged, nanometer-sized mesospheric smoke particles. Such particles have recently been detected in the upper mesosphere, but not yet in immediate connection with sporadic E. Our observations of electron depletions suggest a new process associated with sporadic E.

  11. COL11A1 in FAP polyps and in sporadic colorectal tumors

    International Nuclear Information System (INIS)

    We previously reported that the ?-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of ?-catenin. We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/?-catenin pathway. In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/?-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/?-catenin pathway in FAP and sporadic colorectal cancer

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

    Science.gov (United States)

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

    2011-01-01

    Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) represent two distinct clinical entities belonging to a wider group, generically named as conformational disorders that share common pathophysiologic mechanisms. It is well-established that the APOE ε4 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 ε4 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

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

    LENUS (Irish Health Repository)

    Kimmich, Okka

    2012-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Kim Nora

    2012-07-01

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

  15. 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.)

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

    Directory of Open Access Journals (Sweden)

    B. P. Williams

    2006-07-01

    Full Text Available On 5 July 2002, a MaCWAVE (Mountain and Convective Waves Ascending VErtically payload launched from Andøya Rocket Range, Norway, observed narrow enhanced layers of electron density that were nearly coincident with sporadic sodium layers measured by the Weber sodium lidar at the nearby ALOMAR Observatory. We investigate the formation mechanism of these layers using the neutral wind and temperature profiles measured directly by the lidar and the vertical motion deduced from the sodium mixing ratio. Through comparisons of the lidar data to the sporadic E in situ data, we find support for the concentration and downward motion of ions to an altitude where chemical models predict the rapid conversion of sodium ions to neutral sodium.

  17. Molecular typing of PrPres in human sporadic CJD brain tissue.

    Science.gov (United States)

    Lewis, Victoria; Klug, Genevieve M; Hill, Andrew F; Collins, Steven J

    2008-01-01

    Within the spectrum of sporadic human transmissible spongiform encephalopathies (TSEs), there is considerable diversity of disease phenotypes. At least part of this variation is thought to be on the basis of different "strains" of prions (the infectious agent). Tissue deposition of PrP(res) (the abnormal disease-associated conformation of the prion protein) is considered a hallmark of TSE pathology, and it can be visualized by Western blotting typically as three bands depicting the diglycosylated, monoglycosylated, and unglycosylated species. It is the mobility of the unglycosylated PrP(res), and the relative abundance of the two glycosylated bands, along with the prion protein gene (PRNP) codon 129 genotype, that seem to correlate with distinct clinico-pathological profiles of sporadic Creutzfeldt-Jakob disease. PMID:18576159

  18. Somatic GATA5 mutations in sporadic tetralogy of Fallot.

    Science.gov (United States)

    Huang, Ri-Tai; Xue, Song; Xu, Ying-Jia; Zhou, Min; Yang, Yi-Qing

    2014-05-01

    Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, with high morbidity and mortality rates. Accumulating evidence has demonstrated that genetic defects play an important role in the pathogenesis of TOF. However, the molecular basis of TOF in the majority of patients remains to be determined. In the present study, sequence analysis of the coding exons and exon-intron boundaries of GATA5, a gene encoding a zinc finger?containing transcriptional factor crucial for cardiogenesis, was performed on genomic DNA isolated from resected cardiac tissue and matched blood samples of 85 unrelated patients who underwent surgical repair of TOF. Genotyping was performed on the cardiac tissue and matched blood samples from 63 unrelated patients who underwent cardiac valve replacement due to rheumatic heart disease as well as the blood samples obtained from 200 unrelated healthy individuals. The functional effect of the mutations was evaluated by using a luciferase reporter assay system. As a result, the novel heterozygous GATA5 mutations, p.D203E and p.Y208X, were found in the cardiac tissues of two TOF patients, respectively. There were no mutations in the cardiac tissues obtained from 63 patients with rheumatic heart disease nor in the blood samples obtained from the 348 subjects. Functional analysis revealed that the GATA5 mutants were consistently associated with significantly decreased transcriptional activity compared with their wild-type counterpart. Thus, results of this study showed an association of somatic GATA5 mutations with TOF, providing further insight into the underlying molecular mechanism of TOF. PMID:24573614

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

    OpenAIRE

    Dorfman, Verónica Berta; Pasquini, Laura; Riudavets, Miguel; López-Costa, Juan José; Villegas, Andrés; Troncoso, Juan Carlos; Lopera, Francisco; Castaño, Eduardo Miguel; MORELLI, LAURA

    2008-01-01

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

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

    OpenAIRE

    Pera, Marta; Alcolea, Daniel; Sánchez-Valle, Raquel; Guardia-Laguarta, Cristina; Colom-Cadena, Martí; Badiola, Nahuai; Suárez-Calvet, Marc; Lladó, Albert; Barrera-Ocampo, Alvaro A.; Sepulveda-Falla, Diego; Blesa, Rafael; Molinuevo, José L.; Clarimón, Jordi; Ferrer, Isidre; Gelpi, Ellen

    2012-01-01

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

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

    OpenAIRE

    Lindberg, Daniel

    2007-01-01

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

  2. Sparse Model Uncertainties in Compressed Sensing with Application to Convolutions and Sporadic Communication

    OpenAIRE

    Jung, Peter; Walk, Philipp

    2014-01-01

    The success of the compressed sensing paradigm has shown that a substantial reduction in sampling and storage complexity can be achieved in certain linear and non-adaptive estimation problems. It is therefore an advisable strategy for noncoherent information retrieval in, for example, sporadic blind and semi-blind communication and sampling problems. But, the conventional model is not practical here since the compressible signals have to be estimated from samples taken solel...

  3. Intra-type migrative scheduling of implicit-deadline sporadic tasks on two- type heterogeneous multiprocessor

    OpenAIRE

    Raravi, Gurulingesh; Andersson, Björn; Bletsas, Konstantinos

    2011-01-01

    Consider the problem of scheduling a set of implicit-deadline sporadic tasks to meet all deadlines on a two-type heterogeneous multiprocessor platform. Each processor is either of type-1 or type-2 with each task having different execution time on each processor type. Jobs can migrate between processors of same type (referred to as intra-type migration) but cannot migrate between processors of different types. We present a new scheduling algorithm namely, LP-Relax(THR) which offers...

  4. Endoscopic mucosal resection and endoscopic submucosal dissection in the treatment of sporadic nonampullary duodenal adenomatous polyps

    OpenAIRE

    Marques, Joana; Baldaque-Silva, Francisco; Pereira, Pedro; Arnelo, Urban; Yahagi, Naohisa; Macedo, Guilherme

    2015-01-01

    Although uncommon, sporadic nonampullary duodenal adenomas have a growing detection due to the widespread of endoscopy. Endoscopic therapy is being increasingly used for these lesions, since surgery, considered the standard treatment, carries significant morbidity and mortality. However, the knowledge about its risks and benefits is limited, which contributes to the current absence of standardized recommendations. This review aims to discuss the efficacy and safety of endoscopic mucosal resec...

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

    DEFF Research Database (Denmark)

    Schlehofer, B; Schlaefer, K; Blettner, M; Berg, Gabriele; Böhler, E; Hettinger, I; Kunna-Grass, K; Wahrendorf, J; Schüz, J

    2007-01-01

    The only known risk factor for sporadic acoustic neuroma is high-dose ionising radiation. Environmental exposures, such as radiofrequency electromagnetic fields and noise are under discussion, as well as an association with allergic diseases. We performed a population-based case-control study in Germany investigating these risk factors in 97 cases with acoustic neuroma, aged 30 to 69 years, and in 194 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multi...

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

    Science.gov (United States)

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

    2014-09-01

    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

  7. Microvascular Pathology and Morphometrics of Sporadic and Hereditary Small Vessel Diseases of the Brain

    OpenAIRE

    Craggs, Lucinda JL; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Raj N

    2014-01-01

    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 p...

  8. Comparison of Sporadic Sclerotic Fibroma and Solitary Fibrous Tumor in the Oral Cavity

    OpenAIRE

    Lee, Ju-Han; An, Jung-Suk; Lee, Eung Seok; Kwon, Soon-Young; Kim, Young-Sik

    2007-01-01

    Sporadic sclerotic fibroma (SF) and solitary fibrous tumor (SFT) arising in the oral cavity are very rare. In this report, we describe two cases of oral pathology, one involving SF and the other involving SFT. Both cases presented with well-circumscribed, firm nodules with similar gross findings. However, the histologic findings of the SF and SFT showed rather distinct features. The SF was composed of hyalinized sclerotic collagen bundles arranged in a whorled pattern, whereas the SFT was for...

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

    OpenAIRE

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

    2012-01-01

    Our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer’s disease, both caused by a duplication of the amyloid-? precursor protein gene1 (AP...

  10. Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer.

    Science.gov (United States)

    Joensuu, Emmi I; Nieminen, Taina T; Lotsari, Johanna E; Pavicic, Walter; Abdel-Rahman, Wael M; Peltomäki, Päivi

    2015-12-01

    Molecular mechanisms underlying coordinated hypermethylation of multiple CpG islands in cancer remain unclear and studies of methyltransferase enzymes have arrived at conflicting results. We focused on DNMT1 and DNMT3B, DNA methyltransferases responsible for (de novo) methylation, and EZH2, histone (H3K27) methyltransferase, and examined their roles in tumor suppressor gene (TSG) methylation patterns we have previously established in sporadic and familial cancers. Our investigation comprised 165 tumors, stratified by tissue of origin (117 colorectal and 48 endometrial carcinomas) and sporadic vs. familial disease (57 sporadic vs. 60 familial, mainly Lynch syndrome, colorectal carcinomas). By immunohistochemical evaluation, EZH2 protein expression was associated with a TSG methylator phenotype. DNMT1, DNMT3B, and EZH2 were expressed at significantly higher levels in tumor vs. normal tissues. DNMT1 and EZH2 expression were positively correlated and higher in microsatellite-unstable vs. microsatellite-stable tumors, whether sporadic or hereditary. Ki-67 expression mirrored the same pattern. Promoter methylation of the methyltransferase genes themselves was addressed as a possible cause behind their altered expression. While DNMT1 or EZH2 did not show differential methylation between normal and tumor tissues, DNMT3B analysis corroborated the regulatory role of a distal promoter region. Our study shows that methyltransferase expression in cancer depends on the tissue of origin, microsatellite-instability status, cellular proliferation, and-in the case of DNMT3B-promoter methylation of the respective gene. Translation of methyltransferase expression into DNA methylation appears complex as suggested by the fact that except for EZH2, no clear association between methyltransferase protein expression and TSG methylation was observed. © 2015 Wiley Periodicals, Inc. PMID:26305882

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

    OpenAIRE

    Dallapiccola, Bruno; Mingarelli, Rita

    1995-01-01

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

  12. First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm.

    Science.gov (United States)

    van de Luijtgaarden, Koen M; Heijsman, Daphne; Maugeri, Alessandra; Weiss, Marjan M; Verhagen, Hence J M; IJpma, Arne; Brüggenwirth, Hennie T; Majoor-Krakauer, Danielle

    2015-08-01

    Genetic causes for abdominal aortic aneurysm (AAA) have not been identified and the role of genes associated with familial thoracic aneurysms in AAA has not been explored. We analyzed nine genes associated with familial thoracic aortic aneurysms, the vascular Ehlers-Danlos gene COL3A1 and the MTHFR p.Ala222Val variant in 155 AAA patients. The thoracic aneurysm genes selected for this study were the transforming growth factor-beta pathway genes EFEMP2, FBN1, SMAD3, TGBF2, TGFBR1, TGFBR2, and the smooth muscle cells genes ACTA2, MYH11 and MYLK. Sanger sequencing of all coding exons and exon-intron boundaries of these genes was performed. Patients with at least one first-degree relative with an aortic aneurysm were classified as familial AAA (n = 99), the others as sporadic AAA. We found 47 different rare heterozygous variants in eight genes: two pathogenic, one likely pathogenic, twenty-one variants of unknown significance (VUS) and twenty-three unlikely pathogenic variants. In familial AAA we found one pathogenic and segregating variant (COL3A1 p.Arg491X), one likely pathogenic and segregating (MYH11 p.Arg254Cys), and fifteen VUS. In sporadic patients we found one pathogenic (TGFBR2 p.Ile525Phefs*18) and seven VUS. Thirteen patients had two or more variants. These results show a previously unknown association and overlapping genetic defects between AAA and familial thoracic aneurysms, indicating that genetic testing may help to identify the cause of familial and sporadic AAA. In this view, genetic testing of these genes specifically or in a genome-wide approach may help to identify the cause of familial and sporadic AAA. PMID:26017485

  13. Terdiurnal signatures in sporadic E layers at midlatitudes

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2008-01-01

    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 diseas...

  15. Mutational analysis and genotype-phenotype correlations in southern Indian patients with sporadic and familial aniridia

    OpenAIRE

    Dubey, Sushil Kumar; Mahalaxmi, Nagasubramanian; Vijayalakshmi, Perumalsamy; Sundaresan, Periasamy

    2015-01-01

    Purpose Aniridia is a rare panocular disorder characterized by iris hypoplasia and other associated eye anomalies. Heterozygous null mutations in paired box gene 6 (PAX6) are the major cause of the classic aniridia phenotype. This study aims to detect the mutational spectrum of PAX6 and associated phenotypes in southern Indian patients with sporadic and familial aniridia. Methods Genomic DNA was isolated from peripheral blood from all participants. The coding regions and flanking intronic seq...

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

    OpenAIRE

    Funk, Shelby; Nanadur, Vijaykant

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro; Hald, Tine

    2009-01-01

    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 salmone...

  18. Diet-gene interactions in sporadic and hereditary colorectal carcinogenesis : epidemiological perspectives

    OpenAIRE

    Voskuil, D.

    1999-01-01

    Colorectal cancer is known to develop by accumulation of alterations in regulatory genes. Both familial and environmental factors play a role in the etiology of colorectal cancer and its adenomatous precursor lesions. This thesis examines diet-gene interactions in sporadic and hereditary colorectal carcinogenesis, from two different epidemiological perspectives, as outlined in AIMS 1 and 2.AIM 1: to examine evidence for a role of dietary risk factors in the etiology of Hereditary Non-Polyposi...

  19. KRAS, p53 and BRAF Gene Mutations and Aneuploidy in Sporadic Colorectal Cancer Progression

    OpenAIRE

    CALISTRI, DANIELE; Rengucci, Claudia; Seymour, Ian; Leonardi, Elena; Truini, Mauro; Malacarne, Davide; Castagnola, Patrizio; Giaretti, Walter

    2006-01-01

    Background: The origin and mechanisms of chromosomal instability are still widely unknown. We previously investigated a limited number of human sporadic colorectal cancers (CRCs) and observed a statistically different occurrence of KRAS and p53 mutations among predetermined subgroups of tumors with different degrees of DNA aneuploidy. The aim of the present study was to further verify these observations by including BRAF gene analysis and by investigating a larger series of cases subdivided i...

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

    OpenAIRE

    Kim Vaiphei; Aruna Rangan; Rajinder Singh

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Rudbeck, M.; Jepsen, Martin Rudbeck; Sonne, I.B.; Uldum, Søren Anker; Viskum, S.; Molbak, K.

    2010-01-01

    The aim was to analyse variation in incidence of sporadic Legionnaires' disease in a geographical information system in three time periods (1990-2005) by the application of a grid model and to assess the model's validity by analysing variation according to grid position. Coordinates of the...... grid model we demonstrated that it was possible to detect small areas with excess incidence that were not detected in the present surveillance system...

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

    OpenAIRE

    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

    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 eigh...

  3. Kleine-Levin syndrome. Familial cases and comparison with sporadic cases

    OpenAIRE

    Saad M. Al Suwayri

    2016-01-01

    Objectives: To highlight the occurrence of familial cases and addresses, whether familial Kleine-Levine syndrome (KLS) presents the same spectrum of disease, as that seen in sporadic KLS. Methods: Between September and December 2014, reports of familial cases of KLS were identified by searching the Library of Congress, PubMed, and Web of Science databases restricted to the English language, with no restriction on date of publication. All cases were reviewed to identify familial cases co...

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

    OpenAIRE

    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, Günter

    2006-01-01

    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) syn...

  5. Orbit and radiant of sporadic fireball imaged by the Spanish meteor network

    OpenAIRE

    Alonso Azcárate, Jacinto; Madiedo Gil, José María; Trigo Rodríguez, Josep María; Zamorano, J.; Izquierdo Gómez, Jaime; Ocaña Gónzalez, Francisco; A. Sánchez de Miguel; Lacruz, J.; Toscano, F. M.

    2012-01-01

    The development of a network of meteor observing stations allows for a continuous monitoring of meteor phenomena. One of the main goals of the SPanish Meteor Network (SPMN) is the analysis of the physico-chemical properties of meteoroids from multiple station data. This provides useful data to improve our knowledge about meteoroid streams and meteoroids of sporadic origin, so that we can reach a better understanding of the mechanisms that deliver these materials to ...

  6. Emission spectrum and orbital elements of a sporadic fireball imaged in 2011

    OpenAIRE

    D. Marín; Madiedo Gil, José María; Trigo Rodríguez, Josep María; Ortiz Moreno, José Luis; Castro Tirado, Alberto J.; Pastor, S.; Reyes, J. A. de los

    2013-01-01

    The characterisation of physical and chemical properties of meteoroids can be performed from the analysis of meteor and fireball events. This provides useful information about the origin and evolution of meteoroid streams and meteoroids of sporadic origin, but also about the mechanisms that deliver these materials to the Earth One of the systems that the SPanish Meteor Network (SPMN) employs to study the activity of meteor streams is based on high-sensitivity CCD vi...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial and sporadic cases of IBD in a nationwide cohort study. METHODS: From national registries, covering a population of 8,295,773 individuals, we obtained information on date and year of diagnosis of IBD cas...

  8. Lines identification in the emission spectrum and orbital elements of a sporadic video meteor

    Science.gov (United States)

    Madiedo, J. M.; Zamorano, J.; Ocaña, F.; Izquierdo, J.; Sanchez de Miguel, A.; Trigo-Rodriguez, J. M.; Toscano, F. M.

    2011-10-01

    Since 2006 the SPanish Meteor Network (SPMN) employs high-sensitivity CCD video cameras to monitor meteor and fireball activity over the Iberian Peninsula and neighboring areas. These allow us to obtain the trajectory and orbit for multi-station events and, when combined with holographic diffraction gratings, also provide information about the chemical composition of the corresponding meteoroids. In this context, we analyze here the emission spectrum, trajectory and orbital parameters of a sporadic bolide imaged on 2010.

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

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2008-01-01

    AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The sa...

  11. Sporadic and Familial Congenital Cataracts: Mutational Spectrum and New Diagnoses Using Next-Generation Sequencing.

    Science.gov (United States)

    Ma, Alan S; Grigg, John R; Ho, Gladys; Prokudin, Ivan; Farnsworth, Elizabeth; Holman, Katherine; Cheng, Anson; Billson, Frank A; Martin, Frank; Fraser, Clare; Mowat, David; Smith, James; Christodoulou, John; Flaherty, Maree; Bennetts, Bruce; Jamieson, Robyn V

    2016-04-01

    Congenital cataracts are a significant cause of lifelong visual loss. They may be isolated or associated with microcornea, microphthalmia, anterior segment dysgenesis (ASD) and glaucoma, and there can be syndromic associations. Genetic diagnosis is challenging due to marked genetic heterogeneity. In this study, next-generation sequencing (NGS) of 32 cataract-associated genes was undertaken in 46 apparently nonsyndromic congenital cataract probands, around half sporadic and half familial cases. We identified pathogenic variants in 70% of cases, and over 68% of these were novel. In almost two-thirds (20/33) of these cases, this resulted in new information about the diagnosis and/or inheritance pattern. This included identification of: new syndromic diagnoses due to NHS or BCOR mutations; complex ocular phenotypes due to PAX6 mutations; de novo autosomal-dominant or X-linked mutations in sporadic cases; and mutations in two separate cataract genes in one family. Variants were found in the crystallin and gap junction genes, including the first report of severe microphthalmia and sclerocornea associated with a novel GJA8 mutation. Mutations were also found in rarely reported genes including MAF, VIM, MIP, and BFSP1. Targeted NGS in presumed nonsyndromic congenital cataract patients provided significant diagnostic information in both familial and sporadic cases. PMID:26694549

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

    Science.gov (United States)

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

    2012-01-01

    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

  13. Two-hit model for sporadic congenital anomalies in mice with the disorganization mutation

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, J.L. (Jackson Lab., Bar Harbor, ME (United States) Univ. of Maine, Orono (United States) Vanderbilt Univ. School of Medicine, Nashville, TN (United States)); Varnum, D.S.; Nadeau, J.H. (Jackson Lab., Bar Harbor, ME (United States))

    1993-05-01

    Congenital anomalies have complex etiologies involving both genetic and nongenetic components. Many are sporadic, without obvious evidence for heritability. An important model for these anomalies is a mutation in laboratory mice that is called [open quotes]disorganization[close quotes] (Ds), which functions as a variable autosomal dominant and leads to a wide variety of congenital anomalies involving many developmental processes and systems. Variable expressivity, asymmetrical manifestations, and low penetrance suggest that somatic events determine the location and nature of these anomalies. A statistical analysis suggests that occurrence of anomalies in mice with the Ds mutation follows a Poisson distribution. These results suggest that congenital anomalies in mice with the Ds mutation occur independently of each other. The authors propose that Ds causes a heritable predisposition to congenital anomalies and that Ds and appropriate somatic events combine to compromise normal development. They also propose that some sporadic, nonheritable congenital anomalies involve somatic mutations at Ds-like loci. Ds may therefore serve not only as a model for developmental anomalies in cell fate and pattern formation but also for complex developmental traits showing variable expressivity, low penetrance, and sporadic occurrence in mice and humans. 58 refs., 2 figs., 1 tab.

  14. Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression.

    Science.gov (United States)

    Giglio, Sabrina; Provenzano, Aldesia; Mazzinghi, Benedetta; Becherucci, Francesca; Giunti, Laura; Sansavini, Giulia; Ravaglia, Fiammetta; Roperto, Rosa Maria; Farsetti, Silvia; Benetti, Elisa; Rotondi, Mario; Murer, Luisa; Lazzeri, Elena; Lasagni, Laura; Materassi, Marco; Romagnani, Paola

    2015-01-01

    In children, sporadic nephrotic syndrome can be related to a genetic cause, but to what extent genetic alterations associate with resistance to immunosuppression is unknown. In this study, we designed a custom array for next-generation sequencing analysis of 19 target genes, reported as possible causes of nephrotic syndrome, in a cohort of 31 children affected by sporadic steroid-resistant nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive clinical phenotype. Patients who exhibited extrarenal symptoms, had a familial history of the disease or consanguinity, or had a congenital onset were excluded. We identified a genetic cause in 32.3% of the children with steroid-resistant disease but zero of 38 children with steroid-sensitive disease. Genetic alterations also associated with lack of response to immunosuppressive agents in children with steroid-resistant disease (0% of patients with alterations versus 57.9% of patients without alterations responded to immunosuppressive agents), whereas clinical features, age at onset, and pathologic findings were similar in steroid-resistant patients with and without alterations. These results suggest that heterogeneous genetic alterations in children with sporadic forms of nephrotic syndrome associate with resistance to steroids as well as immunosuppressive treatments. In these patients, a comprehensive screening using such an array may, thus, be useful for genetic counseling and may help clinical decision making in a fast and cost-efficient manner. PMID:25060053

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

    Science.gov (United States)

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

    2005-01-01

    Objective: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene. Methods: Patients referred to the Specialist Cognitive Disorders Clinic at the National Hospital for Neurology and Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for further investigation of suspected CJD were recruited into the study. The neuropsychological test battery evaluated general intelligence, visual and verbal memory, nominal skills, literacy skills, visual perception and visuospatial functions, and visuospatial and executive function. Results: The results indicate that moderate to severe cognitive decline is a characteristic feature of vCJD. Specifically, verbal and visual memory impairments and executive dysfunction were pervasive in all disease groups. Nominal skills were impaired in variant and sporadic CJD, significantly so when compared with the inherited prion disease group. Perceptual impairment was less frequent in the vCJD group than in the sporadic and inherited groups. Conclusion: This study confirms the occurrence of generalised cognitive decline in patients with vCJD. Although decline in cognitive function ultimately affects all domains, there is a suggestion that some components of visual perception may be spared in vCJD. The results also suggest that nominal function may be preserved in some cases with inherited prion disease. PMID:15716521

  16. Genetic analysis of noroviruses associated with sporadic gastroenteritis during winter in Guangzhou, China.

    Science.gov (United States)

    Xue, Liang; Wu, Qingping; Dong, Ruimin; Kou, Xiaoxia; Li, Yonglai; Zhang, Jumei; Guo, Weipeng

    2013-10-01

    Noroviruses are regarded as the major causes of acute gastroenteritis worldwide, but their prevalence in sporadic diarrhea in South China remains unclear. This study was performed to characterize the genotypes of circulating norovirus strains associated with sporadic diarrhea cases in Guangzhou from November 2010 to January 2011. Among fecal specimens collected from 89 patients with acute diarrhea, nine samples (10.11%) were norovirus positive and 32 samples (35.96%) were rotavirus positive. The partial polymerase and the capsid regions of these norovirus samples were sequenced and phylogenetically analyzed. Three genotypes (GII.4, GII.6, and GII.b/GII.3) were identified, among which GII.4-2006b was the most predominant genotype (4/9, 44.4%), followed by GII.6 (3/9, 33.3%). A novel GII.4-2010 variant was first detected in China. Furthermore, the near full-length genome of the GZ2010-L26 strain, which belonged to GII.4-2006b, was sequenced and analyzed. Thus, the results of this study suggested that, second to rotavirus, noroviruses are the important pathogens responsible for sporadic acute gastroenteritis during winter in Guangzhou, and the GII.4-2006b variant remains the predominant genotype. PMID:23947818

  17. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Directory of Open Access Journals (Sweden)

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  18. Extensive Genetic Diversity Identified among Sporadic Methicillin-Resistant Staphylococcus aureus Isolates Recovered in Irish Hospitals between 2000 and 2012

    OpenAIRE

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

    2014-01-01

    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 pat...

  19. Age At Onset Predicts Good Seizure Outcome In Sporadic Non-Lesional and Mesial Temporal Sclerosis Based Temporal Lobe Epilepsy

    OpenAIRE

    Aguglia, Umberto; Beghi , Ettore; Labate, Angelo; Condino, Francesca; Cianci, Vittoria; Mumoli, Laura; Gasperini, Sara; Quattrone, Aldo; Gambardella, Antonio

    2010-01-01

    Abstract Purpose. To study prognosis and prognostic predictors of sporadic, non-lesional temporal lobe epilepsy (TLE). Method. Four hundred seventy-four patients with TLE were consecutively seen from April 1987 to April 2004. One hundred-ninety had a sporadic, non lesional TLE and a follow-up longer than two years. Two hundred eighty four patients were excluded because of family history for TLE, incomplete history, poor compliance with treatment, psychogenic seizures, no brain M...

  20. Promoter methylation and expression changes of BRCA1 in cancerous tissues of patients with sporadic breast cancer

    OpenAIRE

    LI, QIUYUN; Wei, Wei; Jiang, Yi; YANG, HUAWEI; LIU, JIANLUN

    2015-01-01

    BRCA1 is a susceptibility gene that has a genetic predisposition for breast cancer. BRCA1 gene mutation is closely associated with familial hereditary breast cancer, but the BRCA1 gene mutation is rarely found in sporadic breast cancer. According to previous studies, decreased expression of BRCA1 was detected in certain types of sporadic breast cancer. Aberrant methylation of DNA promoter CpG islands is one of the mechanisms by which tumor suppressor gene expression and function is lost. The ...

  1. Physico-chemical properties of sporadic meteoroids inferred from de continuous monitoring of meteor and fireball activity

    OpenAIRE

    González Reina, L. A.; Madiedo Gil, José María; Trigo Rodríguez, Josep María; Toscano, F. M.

    2013-01-01

    Sporadic meteoroids make up the bulk of the meteoroids striking the Earth. The combined action of gravitational and radiation forces have reduced the coherence of the initial orbits of these particles to such a degree that they have become so diffuse as to be no longer recognizable as streams and merge them together into the sporadic meteoroid complex. The development of a continuous meteor and fireball monitoring campaign is fundamental to characterize the physico-...

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

    Science.gov (United States)

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

    2014-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Mehdi Nikbahkt Dastjerdi

    2010-01-01

    Full Text Available Objective: The polymorphic variants at codon 72 of the p53 gene, encoding prolineor arginine at residue 72, produce marked changes in the p53 structure. From theevidence that the DNA mismatch repair system and p53 interact to maintain genomicintegrity, we hypothesized that codon 72 variations may influence the prevalence ofmicrosatellite instability (MSI, a feature of malignancies associated with mismatchrepair deficiency in sporadic colorectal cancer.Materials and Methods: We investigated the frequency of MSI in three P53 codon72 genotypes using genomic DNAs from 144 paraffin blocks of sporadic colorectaladenocarcinomas by testing the BAT-26 poly(A marker. We used PCR-SSCP analysisto detect tumor sample MSI for the nonisotopic detection of deletions in the BAT-26 poly (A mononucleotide repeat. Associations between qualitative variables wereevaluated using the χ2-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.

  4. Sporadic Burkitt Lymphoma Mimicking Osteomyelitis of the Mandible Revealing Clinically Unsuspected HIV Infection.

    Science.gov (United States)

    Sivolella, Stefano; Rizzo, Giovanni; Valente, Marialuisa; Lumachi, Franco

    2015-09-01

    Adult sporadic Burkitt lymphoma is a rare and highly aggressive malignancy, accounting for approximately 1-2% of adult lymphomas in Western countries, and exclusively intra-oral localization is very uncommon. We describe a rare case of a moderately painful sporadic Burkitt lymphoma localized in the posterior third of the left mandibular bone, initially misdiagnosed as osteomyelitis-like lesion, in a patient Epstein-Barr virus infection-negative with unknown human immunodeficiency virus (HIV) positivity and acquired immunodeficiency syndrome. A 52-year-old man was referred to our Department complaining of persistent moderate pain localized in the left mandibular arch. According to clinical and radiological features, a diagnosis of post-extraction osteomyelitis was made and a surgical revision, including soft and hard tissue biopsy, was performed. Histopathology revealed the presence of a diffuse proliferation of lymphoid cells, exhibiting the typical 'starry-sky' appearance that was consistent with the diagnosis of B-type non-Hodgkin lymphoma. Unexpectedly, HIV seropositivity was also found, but the patient was unaware of this, and the history did not reveal any particular risk factor for HIV infection. Positron-emission tomography showed a highly (18)F-fluorodeoxyglucose-avid mass in the left maxillofacial region and extensive disease in bone marrow and mediastinum. Thus, the patient was referred to our onco-hematological team for final assessment and care. In conclusion, sporadic Burkitt lymphoma is an aggressive malignancy, which rarely affects adults with initial intra-oral manifestations. In the presence of abnormal gingival or alveolar lesions, a non-odontogenic disease should be suspected and the appropriate diagnostic test should be performed. PMID:26254375

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

    Directory of Open Access Journals (Sweden)

    Ratner Marcia H.

    2014-09-01

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

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

    OpenAIRE

    M. S. S. R. K. N Sarma; C. Raghava Reddy; K.NIRANJAN

    2009-01-01

    5.5 MHz HF Doppler radar observations of Sporadic E over an Indian low latitude station, Visakhapatnam (17.7° N, 83.3° E and Dip 20°) with 10 s resolution showed quasi-periodic variations of the echo strength and Doppler velocity variations with periods of a few minutes to a few tens of minutes. The echo strength and Doppler velocity variations with time in different range bins of the ES echo showed variations which are some ti...

  7. Astrocytes from Familial and Sporadic ALS Patients are Toxic to Motor Neurons

    OpenAIRE

    Haidet-Phillips, Amanda M.; Hester, Mark E; Miranda, Carlos J; Meyer, Kathrin; Braun, Lyndsey; Frakes, Ashley; Song, SungWon; Likhite, Shibi; Murtha, Matthew J; Foust, Kevin D; Rao, Meghan; Eagle, Amy; Kammesheidt, Anja; Christensen, Ashley; Mendell, Jerry R.

    2011-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron (MN) disease with astrocytes implicated as a significant contributor to MN death in familial ALS (fALS)1–5. However, these conclusions, in part, derive from rodent models of fALS based upon dominant mutations within the superoxide dismutase 1 (SOD1) gene which account for less than 2% of all ALS cases2, 4, 5. Here, we generated astrocytes from post-mortem tissue from both fALS and sporadic ALS (sALS) patients, and show that astrocyte...

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

    Directory of Open Access Journals (Sweden)

    A. J. Foppiano

    2008-07-01

    Full Text Available 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 differences at least for some Es types during winter.

  9. Seasonal tidal variability and descent of midlatitude sporadic layers at Arecibo

    International Nuclear Information System (INIS)

    Complete text of publication follows. Contrary to what the name implies, sporadic E layers (Es) follow regular daily patterns in variability and altitude descent, determined primarily by vertical wind shears in the lower thermosphere. Here, a novel method is used to analyze a large data set of high-resolution sporadic E layer incoherent scatter radar (ISR) measurements. These were made at Arecibo (Geog. Lat. ?18 deg N; Magnetic Dip ? 50 deg) over many years with ISR runs lasting from several hours to several days, covering all seasons. A new methodology is applied, in which both weak and strong layers are clearly traced by using the vertical electron density gradient as a function of altitude and time. By taking a time base equal to the 24-hour local day, statistics were obtained on the seasonal behavior of the diurnal and semidiurnal tidal variability and altitude descent patterns of sporadic E. It turns out that, the diurnal tide is the key agent responsible for the formation of sporadic E at lower altitude for all seasons. Presumably, the layers form at tidal convergence nodes near 108 km at ?06 h local time (LT) and move with the vertical tidal phase speed down to altitudes below 90 km in about 24 hours. In addition, a weaker diurnal trace is also seen at higher altitudes only during summer, starting at ?125 km near 06 LT and moving downwards at about the same speed as the dominant Es trace at lower heights. At higher altitudes, there are two prevailing layers formed by vertical wind shears associated mainly with semidiurnal tides. These include: 1) a daytime layer starting at ?130 km around midday and descending down to 105 km by local midnight, and 2) a less frequent and weaker nighttime layer which starts prior to midnight at ?130 km, descending downwards at somewhat faster rate to reach 110 km by sunrise. The diurnal and semidiurnal-like pattern prevails, with some differences, in all seasons. These results can be useful in the study of the diurnal and semidiurnal tidal characteristics in the lower thermosphere between 90 and 130 km.

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

    Directory of Open Access Journals (Sweden)

    Marocchi Alessandro

    2008-05-01

    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.

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

    Czech Academy of Sciences Publication Activity Database

    Mošna, Zbyšek; Koucká Knížová, Petra

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

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

    DEFF Research Database (Denmark)

    Schlehofer, B; Schlaefer, K; Blettner, M; Berg, Gabriele; Böhler, E; Hettinger, I; Kunna-Grass, K; Wahrendorf, J; Schüz, J

    2007-01-01

    The only known risk factor for sporadic acoustic neuroma is high-dose ionising radiation. Environmental exposures, such as radiofrequency electromagnetic fields and noise are under discussion, as well as an association with allergic diseases. We performed a population-based case-control study in...... Germany investigating these risk factors in 97 cases with acoustic neuroma, aged 30 to 69 years, and in 194 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multiple logistic regression models. Increased risks were found for exposure to persistent noise (OR=2...

  13. Discovering interactions among BRCA1 and other candidate genes associated with sporadic breast cancer

    OpenAIRE

    Lo, Shaw-Hwa; Chernoff, Herman; Cong, Lei; Ding, Yuejing; Zheng, Tian

    2008-01-01

    Analysis of a subset of case-control sporadic breast cancer data, [from the National Cancer Institute's Cancer Genetic Markers of Susceptibility (CGEMS) initiative], focusing on 18 breast cancer-related genes with 304 SNPs, indicates that there are many interesting interactions that form two- and three-way networks in which BRCA1 plays a dominant and central role. The apparent interactions of BRCA1 with many other genes suggests the conjecture that BRCA1 serves as a protective gene and that s...

  14. Myopathy in a rhesus monkey with biopsy findings similar to human sporadic inclusion body myositis.

    Science.gov (United States)

    Skuk, Daniel; Goulet, Marlyne; Paradis, Martin; Tremblay, Jacques P

    2013-02-01

    A rhesus macaque with generalized muscle atrophy and musculotendinous contractures was detected in our research center. Muscle biopsies showed myofibers with rimmed vacuoles and eosinophilic hyaline inclusions, accumulations of CD8+ and CD4+ lymphocytes and expression of major histocompatibility complex class I in myofibers. Intracellular inclusions were positive to Congo red. Semithin sections and transmission electron microscopy showed autophagic vacuoles within myofibers and myonuclei with inclusions of filaments. These morphological observations conform with the diagnostic criteria of human sporadic inclusion body myositis. This is the first report of this myopathy in nonhuman primates. PMID:23200905

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

    DEFF Research Database (Denmark)

    Mølbak, Kåre; Neimann, Jacob

    2002-01-01

    In a prospective case-control study of sporadic Salmonella Enteritidis infection in Denmark (1997-1999), foreign travel was reported by 25% of 455 case patients and 8% of 507 controls (odds ratio (OR) = 3.7, 95% confidence interval (CI): 2.4, 5.5). Among nontravelers, 80% of 335 cases and 81% of 467 controls had consumed eggs or dishes containing raw or undercooked eggs during the week before disease onset or interview, while 35% of cases and 19% of controls had incurred this exposure the day be...

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

    Directory of Open Access Journals (Sweden)

    Fernandez Bridget A

    2012-08-01

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

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

    OpenAIRE

    K.-I. Oyama; K. Hibino; Abe, T.; Pfaff, R.; Yokoyama, T.; Liu, J.Y.

    2008-01-01

    The electron temperature (Te), electron density (Ne), and two components of the electric field were measured from the height of 90 km to 150 km by one of the sounding rockets launched during the SEEK-2 campaign. The rocket went through sporadic E layer (Es) at the height of 102 km–109 km during ascent and 99 km–108 km during decent, respectively. The energy density of ...

  18. Degree of Schedulability of Mixed-Criticality Real-time Systems with Probabilistic Sporadic Tasks

    DEFF Research Database (Denmark)

    Boudjadar, Jalil; David, Alexandre

    2014-01-01

    We present the concept of degree of schedulability for mixed-criticality scheduling systems. This concept is given in terms of the two factors 1) Percentage of Missed Deadlines (PoMD), and 2) Degradation of the Quality of Service (DoQoS). The novel aspect is that we consider task arrival patterns that follow user-defined continuous probability distributions. We determine the degree of schedulability of a single scheduling component which can contain both periodic and sporadic tasks using statistical model checking in the form of UPPAAL SMC. We support uniform, exponential, Gaussian and any user-defined probability distribution.

  19. The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer.

    Science.gov (United States)

    Lipkin, Steven M; Rozek, Laura S; Rennert, Gad; Yang, Wei; Chen, Peng-Chieh; Hacia, Joseph; Hunt, Nathan; Shin, Brian; Fodor, Steve; Kokoris, Mark; Greenson, Joel K; Fearon, Eric; Lynch, Henry; Collins, Francis; Gruber, Stephen B

    2004-07-01

    Most susceptibility to colorectal cancer (CRC) is not accounted for by known risk factors. Because MLH1, MSH2 and MSH6 mutations underlie high-penetrance CRC susceptibility in hereditary nonpolyposis colon cancer (HNPCC), we hypothesized that attenuated alleles might also underlie susceptibility to sporadic CRC. We looked for gene variants associated with HNPCC in Israeli probands with familial CRC unstratified with respect to the microsatellite instability (MSI) phenotype. Association studies identified a new MLH1 variant (415G-->C, resulting in the amino acid substitution D132H) in approximately 1.3% of Israeli individuals with CRC self-described as Jewish, Christian and Muslim. MLH1 415C confers clinically significant susceptibility to CRC. In contrast to classic HNPCC, CRCs associated with MLH1 415C usually do not have the MSI defect, which is important for clinical mutation screening. Structural and functional analyses showed that the normal ATPase function of MLH1 is attenuated, but not eliminated, by the MLH1 415G-->C mutation. The new MLH1 variant confers a high risk of CRC and identifies a previously unrecognized mechanism in microsatellite-stable tumors. These studies suggest that variants of mismatch repair proteins with attenuated function may account for a higher proportion of susceptibility to sporadic microsatellite-stable CRC than previously assumed. PMID:15184898

  20. Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy.

    Science.gov (United States)

    Lal, Dennis; Pernhorst, Katharina; Klein, Karl Martin; Reif, Philipp; Tozzi, Rossana; Toliat, Mohammad R; Winterer, Georg; Neubauer, Bernd; Nürnberg, Peter; Rosenow, Felix; Becker, Felicitas; Lerche, Holger; Kunz, Wolfram S; Kurki, Mitja I; Hoffmann, Per; Becker, Albert J; Perucca, Emilio; Zara, Federico; Sander, Thomas; Weber, Yvonne G

    2015-09-01

    Partial deletions of the RBFOX1 gene encoding the neuronal splicing regulator have been reported in a range of neurodevelopmental diseases including idiopathic/genetic generalized epilepsy (IGE/GGE), childhood focal epilepsy, and self-limited childhood benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy), and autism. The protein regulates alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. Herein, we examined whether structural deletions affecting RBFOX1 exons confer susceptibility to common forms of juvenile and adult focal epilepsy syndromes. We screened 807 unrelated patients with sporadic focal epilepsy, and we identified seven hemizygous exonic RBFOX1 deletions in patients with sporadic focal epilepsy (0.9%) in comparison to one deletion found in 1,502 controls. The phenotypes of the patients carrying RBFOX1 deletions comprise magnetic resonance imaging (MRI)-negative epilepsy of unknown etiology with frontal and temporal origin (n = 5) and two patients with temporal lobe epilepsy with hippocampal sclerosis. The epilepsies were largely pharmacoresistant but not associated with intellectual disability. Our study extends the phenotypic spectrum of RBFOX1 deletions as a risk factor for focal epilepsy and suggests that exonic RBFOX1 deletions are involved in the broad spectrum of focal and generalized epilepsies. PMID:26174448

  1. Genotype-dependent differences in S12-RNase expression lead to sporadic self-compatibility.

    Science.gov (United States)

    Qi, X; Luu, D T; Yang, Q; Maës, O; Matton, D P; Morse, D; Cappadocia, M

    2001-02-01

    Sporadic self-compatibility, the occasional fruit formation after otherwise incompatible pollinations, has been observed in some S12-containing genotypes of Solanum chacoense but not in others. We have sequenced this S12 allele and analyzed its expression in four different genotypes. The S12-RNase levels were generally less abundant than those of other S-RNases present in the same plants. In addition, two-fold and five-fold differences in the amount of S12-RNase and S12 RNA, respectively, were observed among the genotypes analyzed. A comparison with the genetic data showed that genotypes with the highest levels were fully and permanently self-incompatible, whereas those with the lowest levels were those in which sporadic self-compatibility had been observed. The mature protein contains four potential glycosylation sites and genotype-specific differences in the pattern of glycosylation are also observed. Our results suggest the presence of modifier genes which affect, in a genotype-dependent manner, the level of expression and the post-translational modification of the S12-RNase. PMID:11292075

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

    Directory of Open Access Journals (Sweden)

    Xia Ningshao

    2011-04-01

    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.

  3. Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment.

    Science.gov (United States)

    Chakrabarti, Sasanka; Khemka, Vineet Kumar; Banerjee, Anindita; Chatterjee, Gargi; Ganguly, Anirban; Biswas, Atanu

    2015-08-01

    Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, pro-inflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors. PMID:26236550

  4. Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma?

    Science.gov (United States)

    Cordioli, Maria Isabel C Vieira; Moraes, Lais; Cury, Adriano Namo; Cerutti, Janete M

    2015-12-01

    Data from the National Cancer Institute and from the literature have disclosed an increasing incidence of thyroid cancer in children, adolescents and adults. Although children and adolescents with thyroid cancer tend to present with more advanced disease than adults, their overall survival rate is excellent; however, there is no clear explanation for the differences observed in the clinicopathological outcomes in these age groups. There has been an ongoing debate regarding whether the clinicopathological differences may be due to the existence of distinct genetic alterations. Efforts have been made to identify these acquired genetic abnormalities that will determine the tumor's biological behavior and ultimately allow molecular prognostication. However, most of the studies have been performed in radiation-exposed pediatric thyroid carcinoma. Therefore, our understanding of the role of these driver mutations in sporadic pediatric differentiated thyroid cancer development is far from complete, and additionally, there is a strong need for studies in both children and adolescents. The aim of this review is to present an extensive literature review with emphasis on the molecular differences between pediatric sporadic and radiation-exposed differentiated thyroid carcinomas and adult population. PMID:26307021

  5. Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer

    International Nuclear Information System (INIS)

    Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02–1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear

  6. Young-onset CJD: age and disease phenotype in variant and sporadic forms.

    Science.gov (United States)

    Corato, Manuel; Cereda, Cristina; Cova, Emanuela; Ferrarese, Carlo; Ceroni, Mauro

    2006-01-01

    Since 1996, there have been over 140 reports of a Creutzfeldt-Jakob disease variant (vCJD), with a striking prevalence of these cases in the UK. The main peculiarity of vCJD is its onset in young people, but other features also distinguish it from sporadic CJD. Despite epidemiological data suggesting a link with bovine spongiform encephalopathy, the origin of vCJD is not completely understood. We hypothesized that the onset of vCJD at a young age might contribute to the disease phenotype. We searched the Medline/PubMed database for all case reports of CJD in the under-30s and selected 20 sporadic CJD patients with a median age at onset of 25.5 years. Our series displays a long disease duration and other vCJD-like features, suggesting that CJD in young people is different from classic CJD and that the vCJD phenotype may be partly related to young age. PMID:17367581

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

    Directory of Open Access Journals (Sweden)

    Rafati Maryam

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    R. T. Tsunoda

    2005-10-01

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

  9. Early detection of sporadic pancreatic cancer: strategic map for innovation--a white paper.

    Science.gov (United States)

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

    2015-07-01

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

  10. Peripheral blood lymphocyte to monocyte ratio identifies high-risk adult patients with sporadic Burkitt lymphoma.

    Science.gov (United States)

    Wang, Liang; Wang, Hua; Xia, Zhong-Jun; Huang, Hui-Qiang; Jiang, Wen-Qi; Lin, Tong-Yu; Lu, Yue

    2015-10-01

    Adult sporadic Burkitt lymphoma (BL) is a rare subtype of lymphoma. In this retrospective study, we investigated the prognostic value of pretreatment lymphocyte to monocyte ratio (LMR) in a cohort of 62 patients. Using LMR <2.6 as the optimal cutoff point, 24 patients (38.7 %) had LMR <2.6. The complete response rates in high-LMR group and low-LMR group were 90.9 and 65.0 %, respectively (P?=?0.019). At a median follow-up time of 41 months, the 3-year progression-free survival (PFS) rate and overall survival (OS) rates were 76 and 80 %, respectively. In a multivariate Cox regression model, it was found that the presence of bone marrow infiltration and low LMR were independently adverse prognostic factors for both PFS and OS. In the whole group, the addition of rituximab to treatment did not benefit patients significantly in PFS and OS. In subgroup analysis, in patients with high LMR, addition of rituximab can significantly improve survival outcomes (P?=?0.046). In conclusion, we firstly found that low LMR (<2.60) was an independently adverse prognostic factor in adult patients with sporadic BL. Intensive chemotherapy could cure the majority of patients in our study, and the pretreatment LMR might predict the value of rituximab in this age population. PMID:26082333

  11. DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy

    Scientific Electronic Library Online (English)

    Osorio, Abath Neto; Cristiane de Araújo, Martins; Mary, Carvalho; Gerson, Chadi; Katia Werneck, Seitz; Acary Souza Bulle, Oliveira; Umbertina Conti, Reed; Jocelyn, Laporte; Edmar, Zanoteli.

    2015-06-01

    Full Text Available Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes o [...] f inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases.

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

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

    Salmonella spp. and Campylobacter spp. are widespread and important causes of human illness worldwide. Disease is most frequently associated with foodborne transmission, but other routes of exposure, such as direct contact with live animals and person-to-person transmission, are recognized. Identifying the most important sources of human disease is essential for prioritizing food safety interventions and setting public health goals. Numerous case-control studies of sporadic infections of salmonellosis and campylobacteriosis have been published. These studies investigate a variety of potential risk factors for disease, and often use different methodologies and settings. Systematic reviews (SR) consist of a formal process for literature review focused on a specific research question, and include the identification of relevant literature, quality assessment of relevant studies, summarization or statistical analysis of data, and conclusions. With the objective of identifying the most important risk factors for human sporadic salmonellosis and campylobacteriosis, we performed a SR of case-control studies and meta-analysis of the obtained results. From 1,295 identified references, 132 passed the relevance screening, 73 passed the quality assessment stage, and data was extracted from 72. Of these studies, 34 investigated risk factors for human salmonellosis and 37 focused on campylobacteriosis. Heterogeneity between the studies and possible sources of bias were assessed. Information on exposures of cases and controls, and estimated odds ratios for investigated risk factors were recovered and analyzed with the purpose of assisting attribution of human disease. The most significant results were illustrated using forest plots.

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

    Directory of Open Access Journals (Sweden)

    T. Ono

    2005-10-01

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

  14. Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement

    Science.gov (United States)

    Chiapinotto Spiazzi, Cristiano; Bucco Soares, Melina; Pinto Izaguirry, Aryele; Musacchio Vargas, Laura; Zanchi, Mariane Magalhães; Frasson Pavin, Natasha; Ferreira Affeldt, Ricardo; Seibert Lüdtke, Diogo; Prigol, Marina; Santos, Francielli Weber

    2015-01-01

    Alzheimer's disease (AD) is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se) in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, A?, Se, and A? + Se. Single administration of A? peptide (fragments 25–35; 3?nmol/3??L) or distilled water was administered via intracerebroventricular (i.c.v.) injection. Selenofuranoside (5?mg/kg) or vehicle (canola oil) was administered orally 30?min before A? and for 7 subsequent days. Memory was tested through the Morris water maze (MWM) and step-down passive-avoidance (SDPA) tests. Antioxidant defenses along with reactive species (RS) were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the A? group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the A? group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies. PMID:26090073

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

    LENUS (Irish Health Repository)

    Gbadegesin, Rasheed A

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  17. Performance of D-criteria in isolating meteor showers from the sporadic background in an optical data set

    Science.gov (United States)

    Moorhead, Althea V.

    2016-02-01

    Separating meteor showers from the sporadic meteor background is critical for the study of both showers and the sporadic complex. The linkage of meteors to meteor showers, to parent bodies, and to other meteors is done using measures of orbital similarity. These measures often take the form of so-called D-parameters and are generally paired with some cutoff value within which two orbits are considered related. The appropriate cut-off value can depend on the size of the data set (Southworth & Hawkins 1963), the sporadic contribution within the observed size range (Jopek 1995), or the inclination of the shower (Galligan 2001). If the goal is to minimize sporadic contamination of the extracted shower, the cut-off value should also reflect the strength of the shower compared to the local sporadic background. In this paper, we present a method for determining, on a per-shower basis, the orbital similarity cut-off value that corresponds to a chosen acceptable false-positive rate. This method also assists us in distinguishing which showers are significant within a set of data. We apply these methods to optical meteor observations from the NASA All-Sky and Southern Ontario Meteor Networks.

  18. Performance of D-criteria in isolating meteor showers from the sporadic background in an optical data set

    CERN Document Server

    Moorhead, Althea V

    2015-01-01

    Separating meteor showers from the sporadic meteor background is critical for the study of both showers and the sporadic complex. The linkage of meteors to meteor showers, to parent bodies, and to other meteors is done using measures of orbital similarity. These measures often take the form of so-called D-parameters and are generally paired with some cutoff value within which two orbits are considered related. The appropriate cutoff value can depend on the size of the data-set (Southworth & Hawkins 1963), the sporadic contribution within the observed size range (Jopek 1995), or the inclination of the shower (Galligan 2001). If the goal is to minimize sporadic contamination of the extracted shower, the cutoff value should also reflect the strength of the shower compared to the local sporadic background. In this paper, we present a method for determining, on a per-shower basis, the orbital similarity cutoff value that corresponds to a chosen acceptable false-positive rate. This method also assists us in dis...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    AIM: Patients with hereditary non-polyposis colorectal cancer (HNPCC) seem to have a better prognosis than those with sporadic colon cancer (CC)s. The aim was to compare survival after stage III CC in patients with HNPCC with those having sporadic CC. METHOD: 230 patients with hereditary cancer from The Danish HNPCC-Register and 3557 patients with sporadic CC from The Danish Colorectal Cancer Database, diagnosed during May 2001-December 2008 were included. HNPCC patients were classified accordin...

  20. Lack of association between 14-3-3 beta gene (YWHAB) polymorphisms and sporadic Creutzfeldt-Jakob disease (CJD).

    Science.gov (United States)

    Jeong, Byung-Hoon; Jin, Hyoung-Tae; Choi, Eun-Kyoung; Carp, Richard I; Kim, Yong-Sun

    2012-12-01

    14-3-3 proteins are highly abundant in brain tissue. The presence of 14-3-3 at elevated levels in the cerebrospinal fluid has been considered as a biomarker for sporadic Creutzfeldt-Jakob disease (CJD). Recent studies showed that 14-3-3 beta protein interacts with the N-terminal amino acids 1-38 and with the central hydrophobic amino acids 106-126 of prion protein. This interaction may indicate a role of 14-3-3 beta in the biological function of PrP and in the pathogenesis of prion disease. An association between the polymorphisms of 14-3-3 beta gene (YWHAB) and prion disease has not been reported previously. In order to investigate whether YWHAB polymorphisms are associated with sporadic CJD in the Korean population, we compared genotype distribution and allele frequencies of six YWHAB polymorphisms in 244 sporadic CJD patients and 219 healthy Koreans. Of six polymorphisms identified, four single nucleotide polymorphisms (SNPs) were known previously (c.60A>C, c.685-120G>A, c.685-89G>A, 92G>A) and two SNPs were novel (c.185T>A and c.377A>C). Two novel polymorphisms were identified within 3'-untranslated region of exon 6. We could not find significant differences in genotype and allele frequencies of the six YWHAB polymorphisms between the controls and sporadic CJD patients. These results indicate that these six YWHAB polymorphisms are not associated with the genetic susceptibility to sporadic CJD. This is the first genetic association study of YWHAB in sporadic CJD. PMID:23053962

  1. 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 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

  2. Pattern of Respiratory Deterioration in Sporadic Amyotrophic Lateral Sclerosis According to Onset Lesion by Using Respiratory Function Tests

    OpenAIRE

    Kim, Dong-Gun; Hong, Yoon-Ho; Shin, Je-Young; Lee, Kwang-Woo; Park, Kyung Seok; Seong, Seung-Yong; Sung, Jung-Joon

    2015-01-01

    Most amyotrophic lateral sclerosis (ALS) patients show focal onset of upper and lower motor neuron signs and spread of symptoms to other regions or the other side clinically. Progression patterns of sporadic ALS are unclear. The aim of this study was to evaluate the pattern of respiratory deterioration in sporadic ALS according to the onset site by using respiratory function tests. Study participants included 63 (42 cervical-onset [C-ALS] and 21 lumbosacral-onset [L-ALS]) ALS patients and 31 ...

  3. Performance of D-criteria in isolating meteor showers from the sporadic background in an optical data set

    OpenAIRE

    Moorhead, Althea V.

    2015-01-01

    Separating meteor showers from the sporadic meteor background is critical for the study of both showers and the sporadic complex. The linkage of meteors to meteor showers, to parent bodies, and to other meteors is done using measures of orbital similarity. These measures often take the form of so-called D-parameters and are generally paired with some cutoff value within which two orbits are considered related. The appropriate cutoff value can depend on the size of the data-set (Southworth & H...

  4. Hypokalemia-Induced Rhabdomyolysis by Primary Aldosteronism Coexistent With Sporadic Inclusion Body Myositis.

    Science.gov (United States)

    Lee, Jong Ha; Kim, Eunkuk; Chon, Suk

    2015-10-01

    We describes a patient with hypokalemia-induced rhabdomyolysis due to primary aldosteronism (PA), who suffered from slowly progressive muscle weakness after laparoscopic adrenalectomy, and was later diagnosed with coexisting sporadic inclusion body myositis (sIBM). A 54-year-old Asian male presented with severe muscle weakness of both lower extremities. Laboratory findings showed profound hypokalemia, and extreme elevation of the serum creatine phosphokinase levels, suggestive of hypokalemia-induced rhabdomyolysis. Further evaluation strongly suggested PA by an aldosterone-producing adenoma, which was successfully removed surgically. However, muscle weakness slowly progressed one year after the operation and a muscle biopsy demonstrated findings consistent with sIBM. This case is the first report of hypokalemia-induced rhabdomyolysis by PA coexistent with sIBM, to the best of our knowledge. PMID:26605182

  5. C9ORF72 repeat expansion is not detected in sporadic ataxia patients in mainland China.

    Science.gov (United States)

    He, Miao; Yan, Wei-Qian; Zeng, Sheng; Liu, Zhen; Zhou, Yao; Zeng, Xian-Feng; Zeng, Jun-Sheng; Jiang, Hong; Shen, Lu; Tang, Bei-Sha; Wang, Jun-Ling

    2016-02-15

    Expansion of a GGGGCC hexanucleotide repeat in the gene C9ORF72 is a common pathogenic mutation in families with autosomal dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In order to understand whether pathogenic GGGGCC expansions of C9ORF72 are associated with spinocerebellar ataxia (SCA) in mainland China, we performed an experiment to determine the prevalence of pathogenic hexanucleotide expansions of C9ORF72 in a large cohort of Chinese Han patients with SCA. 411 sporadic patients with SCA and 314 healthy controls were screened for pathogenic hexanucleotide expansions of C9ORF72 utilizing a repeat primed polymerase chain reaction assay. However, no pathological repeat expansion of C9ORF72 was detected in either patients or controls. We therefore conclude that an expansion in C9ORF72 may not play a significant role in SCA in our cohort. However, more studies are needed to draw conclusions for the general population. PMID:26810537

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

    Directory of Open Access Journals (Sweden)

    Mauro Rampini

    2012-06-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  8. Risk factors for sporadic infection with Salmonella Infantis: a matched case-control study.

    Science.gov (United States)

    Bassal, R; Reisfeld, A; Nissan, I; Agmon, V; Taran, D; Schemberg, B; Cohen, D; Shohat, T

    2014-04-01

    This matched case-control study investigated the risk factors for sporadic Salmonella Infantis infection in 263 affected children and 263 age-, gender- and neighbourhood-matched controls. Information about exposure to potential risk factors was obtained via telephone interview and evaluated by conditional logistic regression analysis. Age groups ? 1 year (n=77) and >1 year (n = 186) were analysed separately. Of those aged ? 1 year, breastfeeding was a significant protective factor against infection [matched odds ratio (mOR) 0.24, 95% confidence interval (CI) 0.10-0.59, P number of children in the household (mOR 0.72, 95% CI 0.58-0.88, P Breastfeeding should be strongly encouraged by public health authorities. The public must be educated on stringent hygiene practices, especially proper cooking of eggs to reduce infection rates. PMID:23879895

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

    Science.gov (United States)

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

    2014-01-01

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

  10. Annual variation and synodic modulation of the sporadic meteoroid flux to the Moon

    Science.gov (United States)

    Szalay, Jamey R.; Horányi, Mihály

    2015-12-01

    The Lunar Dust Experiment on board NASA's Lunar Atmosphere and Dust Environment Explorer discovered a permanently present, asymmetric dust cloud engulfing the Moon, sustained by meteoroid bombardment. It is most dense at 5-8 lunar local time, with a peak density canted sunward. Here we present analysis on the variation of the cloud density during January to April 2014. We find the lunar dust cloud in the Moon's equatorial plane to be dominantly produced by impacts from three known sporadic meteoroid sources: apex, helion, and antihelion, listed in order of their contribution to ejecta production. The cloud density is also modulated by the Moon's orbital motion about the Earth, peaking during its waning gibbous phase. These results are complementary to ground-based measurements and indicate the Moon can be used as a very sensitive large area dust detector to characterize the meteoroid environment at 1 AU.

  11. Atypical case of sporadic Creutzfeldt-Jakob disease (CJD) in a young adult.

    Science.gov (United States)

    Kozubski, W; Wender, M; Szczech, J; Lenart-Jankowska, D; Liberski, P P

    1998-01-01

    The great concern exists that new variant of CJD (nvCJD) developed as a result of exposure to bovine spongiform encephalopathy (BSE)-infected meat products. Therefore, all cases of CJD in the young, as the one of ours are the matter of interest. The 21-year-old female developed a rapid progression of pyramidal, extrapyramidal and cerebellar signs, visual loss and psychiatric symptoms, leading to death in 16 weeks. The microscopic features were: a neuronal loss accentuated in cerebral cortex with extensive astroglia proliferation and spongiform changes. Immunohistochemical staining, revealed the presence of "synaptic" deposits of PrP in the cerebral cortex and in the cerebellum. No florid amyloid plaques were present. The case was diagnosed as a sporadic CJD, with some features of Heidenhein variant (visual symptoms) and corticostriatocerebellar category. The pathological findings excluded a nv CJD which is linked with BSE. PMID:10079605

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

    Science.gov (United States)

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

    2012-01-01

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

  13. Sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery: A case report

    Directory of Open Access Journals (Sweden)

    Takahiro Kinoshita

    2010-11-01

    Full Text Available We report a case of sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery. A 38-year old asymptomatic woman was referred to our hospital for evaluation of a submucosal tumor of the stomach. Endoscopic examination showed a solitary submucosal tumor without ulceration or central depression on the posterior wall of the antrum and biopsy specimens were not sufficient to determine the diagnosis. Endoscopic ultrasound revealed a tumor nearly 2 cm in diameter arising from the muscle layer and a computed tomography scan showed the tumor enhanced in the arterial phase. Laparoscopic wedge resection was performed for definitive diagnosis. Pathologically, the tumor was shown to be gastric carcinoid infiltrating the muscle layer which indicated the probability of lymph node metastasis. Serum gastrin levels were normal. As a radical treatment, laparoscopy-assisted distal gastrectomy with regional lymphadenectomy was performed 3 wk after the initial surgery. Finally, pathological examination revealed no lymph node metastasis.

  14. Down syndrome individuals with Alzheimer's disease have a distinct neuroinflammatory phenotype compared to sporadic Alzheimer's disease.

    Science.gov (United States)

    Wilcock, Donna M; Hurban, Jennifer; Helman, Alex M; Sudduth, Tiffany L; McCarty, Katie L; Beckett, Tina L; Ferrell, Joshua C; Murphy, M Paul; Abner, Erin L; Schmitt, Frederick A; Head, Elizabeth

    2015-09-01

    Down syndrome (DS) is the most common genetic cause of intellectual disability and is primarily caused by the triplication of chromosome 21. The overexpression of amyloid precursor protein gene may be sufficient to drive Alzheimer's disease (AD) neuropathology that is observed in virtually all individuals with DS by the age of 40 years. There is relatively little information about inflammation in the DS brain and how the genetics of DS may alter inflammatory responses and modify the course of AD pathogenesis in this disorder. Using the macrophage classification system of M1, M2a, M2b, and M2c inflammatory phenotypes, we have shown that the early stages of AD are associated with a bias toward an M1 or M2a phenotype. In later stages of AD, markers of M1, M2a and M2c are elevated. We now report the inflammatory phenotype in a DS autopsy series to compare this with the progression in sporadic AD. Tissue from young DS cases (under 40 years of age, pre-AD) show a bias toward M1 and M2b states with little M2a or M2c observed. Older DS cases (over 40 with AD pathology) show a distinct bias toward an M2b phenotype. Importantly, this is distinct from sporadic AD where the M2b phenotype has been rarely, if ever observed in postmortem studies. Stimulated by immune complex activation of microglial cells and toll-like receptor activation, the M2b phenotype represents a unique neuroinflammatory state in diseased brain and may have significant implications for therapeutic intervention for persons with DS. PMID:26103884

  15. Alterations of the blood-spinal cord barrier in sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Sasaki, Shoichi

    2015-12-01

    The blood-spinal cord barrier (BSCB) of the spinal cord capillary consists of non-fenestrated endothelial cells with tight junctions, basal laminae, pericytes and astrocyte feet processes, referred to as a "neurovascular unit." The primary function of the BSCB is the maintenance and control of homeostasis of the spinal cord parenchyma by the selective transport of molecules and cells from the systemic compartment. Dysfunction of the BSCB shows important function in the etiology or progression of several pathological conditions of the spinal cord, including amyotrophic lateral sclerosis (ALS). However, the role of BSCB in the pathogenesis of ALS is still unclear. Here the changes of BSCB in sporadic ALS patients were studied by electron microscopy to determine whether the BSCB is disrupted and involved in the pathogenesis of motor neuron degeneration. A total of 358 and 366 cross-sectioned capillaries were quantitatively examined in controls and ALS patients, respectively. The frequency of degenerated endothelia and pericytes, vacuolar changes of the cytoplasm in the endothelia and pericytes, and the replication of basement membranes was significantly higher in ALS patients than in the controls (P?=?0.0175). The areas of the capillaries with diameters of???5?µm in the ALS patients were significantly smaller than those in the controls (P?=?0.0124). The frequency of collagen fiber content of more than a moderate degree around the perivascular space was significantly higher in the ALS patients compared to the controls (P?=?0.048), although there was no significant difference in the mild degree of accumulation of collagen fibers. Thus, the BSCB may be disrupted in sporadic ALS patients due to increased permeability and reduced microcirculation, leading to motor neuron degeneration and to the progression of the disease. PMID:26242689

  16. A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson's disease.

    Science.gov (United States)

    Kun-Rodrigues, Celia; Ganos, Christos; Guerreiro, Rita; Schneider, Susanne A; Schulte, Claudia; Lesage, Suzanne; Darwent, Lee; Holmans, Peter; Singleton, Andrew; Bhatia, Kailash; Bras, Jose

    2015-12-01

    Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exome sequencing in full parent-child trios where the proband presents with typical PD to unequivocally identify de novo mutations. This approach allows us to test all genes in the genome in an unbiased manner. We have identified and confirmed 20 coding de novo mutations in 21 trios. We have used publicly available population genetic data to compare variant frequencies and our independent in-house dataset of exome sequencing in PD (with over 1200 cases) to identify additional variants in the same genes. Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by various sources of data to be involved in PD. We show that these genes are reported to be within a protein-protein interaction network with PD genes and that they contain additional rare, case-specific, mutations in our independent cohort of PD cases. Our results support the involvement of these three genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the identification of novel disease-causing genes. PMID:26362251

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

    Science.gov (United States)

    Mošna, Z.; Koucká Knížová, P.

    2012-12-01

    The present study mainly concerns the wave-like activity in the ionospheric sporadic E layer (Es) and in the lower lying stratosphere. The proposed analysis involves parameters describing the state of plasma in the sporadic E layer. Critical frequencies foEs and layer heights hEs were measured at the Pruhonice station (50°N, 14.5°E) during summer campaigns 2004, 2006 and 2008. Further, we use neutral atmosphere (temperature data at 10 hPa) data from the same time interval. The analysis concentrates on vertically propagating wave-like structures within distant atmospheric regions. By means of continuous wavelet transform (CWT) we have detected significant wave-like oscillation at periods covering tidal and planetary oscillation domains both in the Es layer parameters (some of them were reported earlier, for instance in works of Abdu et al., 2003; Pancheva and Mitchel, 2004; Pancheva et al., 2003; Šauli and Bourdillon, 2008) and in stratospheric temperature variations. Further analyses using cross wavelet transform (XWT) and wavelet coherence analysis (WTC) show that despite high wave-like activity in a wide period range, there are only limited coherent wave-like bursts present in both spectra. Such common coherent wave bursts occur on periods close to eigen-periods of the terrestrial atmosphere. We suppose that vertical coupling between atmospheric regions realized by vertically propagating planetary waves occurs predominantly on periods close to those of Rossby modes. Analysis of the phase shift between data from distant atmospheric regions reveals high variability and very likely supports the non-linear scenario of the vertical coupling provided by planetary waves.

  18. Identifying high-risk areas for sporadic measles outbreaks: lessons from South Africa

    Directory of Open Access Journals (Sweden)

    Benn Sartorius

    2013-03-01

    Full Text Available OBJECTIVE: To develop a model for identifying areas at high risk for sporadic measles outbreaks based on an analysis of factors associated with a national outbreak in South Africa between 2009 and 2011. METHODS: Data on cases occurring before and during the national outbreak were obtained from the South African measles surveillance programme, and data on measles immunization and population size, from the District Health Information System. A Bayesian hierarchical Poisson model was used to investigate the association between the risk of measles in infants in a district and first-dose vaccination coverage, population density, background prevalence of human immunodeficiency virus (HIV infection and expected failure of seroconversion. Model projections were used to identify emerging high-risk areas in 2012. FINDINGS: A clear spatial pattern of high-risk areas was noted, with many interconnected (i.e. neighbouring areas. An increased risk of measles outbreak was significantly associated with both the preceding build-up of a susceptible population and population density. The risk was also elevated when more than 20% of infants in a populous area had missed a first vaccine dose. The model was able to identify areas at high risk of experiencing a measles outbreak in 2012 and where additional preventive measures could be undertaken. CONCLUSION: The South African measles outbreak was associated with the build-up of a susceptible population (owing to poor vaccine coverage, high prevalence of HIV infection and high population density. The predictive model developed could be applied to other settings susceptible to sporadic outbreaks of measles and other vaccine-preventable diseases.

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

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

    2008-01-01

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

  20. Familial ulcerative colitis in Israeli Jews: its prevalence and clinical severity compared to sporadic disease

    Science.gov (United States)

    Ben-Horin, Shomron; Tamir, Shira; Kopylov, Uri; Katz, Lion; Nadler, Moshe; Lang, Alon; Avidan, Benjamin; Chowers, Yehuda

    2011-01-01

    Background A family history of inflammatory bowel disease (IBD) is present in some ulcerative colitis (UC) patients. We aimed to investigate the familial occurrence of UC and its impact on disease severity. Methods A structured questionnaire was distributed to patients with UC. Parameters pertaining to disease severity were compared for patients with or without positive family history of IBD. Results The study group consisted of 168 UC patients with a total of 952 first degree relatives. Positive family history for IBD in a first degree relative was reported in 24 patients (14%). Six of the 336 parents (1.8%) had IBD (all with UC). There were 13 siblings with IBD (4 CD, 9 UC) out of 249 (5.4%). Seven of 376 (1.9%) offsprings had IBD (4 CD, 3 UC). Familial patients were more commonly females and have reported significantly more disease exacerbations than the sporadic group (17.7±15 versus 6.8±11, respectively, p=0.006). On multivariate analysis, familial disease was significantly and independently associated with both female sex (OR 4.1, 95% CI 1.1-14.9, p=0.04) and more exacerbations per year (annual OR 1.05, 95% CI 1.01-1.1, p=0.02). However, similar proportions of sporadic and familial patients wherever hospitalized, underwent colectomy or were treated by immune-suppressors. Conclusions Familial occurrence of UC is not uncommon among Jewish patients in Israel. The familial-genetic component may preferentially influence disease occurrence among females, and is possibly associated with more disease flares although other parameters of disease severity do not seem to be impacted. PMID:24713724

  1. Array CGH Analysis of Paired Blood and Tumor Samples from Patients with Sporadic Wilms Tumor.

    Science.gov (United States)

    Cabral de Almeida Cardoso, Leila; Rodriguez-Laguna, Lara; Del Carmen Crespo, María; Vallespín, Elena; Palomares-Bralo, María; Martin-Arenas, Rubén; Rueda-Arenas, Inmaculada; Silvestre de Faria, Paulo Antonio; García-Miguel, Purificación; Lapunzina, Pablo; Regla Vargas, Fernando; Seuanez, Hector N; Martínez-Glez, Víctor

    2015-01-01

    Wilms tumor (WT), the most common cancer of the kidney in infants and children, has a complex etiology that is still poorly understood. Identification of genomic copy number variants (CNV) in tumor genomes provides a better understanding of cancer development which may be useful for diagnosis and therapeutic targets. In paired blood and tumor DNA samples from 14 patients with sporadic WT, analyzed by aCGH, 22% of chromosome abnormalities were novel. All constitutional alterations identified in blood were segmental (in 28.6% of patients) and were also present in the paired tumor samples. Two segmental gains (2p21 and 20q13.3) and one loss (19q13.31) present in blood had not been previously described in WT. We also describe, for the first time, a small, constitutive partial gain of 3p22.1 comprising 2 exons of CTNNB1, a gene associated to WT. Among somatic alterations, novel structural chromosomal abnormalities were found, like gain of 19p13.3 and 20p12.3, and losses of 2p16.1-p15, 4q32.5-q35.1, 4q35.2-q28.1 and 19p13.3. Candidate genes included in these regions might be constitutively (SIX3, SALL4) or somatically (NEK1, PIAS4, BMP2) operational in the development and progression of WT. To our knowledge this is the first report of CNV in paired blood and tumor samples in sporadic WT. PMID:26317783

  2. Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.

    Science.gov (United States)

    Harris, Steven A; Harris, Elizabeth A

    2015-01-01

    This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-? (A?) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of A? damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials. PMID:26401998

  3. Role of Trisomy 21 Mosaicism in Sporadic and Familial Alzheimer's Disease.

    Science.gov (United States)

    Potter, Huntington; Granic, Antoneta; Caneus, Julbert

    2016-01-01

    Trisomy 21 and the consequent extra copy of the amyloid precursor protein (APP) gene and increased beta-amyloid (A?) peptide production underlie the universal development of Alzheimer's disease (AD) pathology and high risk of AD dementia in people with Down syndrome (DS). Trisomy 21 and other forms of aneuploidy also arise among neurons and peripheral cells in both sporadic and familial AD and in mouse and cell models thereof, reinforcing the conclusion that AD and DS are two sides of the same coin. The demonstration that 90% of the neurodegeneration in AD can be attributed to the selective loss of aneuploid neurons generated over the course of the disease indicates that aneuploidy is an essential feature of the pathogenic pathway leading to the depletion of neuronal cell populations. Trisomy 21 mosaicism also occurs in neurons and other cells from patients with Niemann-Pick C1 disease and from patients with familial or sporadic frontotemporal lobar degeneration (FTLD), as well as in their corresponding mouse and cell models. Biochemical studies have shown that A? induces mitotic spindle defects, chromosome mis-segregation, and aneuploidy in cultured cells by inhibiting specific microtubule motors required for mitosis. These data indicate that neuronal trisomy 21 and other types of aneuploidy characterize and likely contribute to multiple neurodegenerative diseases and are a valid target for therapeutic intervention. For example, reducing extracellular calcium or treating cells with lithium chloride (LiCl) blocks the induction of trisomy 21 by A?. The latter finding is relevant in light of recent reports of a lowered risk of dementia in bipolar patients treated with LiCl and in the stabilization of cognition in AD patients treated with LiCl. PMID:26651340

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

    Directory of Open Access Journals (Sweden)

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

    2008-01-01

    Full Text Available AIM: To study the candidate tumor suppressor genes (TSG on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by ?2 test.RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30% by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively. On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030. No relationship was detected on other loci compared with clinicopathological features.CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2 and D4S405 (4p14 locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm.

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

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

  6. Mutational profiling of sporadic versus toxin-associated brain cancer formation: initial findings using loss of heterozygosity profiling.

    Science.gov (United States)

    Ellsworth, Eric M G; Palma, John F; Spence, W Christine; Bleicher, Jamie M; Smith, Dennis M; Finkelstein, Sydney D

    2012-04-01

    The role of environmental and occupational toxin exposure as a cause of or contributing factor for cancer development and progression is incompletely understood. A unique signature of specific mutational change to discriminate toxin-exposed from sporadic cancer is generally sought but not often encountered. We report an approach to better understand cancer causality based on the measurement of the cumulative DNA damage (via loss of heterozygosity) over a defined genomic region (chromosome 3) that is applicable to archival, fixative-treated tissue and cytology specimens of cancer. Our method was applied to (1) a cohort of 10 brain tumor subjects (9 gliomas, 1 hemangioblastoma) with potential exposure to chlorinated solvents and (2) a control cohort of sporadic brain cancer controls (7 gliomas, 1 hemangioblastoma). We show that brain tumors arising in potentially toxin-exposed subjects bear a significantly higher level of passenger LOH mutations compared to sporadic cancer controls. The methodology utilized tissue microdissection, PCR amplification and capillary electrophoresis (fragment analysis for LOH determination, DNA sequencing for specific point mutations), and examined a panel of 15 microsatellite markers distributed along both arms of chromosome 3 that aimed at capturing passenger mutational change accrued during stages of clonal expansion of neoplastic cells. This proof-of-principle study using mutational profiling for passenger LOH mutational damage provides support for the utility of this approach and further studies in order to differentiate between genotoxin-associated versus sporadic (unexposed) cancer development. PMID:21964308

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

    DEFF Research Database (Denmark)

    de Pedro-Cuesta, Jesús; Mahillo-Fernández, Ignacio; Rábano, Alberto; Calero, Miguel; Cruz, Mabel; Siden, Ake; Laursen, Henning; Falkenhorst, Gerhard; Mølbak, Kåre

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Jensen, Thomas Dyrsø; Li, Jian; Wang, Kai; Lindebjerg, Jan; Kølvraa, Steen; Bolund, Lars; Jakobsen, Anders; Bruun-Petersen, Gert; Li, Shengting; Crüger, Dorthe Gylling

    2011-01-01

    Colorectal cancer (CRC) is one of the most common cancers in Denmark and in the western world in general, and the prognosis is generally poor. According to the traditional molecular classification of sporadic colorectal cancer, microsatellite stable (MSS)/chromosome unstable (CIN) colorectal...

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

    Directory of Open Access Journals (Sweden)

    Takuto Hideyama

    2011-11-01

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

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

    Science.gov (United States)

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

    2014-02-01

    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

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

    Scientific Electronic Library Online (English)

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

    2014-03-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2015-02-01

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

  13. SEEK-2 (Sporadic-E Experiment over Kyushu 2 − Project Outline, and Significance

    Directory of Open Access Journals (Sweden)

    R. Pfaff

    2005-10-01

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

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

    International Nuclear Information System (INIS)

    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. 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. HLA class I loss was seen more frequently in MSI-H tumors than in MSS tumors (p < 0.0001). Distinct mechanisms were responsible for HLA class I loss in HNPCC and sporadic MSI-H tumors. Loss of HLA class I expression was associated with ?2m loss in HNPCC tumors, but was correlated with APM component defects in sporadic MSI-H tumors (p < 0.0001). In about half of the cases, loss of expression of HLA class I was concordant with the detection of one or more mutations in the ?2m and APM components genes. 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

  15. Low prevalence of most frequent pathogenic variants of six PARK genes in sporadic Parkinson's disease.

    Science.gov (United States)

    García, Silvia; López-Hernández, Luz Berenice; Suarez-Cuenca, Juan Antonio; Solano-Rojas, Marlene; Gallegos-Arreola, Martha P; Gama-Moreno, Olga; Valdez-Anguiano, Paulina; Canto, Patricia; Dávila-Maldonado, Luis; Cuevas-García, Carlos F; Coral-Vázquez, Ramón Mauricio

    2014-01-01

    Genetic variants that confer susceptibility to Parkinson's disease (PD) show unbalanced distribution among different populations; genetic predisposition to either familial or sporadic forms of PD in Mexican-mestizo population has not been comprehensively studied. The aim of the present study was to analyze genetic variants in six PARK genes in PD patients. In total 381 individuals (173 patients, 208 controls) were genotyped for p.Gly2019Ser and p.Gly2385Arg variants of LRRK2. The p.Gly2019Ser variant was present in two patients and one healthy control; the p.Gly2385Arg variant was not found. In a subgroup of early-onset PD (EOPD), MLPA analysis was done for PARKIN (PARK2), PINK1 (PARK6), DJ-1 (PARK7), LRRK2 (PARK8), SNCA (PARK1/4) and ATP13A2 (PARK9). We found a heterozygous deletion of exon 2 in PARK2 in the youngest patient of the early-onset group, who showed limited response to antiparkinsonian therapy. Although the changes Gly2019Ser and Gly2385Arg of LRRK2 are associated with PD in different populations; they may be a rare cause of PD in our population. Novel population-specific variants may underlie PD susceptibility in Mexican mestizos. Our study suggests that the heterozygous deletion of exon 2 in the PARK2 gene is a risk factor for EOPD. PMID:24729340

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

    Directory of Open Access Journals (Sweden)

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

    2009-02-01

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

  17. Post-Accident Sporadic Releases of Airborne Radionuclides from the Fukushima Daiichi Nuclear Power Plant Site.

    Science.gov (United States)

    Steinhauser, Georg; Niisoe, Tamon; Harada, Kouji H; Shozugawa, Katsumi; Schneider, Stephanie; Synal, Hans-Arno; Walther, Clemens; Christl, Marcus; Nanba, Kenji; Ishikawa, Hirohiko; Koizumi, Akio

    2015-12-15

    The Fukushima nuclear accident (March 11, 2011) caused the widespread contamination of Japan by direct deposition of airborne radionuclides. Analysis of weekly air filters has revealed sporadic releases of radionuclides long after the Fukushima Daiichi reactors were stabilized. One major discharge was observed in August 2013 in monitoring stations north of the Fukushima Daiichi nuclear power plant (FDNPP). During this event, an air monitoring station in this previously scarcely contaminated area suddenly reported (137)Cs activity levels that were 30-fold above the background. Together with atmospheric dispersion and deposition simulation, radionuclide analysis in soil indicated that debris removal operations conducted on the FDNPP site on August 19, 2013 are likely to be responsible for this late release of radionuclides. One soil sample in the center of the simulated plume exhibited a high (90)Sr contamination (78 ± 8 Bq kg(-1)) as well as a high (90)Sr/(137)Cs ratio (0.04); both phenomena have usually been observed only in very close vicinity around the FDNPP. We estimate that through the resuspension of highly contaminated particles in the course of these earthmoving operations, gross (137)Cs activity of ca. 2.8 × 10(11) Bq has been released. PMID:26448161

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

    Science.gov (United States)

    Dorfman, Verónica Berta; Pasquini, Laura; Riudavets, Miguel; López-Costa, Juan José; Villegas, Andrés; Troncoso, Juan Carlos; Lopera, Francisco; Castaño, Eduardo Miguel; Morelli, Laura

    2011-01-01

    Alzheimer’s disease (AD) is characterized by amyloid ? (A?) accumulation in the brain and is classified as familial early-onset (FAD) or sporadic late-onset (SAD). Evidences suggest that deficits in the brain expression of insulin degrading enzyme (IDE) and neprilysin (NEP), both proteases involved in amyloid degradation, may promote A? deposition in SAD. We studied by immunohistochemistry IDE and NEP cortical expression in SAD and FAD samples carrying the E280A presenilin-1 missense mutation. We showed that IDE, a soluble peptidase, is linked with aggregated A?40 isoform while NEP, a membrane-bound protease, negatively correlates with amyloid angiopathy and its expression in the senile plaques is independent of aggregated amyloid and restricted to SAD cases. NEP, but not IDE, is over-expressed in dystrophic neurites, both proteases are immunoreactive in activated astrocytes but not in microglia and IDE was the only one detected in astrocytes of white matter from FAD cases. Collectively, our results support the notion that gross conformational changes involved in the modification from “natively folded-active” to “aggregated-inactive” IDE and NEP may be a relevant pathogenic mechanism in SAD. PMID:19019493

  19. Sporadic Hirschsprung`s disease due to a novel nonsense mutation in the RET protooncogene

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, K.M.; Donis-Keller, H.; Langer, J.C. [and others

    1994-09-01

    Hirschsprung`s disease (HSCR, aganglionic megacolon) is characterized by a lack of ganglion cells along variable lengths of the hindgut. This is most likely due to a failure of the progenitor cells (that are destined to become the ganglion cells of the submucosal and myenteric plexuses) to complete their distal migration in the colon. Recently, mutations in the RET protoocogene have been reported in association with HSCR. We report a novel nonsense mutation resulting in a severely truncated protein. Germline DNA from a panel of 6 HSCR patients was analyzed by SSCP for 20 exons of RET. Eight exons were also directly sequenced. We identified a novel mutation within RET exon 2. The mutation (TAC{sub 36}{yields}TAG{sub 36}), which occurs at nucleotide position 108, involves the replacement of tyrosine with a stop codon and results in a truncated 35 amino acid protein. This mutation is the most 5{prime} nonsense mutation reported thus far. Interestingly, the patient has no prior family history of HSCR and was also diagnosed with multiple developmental anomalies including dysplastic kidney. Recent gene targeting studies with mouse models have shown that RET is essential for normal renal development. However, a parallel phenotype has not been seen in other reported HSCR patients with RET mutations. The observations reported here provide evidence that RET plays a role in human renal development. Ongoing studies will determine the extent of RET involvement in sporadic cases of HSCR.

  20. RET single nucleotide polymorphism in Indonesians with sporadic Hirschsprung’s disease

    Directory of Open Access Journals (Sweden)

    Saryono

    2010-08-01

    Full Text Available The tyrosine kinase receptor RET, which is the protein product of the RET gene, is involved in the development of the mammalian nervous system that causes Hirschsprung’s disease (HSCR. RETs are cell surface molecules that are expressed in cells derived from the neural crest. The purpose of this study was to investigate the polymorphism of the RET gene in HSCR in the Yogyakarta population. Genomic DNA was extracted from surgically removed bowel tissues of 54 unrelated HSCR patients. Exon 2 of the RET gene was amplified by polymerase chain reaction (PCR and analyzed by restriction fragment length polymorphism (RFLP. Molecular results were compared with clinical performance of Hirschsprung patients. RET polymorphism was detected in exon 2 in all of the 54 Indonesian HSCR patients. The allelic distribution of the c135GàA polymorphism in the RET exon 2 indicated that the A allele was more frequent in patients than in control individuals (chi-square test, p= 0.001. Thus the RET variant allele A is over-represented in patients affected with the HSCR phenotype. Polymorphism of exon 2 of the RET gene was found in sporadic Hirschsprung’s disease in the Yogyakarta population, which suggests that the RET gene plays important roles in the pathogenesis of HSCR.

  1. 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.

  2. Mitochondrial D-loop mutations can be detected in sporadic malignant tumours in dogs

    Directory of Open Access Journals (Sweden)

    ?laska Brygida

    2014-12-01

    Full Text Available The aim of this study was to identify mutations in the D-loop region of mtDNA in head, neck, and limb tumours in dogs, and determination of their relationship with the process of neoplastic transformation. Blood and tumour tissue samples from 19 dogs with diagnosed sporadic malignant tumours were analysed. DNA extraction, amplification, and sequencing of the mtDNA D-loop, and bioinformatic analyses were performed. Five mutations and 19 polymorphisms were observed in 68.42% of all tumours. Polymorphic variants were noted in 42.86% of the head and neck tumours and in 58.33% of the limb tumours. Mutations were observed in 21.05% of dogs. The mutations were found in 28.57% of the head and neck tumours and in 16.66% of the limb tumours. The mutations were identified in 50% of the studied epithelial cancers. In the mesenchymal tumours, no mutations in the D-loop region were observed. Mitochondrial haplotype A17 was found in over 40% cases of limb tumours. No association between the age, breed, sex, type of tumour, and detected polymorphic variants were observed. Different mutational changes in the D-loop sequences of mtDNA identified in the blood and tumour tissues may indicate a relationship between the type of tumour and individual changes in the D-loop nucleotide sequences of mtDNA.

  3. Clinical and Genetic Aspects of Sporadic Non-Medullar Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    U Rumjanzeva

    2006-03-01

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

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

    Scientific Electronic Library Online (English)

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

    2008-09-01

    Full Text Available Se ha determinado las variaciones diurnas de la ocurrencia y de varias características de las capas esporádicas de la región E sobre Islas Argentinas (65.3°S; 64.3°W) para otoño, invierno, primavera y verano, tanto durante niveles de actividad solar baja como alta de los ciclos solares 21, 22 y 23. [...] Se intenta identificar posibles variaciones interdecadales, aunque se usó equipos idénticos solo durante los ciclos 22 y 23. Parece haber diferencias reales entre ciclos, al menos para algunos tipos de Es en invierno. Abstract in english The diurnal variations of Sporadic-E layer (Es) occurrence and of various Es characteristics over Argentine Islands (65.3°S; 64.3°W) 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 differences at least for some Es types during winter.

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

    Directory of Open Access Journals (Sweden)

    van der Wall Elsken

    2010-04-01

    Full Text Available Abstract Background Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like type that is known to have a low rate of lympho-vascular invasion (LVI, we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. Methods A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. Results LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78. Conclusion LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.

  6. A sporadic case of late-onset familial amyloid polyneuropathy with a monoclonal gammopathy.

    Science.gov (United States)

    Correia, Ana Sofia; Mendonça, Marcelo; Caetano, André; Medeiros, Elmira

    2015-08-01

    A 77-year-old Portuguese woman reported gradual worsening of burning and numbness in the feet and hands, fatigue, anorexia, weight loss, diarrhoea and decreased visual acuity. She had a medical history of atrial fibrillation and recent episodes of dizziness and blood pressure fluctuations. There was no relevant family history. The diagnostic workup documented a severe axonal sensorimotor peripheral neuropathy, a monoclonal IgG kappa protein on serum, a severe left ventricular hypertrophy on the echocardiogram and probable vitreous deposits of amyloid on ophthalmologic examination. Pain and dysautonomia with an axonal neuropathy and multisystemic involvement raised the possibility of amyloidosis. The presence of a detectable monoclonal protein, older age at disease onset and absence of family history of disease usually suggest immunoglobulin light-chain amyloidosis. However, in this case, both the genetic testing and the biopsy of the salivary glands confirmed transthyretin amyloidosis. In those patients with a monoclonal protein, particularly in sporadic and late-onset cases, the diagnosis of transthyretin amyloidosis can be challenging, mimicking immunoglobulin light-chain amyloidosis. PMID:26055637

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

    DEFF Research Database (Denmark)

    Schlehofer, B; Schlaefer, K

    2007-01-01

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

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

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    Cracco Laura

    2011-10-01

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

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

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    Atanu Biswas

    2013-01-01

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

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

    DEFF Research Database (Denmark)

    Bahl, Justyna Maria Czarna; Heegaard, Niels Henrik Helweg

    2009-01-01

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

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

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    Bourdon Violaine

    2011-01-01

    Full Text Available Abstract Background Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the SMARCB1 (INI1 tumor suppressor gene were described in familial and sporadic schwannomatosis patients. Methods To delineate the SMARCB1 gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas. Results Nine variants scattered along the sequence of SMARCB1 were identified. Five of them were classified as deleterious. All five patients carrying a SMARCB1 mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age. Conclusions These results suggest that patients with schwannomas have a significant probability of carrying a SMARCB1 mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the SMARCB1 gene.

  12. Sporadic medullary thyroid cancer with upper mediastinal extension on pentavalent DMSA [Tc(V)-DMSA

    International Nuclear Information System (INIS)

    Full text: Sporadic medullary thyroid cancer accounts for the majority of all cases of medullary thyroid cancer. They are typically unilateral and there are no associated endocrinopathies (not associated with disease in other endocrine glands). It arises from the parafollicular C-cells and accounts for only 1 to 5% of all thyroid malignancies. Metastases occur early to regional lymph nodes (50-80%), liver, lung, and bone. Pentavalent dimercaptosuccinic acid, DMSA [Tc(V)-DMSA] has had limited use in imaging these tumors. In our case an 83-year-old woman was referred to our department for assessment of her medullary thyroid cancer. She presented with a lump in the left neck with palpable nodules which had increased in size on ultrasound over two years. Biopsy of the supraclavicular area subsequently demonstrated medullary thyroid cancer. Pentavalent DMSA [Tc(V)-DMSA] was used to assess the nodules in the left lobe and for any external thyroidal metastases. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

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

    International Nuclear Information System (INIS)

    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. 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. 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). 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

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

    Science.gov (United States)

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

    2014-09-01

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

  15. Sporadic CJD in a patient with relaplsing-remitting multiple sclerosis on an immunomodulatory treatment.

    Science.gov (United States)

    Gabeli?, Tereza; Habek, Mario; Zerr, Inga; Gawinecka, Joanna; Pavlisa, Goran; Brinar, Vesna V

    2011-09-01

    Creutzfeld-Jacob disease (CJD) is a degenerative, invariably fatal brain disorder. Multiple sclerosis (MS) is a chronic, potentially disabling, immune-mediated inflammatory demyelinating disease of the central nervous system. Here, we report a 50-year-old woman who, two years after the diagnosis of relapsing remitting MS, developed altered consciousness, dystonic posture of the left hand and myoclonic jerks. Repeated brain MRI showed hyperintensities on T2 sequences in basal ganglia bilaterally and diffusion restriction in these areas, and, since typical EEG and CSF features were present, the diagnosis of CJD was made. To the best of our knowledge, this is the first report of a glatiramer acetate-treated MS patient who developed sporadic CJD. This combination is interesting in the light of recent data suggesting that CJD and MS may share similar mechanisms of "molecular mimicry" and autoimmunity. This case also emphasizes the importance of critically assessing every new symptom even in a patient with an established diagnosis of MS. PMID:22141291

  16. On the influence of solar activity on the mid-latitude sporadic E layer

    Science.gov (United States)

    Pezzopane, Michael; Pignalberi, Alessio; Pietrella, Marco

    2015-09-01

    To investigate the influence of solar cycle variability on the sporadic E layer (Es), hourly measurements of the critical frequency of the Es ordinary mode of propagation, foEs, and of the blanketing frequency of the Es layer, fbEs, recorded from January 1976 to December 2009 at the Rome (Italy) ionospheric station (41.8° N, 12.5° E), were examined. The results are: (1) a high positive correlation between the F10.7 solar index and foEs as well as between F10.7 and fbEs, both for the whole data set and for each solar cycle separately, the correlation between F10.7 and fbEs being much higher than the one between F10.7 and foEs; (2) a decreasing long-term trend of the F10.7, foEs and fbEs time series, with foEs decreasing more rapidly than F10.7 and fbEs; (3) clear and statistically significant peaks at 11 years in the foEs and fbEs time series, inferred from Lomb-Scargle periodograms.

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

    Directory of Open Access Journals (Sweden)

    K.-I. Oyama

    2008-09-01

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

  18. The preclinical phase of the pathological process underlying sporadic Alzheimer's disease.

    Science.gov (United States)

    Braak, Heiko; Del Tredici, Kelly

    2015-10-01

    Abnormal tau lesions (non-argyrophilic pretangle material, argyrophilic neuropil threads, neurofibrillary tangles) in select types of neurons are crucial for the pathogenesis of sporadic Alzheimer's disease. Ongoing formation of these tau lesions persists into end-stage Alzheimer's disease and is not subject to remission. The early pretangle disease phase is a focus of increasing interest because only abnormal forms of the microtubule-associated protein tau are involved at that point and, in contrast to late-stage disease when amyloid-? deposition is present, this phase is temporally closer to the prevailing conditions that induce the pathological process underlying Alzheimer's disease. Extracellular and aggregated amyloid-? may only be produced under pathological conditions by nerve cells that contain abnormal tau. One potential trigger for tau protein hyperphosphorylation and conformational change in Alzheimer's disease may be the presence of a non-endogenous pathogen. Subsequently, a predictable regional distribution pattern of the tau lesions develops in phylogenetically late-appearing and ontogenetically late-maturing neurons that are connected via their axons. It is hoped that hypotheses drawn from these considerations, as well as from recent tau dissemination models, from studies of variant tau conformers, and from tau imaging will encourage the development of new preventative and disease-modifying strategies. PMID:26283673

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

    Directory of Open Access Journals (Sweden)

    Fritzsche Markus

    2002-11-01

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

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

    Science.gov (United States)

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

    2015-10-15

    Although Japanese cases of sporadic Creutzfeldt-Jakob disease (sCJD) generally involve longer survival periods compared to those from other countries, details regarding the factors influencing survival are unclear. To determine the influence of certain factors on survival, we retrospectively assessed 51 Japanese MM1-type sCJD patients with respect to background, clinical course, and disease management. No significant differences were found between men and women, tracheotomy and nontracheotomy patients, or patients treated in public and other types of hospitals. Although the survival period of tube-fed patients was significantly longer than that of patients who were not tube fed, survival of patients fed via a nasal tube did not differ significantly from that of gastrostomy-fed patients. The proportion of tube-fed patients was 68.6% (35/51). Disease duration was not significantly associated with age or year of onset. However, it was associated with time from onset to first recognition of myoclonus, first recognition of periodic sharp-wave complexes on electroencephalogram, and progression to the akinetic mutism state. Mechanical ventilation was not performed for any patient. Because the total disease duration increased in cases with a slowly progressive clinical course as a natural outcome, we concluded that the most crucial factor contributing to the prolonged survival of Japanese sCJD patients was tube feeding once the akinetic mutism state had been reached. PMID:26143527

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

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    Rakesh Kumar Manne

    2014-01-01

    Full Text Available Burkitt?s lymphoma (BL is the fastest growing malignancy of the lymphoreticular system to affect humans and has a potential ability to double in size every day. A case of maxillary sporadic BL (sBL associated with neuro-orbital involvement in an Indian male is presented. sBL initially presented as maxillary swelling with no obvious dental and periodontal changes. Histological specimen from incisional biopsy revealed a round cell malignant tumor and immunohistochemistry reactions favored nonHodgkin?s lymphoma consistent with BL. Four weeks later, patient presented with orbital involvement as diplopia, sixth cranial nerve palsy, and medial rectus palsy. Chemotherapy regimen according to LMB 89 protocol was started. During chemotherapy regimen patient showed bradycardia and Babinski response, suggestive of central nervous system involvement. sBL associated with orbital involvement is extremely rare and only seven cases have been reported. Our case showed unusual presentation; despite the aggressive tumor did not show any common clinical, radiological, and hematological findings. We also discussed the role of oral medicine specialist, importance of early diagnosis, and prompt referral in management of maxillary sBL.

  2. Targeted sequencing and identification of genetic variants in sporadic inclusion body myositis.

    Science.gov (United States)

    Weihl, Conrad C; Baloh, Robert H; Lee, Youjin; Chou, Tsui-Fen; Pittman, Sara K; Lopate, Glenn; Allred, Peggy; Jockel-Balsarotti, Jennifer; Pestronk, Alan; Harms, Matthew B

    2015-04-01

    Sporadic inclusion body myositis (sIBM) has clinical, pathologic and pathomechanistic overlap with some inherited muscle and neurodegenerative disorders. In this study, DNA from 79 patients with sIBM was collected and the sequencing of 38 genes associated with hereditary inclusion body myopathy (IBM), myofibrillar myopathy, Emery-Dreifuss muscular dystrophy, distal myopathy, amyotrophic lateral sclerosis and dementia along with C9orf72 hexanucleotide repeat analysis was performed. No C9orf72 repeat expansions were identified, but; 27 rare (minor allele frequency fronto-temporal dementia (IBMPFD). Neither patient had a family history of weakness or manifested other symptoms reported with VCP mutations such as PDB or dementia. In vitro analysis of these VCP variants found that they both disrupted autophagy similar to other pathogenic mutations. Although no clear genetic etiology has been implicated in sIBM pathogenesis, our study suggests that genetic evaluation in sIBM may be clinically meaningful and lend insight into its pathomechanism. PMID:25617006

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

    DEFF Research Database (Denmark)

    MØlbak, Kåre; Neimann, Jacob

    2002-01-01

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

  4. Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-15

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

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

    Directory of Open Access Journals (Sweden)

    Majorana Giovanni

    2006-05-01

    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.

  6. Análisis molecular del cáncer de colon esporádico / Molecular analysis of sporadic colon cancer

    Scientific Electronic Library Online (English)

    Claudia, Hurtado; Ana María, Wielandt; Alejandro J, Zárate; Udo, Kronberg; Magdalena, Castro; Ken, Yamagiwa; Takashi, Ito; Yoshinobu, Eishi; Luis, Contreras; Francisco, López-Köstner.

    2015-03-01

    Full Text Available [...] Abstract in english Background: In Chile, colorectal cancer (CRC) is often diagnosed in late stages. Thus, surgical treatment must be complemented with chemotherapy. KRAS mutations and microsatellite instability have been detected in these tumors. However, the response to treatment in patients without KRAS mutations va [...] ries and requires a better understanding. Aim: To determine the frequency and distribution of somatic point mutations in KRAS, BRAF and PIK3CA genes and microsatellite instability status (MSI) in patients with colon cancer (CC). Material and Methods: A prospective observational study of patients undergoing surgery for colon cancer. Tumor-derived DNA was analyzed by polymerase chain reaction (PCR) for the most frequent mutations of KRAS, BRAF and PIK3CA. PCR was also used to analyze MSI. Results: Fifty-eight patients with sporadic CC were analyzed, 16 showed KRAS mutations (G12R, G12D, G12V, G13D) and out of the 42 patients that did not show any mutation, 10 had mutations in BRAF (V600E) and PIK3CA (E542K, E545D, E545K, Q546E, H1047R). BRAF mutations alone or in combination with PIK3CA mutations were observed in 27% of high MSI tumors and in 2% of tumors without instability (p

  7. Fine structure of sporadic sodium layer observed with a sodium lidar at Tromsø, Norway

    Science.gov (United States)

    Tsuda, T. T.; Nozawa, S.; Kawahara, T. D.; Kawabata, T.; Saito, N.; Wada, S.; Hall, C. M.; Oyama, S.; Ogawa, Y.; Suzuki, S.; Ogawa, T.; Takahashi, T.; Fujiwara, H.; Fujii, R.; Matuura, N.; Brekke, A.

    2011-09-01

    We report a sporadic sodium layer (SSL), in particular its fine structure, observed at 92-98 km between 20:00 and 23:30 UT (21:00-24:30 LT) on 11 January 2011 using a sodium lidar, which was installed in the European incoherent scatter (EISCAT) radar site at Tromsø, Norway (69.6°N, 19.2°E) in early 2010. The sodium lidar measurement with 5-sec time-resolution reveals the details of dramatic sodium-density increase as well as short-period wavelike structure in the SSL. The rate of increase of height-integrated sodium density at the beginning of the SSL event was 6.4-9.6 × 1010 m-2 s-1. Dominant oscillation periods in the wavelike structures were 7-11 min at 95-98 km and 3 min at 92-95 km. The calculated power spectral densities are well represented by power laws, implying the presence of the short-period waves and turbulence in the frequency range of 10-4-10-1 Hz.

  8. Olivopontocerebellar atrophy in two adult cats, sporadic cases or new genetic entity.

    Science.gov (United States)

    Résibois, A; Poncelet, L

    2004-01-01

    Two otherwise healthy adult cats were presented with progressive cerebellar signs of different severity. Owners requested euthanasia. Necropsy disclosed whole cerebellum and pontine atrophy, with a severity paralleling the neurologic dysfunction. We used cell type-specific immunolabelings to characterize the lesions. The severity of the cerebellar cortex atrophy followed a general gradient from the midvermis toward the hemispheres and a local gradient from the depth of the folia toward their tip. Along these gradients, Purkinje cells were the first to disappear, followed by basket, Golgi, and stellate cells, and eventually by granule cells. Bergmann glia cells and unipolar brush cells were preserved. Pontine nuclei and the olivary complex were also severely depopulated. Neurons in the cerebellar nuclei, vestibular nuclei, and other cerebellar system-associated structures were preserved, as well as substantia nigra. Olivopontocerebellar atrophy (OPCA) in a domestic animal species was rarely reported. Some features allow tentative linking to either familial or sporadic OPCA of humans. However, the ordered disappearance of all cortical neuronal types has never been described before. Either this entity is cat specific or it might pinpoint the need for increased knowledge about differential gene expression depending on genetic background, i.e., among different species. It also would open prospects about gene product interactions within neurons. PMID:14715964

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

    LENUS (Irish Health Repository)

    Monecke, Stefan

    2011-04-01

    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.

  10. Less protease-resistant PrP in a patient with sporadic CJD treated with intraventricular pentosan polysulphate.

    Science.gov (United States)

    Terada, T; Tsuboi, Y; Obi, T; Doh-ura, K; Murayama, S; Kitamoto, T; Yamada, T; Mizoguchi, K

    2010-02-01

    Treatment with intraventricular pentosan polysulphate (PPS) might be beneficial in patients with Creutzfeldt-Jakob disease. We report a 68-year-old woman with sporadic Creutzfeldt-Jakob disease who received continuous intraventricular PPS infusion (1-120 microg/kg/day) for 17 months starting 10 months after the onset of clinical symptoms. Treatment with PPS was well tolerated but was associated with a minor, transient intraventricular hemorrhage and a non-progressive collection of subdural fluid. The patient's overall survival time was well above the mean time expected for the illness but still within the normal range. Post-mortem examination revealed that the level of abnormal protease-resistant prion protein in the brain was markedly decreased compared with levels in brains without PPS treatment. These findings suggest that intraventricular PPS infusion might modify the accumulation of abnormal prion proteins in the brains of patients with sporadic Creutzfeldt-Jakob disease. PMID:19804470

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

    Science.gov (United States)

    Oikonomou, Zoi-Sylvia; Dikou, Angela

    2008-11-01

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

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

    Science.gov (United States)

    Oikonomou, Zoi-Sylvia; Dikou, Angela

    2008-11-01

    Available information on the socioeconomic implications of marine protected areas (MPAs) for the socioculturally diverse Mediterranean region is scant. The National Marine Park of Alonissos, Northern Sporades (NMPANS), Greece was established in 1992 as a foundation for the conservation of the endangered Mediterranean monk seal Monachus monachus. The evolution of the degree of acceptance of and satisfaction from the NMPANS by involved stakeholder groups (fishermen, tourism operators, hoteliers and owners of rooms to let, governmental bodies, nongovernmental bodies, students, domestic and foreign tourists) were investigated 13 years after its establishment using written questionnaires delivered during personal interviews. The initial positive attitude of local professionals for the NMPANS has eroded due to the unsatisfactory fulfillment of expectations for socioeconomic development. Fishermen expressed dissatisfaction with, mistrust toward, and a reluctancy to communicate with the NMPANS's management body. They believe that the fishery areas have decreased in actual geographic area because of the prohibitive measures; fish stocks are declining; compensation for damage to fishery equipment by the Mediterranean monk seal and for the prohibitive measures should be provided; and stricter enforcement of regulations should take place. On the other hand, tourism operators, who organize trips for tourists to the NMPANS, unanimously reported direct economic benefits. Furthermore, there was a disparity in the perception of socioeconomic benefits derived from the NMPANS between governmental bodies and local stakeholders. The governmental bodies and the nongovernmental organization MOm-Hellenic Society for the Study and Protection of the Monk Seal postulated that there had been considerable socioeconomic benefits for the local community of Alonissos due to the establishment of the NMPANS, whereas the local nongovernmental organization Ecological and Cultural Movement of Alonissos claimed benefits were scant. Tourists (domestic and foreign) believe that the NMPANS is not the main attraction to Alonissos Island but is part of a composite, including serenity, aesthetic beauty, and small-scale tourism development, which can turn Alonissos Island into an ideal eco-tourism destination; a common aspiration for both the tourists and the local community by general consensus. The aim of the NMPANS to integrate conservation and development lies in (1) the effectiveness of the NMPANS management body in formulating a strategic management plan that would accommodate stakeholders' interests and aspirations and (2) a national policy of conservation and enhancement of natural resources with consistency and continuity. Quantitative assessment of the socioeconomic effectiveness of the Mediterranean MPAs using a common methodology would facilitate the identification of intraregional variation and better planning for the network of MPAs in the Mediterranean. PMID:18626688

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

    Directory of Open Access Journals (Sweden)

    Fleuren Gert

    2007-02-01

    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.

  14. Development of Sporadic Microsatellite Instability in Colorectal Tumors Involves Hypermethylation at Methylated-In-Tumor Loci in Adenoma

    OpenAIRE

    de Maat, Michiel F.G.; Narita, Norihiko; Benard, Anne; Yoshimura, Tetsunori; Kuo, Christine; Tollenaar, Rob A E M; de Miranda, Noel F. C. C.; Turner, Roderick R.; Van De Velde, Cornelis J.H.; Morreau, Hans; Hoon, Dave S.B

    2010-01-01

    Microsatellite instability (MSI) and genomic hypermethylation of methylated-in-tumor (MINT) loci are both strong prognostic indicators in a subgroup of patients with sporadic colorectal cancer (CRC). The present study was designed to determine whether the methylation of MINT loci during the progression of adenoma to CRC is related to MSI in CRC cases. Methylation index (MI) was measured by absolute quantitative assessment of methylated alleles at seven MINT loci in primary CRC with contiguous...

  15. Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

    OpenAIRE

    Detours, V.; Delys, L; Libert, F; Weiss Solís, D; Bogdanova, T.; J.E. Dumont; Franc, B.; Thomas, G.; Maenhaut, C

    2007-01-01

    Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human ly...

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

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro; Hisham Beshara Halasa, Tariq; Hald, Tine

    2012-01-01

    Campylobacter spp. is a widespread and important cause of human illness worldwide. Disease is frequently associated with foodborne transmission, but other routes of exposure, such as direct contact with live animals and person-to-person transmission, are also recognized. Identifying the most important sources of human disease is essential for prioritizing food safety interventions and setting public health goals. Numerous case-control studies of sporadic infections of campylobacteriosis have bee...

  17. Risk factors for osteoporosis, falls and fractures in hereditary myopathies and sporadic inclusion body myositis — A cross sectional survey

    OpenAIRE

    F. Danckworth; N. Karabul; Posa, A; Hanisch, F.

    2014-01-01

    Background: The risk of osteoporosis is known in myopathies requiring long-term steroid treatment and Pompe disease, but not in other hereditary myopathies or sporadic inclusion body myositis (sIBM). Methods: Risk factors of osteoporosis, laboratory parameters of bone metabolism, frequency of falls and fractures, walking ability, and pain were surveyed using questionnaires in 89 patients with sIBM and genetically confirmed myopathies facioscapulohumeral muscular dystrophy (FSHD), myotonic ...

  18. Sporadic Bovine Leukosis: A Description of Eight Calves Received at Animal Diseases Research Institute from 1974-1980

    OpenAIRE

    Bundza, A; GREIG, A.S.; Chander, S.; Dukes, T. W.

    1980-01-01

    Eight calves with sporadic bovine leukosis are described. The common features were generalized lymphadenopathy, visceral involvement and raised total leukocyte and lymphocyte counts. Agar gel immunodiffusion tests for bovine leukemia virus antibodies were negative in eight animals and in all animals from three herds of origin. Lymphocytic nuclear pockets were found in the tissues of one calf but attempts to isolate bovine leukemia virus from two animals were unsuccessful.

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

    OpenAIRE

    Galasko Douglas; Hanse Eric; Gustavsson Mikael K; Harmsen Andreas; Hansson Oskar; Buchhave Peder; Daborg Jonny; Buerger Katharina; Ringman John M; Andreasson Ulf; Portelius Erik; Hampel Harald; Blennow Kaj; Zetterberg Henrik

    2010-01-01

    Abstract Background Alzheimer's disease (AD) is associated with deposition of amyloid ? (A?) in the brain, which is reflected by low concentration of the A?1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional A? peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of A?. Here, we test the hypothesis that AD is characterized by a specific CSF A? isoform pattern that is distinct when comparing sporadic AD (SAD...

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

    OpenAIRE

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

    2008-01-01

    • BACKGROUND: A common polymorphism at codon 72 of TP53 gene has been associated with increased risk for many human cancers. We studied this TP53 polymorphism in colorectal adenocarcinomas in small population selected from Isfahan city.
    • METHODS: Samples: We undertook a case-control study on 180 controls and 180 paraffin block specimens of sporadic colorectal adenocarcinomas. PCR amplification of ...

  1. Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on chromosome 13q12-q13.

    OpenAIRE

    Cleton-Jansen, A M; Collins, N.; Lakhani, S.R.; Weissenbach, J; Devilee, P; Cornelisse, C.J.; Stratton, M.R.

    1995-01-01

    Loss of heterozygosity (LOH) on chromosome 13 occurs on 25-30% of breast tumours. This may reflect the inactivation of the retinoblastoma susceptibility gene RB1. However, recently another candidate tumour-suppressor gene has been identified on chromosome 13 by linkage analysis, the breast cancer susceptibility gene BRCA2. To investigate the involvement of BRCA2 in sporadic breast cancer 200 breast tumours were tested for LOH on chromosome band 13q12-q14, using 11 highly polymorphic microsate...

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

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro; Hisham Beshara Halasa, Tariq; Hald, Tine

    2012-01-01

    Salmonella is an important cause of human illness. Disease is frequently associated with foodborne transmission, but other routes of exposure are recognized. Identifying sources of disease is essential for prioritizing public health interventions. Numerous case-control studies of sporadic salmonellosis have been published, often using different methodologies and settings. Systematic reviews consist of a formal process for literature review focused on a research question. With the objective of id...

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

    Science.gov (United States)

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

    2015-09-01

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

  4. SKCG-1: a new candidate growth regulatory gene at chromosome 11q23.2 in human sporadic Wilms tumours

    OpenAIRE

    K.P. Singh; D. Roy

    2006-01-01

    Using arbitrary primed-PCR (AP-PCR), we have identified a novel genetic alteration located at chromosome 11q23.2 and this genetic alteration was common in 38% of the human Wilms tumour samples analysed. Further characterisation by cloning and sequencing of this genomic region revealed that it represents a part of an uncharacterised gene. We have named this gene as Sporadic Kidney Cancer Gene-1 (SKCG-1). Using fluorescence in situ hybridisation (FISH) approach, we established its localisation ...

  5. Uniparentalism in Sporadic Colorectal Cancer is Independent of Imprint Status, and Coordinate for Chromosomes 14 and 18

    OpenAIRE

    Darbary, Huferesh K.; Dutt, Smitha S; Sait, Sheila J.; Norma J. Nowak; Heinaman, Roy E.; Stoler, Daniel L.; Anderson, Garth R.

    2009-01-01

    Our previous allelotyping studies of 59 sporadic colorectal cancers revealed that loss of heterozygosity is most frequent for regions of chromosomes 14 and 18. Yet subsequent BAC microarray comparative genomic hybridization studies of the same tumor DNAs showed no corresponding pattern of copy number alteration for chromosome 14. To clarify this apparent discrepancy, we utilized hybridization to SNP microarrays; this revealed frequent uniparentalism for chromosome 14 and for chromosome 18. Ba...

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

    Directory of Open Access Journals (Sweden)

    C. Haldoupis

    2005-09-01

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

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

    OpenAIRE

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

    2014-01-01

    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 polymorphis...

  8. Description of a simple test for CADASIL disease and determination of mutation frequencies in sporadic ischaemic stroke and dementia patients

    OpenAIRE

    Wang, T.; Sharma, S.(Physics Department, University of Jammu, Jammu, India); Fox, N.; ROSSOR, M; BROWN, M; Sharma, P.

    2000-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited adult onset disease characterised most commonly by cerebral ischaemic events and dementia. It is caused by mutations in the Notch3 gene with most clustering in exons 3 and 4. Whether these mutations have any influence on common sporadic ischaemic stroke or dementia cases has not been investigated, partly hampered by the lack of a readily usable genetic ...

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Anna Kowalska

    2009-12-01

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

  11. POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions.

    Science.gov (United States)

    Di Fonzo, Alessio; Bordoni, Andreina; Crimi, Marco; Sara, Galbiati; Del Bo, Roberto; Bresolin, Nereo; Comi, Giacomo P

    2003-12-01

    The accumulation of multiple mitochondrial DNA (mtDNA) deletions in stable tissues is a distinctive feature of several autosomal disorders, characterized by Progressive External Ophthalmoplegia (PEO), ptosis, and proximal myopathy. At least three nuclear genes are responsible for these disorders: ANT1 and C10orf2 cause autosomal dominant PEO, while mutations of DNA polymerase gammaA (POLG1 or POLG) gene on chromosome 15q25 causes both autosomal dominant and recessive forms of PEO. To investigate the contribution of these genes to the sporadic cases of PEO with multiple mtDNA deletions, we studied 31 mitochondrial myopathy patients without any family history for the disorder: 23 had PEO with myopathy, with or without the additional features of pigmentary retinopathy, ataxia, neurosensorial hypoacusia and diabetes mellitus, 7 presented isolated myopathy and one a peripheral neuropathy with ptosis. In all patients Southern blot of muscle DNA showed multiple mtDNA deletions; screening for ANT1 and C10ORF2 genes was negative. POLG analysis revealed mutations in eight patients; in six of them the mutations were allelic, while two patients were heterozygous. Five mutations were new, namely one stop codon (c.2407C>T/p.R709X) and four missense mutations (c.1085G>C/p.G268A; c.1967G>A/p.R562Q; c.2702G>C/p.R807P; c.3076C>T/p.H932W). A high degree of conservation was observed for all the new missense mutations. Only patients presenting PEO as part of their clinical phenotype had POLG mutations, in seven of them together with myopathic signs and in one with a sensori-motor peripheral neuropathy. PMID:14635118

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

    Directory of Open Access Journals (Sweden)

    Ennis Sarah

    2007-08-01

    Full Text Available Abstract Background Young women presenting with breast cancer are more likely to have a genetic predisposition to the disease than breast cancer patients in general. A genetic predisposition is known to increase the risk of new primary breast (and other cancers. It is unclear from the literature whether genetic status should be taken into consideration when planning adjuvant treatment in a young woman presenting with a first primary breast cancer. The primary aim of the POSH study is to establish whether genetic status influences the prognosis of primary breast cancer independently of known prognostic factors. Methods/design The study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1st June 2001 to 31st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period. Discussion Power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80% receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforward.

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

    International Nuclear Information System (INIS)

    Young women presenting with breast cancer are more likely to have a genetic predisposition to the disease than breast cancer patients in general. A genetic predisposition is known to increase the risk of new primary breast (and other) cancers. It is unclear from the literature whether genetic status should be taken into consideration when planning adjuvant treatment in a young woman presenting with a first primary breast cancer. The primary aim of the POSH study is to establish whether genetic status influences the prognosis of primary breast cancer independently of known prognostic factors. The study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1st June 2001 to 31st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period. Power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80%) receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforward

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-09-01

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

  15. Surgical resection of sporadic and hereditary hemangioblastoma: Our 10-year experience and a literature review

    Science.gov (United States)

    Bründl, Elisabeth; Schödel, Petra; Ullrich, Odo-Winfried; Brawanski, Alexander; Schebesch, Karl-Michael

    2014-01-01

    Background: Hemangioblastomas (HBLs) are benign neoplasms that contribute to 1-2.5% of intracranial tumors and 7-12% of posterior fossa lesions in adult patients. HBLs either evolve hereditarily in association with von Hippel–Lindau disease (vHL) or, more prevalently, as solitary sporadic tumors. Only few authors have reported on the clinical presentation and the neurological outcome of HBL. Methods: We retrospectively analyzed the clinical, radiological, surgical, and histopathologic records of 24 consecutive patients (11 men, 13 women; mean age 51.3 years) with HBL of the posterior cranial fossa, who had been treated at our center between 2001 and 2012. We reviewed the current literature, and discussed our findings in the context of previous publications on HBL. The study protocol was approved by the local ethics committee (14-101-0070). Results: Mean time to diagnosis was 14 weeks. The extent of resection (EOR) was total in 20 and near total in 4 patients. Four patients required revision within 24 h because of relevant postoperative bleeding. One patient died within 14 days. One patient required permanent shunting. At discharge, 75% of patients [n = 18, modified Rankin scale (mRS) 0-1] showed no or at least resolved symptoms. Mean follow-up was 21 months. Two recurrences were detected during follow-up. Conclusions: In comparison to other benign entities of the posterior fossa, time to diagnosis was significantly shorter for HBL. This finding indicates the rather aggressive biological behavior of these excessively vascularized tumors. In our series, however, the rate of complete resection was high, and morbidity and mortality rates were within the reported range. PMID:25317353

  16. Surgical resection of sporadic and hereditary hemangioblastoma: Our 10-year experience and a literature review

    Directory of Open Access Journals (Sweden)

    Elisabeth Brundl

    2014-01-01

    Full Text Available Background: Hemangioblastomas (HBLs are benign neoplasms that contribute to 1-2.5% of intracranial tumors and 7-12% of posterior fossa lesions in adult patients. HBLs either evolve hereditarily in association with von Hippel-Lindau disease (vHL or, more prevalently, as solitary sporadic tumors. Only few authors have reported on the clinical presentation and the neurological outcome of HBL. Methods: We retrospectively analyzed the clinical, radiological, surgical, and histopathologic records of 24 consecutive patients (11 men, 13 women; mean age 51.3 years with HBL of the posterior cranial fossa, who had been treated at our center between 2001 and 2012. We reviewed the current literature, and discussed our findings in the context of previous publications on HBL. The study protocol was approved by the local ethics committee (14-101-0070. Results: Mean time to diagnosis was 14 weeks. The extent of resection (EOR was total in 20 and near total in 4 patients. Four patients required revision within 24 h because of relevant postoperative bleeding. One patient died within 14 days. One patient required permanent shunting. At discharge, 75% of patients [n = 18, modified Rankin scale (mRS 0-1] showed no or at least resolved symptoms. Mean follow-up was 21 months. Two recurrences were detected during follow-up. Conclusions: In comparison to other benign entities of the posterior fossa, time to diagnosis was significantly shorter for HBL. This finding indicates the rather aggressive biological behavior of these excessively vascularized tumors. In our series, however, the rate of complete resection was high, and morbidity and mortality rates were within the reported range.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrP(Sc)) induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI) showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI) resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG). Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrP(Sc). PMID:20689629

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

    International Nuclear Information System (INIS)

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

  20. Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Rossi, Meghan; Mead, Simon; Collinge, John; Rudge, Peter; Vincent, Angela

    2015-01-01

    Objectives There have been reports of patients with antibodies to neuronal antigens misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Conversely, low levels of antibodies to neuronal proteins have been reported in patients with sCJD. However, the frequency of misdiagnoses, or of antibodies in patients with subsequently confirmed sCJD, is not clear. Methods We reviewed 256 consecutive cases of sCJD seen in the National Prion Clinic, of whom 150 had sera previously referred for selected antibody tests. Eighty-two available samples were retested for antibodies to N-methyl-d-aspartate receptor (NMDAR), the glycine receptor (GlyR), voltage-gated potassium channel (VGKC)-complex and the associated proteins, leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2). Results Four of the initial 150 sera referred were positive; two had antibodies to NMDAR, and two to the VGKC-complex, one of which was also positive for GlyR antibodies. Of the 82 sCJD sera retested, one had VGKC-complex antibodies confirming the previous result, two had CASPR2 and GlyR antibodies and one had CASPR2 and NMDAR antibodies; all antibodies were at low levels. Over the same period three patients with autoimmune encephalitis and high VGKC-complex antibodies were initially referred as sCJD. Conclusions This study indicates that <5% patients with sCJD develop serum antibodies to these neuronal antigens and, when positive, only at low titres. By contrast, three patients referred with possible prion disease had a clinical picture in keeping with autoimmune encephalitis and very high VGKC-complex/LGI1 antibodies. Low titres of neuronal antibodies occur only rarely in suspected patients with sCJD and when present should be interpreted with caution. PMID:25246643

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

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    Yan-hui YANG

    2014-04-01

    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

  2. Clinical findings and diagnostic tests in the MV2 subtype of sporadic CJD.

    Science.gov (United States)

    Krasnianski, Anna; Schulz-Schaeffer, Walter J; Kallenberg, Kai; Meissner, Bettina; Collie, Donald A; Roeber, Sigrun; Bartl, Mario; Heinemann, Uta; Varges, Daniela; Kretzschmar, Hans A; Zerr, Inga

    2006-09-01

    Atypical clinical course and low sensitivity of established diagnostic tests are the main diagnostic problems in the MV2 subtype of sporadic Creutzfeldt-Jakob disease (sCJD). Clinical symptoms and signs, MRI, EEG and biochemical CSF markers were studied in 26 patients. Histological findings were semiquantitatively evaluated. Compared with typical sCJD, the disease duration was prolonged (median 12 months). Dementia, ataxia and psychiatric symptoms were present in all patients. Extrapyramidal signs were observed in 88%. T2-weighted MRI showed basal ganglia hyperintensities in 90%. Increased thalamic signal intensity was detected in 88% on diffusion-weighted MRI. Increased CSF tau-protein was found in 83%, and the 14-3-3 test was positive in 76%. The EEG revealed periodic sharp wave complexes in only two patients. Kuru plaques, severe thalamic and basal ganglia gliosis and spongiform changes, and neuronal loss in the pulvinar were the prominent histological features. At least one of the three diagnostic tests (MRI, tau- and 14-3-3 protein) supported the clinical diagnosis in all patients. MRI was the most sensitive of the diagnostic tests applied. Thalamic hyperintensities were observed unusually frequently. Prolonged disease duration, early and prominent psychiatric symptoms, absence of typical EEG, thalamic hyperintensities on MRI and relatively low 14-3-3 protein sensitivity may be suspicious for variant CJD. However, distinct sensory symptoms and young age at onset, which are often found in the latter, are not common in the MV2 subtype, and the pulvinar sign was observed in only one case. PMID:16720682

  3. Epstein-Barr virus (EBV)-positive sporadic burkitt lymphoma: an age-related lymphoproliferative disorder?

    Science.gov (United States)

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

    2015-02-01

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

  4. Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease.

    Science.gov (United States)

    Correia, Sónia C; Santos, Renato X; Santos, Maria S; Casadesus, Gemma; Lamanna, Joseph C; Perry, George; Smith, Mark A; Moreira, Paula I

    2013-05-01

    This study aimed to show that the rat model of sporadic Alzheimer's disease (sAD) generated by the intracerebroventricular (icv) injection of a sub-diabetogenic dose of streptozotocin (icvSTZ) is characterized by brain mitochondrial abnormalities. Three-month-old male Wistar rats were investigated 5 weeks after a single bilateral icv injection of STZ (3 mg/ Kg) or vehicle. icvSTZ administration induced a decrease in brain weight and cognitive decline, without affecting blood glucose levels. icvSTZ administration also resulted in a significant increase in hippocampal amyloid beta peptide 1-42 (A?(1-42)) levels as well as in cortical and hippocampal hyperphosphorylated tau protein levels. Brain mitochondria from icvSTZ rats revealed deficits in their function, as shown by a decrease in mitochondrial transmembrane potential, repolarization level, ATP content, respiratory state 3, respiratory control ratio and ADP/O index and an increase in lag phase of repolarization. Mitochondria from icvSTZ rats also displayed a decrease in pyruvate and ?-ketoglutarate dehydrogenases and cytochrome c oxidase activities and an increase in the susceptibility to calcium-induced mitochondrial permeability transition. An increase in hydrogen peroxide and lipid peroxidation levels and a reduction in glutathione content were also observed in mitochondria from icvSTZ rats. These results demonstrate that the insulin-resistant brain state that characterizes this rat model of sAD is accompanied by the occurrence of mitochondrial abnormalities reinforcing the validity of this animal model to study sAD pathogenesis and potential therapies. PMID:23061885

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

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    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

    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.

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

    International Nuclear Information System (INIS)

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

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

    Scientific Electronic Library Online (English)

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

    1997-11-01

    Full Text Available 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.

  8. Long-term outcome of sporadic and FAP-associated desmoid tumors treated with high-dose selective estrogen receptor modulators and sulindac: a single-center long-term observational study in 134 patients.

    Science.gov (United States)

    Quast, Daniel Robert; Schneider, Ralph; Burdzik, Emanuel; Hoppe, Steffen; Möslein, Gabriela

    2016-01-01

    Aim of this study is to evaluate the outcome of long-term conservative treatment with sulindac and high-dose selective estrogen receptor modulators (SERMs) for sporadic and FAP-associated desmoid tumors. Desmoids are very rare tumors in the general population but occur frequently in FAP patients, being encountered in 23-38 %. Treatment of desmoids is still most controversial since response cannot be predicted and they are prone to develop recurrence. This study included all desmoid patients that were treated and followed at our institution and had completed at least 1 year of treatment. Response was defined as stable size or regression of desmoid size between two CT or MRI scans. A total of 134 patients were included. 64 (47.8 %) patients had a confirmed diagnosis of FAP, 69 (51.5 %) patients were sporadic. Overall 114 (85.1 %) patients showed regressive or stable desmoid size. Patients with previous history of multiple desmoid-related surgeries showed less-favorable response. The mean time to reach at least stable size was 14.9 (±9.1) months. After regression or stabilization, medication was tapered in 69 (60.5 %) of the treated patients with only one long-term recurrence after >10 years. The results of this study fortify the role of sulindac and high-dose SERMs as an effective and safe treatment for both, sporadic and FAP-associated desmoid tumors. While invasive treatment frequently results in high recurrence rates, high morbidity and high mortality, this conservative treatment is successful in most patients. The recurrence rate is negligible with no desmoid-related mortality in this large series. Therefore surgical resection, especially for mesenteric desmoids, should be deferred favoring this convincingly effective, well tolerated regimen. PMID:26275868

  9. ICOS gene polymorphisms are associated with sporadic breast cancer: a case-control study

    International Nuclear Information System (INIS)

    Inducible costimulator (ICOS), a costimulatory molecular of the CD28 family, provides positive signal to enhance T cell proliferation. Its abnormal expression can disturb the immune response and entail an increased risk of cancer. To investigate whether single nucleotide polymorphisms (SNPs) in the ICOS gene are associated with sporadic breast cancer susceptibility and progression in Chinese women, a case-control study was conducted. In the study cohort, we genotyped five SNPs (rs11889031, rs10932029, rs4675374, rs10183087 and rs10932037) in ICOS gene among 609 breast cancer patients and 665 age-matched healthy controls. Furthermore, the positive results were replicated in an independent validation cohort of 619 patients and 682 age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes. In rs10932029, compared with TT genotype and T allele, the CT genotype and C allele showed a significantly increased risk of breast cancer (P = 0.030, OR = 1.467, 95% CI 1.037-2.077; P = 0.017, OR = 1.481, 95% CI 1.070-2.049, respectively), and the associations were also significant in the validation cohort (P = 0.002, OR = 1.693, 95% CI 1.211-2.357; P = 0.003, OR = 1.607, 95% CI 1.171-2.204, respectively). Haplotype analysis showed that CTCAC haplotype containing rs10932029 T allele had a lower frequency in cases than in controls (P = 0.015), whereas haplotype CCCAC containing rs10932029 C allele was more common in cases than in controls (P = 0.013). In the analysis of clinicopathologic features, rs11889031 CT genotype and T allele were associated with progesterone receptor (PR) status and lymph node metastasis, which were further supported by our validation cohort. Moreover, some haplotypes were associated with estrogen receptor (ER) and PR statuses. These results indicate that ICOS gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in a northern Chinese population

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

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    Wu Yiqing

    2010-03-01

    Full Text Available Abstract Background Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors. Methods 20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs were collected. The mRNA expression of beclin 1 was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island. Results Decreased beclin 1 mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of beclin 1 mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the beclin 1 gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression. Conclusions These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of beclin 1 in breast cancer.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors. 20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs) were collected. The mRNA expression of beclin 1 was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH) was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island. Decreased beclin 1 mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of beclin 1 mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the beclin 1 gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression. These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of beclin 1 in breast cancer

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

    Science.gov (United States)

    Rubenstein, Richard; Chang, Binggong

    2013-01-01

    Human prion diseases are fatal neurodegenerative disorders associated with an accumulation of PrPSc in the central nervous system (CNS). Of the human prion diseases, sporadic Creutzfeldt-Jakob disease (sCJD), which has no known origin, is the most common form while variant CJD (vCJD) is an acquired human prion disease reported to differ from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. Peripheral tissue involvement in prion disease, as judged by PrPSc accumulation in the tonsil, spleen, and lymph node has been reported in vCJD as well as several animal models of prion diseases. However, this distribution of PrPSc has not been consistently reported for sCJD. We reexamined CNS and non-CNS tissue distribution and levels of PrPSc in both sCJD and vCJD. Using a sensitive immunoassay, termed SOFIA, we also assessed PrPSc levels in human body fluids from sCJD as well as in vCJD-infected humanized transgenic mice (Tg666). Unexpectedly, the levels of PrPSc in non-CNS human tissues (spleens, lymph nodes, tonsils) from both sCJD and vCJD did not differ significantly and, as expected, were several logs lower than in the brain. Using protein misfolding cyclic amplification (PMCA) followed by SOFIA, PrPSc was detected in cerebrospinal fluid (CSF), but not in urine or blood, in sCJD patients. In addition, using PMCA and SOFIA, we demonstrated that blood from vCJD-infected Tg666 mice showing clinical disease contained prion disease-associated seeding activity although the data was not statistically significant likely due to the limited number of samples examined. These studies provide a comparison of PrPSc in sCJD vs. vCJD as well as analysis of body fluids. Further, these studies also provide circumstantial evidence that in human prion diseases, as in the animal prion diseases, a direct comparison and intraspecies correlation cannot be made between the levels of PrPSc and infectivity. PMID:23843953

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

    Science.gov (United States)

    Rubenstein, Richard; Chang, Binggong

    2013-01-01

    Human prion diseases are fatal neurodegenerative disorders associated with an accumulation of PrP(Sc) in the central nervous system (CNS). Of the human prion diseases, sporadic Creutzfeldt-Jakob disease (sCJD), which has no known origin, is the most common form while variant CJD (vCJD) is an acquired human prion disease reported to differ from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. Peripheral tissue involvement in prion disease, as judged by PrP(Sc) accumulation in the tonsil, spleen, and lymph node has been reported in vCJD as well as several animal models of prion diseases. However, this distribution of PrP(Sc) has not been consistently reported for sCJD. We reexamined CNS and non-CNS tissue distribution and levels of PrP(Sc) in both sCJD and vCJD. Using a sensitive immunoassay, termed SOFIA, we also assessed PrP(Sc) levels in human body fluids from sCJD as well as in vCJD-infected humanized transgenic mice (Tg666). Unexpectedly, the levels of PrP(Sc) in non-CNS human tissues (spleens, lymph nodes, tonsils) from both sCJD and vCJD did not differ significantly and, as expected, were several logs lower than in the brain. Using protein misfolding cyclic amplification (PMCA) followed by SOFIA, PrP(Sc) was detected in cerebrospinal fluid (CSF), but not in urine or blood, in sCJD patients. In addition, using PMCA and SOFIA, we demonstrated that blood from vCJD-infected Tg666 mice showing clinical disease contained prion disease-associated seeding activity although the data was not statistically significant likely due to the limited number of samples examined. These studies provide a comparison of PrP(Sc) in sCJD vs. vCJD as well as analysis of body fluids. Further, these studies also provide circumstantial evidence that in human prion diseases, as in the animal prion diseases, a direct comparison and intraspecies correlation cannot be made between the levels of PrP(Sc) and infectivity. PMID:23843953

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

    Scientific Electronic Library Online (English)

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

    1999-03-01

    Full Text Available 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.

  16. Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

    International Nuclear Information System (INIS)

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

  17. Genetic variations of NKX2-5 in sporadic atrial septal defect and ventricular septal defect in Chinese Yunnan population.

    Science.gov (United States)

    Cao, Yu; Wang, Junqiang; Wei, Chuanyu; Hou, Zongliu; Li, Yaxiong; Zou, Honglin; Meng, Mingyao; Wang, Wenju; Jiang, Lihong

    2016-01-01

    Congenital heart disease (CHD) is the most common birth abnormality, and more than 40% CHD subtypes are sporadic atrial septal defect (ASD) and ventricular septal defect (VSD). The etiology of ASD and VSD remains largely unknown. NKX2-5 gene is a highly conserved homeobox protein gene and expressed in the developing heart. Its mutations can cause sporadic ASD and VSD. This study aimed to investigate the genetic variations of NKX2-5 in ASD and VSD in Chinese Yunnan population. The whole 2 coding exon and partial flanking intron sequences of NKX2-5 gene were screened using DNA sequencing in 107 ASD patients and 391 VSD patients as well as 487 healthy individuals (control) who had parental origin (three generations) from the Yunnan province in China. Results found that, 4 reported single nucleotide polymorphisms (SNPs) (rs2277923, rs3729753, rs703752 and rs202071628) were detected. A novel heterozygous DNA sequence variant (DSV) (1500G>C) in the 3'UTR region of NKX2-5 gene were identified in 2 VSD patients, but none in ASD and controls. One single nucleotide polymorphism (rs2277923), the frequency of which was significantly higher in ASD group, and the allele and genotype were associated with the occurrence of ASD. Besides, a weak statistical association existed between rs703752 and VSD (uncorrected P=0.028). The novel DSV (1500G>C) of NKX2-5 gene may contribute to a small number of VSD, and rs2277923 SNP may contribute to the risk of sporadic ASD in Chinese Yunnan population. PMID:26297999

  18. Temperature controlled icy dust reservoir of sodium: A possible mechanism for the formation of sporadic sodium layers

    Science.gov (United States)

    Qiu, Shican; Tang, Yihuan; Dou, Xiankang

    2015-06-01

    Using seven years, from 2006 to 2013, sodium lidar observations over Hefei, China (31.80°N, 117.3°E), we attempt to propose a possible mechanism for the formation of sporadic sodium layers (SSLs or NaS). We analyze the relationship between low temperature (SSL occurrence and detect a statistically significant link that the low temperature (SSL with an occurrence rate of 93.4% (57/61). The sharp decrease of water vapor concentration nearby before an SSL and the recover after the SSL are also detected frequently. Based upon these evidences and some case studies, we propose an icy dust reservoir in the formation of an SSL. The icy dust could form in the extremely cold mesopause region where the temperature falls below 150 K and it will absorb sodium atoms to form a solid sodium metal film as a sodium reservoir. The icy dust will then sublimate rapidly when meeting with warm air (e.g., 150 K 190 K and sometimes even >230 K) and form a sporadic sodium layer. Although not conclusive and highly uncertain, the icy dust reservoir model not only provides a good explanation for the observed characteristics of SSLs; it is also in good agreement with many other observations, such as the simultaneous sporadic sodium and iron layers, the behavior of SSLs on small time scale, the deviation of the sodium density profile of SSLs from the normal one, and the sharply decreased scale height above the peak of the sodium layer. These results further suggest that the icy dust might be a viable option of sodium reservoir for the formation of SSLs.

  19. Association between mutation of the NF2 gene and monosomy 22 in menopausal women with sporadic meningiomas

    Science.gov (United States)

    2013-01-01

    Background Meningioma was the first solid tumor shown to contain a recurrent genetic alteration e.g. monosomy 22/del(22q), NF2 being the most relevant gene involved. Although monosomy 22/del(22q) is present in half of all meningiomas, and meningiomas frequently carry NF2 mutations, no study has been reported so far in which both alterations are simultaneously assessed and correlated with the features of the disease. Methods Here, we analyzed the frequency of both copy number changes involving chromosome 22 and NF2 mutations in 20 sporadic meningiomas using high-density SNP-arrays, interphase-FISH and PCR techniques. Results Our results show a significant frequency of NF2 mutations (6/20 patients, 30%), most of which (5/6) had not been previously reported in sporadic meningiomas. NF2 mutations involved five different exons and led to a truncated protein (p.Leu163CysfsX46, p.Phe62LeufsX61, p.Asp281MetfsX15, p.Phe285LeufsX11, p.Gln389ArgfsX37) and an in frame deletion of Phe119. Interestingly, all NF2 mutated cases were menopausal women with monosomy 22 but not del(22q). Conclusions These results confirm and extend on previous observations about the high frequency and heterogeneity of NF2 mutations in sporadic meningiomas and indicate they could be restricted to a well-defined cytogenetic and clinical subgroup of menopausal women. Further studies in large series of patients are required to confirm our observations. PMID:24171707

  20. Description of a simple test for CADASIL disease and determination of mutation frequencies in sporadic ischaemic stroke and dementia patients

    Science.gov (United States)

    Wang, T.; Sharma, S.; Fox, N.; Rossor, M.; Brown, M.; Sharma, P.

    2000-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited adult onset disease characterised most commonly by cerebral ischaemic events and dementia. It is caused by mutations in the Notch3 gene with most clustering in exons 3 and 4. Whether these mutations have any influence on common sporadic ischaemic stroke or dementia cases has not been investigated, partly hampered by the lack of a readily usable genetic test.?An easy to use diagnostic array for CADASIL was designed using various restriction endonucleases for the known mutations in exons 3 and 4 and novel mismatch primers were designed where no such enzymes existed. This array was used to identify the allele frequencies of CADASIL mutations and polymorphisms in selected disease cohorts. Seventy patients with radiologically established sporadic ischaemic stroke and 77 patients from a specialist young dementia clinic were recruited. One hundred and seventeen age and sex matched asymptomatic controls were also identified.?The diagnostic array was found to work well. None of the 14 known mutations and three previously identified polymorphisms (C474A, A587G, and C594A) in exons 3 and 4 were present in 140stroke, 110 dementia, or 234 control chromosomes. Molecular variant C381T occurred with a higher frequency of 0.13, whereas G684A occurred with a lower frequency (0.09) than previously reported, although there were no statistical differences between selected cohorts.?In conclusion, a readily usable genetic test for CADASIL has been devised that was used to determine allele frequencies in well characterised cohorts of sporadic stroke and dementia patients. The data suggest that despite the clinical resemblance, CADASIL is not a common masquerading cause of stroke or dementia. The test will enable units locally to rapidly screen patients with suspected CADASIL.?? PMID:11032621

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

    Directory of Open Access Journals (Sweden)

    M Hashemzadeh Chaleshtori

    2007-05-01

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

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

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

    2012-01-01

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

  3. Dynactin Deficiency in the CNS of Humans with Sporadic ALS and Mice with Genetically Determined Motor Neuron Degeneration

    OpenAIRE

    Ku?ma-Kozakiewicz, Magdalena; Chudy, Agnieszka; Ka?mierczak, Beata; Dziewulska, Dorota; Usarek, Ewa; Bara?czyk-Ku?ma, Anna

    2013-01-01

    Dynactin is a complex motor protein involved in the retrograde axonal transport disturbances of which may lead to amyotrophic lateral sclerosis (ALS). Mice with hSOD1G93A mutation develop ALS-like symptoms and are used as a model for the disease studies. Similar symptoms demonstrate Cra1 mice, with Dync1h1 mutation. Dynactin heavy (DCTN1) and light (DCTN3) subunits were studied in the CNS of humans with sporadic ALS (SALS), mice with hSOD1G93A (SOD1/+), Dync1h1 (Cra1/+), and double (Cra1/SOD1...

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

    OpenAIRE

    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

    2013-01-01

    Pathological deposition of mutated Cu/Zn superoxide dismutase (SOD1) accounts for ?20% of the familial ALS (fALS) cases. Insoluble protein aggregates, immunoreactive for SOD1, have been found in both fALS and sporadic ALS (sALS) patients. To study the molecular origin of SOD1 aggregation, we used a computational approach to discover four segments from SOD1 that form fibril-like aggregates. We found that two of these, 101DSVISLS107 and 147GVIGIAQ153, are likely to trigger the aggregation of fu...

  5. Highly increased CSF tau protein and decreased ?-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease?

    Science.gov (United States)

    Kapaki, E; Kilidireas, K; Paraskevas, G; Michalopoulou, M; Patsouris, E

    2001-01-01

    The aim was to quantify tau protein and ?-amyloid (A?42) in the CSF of patients with sporadic Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), and controls. Double sandwich enzyme linked immunosorbent assays (ELISAs) were used for measurments. Tau was increased 58-fold in CJD and 3.5-fold in AD compared with controls, whereas A?42 was decreased 0.5-fold in both CJD and AD. A cut off level for tau protein at 2131 pg/ml successfully discriminated CJD from AD (100% specificity and 93% sensitivity). Tau protein concentration in CSF is probably an additional useful marker in differentiating CJD from AD.?? PMID:11511720

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

    Directory of Open Access Journals (Sweden)

    Rafael Dariolli

    2015-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Magaly M. Sales

    1999-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

    The genotype (methionine, M or valine, V) at polymorphic codon 129 of the PRNP gene and the type (1 or 2) of abnormal prion protein in the brain are the major determinants of the clinicopathological features of sporadic Creutzfeldt-Jakob disease (CJD), thus providing molecular basis for classification of sporadic CJD, that is, MM1, MM2, MV1, MV2, VV1 or VV2. In addition to these "pure" cases, "mixed" cases presenting mixed neuropathological and biochemical features have also been recognized. The most frequently observed mixed form is the co-occurrence of MM1 and MM2, namely MM1+2. However, it has remained elusive whether MM1+2 could be a causative origin of dura mater graft-associated CJD (dCJD), one of the largest subgroups of iatrogenic CJD. To test this possibility, we performed transmission experiments of MM1+2 prions and a systematic neuropathological examination of dCJD patients in the present study. The transmission properties of the MM1+2 prions were identical to those of MM1 prions because MM2 prions lacked transmissibility. In addition, the neuropathological characteristics of MM2 were totally absent in dCJD patients examined. These results suggest that MM1+2 can be a causative origin of dCJD and causes neuropathological phenotype similar to that of MM1. PMID:25851836

  9. [Sporadic upper urinary tract urothelial cell carcinomas: identification of interaction between toxic carcinogens and individuals genetic susceptibility].

    Science.gov (United States)

    Colin, P; Koenig, P; Ballereau, C; Phé, V; Berthon, N; Villers, A; Biserte, J; Rouprêt, M

    2010-01-01

    Upper urinary tract urothelial cell carcinomas (UUT UCC) are rare sporadic tumors. Recent epidemiologic and molecular data have shown a singular susceptibility of UUT UCCs for specific risk factors. The main exogenic factors involved in UUT UCCs carcinogenesis remain tobacco and occupational exposure (aromatic amines, polycyclic hydrocarbures and chlored solvents). Enzymatic variants of detoxification system may be responsible of carcinogenesis with these toxics. Tumors induced by phenacetine consumption are decreasing since it was banned in the 1970s. Also, acid aristolochic exposure (Balkan nephropathy, Chinese Herb nephropathy) has been demonstrated to specifically induce UUT UCCs. Familial genic polymorphism of detoxification system would explain geographic distribution in endemic areas. In Taiwan, chronic arsenic exposition would constitute the main risk factor of UUT UCC. However, theses mechanisms of carcinogenesis remain unclear. The knowledge of UUT UCC development mechanisms implying toxic detoxification systems is still incomplete. To date, there is a growing body of evidence supporting that the interaction between individual genetic susceptibilities and environmental toxic exposure is a key to explain carcinogenesis in the majority of sporadic UUT UCC occurrence. PMID:20123521

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

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    Feng Qi-Sheng

    2007-07-01

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

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

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    D. L. Hysell

    2004-09-01

    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.

  12. Four-year longitudinal study of clinical and functional endpoints in sporadic inclusion body myositis: implications for therapeutic trials.

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    Hogrel, Jean-Yves; Allenbach, Yves; Canal, Aurélie; Leroux, Gaëlle; Ollivier, Gwenn; Mariampillai, Kuberaka; Servais, Laurent; Herson, Serge; Decostre, Valérie; Benveniste, Olivier

    2014-07-01

    Natural history studies in sporadic inclusion body myositis are of fundamental interest for future therapeutic trials. Previous works have demonstrated the particular relevance of knee extension strength in the follow-up of this disease. This work aimed to extend a preceding natural history over 9 months to a four year period. Thirteen patients were assessed using clinical and functional scales and dynamometry. Except wrist extension torque and manual muscle testing composite score, all the measurements presented a significant decline. The most important changes were observed for knee extension and ankle flexion and extension. The relative change in knee extension strength correlated with the level of strength at baseline. A non-linear correlation was found between 6-minute walk distance and knee extension strength. This study confirms that knee extension strength is particularly relevant to follow patients with sporadic inclusion body myositis. It also shows that a strength loss does not have linear consequences on motor ability. Finally strength and motor ability are complementing each other in the understanding of disease progression. PMID:24857365

  13. Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma

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    Burmer, G.C.; Rabinovitch, P.S.; Loeb, L.A. (Univ. of Washington School of Medicine, Seattle (United States))

    1991-06-01

    Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum of mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.

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

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    Huang Yue

    2012-01-01

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

  15. [Clinical typing and diagnosis of sporadic human prion diseases (classic sproadic CJD, MM2-cortical form CJD, MM2-thalamic form CJD)].

    Science.gov (United States)

    Satoh, Katsuya; Shirabe, Susumu; Eguchi, Katsumi

    2007-08-01

    We described recent knowledge and outline about a diagnosis and clinical typing of sporadic prion disease. Diagnostic procedure and classification based on a pattern of Western blotting of PrP(Sc), neuropathologic findings, and clinical features. In addition, we described a clinical significance of total tau protein, significance of a diffusion-weighted images of MRI. Analysis of 112 cases of sporadic prion diseases showed 92.3% at positive rate. Sensitivity and specificity were 95.5% and 95.7%, respectively by total tau protein assay of 44 cases of prion diseases. PMID:17695279

  16. Legionelosis esporádica: un problema sin resolver Sporadic legionellosis: an unsolved problem egionelose esporádica: um problema não resolvido

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    Mikel Etxeberria Agirresarobe

    2013-06-01

    Full Text Available Objetivo: Resumir los hallazgos más relevantes obtenidos en diferentes estudios dirigidos a investigar el origen de la legionelosis esporádica. Métodos: Se ha realizado una búsqueda bibliográfica en revistas nacionales e internacionales (1990-junio 2012 y se han seleccionado los artículos que se ajustan al objetivo del estudio. Los artículos se han clasificado en tres grupos: (i estudios dirigidos a identificar factores ambientales de riesgo; (ii estudios basados en hipótesis de transmisión a partir de fuentes concretas; y (iii estudios basados en la variabilidad espacio-temporal de la legionelosis. Resultados: De los 27 artículos seleccionados, la mitad (13 se han realizado en Reino Unido o EEUU y 2 en España. Los factores de riesgo ambiental identificados con más frecuencia han sido el historial de viaje durante el período de incubación y ser conductor de profesión. Fuentes de infección relacionadas históricamente con brotes, como las torres de refrigeración y el agua de consumo, también se han asociado con los casos esporádicos. Diferentes autores señalan de forma consistente la influencia de los factores meteorológicos en la incidencia y están adquiriendo importancia los estudios dirigidos a analizar el patrón espacial de presentación de casos. Conclusiones: A pesar de las diferentes hipótesis sobre el origen de la legionelosis esporádica no existe una evidencia epidemiológica clara sobre las fuentes de infección. Se pone en cuestión si las medidas de control y vigilancia realizadas actualmente están siendo suficientemente eficaces para prevenir la aparición de casos esporádicos y se destaca la necesidad de seguir investigando.Objective: To summarize the major findings obtained in different studies focusing on the origin of sporadic legionellosis.Methods: A literature search was conducted in national and international journals (1990-June 2012, and those articles that fell within the scope of the study were selected. The articles have been classified into three groups: (i studies designed to identify environmental risk factors, (ii studies based on the transmission hypothesis from specific sources, and (iii studies based on the spatial-temporal pattern of legionellosis.Results: Of the 27 articles selected, half (13 were conducted in the UK or the USA and 2 in Spain. Having a travel history during the incubation period and being a professional driver were the two most frequently identified environmental risk factors. Sources of infection historically related with outbreaks, such as cooling towers and drinking water systems, have also been associated with sporadic cases. The influence of meteorological factors on incidence of the disease has been indicated in a consistent way by various authors, while studies based on spatial analysis methods are gaining in importance.Conclusions: Despite the different hypotheses proposed about the origin of sporadic legionellosis, there is no clear epidemiological evidence regarding the sources of infection. This calls into question if the current monitoring and surveillance measures are sufficiently effective to prevent the occurrence of sporadic cases, and also highlights the need for further research.Objetivo: Resumir as descobertas mais relevantes obtidas em diversos estudos cujo objetivo é investigar a origem da legionelose esporádica.Métodos: Realizou-se uma pesquisa bibliográfica em revistas nacionais e internacionais (1990-jun 2012 e foram selecionados os artigos que se ajustam ao objetivo do estudo. Os artigos foram classificados em três grupos: (i estudos que visam identificar fatores ambientais de risco; (ii estudos baseados na hipótese de transmissão a partir de fontes concretas; e (iii estudos baseados na variabilidade espaço-tempo da legionelose. Resultados: Dos 27 artigos selecionados, a metade (13 foi realizada no Reino Unido ou nos EUA, e 2 em Espanha. Os fatores de risco ambiental identificados com mais frequência foi o historial de viagem durante o período de incubação e ser motorista de profissão. Fontes de infeção relacionadas historicamente com surtos, como as torres de refrigeração e a água de consumo, também se associaram com os casos esporádicos. Diversos autores assinalam de forma consistente a influência dos fatores meteorológicos na incidência e estão a adquirir importância os estudos cujo objetivo é a análise do padrão espacial de apresentação dos casos.Conclusões: Apesar das diversas hipóteses sobre a origem da legionelose esporádica, não existe uma evidência epidemiológica clara sobre as fontes de infeção. Põe-se em questão se as medidas de controlo e vigilância realizadas atualmente estão a ser suficientemente eficazes para prevenir o aparecimento de casos esporádicos e destaca-se a necessidade de continuar a investigar.

  17. Lidar Probing of the Mesosphere: Simultaneous Observations of Sporadic Sodium and Iron Formations, Calcium Ion Layers, Neutral Temperature and Winds

    Science.gov (United States)

    Kane, Timothy J.; Qian, Jun; Scherrer, Daniel R.; Senft, Daniel C.; Pfenninger, W. Matthew; Papen, George C.; Gardner, Chester S.

    1992-01-01

    Meteoritic ablation in the upper atmosphere is the commonly accepted source of the mesospheric metals between 80 and 105 km. The vertical and temporal behavior of some of these metals can be probed with high accuracy and resolution using resonance fluorescence lidar techniques. Of considerable interest in recent years has been the sporadic and rapid formation of thin, dense enhancements in these metallic layers. Since late Mar. 1991, the UIUC CEDAR lidar system, located at the Urbana Atmospheric Observatory, has been routinely operating at the Fe resonance line of 372 nm in order to probe the mesospheric Fe layer. In Nov. 1991, the capability to investigate mesospheric Ca(+) at the resonance line of 393.4 nm was added. The lidar's eximer-pumped dye laser uses Exciton QUI laser dye dissolved in p-dioxane, which can lase at both the Fe and Ca(+) frequencies. Various aspects of this investigation are discussed.

  18. On the solar cycle dependence of the amplitude modulation characterizing the mid-latitude sporadic E layer diurnal periodicity

    Science.gov (United States)

    Pezzopane, M.; Pignalberi, A.; Pietrella, M.

    2016-01-01

    Spectral analyses are employed to investigate how the diurnal periodicity of the critical frequency of the sporadic E (Es) layer varies with solar activity. The study is based on ionograms recorded at the ionospheric station of Rome (41.8°N, 12.5°E), Italy, from 1976 to 2009, a period of time covering three solar cycles. It was confirmed that the diurnal periodicity is always affected by an amplitude modulation with periods of several days, which is the proof that Es layers are affected indirectly by planetary waves through their nonlinear interaction with atmospheric tides at lower altitudes. The most striking features coming out from this study is however that this amplitude modulation is greater for high-solar activity than for low-solar activity.

  19. Synchronous sporadic medullary carcinoma of the thyroid and small-cell carcinoma of lung: A rare entity

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    Manigreeva Krishnatreya

    2013-01-01

    Full Text Available Synchronous medullary carcinoma of the thyroid and small-cell carcinoma of the lung is a rare phenomenon and both these tumors are characterized by poor treatment outcome and prognosis. A 45-year-old woman presented with a progressive swelling in front and side of the neck of 3-month duration without any pulmonary symptoms. The tumor of the lung was an incidental finding on routine chest radiological examination. The diagnosis of synchronous primary cancers of the thyroid and the lung were made after cytopathological examination of both the lesions. We report here a case of loco-regional sporadic medullary carcinoma of the thyroid associated with limited stage small-cell carcinoma of the lung and its therapeutic challenges.

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

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

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

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

    2008-03-01

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

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

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    Rodríguez-Martínez Ana B

    2012-10-01

    Full Text Available Abstract Introduction The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. Case presentation A 74-year-old Caucasian woman showed a sporadic Creutzfeldt–Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77. Neuropathological findings showed: spongiform change in the patient’s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. Conclusion Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt–Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.

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

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    Schalken Jack A

    2005-06-01

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

  4. Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer.

    Science.gov (United States)

    Yehia, Lamis; Niazi, Farshad; Ni, Ying; Ngeow, Joanne; Sankunny, Madhav; Liu, Zhigang; Wei, Wei; Mester, Jessica L; Keri, Ruth A; Zhang, Bin; Eng, Charis

    2015-11-01

    Cancer-predisposing genes associated with inherited cancer syndromes help explain mechanisms of sporadic carcinogenesis and often inform normal development. Cowden syndrome (CS) is an autosomal-dominant disorder characterized by high lifetime risks of epithelial cancers, such that ?50% of affected individuals are wild-type for known cancer-predisposing genes. Using whole-exome and Sanger sequencing of a multi-generation CS family affected by thyroid and other cancers, we identified a pathogenic missense heterozygous SEC23B variant (c.1781T>G [p.Val594Gly]) that segregates with the phenotype. We also found germline heterozygous SEC23B variants in 3/96 (3%) unrelated mutation-negative CS probands with thyroid cancer and in The Cancer Genome Atlas (TCGA), representing apparently sporadic cancers. We note that the TCGA thyroid cancer dataset is enriched with unique germline deleterious SEC23B variants associated with a significantly younger age of onset. SEC23B encodes Sec23 homolog B (S. cerevisiae), a component of coat protein complex II (COPII), which transports proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Interestingly, germline homozygous or compound-heterozygous SEC23B mutations cause an unrelated disorder, congenital dyserythropoietic anemia type II, and SEC23B-deficient mice suffer from secretory organ degeneration due to ER-stress-associated apoptosis. By characterizing the p.Val594Gly variant in a normal thyroid cell line, we show that it is a functional alteration that results in ER-stress-mediated cell-colony formation and survival, growth, and invasion, which reflect aspects of a cancer phenotype. Our findings suggest a different role for SEC23B, whereby germline heterozygous variants associate with cancer predisposition potentially mediated by ER stress "addiction." PMID:26522472

  5. ?-N-methylamino-l-alanine causes neurological and pathological phenotypes mimicking Amyotrophic Lateral Sclerosis (ALS): the first step towards an experimental model for sporadic ALS.

    Science.gov (United States)

    de Munck, Estefanía; Muñoz-Sáez, Emma; Miguel, Begoña G; Solas, M Teresa; Ojeda, Irene; Martínez, Ana; Gil, Carmen; Arahuetes, Rosa Ma

    2013-09-01

    ?-N-methylamino-l-alanine (L-BMAA) is a neurotoxic amino acid that has been related to various neurodegenerative diseases. The aim of this work was to analyze the biotoxicity produced by L-BMAA in vivo in rats, trying to elucidate its physiopathological mechanisms and to search for analogies between the found effects and pathologies like Amyotrophic Lateral Sclerosis (ALS). Our data demonstrated that the neurotoxic effects in vivo were dosage-dependent. For evaluating the state of the animals, a neurological evaluation scale was developed as well as a set of functional tests. Ultrastructural cell analysis of spinal motoneurons has revealed alterations both in endoplasmic reticulum and mitochondria. Since GSK3? could play a role in some neuropathological processes, we analyzed the alterations occurring in GSK3? levels in L-BMAA treated rats, we have observed an increase in the active form of GSK3? levels in lumbar spinal cord and motor cerebral cortex. On the other hand, (TAR)-DNA-binding protein 43 (TDP-43) increased in L-BMAA treated animals. Our results indicated that N-acetylaspartate (NAA) declined in animals treated with L-BMAA, and the ratio of N-acetylaspartate/choline (NAA/Cho), N-acetylaspartate/creatine (NAA/Cr) and N-acetylaspartate/choline+creatine (NAA/Cho+Cr) tended to decrease in lumbar spinal cord and motor cortex. This project offers some encouraging results that could help establishing the progress in the development of an animal model of sporadic ALS and L-BMAA could be a useful tool for this purpose. PMID:23688553

  6. TCEANC2 rs10788972 and rs12046178 variants in the PARK10 region in Chinese Han patients with sporadic Parkinson's disease.

    Science.gov (United States)

    Guo, Yi; Tan, Ting; Deng, Xiong; Song, Zhi; Yang, Zhijian; Yang, Yan; Deng, Hao

    2015-12-01

    Parkinson's disease (PD) is the second most common chronic neuronal degeneration disorder with motor and nonmotor clinical features. The rs10788972 variant of the transcription elongation factor A (SII) N-terminal and central domain containing 2 (TCEANC2) gene in the PARK10 region was recently identified to be strongly related to sporadic PD in the American population. To evaluate whether the same variant is associated with sporadic PD in Chinese Han population, we researched 513 sporadic PD patients and 512 normal controls of Chinese Han ethnicity in Mainland China. No significant difference in genotypic and allelic distributions between patients and control groups for either rs10788972 (for genotypic distribution, ?(2) = 0.412, p = 0.814, and for allelic distribution, ?(2) = 0.280, p = 0.597) or its neighbor marker rs12046178 (for genotypic distribution, ?(2) = 1.500, p = 0.472, and for allelic distribution, ?(2) = 1.339, p = 0.247) was found. Our data suggest that neither variant is related to sporadic PD in Chinese Han population. PMID:26432391

  7. Mutational Analysis of p27 (CDKN1 B and p18 (CDKN2C in Sporadic Pancreatic Endocrine Tumors Argues against Tumor-Suppressor Function

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    Daniel Lindberg

    2007-07-01

    Full Text Available Pancreatic endocrine tumors (PETs arise sporadically or are associated with multiple endocrine neoplasia type 1 (MENi syndrome or von Hippel-Lindau syndrome. About 90% of patients with familial MENi display detectable MEN1 gene (menin mutations. The cyclin-dependent kinase inhibitor p27 (CDKN1 B is a downstream target of menin and has been recently shown to be responsible for the multiple endocrine neoplasia-like syndrome in rats, where affected animals develop multiple tumors and hyperplasia in endocrine tissues, including the pancreatic islets of Langerhans. A germline nonsense truncation mutation of p27 has been recently described in a suspected MENi family without MENi mutation, raising the possibility that p27 mutation could be responsible for MENi phenotype. Somatic MENi mutations occur at low frequency in sporadic PETs; here, we subjected p27 to mutational analysis in 27 sporadic PETs. As an additional menin target, analysis of the p18(CDKN2C gene was included. In the p27 gene, one common polymorphism (V1 09G and one novel polymorphism (g/a in the noncoding part of exon 2 were identified. Three known polymorphisms were found in the p18 gene. These data suggest that p27 and p18 are unlikely to present classic tumor-suppressor genes in sporadic PETs.

  8. First proteome study of sporadic flowering in bamboo species (Bambusa vulgaris and Dendrocalamus manipureanus) reveal the boom is associated with stress and mobile genetic elements.

    Science.gov (United States)

    Louis, Bengyella; Waikhom, Sayanika Devi; Goyari, Sailendra; Jose, Robinson C; Roy, Pranab; Talukdar, Narayan Chandra

    2015-12-15

    Bamboo species are the fastest-growing plants having a long vegetative cycle. Abrupt switching from the vegetative phase to the reproductive phase via sporadic flowering boom, occasionally leads to death of bamboo clumps, and threatens the existence of many bamboo species. To apprehend the molecular mechanism driving sporadic flowering, proteome changes in the initial and advanced floral buds of two edible bamboo species (Bambusa vulgaris and Dendrocalamus manipureanus) was dissected by two-dimensional gel electrophoresis (2-DE). A total of 39 differentially expressed peptide spots were identified by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF-TOF/MS). In both B. vulgaris and D. manipureanus, identified proteins were categorized as transposon-related, defence and stress-related, cell cycle related, metabolism related, signal transduction related, and some lacked known putative domains. Proteins such as SEPALLATA3, ubiquitin, histone 3, thaumatin-like protein, putative tethering factor, SF-assemblin, polyubiquitin, mitochondrial carrier-like protein and RPT2-like protein were significantly expressed. Differences in D. manipureanus and B. vulgaris suggested that bamboo species have diverse 'drivers' or 'passengers' genes that govern natural sporadic flowering boom. This first floral proteomics analysis of bamboos revealed that sporadic boom is a highly energetic process, associated with stress elements, mobile genetic elements and signal transduction cross-talk elements. PMID:26260016

  9. DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/?-catenin signaling pathway genes.

    Czech Academy of Sciences Publication Activity Database

    Farkas, S. A.; Vymetálková, Veronika; Vodi?ková, Ludmila; Vodi?ka, Pavel; Torbjörn, K. N.

    2014-01-01

    Ro?. 6, ?. 2 (2014), s. 179-191. ISSN 1750-1911 R&D Projects: GA ?R GPP304/11/P715; GA ?R(CZ) GAP304/12/1585; GA MZd NT14329 Institutional support: RVO:68378041 Keywords : CpG * DNA repair genes * sporadic colorectal cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.649, year: 2014

  10. A polymorphism in the YWHAH gene encoding 14-3-3 eta that is not associated with sporadic Creutzfeldt-Jakob disease (CJD).

    Science.gov (United States)

    Yun, Jisuk; Jeong, Byung-Hoon; Kim, Hae-Jung; Park, Young-Jae; Lee, Yun-Jung; Choi, Eun-Kyoung; Carp, Richard I; Kim, Yong-Sun

    2012-04-01

    14-3-3 proteins are abundantly expressed in the brain, particularly neuronal tissue and are thought to serve multiple biological functions involved in neuronal development and cell growth and death. Recent studies have shown associations of 14-3-3 genes with neurodegenerative disorders based on their chromosomal linkage to these diseases and to regulatory functions for the nervous system. Although the role of 14-3-3 proteins in the pathogenesis of prion diseases remains unknown, the detection of altered levels of isoforms of the 14-3-3 protein in the cerebrospinal fluid is considered a biomarker for diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). To identify other susceptibility genes for prion disease, we examined nucleotide variations in YWHAH, a gene encoding 14-3-3 eta. This case-control study included 182 sCJD patients and 206 healthy Koreans. Polymerase chain reaction was used to amplify open reading frame and some 3'-untranslated region (UTR) in exon 2, and direct sequencing was carried out. One polymorphism, 753 G/A, was detected in the 3'-UTR of exon 2 on the YWHAH. The genotype distribution and allele frequencies of the YWHAH 753 G/A polymorphism were not significantly different between controls and sCJD patients. This finding indicates that YWHAH 753 G/A polymorphism is unlikely to be linked to genetic susceptibility or have a modifying effect in sCJD. On analysis stratified by the prion protein gene 129 or 219 genotype, no significant relation was found in genotype and allele frequencies of the YWHAH 753G/A. This is the first genetic association study of YWHAH with sCJD populations. PMID:21739144

  11. Características mamográficas do câncer de mama associadas aos polimorfismos GSTM1 e GSTT1 / Polymorphisms GSTM1 and GSTT1 and sporadic breast cancer mammographic features

    Scientific Electronic Library Online (English)

    Lívia Martins Tavares Scianni, Morais; Cássio, Cardoso Filho; Gustavo Jacob, Lourenço; Julia Yoriko, Shinzato; Luiz Carlos, Zeferino; Carmen Sílvia Passos, Lima; Maria Salete Costa, Gurgel.

    2008-02-01

    Full Text Available 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.

  12. Familial/Bilateral and Sporadic Testicular Germ Cell Tumors Show Frequent Genetic Changes at Loci with Suggestive Linkage Evidence

    Directory of Open Access Journals (Sweden)

    Rolf I. Skotheim

    2001-01-01

    Full Text Available Testicular germ cell tumor (TGCT is the most common tumor type among adolescent and young adult males. Familial clustering and bilateral disease are suggestive of a genetic predisposition among a subgroup of these patients, but susceptibility genes for testicular cancer have not yet been identified. However, suggestive linkage between disease and genetic markers has been reported at loci on chromosome arms 3q, 5q, 12q, 18q, and Xq. We have analyzed primary familial/ bilateral (n=20 and sporadic (n=27 TGCTs, including 28 seminomas and 19 nonseminomas, for allelic imbalance (AI within the autosomal regions. DNA from all tumors were analyzed by fluorescent polymerase chain reaction of 22 polymorphic loci at 3q27-ter, 5q13-35.1, 12q21-ter, and 18q12-ter. All tumor genotypes were evaluated against their corresponding constitutional genotypes. The percentages of TGCTs with genetic changes at 3q, 5q, 12q, and 18q, were 79%, 36%, 53% and 43%, respectively. The frequencies at 3q and 12q in nonseminomas were significantly higher than in seminomas (P=.003 and P=.004. In order to evaluate changes at hemizygous Xq loci, five loci were analyzed by co-amplification with an autosomal reference marker known to reveal retained heterozygosity in the tumor DNA. Gain of Xq sequences was seen in more than 50% of the tumors. The degree of amplification varied among the loci in each of five tumors, and based on these breakpoints, a common region of overlapping gains was found at X828. No significant differences were found between the frequencies of genetic changes in familial /bilateral versus sporadic tumors, an observation speaking in disfavor of the existence of a single susceptibility gene for TGCT in any of the analyzed regions. Our data suggest that gain of genetic material at distal Xq and losses at 5q and 18q contribute to establishment of seminomas, whereas imbalances at 3q as well as gain at distal part of 12q are associated with further progression into nonseminomas.

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

    Directory of Open Access Journals (Sweden)

    Cristiane Moço Canhetti de Oliveira

    2011-04-01

    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.

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

    Scientific Electronic Library Online (English)

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

    2011-04-01

    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. 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.

  15. Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer

    International Nuclear Information System (INIS)

    p53 (encoded by TP53) is involved in DNA damage repair, cell cycle regulation, apoptosis, aging and cellular senescence. TP53 is mutated in around 50% of human cancers. Nevertheless, the consequences of p53 inactivation in colon cancer outcome remain unclear. Recently, a new role of p53 together with CSNK1A1 in colon cancer invasiveness has been described in mice. By combining data on different levels of p53 inactivation, we aimed to predict p53 functionality and to determine its effects on colon cancer outcome. Moreover, survival effects of CSNK1A1 together with p53 were also studied. Eighty-three formalin fixed paraffin embedded colon tumors were enriched for tumor cells using flow sorting, the extracted DNA was used in a custom SNP array to determine chr17p13-11 allelic state; p53 immunostaining, TP53 exons 5, 6, 7 and 8 mutations were determined in combination with mRNA expression analysis on frozen tissue. Patients with a predicted functional p53 had a better prognosis than patients with non functional p53 (Log Rank p=0.009). Expression of CSNK1A1 modified p53 survival effects. Patients with low CSNK1A1 expression and non-functional p53 had a very poor survival both in the univariate (Log Rank p<0.001) and in the multivariate survival analysis (HR=4.74 95% CI 1.45 – 15.3 p=0.009). The combination of mutational, genomic, protein and downstream transcriptional activity data predicted p53 functionality which is shown to have a prognostic effect on colon cancer patients. This effect was specifically modified by CSKN1A1 expression

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

    OpenAIRE

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

    2008-01-01

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

  17. Assessment of risk factors for earlier onset of sporadic Alzheimer?s disease dementia

    OpenAIRE

    Fabricio Ferreira de Oliveira; Paulo Henrique Ferreira Bertolucci; Elizabeth Suchi Chen; Marilia Cardoso Smith

    2014-01-01

    Background: Pharmacological treatment has mild effects for patients with Alzheimer?s disease dementia (AD); therefore, the search for modifiable risk factors is an important challenge. Though risk factors for AD are widely recognized, elements that influence the time of dementia onset have not been comprehensively reported. We aimed to investigate which risk factors might be related to the age of onset of AD in a sample of patients with highly variable educational levels, taking into account ...

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

    Directory of Open Access Journals (Sweden)

    Prakash Neeraj

    2010-11-01

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

  19. Association of CYP1A1 A4889G and T6235C polymorphisms with the risk of sporadic breast cancer in Brazilian women

    Science.gov (United States)

    de Oliveira, Camila Borges Martins; Cardoso-Filho, Cássio; Bossi, Leonardo Silveira; Lourenço, Gustavo Jacob; Costa-Gurgel, Maria Salete; Lima, Carmen Silvia Passos

    2015-01-01

    OBJECTIVES: We examined the influence of CYP1A1 A4889G and T6235C polymorphisms on the risk of sporadic breast cancer. METHOD: DNA from 742 sporadic breast cancer patients and 742 controls was analyzed using the polymerase chain reaction, followed by the restriction fragment length polymorphism technique. RESULTS: More patients had the CYP1A1 4889AG+GG genotype compared to controls (29.0% versus 23.2%, p=0.004). The G allele carriers had a 1.50-fold increased risk (95% CI: 1.14–1.97) of sporadic breast cancer compared to the other study participants. The frequency of the 4889AG+GG genotype among the Caucasian patients was higher than in the non-Caucasian patients (30.4% versus 20.2%, p=0.03) and controls (30.4% versus 23.2%, p=0.002). Caucasians and G allele carriers had a 1.61-fold increased risk (95% CI: 1.20–2.15) of sporadic breast cancer compared to other subjects. The CYP1A1 4889AG+GG genotype was more common among patients with a younger median age at first full-term pregnancy than among controls (33.8% versus 23.2%, p=0.001) and subjects whose first full-term pregnancies occurred at an older age (33.8% versus 26.1%, p=0.03). Women with the CYP1A1 4889AG+GG genotype and earlier first full-term pregnancies had a 1.87-fold (95% CI: 1.32–2.67) increased risk of sporadic breast cancer compared to the other study participants. Excess CYP1A1 4889AG+GG (39.8% versus 27.1%, p=0.01) and 6235TC+CC (48.4% versus 35.9%, p=0.02) genotypes were also observed in patients with grade I and II tumors compared to patients with grade III tumors and controls (39.8% versus 23.2%, p=0.04; 48.4% versus 38.6%, p=0.04). The G and C allele carriers had a 2.44-fold (95% CI: 1.48–4.02) and 1.67-fold (95% CI: 1.03–2.69) increased risk, respectively, of developing grade I and II tumors compared to other subjects. CONCLUSIONS: The CYP1A1 A4889G and T6235C polymorphisms may alter the risk of sporadic breast cancer in Brazilian women. PMID:26598080

  20. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

    International Nuclear Information System (INIS)

    Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive. DNA was extracted from paraffin embedded formalin fixed tissues for the familial cases, and from fresh frozen specimen from the sporadic cases. All cases were treated at our hospital according to protocol. Mutation analyses of exon 2 – 11 were performed using TTGE, followed by sequencing. Survival rates for BRCA1-familial cases with TP53 mutations were not significantly lower than for familial cases without TP53 mutations (p = 0.25, RR = 1.64, 95% CI [0.71–3.78]). Median age at diagnosis for sporadic (59 years) and familial (49 years) cases differed significantly (p < 0.001) with or without TP53 mutations. Age at diagnosis between the two types of familial carriers were not significantly different, with median age of 47 for 1675delA and 52.5 for 1135insA carriers (p = 0.245). For cases ?50 years at diagnosis, a trend toward longer survival for sporadic over familial cases was observed (p = 0.08). The opposite trend was observed for cases <50 years at diagnosis. There do not seem to be a protective advantage for familial BRCA1 carriers without TP53 mutations over familial cases with TP53 mutations. However, there seem to be a trend towards initial advantage in survival for familial cases compared to sporadic cases diagnosed before the age of 50 both with and without TP53 mutations. However, this trend diminishes over time and for cases diagnosed ?50 years the sporadic cases show a trend towards an advantage in survival over familial cases. Although this data set is small, if confirmed, this may be a link in the evidence that the differences in ovarian cancer survival reported, are not due to the type of BRCA1 mutation, but may be secondary to genetic factors shared. This may have clinical implications for follow-up such as prophylactic surgery within carriers of the two most frequent Norwegian BRCA1 founder mutations

  1. Application of genetic testing to define the surgical approach in a sporadic case of multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Cesar Luiz Boguszewski

    2010-11-01

    Full Text Available We report the use of a genetic test for therapeutic decision making in a case of primary hyperparathyroidism associated with Cushing's disease (CD. A 20-year-old woman was evaluated for gradual weight gain, asthenia, muscle pain, and hypertension. Biochemical and radiologic tests confirmed CD and she underwent transsphenoidal surgery. Immunohistochemistry of the microadenoma was positive for adrenocorticotropic hormone (ACTH. On follow-up, hypercalcemia with high parathyroid hormone (PTH levels was detected, associated with nephrolithiasis and low bone mineral density in the spine and hip. Parathyroid scintigraphy showed tracer uptake in the inferior region of the left thyroid lobe, and cervical ultrasound showed a heterogeneous nodule in the same area, suggestive of a parathyroid adenoma (PA. Genetic testing detected mutation in the MEN 1 gene and total parathyroidectomy with the implantation of a fragment of one gland in the forearm was performed. Pathology showed a PA and 3 normal parathyroid glands, without hyperplasia, despite the diagnosis of MEN 1. This case illustrates the role of genetic testing in defining the therapeutic approach for sporadic MEN 1.

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

    Science.gov (United States)

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

    2015-03-01

    A molecular epidemiological study of Norovirus (NoV) infections in children aged Fecal samples were collected from 354 pediatric patients with acute gastroenteritis, and were screened for the presence of NoV with one-step real-time reverse-transcription polymerase chain reaction (RT-PCR). NoV genogroup II (GII) was detected in 28.5% (101/342) of samples, but no NoV GI was found. Eighty-four of the NoV GII strains were successfully sequenced, and they were clustered into seven genotypes: GII.4 (77.4%), GII.2 (8.3%), GII.14 (4.8%), GII.7 (3.6%), GII.3 (2.4%), GII.6 (2.4%), and GII.12 (1.2%). The predominant GII.4 variant in circulation was variant 2006b (92.3%). Importantly, the emergence of variant GII.4 2010 was detected. NoV was detected throughout the year, but mainly during the cold months. The highest prevalence of NoV was detected in young children aged genetic diversity of NoVs in children with sporadic acute gastroenteritis in Nanning. Our study findings indicate the need for continual surveillance to monitor epidemiological changes and potential new variants of these viruses. PMID:25604456

  3. Evidence for lightning-associated enhancement of the ionospheric sporadic E layer dependent on lightning stroke energy

    Science.gov (United States)

    Yu, Bingkun; Xue, Xianghui; Lu, Gaopeng; Ma, Ming; Dou, Xiankang; Qie, Xiushu; Ning, Baiqi; Hu, Lianhuan; Wu, Jianfei; Chi, Yutian

    2015-10-01

    In this study we analyze the lightning data obtained by the World-Wide Lightning Location Network (WWLLN) and hourly ionospheric data observed by ionosondes located at Sanya and Beijing, to examine the changes in ionospheric electron density in response to the underlying thunderstorms and to investigate the possible connection between lightning discharges and the enhancement of the ionospheric sporadic E(Es) layer. We identify a statistically significant enhancement and a decrease in altitude of the Es layer at Sanya station, in agreement with the results found at Chilton, UK. However, the lightning-associated modification of the Es layer investigated using the same approach is not evident at Beijing station. Furthermore, we compare the responses to weak and strong lightning strokes using WWLLN-determined energies at Sanya in 2012. The lightning-associated enhancement of the Es layer is predominantly attributed to powerful strokes with high stroke energy. A statistically significant intensification of the Es layer with higher-energy strokes at Sanya, along with the statistical dependence of lightning-associated enhancement of the Es layer on stroke energy, leads us to conclude that the magnitude of the enhancement is likely associated with lightning stroke energy.

  4. Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata—Possible Routes of Infection and Host Susceptibility

    Science.gov (United States)

    Iacono, Diego; Ferrari, Sergio; Gelati, Matteo; Zanusso, Gianluigi; Mariotto, Sara; Monaco, Salvatore

    2015-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disorder, is characterized by remarkable phenotypic variability, which is influenced by the conformation of the pathologic prion protein and the methionine/valine polymorphic codon 129 of the prion protein gene. While the etiology of sCJD remains unknown, it has been hypothesized that environmental exposure to prions might occur through conjunctival/mucosal contact, oral ingestion, inhalation, or simultaneous involvement of the olfactory and enteric systems. We studied 21 subjects with definite sCJD to assess neuropathological involvement of the dorsal motor nucleus of the vagus and other medullary nuclei and to evaluate possible associations with codon 129 genotype and prion protein conformation. The present data show that prion protein deposition was detected in medullary nuclei of distinct sCJD subtypes, either valine homozygous or heterozygous at codon 129. These findings suggest that an “environmental exposure” might occur, supporting the hypothesis that external sources of contamination could contribute to sCJD in susceptible hosts. Furthermore, these novel data could shed the light on possible causes of sCJD through a “triple match” hypothesis that identify environmental exposure, host genotype, and direct exposure of specific anatomical regions as possible pathogenetic factors. PMID:26457299

  5. PEMT G523A (V175M) is associated with sporadic Alzheimer's disease in a Chinese population.

    Science.gov (United States)

    Bi, Xiu-Hua; Zhao, Hua-Lu; Zhang, Zhen-Xin; Zhang, Jun-Wu

    2012-03-01

    There is evidence that increased concentrations of circulating homocysteine are associated with Alzheimer's disease (AD). Phosphatidylethanolamine N-methyltransferase (PEMT) is an important catalyst involved in the production of homocysteine. We investigated the association of a functional single nucleotide polymorphism (rs7946) in PEMT with sporadic AD risk in a Han Chinese population that included 386 AD patients and 366 controls. PEMT G523A was genotyped by either sequencing or PCR-restriction fragment length polymorphism analysis. The plasma homocysteine concentrations of 210 subjects were determined by high-performance liquid chromatography. Significant higher frequency of the A allele was detected in AD cases than in controls (A vs. G, p?=?0.007, OR?=?1.482, 95% CI 1.114-1.972). After adjusting for gender, age/age at onset, and APOE ?4 status, logistic analysis showed rs7946 was associated with AD in a dominant model (AA?+?GA vs. GG, p?=?0.007, OR?=?1.596, 95% CI 1.138-2.240). When stratified by APOE ?4 status or gender, the significant difference was only observed in the APOE ?4 non-carriers and in the female subjects, respectively. We did not find a relationship of this polymorphism with plasma homocysteine levels. These results suggested that PEMT G523A is associated with AD and that the A allele is an APOE ?4-independent risk factor for AD among Han Chinese women. PMID:21881829

  6. Treatment decision-making for sporadic small vestibular schwannoma in a pediatric patient: A case report and literature review

    Science.gov (United States)

    WANG, JUN; XU, YAJING; LEI, TING; ZENG, LIANG

    2015-01-01

    The current study reports the case of a 15-year-old male who presented with hearing loss due to a small left-sided vestibular schwannoma (VS) not associated with neurofibromatosis type 2 (NF2), which had been apparent for six months. Magnetic resonance imaging with gadolinium diethylenetriamine penta-acetic acid revealed a mass, 10 mm in diameter, located in the left inner auditory canal. The patient had no family history of NF2 and gene mutation analysis showed no signs of the condition. Small sporadic or non-NF2 VS is extremely rare and the treatment decision-making process is complicated in children when considering the implications for the impairment of childhood development and lifelong disability. Following careful consideration, the patient in the present study underwent treatment with stereotactic radiosurgery. The five-year post-operative follow-up examination showed tumor stability without additional neurological deficits and at the time of writing the patient was alive and well. PMID:26137073

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

    Science.gov (United States)

    Berghoff, Anna S; Trummert, Anita; Unterberger, Ursula; Ströbel, Thomas; Hortobágyi, Tibor; Kovacs, Gabor G

    2015-08-01

    We describe an atypical neuropathological phenotype of sporadic Creutzfeldt-Jakob disease in a 76-year-old man. The clinical symptoms were characterized by progressive dementia, gait ataxia, rigidity and urinary incontinence. The disease duration was 6 weeks. MRI did not show prominent atrophy or hyperintensities in cortical areas, striatum or thalamus. Biomarker examination of the cerebrospinal fluid deviated from that seen in pure Alzheimer's disease. Triphasic waves in the EEG were detected only later in the disease course, while 14-3-3 assay was positive. PRNP genotyping revealed methionine homozygosity (MM) at codon 129. Neuropathology showed classical CJD changes corresponding to the MM type 1 cases. However, a striking feature was the presence of abundant kuru-type plaques in the white matter. This rare morphology was associated with neuropathological signs of intranuclear inclusion body disease and advanced stage of argyrophilic grain disease. These alterations did not show correlation with each other, thus seemed to develop independently. This case further highlights the complexity of neuropathological alterations in the ageing brain. PMID:25783686

  8. Detection of low-prevalence somatic TSC2 mutations in sporadic pulmonary lymphangioleiomyomatosis tissues by deep sequencing.

    Science.gov (United States)

    Fujita, Atsushi; Ando, Katsutoshi; Kobayashi, Etsuko; Mitani, Keiko; Okudera, Koji; Nakashima, Mitsuko; Miyatake, Satoko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Seyama, Kuniaki; Miyake, Noriko; Matsumoto, Naomichi

    2016-01-01

    Lymphangioleiomyomatosis (LAM) (MIM #606690) is a rare lung disorder leading to respiratory failure associated with progressive cystic destruction due to the proliferation and infiltration of abnormal smooth muscle-like cells (LAM cells). LAM can occur alone (sporadic LAM, S-LAM) or combined with tuberous sclerosis complex (TSC-LAM). TSC is caused by a germline heterozygous mutation in either TSC1 or TSC2, and TSC-LAM is thought to occur as a result of a somatic mutation (second hit) in addition to a germline mutation in TSC1 or TSC2 (first hit). S-LAM is also thought to occur under the two-hit model involving a somatic mutation and/or loss of heterozygosity in TSC2. To identify TSC1 or TSC2 changes in S-LAM patients, the two genes were analyzed by deep next-generation sequencing (NGS) using genomic DNA from blood leukocytes (n = 9), LAM tissue from lung (n = 7), LAM cultured cells (n = 4), or LAM cell clusters (n = 1). We identified nine somatic mutations in six of nine S-LAM patients (67 %) with mutant allele frequencies of 1.7-46.2 %. Three of these six patients (50 %) showed two different TSC2 mutations with allele frequencies of 1.7-28.7 %. Furthermore, at least five mutations with low prevalence (NGS. PMID:26563443

  9. Sodium lidar-observed gravity wave breaking followed by an upward propagation of sporadic sodium layer over Hefei, China

    Science.gov (United States)

    Ban, Chao; Li, Tao; Fang, Xin; Dou, Xiankang; Xiong, Jiangang

    2015-09-01

    The University of Science and Technology of China sodium temperature/wind lidar observed a strong zonal wind shear (~60 m/s/km) near 98 km between 1315 and 1330 UT on 29 July 2013 and a cooling near 96-100 km (above a warming near 90-95 km) between 1330 and 1430 UT. This suggests a possible gravity wave (GW) breaking event. Comparison of the lidar results with observations from a nearby meteor radar and with satellite results indicated that the GW likely broke down over a large horizontal area. In addition, the sodium number density suddenly increased 10-12 times (˜13, 000atm/cm3) near 95 km at 1400 UT, immediately following the GW breaking. This sporadic sodium layer (SSL), which is different from most previously observed SSL events (which propagate downward), tended to propagate upward and also appeared ~2 min earlier in the west channel than in the east channel. The horizontal propagation direction of the SSL was aligned with the horizontal wind direction, which was likely due to the propagation of a high-density sodium layer from the northwest of the lidar site, and was possibly related to the earlier GW breaking event.

  10. A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females

    International Nuclear Information System (INIS)

    Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples. 32P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue. cDNA probes were hybridized to microarrays and expression levels registered using a phosphorimager. Expression levels of some genes were validated by real time RT-PCR and immunohistochemical assays. We identified two subgroups of tumors according to their expression profiles, probably related with cancer progression. Ten genes, unexpressed in normal tissue, were turned on in some tumors. We found consistent high expression of Bik gene in 14/15 tumors with predominant cytoplasmic distribution. Recently, the product of the Bik gene has been associated with tumoral reversion in different neoplasic cell lines, and was proposed as therapy to induce apoptosis in cancers, including breast tumors. Even though a relationship among genes, for example those from a particular pathway, can be observed through microarrays, this relationship might not be sufficient to assign a definitive role to Bik in development and progression of the neoplasia. The findings herein reported deserve further investigation

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

    Energy Technology Data Exchange (ETDEWEB)

    Hagen, B.

    1986-08-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Carmody J

    2011-04-01

    Full Text Available John Carmody1, Raghunath P Misra1,2, Marlyn P Langford1, William A Byrd1, Lauren Ditta1, Bryan Vekovius1, Donald E Texada11Department of Ophthalmology, 2Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USAAbstract: A case of sporadic Burkitt lymphoma (sBL presenting with jaw and lid involvement in a diabetic adult African American female and a review of adult orbital Burkitt lymphoma cases are presented. Lid edema, visual loss, ophthalmoparesis, proptosis, and sinusitis progressed over 4 weeks despite antibiotic and steroid treatment. Upper lid biopsy histopathological evaluation and immunophenotyping revealed a homogenous mass of atypical CD10 and CD20-negative B-cells and tingible body macrophages yielding a "starry sky" appearance. Cytogenetic analysis detected a minor variant c-MYC translocation, but no Epstein–Barr virus RNA. Detection of multiple lesions prompted a diagnosis of stage IV disease that totally regressed following radiation and chemotherapy. Review results of the six adult orbital sBL cases support a poor prognosis and a heightened suspicion of variant CD10, CD20 and BCL6 positive sBL in adults presenting with jaw pain and rapidly progressive orbital symptoms, particularly in female, African American, and diabetic patients.Keywords: B-cells, Burkitt lymphoma, cancer, diabetes, eye, Epstein–Barr virus, orbit, tumor

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

    Directory of Open Access Journals (Sweden)

    M Hashemzadeh Chaleshtori

    2006-05-01

    Full Text Available Despite the enormous heterogeneity of genetic hearing loss, mutations in the GJB2 (connexin 26 gene located on “DFNB1” locus (13q12 account for up to 50% of cases of autosomal recessive non-syndromic hearing loss (ARNSHL in some populations. This study describes the analysis of 100 autosomal recessive and sporadic nonsyndromic hearing loss individuals from 79 families each having at least one deaf child in Chehar Mahal va Bakhtiari province in west of Iran. We have investigated the prevalence of the connexin 26 gene mutations using nested PCR strategy to screen the predominant 35delG mutation and subsequent direct sequencing to detect other Cx26 mutations. Seven different genetic variants were detected from which one novel variant was including 363delC. The 35delG was the most common mutation found in 5 of 79 families (6.3%. Cx26 related deafness mutations (35delG, [V27I; E114G] and R127H were found in 12 of 158 chromosomes studied (7.8%. We conclude that the association of Cx26 mutations with deafness in Chehar Mahal va Bakhtiari province is low and looks like most other populations of Iran.

  14. Regular effects of random inhomogeneities of the ionosphere in the case of inclined radiowave reflection from the sporadic E layer

    International Nuclear Information System (INIS)

    Medium models and calculation methods are proposed for interpretation of ionospheric radiowave propagation regularities. It is shown that the random inhomogeneities of a medium changes essentially radiowave reflection from the Es layer. In this case maximum radiowave frequencies increase more than by two times and the place angles - by 4-5 deg. The obtained results are explained

  15. A case-control study of risk factors for sporadic campylobacter infections in Denmark

    DEFF Research Database (Denmark)

    Neimann, J.; Engberg, J.

    2003-01-01

    A case control study comprising 282 cases and 319 matched controls was conducted in Denmark during 1996-7. Two estimates of the odds ratio (OR) were determined for each risk factor with and without 'protective factors' fitted into the final model. Consumption of undercooked poultry (OR 4(.)5; 8(.)2), consumption of red meat at a barbecue (OR 2(.)3; 4(.)1), consumption of grapes (OR 1(.)6; 2(.)8) and drinking unpasteurized milk (OR 2(.)3; 11(.)8) were identified as risk factors in both models. Frequent consumption of pork chops (OR 4(.)4) and daily contact with domestic animals and pets were identified as risk factors in one of the two models only. Finally, foreign travel was found to be a significant risk factor (OR 2(.)5). Seasonal and regional interaction was observed for several risk factors and the time elapsed from interviewing of cases to interviewing of controls seemed to influence the effect of certain seasonal dependent risk factors.

  16. Sporadic distribution of prion-forming ability of Sup35p from yeasts and fungi.

    Science.gov (United States)

    Edskes, Herman K; Khamar, Hima J; Winchester, Chia-Lin; Greenler, Alexandria J; Zhou, Albert; McGlinchey, Ryan P; Gorkovskiy, Anton; Wickner, Reed B

    2014-10-01

    Sup35p of Saccharomyces cerevisiae can form the [PSI+] prion, an infectious amyloid in which the protein is largely inactive. The part of Sup35p that forms the amyloid is the region normally involved in control of mRNA turnover. The formation of [PSI+] by Sup35p's from other yeasts has been interpreted to imply that the prion-forming ability of Sup35p is conserved in evolution, and thus of survival/fitness/evolutionary value to these organisms. We surveyed a larger number of yeast and fungal species by the same criteria as used previously and find that the Sup35p from many species cannot form prions. [PSI+] could be formed by the Sup35p from Candida albicans, Candida maltosa, Debaromyces hansenii, and Kluyveromyces lactis, but orders of magnitude less often than the S. cerevisiae Sup35p converts to the prion form. The Sup35s from Schizosaccharomyces pombe and Ashbya gossypii clearly do not form [PSI+]. We were also unable to detect [PSI+] formation by the Sup35ps from Aspergillus nidulans, Aspergillus fumigatus, Magnaporthe grisea, Ustilago maydis, or Cryptococcus neoformans. Each of two C. albicans SUP35 alleles can form [PSI+], but transmission from one to the other is partially blocked. These results suggest that the prion-forming ability of Sup35p is not a conserved trait, but is an occasional deleterious side effect of a protein domain conserved for another function. PMID:25081567

  17. Interaction between lifestyle factors and the XRCC1, XPD, and XRCC3 genetic variations modulates the risk for sporadic colorectal cancer

    OpenAIRE

    Procopciuc Lucia Maria; Osian Gelu

    2014-01-01

    Introducere: Variațiile genetice, cum ar fi cele care influențează sistemele de reparare a defectelor de replicare a ADN, pot reprezenta factori de susceptibilitate în cancerul colorectal sporadic (CCR) ca urmare a interacțiunii cu factori de mediu. Material și metodă: 80 de femei și 70 de bărbați, pacienți diagnosticați cu CCR sporadic în Clinica Chirurgie III Cluj au fost genotipați pentru Arg399Gln-XRCC1, Lys751Gln-XPD și Met241Thr-XRCC3 utilizând metodele PCR-RFLP. Am determinat de asemen...

  18. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

    Science.gov (United States)

    Asante, Emmanuel A.; Linehan, Jacqueline M.; Desbruslais, Melanie; Joiner, Susan; Gowland, Ian; Wood, Andrew L.; Welch, Julie; Hill, Andrew F.; Lloyd, Sarah E.; Wadsworth, Jonathan D.F.; Collinge, John

    2002-01-01

    Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure. PMID:12456643

  19. Intermittent thermal plasma acceleration linked to sporadic motions of the magnetopause, first Cluster results

    Directory of Open Access Journals (Sweden)

    J.-A. Sauvaud

    Full Text Available This paper presents the first observations with Cluster of a very dense population of thermal ionospheric ions (H+, He+, O+ locally "accelerated" perpendicularly to the local magnetic field in a region adjacent to the magnetopause and on its magnetospheric side. The observation periods follow a long period of very weak magnetic activity. Recurrent motions of the magnetopause are, in the presented cases, unexpectedly associated with the appearance inside closed field lines of recurrent energy structures of ionospheric ions with energies in the 5 eV to  ~1000 eV range. The heaviest ions were detected with the highest energies. Here, the ion behaviour is interpreted as resulting from local electric field enhancements/decreases which adiabatically enhance/lower the bulk energy of a local dense thermal ion population. This drift effect, which is directly linked to magnetopause motions caused by pressure changes, allows for the thermal ions to overcome the satellite potential and be detected by the suprathermal CIS Cluster experiment. When fast flowing, i.e. when detectable, the density (~ 1 cm-3 of these ions from a terrestrial origin is (in the cases presented here largely higher than the local density of ions from magnetospheric/plasma sheet origin which poses again the question of the relative importance of solar and ionospheric sources for the magnetospheric plasma even during very quiet magnetic conditions.

    Key words. Ionosphere (planetary ionosphere; plasma convection Magnetospheric physics (magnetopause, cusp and boundary layers

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

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    Elias Karakas

    2012-01-01

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

  1. Assessment of risk factors for earlier onset of sporadic Alzheimer′s disease dementia

    Directory of Open Access Journals (Sweden)

    Fabricio Ferreira de Oliveira

    2014-01-01

    Full Text Available Background: Pharmacological treatment has mild effects for patients with Alzheimer′s disease dementia (AD; therefore, the search for modifiable risk factors is an important challenge. Though risk factors for AD are widely recognized, elements that influence the time of dementia onset have not been comprehensively reported. We aimed to investigate which risk factors might be related to the age of onset of AD in a sample of patients with highly variable educational levels, taking into account the Framingham risk scoring as the sole measure of vascular risk. Subjects and Methods: We included 209 consecutive late-onset AD patients to find out which factors among educational levels, coronary heart disease risk estimated by way of Framingham risk scores, history of head trauma or depression, surgical procedures under general anesthesia, family history of neurodegenerative diseases, gender, marital status and APOE haplotypes might be related to the age of dementia onset in this sample of patients with low mean schooling. Results: Mean age of AD onset was 73.38 ± 6.5 years old, unaffected by schooling or family history of neurodegenerative diseases. Patients who were APOE-ε4 carriers, married, or with history of depression, had earlier onset of AD, particularly when they were women. Coronary heart disease risk was marginally significant for later onset of AD. Conclusions: APOE haplotypes, marital status and history of depression were the most important factors to influence the age of AD onset in this sample. While midlife cerebrovascular risk factors may increase incidence of AD, they may lead to later dementia onset when present in late life.

  2. Mutational Analysis of p27 (CDKN1B) and p18 (CDKN2C) in Sporadic Pancreatic Endocrine Tumors Argues against Tumor-Suppressor Function1

    OpenAIRE

    Lindberg, Daniel; Åkerström, Göran; Westin, Gunnar

    2007-01-01

    Pancreatic endocrine tumors (PETs) arise sporadically or are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome or von Hippel-Lindau syndrome. About 90% of patients with familial MEN1 display detectable MEN1 gene (menin) mutations. The cyclin-dependent kinase inhibitor p27 (CDKN1B) is a downstream target of menin and has been recently shown to be responsible for the multiple endocrine neoplasia-like syndrome in rats, where affected animals develop multiple tumors and hyperpla...

  3. BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma: Association with low expression of BRCA1, improved survival and co-expression of DNA methyltransferases

    OpenAIRE

    BAI, XUEFENG; Fu, Yingzi; Xue, Hui; Guo, Kejun; Song, Zhiguo; Yu, Zhaojin; JIA, TIANHONG; YAN, YUANYUAN; Zhao, Lin; Mi, Xiaoyi; Wang, Enhua; ZHENG, ZHIHONG; Zhao, Haishan; Yao, Weifan; Wei, Minjie

    2014-01-01

    The breast cancer susceptibility gene 1 (BRCA1) inactivation in sporadic epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is associated with promoter hypermethylation. The clinical validation of BRCA1 methylation as a prognostic marker in EOC remains unresolved. The aim of the present study was to determine the aberrant promoter methylation of BRCA1 in benign and malignant ovarian tumor tissues, to establish the association with the clinicopathological significance and th...

  4. Enhanced Sensitivity for Detection of Low-Level Germline Mosaic RB1 Mutations in Sporadic Retinoblastoma Cases Using Deep Semiconductor Sequencing

    OpenAIRE

    Chen, Zhao; Moran, Kimberly; Richards-Yutz, Jennifer; Toorens, Erik; Gerhart, Daniel; Ganguly, Tapan; Carol L. Shields; Ganguly, Arupa

    2013-01-01

    Sporadic retinoblastoma (RB) is caused by de novo mutations in the RB1 gene. Often, these mutations are present as mosaic mutations that cannot be detected by Sanger sequencing. Next-generation deep sequencing allows unambiguous detection of the mosaic mutations in lymphocyte DNA. Deep sequencing of the RB1 gene on lymphocyte DNA from 20 bilateral and 70 unilateral RB cases was performed, where Sanger sequencing excluded the presence of mutations. The individual exons of the RB1 gene from eac...

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

    Directory of Open Access Journals (Sweden)

    Jeong Byung-Hoon

    2011-08-01

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

  6. Protease-Sensitive Conformers in Broad Spectrum of Distinct PrPSc Structures in Sporadic Creutzfeldt-Jakob Disease Are Indicator of Progression Rate

    OpenAIRE

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

    2011-01-01

    The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD), are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrPSc) using novel conformational methods derived from a conformation-dependent immunoassay (CDI). In 46 brains o...

  7. WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer

    OpenAIRE

    Serafino, Annalucia; Moroni, Noemi; Zonfrillo, Manuela; Andreola, Federica; Mercuri, Luana; Nicotera, Giuseppe; Nunziata, Joseph; Ricci, Riccardo; Antinori, Armando; Rasi, Guido; Pierimarchi, Pasquale

    2014-01-01

    The key role of the Wnt/?-catenin signaling in colorectal cancer (CRC) insurgence and progression is now recognized and several therapeutic strategies targeting this pathway are currently in developing. Wnt/?-catenin signaling not only dominates the early stages of sporadic colorectal cancer (SCC), but could also represent the connection between inflammatory bowel diseases (IBD) and increased risk of developing SCC. The knowledge on the sequential molecular events of Wnt-signaling cascade in ...

  8. Diagnostic microRNA markers to screen for sporadic human colon cancer in blood.

    Science.gov (United States)

    Ahmed, Farid E; Amed, Nancy C; Vos, Paul W; Bonnerup, Chris; Atkins, James N; Casey, Michelle; Nuovo, Gerard J; Naziri, Wade; Wiley, John E; Allison, Ron R

    2012-01-01

    We carried out this study to present proof-of-principal application, showing that by using a global microarray expression analysis, followed by quantitative stem-loop reverse transcriptase in conjunction with TaqMan® polymerase chain reaction (PCR) analysis of micro(mi)RNA genes, on limited number of plasma and tissue samples obtained from 20 individuals (five healthy, five TNM stage 0-1 colon cancer, five stage 2 and five stage 3), we were able to quantitatively monitor miRNA changes at the various TNM stages of colon cancer progression, particularly at the early, pre-malignant adenoma stage (e.g. polyps ≥ 1 cm with high grade dysplasia). The expression of some of the tested miRNAs showed less variability in tissue than in plasma. Nevertheless, our limited preliminary data on the plasma by itself show that plasma is well-suited for screening, and that the quantitative changes in the expression of a few cell-free circulatory mature miRNA molecules in plasma, that are associated with colon cancer progression, would provide for more sensitive and specific markers than those tests currently available on the market. In addition, analysis of miRNA molecules offers a quantitative and cost-effective non-invasive diagnostic approach for screening, than currently employed methods in a prevalent cancer that can be cured if it is detected at the early TNM stages, and that becomes deadly if not diagnosed before metastasis. Thus, a larger prospective and properly randomized clinical study using plasma derived from many control individuals and at various stages of colon cancer (TNM stages 0-IV) from patients, in order to corroborate the initial results, is now urgently needed in order to allow for a statistically valid analysis, standardizing test conditions which will provide a means for determining the true sensitivity and specificity of a miRNA-screening approach. This approach, when combined with bioinformatics analysis to correlate miRNA seed data with mRNA target data, would allow for a mechanistic understanding of how miRNAs regulate mRNA gene expression, and would offer a better comprehensive diagnostic screening test for early-detection of colon cancer non-invasively. PMID:22798503

  9. Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia.

    Science.gov (United States)

    Meyer, Stefan; Barber, Lisa M; White, Daniel J; Will, Andrew M; Birch, Jillian M; Kohler, Janice A; Ersfeld, Klaus; Blom, Eric; Joenje, Hans; Eden, Tim O B; Malcolm Taylor, G

    2006-05-01

    Childhood acute myeloid leukaemia (AML) is uncommon. Children with Fanconi anaemia (FA), however, have a very high risk of developing AML. FA is a rare inherited disease caused by mutations in at least 12 genes, of which Fanconi anaemia group G gene (FANCG) is one of the commonest. To address to what extent FANCG variants contribute to sporadic childhood AML, we determined the spectrum of FANCG sequence variants in 107 children diagnosed with sporadic AML, using polymerase chain reaction (PCR), fluorescent single-strand conformational polymorphism (SSCP) and sequencing methodologies. The significance of variants was determined by frequency analysis and assessment of evolutionary conservation. Seven children (6.5%) carried variants in FANCG. Two of these carried two variants, including the known IVS2 + 1G>A mutation with the novel missense mutation S588F, and R513Q with the intronic deletion IVS12-38 (-28)_del11, implying that these patients might have been undiagnosed FA patients. R513Q, which affects a semi-conserved amino acid, was carried in two additional children with AML. Although not significant, the frequency of R513Q was higher in children with AML than unselected cord bloods. While FANCG mutation carrier status does not predispose to sporadic AML, the identification of unrecognised FA patients implies that FA presenting with primary AML in childhood is more common than suspected. PMID:16643430

  10. The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls

    International Nuclear Information System (INIS)

    Breast cancers in BRCA1 gene mutation carriers often have specific histologic features: grade III tumors with pushing margins. Our purpose was to compare the mammographic and histologic features of breast cancers in carriers with those in age-matched sporadic controls. The features of breast cancers in 27 BRCA1 carriers found during annual surveillance were compared to those in 107 age-matched sporadic controls. The carriers had no (classic) spiculated mammographic lesions, a high percentage of well-defined masses and hardly any masses with microcalcifications, whereas the controls had significantly fewer well-defined ones and only in 27% spiculated lesions on the mammogram. The well-defined mammographic tumors correlated in 83% of the carriers and in 70% of the controls with histologic circumscribed tumor margins. Spiculated mammographic lesions in the controls were in 90% grade I or II tumors. DCIS with or without infiltration was seen in 22% of the carriers and in 45% of the controls. In conclusion, breast cancers diagnosed in BRCA1 carriers do not have classic malignant mammographic features. A minority of the young sporadic controls show the classic malignant lesion on the mammogram. Both carriers and controls generally show a good correlation between their mammographic- and histologic tumor pattern. (orig.)

  11. The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls

    Energy Technology Data Exchange (ETDEWEB)

    Kaas, R. [The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Department of Surgery, Amsterdam (Netherlands); Kroger, R.; Muller, S.H. [The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); Peterse, J.L. [The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Pathology, Amsterdam (Netherlands); Hart, A.A.M. [The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Department of Radiotherapy, Amsterdam (Netherlands)

    2006-12-15

    Breast cancers in BRCA1 gene mutation carriers often have specific histologic features: grade III tumors with pushing margins. Our purpose was to compare the mammographic and histologic features of breast cancers in carriers with those in age-matched sporadic controls. The features of breast cancers in 27 BRCA1 carriers found during annual surveillance were compared to those in 107 age-matched sporadic controls. The carriers had no (classic) spiculated mammographic lesions, a high percentage of well-defined masses and hardly any masses with microcalcifications, whereas the controls had significantly fewer well-defined ones and only in 27% spiculated lesions on the mammogram. The well-defined mammographic tumors correlated in 83% of the carriers and in 70% of the controls with histologic circumscribed tumor margins. Spiculated mammographic lesions in the controls were in 90% grade I or II tumors. DCIS with or without infiltration was seen in 22% of the carriers and in 45% of the controls. In conclusion, breast cancers diagnosed in BRCA1 carriers do not have classic malignant mammographic features. A minority of the young sporadic controls show the classic malignant lesion on the mammogram. Both carriers and controls generally show a good correlation between their mammographic- and histologic tumor pattern. (orig.)

  12. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD)-Novel and Unique Pathological Features

    Science.gov (United States)

    Zhao, Yuhai; Pogue, Aileen I.; Lukiw, Walter J.

    2015-01-01

    Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA–mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer’s disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-?B-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS. PMID:26694372

  13. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

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    Cobbs Gary A

    2007-05-01

    Full Text Available Abstract Background N-acetyltransferase 1 (NAT1 and 2 (NAT2 are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD consist of Crohn's disease (CD and ulcerative colitis (UC, both are associated with increased colorectal cancer (CRC risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD. Methods A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes. Results No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs. Conclusion This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-15

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

  15. Promoter Hypermethylation of Estrogen Receptor Alpha Gene Is Correlated to Estrogen Receptor Negativity in Iranian Patients with Sporadic Breast Cancer

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    Mohammad Taghi Akbari

    2012-01-01

    Full Text Available Objective: Breast Cancer is the most common cancer in Iranian women. Breast tumors are classified based on the estrogen receptor alpha (ER? expression status into ER negative and ER positive tumors. ER negative tumors tend to have worse prognosis and less likely to respond to endocrine therapy. Aberrant methylation of gene promoter is one of the mechanisms for gene silencing in breast tumors. Because of its reversible nature, promoter methylation is a good target for new therapeutic strategies. We aimed to evaluate the frequency of this epigenetic event in ER? gene and its association to clinicopathological features in Iranian breast cancer patients.Materials and Methods: In this case control study the patient series consisted of 100 sporadic primary breast cancer cases (51 ER negative and 49 ER positive tumors. None of the participants had chemo or radiotherapy before surgery. In breast tumors ER? promoter methylation were assessed with methylation specific polymerase chain reaction (MSP. Data was collected on clinicopathological features of the patients. Correlation between ER? methylation and clinicopathological characteristics of the patients was investigated by Pearson Chi-Square and Fisher’s exact test.Results: ER? methylation was detected in 98% of ER negative and 65% of ER positive breast tumors. A strong correlation was found between ER? methylation and ER negativity in tumors (p<0.0001. Also, ER? methylation has associated to progesterone receptor negativity (p<0.008 and double receptor negative status (p<0.0001 in breast tumors.Conclusion: ER? methylation occurs with high frequency in the breast tumors of Iranian breast cancer patients and may play a considerable role in pathogenesis of ER? negative tumors as a poor prognosis and more aggressive category. The reversible nature of DNA methylation may provide new therapeutic possibilities in ER negative breast tumors.

  16. Sporadic Creutzfeldt-Jakob disease diagnostic accuracy is improved by a new CSF ELISA 14-3-3γ assay.

    Science.gov (United States)

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

    2016-05-13

    Protein 14-3-3 is a reliable marker of rapid neuronal damage, specifically increased in cerebrospinal fluid (CSF) of sporadic Creutzfeldt-Jakob disease (sCJD) patients. Its detection is usually performed by Western Blot (WB), prone to methodological issues. Our aim was to evaluate the diagnostic performance of a recently developed quantitative enzyme-linked immunosorbent (ELISA) assay for 14-3-3γ, in comparison with WB and other neurodegeneration markers. CSF samples from 145 patients with suspicion of prion disease, later classified as definite sCJD (n=72) or Non-prion diseases (Non-CJD; n=73) comprised our population. 14-3-3 protein was determined by WB and ELISA. Total Tau (t-Tau) and phosphorylated Tau (p-Tau) were also evaluated. Apolipoprotein E gene (ApoE) and prionic protein gene (PRNP) genotyping was assessed. ELISA 14-3-3γ levels were significantly increased in sCJD compared to Non-CJD patients (pAUC=0.982; sensitivity=97%; specificity=94%), and matching WB results in 81% of all cases. It strongly correlated with t-Tau and p-Tau (p<0.0001), showing slightly higher specificity (14-3-3 WB - 63%; Tau - 90%; p-Tau/t-Tau ratio - 88%). From WB inconclusive results (n=44), ELISA 14-3-3γ correctly classified 41 patients. Additionally, logistic regression analysis selected ELISA 14-3-3γ as the best single predictive marker for sCJD (overall accuracy=93%). ApoE and PRNP genotypes did not influence ELISA 14-3-3γ levels. Despite specificity for 14-3-3γ isoform, ELISA results not only match WB evaluation but also help discrimination of inconclusive results. Our results therefore reinforce this assay as a single screening test, allowing higher sample throughput and unequivocal results. PMID:26940479

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

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    Galasko Douglas

    2010-01-01

    Full Text Available Abstract Background Alzheimer's disease (AD is associated with deposition of amyloid ? (A? in the brain, which is reflected by low concentration of the A?1-42 peptide in the cerebrospinal fluid (CSF. There are at least 15 additional A? peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of A?. Here, we test the hypothesis that AD is characterized by a specific CSF A? isoform pattern that is distinct when comparing sporadic AD (SAD and familial AD (FAD due to different mechanisms underlying brain amyloid pathology in the two disease groups. Results We measured A? isoform concentrations in CSF from 18 patients with SAD, 7 carriers of the FAD-associated presenilin 1 (PSEN1 A431E mutation, 17 healthy controls and 6 patients with depression using immunoprecipitation-mass spectrometry. Low CSF levels of A?1-42 and high levels of A?1-16 distinguished SAD patients and FAD mutation carriers from healthy controls and depressed patients. SAD and FAD were characterized by similar changes in A?1-42 and A?1-16, but FAD mutation carriers exhibited very low levels of A?1-37, A?1-38 and A?1-39. Conclusion SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF A? isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of A?1-37, A?1-38 and A?1-39; fragments that are normally produced by ?-secretase, suggesting that the PSEN1 A431E mutation modulates ?-secretase cleavage site preference in a disease-promoting manner.

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

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    Mehdi Nikbakht Dastjerdi

    2008-12-01

    Full Text Available

    • BACKGROUND: A common polymorphism at codon 72 of TP53 gene has been associated with increased risk for many human cancers. We studied this TP53 polymorphism in colorectal adenocarcinomas in small population selected from Isfahan city.
    • METHODS: Samples: We undertook a case-control study on 180 controls and 180 paraffin block specimens of sporadic colorectal adenocarcinomas. PCR amplification of TP53 codon 72 polymorphism: TP53 codon 72 genotypes were detected by PCR using specific primer pairs for amplifying the Proline or the Arginine alleles.
    • STATISTICAL ANALYSES: The 42-test was used to assess the significance of any difference in the prevalence of TP53 codon 72 polymorphism between colorectal cancer patients and controls.
    • RESULTS: In control samples, the genotype distribution for TP53 polymorphism showed 28.3%, 48.9% and 22.8% for the Arginine/Arginine, Arginine/Proline and Proline/Proline genotypes, respectively. In the cancer group 40% of the cases were Arginine/Arginine, 42.2% were Arginine/Proline and 17.8% were Proline/Proline. A significant difference between cases and controls was found for the Arginine/Arginine genotype compared with (grouped Arginine/Proline and Proline/Proline genotypes (Odds Ratio = 1.686 (1.085-2.620, P = 0.02.
    • CONCLUSIONS: TP53 codon 72 polymorphism may be a genetic predisposing factor for colorectal adenocarcinomas in Isfahan city.
    • KEYWORDS: Colorectal adenocarcinoma, TP53, Arginine, Proline, Polymorphism.

  19. Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients.

    Science.gov (United States)

    Yam, Y Y; Hoh, B P; Othman, N H; Hassan, S; Yahya, M M; Zakaria, Z; Ankathil, R

    2013-01-01

    Colorectal cancer is one of the most common cancers in many countries, including Malaysia. The accumulation of genomic alterations is an important feature of colorectal carcinogenesis. A better understanding of the molecular events underlying the stages of colorectal carcinogenesis might be helpful in the detection and management of the disease. We used a commercially available single-nucleotide polymorphism genotyping array to detect both copy number abnormalities (CNAs) and copy-neutral loss of heterozygosity (LOH) in sporadic colorectal carcinomas. Matched tumor and normal tissues of 13 colorectal carcinomas (Dukes' stages A-D) were analyzed using a 250K single nucleotide polymorphism array. An additional assay was performed to determine the microsatellite instability status by using the National Cancer Institute-recommended BAT-26 panel. In general, copy number gain (92.3%) was most common, followed by copy number loss (53.8%) and copy-neutral LOH (46.2%). Frequent CNAs of gains and losses were observed on chromosomes 7p, 8, 13q, 17p, 18q, and 20q, and copy-neutral LOH was observed on chromosomes 2, 6, 12, 13q, 14q, 17, 20p, 19q, and 22q. Even though genomic alterations are associated with colorectal cancer progression, our results showed that DNA CNAs and copy-neutral LOH do not reflect disease progression in at least 50% tumors. Copy-neutral LOH was observed in both early and advanced tumors, which favors the involvement of these genomic alterations in the early stages of tumor development. PMID:23420356

  20. Electron density and plasma waves in mid-latitude sporadic-E layer observed during the SEEK-2 campaign

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    H. Mori

    2005-10-01

    Full Text Available The SEEK-2 campaign was carried out over Kyushu Island in Japan on 3 August 2002, by using the two sounding rockets of S310-31 and S310-32. This campaign was planned to elucidate generation mechanisms of Quasi-Periodic Echoes (QPEs associated with mid-latitude sporadic-E (Es layers. Electron number densities were successfully measured in the Es layers by using the impedance probe on board two rockets. The plasma waves in the VLF and ELF ranges were also observed on board the S310-32 rocket. Results of electron density measurement showed that there were one or two major peaks in the Es layers along the rockets' trajectories near the altitude of about 10km. There were some smaller peaks associated with the main Es layers in the altitude range from 90 to 120 km. These density peaks were distributed in a very large extent during the SEEK-2 campaign. The Es layer structure is also measured by using the Fixed Bias Probe (FBP, which has a high spatial resolution of several meters (the impedance probe has an altitude resolution of about 400 m. The comparison with the total electron content (TEC measured by the Dual Band Beacon revealed that the Es layer was also modulated in the horizontal direction with the scale size of 30–40 km. It was shown that the QP echoes observed by the ground-based coherent radar come from the major density peak of the Es layer. The plasma wave instrument detected the enhancement of VLF and ELF plasma waves associated with the operation of the TMA release, and also with the passage of the Es layers. Keywords. Ionosphere (Ionospheric irregularities; Midlatitude ionosphere; Plasma temeperature and density

  1. Risk Factors for Sporadic Domestically Acquired Campylobacter Infections in Norway 2010–2011: A National Prospective Case-Control Study

    Science.gov (United States)

    Mexia, Ricardo; Bruun, Tone; Kapperud, Georg; Lange, Heidi; Nygård, Karin; Vold, Line

    2015-01-01

    Background Campylobacteriosis is the most frequently reported food- and waterborne infection in Norway. We investigated the risk factors for sporadic Campylobacter infections in Norway in order to identify areas where control and prevention measures could be improved. Methods A national prospective case-control study of factors associated with Campylobacter infection was conducted from July 2010 to September 2011. Cases were recruited from the Norwegian Surveillance System of Communicable Diseases (MSIS). Controls were randomly selected from the Norwegian Population Registry. Cases and controls were mailed a paper questionnaire with a prepaid return envelope. Univariable analyses using logistic regression were conducted for all exposures. A final parsimonious multivariable model was developed using regularized/penalized logistic regression, and adjusted odds ratios were calculated. Results A total of 995 cases and 1501 controls were included in the study (response proportion 55% and 30%, respectively). Exposures that had significant increases in odds of Campylobacter infection in multivariable analysis were drinking water directly from river, stream, or lake (OR: 2.96), drinking purchased bottled water (OR: 1.78), eating chicken (1.69), eating meat that was undercooked (OR: 1.77), eating food made on a barbecue (OR: 1.55), living on a farm with livestock (OR: 1.74), having a dog in the household (OR: 1.39), and having household water supply serving fewer than 20 houses (OR: 1.92). Conclusions Consumption of poultry and untreated water remain important sources of Campylobacter infection in Norway, despite ongoing control efforts. The results justify the need for strengthening education for consumers and food handlers about the risks of cross-contamination when preparing poultry and with consuming raw or undercooked chicken. The public should also be reminded to take precautions when drinking untreated water in nature and ensure continued vigilance in order to protect and maintain the quality of water from small-scale water supply systems. PMID:26431341

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

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    Sierra-Moros Maríajosé

    2006-07-01

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

  3. Sporadic meningioangiomatosis-associated atypical meningioma mimicking parenchymal invasion of brain: a case report and review of the literature

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    Luo Bo-ning

    2010-06-01

    Full Text Available Abstract Meningioangiomatosis is a rare hamartomatous lesion or meningiovascular malformation in brain. In extremely rare condition, meningioma may occur together with meningioangiomatosis, and only 19 cases have been described in English literature until now. We now report a case of meningioangiomatosis-associated meningioma with atypical and clear cell variant. A 34-year-old man presented a 3-month history of progressive numbness and weakness of his left lower extremity. He had no stigmata of neurofibromatosis type 2. Magnetic resonance imaging (MRI revealed multifocal lesions in the right frontoparietal lobe. The lesions were totally removed. Microscopically, parts of lesions were atypical and clear cell meningioma corresponding to WHO grade II. The adjacent brain parenchyma showed the histological features of meningioangiomatosis. Neoplastic cells in atypical meningioma area were immunoreactive to epithelial membrane antigen (EMA with high MIB-1 index of up to 20%. However, the spindle cells in meningioangiomatosis area were negative for EMA with low MIB-1 index of up to 1%. The diagnosis of atypical meningioma associated with sporadic meningioangiomatosis was made. To our knowledge, this is the first case of a meningioangiomatosis-associated meningioma with atypical and clear cell variant component to be described. The patient had been followed-up for 11 months without adjuvant radiotherapy or chemotherapy. No tumor recurrence was found during this period. Meningioangiomatosis-associated meningioma is more likely to occur in younger patients and histologically to mimic parenchymal invasion of brain. We suggest that postoperative radiotherapy or chemotherapy should be given careful consideration to avoid over-treatment due to erroneously interpret as malignant meningioma.

  4. Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids

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    Ogata Hiroyuki

    2011-09-01

    Full Text Available Abstract Background The Mre11/Rad50 complex and the homologous SbcD/SbcC complex in bacteria play crucial roles in the metabolism of DNA double-strand breaks, including DNA repair, genome replication, homologous recombination and non-homologous end-joining in cellular life forms and viruses. Here we investigated the amino acid sequence of the Mimivirus R555 gene product, originally annotated as a Rad50 homolog, and later shown to have close homologs in marine microbial metagenomes. Results Our bioinformatics analysis revealed that R555 protein sequence is constituted from the fusion of an N-terminal Mre11-like domain with a C-terminal Rad50-like domain. A systematic database search revealed twelve additional cases of Mre11/Rad50 (or SbcD/SbcC fusions in a wide variety of unrelated organisms including unicellular and multicellular eukaryotes, the megaplasmid of a bacterium associated to deep-sea hydrothermal vents (Deferribacter desulfuricans and the plasmid of Clostridium kluyveri. We also showed that R555 homologs are abundant in the metagenomes from different aquatic environments and that they most likely belong to aquatic viruses. The observed phyletic distribution of these fusion proteins suggests their recurrent creation and lateral gene transfers across organisms. Conclusions The existence of the fused version of protein sequences is consistent with known functional interactions between Mre11 and Rad50, and the gene fusion probably enhanced the opportunity for lateral transfer. The abundance of the Mre11/Rad50 fusion genes in viral metagenomes and their sporadic phyletic distribution in cellular organisms suggest that viruses, plasmids and transposons played a crucial role in the formation of the fusion proteins and their propagation into cellular genomes.

  5. Genetic variants at chromosome 8q24, colorectal epithelial cell proliferation, and risk for incident, sporadic colorectal adenomas.

    Science.gov (United States)

    Yang, Baiyu; Thyagarajan, Bharat; Gross, Myron D; Goodman, Michael; Sun, Yan V; Bostick, Roberd M

    2014-02-01

    Three polymorphic sites at chromosome 8q24 (rs7837328, rs10808555, rs6983267) have been associated with risk for colorectal adenomas. It was also previously reported that the single nucleotide polymorphism (SNP) rs6983267 may enhance Wnt signaling, which regulates cell proliferation. To investigate associations between the 8q24 variants and colorectal epithelial cell proliferation in the normal-appearing colorectal mucosa, as well as with colorectal adenoma, we analyzed data from a previously conducted pilot, colonoscopy-based case-control study of incident, sporadic colorectal adenoma (n = 90 cases, 132 controls). Proliferation was measured in biopsies of the normal-appearing mucosa of the rectum, sigmoid colon, and cecum using immunohistochemistry for proliferating cell nuclear antigen (PCNA). The direct associations of each SNP with colorectal adenoma were consistent with those in previous reports. For all three SNPs, proliferation tended to be higher among those homozygous for the risk alleles compared to those heterozygous or homozygous for the nonrisk alleles combined; among the controls, proliferation was 32.1% higher (P = 0.23) for those with the rs10808555 GG genotype, 16.4% higher (P = 0.16) for those with the rs7837328 AA genotype, and 6.5% higher (P = 0.52) for those with the rs6983267 GG genotype. These preliminary findings, which are consistent with previously reported direct associations between genetic variants at chromosome 8q24 and risk for colorectal adenoma, suggest that the genetic variants may also be associated with higher levels of colorectal epithelial cell proliferation, thus providing support for further investigation of the hypothesis that 8q24 variants may increase risk via enhanced Wnt signaling. PMID:23776012

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

    International Nuclear Information System (INIS)

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

  7. 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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    Pooneh Mokarram, Fakhraddin Naghibalhossaini, Mehdi Saberi Firoozi, Seyed Vahid Hosseini, Ahmad Izadpanah, Heshmetalah Salahi, Seyed Ali Malek-Hosseini, Abdoulrasool Talei, Mehra Mojallal

    2008-06-01

    Full Text Available AIM: To evaluate joint effects of Methylentetrahydrofolate reductase (MTHFR C677T genotypes, and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients.METHODS: We examined the associations between MTHFR C677T genotype, and promoter methylation of P16, hMLH1, and hMSH2 tumor-related genes among 151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit.RESULTS: We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison, we did not find a significant association between methylation in tumors and any single genotype. However, in comparison to controls with the CC genotype, an increased risk of tumor methylation was associated with the CT genotype (OR = 2.5; 95% CI, 1.1-5.6. In case-case comparisons, folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high (above median versus low (below median serum folate/vitamin B12 levels were 4.9 (95% CI, 1.4-17.7, and 3.9 (95% CI, 1.1-13.9, respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group, especially in those with MTHFR CT (P = 0.01, and CT/TT (P = 0.002 genotypes, but not in those with the CC genotype (P = 1.0.CONCLUSION: We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes.

  8. CADASIL: Una forma de demencia vascular hereditaria: Presentación de un caso clínico aparentemente esporádico / CADASIL: Hereditary vascular dementia: Description of an apparently sporadic clinical case

    Scientific Electronic Library Online (English)

    David, Sáez; Osvaldo, Trujillo; Jorge, Nogales-Gaete; Tatiana, Figueroa; Daniel, Valenzuela.

    2003-01-01

    Full Text Available Presentamos un caso de CADASIL (acrónimo inglés de arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía), que corresponde al primero de una serie de 4 casos diagnosticados en nuestro servicio desde 1998, con correlato clínico, imageno-lógico y de ultrapatología [...] muscular (microscopia electrónica). Se trata de una paciente mujer con historia de dos crisis isquémicas cerebrales transitorias a los 29 años, sin factores de riesgo tradicionales para patología cerebrovascular, que luego de 7 años desarrolló síntomas de tipo depresivos, asociados a un cuadro de retraimiento sicomotor y parkinsonismo de carácter progresivo y sin respuesta a terapia farmacológica convencional. En su estudio, la resonancia nuclear magnética de cerebro mostró extensas alteraciones en sustancia blanca a nivel fronto-occipital, bilaterales, hiperintensas en T2 e hipointensas en T1, cuya señal no se reforzó con gadolinio, sin efecto de masa, asociadas a leucoaraiosis, compatibles con el diagnóstico de CADASIL. El estudio de una biopsia muscular mediante microscopia electrónica, confirmó una arteriopatia con depósito de material granular osmiofílico en los vasos sanguíneos, tipo CADASIL. No encontramos antecedentes de cuadros demenciales ni cerebrovasculares sintomáticos en otros parientes de la paciente, madre, padre, tíos, abuelos, por lo que es probable que se trate de un cuadro esporádico. No realizamos estudio genético ni biopsico de los parientes asintomáticos. Las características de la paciente ilustran cuando sospechar el diagnóstico de CADASIL, aún frente a un caso aparentemente esporádico Abstract in english We describe a patient with CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), the first of four patients diagnosed in our service since 1998, correlating clinical, imaging, and muscular pathology (on electronic microscopy) data. The patient is a wom [...] an with no risk factors for cerebrovascular pathology who suffered two transient ischemic attacks at the age of 29. Seven years later, she developed symptoms of depression manifested as psychomotor withdrawal and progressive Parkinsonism that did not respond to pharmacological treatment. An MRI brain scan showed extensive bilateral alterations in the white matter in the frontal and occipital regions, hyperintense in T2 and hypointense in T1-weighted images, without gadolinium enhancement. They had no mass effect, were associated with leukoaraiosis, and were compatible with the diagnosis of CADASIL. Muscle biopsy showed an arteriopathy with CADASIL-type osmiophilic granular deposits in the blood vessels. No history of symptomatic dementia or cerebrovascular disorders were found among the patient’s mother, father, aunts, uncles, or grandparents. This is most likely a sporadic case. No genetic studies or biopsies were done in asymptomatic relatives

  9. CADASIL: Una forma de demencia vascular hereditaria: Presentación de un caso clínico aparentemente esporádico CADASIL: Hereditary vascular dementia: Description of an apparently sporadic clinical case

    Directory of Open Access Journals (Sweden)

    David Sáez

    2003-01-01

    Full Text Available Presentamos un caso de CADASIL (acrónimo inglés de arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía, que corresponde al primero de una serie de 4 casos diagnosticados en nuestro servicio desde 1998, con correlato clínico, imageno-lógico y de ultrapatología muscular (microscopia electrónica. Se trata de una paciente mujer con historia de dos crisis isquémicas cerebrales transitorias a los 29 años, sin factores de riesgo tradicionales para patología cerebrovascular, que luego de 7 años desarrolló síntomas de tipo depresivos, asociados a un cuadro de retraimiento sicomotor y parkinsonismo de carácter progresivo y sin respuesta a terapia farmacológica convencional. En su estudio, la resonancia nuclear magnética de cerebro mostró extensas alteraciones en sustancia blanca a nivel fronto-occipital, bilaterales, hiperintensas en T2 e hipointensas en T1, cuya señal no se reforzó con gadolinio, sin efecto de masa, asociadas a leucoaraiosis, compatibles con el diagnóstico de CADASIL. El estudio de una biopsia muscular mediante microscopia electrónica, confirmó una arteriopatia con depósito de material granular osmiofílico en los vasos sanguíneos, tipo CADASIL. No encontramos antecedentes de cuadros demenciales ni cerebrovasculares sintomáticos en otros parientes de la paciente, madre, padre, tíos, abuelos, por lo que es probable que se trate de un cuadro esporádico. No realizamos estudio genético ni biopsico de los parientes asintomáticos. Las características de la paciente ilustran cuando sospechar el diagnóstico de CADASIL, aún frente a un caso aparentemente esporádicoWe describe a patient with CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, the first of four patients diagnosed in our service since 1998, correlating clinical, imaging, and muscular pathology (on electronic microscopy data. The patient is a woman with no risk factors for cerebrovascular pathology who suffered two transient ischemic attacks at the age of 29. Seven years later, she developed symptoms of depression manifested as psychomotor withdrawal and progressive Parkinsonism that did not respond to pharmacological treatment. An MRI brain scan showed extensive bilateral alterations in the white matter in the frontal and occipital regions, hyperintense in T2 and hypointense in T1-weighted images, without gadolinium enhancement. They had no mass effect, were associated with leukoaraiosis, and were compatible with the diagnosis of CADASIL. Muscle biopsy showed an arteriopathy with CADASIL-type osmiophilic granular deposits in the blood vessels. No history of symptomatic dementia or cerebrovascular disorders were found among the patient’s mother, father, aunts, uncles, or grandparents. This is most likely a sporadic case. No genetic studies or biopsies were done in asymptomatic relatives

  10. Serological profile of sporadic acute viral hepatitis in an area of hyper-endemic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Ayoola Ayobanji

    2001-01-01

    Full Text Available Background: Located in the south western part of Saudi Arabia, the Gizan region is largely a rural community in which hepatitis B and chronic liver disease including hepatocellular carcinoma are highly prevalent. Aim of study: To determine the relative frequencies of acute hepatitis A, B, C and E in acute viral hepatitis in an area of hyperendemic hepatitis B infection. Methods and materials: In a prospective study 246 consecutive patients (179 males and 67 females diagnosed in a 2-year period were tested for markers of Hepatitis A virus (HAV, hepatitis B virus (HBV, hepatitis C (HCV and hepatitis E virus (HEV. Results: Of the patients tested, 131 (53.3% were children (< 10 years, and 42 (17% were 11 - 20 years in age. Ig M anti -HAV, IgM anti-HBV, anti- HCV and IgM anti-HEV were positive in 37%, 19.1%, 3.7% and 13.7% respectively. Markers of these viruses were absent in 24.4%. Among 131 children (< 10 years the commonest cause of AVH was HAV occurring in 57.3% of the cases. In adults (> 21 years HBV was found in 35.6% and IgM anti -HAV was detected in only 6.8%. In contrast to the age- related decline in the frequency of acute HA, the proportion of acute HE were similar in all age groups (13.7% in children, 16.7% in adolescents and 11.0% in adults. Conclusion: The study indicated that HAV is still a common cause of AVH particularly among children in Gizan. Acute 1-113 had a low occurrence among the children, evidently as a consequence of the integration of HB vaccine into the Saudi Arabian national EPI, 10 years ago. With the availability of combined HB and HA vaccines, It should be possible to graft the vaccination against HAV on to the existing program in Saudi Arabia. Affecting 13.4% of the group studied, sporadic HEV constitute a significant cause of AVH in this population. Until HEV vaccine becomes widely available, its prevention would be mainly by the improvement of socio - economic and hygienic standards of the population.

  11. Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.

    Science.gov (United States)

    Xie, Tong; Deng, Libin; Mei, Puming; Zhou, Yiyi; Wang, Bo; Zhang, Jie; Lin, Jiari; Wei, Yi; Zhang, Xiong; Xu, Renshi

    2014-07-01

    Sporadic amyotrophic lateral sclerosis (sALS) is a severe neurodegenerative disease that causes progressive motor neuron death. Although the etiology of sALS remains unknown, genetic variants are thought to predispose individuals to the disease. Several recent genome-wide association studies have identified a number of loci that increase sALS susceptibility, but these only explain a small proportion of the disease. To extend the current genetic evidence and to identify novel candidates of sALS, we performed a pooling genome-wide association study by 859,311 autosomal single-nucleotide polymorphisms of IlluminaHumanOmniZhongHua-8 combining pathway analysis in 250 typical sALS cases precluding age, clinical course, and phenotype interference and 250 control subjects from Chinese Han populations (CHP). The results revealed that 8 novel loci of 1p34.3, 3p21.1, 3p22.2, 10p15.2, 22q12.1, 3q13.11, 11q25, 12q24.33, and 5 previously reported loci of CNTN4 (kgp11325216), ATXN1 (kgp8327591), C9orf72 (kgp6016770), ITPR2 (kgp3041552), and SOD1 (kgp10760302) were associated with sALS from CHP. Furthermore, the pathway analysis based on the Gene Set Analysis Toolkit V2 showed that 10 top pathways were strongly associated with sALS from CHP, and among them, the 7 most potentially candidate pathways were phosphatidylinositol signaling system, Wnt signaling pathway, axon guidance, MAPK signaling pathway, neurotrophin signaling pathway, arachidonic acid metabolism, and T-cell receptor signaling pathway, a total of 39 significantly associate genes in 7 candidate pathways was suggested to involve in the pathogenesis of sALS from CHP. In conclusion, our results revealed several new loci and pathways related to sALS from CHP and extend the association evidence for partial loci, genes, and pathways, which were previously identified in other populations. Thus, our data provided new clues for exploring the pathogenesis of sALS. PMID:24529757

  12. Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer.

    Science.gov (United States)

    Murria Estal, Rosa; Palanca Suela, Sarai; de Juan Jiménez, Inmaculada; Alenda Gonzalez, Cristina; Egoavil Rojas, Cecilia; García-Casado, Zaida; López Guerrero, Jose Antonio; Juan Fita, María José; Sánchez Heras, Ana Beatriz; Segura Huerta, Ángel; Santaballa Bertrán, Ana; Chirivella González, Isabel; Llop García, Marta; Pérez Simó, Gema; Barragán González, Eva; Bolufer Gilabert, Pascual

    2016-04-01

    The study aims to identify the relevance of immunohistochemistry (IHC), copy number aberrations (CNA) and epigenetic disorders in BRCAness breast cancers (BCs). We studied 95 paraffin included BCs, of which 41 carried BRCA1/BRCA2 germline mutations and 54 were non hereditary (BRCAX/Sporadic). Samples were assessed for BRCA1ness and CNAs by Multiplex Ligation-dependent Probe Amplification (MLPA); promoter methylation (PM) was assessed by methylation-specific-MLPA and the expression of miR-4417, miR-423-3p, miR-590-5p and miR-187-3p by quantitative RT-PCR. IHC markers Ki67, ER, PR, HER2, CK5/6, EGFR and CK18 were detected with specific primary antibodies (DAKO, Denmark). BRCAness association with covariates was performed using multivariate binary logistic regression (stepwise backwards Wald option). BRCA1/2 mutational status (p = 0.027), large tumor size (p = 0.041) and advanced histological grade (p = 0.017) among clinic-pathological variables; ER (p < 0.001) among IHC markers; MYC (p < 0.001) among CNA; APC (p = 0.065), ATM (p = 0.014) and RASSF1 (p = 0.044) among PM; and miR-590-5p (p = 0.001), miR-4417 (p = 0.019) and miR-423 (p = 0.013) among microRNA expression, were the selected parameters significantly related with the BRCAness status. The logistic regression performed with all these parameters selected ER+ as linked with the lack of BRCAness (p = 0.001) and MYC CNA, APC PM and miR-590-5p expression with BRCAness (p = 0.014, 0.045 and 0.007, respectively). In conclusion, the parameters ER expression, APC PM, MYC CNA and miR-590-5p expression, allowed detection of most BRCAness BCs. The identification of BRCAness can help establish a personalized medicine addressed to predict the response to specific treatments. PMID:26723934

  13. Limited family structure and triple-negative breast cancer (TNBC) subtype as predictors of BRCA mutations in a genetic counseling cohort of early-onset sporadic breast cancers.

    Science.gov (United States)

    Zugazagoitia, Jon; Pérez-Segura, Pedro; Manzano, Arancha; Blanco, Ignacio; Vega, Ana; Custodio, Ana; Teulé, Alex; Fachal, Laura; Martínez, Beatriz; González-Sarmiento, Rogelio; Cruz-Hernández, Juan Jesús; Chirivella, Isabel; Garcés, Vicente; Garre, Pilar; Romero, Atocha; Caldés, Trinidad; Díaz-Rubio, Eduardo; de la Hoya, Miguel

    2014-11-01

    Early-onset diagnosis is an eligibility criterion for BRCA1 and BRCA2 (BRCA) testing in sporadic breast cancer patients. Limited family structure has been proposed as a predictor of BRCA mutation status in this group of patients. An overwhelming amount of data supports a strong association between BRCA1 mutations and triple-negative breast cancer (TNBC). Here, we analyze the feasibility of using limited family structure and TNBC as predictors of BRCA mutation status in early-onset breast cancer patients attending genetic counseling units. We have conducted the study in a cohort of sporadic early-onset (?35 years) breast cancer patients (N = 341) previously selected for BRCA genetic testing in Academic Hereditary Cancer Clinics from Spain. A retrospective review of medical records available at the time of risk assessment allowed us classifying patients according to family structure and TNBC. In addition, BRCAPRO score was calculated for all patients. Association between categorical variables was investigated using the Fisher's exact test. Binary Logistic Regression Analysis was used for multivariate analysis. Limited family structure (OR 3.61, p = 0.013) and TNBC (OR 3.14, p = 0.013) were independent predictors of BRCA mutation status. Mutation prevalence in the subgroup of patients with at least one positive predictor was 14%, whereas it dropped to 3% in non-TNBCs with adequate family history (OR 5.31, 95% CI 1.38-23.89, p = 0.006). BRCAPRO correctly discerned between limited and adequate family structures. Limited family structure and TNBC are feasible predictors of BRCA mutation status in sporadic early-onset (?35 years) breast cancer patients attending genetic counseling units. The low prevalence of mutations observed in non-TNBCs with adequate family structure suggests that this subgroup of patients might be excluded from genetic testing. PMID:25342642

  14. Differences in the Expression of Cold Stress-Related Genes and in the Swarming Motility Among Persistent and Sporadic Strains of Listeria monocytogenes.

    Science.gov (United States)

    Cabrita, Paula; Trigo, Maria João; Ferreira, Ricardo Boavida; Brito, Luisa

    2015-07-01

    The persistence of certain Listeria monocytogenes strains in food-related environments suggests niche adaptation of these strains and therefore constitutes a major risk to consumer health and results in economic losses for the food producer. In this study, a set of 23 L. monocytogenes isolates, including a group of persistent and a group of sporadic strains, was evaluated regarding their swarming motility at 11°C. In each group, significant (p<0.05) differences in motility were observed. The transcript levels of nine cold stress-related genes were analyzed by real-time quantitative PCR in two representatives of persistent (CBISA3077) and sporadic (CBISA3049) strains isolated from the dairy environment, and significant (p<0.05) differences between the two strains were observed. The persistent strain showed significantly higher transcript levels of dtpT and sigB genes, and significantly lower levels of flaA, oppA, lmo1722, and lmo0866 genes. In the persistent strain, the upregulation of sigB, involved in the tolerance to low temperature and to osmotic stress, could account for the persistence of this strain in its original dairy environment. In a similar way, the downregulation of two helicase-encoding genes lmo1722 and lmo0866, in this strain, may be an evolutionary trait that could facilitate cold stress adaptation. Even though this analysis should be extended to more sporadic and more persistent strains, the results presented here strongly suggest gene expression networks differently adjusted, in the two strains, to the low-temperature environment from where they were collected. Moreover, our findings suggest that bacterial motility per se should not be considered a key feature for the persistence of L. monocytogenes in the food environment. PMID:25974395

  15. Negative Regulation of BRCA1 Gene Expression by HMGA1 Proteins Accounts for the Reduced BRCA1 Protein Levels in Sporadic Breast Carcinoma

    OpenAIRE

    Baldassarre, Gustavo; Battista, Sabrina; Belletti, Barbara; Thakur, Sanjay; PENTIMALLI, FRANCESCA; Trapasso, Francesco; Fedele, Monica; Pierantoni, Giovanna; Croce, Carlo M.; Fusco, Alfredo

    2003-01-01

    A drastic reduction in BRCA1 gene expression is a characteristic feature of aggressive sporadic breast carcinoma. However, the mechanisms underlying BRCA1 downregulation in breast cancer are not well understood. Here we report that both in vitro and in vivo HMGA1b protein binds to and inhibits the activity of both human and mouse BRCA1 promoters. Consistently, murine embryonic stem (ES) cells with the Hmga1 gene deleted display higher Brca1 mRNA and protein levels than do wild-type ES cells. ...

  16. Morphology and dynamics of daytime mid-latitude sporadic-E patches revealed by GPS total electron content observations in Japan

    Science.gov (United States)

    Maeda, Jun; Heki, Kosuke

    2015-12-01

    Morphological characteristics of daytime mid-latitude sporadic-E (Es) patches are studied by two-dimensional total electron content (TEC) maps drawn using the Japanese dense network of Global Positioning System (GPS) receivers. By analyzing over 70 cases, we found that their horizontal shapes are characterized by frontal structure typically elongated in east-west by ~100 km. They are observed to migrate mainly northward in the morning and southward in the afternoon with speeds of 30-100 m/s. This may reflect the velocities of neutral winds controlled by the atmospheric tides. Such frontal structures are often found to include smaller scale structures.

  17. Fibrodysplasia ossificans progressiva with minor unilateral hallux anomaly in a sporadic case from Northern Tanzania with the common ACVR1c.617G>A mutation

    Science.gov (United States)

    Saleh, Mohammed; Commandeur, Joost; Bocciardi, Renata; Kinabo, Grace; Hamel, Ben

    2015-01-01

    Fibrodysplasia ossificans progressiva is a rare autosomal dominantly inherited disorder of connective tissue caused by mutations in the gene encoding for ACVR1/ALK2, a bone morphogenetic protein type I receptor. It is mainly characterized by congenital malformations of the great toes and the formation of qualitatively normal bone in extra-skeletal sites leading to severe disability and eventually death. We present a sporadic case from Northern Tanzania with a minor unilateral hallux anomaly and the common ACVR1 c.617G>A mutation.

  18. Optimal diagnostic tests for sporadic Creutzfeldt-Jakob disease based on support vector machine classification of RT-QuIC data

    OpenAIRE

    Hulme, William; Richtárik, Peter; McGuire, Lynne; Green, Alison

    2012-01-01

    In this work we study numerical construction of optimal clinical diagnostic tests for detecting sporadic Creutzfeldt-Jakob disease (sCJD). A cerebrospinal fluid sample (CSF) from a suspected sCJD patient is subjected to a process which initiates the aggregation of a protein present only in cases of sCJD. This aggregation is indirectly observed in real-time at regular intervals, so that a longitudinal set of data is constructed that is then analysed for evidence of this aggre...

  19. Sporadic amyotrophic lateral sclerosis: new hypothesis regarding its etiology and pathogenesis suggests that astrocytes might be the primary target hosting a still unknown external agent

    Directory of Open Access Journals (Sweden)

    Roberto E.P. Sica

    2011-08-01

    Full Text Available This article briefly describes the already known clinical features and pathogenic mechanisms underlying sporadic amyotrophic lateral sclerosis, namely excitoxicity, oxidative stress, protein damage, inflammation, genetic abnormalities and neuronal death. Thereafter, it puts forward the hypothesis that astrocytes may be the cells which serve as targets for the harmful action of a still unknown environmental agent, while neuronal death may be a secondary event following the initial insult to glial cells. The article also suggests that an emergent virus or a misfolded infectious protein might be potential candidates to accomplish this task.

  20. Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Wong Nora

    2006-01-01

    Full Text Available Abstract Background Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle and the mitochondrial respiratory chain (succinate:ubiquinone oxidoreductase or complex II. Methods Using conformation sensitive gel electrophoresis (CSGE and direct DNA sequencing to analyse genomic DNA from peripheral blood lymphocytes, here we describe the mutation analysis of the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family history head and neck paraganglioma and five pheochromocytoma and/or paraganglioma families. Results Two sporadic patients were found to have a SDHB splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys missense mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif that constitutes the quinone-binding site of the succinate: ubiquinone oxidoreductase (SQR complex in E. coli. Together with our previous results, we found 27 germline mutations of SDH genes in 95 cases (28% of sporadic head and neck paraganglioma. In addition all index patients of five families showing hereditary pheochromocytoma-paraganglioma were found to carry germline mutations of SDHB: four of which were novel, c.343C>T (p.Arg115X, c.141G>A (p.Trp47X, c.281G>A (p.Arg94Lys, and c.653G>C (p.Trp218Ser, and one reported previously, c.136C>T, p.Arg46X. Conclusion In conclusion, these data indicate that germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma and further underline the importance of germline SDHB mutations in cases of familial pheochromocytoma-paraganglioma.

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

    OpenAIRE

    Charnock F Mark L; Wells R Spencer; Beck Stephan; Mungall Andrew J; Dunham Ian; Emilion Gracy; Dodds Phillippa; Liu Ying; Ganesan Trivadi S

    2002-01-01

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

  2. Clinical and epidemiological evaluation of patients with sporadic colorectal cancer / Avaliação clínica e epidemiológica de pacientes com câncer colorretal esporádico

    Scientific Electronic Library Online (English)

    Glaucia Maria de Mendonça, Fernandes; Cássia Veridiana Dourado, Leme; Mariângela Torreglosa, Ruiz-Cintra; Érika Cristina, Pavarino; João Gomes, Netinho; Eny Maria, Goloni-Bertollo.

    2014-12-01

    Full Text Available Experiência: O presente estudo tem como objetivo realizar um levantamento de dados clínicos e fatores sociodemográficos e de risco de pacientes com câncer colorretal esporádico (CCRE) tratados entre 2004 e 2008 no Serviço de Coloproctologia de um hospital-escola na região Noroeste de São Paulo. M [...] étodos: Foram analisados 749 prontuários clínicos. Destes, 460 foram de pacientes com câncer de cólon e de 289 de pacientes com câncer retal. A maioria dos indivíduos era da raça branca, com mais de 62 anos de idade. As variáveis analisadas foram gênero, idade, cor da pele, ocupação profissional, consumo de álcool e tabagismo, história familiar de câncer e co-morbidades. A identificação do perfil clínico-sociodemográfico e dos fatores de risco em uma população com CCRE na região noroeste de São Paulo foi realizada para colaborar com as estratégias de prevenção. Resultados: A ocorrência de CCRE não diferiu muito entre gêneros. As ocupacões profissionais mais prevalentes foram as relacionadas aos afazeres domésticos, atividades agrícolas e comerciais. Entre as comorbidades, hipertensão e colelitíase foram as mais representativas. O método de diagnóstico e de tratamento mais comum para a maioria dos pacientes foi colonoscopia e cirurgia, respectivamente. Em média, o tempo de progressão da doença foi de oito meses. O número mediano de linfonodos extirpados variou entre 11 e 14. A metástase mais comum foi a hepática. Conclusão: A ocorrência de câncer colorretal é mais frequente em homens de pele branca com idade superior a 62 anos. A ocupação profissional parece ser mais importante para as pessoas expostas a agentes cancerígenos. Este tipo de tumor afeta principalmente as regiões distais do cólon e do reto, com a ocorrência de metástases no fígado. Geralmente, os indivíduos afetados exibem baixa sobrevida, devido à alta agressividade dessa neoplasia. Abstract in english Background: This study aims to perform a survey on clinical data, sociodemographic and risk factors from patients with sporadic colorectal cancer (SCRC) treated between 2004 and 2008 in the Coloproctology Service of a teaching hospital in the North-western region of São Paulo. Methods: We analyze [...] d 749 medical records. Of these, 460 were from colon cancer patients and 289 from rectal cancer patients. Most of the individuals had white skin and were aged over 62 years. The variables that were analyzed included gender, age, skin color, professional occupation, alcohol drinking and cigarette smoking, family history of cancer, and comorbidities. The identification of the clinical-sociodemographic profile and risk factors in a population with the SCRC the northwest region of São Paulo was performed to collaborate with prevention strategies. Results: The occurrence of SCRC did not differ much between genders. The most prevalent professional occupations were those related to household chores, agricultural and commercial activities. Among the comorbidities, hypertension and cholelithiasis were the most representative. The most common diagnosis method and treatment for the majority of patients were coloscopy and surgery, respectively. On average, the time of the disease progression was eight months. The median number of lymph nodes excised ranged between 11 and 14. The most common metastasis was hepatic. Conclusion: The occurrence of colorectal cancer is more frequent in men's white skin with aged over 62 years. Professional occupation seems to be more important for those exposed to carcinogenic agents. This type of tumor mostly affects the distal regions of the colon and rectum with the occurrence of liver metastasis. The affected individuals usually have low survival due to its high aggressiveness.

  3. Interaction between lifestyle factors and the XRCC1, XPD, and XRCC3 genetic variations modulates the risk for sporadic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Procopciuc Lucia Maria

    2014-03-01

    Full Text Available Introducere: Variațiile genetice, cum ar fi cele care influențează sistemele de reparare a defectelor de replicare a ADN, pot reprezenta factori de susceptibilitate în cancerul colorectal sporadic (CCR ca urmare a interacțiunii cu factori de mediu. Material și metodă: 80 de femei și 70 de bărbați, pacienți diagnosticați cu CCR sporadic în Clinica Chirurgie III Cluj au fost genotipați pentru Arg399Gln-XRCC1, Lys751Gln-XPD și Met241Thr-XRCC3 utilizând metodele PCR-RFLP. Am determinat de asemenea, genotipurile pentru 100 femei și 62 bărbați , care au format grupul de control. Rezultatele au fost analizate din punct de vedere al relației cu factorii de risc de mediu, fumatul și dieta. Rezultate: Bărbații fumători purtători ai variațiilor genetice Arg399Gln, Lys751Gln, Met241Thr au avut un risc semnificativ crescut de 4.09 (95%IC[0.96-19.98],p=0.05, 5.95(95%IC[1.08-43.22],p=0.03 și respectiv 3.73(95%IC[0.86-18.53],p=0.05 de a dezvolta cancer colorectal sporadic. Un risc semnificativ crescut de a dezvolta cancer colorectal sporadic a fost observat în cazul femeilor și bărbaților cu o dietă bogată în carne roșie prăjită purtători ai variațiilor genetice Arg399Gln (OR 2.77 95%IC [1.34-6.82],p=0.015 și OR 8.64 95%IC[2.67-29.14],p<0.001, Lys751Gln (OR 4.12 95%IC[1.37-12.74],p=0.007 și OR 5.06 95%IC[1.4- 19.02],p=0.006, Met241Thr (OR5.92 95%IC[2.21-16.23],p<0.001 și OR 5.64 95%IC[1.52-21.7],p=0.022. Femeile a căror dietă a inclus cantități mari de carne roșie prăjită au avut un risc semnificativ crescut de a dezvolta timpuriu cancer colorectal sporadic dacă au fost purtătoare a variațiilor genetice Arg399Gln-XRCC1 (OR 5.14 95%IC[0.99-28.3],p=0.047, Thr241Met-XRCC3 (OR 6.67 95%IC[1.05-46.67],p=0.025 și Lys751Gln-XPD (OR 4.7 95%IC[0.99-23.32],p=0.034. Concluzii: În cazul populației de origine română, asocierea genotipurilor mutante cu factori de mediu modulează riscul pentru CCR sporadic. La femei, fumatul în asociere cu variația genetică Arg399Gln-XRCC1 influențează debutul timpuriu al cancerului colorectal sporadic. Tot în cazul femeilor, dieta bogată în carne roșie prăjită în asociere cu variațiile genetice Arg399Gln-XRCC1, Lys751Gln-XPD și Thr241Met- XRCC3 influențează semnificativ riscul de apariție al cancerului colorectal sporadic.

  4. An assessment of the frequency of mutations in the GBA and VPS35 genes in Hungarian patients with sporadic Parkinson's disease.

    Science.gov (United States)

    Török, Rita; Zádori, Dénes; Török, Nóra; Csility, Éva; Vécsei, László; Klivényi, Péter

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, with cases of either familial or sporadic origin. Several polymorphisms in a number of genes have been proved to have an important role in the development of PD. Particular attention has recently been paid to genes of the glucocerebrosidase (GBA) and the vacuolar protein sorting-associated protein 35 (VPS35). In this study, the three most common mutations (L444P, N370S and R120W) of the GBA gene and the D620N mutation of the VPS35 gene were examined in 124 Hungarian patients diagnosed with sporadic PD (SPD) and 122 control subjects. The frequency of the L444P mutation of the GBA gene proved to be higher in the PD patients (2.4%) than in the controls (0%), although the difference was not statistically significant. All the patients who carried the mutant allele were in the early-onset PD (EOPD) group. However, neither the R120W nor the N370S variant of the GBA gene nor D620N mutation of the VPS35 gene were detected among the PD cases or the controls. Even though these results suggest that the studied mutations are quite rare in SPD patients, the most frequent L444P mutation of the GBA gene may be associated with the development of EOPD in the Hungarian population. PMID:26547032

  5. Sporadic renal hemangioblastoma with CA9, PAX2 and PAX8 expression: diagnostic pitfall in the differential diagnosis from clear cell renal cell carcinoma.

    Science.gov (United States)

    Kuroda, Naoto; Agatsuma, Yoshiko; Tamura, Masato; Martinek, Petr; Hes, Ondrej; Michal, Michal

    2015-01-01

    To date, 13 cases of sporadic renal hemangioblastoma have been reported. In this article, we report such a case that might cause the diagnostic pitfall. A 37-year-old Japanese was found to have a renal mass by periodic medical check-up. He underwent radical nephrectomy. Macroscopically, the tumor was well-defined without fibrous capsule and the cut surface of the tumor exhibited light brown to gray-tan color without hemorrhage or necrosis. Microscopically, the tumor was made up of large polygonal to short spindle cells with eosinophilic cytoplasm with occasional vacuolization and abundant arborizing capillary network. Immunohistochemically, neoplastic cells showed diffuse positivity for inhibin-alpha, S-100 protein, vimentin, CA9, PAX2 and PAX8, but negativity for cytokeratin CAM5.2, alpha smooth muscle actin, Melanosome, Melan A, TFE3 and cathepsin K. In genetic analyses, this tumor showed no changes of VHL gene mutation, hypermethylation and loss of heterozygosity of chromosome 3p. Additionally, G-band karyotype and array comparative genomic hybridization studies showed a normal chromosome. In conclusion, the positivity for CA9, PAX2 and PAX8 in sporadic renal hemangioblastoma may cause the critical diagnostic pitfall in the differential diagnosis from clear cell renal cell carcinoma. Pathologists need to pay attention to systemic evaluation including macroscopic, microscopic and immunohistochemical findings. In some cases, molecular genetic study may be necessary. PMID:25973115

  6. A statistical study of sporadic sodium layer observed by Sodium lidar at Hefei (31.8° N, 117.3° E

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    S. Qiu

    2009-06-01

    Full Text Available Sodium lidar observations of sporadic sodium layers (SSLs during the past 3 years at a mid-latitude location (Hefei, China, 31.8° N, 117.3° E are reported in this paper. From 64 SSL events detected in about 900 h of observation, an SSL occurrence rate of 1 event every 14 h at our location was obtained. This result, combined with previous studies, reveals that the SSL occurrence can be relatively frequent at some mid-latitude locations. Statistical analysis of main parameters for the 64 SSL events was performed. By examining the corresponding data from an ionosonde, a considerable correlation was found with a Pearson coefficient of 0.66 between seasonal variations of SSL and those of sporadic E (Es during nighttime, which was in line with the research by Nagasawa and Abo (1995. From comparison between observations from the University of Science and Technology of China (USTC lidar and from Wuhan Institute of Physics and Mathematics (WIPM lidar (Wuhan, China, 31° N, 114° E, the minimum horizontal range for some events was estimated to be over 500 km.

  7. The Southern Argentina Agile MEteor Radar Orbital System (SAAMER-OS): An Initial Sporadic Meteoroid Orbital Survey in the Southern Sky

    Science.gov (United States)

    Janches, D.; Close, S.; Hormaechea, J. L.; Swarnalingam, N.; Murphy, A.; O'Connor, D.; Vandepeer, B.; Fuller, B.; Fritts, D. C.; Brunini, C.

    2015-08-01

    We present an initial survey in the southern sky of the sporadic meteoroid orbital environment obtained with the Southern Argentina Agile MEteor Radar (SAAMER) Orbital System (OS), in which over three-quarters of a million orbits of dust particles were determined from 2012 January through 2015 April. SAAMER-OS is located at the southernmost tip of Argentina and is currently the only operational radar with orbit determination capability providing continuous observations of the southern hemisphere. Distributions of the observed meteoroid speed, radiant, and heliocentric orbital parameters are presented, as well as those corrected by the observational biases associated with the SAAMER-OS operating parameters. The results are compared with those reported by three previous surveys performed with the Harvard Radio Meteor Project, the Advanced Meteor Orbit Radar, and the Canadian Meteor Orbit Radar, and they are in agreement with these previous studies. Weighted distributions for meteoroids above the thresholds for meteor trail electron line density, meteoroid mass, and meteoroid kinetic energy are also considered. Finally, the minimum line density and kinetic energy weighting factors are found to be very suitable for meteroid applications. The outcomes of this work show that, given SAAMER’s location, the system is ideal for providing crucial data to continuously study the South Toroidal and South Apex sporadic meteoroid apparent sources.

  8. Homozygous T172T and Heterozygous G135C Variants of Homologous Recombination Repairing Protein RAD51 are Related to Sporadic Breast Cancer Susceptibility.

    Science.gov (United States)

    Al-Zoubi, Mazhar Salim; Mazzanti, Chiara Maria; Zavaglia, Katia; Hamad, Mohammad Al; Armogida, Ivana; Lisanti, Michael P; Bevilacqua, Generoso

    2016-02-01

    Breast cancer (BC) is the most common cancer and the second leading cause of death among women worldwide. Only 10% of BC cases have been related to genetic predisposition. Rad51, a homologous recombination (HR) protein plays an important role in HR in meiosis and repairing DNA double-strand breaks. Expression of RAD51 may be a predictive biomarker in certain types of cancers. The exact mechanisms involved in the regulation of RAD51 expression are not fully understood, but certain transcription factors have been suggested to be the tuning mechanism of its expression. In this study, we propose that polymorphisms in the 5'-UTR promoter region of the RAD51 gene are prognostic factors for BC development. Direct sequencing of 106 samples from sporadic BC patients and 54 samples from a control group was performed. FFPE samples were the choice of sample collection, which might be a limitation of our study. Homologous variant T172T alone was found to be significantly associated with BC risk (OR 3.717, 95% CI 2.283-6.052, p  0.05). Moreover, both variants; homozygous T172T and heterozygous G135C together; showed a significant relationship with sporadic BC susceptibility. PMID:26650628

  9. Factores de riesgo de casos esporádicos de gastroenteritis por Campylobacter en niños Risk factors for sporadic cases of Campylobacter infection in children

    Directory of Open Access Journals (Sweden)

    Marta Fajó-Pascual

    2009-08-01

    Full Text Available Objetivos: Identificar factores de riesgo en casos esporádicos de gastroenteritis por Campylobacter en niños 2 veces (ORa:4,2; IC95%:1,2-14,7, pollo >3 veces (ORa:3,6; IC95%:1,1-11,1 y toma previa de antibióticos (ORa:4,7; IC95%:1,1-19,6 se asociaron independientemente con la enfermedad. Conclusiones Se identificó la carne de pollo como factor de riesgo de campilobacteriosis, bien por consumo o por manipulación inadecuada que podría ocasionar contaminación cruzada de otros alimentos «listos para comer», como los fiambres.Objectives: To identify risk factors for sporadic cases of Campylobacter infection in children aged 2 times (ORa:4.2, 95%CI:1.2-14.7, chicken >3 times (ORa:3.6, 95%CI:1.1-11.1 in the week before symptom onset, and previous antibiotic intake (ORa:4.7, 95%CI:1.1-19.6. Conclusions: Chicken meat was a risk factor for sporadic cases of campylobacteriosis in children, whether through consumption or through cross-contamination with other «ready-to-eat» foods such as cooked deli meat.

  10. Patients with familial non-medullary thyroid cancer have an outcome similar to that of patients with sporadic papillary thyroid tumors

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    Fabián Pitoia

    2011-04-01

    Full Text Available OBJECTIVE:The purpose of this study was to determine whether familial non-medullary thyroid cancer (FNMTC is more aggressive than sporadic thyroid cancer. SUBJECTS AND METHODS: We compared the clinical behavior and outcome of 16 subjects with FNMTC from 7 unrelated kindred with those observed in 160 subjects with sporadic PTC (SPTC from our database. RESULTS: The only different baseline characteristics observed between both groups were: bilateral malignancy, 38% vs. 24%, respectively (p = 0.03, and lymph node metastasis, 56.2% vs. 39%, respectively (p = 0.01. Considering the outcome, in the FNMTC, 9 (56.2% patients were rendered free of disease, one patient died from thyroid cancer (6%, and 6/16 (37.5% had persistent disease. In the SPTC Group, 87 (54% patients were considered free of disease, 11 (7% died due to PTC, and 62 (38% had persistent disease (p = ns. CONCLUSIONS: Despite the higher incidence of lymph node metastasis in FNMTC patients this situation seemed not to alter the compared outcome.

  11. Replication analysis of genetic variants on 17q11.2 and 9p21.2 with sporadic amyotrophic lateral sclerosis and Parkinson's disease in a Chinese population.

    Science.gov (United States)

    Chen, Xueping; Chen, Yongping; Guo, Xiaoyan; Cao, Bei; Wei, Qianqian; Ou, Ruwei; Zhao, Bi; Song, Wei; Wu, Ying; Shang, Hui-Fang

    2015-11-01

    We performed a replication study of the 2 genetic variants, rs34517613 on 17q11.2 and rs3849942 on 9p21.2 in patients with sporadic amyotrophic lateral sclerosis (ALS) and Parkinson's disease in a Chinese population. These 2 variants are identified to be associated with increased risk of ALS in European-descended populations by genome-wide association studies. Both rs34517613 and rs3849942 showed no evidence of association in Chinese. These loci are not risk factors for sporadic ALS and Parkinson's disease in the western Han Chinese population. PMID:26304631

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

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    Banshi Lal Kumawat

    2015-01-01

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

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

    Science.gov (United States)

    Kumawat, Banshi Lal; Sharma, Chandra Mohan; Nath, Kunal; Acharya, Mihir; Khandelwal, Dinesh; Jain, Deepak

    2015-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) can have varied clinical presentation depending upon the genotype at codon 129. The common presenting clinical features of sCJD are rapid onset cognitive impairment, ataxia, psychosis and visual signs (field defects, distortion, cortical blindness). Alien limb sign was first described in patients with corpus callosal tumors and later with other neurodegenerative conditions like corticobasal degeneration. Alien hand complaints as the presenting feature of sCJD has been described in literature, but simultaneous alien hand and leg has been rarely described as presenting feature of sCJD. We describe here a case of a 55-year-old man who presented with progressive left alien hand and leg as the sole clinical manifestation of probable sCJD. PMID:25745324

  14. Rydberg Matter clusters of alkali metal atoms: the link between meteoritic matter, polar mesosphere summer echoes (PMSE), sporadic sodium layers, polar mesospheric clouds (PMCs, NLCs), and ion chemistry

    CERN Document Server

    Olofson, Frans; Holmlid, Leif

    2010-01-01

    A material exists which links together the influx of meteoritic matter from interplanetary space, the polar mesosphere summer echoes (PMSE), the sporadic sodium layers, the polar mesospheric clouds (PMCs, NLCs), and the observed ion chemistry in the mesosphere. The evidence in these research fields is here analyzed and found to agree well with the properties of Rydberg Matter (RM). This material has been studied with numerous methods in the laboratory. Alkali atoms, mainly Na, reach the mesosphere in the form of interplanetary (meteoritic, cometary) dust. The planar RM clusters NaN usually contain N = 19, 37 or 61 atoms, and have the density of air at 90 km altitude where they float. The diameters of the clusters are 10-100 nm from laboratory high precision radio frequency spectroscopic studies. Such experiments show that RM clusters interact strongly with radar frequencies: this explains the radio frequency heating and reflection studies of PMSE layers. The clusters give the low temperature in the mesosphere...

  15. Sporadic Nucleation and Growth in the Microphase Separation Process of an I2S Miktoarm Star Block Copolymer and its Blends with Homopolymer

    Science.gov (United States)

    Yang, Lizhang; Pochan, Darrin J.; Gido, Samuel P.; Pispas, Stergios; Hong, Kunlun; Mays, Jimmy W.

    2000-03-01

    A selective solvent and annealing study was done to investigate the morphology behavior of an I2S miktoarm star block copolymer and its blends with homopolyisoprene. Casting from cyclohexane, a selective solvent for polyisoprene, the neat star shaped I2S block copolymer only partially microphase separated, and formed a unique layered morphology inside a homogeneous media. During annealing, the layered phase and the homogeneous phase both transformed into a randomly oriented worm morphology. The path of this transformation is different depending on whether the starting state is layered or homogenous. The I2S/homopolyisoprene blend formed a mostly homogeneous phase after casting from cyclohexane. Annealing produced slow microphase separation which was observed at various stages by TEM. Based on these observations, a sporadic nucleation process of microphase separation is proposed.

  16. Screening for sporadic or familial medullary thyroid carcinoma. Scintiscan s and radio-immunotherapy; Depistage des cancers medullaires de la thyroide sporadiques et familiaux. Techniques scintigraphiques et radioimmunotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Rhmer, V. [Centre Hospitalier Universitaire, Service de Medecine, 49 - Angers (France); Murat, A. [Centre Hospitalier Universitaire, Clinique d' Endocrinologie, 44 - Nantes (France)

    2000-08-01

    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)

  17. Perfil da fluência: análise comparativa entre gagueira desenvolvimental persistente familial e isolada / Speech fluency profile: comparative analysis between the sporadic and familial persistent developmental stuttering

    Scientific Electronic Library Online (English)

    Cristiane Moço Canhetti de, Oliveira; Michele, Fiorin; Paula Roberta, Nogueira; Cecília Piccin, Laroza.

    2013-12-01

    Full Text Available OBJETIVO: avaliar e comparar a fluência de indivíduos com Gagueira Desenvolvimental Persistente Familial e de indivíduos com Gagueira Desenvolvimental Persistente Isolada, caracterizando a tipologia das disfluências, a porcentagem de disfluências, a taxa de elocução e a gravidade da gagueira. MÉTODO [...] : participaram 40 indivíduos, entre 6 e 42 anos de idade, divididos em dois grupos de 20 participantes cada um: Gagueira Desenvolvimental Persistente Familial e Gagueira Desenvolvimental Persistente Isolada. Os procedimentos utilizados nos grupos foram: histórias clínica e familial, avaliação da fluência e Instrumento de Gravidade da Gagueira. RESULTADOS: não houve diferenças estatisticamente significantes entre os grupos quanto à porcentagem de disfluências gagas, ao fluxo de sílabas e palavras por minuto, e a gravidade da gagueira. Nota-se uma tendência do grupo de pessoa com gagueira familial apresentar uma maior variabilidade da gravidade da gagueira, que foi de leve a muito grave, enquanto que, no grupo de pessoas com gagueira isolada, a gravidade variou de leve a grave. CONCLUSÃO: este estudo representa um primeiro esforço para a caracterização do perfil da fluência de subgrupos de pessoas que gaguejam, a saber, gagueira desenvolvimental persistente familial e gagueira desenvolvimental persistente isolada. Pode-se concluir que o perfil da fluência de pessoas com gagueira, independente do histórico familial, é semelhante. Vale ressaltar que a ocorrência de algumas tipologias gagas, repetição de palavra monossilábica, bloqueio e intrusão foram distintas entre os grupos. Abstract in english PURPOSE: to evaluate and compare the fluency between the familial and the sporadic persistent developmental stuttering, characterizing the typology and the frequency of the disfluencies, the speech rate and the severity of the stuttering. METHOD: 40 participants aged from 6 to 42 years old, divided [...] in two groups with twenty participants in each one: Familial Persistent Developmental Stuttering and Sporadic Persistent Developmental Stuttering. The procedures used were: clinical and familial history, assessment of fluency and Stuttering Severity Instrument. RESULTS: there were no statistically significant differences between the groups regarding the frequency of stuttering like disfluencies, the flow of syllables and words per minute and the severity of stuttering. It was noted a tendency of the group with familial stuttering to show a bigger variability of the severity of stuttering, going from mild to very severe, whereas in the group with sporadic stuttering, the severity varied from mild to severe. CONCLUSION: this study represents the first effort to the characterization of the speech fluency profile of the subgroups of people who stutter, namely familial persistent developmental stuttering and sporadic persistent developmental stuttering. It is possible to conclude that the speech fluency profile of people who stutter, independently of the familial history, is similar. It is noteworthy that the occurrence of some stuttering-like disfluencies, monosyllabic word repetition, block and intrusion were different between groups.

  18. Xenotropic Murine Leukemia Virus-Related Virus and RNase L R462Q Variants in Iranian Patients With Sporadic Prostate Cancer

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    Babaei

    2015-12-01

    Full Text Available Background Although several studies have confirmed the association of xenotropic murine leukemia virus-related virus (XMRV and prostate cancer, this association is still controversial, as most studies did not detect XMRV in prostate tissue samples. Furthermore, some genetic and epidemiological studies have highlighted a role for RNase L polymorphisms, particularly R462Q, in the progression of prostate cancer. Objectives The focus of this study was on the association of XMRV and RNase L R462Q variants with the risk of prostate cancer in Iranian patients. Patients and Methods In this case-control study, 40 and 80 individuals with sporadic prostate cancer and benign prostatic hyperplasia, respectively, were included. The presence of XMRV was evaluated by real-time polymerase chain reaction (PCR of integrase and nested-PCR for the gag genes. The RNase L R462Q polymorphism analysis was carried out by PCR and sequencing. Results In a total of 40 sporadic prostate cancer and 80 benign prostatic hyperplasia cases, no XMRV was detected by real-time PCR and nested-PCR. RNase L R462Q polymorphism analysis reveals that although there was an increase in the risk of prostate cancer correlated with the Q/Q allele of RNase L at position 462, the frequencies of the RNase L R462Q alleles were not statistically significant between the prostate cancer and benign prostatic hyperplasia groups (OR = 2.75 (95% CI = 0.67 - 11.3, P = 0.29. Conclusions These results did not support the presence of XMRV in the samples with prostate cancer and showed that RNase L R462Q variants had relatively little or no impact on the risk of prostate cancer in Iranian population.

  19. LAPAROSCOPIC CRYOABLATION OF ANGIOMYOLIPOMAS IN ADOLESCENTS AND YOUNG ADULTS: A REPORT OF 4 CASES ASSOCIATED WITH TUBEROUS SCLEROSIS AND 1 CASE OF SPORADIC ORIGIN

    DEFF Research Database (Denmark)

    Trelborg, Karina; Nielsen, Tommy Kjærgaard

    PURPOSE The present study reports the first series of laparoscopic cryoablation of renal angiomyolipomas (AML) in adolescents and young adults. MATERIAL AND METHODS From October 2009 to September 2013 five patients at our institution were diagnosed with AML requiring treatment. Four patients had tuberous sclerosis (TS) and one had AML of sporadic origin, all five patients underwent laparoscopic cryoablation. Perioperative data was prospectively registered in a nation-wide laparoscopy database with follow-up data collected from the patients’ chart. Independent radiologists reassessed all imaging. RESULTS Median age was 16 (13–27) years. Eight AMLs in five patients, with a median size of 3.9 (2.1-7.7) cm were treated. Indication for intervention within the TS group was prophylactic due to tumor size and rapid growth. The patient with sporadic AML was treated due to tumor size and a former bleeding episode. From time of diagnosis until intervention the patients with TS were followed with renal imaging for a median time of 117 (1–140) months. After cryoablation AML-status was followed by CT and MRI for a median follow up time of 37 (6–59) months. On follow-up imaging, all lesions showed a reduction in tumor size, and no regrowth was recognized. The procedure was well tolerated, with few minor intraoperative complications and all patients scored zero in the Clavien-Dindo classification as no postoperative complications occurred. CONCLUSIONS Treating AMLs with laparoscopic cryoablation appears to be a safe and feasible nephron-sparing approach in adolescents and young adults, thus supporting the future use of cryoablation in this patient group. For inferior, lateral and peripherally located lesions, percutaneous cryoablation is a less invasive option, but none of our patients had lesions appropriate for this approach. Treatment with mTOR inhibitors is an alternative and promising non-invasive treatment for TS-patients with AMLs not requiring immediate surgery.

  20. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    International Nuclear Information System (INIS)

    The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Mutations at the phosphorylation sites (codons 31, 33, 37, and 45) in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656) and 36% (235/656), respectively). Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656). Nine percent of all tumours (58/656) lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency

  1. Style-by-style analysis of two sporadic self-compatible Solanum chacoense lines supports a primary role for S-RNases in determining pollen rejection thresholds.

    Science.gov (United States)

    Qin, Xike; Liu, Bolin; Soulard, Jonathan; Morse, David; Cappadocia, Mario

    2006-01-01

    A method for the quantification of S-RNase levels in single styles of self-incompatible Solanum chacoense was developed and applied toward an experimental determination of the S-RNase threshold required for pollen rejection. It was found that, when single style values are averaged, accumulated levels of the S(11)- and S(12)-RNases can differ up to 10-fold within a genotype, while accumulated levels of the S(12)-RNase can differ by over 3-fold when different genotypes are compared. Surprisingly, the amount of S(12)-RNase accumulated in different styles of the same plant can differ by over 20-fold. A low level of 160 ng S-RNase in individual styles of fully incompatible plants, and a high value of 68 ng in a sporadic self-compatible (SSC) line during a bout of complete compatibility was measured, suggesting that these values bracket the threshold level of S-RNase needed for pollen rejection. Remarkably, correlations of S-RNase values to average fruit sets in different plant lines displaying sporadic self-compatibility (SSC) to different extents as well as to fruit set in immature flowers, are all consistent with a threshold value of 80 ng S(12)-RNase. Taken together, these results suggest that S-RNase levels alone are the principal determinant of the incompatibility phenotype. Interestingly, while the S-RNase threshold required for rejection of S(12)-pollen from a given genetic background is the same in styles of different genetic backgrounds, it is different when pollen donors of different genetic backgrounds are used. These results reveal a previously unsuspected level of complexity in the incompatibility reaction. PMID:16720600

  2. Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients

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    Gemela Orsolya

    2007-03-01

    Full Text Available Abstract Background Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD is a typical example as patients with longstanding IBD are at an increased risk for developing colorectal cancer (CRC and mutations of the NOD2/CARD15 gene increase the risk for Crohn's disease (CD. Recently, NOD2/CARD15 has been associated with a risk for CRC in some studies, which stemmed from ethnically diverse populations. Our aim was to identify common NOD2/CARD15 mutations in Hungarian patients with sporadic CRC. Methods A total of 194 sporadic CRC patients (m/f: 108/86, age at diagnosis of CRC: 63.2 ± 9.1 years old and 200 healthy subjects were included. DNA was screened for SNP8, SNP12 and SNP13 NOD2/CARD15 mutations by denaturing-HPLC and confirmed by direct sequencing. Results NOD2/CARD15 mutations were found in 28 patients (14.4% and in 23 controls (11.5%, p = NS. Allele frequencies for SNP8/R702W (1.8% vs. 1.5% SNP12/G908R (1.8% vs. 1.8% and SNP13/3020insC (3.6% vs. 2.5% were also not statistically different between patients and controls. The clinicopathologic characteristics of CRC patients with or without NOD2/CARD15 mutations were not significantly different. Conclusion Our results suggest that common NOD2/CARD15 mutations alone do not contribute to CRC risk in the Hungarian population.

  3. Enfermedad de Creutzfeldt-Jakob esporádica: dos casos en medicina intensiva Sporadic Creutzfeldt-Jakob disease: two cases in intensive care

    Directory of Open Access Journals (Sweden)

    P. Cardinal

    2011-02-01

    Full Text Available Las enfermedades priónicas o encefalopatías espongiformes son una familia de raras patologías neurodegenerativas caracterizadas por periodos de incubación prolongados asociados a una lenta, irreversible e invariablemente mortal evolución. En humanos se las clasifica en esporádica, adquirida y hereditaria o genética. Realizar el diagnóstico de «enfermedad de Creutzfeldt-Jakob» es un verdadero desafío para el médico intensivista dada la variabilidad en la presentación clínica y su baja incidencia. Se presentan 2 pacientes admitidos en la UCI en los que, tras descartar varias patologías, se diagnosticó con un nivel de «probabilidad», de acuerdo a la clasificación de la OMS, enfermedad de Creutzfeldt-Jakob esporádica. Se analizan aspectos diagnósticos clínicos y analíticos de la enfermedad resaltando la utilidad de la identificación de la proteína 14-3-3 en el líquido cefalorraquídeo.Prion diseases or spongiform encephalopathies are a family of rare neurodegenerative diseases characterized by long incubation periods associated with slow, irreversible and invariably fatal evolution. In humans, they are classified as sporadic, acquired and hereditary or genetic. Diagnosing sporadic "Creutzfeldt-Jakob Disease" (sCJD is a real challenge for the intensive care physician, given the variability in its clinical presentation and its low incidence. The cases of two patients admitted to the Intensive Care Unit are presented. After ruling out other diseases, they were diagnosed with sCJD with a likelihood level according to the World Health Organization Classification. Clinical and laboratory diagnostic aspects of the disease were analyzed, highlighting the utility of 14-3-3 protein identification in the cerebrospinal fluid.

  4. Comparative genomic analysis of two novel sporadic Shiga toxin-producing Escherichia coli O104:H4 strains isolated 2011 in Germany.

    Science.gov (United States)

    Tietze, Erhard; Dabrowski, Piotr Wojciech; Prager, Rita; Radonic, Aleksandar; Fruth, Angelika; Auraß, Philipp; Nitsche, Andreas; Mielke, Martin; Flieger, Antje

    2015-01-01

    A large outbreak of gastrointestinal disease occurred in 2011 in Germany which resulted in almost 4000 patients with acute gastroenteritis or hemorrhagic colitis, 855 cases of a hemolytic uremic syndrome and 53 deaths. The pathogen was an uncommon, multiresistant Escherichia coli strain of serotype O104:H4 which expressed a Shiga toxin characteristic of enterohemorrhagic E. coli and in addition virulence factors common to enteroaggregative E. coli. During post-epidemic surveillance of Shiga toxin-producing E. coli (STEC) all but two of O104:H4 isolates were indistinguishable from the epidemic strain. Here we describe two novel STEC O104:H4 strains isolated in close spatiotemporal proximity to the outbreak which show a virulence gene panel, a Shiga toxin-mediated cytotoxicity towards Vero cells and aggregative adherence to Hep-2 cells comparable to the outbreak strain. They differ however both from the epidemic strain and from each other, by their antibiotic resistance phenotypes and some other features as determined by routine epidemiological subtyping methods. Whole genome sequencing of these two strains, of ten outbreak strain isolates originating from different time points of the outbreak and of one historical sporadic EHEC O104:H4 isolate was performed. Sequence analysis revealed a clear phylogenetic distance between the two variant strains and the outbreak strain finally identifying them as epidemiologically unrelated isolates from sporadic cases. These findings add to the knowledge about this emerging pathogen, illustrating a certain diversity within the bacterial core genome as well as loss and gain of accessory elements. Our results do also support the view that distinct new variants of STEC O104:H4 repeatedly might originate from yet unknown reservoirs, rather than that there would be a continuous diversification of a single epidemic strain established and circulating in Germany after the large outbreak in 2011. PMID:25836671

  5. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    Directory of Open Access Journals (Sweden)

    de Bruïne Adriaan P

    2005-12-01

    Full Text Available Abstract Background The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1 and Ras (K-ras pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. Methods In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Results Mutations at the phosphorylation sites (codons 31, 33, 37, and 45 in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656 and 36% (235/656, respectively. Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656. Nine percent of all tumours (58/656 lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. Conclusion CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.

  6. Enhanced enteric virus detection in sporadic gastroenteritis using a multi-target real-time PCR panel: a one-year study.

    Science.gov (United States)

    Pang, Xiaoli L; Preiksaitis, Jutta K; Lee, Bonita E

    2014-09-01

    Viral gastroenteritis causes significant mortality and morbidity worldwide. Identifying the etiology of viral gastroenteritis is a challenge as most enteric viruses (EVs) are non-culturable. This study is to develop an EV testing panel using real-time PCR (EVPrtPCR) to simultaneously detect rotavirus, norovirus, sapovirus, astrovirus, and enteric adenovirus in stool samples. EVPrtPCR using universal amplification conditions was run in a single instrument run. EVPrtPCR was used to test 2,486 sporadic gastroenteritis samples submitted for EV testing using electron microscopy (EM) between July 2008 and July 2009. Retesting spiked negative stool samples and Salmon DNA as internal control were used to evaluate inhibition. EVPrtPCR detected viruses in significantly more samples: 748 (34%) as compared to 94 (3.8%) by EM. EM did not detect any norovirus, sapovirus, and mixed infection, and detected only 39% of rotavirus and 38.2% of enteric adenovirus positive samples. Four samples that tested positive for rotavirus and two for adenovirus and for small-round-structured viruses by EM were negative by EVPrtPCR. Norovirus was the most common virus detected (17.6%) with 92.4% as genogroup II, followed by rotavirus (6.8%), sapovirus (4.2%), astrovirus (2.0%), and enteric adenovirus (1.4%) with 9% samples positive for mixed infection. Overall, EV identification followed a U-shaped age distribution; positive samples were more common in children ?5 years old and adults >60 years old. Norovirus, sapovirus and astrovirus showed winter predominance and rotavirus peaked in the spring. No inhibition was observed. Molecular technology significantly enhanced the identification of EV causing sporadic gastroenteritis in Alberta. PMID:24242161

  7. Rearrangements at the 11p15 locus and overexpression of insulin-like growth factor-II gene in sporadic adrenocortical tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gicquel, C.; Schneid, H.; Le Bouc, Y. [Hopital Trousseau, Paris (France); Bertagna, X.; Francillard-Leblond, M.; Luton, J.P.; Girard, F. [Hopital Cochin, Paris (France)

    1994-06-01

    Little is known about the pathophysiology of sporadic adrenocortical tumors in adults. Because loss of heterozygosity at the 11p15 locus has been described in childhood tumors, particularly in adrenocortical tumors associated with the Beckwith-Wiedemann syndrome, and because insulin-like growth factor-II (IGF-II) is a crucial regulator of fetal adrenal growth, the authors looked for structural analysis at the 11p15 locus and IGF-II gene expression in 23 sporadic adrenocortical adult tumors: 6 carcinomas (5 with Cushing`s syndrome and 1 nonsecreting) and 17 benign adenomas (13 with Cushing`s syndrome, 1 pure androgen secreting, and 3 nonsecreting). Twenty-one patients were informative at the 11p15 locus, and six (four carcinomas and two adenomas) of them (28.5%) exhibited 11p15 structural abnormalities in tumor DNA (five, a uniparental disomy and one, a mosaicism). In a single case that could be further studied, a paternal isodisomy was observed. Very high IGF-II mRNA contents were detected in seven tumors (30%; 5 of the 6 carcinomas and 2 of the 17 adenomas). They were particularly found in tumors with uniparental disomy at the 11p15 locus. Overall, a strong correlation existed between IGF-II mRNA contents and DNA demethylation at the IGF-II locus. These data show that genetic alterations involving the 11p15 locus were highly frequent in malignant tumors, but found only in rare adenomas. These results in combination with evidence for overexpression of IGF-II from the 11p15.5 locus suggest that abnormalities in structure and/or expression of the IGF-II gene play a role as a late event of a multistep process of tumorigenesis. 58 refs., 6 figs., 4 tabs.

  8. Sporadic salmonellosis in Lower Saxony, Germany, 2011-2013: raw ground pork consumption is associated with Salmonella Typhimurium infections and foreign travel with Salmonella Enteritidis infections.

    Science.gov (United States)

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

    2015-10-01

    To investigate risk factors for sporadic salmonellosis, for each notified case four randomly selected population controls matched for age, sex and geographical region were interviewed via self-administered questionnaire. Conditional logistic regression analysis of 285 matched pairs revealed significant associations for raw ground pork consumption [odds ratio (OR) 6·0, 95% confidence interval (CI) 1·8-20·1], taking antacids (OR 5·8, 95% CI 1·4-24·5), eating meat outside the home (OR 5·7, 95% CI 2·2-14·6) and daily changing or cleaning of dishcloth (OR 2·1, 95% CI 1·2-3·9). Animal contact and ice cream consumption were negatively associated with salmonellosis (OR 0·5, 95% CI 0·2-1 and OR 0·3, 95% CI 0·1-0·6, respectively). S. Typhimurium infections were significantly associated with raw ground pork consumption (OR 16·7, 95% CI 1·4-194·4) and S. Enteritidis infections with having travelled abroad (OR 9·7, 95% CI 2·0-47·3). Raw egg consumption was not a risk factor, substantiating the success of recently implemented national control programmes in the poultry industry. Unexpectedly, hygienic behaviour was more frequently reported by cases, probably because they overestimated their hygiene precautions retrospectively. Although animal contact might enhance human immunocompetence, underreporting of salmonellosis by pet owners could have occurred. Eating raw pork products is the major risk factor for sporadic human S. Typhimurium infections in Lower Saxony. PMID:25626727

  9. Subtype Analysis of Cryptosporidium Specimens from Sporadic Cases in Colorado, Idaho, New Mexico, and Iowa in 2007: Widespread Occurrence of One Cryptosporidium hominis Subtype and Case History of an Infection with the Cryptosporidium Horse Genotype?

    OpenAIRE

    Xiao, Lihua; Hlavsa, Michele C.; Yoder, Jonathan; Ewers, Christina; Dearen, Theresa; Yang, Wenli; Nett, Randall; Harris, Stephanie; Brend, Sarah M; Harris, Meghan; Onischuk, Lisa; Valderrama, Amy L.; Cosgrove, Shaun; Xavier, Karen; Hall, Nancy

    2009-01-01

    Subtyping was conducted in late 2007 on 57 Cryptosporidium specimens from sporadic cases in Colorado, Idaho, New Mexico, and Iowa. One previously rare Cryptosporidium hominis subtype was indentified in 40 cases (70%) from all four states, and the Cryptosporidium horse genotype was identified in a pet shop employee with severe clinical symptoms.

  10. Nearby Supernova Factory Observations of SN 2006D: On SporadicCarbon Signatures in Early Type Ia Supernova Spectra

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, R.C.; Aldering, G.; Antilogus, P.; Aragon, C.; Bailey,S.; Baltay, C.; Baron, E.; Bauer, A.; Buton, C.; Bongard, S.; Copin, Y.; Gangler, E.; Gilles, S.; Kessler, R.; Loken, S.; Nugent, P.; Pain, R.; Parrent, J.; Pecontal, E.; Pereira, R.; Perlmutter, S.; Rabinowitz, D.; Rigaudier, G.; Runge, K.; Scalzo, R.; Smadja, G.; Wang, L.; Weaver, B.A.

    2006-10-12

    We present four spectra of the Type Ia supernova SN Ia 2006Dextending from -7 to +13 days with respect to B-band maximum. The spectrainclude the strongest signature of unburned material at photosphericvelocities observed in a SN Ia to date. The earliest spectrum exhibits CII absorption features below 14,000 km/s, including a distinctive C IIlambda 6580 absorption feature. The carbon signatures dissipate as the SNapproaches peak brightness. In addition to discussing implications ofphotospheric-velocity carbon for white dwarf explosion models, we outlinesome factors that may influence the frequency of its detection before andaround peak brightness. Two effects are explored in this regard,including depopulation of the C II optical levels by non-LTE effects, andline-of-sight effects resulting from a clumpy distribution of unburnedmaterial with low volume-filling factor.

  11. Factores de riesgo de casos esporádicos de gastroenteritis por Campylobacter en niños / Risk factors for sporadic cases of Campylobacter infection in children

    Scientific Electronic Library Online (English)

    Marta, Fajó-Pascual; Pere, Godoy García; Jesús, Aramburu Arnuelos; Antoni, Nogués Biau.

    2009-08-01

    Full Text Available Objetivos: Identificar factores de riesgo en casos esporádicos de gastroenteritis por Campylobacter en niños [...] obacter. Se recogió información telefónicamente mediante cuestionario estructurado sobre predisposición individual, exposiciones alimentarias y no alimentarias. Mediante multivariado de regresión logística condicional se estimó la odds ratio ajustada (ORa) y el intervalo de confianza del 95% (IC95%). Resultados: Se incluyeron 45 casos y 45 controles. La edad mediana de los casos fue de 1,6 años. El consumo de fiambre >2 veces (ORa:4,2; IC95%:1,2-14,7), pollo >3 veces (ORa:3,6; IC95%:1,1-11,1) y toma previa de antibióticos (ORa:4,7; IC95%:1,1-19,6) se asociaron independientemente con la enfermedad. Conclusiones Se identificó la carne de pollo como factor de riesgo de campilobacteriosis, bien por consumo o por manipulación inadecuada que podría ocasionar contaminación cruzada de otros alimentos «listos para comer», como los fiambres. Abstract in english Objectives: To identify risk factors for sporadic cases of Campylobacter infection in children aged [...] cter. Information was gathered by telephone using a structured questionnaire on individual susceptibility and food and non-food exposures. A multivariate conditional logistic regression model was used to estimate adjusted odds ratios (ORa) and their 95% confidence intervals (95%CI). Results: Forty-five cases and 45 controls were included in the analysis. The median age of cases was 1.6 years. Factors independently associated with disease were consumption of cooked deli meat >2 times (ORa:4.2, 95%CI:1.2-14.7), chicken >3 times (ORa:3.6, 95%CI:1.1-11.1) in the week before symptom onset, and previous antibiotic intake (ORa:4.7, 95%CI:1.1-19.6). Conclusions: Chicken meat was a risk factor for sporadic cases of campylobacteriosis in children, whether through consumption or through cross-contamination with other «ready-to-eat» foods such as cooked deli meat.

  12. PTH(1-34) Replacement Therapy in a Child With Hypoparathyroidism Caused by a Sporadic Calcium Receptor Mutation

    OpenAIRE

    Theman, Todd A; Collins, Michael T.; Dempster, David W.; Zhou, Hua; Reynolds, James C.; Brahim, Jaime S; Roschger, Paul; Klaushofer, Klaus; Winer, Karen K.

    2008-01-01

    Autosomal dominant hypocalcemia (ADH) is an inherited form of hypoparathyroidism caused by activating mutations in the calcium-sensing receptor (CaR). Treatment with PTH(1-34) may be superior to conventional therapy but is contraindicated in children, and long-term effects on the skeleton are unknown. The patient is a 20-yr-old female with ADH treated with PTH continuously since 6 yr and 2 mo of age. A bone biopsy was obtained for histomorphometry and quantitative backscattered electron imagi...

  13. Characterisation of human outbreaks of brucellosis and sporadic cases by the use of hyper-variable octameric oligonucleotide fingerprint (HOOF) variable number tandem repeats.

    Science.gov (United States)

    Valdezate, S; Cervera, I; Hernandez, P; Navarro, A; Saéz Nieto, J A

    2007-09-01

    Hyper-variable octameric oligonucleotide fingerprints (HOOFs) enable typing of Brucella spp. by targeting the 8-bp tandem repeat in eight loci that vary in number (variable number tandem repeats; VNTRs). Brucella is one of the most important zoonotic pathogens, because of its public health and economic consequences. To assess the role of HOOFs as epidemiological markers for Brucella melitensis, which is the main species involved in human brucellosis in Spain, 87 sporadic and outbreak isolates were investigated; these originated from broad or more restricted geographical locations, including unrelated (n = 42), semi-related (n = 19) and closely related (n = 26) groups of isolates. Distinct HOOFs were detected in the entire (n = 74), unrelated (n = 42), semi-related (n = 19) and closely related (n = 13) groups. Seven of the eight VNTR markers investigated identified multiple alleles in the four groups of isolates. Using the composite data for eight VNTRs, a diversity value of 0.98 was calculated for the entire population, taking into account single- and double-locus variants. A high correlation (R = 0.98) between the maximum copy number and the number of alleles was observed. The most polymorphic markers were VNTR-1, VNTR-4, VNTR-5 and VNTR-7 (D > OR = 0.8). Characterisation of B. melitensis isolates by HOOFs enabled the recognition of related human cases and the exchange of molecular epidemiological information concerning a spreading clone, thus improving brucellosis surveillance. PMID:17686139

  14. Comparative peptidome analyses of the profiles of the peptides ranging from 1-10 KD in CSF samples pooled from probable sporadic CJD and non-CJD patients.

    Science.gov (United States)

    Chen, Cao; Xiao, Di; Zhou, Wei; Zhang, Yong-Chan; Shi, Qi; Tian, Chan; Zhang, Jin; Zhou, Chun-Xi; Zhang, Jian-Zhong; Dong, Xiao-Ping

    2012-01-01

    The shotgun strategy applying tandem mass spectrometry has been widely used to identify the proteins that are differentially distributed among diseases for its high reliability and efficiency. To find out the potential difference of protein profiles in cerebrospinal fluids (CSF) between Creutzfeldt-Jakob disease (CJD) and non-CJD patients, especially in the fraction ranging from 1-10 KD, the CSF samples of 40 probable sporadic CJD (sCJD) patients, 32 non-CJD cases with dementia and 17 non-CJD cases without dementia were separately pooled and enriched by the magnetic beads based weak cation exchange chromatography (MB-WCX). After trypsin digestion, each enriched CSF was separated and identified by RP-HPLC-ESI-QTOF MS/MS. In total, 42, 53 and 47 signals of proteins were identified in the pooled CSF fraction less than 10 KD of probable sCJD, non-CJD with dementia and non-CJD without dementia, respectively. Compared with that of probable sCJD, the similarity of CSF protein profiles of non-CJD with dementia (76.2%) were higher than that of non-CJD without dementia (57.1%). Nine CSF proteins were found to be specially observed in probable sCJD group. Those data may help to select the potential biomarkers for diagnosis of CJD. Additionally, further studies of the small segments of cellular proteins in CSF of CJD patients may also provide scientific clues for understanding the neuropathogenesis of TSEs. PMID:22453178

  15. Comparative peptidome analyses of the profiles of the peptides ranging from 1–10 KD in CSF samples pooled from probable sporadic CJD and non-CJD patients

    Science.gov (United States)

    Zhou, Wei; Zhang, Yong-Chan; Shi, Qi; Tian, Chan; Zhang, Jin; Zhou, Chun-Xi

    2012-01-01

    The shotgun strategy applying tandem mass spectrometry has been widely used to identify the proteins that are differentially distributed among diseases for its high reliability and efficiency. To find out the potential difference of protein profiles in cerebrospinal fluids (CSF) between Creutzfeldt-Jakob disease (CJD) and non-CJD patients, especially in the fraction ranging from 1–10 KD, the CSF samples of 40 probable sporadic CJD (sCJD) patients, 32 non-CJD cases with dementia and 17 non-CJD cases without dementia were separately pooled and enriched by the magnetic beads based weak cation exchange chromatography (MB-WCX). After trypsin digestion, each enriched CSF was separated and identified by RP-HPLC-ESI-QTOF MS/MS. In total, 42, 53 and 47 signals of proteins were identified in the pooled CSF fraction less than 10 KD of probable sCJD, non-CJD with dementia and non-CJD without dementia, respectively. Compared with that of probable sCJD, the similarity of CSF protein profiles of non-CJD with dementia (76.2%) were higher than that of non-CJD without dementia (57.1%). Nine CSF proteins were found to be specially observed in probable sCJD group. Those data may help to select the potential biomarkers for diagnosis of CJD. Additionally, further studies of the small segments of cellular proteins in CSF of CJD patients may also provide scientific clues for understanding the neuropathogenesis of TSEs. PMID:22453178

  16. Cervical dystonia: about familial and sporadic cases in 88 patients / Distonia cervical: considerações sobre casos esporádicos e familiares em 88 pacientes

    Scientific Electronic Library Online (English)

    Carlos Henrique F., Camargo; Sarah Teixeira, Camargos; Nilson, Becker; Renato Puppi, Munhoz; Salmo, Raskin; Francisco Eduardo C., Cardoso; Hélio Afonso G., Teive.

    2014-02-01

    Full Text Available A distonia cervical (CD) afeta a musculatura do pescoço de modo focal ou em combinação com outras partes do corpo. O objetivo deste estudo foi identificar diferenças clínicas entre pacientes com distonia com história familiar e pacientes sem história familiar (esporádicos). Foram selecionados 88 pac [...] ientes com DC no Setor de Distúrbios do Movimento entre julho de 2008 e junho de 2009. Somente os pacientes sem diagnóstico etiológico foram admitidos para análise. A idade de início dos sintomas foi mais tardia em pacientes com distonia focal e segmentar do que em pacientes com distonia generalizada (p Abstract in english Cervical dystonia (CD) affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic). Eighty-eight patients with [...] CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p

  17. No evidence that associations of incident, sporadic colorectal adenoma with its major modifiable risk factors differ by chromosome 8q24 region rs6983267 genotype.

    Science.gov (United States)

    Yang, Baiyu; Thyagarajan, Bharat; Gross, Myron D; Fedirko, Veronika; Goodman, Michael; Bostick, Roberd M

    2014-02-01

    A single nucleotide polymorphism (SNP), rs6983267, in the chromosome 8q24 region, has been associated with higher risk for colorectal neoplasms, but its relation to carcinogenic mechanisms is unclear. To investigate whether associations of colorectal adenoma with its major modifiable risk factors differ according to rs6983267 genotype, we performed a pooled analysis of the White participants (n = 401 cases, 518 controls) from three colonoscopy-based, case-control studies of incident, sporadic colorectal adenoma conducted between 1991 and 2002. There was a statistically significant direct association of rs6983267 with colorectal adenoma that was consistent with those in previous reports. We found no clear indications that rs6983267 impacts the association of colorectal adenomas with the following risk factors: physical activity, body mass index (BMI), nonsteroidal anti-inflammatory drug (NSAID) use, tobacco or alcohol use, hormone replacement therapy among women, blood 25-OH-vitamin D3 levels, oxidative balance, or total energy, calcium, red meat, vegetable and fruit, and folate intakes. These findings, together with previously reported null results on 8q24-environment interactions for colorectal cancer, suggest that associations of colorectal adenoma with its major modifiable risk factors may not differ according to chromosome 8q24 region rs6983267 genotype. PMID:24115145

  18. PTH(1-34) replacement therapy in a child with hypoparathyroidism caused by a sporadic calcium receptor mutation.

    Science.gov (United States)

    Theman, Todd A; Collins, Michael T; Dempster, David W; Zhou, Hua; Reynolds, James C; Brahim, Jaime S; Roschger, Paul; Klaushofer, Klaus; Winer, Karen K

    2009-05-01

    Autosomal dominant hypocalcemia (ADH) is an inherited form of hypoparathyroidism caused by activating mutations in the calcium-sensing receptor (CaR). Treatment with PTH(1-34) may be superior to conventional therapy but is contraindicated in children, and long-term effects on the skeleton are unknown. The patient is a 20-yr-old female with ADH treated with PTH continuously since 6 yr and 2 mo of age. A bone biopsy was obtained for histomorphometry and quantitative backscattered electron imaging (qBEI). Her data were compared with one age-, sex-, and length of hypoparathyroidism-matched control not on PTH and two sex-matched ADH controls before and after 1 yr of PTH. The patient's growth was normal. Hypercalciuria and hypermagnesuria persisted despite normal or subnormal serum calcium and magnesium levels. Nephrocalcinosis, without evidence of impaired renal function, developed by 19 yr of age. Cancellous bone volume was dramatically elevated in the patient and in ADH controls after 1 yr of PTH. BMD distribution (BMDD) by qBEI of the patient and ADH controls was strikingly shifted toward lower mineralization compared with the non-ADH control. Moreover, the ADH controls exhibited a further reduction in mineralization after 1 yr of PTH. These findings imply a role for CaR in bone matrix mineralization. There were no fractures or osteosarcoma. In conclusion, long-term PTH replacement in a child with ADH was not unsafe, increased bone mass without negatively impacting mineralization, and improved serum mineral control but did not prevent nephrocalcinosis. Additionally, this may be the first evidence of a role for CaR in human bone. PMID:19063686

  19. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial)

    OpenAIRE

    Mead, Graham M.; Barrans, Sharon L.; Qian, Wendi; Walewski, Jan; John A Radford; Wolf, Max,; Clawson, Simon M.; Stenning, Sally P; Yule, Claire L.; Jack, Andrew S

    2008-01-01

    This prospective study aimed to develop reproducible diagnostic criteria for sporadic Burkitt lymphoma (BL), applicable to routine practice, and to evaluate the efficacy of dose-modified (dm) CODOX-M/IVAC in patients diagnosed using these criteria. The study was open to patients with an aggressive B-cell lymphoma with an MKI67 fraction approaching 100%. Immunophenotype and fluorescent in situ hybridization (FISH) were used to separate BL from other aggressive B-cell lymphomas. BL was characte...

  20. Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases

    OpenAIRE

    Gilson Costa dos Santos-Jr; Andréa Carla de Souza Góoes; Humberto de Vitto; Carla Cristina Moreira; Elizabeth Avvad; Franklin David Rumjanek; Claudia Vitoria de Moura Gallo

    2012-01-01

    OBJECTIVE: Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data. METHODS: We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples ...